BiP/GRP78 is a pro-viral factor for diverse dsDNA viruses that promotes the survival and proliferation of cells upon KSHV infection.

The Endoplasmic Reticulum (ER)-resident HSP70 chaperone BiP (HSPA5) plays a crucial role in maintaining and restoring protein folding homeostasis in the ER. BiP's function is often dysregulated in cancer and virus-infected cells, conferring pro-oncogenic and pro-viral advantages. We explored BiP's functions during infection by the Kaposi's sarcoma-associated herpesvirus (KSHV), an oncogenic gamma-herpesvirus associated with cancers of immunocompromised patients.

The mechanics of correlated variability in segregated cortical excitatory subnetworks.

Understanding the genesis of shared trial-to-trial variability in neuronal population activity within the sensory cortex is critical to uncovering the biological basis of information processing in the brain. Shared variability is often a reflection of the structure of cortical connectivity since it likely arises, in part, from local circuit inputs. A series of experiments from segregated networks of (excitatory) pyramidal neurons in the mouse primary visual cortex challenge this view.

Evaluation of self-collected nasal, urine, and saliva samples for molecular detection of SARS-CoV-2 using an EUA approved RT-PCR assay and a laboratory developed LAMP SARS-CoV-2 test.

As the SARS-CoV-2 virus spread throughout the world, millions of positive cases of COVID-19 were registered and, even though there are millions of people already vaccinated against SARS-CoV-2, a large part of the global population remains vulnerable to contracting the virus. Massive nasopharyngeal sample collection in Puerto Rico at the beginning of the pandemic was limited by the scarcity of trained personnel and testing sites. To increase SARS-CoV-2 molecular testing availability, we evaluated the diagnostic accuracy of self-collected nasal, saliva, and urine samples using the TaqPath reverse transcription polymerase chain reaction (RT-PCR) COVID-19 kit to detect SARS-CoV-2.

The mechanics of correlated variability in segregated cortical excitatory subnetworks.

Understanding the genesis of shared trial-to-trial variability in neural activity within sensory cortex is critical to uncovering the biological basis of information processing in the brain. Shared variability is often a reflection of the structure of cortical connectivity since this variability likely arises, in part, from local circuit inputs. A series of experiments from segregated networks of (excitatory) pyramidal neurons in mouse primary visual cortex challenge this view.

Genetic activation of glucokinase in a minority of pancreatic beta cells causes hypoglycemia in mice.

Aims: Glucokinase (GK) is expressed in the glucose-sensing cells of the islets of Langerhans and plays a critical role in glucose homeostasis. Here, we tested the hypothesis that genetic activation of GK in a small subset of β-cells is sufficient to change the glucose set-point of the whole islet.

Material And Methods: Mouse models of cell-type specific GK deficiency (GKKO) and genetic enzyme activation (GKKI) in a subset of β-cells were obtained by crossing the αGSU (gonadotropin alpha subunit)-Cre transgene with the appropriate GK mutant alleles.

Development of the gonadotropin-releasing hormone system.

This review summarizes the current understanding of the development of the neuroendocrine gonadotropin-releasing hormone (GnRH) system, including discussion on open questions regarding (1) transcriptional regulation of the Gnrh1 gene; (2) prenatal development of the GnRH1 system in rodents and humans; and (3) paracrine and synaptic communication during migration of the GnRH cells.

Deficiency of arcuate nucleus kisspeptin results in postpubertal central hypogonadism.

Kisspeptin (encoded by ), a neuropeptide critically involved in neuroendocrine regulation of reproduction, is primarily synthesized in two hypothalamic nuclei: the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC). AVPV kisspeptin is thought to regulate the estrogen-induced positive feedback control of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH), and the preovulatory LH surge in females. In contrast, ARC kisspeptin neurons, which largely coexpress neurokinin B and dynorphin A (collectively named KNDy neurons), are thought to mediate estrogen-induced negative feedback control of GnRH/LH and be the major regulators of pulsatile GnRH/LH release.

Ectopic Lymphoid Follicles in Multiple Sclerosis: Centers for Disease Control?

While the contribution of autoreactive CD4 T cells to the pathogenesis of Multiple Sclerosis (MS) is widely accepted, the advent of B cell-depleting monoclonal antibody (mAb) therapies has shed new light on the complex cellular mechanisms underlying MS pathogenesis. Evidence supports the involvement of B cells in both antibody-dependent and -independent capacities. T cell-dependent B cell responses originate and take shape in germinal centers (GCs), specialized microenvironments that regulate B cell activation and subsequent differentiation into antibody-secreting cells (ASCs) or memory B cells, a process for which CD4 T cells, namely follicular T helper (T) cells, are indispensable.

High-Fat Diet Alters LH Secretion and Pulse Frequency in Female Mice in an Estrous Cycle-Dependent Manner.

Reproductive fitness in females is susceptible to obesogenic diets. Energy balance and reproduction are tightly regulated, in part, by hypothalamic neurons in the arcuate nucleus (ARC), and high-fat diet (HFD) can steadily increase estradiol levels in rodents. Estradiol regulates the reproductive axis via negative feedback mechanisms in ARC neurons by modulating pulsatile release of the gonadotropin luteinizing hormone (LH).

Uterine Gpr83 mRNA is highly expressed during early pregnancy and GPR83 mediates the actions of PEN in endometrial and non-endometrial cells.

Objective: To characterize the expression and signaling of uterine GPR83 in vivo in the nonpregnant and pregnant mouse and in vitro in human endometrial and nonendometrial cells.

Design: Controlled laboratory study.

Setting: Not applicable.

Hospitalization and definitive radiotherapy in lung cancer: incidence, risk factors and survival impact.

Background: Unplanned hospitalization during cancer treatment is costly, can disrupt treatment, and affect patient quality of life. However, incidence and risks factors for hospitalization during lung cancer radiotherapy are not well characterized.

Methods: Patients treated with definitive intent radiation (≥45 Gy) for lung cancer between 2008 and 2018 at a tertiary academic institution were identified.

Targeted Deletion of PTEN in Kisspeptin Cells Results in Brain Region- and Sex-Specific Effects on Kisspeptin Expression and Gonadotropin Release.

Kisspeptin-expressing neurons in the anteroventral periventricular nucleus (AVPV) and the arcuate nucleus (ARC) of the hypothalamus relay hormonal and metabolic information to gonadotropin-releasing hormone neurons, which in turn regulate pituitary and gonadal function. Phosphatase and tensin homolog (PTEN) blocks phosphatidylinositol 3-kinase (PI3K), a signaling pathway utilized by peripheral factors to transmit their signals. However, whether PTEN signaling in kisspeptin neurons helps to integrate peripheral hormonal cues to regulate gonadotropin release is unknown.

Exploring the Relationship of Radiation Dose Exposed to the Length of Esophagus and Weight Loss in Patients with Lung Cancer.

Purpose: We investigate whether esophageal dose-length parameters (L) can robustly predict significant weight loss-≥5% weight loss during radiation therapy (RT) compared with the weight before RT-in patients with lung cancer treated with definitive intent.

Methods And Materials: Patients with lung cancer treated with conventionally fractionated RT between 2010 and 2018 were retrospectively identified. L and L, the length of full- and partial-circumferential esophagus receiving greater than a threshold dose in Gy, respectively, were created.

Maize-Produced Ag2 as a Subunit Vaccine for Valley Fever.

Coccidioides is the causative agent of San Joaquin Valley fever, a fungal disease prevalent in the semiarid regions of the Americas. Efforts to develop a fungal vaccine over the last 2 decades were unsuccessful. A candidate antigen, Antigen 2 (Ag2), is notoriously difficult to express in Escherichia coli, and this study sought to accumulate the antigen at high levels in maize.

The role of B cells in multiple sclerosis: Current and future therapies.

While it was long held that T cells were the primary mediators of multiple sclerosis (MS) pathogenesis, the beneficial effects observed in response to treatment with Rituximab (RTX), a monoclonal antibody (mAb) targeting CD20, shed light on a key contributor to MS that had been previously underappreciated: B cells. This has been reaffirmed by results from clinical trials testing the efficacy of subsequently developed B cell-depleting mAbs targeting CD20 as well as studies revisiting the effects of previous disease-modifying therapies (DMTs) on B cell subsets thought to modulate disease severity. In this review, we summarize current knowledge regarding the complex roles of B cells in MS pathogenesis and current and potential future B cell-directed therapies.

Glucan-Chitin Particles Enhance Th17 Response and Improve Protective Efficacy of a Multivalent Antigen (rCpa1) against Pulmonary Coccidioides posadasii Infection.

Developing an effective and safe recombinant vaccine requires microbe-specific antigens combined with an adjuvant/delivery system to strengthen protective immunity. In this study, we designed and expressed a multivalent recombinant polypeptide antigen (rCpa1) that consists of three previously identified antigens (i.e.

The 3 World Conference on Kisspeptin, "Kisspeptin 2017: Brain and Beyond":Unresolved questions, challenges and future directions for the field.

The 3 World Conference on Kisspeptin, "Kisspeptin 2017: Brain and Beyond" was held March 30-31 at the Rosen Centre Hotel in Orlando, Florida, providing an international forum for multidisciplinary scientists to meet and share cutting-edge research on kisspeptin biology and its relevance to human health and disease. The meeting built upon previous world conferences focused on the role of kisspeptin and associated peptides in the control of gonadotropin-releasing hormone (GnRH) secretion and reproduction. Based on recent discoveries, the scope of this meeting was expanded to include functions of kisspeptin and related peptides in other physiological systems including energy homeostasis, pregnancy, ovarian and uterine function, and thermoregulation.

Loss of PI3K p110 in the Adipose Tissue Results in Infertility and Delayed Puberty Onset in Male Mice.

Deletion of PI3K catalytic subunit p110 in adipose tissue (aP2-Cre/p110, -/- hereafter) results in increased adiposity, glucose intolerance, and liver steatosis. Because this endocrine organ releases hormones like leptin, which are important in reproductive physiology, we investigated the reproductive phenotype of -/- males. Compared to controls, -/- males displayed delayed onset of puberty accompanied by a reduction in plasma LH levels and testicular weight.

Comparative Resuscitative Methods for Venlafaxine Toxicity in a Swine Model.

Objectives: Venlafaxine overdose can lead to cardiovascular collapse that is difficult to resuscitate with traditional Advanced Cardiovascular Life Support protocols. Evidence has suggested that lipid emulsion infusion therapy has been successful in the treatment of antidepressant overdose. No studies have determined the optimal combination of lipid/advanced cardiovascular life support therapy for treatment.

[C677T polymorphism of the methylentetrahydrofolate reductase gene in mothers of children affected with neural tube defects].

Neural tube defects (NTD) are the most common congenital anomalies of the central nervous system, with a multifactorial pattern of inheritance, presumably involving the interaction of several genetic and environmental factors. The methylenetetrahydrofolate reductase (MTHFR) gene 677C>T polymorphism has been implicated as a risk factor for NTD. The main objective of this research was to investigate the association of the 677C>T polymorphism of the MTHFR gene as a genetic risk factor for NTD.

Prolonged hyperglycemia & hyperinsulinemia increases BDNF mRNA expression in the posterior ventromedial hypothalamus and the dorsomedial hypothalamus of fed female rats.

Brain-derived neurotrophic factor (BDNF) plays a key role in neuronal development, synaptic plasticity, and the central control of energy homeostasis. Peripheral metabolic signals such as leptin and glucose regulate hypothalamic BDNF gene expression. However, the effects of long-term hyperglycemia and/or hyperinsulinemia on BDNF mRNA levels in the hypothalamus and other brain regions where BDNF regulates physiological functions have not been investigated.

Kisspeptin cell-specific PI3K signaling regulates hypothalamic kisspeptin expression and participates in the regulation of female fertility.

Hypothalamic kisspeptin neurons integrate and translate cues from the internal and external environments that regulate gonadotropin-releasing hormone (GnRH) secretion and maintain fertility in mammals. However, the intracellular signaling pathways utilized to translate such information into changes in kisspeptin expression, release, and ultimately activation of the kisspeptin-receptive GnRH network have not yet been identified. PI3K is an important signaling node common to many peripheral factors known to regulate kisspeptin expression and GnRH release.

Galanin-like peptide (GALP) neurone-specific phosphoinositide 3-kinase signalling regulates GALP mRNA levels in the hypothalamus of males and luteinising hormone levels in both sexes.

Galanin-like peptide (GALP) neurones participate in the metabolic control of reproduction and are targets of insulin and leptin regulation. Phosphoinositide 3-kinase (PI3K) is common to the signalling pathways utilised by both insulin and leptin. Therefore, we investigated whether PI3K signalling in neurones expressing GALP plays a role in the transcriptional regulation of the GALP gene and in the metabolic control of luteinising hormone (LH) release.

A clock reaction based on molybdenum blue.

Clock reactions are rare kinetic phenomena, so far limited mostly to systems with ionic oxoacids and oxoanions in water. We report a new clock reaction in cyclohexanol that forms molybdenum blue from a noncharged, yellow molybdenum complex as precursor, in the presence of hydrogen peroxide. Interestingly, the concomitant color change is reversible, enabling multiple clock cycles to be executed consecutively.