Cholate Shunt, Oral Cholate Challenge and Endoscopic Lesions of Portal Hypertension: The SHUNT-V Study.

Background: The accuracy of current criteria for ruling out large oesophageal varices (LEV) and other endoscopic lesions of portal hypertension (PH) may be compromised by obesity and MASLD/MASH.

Aims: In the US multicentre SHUNT-V study, we evaluated the disease severity index (DSI) for detecting LEV and other lesions of PH at endoscopy.

Methods: Subjects were adults with compensated cirrhosis scheduled for endoscopy to screen for varices.

χ-Conotoxins are an Evolutionary Innovation of Mollusk-Hunting Cone Snails as a Counter-Adaptation to Prey Defense.

Mollusk-hunting (molluscivorous) cone snails belong to a monophyletic group in Conus, a genus of venomous marine snails. The molluscivorous lineage evolved from ancestral worm-hunting (vermivorous) snails ∼18 Ma. To enable the shift to a molluscivorous lifestyle, molluscivorous cone snails must solve biological problems encountered when hunting other gastropods, namely: (i) preventing prey escape and (ii) overcoming the formidable defense of the prey in the form of the molluscan shell, a problem unique to molluscivorous Conus.

The Oral Cholate Challenge Test Quantifies Risk for Liver-Related Clinical Outcomes in Primary Sclerosing Cholangitis.

Background And Aims: We quantified hepatic functional impairment using quantitative function tests and linked severity of functional impairment to liver-related complications and outcome in primary sclerosing cholangitis.

Methods: Forty-seven patients had baseline testing, and 40 were retested after 1 year. For each test, cholates labeled with cold, nonradioactive isotopes were administered orally (DuO, SHUNT tests) and intravenously (SHUNT test), and blood was analyzed at 20 and 60 minutes (DuO), or 0, 5, 20, 45, 60, and 90 minutes (SHUNT).

Optimization of fungicidal and acaricidal metabolite production by endophytic fungus Aspergillus sp. SPH2.

The endophytic fungus Aspergillus sp. SPH2 was isolated from the stems of the endemic plant Bethencourtia palmensis and its extracts were found to have strong fungicidal effects against Botrytis cinerea and ixodicidal effects against Hyalomma lusitanicum at different fermentation times. In this study, the fungus was grown using three different culture media and two methodologies, Microparticulate Enhancement Cultivation (MPEC) and Semi-Solid-State Fermentation (Semi-SSF), to increase the production of secondary metabolites during submerged fermentation.

Using Constellation Pharmacology to Characterize a Novel α-Conotoxin from .

The venom of cone snails has been proven to be a rich source of bioactive peptides that target a variety of ion channels and receptors. α-Conotoxins (αCtx) interact with nicotinic acetylcholine receptors (nAChRs) and are powerful tools for investigating the structure and function of the various nAChR subtypes. By studying how conotoxins interact with nAChRs, we can improve our understanding of these receptors, leading to new insights into neurological diseases associated with nAChRs.

Nodule-specific Cu -chaperone NCC1 is required for symbiotic nitrogen fixation in Medicago truncatula root nodules.

Cu -chaperones are a diverse group of proteins that allocate Cu ions to specific copper proteins, creating different copper pools targeted to specific physiological processes. Symbiotic nitrogen fixation carried out in legume root nodules indirectly requires relatively large amounts of copper, for example for energy delivery via respiration, for which targeted copper deliver systems would be required. MtNCC1 is a nodule-specific Cu -chaperone encoded in the Medicago truncatula genome, with a N-terminus Atx1-like domain that can bind Cu with picomolar affinities.

Clinical utility of measuring CD4 T follicular cells in patients with immune dysregulation.

Mechanistic studies of autoimmune disorders have identified circulating T follicular helper (cTfh) cells as drivers of autoimmunity. However, the quantification of cTfh cells is not yet used in clinical practice due to the lack of age-stratified normal ranges and the unknown sensitivity and specificity of this test for autoimmunity. We enrolled 238 healthy participants and 130 patients with common and rare disorders of autoimmunity or autoinflammation.

Forging a symbiosis: transition metal delivery in symbiotic nitrogen fixation.

Symbiotic nitrogen fixation carried out by the interaction between legumes and rhizobia is the main source of nitrogen in natural ecosystems and in sustainable agriculture. For the symbiosis to be viable, nutrient exchange between the partners is essential. Transition metals are among the nutrients delivered to the nitrogen-fixing bacteria within the legume root nodule cells.

Clinical utility of measuring CD4 T follicular cells in patients with immune dysregulation.

Mechanistic studies of autoimmune disorders have identified circulating T follicular helper (cTfh) cells as drivers of autoimmunity. However, the quantification of cTfh cells is not yet used in clinical practice due to the lack of age-stratified normal ranges and the unknown sensitivity and specificity of this test for autoimmunity. We enrolled 238 healthy participants and 130 patients with common and rare disorders of autoimmunity or autoinflammation.

A directed genome evolution method to enhance hydrogen production in .

Nitrogenase-dependent H production by photosynthetic bacteria, such as , has been extensively investigated. An important limitation to increase H production using genetic manipulation is the scarcity of high-throughput screening methods to detect possible overproducing mutants. Previously, we engineered strains that emitted fluorescence in response to H and used them to identify mutations in the nitrogenase Fe protein leading to H overproduction.

Somatostatin venom analogs evolved by fish-hunting cone snails: From prey capture behavior to identifying drug leads.

Somatostatin (SS) is a peptide hormone with diverse physiological roles. By investigating a deep-water clade of fish-hunting cone snails, we show that predator-prey evolution has generated a diverse set of SS analogs, each optimized to elicit specific systemic physiological effects in prey. The increased metabolic stability, distinct SS receptor activation profiles, and chemical diversity of the venom analogs make them suitable leads for therapeutic application, including pain, cancer, and endocrine disorders.

A systemic review and meta-analysis exploring the predictors of sperm retrieval in patients with non-obstructive azoospermia and chromosomal abnormalities.

To identify the most prevalent chromosomal abnormalities in patients with non-obstructive azoospermia (NOA), consolidate their surgical sperm retrieval (SSR) rates and determine the significant predictors of positive SSR in this patient population. A systematic review and meta-analysis were performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Fifty-three studies including 2965 patients were identified through searching the PubMed database.

The Bradyrhizobium Sp. LmicA16 Type VI Secretion System Is Required for Efficient Nodulation of Lupinus Spp.

Many bacteria of the genus Bradyrhizobium are capable of inducing nodules in legumes. In this work, the importance of a type VI secretion system (T6SS) in a symbiotic strain of the genus Bradyrhizobium is described. T6SS of Bradyrhizobium sp.

Non-Peptidic Small Molecule Components from Cone Snail Venoms.

Venomous molluscs (Superfamily Conoidea) comprise a substantial fraction of tropical marine biodiversity (>15,000 species). Prior characterization of cone snail venoms established that bioactive venom components used to capture prey, defend against predators and for competitive interactions were relatively small, structured peptides (10-35 amino acids), most with multiple disulfide crosslinks. These venom components ("conotoxins, conopeptides") have been widely studied in many laboratories, leading to pharmaceutical agents and probes.

Medicago truncatula Yellow Stripe-Like7 encodes a peptide transporter participating in symbiotic nitrogen fixation.

Yellow Stripe-Like (YSL) proteins are a family of plant transporters that are typically involved in transition metal homeostasis. Three of the four YSL clades (I, II and IV) transport metals complexed with the non-proteinogenic amino acid nicotianamine or its derivatives. No such capability has been shown for any member of clade III, but the link between these YSLs and metal homeostasis could be masked by functional redundancy.

Cannabinoid receptor agonists from Conus venoms alleviate pain-related behavior in rats.

Cannabinoid (CB) receptor agonists show robust antinociceptive effects in various pain models. However, most of the clinically potent CB1 receptor-active drugs derived from cannabis are considered concerning due to psychotomimetic side effects. Selective CB receptor ligands that do not induce CNS side effects are of clinical interest.

Multicenter, Double-Blind, Randomized Trial of Emricasan in Hepatitis C-Treated Liver Transplant Recipients With Residual Fibrosis or Cirrhosis.

Despite achieving sustained virologic response (SVR) to hepatitis C virus (HCV) therapy, there remains a post liver transplantation population with advanced fibrosis/cirrhosis. Emricasan is an orally active, pan-caspase inhibitor that suppresses apoptosis and inflammation, potentially decreasing hepatic inflammation and fibrosis. We aimed to determine the safety and efficacy of emricasan (IDN-6556-07) in a double-blind, randomized, placebo-controlled, multicenter study in reducing or preventing the progression of hepatic fibrosis in HCV liver transplant recipients with residual fibrosis or cirrhosis after achieving SVR.

MtCOPT2 is a Cu transporter specifically expressed in Medicago truncatula mycorrhizal roots.

Arbuscular mycorrhizal fungi are critical participants in plant nutrition in natural ecosystems and in sustainable agriculture. A large proportion of the phosphorus, nitrogen, sulfur, and transition metal elements that the host plant requires are obtained from the soil by the fungal mycelium and released at the arbuscules in exchange for photosynthates. While many of the plant transporters responsible for obtaining macronutrients at the periarbuscular space have been characterized, the identities of those mediating transition metal uptake remain unknown.

The Medicago truncatula Yellow Stripe1-Like3 gene is involved in vascular delivery of transition metals to root nodules.

Symbiotic nitrogen fixation carried out in legume root nodules requires transition metals. These nutrients are delivered by the host plant to the endosymbiotic nitrogen-fixing bacteria living within the nodule cells, a process in which vascular transport is essential. As members of the Yellow Stripe-Like (YSL) family of metal transporters are involved in root to shoot transport, they should also be required for root to nodule metal delivery.

Fluoroscopy Time During Endoscopic Retrograde Cholangiopancreatography Performed for Children and Adolescents is Significantly Higher With Low-volume Endoscopists.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is a fluoroscopy and endoscopy-based procedure important for diagnosis and management of pediatric pancreaticobiliary disorders. Patient, procedure, endoscopist, and facility characteristics have been shown to influence ERCP complexity and procedure outcomes as well as fluoroscopy utilization in adults; however, the extent to which this is true in pediatric patients remains under-studied and there are minimal data regarding fluoroscopy utilization in pediatric ERCP.

Methods: We retrospectively analyzed ERCPs performed on patients <18 years of age at our tertiary care children's hospital from 2002 to 2017 using our institution's paper and electronic medical record system along with a prospectively maintained radiation exposure database.

Rhizobium ruizarguesonis sp. nov., isolated from nodules of Pisum sativum L.

Four strains, coded as UPM1132, UPM1133, UPM1134 and UPM1135, and isolated from nodules of Pisum sativum plants grown on Ni-rich soils were characterised through a polyphasic taxonomy approach. Their 16S rRNA gene sequences were identical and showed 100% similarity with their closest phylogenetic neighbors, the species included in the 'R. leguminosarum group': R.

Medicago truncatula Ferroportin2 mediates iron import into nodule symbiosomes.

Iron is an essential cofactor for symbiotic nitrogen fixation, required by many of the enzymes involved, including signal transduction proteins, O homeostasis systems, and nitrogenase itself. Consequently, host plants have developed a transport network to deliver essential iron to nitrogen-fixing nodule cells. Ferroportin family members in model legume Medicago truncatula were identified and their expression was determined.

Polyphenol-Functionalized Plant Viral-Derived Nanoparticles Exhibit Strong Antimicrobial and Antibiofilm Formation Activities.

(-)-Epigallocatechin gallate (EGCG) is a polyphenolic compound that shows a number of health-promoting effects, especially a broad antimicrobial activity. Virus-derived nanoparticles (VNPs) represent a promising drug carrier since they possess properties like biodegradability and their surface and interior are highly modifiable. Turnip mosaic virus (TuMV) VNPs offer an attractive number of conjugation sites on the external surface.

Complete Circularized Genome Data of Two Spanish strains of (IVIA5235 and IVIA5901) Using Hybrid Assembly Approaches.

is an economically important plant pathogenic bacterium of global importance associated, since 2013, with a devastating epidemic in olive trees in Italy. Since then, several outbreaks of this pathogen have been reported in other European member countries including Spain, France, and Portugal. In Spain, the three major subspecies (subsp.