The Mla pathway promotes re-expansion from stationary phase.

Unlabelled: Bacteria have evolved diverse strategies to ensure survival under nutrient-limited conditions, where rapid energy generation is not achievable. Here, we performed a transposon insertion site sequencing loss-of-function screen to identify genes that promote pathogen fitness in stationary phase. We discovered that the aintenance of ipid symmetry (Mla) pathway, which is crucial for transferring phospholipids from the outer to the inner membrane, is critical for stationary phase fitness.

A Field-to-Parameter Pipeline for Analyzing and Simulating Root System Architecture of Woody Perennials: Application to Grapevine Rootstocks.

Understanding root system architecture (RSA) is essential for improving crop resilience to climate change, yet assessing root systems of woody perennials under field conditions remains a challenge. This study introduces a pipeline that combines field excavation, in situ 3-dimensional digitization, and transformation of RSA data into an interoperable format to analyze and model the growth and water uptake of grapevine rootstock genotypes. Eight root systems of each of 3 grapevine rootstock genotypes ("101-14", "SO4", and "Richter 110") were excavated and digitized 3 and 6 months after planting.

Temperature Dependence of Thermal Conductivity of Proteins: Contributions of Thermal Expansion and Grüneisen Parameter.

The thermal conductivity of many materials depends on temperature due to several factors, including variation of heat capacity with temperature, changes in vibrational dynamics with temperature, and change in volume with temperature. For proteins some, but not all, of these influences on the variation of thermal conductivity with temperature have been investigated in the past. In this study, we examine the influence of change in volume, and corresponding changes in vibrational dynamics, on the temperature dependence of the thermal conductivity.

Raphe and ventrolateral medulla proteomics in sudden unexplained death in childhood with febrile seizure history.

Sudden unexplained death in childhood (SUDC) is death of a child ≥ 12 months old that is unexplained after autopsy and detailed analyses. Among SUDC cases, ~ 30% have febrile seizure (FS) history, versus 2-5% in the general population. SUDC cases share features with sudden unexpected death in epilepsy (SUDEP) and sudden infant death syndrome (SIDS), in which brainstem autonomic dysfunction is implicated.

SMOC1 colocalizes with Alzheimer's disease neuropathology and delays Aβ aggregation.

SMOC1 has emerged as one of the most significant and consistent new biomarkers of early Alzheimer's disease (AD). Recent studies show that SMOC1 is one of the earliest changing proteins in AD, with levels in the cerebrospinal fluid increasing many years before symptom onset. Despite this clear association with disease, little is known about the role of SMOC1 in AD or its function in the brain.

SMOC1 colocalizes with Alzheimer's disease neuropathology and delays Aβ aggregation.

SMOC1 has emerged as one of the most significant and consistent new biomarkers of early Alzheimer's disease (AD). Recent studies show that SMOC1 is one of the earliest changing proteins in AD, with levels in the cerebrospinal fluid increasing many years before symptom onset. Despite this clear association with disease, little is known about the role of SMOC1 in AD or its function in the brain.

The Mla pathway promotes re-expansion from stationary phase.

Bacteria have evolved diverse strategies to ensure survival under nutrient-limited conditions, where rapid energy generation is not achievable. Here, we performed a transposon insertion site sequencing loss-of-function screen to identify genes that promote the pathogen's fitness in stationary phase. We discovered that the Mla (maintenance of lipid asymmetry) pathway, which is crucial for transferring phospholipids from the outer to the inner membrane, is critical for stationary phase fitness.

Synthesis and electrochemical properties of molybdenum nitrido complexes supported by redox-active NHC and MIC ligands.

We report the synthesis of a series of molybdenum nitrido complexes supported by bis-phenolate N-heterocyclic and mesoionic carbenes (NHC & MIC). The reaction between MoN(OBu) and the corresponding azolium salts [H3L1]Cl and [H3L2]Cl (with L1 = bis-phenolate triazolylidene and L2 = bis-phenolate benzimidazolylidene) gives clean access to the corresponding NHC/MIC complexes 1-Cl and 2-Cl. Electrochemical investigations of these complexes showed that they can be reversibly reduced at potentials of -1.

Mouse enteric neurons control intestinal plasmacytoid dendritic cell function via serotonin-HTR7 signaling.

Serotonergic neurons in the central nervous system control behavior and mood, but knowledge of the roles of serotonergic circuits in the regulation of immune homeostasis is limited. Here, we employ mouse genetics to investigate the functions of enteric serotonergic neurons in the control of immune responses and find that these circuits regulate IgA induction and boost host defense against oral, but not systemic Salmonella Typhimurium infection. Enteric serotonergic neurons promote gut-homing, retention and activation of intestinal plasmacytoid dendritic cells (pDC).

A Strategy for Modeling Nonstatistical Reactivity Effects: Combining Chemical Activation Estimates with a Vibrational Relaxation Model.

The kinetics of many chemical reactions can be readily explained with a statistical approach, for example, using a form of transition state theory and comparing calculated Gibbs energies along the reaction coordinate(s). However, there are cases where this approach fails, notably when the vibrational relaxation of the molecule to its statistical equilibrium occurs on the same time scale as the reaction dynamics, whether it is caused by slow relaxation, a fast reaction, or both. These nonstatistical phenomena are then often explored computationally using (quasi)classical ab initio molecular dynamics by calculating a large number of trajectories while being prone to issues such as zero-point energy leakage.

Transferrin Receptor-Mediated Cellular Uptake of Fluorinated Chlorido[,'-bis(salicylidene)-1,2-phenylenediamine]iron(III) Complexes.

Fluorinated chlorido[salophene]iron(III) complexes (salophene = ,'-bis(salicylidene)-1,2-phenylenediamine) are promising anticancer agents. Apoptosis and necrosis induction have already been described as part of their mode of action. However, the involvement of ferroptosis in cell death induction, as confirmed for other chlorido[salophene]iron(III) complexes, has not yet been investigated.

Factors Affecting Resilience and Prevention of Alzheimer's Disease and Related Dementias.

Alzheimer's disease (AD) is a devastating, age-associated neurodegenerative disorder and the most common cause of dementia. The clinical continuum of AD spans from preclinical disease to subjective cognitive decline, mild cognitive impairment, and dementia stages (mild, moderate, and severe). Neuropathologically, AD is defined by the accumulation of amyloid β (Aβ) into extracellular plaques in the brain parenchyma and in the cerebral vasculature, and by abnormally phosphorylated tau that accumulates intraneuronally forming neurofibrillary tangles (NFTs).

Design, synthesis, and biological evaluation of novel halogenated chlorido[N,N'-bis(salicylidene)-1,2-bis(3-methoxyphenyl)ethylenediamine]iron(III) complexes as anticancer agents.

Iron(III) complexes based on N,N´-bis(salicylidene)ethylenediamine (salene) scaffolds have demonstrated promising anticancer features like induction of ferroptosis, an iron dependent cell death. Since poor cellular uptake limits their therapeutical potential, this study aimed to enhance the lipophilic character of chlorido[N,N'-bis(salicylidene)-1,2-bis(3-methoxyphenyl)ethylenediamine]iron(III) complexes by introducing lipophilicity improving ligands such as fluorine (X1), chlorine (X2) and bromine (X3) in 5-position in the salicylidene moieties. After detailed characterization the binding to nucleophiles, logP values and cellular uptake were determined.

Vibrational Energy Landscapes and Energy Flow in GPCRs.

We construct and analyze disconnectivity graphs to provide the first graphical representation of the vibrational energy landscape of a protein, in this study βAR, a G-protein coupled receptor (GPCR), in active and inactive states. The graphs, which indicate the relative free energy of each residue and the minimum free energy barriers for energy transfer between them, reveal important composition, structural and dynamic properties that mediate the flow of energy. Prolines and glycines, which contribute to GPCR plasticity and function, are identified as bottlenecks to energy transport along the backbone from which alternative pathways for energy transport via nearby noncovalent contacts emerge, seen also in the analysis of first passage time (FPT) distributions presented here.

Differences in the cerebral amyloid angiopathy proteome in Alzheimer's disease and mild cognitive impairment.

Cerebral amyloid angiopathy (CAA) is characterized by amyloid beta (Aβ) deposition in cerebrovasculature. It is prevalent with aging and Alzheimer's disease (AD), associated with intracerebral hemorrhage, and contributes to cognitive deficits. To better understand molecular mechanisms, CAA(+) and CAA(-) vessels were microdissected from paraffin-embedded autopsy temporal cortex of age-matched Control (n = 10), mild cognitive impairment (MCI; n = 4), and sporadic AD (n = 6) cases, followed by label-free quantitative mass spectrometry.

The influence of APOE on the pTau interactome in sporadic Alzheimer's disease.

APOE is the major genetic risk factor for sporadic Alzheimer's disease (AD). Although APOE is known to promote Aβ pathology, recent data also support an effect of APOE polymorphism on phosphorylated Tau (pTau) pathology. To elucidate these potential effects, the pTau interactome was analyzed across APOE genotypes in the frontal cortex of 10 advanced AD cases (n = 5 APOE and n = 5 APOE), using a combination of anti-pTau pS396/pS404 (PHF1) immunoprecipitation (IP) and mass spectrometry (MS).

Prioritizing sexual and reproductive health research and care for people with cystic fibrosis: A 2023 workshop report from the Cystic Fibrosis Foundation Sexual Health, Reproduction, and Gender (SHARING) Research Working Group.

Background: To address sexual and reproductive health (SRH) concerns among people with cystic fibrosis(PwCF), the CF Foundation created the Sexual Health, Reproduction, and Gender Research (SHARING) Working Group. This report summarizes CF community SRH research priorities and workshop discussions/future study planning.

Methods: Pre-workshop, we distributed a community prioritization survey on CF SRH research/care.

Peripheral serotonergic neurons regulate gut motility and anxiety-like behavior.

Serotonergic circuits in the central nervous system play important roles in regulating mood and behavior, yet the functions of peripheral serotonergic neurons are less understood. Here, we engineered mice lacking the serotonin-producing enzyme Tph2 in peripheral neurons but with intact Tph2 in central neurons. In contrast to mice lacking Tph2 in all neurons, mice lacking Tph2 in peripheral serotonergic neurons did not exhibit increased territorial aggression.

Effect of United States Medical Licensing Examination Score Cutoffs on Recruitment of Underrepresented Applicants in the Urology Match.

Objective: To determine how the use of United States Medical Licensing Examination (USMLE) score cutoffs during the screening process of the Urology Residency Match Program may affect recruitment of applicants who are underrepresented in medicine (URM).

Materials And Methods: Deidentified data from the Association of American Medical Colleges' (AAMC) Electronic Residency Application Service (ERAS) system was reviewed, representing all applicants to our institution's urology residency program from 2018 to 2022. We analyzed self-reported demographic variables including race/ethnicity, age, sex/gender, as well as USMLE Step 1 and Step 2 scores.

Similar brain proteomic signatures in Alzheimer's disease and epilepsy.

The prevalence of epilepsy is increased among Alzheimer's Disease (AD) patients and cognitive impairment is common among people with epilepsy. Epilepsy and AD are linked but the shared pathophysiological changes remain poorly defined. We aim to identify protein differences associated with epilepsy and AD using published proteomics datasets.

Design, Synthesis, Electrochemical, and Biological Evaluation of Fluorescent Chlorido[,'-bis(methoxy/hydroxy)salicylidene-1,2-bis(4-methoxyphenyl)ethylenediamine]iron(III) Complexes as Anticancer Agents.

The impact of methoxy and hydroxyl groups at the salicylidene moiety of chlorido[,'-bis(methoxy/hydroxy)salicylidene-1,2-bis(4-methoxyphenyl)ethylenediamine]iron(III) complexes was evaluated on human MDA-MB 231 breast cancer and HL-60 leukemia cells. Methoxylated complexes (-) inhibited proliferation, migration, and metabolic activity in a concentration-dependent manner following the rank order: > > . In particular, was highly cytotoxic with an IC of 4.