Dysfunction of Gpl1-Gih35-Wdr83 Complex in S. pombe Affects the Splicing of DNA Damage Repair Factors Resulting in Increased Sensitivity to DNA Damage.

Pre-mRNA splicing plays a key role in the regulation of gene expression. Recent discoveries suggest that defects in pre-mRNA splicing, resulting from the dysfunction of certain splicing factors, can impact the expression of genes crucial for genome surveillance mechanisms, including those involved in cellular response to DNA damage. In this study, we analyzed how cells with a non-functional spliceosome-associated Gpl1-Gih35-Wdr83 complex respond to DNA damage. Additionally, we investigated the role of this complex in regulating the splicing of factors involved in DNA damage repair. Our findings reveal that the deletion of any component within the Gpl1-Gih35-Wdr83 complex leads to a significant accumulation of unspliced pre-mRNAs of DNA repair factors. Consequently, mutant cells lacking this complex exhibit increased sensitivity to DNA-damaging agents. These results highlight the importance of the Gpl1-Gih35-Wdr83 complex in regulating the expression of DNA repair factors, thereby protecting the stability of the genome following DNA damage.

A mathematical model of obesity-induced type 2 diabetes and efficacy of anti-diabetic weight reducing drug.

The dominant paradigm for modeling the obesity-induced T2DM (type 2 diabetes mellitus) today focuses on glucose and insulin regulatory systems, diabetes pathways, and diagnostic test evaluations. The problem with this approach is that it is not possible to explicitly account for the glucose transport mechanism from the blood to the liver, where the glucose is stored, and from the liver to the blood. This makes it inaccurate, if not incorrect, to properly model the concentration of glucose in the blood in comparison to actual glycated hemoglobin (A1C) test results. In this paper, we develop a mathematical model of glucose dynamics by a system of ODEs. The model includes the mechanism of glucose transport from the blood to the liver, and from the liver to the blood, and explains how obesity is likely to lead to T2DM. We use the model to evaluate the efficacy of an anti-T2DM drug that also reduces weight.

Efectos en la motilidad de fármacos para obesidad: impacto en la práctica clínica y endoscópica / Effects of obesity drugs on gastrointestinal motility: impact on clinical and endoscopic practice

Obesity is a very common pathology worldwide. Among the management alternatives are glucagon-like peptide-1 (GLP-1) analogues, a hormone secreted mainly by the intestine. Apart from its effects as an incretin, effects on gastrointestinal motility have been described, which seem to be fundamental for its effect on obesity, but also the cause of its most frequent potential adverse effects. There is discussion regarding the large number of case reports in relation to the retention of gastric contents at the time of endoscopy. There is currently insufficient evidence to state categorically that they produce a significant change in gastric emptying. Nevertheless, it is recommended to inquire about the use of these drugs before endoscopic procedures that require sedation and, in the presence of symptoms, to suggest changes in the preparation

La obesidad es una patología muy frecuente a nivel global. Dentro de las alternativas del manejo están los análogos del péptido 1 similar al glucagón (GLP-1), hormona secretada principalmente por el intestino. Aparte de sus efec- tos como incretina, se han descrito efectos sobre la motilidad gastrointestinal, los que parecen ser fundamentales para su efecto sobre la obesidad, pero también los causales de sus potenciales efectos adversos más frecuentes. Existe discusión en relación con la gran cantidad de reportes de casos en relación con la retención de contenido gástrico al momento de una endoscopia. Actualmente no existe evidencia suficiente para afirmar categóricamente que producen un cambio significativo en el vaciamiento gástrico. No obstante, se recomienda indagar sobre el uso de estos fármacos antes de procedimientos endoscópicos que requieran sedación y, ante la presencia de síntomas, sugerir cambios en la preparación.

Defining the Functional Interactome of Spliceosome-Associated G-Patch Protein Gpl1 in the Fission Yeast Schizosaccharomyces pombe.

Pre-mRNA splicing plays a fundamental role in securing protein diversity by generating multiple transcript isoforms from a single gene. Recently, it has been shown that specific G-patch domain-containing proteins are critical cofactors involved in the regulation of splicing processes. In this study, using the knock-out strategy, affinity purification and the yeast-two-hybrid assay, we demonstrated that the spliceosome-associated G-patch protein Gpl1 of the fission yeast S. pombe mediates interactions between putative RNA helicase Gih35 (SPAC20H4.09) and WD repeat protein Wdr83, and ensures their binding to the spliceosome. Furthermore, RT-qPCR analysis of the splicing efficiency of deletion mutants indicated that the absence of any of the components of the Gpl1-Gih35-Wdr83 complex leads to defective splicing of fet5 and pwi1, the reference genes whose unspliced isoforms harboring premature stop codons are targeted for degradation by the nonsense-mediated decay (NMD) pathway. Together, our results shed more light on the functional interactome of G-patch protein Gpl1 and revealed that the Gpl1-Gih35-Wdr83 complex plays an important role in the regulation of pre-mRNA splicing in S. pombe.

Genetic variants associated with glycemic response to treatment with dipeptidylpeptidase 4 inhibitors.

Aim: We examined associations of eight SNPs in/near seven candidate genes with glycemic response to 6 month treatment with DPP4 inhibitors. Patients & methods: 206 patients with type 2 diabetes (116 men and 90 women) were treated with sitagliptin or vildagliptin (both 100 mg/day) in combination with metformin or metformin/sulphonylurea over 6 months, and the reduction in glycated hemoglobin (HbA1c) was measured. Results: Rs6923761 in GLP1R was significantly associated with a reduction in HbA1c (adjusted p = 0.006). Homozygotes for the minor A allele had smaller reduction in HbA1c by 0.4% (4 mmol/mol) than the G allele carriers (p = 0.016). Conclusion: The missense variant rs6923761 in the GLP1R gene was associated with a smaller glycemic response to 6 month gliptin therapy in diabetic patients of central European origin.

Determination of immunoreactivity ofPlasmodium falciparum antigens, serum dilutions and biomaterials.

Immunoreactivity properties of serum dilutions andPlasmodium falciparum malaria antigens were measured and compared by ELISA technique using different ELISA plates to evaluate the role of antigens and serum dilutions for optimum binding. Also effort has been made to see the effect of reaction surface and material i.e. ELISA plates for binding capacity. Serological properties were estimated by ELISA methods for detection of malaria and determination of immunological characteristics. Three Pf antigens (PfAg) i.e. ring infected erythrocyte surface antigen: AR-1 (RESA), histidine-rich protein 2 antigen (HRP-2) and glycophospholipid antigen (grown and developed Pf antigen from PSJ-M strain): GPL1 have been used for serological testing of human blood samples by Enzyme Link Immunosorbant Assay (ELISA). 1∶100, 1∶1000 and 1∶10000 dilutions of Pf positive and negative serum (50 samples in each group) and 1∶1000 dilution of Pf antigens were used to measure immunoreactive properties by ELISA method. Result of PfAg-serum immunoreactivity study showed that GPL1 has the highest degree of immuno binding reactivity compared to other Pf antigens. HRP-2 and RESA antigens showed no significant difference to each other. Study also found that Costar and Fastec ELISA plates have a better Ag-Ab binding capability compared to immulon and Falcon plates at all dilutions of serum. Serum dilution of 1∶100 showed best binding and reactivity with Pf antigens followed by 1∶1000 and 1∶10000 showed lowest reactivity.