Phosphorylation Toggles the SARS-CoV-2 Nucleocapsid Protein Between Two Membrane-Associated Condensate States.

The SARS-CoV-2 Nucleocapsid protein (N) performs several functions during the viral lifecycle, including transcription regulation and viral genome encapsulation. We hypothesized that N toggles between these functions via phosphorylation-induced conformational change, thereby altering N interactions with membranes and RNA. We found that phosphorylation changes how biomolecular condensates composed of N and RNA interact with membranes: phosphorylated N (pN) condensates form thin films, while condensates with unmodified N are engulfed.

Mapping Biomaterial Complexity by Machine Learning.

Biomaterials often have subtle properties that ultimately drive their bespoke performance. Given this nuanced structure-function behavior, the standard scientific approach of one experiment at a time or design of experiment methods is largely inefficient for the discovery of complex biomaterials. More recently, high-throughput experimentation coupled with machine learning methods has matured beyond expert users allowing scientists and engineers from diverse backgrounds to access these powerful data science tools.

Ney Bienvenido Arias Lora (1926-2007): The Dominican Republic's First Neurosurgeon.

Background: Dr. Ney Bienvenido Arias Lora emerged not only as a pioneer in neurosurgery but a community leader in the Dominican Republic (DR), contributing significantly to a region where both fundamental and neurosurgical resources were scarce. This account aims to shed light on the remarkable life and career of Dr.

Cannabis Use in Adolescent and Young Adult Athletes: A Clinical Review.

Context: Cannabis use among the general population has increased over time, in part due to decriminalization of use and greater social acceptance of cannabis use. These changes have contributed to increased availability of cannabis products, thus raising the likelihood that a subset of adolescent and young adult athletes will use cannabis. Therefore, it is imperative that clinicians and other providers working with young athletes have a thorough understanding of the impact cannabis can have on the athletic performance and overall health of a young athlete.

Clarence Sumner Greene, Sr. (1901-1957): The First Board-Certified Black Neurosurgeon in the United States.

Background: This historical account reviews the life and lasting impact of Dr. Clarence Sumner Greene Sr. in neurosurgery.

Mechanomorphological Guidance of Colloidal Gel Regulates Cell Morphogenesis.

Microstructural morphology of the extracellular matrix guides the organization of cells in 3D. However, current biomaterials-based matrices cannot provide distinct spatial cues through their microstructural morphology due to design constraints. To address this, colloidal gels are developed as 3D matrices with distinct microstructure by aggregating ionic polyurethane colloids via electrostatic screening.

A User's Guide to Machine Learning for Polymeric Biomaterials.

The development of novel biomaterials is a challenging process, complicated by a design space with high dimensionality. Requirements for performance in the complex biological environment lead to difficult rational design choices and time-consuming empirical trial-and-error experimentation. Modern data science practices, especially artificial intelligence (AI)/machine learning (ML), offer the promise to help accelerate the identification and testing of next-generation biomaterials.

Antifungal activity against anthracnose-causing species of homopterocarpin derivatives.

Derivatives of 3,9-dimethoxypterocarpan (, homopterocarpin) were prepared by nitration, amination, and oxidation reactions, among others, and their antifungal activity was evaluated against the phytopathogenic fungi and . Derivatives were purified by chromatographic techniques and identified by nuclear magnetic resonance spectroscopy. Eight derivatives were obtained from corresponding to 3,9-dimethoxy-8-nitropterocarpan (), 3,9-dimethoxy-2,8-dinitropterocarpan (), 3,9-dimethoxy-2,8,10-trinitropterocarpan (), 2,8-diamino-3,9-dimethoxypterocarpan (), 3,9-dimethylcoumestan (), medicarpin (), 2'-hydroxy-4-(2-hydroxyethylsulfanyl)-7,4'-dimethoxyisoflavan (), and 4-(2-hydroxyethylsulfanyl)-7,2',4'-trimethoxyisoflavan ().

GECOP-MMC: phase IV randomized clinical trial to evaluate the efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) with mytomicin-C after complete surgical cytoreduction in patients with colon cancer peritoneal metastases.

Background: The French PRODIGE 7 trial, published on January 2021, has raised doubts about the specific survival benefit provided by HIPEC with oxaliplatin 460 mg/m (30 minutes) for the treatment of peritoneal metastases from colorectal cancer. However, several methodological flaws have been identified in PRODIGE 7, specially the HIPEC protocol or the choice of overall survival as the main endpoint, so its results have not been assumed as definitive, emphasizing the need for further research on HIPEC. It seems that the HIPEC protocol with high-dose mytomicin-C (35 mg/m) is the preferred regime to evaluate in future clinical studies.

Coupling Stable Isotope Labeling and Liquid Chromatography-Trapped Ion Mobility Spectrometry-Time-of-Flight-Tandem Mass Spectrometry for Mosquito Ovarian Lipid Studies.

There is a need to better understand lipid metabolism during mosquito ovarian development. Lipids are the major source of energy supporting ovarian follicles development in mosquitoes. In this paper, we describe the complementary use of stable isotope labeling (SIL) and high-resolution mass spectrometry-based tools for the investigation of triglycerides (TG) and diglycerides (DG) during the ovarian previtellogenic (PVG) stage (4-6 days posteclosion) of female adult .

Sexual dimorphism of diapause regulation in the hemipteran bug Pyrrhocoris apterus.

Diapause is one of the major strategies for insects to prepare for and survive harsh seasons. In females, the absence of juvenile hormone (JH) is a hallmark of adult reproductive diapause, a developmental arrest, which is much less characterized in males. Here we show that juvenile hormone III skipped bisepoxide (JHSB) titers in hemolymph remarkably differ between reproductive males and females of the linden bug Pyrrhocoris apterus, whereas no JH was detected in diapausing adults of both sexes.

Epoxidation of juvenile hormone was a key innovation improving insect reproductive fitness.

Methyl farnesoate (MF) plays hormonal regulatory roles in crustaceans. An epoxidated form of MF, known as juvenile hormone (JH), controls metamorphosis and stimulates reproduction in insects. To address the evolutionary significance of MF epoxidation, we generated mosquitoes completely lacking either of the two enzymes that catalyze the last steps of MF/JH biosynthesis and epoxidation, respectively: the JH acid methyltransferase (JHAMT) and the P450 epoxidase CYP15 (EPOX).

Comprehensive Screening of Polycyclic Aromatic Hydrocarbons and Similar Compounds Using GC-APLI-TIMS-TOFMS/GC-EI-MS.

In the present work, a novel workflow based on complementary gas-phase separations for the identification of isomeric PAHs from complex mixtures is described. This is the first report on the coupling of gas chromatography (GC), atmospheric pressure laser ionization (APLI), and trapped ion mobility spectrometry-mass spectrometry (TIMS-MS) for the characterization of polycyclic aromatic hydrocarbons. Over a hundred known unknowns are uniquely identified based on the molecular ion retention indices (5%), mobility (RSD < 0.

The naked mole-rat has a functional purinergic pain pathway despite having a non-functional peptidergic pain pathway.

Naked mole-rats () have adaptations within their pain pathway that are beneficial to survival in large colonies within poorly ventilated burrow systems, with lower O and higher CO ambient levels than ground-level environments. These adaptations ultimately lead to a partial disruption of the C-fiber pain pathway, which enables naked mole-rats to not feel pain from the acidosis associated with CO accumulation. One hallmark of this disruption is that naked mole-rats do not express neuropeptides, such as Substance P and calcitonin gene-related peptide in their cutaneous C-fibers, effectively making the peptidergic pain pathway hypofunctional.

Molecular Characterization of Tc964, A Novel Antigenic Protein from .

The Tc964 protein was initially identified by its presence in the interactome associated with the LYT1 mRNAs, which code for a virulence factor of . Tc964 is annotated in the genome as a hypothetical protein. According to phylogenetic analysis, the protein is conserved in the different genera of the Trypanosomatidae family; however, recognizable orthologues were not identified in other groups of organisms.

The juvenile hormone described in Rhodnius prolixus by Wigglesworth is juvenile hormone III skipped bisepoxide.

Juvenile hormones (JHs) are sesquiterpenoids synthesized by the corpora allata (CA). They play critical roles during insect development and reproduction. The first JH was described in 1934 as a "metamorphosis inhibitory hormone" in Rhodnius prolixus by Sir Vincent B.

Controlling anthracnose by means of extracts, and their major constituents, from Taub.

Anthracnose, caused by the fungus (Penz.) Penz. & Sacc.

Common structural features facilitate the simultaneous identification and quantification of the five most common juvenile hormones by liquid chromatography-tandem mass spectrometry.

This study reports the development and application of a liquid chromatography method coupled to electrospray tandem mass spectrometry (LC-MS/MS) for the identification and quantification of the five most common juvenile hormone (JH) homologs and methyl farnesoate (MF). The protocol allows the simultaneous analysis in a single LC run of JH I, JH II, JH III, JH III bisepoxide (JHB) and JH III skipped bisepoxide (JHSB). The identification of JHs is based on multiple reaction monitoring (MRM), using two of the most abundant fragmentation transitions for each hormone.

Three Dimensional Secondary Ion Mass Spectrometry Imaging (3D-SIMS) of ovarian follicles.

The mobilization of nutrient reserves into the ovaries of mosquitoes after sugar-feeding plays a vital role in the female's reproductive maturation. In the present work, three-dimensional secondary ion mass spectrometry imaging (3D-SIMS) was used to generate ultrahigh spatial resolution (~1 μm) chemical maps and study the composition and spatial distribution of lipids at the single ovarian follicle level (~100 μm in size). 3D-Mass Spectrometry Imaging (3D-MSI) allowed the identification of cellular types in the follicle (oocyte, nurse and follicular cells) using endogenous markers, and revealed that most of the triacyglycerides (TGs) were compartmentalized in the oocyte region.

Inhibition of juvenile hormone synthesis in mosquitoes by the methylation inhibitor 3-deazaneplanocin A (DZNep).

Juvenile hormone (JH), synthesized by the corpora allata (CA), controls development and reproduction in mosquitoes through its action on thousands of JH-responsive genes. These JH-dependent processes can be studied using tools that increase or decrease JH titers in vitro and in vivo. Juvenile hormone acid methyl transferase (JHAMT) is a critical JH biosynthetic enzyme.

Effective Liquid Chromatography-Trapped Ion Mobility Spectrometry-Mass Spectrometry Separation of Isomeric Lipid Species.

Lipids are a major class of molecules that play key roles in different biological processes. Understanding their biological roles and mechanisms remains analytically challenging due to their high isomeric content (e.g.

Juvenile hormone controls ovarian development in female Anopheles albimanus mosquitoes.

Anophelinae mosquitoes are vectors of human malaria, a disease that infects hundreds of millions of people and causes almost 600,000 fatalities annually. Despite their medical importance, laboratory studies on key aspects of Anophelinae reproductive biology have been limited, and in particular, relatively little is known about the role of juvenile hormone (JH) in the control of female reproduction. The study presented here attempts to fill a gap of knowledge in our understanding of the JH control of ovarian development in female Anophelinae mosquitoes, using Anopheles albimanus as a model.

Discovery and targeted monitoring of polychlorinated biphenyl metabolites in blood plasma using LC-TIMS-TOF MS.

In the present work, the potential for rapid, targeted analysis of hydroxylated metabolites of polychlorinated biphenyls (OH-PCBs) in diluted human blood plasma using liquid chromatography coupled with trapped ion mobility spectrometry and TOF high resolution mass spectrometry (LC-TIMS-TOF MS) was evaluated. Experimental OH-PCB collisional cross section (CCS) and gas-phase candidate structures (<3% error) are reported for the first time and used, in addition to the LC retention time and accurate /, as OH-PCB identification features in order to increase the detection selectivity. The proposed LC-TIMS-TOF MS workflow combines a "dilute-and-shoot" sample preparation strategy, a robust liquid chromatography step, a high-resolving power mobility separation (R ~ 150-250) and high-resolution mass spectrometry (R ~ 30-40k) for the separation, identification and quantification of common OH-PCB isomers with limits of detection comparable to traditional workflows (e.

Coupling trapped ion mobility spectrometry to mass spectrometry: trapped ion mobility spectrometry-time-of-flight mass spectrometry versus trapped ion mobility spectrometry-Fourier transform ion cyclotron resonance mass spectrometry.

Rationale: There is a need for fast, post-ionization separation during the analysis of complex mixtures. In this study, we evaluate the use of a high-resolution mobility analyzer with high-resolution and ultrahigh-resolution mass spectrometry for unsupervised molecular feature detection. Goals include the study of the reproducibility of trapped ion mobility spectrometry (TIMS) across platforms, applicability range, and potential challenges during routine analysis.

Analysis of isomeric opioids in urine using LC-TIMS-TOF MS.

In the present work, a fast separation, identification and quantification workflow based on liquid chromatography coupled to trapped ion mobility in tandem with mass spectrometry (LC-TIMS-MS) is described for the analysis of common isomeric drugs of abuse and their metabolites in human urine. In particular, the analytical performance of LC-TIMS-MS is shown for identification based on retention time, collision cross section and accurate mass for three sets of common isomeric opioids and their deuterated analogs in urine. The LC-TIMS-MS analysis provided limits of detection of 1.