Small-Molecule-Directed Endogenous Regeneration of Visual Function in a Mammalian Retinal Degeneration Model.

Degenerative retinal diseases associated with photoreceptor loss are a leading cause of visual impairment worldwide, with limited treatment options. Phenotypic profiling coupled with medicinal chemistry were used to develop a small molecule with proliferative effects on retinal stem/progenitor cells, as assessed in vitro in a neurosphere assay and in vivo by measuring Msx1-positive ciliary body cell proliferation. The compound was identified as having kinase inhibitory activity and was subjected to cellular pathway analysis in non-retinal human primary cell systems.

Hemispherically asymmetric Hadley cell response to CO removal.

A poleward shift of the Hadley cell (HC) edge in a warming climate, which contributes to the expansion of drought-prone subtropical regions, has been widely documented. The question addressed here is whether this shift is reversible with CO removal. By conducting large-ensemble experiments where CO concentrations are systematically increased and then decreased to the present-day level, we show that the poleward-shifted HC edge in a warming climate does not return to its present-day state when CO concentrations are reduced.

Activation of adult mammalian retinal stem cells in vivo via antagonism of BMP and sFRP2.

Background: The adult mammalian retina does not have the capacity to regenerate cells lost due to damage or disease. Therefore, retinal injuries and blinding diseases result in irreversible vision loss. However, retinal stem cells (RSCs), which participate in retinogenesis during development, persist in a quiescent state in the ciliary epithelium (CE) of the adult mammalian eye.

The winding path towards symbiotic autonomous systems.

Over the next 10 years, we are likely to see the convergence of two independent evolutionary paths: one leading to an augmentation of machine capabilities; the other with the augmentation of human capabilities. This convergence will not happen at a specific point in time; instead, it will be the result of progressive overlapping, to the point that it might be difficult to identify a defining moment. The following decade will likely be quite different from the present one.

Harnessing the Power of Smart and Connected Health to Tackle COVID-19: IoT, AI, Robotics, and Blockchain for a Better World.

As COVID-19 hounds the world, the common cause of finding a swift solution to manage the pandemic has brought together researchers, institutions, governments, and society at large. The Internet of Things (IoT), artificial intelligence (AI)-including machine learning (ML) and Big Data analytics-as well as Robotics and Blockchain, are the four decisive areas of technological innovation that have been ingenuity harnessed to fight this pandemic and future ones. While these highly interrelated smart and connected health technologies cannot resolve the pandemic overnight and may not be the only answer to the crisis, they can provide greater insight into the disease and support frontline efforts to prevent and control the pandemic.

Glucocorticoid agonists enhance retinal stem cell self-renewal and proliferation.

Background: Adult mammalian retinal stem cells (RSCs) readily proliferate, self-renew, and generate progeny that differentiate into all retinal cell types in vitro. RSC-derived progeny can be induced to differentiate into photoreceptors, making them a potential source for retinal cell transplant therapies. Despite their proliferative propensity in vitro, RSCs in the adult mammalian eye do not proliferate and do not have a regenerative response to injury.

Induction of rod versus cone photoreceptor-specific progenitors from retinal precursor cells.

During development, multipotent progenitors undergo temporally-restricted differentiation into post-mitotic retinal cells; however, the mechanisms of progenitor division that occurs during retinogenesis remain controversial. Using clonal analyses (lineage tracing and single cell cultures), we identify rod versus cone lineage-specific progenitors derived from both adult retinal stem cells and embryonic neural retinal precursors. Taurine and retinoic acid are shown to act in an instructive and lineage-restricted manner early in the progenitor lineage hierarchy to produce rod-restricted progenitors from stem cell progeny.

CMIP5 models' shortwave cloud radiative response and climate sensitivity linked to the climatological Hadley cell extent.

This study analyzes Coupled Model Intercomparison Project phase 5 (CMIP5) model output to examine the covariability of interannual Southern Hemisphere Hadley cell (HC) edge latitude shifts and shortwave cloud radiative effect (SWCRE). In control climate runs, during years when the HC edge is anomalously poleward, most models substantially reduce the shortwave radiation reflected by clouds in the lower midlatitude region (LML; ~28°S-~48°S), although no such reduction is seen in observations. These biases in HC-SWCRE covariability are linked to biases in the climatological HC extent.

Aerobic Endurance Training Does Not Protect Bone Against Poorly Controlled Type 1 Diabetes in Young Adult Rats.

Streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM) decreases trabecular bone volume and bone strength in rodents. The current study investigated the potential protective effects of aerobic endurance training (AET) on bone in STZ-induced T1DM young adult rats. Sixty-four 8-week-old male Sprague-Dawley rats were randomly divided into 4 groups of 16: control non-T1DM sedentary (CS) and exercised (CX), T1DM sedentary (DS) and exercised (DX).

The glucoregulatory response to high-intensity aerobic exercise following training in rats with insulin-treated type 1 diabetes mellitus.

An acute bout of exercise elicits a rapid, potentially deleterious, reduction in blood glucose in patients with type 1 diabetes mellitus (T1DM). In the current study, we examined whether a 10-week aerobic training program could alleviate the rapid exercise-associated reduction in blood glucose through changes in the glucoregulatory hormonal response or increased hepatic glycogen storage in an insulin-treated rat model of T1DM. Thirty-two male Sprague-Dawley rats were divided evenly into 4 groups: non-T1DM sedentary (C) (n = 8), non-T1DM exercised (CX) (n = 8), T1DM sedentary (D) (n = 8), and T1DM exercised (DX) (n = 8).

High Intensity Aerobic Exercise Training Improves Deficits of Cardiovascular Autonomic Function in a Rat Model of Type 1 Diabetes Mellitus with Moderate Hyperglycemia.

Indices of cardiovascular autonomic neuropathy (CAN) in experimental models of Type 1 diabetes mellitus (T1DM) are often contrary to clinical data. Here, we investigated whether a relatable insulin-treated model of T1DM would induce deficits in cardiovascular (CV) autonomic function more reflective of clinical results and if exercise training could prevent those deficits. Sixty-four rats were divided into four groups: sedentary control (C), sedentary T1DM (D), control exercise (CX), or T1DM exercise (DX).

The relationship between blood pressure and sciatic nerve blood flow velocity in rats with insulin-treated experimental diabetes.

Peripheral nerve blood flow (NBF) does not autoregulate but, instead, responds passively to changes in mean arterial pressure (MAP). How this relationship is impacted by insulin-treated experimental diabetes (ITED) is unknown. We tested the hypothesis that ITED will reduce NBF across a range of MAP in Sprague Dawley rats.

Exercise training enhances insulin-stimulated nerve arterial vasodilation in rats with insulin-treated experimental diabetes.

Insulin stimulates nerve arterial vasodilation through a nitric oxide (NO) synthase (NOS) mechanism. Experimental diabetes reduces vasa nervorum NO reactivity. Studies investigating hyperglycemia and nerve arterial vasodilation typically omit insulin treatment and use sedentary rats resulting in severe hyperglycemia.

The role of resistance and aerobic exercise training on insulin sensitivity measures in STZ-induced Type 1 diabetic rodents.

Unlabelled: Individuals with Type 1 Diabetes Mellitus (T1DM) can develop insulin resistance. Regular exercise may improve insulin resistance partially through increased expression of skeletal muscle GLUT4 content.

Objective: To examine if different exercise training modalities can alter glucose tolerance through changes in skeletal muscle GLUT4 content in T1DM rats.

Glucose-stimulated insulin secretion causes an insulin-dependent nitric oxide-mediated vasodilation in the blood supply of the rat sciatic nerve.

This study tested the hypothesis that acute hyperglycemia reduces sciatic nerve blood flow in Sprague-Dawley rats. Anesthetized rats underwent cannulation of their right jugular vein (for anesthetic/nutrient/drug infusion) and right carotid artery (for continuous blood pressure measurement via pressure transducer). The left sciatic nerve was exposed and nerve blood velocity (NBV) was assessed from an arterial segment lying superficially along the sciatic nerve (Doppler ultrasound, 40 MHz).

A model of poorly controlled type 1 Diabetes Mellitus and its treatment with aerobic exercise training.

Background: Modern exogenous insulin therapy can improve the quality of life of Type 1 Diabetic Mellitus (T1DM) patients, although maintenance of normal glycaemic levels is often a challenge given the variety of factors that alter it. A number of studies have examined the effect of exercise in T1DM; however, the majority of experimental studies have utilized diabetic rodents with severe hyperglycaemia. Given that T1DM patients are likely to refrain from hyperglycaemia, studies examining the effects of regular exercise in which blood glucose is poorly controlled would better represent the T1DM population.

Acute endurance exercise induces changes in vasorelaxation responses that are vessel-specific.

The dynamic adjustment and amplitude of the endothelium-dependent vasorelaxation of the carotid, aorta, iliac, and femoral vessels were measured in response to acute low- (LI) or high-intensity (HI) endurance exercise. Vasorelaxation to 10(-4) M ACh was evaluated in 10 control, 10 LI, and 10 HI rats. Two-millimeter sections of carotid, aorta, iliac, and femoral arteries were mounted onto a myography system.

Peptide YY improves local and systemic parameters and prevents death in lethal necrotizing pancreatitis.

Introduction: Peptide YY (PYY) is a gastrointestinal hormone with multiple inhibitory effects on the proximal digestive tract, including suppression of secretion by the exocrine pancreas.

Aim: To determine whether peptide YY would reduce mortality in a lethal model of necrotizing pancreatitis by improving local and systemic parameters of this disease.

Methodology: Necrotizing pancreatitis was induced in three groups of 30 mice by feeding a choline-deficient ethionine-supplemented diet.

Anastomotic technique influences outcomes after partial gastrectomy for adenocarcinoma.

The proper reconstructive technique after partial gastrectomy for adenocarcinoma of the stomach is often debated, but few data exist to clarify the issue. We evaluated outcomes after different anastomoses used during partial gastrectomy for gastric adenocarcinoma. We reviewed the hospital records of all 277 patients who underwent operation for gastric cancer at our institution from 1970 to 1996.

Hyperthermia induces heat-shock protein expression, reduces pancreatic injury, and improves survival in necrotizing pancreatitis.

Heat-shock proteins (HSPs) function in the cellular response to injury. Increased expression of these proteins was first described in response to hyperthermia, although their production may be prompted by a variety of metabolic insults. HSPs protect cellular proteins from degradation.

Peptide YY inhibits growth of human breast cancer in vitro and in vivo.

Background: Hormonal manipulation is important in the treatment of breast cancer. Gastrointestinal hormones may have antiproliferative effects on malignancies arising outside the gastrointestinal tract. Peptide YY (PYY) suppresses growth of, and levels of, intracellular cyclic adenosine monophosphate (cAMP) in pancreatic adenocarcinoma.

Gastric cancer: three decades of surgical management.

Hospital records of all 277 patients who underwent surgery for gastric adenocarcinoma at the University of California at Los Angeles Medical Center from 1970 through 1996 were reviewed. Patients were stratified into three groups comprising 1970 to 1979, 1980 to 1989, and 1990 to 1996. The incidence of stage IV disease decreased by 50 per cent over the course of the study (P < 0.