Hydrothorax and air fluid levels in the right chest - a diagnostic dilemma.

A diaphragmatic defect that permits abdominal contents to herniate into the right side of the chest is rare. In adults with right-sided diaphragmatic hernias, few occur without a history of trauma, and even fewer are symptomatic. This case report illustrates such a case and the rare entity of an anterolaterally located hernia.

Effects of small molecule-induced dimerization on the programmed death ligand 1 protein life cycle.

The programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) checkpoint blockade is central to Immuno-Oncology based therapies, and alternatives to antibody blockers of this interaction are an active area of research due to antibody related toxicities. Recently, small molecule compounds that induce PD-L1 dimerization and occlusion of PD-1 binding site have been identified and developed for clinical trials. This mechanism invokes an oligomeric state of PD-L1 not observed in cells previously, as PD-L1 is generally believed to function as a monomer.

Lower Extremity Salvage in a Diabetic Patient With Cutaneous Mucormycosis and COVID-19 After Open Patella Fracture.

Cutaneous mucormycosis, while less common than sinonasal or pulmonary infections, can cause widespread tissue necrosis after seemingly innocuous encounters. The most common location of cutaneous mucormycosis is the extremities, and extensive infection has been reported after trauma or orthopedic procedures. A 60-year-old female with poorly controlled type 2 diabetes mellitus sustained an open patella fracture after a fall.

Mind the gap - unequal from the start: evidence from the early years of the longitudinal study.

is this country's largest contemporary longitudinal study of child development. The study has been designed to provide insight into the lives of children and young people growing up in the context of twenty-first century New Zealand. The cohort recruited 6853 children representative of the current ethnic and socioeconomic diversity of births in Aotearoa, New Zealand in 2009 and 2010.

The potential impact of an implemented income redistribution package on obesity prevalence in New Zealand.

Aim: This study quantified associations between (absolute and relative) individual income and obesity prevalence. These associations were then used to model the potential effect of a New Zealand (NZ) Government's income redistributive policy (the Families Package) on adult obesity prevalence.

Methods: Logistic regressions were used to investigate associations between absolute individual income and adult obesity prevalence in NZ.

Protein Footprinting and X-ray Crystallography Reveal the Interaction of PD-L1 and a Macrocyclic Peptide.

Blocking interactions between PD-1 and PD-L1 opens a new era of cancer treatment involving immunity modulation. Although most immunotherapies use monoclonal antibodies, small-molecule inhibitors offer advantages. To facilitate development of small-molecule therapeutics, we implemented a rapid approach to characterize the binding interfaces of small-molecule inhibitors with PD-L1.

Diverse mechanisms of metaeffector activity in an intracellular bacterial pathogen, Legionella pneumophila.

Pathogens deliver complex arsenals of translocated effector proteins to host cells during infection, but the extent to which these proteins are regulated once inside the eukaryotic cell remains poorly defined. Among all bacterial pathogens, Legionella pneumophila maintains the largest known set of translocated substrates, delivering over 300 proteins to the host cell via its Type IVB, Icm/Dot translocation system. Backed by a few notable examples of effector-effector regulation in L.

The contribution of unsafe blood transfusion to human immunodeficiency virus incidence in sub-Saharan Africa: reexamination of the 5% to 10% convention.

Background: Historical estimates have attributed 5% to 10% of new human immunodeficiency virus (HIV) infections in sub-Saharan Africa (SSA) to unsafe blood transfusions. Although frequently cited, the validity of this statistic is uncertain or outdated. Recent estimates suggest blood transfusion's contribution to new HIV infections in the region may be much lower.

Structure-Function Analysis of a Mixed-linkage β-Glucanase/Xyloglucanase from the Key Ruminal Bacteroidetes Prevotella bryantii B(1)4.

The recent classification of glycoside hydrolase family 5 (GH5) members into subfamilies enhances the prediction of substrate specificity by phylogenetic analysis. However, the small number of well characterized members is a current limitation to understanding the molecular basis of the diverse specificity observed across individual GH5 subfamilies. GH5 subfamily 4 (GH5_4) is one of the largest, with known activities comprising (carboxymethyl)cellulases, mixed-linkage endo-glucanases, and endo-xyloglucanases.

Crystal structure of the Legionella pneumophila Lem10 effector reveals a new member of the HD protein superfamily.

Legionella pneumophila, the intracellular pathogen that can cause severe pneumonia known as Legionnaire's disease, translocates close to 300 effectors inside the host cell using Dot/Icm type IVB secretion system. The structure and function for the majority of these effector proteins remains unknown. Here, we present the crystal structure of the L.

Structural and functional plasticity of antibiotic resistance nucleotidylyltransferases revealed by molecular characterization of lincosamide nucleotidylyltransferases lnu(A) and lnu(D).

One of the main mechanisms of resistance to lincosamide and aminoglycoside antibiotics is their inactivation by O-nucleotidylyltransferases (NTases). Significant sequence variation of lincomycin nucleotidylyltransferase (Lnu) and aminoglycoside nucleotidylyltransferase (ANT) enzymes plus lack of detailed information about the molecular basis for specificity of these enzymes toward chemically distinct antibiotic scaffolds hinders development of a general strategy to curb this resistance mechanism. We conducted an extensive sequence analysis identifying 129 putative antibiotic NTases constituting six distinct subfamilies represented by Lnu(A), Lnu(B), Lnu(C), Lnu(D), Lnu(F)/(G) plus ANT(2") enzymes.

The chromatin-modifying enzyme Ezh2 is critical for the maintenance of regulatory T cell identity after activation.

Regulatory T cells (Treg cells) are required for immune homeostasis. Chromatin remodeling is essential for establishing diverse cellular identities, but how the epigenetic program in Treg cells is maintained throughout the dynamic activation process remains unclear. Here we have shown that CD28 co-stimulation, an extracellular cue intrinsically required for Treg cell maintenance, induced the chromatin-modifying enzyme, Ezh2.

Interleukin-5-producing group 2 innate lymphoid cells control eosinophilia induced by interleukin-2 therapy.

Interleukin (IL)-2 promotes regulatory T-cell development and function, and treatment with IL-2 is being tested as therapy for some autoimmune diseases. However, patients receiving IL-2 treatment also experience eosinophilia due to an unknown mechanism. Here, we show that patients receiving low-dose IL-2 have elevated levels of serum IL-5, and this correlates with their degree of eosinophilia.

microRNA-17-92 regulates IL-10 production by regulatory T cells and control of experimental autoimmune encephalomyelitis.

microRNAs (miRNA) are essential for regulatory T cell (Treg) function but little is known about the functional relevance of individual miRNA loci. We identified the miR-17-92 cluster as CD28 costimulation dependent, suggesting that it may be key for Treg development and function. Although overall immune homeostasis was maintained in mice with miR-17-92-deficient Tregs, expression of the miR-17-92 miRNA cluster was critical for Treg accumulation and function during an acute organ-specific autoimmune disease in vivo.

The microRNA cluster miR-17∼92 promotes TFH cell differentiation and represses subset-inappropriate gene expression.

Follicular helper T cells (TFH cells) are the prototypic helper T cell subset specialized to enable B cells to form germinal centers (GCs) and produce high-affinity antibodies. We found that expression of microRNAs (miRNAs) by T cells was essential for TFH cell differentiation. More specifically, we show that after immunization of mice with protein, the miRNA cluster miR-17∼92 was critical for robust differentiation and function of TFH cells in a cell-intrinsic manner that occurred regardless of changes in proliferation.

The comprehensive antibiotic resistance database.

The field of antibiotic drug discovery and the monitoring of new antibiotic resistance elements have yet to fully exploit the power of the genome revolution. Despite the fact that the first genomes sequenced of free living organisms were those of bacteria, there have been few specialized bioinformatic tools developed to mine the growing amount of genomic data associated with pathogens. In particular, there are few tools to study the genetics and genomics of antibiotic resistance and how it impacts bacterial populations, ecology, and the clinic.

Gamma interferon (IFN-γ) receptor restricts systemic dengue virus replication and prevents paralysis in IFN-α/β receptor-deficient mice.

We previously reported that mice lacking alpha/beta and gamma interferon receptors (IFN-α/βR and -γR) uniformly exhibit paralysis following infection with the dengue virus (DENV) clinical isolate PL046, while only a subset of mice lacking the IFN-γR alone and virtually no mice lacking the IFN-α/βR alone develop paralysis. Here, using a mouse-passaged variant of PL046, strain S221, we show that in the absence of the IFN-α/βR, signaling through the IFN-γR confers approximately 140-fold greater resistance against systemic vascular leakage-associated dengue disease and virtually complete protection from dengue-induced paralysis. Viral replication in the spleen was assessed by immunohistochemistry and flow cytometry, which revealed a reduction in the number of infected cells due to IFN-γR signaling by 2 days after infection, coincident with elevated levels of IFN-γ in the spleen and serum.

Trafficking and replication patterns reveal splenic macrophages as major targets of dengue virus in mice.

Human postmortem studies of natural dengue virus (DENV) infection have reported systemically distributed viral antigen. Although it is widely accepted that DENV infects mononuclear phagocytes, the sequence in which specific tissues and cell types are targeted remains uncharacterized. We previously reported that mice lacking alpha/beta and gamma interferon receptors permit high levels of DENV replication and show signs of systemic disease (T.

Formylglycinamide ribonucleotide amidotransferase from Salmonella typhimurium: role of ATP complexation and the glutaminase domain in catalytic coupling.

Formylglycinamide ribonucleotide (FGAR) amidotransferase (FGAR-AT) takes part in purine biosynthesis and is a multidomain enzyme with multiple spatially separated active sites. FGAR-AT contains a glutaminase domain that is responsible for the generation of ammonia from glutamine. Ammonia is then transferred via a channel to a second active site located in the synthetase domain and utilized to convert FGAR to formylglycinamidine ribonucleotide (FGAM) in an adenosine triphosphate (ATP) dependent reaction.

MicroRNA 10a marks regulatory T cells.

MicroRNAs (miRNAs) are crucial for regulatory T cell (Treg) stability and function. We report that microRNA-10a (miR-10a) is expressed in Tregs but not in other T cells including individual thymocyte subsets. Expression profiling in inbred mouse strains demonstrated that non-obese diabetic (NOD) mice with a genetic susceptibility for autoimmune diabetes have lower Treg-specific miR-10a expression than C57BL/6J autoimmune resistant mice.

Mechanism and diversity of the erythromycin esterase family of enzymes.

Macrolide antibiotics such as azithromycin and erythromycin are mainstays of modern antibacterial chemotherapy, and like all antibiotics, they are vulnerable to resistance. One mechanism of macrolide resistance is via drug inactivation: enzymatic hydrolysis of the macrolactone ring catalyzed by erythromycin esterases, EreA and EreB. A genomic enzymology approach was taken to gain insight into the catalytic mechanisms and origins of Ere enzymes.

Antibiotic resistance is ancient.

The discovery of antibiotics more than 70 years ago initiated a period of drug innovation and implementation in human and animal health and agriculture. These discoveries were tempered in all cases by the emergence of resistant microbes. This history has been interpreted to mean that antibiotic resistance in pathogenic bacteria is a modern phenomenon; this view is reinforced by the fact that collections of microbes that predate the antibiotic era are highly susceptible to antibiotics.

CD4+ T cells are not required for the induction of dengue virus-specific CD8+ T cell or antibody responses but contribute to protection after vaccination.

The contribution of T cells to the host response to dengue virus (DENV) infection is not well understood. We previously demonstrated a protective role for CD8(+) T cells during primary DENV infection using a mouse-passaged DENV strain and IFN-α/βR(-/-) C57BL/6 mice, which are susceptible to DENV infection. In this study, we examine the role of CD4(+) T cells during primary DENV infection.

The genomic enzymology of antibiotic resistance.

The need for new antibiotic therapies is acute and growing in large part because of the emergence of drug-resistant pathogens. A vast number of resistance determinants are, however, found in nonpathogenic micro-organisms. The resistance totality in the global microbiota is the antibiotic resistome and includes not only established resistance genes but also genes that have the potential to evolve into resistance elements.

Structure and mechanism of the lincosamide antibiotic adenylyltransferase LinB.

Lincosamides make up an important class of antibiotics used against a wide range of pathogens, including methicillin-resistant Staphylococcus aureus. Predictably, lincosamide-resistant microorganisms have emerged with antibiotic modification as one of their major resistance strategies. Inactivating enzymes LinB/A catalyze adenylylation of the drug; however, little is known about their mechanistic and structural properties.