Leishmania mexicana N-Acetyltransferease 10 Is Important for Polysome Formation and Cell Cycle Progression.

Leishmania presents a complex life cycle that involves both invertebrate and vertebrate hosts. By regulating gene expression, protein synthesis, and metabolism, the parasite can adapt to various environmental conditions. This regulation occurs mainly at the post-transcriptional level and may involve epitranscriptomic modifications of RNAs.

Identifying candidate genes for sugar accumulation in sugarcane: an integrative approach.

Background: Elucidating the intricacies of the sugarcane genome is essential for breeding superior cultivars. This economically important crop originates from hybridizations of highly polyploid Saccharum species. However, the large size (10 Gb), high degree of polyploidy, and aneuploidy of the sugarcane genome pose significant challenges to complete genome sequencing, assembly, and annotation.

An experimental target-based platform in yeast for screening Plasmodium vivax deoxyhypusine synthase inhibitors.

The enzyme deoxyhypusine synthase (DHS) catalyzes the first step in the post-translational modification of the eukaryotic translation factor 5A (eIF5A). This is the only protein known to contain the amino acid hypusine, which results from this modification. Both eIF5A and DHS are essential for cell viability in eukaryotes, and inhibiting DHS is a promising strategy to develop new therapeutic alternatives.

Rational Exploration of 2,4-Diaminopyrimidines as DHFR Inhibitors Active against and , Two Emerging Human Pathogens.

Nontuberculous mycobacteria (NTM) are emerging human pathogens linked to severe pulmonary diseases. Current treatments involve the prolonged use of multiple drugs and are often ineffective. Bacterial dihydrofolate reductase (DHFR) is a key enzyme targeted by antibiotics in Gram-negative bacterial infections.

Novel variants in the SOX11 gene: clinical description of seven new patients.

Pathogenic SOX11 variants have been associated with intellectual developmental disorder with microcephaly, and with or without ocular malformations or hypogonadotropic hypogonadism (HH) (IDDMOH, OMIM # 615866). In this article, we report seven new patients with de novo SOX11 variants. Five of the variants are missense, one nonsense, and one whole-gene deletion, most of them are novel variants.

An Intricate Network Involving the Argonaute ALG-1 Modulates Organismal Resistance to Oxidative Stress.

Cellular response to redox imbalance is crucial for organismal health. microRNAs are implicated in stress responses. ALG-1, the C.

X-linked congenital adrenal hypoplasia: Report of long clinical follow-up and description of a new complex variant in the NR0B1 gene.

Adrenal hypoplasia congenita, attributed to NR0B1 pathogenic variants, accounts for more than 50% of the incidence of primary adrenal insufficiency in children. Although more than 250 different deleterious variations have been described, no genotype-phenotype correlation has been defined to date. We report a case of an adopted boy who reported the onset of an adrenal crisis at 2 weeks of age, requiring replacement therapy with mineralocorticoids and glucocorticoids for 4 months.

Discovery of pyrazolo[3,4-d]pyrimidines as novel mitogen-activated protein kinase kinase 3 (MKK3) inhibitors.

The dual-specificity protein kinase MKK3 has been implicated in tumor cell proliferation and survival, yet its precise role in cancer remains inconclusive. A critical step in elucidating the kinase's involvement in disease biology is the identification of potent, cell-permeable kinase inhibitors. Presently, MKK3 lacks a dedicated tool compound for these purposes, along with validated methods for the facile screening, identification, and optimization of inhibitors.

Genome-wide family prediction unveils molecular mechanisms underlying the regulation of agronomic traits in .

Tropical forage grasses, particularly those belonging to the genus, play a crucial role in cattle production and serve as the main food source for animals in tropical and subtropical regions. The majority of these species are apomictic and tetraploid, highlighting the significance of , a sexual diploid species that can be tetraploidized for use in interspecific crosses with apomictic species. As a means to support breeding programs, our study investigates the feasibility of genome-wide family prediction in families to predict agronomic traits.

DHX37 and the Implications in Disorders of Sex Development: An Update Review.

Background: DHX37 is an autosomal gene responsible for encoding a helicase from the DExD/H-box family that plays an essential role in ribosome biogenesis. Variants in this gene were previously reported in two different phenotypes: neurodevelopmental disorders and disorders/differences of sex development (DSD). Particularly for the DSD group, variants were mainly reported associated with gonadal dysgenesis and testicular regression syndrome.

Improved protocol for polymerase and reverse transcriptase production and application to a point-of-care diagnostics system.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has raised awareness in the scientific community about the importance of being prepared for sanitary emergencies. Many measures implemented during the COVID pandemic are now being expanded to other applications. In the field of molecular and immunological diagnostics, the need to massively test the population worldwide resulted in the application of a variety of methods to detect viral infection.

Deregulation of ABCG1 early in life contributes to prostate carcinogenesis in maternally malnourished offspring rats.

The developmental Origins of Health and Disease (DOHaD) concept has provided the framework to assess how early life experiences can shape health and disease throughout the life course. Using a model of maternal exposure to a low protein diet (LPD; 6% protein) during the gestational and lactational periods, we demonstrated changes in the ventral prostate (VP) transcriptomic landscape in young rats exposed to maternal malnutrition. Male offspring Sprague Dawley rats were submitted to maternal malnutrition during gestation and lactation, and they were weighed, and distance anogenital was measured, followed were euthanized by an overdose of anesthesia at 21 postnatal days.

Inference of differential key regulatory networks and mechanistic drug repurposing candidates from scRNA-seq data with SCANet.

Motivation: The reconstruction of small key regulatory networks that explain the differences in the development of cell (sub)types from single-cell RNA sequencing is a yet unresolved computational problem.

Results: To this end, we have developed SCANet, an all-in-one package for single-cell profiling that covers the whole differential mechanotyping workflow, from inference of trait/cell-type-specific gene co-expression modules, driver gene detection, and transcriptional gene regulatory network reconstruction to mechanistic drug repurposing candidate prediction. To illustrate the power of SCANet, we examined data from two studies.

Interactions of the male contraceptive target EPPIN with semenogelin-1 and small organic ligands.

Novel male contraceptives will promote gender equality in sharing contraceptive responsibility. The sperm-associated protein epididymal protease inhibitor (EPPIN) is a promising target for non-hormonal male contraception. EPPIN interacts with the semen coagulum protein semenogelin-1 (SEMG1) on the sperm surface, leading to transient inhibition of sperm motility after ejaculation.

The CCP4 suite: integrative software for macromolecular crystallography.

The Collaborative Computational Project No. 4 (CCP4) is a UK-led international collective with a mission to develop, test, distribute and promote software for macromolecular crystallography. The CCP4 suite is a multiplatform collection of programs brought together by familiar execution routines, a set of common libraries and graphical interfaces.

and Variants Identified in Patients with 46,XY Partial Gonadal Dysgenesis.

The group of disorders known as 46,XY gonadal dysgenesis (GD) is characterized by anomalies in testis determination, including complete and partial GD (PGD) and testicular regression syndrome (TRS). Several genes are known to be involved in sex development pathways, however approximately 50% of all cases remain elusive. Recent studies have identified variants in , a gene encoding a putative RNA helicase essential in ribosome biogenesis and previously associated with neurodevelopmental disorders, as a cause of PGD and TRS.

A novel BRET-based assay to investigate binding and residence time of unmodified ligands to the human lysosomal ion channel TRPML1 in intact cells.

Here, we report a bioluminescence resonance energy transfer (BRET) assay as a novel way to investigate the binding of unlabeled ligands to the human transient receptor potential mucolipin 1 (hTRPML1), a lysosomal ion channel involved in several genetic diseases and cancer progression. This novel BRET assay can be used to determine equilibrium and kinetic binding parameters of unlabeled compounds to hTRPML1 using intact human-derived cells, thus complementing the information obtained using functional assays based on ion channel activation. We expect this new BRET assay to expedite the identification and optimization of cell-permeable ligands that interact with hTRPML1 within the physiologically relevant environment of lysosomes.

Whole-genome sequencing and comparative genomic analysis of potential biotechnological strains of Trichoderma harzianum, Trichoderma atroviride, and Trichoderma reesei.

Trichoderma atroviride and Trichoderma harzianum are widely used as commercial biocontrol agents against plant diseases. Recently, T. harzianum IOC-3844 (Th3844) and T.

Comparative transcriptome analysis of endothelial progenitor cells of HbSS patients with and without proliferative retinopathy.

Among sickle cell anemia (SCA) complications, proliferative sickle cell retinopathy (PSCR) is one of the most important, being responsible for visual impairment in 10-20% of affected eyes. The aim of this study was to identify differentially expressed genes (DEGs) present in pathways that may be implicated in the pathophysiology of PSCR from the transcriptome profile analysis of endothelial progenitor cells. RNA-Seq was used to compare gene expression profile of circulating endothelial colony-forming cells (ECFCs) from HbSS patients with and without PSCR.

Association of variants in the (rs7137828), (rs2745572) and (rs35934224) genes as risk factors for primary open-angle glaucoma development in a Brazilian cohort.

Background: Primary open-angle glaucoma (POAG), the world's main cause of irreversible blindness, is an asymptomatic and neurodegenerative disease of multifactorial etiology with ethnic and geographic disparities. Multiethnic genome-wide association studies (GWAS) identified single nucleotide variants (SNVs) in , and loci as risk factors for POAG pathophysiology and/or endophenotypes. The aim of this case-control study was to investigate the association of the variants rs7137828 (), rs2745572 (), and rs35934224 (), as risk factors for POAG development, additionally to rs7137828 association with glaucoma clinical parameters in a Brazilian cohort from the Southeast and South regions.

Classification and genetics of pediatric B-other acute lymphoblastic leukemia by targeted RNA sequencing.

Acute lymphoblastic leukemia (ALL) can be classified into different subgroups based on recurrent genetic alterations. Here, targeted RNA sequencing was used to identify the novel subgroups of ALL in 144 B-other and 40 "classical" ALL samples. The classical TCF3-PBX1, ETV6-RUNX1, KMT2A-rearranged, and BCR-ABL1, and novel P2RY8-CRLF2, ABL-, JAK2-, ZNF384-, MEF2D-, and NUTM1-fusions were easily identified by fusion transcript analysis.

UHMK1 is a novel splicing regulatory kinase.

The U2AF Homology Motif Kinase 1 (UHMK1) is the only kinase that contains the U2AF homology motif, a common protein interaction domain among splicing factors. Through this motif, UHMK1 interacts with the splicing factors SF1 and SF3B1, known to participate in the 3' splice site recognition during the early steps of spliceosome assembly. Although UHMK1 phosphorylates these splicing factors in vitro, the involvement of UHMK1 in RNA processing has not previously been demonstrated.