Biochemical characterization of the self-sacrificing p-aminobenzoate synthase from Nitrosomonas europaea reveals key residues involved in selecting a Fe/Fe or Mn/Fe cofactor.

A noncanonical route for p-aminobenzoate (pABA) biosynthesis in select bacteria utilizes a novel self-sacrificing heme oxygenase-like domain-containing oxidase/oxygenase (HDO) superfamily member. The recently characterized self-sacrificing pABA synthase from Chlamydia trachomatis ("CADD") requires manganese and likely employs a heterobimetallic Mn/Fe cofactor. A conserved active site tyrosine residue is cleaved from the protein backbone to serve as the substrate for pABA synthesis and a lysine residue is the amino group donor.

Indirectly acquired fear memories have distinct, sex-specific molecular signatures from directly acquired fear memories.

Post-traumatic stress disorder (PTSD) is a severe anxiety disorder that affects women more than men. About 30% of patients suffering from PTSD develop the disorder by witnessing a traumatic event happen to someone else. However, as the focus has remained on those directly experiencing the traumatic event, whether indirectly acquired fear memories that underlie PTSD have the same molecular signature as those that are directly acquired remains unknown.

Decreases in K63 Polyubiquitination in the Hippocampus Promote the Formation of Contextual Fear Memories in Both Males and Females.

Over 90% of protein degradation in eukaryotic cells occurs through the ubiquitin-proteasome system (UPS). In this system, the ubiquitin protein can bind to a substrate on its own or it can form a chain with multiple ubiquitin molecules in a process called polyubiquitination. There are 8 different sites on ubiquitin at which polyubiquitin chains can be formed, the second most abundant of which, lysine-63 (K63), is independent of the degradation process, though this mark has rarely been studied in the brain or during learning-dependent synaptic plasticity.

Latent infection of an active giant endogenous virus in a unicellular green alga.

Latency is a common strategy in a wide range of viral lineages, but its prevalence in giant viruses remains unknown. Here we describe the activity and viral production from a 617 kbp integrated giant viral element in the model green alga . We resolve the integrated viral region using long-read sequencing and show that viral particles are produced and released in otherwise healthy cultures.

Dysregulation of baseline and learning-dependent protein degradation in the aged hippocampus.

The ubiquitin-proteasome system (UPS) controls the majority of protein degradation in cells and dysregulation of the UPS has been implicated in the pathophysiology of numerous neurodegenerative disorders, including Alzheimer's disease. Further, strong evidence supports a critical role for the UPS in synaptic plasticity and memory formation. However, while proteasome function is known to decrease broadly in the brain across the lifespan, whether it changes in the hippocampus, a region critical for memory storage and among the first impacted in Alzheimer's disease, at rest and following learning in the aged brain remains unknown.

Androgen and glucocorticoid profiles throughout extended uniparental paternal care in the eastern hellbender salamander (Cryptobranchus a. alleganiensis).

The behavioral endocrinology associated with reproduction and uniparental male care has been studied in teleosts, but little is known about hormonal correlates of uniparental male care in other ectotherms. To address this gap, we are the first to document the seasonal steroid endocrinology of uniparental male hellbender salamanders during the transition from pre-breeding to nest initiation, and through the subsequent eight months of paternal care. In doing so, we investigated the correlates of nest fate and clutch size, exploring hellbenders' alignment with several endocrinological patterns observed in uniparental male fish.

Sex-differences in proteasome-dependent K48-polyubiquitin signaling in the amygdala are developmentally regulated in rats.

Background: Sex differences have been observed in several brain regions for the molecular mechanisms involved in baseline (resting) and memory-related processes. The ubiquitin proteasome system (UPS) is a major protein degradation pathway in cells. Sex differences have been observed in lysine-48 (K48)-polyubiquitination, the canonical degradation mark of the UPS, both at baseline and during fear memory formation within the amygdala.

Dangling Bonds as Possible Contributors to Charge Noise in Silicon and Silicon-Germanium Quantum Dot Qubits.

Spin qubits based on Si and SiGe quantum dot architectures exhibit among the best coherence times of competing quantum computing technologies, yet they still suffer from charge noise that limit their qubit gate fidelities. Identifying the origins of these charge fluctuations is therefore a critical step toward improving Si quantum-dot-based qubits. Here, we use hybrid functional calculations to investigate possible atomistic sources of charge noise, focusing on charge trapping at Si and Ge dangling bonds (DBs).

Proteasome-independent K63 polyubiquitination selectively regulates ATP levels and proteasome activity during fear memory formation in the female amygdala.

Females are more likely than males to develop post-traumatic stress disorder (PTSD). However, the neurobiological mechanisms responsible for these sex differences remain elusive. The ubiquitin proteasome system (UPS) is involved in fear memory formation and implicated in PTSD development.

Selective sorption of oxygen and nitrous oxide by an electron donor-incorporated flexible coordination network.

Incorporating strong electron donor functionality into flexible coordination networks is intriguing for sorption applications due to a built-in mechanism for electron-withdrawing guests. Here we report a 2D flexible porous coordination network, [Ni(4,4'-bipyridine)(VTTF)]n(1) (where HVTTF = 2,2'-[1,2-bis(4-benzoic acid)-1,2ethanediylidene]bis-1,3-benzodithiole), which exhibits large structural deformation from the as-synthesized or open phase (1α) into the closed phase (1β) after guest removal, as demonstrated by X-ray and electron diffraction. Interestingly, upon exposure to electron-withdrawing species, 1β reversibly undergoes guest accommodation transitions; 1α⊃O (90 K) and 1α⊃NO (185 K).

The Chlamydia trachomatis p-aminobenzoate synthase CADD is a manganese-dependent oxygenase that uses its own amino acid residues as substrates.

CADD (chlamydia protein associating with death domains) is a p-aminobenzoate (pAB) synthase involved in a noncanonical route for tetrahydrofolate biosynthesis in Chlamydia trachomatis. Although previously implicated to employ a diiron cofactor, here, we show that pAB synthesis by CADD requires manganese and the physiological cofactor is most likely a heterodinuclear Mn/Fe cluster. Isotope-labeling experiments revealed that the two oxygen atoms in the carboxylic acid portion of pAB are derived from molecular oxygen.

Hydrogen Storage in Partially Exfoliated Magnesium Diboride Multilayers.

Metal boride nanostructures have shown significant promise for hydrogen storage applications. However, the synthesis of nanoscale metal boride particles is challenging because of their high surface energy, strong inter- and intraplanar bonding, and difficult-to-control surface termination. Here, it is demonstrated that mechanochemical exfoliation of magnesium diboride in zirconia produces 3-4 nm ultrathin MgB nanosheets (multilayers) in high yield.

Selective Detection of Misfolded Tau From Postmortem Alzheimer's Disease Brains.

Tau aggregates are present in multiple neurodegenerative diseases known as "tauopathies," including Alzheimer's disease, Pick's disease, progressive supranuclear palsy, and corticobasal degeneration. Such misfolded tau aggregates are therefore potential sources for selective detection and biomarker discovery. Six human tau isoforms present in brain tissues and both 3R and 4R isoforms have been observed in the neuronal inclusions.

Protein SUMOylation is a sex-specific regulator of fear memory formation in the amygdala.

Strong evidence has implicated ubiquitin signaling in the process of fear memory formation. While less abundant than ubiquitination, evidence suggests that protein SUMOylation may also be involved in fear memory formation in neurons. However, the importance of amygdala protein SUMOylation in fear memory formation has never been directly examined.

Understanding Hydrogenation Chemistry at MgB Reactive Edges from Molecular Dynamics.

Solid-state hydrogen storage materials often operate via transient, multistep chemical reactions at complex interfaces that are difficult to capture. Here, we use direct molecular dynamics simulations at accelerated temperatures and hydrogen pressures to probe the hydrogenation chemistry of the candidate material MgB without assumption of reaction pathways. Focusing on highly reactive (101̅0) edge planes where initial hydrogen attack is likely to occur, we track mechanistic steps toward the formation of hydrogen-saturated BH units and key chemical intermediates, involving H dissociation, generation of functionalities and molecular complexes containing BH and BH motifs, and B-B bond breaking.

Proteomic Analysis Reveals Sex-Specific Protein Degradation Targets in the Amygdala During Fear Memory Formation.

Ubiquitin-proteasome mediated protein degradation has been widely implicated in fear memory formation in the amygdala. However, to date, the protein targets of the proteasome remain largely unknown, limiting our understanding of the functional significance for protein degradation in fear memory formation. Additionally, whether similar proteins are targeted by the proteasome between sexes has yet to be explored.

Preclinical development of a bispecific TNFα/IL-23 neutralising domain antibody as a novel oral treatment for inflammatory bowel disease.

Anti-TNFα and anti-IL-23 antibodies are highly effective therapies for Crohn's disease or ulcerative colitis in a proportion of patients. V56B2 is a novel bispecific domain antibody in which a llama-derived IL-23p19-specific domain antibody, humanised and engineered for intestinal protease resistance, V900, was combined with a previously-described TNFα-specific domain antibody, V565. V56B2 contains a central protease-labile linker to create a single molecule for oral administration.

Sex-Specific Linear Polyubiquitination Is a Critical Regulator of Contextual Fear Memory Formation.

Strong evidence supports that protein ubiquitination is a critical regulator of fear memory formation. However, as this work has focused on protein degradation, it is currently unknown whether polyubiquitin modifications that are independent of the proteasome are involved in learning-dependent synaptic plasticity. Here, we present the first evidence that atypical linear (M1) polyubiquitination, the only ubiquitin chain that does not occur at a lysine site and is largely independent of the proteasome, is critically involved in contextual fear memory formation in the amygdala in a sex-specific manner.

Females, but not males, require protein degradation in the hippocampus for contextual fear memory formation.

Strong evidence supports a role for protein degradation in fear memory formation. However, these data have been largely done in only male animals. Here, we found that following contextual fear conditioning, females, but not males, had increased levels of proteasome activity and K48 polyubiquitin protein targeting in the dorsal hippocampus, the latter of which occurred at chaperones or RNA processing proteins.

Simulation training for embryo transfer: findings from the American Society for Reproductive Medicine Embryo Transfer Certificate Course.

Objective: To assess the value of the American Society for Reproductive Medicine Embryo Transfer Certificate Course in confidence and skill building for performing a live embryo transfer (ET).

Design: Prospective cohort study.

Setting: Two-day simulation workshops of reproductive endocrine and infertility (REI) fellows from American Board of Obstetrics and Gynecology-approved training programs, using four different uterine models (A-D).

Cellular Stoichiometry of Chemotaxis Proteins in .

Chemotaxis systems enable microbes to sense their immediate environment, moving toward beneficial stimuli and away from those that are harmful. In an effort to better understand the chemotaxis system of , a symbiont of the legume alfalfa, the cellular stoichiometries of all ten chemotaxis proteins in were determined. A combination of quantitative immunoblot and mass spectrometry revealed that the protein stoichiometries in varied greatly from those in and To compare protein ratios to other systems, values were normalized to the central kinase CheA.

A Mechanistic Analysis of Phase Evolution and Hydrogen Storage Behavior in Nanocrystalline Mg(BH) within Reduced Graphene Oxide.

Magnesium borohydride (Mg(BH), abbreviated here MBH) has received tremendous attention as a promising onboard hydrogen storage medium due to its excellent gravimetric and volumetric hydrogen storage capacities. While the polymorphs of MBH-alpha (α), beta (β), and gamma (γ)-have distinct properties, their synthetic homogeneity can be difficult to control, mainly due to their structural complexity and similar thermodynamic properties. Here, we describe an effective approach for obtaining pure polymorphic phases of MBH nanomaterials within a reduced graphene oxide support (abbreviated MBHg) under mild conditions (60-190 °C under mild vacuum, 2 Torr), starting from two distinct samples initially dried under Ar and vacuum.

Functional annotation of serine hydrolases in the asexual erythrocytic stage of Plasmodium falciparum.

Enzymes of the serine hydrolase superfamily are ubiquitous, highly versatile catalysts that mediate a wide variety of metabolic reactions in eukaryotic cells, while also being amenable to selective inhibition. We have employed a fluorophosphonate-based affinity capture probe and mass spectrometry to explore the expression profile and metabolic roles of the 56-member P. falciparum serine hydrolase superfamily in the asexual erythrocytic stage of P.

Oral Anti-Tumour Necrosis Factor Domain Antibody V565 Provides High Intestinal Concentrations, and Reduces Markers of Inflammation in Ulcerative Colitis Patients.

V565 is an engineered TNFα-neutralising single domain antibody formulated into enteric coated mini-tablets to enable release in the intestine after oral administration as a possible oral treatment for inflammatory bowel disease (IBD). Following oral administration, ileal recovery of V565 was investigated in four patients with terminal ileostomy. Intestinal and systemic pharmacokinetics were measured in six patients with Crohn's disease and evidence of target engagement assessed in five patients with ulcerative colitis.