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Category Archives: Transhuman News

Pretzel Therapeutics Launches With $72.5 Million Series A Financing to Pioneer Mitochondrial Therapies – Business Wire

Posted: September 17, 2022 at 11:25 pm

WALTHAM, Mass.--(BUSINESS WIRE)--Pretzel Therapeutics, a biotechnology company harnessing the intricacies of mitochondrial biology to develop groundbreaking therapies, launched today with a $72.5 million Series A financing to pioneer novel therapies to modulate mitochondrial function. The financing was led by ARCH Venture Partners and Mubadala Capital with participating investors HealthCap, Cambridge Innovation Capital, Cambridge Enterprise, Angelini Ventures, GV, Invus, Eir Ventures, GU Ventures, and Karolinska Institutet Holding.

We are excited to pioneer a new era in the treatment of diseases related to mitochondrial dysfunction. The expertise we have assembled and the platform technologies we have created will allow new inroads into treating both rare genetic diseases as well as common diseases of aging, said Jay Parrish, Ph.D., Chairman of the Board and Chief Executive Officer of Pretzel. Were proud to be backed by an outstanding investor syndicate, with a Series A financing that will allow us to prosecute preclinical development across our pipeline and continue to build out our talented team.

Pretzel is advancing a first-of-its-kind platform to modulate mitochondrial biology, with a vast range of potential applications across rare and common disorders, said Alaa Halawa, MBA, Partner and Head of the U.S. Ventures business at Mubadala Capital. As investors focused on partnering early with companies that will positively impact patients lives, were proud to co-lead the companys Series A financing and to partner with Pretzel on their journey to build the worlds leading center of excellence addressing diseases of mitochondrial dysfunction.

Dysfunctional mitochondria are involved in more than 50 diseases. The most severe of these are broadly termed mitochondrial diseases, a group of rare genetic conditions which affect individuals of all ages. Mitochondrial dysfunction also plays an important role in more common diseases, including aging-related disorders such as Alzheimers and Parkinsons diseases. In addition, modulating mitochondrial biology presents a potential approach to the treatment of diseases not directly caused by mitochondrial dysfunction, for instance cancer and metabolic diseases.

Pretzels platform encompasses three primary technologies to modulate mitochondrial function: Genome correction, genome expression modulation, and mitochondrial quality control. The companys genome correction therapeutics will utilize specialized gene-editing tools to reduce mutated mitochondrial DNA and increase the levels of healthy mitochondrial DNA. Genome expression modulation will be accomplished using small molecules that act on the enzymes involved in mitochondrial DNA replication, transcription, and translation. Finally, mitochondrial quality control will be targeted using small molecules that modulate mitochondrias built-in quality control system.

Founders and Team

Pretzels founders include three leading academics in the field of mitochondrial biology. Claes Gustafsson, M.D., Ph.D., is professor of medical biochemistry at the University of Gothenburg and an expert in mitochondrial gene expression. Michal Minczuk, Ph.D., is a Group Leader and MRC Investigator at the MRC Mitochondrial Biology Unit, University of Cambridge and an expert in mitochondrial genome engineering. Nils-Gran Larsson, M.D., Ph.D., is professor of mitochondrial genetics at the Department of Medical Biochemistry and Biophysics at Karolinska Institutet who has published over 150 articles on mitochondrial biology.

In addition to Drs. Gustafsson, Minczuk, and Larsson, founders Gabriel Martinez, Ph.D. and Paul Thurk, Ph.D., played a formative role in the companys creation based on their deep biotechnology industry expertise. Finally, the company recognizes the contributions of Gunther Kern, Ph.D., MBA; Jeremy Green, Ph.D.; and Christina Trojel-Hansen, Ph.D., to the formation of Pretzel.

Mitochondria have historically been a challenging cellular organelle to target therapeutically, in part because mitochondrial diseases are extremely diverse, both genetically and phenotypically, but also due to the distinctive characteristics of mitochondrial genome function. However, scientific understanding of mitochondrial biology has greatly advanced in recent years, allowing new insights into their role in many prevalent diseases, as well as how they can be therapeutically targeted, said Claes Gustafsson. Its gratifying to form Pretzel to translate these insights into therapies that could meaningfully improve peoples lives.

Pretzel is led by accomplished experts in drug discovery, drug development, and company foundation, and is advised by a Board of Directors and Scientific Advisory Board with deep scientific and industry expertise.

Pretzels leadership team is comprised of:

The companys Board of Directors is comprised of:

The companys Scientific Advisory Board is comprised of:

About Pretzel Therapeutics

Pretzel Therapeutics is a biotechnology company harnessing the intricacies of mitochondrial biology to develop groundbreaking therapies. Pretzel was founded by leading academic experts in mitochondrial biology and is backed by a world-class investor syndicate. The company is headquartered in Waltham, MA and has research facilities in Gothenburg, Sweden. For more information, visit http://www.pretzeltx.com.

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Pretzel Therapeutics Launches With $72.5 Million Series A Financing to Pioneer Mitochondrial Therapies - Business Wire

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Infographic: Noncoding RNA in the Brain – The Scientist

Posted: at 11:25 pm

Bursts in microRNA (miRNA) diversity often line up with sudden increases in morphological complexity, especially in the context of the nervous system. In a 2022 bioRxiv preprint, researchers uncovered an miRNA repertoire expansion (orange) in the ancestor of coleoid cephalopodsthe group that includes squids and octopuses, generally thought to be more intelligent than any other invertebrateson par with ones seen in the ancestors of vertebrates (blue) and placental mammals (green).

The term noncoding RNA is a catch-all for sequences in the genome that are transcribed but typically not translated. These molecules, which account for the majority of the transcribed sequences in the genome, are now thought to play key roles in brain evolution and function. Noncoding RNAs can be classified based on their size, structure, location, or function, with dozens of different kinds described to date. Here are four types of noncoding RNA frequently studied in brain tissues.

Long noncoding RNAs (lncRNAs) are generally described as any noncoding RNAs greater than 200 nucleotides in length. Because of their variable size and composition, they can have complex shapes and perform a variety of cellular activities, though most lncRNAs await functional investigation.

Example: The human and chimpanzee versions of a lncRNA called HAR1 differ by 18 nucleotides, which impacts the molecules secondary structure. The human version is predicted to be more stable, but exactly how that translates into differences in brain form or function isnt yet clear.

MicroRNAs (miRNAs) are small noncoding RNAs of just ~2026 nucleotides (teal) that are cleaved from larger precursors. Their most well-described function is the regulation of gene expression via binding to messenger RNAs, where they generally inhibit translation and, therefore, reduce the amount of protein produced from a given gene.

Example: Overexpression of miRNA-124 leads to Alzheimers-like pathologies in mice, and elevated levels of the miRNA are found in the brains of people who died from the disease.

As the name suggests, circular RNAs (circRNAs) are noncoding RNAs with joined ends, creating a more stable, circular molecule. Many questions remain as to the functions of circRNAs, but some are known to bind miRNAs, likely acting as sponges to modulate the miRNAs translation-suppressing effects.

Example:The circRNA CDR1-AS fine tunes neuronal development in humans, binding microRNAs (teal) highly expressed in secretory neurons that regulate developmental gene expression.

Transfer RNAs primary job is to shuttle amino acids to growing peptide chains during translation. In the brain specifically, theres emerging evidence that modifications to tRNAs play important roles in neuronal health and disease. Furthermore,tRNA fragmentssmall chunks from tRNA breakdownseem to have their own functions, including in neurodegeneration.

Example: When researchers exposed Drosophilaneuron cultures to synthetic tRFGln-CTG(teal)a fragment of the tRNA for glutaminethe cells swelled and died, suggesting the fragment could play a role in neuronal necrosis.

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Discovery, isolation, heterologous expression and mode-of-action studies of the antibiotic polyketide tatiomicin from Amycolatopsis sp. DEM30355 |…

Posted: at 11:25 pm

The actinomycete DEM30355 was isolated from a soil sample, collected from the El Tatio geyser field within an arid part of the Atacama Desert in Chile17. Strain DEM30355 was recovered in the genus Amycolatopsis, based on 16S rRNA analysis, forming a subgroup with Amycolatopsis vancoresmycina DSM 44592T and Amycolatopsis bullii SF27T (see ESI). The genus Amycolatopsis contains 94 species and four subspecies encompassing both extremophiles and producers of bioactive secondary metabolites, including the clinically used vancomycin and rifamycin antibiotics19,20. Preliminary bioactivity screening showed that extracts of Amycolatopsis sp. DEM30355 displayed promising antibiotic activity against B. subtilis, thus we decided to examine the genome of Amycolatopsis sp. DEM30355 for novel biosynthetic potential. Purified genomic DNA from Amycolatopsis sp. DEM30355 was analysed using both PacBio and Illumina sequencing technologies and genome assembly was performed using the combined datasets to give a 9.6Mb draft genome, in 13 contigs. The draft genome of Amycolatopsis sp. DEM30355 was examined using the secondary metabolite analysis software AntiSMASH 6.0.121. Of the 31 biosynthetic gene clusters (BGCs) detected, a PKS cluster was identified showing moderate overall similarity (81%) to that which encodes for rishirilides A and B22,23,24,25,26. These compounds are anthracenone polyketides, originally isolated from Streptomyces rishiriensis OFR-1056, with no reported antibiotic activity. Rishirilide B has been shown to be a moderately potent inhibitor of 2-macroglobulin, glutathione S-transferase and asparaginyl-tRNA synthetase, whilst little is known about the biological role of rishirilide A (Fig.1)18,27,28.

Top ()-Rishirilide A (1) and (+)-rishirilide B (2). Relative stereochemistry of ()-1 and absolute stereochemistry of (+)-2 shown. Bottom. Structure of ()-tatiomicin (3) as derived from NMR and SCXRD experiments. Key COSY (red) and HMBC (blue) correlations shown. Absolute stereochemistry as shown by both vibrational circular dichroism (VCD) and single-crystal X-ray diffraction (SCXRD) resonant scattering experiments. Structural differences of rishirilide A and tatiomicin are highlighted (magenta).

Further inspection of the BGC from Amycolatopsis sp. DEM30355 revealed a highly altered gene synteny (see ESI), compared to the rishirilide BGC, along with the presence of several new genes: one postulated to be involved in PKS biosynthesis (tatS1), two encoding methyltransferases (tatM1 and tatM2), two encoding cyclases (tatC4 and tatC5) and one cytochrome p450 oxidoreductase (tatO11) (Fig.2). Due to the significant variation in the genetic make-up of the BGC, we postulated that it may code for the production of an as yet undiscovered polyketide and as such we set about attempting to identify this molecule from the metabolome of Amycolatopsis sp. DEM30355.

Organization of the tatiomicin BGC. Genes coding for polyketide biosynthesis (red; tatS=starter unit biosynthesis, tatK=chain biosynthesis), polyketide modification (blue; tatO=oxidoreductases, tatC=cyclases, tatM=methyltransferases), regulation (yellow; tatR), transport (green, tatT) and others (grey; tatP=phosphorylase, black; genes not assigned to the tatiomicin BGC based on homology to the rishirilide BGC and proposed biosynthetic pathway)).

Preliminary analysis of the fermentation supernatant of Amycolatopsis sp. DEM30355 by HPLC-HRMS showed the presence of a large number of secondary metabolites, in keeping with the predicted number of BGCs, including a compound with activity against Gram-positive bacteria (MW of 402Da, m/z=403 [M+H]+, m/z=425 [M+Na]+, ()-tatiomicin (3)). Fermentation of Amycolatopsis sp. DEM30355, removal of the biomass, extraction of the supernatant and bioactivity guided fractionation by multiple chromatography steps resulted in a fraction which retained antimicrobial activity and contained two closely related compounds. HRMS analysis suggested that these compounds were stereoisomers of each other, the major compound showing m/z=425.1221 [M+Na]+ corresponding to a molecular formula of C21H22O8 for both molecules (see ESI).

Structural determination of the major component was initially performed by NMR, which provided the majority of molecular connectivity with the exception of the ordering of the three contiguous quaternary centres at the C-3, C-4 and C-4a positions. Structural assignment was completed via single-crystal X-ray diffraction (XRD) analysis, revealing a highly oxygenated anthracenone polyketide, structurally consistent with the BGC of interest, which we named ()-tatiomicin (3) (Fig.1)29.

NMR and HPLC experiments demonstrated that the minor compound was the C-2 epimer, capable of equilibrating with ()-(3) under acidic conditions (see ESI).

Determination of the absolute stereochemistry of ()-3 was undertaken in parallel via vibrational and electronic circular dichroism spectroscopies and additional single-crystal X-ray diffraction (SCXRD) experiments.

Absolute configuration determination by vibrational circular dichroism (VCD) was based on a comparison of experimental and computationally predicted spectra, taking into account the presence of two epimers of ()-3. Conformational analysis (see ESI), removal of redundant geometries and final optimization at the B3LYP/6311++G(d,p) level allowed Boltzmann-weighted VCD spectra for both epimers of ()-3 to be constructed. The final predicted spectrum was obtained by applying a 3:1 ratio to account for the experimentally analysed mixture of epimers. Numerical analysis was used to establish agreement between experiment and theory, the neighbourhood similarity values (IR=92.0, VCD=71.2, ESI=57.8) suggesting an absolute stereochemical assignment of (2S,3S,4R,4aR,10R) (Fig.3 and ESI)30. The assignment was supported through similar electronic circular dichroism (ECD) experiments; however, in this case correlation between experiment and prediction was weaker (see ESI).

Experimental IR (top) and VCD spectra (bottom) of ()-tatiomicin 3 (CDCl3) with predicted spectra obtained at the B3LYP/PCM/6311++G(d,p) level of theory. VCD: Solid line=(2R,3R,4S,4aS,10S), dashed line=(2S,3S,4R,4aR,10R). Spectra have been frequency scaled Black line (=0.987) to yield maximal similarity grey line between the computed and experimental VCD spectra.

A suitable, albeit small, single-crystal of tatiomicin (3) was grown via slow evaporation from a benzene solution. Due to the crystals dimensions, diffraction data were collected at beam line I19 at the Diamond Light Source using synchrotron radiation at standard operating wavelength (=0.6889), providing a data set of sufficient quality to allow for structural confirmation. ()-Tatiomicin (3) crystallized as an H-bonded dimer in the unit cell (Z=2) along with a single molecule of solvent (benzene). To validate the absolute stereochemical assignment a further single-crystal X-ray diffraction experiment was undertaken at I19, employing non-typical, longer wavelength synchrotron radiation (=1.4879) to enhance resonant scattering contributions (also known inappropriately as anomalous dispersion). The absolute-structure (Flack) parameter (0.05(6)) was insignificantly different from zero and with a small standard uncertainty, indicating the correct absolute configuration in the refined (2S,3S,4R,4aR,10R) structure (see ESI)29. Interestingly, following extensive stereochemical debate and several reported total syntheses, the absolute stereochemistry of the congeneric (+)-rishirilide B (2) was recently revised (2S,3S,4S), matching that of ()-(3) over the three common stereocentres, suggesting a similar biosynthetic pathway for both sets of natural products (Fig.4)31,32,33,34,35.

Displacement ellipsoid plot of the molecular structure of ()-tatiomicin (3), absolute stereochemistry as shown determined by resonant scatteringthe dimer molecular structure (Flack parameter=0.05(6)). Displacement ellipsoids shown at 50% probability level.

To verify that the BGC previously identified does indeed encode the biosynthetic pathway for tatiomicin (3), a high molecular-weight P1 artificial chromosome (PAC) library was obtained, consisting of 2,688 clones with an average insert size of 138kb which contained resistant markers for kanamycin (for E. coli) and thiostreptone (for S. coelicolor). The PAC library was screened by PCR, using four primer pairs for the putative BGC. A single PAC clone was identified with the required PCR profile, which was then transferred into E. coli strain ET12567/pR9604 (dam- dcm-), the plasmid was subsequently transferred into S. coelicolor M1152 via conjugation. Exconjugants containing the plasmid integrated on the chromosome were selected for resistance to thiostrepton. Ninety-six putatively identified exconjugants were arrayed into 24 well plates and screened for the production of tatiomicin (3) by TLC, with detection based on the characteristic fluorescence upon UV irradiation at 365nm. Based on these screening parameters, S. coelicolor M1152::tat was identified as a producer of tatiomicin (3) (see ESI).

Growth of S. coelicolor M1152::tat was examined on solid medium, the agar was extracted (EtOAc) and analysed by LCMS alongside similar fermentation extracts from both the parent strain M1152, Amycolatopsis sp. DEM30355 and a tatiomicin (3) standard. An LCMS peak corresponding to tatiomicin (3) was observed in the extract from S. coelicolor M1152::tat but was absent in that of the parent strain M1152 (Fig.6).

Tatiomicin (3) was subsequently isolated from the fermentation of S. coelicolor M1152::tat in liquid medium (GYMG), as demonstrated by HRMS ([M+H]+=403.1403), with a production level in the heterologous host estimated at 0.57mg/L, confirming the identity of the tatiomicin BGC (Fig.5).

Detection of tatiomicin from the fermentation of heterologous host S. coelicolor M1152::tat. Top) Extracted ion chromatogram (EIC) based on m/z=827.25. S. coelicolor M1152 (purple), S. coelicolor M1152::tat (blue), Amycolatopsis sp. DEM30355 (black) and tatiomicin standard (red). Bottom) MS spectrum of tatiomicin (3) purified from the heterologous host S. coelicolor M1152::tat.

Based on a comparison between the tatiomicin and rishirilide BGCs22,23,24,25,26 we propose the following biosynthetic pathway operates for the assembly of tatiomicin (3) (See ESI). The modular type I polyketide synthase TatS1 is likely responsible for the biosynthesis of the polyketide starter unit, cis-crotonyl-ACP, which is then elongated via the attachment of eight malonyl-CoA by minimal PKS enzymes TatK1, TatK2, and TatK3. TatC1, TatC2, TatC3 and TatO10 show close homology to rishirilide cyclases RslC1, RslC2, and RslC3 and C9-ketoreductase RslO10, respectively. Thus, TatC1 and TatO10 likely act together to form the A ring of tatiomicin (3), whilst TatC2 and TatC3 catalyse the formation of the B and C rings. Tailoring of the polyketide core likely involves oxidation of the C ring by TatO4, and installation of the C ring epoxide by flavin mononucleotide (FMN)-dependent monooxygenase TatO1 together with a putative flavin reductase, TatO2. Opening of the epoxide is proposed to be mediated by NADPH:acceptor oxidoreductase TatO5, followed by the key BaeyerVilliger oxidation/rearrangement controlled by TatO9 and finally reduction of the B ring ketone by ketoreductase TatO8.

Three additional tailoring enzymes are present in the BGC of tatiomicin (3) for which no homologues are present in that of rishirilide, TatO11, TatM1 and TatM2. TatO11 is a cytochrome p450 oxidoreductase, likely responsible for oxidation of the A ring to the hydroquinone form, followed by double methylation by the two methyl transferases TatM1 and TatM2 to yield the completed molecule (Fig.6).

Top) Proposed pathway for the biosynthesis of ()-tatiomicin (3) based on homology with the biosynthetic gene cluster for the rishirilides. Enzymes shown in red have no direct congener in the rishirilide BGC and their biosynthetic role is hypothesised, based on BLAST analysis. Bottom) comparison of the rishirilide and (-) tatiomicin gene cluter based on BLAST analysis. (red; tatS=starter unit biosynthesis, tatK or rslK=chain biosynthesis), polyketide modification (blue; tatO or rslO=oxidoreductases, tatC or rslO=cyclases), regulation (yellow; tatR or rslR), transport (green, tatT or rslT) and others (grey; tatP or rslP=phosphorylase; tatM=methyltransferases, black; genes not assigned to the tatiomicin BGC based on homology to the rishirilide BGC and proposed biosynthetic pathway)).

The enzymes TatC4 and TatC5, which are not present in the rishirilide cluster, encode for a dehydrogenase and a monooxygenase and are located in the centre of the biosynthetic gene cluster. The tatiomicin BGC contains all orthologous genes responsible for the synthesis of rishirilide. The function of these additional genes is therefore not immediate obvious and might be a result of evolutionary divergence.

()-Tatiomicin (3) showed no detectable antimicrobial activity (MIC>64g/mL) against ten Gram-negative bacteria and two eukaryotic microorganisms (Candida spp.) (see ESI). However, antibacterial activity was observed against a sub-set of Gram-positive bacteria (MIC=48g/mL), namely Staphylococcus and Streptococcus species. Due to the interest in developing new antibiotics against drug-resistant Staphylococcus infections, we further evaluated ()-3 against a panel of MRSA clinical isolates, including twenty-four EMRSA-15 and EMRSA-16 strains (the main causative agents of nosocomial epidemic MRSA bacteraemia in the UK, with resistance to penicillin, ciprofloxacin and erythromycin)36, and twelve MRSA strains isolated from Belgian, Finnish, French and German hospitals (see SI). In all cases antibiotic activity was maintained (MIC=48g/mL), suggesting that ()-3 does not operate via a mode-of-action previously encountered by these strains, prompting us towards further investigation.

Elucidation of the mode-of-action (MOA) for a new antibacterial agent is a significant experimental challenge. The characterization of resistance mutations can be informative, however all attempts to isolate Bacillus subtilis mutants resistant to ()-tatiomicin (3) proved unsuccessful (see ESI). Also, no positive responses were seen with a panel of B. subtilis strains containing lacZ reporter genes used to indicate common antibacterial mechanisms of action, including: fatty acid synthesis (fabHA), DNA damage (105 prophage induction), RNA polymerase (RNAP) inhibition (helD), cell wall damage (ypuA), gyrase inhibition (gyrA), and cell envelope stress (liaI)) (see ESI)37,38,39.

Due to the presence of an, albeit electron-rich, ,-unsaturated carbonyl moiety, we postulated that the observed biological activity of ()-tatiomicin (3) may involve the covalent modification of thiol-containing enzymes through a conjugate or Michael addition of the thiol to the ,-unsaturated carbonyl. Thus, ()-tatiomicin (3) was reacted with L-cysteine hydrochloride, L-cysteine methyl ester hydrochloride and a short thiol-containing peptide (LcrV (271291)) as an enzyme proxy, under biologically relevant conditions. In all cases thiol adducts could be detected by LCMS, suggesting that ()-tatiomicin (3) may have biologically relevant Michael acceptor activity (see ESI).

To gain further insight into a potential mode-of-action, we undertook a bacterial cytological profiling experiment in which antibacterial induced changes in the morphology of test bacteria are compared to those induced by known mode-of-action antibacterials40,41. B. subtilis 168CA-CRW419 expresses two fusion proteins, HbsU-GFP and WALP23-mCherry, allowing simultaneous visualization of both the chromosomal DNA and the bacterial cell membrane by fluorescence microscopy. The cytoplasmic membrane was unaffected unlike in the control compound nisin, which forms large pores in the membrane42. Interestingly, treatment with ()-tatiomicin (3) induced chromosome decondensation in B. subtilis 168CA-CRW419, similar to the effects elicited by the RNAP inhibitor rifampicin (Fig.7).

Single-cell analysis of chromosome and membrane integrity. Phase contrast (top panels) and fluorescence microscopy of B. subtilis cells treated with various antibiotics (indicated above). DNA was visualized with an HsbU-GFP fusion (middle panels) and the cytoplasmic membrane with a WALP23-mCherry fusion (bottom panels).

The combination of the negative result observed with the helD reporter strain, cell lysis after prolonged incubation with the compound and the inability to create resistant mutants suggest that direct RNAP inhibition is unlikely. We therefore attempted to examine the integrity of the cytoplasmic membrane using the voltage sensitive dye DiSC3(5). This dye accumulates in well-energised cells in the cytoplasmic membrane15,43 but is released upon depolarisation of the membrane, and this release can be measured by fluorescence microscopy. DiSC3(5) is used in parallel with Sytox Green, a membrane-impermeable DNA stain used as a reporter for pore formation44. Upon addition of nisin, which forms large pores in the B. subtilis membrane42, both a loss of DiSC3(5) and uptake of Sytox Green was observed. In contrast gramicidin, which forms small cation-specific channels45, showed loss of DiSC3(5) without Sytox Green staining. Treatment with ()-tatiomicin (3) showed a similar effect to that of gramicidin, i.e. loss of DiSC3(5) without Sytox Green staining. Hence tatiomicin probably acts to dissipate the membrane potential without the formation of large pores (Fig.8).

Single-cell measurement of membrane potential and permeability. Phase contrast (top panels) and fluorescence microscopy of B. subtilis cells stained with the voltage-sensitive dye DiSC3(5) (middle panels) and the membrane permeability indicator Sytox Green (bottom panels) in the presence and absence of 32 g/mL of tatiomicin. As positive controls, the cells were treated with 5 g/mL of gramicidin (membrane depolarisation without pore formation) and 10 M nisin (membrane depolarisation through pore formation). Cellular DiSC3(5) and Sytox Green fluorescence values were quantified for cells treated with tatiomicin (32 g/mL), gramicidin (5 g/mL), and nisin (10 M) (see SI).

In an attempt to ascertain whether the observed loss of membrane potential is a downstream effect or occurs at the same time as chromosome depolarisation we performed a time-course experiment using DiSC3(5) in combination with a HsbU-GFP fusion to assess chromosome decondensation with images taken every two minutes. This showed that the loss of membrane potential occurred simultaneously with the chromosome decondensation, between 2 to 4min, suggesting that they are closely linked events (Fig.9).

Single-cell measurement of chromosome decondensation and membrane potential in a time course experiment in the presence of tatiomicin (32 g/mL). Phase contrast (top panels), fluorescence microscopy of B. subtilis HsbUGFP (chromosome marker) (middle panel) and stained with the voltage sensitive dye DiSC3(5) bottom panel. Cellular DiSC3(5) fluorescence values where quantified over time. The bar chart depicts the fluorescent intensity values of individual cells (> 30) (see SI).

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Discovery, isolation, heterologous expression and mode-of-action studies of the antibiotic polyketide tatiomicin from Amycolatopsis sp. DEM30355 |...

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Preston Manning: Beyond Left and Right – The Epoch Times

Posted: September 15, 2022 at 10:09 pm

Commentary

Much of the current commentary on North American politics is still couchedtoo much sowithin the old left-right-centre conceptualization of political ideology and parties.

The Biden Democrats in the United States and the Trudeau Liberals in Canada both denounce their principal opponents as right-wing extremists. Conservatives in both countries accuse their federal governments of catering to the left far too often. Political moderates in both counties claim to be representing an ever-shifting, ill-defined centre whose distinguishing feature is that it is neither left nor right. And political pundits of all stripes continue to overuse the terms of left, right, and centre despite their declining relevance.

Canadians, especially younger Canadians, can rightfully question why we insist on discussing 21st-century politics within an 18th-century conceptual framework. Why should we be conceptualizing contemporary politics within a framework derived from the seating arrangement in Frances 18th-century post-revolution assembly, where members of the land-owning aristocracy sat on the right and representatives of the working class and pro-revolutionary forces sat on the left?

Is there a more reasonable and relevant framework for conceptualizing and discussing contemporary North American politics? Yes, there is! And ironically it is a framework suggested by a Frenchman, Alexis de Tocqueville, in his famous book Democracy in America.

Although these words of De Tocqueville were written in 1840, they remain amazingly descriptive of the North American political landscape today:

[T]he secret propensities that govern the factions of America, (are) those two great divisions which have always existed in free communities the object of the one is to limit and that of the other to extend the authority of the people. I affirm thataristocratic or democratic passions may easily be detected at the bottom of all parties, and that, although they escape a superficial observation, they are the main point and soul of every faction in the United States.

And we might add, of every political faction in Canada also.

It is far more relevant today to categorize North American voters as pro-establishment or anti-establishment than it is to categorize them as left, right, or centristto separate the sheep from the goats by asking: Are you in favour of limiting or extending the influence of ordinary people in the political arena?

Today, the aristocratic passion resides politically, not so much in the old aristocracy of the wealthy but in an intellectual aristocracy that considers itself superior to the average voter, denounces bottom-up expression of political opinion at every opportunity, and seeks to limit rather than extend the authority of the people.

At the same time, the democratic passion is finding expression through a new breed of political leadership which draws its support from a growing segment of the electorate who feel increasingly disenfranchised by the political system and the elites who control its commanding heights. These voters resent having their opinions labelled as politically incorrect, their interests ignored or dismissed as illegitimate, and their political actions demeaned as misguided populism.

In Canada, we currently have a prime minister who typifies the modern political aristocrat: inclined to display his imagined intellectual superiority by lecturing the rabble at every opportunity and quite prepared to constrain the authority of the people whenever possible. But now, in the elevation of Pierre Poilievre to the leadership of the Conservative Party of Canada, we have an alternative leader arising from humble circumstances and inclined to trust rather than mistrust the rank and file of Canadians. In other words, a leader animated by the democratic rather than the aristocratic passion.

As a Canadian voter considering whom to vote for in the next federal election, which framework best describes your optionsthe old left-right-centre framework or the aristocratic/democratic framework? The champions of the aristocratic framework will of course tell you that expanding the authority of the people is dangerous and leads to extremism. But that charge is best answered in the words of Thomas Jefferson, one of the original framers of the U.S. Constitution, when he was asked near the end of his life where the ultimate political authority of a free society should be vested.

Jefferson replied: I know no safe depository of the ultimate powers of the society but the people themselves. And anticipating the objections of the aristocratic elites, he added: And if we think them (the people) not enlightened enough to exercise their control with a wholesome discretion, the remedy is not to take it from them, but to inform their discretion.

Views expressed in this article are the opinions of the author and do not necessarily reflect the views of The Epoch Times.

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Preston Manning served as a member of the Canadian Parliament from 1993 to 2001, and as leader of the Opposition from 1997 to 2000. He founded two political parties: the Reform Party of Canada and the Canadian Reform Conservative Alliance. Both of these became the Official Opposition in Parliament and led to the creation of the Conservative Party of Canada, which formed the federal government from 2004-2015.

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Recovering the Right to Parent – The Catholic Thing

Posted: at 10:09 pm

In the wake of Dobbs, pro-abortionists will leave no stone unturned to use as they did before Roe the most extreme cases, (like the 10-year-old Ohio girl who went to Indiana for an abortion) to tar the latest Supreme Court decision as extremist, while attempting to codify truly extremist abortion policy into law.

Today, as was true before Roe (1973), the vast majority of abortions conservatively, at least 96 percent are performed for social, economic, and other non-medical reasons.

Back then, that motivation was called convenience, a term clearly politically incorrect in contemporary discourse. Calling abortion reproductive health care now is how abortion advocates seek to disguise the reality: by redefining health in ever more elastic and innovative ways.

We need to be clear about pro-abortion extremism. While pro-abortionists will cite hard cases, their goal is not to debate them but to exclude any consideration of motivation from the abortion decision, a move necessary to shield the 96 percent-plus of abortions chosen that have nothing to do with rape, incest, or medical necessity.

Like the no-fault divorce movement, pro-abortionists aim to exclude any consideration of cause or reason for the choice. These are moral positions disguised under seemingly neutral legal terminology. What they really mean is that no marriage should ever be immune from dissolution, no pregnancy from termination.

This is wholly in keeping with a morally relativistic viewpoint that refuses to examine causes, but wants only to deal with consequences. Pre-teens should not be stopped from having sex; they should be issued condoms. If they get pregnant, they obviously should have abortions.

And if parents get in the way, well, Americas public schools should assimilate these children to the mores of liberal democracy, not their parents outdated views. After all, children have rights!

A full-on, frontal assault on this widespread propaganda is likely to be ineffective, largely because our culture has traded reasoned discourse for gripping soundbites, an exchange that benefits politicians even as it impoverishes political discourse.

So, I suggest an incremental approach, not because the rights of the unborn only deserve partial protection, but because the cultural corruption that has metastasized in the half-century-long culture of death following Roe will require baby steps to walk back. But as with every major turn in the moral life, everything starts with small steps.

Parents currently filling in school forms must sign multiple waivers to allow medication to be given to a child by a school during school hours.

Yet among Roes bastard jurisprudential offspring was Planned Parenthood v. Danforth, which launched a long line of federal and state court decisions limiting a parents right to consent or even to know if an underage daughter seeks an abortion via a judicial bypass provision, because a judge, unlike father, always knows best.

Those seeking to codify Roe admit their proposals continue this curtailing of parental rights. And their codifications of Roe dont just allow children to get everyday drugs like aspirin at school. They effectively exclude parents from a minor daughters abortion (though the parents, not a federal judge or a Congressperson, will have to care for the girl if something goes wrong).

Even in the states that have codified abortion places like New Jersey or New York local right-to-life groups should consider reopening those debates using parental rights as a wedge.

The same might be tried in places like Alaska where state supreme courts have belatedly discovered abortion rights in state constitutions. Or a place like Virginia, where there seem to be possibilities for moving beyond the old status quo and into the new moment post-Dobbs.

Parental rights can help advance the debate. You might not want to ban abortion after week X, but you certainly would see the value of parental involvement.

If change cant be achieved in a given state legislature, parents should press boards of education to adopt pro-life policies regarding teen pregnancy. Find ways to emphasize the simplicity of the message. Hold up an aspirin or an asthma inhaler, and ask why those items, truly for healthcare, require parental knowledge and consent, but abortion does not.

If you succeed but the state claims the right to preempt such local policies, its an opportunity to re-litigate parental rights in the courts, which again shines a public light on the usurpation of parental rights.

The growing parental-rights counterrevolution against efforts to use schools to advance liberal race and gender ideologies against the consent and without the knowledge of parents offers a winning political dynamic that pro-lifers should latch on to.

And remember: all this is no more than the advancing of two key principles of Catholic social thought: that the most vulnerable, including the unborn, deserve protection of their fundamental rights from conception; and that parents, not the state, are the primary teachers and guides of their children.

This is not politics; its basic theology.

*Image: The Guardian Angel Protecting a Child from the Demon by Bartolomeo Gennari, c. 1640 [Muse Magnin, Dijon, France]

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Daily Insider: The BizNews team in Bryanston is looking for a roomie – BizNews

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LATEST ON BIZNEWS RADIO:Neal Froneman Hersov is right; SA Govt can take leaf out of Sibanye book, urgently address Good, Bad and Ugly.(For Spotify,click here)

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During the opening minutes of his powerful keynote at BNC#4, Rob Hersov quipped that the audience better keep an eye out for a snipers red laser rangefinder as what followed would make him a marked man. That wasnt too big an exaggeration. His explosive talk reverberated in the portals of power and hit a sweet spot among gatvol countrymen.

Over 70,000 members of the BizNews community had watched the recording within 24 hours of itspublication on YouTubeTuesday evening. Among the appreciative crowd was Sibanyes similarly outspoken CEO Neal Froneman who referred favourably to Hersovs messagein our interviewyesterday.

Thats the kind of politically incorrect material we do not shy away from. And serves as something of a disclaimer for my request. As BizNews is reverting to a mostly-remote model, were looking for a like-minded company to share our beautiful 250m of office space in Bryanston. Because we simply no longer need all of it.

So, if youre not afraid of ducking an occasional laser rangefinder (just kidding), need super fast connectivity, immunity to loadshedding and would like to share your workspace with a bunch of passionate journalists, please drop a line to[emailprotected]. Let her know a bit about yourself and your needs and, of course, contact details. And perhaps well soon be roomies.

To receive the Daily Insider every weekday at 6am in your inboxclick here. You can alsosign upto the weekends BizNews Digest for a wrap of the best content BizNews has to offer, for a leisurely Saturday read.

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Bold, Inspiring And Grabbing Headlines – The – The Draft

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Street Art has origins from a time we are yet to fathom and, in time, discover, writesGajanan Khergamker

Limited as we are by man-made language, nomenclature, and terminology besides the means so simplistic and apparent like paper and other media, like say walls, Art, and in particular, Street Art, is an extension of that what can be generated on traditional medium but extends to public spaces.

On the European front, skewedly propagated as a world platform, it was in the French Revolutions iconoclasm era, when rebels defaced high-end art to protest French societys toxic hierarchy creating a niche called graffiti that became synonymous with vandalism. It was the waves of political and economic turbulence that triggered the rise of street art around the world: The Berlin Wall's one-sided graffiti being projected as a fight of colourful expression on one side versus the stark totalitarianism of bland emptiness on the other being a rather simplistic definition.

So, French Street Artist James Colomina's installation of Vladimir Putin in Central Park in early August 2022, five months after the Ukraine war started, was predictably bold in both its content and process. The artist who does not reveal himself because most of his installations "are unauthorised," is "already facing problems with the authorities."

Ironically the installation, bold as it was, appeared in New York City of the United States of America where, according to a recent Data USA study, 85.4 per cent of archivists, curators, and museum technicians were White and the next most common ethnicity (Hispanic White) clocked in at a mere five per cent.

The statistics conveniently exclude those who do not fit in with them. Technically, and those valued, artists are predominantly White men, with 85.4 per cent of works in all major US museums belonging to White artists, 87.4 per cent by men.

The diversity is not much greater for museums that specialise in modern art. At the Museum of Modern Art in New York City, for example, only 11 per cent of the artists in the collection are female, 10 per cent are Asian, and two per cent are black or African-American. At theSan Francisco Museum of Modern Art, 18 per cent of the artists are female, seven per cent Asian, and two per cent black or African-American.

Wealthy Patrons Decide Merit Of Art

It is the acute dearth of public funding owing to which museums and galleries are forced to rely on the wealthy patrons sitting on their executive boards to influence what art is worthy for public display. In October 2019, aNew York Timesanalysis revealed that 40 per cent of museum trustees are Wall Street tycoons revealing that control on high-end art world isn't merely determined by if a trustee is wealthy, but also where they derive their wealth from.

Street Art is different. And what makes Street Art this way is its ability to steer clear, well mostly, of political influence and economic compulsions. What binds Street Art and its proponents across the world is the 'unauthorised' nature of its existence and populist accolades derived from swimming against the current.

James Colomina's installations are a case in point. And, James, on his part, is clear with his modus operandi. "I'm not really afraid of the authorities. It's a bit of a cat-and-mouse game. You must not get caught otherwise the installation is ruined," he says gleefully.

James' last installation in Berlin where he installed a sculpture of a little girl going over the wall and another above the railway tracks caused quite a flurry. The authorities had to close the tracks for two hours to remove the sculpture.

"Why, even train-drivers slowed down as they approached the sculpture. They thought it was a real child," he recalls with relish. Another facet of Street Art is that it must not, ordinarily, always be liked or be popular. "A lot of people don't like me, but that's okay. It's even so much the better. It would bother me to please everyone. I try to tell the truth with my sculptures and sometimes it hurts," he says.

Art Can Be Politically Incorrect, Hurt Too

Much on the lines of James installation in New York City's Central Park, a thousand odd miles away in South Minneapolis, atop the Cup Foods convenience store, where a 911 call led to George Floyd's police killing, today stands a hoarding complete with memorial art. This one, as opposed to Putins, for sure, is not as popular.

Local illustrator, muralist and teacher Melodee Strong created 'Mama' after George Floyd's dying plea, depicting grieving black mothers, against a backdrop of the US flag.

"I am a mother, and when George cried out for his 'mama' as he was taking his last breaths, I also cried," revealed Strong.

"That's what we do when we are in trouble or scared, we cry out for God or our mothers. My son has been harassed and mistreated by the police. I have witnessed numerous times how the people I love have been abused by police.

"The anguish we feel from the fear and the experiences of those too many incidences is what I feel in the faces I painted Even though this piece is about George Floyd, it's more a dedication to all the mothers who have lost their child to police violence." Melodees cry resonates with those of mothers across the world and how.

Predictably, followingBlack Lives Matterprotests erupting in cities, large corporations all around the country responded by nailing plywood across their doors and massive windows, to deter the possibilities of violent interludes.

Yet, even after protests end, it's the Street Art in the form of graffiti that stands tall as a testament to the protestors' collective voice. It is, today through social media that belongs to the masses instead of selective and controlled fora, that protests get documented and become a part of history.

Calling Macrons Bluff, Through Art

Like the time when French President Emmanuel Macron was elected, he made loud proclamations that there would be no more homeless people but, as usual, it was far from being true. "It was even worse, so I put him in a tent with homeless people," says Colomina.

"Why, the homeless were delighted with the move. The site stands on the edge of the Saint-Martin canal in Paris. At first, I asked some homeless people if they would welcome President Macron with them in a tent. They told me they were delighted; So, for his birthday, I put him in a tent to shed some light on the homeless," he added.

"My intention was also to put the one who is at the very top of the pyramid, at the very bottom."

It was in the 1970s, that graffiti artists in America successfully unionised for the first time. Between 1974 and 1980, over 20,000 artists and arts support staff secured full-time employment through Comprehensive Employment and Training Act (CETA) making it the largest federally-funded arts project since the Works Progress Administration (WPA) created during the Great Depression, putting more than 8.5 million people to work.

In New York City, the Cultural Council Foundation (CCF) launched the CETA Artists Project in 1978, with a budget of USD 4.5 million a year to fund the work of 300 artists, paying them USD 10,000 year plus benefits (nearly USD 46,000 today) to work directly with community organisations, on project teams, with performing companies, or on a wide array of public works.

Showcasing Only A Few For High-End World

Then, the wealthy responded by carefully choosing only certain graffiti artists to amplify and opened up the high-end art world selectively, incentivising street art for the sole purpose of earning money within the curated spaces set up by the elite. As a result, and inevitably, there was infighting and resentment that led to the unions eroding.

Today, the present-day continuation of excluding non-male and non-White artists from museums and the wealth associated with high-end art is no coincidence. The statistics highlight the high-brow art world as another example of the White and Wealthy very conveniently excluding those who do not fit in with them.

Activists like California-based Nancypili Hernandez use Street Art as a crucial tool in telling suppressed stories. Creating and directing many different murals, working in San Franciscos Latinx community to document peoples history that isnt told in the history books, it's her work in the Mission District that highlights the struggles of the Latinx residents, amplifying the stories of a native community passed over by San Franciscos tour guides.

In 2015, Polish street artist based in New York City, Agata Oleksiak aka Olek arrived in New Delhi in 2015 to work on a massive project and use the technique of crocheting to give expression to everyday occurrences and inspirations; her artwork often examines sexuality, feminist ideas and the evolution of communication.

She visually transformed one of the 184 homeless shelters in New Delhi, to raise awareness about the lives of the desperate people who live in them. Covering the entire 40 feet long and 8 feet high structure with crocheted yarn with a team of local volunteers, she worked for seven days to put together the entire installation that was part of the Rain Basera project.

Dressing Up A Charging Bull, At Night

Why, on Christmas Eve in 2010, she even cloaked the iconic "Charging Bull" statue on Wall Street - from horn to hoof - with a pink, camouflage-patterned cover that she crocheted herself at 3 am! It took her miles of yarn to create the fabric over Six seasons ofLost' as she puts it.

While she kept waiting for the police to stop her, they didn't. "They were human and understood that I didn't want to harm the statue," but the installation lasted for merely two hours as 'a grumpy city worker tore it down'.

Ironically, the Charging Bull itself had appeared as a Christmas gift to New York City from Arturo Di Modica, an Italian sculptor. Di Modica, who moved to New York in the 1970s, sensing the concern and uncertainty in the United States after the crash in 1987, wanted to create a powerful symbol of the strength of the American economy.

He made plans to create a three-and-a-half ton, 18-foot-long bronze bull to reference a bull market, a robust stock market where share prices are rising, encouraging investors to buy more.

And, in the morning of 15 December 1989, Di Modica and a few friends parked a truck outside of the New York Stock Exchange. Within moments, they placed the bull under a Christmas tree and left.

Di Modica hadnt expected for the bull to stay there in the long term as he thought of it as a temporary gift. And, the New York Stock Exchange, predictably, didnt like the idea and had it removed. However, in time, it returned and went on to become one of the most visited spots of Manhattan and a hot favourite tourist destination of New York.

Opponents Say Stay Legal, Display In Private

Generally, Street Art is quickly dismissed as 'vandalism' and an illegal activity when not in private galleries or sponsored by non-profits. Those opposing Street Art keep insisting artists must resort only to legal methods of art in the privacy of their homes, while conveniently ignoring the glaring fact that the high-end art world is discriminatory, much to a selective convenience.

Keep America Beautiful(KAB), a large non-profit with corporate sponsors like H&M, PepsiCo, and McDonalds, began a program in 2007 calledGraffiti Hurts. They even offer grants upwards of USD 2,000 to local governments and police departments for fighting Street Art. Their slogan? We keep America beautiful so Americans can do beautiful things. Now, the non-profit is conveniently silent on which Americans are given the right to create those beautiful things? And, at whose expense?

KAB maintains that while graffiti vandals known as guerrilla artists believe their actions harm no one, graffiti hurts everyonehomeowners, communities, businesses, schools, and you. They maintain, those who practice it risk personal injury, violence, and arrest. The prime difference between Graffiti and Art remainsPermission!

Over the summer of 2020, a portrait recurred on city walls across the world: an image of the black American George Floyd, who was brutally suffocated to death by police officer David Chauvin on 25 May 2020. Most of these portraits were based on Floyd's 2016 selfie, taken from his own Facebook account; many referred to the torment of his killing, and his final words.

Support To Floyd From Pakistan, India

Thousands of miles from the US protests, numerous graffiti tributes to Floyd appeared in European cities and in Asia, Africa and Australia. In what transcended borders, even bridged differences between two sworn enemies was Karachi-based truck artist Haider Ali's portrait of Floyd inscribed with English tags '#blacklivesmatter' and song lyrics 'Goron Ki Na Kalon Ki, Duniya Hai Dilwalon Ki' meaning The World does not belong to the Whites or Blacks but to those with hearts and Hum Kale Hain Toh Kya Hua Dilwale Hain meaning So what if we are Black, we have hearts.

Interestingly, the Pakistani artist has used lyrics from a 1982 Indian Hindi film Disco Dancer song penned by Indian lyricist Anjaan and sung by Suresh Wadkar and Usha Mangeshkar. The second song has lyrics from a 1964 Indian Hindi movie Gumnaam song penned by Indian lyricist Shailendra and sung by Mohammad Rafi and Mehmood.

The truck artist's brilliant blending of George Floyd's portrait tackling the issue of colour and hate in the USA with neighbouring India's legendary love-hate relationship with Pakistan, was an exquisite work of art in itself, to say the least.

The very public horror of Floyd's killing (captured on videocam) lingers in recent memory but his isn't a case in isolation. Memorials also say the names of generations of innocent black US victims: among them, Breonna Taylor (killed by the police in her own home, 13 March 2020); 12-year-old Tamir Rice (fatally shot by the police, 22 November 2014); 14-year-old Emmett Till (lynched by racists, 28 August 1955) and more.

Testament To Protestors Collective Voice

In graffiti, evidently unauthorised, illegal and without permission, international artists find resonance who then bring to focus their issues like accusations of police brutality in Kenya and others.

That the Black Lives Matter movement has transgressed beyond borders is evident in the works of contemporary artists who continue to embody its energy. The works of London-based Ghanian Street Artist and educator Dreph (aka Neequaye Dsane) appearing around the world, including residencies in Brazil and Cape Verde, says, "We are bombarded with negative imagery all day long; what do we do with that energy? It's got to be moulded into something positive I want to constantly make authentic, inspiring, meaningful, thought-provoking work, regardless of the context."

In Britain, his street-portrait series includesMigrations, a celebration of multi-cultural local heroes especially resonant around the Windrush scandal, where hundreds of Britons of Caribbean descent were wrongly threatened with deportation and refused vital services through the UK government's "hostile environment" policy.

Dreph sums it up when he says, he can go pretty much to any country in the world and meet a local within minutes because of the graffiti movement. Its a network.

Born in 1961 in Larache, a harbour town in northern Morocco, Drephs father emigrated to England in the 60s, so he spent his formative years with his mother, auntie, grandma and sisters.

He moved to North London in 1973 when he was 12 to join his father. He recalls it as being a tough time, where he was unable to speak English and was immersed in a new culture, in a time where London wasnt as cosmopolitan as it is today.

Free Art Elbows Compulsions Of Commerce

In Londons multicultural Brixton, a sizeable chunk of the 30-foot-tall Michelle Obama mural remains painted over as Dorrell Place becomes the place for graffiti artists/taggers/scrawlers to showcase their works of art. The homage to the former First Lady of the United States that first appeared on the side of the Marks & Spencer store in October 2018 was the creation of Dreph who made the advert in collaboration with Penguin Random House to promote the publication of Obamas autobiography Becoming, released on 13 November 2018.

Yet, by February 2021 the bottom half was painted over, and in the last couple of years the rest of the mural has dwindled to naught, almost symbolising the triumph of free art over the compulsions of commerce.

One of Drephs latest murals depicts Hassan Hajjaj who joined the burgeoning west London immigrant community. He felt very much a foreigner and many of the people he befriended were people who had had a similar journey and shared experiences of being the outsider. In this period, he made a lot of friends, many from the Caribbean, India and Pakistan, and says that they stuck together and looked after one another.

That said, strife is perhaps the most significant commonality in Street Art; and, its this strife that is symbolical of the processes even the resistance to populist trends and capitalist markets.

In India, the Street Art scenario in financial capital Mumbai, in the absence of creative spunk even controlled by political entities and permitted more often than growing organically as in the rest of the world, has failed to impress in comparison.

The two-month long St+art Urban Art Festival for Mumbais Sassoon Dock Art Project kickstarted on 11 November 2017 and ran until 30 December 2017 featuring an exhibition of structures and images of workers at Indias first wet dock and the oldest in Mumbai, situated in Colaba.

Pitched as having remained a forgotten space of Mumbai, only home to the native Kolis living in a world of their own making, the paintings depicted Kolis, a community that has grown organically even before the formation of Mumbai and live and work in the sea on the other side of Colaba at Machchimar Nagar, having poor little to do with the trade at Sassoon Docks.

Glossing Over Details To Fact, Flavour

Sassoon Docks instead, is a commercial venture with docks where fish are cleaned, packed and exported to markets across the world. The Sassoon Docks provides livelihood for a range of communities from across India, apart from Kolis, who, at best, buy the fish locally for sale in markets in suburban Mumbai. The depiction in the Street Art seemed way off the mark and the local flavour and details to facts, sadly amiss.

In the same year, under an initiative of St+art Foundation, Asian Paints and Western Railways, a mural depicting Mahatma Gandhi exiting a train was created by Brazilian artist Eduardo Kobra at South Mumbais Churchgate Railway Station. A structural audit of the faade, even declared it fit during an inspection in 2018.

However, a part of the cladding of the 81 ft x 54 ft mural broke loose during a cyclone in 2019 and fell on a 62-year-old pedestrian, killing him. The entire faade including the painting was ultimately brought down by the Western Railways.

I have been painting nature, architecture, and local heritage on walls and in public spaces across the city, says self-taught street artist Sapna Patil who has been involved with painting real-life thematic images in and around Mumbai.

Sapna is known for her painting of a seemingly-real train across a wall at Budhwar Park, in what was earlier a rather drab-looking passage, connecting South Mumbais Fourth Pasta Lane to Machchimar Nagar on the other side of the zone and passing through a Railway Colony.

Her detailed depiction of the train, complete with windows, bars, steps even handles is exquisite. I wish I get more opportunities to paint about issues that affect people too, she says.

Sapna Patils works are symbolic of theChanging Colours of Colabaand transformations in Mumbai's oldest precinct where, among other changes, public walls are given colourful make-overs through strategic paintings depicting the zones architecture and life.

On similar lines is the work of Chandigarhs Sachita Aditi Sharma now based out of Himachal Pradesh in North India. After having painted an entire village in Punjab to inspire villagers and show them a life that goes beyond drugs, walls in Goa even at venues in Hyderabad," Sachita now works across India.

Ive cleaned little corners and walls in cities strewn with garbage and excreta and created works of art, says Sachita who feels the entire ordeal of getting permissions from local administration which is either inaccessible or simply not keen to comply, defeats the purpose of beautifying public zones.

Delhi-based artist and President Awardee Roop Chand feels the potential of artists being able to tap on public sentiment and educate masses has not been utilised to its fullest potential. "There is so much that artists can do to contribute. It's just that their potential has not been realised," maintains Roop Chand.

Why, he feels that something as simple as propping up a social message on a brightly-painted waste-bin in a public place may make all the difference. I have done it personally and seen it work. People actually stop, read and take in the message, he says.

A Film Industry Splashed On Public Walls

The walls adjoining the streets of Mumbai's Western suburb Bandra are strewn with art works depicting old Hindi films, graffiti and the works, converting the zone into a virtual art-lovers paradise. The wall-paintings are impressively colossal in size, strategically placed and sure to leave an indelible mark in public memory.

The Street Art that has begun making pleasant appearances across Mumbais streets has been facilitated by the civic authorities and overseen by local politicians. With all permissions in place and authorisations, even financial support provided through non-profits involved in the venture, Mumbais Street Art completely overlooks issues of strife and sensitivity that feature on public walls in most other foreign cities.

Unlike French Street Artist James Colomina, who literally lives underground and refuses to even identify himself or his family for fear of reprise, the artists working across Mumbais streets feature, without fear, across media. Why, most of them are art teachers, commercial artists, some even out-of-work poster artists who have been provided livelihood by the surge in Street Art across Indias financial capital.

There is simply no element of conflict in the Street Art across the public spaces of Mumbai. Theres a slim chance of an artwork being politically incorrect or harming populist sentiments when all of it has to go through the fine comb of a local politician before being vetted thoroughly by the authorities before seeing the light of the day.

And, that, is the difference in Street Art in India. Not that it isnt good or lacks punch. Its just that its different. Positively different, colourful yet bordering on inane and socially irrelevant. I wish I can use art to highlight the issues faced by my community, in time, sums up Sapna Patil, herself an Agri tribal based out of Thane in Maharashtra.

Figures On Walls To Lead The Way

Look at Swaero Artists For Empowerment of Society (SAFE), an alumna of artists who studied in state-run social welfare schools and colleges who feel, Education is the most powerful weapon which you can use to change the world; "Swaero Bano-Hero Bano"; "If not now, when? If not we, then who?"

A tiny Dalit colony in Kollapadakal village of Maheshwaram that lies an hour away from Hyderabad registers the inspirational lines on a colourful mural that has become all-too-familiar to locals.

In different colours on the walls of homes, over 30 murals, featuring prominent world leaders, are popular selfie points in the area. The Street Art walls were inaugurated by senior IPS officer RS Praveen Kumar Swaero, the secretary of the Telangana Social & Tribal Welfare Residential Educational Institutions Society in 2020.

Interestingly, several murals of contemporary student achievers that include mountaineer Malavat Poorna, Kamatam Madhuri, Nemali Siddharth, Darshanala Sushma, Praveen Kumar IPS and Dalit billionaire Pagidipati Devaiah were also painted on the walls. And because, as the SAFE president feels "painting local figures will make students think to become one of them.

Empowering Marginalised With Art To Start Anew

Literally transforming the face of Mumbais slums has been Misaal Mumbai a slum painting and repairing initiative by artist, muralist and social worker Rouble Nagi started after Paint Dharavi in 2016 in Mumbai where she, with her team, painted and water-proofed houses. The aim being not just to beautify the walls of the slums but to connect to people through Art and bring a positive change in their mindset.

Plugged as the first slum painting initiative in India, the Rouble Nagi Art Foundation painted and repaired 1,50,000 plus homes to date and are currently working in over 163 slums and villages across India.

Educating through art about the importance of children education, empowering women, creating job opportunities for youth, cleanliness, hygiene, sanitation, waste management, and children health in slums and villages, Rouble Nagi reaches out key messages through Street Art.

Besides being a quick way to create visual impact, our projects employ people and give them a sense of ownership over the artworks they create in their own community while improving the condition of their houses, says Rouble.

And now, with Misaal Kashmir underway, the Mumbai-based artist with 800 murals to her credit and having organised over 150 exhibitions, is focusing on the youth of Kashmir. She believes that they need to navigate their lives with the vision of growth and positivity, stop following peers and politicians "if you feel they are leading you towards a negative path".

Along with her team, Rouble has been travelling through Watlab, Sangrama, Handwara, Langate and the rural belt of Pulwama armed with nothing but art and paints to empower women to generate a livelihood for themselves.

The village reformation project, 'Misaal Kashmir' helps artists transform the community by tapping the local creative energy. Its part of the 'Misaal India' initiative launched in 2018. Rouble Nagis attempts are bearing fruit, slowly yet surely, heralding a new beginning for those for whom all seemed lost.

Art Provides Healing Balm, Soothes The Hurt

Probably the most peaceful yet powerful influence of Street Art can be gauged by Japanese garden designer Itaru Sasaki who initiated the Wind Phone project in 2010 to help cope with his cousin's death.

After Itaru lost his cousin to terminal cancer, he set up an old telephone booth in his garden in December 2010, to continue to feel connected to him by "talking" to him on the phone. The wind phone was not designed with any specific religious connotation but as a way to reflect on his loss.

On 7 January 2017, strong winds blew off the roof of the wind phone and broke the glass doors. On hearing about it, local carpenters, including ones who had previously visited the wind phone, swiftly volunteered to repair it on 10 January 2017 and the wind phone was reopened by the very next day.

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Who is Ryder Ripps, Artist Trying To Take Down Bored Ape Yacht Club ARTnews.com – ARTnews

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When Bored Ape Yacht Club launched at the height of last years NFT frenzy, Ryder Ripps shrugged off the collections off-putting imagery. The series of 10,000 cartoon apes were rife with the meme aesthetics of the internets darkest corners, but if you spend enough time online, its something you tend to just look past. Then a few months later, a friend showed him the collections logo beside the Totenkopf, a skull-and-cross bones insignia widely used in Nazi Germany. It dawned on him: The Apes, now viral and promoted widely by crypto-hawking celebrities, might be an elaborate, malicious troll.

I realized this shit was intentional, Ripps, a 36-year-old conceptual artist and creative director who has worked with major artists like Kanye West and Grimes and brands like Nike, Red Bull, and Gucci, told ARTnews. Theyre ruining the internet.

Since December, Ripps has led a crusade against the irreverent collection, its parent company Yuga Labs currently valued at a whopping $4 billion and founders Greg Solano, Wiley Aronow, Kerem Atalay, and Zeshan Ali.

Ripps contends that BAYC, from its logo to the Apes accessories like sushi chef headbands inscribed with kamikaze in Japanese kanji and spiked Prussian Pickelhaube helmets is threaded with racist imagery and ties to the online alt-right. Ripps and Yuga Labs are currently embroiled in a legal battle after the company sued the artist for creating copycat NFTs that Ripps says are meant to satirize the collection. (Yuga Labs and BAYC have previously denied the allegations of racism.)

Ripps has cast himself as Laocoon the priest who begged the Trojans not to let the Greek horse into the city warning that Yugas founders are trying to slip toxic imagery and ideas into the larger culture by packaging it as just another absurd, but ultimately innocuous NFT collection. But is he the best messenger for his warning?

When asked why hes so sure that Solano, Aronow and their counterparts are trolls, Ripps laughed. Takes one to know one, he said.

The rest is here:
Who is Ryder Ripps, Artist Trying To Take Down Bored Ape Yacht Club ARTnews.com - ARTnews

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Daniel Craig will be honored at Montclair Film Festival – New Jersey 101.5 FM

Posted: at 10:09 pm

Considering he said he was glad to be rid of the role, Im sure actor Daniel Craig doesnt appreciate his name being linked to the character of James Bond, but its what catapulted him to stardom so Im going to do it.

Daniel Craig, best known for playing secret agent James Bond, will be honored at the Montclair Film Festival and his latest film will open the festival at the Wellmont Theater in Montclair.

Craigs new film Glass Onion: a Knives Out Mystery, described by the festivals website:

In this follow up to KNIVES OUT, Detective Benoit Blanc (Daniel Craig) travels to Greece to peel back the layers of a mystery involving a new cast of colorful suspects, featuring Edward Norton, Janelle Mone, Kathryn Hahn, Leslie Odom Jr., Jessica Henwick, and Madelyn Cline with Kate Hudson and Dave Bautista. Written and Directed by Rian Johnson, GLASS ONION: A KNIVES OUT MYSTERY will release globally on Netflix on December 23.

Craig will be interviewed on stage by Stephen Colbert (theyre calling it a conversation not an interview), the late-night host whose wife is the president of the festivals board of trustees.

"MacBeth" Broadway Opening Night

The festival begins on Oct. 21 at the Wellmont, but the conversation with Daniel Craig is on the 28th at the New Jersey Performing Arts Center (NJPAC).

We are thrilled to honor Daniel Craig at the Montclair Film Festival with our 2022 Tribute, and to share his work in Rian Johnsons uproarious new thriller Glass Onion on opening night, Tom Hall, co-head and artistic director of Montclair Film, said in a statement. We look forward to welcoming Mr. Craig to the festival and to a fun, celebratory evening hosted by Stephen Colbert exploring Mr. Craigs unforgettable roles and his exceptional career.

Tickets go on sale Sep. 17 to the public and are available through Ticketmaster.

Opinions expressed in the post above are those of New Jersey 101.5 talk show host Bill Doyle only.

You can now listen to Deminski & Doyle On Demand! Hear New Jerseys favorite afternoon radio show any day of the week. Download the Deminski & Doyle show wherever you get podcasts, on our free app, or listen right now.

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Daniel Craig will be honored at Montclair Film Festival - New Jersey 101.5 FM

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Alister Jack and Gordon Brown ‘fume over BBC linking Queen’s death to indy’ – The National

Posted: at 10:09 pm

THE BBCs wall-to-wall coverage of the macabre pomp and ceremony following the Queens death has angered, annoyed, bored and generally bothered most not utterly obsessed with the royal family.

Even BBC Question Time favourite and letter-writer-in-chief for the Unionist cause Jane Lax described it as dire.

But amid Nicholas Witchell pontificating on the late monarchs feelings about independence and the plainly incorrect assertion the Protestant reformer John Knox cleared the Catholics out of Scotland (a suggestion met with laughter by other presenters), there have been some moments of sanity among the coverage.

Enter Alan Little, a veteran BBC presenter who led the broadcasters controversial coverage of the 2014 independence referendum.

READ MORE:Celtic fans unveil 'f*** the crown' banner prior to Shakhtar Donetsk tie

To the rumouredannoyance of Gordon Brown and the Scottish Secretary, Little stated some plain facts about the political state of play.

The Telegraph reports he said on the Ten OClock News on Monday that Scotland had been diverging from the rest of the UK politically for 40 years, where support for independence is as high as its ever been.

Well, whats wrong with that? Its basically correct, isnt it?

Not if youre the former PM or Alister Union Jack who were said to be privately fizzing about the comments.

They may have become catatonic when the BBC man added that Charlies reign could be defined by the eventual dissolution of the United Kingdom itself.

READ MORE:Prince Andrew continues role which could see him stand in for King Charles

Someone who is not Brown appears to have complained to the Telegraph that Littles lines echo that of the SNP. They might also echo authoritative works on the recent political history of Scotland and the Union, but thats beside the point.

A "source close to" Alister Union Jack added: The BBC should really not be introducing the independence debate into the Queens death - theres no link.

Littles comments came amid a veritable tsunami of political interventions by BBC pundits, talking heads and hacks who wondered idly about the Queens diplomatic role (did she bring about peace in Northern Ireland?) and her apparently grave concern the country she spent her summer holidays in could become foreign.

There was significantly less noise from the Unionist press about those musings, needless to say.

Jack had sufficiently recovered himself to take on a role standing guard at the Queens coffin in Westminster today, in his role as a member of the Royal Company of Archers the monarchs Scottish bodyguard.

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Alister Jack and Gordon Brown 'fume over BBC linking Queen's death to indy' - The National

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