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Category: chemistry

Building a better, more precise droplet

A humble droplet can be an immensely useful tool for a number of fields, from medicine to manufacturing. Controlling the size of the droplet, though, is an important—and very tricky—task. With unprecedented precision, a team of researchers determined how droplets break up into smaller ones, at what size, and under what conditions. The results of this study are published in Soft Matter.

“Droplets can be used as microcontainers that encapsulate small amounts of fluid and other components,” said Prof. Corey O’Hern, who led the study. Because of that, he said, they can be used to deliver drugs to the body, or to find the genomic signatures of a single cell.

“Another cool application involves microreactors. You can put different concentrations of chemical species into the droplet, allow them to mix, and determine how they react.”

Fluorescent dye that works in superacidic conditions expands possibilities for imaging in extreme environments

Since the 1960s, boron–dipyrromethene dyes, commonly called BODIPY dyes, have been widely used for their strong fluorescence, especially in bioimaging, molecular and ion sensing, and as photosensitizers. Researchers especially like how, with simple modifications to BODIPY molecules, their emission color can be tuned—an indispensable quality for multicolor imaging applications.

However, conventional BODIPY dyes are unstable in acidic environments. Strong acids can disrupt their structure by removing the boron atom and causing the dye to lose its fluorescence. This has limited their use in highly acidic conditions.

In a new breakthrough, researchers from Hokkaido University have developed a superacid-resistant BODIPY dye. The research team, led by Professor Yasuhide Inokuma at the Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), reports the findings in Nature Communications.

Milkweed evolves ‘mind-blowing’ tactic to fight monarchs

Milkweed has found a new strategy in its epic evolutionary battle with monarch butterflies: upgrading its toxins to outmaneuver the monarch’s resistance. In a new study, published in the Proceedings of the National Academy of Sciences, researchers find that adding a small structural element containing nitrogen and sulfur to milkweed’s toxins circumvents monarchs’ ability to block them. The research sheds light on an underappreciated evolutionary tactic for plants: that not only can they increase their levels of toxicity, they can also structurally innovate to create new classes or subclasses of toxins.

“This structural innovation is a new axis for defining chemical toxins in the natural world,” said co-author Christophe Duplais, associate professor of entomology at Cornell AgriTech, in the College of Agriculture and Life Sciences (CALS). “This very simple modification makes a huge difference in terms of its ecological effect, because now this molecule is toxic to the monarch.”

Milkweed and monarchs have coevolved over millions of years, each building defenses and counter-defenses. One such defense is the monarchs’ ability to block milkweed’s toxins, called cardenolides, from binding to their target enzyme in the monarch’s cells. Monarchs have even evolved to sequester the toxins in their wings, to poison birds that peck at them.

Single-cell analysis identifies RETN+ monocyte-derived Resistin as a therapeutic target in hepatitis B virus-related acute-on-chronic liver failure

GUTImage from the paper by Xu et al entitled.

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HepatitisB HBV

Background Acute-on-chronic liver failure (ACLF) is characterised by intense systemic inflammation and high short-term mortality, yet effective targeted therapies are lacking.

Objective To explore monocyte heterogeneity in HBV-related ACLF (HBV-ACLF) to identify specific subsets and associated therapeutic targets.

Design Peripheral blood mononuclear cells from healthy controls (n=4), patients with acute decompensation (n=5), and patients with ACLF (n=9) underwent single-cell RNA sequencing (scRNA-seq). Findings were integrated with hepatic scRNA-seq, bulk transcriptomics, multiplex immunohistochemistry and in vitro functional assays. The in vivo roles of candidate targets were validated in two murine ACLF models.

Continue reading “Single-cell analysis identifies RETN+ monocyte-derived Resistin as a therapeutic target in hepatitis B virus-related acute-on-chronic liver failure” | >

Consequences of the Novel ALS-Associated KIF5A Variant c.2993-6C

Regulation and activation of UvrD-family DNA helicases/ translocases.

For the past few decades, the active form of superfamily 1A (SF1A) UvrDfamily helicases has been controversial due to the absence of structures of the active dimeric form of these enzymes.

A key interaction in the monomeric structures is between a regulatory domain (2B) and duplex DNA that was proposed to facilitate DNA unwinding but is likely inhibitory.

However, recent cryo-EM structures show that Mycobacterium tuberculosis UvrD1 forms a covalent dimer, with dimerization occurring between the 2B domains of each subunit, resulting in major reorientations of the 2B domains that prevent the 2B–DNA interaction, thus relieving its inhibitory effect.

The same dimerization interface is used in Escherichia coli UvrD dimers, suggesting that this is a general mechanism to activate most SF1A helicases.

Due to these insights, textbook descriptions of helicase mechanisms based on the monomeric structures require re-evaluation. sciencenewshighlights ScienceMission https://sciencemission.com/conundrum-resolved

Continue reading “Consequences of the Novel ALS-Associated KIF5A Variant c.2993-6C” | >

AI rebuilds molecules from exploding fragments

Researchers at the Department of Energy’s SLAC National Accelerator Laboratory and collaborating institutions recently built a generative AI model that can recreate molecular structures from the movement of the molecule’s ions after they are blasted apart by X-rays, a technique called Coulomb explosion imaging.

The research, published in Nature Communications, is an important step toward being able to take snapshots of molecules during chemical reactions—an advance that could have important impacts in medicine and industry. The machine learning model closely predicted the geometries of a range of different molecules made of less than ten atoms, paving the way for applying the technique to larger molecules.

“We were pretty excited about this,” said Xiang Li, an associate scientist at SLAC’s Linac Coherent Light Source (LCLS) and lead author of the study. “It is the first AI model built for molecular structure reconstruction from Coulomb explosion imaging.”

Most mass spectrometers can process just a few molecules at once: Reengineered prototype does a billion simultaneously

Mass spectrometry is already a powerful tool for determining what kind and how many molecules are present in a given sample. But most instruments still analyze their molecules one or just a few at a time, an approach that is inefficient and costly, and in which rare, but significant molecules can easily fall between the cracks.

A more powerful version of the technology could one day allow scientists to read the full molecular contents of a single cell, track thousands of chemical reactions at once, and ultimately accelerate efforts like drug development.

Now, a new study describes the first big step in that direction by producing a prototype, dubbed MultiQ-IT, that’s capable of handling vast numbers of molecules at once. The findings, published in the journal Science Advances, offer a blueprint for faster, more sensitive instruments that could position mass spectrometry for the kind of transformation that reshaped genomics and computing.

New DNA base editor minimizes bystander edits while maintaining high efficiency

The trajectory of base editing has been remarkable, progressing from the laboratory to patient care, treating debilitating or terminal illnesses, in less than a decade. A type of gene editing that makes chemical changes to our DNA, base editing was developed by Alexis Komor, associate professor in the Department of Biochemistry and Molecular Biophysics at the University of California San Diego.

For all of base editing’s success, it is still a relatively new technology, and researchers like Komor are working to improve its efficiency, while lowering the incidence of unwanted edits. One type of unwanted edit is called a bystander edit. This occurs when a base editor not only edits the desired nucleobase, but also edits surrounding bases as well. Komor’s lab has developed a way to minimize bystander edits. This work appears in Nature Biotechnology.

The Effect of Exogenous Acid Identity on Iron Tetraphenylporphyrin-Catalyzed CO2 ReductionClick to copy article linkArticle link copied!

‘The Effect of Exogenous Acid Identity on Iron Tetraphenylporphyrin-Catalyzed CO2 Reduction’ from Inorganic Chemistry is currently free to read as an ACSEditorsChoice.

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Iron tetraphenylporphyrin (FeTPP) is a privileged electrocatalyst for the 2e–/2H+ reduction of CO2 to CO. FeTPP-catalyzed CO2 reduction typically employs phenol as an exogenous acid to promote the rate-limiting proton-coupled electron transfer. Beyond the observation that catalytic rates increase with decreasing pKa, the effects of acid identity on reaction kinetics are largely unexplored. Herein, we report rates of FeTPP-catalyzed CO2 reduction with structurally diverse O–H, N–H, and C–H acids. While many of these acids follow the expected Brønsted relationship, there are several notable exceptions: the fluorinated alcohols hexafluoroisopropanol (log(kcat) = 4.54) and 2,2,2-trifluoroethanol (log(kcat) = 3.55)─and the N–H acid imidazole (log(kcat) = 4.41)─display catalytic rates that are several times greater than rates obtained with similarly acidic phenols. Amides with pKas 19 (in dimethyl sulfoxide) display similar activity as comparably acidic O–H acids, while rates obtained with less acidic amides are ∼2 orders of magnitude slower than O–H donors of similar pKa. Each C–H acid affords poor activity. An Eyring analysis suggests that acids enforcing less ordered transition states afford superior kinetics. This study reveals that acid pKa is only one relevant parameter for altering catalytic rates, and judicious selection of the acid is crucial for enhancing catalytic rates.

Study maps gene activity linked to neurotransmission in living brains

Researchers have identified a distinct and reproducible gene expression program associated with neurotransmission in the living human brain, offering unprecedented insight into the molecular mechanisms that support human cognition, emotion, and behavior. The findings were published February 19 in Molecular Psychiatry.

Neurotransmission-the electrical and chemical signaling between neurons-is fundamental to all brain function. Until now, most gene expression studies of the human brain have relied on postmortem tissue, limiting scientists’ ability to understand which genes are actively involved in real-time neuronal communication.

In this study, investigators integrated gene expression profiling from the prefrontal cortex with direct intracranial measures of neurotransmission collected from the brains of more than 100 individuals as they underwent neurosurgical procedures. By combining molecular data with real-time physiological recordings, the team identified a coordinated set of genes whose activity tracks with neuronal signaling-a transcriptional program associated with neurotransmission.

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