The impact of chronic intermittent hypoxia on enzymatic activity in memory-associated brain regions of male and female rats.

Background: Obstructive sleep apnea (OSA) is an intermittent hypoxia disorder associated with cognitive dysfunction, including learning and memory impairments. There is evidence that alterations in protease activity and neuronal activation as associated with cognitive dysfunction, are dependent on sex, and may be brain region-specific. However, the mechanisms mediating OSA-induced cognitive impairments are unclear.

A Case of BRASH Syndrome Presenting With Refractory Hyperkalemia Requiring Intermittent Hemodialysis.

BRASH syndrome characterized by bradycardia, renal dysfunction, atrioventricular nodal blockade (AVNB), shock, and hyperkalemia presents diagnostic and management challenges due to its complex pathophysiology and varied clinical presentations. We describe a 90-year-old woman with a history of multiple comorbidities who was on beta blockers bisoprolol for heart failure, presented with shock, refractory hyperkalemia along with bradycardia that required intermittent hemodialysis. Initial management involved aggressive hyperkalemia medical therapy and fluid resuscitation, with subsequent consideration of renal replacement therapy hemodialysis following collaboration with a multidisciplinary team, including cardiology and nephrology specialists.

CRISPR screens unveil nutrient-dependent lysosomal and mitochondrial nodes impacting intestinal tissue-resident memory CD8 T cell formation.

Nutrient availability and organelle biology direct tissue homeostasis and cell fate, but how these processes orchestrate tissue immunity remains poorly defined. Here, using in vivo CRISPR-Cas9 screens, we uncovered organelle signaling and metabolic processes shaping CD8 tissue-resident memory T (T) cell development. T cells depended on mitochondrial translation and respiration.

Elderly care in Nepal: Are existing health and community support systems enough.

In Nepal, a few governmental and community-based programmes for elderly care are in place; however, information about successful implementation and overall effectiveness of these programmes is not well understood. In this article, we introduced these programmes and discussed existing programmes' gaps and implementation problems in light of existing grey and peer-reviewed evidence. A few notable governmental programmes, such as providing monthly allowances, pensions and free health care, have targeted specifically the elderly individuals.

Risk Assessment in Artisanal Fisheries in Developing Countries: A Systematic Review.

Introduction: Artisanal fisheries generally do not have injury prevention plans and safety or quality management systems on board, thus making them prone to more fatal and nonfatal injuries. The objective of the study is to systematically review and synthesize the literature to identify the risks of injuries (fatal and nonfatal) and health problems in artisanal fisheries in developing countries.

Methods: A systematic literature search was carried out from December 2019 to March 2020.

Maintenance of CD4 T cell fitness through regulation of Foxo1.

Foxo transcription factors play an essential role in regulating specialized lymphocyte functions and in maintaining T cell quiescence. Here, we used a system in which Foxo1 transcription-factor activity, which is normally terminated upon cell activation, cannot be silenced, and we show that enforcing Foxo1 activity disrupts homeostasis of CD4 conventional and regulatory T cells. Despite limiting cell metabolism, continued Foxo1 activity is associated with increased activation of the kinase Akt and a cell-intrinsic proliferative advantage; however, survival and cell division are decreased in a competitive setting or growth-factor-limiting conditions.

Metabolism in Immune Cell Differentiation and Function.

The immune system is a central determinant of organismal health. Functional immune responses require quiescent immune cells to rapidly grow, proliferate, and acquire effector functions when they sense infectious agents or other insults. Specialized metabolic programs are critical regulators of immune responses, and alterations in immune metabolism can cause immunological disorders.

Homeostatic control of metabolic and functional fitness of T cells by LKB1 signalling.

Regulatory T cells (T cells) have a pivotal role in the establishment and maintenance of immunological self-tolerance and homeostasis. Transcriptional programming of regulatory mechanisms facilitates the functional activation of T cells in the prevention of diverse types of inflammatory responses. It remains unclear how T cells orchestrate their homeostasis and interplay with environmental signals.

mTORC1 and mTORC2 Kinase Signaling and Glucose Metabolism Drive Follicular Helper T Cell Differentiation.

Follicular helper T (Tfh) cells are crucial for germinal center (GC) formation and humoral adaptive immunity. Mechanisms underlying Tfh cell differentiation in peripheral and mucosal lymphoid organs are incompletely understood. We report here that mTOR kinase complexes 1 and 2 (mTORC1 and mTORC2) are essential for Tfh cell differentiation and GC reaction under steady state and after antigen immunization and viral infection.

Metabolic reprogramming of alloantigen-activated T cells after hematopoietic cell transplantation.

Alloreactive donor T cells are the driving force in the induction of graft-versus-host disease (GVHD), yet little is known about T cell metabolism in response to alloantigens after hematopoietic cell transplantation (HCT). Here, we have demonstrated that donor T cells undergo metabolic reprograming after allogeneic HCT. Specifically, we employed a murine allogeneic BM transplant model and determined that T cells switch from fatty acid β-oxidation (FAO) and pyruvate oxidation via the tricarboxylic (TCA) cycle to aerobic glycolysis, thereby increasing dependence upon glutaminolysis and the pentose phosphate pathway.

Autophagy enforces functional integrity of regulatory T cells by coupling environmental cues and metabolic homeostasis.

Regulatory T (Treg) cells respond to immune and inflammatory signals to mediate immunosuppression, but how the functional integrity of Treg cells is maintained under activating environments is unclear. Here we show that autophagy is active in Treg cells and supports their lineage stability and survival fitness. Treg cell-specific deletion of Atg7 or Atg5, two essential genes in autophagy, leads to loss of Treg cells, greater tumor resistance and development of inflammatory disorders.

Treg cells require the phosphatase PTEN to restrain TH1 and TFH cell responses.

The interplay between effector T cells and regulatory T cells (Treg cells) is crucial for adaptive immunity, but how Treg cells control diverse effector responses is elusive. We found that the phosphatase PTEN links Treg cell stability to repression of type 1 helper T cell (TH1 cell) and follicular helper T cell (TFH cell) responses. Depletion of PTEN in Treg cells resulted in excessive TFH cell and germinal center responses and spontaneous inflammatory disease.

Tsc1 promotes the differentiation of memory CD8+ T cells via orchestrating the transcriptional and metabolic programs.

Memory CD8(+) T cells are an essential component of protective immunity. Signaling via mechanistic target of rapamycin (mTOR) has been implicated in the regulation of the differentiation of effector and memory T cells. However, little is understood about the mechanisms that control mTOR activity, or the effector pathways regulated by mTOR.

T cell exit from quiescence and differentiation into Th2 cells depend on Raptor-mTORC1-mediated metabolic reprogramming.

Naive T cells respond to antigen stimulation by exiting from quiescence and initiating clonal expansion and functional differentiation, but the control mechanism is elusive. Here we describe that Raptor-mTORC1-dependent metabolic reprogramming is a central determinant of this transitional process. Loss of Raptor abrogated T cell priming and T helper 2 (Th2) cell differentiation, although Raptor function is less important for continuous proliferation of actively cycling cells.

The S1P(1)-mTOR axis directs the reciprocal differentiation of T(H)1 and T(reg) cells.

Naive CD4(+) T cells differentiate into diverse effector and regulatory lineages to orchestrate immunity and tolerance. Here we found that the differentiation of proinflammatory T helper type 1 (T(H)1) cells and anti-inflammatory Foxp3(+) regulatory T cells (T(reg) cells) was reciprocally regulated by S1P(1), a receptor for the bioactive lipid sphingosine 1-phosphate (S1P). S1P(1) inhibited the generation of extrathymic and natural T(reg) cells while driving T(H)1 development in a reciprocal manner and disrupted immune homeostasis.