Recommendable!
Tuesday, January 31, 2023
Malaysia's new Prime Minister Anwar tightens Singapore ties in ASEAN travel rush
Good news! Sounds promising!
"Malaysian Prime Minister Anwar Ibrahim on Monday met Singaporean counterpart Lee Hsien Loong in his first official visit to the city-state as leader, sealing a trio of deals and cementing relations with a key neighbor.
After taking office last November, following a tumultuous election, Anwar has kicked off 2023 with a string of trips to fellow members of the Associations of Southeast Asian Nations. In the span of a month he has also visited Indonesian President Joko "Jokowi" Widodo in Jakarta and gone to Brunei to see Sultan Hassanal Bolkiah. ..."
Mutations in Autism-Linked Gene TAOK1 Cause Membrane Mischief
Good news! Progress in this area of research is very slow and piecemeal!
"... TAOK1, a gene strongly linked to autism and other neurodevelopmental conditions, helps to mold the membrane, and mutations in the gene deform the neuronal surface, a new study shows. Those irregularities could contribute to core traits associated with TAOK1 mutations, such as intellectual disability.
The gene belongs to a family of three TAO kinases that add phosphate groups to signaling proteins. All three enzymes contribute to brain development, and mutations that disrupt their function have been linked to autism in earlier work. ..."
From the abstract:
"Mutations in TAOK1, which encodes a serine-threonine kinase, are associated with both autism spectrum disorder (ASD) and neurodevelopmental delay (NDD). Here, we investigated the molecular function of this evolutionarily conserved kinase and the mechanisms through which TAOK1 mutations may lead to neuropathology. We found that TAOK1 was abundant in neurons in the mammalian brain and remodeled the neuronal plasma membrane through direct association with phosphoinositides. Our characterization of four NDD-associated TAOK1 mutations revealed that these mutants were catalytically inactive and were aberrantly trapped in a membrane-bound state, which induced abnormal membrane protrusions. Expression of these TAOK1 mutants in cultured mouse hippocampal neurons led to abnormal growth of the dendritic arbor. The coiled-coil region carboxyl-terminal to the kinase domain was predicted to fold into a triple helix, and this region directly bound phospholipids and was required for both membrane association and induction of aberrant protrusions. Autophosphorylation of threonine-440 and threonine-443 in the triple-helical region by the kinase domain blocked the plasma membrane association of TAOK1. These findings define TAOK1 as a plasma membrane remodeling kinase and reveal the underlying mechanisms through which TAOK1 dysfunction may lead to neurodevelopmental disorders."
Neurodevelopmental disorder–associated mutations in TAOK1 reveal its function as a plasma membrane remodeling kinase (no public access)
Shape shifter: TAOK1 (blue) binds to and molds the plasma membrane in hippocampal neurons from rat embryos.
Israel and Jordan to speed up water for electricity deal
Good news! Blessed are the peacemakers! Cooperation beats antagonism anytime!
"... there was significant progress on two inter-related issues.
Firstly Jordan showed a willingness not to condition progress on economic and political issues with Israel on the Palestinian issue, as the countries that signed the Abraham Accords agreed and many years before that in the peace accord with Egypt.
The second topic that came up in the talks between the Israeli and Jordanian leaders was the promotion of the Green and Blue Prosperity Agreement signed between Israel, UAE and Jordan by the previous government. Sources familiar with the meeting told "Globes" that it was agreed that the two governments would speed up the implementation of both parts of the agreement. ...
it was agreed that Jordan would build huge solar fields to supply electricity to Israel. In exchange, Israel will build a large desalination plant on the Mediterranean to supply water to Jordan. The UAE will finance the projects through its energy and water companies.
Israel already sells water to Jordan at cost price as part of the agreements between the countries due to the severe water shortage in the Hashemite kingdom. According to the new agreement, Israel will sell Jordan 300 million cubic meters of desalinated water per year at a price of around NIS 500 million, while purchasing 600 megawatts of solar electricity from Jordan. ..."
Time-restricted eating reshapes gene expression throughout the body
There can never be enough studies on eating and food! A craving that never ends! Are you hungry already? đ
"... scientists show in mice how time-restricted eating influences gene expression across more than 22 regions of the body and brain. ...
The findings ... have implications for a wide range of health conditions where time-restricted eating has shown potential benefits, including diabetes, heart disease, hypertension, and cancer. ...
The findings ... have implications for a wide range of health conditions where time-restricted eating has shown potential benefits, including diabetes, heart disease, hypertension, and cancer. ...
After seven weeks, tissue samples were collected from 22 organ groups and the brain at different times of the day or night and analyzed for genetic changes. Samples included tissues from the liver, stomach, lungs, heart, adrenal gland, hypothalamus, different parts of the kidney and intestine, and different areas of the brain.
The authors found that 70 percent of mouse genes respond to time-restricted eating. ...
Nearly 40 percent of genes in the adrenal gland, hypothalamus, and pancreas were affected by time-restricted eating. These organs are important for hormonal regulation. ...
Nearly 40 percent of genes in the adrenal gland, hypothalamus, and pancreas were affected by time-restricted eating. These organs are important for hormonal regulation. ...
not all sections of the digestive tract were affected equally. While genes involved in the upper two portions of the small intestine—the duodenum and jejunum—were activated by time-restricted eating, the ileum, at the lower end of the small intestine, was not. ... The researchers also found that time-restricted eating aligned the circadian rhythms of multiple organs of the body. ..."
From the highlights and abstract:
"Highlights
• 80% of genes are differentially expressed or rhythmic under TRF in at least one tissue
• TRF decreases genes involved in inflammatory signaling and glycerolipid metabolism
• TRF increases genes involved in RNA processing, protein folding, and autophagy
• TRF causes multi-tissue rewiring of BCAA, glucose, and lipid metabolism
Summary
Time-restricted feeding (TRF) is an emerging behavioral nutrition intervention that involves a daily cycle of feeding and fasting. In both animals and humans, TRF has pleiotropic health benefits that arise from multiple organ systems, yet the molecular basis of TRF-mediated benefits is not well understood. Here, we subjected mice to isocaloric ad libitum feeding (ALF) or TRF of a western diet and examined gene expression changes in samples taken from 22 organs and brain regions collected every 2 h over a 24-h period. We discovered that TRF profoundly impacts gene expression. Nearly 80% of all genes show differential expression or rhythmicity under TRF in at least one tissue. Functional annotation of these changes revealed tissue- and pathway-specific impacts of TRF. These findings and resources provide a critical foundation for future mechanistic studies and will help to guide human time-restricted eating (TRE) interventions to treat various disease conditions with or without pharmacotherapies."
Diurnal transcriptome landscape of a multi-tissue response to time-restricted feeding in mammals (open access)
Graphical abstract
Traces of possible Silk Road uncovered in Israeli desert
Amazing stuff!
"Cotton and silk fabric imported from the Far East dating back to the early Islamic period some 1,300 years ago was recently found by a team of Israeli and German researchers in Israel’s Arava region, suggesting that the ancient Silk Road trading routes from the Far East passed through Israel en route to Europe. ..."
A site where ancient cotton and silk fabrics were uncovered in the Arava Desert.
A Brief History of California’s Eugenics Program (1909-2013)
Recommendable! (Caveat: I did not have time to read the whole story)
Grundsteuererklärung: Der Staat verspielt das Vertrauen der Bßrger
Versäumnisse in der Digitalisierung des Staates? Klingt typisch Bananenrepublik D!
Wie wäre es mit der Abschaffung der Grundsteuer im Hochsteuerland D? Wäre es nicht vielleicht einfacher die Kommunen erheben einen separaten Steuersatz auf die Einkommen der Bewohner?
Chart of the day
Looks like Western countries are hardly to blame, except for their massive exports of plastic waste to developing countries!
Alert: Plastophobia is a serious disease. Please seek immediate medical attention! (Caution: satire)
"... One river alone, the Pasig in the Philippines, is responsible for 6.4 percent of the waste that enters the world’s oceans through rivers ...
After all, Europe in particular is literally exporting its plastic problem. In 2019 alone, the EU exported 1.5 million metric tons of plastic waste to developing countries, which are clearly overburdened with the task of recycling and recovering such masses. ..."
Monday, January 30, 2023
Tucker Carlson: Eggs and poultry food supply is a matter of national survival
Recommendable! Wondered lately why eggs have become more expensive and not well stocked in grocery stores in the U.S.?
Generative AI funding exploded over the past 2 years from $200m to $1.4b
Very impressive! They say money talks! Put your money where one's mouth is!
Over 165 million Nigerians need treatment for Neglected Tropical Diseases - Study. Really!
This article was featured in today's Johns Hopkins Bloomberg School of Public Health: Global Health NOW newsletter!
It is a typical sensationalism, alarmism and hysteria type of article! Or was it written to attract funding from gullible donors?
I was not able to quickly find the study about Nigeria!
What is the total population of Nigeria? About 214 million. So either the so called Neglected Tropical Diseases (NTD) are generally fairly harmless or e.g. some serious overcounting most likely took place.
"... The study which was commissioned by the END Fund and conducted by Deloitte Nigeria, said the Nigerian economy stands to reap $18.9 billion from its citizens and increased productivity if elimination of NTDs is achieved by 2030. ..."
The Impact Of Neglected Tropical Diseases Neglected tropical diseases (NTDs) are a group of parasitic and bacterial infectious diseases that affect more than 1.7 billion people, including more than 1 billion children. Over 40% of the global NTD burden is concentrated in Africa, where the END Fund focuses the majority of our work.
Toroidal propellers: A effective noise reduction and gain in efficiency in air and water
Good news! It is not really new and still too expensive for now.
"... Sharrow Marine has been getting frankly spectacular results from boat propellers that use toroidal loops instead of standard blades. After several years of development, the company has now tested its props against hundreds of standard propellers, and the difference is incredible. Sharrow's props simply don't create tip vortices – a major source of energy loss and a surprisingly large component in the overall noise of an outboard engine. ...
The drawback here is price; they cost US$4,999 a pop regardless of which model, where a regular propeller might go for closer to US$500. ..."
The drawback here is price; they cost US$4,999 a pop regardless of which model, where a regular propeller might go for closer to US$500. ..."
The gain in efficiency is ridiculous in the water at midrange RPMs, filling in a pronounced hole in a boat's acceleration curve and conserving huge amounts of energy
Toroidal propellers: a radically quieter and more efficient design that can boost fuel economy by 20% when swapped onto a marine motor
Bundesfinanzhof zur VerfassungsmäĂigkeit des Solidaritätszuschlags
Typisch Bananenrepublik D!
Alleine die endlose Fortdauer dieses sog. Solidaritätszuschlags ist verfassungswidrig! Ein Steuerzuschlag ist per Definition eine kurzfristige Sondersteuer, um einen besonderen extra Einahmebedarf des Staates wegen einer temporären Ausnahme zu befriedigen. Als Daumenregel kann man vielleicht eine Maximaldauer von 5 Jahren ansetzen fßr einen Steuerzuschlag.
Was fßr ein Solidaritätszuschlag ist das eigentlich, wenn nur noch per Gesetz etwa 10% der Steuerzahler (sog. Spitzenverdiener) dafßr aufkommen mßssen. Extrem widersprßchlich Das alleine ist auch verfassungswidrig!
"... Allerdings wurden aus sozialen und konjunkturellen GrĂźnden rund 90 Prozent der Steuerpflichtigen ab dem Jahr 2021 von der Abgabenpflicht befreit. Nur Spitzenverdiener mĂźssen seitdem die Ergänzungsabgabe noch entrichten. In der BegrĂźndung des Gesetzes wird ausgefĂźhrt, es bestehe weiterhin eine besondere wiedervereinigungsbedingte Finanzlast des Bundes, etwa in der Rentenversicherung, im Arbeitsmarkt, im Bereich der Anspruchs- und AnwartschaftsĂźberfĂźhrung und im Hinblick auf besondere Leistungen fĂźr die ostdeutschen Bundesländer. In der Folge sank das Aufkommen aus dem Solidaritätszuschlag von rund 19 Milliarden € im Jahr 2020 auf rund 11 Milliarden im Jahr 2021. ..."
Mass-market military drones have changed the way wars are fought
Recommendable! Nice overview article!
"... Commercial technology makes the [Turkish] TB2 appealing for another reason: while the US-made Reaper drone costs $28 million, the TB2 only costs about $5 million. Since its development in 2014, the TB2 has shown up in conflicts in Azerbaijan, Libya, Ethiopia, and now Ukraine. The drone is so much more affordable than traditional weaponry that Lithuanians have run crowdfunding campaigns to help buy them for Ukrainian forces.
The TB2 is just one of several examples of commercial drone technology being used in combat. The same DJI Mavic quadcopters that help real estate agents survey property have been deployed in conflicts in Burkina Faso and the Donbas region of Ukraine. Other DJI drone models have been spotted in Syria since 2013, and kit-built drones, assembled from commercially available parts, have seen widespread use.
These cheap, good-enough drones that are free of export restrictions have given smaller nations the kind of air capabilities previously limited to great military powers. ..."
The Turkish military drone Bayraktar TB2
Very impressive! Turkey of all places?
Apparently, the Ukraine made best use of these military drones in their defense against the war of aggression by Putin the Terrible! Presumably, several dozens of these drones have been deployed by the Ukraine in this war.
"The Bayraktar TB2 is a medium-altitude long-endurance (MALE) unmanned combat aerial vehicle (UCAV) capable of remotely controlled or autonomous flight operations. It is manufactured by the Turkish company Baykar Makina Sanayi ve Ticaret A.Ĺ., primarily for the Turkish Armed Forces. The aircraft are monitored and controlled by an aircrew in a ground control station, including weapons employment. The development of the UAV has been largely credited to Selçuk Bayraktar, a former MIT graduate student.
By November 2021, the TB2 drone had completed 400,000 flight-hours globally. ..."
Some basic flight performance criteria & technical specifications: "
- 18,000 Feet Operational Altitude
- 27 Hours Maximum Airtime
- Fully Automatic Flight Control and 3 Redundant Autopilot System (Triple Redundant)
- Fully Automatic Landing and Take-off Feature Without Dependence on Ground Systems
- Navigation with Internal Sensor Fusion Without Dependency on GPS
- 25,000 Feet Max Altitude
- Communication Range <300 km
- Travel - Maximum Speed 70 knot - 120 knot
- Payload Capacity 150 kg
- Payload - ISR: Switchable EO/IR/LD or Multi-Purpose AESA Radar
- Payload - Munitions: 4 Laser Guided Smart Ammunition "
Sunday, January 29, 2023
Rare Earths: Can Sweden End Europe’s Dependence on China?
Very recommendable! Quite possibly, Sweden will also build small modular nuclear reactors to bring the share of electricity generation from nuclear power closer to 50%.
How Huntington’s disease affects two distinct cell populations in the striatum
Good news!
"In patients with Huntington’s disease, neurons in a part of the brain called the striatum are among the hardest-hit. Degeneration of these neurons contributes to patients’ loss of motor control, which is one of the major hallmarks of the disease.
Neuroscientists ... have now shown that two distinct cell populations in the striatum are affected differently by Huntington’s disease. They believe that neurodegeneration of one of these populations leads to motor impairments, while damage to the other population, located in structures called striosomes, may account for the mood disorders that are often seen in the early stages of the disease.
“As many as 10 years ahead of the motor diagnosis, Huntington’s patients can experience mood disorders, and one possibility is that the striosomes might be involved in these,” ...
Using single-cell RNA sequencing to analyze the genes expressed in mouse models of Huntington’s disease and postmortem brain samples from Huntington’s patients, the researchers found that cells of the striosomes and another structure, the matrix, begin to lose their distinguishing features as the disease progresses. ...
This kind of analysis could also shed light on other brain disorders that affect the striatum, such as Parkinson’s disease and autism spectrum disorder, the researchers say. ...
The researchers also found that these four major cell types begin to lose their identifying molecular identities and become more difficult to distinguish from one another in Huntington’s disease. “Overall, the distinction between striosomes and matrix becomes really blurry,” ...
Previous research has shown that overactivity of striosomes can lead to the development of repetitive behaviors such as those seen in autism, obsessive compulsive disorder, and Tourette’s syndrome. ..."
Using single-cell RNA sequencing to analyze the genes expressed in mouse models of Huntington’s disease and postmortem brain samples from Huntington’s patients, the researchers found that cells of the striosomes and another structure, the matrix, begin to lose their distinguishing features as the disease progresses. ...
This kind of analysis could also shed light on other brain disorders that affect the striatum, such as Parkinson’s disease and autism spectrum disorder, the researchers say. ...
The researchers also found that these four major cell types begin to lose their identifying molecular identities and become more difficult to distinguish from one another in Huntington’s disease. “Overall, the distinction between striosomes and matrix becomes really blurry,” ...
Previous research has shown that overactivity of striosomes can lead to the development of repetitive behaviors such as those seen in autism, obsessive compulsive disorder, and Tourette’s syndrome. ..."
From the abstract:
"Striatal projection neurons (SPNs), which progressively degenerate in human patients with Huntington’s disease (HD), are classified along two axes: the canonical direct-indirect pathway division and the striosome-matrix compartmentation. It is well established that the indirect-pathway SPNs are susceptible to neurodegeneration and transcriptomic disturbances, but less is known about how the striosome-matrix axis is compromised in HD in relation to the canonical axis. Here we show, using single-nucleus RNA-sequencing data from male Grade 1 HD patient post-mortem brain samples and male zQ175 and R6/2 mouse models, that the two axes are multiplexed and differentially compromised in HD. In human HD, striosomal indirect-pathway SPNs are the most depleted SPN population. In mouse HD models, the transcriptomic distinctiveness of striosome-matrix SPNs is diminished more than that of direct-indirect pathway SPNs. Furthermore, the loss of striosome-matrix distinction is more prominent within indirect-pathway SPNs. These results open the possibility that the canonical direct-indirect pathway and striosome-matrix compartments are differentially compromised in late and early stages of disease progression, respectively, differentially contributing to the symptoms, thus calling for distinct therapeutic strategies."
Transcriptional vulnerabilities of striatal neurons in human and rodent models of Huntington’s disease (open access)
Fig. 1: Identification and characterization of human and rodent SPN cell-type-specific markers
Synergistic treatment of cancer with multidrug bottlebrush shaped nanoparticles
Amazing stuff! Cancer is history (soon)!
"... chemists have designed a bottlebrush-shaped nanoparticle that can be loaded with multiple drugs, in ratios that can be easily controlled. Using these particles, the researchers were able to calculate and then deliver the optimal ratio of three cancer drugs used to treat multiple myeloma. ...
This nanoparticle platform could potentially be deployed to deliver drug combinations against a variety of cancers, the researchers say. ...
Using nanoparticles to deliver cancer drugs allows the drugs to accumulate at the tumor site and reduces toxic side effects because the particles protect the drugs from being released prematurely. However, only a handful of nanoparticle drug formulations have received FDA approval to treat cancer, and only one of these particles carries more than one drug. ..."
This nanoparticle platform could potentially be deployed to deliver drug combinations against a variety of cancers, the researchers say. ...
Using nanoparticles to deliver cancer drugs allows the drugs to accumulate at the tumor site and reduces toxic side effects because the particles protect the drugs from being released prematurely. However, only a handful of nanoparticle drug formulations have received FDA approval to treat cancer, and only one of these particles carries more than one drug. ..."
From the abstract:
"Cancer therapies often have narrow therapeutic indexes and involve potentially suboptimal combinations due to the dissimilar physical properties of drug molecules. Nanomedicine platforms could address these challenges, but it remains unclear whether synergistic free-drug ratios translate to nanocarriers and whether nanocarriers with multiple drugs outperform mixtures of single-drug nanocarriers at the same dose. Here we report a bottlebrush prodrug (BPD) platform designed to answer these questions in the context of multiple myeloma therapy. We show that proteasome inhibitor (bortezomib)-based BPD monotherapy slows tumour progression in vivo and that mixtures of bortezomib, pomalidomide and dexamethasone BPDs exhibit in vitro synergistic, additive or antagonistic patterns, respectively, distinct from their corresponding free-drug counterparts. BPDs carrying a statistical mixture of three drugs in a synergistic ratio outperform the free-drug combination at the same ratio as well as a mixture of single-drug BPDs in the same ratio. Our results address unanswered questions in the field of nanomedicine, offering design principles for combination nanomedicines and strategies for improving current front-line monotherapies and combination therapies for multiple myeloma."
Molecular bottlebrush prodrugs as mono- and triplex combination therapies for multiple myeloma (no public access)
MIT chemists designed a bottlebrush-shaped nanoparticle that can be loaded with multiple drugs, in ratios that can be easily controlled.
Engineered Bacteria Tackle Pathogenic Biofilms of another bacteria in Mice to effectively treat lung infections
Amazing stuff! Good news! Ventilator associated pneumonia is particularly nasty: "The mortality in ventilator-associated pneumonia is high despite the availability of effective antibiotics." (Source)
"Mycoplasma pneumoniae are tiny bacteria typically known to cause lung infections. ... Genetically engineered Mycoplasma helped break down biofilms of another pathogenic microbe, Pseudomonas aeruginosa, in a mouse model of ventilator-associated pneumonia and on tube samples taken from human patients ... It is one of the first times that scientists have used live bacteria to treat a lung disease, and is the first therapeutic use of Mycoplasma. ...
Because of their complicated structure, biofilms are often resistant to antimicrobial treatments even when the individual bacteria in the film are not ...
Because of their complicated structure, biofilms are often resistant to antimicrobial treatments even when the individual bacteria in the film are not ...
chose Mycoplasma pneumoniae, a bacteria known for infecting the human respiratory system, for their experiments. Unlike many bacteria, M. pneumoniae cannot recombine, making it a safe candidate for bioengineering that won’t spread its modified genome to other bacteria. It also has a relatively small genome and lacks a cell wall, making it less likely to generate an immune reaction.
The researchers removed the pathogenic genes from M. pneumoniae to ensure the bacteria were safe to use. They then assembled sets of engineered genomes in E. coli, which scientists ... use to engineer bacterial treatments for the gut. These genomes contained a one-two punch to tackle the biofilm: a genetic cassette that codes for the production of biofilm-breaking enzymes and the gene for a toxin that can kill P. aeruginosa. They then transferred the genes in the form of isolated DNA to M. pneumoniae. ..."
From the abstract:
"Engineered live bacteria could provide a new modality for treating lung infections, a major cause of mortality worldwide. In the present study, we engineered a genome-reduced human lung bacterium, Mycoplasma pneumoniae, to treat ventilator-associated pneumonia, a disease with high hospital mortality when associated with Pseudomonas aeruginosa biofilms. After validating the biosafety of an attenuated M. pneumoniae chassis in mice, we introduced four transgenes into the chromosome by transposition to implement bactericidal and biofilm degradation activities. We show that this engineered strain has high efficacy against an acute P. aeruginosa lung infection in a mouse model. In addition, we demonstrated that the engineered strain could dissolve biofilms formed in endotracheal tubes of patients with ventilator-associated pneumonia and be combined with antibiotics targeting the peptidoglycan layer to increase efficacy against Gram-positive and Gram-negative bacteria. We expect our M. pneumoniae-engineered strain to be able to treat biofilm-associated infections in the respiratory tract."
Fig. 5: In vivo treatment of mice with acute respiratory PAO1 infection.
Saturday, January 28, 2023
Fossilized pollen provides a glimpse at the end of the Permian extinction
Amazing stuff!
"Chemical clues in fossilized pollen grains suggest the world’s greatest mass extinction was a sunny affair ... As the Permian period gave way to the Triassic period about 250 million years ago, massive volcanic eruptions in present-day Siberia triggered a cataclysmic combination of greenhouse gas emissions, widespread mercury pollution, and a host of other atmospheric disturbances. Yet the full picture remains murky, including the possibility that damage to the ozone layer may have cooked many of the species already struggling to survive concurrent calamities ...
To investigate, Fraser and his colleagues turned their attention to tiny grains of fossilized pollen from southern Tibet. This collection contains around 800 pollen grains that come from the ancient relatives of ferns and conifers—plant types which survived the extinction event—and date back to time points spanning the Permian-Triassic boundary period. The tough outer coating of the pollen grains not only helped them stand the test of time in the fossil record, but also preserved traces of para-coumaric acid and ferulic acid. These phenolic compounds absorb ultraviolet B light, which helped shield the pollen from harmful solar radiation. Using Fourier transform infrared microspectroscopy, the researchers found that the abundance of UVB-absorbing compounds in their pollen-based chronology spiked around the same time as mercury and other signs of violent volcanic activity did. ..."
From the abstract:
"Land plants can adjust the concentration of protective ultraviolet B (UV-B)–absorbing compounds (UACs) in the outer wall of their reproductive propagules in response to ambient UV-B flux. To infer changes in UV-B radiation flux at Earth’s surface during the end-Permian mass extinction, we analyze UAC abundances in ca. 800 pollen grains from an independently dated Permian-Triassic boundary section in Tibet. Our data reveal an excursion in UACs that coincide with a spike in mercury concentration and a negative carbon-isotope excursion in the latest Permian deposits, suggesting a close temporal link between large-scale volcanic eruptions, global carbon and mercury cycle perturbations, and ozone layer disruption. Because enhanced UV-B radiation can exacerbate the environmental deterioration induced by massive magmatism, ozone depletion is considered a compelling ecological driver for the terrestrial mass extinction."
Dying in the Sun: Direct evidence for elevated UV-B radiation at the end-Permian mass extinction (open access)
Phenolic compounds preserved in the tough outer coating of Alisporites tenuicorpus pollen grains provide a glimpse of scorching solar radiation during Earth’s largest mass extinction.
Spectacular and very unusual supernova remnant discovered linked to a supernova observed in 1181 CE
Amazing stuff!
"... It is the most unusual remnant that researchers have ever found, and could point to a rare type of supernova that astronomers have long struggled to explain. ...
In 2013, amateur astronomer Dana Patchick discovered the object in archived images from NASA’s Wide-field Infrared Survey Explorer. Over the next decade, several teams studied the remnant, known as Pa 30, but the results became only more and more baffling. ...
found an extremely unusual star in 2019 at the dead center of Pa 302. That star had a surface temperature of roughly 200,000 kelvin, with a stellar wind travelling outward at 16,000 kilometres per second ...
In 2013, amateur astronomer Dana Patchick discovered the object in archived images from NASA’s Wide-field Infrared Survey Explorer. Over the next decade, several teams studied the remnant, known as Pa 30, but the results became only more and more baffling. ...
found an extremely unusual star in 2019 at the dead center of Pa 302. That star had a surface temperature of roughly 200,000 kelvin, with a stellar wind travelling outward at 16,000 kilometres per second ...
Pa 30 was again the subject of intrigue in 2021 ... proposed that the remnant is the aftermath of a supernova that lit up the sky nearly 850 years ago, in 1181. Chinese and Japanese astronomers observed the object for roughly six months before it faded.
During their examination of Pa 30, ... noted that the remnant’s emission spectrum contained a particular line associated with the element sulfur. ... later imaged the remnant with an optical filter that is sensitive to that line using the 2.4-metre Hiltner Telescope at the Michigan–Dartmouth–MIT Observatory at Kitt Peak, Arizona.
The data they collected not only helped to confirm that Pa 30 is indeed what’s left of the supernova observed in 1181, but also yielded an image of the remnant unlike any other. It contains hundreds of fine filaments radiating outwards. ..."
The data they collected not only helped to confirm that Pa 30 is indeed what’s left of the supernova observed in 1181, but also yielded an image of the remnant unlike any other. It contains hundreds of fine filaments radiating outwards. ..."
From the abstract:
"A newly recognized young Galactic SN remnant, Pa 30 (G123.1+4.6), centered on a hot central star with a ~16,000 km/s wind velocity has recently been proposed to be the result of a double-degenerate merger leading to a SN Iax event associated with the guest star of 1181 CE. Here we present deep optical [S II] 6716,6731 images of Pa 30 which reveal an extraordinary and highly structured nebula 170" in diameter with dozens of long (5" - 20") radially aligned filaments with a convergence point near the hot central star. Optical spectra of filaments indicate a peak expansion velocity ~1100 km/s with electron densities of 100 to 700 cm^-3, and a thick shell-like structure resembling its appearance in 22 micron WISE images. No H-alpha emission was seen (6716/H-alpha >8), with the only other line emission detected being faint [Ar III] 7136 suggesting a S, Ar-rich but H-poor remnant. The nebula's angular size, estimated 2.3 kpc distance, and 1100 km/s expansion velocity are consistent with an explosion date around 1181 CE. The remnant's unusual appearance may be due to the photoionization of wind-driven ejecta due to clump-wind interactions caused by the central star's high-luminosity wind."
An ALS patient set a record communicating through a brain implant: 62 words per minute
Good news! Even better would be to diagnose, stop and reverse neurodegenerative diseases as early as possible!
"Eight years ago, a patient lost her power of speech because of ALS, or Lou Gehrig’s disease, which causes progressive paralysis. She can still make sounds, but her words have become unintelligible, leaving her reliant on a writing board or iPad to communicate.
Now, after volunteering to receive a brain implant, the woman has been able to rapidly communicate phrases like “I don’t own my home” and “It’s just tough” at a rate approaching normal speech. ...
The brain-computer interfaces that Shenoy’s team works with involve a small pad of sharp electrodes embedded in a person’s motor cortex, the brain region most involved in movement. This allows researchers to record activity from a few dozen neurons at once and find patterns that reflect what motions someone is thinking of, even if the person is paralyzed. ..."
The brain-computer interfaces that Shenoy’s team works with involve a small pad of sharp electrodes embedded in a person’s motor cortex, the brain region most involved in movement. This allows researchers to record activity from a few dozen neurons at once and find patterns that reflect what motions someone is thinking of, even if the person is paralyzed. ..."
From the abstract:
"Speech brain-computer interfaces (BCIs) have the potential to restore rapid communication to people with paralysis by decoding neural activity evoked by attempted speaking movements into text or sound. Early demonstrations, while promising, have not yet achieved accuracies high enough for communication of unconstrainted sentences from a large vocabulary. Here, we demonstrate the first speech-to-text BCI that records spiking activity from intracortical microelectrode arrays. Enabled by these high-resolution recordings, our study participant, who can no longer speak intelligibly due amyotrophic lateral sclerosis (ALS), achieved a 9.1% word error rate on a 50 word vocabulary (2.7 times fewer errors than the prior state of the art speech BCI) and a 23.8% word error rate on a 125,000 word vocabulary (the first successful demonstration of large-vocabulary decoding). Our BCI decoded speech at 62 words per minute, which is 3.4 times faster than the prior record for any kind of BCI and begins to approach the speed of natural conversation (160 words per minute). Finally, we highlight two aspects of the neural code for speech that are encouraging for speech BCIs: spatially intermixed tuning to speech articulators that makes accurate decoding possible from only a small region of cortex, and a detailed articulatory representation of phonemes that persists years after paralysis. These results show a feasible path forward for using intracortical speech BCIs to restore rapid communication to people with paralysis who can no longer speak."
A high-performance speech neuroprosthesis (preprint, open access)
The benefits of dancing (even if you're not good at it)
When was the last time you danced? Dance all your troubles away! đ
Why Lego Isn’t (Just) a Toy Company
Wow! The company has evolved from when I was playing with Lego bricks some 50 years ago! I did not realize!
Friday, January 27, 2023
Pablo Escobar’s Dream: Is Belgium Becoming a Narco-State?
Recommendable! Antwerp is one of the most important ports in the EU for illegal narcotics imports from South America.
The emerging roles of γδ T cells in cancer immunotherapy
Good news! Cancer is history (soon)!
"We know that CD8+ T cells contribute to the effect of immunotherapy on cancer — but researchers have now discovered that γδ T cells are also at work. Researchers compared colon cancers that had been exposed to an immunotherapy called immune checkpoint inhibitors with tumours that did not receive this treatment. The γδ T cells helped the immunotherapy to work in a kind of tumour that lacks the conventional immune response involving CD8+ T cells. γδ T cells have emerged as a viable and promising approach for cancer immunotherapy in recent years."
From the abstract and key points:
"Current cancer immunotherapies are primarily predicated on ιβ T cells, with a stringent dependence on MHC-mediated presentation of tumour-enriched peptides or unique neoantigens that can limit their efficacy and applicability in various contexts. After two decades of preclinical research and preliminary clinical studies involving very small numbers of patients, γδ T cells are now being explored as a viable and promising approach for cancer immunotherapy. The unique features of γδ T cells, including their tissue tropisms, antitumour activity that is independent of neoantigen burden and conventional MHC-dependent antigen presentation, and combination of typical properties of T cells and natural killer cells, make them very appealing effectors in multiple cancer settings. ...
Key points
- Human γδ T cells comprise subsets with distinct tissue tropisms: Vδ1+ cells are enriched in mucosal tissues (and often predominate within carcinomas), whereas Vδ2+ cells are most abundant in the blood and lymphoid organs.
- Most human γδ T cells have antitumour functions, but have also been reported to have pro-tumour properties in specific contexts.
- γδ T cells have prognostic value in patients with cancer, being associated with favourable outcomes for most tumour types, especially when focusing on Vδ1+ cells.
- γδ T cells are endowed with antitumour mechanisms of both ιβ T cells and natural killer (NK) cells, mediated not only by T cell receptor (TCR) and co-stimulatory signals but also by activating NK cell receptors.
- γδ T cells mostly act in a manner independent of MHC class I-mediated antigen presentation, making them suitable for treatment of MHC class I-deficient tumours, as well as for application in allogeneic settings.
- Emerging therapeutic approaches based on γδ T cells comprise cell engagers, adoptive transfer of expanded Vδ1+ or Vδ2+ T cell subsets, and genetic engineering of γδ T cells to express chimeric antigen receptors (CARs) or ιβ T cells to express specific γδTCRs."
From the abstract:
"DNA mismatch repair-deficient (MMR-d) cancers present an abundance of neoantigens that is thought to explain their exceptional responsiveness to immune checkpoint blockade (ICB). Here, in contrast to other cancer types, we observed that 20 out of 21 (95%) MMR-d cancers with genomic inactivation of β2-microglobulin (encoded by B2M) retained responsiveness to ICB, suggesting the involvement of immune effector cells other than CD8+ T cells in this context. We next identified a strong association between B2M inactivation and increased infiltration by γδ T cells in MMR-d cancers. These γδ T cells mainly comprised the Vδ1 and Vδ3 subsets, and expressed high levels of PD-1, other activation markers, including cytotoxic molecules, and a broad repertoire of killer-cell immunoglobulin-like receptors. In vitro, PD-1+ γδ T cells that were isolated from MMR-d colon cancers exhibited enhanced reactivity to human leukocyte antigen (HLA)-class-I-negative MMR-d colon cancer cell lines and B2M-knockout patient-derived tumour organoids compared with antigen-presentation-proficient cells. By comparing paired tumour samples from patients with MMR-d colon cancer that were obtained before and after dual PD-1 and CTLA-4 blockade, we found that immune checkpoint blockade substantially increased the frequency of γδ T cells in B2M-deficient cancers. Taken together, these data indicate that γδ T cells contribute to the response to immune checkpoint blockade in patients with HLA-class-I-negative MMR-d colon cancers, and underline the potential of γδ T cells in cancer immunotherapy."
Extended Data Fig. 5: Phenotype and reactivity of γδ T cells towards cancer cell lines
Targeting immuno evasive gene TBK1 to overcome resistance to cancer immunotherapy
Good news! Cancer is history (soon)!
"Researchers have discovered a gene – TBK1 — that helps tumours to resist immunotherapy. Deleting this gene, or blocking the protein that it encodes, made tumours more vulnerable to immune attack in mouse and human-derived tumour models. ..."
From the abstract:
"Despite the success of PD-1 blockade in melanoma and other cancers, effective treatment strategies to overcome resistance to cancer immunotherapy are lacking. We identified the innate immune kinase TANK-binding kinase 1 (TBK1) as a candidate immune evasion gene in a pooled genetic screen. Using a suite of genetic and pharmacologic tools across multiple experimental model systems, we confirm a role for TBK1 as an immune evasion gene. Targeting TBK1 enhances response to PD-1 blockade by lowering the cytotoxicity threshold to effector cytokines (TNFÎą/IFNÎł). TBK1 inhibition in combination with PD-1 blockade also demonstrated efficacy using patient-derived tumour models, with concordant findings in matched patient-derived organotypic tumour spheroids (PDOTS) and matched patient-derived organoids (PDOs). Tumour cells lacking TBK1 are primed to undergo RIPK- and caspase-dependent cell death in response to TNFÎą/IFNÎł in a JAK/STAT-dependent manner. Taken together, our results demonstrate that targeting TBK1 is a novel and effective strategy to overcome resistance to cancer immunotherapy."
Targeting TBK1 to overcome resistance to cancer immunotherapy (no public access)
AuĂenministerin blamiert Deutschland und beschert Putin einen Propagandasieg
Typisch Bananenrepublik D.! ĂuĂerst peinlich! Extrem falsch! Unglaublich!
Der Westen hilft der Ukraine sich gegen einen brutalen Angriffskrieg durch Putin der Schreckliche zu verteidigen!
„We are fighting a war against Russia and not against each other“
Opioids Recruit the Immune System to Cause Withdrawal Symptoms
Good news! Will we finally be able to defeat or treat withdrawal symptoms?
"... Although the immune system has long been implicated in opioid withdrawal, the new findings, published January 19 in Cell, are the first to link the immune system’s interactions with the central nervous system and especially the blood-brain barrier to withdrawal ...
“The work represents a major advance in the emerging field of neural-immune interactions and the role of immune cells and mediators in modulating neural processes during opioid exposure,” ...
With the mechanism pieced together, the researchers also showed that they could break it down, at least in mice. In both IFN-Îł knockout mice and mice treated with an IFN-Îł-neutralizing antibody prior to opioid treatment, neural connects remained strong and unchanged throughout withdrawal even though the fragile-like Treg cells still infiltrated the brain. In these experiments, mice displayed reduced and shorter-lived withdrawal symptoms—in one case for just 12 hours instead of 60. ..."
“The work represents a major advance in the emerging field of neural-immune interactions and the role of immune cells and mediators in modulating neural processes during opioid exposure,” ...
With the mechanism pieced together, the researchers also showed that they could break it down, at least in mice. In both IFN-Îł knockout mice and mice treated with an IFN-Îł-neutralizing antibody prior to opioid treatment, neural connects remained strong and unchanged throughout withdrawal even though the fragile-like Treg cells still infiltrated the brain. In these experiments, mice displayed reduced and shorter-lived withdrawal symptoms—in one case for just 12 hours instead of 60. ..."
From the highlights and abstract:
"Highlights
• An expansion of fragile-like Tregs is identified in heroin-associated blood
• Opioid-induced global hypoxia triggers Treg fragility
• Fabp7 protects BBB integrity from opioid-induced hyperpermeability
• IFN-Îł regulates opioid-induced NAc synaptic remodeling and withdrawal signs
Summary
Dysregulation of the immune system is a cardinal feature of opioid addiction. Here, we characterize the landscape of peripheral immune cells from patients with opioid use disorder and from healthy controls. Opioid-associated blood exhibited an abnormal distribution of immune cells characterized by a significant expansion of fragile-like regulatory T cells (Tregs), which was positively correlated with the withdrawal score. Analogously, opioid-treated mice also showed enhanced Treg-derived interferon-Îł (IFN-Îł) expression. IFN-Îł signaling reshaped synaptic morphology in nucleus accumbens (NAc) neurons, modulating subsequent withdrawal symptoms. We demonstrate that opioids increase the expression of neuron-derived C-C motif chemokine ligand 2 (Ccl2) and disrupted blood-brain barrier (BBB) integrity through the downregulation of astrocyte-derived fatty-acid-binding protein 7 (Fabp7), which both triggered peripheral Treg infiltration into NAc. Our study demonstrates that opioids drive the expansion of fragile-like Tregs and favor peripheral Treg diapedesis across the BBB, which leads to IFN-Îł-mediated synaptic instability and subsequent withdrawal symptoms."
Opioid-induced fragile-like regulatory T cells contribute to withdrawal (no public access)
Graphical abstract
Why Germany's military is in a dire state, and what is being done to fix it
Typical banana republic! This neglect has been going on since the reunification of Germany in 1990!
Thursday, January 26, 2023
US shuts down ransomware group Hive; group extorted over $100 million from over 1,500 victims worldwide
Good news! What takes so long!
Earth’s inner core may be reversing its rotation
Amazing stuff!
Perhaps, geology has more to do with climate change than humans! đ The two popular science articles below omit to mention this entirely! You wonder why!
"Earth’s inner core may have temporarily stopped rotating relative to the mantle and surface, researchers report in the January 23 Nature Geoscience. Now, the direction of the inner core’s rotation may be reversing — part of what could be a roughly 70-year-long cycle that may influence the length of Earth’s days and its magnetic field — though some researchers are skeptical.
“We see strong evidence that the inner core has been rotating faster than the surface, [but] by around 2009 it nearly stopped,” says geophysicist Xiaodong Song of Peking University in Beijing. “Now it is gradually mov[ing] in the opposite direction.”"
From the abstract:
"Differential rotation of Earth’s inner core relative to the mantle is thought to occur under the effects of the geodynamo on core dynamics and gravitational core–mantle coupling. This rotation has been inferred from temporal changes between repeated seismic waves that should traverse the same path through the inner core. Here we analyse repeated seismic waves from the early 1990s and show that all of the paths that previously showed significant temporal changes have exhibited little change over the past decade. This globally consistent pattern suggests that inner-core rotation has recently paused. We compared this recent pattern to the Alaskan seismic records of South Sandwich Islands doublets going back to 1964 and it seems to be associated with a gradual turning-back of the inner core as a part of an approximately seven-decade oscillation, with another turning point in the early 1970s. This multidecadal periodicity coincides with changes in several other geophysical observations, especially the length of day and magnetic field. These observations provide evidence for dynamic interactions between the Earth’s layers, from the deepest interior to the surface, potentially due to gravitational coupling and the exchange of angular momentum from the core and mantle to the surface."
From the research article:
"... Interestingly, the same multidecadal periodicity is also well observed in the Earth’s climate system, especially the global mean temperature and sea level rise. An ultimate explanation for the multidecadal climate oscillations is still being sought that includes extraterrestrial origins. On the other hand, high correlations are also found recently, at zero lag, between global mean temperature and −ÎLOD46 and between global mean sea level and magnetic dipole changes. In addition, both vertical and horizontal displacements at the Earth surface can be excited by an oscillating inner core and torsional outer-core flows under gravitational coupling. Consequently, the multidecadal periodicity of the climate system might also originate from the oscillating core–mantle system, through the surface deformations and the exchange of angular momentum from the core and mantle to the surface. As such, our finding"
The Spin of Earth’s Inner Core May Be Changing, Scientists Say (article contains a link to the PDF file) A new study finds our planet’s iron center shifts between spinning slightly faster and slightly slower than the surface—but not all experts agree
Multidecadal variation of the Earth’s inner-core rotation (no public access, but article above contains a link to the PDF file)
What are peptides: the building blocks of life
Recommendable! Nice, brief overview article!
Russians Mourn Ukrainians Killed in War at two Statues of two different Ukrainian Poets in Moscow and Saint Petersburg
The Russian people versus Putin the Terrible! A toast to the human spirit!
I readily admit, I was not familiar with any of the two authors.
"Every few minutes, the mourners came, alone, in pairs or in families, to a statue of a Ukrainian writer standing in the center of the Russian capital, laying flowers and stuffed animals at her bronze feet.
Some said a prayer and left quickly. Others wept. Still others sat for hours on benches nearby, watching in silence as a small but regular flow of people visited what has become a makeshift memorial to victims of Russia’s invasion of Ukraine. ..."
"Lesya Ukrainka (Ukrainian: ĐĐľŃŃ ĐŁĐşŃĐ°Ńнка [ËlÉsĘ˛É ĘkrÉËjinkÉ]; born Larysa Petrivna Kosach, Ukrainian: ĐĐ°ŃиŃĐ° ĐĐľŃŃŃвна ĐĐžŃĐ°Ń; 25 February [O.S. 13 February] 1871 – 1 August [O.S. 19 July] 1913) was one of Ukrainian literature's foremost writers, best known for her poems and plays. She was also an active political, civil, and feminist activist. ..." (Wikipedia)
"Taras Hryhorovych Shevchenko (Ukrainian: ТаŃĐ°Ń ĐŃигОŃĐžĐ˛Đ¸Ń Đ¨ĐľĐ˛ŃонкО [tÉËrÉz ÉŚrÉŞËÉŚÉrowÉŞtĘ Ęeu̯ËtĘÉnko], pronounced [tÉËrÉs] without the middle name; 9 March [O.S. 25 February] 1814 – 10 March [O.S. 26 February] 1861), also known as Kobzar Taras, or simply Kobzar (a kobzar is a bard in Ukrainian culture), was a Ukrainian poet, writer, artist, public and political figure, folklorist and ethnographer. His literary heritage is regarded to be the foundation of modern Ukrainian literature and, to a large extent, the modern Ukrainian language, though this is different from the language of his poems. He also wrote some works in Russian (nine novellas, a diary, and an autobiography)." (Wikipedia)
The statue of the Ukrainian writer Lesya Ukrainka in Moscow has become a makeshift memorial to Ukrainian victims of Russia’s invasion.
A view shows the monument to Ukrainian poet Taras Shevchenko with flowers laid in memory of the victims of the Russian missile strike on an apartment block in the Ukrainian city of Dnipro, in Saint Petersburg, Russia January 20, 2023.
What time is it on the Moon the first colonizers may ask?
Have you ever wondered? Will the time on the dark side of the moon be different? When is it time for tea? đ
Do we need weather stations on the moon too? (just kidding, but who knows)
"The coming decade will see a resurgence in lunar exploration — including dozens of missions and plans to establish permanent bases on the Moon. The endeavours pose myriad challenges. Among them is a subtle, but fundamental, question that metrologists worldwide are working to answer: what time is it on the Moon? ..."
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