Somato-dendritic vasopressin and oxytocin secretion in endocrine and autonomic regulation

Somato‐dendritic secretion was first demonstrated over 30 years ago. However, although its existence has become widely accepted, the function of somato‐dendritic secretion is still not completely understood. Hypothalamic magnocellular neurosecretory cells were among the first neuronal phenotypes in which somato‐dendritic secretion was demonstrated and are among the neurones for which the functions of somato‐dendritic secretion are best characterised. These neurones secrete the neuropeptides, vasopressin and oxytocin, in an orthograde manner from their axons in the posterior pituitary gland into the blood circulation to regulate body fluid balance and reproductive physiology. Retrograde somato‐dendritic secretion of vasopressin and oxytocin modulates the activity of the neurones from which they are secreted, as well as the activity of neighbouring populations of neurones, to provide intra‐ and inter‐population signals that coordinate the endocrine and autonomic responses for the control of peripheral physiology. Somato‐dendritic vasopressin and oxytocin have also been proposed to act as hormone‐like signals in the brain. There is some evidence that somato‐dendritic secretion from magnocellular neurosecretory cells modulates the activity of neurones beyond their local environment where there are no vasopressin‐ or oxytocin‐containing axons but, to date, there is no conclusive evidence for, or against, hormone‐like signalling throughout the brain, although it is difficult to imagine that the levels of vasopressin found throughout the brain could be underpinned by release from relatively sparse axon terminal fields. The generation of data to resolve this issue remains a priority for the field.http://wileyonlinelibrary.com/journal/jne2021-04-17hj2020Immunolog

HAX-1 overexpression, splicing and cellular localization in tumors

<p>Abstract</p> <p>Background</p> <p>HAX-1 has been described as a protein potentially involved in carcinogenesis and especially metastasis. Its involvement in regulation of apoptosis and cell migration along with some data indicating its overexpression in cancer cell lines and tumors suggests that HAX-1 may play a role in neoplastic transformation. Here we present the first systematic analysis of HAX-1 expression in several solid tumors.</p> <p>Methods</p> <p>Using quantitative RT-PCR, we have determined the mRNA levels of <it>HAX1 </it>splice variant I in several solid tumors. We have also analyzed by semiquantitative and quantitative RT-PCR the expression of five <it>HAX-1 </it>splice variants in breast cancer samples and in normal tissue from the same individuals. Quantitative PCR was also employed to analyze the effect of estrogen on <it>HAX1 </it>expression in breast cancer cell line. Immunohistochemical analysis of HAX-1 was performed on normal and breast cancer samples.</p> <p>Results</p> <p>The results reveal statistically important <it>HAX1 </it>up-regulation in breast cancer, lung cancer and melanoma, along with some minor variations in the splicing pattern. HAX-1 up-regulation in breast cancer samples was confirmed by immunohistochemical analysis, which also revealed an intriguing HAX-1 localization in the nuclei of the tumor cells, associated with strong ER status.</p> <p>Conclusion</p> <p>HAX-1 elevated levels in cancer tissues point to its involvement in neoplastic transformation, especially in breast cancer. The connection between HAX-1 nuclear location and ER status in breast cancer samples remains to be clarified.</p

Cardiopoietic cell therapy for advanced ischemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial

Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort

Expected policy gradients for reinforcement learning

We propose expected policy gradients (EPG), which unify stochastic policy gradients (SPG) and deterministic policy gradients (DPG) for reinforcement learning. Inspired by expected sarsa, EPG integrates (or sums) across actions when estimating the gradient, instead of relying only on the action in the sampled trajectory. For continuous action spaces, we first derive a practical result for Gaussian policies and quadratic critics and then extend it to a universal analytical method, covering a broad class of actors and critics, including Gaussian, exponential families, and policies with bounded support. For Gaussian policies, we introduce an exploration method that uses covariance proportional to eH, where H is the scaled Hessian of the critic with respect to the actions. For discrete action spaces, we derive a variant of EPG based on softmax policies. We also establish a new general policy gradient theorem, of which the stochastic and deterministic policy gradient theorems are special cases. Furthermore, we prove that EPG reduces the variance of the gradient estimates without requiring deterministic policies and with little computational overhead. Finally, we provide an extensive experimental evaluation of EPG and show that it outperforms existing approaches on multiple challenging control domains

OFFER: Off-environment reinforcement learning

Policy gradient methods have been widely applied in reinforcement learning. For reasons of safety and cost, learning is often conducted using a simulator. However, learning in simulation does not traditionally utilise the opportunity to improve learning by adjusting certain environment variables - state features that are randomly determined by the environment in a physical setting but controllable in a simulator. Exploiting environment variables is crucial in domains containing significant rare events (SREs), e.g., unusual wind conditions that can crash a helicopter, which are rarely observed under random sampling but have a considerable impact on expected return. We propose off environment reinforcement learning (OFFER), which addresses such cases by simultaneously optimising the policy and a proposal distribution over environment variables. We prove that OFFER converges to a locally optimal policy and show experimentally that it learns better and faster than a policy gradient baseline

Fourier policy gradients

We propose a new way of deriving policy gradient updates for reinforcement learning. Our technique, based on Fourier analysis, recasts integrals that arise with expected policy gradients as convolutions and turns them into multiplications. The obtained analytical solutions allow us to capture the low variance benefits of EPG in a broad range of settings. For the critic, we treat trigonometric and radial basis functions, two function families with the universal approximation property. The choice of policy can be almost arbitrary, including mixtures or hybrid continuous-discrete probability distributions. Moreover, we derive a general family of sample-based estimators for stochastic policy gradients, which unifies existing results on sample-based approximation. We believe that this technique has the potential to shape the next generation of policy gradient approaches, powered by analytical results

An Innovative Dual-Column System for Heavy Metallic Ion Sorption by Natural Zeolite

This study investigates the design and performance of a novel sorption system containing natural zeolite. The apparatus consists of packed, fixed-bed, dual-columns with custom automated controls and sampling chambers, connected in series and stock fed by a metering pump at a controlled adjustable distribution. The purpose of the system is to remove heavy metallic ions predominately found in acid mine drainage, including lead (Pb2+), copper (Cu2+), iron (Fe3+), nickel (Ni2+) and zinc (Zn2+), combined in equal equivalence to form an acidified total 10 meq/L aqueous solution. Reported trends on the zeolite’s preference to these heavy metallic ions is established in the system breakthrough curve, as Pb2+ &gt;&gt; Fe3+ &gt; Cu2+ &gt; Zn2+ &gt;&gt; Ni2+. Within a 3-h contact period, Pb2+ is completely removed from both columns. Insufficient Ni2+ removal is achieved by either column with the promptest breakthrough attained, as zeolite demonstrates the least affinity towards it; however, a 48.97% removal is observed in the cumulative collection at the completion of the analysis period. The empty bed contact times for the first and second columns are 20 and 30 min, respectively; indicating a higher bed capacity at breakthrough and a lower usage rate of the zeolite mineral in the second column. This sorption system experimentally demonstrates the potential for industrial wastewater treatment technology development

Globe flower Trollius europaeus L. in forest and forest edge communities in the northern part of the Poludniowopodlaska Lowland

The distribution of Trollius europaeus in the northern part of the Południowopodlaska Lowland was described and a phytosociological study made of the localities where it was present between 2010 and 2012. The condition of all sites where T. europaeus was historically present was also verified. These field studies reveal that the number of sites of occurrence and the abundance of T. europaeus populations have rapidly diminished over recent years. Only 15 populations of the species in the vicinity of 7 sites were confirmed. Trollius europaeus is usually considered a species characteristic of moist meadows of ordo Molinietalia and in the plant community type, Polygono bistortae-Trollietum. In the northern part of the Po³udniowopodlaska Lowland, no meadow sites containing Trollius europaeus still remain according to our survey. All the confirmed stands are situated in deciduous forests of class Querco-Fagetea (Tilio-Carpinetum and Potentillo albae-Quercetum) and moist forest edge communities of ordo Glechometalia. The disappearance of all meadow populations is mainly considered a result of intensification of the agricultural use of these habitats. We suggest that the category of threat to Trollius europaeus is increased on the regional list from VU to EN, and consolidated with further monitoring and active protection of stands where it is present

Fourier policy gradients

We propose a new way of deriving policy gradient updates for reinforcement learning. Our technique, based on Fourier analysis, recasts integrals that arise with expected policy gradients as convolutions and turns them into multiplications. The obtained analytical solutions allow us to capture the low variance benefits of EPG in a broad range of settings. For the critic, we treat trigonometric and radial basis functions, two function families with the universal approximation property. The choice of policy can be almost arbitrary, including mixtures or hybrid continuous-discrete probability distributions. Moreover, we derive a general family of sample-based estimators for stochastic policy gradients, which unifies existing results on sample-based approximation. We believe that this technique has the potential to shape the next generation of policy gradient approaches, powered by analytical results

The station of the hop tree (Ptelea trifoliata L. ssp. trifoliata) in forests of the Wyszkow Forest District

This research was carried out on two experimental plots located in the Rymanów and Nawojowa forest districts. In the second and fifth year after planting, at three and six years of age respectively, survival and height of 25 beech progenies of selected stands were measured. Furthermore, we show the effect of beech origin and growth environment (significant ‘provenance × block’ and ‘provenance × test plot’ interactions). Beeches from both experimental plots differed significantly in growth and survival and this difference increased with tree age. The highest provenance heritability was obtained for the tree height after two years of growth in Rymanów. In Nawojowa, the heritability of beech survival reached zero after five years of growth. An evaluation of the stability of beech provenances (genotypes) in terms of survival and height under the habitat conditions of our experimental plots was done using the Finlay and Wilkinson method. The beech provenances of 469–Nawojowa and 452–Lesko (regional standard) were included as a stable basis for reference. A high degree of stability and high average values for the characteristics investigated indicate highprogeny quality within these stands