The Stress Response of the Holothurian Central Nervous System: A Transcriptomic Analysis

Injury to the central nervous system (CNS) results in permanent damage and lack of function in most vertebrate animals, due to their limited regenerative capacities. In contrast, echinoderms can fully regenerate their radial nerve cord (RNC) following transection, with little to no scarring. Investigators have associated the regenerative capacity of some organisms to the stress response and inflammation produced by the injury. Here, we explore the gene activation profile of the stressed holothurian CNS. To do this, we performed RNA sequencing on isolated RNC explants submitted to the stress of transection and enzyme dissection and compared them with explants kept in culture for 3 days following dissection. We describe stress-associated genes, including members of heat-shock families, ubiquitin-related pathways, transposons, and apoptosis that were differentially expressed. Surprisingly, the stress response does not induce apoptosis in this system. Other genes associated with stress in other animal models, such as hero proteins and those associated with the integrated stress response, were not found to be differentially expressed either. Our results provide a new viewpoint on the stress response in the nervous system of an organism with amazing regenerative capacities. This is the first step in deciphering the molecular processes that allow echinoderms to undergo fully functional CNS regeneration, and also provides a comparative view of the stress response in other organisms.     

Study of the Ghrelin/LEAP-2 Ratio in Humans and Rats during Different Phases of Pregnancy

The Liver-Expressed Antimicrobial Peptide 2 (LEAP-2) has emerged as an endogenous GHS-R antagonist and blunts the orexigenic action of ghrelin. This study aimed to determine the Ghrelin/LEAP-2 ratio in humans and rats during pregnancy. In humans, we conducted a nested case-control study within an observational prospective cohort. Healthy and mild preeclamptic pregnant women were studied at each trimester of gestation and three months postpartum. In addition, a group of non-pregnant women was studied into the follicular and luteal phases of the menstrual cycle. Furthermore, Ghrelin/LEAP-2 ratio was investigated in non-pregnant rats and at different periods of rat pregnancy. Human and rat serum ghrelin and LEAP-2 levels were determined using the commercially available ELISA kits. The Ghrelin/LEAP-2 ratio peak around the second trimester of gestation in healthy pregnant women (p < 0.05). Additionally, there were no statistically significant differences in Ghrelin/LEAP-2 ratio between healthy and preeclamptic pregnant women at each trimester of gestation (p > 0.05). The Ghrelin/LEAP-2 ratio in pregnant rat reached the peak around mid-gestation with a similar pattern to the human pregnancy. LEAP-2 was visualized by immunohistochemistry in human term placenta and rat placentas on days 12, 16 and 21 of pregnancy. In conclusion, this study provides the first evidence of a Ghrelin/LEAP-2 ratio peak around the half-way point of pregnancy onwards during human and rat pregnancy, and it might be associated with increased rates of weight gain during pregnancy. Thus, this study suggests that LEAP-2 and Ghrelin/LEAP-2 ratio might play an important role in maternal physiology adaptation of weight gain during pregnancy.     

Circadian Rhythm Dysregulation and Leukemia Development: The Role of Clock Genes as Promising Biomarkers

The circadian clock (CC) is a daily system that regulates the oscillations of physiological processes and can respond to the external environment in order to maintain internal homeostasis. For the functioning of the CC, the clock genes (CG) act in different metabolic pathways through the clock-controlled genes (CCG), providing cellular regulation. The CC’s interruption can result in the development of different diseases, such as neurodegenerative and metabolic disorders, as well as cancer. Leukemias correspond to a group of malignancies of the blood and bone marrow that occur when alterations in normal cellular regulatory processes cause the uncontrolled proliferation of hematopoietic stem cells. This review aimed to associate a deregulated CC with the manifestation of leukemia, looking for possible pathways involving CG and their possible role as leukemic biomarkers.     

Global stabilization of linear discrete-time systems with bounded feedback

This paper deals with the problem of global stabilization of linear discrete time systems by means of bounded feedback laws. The main result proved is an analog of one proved for the continuous time case by the authors, and shows that such stabilization is possible if and only if the system is stabilizable with arbitrary controls and the transition matrix has spectral radius less than or equal to one. The proof provides in principle an algorithm for the construction of such feedback laws, which can be implemented either as cascades or as parallel connections (“single hidden layer neural networks”) of simple saturation functions.     

Inductive transfer for learning Bayesian networks

In several domains it is common to have data from different, but closely related problems. For instance, in manufacturing, many products follow the same industrial process but with different conditions; or in industrial diagnosis, where there is equipment with similar specifications. In these cases it is common to have plenty of data for some scenarios but very little for others. In order to learn accurate models for rare cases, it is desirable to use data and knowledge from similar cases; a technique known as transfer learning. In this paper we propose an inductive transfer learning method for Bayesian networks, that considers both structure and parameter learning. For structure learning we use conditional independence tests, by combining measures from the target task with those obtained from one or more auxiliary tasks, using a novel weighted sum of the conditional independence measures. For parameter learning, we propose two variants of the linear pool for probability aggregation, combining the probability estimates from the target task with those from the auxiliary tasks. To validate our approach, we used three Bayesian networks models that are commonly used for evaluating learning techniques, and generated variants of each model by changing the structure as well as the parameters. We then learned one of the variants with a small dataset and combined it with information from the other variants. The experimental results show a significant improvement in terms of structure and parameters when we transfer knowledge from similar tasks. We also evaluated the method with real-world data from a manufacturing process considering several products, obtaining an improvement in terms of log-likelihood between the data and the model when we do transfer learning from related products.     

Numerical analysis of rapid drawdown:Applications in real cases

In this study, rapid drawdown scenarios were analyzed by means of numerical examples as well as modeling of real cases with in situ measurements. The aim of the study was to evaluate different approaches available for calculating pore water pressure distributions during and after a drawdown. To do that, a single slope subjected to a drawdown was first analyzed under different calculation alternatives, and numerical results were discussed. Simple methods, such as undrained analysis and pure flow analysis, implicitly assuming a rigid soil skeleton, lead to significant errors in pore water pressure distributions when compared with coupled flow-deformation analysis. A similar analysis was performed for the upstream slope of the Glen Shira Dam, Scotland, and numerical results were compared with field measurements during a controlled drawdown. Field records indicate that classical undrained calculations are conservative but unrealistic. Then, a recent case of a major landslide triggered by a rapid drawdown in a reservoir was interpreted. A key aspect of the case was the correct characterization of permeability of a representative soil profile. This was achieved by combining laboratory test results and a back analysis of pore water pressure time records during a period of reservoir water level fluctuations. The results highlight the difficulty of predicting whether the pore water pressure is overestimated or underestimated when using simplified approaches, and it is concluded that predicting the pore water pressure distribution in a slope after a rapid drawdown requires a coupled flow-deformation analysis in saturated and unsaturated porous media.     

Impact of Zinc on Oxidative Signaling Pathways in the Development of Pulmonary Vasoconstriction Induced by Hypobaric Hypoxia

Hypobaric hypoxia is a condition that occurs at high altitudes (>2500 m) where the partial pressure of gases, particularly oxygen (PO₂), decreases. This condition triggers several physiological and molecular responses. One of the principal responses is pulmonary vascular contraction, which seeks to optimize gas exchange under this condition, known as hypoxic pulmonary vasoconstriction (HPV); however, when this physiological response is exacerbated, it contributes to the development of high-altitude pulmonary hypertension (HAPH). Increased levels of zinc (Zn²⁺) and oxidative stress (known as the “ROS hypothesis”) have been demonstrated in the vasoconstriction process. Therefore, the aim of this review is to determine the relationship between molecular pathways associated with altered Zn²⁺ levels and oxidative stress in HPV in hypobaric hypoxic conditions. The results indicate an increased level of Zn²⁺, which is related to increasing mitochondrial ROS (mtROS), alterations in nitric oxide (NO), metallothionein (MT), zinc-regulated, iron-regulated transporter-like protein (ZIP), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-induced protein kinase C epsilon (PKCε) activation in the development of HPV. In conclusion, there is an association between elevated Zn²⁺ levels and oxidative stress in HPV under different models of hypoxia, which contribute to understanding the molecular mechanism involved in HPV to prevent the development of HAPH.     

A non-conserved sequence in the 5'region of the CYH2 intron from Saccharomyces cerevisiae controls splicing efficiency of the pre-mRNA

The CYH2 gene from Saccharomyces cerevisiae containing one 510 bp intron is spliced inefficiently. We have shown previously that a non-conserved sequence within the intron is responsible for this low splicing efficiency. Using synthetic oligonucleotides comprising the identified region we show in this report that a very short region contains the specificity to act negatively on the splicing efficiency of the CYH2 gene. Furthermore, this sequence influences the splicing efficiency only when it is placed close to the 5' splice site of the gene. Investigations with chimeric CYH2/beta-actin genes show that this sequence acts independent from its natural surroundings. We propose that this sequence might interact with splicing factor(s).     

The effect of cooking and processing on the glucosinolate content: Studies on four varieties of portuguese cabbage and hybrid white cabbage

The concentrations of individual and total glucosinolates were measured in four types of Portuguese cabbage and in one hybrid white cabbage before and after cooking. Typical Portuguese culinary procedures include boiling the cabbage for 10 min but for particular kale types the leaves are first shredded then boiled for 5 min (Caldo verde). Analysis of the fresh cabbage, cooked leaves and cooking water showed that the glucosinolate content of the cabbages is reduced by more than 50%. Almost all of this loss is accounted for as intact glucosinolates in the cooking water, normally used for soups in Portugal.