Lifeboat Foundation

A structural model of the SARS-CoV-2 spike protein as the virus fuses with host human cells reveals an opportunity to disrupt dynamics and halt transmission.

Scientists have simulated the transition of the SARS-CoV-2 spike protein structure from when it recognizes the host cell to when it gains entry, according to a study published on August 31 2021, in eLife.

The research shows that a structure enabled by sugar molecules on the spike protein could be essential for cell entry and that disrupting this structure could be a strategy to halt virus transmission.

Baricitinib is an oral selective Janus kinase 1/2 inhibitor with known anti-inflammatory properties. This study evaluates the efficacy and safety of baricitinib in combination with standard of care for the treatment of hospitalised adults with COVID-19.

In this phase 3 double-blind, randomised, placebo-controlled trial, participants were enrolled from 101 centres across 12 countries in Asia, Europe, North America, and South America. Hospitalised adults with COVID-19 receiving standard of care were randomly assigned (1:1) to receive once-daily baricitinib (4 mg) or matched placebo for up to 14 days. Standard of care included systemic corticosteroids, such as dexamethasone, and antivirals, including remdesivir. The composite primary endpoint was the proportion who progressed to high-flow oxygen, non-invasive ventilation, invasive mechanical ventilation, or death by day 28 assessed in the intention-to-treat population. All-cause mortality by day 28 was a key secondary endpoint, and all-cause mortality by day 60 was an exploratory endpoint; both were assessed in the intention-to-treat population. Safety analyses were done in the safety population defined as all randomly allocated participants who received at least one dose of study drug and who were not lost to follow-up before the first post-baseline visit. This study is registered with ClinicalTrials-gov, NCT04421027.

Although there was no significant reduction in the frequency of disease progression overall, treatment with baricitinib in addition to standard of care (including dexamethasone) had a similar safety profile to that of standard of care alone, and was associated with reduced mortality in hospitalised adults with COVID-19.

Continue reading “Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial” »

Over a year since the history-making operation, the recipient of the world’s first total penis and scrotum transplant – an injured veteran of the US Armed Forces – is “feeling whole” again and recovering well, doctors report in a case note on the pioneering procedure.

The man, who remains anonymous, was on patrol with his squad in Afghanistan when Taliban fighters ambushed them. As he went to give first aid to another soldier, he stepped on an improvised explosive device hidden on the road. In an instant, the blast took away much of the lower half of his body.

“I remember everything froze and I was upside down,” the man told MIT Technology Review. “I remember thinking a quick thought: ‘This isn’t good.’”

Nature’s pitfall trap: salamanders as rich prey for carnivorous plants in a nutrient-poor northern bog ecosystem.

Botanical carnivory is an evolutionary marvel of the plant kingdom that has long fascinated general onlookers and naturalists alike. Darwin even dedicated serious study to these “most wonderful plants in the world” (Darwin 1,875 Ellison and Gotelli 2009). Carnivory in plants has evolved multiple times across the world, often in wet, open, and nutrient-poor environments, as an alternative pathway of nutrient acquisition (Butler et al. 2005). Among carnivorous plants, the pitcher plants (family Sarraceniaceae), and specifically the northern pitcher plant (Sarracenia purpurea purpurea L.), intrigued early natural historians (e.g., Macbride 1,815 Riley 1,874 James 1883). Sarracenia purpurea is found across eastern North America, from the Gulf Coast of Florida north to Nova Scotia and west to the Rocky Mountains (Schnell 2002), making it the subject of early and contemporary observational and experimental studies. Naturally, much research has focused on the ability of these fascinating plants to capture prey and make use of prey nutrients. The specialized bell-shaped leaves of these pitcher plants collect rainwater in which prey dies, decomposes, and breaks down because of both inquiline microorganisms (aquatic larval insects, rotifers, mites, protozoa, and bacteria) that live within the pitcher and digestive enzymes produced by the plant. These digestive actions liberate nutrients for plant growth and reproduction (Adlassnig et al. 2011).

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Recent advances have put some interesting possibilities on the table when it comes to tackling hair loss, from topical solutions packed with stem cells, to 3D-printed hair farms, to growing hair with a patient’s own cells. Scientists in China are now throwing another one into the mix that uses a dissolvable microneedle patch to stimulate hair growth, with the technology proving high effective in mouse models of hereditary pattern baldness.

Led by scientists at China’s Zhejiang University, the researchers set out to develop new treatments for the most common of hair loss conditions: male-and female-pattern baldness, also known as androgenic alopecia. The scientists sought to tackle the issue by focusing on what they say are the primary mechanisms behind this, namely oxidative stress and poor circulation.

This relates to the combination of accumulating reactive oxygen species in the scalp that kill off the cells behind new hair growth, and a lack of blood vessels around the follicles to provide them with nutrients and essential molecules. In this way, the team hoped to come up with a two-pronged approach to androgenic alopecia, and their solution starts with previous research carried out on liver injuries and Alzheimer’s.

A tumor in the human body is like a city at war, bustling with cancer cells, immune cells, blood vessels, signaling molecules and surrounding tissue. A simple census of these players will provide some basic information on their battle, but won’t tell you their organization or strategy.

A team of researchers has gained new insight into this organization. They have discovered that immune cells in some human colorectal tumors gather together in clusters, like soldiers mobilizing in formation. By using a unique combination of single-cell profiling and imaging technologies, along with newly developed data analysis approaches, the scientists found a level of spatial organization of cells not observed before in tumors.

The findings, published in Cell, point to networks of interacting immune cells in certain types of colorectal tumors that tend to be more readily “seen” by the immune system. This suggests that cancers containing these hubs may be more likely to respond to cancer drugs called immunotherapies, which spur the immune system to kill cancer cells. The scientists, from the Broad Institute of MIT and Harvard, Massachusetts General Hospital, MIT, the Evergrande Center for Immunologic Diseases at Brigham and Women’s Hospital and Harvard Medical School, and Dana-Farber Cancer Institute, say the study could shed light on how to make other tumors more responsive to such treatments.

The study investigated whether electrical therapy, coupled with exercise, would show promise in treating tendon disease or ruptures. It showed that tendon cell function and repair can be controlled through electrical stimulation from an implantable device which is powered by body movement.

Researchers at CÚRAM, the SFI Research Centre for Medical Devices based at NUI Galway, have shown how the simple act of walking can power an implantable stimulator device to speed up treatment of musculoskeletal diseases.

The results of have been published in the prestigious journal Advanced Materials.

Continue reading “Researchers discover way to switch on and speed up tendon healing” »

We think of DNA as the vitally important molecules that carry genetic instructions for most living things, including ourselves. But not all DNA actually codes proteins; now, we’re finding more and more functions involving the non-coding DNA scientists used to think of as ‘junk’.

A new study suggests that satellite DNA – a type of non-coding DNA arranged in long, repetitive, apparently nonsensical strings of genetic material – may be the reason why different species can’t successfully breed with each other.

It appears that satellite DNA plays an essential role in keeping all of a cell’s individual chromosomes together in a single nucleus, through the work of cellular proteins.

Mitochondrial DNA diseases are common neurological conditions caused by mutations in the mitochondrial genome or nuclear genes responsible for its maintenance. Current treatments for these disorders are focused on the management of the symptoms, rather than the correction of biochemical defects caused by the mutation. Now, scientists at Kyoto University’s Institute for Integrated Cell-Material Science (iCeMS) in Japan report a new approach where mutant DNA sequences inside cellular mitochondria can be eliminated using a bespoke chemical compound. The approach may lead to better treatments for mitochondrial diseases.

Their findings are published in the journal Cell Chemical Biology in a paper titled, “Targeted elimination of mutated mitochondrial DNA by a multi-functional conjugate capable of sequence-specific adenine alkylation.”

“Mutations in mitochondrial DNA (mtDNA) cause mitochondrial diseases, characterized by abnormal mitochondrial function,” the researchers wrote. “Although eliminating mutated mtDNA has potential to cure mitochondrial diseases, no chemical-based drugs in clinical trials are capable of selective modulation of mtDNA mutations. Here, we construct a class of compounds encompassing pyrrole-imidazole polyamides (PIPs), mitochondria-penetrating peptide, and chlorambucil, an adenine-specific DNA-alkylating reagent.”