Howard Hughes Medical Institute expands its open-access policy

Good news!

How long is Howard Hughes dead? Since 1976, but his legacy still keeps on giving!

Notice HHMI specifically mentions "substantially revised" manuscripts need to be released as preprint to. I also noticed that some researchers publish an early version as preprint, but then they do not update anymore and what gets later published in a journal is sometimes quite different from the earlier preprint version.

"The Howard Hughes Medical Institute (HHMI) last week expanded its requirements for the investigators it funds to make research articles immediately free to read, part of its efforts to shake up journals’ hold on scientific communication.

HHMI already requires investigators to make their papers available open access when published; over half of their recently published work appeared first as a preprint. 

The new policy goes even further, requiring investigators to publish their “major works”—defined as papers on which the investigator is a first, last, or corresponding author—as preprints when the manuscript is first completed and again after it is “substantially revised” in response to peer review or for other reasons. The policy is also triggered by such revisions after nontraditional forms of peer review, such as by reviewing services unaffiliated with a journal or public comments on a preprint server. ..."

ScienceAdviser

Investigator Charles Zuker and his team explore How We Taste Sweetness

Good news! That is funny! Zucker is the German word for sugar! Sometimes a name presents a calling (not to be confused with name calling). 😊

"... have unveiled the structure of the human sweet receptor, adding fundamental insights into taste detection and our understanding of the taste system, and paving the way for modern-day confectioners to reduce the amount of sugar in consumer products – all without sacrificing sweetness. ...

In 2001, Zuker’s laboratory discovered the genes that encode the sweet receptor. When we enjoy our favorite candies and desserts, these foods taste sweet solely because they activate this receptor.  ...

to cut back on the amount of sugar and calories in products, food and beverage makers could simply use less sugar and add a modulator to their product ..."

From the highlights and abstract:

"Highlights

• Two GPCR subunits assemble to recognize sweet ligands

• The TAS1R2 subunit binds the ligands and couples to the G protein

• A common binding pocket recognizes sucralose and aspartame

• 3D variability analysis shows coordinated structural changes between the subunits

Summary

In humans, the detection and ultimately the perception of sweetness begin in the oral cavity, where taste receptor cells (TRCs) dedicated to sweet-sensing interact with sugars, artificial sweeteners, and other sweet-tasting chemicals.

Human sweet TRCs express on their cell surface a sweet receptor that initiates the cascade of signaling events responsible for our strong attraction to sweet stimuli. Here, we describe the cryo-electron microscopy (cryo-EM) structure of the human sweet receptor bound to two of the most widely used artificial sweeteners—sucralose and aspartame.

Our results reveal the structural basis for sweet detection, provide insights into how a single receptor mediates all our responses to such a wide range of sweet-tasting compounds, and open up unique possibilities for designing a generation of taste modulators informed by the structure of the human receptor."

Scientists Unveil the Structure of the Receptor Responsible for How We Taste Sweetness | HHMI

The structure of human sweetness (open access)

Graphical abstract

Figure S2 Cryo-EM data processing workflow, related to STAR Methods

Charles Zuker

Howard Hughes Medical Institute Wins 2024 Nobel in Chemistry

The great philanthropy of Howard Hughes lives on!

Unfortunately, the HHMI has engaged in and supports DEI! What would their original donor Howard Hughes think about that? To use a German expression translated in English: Ungratefulness is the reward of the world! (Undank ist der Welten Lohn)

HHMI's David Baker Wins 2024 Nobel in Chemistry "Baker, of the University of Washington School of Medicine, was among three scientists honored by the Royal Swedish Academy of Sciences for his work on computational protein design. He shares the 2024 Nobel Prize in Chemistry with Demis Hassabis and John M. Jumper of Google DeepMind for protein structure prediction."

David Baker, investigator at HHMI

HHMI Awards 50 New Gilliam Fellowships to Advance Equity and Inclusion in Science. Really!

The famous Howard Hughes is probably wildly spinning in his grave! What a betrayal of his legacy!

HHMI Awards 50 New Gilliam Fellowships to Advance Equity and Inclusion in Science | HHMI

Howard Hughes Medical Institute: Investigator Carolyn Bertozzi Awarded the 2022 Nobel Prize in Chemistry

Congratulations!

The legacy of Howard Hughes lives on!

HHMI Investigator Carolyn Bertozzi Awarded the 2022 Nobel Prize in Chemistry | HHMI The Royal Swedish Academy of Sciences announced today that HHMI Investigator Carolyn Bertozzi of Stanford University, Morten Meldal of University of Copenhagen, and K. Barry Sharpless of Scripps Research Institute are the recipients of the 2022 Nobel Prize in Chemistry for the development of click chemistry and bioorthogonal chemistry.

Howard Hughes Medical Institute to Award More than $1 Billion to Promote Equity in Research Nonsense

Is this not a violation of the original donor's intent? Howard Hughes is probably spinning in his grave!

This obsession with race, diversity, and ethnic background in science is extremely annoying and disturbing!

"The Howard Hughes Medical Institute (HHMI) has announced a nearly $1.3 billion program for early-career scientists in an effort to increase diversity in the scientific workforce.

“For academic science to thrive in an increasingly diverse world, we need to attract and support scientists from a wide variety of racial and ethnic backgrounds,” says HHMI president Erin O’Shea ..."

HHMI to Award More than $1 Billion to Promote Equity in Research | The Scientist Magazine®

Howard Hughes Medical Institute: Mentoring, Diversity and Inclusion Are Top Priority for 50 New Gilliam Fellows

I am not sure what the late Howard Hughes thinks about this perversion! Is this another case of violation of original donor intent? Quite possible!

When leftist ideology invades and pervades outstanding scientific research!

"... They come from 38 schools across the country. Their research spans the life sciences, from plant biology to evolution. And they represent the largest group of fellows selected in the Gilliam Program’s history.

Today, the Howard Hughes Medical Institute (HHMI) announces 50 new Gilliam fellowships awarded to graduate students conducting outstanding research in their respective scientific fields and their advisers, who are committed to building a more inclusive scientific ecosystem. For up to three years, each adviser-student pair will receive an annual award totaling $50,000. ..."

Mentoring and Inclusion Are Top Priority for 50 New Gilliam Fellows and Their Advisers | HHMI The Howard Hughes Medical Institute has selected the 2021 class of Gilliam adviser-student pairs as part of a program to advance diversity and inclusion in science.

SARS-CoV-2 Needs Cholesterol to Invade Cells and Form Mega Cells

Amazing stuff! Good news!

"... To cause COVID-19, the SARS-CoV-2 virus must force its way into people’s cells – and it needs an accomplice. Cholesterol, the waxy compound better known for clogging arteries, helps the virus open cells up and slip inside ... Without cholesterol, the virus cannot sneak past a cell’s protective barrier and cause infection ...
“Cholesterol is an integral part of the membranes that surround cells and some viruses, including SARS-CoV-2. ...
These experiments and others suggested that if SARS-CoV-2’s membrane lacks cholesterol, the virus cannot enter its target cell. ...
This isn’t the first evidence implicating cholesterol. The previous study ... found that the body’s immune response to the virus produces a compound that depletes cholesterol – but in this case from the cell’s own membrane, not the virus’s. ...
The interesting thing is that cholesterol’s role in viral entry varies a lot between viruses.” It’s not clear exactly how cholesterol aids SARS-CoV-2, but understanding that process could offer clues about the biology of infection ...

“People already knew that the COVID-19 virus will create syncytia, but the researchers were able to visualize the process beautifully,” ... “Cell-cell fusion is itself a really under-studied area in biology.”

The experiments likely illustrate how mega cells found in patients’ lungs form ... “The formation of syncytia can be very injurious in the case of COVID, where it can destroy lung tissues and lead to death.” ... it’s not clear yet whether or not syncytia play a major role in the progression of COVID-19. ..."

"Many enveloped viruses induce multinucleated cells (syncytia), reflective of membrane fusion events caused by the same machinery that underlies viral entry. These syncytia are thought to facilitate replication and evasion of the host immune response. ...
Together with cell biological and biophysical approaches, the screen reveals an essential role for membrane cholesterol in spike-mediated fusion, which extends to replication-competent SARS-CoV-2 isolates. Our findings provide a molecular basis for positive outcomes reported in COVID-19 patients taking statins, and suggest new strategies for therapeutics targeting the membrane of SARS-CoV-2 and other fusogenic viruses. ..."

SARS-CoV-2 Needs Cholesterol to Invade Cells and Form Mega Cells | HHMI.org People taking cholesterol-lowering drugs may fare better than others if they catch the novel coronavirus. A new study hints at why: the virus relies on the fatty molecule to get past the cell’s protective membrane.

Here is the link to the underlying research paper:

SARS-CoV-2 Requires Cholesterol for Viral Entry and Pathological Syncytia Formation

Researchers engineered cells to carry either a protein (green) from SARS-CoV-2 or its human target ACE2 (magenta). When near each other, the cells’ membranes fused. Researchers think a similar process lets the virus slip into cells.

Discovery of Malaria Parasite’s Clock Could Pave Way to New Treatments

Good news and amazing stuff! Certain parasites have circadian rhythms too! This applies also to the parasite that causes sleeping sickness.

Just a reminder a Covid-19 pandemic reminder: Malaria kills over 400,000 people each year, among them many young children. Why have we still not eradicated this scourge of humanity?

Discovery of Malaria Parasite’s Clock Could Pave Way to New Treatments | HHMI.org The parasite that causes malaria has its own internal clock, explaining the disease’s rhythmic fevers and opening new pathways for therapeutics.

Malaria Parasites’ Biological Clocks Coordinate Cell Destruction

Two studies show that Plasmodium—the genus of protozoans that cause malaria—have an internal sense of time that synchronizes with their host’s circadian rhythms and allows the parasites to collectively attack blood cells.

A Gut-to-Brain Circuit Drives Sugar Preference and May Explain Sugar Cravings

Recommendable! So it is not a sweet tooth, but a sweet nerve via sensors in the gut? :-) Or why artificial sweeteners have not been very succesful!

"Here we examined the neural basis for sugar preference and demonstrate that a population of neurons in the vagal ganglia and brainstem are activated via the gut–brain axis to create preference for sugar. These neurons are stimulated in response to sugar but not artificial sweeteners, and are activated by direct delivery of sugar to the gut."

"By visualizing brain activity when the rodents consumed sugar versus artificial sweetener or water, the researchers for the first time identified the brain region that responds solely to sugar: the caudal nucleus of the solitary tract (cNST). Found in the brain stem, separate from where mice process taste, the cNST is a hub for information about the state of the body."

One of the research paper's authors happens to be Charles S. Zuker! The German word for sugar is Zucker. What a coincidence!

The gut–brain axis mediates sugar preference (published in Nature 4/15/2020)

A Gut-to-Brain Circuit Drives Sugar Preference and May Explain Sugar Cravings | HHMI.org: The sensation of sweetness starts on the tongue, but sugar molecules also trip sensors in the gut that directly signal the brain. This could explain why artificial sweeteners fail to satisfy the insatiable craving for sugar.

New Microscopy Technique Shows Cells’ 3-D Ultrastructure in New Detail

The revolution in new microscopy technologies continues! Amazing images! We have come a long way since Antonie van Leeuwenhoek and others!

"The technique, called cryo-SR/EM, melds images captured from electron microscopes and super-resolution light microscopes, resulting in brilliant, clear, detailed views of the inside of cells – in 3-D."

New Microscopy Technique Shows Cells’ 3-D Ultrastructure in New Detail | HHMI.org: The method melds the best of super-resolution fluorescence and electron microscopy to show how proteins relate to cells’ fine structure.

Surveying All the Proteins on a Neuron’s Surface

Another great work by the Howard Hughes Medical Institute!

"As if casting a tiny net, a new technique has rounded up all the proteins on the surface of neurons in the brains of fruit flies. The roundup uncovered 20 new molecules involved in wiring the developing brain. ... The find furthers scientists’ understanding of how neurons in the brain form complex networks, ... And it demonstrates for the first time that this protein-finding method actually works in intact brain tissues – not just cells grown in the lab ...
That’s important because the tissue environment is crucial for cells’ development, and lab cell cultures can’t replicate it."

Surveying All the Proteins on a Neuron’s Surface | HHMI.org: Scientists have found a new way to home in on the proteins covering a particular cell’s surface. The feat offers insight into how brain cells form intricate networks during development.

How to “Read” the Brain Signals Underlying Human Speech

Recommendable! This research has the potential to rewrite textbooks!


"“We’ve laid the groundwork for synthesizing speech from neural activity,” "

"There’s an idea that’s literally in textbooks that certain regions along the motor cortex strip relate to different parts of the body. High up on the head, you’ve got the leg, and lower down, you have voice.
Stavisky: The canonical textbook picture is of a human body draped over the brain.
Shenoy: It’s called the homunculus. It dates back over 70 years and has become indoctrinated – Sergey directly questioned it. He said maybe a brain area for the hand and arm is also related to speech."

"[the researchers] wondered if the hand knob brain area [of the motor cortex] might be active during more than just attempted hand and arm movements. Previous studies, for example, had hinted that the neural circuits for manual gestures might be interlinked with those for speech. ...

[researcher] recorded neural activity when participants repeated short words like “beet” and “seal.” The words sparked different brain activity patterns, his team found. ... could then “read” the patterns to decipher which words or syllables had been spoken.

“We’ve found that this part of the brain is active when moving your tongue, mouth, and face,” ... There’s some evidence in the literature that there’s a close relationship between our neural circuits for hand gestures and speech gestures – movement of the tongue, the lips, the jaw ... 

We know very little about speech because, until now, we’ve had very little access to it at single-neuron resolution. People have studied speech using other methods – like ECoG [electrocorticography], where electrodes are placed on the surface of the brain. But that averages together the activity of thousands of neurons. Our study is the first time activity from over a hundred electrodes – each recording from one or just a handful of individual cells from motor areas of the brain – has been studied in relation to producing speech. That’s the key distinction. ... The participants in this study have tetraplegia caused by spinal cord injury – they can’t use their arms or legs – but they can still talk."

How to “Read” the Brain Signals Underlying Human Speech | HHMI.org: Scientists have discovered that a brain region that controls hand and arm movement also offers a window into studying speech. The work brings researchers a step closer to building medical devices that help people who cannot speak.