Monthly Archives: September 2023

An international consortium of scientists, led by Jeff Kidd, Ph.D. of University of Michigan, Jennifer R. S. Meadows of Uppsala University in Sweden, and Elaine A. Ostrander, Ph.D. of the NIH National Human Genome Research Institute, is using an unprecedentedly large database of canine DNA to take an unbiased look at how our furry friends evolved into the various breeds we know and love.

A new paper, published in the journal Genome Biology, outlines what the Dog10K project discovered after sequencing the genomes of close to 2000 samples from 321 different breed dogs, wild dogs, coyotes, and wolves, and comparing them to one reference sample -- that of a German Shepherd named Mischka.

Analyzing more than 48 million pieces of genetic information, they discovered that each breed dog had around 3 million single nucleotide polymorphism differences. These SNPs or "snips" are what account for most of the genetic variation among people and dogs alike. They also found 26,000 deleted sequences that were present in the German Shepherd but not in the comparison breed and 14,000 that were in the compared breed but missing from Mischka's DNA.

"We did an analysis to see how similar the dogs were to each other, and it ended up that we could divide them into around 25 major groups that pretty much match up with what people would have expected based on breed origin, the dogs' type, size and coloration," said Kidd, a professor of Human Genetics and Computational Medicine and Bioinformatics at the U-M Medical School.

Most of the varying genes, he added, had to do with morphology, confirming that the breed differences were driven by how the dogs look.

Relative to dogs, wolves had around 14 percent more variation. And wild village dogs -- dogs that live amongst people in villages or cities but aren't kept as pets -- exhibited more genetic variation than breed dogs.

The data set, which was processed using the Great Lakes high-performing computing cluster at U-M, also revealed an unusual amount of retrogenes, a new gene that forms when RNA gets turned back into DNA and inserted back into the genome in a different spot. The study found 926 retrogenes, the most famous of which, says Kidd, is a retrogene called FGF4, which results in the short leg phenotype seen in dachshunds and corgis.

"Dogs tend to have an increased amount of retrogenes which have resulted in mutations that were selected for, that perhaps people found cute and bred more of," said Kidd. His lab is attempting to figure out why retrogenes and insertions happen so frequently in dogs.

One of the benefits of the Dog10K consortium is its size, which will enable researchers at U-M and elsewhere to examine the genetic underpinnings of other canine characteristics and even common diseases in dogs, such as cancer.

Read this article:
Dog diversity unveiled by international DNA database - Science Daily

Editors note: The Cap Times has withheld many details about this crime in consideration of the victims privacy and the potential trauma for some readers; however, the story includes information about sexual violence that may still be difficult to read. Caution is advised. The National Sexual Assault Hotline provides 24/7 crisis counseling at online.rainn.org or 1-800-656-4673.

DNA from a man accused of viciously attacking and nearly killing a University of Wisconsin student last weekend contained the most identifiable match possible to evidence found at the crime scene, according to a criminal complaint.

Beyond the biological evidence, Madison police also used business and residential surveillance videos, a Fitchburg officers body cam footage and the suspects own statements about being a monster who saw red to conclude that Brandon A. Thompson stalked and then physically and sexually assaulted the woman sometime between 2:30 and 3 a.m. Sunday in a downtown neighborhood, the complaint shows.

Dane County prosecutors filed three felony charges against Thompson, 26, Thursday in the random attack after police arrested him Wednesday morning.

Thompson, who is a resident of Brooklyn, Wisconsin, was charged with first-degree sexual assault, first-degree reckless injury, and strangulation and suffocation. The woman attacked, whose name has not been released to the news media, was found in critical condition along the 500 block of West Wilson Street around 3:20 a.m. Sunday, according to the Madison Police Department incident report. She is in her 20s and is expected to survive despite suffering injuries so severe she was temporarily in a medically induced coma, according to prosecutors and an update from police on Tuesday.

Videos submitted by members of the public helped lead police to Thompson, who remained at the scene of the attack and told nearby residents that he found the injured victim, according to the criminal complaint obtained by the Cap Times.

Cash bail is set for $1 million and a preliminary hearing will take place on Sep. 25 in the Dane County Courthouse.

Police Sgt. Daniel Sherrick was the first on the scene, according to the complaint, and said the students condition was "one of the most horrifying things I've seen." She was unable to communicate to police when they arrived and was transported to UW Hospital with life-threatening injuries.

The student had multiple facial fractures, including a broken jaw and broken nose, a missing tooth and a traumatic brain injury and an MRI showed a small brain bleed. She needed eight stitches to repair her upper lip, and nurses in the hospitals emergency department confirmed the student was strangled and sexually assaulted.

The student is currently on a feeding tube and unable to provide a statement as she shows extreme signs of confusion when awake, the complaint said.

The UW student arrived at a friends apartment at 7:56 p.m. on Saturday and left between 2:16 a.m. and 2:18 a.m. Sunday, according to a witness statement described in the complaint. The witness told officers she texted the victim at 2:43 a.m. asking if she made it home safely but the text was never read or responded to. The witness stated the victim is not a person who partied or a drug user.

Initial police reports state that residents in the 500 block of West Wilson Street called 911 after being alerted by a male who identified himself as Brandon. One witness said she was in her house when she heard a male voice yell to her through an open window that a female needed help.

The witness said Thompson claimed he was out for a "high walk" when he came upon the victim and seemed concerned for her wellbeing, according to the complaint. When the witness realized the victim was covered in blood and called the police, Thompson appeared to become "antsy," claimed he did not want to be around police when he was high and left the scene.

A different witness at the scene said he noticed dried blood on the mans hands. The man, whom police later identified as Thompson, told the witnesses he had carried the students bloodied body to that site after finding her nearby in the street. Police investigators said they found blood only in the location where the woman was found by other witnesses, not in the street.

Neighborhood surveillance videos in the area captured a man matching Thompsons description walking behind the victim just prior to the assault, Madison Police Chief Shon Barnes said at a press conference Wednesday. That information was repeated in the complaint filed Thursday. The complaint says Thompson was later located and arrested at Meriter Hospital, although the report does not describe why he sought medical treatment.

Videos from the area also showed a man believed to be Thompson exiting a car parked at Brittingham Park not long before the attack, according to the complaint. The vehicle's description and plate number matched a car Fitchburg Police had pulled over a few hours before the assault for a registration violation. The Fitchburg body camera video showed Thompson, who was driving, wearing clothes that matched those of the man seen in surveillance videos before the assault.

During an interview with detectives, he made incriminating statements, saying he was mad and wanted to hit something, according to the complaint. Thompson also told police the victim "came across a monster" that night.

Thompson admitted to encountering a woman and saw red and didn't know what was going on, the complaint says. Thompson stated the next thing he remembered was the female on the ground in front of him. He also stated, I went into a rage, when I came to, she was on the ground. The only thing I remember is just hitting.

When questioned further about the sexual assault, Thompson said something like, "I don't remember it during the actual assault, I just kind of zoned out during the rage," according to the complaint. When detectives asked Thompson if he could have sexually assaulted the victim, he stated, "I could have."

DNA from a Forensic Nurse Examination of the victim is consistent with the profile of Brandon Thompson, the complaint says, with a probability of one in one quadrillion. The DNA analyst said one in one quadrillion is the highest probability that the Wisconsin State Crime Lab will identify.

See original here:
DNA from UW student attack 'one in one quadrillion' match to suspect - The Capital Times

TAG Heuer presents their Motorsports Experience in a popup outside of Ion Orchard. And you are invited to visit!

The two storey popup structure is at the open area outside Ion and will be open to the public daily from 10am to 9:30pm from now till 17 September, 2023. Max Verstappen and Sergio Perez will make an appearance at 5pm on September 14.

In their F1 partnership with Oracle Red Bull Racing, TAG Heuer will showcase the 2018 Red Bulls actual F1 car used in the season.

Also in the booth is a wall to test your reflexes, perhaps in a competition with your friends.

But also, as importantly for us watch enthusiasts, TAG Heuer will also display some of the iconic and historic Monaco timepieces to show the transformation over the years. On display, is a tribute to the first Monaco watch, sports the iconic shade Monaco blue and is skeletonised for the first time in its history. Also on display is the TAG Heuer Carrera collection, which is also closely linked to motorsports. It was first created in 1963 by TAG Heuers legendary former CEO Jack Heuer designed for professional drivers and sports-car enthusiasts.

And as the ultimate challenge, you can step into the shoes of a professional race car driver at the Singapore Circuit Race Simulator. The champion of this simulator will be invited to the TAG Heuer launch event which will be revealed when the countdown clock outside the popup hits 0.

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Invitation: TAG Heuer popup to showcase its DNA and motorsports - - Deployant

Identification and assembly of C. tetani-related genomes from aDNA samples

To explore the evolution and diversity of C. tetani, we performed a large-scale search of the entire NCBI Sequence Read Archive (SRA; 10,432,849 datasets from 291,458 studies totaling ~18 petabytes; June 8, 2021) for datasets potentially containing C. tetani DNA signatures. Since typical homology-based search methods (e.g., BLAST29) could not be applied at such a large scale, we used the recently developed Sequence Taxonomic Analysis Tool (STAT)30 to search the SRA and identified 136 sequencing datasets possessing the highest total C. tetani DNA content [k-mer abundance >23,000 reads, k=32 base pair fragments mapping to the C. tetani genome] (Fig.1a and Supplementary Data1). Our search identified 28 previously sequenced C. tetani genomes (which serve as positive controls), as well as 108 uncharacterized sequencing runs (79 of human origin) with high predicted levels of C. tetani DNA content. Unexpectedly, 76 (96.2%) of these are aDNA datasets collected from human archeological specimens (Fig.1a), with the remaining three datasets being from modern human gut microbiome samples.

a General bioinformatic workflow starting with the analysis of 43,620 samples from the NCBI sequence read archive. Each sample is depicted according to its C. tetani k-mer abundance (y axis) versus the natural log of the overall dataset size in megabases (x axis). A threshold was used to distinguish samples with high detected C. tetani DNA content, and these data points are colored by sample origin: modern C. tetani genomes (red), non-human (light blue), modern human (blue), ancient human (black). The pie chart displays a breakdown of identified SRA samples with a high abundance of C. tetani DNA signatures. The 38 aDNA samples predicted to contain C. tetani DNA were further analyzed as shown in the bioinformatic pipeline on the right. b Topdensity plot of the percentage identities of all BLAST local alignments detected between acBins and reference genomes including C. tetani, C. cochlearium, and other Clostridium spp. Bottomdensity plot of the checkM results for the 38 acBins including estimated completeness, contamination, and strain heterogeneity levels. Completeness and contamination levels are percentage values. c MapDamage damage rates (5 CT misincorporation frequency) for acBins (n=38 biologically independent samples) subdivided by UDG treatment [none (n=27), partial (n=5), and full (n=6)]. Also shown are the damage rates for modern C. tetani genomes (n=21 biologically independent samples). The boxplots depict the lower quartile, median, and upper quartile of the data, with whiskers extending to 1.5 times the interquartile range (IQR) above the third quartile or below the first quartile. d Damage plots for the top five acBins with the highest damage rates, and corresponding mtDNA damage plots. Shown is the frequency of CT (red) and GA (blue) misincorporations at the first and last 25 bases of sequence fragments. Increased misincorporation frequency at the edges of reads is characteristic of ancient DNA. Source data for (ad) are provided as a Source Data file.

These 76 ancient DNA datasets are sequencing runs derived from 38 distinct archeological samples, which include tooth samples from aboriginal inhabitants of the Canary Islands from the 7th to 11th centuries CE31, tooth samples from the Sanganji Shell Mound of the Jomon in Japan (~1044 BCE)32, Egyptian mummy remains from ~1879 BCE to 53 CE33, and ancient Chilean Chinchorro mummy remains from ~3889 BCE34 (Supplementary Data2). The 38 aDNA samples vary in terms of sample type (31 tooth, 6 bone and 1 chest extract), burial practices (27 regular inhumation and 11 mummies), sequencing method (26 shotgun datasets and 12 bait-capture approaches), and DNA treatment (6 UDG-treated, 5 partial UDG-treated and 27 untreated samples), all of which needs to be considered for interpretation of downstream analysis (Supplementary Data2).

Although these archeological samples are of human origin, STAT analysis of the 38 DNA samples predicted a predominantly microbial composition (~90% median across samples, Supplementary Fig.1). The predominance of microbial DNA in ancient human tooth samples is expected and consistent with previous studies which have shown microbial DNA proportions as high as 9599%13,17,18,35. C. tetani-related DNA was consistently abundant among predicted microbial communities, detected at 13.8% average relative abundance (Supplementary Fig.1 and Supplementary Data3). A total of 85 species were detected at >= 2% abundance in at least one sample (Supplementary Data4). While 65 of these species have been associated with humans or animals, 20 species have an environment-specific origin, and provide an estimate of possible environmental microbial contamination that could aid in interpretation of results (Supplementary Data4, Supplementary Fig.2). Putative environment-specific microbes make up a low proportion of the microbially classified reads at levels <=10% for 33 samples, and <=5% for 24 samples (Supplementary Data5). The three samples with the highest estimated proportions of reads from putative environment-specific microbes were Tenerife-012-Tooth, Vc-Mummy-Tissue, and Tenerife-013-Tooth (Supplementary Data5). Also noteworthy is that M. tuberculosis and Y. pestis were detected (Supplementary Fig.1) in several datasets associated with bait-capture sequencing of M. tuberculosis and Y. pestis from archeological samples36,37,38.

To further explore the putative C. tetani in aDNA samples, we performed metagenome assembly using MEGAHIT39 for each individual sample and taxonomically classified assembled contigs using both Kaiju40 and BLAST29 to identify those mapping unambiguously to C. tetani and not other bacterial species (Supplementary Data6 and 7). A majority (73%) of the alignments between assembled contigs and reference C. tetani genomes had percentage identities exceeding 99% (Fig.1b). Ninety percent of the alignments had percentage identities exceeding 90%, suggesting that a large fraction of assembled contigs are highly similar to regions of modern C. tetani genomes. Based on mapping of reads to the C. tetani chromosome, the 38 samples had a 1 percent coverage ranging from 28 to 94% (mean of 78.3%) and a 5 coverage ranging from 9 to 93% (mean of 57.5%) (Supplementary Data2). A subset of 16 samples had a 1 C. tetani chromosome coverage exceeding 90%.

For each of the ancient DNA samples, we binned together all C. tetani-like contigs to result in 38 putative, ancient DNA-associated clostridial genome bins or acBins. We then performed QC analysis of each acBin using CheckM41 to estimate genome completeness and contamination (Fig.1b and Supplementary Data8). CheckM estimates genome completeness based on the detected presence of taxon-specific marker genes, and uses duplicated marker genes (if present) to estimate contamination and heterogeneity41. Eighteen acBins were more than 50% complete and 11 were more than 70% complete. Thirty-seven acBins had low (<10%) checkM contamination (Supplementary Data8). acBins with higher genome completeness were associated with datasets produced by shotgun sequencing rather than capture methods, as these datasets had higher levels of C. tetani DNA content (Supplementary Fig.3). We also examined the acBins for potential strain heterogeneity using two independent approaches: CheckM estimation (Supplementary Data8) as well as quantification of per-base heterogeneity from mapped reads (Supplementary Data2). These two metrics had a weak but significant correlation (r=0.38, P=0.019) (Supplementary Fig.4a). Five strains (Sanganji-A2-Tooth, Chinchorro-Mummy-Bone, SLC-France-Tooth, Karolva-Tooth, Chincha-UC12-24-Tooth) were identified as possessing higher estimated levels of strain variation, but all were below 6% (CheckM) and 1.1% (average base heterogeneity).

Using the tools MapDamage242 and pyDamage43, we then examined the 38 acBins for elevated CT misincorporation rates at the ends of molecules, a characteristic pattern of aDNA damage19,20. Since these patterns are known to be affected by UDG treatment, we examined damage rates separately for full UDG, partial UDG, and untreated samples (Fig.1c). As expected, we observed the highest damage rates in the untreated samples, and the lowest damage rates in the full UDG-treated samples, indicating that the damage rates have been suppressed in some samples by UDG treatment. The damage rates calculated by MapDamage and PyDamage were highly similar with a Pearson correlation of r=0.99 (Supplementary Data2). Damage plots for all samples are shown in Supplementary Fig.5 with additional data available in Supplementary Data9 and 10.

Overall, seven acBins possessed a damage rate (5 CT misincorporation rate) exceeding 10%, which is indicative of aDNA21 (top 5 shown in Fig.1d). In addition, all of the acBins except one (Chincha-UC12-12-Tooth) were verified by pyDamage as containing ancient contigs with q values<0.01 (Supplementary Data10). The highest damage rate (17.9%) occurred in the acBin from the Augsburg-Tooth sample, which is the third oldest sample in our dataset (~2253 BCE), despite this sample being partially UDG-treated (Fig.1d). As controls, evidence of ancient DNA damage was also observed in the corresponding human mitochondrial DNA (mtDNA) from the same ancient samples (Supplementary Fig.5 and Supplementary Data2), but not for modern C. tetani samples (Fig.1c). In addition, no damage was detected in the three human gut-derived C. tetani bins identified by our screen.

In general, we observed a significant correlation between damage rates of acBin DNA and corresponding human mtDNA from the same sample (R2=0.38, P=2.8E-03, two-sided Pearson) (Supplementary Fig.6). However, acBin damage rates were generally lower than the corresponding human mtDNA rates, especially for some samples (e.g., Tenerife-004, Tenerife-013, Chinchorro-Mummy-Bone) (Supplementary Figs.5 and6), which may suggest that a subset of the archeological samples have been colonized by C. tetani at later dates (see Discussion). Damage rates were higher for noncapture datasets as these generally received no UDG treatment (Supplementary Fig.7a), and higher for samples associated with regular inhumations than those from mummies (Supplementary Fig.7b). We also observed a significant correlation between acBin damage level and sample age, but only for mummy-derived samples (R2=0.50, P=0.014) (Supplementary Fig.7c). Together, these data suggest that a subset of the acBins display evidence of ancient DNA damage and are plausibly of an ancient origin.

To explore the phylogenetic relationships between the acBins and modern C. tetani strains, we first aligned their contigs to the reference C. tetani genome along with 41 existing, non-redundant C. tetani genomes10, and clustered the genomes to produce a dendrogram (Fig.2a). Five acBins were omitted due to extremely low (<1%) genome coverage (see Methods), which could result in phylogenetic artifacts. We also included C. cochlearium as an outgroup, as it is the closest known related species to C. tetani based on phylogenomic analysis of available genomes44,45. Assessment of the genome-wide alignment for potential recombination showed no difference in estimated recombination levels for acBins compared to modern C. tetani genomes (Supplementary Fig.8).

a Dendrogram depicting relationships of acBins from ancient samples with modern C. tetani genomes. Novel branches are labeled X and Y, which are phylogenetically distinct from existing C. tetani genomes. Shown on the right of the dendrogram are metadata and statistics associated with each acBin including the estimated date of the associated archeological sample. All metadata can be found in Supplementary Data2. b Geographic distribution of ancient DNA samples from which the 38 acBins were identified. Each sample is colored based on the acBin clustering pattern shown in (a). The global map was derived from the Natural Earth [https://www.naturalearthdata.com/] medium-scale data and plotted using the rnaturalearth and ggplot2 R packages. c SNP-based phylogenetic tree of a subset of acBins from lineage 1 and 2 showing high similarity and coverage to the C. tetani reference genome. See Supplementary Fig.9 for more details. Source data for (a, c) are provided as a Source Data file.

The genome-based dendrogram of the acBins and modern C. tetani strains (Fig.2a) matches the expected phylogenetic structure and contains all previously established C. tetani lineages10. Ultimately, the acBins can be subdivided into those that cluster clearly within existing C. tetani lineages 1 or 2 and those that do not, which we have labeled X (8 acBins) and Y (1 acBin). Visualization of the acBin samples on the world map revealed a tendency for geographical clustering among acBins from the same phylogenetic lineage (Fig.2b). For example, lineage 1H acBins originate from ancient samples collected in the Americas, whereas most lineage 2 acBins originate outside of the Americas, and most clade X samples originate in Europe (Fig.2b). Interestingly, some samples from the same region (e.g., Canary Island samples, and Egyptian samples) contain diverse C. tetani lineages, which may be influenced by several factors (see Discussion).

Twenty-four acBins fall within the C. tetani tree and possess average nucleotide identities (ANIs) of 96.4% to 99.7% to the E88 reference genome (Supplementary Data2), which is within the range considered to be the same species46. These include new members of clades 1B (1 acBin), 1F (1 acBin), 1H (9 acBins), and 2 (9 acBins), expanding the known genomic diversity of clade 1H which previously contained a single strain and clade 2 which previously contained five strains (Fig.2a). Four additional acBins clustered generally within clade 1 but outside of established sublineages (Fig.2a).

In addition, we used Parsnp47 to construct a more stringent, core SNP-based phylogeny from a reduced set of 11 acBins that aligned to the reference C. tetani genome and passed several criteria (see Methods) (Fig.2c and Supplementary Fig.9). Only acBins from established C. tetani lineages 1 and 2 passed these criteria, and their phylogenetic positioning is consistent with their clustering pattern (Fig.2a). The reads associated with the core SNP alignment also showed reduced per-base heterogeneity when mapped to contigs (Supplementary Fig.4b). Notably, acBins from the Sanganji, Tenerife, Chinchorro, and Chincha samples do not show evidence of branch shortening in the tree indicative of ancient genomes, and instead cluster with modern strains. These acBins tend to have higher rates of strain variation, which could affect branch lengths, or low damage rates potentially indicative of a more recent origin (Supplementary Data2).

We also assembled a novel strain of C. tetani from a human gut sample (SRR10479805) which phylogenetically clustered with strain NCTC539 (98.7% average nucleotide identity; Supplementary Data11) from lineage 1G. The other two identified human gut samples were removed from further analysis as they predominantly matched C. cochlearium based on BLAST analysis.

Nine acBins clustered outside of the C. tetani species clade. Eight of these cluster together as part of a divergent clade (labeled X) (Fig.2a). These samples span a large timeframe from ~2290 BCE to 1787 CE, are predominantly (7 of 8) of European origin (Fig.2b and Supplementary Fig.10), and come from variable burial contexts including single cave burials, cemeteries, mass graves and burial pits37,48,49,50,51,52,53 (Supplementary Data2). Two of the samples from sites in Latvia and France are from plague (Y. pestis) victims37,53, and another is from an individual with tuberculosis38. The highest quality clade X acBin is from sample Augsburg-Tooth (~2253 BCE), with 53.9% estimated completeness and 4.11% contamination (Supplementary Data8). Comparison of clade X acBins to other Clostridium species revealed that they are closer to C. tetani and C. cochlearium than any other Clostridium species available in the existing NCBI database, but are divergent enough to be considered a distinct species. On average, based on fastANI54 analysis of orthologous sequences54 Clade X genomes have 86.5+ 1.7% ANI to C. tetani strain E88, and 85.1+ 1.3% ANI to C. cochlearium (Supplementary Fig.11a and Supplementary Data12). Based on ANI analysis of the whole genome alignment, clade X genomes have 90.8+ 0.22% ANI to strain E88 (Supplementary Data2). These similarities were confirmed by analysis of BLAST alignment identities between clade X contigs and reference genomes (Supplementary Fig.11b). As in the genome-wide tree, individual marker genes (rpsL, rpsG, and recA) from clade X acBins also clustered as divergent branches distinct from C. tetani and C. cochlearium (Supplementary Figs.1214). Finally, we re-examined the damage patterns according to phylogenetic clade, and found that clade X genomes possess the highest mean damage; 6/8 clade X genomes have a damage level exceeding 5% and 3/8 exceed 10% (Supplementary Fig.7d and Supplementary Data2). These analyses suggest that clade X may represent a previously unidentified lineage of Clostridium, including members of ancient origin. We designated this group Clostridium sp. X.

One sample (GranCanaria-008-Tooth from the Canary Islands dated to ~935 CE) also formed a single divergent branch (labeled Y) clustering outside all other C. tetani genomes (Fig.2a). Based on CheckM analysis, this acBin is of moderate quality with 74% completeness, and 0.47% contamination (Supplementary Data8). A comparison of the GranCanaria-008-Tooth acBin to the NCBI genome database revealed that it is closely related to C. tetani and more distant to other available Clostridium genomes (Supplementary Data13). Based on fastANI54, it exhibits an ANI of 87.3% to C. tetani E88, and 85.1% to C. cochlearium, below the 95% threshold typically used for species assignment (Supplementary Data13). Based on ANI analysis of the whole genome alignment, it has a 91.2% ANI to strain E88 (Supplementary Data2). To further investigate the phylogenetic position of this species, we built gene-based phylogenies with ribosomal marker genes rpsL, rpsG and recA (see Supplementary Figs.1214). Each of these three genes support the GranCanaria-008-Tooth lineage as a divergent species distinct from C. tetani. The damage level for this acBin is relatively low (~4.0%), whereas its human mtDNA damage level is ~11.6% (Supplementary Fig.5). We designated this acBin Clostridium sp. Y.

We next carried out a comprehensive comparison of genome content and structure between the acBins and modern C. tetani strains. We first clustered protein-coding sequences from all modern genomes and acBins into a set of 3729 orthologous groups, and compared their presence/absence across all strains (see Methods and Supplementary Data14). Based on this analysis, we observed considerable overlap in gene content between the acBins versus the modern reference genomes, with the greatest overlap observed between acBins from C. tetani lineages (1 and 2) and the smallest overlap observed for Clostridium sp. X (Supplementary Fig.11c). For instance, plasmid genes from the E88 reference genome were on average detected in 61% of the most complete acBins from Fig.1c (comparable to 69% in modern C. tetani genomes), and only 35% of other acBins (Supplementary Data15). Twenty orthogroups from the E88 plasmid were found in all of these acBins, including the plasmid-specific genes repA, colT, and tent (Supplementary Data15). In addition to these genes, sporulation-related genes are also highly conserved across the most complete acBins. Of 80 identified sporulation-related genes present in strain E88, 52 of these were detected in 100% of the most complete acBins, and 69/80 were present at over 90% frequency (Supplementary Data16). Thus, we conclude that key C. tetani functions, including plasmid replication, collagen degradation, neurotoxin production, and sporulation, are conserved in a subset of acBins (i.e., those in Fig.1c) for which enough genomic data was available to assemble genomes with moderate-high completeness.

We then examined genome similarities by visualizing the alignment of each genome to the reference E88 chromosome and plasmid (Fig.3a). Several low-coverage acBins can be seen in C. tetani lineages 1 and 2 (Fig.3a), which is expected given their low completeness estimates (Fig.2a). However, the divergent GranCanaria-008-Tooth genome (branch Y) and Clostridium sp. X consistently have a low alignment coverage, similar to that of C. cochlearium (Fig.3a), which we suspected may be due in part to these species being more distantly related to C. tetani. Consistent with the idea that clade X represents a distinct species from C. tetani, we identified fourteen genes present in four or more clade X members and absent from all other C. tetani genomes. The genomic context of four of these genes (labeled by orthogroup) is shown in Supplementary Fig.15. Although these genes are unique to clade X, their surrounding genes are conserved in other C. tetani genomes, implying that genome rearrangements may have resulted in these genes being either gained in Clostridium sp. X or lost in C. tetani.

a Visualization of the chromosomal and plasmid multiple sequence alignment. Orthologous blocks are shown in black and the missing sequence is colored white. The reference gene locations are plotted above the alignments. b Gene neighborhoods surrounding the repA gene (left) and tent gene (right) in modern strains versus acBins. Selected unique differences identified in acBin gene neighborhoods are highlighted. The boxed region shows the assembled tent locus in two clade X acBins. Comparison reveals a putative deletion event in the clade X strains that has removed the majority of the tent gene along with five upstream genes, leaving behind conserved flanking regions. See Supplementary Fig.18 for more information. c Per-clade coverage of the tent gene normalized to the coverage of repA. The data include n=33 biologically independent samples, including acBins from clade 1 (n=3), 1B (n=1), 1F (n=1), 1H (n=8), 2 (n=9), X (n=7), Y (n=1), and acBins whose clade affiliation could not be determined (N.D., n=3). The coverage was calculated as the average depth of coverage based on mapped reads to each gene. The boxplots depict the lower quartile, median, and upper quartile of the data, with whiskers extending to 1.5 times the interquartile range (IQR) above the third quartile or below the first quartile. See Supplementary Fig.17 for the associated read pileups. Source data for (ac) are provided as a Source Data file.

To examine differences in plasmid gene content and structure directly, we then compared the gene neighborhoods surrounding the plasmid-marker genes repA and colT (Fig.3b, expanded data shown in Supplementary Fig.16). In several acBins from C. tetani lineages 1 or 2, the gene neighborhoods surrounding these genes are similar to that in modern strains (Supplementary Fig.16). However, particularly in Clostridium sp. X and Y, we identified unique gene clusters distinct from those in modern strains. For example, in two Clostridium sp. X genomes and the Clostridium sp. Y genome, we identified a conserved toxin/antitoxin pair and a phage integrase flanking the repA gene (Fig.3b). In Clostridium sp. Y, these genes were found on an assembled 53.6kb contig (SAMEA104281224_k141_98912), which was indeed predicted as a plasmid by the RFplasmid program with a 70.4% vote using the Clostridium model55. We also observed a unique gene arrangement surrounding colT that is conserved in two clade X genomes (Supplementary Fig.16). Additional differences were identified in a few lineage 2 acBins; for example, Tenerife-004-Tooth contains unique genes neighboring repA, and the Tenerife-013-Tooth acBin uniquely encodes the repA gene adjacent to its tent and tetR gene (Fig.3b).

We then performed a detailed comparison of the plasmid-encoded neurotoxin gene, tent, and its gene neighborhood (where possible) across the strains. As shown in Fig.3a as well as based on mapped read coverage to these regions (Fig.3c, Supplementary Fig.17, and Supplementary Data17), the tent gene was detected at a relatively high depth of coverage in acBins from C. tetani lineages 1 and 2. The tent gene neighborhood structure from lineage 1 or 2 acBin strains is also similar or identical to that in modern strains, with the exception of Tenerife-013-Tooth (as it encodes the repA gene nearby) (Fig.3b).

However, in the acBins from lineage X and Y, the tent gene was either missing or was fragmented, suggesting a possible gene loss or pseudogenization event (Fig.3c). This pattern can be seen clearly in read coverage plots (Supplementary Fig.17) and when normalizing tent depth of coverage to that of the plasmid-marker gene, repA (Fig.3c). The tent locus in the two Clostridium sp. X genomes for which assembly data is available over this region appears to have undergone a deletion event resulting in the deletion of over 90% of the tent sequence as well as 3 neighboring genes (Fig.3b and Supplementary Fig.18). This analysis further supports the idea that the tent fragment may be a nonfunctional pseudogene in these clade X strains.

Ultimately, our comparative genomic analysis of gene content and neighborhood structure demonstrates that the plasmids in several of the ancient samples (particularly those of Clostridium sp. X) are distinct from modern C. tetani plasmids, while the plasmids of acBins from lineages 1 and 2 are similar to those of existing C. tetani strains. This reinforces our earlier phylogenetic analysis indicating that clade X and branch Y represent new Clostridium species that are closely related to but distinct from C. tetani.

Given the considerable scientific and biomedical importance of clostridial neurotoxins, we next focused on tent and reconstructed a total of 18 tent gene sequences (all from lineage 1 and 2 acBins) from aDNA using a sensitive variant calling pipeline (see Methods). Six tent sequences have complete coverage, and 12 have 75-99.9% coverage (Supplementary Data18). Six partial tent sequences were also reconstructed but had lower average depth of coverage as shown in the read pileups (Supplementary Fig.17). Four of the reconstructed tent sequences are identical to modern tent sequences, while 14 (including two identical sequences) are novel tent variants with 99.199.9% nucleotide identity to modern tent, comparable to the variation seen among modern tent genes (98.6100%). We then built a phylogeny including the 18 tent genes from aDNA and all 12 modern tent sequences (Fig.4a). The tent genes clustered into three subgroups with modern and aDNA-associated tent genes found in subgroups 1 and 2, and aDNA-associated tent genes forming a novel subgroup 3 (Fig.4a). All three of the tent sequences in the novel tent subgroup 3 are from clade 1H aDNA strains.

a Maximum-likelihood phylogenetic tree of tent genes including novel tent sequences assembled from ancient DNA samples and a non-redundant set of tent sequences from existing strains in which duplicates have been removed (see Methods for details). The phylogeny has been subdivided into three subgroups. Sequences are labeled according to sample followed by their associated clade in the genome-based tree (Fig.2a), except for the Barcelona-3031-Tooth sequence (*) as it fell below the coverage threshold. b Visualization of tent sequence variation, with vertical bars representing nucleotide substitutions found uniquely in tent sequences from ancient DNA samples. On the right, a barplot is shown that indicates the number of unique substitutions found in each sequence, highlighting the uniqueness of subgroup 3. c Structural model of TeNT/Chinchorro indicating all of its unique amino acid substitutions, which are not observed in modern TeNT sequences. Also shown is a segment of the translated alignment for a specific N-terminal region of the TeNT protein (residues 141149, Uniprot ID P04958). This sub-alignment illustrates a segment containing a high density of unique amino acid substitutions, four of which are shared in TeNT/El-Yaral and TeNT/Chinchorro. d MapDamage analysis of the tent/Chinchorro gene, and associated C. tetani contigs and mtDNA from the Chinchorro-Mummy-Bone sample. e Cultured rat cortical neurons were exposed to full-length toxins in culture medium at the indicated concentration for 12h. Cell lysates were analyzed by immunoblot, and the image shown is a representative of four independent experiments. WT TeNT (uniprot accession # P04958) and TeNT/Chinchorro (ch) showed similar levels of activity in cleaving VAMP2 in neurons. f, g Full-length toxins ligated by sortase reaction were injected into the gastrocnemius muscles of the right hind limb of mice. The extent of muscle rigidity was monitored and scored for 4 days (meanss.e.; n=3 per group, 9 total). TeNT/Chinchorro (ch) induced typical spastic paralysis and showed a potency similar to WT TeNT. Source data for (a, b, d, e, g) are provided as a Source Data file.

We then visualized the uniqueness of aDNA-associated tent genes by mapping nucleotide substitutions onto the phylogeny (Fig.4b and Supplementary Fig.19), and focusing on unique tent substitutions found only in ancient samples and not in modern tent sequences. We identified a total of 46 such substitutions that are completely unique to one or more aDNA-associated tent genes (Fig.4b, Supplementary Fig.20, and Supplementary Data19), which were statistically supported by the stringent variant calling pipeline (Supplementary Data20). The largest number of unique substitutions occurred in tent/Chinchorro from tent subgroup 3, which is the oldest sample in our dataset (Chinchorro mummy bone, ~3889 BCE). tent/Chinchorro possesses 18 unique substitutions not found in modern tent, and 12 of these are shared with tent/El-Yaral and 10 with tent/Chiribaya (Fig.4b). The three associated acBins also cluster as neighbors in the phylogenomic tree (Fig.2a), and the three associated archeological samples originate from a similar geographic region in Peru and Chile (Supplementary Fig.21). These shared patterns suggest a common evolutionary origin for these C. tetani strains and their unique neurotoxin genes and highlight tent subgroup 3 as a distinct group of tent variants exclusive to ancient samples (Fig.4a).

We then focused on tent/Chinchorro as a representative sequence of this group as its full-length gene sequence could be completely assembled. The 18 unique substitutions present in the tent/Chinchorro gene result in 12 unique amino acid substitutions, absent from modern TeNT protein sequences (L140S, E141K, P144T, S145N, A147T, T148P, T149I, P445T, P531Q, V653I, V806I, H924R) (Supplementary Data21). Seven of these substitutions are spatially clustered within a surface loop on the TeNT structure56 and represent a potential mutation hot spot (Fig.4c). Interestingly, 7/12 amino acid substitutions found in TeNT/Chinchorro are also shared with TeNT/El-Yaral and 5/12 are shared with TeNT/Chiribaya (Supplementary Data21). As highlighted in Fig.4c, TeNT/Chinchorro and TeNT/El-Yaral share a divergent 9-aa segment (amino acids 141149 in TeNT, P04958) that is distinct from all other TeNT sequences. Reads mapping to the tent/Chinchorro gene show a low damage level similar to that seen in the C. tetani contigs from this sample, and their damage pattern is weaker than the corresponding damage pattern from the associated human mitochondrial DNA (Fig.4d).

Given the phylogenetic novelty and unique pattern of substitutions observed for the tent/Chinchorro gene, we sought to determine whether it encodes an active tetanus neurotoxin. For biosafety reasons, we avoided the production of a tent/Chinchorro gene construct and instead used sortase-mediated ligation to produce limited quantities of full-length protein toxin (Supplementary Fig.22), as done previously for other neurotoxins57,58. This involved producing two recombinant proteins in E. coli, one constituting the N-terminal fragment and another containing the C-terminal fragment of TeNT/Chinchorro, and then ligating these together using sortase. The resulting full-length TeNT/Chinchorro protein cleaved the canonical TeNT substrate, VAMP2, in cultured rat cortical neurons (Fig.4e), and can be neutralized with anti-TeNT anti-sera (Supplementary Fig.22). TeNT/Chinchorro induced spastic paralysis in vivo in mice when injected to the hind leg muscle, which displayed a classic tetanus-like phenotype identical to that seen for wild-type TeNT (Fig.4f). Quantification of muscle rigidity following TeNT and TeNT/Chinchorro exposure demonstrated that TeNT/Chinchorro exhibits a potency that is indistinguishable from TeNT (Fig.4g). Together, these data demonstrate that the reconstructed tent/Chinchorro gene encodes an active and highly potent TeNT variant.

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'I don't think it's in her DNA': Man who co-authored Murdaugh book with Colleton Co. Clerk of Court discusses allegations  ABC NEWS 4

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'I don't think it's in her DNA': Man who co-authored Murdaugh book with Colleton Co. Clerk of Court discusses allegations - ABC NEWS 4

For many years, nobody in the Daly family knew what had become of their long lost relative who had simply upped and vanished one day. His mother, as well as his brothers and sisters, had all died without getting any answers.

Frances Daly (50), originally from Carrickmacross, Co Monaghan, but now living in Dublin, describes using her DNA to solve this family mystery of her fathers uncle, who was named John Daly, as one of her proudest moments.

He used to get remembered at various family events, recalls Daly. He would regularly get a decade of the rosary said for him. Everybody thought he just went off and made his fortune, but unfortunately that didnt happen.

It was only when Daly took an interest in tracing her family tree that she came up with answers.

I saw him in the Census, and then I found him two years later, dead in Australia at 23 from typhoid, she says. I found a guy coming in from London on a boat to Perth, and I think its him. His name is too common to be absolutely sure.

But if it is him, he got the whole way across Australia and then got bitten by something. He was in the sugar cane territory so there would have been regular outbreaks of diseases.

Daly managed to find his grave in Brisbane, and also found a small article in a newspaper marking his death. The big question left for Daly and her family was why this man had travelled all the way to the other side of the world without a word to anybody.

It was only when she sent her DNA to a genealogy company, which operates by building a database and cross-referencing peoples genetic codes, that she finally closed the circle and got what is at least plausible explanation for what happened.

He had two maternal aunts in New Zealand, and it seems he was going out to them, she says. Well never know for sure, but I didnt know about the New Zealand people until I did the DNA so that kind of closed a circle for me.

It brought great comfort to some of the older relatives to know he was buried properly and there was a priest and everything there with him. My father had a cousin who was a priest so to be able to tell him everything was done right was special.

Daly, whose family are spread over counties Louth, Monaghan and Kildare, also unearthed relatives from Melbourne, Montana, Canada, and New Zealand through the DNA testing.

I call them my new relatives, she says. Its great to be able to show them photographs of the homestead, or the graves weve some very old graves in the family and share stories. To be able to show them, this is your auntie Mary, or whatever the case may be.

Ive gone off and taken photographs of fields and old houses and farmyards and sent them away to people. You can see family resemblances and traits in photographs of people going back generations too.

A number of these people even made the long journeys back to Ireland to meet Daly and see these familial landmarks for themselves. Sometimes the biggest connection is to be able to go and put some flowers on a grave and acknowledge somebody, she says.

Part of the appeal of all this, Daly adds, is putting the pieces of the jigsaw together without having the picture on the box to help you along. For her, it isnt just about what happened, but why.

They were farmers from the country so they left for economic reasons a chance of a better life, she says. Back in the day, if there was a small farmer and the eldest son got the land and there were three other sons, the others had no choice but to go.

I have relatives who went out to mining towns in Montana. A lot of people from Carrickmacross went there for some reason. I dont know why because there isnt much of a mining tradition in Carrickmacross.

Claire Bradley, a professional genealogist specialising in Irish family history, says there are huge leaps that can be made in tracing family trees through the use of DNA, but stresses it must be used as a compliment to paper records.

In Ireland, we are really hampered by the fire in the Four Courts in 1922 when a lot of records were destroyed, largely Census records, but also wills and things like that, she says. I have gone from about 1,000 in my family tree when I started using DNA to about 4,000 now.

Claire Bradley, a professional genealogist specialising in Irish family history

All that being said, many people have raised concerns around the idea of handing their DNA over to private companies and what the implications of that could be down the road. Unsurprisingly, perhaps, Bradley dismisses much of this as scaremongering.

Youre agreeing to give it over, she says. You can have it removed from the database if you change your mind. I think there is a lot of scaremongering in it. I think people give away a lot more information on Facebook than they do with a DNA swab.

[Centuries of documents burned in the Four Courts in 1922. Now theyre being recreated]

[Irish DNA atlas maps genes of the people of Ireland]

Bradley says the DNA aspect of genealogy is more adept at widening family trees than it is at tracing backwards. This was the case for Gina Dooley (46) from Limerick who describes herself as a newcomer to all this.

About a month before the Covid-19 pandemic hit Irish shores, her grandmother died. During the grieving process, a lot of old photographs were taken out and pored over as the family took stock.

It was when she looked at a photograph of her great-grandmother that she was stopped in her tracks. I was struck by how I knew nothing about this woman, yet she looked so much like me and my mother, she says. So, she started digging, and later did the DNA test.

She didnt uncover any terrible secrets and describes her family history as a normal one regular peasant farmers but remarks that building a picture of the time they lived in and the town they came from makes them feel more real and me feel more grounded.

One particular story of a second cousin she discovered in Australia stands out. After they made contact, the man told her about an uncle of his with whom he had lived as a child. She then went to the Military Archives to find out more about him.

I dont know how to describe the feeling of sitting in the Military Archive holding pages that he wrote, she says. I never met this man he was my grandmothers uncle but it was like a piece of him was still alive.

I could share that with James in Australia, and he could relay to me things he remembered of this man, and how he used to go off on a rant about Ian Paisley. James was five years old, and he didnt know who Ian Paisley was, but that is all he remembers of this man.

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Using DNA to solve a family mystery: 'It brought great comfort to ... - The Irish Times

Epigenetic factors regulate the genes youre born with and can cause them to malfunction, from the impact of stress, adversity and pollution to diet, exercise and whether or not you drink and/or smoke. Illustration / Getty Images

Halfway through a challenge to lower her cellular age before a significant birthday, Joanna Wane looks at how a biological clock based on data from the world-famous Dunedin Study can show whether youre speeding up or slowing down time

When Terrie Moffitt first came out from the United States to work on the Dunedin Study as a PhD graduate, the 1000-plus people whove been involved in the project since birth were in their early teens. Next year, when the latest round of exhaustive tests and interviews begins, theyll be turning 52.

Back then, in the mid-80s, a few of them were already causing minor havoc. Shoplifting at Woolworths. Converting cars. Sniffing glue in the Octagon. Drugs, alcohol, risky sex. Moffitts research over the following years into why some kids grow out of juvenile delinquency (or goofing around, as she calls it) and others grow up to be career criminals is still widely cited by criminologists worldwide.

Moffitt is now associate director of the Dunedin Study and the clear link she identified between serious adult offending and childhood trauma bears revisiting amid the current political rhetoric over getting tough on youth crime. Once they got out the other side [from their teens], we began to see those two groups diverge, she tells Canvas, from her home in North Carolina. Then you could look back and see that the ones who continued with crime into their 20s and 30s were the ones who had a lot of difficulties as very young children and grew up in very adverse homes.

The major contribution [of the research] was pointing out to governments and the justice system that the vast majority of teenagers who break the law are not going to develop into hardcore criminals, so you should really help them not get a prison record. Give them a chance to grow out of it and reform themselves and they will naturally.

What the Dunedin Study has shown over more than five decades now is that childhood exposure to poverty, trauma or victimisation leaves a lasting cellular imprint on the body, too. A tough start in life means youre likely to age faster and die earlier, you increase the risk of developing chronic age-related conditions such as cardiovascular disease, dementia, hypertension, type 2 diabetes and cancer.

Of course, the reverse is also true if youve been dealt a better hand and make the most of it, increasing your chances of an extended healthspan, defined as the number of quality years where youre generally healthy, active and free from disease.

The impact, for better or worse, of both the environment you live in and the way you behave in it holds more power over your life than you might think. Epigenetic factors regulate the genes youre born with and can cause them to malfunction, from the impact of stress, adversity and pollution to diet, exercise and whether or not you drink and/or smoke. This process of DNA methylation is the most significant influence on how well people age; some estimates put it as high as 70 to 80 per cent.

Moffitt, a professor of psychology and neuroscience at Duke University in North Carolina and a professor of social behaviour and development at Kings College, London, has remained closely involved with the Dunedin Study. Having followed the cohort from adolescence to midlife, shell be back in New Zealand next year for the latest phase of research, which will look at how well theyre preparing for old age.

Since the study members turned 26, data has been collected every five or six years on a series of key biomarkers widely used as an indicator of risk for disease, including cholesterol levels, blood pressure, gum recession, lung function, heart health and blood glucose (a potential red flag for pre-diabetes). Physical functions have been added: how long they can stand on one leg, how many times they can get up out of a chair in 30 seconds without using their hands. Brain scans, first done at age 45, will also be repeated next year.

The first epigenetic clock was invented a decade or so ago, using DNA methylation levels as a way to measure biological ageing. However, what makes the Dunedin Study so unique is its access to waves of progressive data on the same group of people. We figured out, hey, I bet we could do the same thing [as the other epigenetic clocks] but using our biomarkers, says Moffitt. So thats what we did. And we determined there were 173 of those methylation marks on top of genes that differentiated between those who were falling apart swiftly over the past 20 years, those who were holding steady and those who were staying young.

The DunedinPACE algorithm, developed in collaboration with Duke University and Columbia University in New York, analyses those epigenetic marks via a pin-prick blood test. Its now considered the most precise measure of how fast or slowly a person is ageing and the best predictor of future health outcomes. Unlike other epigenetic clocks that have been named after the scientists who invented them (Horvath, Hannum, Levine), DunedinPACE acknowledges the members of the study whove made it possible.

Likened to a speedometer, the test captures a specific moment in time and is a fluid measure that can show significant change in as little as eight weeks reflecting a lifestyle change, perhaps, or the efficacy of a new medication. The fastest rate of ageing recorded so far is 1.4, which means that a person is ageing biologically by almost five extra months for every chronological year. The slowest rate of ageing thats been measured is 0.6.

Moffitt hasnt been surprised to find such a huge variation between fast and slow agers. There are people [in the Dunedin Study] who are Olympic athletes and there are people who lead a really down-and-out life, in and out of prison, on and off addictive drugs. So I knew some were taking care of themselves and some were really not, she says. When study members came to the unit for assessment day, some would look so young while others really showed their age. Seeing that reflected in the [rate of ageing] numbers was quite amazing.

The Dunedin cohort is predominantly Pkeh but comparative studies internationally have applied the DunedinPACE algorithm successfully across ethnicities and among the elderly. Moffitt is also co-director of a longitudinal study following twins born into 1100 British families in the mid-90s and has analysed blood samples from them that show the same trajectories. Its miraculous, she says. Born 20,000 miles and 20 years apart from the Dunedin Study and yet the DunedinPACE can still tell you something about them.

Ironically, no equivalent trials have yet been done on Mori and Pasifika in New Zealand.

On my 59th birthday last November, I took a DNA Age test through Auckland-based biotechnology company SRW and sent it off to TruDiagnostics in the US for analysis. A whole swag of results came back, including my extrinsic epigenetic age (a shade under 44) and my DunedinPACE value at 0.71. A follow-up test, done six months later, shows my rate of ageing holding steady. The other big news was that the length of my telomeres had extended markedly.

Protective caps on the tips of chromosome DNA strands, telomeres have been likened to the aglets that protect shoelaces from fraying. Each time a cell divides, our telomeres shorten and they shorten faster under oxidative stress. Once they reach a critical length, the cell dies. Research in adults has shown that telomere length is a predictor of lifespan and is causally linked to age-related diseases. According to the latest test results, mine have actually extended from 7.01 to 7.24 kilobases, longer than 97.94 per cent of people my age. On this measurement, my predicted biological age is 30.90.

Before I celebrate too hard, though, the full reveal of how my baseline data has shifted over a period of 12 months will come when I do a final test, on the day of my 60th birthday.

Over the past year, Ive made some lifestyle tweaks in an attempt to shift the dial in the right direction more alcohol-free days, a bit more exercise (hampered by a knee and shoulder injury), a daily dose of the blackcurrant-based brain drink repa, a monthly visit to my osteopath Glyn Flutey, and a regime of SRW supplements, Cel1, Cel2 and Cel3, developed in collaboration with leading scientists around the world to support nine key cellular functions that decline with age.

One of the molecules in Cel1 is astragaloside, a compound found in a plant root that stimulates telomere repair. Ill never know for sure but it seems likely the supplements have contributed to my positive result. An observational trial by the company in New Zealand showed a biological age reduction of two and a half years in people who took the full suite of Cel supplements for six months. An independent 12-month trial SRW hopes will verify those findings is now underway in the US.

Apart from a regular yoga class, and a hypnotherapy session to help break a lifetime habit of grinding my teeth, I havent specifically targeted stress reduction yet as a way to work on lowering my biological age. I did a transcendental meditation course once, in my early 30s, and I know my brain needs some time to slow down, but fitting in two 20-minute sessions a day just never seemed realistic to me.

Rachel Grunwell, a former investigative journalist-turned-wellness coach, teaches mindfulness meditation through her company Inspired Health to a whole range of clients, from people like me to corporate directors and high-performance athletes. The mother of three boys and a former Herald columnist, she interviewed 30 global experts for her recent book Balance: Food, Health + Happiness and found plenty of science to support the idea that lowering stress levels can help slow down ageing.

We live on a planet thats speeding up; everything is getting faster and faster, she says. I feel anxious just thinking about the idea of having to fit 20 minutes of meditation into my life! But even taking a minute can be incredibly powerful to slow down your breathing, be in the moment and reset a stressed nervous system.

ONE-MINUTE MEDITATIONS

Chronic stress hammers the body physically, increasing your risk of everything from heart disease (particularly for women post-menopause) and high cholesterol to depression and cognitive problems. It can actually shrink your brain. Here are three mindful minute tools wellness coach Rachel Grunwell recommends to help de-stress your nervous system:

Box breathing meditation: Breathe in for four counts, pause for four counts, breathe out for four counts, pause for four counts. Repeat. This forces you to slow down your breathing and focusing on the count is a good distraction.

20-second hack: Practise belly breathing by imagining youre blowing up a balloon in your belly as you inhale. Then, as you breathe out, picture the balloon deflating. To check if youre doing it right, place one hand on your chest and the other on your stomach to see which one moves as you breathe.

Body scan meditation: You can do this sitting, lying down or with your legs up the wall. Taking deep belly breaths, scan yourself from the feet up, relaxing the different parts of your body on each exhalation. Especially good just before sleep.

10-second hack: Most of us carry tension in our shoulders. Grab a few seconds to take a deep breath, squeeze your shoulders up towards your ears as high as you can, hold for a beat or two, then release with a strong out-breath.

Senses meditation: When youre having a hot drink, at home or at a cafe, tune into all your senses to be present and aware in the moment. Savour the feeling of the warm cup in your hands, the patterns you see in the crema, the sounds you can hear around you, the aromas you can smell, the taste in your mouth.

10-minute hack: If youre in a virtual meeting where you need to listen but not participate, pop in your earbuds and go for a quick walk. You cant be entirely anxious when youre walking, says Grunwell. Part of your brain disengages. Or just be still and look for shapes in the clouds.

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How to live longer: DNA, wellbeing and ageing - New Zealand Herald

Summary

Terminators are some of the most formidable and deadly Sci-Fi villains in the history of the genre, but they didnt reach their peak until they merged with another science fiction monster, Aliens Xenomorph. The hybridization of the two creatures unlocked the Terminators' ultimate weapon, one that it could never have wielded without Xenomorph DNA.

Despite the fact that these respective franchises originally had nothing to do with each other upon their films initial releases, their crossover comic series Aliens vs Predator vs The Terminator asserts that Alien and The Terminator have been a part of the same continuity all along. Apparently, Alien takes place in the future after Skynets attack on Planet Earth and the AIs subsequent defeat to the Human Resistance led by John Connor. It seems Skynets reign was pretty short-lived, though remnants of the evil artificial intelligence remained scattered across the galaxy. As humanity rebuilt from the ashes of Skynets assault on the planet and became the space-faring race of humans introduced in 1979s Alien, a rogue squadron of surviving Terminators is plotting the return of Skynet. By the time of this crossover - which takes place after Alien Resurrection - those rogue Terminators finally figured out how they were going to pull it off.

In Aliens vs Predator vs The Terminator by Mark Schultz and Mel Rubi, the remaining Terminators are able to successfully create Terminator/Xenomorph hybrids. These creatures have the biological weapons inherent in every Xenomorph, along with the ferocity and hive-mind-like coordination of the perfect organism, but thats not all. This hybridization also gave the Terminators an entirely new ability, one that isnt derived from either the Xenomorph or the Terminators entirely, but is rather a unique result of their merging: the Absorption Matrix. This ability allows the hybrids to literally absorb their physical surroundings, which both makes themselves more durable in any given situation with the added benefit of absolutely demolishing their surroundings, which is an aspect to the ability that can be weaponized in and of itself given the right circumstances (like inside a spaceship or within a highly volatile laboratory, for instance).

This ability manifested through the sheer malleability of Xenomorph DNA, and the Terminators ability to manipulate it to suit their needs. It is well established in Alien canon that Xenomorphs adapt gradually to their surroundings with each generation, as their hosts allow them to evolve through genetic imprint, which naturally makes them better suited for their environment. The Terminators know this, but since they cant impart pieces of themselves with every new generation of Xenomorph in the more natural way (if one considers Facehugger impregnation natural), they opted to speed up that process through experimentation.

These experiments conducted by the Terminators to create the best versions of themselves for the resurgence of Skynet results in perhaps the most ferocious Terminator in the history of the franchise, one with an ultimate attack it could never have had without the DNA of Aliens Xenomorph.

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Terminator's Ultimate Weapon Was Only Unlocked by Alien DNA - Screen Rant