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In contrast, males consistently released sperm in response to both the injection (100% response; 1, 5 or 10 μg), or topical application (80-100% response; 50, 50 + DMSO or 100 μg) of GnRH-a. Overall, the administration of GnRH-a was more effective at inducing spermiation than hCG. Mean total sperm and sperm concentration were highest in response to the optimal topically applied dose of 100 μg GnRH-a (mean total sperm = 2.44 × 103, sperm concentration = 1.48 × 105 sperm/ml). We provide novel evidence that topical application provides a viable alternative to injection for the administration of GnRH-a to induce spermiation in amphibians.In the face of insect declines, identifying phases of the life cycle when insects are particularly vulnerable to mortality is critical to conservation efforts. For numerous annual insect groups, diapause is both a key adaptation that allows survival of inhospitable conditions and a physiologically demanding life stage that can result in high rates of mortality. As bees continue to garner attention as a group experiencing high rates of decline, improving our understanding of how annual bees prepare for diapause and identifying factors that reduce survival is imperative. Here, we studied factors affecting diapause survival length and their underlying mechanisms using an economically and ecologically important annual bee species, Bombus impatiens. We examined how age and mass upon diapause onset correlate with diapause survival length, and the mechanistic role of nutrient acquisition and oxidative stress post pupal eclosion in mediating these effects. Our findings show that both age and mass were strong predictors of diapause survival length. Heavier queens or queens in the age range of ~6-17 days survived longer in diapause. Mass gain was attributed to increases in lipid, protein and glycerol amounts following pupal eclosion, and the ability to deal with oxidative stress was significantly compromised in older pre-diapause queens. Our results demonstrate that age-related shifts in bee physiology and timing of nutrient acquisition may both be critical factors driving diapause survival.Metabolically important traits, such as gill surface area and metabolic rate, underpin life histories, population dynamics and extinction risk, as they govern the availability of energy for growth, survival and reproduction. Estimating both gill surface area and metabolic rate can be challenging, especially when working with large-bodied, threatened species. Ideally, these traits, and respiratory physiology in general, could be inferred from external morphology using a faster, non-lethal method. Gill slit height is quick to measure on live organisms and is anatomically connected to the gill arch. Here, we relate gill slit height and gill surface area for five Carcharhiniform sharks. We compared both total and parabranchial gill surface area to mean and individual gill slit height in physical specimens. We also compared empirical measurements of relative gill slit height (i.e. in proportion to total length) to those estimated from field guide illustrations to examine the potential of using anatomical drawings to measure gill slit height. We find strong positive relationships between gill slit height and gill surface area at two scales (i) for total gill surface area and mean gill slit height across species and (ii) for parabranchial gill surface area and individual gill slit height within and across species. We also find that gill slit height is a consistent proportion of the fork length of physical specimens. Consequently, relative gill slit height measured from field guide illustrations proved to be surprisingly comparable to those measured from physical specimens. selleckchem While the generality of our findings needs to be evaluated across a wider range of taxonomy and ecological lifestyles, they offer the opportunity that we might only need to go to the library and measure field guide illustrations to yield a non-lethal, first-order approximation of the respiratory physiology of sharks.Light pollution is a rapidly growing threat to biodiversity, with many unknown or poorly understood effects on species and ecosystems spanning terrestrial and aquatic environments. Relative to other taxa, the effects of artificial light at night on aquatic invertebrates are poorly understood, despite the abundance and integral significance of invertebrates to marine and freshwater ecosystems. We affixed heart rate and acceleration biologgers to adult Caribbean spiny lobster (Panulirus argus), an ecologically, culturally and economically significant species in the western Atlantic ocean, to test the effect of artificial light at night on this species' physiology and behaviour relative to appropriate controls. The experiment was conducted in a simulated reef mesocosm in The Bahamas with incandescent lighting used to illuminate it at 1 lux, approximating light levels offshore of urban areas. In the conditions tested here, artificial light at night was found to have no effect on heart rate or locomotor activity in P. argus. We observed a dissociation between activity and heart rate at both short-term and long-term temporal scales. Lobsters were more active at night and nocturnal activity was higher in trials closer to new moon; however, heart rate did not vary with diel or lunar cycle. There was less than 8% difference between daytime and night time average heart rate despite the average percentage of time spent active almost tripling in nights versus days, to 19.5% from 7.2%, respectively. Our findings suggest P. link2 argus may have some resilience to low levels of light pollution, which warrants further research on aspects of this species' life history, performance and fitness in the face of this potential anthropogenic disturbance.Health assessments of wildlife species are becoming increasingly important in an ever-changing environment. Kemp's ridley sea turtles (Lepidochelys kempii; hereafter, Kemp's ridleys) are critically endangered and incur several on-going threats to their population recovery; therefore, it is imperative to advance the understanding of baseline blood analyte data as a diagnostic and monitoring tool. For in-water, trawl-captured, immature Kemp's ridleys (minimum N = 31) from Georgia, USA, the objectives of this study were to (1) establish reference intervals (RIs) for packed cell volume (PCV) and 27 plasma biochemistry analytes and (2) determine length-specific relationships in blood analytes. We observed significant positive correlations between minimum straight carapace length and PCV, amylase, calciumphosphorus ratio, cholesterol, magnesium, triglycerides, total solids, total protein and all protein fractions (e.g. link3 alpha-, beta- and gamma-globulins); aspartate aminotransferase and chloride showed significant negative relationships. These results suggest that certain blood analytes in Kemp's ridleys change as these animals grow, presumptively due to somatic growth and dietary shifts. The information presented herein, in due consideration of capture technique that may have impacted glucose and potassium concentrations, represents the first report of blood analyte RIs for Kemp's ridley sea turtles established by guidelines of the American Society for Veterinary Clinical Pathology and will have direct applications for stranded individuals in rehabilitative care and for future investigations into the health status of wild individuals from this population.
COVID-19 can lead to a hyperinflammatory state. CD6 is a glycoprotein expressed on mature T lymphocytes which is a crucial regulator of the T-cell activation. Itolizumab is a humanised antibody targeting CD6. Nonclinical and clinical data in autoimmune diseases indicate that it lowers multiple cytokines primarily involving the Th1/Th17 pathway. The primary objective of this study was to assess the impact of itolizumab in arresting the lung function deterioration of COVID-19 patients. Secondary objectives included safety, duration of ventilation, 14-day mortality and evaluation of interleukin 6 concentration.
Patients with confirmed SARS-CoV-2 received itolizumab in combination with other therapies included in the national protocol for COVID-19.
Seventy critical, severe or moderate patients were treated with itolizumab in 10 Cuban hospitals. Median age was 68, and 94% had comorbidities. After 72h, most patients improved the PO
/FiO
ratio and reduced FiO2 requirements. Ventilation time was 8days for critical and 1day for severe cases. Ten patients had related adverse events while 3 subjects developed related serious events. In 30 patients, interleukin 6 decreased in individuals with high level and did not change in those with lower concentration. Fourteen-day lethality rate was 4% and 18% for moderate and severe patients, respectively. The proportion of moderate or severe patients with ventilation or death at day 14 was 9.8%. Time to treatment, neurological manifestations and biomarkers such as NLR were significantly associated with higher lethality.
The opportune administration of itolizumab might interrupt the hyperinflammatory cascade and prevent COVID-19 morbidity and mortality.
The opportune administration of itolizumab might interrupt the hyperinflammatory cascade and prevent COVID-19 morbidity and mortality.
Genetic or acquired defects in FOXP3
regulatory T cells (Tregs) play a key role in many immune-mediated diseases including immune dysregulation polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. Previously, we demonstrated CD4
T cells from healthy donors and IPEX patients can be converted into functional Treg-like cells by lentiviral transfer of
(CD4
). These CD4
cells have potent regulatory function, suggesting their potential as an innovative therapeutic. Here, we present molecular and preclinical
data supporting CD4
cell clinical progression.
The molecular characterisation of CD4
cells included flow cytometry, qPCR, RNA-seq and TCR-seq. The
suppressive function of CD4
cells was assessed in xenograft-versus-host disease (xeno-GvHD) and FOXP3-deficient IPEX-like humanised mouse models. The safety of CD4
cells was evaluated using peripheral blood (PB) humanised (hu)- mice testing their impact on immune response against pathogens, and immune surveillance against tumor antigens.
We demonstrate that the conversion of CD4
T cells to CD4
cells leads to specific transcriptional changes as compared to CD4
T-cell transduction in the absence of FOXP3, including upregulation of Treg-related genes. Furthermore, we observe specific preservation of a polyclonal TCR repertoire during
cell production. Both allogeneic and autologous CD4
cells protect from xeno-GvHD after two sequential infusions of effector T cells. CD4
cells prevent hyper-proliferation of CD4
memory T cells in the FOXP3-deficient IPEX-like hu-mice. CD4
cells do not impede
expansion of antigen-primed T cells or tumor clearance in the PB hu-mice.
These data support the clinical readiness of CD4
cells to treat IPEX syndrome and other immune-mediated diseases caused by insufficient or dysfunctional FOXP3
Tregs.
These data support the clinical readiness of CD4LVFOXP3 cells to treat IPEX syndrome and other immune-mediated diseases caused by insufficient or dysfunctional FOXP3+ Tregs.
My Website: https://www.selleckchem.com/products/Vandetanib.html
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