Investigating the C2 Modulation of the Imidazo[1,2-a]pyrazine-Based Hit Compound CTN1122: Synthesis, in vitro Antileishmanial Activity, Cytotoxicity and Casein Kinase 1 Inhibition.

Our research group previously discovered CTN1122, an imidazo[1,2-a]pyrazine compound with promising antileishmanial activity against intramacrophage amastigotes of Leishmania major and L. donovani strains. CTN1122 effectively targets Leishmania casein kinase 1 (L-CK1.

Small bowel perforation following accidental ingestion of grill brush bristle. A case report.

Introduction: Ingested foreign bodies are common in otolaryngology and gastrointestinal surgery, with grill brush bristles posing different risks. This case report describes a small bowel perforation after ingestion of a grill brush bristle. This is an extremely rare complication.

Novel Thiazole-Fused [4,5-] or [5,4-]Quinazolin-8-ones and Their Quinazoline Analogues: Synthesis and Biological Evaluation.

In connection with previous work on V-shaped polycyclic thiazolo[5,4-]quinazolin-9-one and [5,4-]quinazoline derivatives that can modulate the activity of various kinases, the synthesis of straight thiazole-fused [4,5-] or [5,4-]quinazolin-8-ones and quinazoline derivatives hitherto undescribed was envisioned. An innovative protocol allowed to obtain the target structures. The synthesis of inverted thiazolo[4,5-] and [5,4-]quinazolin-8-one derivatives was also explored with the aim of comparing biological results.

Coenzyme A fueling with pantethine limits autoreactive T cell pathogenicity in experimental neuroinflammation.

Background: Immune cell metabolism governs the outcome of immune responses and contributes to the development of autoimmunity by controlling lymphocyte pathogenic potential. In this study, we evaluated the metabolic profile of myelin-specific murine encephalitogenic T cells, to identify novel therapeutic targets for autoimmune neuroinflammation.

Methods: We performed metabolomics analysis on actively-proliferating encephalitogenic T cells to study their overall metabolic profile in comparison to resting T cells.

New Fusarochromanone Derivatives from the Marine Fungus UBOCC-A-117302.

Two new fusarochromanone derivatives, deacetylfusarochromene () and deacetamidofusarochrom-2',3-diene (), along with the previously reported metabolites fusarochromanone TDP-2 (), fusarochromene (), 2,2-dimethyl-5-amino-6-(2'-ene-4'-hydroxylbutyryl)-4-chromone (), fusarochromanone (), (-)-chrysogine (), and equisetin (), were isolated from the marine fungus UBOCC-A-117302. The structures of the compounds were determined by extensive spectrometric (HRMS) and spectroscopic (1D and 2D NMR) analyses, as well as specific rotation. Among them, and showed inhibition of three protein kinases with IC values ranging from 1.

XPS Investigation of Co-Ni Oxidized Compounds Surface Using Peak-On-Satellite Ratio. Application to CoNi Passive Layer Structure and Composition.

XPS data processing for cobalt and nickel core-level peaks can be complicated. This is especially true when analyzing a mixture of oxide/oxyhydroxide/hydroxide compounds of these metals. The objective of this study is to develop a method for decomposing XPS spectra of 2p core levels for nickel and cobalt-oxidized compounds.

Effects of climate warming on energetics and habitat of the world's largest marine ectotherm.

Responses of organisms to climate warming are variable and complex. Effects on species distributions are already evident and mean global surface ocean temperatures are likely to warm by up to 4.1 °C by 2100, substantially impacting the physiology and distributions of ectotherms.

Muscle matters: Skeletal muscle index and body mass index impact on complications and survival in renal cancer.

Objective: The objective of this study is to independently assess skeletal muscle index (SMI) and body mass index (BMI) as prognostic determinants for renal cell carcinoma (RCC) and investigate their correlation with surgical outcomes.

Patients And Methods: A retrospective cohort study of 524 RCC patients diagnosed between August 2010 and July 2018 was conducted using data from the Zealand University Hospital Renal Cancer Database in Denmark. Patient information was extracted from electronic patient records and the National Cancer Registry and encompassed demographics, clinical factors, tumour characteristics and surgical details.

Stratification to Neoadjuvant Radiotherapy in Rectal Cancer by Regimen and Transcriptional Signatures.

Unlabelled: Response to neoadjuvant radiotherapy (RT) in rectal cancer has been associated with immune and stromal features that are captured by transcriptional signatures. However, how such associations perform across different chemoradiotherapy regimens and within individual consensus molecular subtypes (CMS) and how they affect survival remain unclear. In this study, gene expression and clinical data of pretreatment biopsies from nine cohorts of primary rectal tumors were combined (N = 826).

A low molecular weight dextran sulphate, ILB®, for the treatment of amyotrophic lateral sclerosis (ALS): An open-label, single-arm, single-centre, phase II trial.

Background: Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig´s disease, is a rare neurological condition and is the most common motor neurone disease. It is a fatal disease with specific loss of motor neurons in the spinal cord, brain stem, and motor cortex leading to progressive paralysis and usually death within five years of diagnosis. There remains no cure for ALS, and management is focused on a combination of neuroprotective medication, respiratory support, and management by multidisciplinary clinics.

Ethaverine and Papaverine Target Cyclin-Dependent Kinase 5 and Inhibit Lung Cancer Cell Proliferation and Migration.

CDK5 kinase plays a central role in the regulation of neuronal functions, and its hyperactivation has been associated with neurodegenerative pathologies and more recently with several human cancers, in particular lung cancer. However, ATP-competitive inhibitors targeting CDK5 are poorly selective and suffer limitations, calling for new classes of inhibitors. In a screen for allosteric modulators of CDK5, we identified ethaverine and closely related derivative papaverine and showed that they inhibit cell proliferation and migration of non small cell lung cancer cell lines.

Transcriptomic characterization of human lateral septum neurons reveals conserved and divergent marker genes across species.

The lateral septum (LS) is a midline, subcortical structure, which regulates social behaviors that are frequently impaired in neurodevelopmental disorders including schizophrenia and autism spectrum disorder. Mouse studies have identified neuronal populations within the LS that express a variety of molecular markers, including vasopressin receptor, oxytocin receptor, and corticotropin releasing hormone receptor, which control specific facets of social behavior. Despite its critical role in regulating social behavior and notable gene expression patterns, comprehensive molecular profiling of the human LS has not been performed.

An International Expert-Based Consensus on the Definition of a Clinical Near-Complete Response After Neoadjuvant (Chemo)radiotherapy for Rectal Cancer.

Background: A variety of definitions for a clinical near-complete response after neoadjuvant (chemo) radiotherapy for rectal cancer are currently used. This variety leads to inconsistency in clinical practice, long-term outcome, and trial enrollment.

Objective: The aim of this study was to reach expert-based consensus on the definition of a clinical near-complete response after (chemo) radiotherapy.

Identifying priority sites for whale shark ship collision management globally.

The expansion of the world's merchant fleet poses a great threat to the ocean's biodiversity. Collisions between ships and marine megafauna can have population-level consequences for vulnerable species. The Endangered whale shark (Rhincodon typus) shares a circumglobal distribution with this expanding fleet and tracking of movement pathways has shown that large vessel collisions pose a major threat to the species.

Target fishing reveals PfPYK-1 and PfRab6 as potential targets of an antiplasmodial 4-anilino-2-trichloromethylquinazoline hit compound.

We present investigations about the mechanism of action of a previously reported 4-anilino-2-trichloromethylquinazoline antiplasmodial hit-compound (Hit A), which did not share a common mechanism of action with established commercial antimalarials and presented a stage-specific effect on the erythrocytic cycle of P. falciparum at 8 < t < 16 h. The target of Hit A was searched by immobilising the molecule on a solid support via a linker and performing affinity chromatography on a plasmodial lysate.

Distinct roles of Bdnf I and Bdnf IV transcript variant expression in hippocampal neurons.

Brain-derived neurotrophic factor (Bdnf) plays a critical role in brain development, dendritic growth, synaptic plasticity, as well as learning and memory. The rodent Bdnf gene contains nine 5' non-coding exons (I-IXa), which are spliced to a common 3' coding exon (IX). Transcription of individual Bdnf variants, which all encode the same BDNF protein, is initiated at unique promoters upstream of each non-coding exon, enabling precise spatiotemporal and activity-dependent regulation of Bdnf expression.

Generation of a human induced pluripotent stem cell line (UMGACBi001-A) from urine cells of a chronic kidney disease patient with hypertension, diabetic nephropathy and acute sepsis.

Chronic kidney disease is a major public health burden associated with a drastically reduced quality of living and life span that lacks suitable, individualized therapeutic strategies. Here we present a human induced pluripotent stem cell line (iPSC, UMGACBi001-A) reprogrammed from urine cells of an acute septic dialysis patient suffering from chronic kidney disease using non-integrating administration of RNAs. The generated iPSCs were positively characterized for typical morphology, pluripotency marker expression, directed differentiation potential, non-contamination, chromosomal consistency and donor identity.

Rett syndrome in Ireland: a demographic study.

Background: Rett syndrome (RTT) is a rare neurodevelopmental condition associated with mutations in the gene coding for the methyl-CpG-binding protein 2 (MECP2). It is primarily observed in girls and affects individuals globally. The understanding of the neurobiology of RTT and patient management has been improved by studies that describe the demographic and clinical presentation of individuals with RTT.