Genome-informed Discovery of Monchicamides A-K: Cyanobactins from the Microcoleaceae Cyanobacterium LEGE 16532.

Genome mining has emerged as an important tool for the discovery of natural products and is particularly effective for the swift identification of ribosomally synthesized and post-translationally modified peptides (RiPPs). Among RiPPs, cyanobactins have gained attention due to their diverse structures and bioactive properties. Here, we explored the Microcoleaceae cyanobacterium LEGE 16532 strain and identified the biosynthetic gene cluster (BGC), which was predicted to encode cyanobactin-like molecules.

UBXN3B is crucial for B lymphopoiesis.

Background: The ubiquitin regulatory X (UBX) domain-containing proteins (UBXNs) are putative adaptors for ubiquitin ligases and valosin-containing protein; however, their in vivo physiological functions remain poorly characterised. We recently showed that UBXN3B is essential for activating innate immunity to DNA viruses and controlling DNA/RNA virus infection. Herein, we investigate its role in adaptive immunity.

Neutrophils insert elastase into hepatocytes to regulate calcium signaling in alcohol-associated hepatitis.

Neutrophil infiltration occurs in a variety of liver diseases, but it is unclear how neutrophils and hepatocytes interact. Neutrophils generally use granule proteases to digest phagocytosed bacteria and foreign substances or neutralize them in neutrophil extracellular traps. In certain pathological states, granule proteases play a destructive role against the host as well.

A dual-acting DNASE1/DNASE1L3 biologic prevents autoimmunity and death in genetic and induced lupus models.

A defining feature of systemic lupus erythematosus (SLE) is loss of tolerance to self-DNA, and deficiency of DNASE1L3, the main enzyme responsible for chromatin degradation in blood, is also associated with SLE. This association can be found in an ultrarare population of pediatric patients with DNASE1L3 deficiency who develop SLE, adult patients with loss-of-function variants of DNASE1L3 who are at a higher risk for SLE, and patients with sporadic SLE who have neutralizing autoantibodies against DNASE1L3. To mitigate the pathogenic effects of inherited and acquired DNASE1L3 deficiencies, we engineered a long-acting enzyme biologic with dual DNASE1/DNASE1L3 activity that is resistant to DNASE1 and DNASE1L3 inhibitors.

Transient Lactic Acidosis and Elevation of Transaminases after the Introduction of Remdesivir in a Patient with Acute Kidney Injury.

A 56-year-old woman was transferred to the intensive care unit (ICU) two days after an allogeneic stem cell transplantation (ASCT) when she presented acute respiratory distress due to the relapse of a SARS-CoV-2 infection. Following that, she received two intravenous doses of 100 mg remdesivir. Subsequently, the patient developed multiple instances of diarrhea, progressing to oliguria and acute kidney injury, necessitating continuous venovenous hemofiltration (CVVH).

McArdle's, a Rare Disease That Every Family Doctor Can Manage: A Case Report.

McArdle's disease is a rare autosomal recessive disorder that affects glycogen storage. It typically manifests in adolescence or early adulthood with presenting symptoms, such as fatigue, myalgia, exercise intolerance, and cramps, which can be easily overlooked. This case report seeks to offer a comprehensive overview of the perspective of a patient living with McArdle's disease, emphasizing the importance of treatment encouragement.

Topflight endoscopic submucosal dissection: a novel strategy for the resection of gastric fundus tumors.

Video 1Resection of a gastric lesion using Topflight ESD.

Replacing Harmful Flame Retardants with Biodegradable Starch-Based Materials in Polyethylene Formulations.

The addition of toxic flame retardants to commercially available polymers is often required for safety reasons due to the high flammability of these materials. In this work, the preparation and incorporation of efficient biodegradable starch-based flame retardants into a low-density polyethylene (LDPE) matrix was investigated. Thermoplastic starch was first obtained by plasticizing starch with glycerol/water or glycerol/water/choline phytate to obtain TPS-G and TPS-G-CPA, respectively.

Spatiotemporal dynamics of cytokines expression dictate fetal liver hematopoiesis.

During embryogenesis, yolk-sac and intra-embryonic-derived hematopoietic progenitors, comprising the precursors of adult hematopoietic stem cells, converge into the fetal liver. With a new staining strategy, we defined all non-hematopoietic components of the fetal liver and found that hepatoblasts are the major producers of hematopoietic growth factors. We identified mesothelial cells, a novel component of the stromal compartment, producing Kit ligand, a major hematopoietic cytokine.

Cell circuits between leukemic cells and mesenchymal stem cells block lymphopoiesis by activating lymphotoxin beta receptor signaling.

Acute lymphoblastic and myeloblastic leukemias (ALL and AML) have been known to modify the bone marrow microenvironment and disrupt non-malignant hematopoiesis. However, the molecular mechanisms driving these alterations remain poorly defined. Using mouse models of ALL and AML, here we show that leukemic cells turn off lymphopoiesis and erythropoiesis shortly after colonizing the bone marrow.

Mature B cells and mesenchymal stem cells control emergency myelopoiesis.

Systemic inflammation halts lymphopoiesis and prioritizes myeloid cell production. How blood cell production switches from homeostasis to emergency myelopoiesis is incompletely understood. Here, we show that lymphotoxin-β receptor (LTβR) signaling in combination with TNF and IL-1 receptor signaling in bone marrow mesenchymal stem cells (MSCs) down-regulates expression to shut down lymphopoiesis during systemic inflammation.

Dysregulated stem cell niches and altered lymphocyte recirculation cause B and T cell lymphopenia in WHIM syndrome.

Gain-of-function (GOF) mutations in CXCR4 cause WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome, characterized by infections, leukocyte retention in bone marrow (BM), and blood leukopenias. B lymphopenia is evident at early progenitor stages, yet why do CXCR4 GOF mutations that cause B (and T) lymphopenia remain obscure? Using a CXCR4 R334X GOF mouse model of WHIM syndrome, we showed that lymphopoiesis is reduced because of a dysregulated mesenchymal stem cell (MSC) transcriptome characterized by a switch from an adipogenic to an osteolineage-prone program with limited lymphopoietic activity. We identify lymphotoxin beta receptor (LTβR) as a critical pathway promoting interleukin-7 (IL-7) down-regulation in MSCs.

Fetal Deaths in SARS-CoV-2-Infected Pregnant Women: A Portuguese Case Series.

Introduction: Stillbirth has been documented as an outcome of SARS-CoV-2 infection in pregnancy. Placental hypoperfusion and inflammation secondary to maternal immune response seem to play a role in the cascade of events that contribute to fetal death. The aim of our study is to report a perinatal outcome of SARS-CoV-2 infection in pregnancy adding information to the pool of data on COVID-19 pregnancy outcomes.

Competition between hematopoietic stem and progenitor cells controls hematopoietic stem cell compartment size.

Cellular competition for limiting hematopoietic factors is a physiologically regulated but poorly understood process. Here, we studied this phenomenon by hampering hematopoietic progenitor access to Leptin receptor mesenchymal stem/progenitor cells (MSPCs) and endothelial cells (ECs). We show that HSC numbers increase by 2-fold when multipotent and lineage-restricted progenitors fail to respond to CXCL12 produced by MSPCs and ECs.

Esophagomediastinal fistula: a rare case of gastrointestinal tuberculosis.

A 40-year-old male with history of HIV infection was admitted to the hospital with a one-month history of productive cough, vespertine fever, night sweats, loss of appetite and unintentional 10-Kg weight loss. Physical exam was remarkable for cachexia. Blood tests revealed a CD4+ T lymphocyte count of 23 cells/mm3 and HIV viral load of 837,678 copies/ml.

When needles are not enough, forceps delivers!

A 35-year-old male with a history of recurrent pleuritic chest pain was referred for evaluation of a mediastinal mass detected on CT. MRI showed a 10.5 x 7 x 3 cm lesion in the posterior mediastinum.

Pilot Study to Reduce Added Salt on a University Canteen through the Use of an Innovative Dosage Equipment.

Background: This study aims to demonstrate the practical application of an innovative easy-to-use equipment to dosage cooking salt, and evaluate the effectiveness in reducing 30% of the added salt in meals and the impact on consumer's satisfaction and food waste.

Methods: Two canteens from one public university where randomized in one control arm and one intervention arm. The first step was to evaluate the salt added to food through atomic emission spectrophotometry in both canteens, and the second step was to perform gradual reductions of up to 30% of cooking salt in the intervention canteen using the Salt Control-C (SC-C) equipment.

Increased Angiotensin-Converting Enzyme 2 and Loss of Alveolar Type II Cells in COVID-19-related Acute Respiratory Distress Syndrome.

ACE2 (angiotensin-converting enzyme 2), the entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is expressed in type 2 alveolar epithelial cells (AT2) that may play key roles in postinjury repair. An imbalance between ACE2 and ACE has also been hypothesized to contribute to lung injury. To characterize the expression and distribution of ACE2 and ACE and to compare AT2 with endothelial cell expression in coronavirus disease (COVID-19)-related or -unrelated acute respiratory distress syndrome (ARDS) and controls.

GIMAP5 maintains liver endothelial cell homeostasis and prevents portal hypertension.

Portal hypertension is a major contributor to decompensation and death from liver disease, a global health problem. Here, we demonstrate homozygous damaging mutations in GIMAP5, a small organellar GTPase, in four families with unexplained portal hypertension. We show that GIMAP5 is expressed in hepatic endothelial cells and that its loss in both humans and mice results in capillarization of liver sinusoidal endothelial cells (LSECs); this effect is also seen when GIMAP5 is selectively deleted in endothelial cells.

Hematopoietic Stem Cell Niches and Signals Controlling Immune Cell Development and Maintenance of Immunological Memory.

Studies over the last couple of decades have shown that hematopoietic stem cells (HSCs) are critically dependent on cytokines such as Stem Cell Factor and other signals provided by bone marrow niches comprising of mesenchymal stem and progenitor cells (MSPCs) and endothelial cells (ECs). Because of their critical roles in HSC maintenance the niches formed by MSPCs and ECs are commonly referred to as HSC niches. For the most part, the signals required for HSC maintenance act in a short-range manner, which imposes the necessity for directional and positional cues in order for HSCs to localize and be retained properly in stem cell niches.

Should I Stay or Should I Flow: HSCs Are on the Move!

Stem cell biologists have been yearning to visualize hematopoietic stem cells (HSCs) in live animals since Kiel et al. (2005) first visualized them in bone cavities. With two recent papers from Christodoulou et al.

Towards Therapeutic Alternatives for Mercury Neurotoxicity in the Amazon: Unraveling the Pre-Clinical Effects of the Superfruit Açaí (, Mart.) as Juice for Human Consumption.

Methylmercury (MeHg) exposure is a serious problem of public health, especially in the Amazon. Exposure in riverine populations is responsible for neurobehavioral abnormalities. It was hypothesized that consumption of Amazonian fruits could protect by reducing mercury accumulation.

Effector T17 Cells Give Rise to Long-Lived T Cells that Are Essential for an Immediate Response against Bacterial Infection.

Adaptive immunity provides life-long protection by generating central and effector memory T cells and the most recently described tissue resident memory T (T) cells. However, the cellular origin of CD4 T cells and their contribution to host defense remain elusive. Using IL-17A tracking-fate mouse models, we found that a significant fraction of lung CD4 T cells derive from IL-17A-producing effector (T17) cells following immunization with heat-killed Klebsiella pneumonia (Kp).