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A CNIC study highlights the risks of mitochondrial therapeutic interventions – EurekAlert

Posted: March 21, 2022 at 9:06 am

image:Ana Victoria Lechuga-Vieco, Raquel Justo, Jos Antonio Enrquez, Jess Vzquez y Enrique Calvo. view more

Credit: CNIC

Research carried out at the Centro Nacional de Investigaciones Cardiovasculares (CNIC) has demonstrated that mixing mitochondrial DNAs (mtDNAs) of different origins can have damaging effects over the medium and long term. mtDNA is a component of the genetic material that is transmitted exclusively from mothers to their children.

The study, published in Circulation, provides invaluable information about how to identify and avoid possible risks associated with mitochondrial therapeutic interventions. The most popular of these methods include the injection of mitochondria from a donor egg into the egg of a woman with fertility problems and mitochondrial replacement therapy aimed at preventing the transmission of disease-causing mutations to descendents, popularly known as "three-parent children". Mitochondrial replacement therapy has already been approved in the United Kingdom.

The new study shows that, while most cells do not tolerate the presence of two mitochondrial genetic variants and progressively eliminate one of the two mtDNAs, some major organs are unable to do this, including the heart, lungs, and skeletal muscle.

For lead researcher Dr. Jos Antonio Enrquez, who heads the Functional Genetics of the Oxidative Phosphorylation System (GENOXPHOS) group at the CNIC, the findings have major implications for treatments involving the transfer of donor mitochondria because they show that animals generated through these procedures appear healthy early in life but go on to suffer in later life from heart failure, pulmonary hypertension, loss of muscle mass, frailty, and premature death.

In the body, most of the DNA is contained in the cell nuclei. In humans, this is where approximately 20 000 genes of the genome are located. However, another 37 genes are located outside the nucleus. These genes are located in cellular compartments called mitochondria and constitute the mitochondrial DNA, explained Dr. Enrquez.

Nuclear DNA is transmitted from parents to their offspring, with the mother and father contributing 50% shares that mix when an egg is fertilized by a sperm.

In contrast, mtDNA is inherited only from the mother because the sperm mitochondria are destroyed in the interior of the fertilized egg. Uniparental transmission of mtDNA is found in almost all organisms. In addition, mtDNA is present in multiple copies per cell, and these copies are all essentially identical, a phenomenon known as homoplasmy.

The presence of more than one mtDNA genetic variant in the cell is called heteroplasmy. Although very rare, heteroplasmy sometimes occurs naturally as a result of mtDNA mutations and can cause several diseases. New therapeutic approaches proposed in recent years and aimed at preventing disease or treating infertility can generate a new form of heteroplasmy in people.

This new form of heteroplasmy, involving distinct non-mutated mtDNA variants, is produced when an individuals cells contain both the original recipient mtDNA and the donor mtDNA transferred during the intervention. In the GENOXPHOS group at the CNIC, we have been investigating whether this breaching of a natural biological barrier has detectable physiological effects, said Dr. Enrquez.

The researchers show that the selection between mtDNA variants coexisting in the same cell depends on their impact on cell metabolism and can be modulated by variations in gene function, drug actions, and dietary changes. All of these factors help to determine the preference for one type of mitochondrial genome over another, they write.

The question as to why mtDNA is transmitted to descendents from only one parent has yet to be answered, but until now the issue had no health implications, said first author Dr. Ana Victoria Lechuga-Vieco. The new medical therapies that breach this biological barrier can generate, intentionally or non-intentionally, mixtures of mtDNA from more than one individual in the same cell.

Before the publication of the new study, we did not know what impact this mtDNA mixing had for the individual, said Dr. Enrquez.

To address this question, the GENOXPHOS group generated mice with a single nuclear genome but with all their cells simultaneously containing two distinct mtDNA variants. This mouse strain was fertile, and young animals showed no related disease, explained Dr. Lechuga-Vieco.

But long-term analysis over the full lifetime of these mice showed that the coexistence of two mtDNA variants in the same cell compromised mitochondrial function.

We observed that cells rejected the presence of two mitochondrial genomes, and most of them progressively eliminated one of the mtDNA variants. Surprisingly, however, major organs like the heart, lungs, and skeletal muscle were unable to do this, explained Dr. Lechuga-Vieco.

Organs that could eliminate one of the mtDNA variants, like the liver, recovered their mitochondrial metabolism and cellular health, but those that could not progressively deteriorated as the animals aged, continued Dr. Enrquez.

Thus the animals, which appeared healthy in their youth, in later life suffered from heart failure, pulmonary hypertension, loss of muscle mass, frailty, and premature death.

The researchers conclude that the dangerous effects of mitochondrial therapeutic interventions identified in the new study show the need for caution in the selection of the donor mtDNA genotype.

As the authors state in their article, the results of the Circulation study also imply that Even the most promising method, for the replacement of oocyte mitochondria carrying known pathological mtDNA mutations, may fail to achieve 100% replacement.

The study shows that recipient cells have a high capacity to select and amplify the original, pre-existing mtDNA variant, which may have been undetectable before transfer of the donor mtDNA. The procedure thus has the potential to result in a mix of mtDNA from two individuals in descendent cells. The same problem arises with oocyte rejuvenation by microinjection of donor cytoplasm, pointed out Dr. Enrquez.

Similarly, added Dr. Enrquez, A similar risk can arise when purified donor mitochondria are used to treat damaged cells implicated in cardiopulmonary or neurlogical diseases.

Dr. Enrquez stressed that these risks do not mean that mitochondrial replacement therapy should be abandoned. In the same way as blood transfusions and organ transplants require careful control of compatibility between recipient and donor, Dr. Enrquez recommends that any therapeutic strategy that risks the mixing of healthy mtDNA variants from two individuals should ensure full compatibility between the donor and recipient mitochondrial genomes.

The study was supported by the following funding bodies: Ministerio de Asuntos Econmicos y Transformacin Digital (MINECO); Ministerio de Economa, Industria y Competitividad (MEIC); Human Frontier Science Program; European Molecular Biology Organization; Programa Red Guipuzcoana de Ciencia, Tecnologa e Informacin del Gobierno Vasco; and the ELKARTEK Program Department of Industry, Innovation, Commerce, and Tourism.

About the CNIC

The Centro Nacional de Investigaciones Cardiovasculares (CNIC), directed by Dr. Valentn Fuster, is dedicated to cardiovascular research and the translation of knowledge gained into real benefits for patients. The CNIC, recognized by the Spanish government as a Severo Ochoa center of excellence, is financed through a pioneering public-private partnership between the government (through the Carlos III Institute of Health) and the Pro-CNIC Foundation, which brings together 12 of the most important Spanish private companies.

Experimental study

Animals

Heteroplasmy of Wild Type Mitochondrial DNA Variants in Mice Causes Metabolic Heart Disease With Pulmonary Hypertension and Frailty

3-Mar-2022

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Genetic and morphological variation of Vespa velutina nigrithorax which is an invasive species in a mountainous area | Scientific Reports – Nature.com

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Ukraine War Update: Refusing to surrender Mariupol to …

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Pierre Crom/Getty Images News

Here are the latest headlines in the Russia-Ukraine crisis:

Fighting intensifies in Mariupol

"There can be no question of surrendering or assembling weapons," Ukrainian Deputy Prime Minister Iryna Vereshchuk told Ukrainska Pravda. "We have already informed the Russian side about this." Instead, the country said Moscow should let residents leave the besieged city in southern Ukraine and deliver humanitarian aid to those who want to stay. The fall of Mariupol would mark a battlefield advance for the Russians, who are largely stalled outside major cities after more than three weeks of fighting.

Going hypersonic

With Russia claiming to have deployed hypersonic missiles against targets in Ukraine over the weekend - marking the weapon's first use in combat - the U.S. is rushing the development of its own hypersonic arsenal. General Dynamics subsidiary Bath Iron Works will begin engineering and design work on changes necessary to install the weapon system on three Zumwalt-class destroyers in fiscal year 2023. Current hypersonic use by Russia is not a "game changer," cautions U.S. Defense Secretary Lloyd Austin. "The reason that [Vladimir Putin] is resorting to using these types of weapons is because he's trying to reestablish some momentum."

EU oil embargo?

The White House has announced President Biden will visit Poland as part of his European trip this week for talks with allies about the war in Ukraine. Ahead of the meeting, the European Union is considering whether to impose an oil embargo on Russia. The decision could prompt Moscow to close flows on the Nord Stream 1 pipeline, which help provide the 27-country EU with 40% of its natural gas needs.

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Ukraine Maps & Facts – World Atlas

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Ukraine is the largest country that is entirely within Europe. The country sits on the southwestern part of the Russian Plain and has a largely low terrain. The average elevation of the land is only 574 ft (175 m).

As observed on the physical map of Ukraine above, about 5% of the country is mountainous. The northern reaches of the Carpathian Mountains stretch across western Ukraine. The country's highest point is located there; Hoverla Mountain, at 2061 m (6762 ft) tall. It has been marked on the map above by a yellow upright triangle.

As can be seen on the map above, the southern lowland of Ukraine continues into the Crimean Peninsula, a peninsula jutting into the sea from southern Ukraine via the Perekop Isthmus. It is a disputed territory.

The Crimean Mountains front the southern edges of the Crimean Peninsula, and some lower, heavily-eroded mountains extend intoRussiajust north of the Sea of Azov.

Much of central Ukraine is covered by plateaus and fertile plains (steppes), somewhat hilly areas of grasslands and shrublands.

The Black Sea Coastal Lowlands cover the southern edges of the country.

Ukraine is bordered by the waters of the Black Sea and the Sea of Azov.

Major rivers include the Desna, Dnieper, Dniester, Donets and the Southern Bug. Numerous waterfalls are found in both the Carpathian and Crimean Mountains.

The Dnieper River, one of the major rivers of Europe (fourth by length) flows from Russia, through Belarus and Ukraine, to the Black Sea. The river's total length is 2,285 km (1,420 mi).

Ukraine is divided into 24 provinces (oblast), 1 autonomous republic (avtonomna respublika) and 2 municipalities (mista). In alphabetical order, these provinces are: Cherkasy, Chernihiv, Chernivtsi, Dnipropetrovsk (Dnipro), Donetsk, Ivano-Frankivsk, Kharkiv, Kherson, Khmelnytskyy, Kirovohrad (Kropyvnytskyy), Kyiv, Luhansk, Lviv, Mykolayiv, Odesa, Poltava, Rivne, Sumy, Ternopil, Vinnytsya, Volyn (LutsK), Zakarpattya (Uzhhorod), Zaporizhzhya and Zhytomyr. Crimea or Avtonomna Respublika Krym (Simferopol) is an autonomous republic. Kyiv (Kiev) and Sevastopol are two municipalities of special status. The 24 oblasts and Crimea are further subdivided into 136 raions (district) and city municipalities.

With an area of 603,628 sq. km (which also includes the area covered by the Crimean Peninsula), Ukraine is the 2nd largest country by area in Europe and the 46th largest country in the world. With a population over 42 million people, Ukraine is the 7th/8th most populous county in Europe and the 32nd most populous country in the world. Located in the north-central part of the country, along the Dnieper River is Kiev (Kyiv) the capital and the most populous city of Ukraine. Kiev is the chief cultural and industrial center of Eastern Europe.

Ukraine is an Eastern European country. It is situated both in the Northern and Eastern hemispheres of the earth. Ukraine is bordered by 7 European Nations: by Belarus in the north; by Hungary, Slovakia and Poland in the west; by Moldova and Romania in the southwest; and by Russia in the east and northeast. It is bounded by the Black Sea and the Sea of Azov in the south. The Autonomous Republic of Crimea borders Ukraine to the south.

Ukraine Bordering Countries: Russia, Hungary, Romania, Moldova, Slovakia, Belarus, Poland.

Regional Maps: Map of Europe

The above blank outline map is of Ukraine, a country in eastern Europe. The map can be downloaded, printed and used for education work or for coloring.

The above map represents Ukraine, a country in Eastern Europe.

This page was last updated on February 24, 2021

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Ukraines leader warns war will cost Russia for generations – Al Jazeera English

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Ukraines president has warned Russians that continuing the invasion would exact a toll for generations after tens of thousands attended a nationalist event to hear a speech by President Vladimir Putin.

The remarks by President Volodymyr Zelenskyy on Saturday came after a mass rally was held in support of Russian forces in Moscow the previous night.

Noting the 200,000 people reported to have attended the rally was similar to the number of Russian forces deployed to Ukraine, Zelenskyy said Fridays event in Moscow illustrated the high stakes of the largest ground conflict in Europe since World War II.

Picture for yourself that in that stadium in Moscow there are 14,000 dead bodies and tens of thousands more injured and maimed, the Ukrainian leader said.Those are the Russian costs throughout the invasion.

Putin lavished praise on his countrys military forces during Fridays flag-waving rally, which took place on the anniversary of Russias 2014 annexation of Crimea from Ukraine. The event included patriotic songs such as Made in the USSR, with the opening lines Ukraine and Crimea, Belarus and Moldova, its all my country.

We have not had unity like this for a long time, Putin told the cheering crowd.

Taking to the stage where a sign read For a world without Nazism, he railed against his foes in Ukraine with a claim they are neo-Nazis and insisted his actions were necessary to prevent genocide.

The rally took place as Russia has faced heavier-than-expected losses on the battlefield and increasingly authoritarian rule at home. Russian police have detained thousands of antiwar protesters.

Fighting raged on multiple fronts in Ukraine more than three weeks after Russias February 24 invasion.

The northwest Kyiv suburbs of Bucha, Hostomel, Irpin and Moshchun were under fire on Saturday, the Kyiv regional administration reported. The city of Slavutich, 165km (103 miles) north of the capital, was completely isolated, the administration said.

In the besieged port city of Mariupol, the site of some of the wars greatest suffering, Ukrainian and Russian forces battled over the Azovstal steel plant, one of the biggest in Europe, Vadym Denysenko, adviser to Ukraines interior minister, said on Saturday.

Ukrainian and Russian officials agreed to establish 10 humanitarian corridors for bringing aid in and residents out one from Mariupol and several around Kyiv and in the eastern Luhansk region, Ukrainian Deputy Prime Minister Iryna Vereshchuk said.

She also announced plans to deliver humanitarian aid to the southern city of Kherson, which was seized by Russian forces.

In his nightly video address, Zelenskyy said Russian forces were blockading the largest cities with the goal of creating such miserable conditions that Ukrainians will surrender. But he warned Russia would pay the ultimate price.

The time has come to restore territorial integrity and justice for Ukraine. Otherwise, Russias costs will be so high that you will not be able to rise again for several generations, he said.

Vladimir Medinsky, who has led Russian negotiators in several rounds of talks with Ukraine, said on Friday the two sides have moved closer to an agreement on the issue of Ukraine dropping its bid to join NATO and adopting a neutral status.

In remarks carried by Russian media, he said the sides are now halfway on issues regarding the demilitarisation of Ukraine.

However, Mikhailo Podolyak, an adviser to Zelenskyy, alleged that Moscows characterisation was intended to provoke tension in the media.

Our positions are unchanged. Ceasefire, withdrawal of troops & strong security guarantees with concrete formulas, he tweeted.

Britains foreign minister accused Putin of using the talks as a smokescreen while his forces regroup. We dont see any serious withdrawal of Russian troops or any serious proposals on the table, Foreign Secretary Liz Truss told The Times newspaper.

In a phone call with Turkeys President Recep Tayyip Erdogan, Putin laid out plans for ending the war, according to the Turkish presidential spokesman, Ibrahim Kalin.

President Putin thinks the positions on the Donbas and Crimea are not close enough to meet President Zelenskyy. What we need is a strategic-level meeting between the two leaders. There seems to be growing consensus We are hoping there will be more convergence on these issues, and this meeting will take place sooner than later, because we all want this war to come to an end, Kalin told Al Jazeera.

US Defense Secretary Lloyd Austin, during a Saturday visit to NATO ally Bulgaria, said the Russian invasion had stalled on a number of fronts but the United States had not yet seen signs that Putin was deploying additional forces.

Major General Oleksandr Pavlyuk, who is leading the defence of the region around Kyiv, said his forces are well-positioned to defend the city.

We will never give up. We will fight until the end. To the last breath and to the last bullet, said Pavlyuk.

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SWIFT, hedgehog, MiG: Here’s a guide to the terms of war in Ukraine – NPR

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Pedestrians cross a street in front of a billboard displaying the letter "Z" in the colors of the ribbon of St. George and a slogan: "We don't give up on our people," in support of the Russian armed forces, in St. Petersburg, Russia, on March 7. AFP via Getty Images hide caption

Pedestrians cross a street in front of a billboard displaying the letter "Z" in the colors of the ribbon of St. George and a slogan: "We don't give up on our people," in support of the Russian armed forces, in St. Petersburg, Russia, on March 7.

Russia's invasion of Ukraine has many of us using new words and phrases, from geopolitical terms like "rump state" to military lingo such as "MANPADS."

We're also learning to decipher slogans and spot differences between Russian and Ukrainian spellings during a conflict in which information is treated as its own battlefield.

Tracking surges in the words we use is part of linguist Grant Barrett's job. He is the co-host of A Way with Words, a public radio show about words and language, and a vice president of the American Dialect Society.

"As a word watcher, we get a sense of the worries of the world," he told NPR.

Barrett points out how the term Cold War has now been supplanted by the term "hot war" a violent conflict with many of the worst burdens borne by civilians.

With Barrett's help, NPR created a kind of war glossary, explaining some of the terms people are using to discuss the war Russia and President Vladimir Putin are waging on Ukraine.

The Western world is debating whether permitting Putin to retain some of the territory he has seized would "be like the 1938 appeasement of Hitler by British Prime Minister Neville Chamberlain," Barrett said.

Some experts, noting that Russia seized Crimea in 2014, warn that Putin could be further emboldened by any accommodations.

The circumstances have led to talk of a "smell of Munich" being in the air, Barrett said, referring to the 1938 Munich Agreement that allowed Nazi Germany to annex part of Czechoslovakia an unsuccessful attempt to prevent further fighting.

The Ukrainian word for bomb shelter a new necessity that's forced libraries and other facilities into new roles of protecting civilians.

Ukrainians prepare tea in a bomb shelter in Irpin, on the outskirts of Kyiv, Ukraine, on March 13. Felipe Dana/AP hide caption

Ukrainians prepare tea in a bomb shelter in Irpin, on the outskirts of Kyiv, Ukraine, on March 13.

In general, a "cessation of hostilities" is temporary and can be localized, while a cease-fire is meant to be permanent and comprehensive.

The United Nations lists at least seven terms that describe pauses in violence, many of which are aimed at allowing civilians to reach safety or access help or, in the best cases, providing time to negotiate a lasting peace.

From the earliest days of the war, human rights groups accused Russia of using these controversial weapons, which open midair and indiscriminately spray wide areas with dozens or even hundreds of small "bomblets" often with tragic effects, especially in urban or civilian settings.

Unexploded cluster bombs are seen here in 2020, collected during the military conflict between Armenia and Azerbaijan over the breakaway region of Nagorno-Karabakh. Aris Messinis/AFP via Getty Images hide caption

Unexploded cluster bombs are seen here in 2020, collected during the military conflict between Armenia and Azerbaijan over the breakaway region of Nagorno-Karabakh.

A U.N. convention banning the use of cluster munitions took effect in 2010; but Russia, Ukraine nor the U.S. have agreed to that ban.

"Donbas" comes from an abbreviation meaning "Donets coal basin," Barrett said. Leaders in this region of eastern Ukraine have recently favored Russian control, and it's home to Luhansk and Donetsk the Ukrainian territories that Russia recognized as independent republics.

The term describes a nation that, while technically neutral and independent on the international stage, yields to the policies of a larger, more powerful neighbor, as Finland deferred to the USSR during the Cold War in return for maintaining its sovereignty.

In the weeks before the war, the term made occasional headlines in part because it's generally seen as a pejorative. It could resurface if Ukraine and Russia agree to negotiate.

Also known as the Czech hedgehog, the spiky-looking steel obstacles can divert or delay tanks. Ukrainian civilians have been DIY-ing hedgehogs, welding two bars or beams at an angle to make a cross and then adding a third to ensure it holds its shape even if it's knocked over.

Volunteers connect I-beams to make anti-tank obstacles known as Czech hedgehogs, in a workshop in Lviv, western Ukraine, on March 3. Daniel Leal/AFP via Getty Images hide caption

Volunteers connect I-beams to make anti-tank obstacles known as Czech hedgehogs, in a workshop in Lviv, western Ukraine, on March 3.

"Specific routes and logistical methods agreed upon by all relevant parties to allow the safe passage of humanitarian goods and/or people from one point to another in an area of active fighting," the United Nations said.

People rest as they take shelter from attacks in a metro station in Kharkiv, Ukraine, on March 10. Emre Caylak/AFP via Getty Images hide caption

People rest as they take shelter from attacks in a metro station in Kharkiv, Ukraine, on March 10.

The anti-tank missiles are "very, very effective" at knocking out tanks and armored vehicles, retired U.S. Army Brig. Gen. Peter Zwack told NPR. Javelins went into full-scale production in 1997.

A U.S. soldier walks with a Javelin surface-to-air missile launcher in the countryside of Deir Ezzor in northeastern Syria in December 2021. Delil Souleiman/AFP via Getty Images hide caption

A U.S. soldier walks with a Javelin surface-to-air missile launcher in the countryside of Deir Ezzor in northeastern Syria in December 2021.

The weapon's ability to destroy Russian armor has made it a cultural phenomenon in Ukraine, where it even has its own meme: St. Javelin.

A derisive Ukrainian nickname for pro-Russian separatists, many of whom wear orange-and-black St. George ribbons that symbolize Russia's military strength.

George was a Roman army officer who became a martyr because of his Christian faith. The Order of St. George is among Russia's highest military honors, dating back to 1769 after a hiatus, it was reinstated by Putin's government in 2000.

Koloradi is also the Ukrainian term for the Colorado potato beetle, an invasive, destructive pest whose stripes resemble the ribbons.

Man-portable air-defense systems, sometimes called MPADS, are portable surface-to-air missiles. In Ukraine, they've been seen carried by soldiers and reportedly bringing down Russian aircraft.

There are many types of MANPADS, although the most famous is the U.S.-made Stinger.

The jet warplanes are named after the Mikoyan-Gurevich aviation company. The MiG-15 fought in the Korean War of the 1950s. Ukraine's air force uses the MiG-29 and Poland recently threw the U.S. a curveball by announcing a plan to give Ukraine more Russian-made MiG-29s.

A MiG-31 fighter of the Russian air force takes off at an air base during military drills in Tver region, Russia, in a photo provided by the Russian Defense Ministry Press Service in February. Russian Defense Ministry Press Service via AP hide caption

A MiG-31 fighter of the Russian air force takes off at an air base during military drills in Tver region, Russia, in a photo provided by the Russian Defense Ministry Press Service in February.

The phrase is used by Russians who are against the war in Ukraine even under the threat of detention, arrests, steep fines and other punishments. Even children have been taken into custody for holding homemade signs.

The Kremlin's harsh response to anti-war sentiments has recalled the mass purges of Russia's Stalinist era.

Ukrainian leaders have repeatedly asked their allies in Europe and the U.S. to "close the skies" over Ukraine to give their ground forces a chance against Russia's invading military. But Western nations have stopped short of calling for this measure.

A protester in Paris calls on NATO to enforce a no-fly zone over Ukraine during a demonstration on Feb. 26. Peter Dejong/AP hide caption

A protester in Paris calls on NATO to enforce a no-fly zone over Ukraine during a demonstration on Feb. 26.

"The only way to actually implement something like a no-fly zone is to send NATO planes into Ukrainian airspace and to shoot down Russian planes, and that could lead to a full-fledged war in Europe," U.S. Secretary of State Antony Blinken said. "President Biden has been clear that we are not going to get into a war with Russia."

"A very wealthy businessperson with strong political ties," Barrett said, adding, "wealth alone does not make one an oligarch."

"The use of 'oligarch' to refer specifically to wealthy Russians dates to the 1990s, although general use of the term dates to the 1600s," he said.

Ukrainians have invoked the Lord of the Rings villains to refer to Russia's force, saying the hordes were being sent to loot their country and dismantle its democracy. Those using the term include a doctor in Melitopol who filmed and posted video of a protest to social media.

Ukraine's defense intelligence service features an owl in its insignia. In it, the owl hovers above a global map, stabbing a sword down from the sky into Russia. The service recently promised that its owls would track down Russian marines that Ukraine says attacked civilians.

Ukraine's defense intelligence service uses an owl in its insignia and the owl is pointing a sword directly at Russia.

Critics of Putin use a range of "blended names" for the Russian leader. Barrett cites a chapter from Language of Conflict: Discourses of the Ukrainian Crisis, published in 2020, for some examples:

Russian President Vladimir Putin has gained a number of unflattering nicknames as of late. Alexei Nikolsky/AP hide caption

Russian President Vladimir Putin has gained a number of unflattering nicknames as of late.

The term refers to any nation that has seen a large portion of its territory carved away and absorbed into another country.

The Russian Federation is sometimes considered to be a rump state of the USSR. Now Putin wants to turn Ukraine into a rump state, expert Fiona Hill recently said.

"Glory to Ukraine!" now peppers many statements coming out of Ukraine. It's often followed by the reply, "Heroiam slava!" glory to the heroes.

People stand in front of a huge banner with the lettering "Slava Ukraini" as they take part in a demonstration in support of Ukraine on Freedom Square in Tallinn, Estonia, on Feb. 26. Raigo Pajula/AFP via Getty Images hide caption

People stand in front of a huge banner with the lettering "Slava Ukraini" as they take part in a demonstration in support of Ukraine on Freedom Square in Tallinn, Estonia, on Feb. 26.

House Speaker Nancy Pelosi used the phrase in Congress as she introduced Zelenskyy ahead of his March 16 speech to U.S. lawmakers.

The phrase dates at least as far back as Ukraine's war for independence (1917-1921); it also had a resurgence when Ukraine left the Soviet Union in 1991.

Putin's term for his country's attack on Ukraine is, at best, a euphemism and, at worst, a sign of the gap between the reality of what is taking place in Ukraine and the narrative many Russian people are being fed. While the rest of the world sees a tragic humanitarian crisis, the Kremlin has insisted it is on a peacekeeping effort in Ukraine.

The global bank messaging system operated by the Society for Worldwide Interbank Financial Telecommunications is a crucial part of the harsh sanctions on Russia.

Images and other evidence show that Russia has brought thermobaric weapons to Ukraine.

Russian Army TOS-1A "Solntsepyok (Blazing Sun)" multiple rocket launcher and thermobaric weapon mounted on a T-72 tank chassis seen during the annual Army Games defense technology international exhibition. Leonid Faerberg/SOPA Images/LightRocket via Getty Images hide caption

Russian Army TOS-1A "Solntsepyok (Blazing Sun)" multiple rocket launcher and thermobaric weapon mounted on a T-72 tank chassis seen during the annual Army Games defense technology international exhibition.

"These are very devastating weapons that create a gas [fuel] cloud that then explodes," Jeffrey Edmonds, a research scientist who is a former director for Russia at the National Security Council, told NPR. "These are the weapons they used to clear out Aleppo" in Syria.

Edmonds describes them as "very indiscriminate weapons that cause mass destruction." Thermobaric weapons are not explicitly banned the U.S. has them as well but critics question their legality.

The letter, which isn't part of the Cyrillic alphabet used by both Ukraine and Russia, is now seen as a Russian pro-war symbol. It was painted on Russian tanks and other military vehicles as a large white Z. It's also often rendered in the same colors of the ribbon of St. George, orange and black.

"In the beginning, it looks like it was just simply a way for the Russians to mark their vehicles in some kind of internal classification," Barrett said. "But the Russians quickly realized that they could capitalize on it and use it as kind of a badge of honor."

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SWIFT, hedgehog, MiG: Here's a guide to the terms of war in Ukraine - NPR

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The power of the new Ukraine – The Guardian

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Ukraine has been an independent country for more than half Vladimir Putins adult life (he turns 70 this year). Its been a free republic for more than 30 years, long enough for the first generation of Ukrainians born since independence to have school-age children of their own. Its had seven different leaders, all of them still alive.

It would be sentimental and patronising to talk about a country having grown up. But 30 years is long enough for countries to change, for better or for worse; long enough for countries to have eras. Ukraine was well into its second era, its European era, when Putin invaded last month. Putin never accepted the right of post-Soviet Ukraine to exist in independent Ukraines first era. In terms of understanding the country, thats the period hes stuck in; Putin doesnt acknowledge that a second era began.

The west shares many of the Kremlins misapprehensions about Ukraine. We are still too ready to see the country through the cliche of a nationalist, Ukrainian-speaking west and a Russia-friendly, Russian-speaking south and east. Or, more crudely and colourfully, neo-communist miners in the east, neo-Nazis in the west. Of course it was never that simple, even in post-Soviet Ukraine. But European-era Ukraine, which emerged in 2014, overturned its own political fundamentals. Faced with an existential struggle against a powerful, ruthless neighbour, Russia, where nationalism now serves autocracy, an emergent class of Ukrainian liberals made common cause with Ukrainian nationalists. Its been an uncomfortable alliance but it has kept the country together. As Ukraine defends itself against Putins terror campaign, mutually estranged liberals and nationalists in other countries the US, England, France would do well to watch.

To talk about European Ukraine isnt to describe an achieved state but a state of hope: hope of membership in the European Union more meaningful to Ukraine, at least until Russia attacked, than membership of Nato.

Ukraines hope of Europe had its material side, a hope of grants, jobs and trade. Since the revolution of dignity also known as Maidan in 2014, trade with the EU soared while trade with Russia plunged. More than a million Ukrainians went to work, legally or otherwise, in the EU. Since Russia invaded Ukraine on 24 February, much has been made in Britain of the EUs openness to Ukrainian refugees compared with the barriers put up by London. But its a depressing reflection of how mainstream anti-immigrant assumptions have become in the UK that virtually no one in Britain is aware the EU gave Ukrainians visa-free access years ago, as a reward for their countrys sacrifices in Europes name. Since 2017, as a result of that and of Brexit, Ukrainians have levelled up and Britons levelled down to identical rights of EU entry: 90 days stay without a visa.

Beyond the material hopes of European-era Ukraine, there is the prospect, less tangible and more powerful, of an alternative form of nationhood. Rather than the archaic, romantic, racial mystifications of old Ukrainian nationalism, or Putins neo-imperial vision of Ukraine pulverised and remade as a puppet state to serve Russian nationalism, its of Ukraine pursuing its free course as an equal member of a self-constraining, self-governing association of countries, the EU.

The beauty of the EU, for Ukraine, is the capaciousness of its model for both liberals and nationalists. In some ways, the aims of European-era Ukraine closely resemble those of the Scottish National party and the Irish republic: to use the economic power of the EU to leverage their own, to break out of the orbit of a delusional post-imperial culture, to find national self-determination by accepting multinational rules. As Tom Nairn wrote of Scotland, a country could aspire to a new interdependence where our nationhood will count, rather than towards mere isolation.

For Ukraines more conservative nationalists, its Poland and Hungary that offer the more appealing EU models stridently patriotic, subordinating media, courts and education to national ideals and social conservatism, all while getting subsidies and trading freely within the EU.

The prelude to Ukraines European era occurred in 2013 under president Viktor Yanukovych, a profoundly corrupt politician from the east of the country. Although seen as a proxy for Kremlin interests, and generally loyal to the idea of post-Soviet Ukraine as a Russian client state, he threw his weight behind an association agreement with the EU. He had his country on side, but Putin gave it to be understood that he considered it a betrayal Ukraine could partner with the EU or Russia, not both.

Whether Yanukovych was genuinely up for the deal with Brussels, or simply angling for a bigger bung from Moscow, he changed his mind at the last minute, took a large loan from Putin and turned his back on the EU.

It was November. Protests began in Kyiv against abandonment of the EU deal. There were calls for Yanukovych to resign. Small, peaceful protests were put down violently by the police. Parliament, then controlled by Yanukovych allies, passed repressive laws against free speech and gatherings. As 2013 passed into 2014, the protests grew, their demands expanded and their base spread. Opposition to Yanukovych and calls for deeper ties to Europe evolved into attacks on the entire corrupt, oligarchic system of business and government.

Young members of the liberal intelligentsia were joined by radical nationalist groups, by small-business owners and by factory workers. Opposition MPs aligned themselves with the protesters. Increasingly violent street battles were waged around Kyivs central square, Maidan Nezalezhnosti. Barricades went up. Weapons escalated from clubs and stones and shields to molotov cocktails, to stun grenades and rubber bullets, to actual bullets. Some police were shot; more than 100 protesters were killed.

In the third week of February, for reasons still mysterious perhaps because the security forces ceased to believe in the president the regime collapsed. European foreign ministers brokered a peace deal with Yanukovych, the Maidan crowd refused to accept it, and Yanukovych fled the country. Parliament voted in an interim government and prepared for new elections.

Barely had the revolutionaries victory sunk in before Russia annexed Crimea in a nearly bloodless coup de main. In Yanukovychs home region of Donbas, on the border with Russia, locals angry at the treatment of their lawfully elected president seized administrative buildings. They were quickly ousted, only to be replaced, in April, by a new wave of rebels helped by volunteers from Russia. Fighting escalated to a full-scale war, culminating in incursions by regular Russian troops. Thousands of people were killed. By 2015, the front lines had stabilised and fighting lessened, with part of Donbas under joint Russian-rebel control. The rest of Ukraine was at peace. In 2017, the association agreement with the EU came into force.

Even before the war in the Donbas began, there were warnings of what the longer term held. In what reads now as an astonishingly accurate forecast of what was to come, in an interview with a Ukrainian paper in March 2014, the former Putin adviser Andrei Illarionov spelled it out, failing only to predict that eight years would pass first. Theres an aim and a plan to attack Ukraine which was put together years ago, he said. It has many different elements Crimea, the south-east and, of course, a change of power in Kyiv. And then there are other things: a new [Ukrainian] constitution, to be written in the Kremlin, disarmament of the Ukrainian people, liquidation of Maidan, and so on.

Liquidation of Maidan sounds different from the current Kremlin programme, until you realise this is simply denazification by another name.

It might seem trivial now, when Ukraine is on fire and hundreds are being killed every day, when all that seems important is how many Russian tanks and planes and soldiers the Ukrainians have to blow up to make Putin stop, to talk about abstractions like nationalism and liberalism. And yet without these forces coming together over the past seven years of semi-peace, would Ukraine have held out this long?

I remember being surprised, when I visited Kyiv at the end of February 2014, to see how focused liberals and nationalists alike were on a European future. The spokesman for one of the most notorious radical nationalist groups, Right Sector, talked to me about Poland as a model for the country. European flags were everywhere. I went for dinner one evening with a friend of a friend, a successful businesswoman. The Maidan was very localised; a huge encampment of brown tents crowded together, wreathed in the smoke of hundreds of stoves, in which exhausted people, who had fought nightly battles in freezing conditions, lived difficult lives away from home. But right next door to it were expensive restaurants with waiters in spotless white shirts serving fine wines and tuna carpaccio. You know, the nationalists were very important, said the businesswoman, sipping her grenache. They did very good work at the leading edge.

Ive always been in two minds about that conversation with someone who had been very kind to me. On the one hand, it had that air of somebody being grateful that somebody else was doing their dirty work; that one person had education, good taste and proper gentle sentiments, and they were grateful that their interests were being protected by another person who risked their life with a petrol bomb and a brick, and whose most conservative, chauvinist views the first person would definitely not want to hear at their dinner table in peacetime. On the other hand, my friends friend was being honest about the realities of a dangerous situation, and resistance towards a nasty, increasingly repressive regime: that she was not one of natures fighters, and she was glad to have people prepared to fight for their country on her side. Nationalist and liberal, after all, are words with an extremely broad range of meanings.

For me, national is what allows me to defend Ukraine as an independent, sovereign nation, said the Ukrainian philosopher Evhen Bistritsky in 2018, at a time when disillusionment with Ukraines post-Maidan failures to get to grips with corruption and institutional inertia was running deep.

I am a liberal, defending the independence of Ukraine. Part of Ukrainian society supports conservative values, linking them to security. If were really only going to preach universal, classical, liberal values we promote discord in the country.

In a country not fighting for its existence, in the US, perhaps, or Britain, or France, in some safe part of the EU, such language would have marked Bistritsky out as a centrist, a moderate, even, more pejoratively, an undemocratic compromiser. In the present Ukrainian context, faced with the Russian killing machine, discord becomes failure to fill the ranks.

Recently the Ukrainian writer Artem Chekh published Absolute Zero, his memoir of service in the Ukrainian army on the Donbas front in 2015. In it he faces up to the strangeness of being a liberal, cosmopolitan, intellectual man serving alongside workers and farmers who see the world in patriotic, if cynical, absolutes. I went around to his flat in Kyiv a few weeks ago for coffee and cake. Now he has taken up a gun again to protect the city against the invader. In an article for the London Review of Books blog, he lists his comrades: a music producer, an owner of a household chemicals store, a teacher, an artist, a bank clerk, a former investigator, a doctor. The ability to write, paint, act, play a musical instrument or dance doesnt matter now. What counts is military experience.

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The power of the new Ukraine - The Guardian

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What Happened on Day 23 of Russias Invasion of Ukraine – The New York Times

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KYIV, Ukraine A tall woman with blonde and pink hair and a small dachshund stood out among the crowd of police officers and volunteers at the checkpoint on the edge of Kyiv. She looked as if she were out for a stroll, but she had just survived a dangerous evacuation under mortar fire.

The woman, Sasha Myhova, 21, and her boyfriend, Stas Burykov, 19, were evacuated Friday from their home in Irpin, the northwestern suburb that has become one of the most fiercely contested areas in the three weeks of fighting since Russias invading troops advanced toward the capital and Ukrainian troops blocked their way.

It was dangerous, she said. They were bombing as we drove.

The heavy boom of artillery sounded again as she spoke. Shells were landing right in our yard, she said, pulling out a piece of metal shrapnel she had kept.

As the war in Ukraine settles into its fourth week, the suburbs on the edge of Kyiv have become important if unlikely front lines of the war, where the Russian and Ukrainian forces are stuck in a savage give-and-take at one of the gateways to the capital, in positions that have not really moved.

Blocked and badly mauled, Russian forces have nevertheless established positions around three sides of the capital. Ukrainian forces have successfully stalled them, and on Wednesday mounted a series of coordinated counterattacks to challenge those positions.

President Volodymyr Zelensky of Ukraine hailed the defense of Kyiv, led by the commander of land forces, Oleksandr Syrsky, saying that Ukrainian forces had regained control of 30 settlements around the city in the counterattack. The enemy suffered significant losses and was driven away from the capital, he said.

Yet the mortar fire and gunfire was so heavy in Irpin that the Ukrainians stopped attempting further evacuations after the one that included Ms. Myhova. The Ukrainian counterattack seems to have been met by a ferocious response from Russian forces. Residents and volunteers helping evacuate them said Russian artillery fire and even machine gun fire had intensified over the last few days.

One man, Vitaliy Kalman, was standing beside his suitcase hoping for a lull in the fighting. He said he had tried to go back into the district to retrieve some clothes from his apartment but came under mortar fire just beyond the ruined bridge that marks the entrance into Irpin. The bridge was destroyed by Ukrainian troops to forestall advancement by Russian troops in the first days of the war.

They are very close, he said of the Russians. I saw the shell explode just near my house, and I ran back here with the evacuation team.

A volunteer member of the Territorial Defense Forces described the street fighting in Irpin as an all-out guerrilla war. On the attacking side are the Russian troops, which Western military analysts say are likely elite airborne Special Forces units.

Defending against them are local volunteers, many of whom had just been handed rifles a few days before the Russians arrived in their town, alongside veteran militia fighters and uniformed troops.

Street fighting had been raging for days, according to soldiers interviewed on the edge of the town on Saturday. As of then, Russians controlled one of the three main thoroughfares, one was contested and the third was under tenuous Ukrainian control.

The locals have been slipping out at night and shooting at Russian positions, said the volunteer, who asked only to be identified by his nickname, Spotter, for security reasons. Its understood that they will be taking no prisoners, he said of the firefights. These are people who have weapons and know the local area perfectly.

A doctor at a nearby hospital said it had received 25 wounded soldiers on Wednesday on the first day of the counterattack.

Ms. Myhova said Russian troops had twice entered her home in recent days. First, two soldiers who seemed to be scouts came into the yard, then three days ago, just before the Ukrainian counterattack, 10 Russian soldiers entered the house.

They searched everything, she said. They said they had picked up a telephone signal from the house.

The soldiers warned the family that if they informed anyone about the location of the Russian troops, they would shoot them. They pointed their guns at us, she said. They said, We can shoot you because we know your location.

When Mr. Burykovs 70-year-old grandfather, the owner of the house, began to remonstrate with them, the Russian soldiers told them that they were securing control over what was Russian land, citing the medieval kingdom of Kievan Rus, which Russia claims as its ancestral state.

My grandfather tried to argue, Mr. Burykov said. He said, Its rubbish that its your land. I was born here. Go away.

On Wednesday, the day Ukraine mounted its counter-strikes, residents said the shelling worsened dramatically. There were four explosions around the house that shook the doors, and the sound of gunfire from assault rifles in the yard, Ms. Myhova said.

When they learned that volunteers were evacuating an elderly woman nearby, the couple, along with a sister of Mr. Burykov, asked to get out. But Mr. Burykovs parents, grandfather and other siblings stayed behind.

They want to go when there is a green corridor, Ms. Myhova said, referring to a humanitarian evacuation with guarantees of safety. But there will not be any, she said, since even if one is agreed, they shoot at the cars.

The Ukrainian army and volunteers evacuated about 150 residents from Irpin on Thursday, many of them pensioners who were struggling to survive after the fighting disrupted water, gas and electricity.

They are out of strength, said a volunteer paramedic, Oleh Lutsenko, 32, who was on duty at the entrance to Irpin Thursday. He treated three wounded soldiers, one with severe wounds from artillery fire, among the evacuees, and his team also brought out the bodies of three dead civilians all grandmothers, as he called them. Maybe they died from hunger, he said.

As his team pulled out just before 5 p.m., they came under machine gun fire, he said. Despite two days of counterattack, they were still in range of Russian guns.

While Ukrainian troops had success in stalling the Russian advance as it lumbered down the main highways toward Kyiv, Russian units have continued pushing south on the eastern and western flanks of the capital in an attempt to encircle it, military analysts have said.

The long columns of tanks that had backed up on highways to the north of Irpin have now fanned out into villages and forests outside of Kyiv, according to the volunteer, Spotter, who was interviewed at a gas station in a western district of the capital.

In his mid 50s, with a salt and pepper beard, he carried a walkie-talkie and said he ran an ad hoc intelligence unit, collecting information on the Russians positions in the suburbs and outlying villages.

They are hiding tanks in villages between houses, he said, adding that soldiers were also quartering in homes to avoid the cold.

Their dispersal was complicating the Ukrainian counterattack, since the Russian armor was interspersed in villages, where civilians lived, even if most people have fled the area.

After two major ambushes on Russian positions outside Kyiv, in the suburban towns of Bucha and Brovary, which together left dozens of charred tanks on main roads, the armored vehicles are now avoiding traveling in columns, he said.

They are now digging in, Spotter said of Russian soldiers, as Ukraines artillery has been pounding them from the edge of Kyiv. They didnt expect this resistance.

Volunteers guarding the checkpoint on the main western highway that heads out of Kyiv to the city of Zhytomyr said Russian troops had seized control of the road and vehicles could no longer safely use the highway except to a nearby settlement of Chaika.

It was unclear, Spotter said, how far south Russian troops had moved after crossing the Zhytomyr highway, though it appeared the intention of the Russian forces was to keep encircling the capital and eventually seal off access routes.

The advance was now stalled. They are regrouping, he said.

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What Happened on Day 23 of Russias Invasion of Ukraine - The New York Times

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The Complexities of the Ukraine Dilemma – The New Yorker

Posted: at 9:05 am

In September,1949, two Ukrainian agents working with the C.I.A. landed near Lviv, in what was then the Soviet Union. They were the vanguard of an operation that would acquire the code name Redsox. Its aim was to connect with anti-Soviet insurgents fighting by the tens of thousands in Ukraine, as well as in smaller numbers elsewhere on Russias rim. Soviet moles betrayed the program, however, and at least three-quarters of the Redsox agents disappeared. By the mid-nineteen-fifties, Moscow had quelled Ukraines rebellion while forcibly displacing or killing hundreds of thousands of people. The C.I.A.s glancing intervention was ill-fated and tragic, an internal history concluded.

Since Vladimir Putin ordered Russias unprovoked invasion of Ukraine, on February24th, the United States has acted as if to redeem itself; the Biden Administration has led its NATO allies to airlift planeloads of Javelin anti-tank weapons and Stinger anti-aircraft missiles to Ukrainian forces, while pledging billions of dollars more in military assistance and imposing punishing sanctions on Russias economy and Putins lite. More than three weeks after the crisis began, the mood in Western capitals remains pugnacious and emotive. Last week, the Ukrainian President, Volodymyr Zelensky, appeared by video before Canadas Parliament, and, the next day, he addressed a joint session of Congress. In both venues, politicians rose to applaud and chanted an improbably viral invocation of Ukrainian glory: Slava Ukraini!

Yet NATO has declined to provide Ukraine what Zelensky has repeatedly soughta no-fly zone to ground Russian warplanes or a transfer of fighter jetsfor fear that such actions would bring the U.S. and Russia into direct combat. We will not fight a war against Russia in Ukraine, Joe Biden reiterated on Twitter recently. A direct confrontation between NATO and Russia is World War III. And something we must strive to prevent. The President is, of course, right about that, and yet, as Russian planes and artillery daily pound Ukrainian apartment buildings and hospitals, he can surely understand why Zelensky is pressing for more.

Zelensky has been justly celebrated for his personal courage and his adaptations of Churchillian rhetoric for the TikTok era. His presentation to Congress last week was a study in discomforting moral provocation. He invoked Pearl Harbor and September 11th to describe Ukraines daily experience under Russian missiles and bombs, then showed a graphic video depicting the recent deaths of children and other innocents. Later that day, Biden called Putin a war criminal and announced a new package of military supplies, including anti-aircraft systems and drones. The aid may help, but it cannot relieve Zelensky of the terrible predicaments he must manage in the weeks ahead. Ukraine may be facing a long war costing the lives of hundreds of thousands of its citizens, a war that may not be winnable, even with the most robust assistance that NATO is likely to provide. In any event, NATOs greatest priority is to strengthen its own defenses and dissuade Putin from attacking the alliance.

Zelenskys alternative may be to pursue a ceasefire deal with Putin that could require Ukraine to forswear future NATO membership, among other bitter concessions. In the light of Putins annexation of Crimea, in 2014, and his years-long armed support for pro-Russian enclaves in Ukraines east, such a deal would be unstable and unreliable. Still, Zelensky appears torn. Even as he asked Congress last week to do more for Ukraines war effort, he pleaded with Biden to lead the world to peace, and he recently signalled his willingness to bargain with Putin on Ukraines relationship with nato. The countrys past failure to win admission to the alliance is a truth that must be recognized, he said.

It has become common to describe Russias invasion as a watershed in history comparable to 9/11 or to the fall of the Berlin Wall. The war in Ukraine marks a turning point for our continent and our generation, President Emmanuel Macron, of France, said earlier this month. Perhaps, but some of this speculation about Europes destiny and the future of Great Power competition may be premature. Certainly, the war has already produced a humanitarian disaster of shocking and destabilizing dimensions. Three million Ukrainians have fled their country. The 1.8million of them who have gone to Poland constitute a population roughly the size of Warsaws. If the fighting drags on and Ukraine implodes, the country will export many more destitute people, and, as happened in the former Yugoslavia during the nineteen-nineties, it may also draw in opportunists, including mercenaries and extremists.

Meanwhile, Russias economy, according to the International Monetary Fund, could shrink by thirty-five per cent this year under the weight of Western sanctions. Putins oligarchs and enablers can endure the loss of super-yachts and private jets, but a sudden economic contraction on that scale would crush ordinary Russians and inevitably cost lives. (Our economy will need deep structural changes, Putin acknowledged last week, adding, They wont be easy.) Russias isolation from large swaths of global banking and trade, and its loss of access to advanced U.S. technologies, could last a long time, too: democracies often find it easier to impose sanctions than to remove them, even when the original cause of a conflict subsides. (Ask Cuba.) When the history of this era is written, Putins war on Ukraine will have left Russia weaker and the rest of the world stronger, Biden said in his recent State of the Union address.

Still, some introspection may be in order. In his address, the President also declared that, in the battle between democracy and autocracies, democracies are rising to the moment. But Europe is troubled by illiberal populism, including in Poland. And Donald Trumpwho, just two days before Russia rolled into Ukraine, called Putins preparatory moves geniusretains a firm hold on the Republican Party, and appears to be all in for a relection campaign in 2024. As long as Trumps return to the White House is a possibility, Bidens declarations will require some asterisks.

Every night for three weeks now, Zelensky told Congress, various Ukrainian cities, Odessa and Kharkiv, Chernihiv and Sumy, Zhytomyr and Lviv, Mariupol and Dnipro, have endured attacks. We are asking for a reply, for an answer to this terror. Ukraine is an unlucky country, and the restoration of its independence and security may be a long and costly project, but it is one the U.S. cannot afford to abandon again.

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The Complexities of the Ukraine Dilemma - The New Yorker

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Putin appears at big rally as troops press attack in Ukraine – The Associated Press – en Espaol

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Russian President Vladimir Putin appeared at a huge flag-waving rally at a packed Moscow stadium Friday and lavished praise on his troops fighting in Ukraine, three weeks into the invasion that has led to heavier-than-expected Russian losses on the battlefield and increasingly authoritarian rule at home.

Meanwhile, the leader of Russias delegation in diplomatic talks with Ukraine said the sides have narrowed their differences. The Ukrainian side said its position remained unchanged.

The invasion has touched off a burst of antiwar protests inside Russia, and the Moscow rally was surrounded by suspicions it was a Kremlin-manufactured display of patriotism. Several Telegram channels critical of the Kremlin reported that students and employees of state institutions in a number of regions were ordered by their superiors to attend rallies and concerts marking the eighth anniversary of Moscows annexation of Crimea, which was seized from Ukraine. Those reports could not be independently verified.

Elsewhere, Russian troops continued to rain lethal fire on Ukrainian cities, including the capital, Kyiv, and pounded an aircraft repair installation on the outskirts of Lviv, close to the Polish border. Ukrainian officials said late Friday that the besieged southern port city of Mariupol lost its access to the Azov Sea, and Russian forces were still trying to storm the city. It was unclear whether they had seized it.

Ukrainian President Volodymyr Zelenskyy said Russian forces are blockading the largest cities to create a humanitarian catastrophe with the goal of persuading Ukrainians to cooperate. He said the Russians are preventing supplies from reaching surrounded cities in central and southeastern Ukraine.

This is a totally deliberate tactic, Zelenskyy said in his nighttime video address to the nation, which was recorded outside in Kyiv, with the presidential office behind him.

In a rare public appearance by Putin since the start of the war, he praised Russian troops: Shoulder to shoulder, they help and support each other, he said. We have not had unity like this for a long time, he added to cheers from the crowd.

Moscow police said more than 200,000 people were in and around the Luzhniki stadium. The event included patriotic songs, including a performance of Made in the U.S.S.R., with the opening lines Ukraine and Crimea, Belarus and Moldova, its all my country.

Seeking to portray the war as just, Putin paraphrased the Bible to say of Russias troops: There is no greater love than giving up ones soul for ones friends.

Taking to the stage where a sign read For a world without Nazism, he railed against his foes in Ukraine with a baseless claim that they are neo-Nazis. Putin continued to insist his actions were necessary to prevent genocide an idea flatly rejected by leaders around the globe.

Video feeds of the event cut out at times but showed a loudly cheering crowd that broke into chants of Russia!

Putins appearance marked a change from his relative isolation of recent weeks, when he has been shown meeting with world leaders and his staff either at extraordinarily long tables or via videoconference.

In the wake of the invasion, the Kremlin has clamped down harder on dissent and the flow of information, arresting thousands of antiwar protesters, banning sites such as Facebook and Twitter, and instituting tough prison sentences for what is deemed to be false reporting on the war, which Moscow refers to as a special military operation.

The OVD-Info rights group that monitors political arrests reported that at least seven independent journalists had been detained ahead of or while covering the anniversary events in Moscow and St. Petersburg.

High above the conflict, three Russian cosmonauts arrived Friday at the International Space Station wearing bright yellow flight suits with blue accents matching the colors of the Ukrainian flag. Video of one of the cosmonauts taken as the capsule prepared to dock with the space station showed him wearing a blue flight suit. It was unclear what, if any, message the yellow uniforms were intended to send.

When cosmonaut Oleg Artemyev was asked about the yellow suits, he said every crew chooses its own suits, and they had a lot of yellow material they needed to use so thats why we had to wear yellow.

Since the war started, many people have used the Ukrainian flag and its colors to show solidarity with the country.

Back in Moscow, Putin stood on stage in a white turtleneck and a blue down jacket and spoke for about five minutes. Some people, including presenters at the event, wore T-shirts or jackets with a Z a symbol seen on Russian tanks and other military vehicles in Ukraine and embraced by supporters of the war.

Putins quoting of the Bible and an 18th-century Russian admiral reflected his increasing focus in recent years on history and religion as binding forces in Russias post-Soviet society. His branding of his enemies as Nazis evoked what many Russians consider their countrys finest hour, the defense of the motherland from Germany during World War II.

The rally came as Vladimir Medinsky, who led Russian negotiators in several rounds of talks with Ukraine, said that the sides have moved closer to agreement on the issue of Ukraine dropping its bid to join NATO and adopting a neutral status.

That is the issue where the parties have made their positions maximally close, Medinsky said in remarks carried by Russian media. He added that the sides are now halfway on issues regarding the demilitarization of Ukraine.

Mikhailo Podolyak, an adviser to Zelenskyy, characterized the Russian assessment as intended to provoke tension in the media. He tweeted: Our positions are unchanged. Ceasefire, withdrawal of troops & strong security guarantees with concrete formulas.

Zelenskyy again appealed to Putin to hold talks with him directly. Its time to meet, time to speak, he said. I want to be heard by everyone, especially in Moscow.

In other developments, U.S. President Joe Biden and Chinese leader Xi Jinping spoke for nearly two hours in a bid by the U.S. to deter Beijing from providing military or economic assistance for Russias invasion.

Earlier Friday, one person was reported killed in the missile attack near Lviv. Satellite photos showed the strike destroyed a repair hangar and appeared to damage two other buildings. Ukraine said it had shot down two of six missiles in the volley, which came from the Black Sea.

The early morning attack was the closest strike yet to the center of Lviv, which has become a crossroads for people fleeing from other parts of Ukraine and for others entering to deliver aid or join the fight. The war has swelled the citys population by some 200,000.

Zelenskyy boasted that Ukraines defenses have proved much stronger than expected, and Russia didnt know what we had for defense or how we prepared to meet the blow.

But British Chief of Defense Intelligence Lt. Gen. Jim Hockenhull warned that after failing to take major Ukrainian cities, Russian forces are shifting to a strategy of attrition that will entail reckless and indiscriminate use of firepower, resulting in higher civilian casualties and a worsening humanitarian crisis.

In city after city around Ukraine, hospitals, schools and buildings where people sought safety have been attacked. Rescue workers continued to search for survivors in the ruins of a theater that was being used a shelter when it was blasted by a Russian airstrike Wednesday in Mariupol.

Ludmyla Denisova, the Ukrainian Parliaments human rights commissioner, said at least 130 people had survived the theater bombing.

But according to our data, there are still more than 1,300 people in these basements, in this bomb shelter, Denisova told Ukrainian television. We pray that they will all be alive, but so far there is no information about them.

Satellite images on Friday from Maxar Technologies showed a long line of cars leaving Mariupol as people tried to evacuate, as well as devastation to homes, apartment buildings and stores.

Early morning barrages also hit a residential building in the Podil neighborhood of Kyiv, killing at least one person, according to emergency services, who said 98 people were evacuated from the building. Kyiv Mayor Vitali Klitschko said 19 were wounded in the shelling.

Ukrainian officials said a fireman was killed when Russian forces shelled an area where firefighters were trying to put out a blaze in the village of Nataevka, in the Zaporizhzhia region.

Two others were killed when strikes hit residential and administrative buildings in the eastern city of Kramatorsk, according to the regional governor, Pavlo Kyrylenko.

Maj. Gen. Oleksandr Pavlyuk, who is leading the defense of the region around Ukraines capital, said his forces are well-positioned to defend the city and vowed: We will never give up. We will fight until the end. To the last breath and to the last bullet.

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Associated Press writer Yuras Karmanau in Lviv, Ukraine, and other AP journalists around the world contributed to this report.

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Follow the APs coverage of the war at https://apnews.com/hub/russia-ukraine

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Putin appears at big rally as troops press attack in Ukraine - The Associated Press - en Espaol

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