Nucleoside Reverse Transcriptase Inhibitor (NRTI)-Induced Neuropathy and Mitochondrial Toxicity: Limitations of the Poly-γ Hypothesis and the Potential Roles of Autophagy and Drug Transport.

Nucleoside reverse transcriptase inhibitors (NRTIs) are the backbone of highly active antiretroviral therapy (HAART)-the current standard of care for treating human immunodeficiency virus (HIV) infection. Despite their efficacy, NRTIs cause numerous treatment-limiting adverse effects, including a distinct peripheral neuropathy, called antiretroviral toxic neuropathy (ATN). ATN primarily affects the extremities with shock-like tingling pain, a pins-and-needles prickling sensation, and numbness.

A strategy for quantifying microplastic particles in membrane filtration processes using flow cytometry.

Microplastic (MP) pollution is ubiquitous in the aquatic environment, with significant quantities of MPs originating from municipal wastewater treatment plants. Efforts to evaluate and implement MP removal processes are underway, with membrane technologies often recommended as an "ideal" solution. A key challenge in evaluating these technologies involves efficiently quantifying MP concentrations in samples.

C/EBPβ deletion in macrophages impairs mammary gland alveolar budding during the estrous cycle.

Macrophages have important roles in mammary gland development and tissue homeostasis, but the specific mechanisms that regulate macrophage function need further elucidation. We have identified C/EBPβ as an important transcription factor expressed by multiple macrophage populations in the normal mammary gland. Mammary glands from mice with C/EBPβ-deficient macrophages ( ) show a significant decrease in alveolar budding during the diestrus stage of the reproductive cycle, whereas branching morphogenesis remains unchanged.

An Individual Barrier Enclosure Actively Removing Aerosols for Airborne Isolation: A Vacuum Tent.

Background: Aerosol barrier enclosure systems have been designed to prevent airborne contamination, but their safety has been questioned. A vacuum tent was designed with active continuous suctioning to minimize risks of aerosol dispersion. We tested its efficacy, risk of rebreathing, and usability on a bench, in healthy volunteers, and in an ergonomic clinical assessment study.

Nuclear corepressors NCOR1 and NCOR2 entrain thymocyte signaling, selection, and emigration.

T cell development proceeds via discrete stages that require both gene induction and gene repression. Transcription factors direct gene repression by associating with corepressor complexes containing chromatin-remodeling enzymes; the corepressors NCOR1 and NCOR2 recruit histone deacetylases to these complexes to silence transcription of target genes. Earlier work identified the importance of NCOR1 in promoting the survival of positively-selected thymocytes.

Scedosporium infection disseminated "from toe to head" in allogeneic stem cell transplant recipient: a case report.

Background: Scedosporium is a lesser-known non-Aspergillus genus of mold that can present in unsuspecting ways. If overlooked, it may disseminate and cause high mortality in high-risk allogeneic stem cell transplant recipients.

Case Presentation: This case report describes a 65-year-old patient with Acute Myeloid Leukemia who underwent an allogeneic hematopoietic stem cell transplant after a period of prolonged neutropenia with fluconazole prophylaxis.

BET Bromodomain Inhibitors: Novel Design Strategies and Therapeutic Applications.

The mammalian bromodomain and extra-terminal domain (BET) family of proteins consists of four conserved members (Brd2, Brd3, Brd4, and Brdt) that regulate numerous cancer-related and immunity-associated genes. They are epigenetic readers of histone acetylation with broad specificity. BET proteins are linked to cancer progression due to their interaction with numerous cellular proteins including chromatin-modifying factors, transcription factors, and histone modification enzymes.

Development of an Interferon-Gamma Release Assay (IGRA) to Aid Diagnosis of Histoplasmosis.

Establishing diagnosis of latent and active histoplasmosis is challenging. Interferon gamma-release assays (IGRAs) may provide evidence of latent and active infection. An enzyme-linked immunospot (ELISpot) assay was developed using yeast cell lysate (YCL) antigen prepared from a representative North American Histoplasma capsulatum strain.

Attitudes and Awareness of Cornea Specialists and Oculoplastic Surgeons toward Methicillin-Resistant Decolonization.

Methicillin-resistant (MRSA) decolonization is widely utilized in many medical subspecialities to reduce surgical site infections, but routine ophthalmic implementation has been limited. The aim of this study was to investigate the attitudes and actual practice of corneal specialists and oculoplastic surgeons toward MRSA decolonization as a preventive measure in ophthalmic surgery. A web-based survey was sent to cornea specialists and oculoplastic surgeons to assess their knowledge, beliefs, and practices regarding MRSA prophylaxis and the use of MRSA decolonization to prevent post-operative infections.

Successful liver transplantation in patients with active SARS-CoV-2 infection.

The Coronavirus Disease 2019 (COVID-19) pandemic has substantially impacted solid organ transplantation, including temporary inactivation of waitlist candidates with COVID-19 infection. We report two cases of liver transplantation (LT) in individuals with asymptomatic COVID-19 infection. The first patient is a 68-year-old female with decompensated cirrhosis complicated by worsening frailty and sarcopenia.

MRSA Decolonization and the Eye: A Potential New Tool for Ophthalmologists.

Purpose: Methicillin-resistant Staphylococcus aureus (MRSA) is an opportunistic pathogen that can cause vision-threatening infections of the ocular surface, orbit, and periorbital structures. MRSA decolonization is a widespread technique employed outside of ophthalmology to reduce MRSA transmission and infection rates. Herein we explore whether decolonization protocols have a place in ophthalmology for combatting ocular MRSA infections.

Identification and Optimization of a Novel HIV-1 Integrase Inhibitor.

Human immunodeficiency virus-1 (HIV-1) is the causative agent of acquired immunodeficiency syndrome (AIDS). HIV-1, like all retroviruses, stably integrates its vDNA copy into host chromatin, a process allowing for permanent infection. This essential step for HIV-1 replication is catalyzed by viral integrase (IN) and aided by cellular protein LEDGF/p75.

Laser-induced thermal source for cold atoms.

We demonstrate a simple and compact approach to laser cool and trap atoms based on laser-induced thermal ablation (LITA) of a pure solid granule. A rapid thermalisation of the granule leads to a fast recovery of the ultra-high vacuum condition required for a long trapping lifetime of the cold gas. We give a proof-of-concept of the technique, performing a magneto-optical trap on the 461 nm [Formula: see text] transition of strontium.

Conformation of HIV-1 Envelope Governs Rhesus CD4 Usage and Simian-Human Immunodeficiency Virus Replication.

Infection of rhesus macaques with simian-human immunodeficiency viruses (SHIVs) is the preferred model system for vaccine development because SHIVs encode human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (Envs)-a key target of HIV-1 neutralizing antibodies. Since the goal of vaccines is to prevent new infections, SHIVs encoding circulating HIV-1 Env are desired as challenge viruses. Development of such biologically relevant SHIVs has been challenging, as they fail to infect rhesus macaques, mainly because most circulating HIV-1 Envs do not use rhesus CD4 (rhCD4) receptor for viral entry.

Prototype Foamy Virus Integrase Displays Unique Biochemical Activities among Retroviral Integrases.

Integrases of different retroviruses assemble as functional complexes with varying multimers of the protein. Retroviral integrases require a divalent metal cation to perform one-step transesterification catalysis. Tetrameric prototype foamy virus (PFV) intasomes assembled from purified integrase and viral DNA oligonucleotides were characterized for their activity in the presence of different cations.

Single-cell analysis identifies dynamic gene expression networks that govern B cell development and transformation.

Integration of external signals and B-lymphoid transcription factor activities organise B cell lineage commitment through alternating cycles of proliferation and differentiation, producing a diverse repertoire of mature B cells. We use single-cell transcriptomics/proteomics to identify differentially expressed gene networks across B cell development and correlate these networks with subtypes of B cell leukemia. Here we show unique transcriptional signatures that refine the pre-B cell expansion stages into pre-BCR-dependent and pre-BCR-independent proliferative phases.

The intrinsic kinase activity of BRD4 spans its BD2-B-BID domains.

Bromodomain protein 4 (BRD4) is a transcriptional and epigenetic regulator that is a therapeutic target in many cancers and inflammatory diseases. BRD4 plays important roles in transcription as an active kinase, which phosphorylates the carboxy-terminal domain (CTD) of RNA polymerase II (Pol II), the proto-oncogene c-MYC, and transcription factors TAF7 and CDK9. BRD4 is also a passive scaffold that recruits transcription factors.

Development of Murine Leukemia Virus Integrase-Derived Peptides That Bind Brd4 Extra-Terminal Domain as Candidates for Suppression of Acute Myeloid Leukemia.

The bromodomain and extra-terminal (BET) domain family of proteins, which include its prototypical member Brd4, is implicated in a variety of cancers and viral infections due to their interaction with cellular and viral proteins. BET proteins contain two bromodomains, a common protein motif that selectively binds acetylated lysine on histones. However, they are structurally distinct from other bromodomain-containing proteins because they encode a unique C-terminal extra-terminal (ET) domain that is important for the protein-protein interactions including jumonji C-domain-containing protein 6 (JMJD6) and histone-lysine -methyltransferase NSD3 (NSD3).

Treatment of Food Selectivity in an Adult With Autism Spectrum Disorder.

Food selectivity is common among individuals with autism spectrum disorder (ASD). Left untreated, food selectivity may continue into adulthood, leading to social and nutritional deficits. Although effective treatments have been identified for young children and the school-aged population, these treatments may not be feasible with adults.

Diagnosis of Histoplasmosis Using the MVista Galactomannan Antigen Qualitative Lateral Flow-Based Immunoassay: A Multicenter Study.

Background: Accurate and timely methods for the diagnosis of histoplasmosis in resource-limited countries are lacking. antigen detection by enzyme immunoassay (EIA) is widely used in the United States (US) but not in resource-limited countries, leading to missed or delayed diagnoses and poor outcomes. Lateral flow assays (LFAs) can be used in this setting.

Identification of mutations that cooperate with defects in B cell transcription factors to initiate leukemia.

The transcription factors PAX5, IKZF1, and EBF1 are frequently mutated in B cell acute lymphoblastic leukemia (B-ALL). We demonstrate that compound heterozygous loss of multiple genes critical for B and T cell development drives transformation, including Pax5xEbf1, Pax5xIkzf1, and Ebf1xIkzf1 mice for B-ALL, or Tcf7xIkzf1 mice for T-ALL. To identify genetic defects that cooperate with Pax5 and Ebf1 compound heterozygosity to initiate leukemia, we performed a Sleeping Beauty (SB) transposon screen that identified cooperating partners including gain-of-function mutations in Stat5b (~65%) and Jak1 (~68%), or loss-of-function mutations in Cblb (61%) and Myb (32%).

Navigating Performance Standards for Face Mask Materials: A Custom-Built Apparatus for Measuring Particle Filtration Efficiency.

Public health agencies have recommended the community use of face masks to reduce the transmission of airborne diseases like COVID-19. Virus transmission is reduced when masks act as efficient filters, thus evaluating mask particle filtration efficiency (PFE) is essential. However, the high cost and long lead times associated with purchasing turn-key PFE systems or hiring certified laboratories hampers the testing of filter materials.