Depletion Interactions at Interfaces Induced by Ferromagnetic Colloidal Polymers.

The pair-interaction force profiles for two non-magnetic colloids immersed in a suspension of ferromagnetic colloidal polymers are investigated via Langevin simulations. A quasi-two-dimensional approach is taken to study the interface case and a range of colloidal size ratios (non-magnetic:magnetic) from 6:1 up to 20:1 have been considered in this work. Simulations show that when compared with non-magnetic suspensions, the magnetic polymers strongly modify the depletion force profiles leading to strongly oscillatory behavior. Larger polymer densities and size ratios increase the range of the depletion forces, and in general, also their strength; the force barrier peaks at short distances show more complex behavior. As the length of the ferromagnetic polymers increases, the force profiles become more regular, and stable points with their corresponding attraction basins develop. The number of stable points and the distance at which they occur can be tuned through the modification of the field strength H and the angle θ formed by the field and the imaginary axis joining the centers of the two non-magnetic colloids. When not constrained, the net forces acting on the two colloids tend to align them with the field till θ=0∘. At this angle, the force profiles turn out to be purely attractive, and therefore, these systems could be used as a funneling tool to form long linear arrays of non-magnetic particles. Torsional forces peak at θ=45∘ and have minimums at θ=0∘ as well as θ=90∘ which is an unstable orientation as slight deviations will evolve towards θ→0∘. Nonetheless, results suggest that the θ=90∘ orientation could be easily stabilized in several ways. In such a case, the stable points that the radial force profiles exhibit for this orthogonal orientation to the field could be used to control the distance between the two large colloids: their position and number can be controlled via H. Therefore, suspensions made of ferromagnetic colloidal polymers can be also useful in the creation of magnetic colloidal tweezers or ratchets. A qualitative explanation of all the observed phenomena can be provided in terms of how the geometrical constraints and the external field modify the conformations of the ferromagnetic polymers near the two large particles, and in turn, how both factors combine to create unbalanced Kelvin forces that oscillate in strength with the distance between the two non-magnetic colloids.

Genetic adaptations for the oceanic success of fish eggs.

Genetic adaptations of organisms living in extreme environments are fundamental to our understanding of where life can evolve. Water is the single limiting parameter in this regard, yet when released in the oceans, the single-celled eggs of marine bony fishes (teleosts) have no means of acquiring it. They are strongly hyposmotic to seawater and lack osmoregulatory systems. Paradoxically, modern teleosts successfully release vast quantities of eggs in the extreme saline environment and recorded the most explosive radiation in vertebrate history. Here, we highlight key genetic adaptations that evolved to solve this paradox by filling the pre-ovulated eggs with water. The degree of water acquisition is uniquely prevalent to marine teleosts, permitting the survival and oceanic dispersal of their eggs.

Effectiveness and Health Outcomes of Collaborative Nurse Prescribing for Patients Anticoagulated with Antivitamin K in Primary Care: A Study Protocol.

The development of collaborative nurse prescribing (NP) in Andalusia (Spain) in 2018 gives us the opportunity to measure the impact of this practice. Scientific evidence indicates that prescribing is not more costly when performed by nurses and, in fact, is more economical in some cases. The aim of this study is to determine the effects of NP on the effectiveness, health outcomes and adverse events related to prescribing including in the follow-up of patients treated with antivitamin K oral anticoagulants in primary care (PC) by nurses. The design is a randomized clinical trial. The population comprises 1208 anticoagulated patients in 2019. The sample size calculation considers an alpha error of 0.05, a power of 99% and an effect size of 0.5, resulting in 127 users per group. Therefore, a total sample of 254 participants is needed. However, as the project intends to treat patients it will include the universal sample that meets the criteria in the two health centers participating in the study, with 575 participants in total. Data collection was carried out in the PC District of the Alamillo-San Jerónimo Clinical Management Unit of Sevilla for one year from January 2020. Data analysis is performed using the SPSS Statistics 25 package. We intend to study if nurse collaborative prescription in the follow-up and management of patients taking antivitamin K oral anticoagulants in PC is as effective as the traditional approach to follow-ups carried out by a family physician.

Aquaporin splice variation differentially modulates channel function during marine teleost egg hydration.

Aquaporin-mediated oocyte hydration is a developmentally regulated adaptive mechanism that co-occurs with meiosis resumption in marine teleosts. It provides the early embryos with vital water until osmoregulatory systems develop, and in the majority of marine teleosts causes their eggs to float. Recent studies have shown that the subdomains of two water channels (Aqp1ab1 and Aqp1ab2) encoded in a teleost-specific aquaporin-1 cluster (TSA1C) co-evolved with duplicated Ywhaz-like (14-3-3ζ-like) binding proteins to differentially control their membrane trafficking for maximal egg hydration. Here, we report that in species that encode the full TSA1C, in-frame intronic splice variants of Aqp1ab1 result in truncated proteins that cause dominant-negative inhibition of the canonical channel trafficking to the plasma membrane. The inhibition likely occurs through hetero-oligomerization and retention in the endoplasmic reticulum (ER) and ultimate degradation. Conversely, in species that only encode the Aqp1ab2 channel we found an in-frame intronic splice variant that results in an intact protein with an extended extracellular loop E, and an out-of frame intronic splice variant with exon readthrough that results in a truncated protein. Both isoforms cause dominant-negative enhancement of the degradation pathway. However, the extended and truncated Aqp1ab2-type variants can also partially escape from the ER to reach the oocyte plasma membrane, where they dominantly-negatively inhibit water flux. The ovarian follicular expression ratios of the Aqp1ab2 isoforms in relation to the canonical channel are lowest during oocyte hydration, but subsequently highest when the canonical channel is recycled, thus leaving the eggs endowed with >90% water. These findings suggest that the expression of inhibitory isoforms of Aqp1ab1 and Aqp1ab2 may represent a new regulatory mechanism through which the cell-surface expression and the activity of the canonical channels can be physiologically modulated during oocyte hydration in marine teleosts.

Neurohypophysial and paracrine vasopressinergic signaling regulates aquaporin trafficking to hydrate marine teleost oocytes.

The dual aquaporin (Aqp1ab1/Aqp1ab2)-mediated hydration of marine teleost eggs, which occurs during oocyte meiosis resumption (maturation), is considered a key adaptation underpinning their evolutionary success in the oceans. However, the endocrine signals controlling this mechanism are almost unknown. Here, we investigated whether the nonapeptides arginine vasopressin (Avp, formerly vasotocin) and oxytocin (Oxt, formerly isotocin) are involved in marine teleost oocyte hydration using the gilthead seabream (Sparus aurata) as a model. We show that concomitant with an increased systemic production of Avp and Oxt, the nonapeptides are also produced and accumulated locally in the ovarian follicles during oocyte maturation and hydration. Functional characterization of representative Avp and Oxt receptor subtypes indicates that Avpr1aa and Oxtrb, expressed in the postvitellogenic oocyte, activate phospholipase C and protein kinase C pathways, while Avpr2aa, which is highly expressed in the oocyte and in the follicular theca and granulosa cells, activates the cAMP-protein kinase A (PKA) cascade. Using ex vivo, in vitro and mutagenesis approaches, we determined that Avpr2aa plays a major role in the PKA-mediated phosphorylation of the aquaporin subdomains driving membrane insertion of Aqp1ab2 in the theca and granulosa cells, and of Aqp1ab1 and Aqp1ab2 in the distal and proximal regions of the oocyte microvilli, respectively. The data further indicate that luteinizing hormone, which surges during oocyte maturation, induces the synthesis of Avp in the granulosa cells via progestin production and the nuclear progestin receptor. Collectively, our data suggest that both the neurohypophysial and paracrine vasopressinergic systems integrate to differentially regulate the trafficking of the Aqp1ab-type paralogs via a common Avp-Avpr2aa-PKA pathway to avoid competitive occupancy of the same plasma membrane space and maximize water influx during oocyte hydration.

Functional Evolution of Clustered Aquaporin Genes Reveals Insights into the Oceanic Success of Teleost Eggs.

Aquaporin-mediated oocyte hydration is considered important for the evolution of pelagic eggs and the radiative success of marine teleosts. However, the molecular regulatory mechanisms controlling this vital process are not fully understood. Here, we analyzed >400 piscine genomes to uncover a previously unknown teleost-specific aquaporin-1 cluster (TSA1C) comprised of tandemly arranged aqp1aa-aqp1ab2-aqp1ab1 genes. Functional evolutionary analysis of the TSA1C reveals a ∼300-million-year history of downstream aqp1ab-type gene loss, neofunctionalization, and subfunctionalization, but with marine species that spawn highly hydrated pelagic eggs almost exclusively retaining at least one of the downstream paralogs. Unexpectedly, one-third of the modern marine euacanthomorph teleosts selectively retain both aqp1ab-type channels and co-evolved protein kinase-mediated phosphorylation sites in the intracellular subdomains together with teleost-specific Ywhaz-like (14-3-3ζ-like) binding proteins for co-operative membrane trafficking regulation. To understand the selective evolutionary advantages of these mechanisms, we show that a two-step regulated channel shunt avoids competitive occupancy of the same plasma membrane space in the oocyte and accelerates hydration. These data suggest that the evolution of the adaptive molecular regulatory features of the TSA1C facilitated the rise of pelagic eggs and their subsequent geodispersal in the oceanic currents.

A Narrative Review: Analysis of Supplemental Parenteral Nutrition in Adults at the End of Life.

"End of life" is a stage defined by the existence of an irreversible prognosis that ends with a person's death. One of the aspects of interest regarding end of life focuses on parenteral nutrition, which is usually administered in order to avoid malnutrition and associated complications. However, parenteral nutrition can be adapted to specific circumstances and evolve in its functionality through supplementation with certain nutrients that can have a beneficial effect. This narrative review aims to carry out a situation analysis of the role that could be adopted by supplemental parenteral nutrition in attenuating alterations typical of end of life and potential improvement in quality of life.

Role of Ion Channels in the Maintenance of Sperm Motility and Swimming Behavior in a Marine Teleost.

In oviparous marine fishes, the hyperosmotic induction of sperm motility in seawater (SW) is well established, however, the potential function of ion channels in the maintenance of post activated spermatozoon swimming performance remains largely unknown. Here, we investigated the influence of ion channels on the spermatozoon swimming parameters using the gilthead seabream (Sparus aurata) as a model for modern marine teleosts. Our data show that the SW-induced activation of seabream sperm motility requires three concomitant processes, the hyperosmotic shock, an ion-flux independent increase of the intracellular concentration of Ca2+ ([Ca2+]i), but not of [K+]i or [Na+]i, and the alkalization of the cytosol. The combination of all three processes is obligatory to trigger flagellar beating. However, the time-course monitoring of sperm motion kinetics and changes in the [Ca2+]i, [K+]i and [Na+]i in SW or in non-ionic activation media, showed that the post activated maintenance of spermatozoa motility is dependent on extracellular Ca2+ and K+. A meta-analysis of a seabream sperm transcriptome uncovered the expression of multiple ion channels, some of which were immunolocalized in the head and/or tail of the spermatozoon. Selective pharmacological inhibition of these ion channel families impaired the long-term motility, progressivity, and velocity of SW-activated spermatozoa. The data further revealed that some antagonists of K+-selective or Ca2+-selective channels, as well as of stretch-activated and mechanosensitive channels, altered the trajectory of spermatozoa, suggesting that these ion channels are likely involved in the control of the swimming pattern of the post activated spermatozoon. These combined findings provide new insight into the signaling pathways regulating spermatozoon activation and swimming performance in marine fishes.

Developmental RNA-Seq transcriptomics of haploid germ cells and spermatozoa uncovers novel pathways associated with teleost spermiogenesis.

In non-mammalian vertebrates, the molecular mechanisms involved in the transformation of haploid germ cells (HGCs) into spermatozoa (spermiogenesis) are largely unknown. Here, we investigated this process in the marine teleost gilthead seabream (Sparus aurata) through the examination of the changes in the transcriptome between cell-sorted HGCs and ejaculated sperm (SPZEJ). Samples were collected under strict quality controls employing immunofluorescence microscopy as well as by determining the sperm motion kinematic parameters by computer-assisted sperm analysis. Deep sequencing by RNA-seq identified a total of 7286 differentially expressed genes (DEGs) (p-value < 0.01) between both cell types, of which nearly half were upregulated in SPZEJ compared to HCGs. In addition, approximately 9000 long non-coding RNAs (lncRNAs) were found, of which 56% were accumulated or emerged de novo in SPZEJ. The upregulated transcripts are involved in transcriptional and translational regulation, chromatin and cytoskeleton organization, metabolic processes such as glycolysis and oxidative phosphorylation, and also include a number of ion and water channels, exchangers, transporters and receptors. Pathway analysis conducted on DEGs identified 37 different signaling pathways enriched in SPZEJ, including 13 receptor pathways, from which the most predominant correspond to the chemokine and cytokine, gonadotropin-releasing hormone receptor and platelet derived growth factor signaling pathways. Our data provide new insight into the mRNA and lncRNA cargos of teleost spermatozoa and uncover the possible involvement of novel endocrine mechanisms during the differentiation and maturation of spermatozoa.

[Consequences of the COVID-19 lockdown in patients with chronic diseases in Andalusia]. / Repercusiones del confinamiento por COVID-19 en pacientes crónicos de Andalucía.

OBJECTIVE: To understand the consequences of the COVID-19 pandemic lockdown on the self-care of people living with chronic diseases and on their self-perceived health, and to identify factors that may influence the management of their disease in emergency situations. METHOD: A qualitative study conducted in 2020 (March and April) in Andalusia (Spain) during the COVID-19 pandemic lockdown, through virtual focus groups, using the Zoom telematics tool. Three virtual focus groups were conducted, including 34 patients from Andalusia with different chronic conditions such as arthritis, diabetes, cardiovascular disease, inflammatory bowel disease, breast cancer and fibromyalgia. RESULTS: People with chronic diseases reported effects of the lockdown in relation to their emotional experience, their coping resources, the information they received, the difficulties to manage self-care, and the contact or access to health services. They also suggested some lessons learned for the future. The need for more and better information, patient training, involving patient associations, and improving telematics access to health services are the main areas for improvement to minimize the impact of future quarantines on the self-care and the health of people with chronic diseases. CONCLUSIONS: Besides the risk of contracting COVID-19, the difficulties encountered by people with chronic diseases during the lockdown include interferences in the self-care and the health care received. Health crisis situations demand more information, training for patients and improvements in the health services accessibility for patients with chronic conditions.

Streaming cascade-based speech translation leveraged by a direct segmentation model.

The cascade approach to Speech Translation (ST) is based on a pipeline that concatenates an Automatic Speech Recognition (ASR) system followed by a Machine Translation (MT) system. Nowadays, state-of-the-art ST systems are populated with deep neural networks that are conceived to work in an offline setup in which the audio input to be translated is fully available in advance. However, a streaming setup defines a completely different picture, in which an unbounded audio input gradually becomes available and at the same time the translation needs to be generated under real-time constraints. In this work, we present a state-of-the-art streaming ST system in which neural-based models integrated in the ASR and MT components are carefully adapted in terms of their training and decoding procedures in order to run under a streaming setup. In addition, a direct segmentation model that adapts the continuous ASR output to the capacity of simultaneous MT systems trained at the sentence level is introduced to guarantee low latency while preserving the translation quality of the complete ST system. The resulting ST system is thoroughly evaluated on the real-life streaming Europarl-ST benchmark to gauge the trade-off between quality and latency for each component individually as well as for the complete ST system.

Lineage-level divergence of copepod glycerol transporters and the emergence of isoform-specific trafficking regulation.

Transmembrane conductance of small uncharged solutes such as glycerol typically occurs through aquaglyceroporins (Glps), which are commonly encoded by multiple genes in metazoan organisms. To date, however, little is known concerning the evolution of Glps in Crustacea or what forces might underly such apparent gene redundancy. Here, we show that Glp evolution in Crustacea is highly divergent, ranging from single copy genes in species of pedunculate barnacles, tadpole shrimps, isopods, amphipods and decapods to up to 10 copies in diplostracan water fleas although with monophyletic origins in each lineage. By contrast the evolution of Glps in Copepoda appears to be polyphyletic, with surprisingly high rates of gene duplication occurring in a genera- and species-specific manner. Based upon functional experiments on the Glps from a parasitic copepod (Lepeophtheirus salmonis), we show that such lineage-level gene duplication and splice variation is coupled with a high rate of neofunctionalization. In the case of L. salmonis, splice variation of a given gene resulted in tissue- or sex-specific expression of the channels, with each variant evolving unique sites for protein kinase C (PKC)- or protein kinase A (PKA)-regulation of intracellular membrane trafficking. The combined data sets thus reveal that mutations favouring a high fidelity control of intracellular trafficking regulation can be a selection force for the evolution and retention of multiple Glps in copepods.

Colloidal magnetic brushes: influence of the magnetic content and presence of short-range attractive forces in the micro-structure and field response.

The behaviour of supramolecular brushes, whose filaments are composed of sequences of magnetic and non-magnetic colloidal particles, has been studied using Langevin dynamics simulations. Two types of brushes have been considered: sticky or Stockmayer brushes (SB) and non-sticky magnetic brushes (NSB). In both cases, the microstructure and the collective behaviour have been analysed for a wide range of magnetic field strengths including the zero-field case, and negative fields. The results show that, for the same magnetic content, SB placed in a magnetic field present an extensibility up to two times larger than NSB. The analysis of the microstructure of SB at zero field shows that magnetic particles belonging to different filaments in the brush self-organize into ring and chain aggregates, while magnetic colloids in NSB mainly remain in a non-aggregated state. Clustering among magnetic particles belonging to different filaments is observed to gradually fade away as the magnetic content of SB filaments increases towards 100%. Under an external field, SB are observed to form chains, threads and sheets depending on the magnetic content and the applied field strength. The chain-like clusters in SB are observed to decrease in size as the magnetic content in the filaments increases. A non-monotonic field dependence is observed for the average size of these clusters. In spite of the very different microstructure, both NSB and SB are observed to have a very similar magnetization, especially in high strength fields.

A multiplier peroxiporin signal transduction pathway powers piscine spermatozoa.

The primary task of a spermatozoon is to deliver its nuclear payload to the egg to form the next-generation zygote. With polyandry repeatedly evolving in the animal kingdom, however, sperm competition has become widespread, with the highest known intensities occurring in fish. Yet, the molecular controls regulating spermatozoon swimming performance in these organisms are largely unknown. Here, we show that the kinematic properties of postactivated piscine spermatozoa are regulated through a conserved trafficking mechanism whereby a peroxiporin ortholog of mammalian aquaporin-8 (Aqp8bb) is inserted into the inner mitochondrial membrane to facilitate H2O2 efflux in order to maintain ATP production. In teleosts from more ancestral lineages, such as the zebrafish (Danio rerio) and the Atlantic salmon (Salmo salar), in which spermatozoa are activated in freshwater, an intracellular Ca2+-signaling directly regulates this mechanism through monophosphorylation of the Aqp8bb N terminus. In contrast, in more recently evolved marine teleosts, such the gilthead seabream (Sparus aurata), in which spermatozoa activation occurs in seawater, a cross-talk between Ca2+- and oxidative stress-activated pathways generate a multiplier regulation of channel trafficking via dual N-terminal phosphorylation. These findings reveal that teleost spermatozoa evolved increasingly sophisticated detoxification pathways to maintain swimming performance under a high osmotic stress, and provide insight into molecular traits that are advantageous for postcopulatory sexual selection.

The Xenopus Oocyte as an Expression System for Functional Analyses of Fish Aquaporins.

Aquaporins are membrane proteins present in all organisms that selectively transport water and small, uncharged solutes across biological membranes along an osmotic gradient. Recent gene editing technologies in zebrafish (Danio rerio) have started to uncover the physiological functions of the aquaporins in teleosts, but these approaches require methods to establish the effects of specific mutations on channel function. The oocytes of the South African frog Xenopus laevis are widely used for the expression of bacterial, plant, and animal aquaporins, and this heterologous system has contributed to numerous discoveries in aquaporin biology. This chapter focuses on techniques used for oocyte preparation and aquaporin expression and gives an overview of specific methods to determine water and solute permeability of the channels and their intracellular trafficking in oocytes.

Kisspeptin Influences the Reproductive Axis and Circulating Levels of microRNAs in Senegalese Sole.

Kisspeptin regulates puberty and reproduction onset, acting upstream of the brain-pituitary-gonad (HPG) axis. This study aimed to test a kisspeptin-based hormonal therapy on cultured Senegalese sole (G1) breeders, known to have reproductive dysfunctions. A single intramuscular injection of KISS2-10 decapeptide (250 µg/kg) was tested in females and males during the reproductive season, and gonad maturation, sperm motility, plasma levels of gonadotropins (Fsh and Lh) and sex steroids (11-ketotestosterone, testosterone and estradiol), as well as changes in small non-coding RNAs (sncRNAs) in plasma, were investigated. Fsh, Lh, and testosterone levels increased after kisspeptin injection in both sexes, while sperm analysis did not show differences between groups. Let7e, miR-199a-3p and miR-100-5p were differentially expressed in females, while miR-1-3p miRNA was up-regulated in kisspeptin-treated males. In silico prediction of mRNAs targeted by miRNAs revealed that kisspeptin treatment might affect paracellular transporters, regulate structural and functional polarity of cells, neural networks and intracellular trafficking in Senegalese sole females; also, DNA methylation and sphingolipid metabolism might be altered in kisspeptin-treated males. Results demonstrated that kisspeptin stimulated gonadotropin and testosterone secretion in both sexes and induced an unanticipated alteration of plasma miRNAs, opening new research venues to understand how this neuropeptide impacts in fish HPG axis.

Adsorption transition of a grafted ferromagnetic filament controlled by external magnetic fields.

Extensive Langevin dynamics simulations are used to characterize the adsorption transition of a flexible magnetic filament grafted onto an attractive planar surface. Our results identify different structural transitions at different ratios of the thermal energy to the surface attraction strength: filament straightening, adsorption, and the magnetic flux closure. The adsorption temperature of a magnetic filament is found to be higher in comparison to an equivalent nonmagnetic chain. The adsorption has been also investigated under the application of a static homogeneous external magnetic field. We found that the strength and the orientation of the field can be used to control the adsorption process, providing a precise switching mechanism. Interestingly, we have observed that the characteristic field strength and tilt angle at the adsorption point are related by a simple power law.

Unravelling the Complex Duplication History of Deuterostome Glycerol Transporters.

Transmembrane glycerol transport is an ancient biophysical property that evolved in selected subfamilies of water channel (aquaporin) proteins. Here, we conducted broad level genome (>550) and transcriptome (>300) analyses to unravel the duplication history of the glycerol-transporting channels (glps) in Deuterostomia. We found that tandem duplication (TD) was the major mechanism of gene expansion in echinoderms and hemichordates, which, together with whole genome duplications (WGD) in the chordate lineage, continued to shape the genomic repertoires in craniates. Molecular phylogenies indicated that aqp3-like and aqp13-like channels were the probable stem subfamilies in craniates, with WGD generating aqp9 and aqp10 in gnathostomes but aqp7 arising through TD in Osteichthyes. We uncovered separate examples of gene translocations, gene conversion, and concerted evolution in humans, teleosts, and starfishes, with DNA transposons the likely drivers of gene rearrangements in paleotetraploid salmonids. Currently, gene copy numbers and BLAST are poor predictors of orthologous relationships due to asymmetric glp gene evolution in the different lineages. Such asymmetries can impact estimations of divergence times by millions of years. Experimental investigations of the salmonid channels demonstrated that approximately half of the 20 ancestral paralogs are functional, with neofunctionalization occurring at the transcriptional level rather than the protein transport properties. The combined findings resolve the origins and diversification of glps over >800 million years old and thus form the novel basis for proposing a pandeuterostome glp gene nomenclature.