Rice (Oryza sativa L.) yield enhancement is one of the prime objectives of plant breeders. Elucidation of the inheritance of grain weight, a key yield component trait, is of paramount importance for raising the yield thresholds in rice. In the present investigation, we employed Next-Generation Sequencing based QTL-seq approach to identify major genomic regions associated with grain weight using mapping populations derived from a cross between BPT5204 and MTU3626. QTL-seq analysis identified three grain weight quantitative trait loci (QTL) viz., qGW1 (35-40 Mb), qGW7 (10-18 Mb), and qGW8 (2-5 Mb) on chromosomes 1, 7 and 8, respectively and all are found to be novel. Further, qGW8 was confirmed through conventional QTL mapping in F2, F3 and BC1F2 populations and found to explain the phenotypic variance of 17.88%, 16.70% and 15.00%, respectively, indicating a major QTL for grain weight. Based on previous reports, two candidate genes in the qGW8 QTL were predicted i.e., LOC_Os08g01490 (Cytochrome P450), and LOC_Os08g01680 (WD domain, G-beta repeat domain containing protein) and through in silico analysis they were found to be highly expressed in reproductive organs during different stages of grain development. Here, we have demonstrated that QTL-seq is one of the rapid approaches to uncover novel QTLs controlling complex traits. The candidate genes identified in the present study undoubtedly enhance our understanding of the mechanism and inheritance of the grain weight. These candidate genes can be exploited for yield enhancement after confirmation through complementary studies.Polycystic ovary syndrome (PCOS) is a complex disease that causes an ovulatory infertility in approximately 10% of reproductive-age women. We searched for candidate proteins that might contribute to endometrial receptivity defects in PCOS patients, and result in adverse reproductive outcomes. Shotgun proteomics approach was used to investigate the proteome profile of the endometrium at the luteal phase in PCOS patients compared to healthy fertile individuals. Biological process and pathway analyses were conducted to categorize the proteins with differential expressions. Confirmation was performed for a number of proteins via immunoblotting in new samples. 150 proteins with higher abundance, and 46 proteins with lower abundance were identified in the endometrial tissue from PCOS patients compared to healthy fertile individuals. The proteins with higher abundance were enriched in protein degradation, cell cycle, and signaling cascades. Proteins with lower abundance in PCOS patients were enriched in extracellular matrix (ECM) composition and function, as well as the salvage pathway of purine biosynthesis. Metabolism was the most affected biological process with over 100 up-regulated, and approximately 30 down-regulated proteins. Our results indicate significant imbalances in metabolism, proteasome, cell cycle, ECM related proteins, and signaling cascades in endometrial tissue of PCOS, which may contribute to poor reproductive outcomes in these patients. We postulate that the endometria in PCOS patients may not be well-differentiated and synchronized for implantation. https://www.selleckchem.com/products/ot-82.html Possible roles of the above-mentioned pathways that underlie implantation failure in PCOS will be discussed. Our findings need to be confirmed in larger populations.Thiamine deficiency is associated with cerebellar dysfunction; however, the consequences of thiamine deficiency on the electrophysiological properties of cerebellar Purkinje cells are poorly understood. Here, we evaluated these parameters in brain slices containing cerebellar vermis. Adult mice were maintained for 12-13 days on a thiamine-free diet coupled with daily injections of pyrithiamine, an inhibitor of thiamine phosphorylation. Morphological analysis revealed a 20% reduction in Purkinje cell and nuclear volume in thiamine-deficient animals compared to feeding-matched controls, with no reduction in cell count. Under whole-cell current clamp, thiamine-deficient Purkinje cells required significantly less current injection to fire an action potential. This reduction in rheobase was not due to a change in voltage threshold. Rather, thiamine-deficient neurons presented significantly higher input resistance specifically in the voltage range just below threshold, which increases their sensitivity to current at these critical membrane potentials. In addition, thiamine deficiency caused a significant decrease in the amplitude of the action potential afterhyperpolarization, broadened the action potential, and decreased the current threshold for depolarization block. When thiamine-deficient animals were allowed to recover for 1 week on a normal diet, rheobase, threshold, action potential half-width, and depolarization block threshold were no longer different from controls. We conclude that thiamine deficiency causes significant but reversible changes to the electrophysiology properties of Purkinje cells prior to pathological morphological alterations or cell loss. Thus, the data obtained in the present study indicate that increased excitability of Purkinje cells may represent a leading indicator of cerebellar dysfunction caused by lack of thiamine.
A post hoc analysis of a double-blind (DB) active control trial and an open-label extension (OLE) study was conducted to evaluate the long-term effects of lurasidone in patients with schizophrenia.

In the DB trial, patients were randomised to receive lurasidone or risperidone for 12months. In OLE, all patients received lurasidone for an additional 6months. Treatment-emergent adverse events (TEAEs) were evaluated. Efficacy assessments included relapse rate (DB trial only), and Positive and Negative Syndrome Scale, Clinical Global Impression-Severity scale, and Montgomery-Åsberg Depression Rating Scale.

In the DB trial, patients with schizophrenia were randomised to lurasidone (n = 399) and risperidone (n = 190), of whom 129 and 84 continued into OLE, respectively. During the DB trial, incidence of TEAEs was similar for lurasidone (84.1%) and risperidone (84.2%). Lurasidone was associated with minimal changes in metabolic variables and prolactin levels, whereas risperidone was associated with clinically sidone experienced improvements in metabolic parameters and prolactin levels. These findings confirm lurasidone's long-term effectiveness and favourable metabolic profile in patients with schizophrenia.

ClinicalTrials.gov identifier NCT00641745.
ClinicalTrials.gov identifier NCT00641745.
Tissue engineering centers on creating a niche similar to the natural one, with a purpose of developing an organ construct. A natural scaffold can replace none while creating a scaffold unique to each tissue in composition, architecture and cues that regulate the character of cells.

Whole pancreas from mouse was decellularized using detergent and enzymes, followed by recellularizing with MSC from human placenta. This construct was transplanted in streptozotocin induced diabetic mice. Histopathology of both decellularized and recellularized transplanted pancreas and qPCR analysis were performed to assess its recovery.

Decellularization removes the cells leaving behind extracellular matrix rich natural scaffold. After reseeding with mesenchymal stem cells, these cells differentiate into pancreas specific cells. Upon transplantation in streptozotocin induced diabetic mice, this organ was capable of restoring its histomorphology and functioning. Restoration of endocrine (islets), the exocrine region (acinar) and vascular network was seen in transplanted pancreas. The process of functional recovery of endocrine system took about 20days when the mice start showing blood glucose reduction, though none achieved gluconormalization.

Natural decellularized scaffolds of soft organs can be refunctionalized using recipient's mesenchymal stem cells to restore structure and function; and counter immune problems arising during transplantation.
Natural decellularized scaffolds of soft organs can be refunctionalized using recipient's mesenchymal stem cells to restore structure and function; and counter immune problems arising during transplantation.Direct reprogramming/direct conversion/transdifferentiation is a process that induces conversion between completely different matured (differentiated) cells in higher organisms. Unlike the process of reprogramming of differentiated cells into induced pluripotent stem cells (iPSCs) and re-differentiation into the desired cell types, differentiated cells undergo the conversion into another type of differentiated cells without going through the iPSCs state. Osteoarthritis (OA) is the most common type of arthritis that causes a significant deterioration in patients' quality of life. The high prevalence of OA as well as the current lack of disease-modifying drugs has led to a rise in regenerative strategy for OA treatment. Regenerative therapy in OA started with the concept of engraftment of the administered cells within the cartilage lesion and differentiation to chondrocytes after the engraftment. However, recent studies show that cells, particularly when injected in suspension, rapidly undergo apoptosis after exerting a transient paracrine effect. In this perspective review, the general overview and current status of direct conversion are introduced along with the conceptual strategy and future directions for possible application of regenerative therapy using stem cells in OA. In vivo direct conversion may open a new stage of regenerative medicine for OA treatment. Recent advances in in vivo gene transfer and smart biomaterials can bring the concept into reality in near future. Direct conversion can be a new type of treatment technology that has the potential to overcome the limitations of current cell therapy.Forkhead box (FOX) proteins have been identified as key transcription factors in diverse biological processes involved in tumor progression. A large number of FOX proteins are implicated in tumorigenesis of papillary thyroid carcinoma (PTC). Here we investigated the role of Forkhead box K1 (FOXK1) in PTC progression. First, we found that FOXK1 was elevated in both PTC tissues (N = 68) and cell lines. Moreover, up-regulated FOXK1 was associated with shorter overall survival of PTC patients. Second, in vitro functional assays showed that FOXK1 promoted progression of PTC. Mechanistically, FOXK1 could bind to the promoter of cysteine-rich angiogenic inducer 61 (CYR61) and regulate connective tissue growth factor (CTGF) expression through CYR61. Notably, over-expression of CTGF weakened suppression of PTC progression induced by FOXK1 knockdown. Finally, in vivo xenotransplant tumor model indicated that knockdown of FOXK1 suppressed PTC growth. In conclusion, our results indicate that FOXK1 exerts oncogenic roles in PTC via CYR61/CTGF axis, which suggests FOXK1 might act as a potential therapeutic target.Microbes like viruses, bacteria, and fungi have all been reported in the brain of Alzheimer's postmortem patients and/or AD mouse model; however, the relationship between brain microbes and Aβ plaque deposition remains to be elucidated. In the present study, we first analyzed bacteria populations in the brain of 4-, 5-, and 6-month-old APP/PS1 mice and then examined the Aβ-positive loads of APP/PS1 mouse at 9 months old to identify bacteria in the brain by 16S rDNA sequencing. Finally, blood-brain barrier permeability was measured by injecting dextrans through the tail vein. Surprisingly, the diversity of microbial community gradually decreased in APP/PS1 mouse while wild-type mouse showed no obvious regularity. Moreover, Aβ-positive deposits in the brain showed a significantly higher relative abundance of microbiota than Aβ-negative tissues and age-matched wild-type mouse brain tissues. In addition, an increase in blood-brain barrier permeability was also observed in APP/PS1 mouse. The present study revealed the exact location of microbes within the Aβ plaques in the brain and suggested the potential antimicrobial effect of the Aβ peptide.