BubR1 Controls Heart Development by Promoting Expression of Cardiogenesis Regulators.

Background: Congenital heart defects are structural anomalies present at birth that can affect the function of the heart. Aneuploidy is a significant risk factor for congenital heart defects. Mosaic variegated aneuploidy syndrome, caused by mutations in (encoding BubR1, a mitotic checkpoint protein), leads to congenital heart defects such as septal defects.

Role of spindle assembly checkpoint proteins in gametogenesis and embryogenesis.

The spindle assembly checkpoint (SAC) is a surveillance mechanism that prevents uneven segregation of sister chromatids between daughter cells during anaphase. This essential regulatory checkpoint prevents aneuploidy which can lead to various congenital defects observed in newborns. Many studies have been carried out to elucidate the role of proteins involved in the SAC as well as the function of the checkpoint during gametogenesis and embryogenesis.

BubR1 and SIRT2: Insights into aneuploidy, aging, and cancer.

Aging is a significant risk factor for cancer which is due, in part, to heightened genomic instability. Mitotic surveillance proteins such as BubR1 play a pivotal role in ensuring accurate chromosomal segregation and preventing aneuploidy. BubR1 levels have been shown to naturally decline with age and its loss is associated with various age-related pathologies.

Effect of Divalent Metal Ions on the Ribonuclease Activity of the Toxin Molecule HP0894 from .

Bacteria and archaea respond and adapt to environmental stress conditions by modulating the toxin-antitoxin (TA) system for survival. Within the bacterium , the protein HP0894 is a key player in the HP0894-HP0895 TA system, in which HP0894 serves as a toxin and HP0895 as an antitoxin. HP0894 has intrinsic ribonuclease (RNase) activity that regulates gene expression and translation, significantly influencing bacterial physiology and survival.

PKCμ promotes keratinocyte cell migration through Cx43 phosphorylation-mediated suppression of intercellular communication.

Downregulation of intercellular communication through suppression of gap junctional conductance is necessary during wound healing. Connexin 43 (Cx43), a prominent gap junction protein in skin, is downregulated following wounding to restrict communication between keratinocytes. Previous studies found that PKCμ, a novel PKC isozyme, regulates efficient cutaneous wound healing.

Recent Progress in Modulation of WD40-Repeat Domain 5 Protein (WDR5): Inhibitors and Degraders.

WD40-repeat (WDR) domain proteins play a crucial role in mediating protein-protein interactions that sustain oncogenesis in human cancers. One prominent example is the interaction between the transcription factor MYC and its chromatin co-factor, WD40-repeat domain protein 5 (WDR5), which is essential for oncogenic processes. The MYC family of proteins is frequently overexpressed in various cancers and has been validated as a promising target for anticancer therapies.

Medical libraries and their complicated past: an exploration of the historical connections between medical collections and racial science.

For over a millennium, libraries and library workers have advanced the knowledge of human science by building, preserving, and sharing collections and research. Historically, libraries have also aligned their institutional responsibilities to adhere to and support the values and virtues of oppressive and colonial practices. Library history has shown the mistreatments and denials of information access of marginalized groups.

Role of Connexin 43 phosphorylation on Serine-368 by PKC in cardiac function and disease.

Intercellular communication mediated by gap junction channels and hemichannels composed of Connexin 43 (Cx43) is vital for the propagation of electrical impulses through cardiomyocytes. The carboxyl terminal tail of Cx43 undergoes various post-translational modifications including phosphorylation of its Serine-368 (S368) residue. Protein Kinase C isozymes directly phosphorylate S368 to alter Cx43 function and stability through inducing conformational changes affecting channel permeability or promoting internalization and degradation to reduce intercellular communication between cardiomyocytes.

Growth Characteristics of Female Radiation/Clinical Oncologists in South Asia: Assessment of Gender Neutrality and Leadership Position.

Aim: To evaluate the temporal growth pattern of female radiation/clinical oncologists (FRCOs) and, if applicable, predict the gender neutrality in different countries of South Asia.

Materials And Methods: South Asia is composed of Afghanistan, Bhutan, Maldives, Bangladesh, India, Nepal, Pakistan and Sri Lanka. The growth pattern of FRCOs in the latter five countries having radiation oncology facilities was evaluated from respective national registration data.

mTOR-driven neural circuit changes initiate an epileptogenic cascade.

Mutations in genes regulating mTOR pathway signaling are now recognized as a significant cause of epilepsy. Interestingly, these mTORopathies are often caused by somatic mutations, affecting variable numbers of neurons. To better understand how this variability affects disease phenotype, we developed a mouse model in which the mTOR pathway inhibitor Pten can be deleted from 0 to 40 % of hippocampal granule cells.

Impact of mTOR hyperactive neurons on the morphology and physiology of adjacent neurons: Do PTEN KO cells make bad neighbors?

Hyperactivation of the mechanistic target of rapamycin (mTOR) pathway is associated with epilepsy, autism and brain growth abnormalities in humans. mTOR hyperactivation often results from developmental somatic mutations, producing genetic lesions and associated dysfunction in relatively restricted populations of neurons. Disrupted brain regions, such as those observed in focal cortical dysplasia, can contain a mix of normal and mutant cells.

Self-reinforcing effects of mTOR hyperactive neurons on dendritic growth.

Loss of the mTOR pathway negative regulator PTEN from hippocampal dentate granule cells leads to neuronal hypertrophy, increased dendritic branching and aberrant basal dendrite formation in animal models. Similar changes are evident in humans with mTOR pathway mutations. These genetic conditions are associated with autism, cognitive dysfunction and epilepsy.

PTEN deletion increases hippocampal granule cell excitability in male and female mice.

Unlabelled: Deletion of the mTOR pathway inhibitor PTEN from postnatally-generated hippocampal dentate granule cells causes epilepsy. Here, we conducted field potential, whole cell recording and single cell morphology studies to begin to elucidate the mechanisms by which granule cell-specific PTEN-loss produces disease. Cells from both male and female mice were recorded to identify sex-specific effects.

Disrupted hippocampal network physiology following PTEN deletion from newborn dentate granule cells.

Abnormal hippocampal granule cells are present in patients with temporal lobe epilepsy, and are a prominent feature of most animal models of the disease. These abnormal cells are hypothesized to contribute to epileptogenesis. Isolating the specific effects of abnormal granule cells on hippocampal physiology, however, has been difficult in traditional temporal lobe epilepsy models.

MicroRNA-Mediated Downregulation of the Potassium Channel Kv4.2 Contributes to Seizure Onset.

Seizures are bursts of excessive synchronized neuronal activity, suggesting that mechanisms controlling brain excitability are compromised. The voltage-gated potassium channel Kv4.2, a major mediator of hyperpolarizing A-type currents in the brain, is a crucial regulator of neuronal excitability.

Olfactory Bulbectomy Leads to the Development of Epilepsy in Mice.

There is a clear link between epilepsy and depression. Clinical data demonstrate a 30-35% lifetime prevalence of depression in patients with epilepsy, and patients diagnosed with depression have a three to sevenfold higher risk of developing epilepsy. Traditional epilepsy models partially replicate the clinical observations, with the demonstration of depressive traits in epileptic animals.

Dengue in western Terai region of Nepal.

Background: Dengue Fever (DF) is an emerging mosquito-borne disease. It is a nagging public health problem in the low lands of Terai, expanding to new areas of Nepal in recent years.

Methods: A cross-sectional study was conducted to determine anti-Dengue IgM positive rate in Mahendranagar, Dhangadi and Dang between August 2008 and November 2009.

Impact of corticosterone treatment on spontaneous seizure frequency and epileptiform activity in mice with chronic epilepsy.

Stress is the most commonly reported precipitating factor for seizures in patients with epilepsy. Despite compelling anecdotal evidence for stress-induced seizures, animal models of the phenomena are sparse and possible mechanisms are unclear. Here, we tested the hypothesis that increased levels of the stress-associated hormone corticosterone (CORT) would increase epileptiform activity and spontaneous seizure frequency in mice rendered epileptic following pilocarpine-induced status epilepticus.

Excessive activation of mTOR in postnatally generated granule cells is sufficient to cause epilepsy.

The dentate gyrus is hypothesized to function as a "gate," limiting the flow of excitation through the hippocampus. During epileptogenesis, adult-generated granule cells (DGCs) form aberrant neuronal connections with neighboring DGCs, disrupting the dentate gate. Hyperactivation of the mTOR signaling pathway is implicated in driving this aberrant circuit formation.

Prognostic value of rapid test for diagnosis of dengue in Nepalese patients during 2010 epidemic.

Background: Dengue is an emerging vector borne disease in Nepal and rapid diagnostic test is important for early diagnosis of the disease.

Objectives: The aim of the study was to evaluate the diagnostic accuracy of commonly used rapid immunochromatographic test kit in Nepal during 2010 dengue epidemic and to assess disease burden of dengue.

Methods: A total of 131 acute and nonacute serum samples were collected during recent epidemic of dengue in 2010 from clinically suspected Nepalese patients of different hospitals.

Acute dengue infection in the western terai region of Nepal.

Introduction: Dengue fever is an emerging mosquito borne disease in Nepal claiming substantial morbidity and mortality. The objective of the study was to find out frequency of acute dengue infection in patients from the hospitals of the western Nepal.

Methods: The study was conducted between August 2007 and July 2008 in patients visiting hospitals of the western terai of Nepal with chief complains of fever.

Contributions of mature granule cells to structural plasticity in temporal lobe epilepsy.

During the development of epilepsy in adult animals, newly generated granule cells integrate abnormally into the hippocampus. These new cells migrate to ectopic locations in the hilus, develop aberrant basal dendrites, contribute to mossy fiber sprouting, and exhibit changes in apical dendrite structure and dendritic spine number. Mature granule cells do not appear to exhibit migration defects, basal dendrites, and mossy fiber sprouting, but whether they exhibit apical dendrite abnormalities or spine changes is not known.

Heterogeneous integration of adult-generated granule cells into the epileptic brain.

The functional impact of adult-generated granule cells in the epileptic brain is unclear, with data supporting both protective and maladaptive roles. These conflicting findings could be explained if new granule cells integrate heterogeneously, with some cells taking neutral or adaptive roles and others contributing to recurrent circuitry supporting seizures. Here, we tested this hypothesis by completing detailed morphological characterizations of age- and experience-defined cohorts of adult-generated granule cells from transgenic mice.