Transcriptomic analysis of turbot (Scophthalmus maximus) treated with zymosan a reveals that lncRNAs and inflammation-related genes mediate the protection conferred against Aeromonas salmonicida.

Aeromonas salmonicida is one of the most harmful pathogens in finfish aquaculture worldwide. Immunostimulants such as ß-glucans are used to enhance the immunity of cultured fish. However, their effects on fish physiology are not completely understood. In the present work, we evaluated the effect of a single intraperitoneal (ip) injection of zymosan A on fish survival against A. salmonicida infection. A single administration of this compound protected fish against A. salmonicida challenge and reduce the bacterial load in the head kidney one week after its administration. Transcriptome analyses of head kidney samples revealed several molecular mechanisms involved in the protection conferred by zymosan A and their regulation by long noncoding RNAs. The transcriptome profile of turbot exposed only to zymosan A was practically unaltered one week after ip injection. However, the administration of this immunostimulant induced significant transcriptomic changes once the fish were in contact with the bacteria and increased the survival of the infected turbot. Our results suggest that the restraint of the infection-induced inflammatory response, the management of apoptotic cell death, cell plasticity and cellular processes involving cytoskeleton dynamics support the protective effects of zymosan A. All this information provides insights on the cellular and molecular mechanisms involved in the protective effects of this widely used immunostimulant.

A Perspective on Lifelong Open-Ended Learning Autonomy for Robotics through Cognitive Architectures.

This paper addresses the problem of achieving lifelong open-ended learning autonomy in robotics, and how different cognitive architectures provide functionalities that support it. To this end, we analyze a set of well-known cognitive architectures in the literature considering the different components they address and how they implement them. Among the main functionalities that are taken as relevant for lifelong open-ended learning autonomy are the fact that architectures must contemplate learning, and the availability of contextual memory systems, motivations or attention. Additionally, we try to establish which of them were actually applied to real robot scenarios. It transpires that in their current form, none of them are completely ready to address this challenge, but some of them do provide some indications on the paths to follow in some of the aspects they contemplate. It can be gleaned that for lifelong open-ended learning autonomy, motivational systems that allow finding domain-dependent goals from general internal drives, contextual long-term memory systems that all allow for associative learning and retrieval of knowledge, and robust learning systems would be the main components required. Nevertheless, other components, such as attention mechanisms or representation management systems, would greatly facilitate operation in complex domains.

Human Sperm Head Vacuoles Are Related to Nuclear-Envelope Invaginations.

Nuclear vacuoles are specific structures present on the head of the human sperm of fertile and non-fertile men. Human sperm head vacuoles have been previously studied using motile sperm organelle morphology examination (MSOME) and their origin related to abnormal morphology, abnormal chromatin condensation and DNA fragmentation. However, other studies argued that human sperm vacuoles are physiological structures and consequently, to date, the nature and origin of the nuclear vacuoles remains to be elucidated. Here, we aim to define the incidence, position, morphology and molecular content of the human sperm vacuoles using transmission electron microscopy (TEM) and immunocytochemistry techniques. The results showed that ~50% of the analyzed human sperm cells (n = 1908; 17 normozoospermic human donors) contained vacuoles mainly located (80%) in the tip head region. A significant positive correlation was found between the sperm vacuole and nucleus areas. Furthermore, it was confirmed that nuclear vacuoles were invaginations of the nuclear envelope from the perinuclear theca and containing cytoskeletal proteins and cytoplasmic enzyme, discarding a nuclear or acrosomal origin. According to our findings, these human sperm head vacuoles are cellular structures originating from nuclear invaginations and contain perinuclear theca (PT) components, allowing us to define a new term of 'nuclear invaginations' rather than 'nuclear vacuoles'.

Coronavirus Disease 2019 (COVID-19) and Its Neuroinvasive Capacity: Is It Time for Melatonin?

The world faces an exceptional new public health concern caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), subsequently termed the coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO). Although the clinical symptoms mostly have been characterized, the scientific community still doesn´t know how SARS-CoV-2 successfully reaches and spreads throughout the central nervous system (CNS) inducing brain damage. The recent detection of SARS-CoV-2 in the cerebrospinal fluid (CSF) and in frontal lobe sections from postmortem examination has confirmed the presence of the virus in neural tissue. This finding reveals a new direction in the search for a neurotherapeutic strategy in the COVID-19 patients with underlying diseases. Here, we discuss the COVID-19 outbreak in a neuroinvasiveness context and suggest the therapeutic use of high doses of melatonin, which may favorably modulate the immune response and neuroinflammation caused by SARS-CoV-2. However, clinical trials elucidating the efficacy of melatonin in the prevention and clinical management in the COVID-19 patients should be actively encouraged.

Do rates of dental wear in extant African great apes inform the time of weaning?

Reconstructing the life histories of extinct hominins remains one of the main foci of paleoanthropological inquiry, as an extended juvenile period impacts the social and cognitive development of species. However, the paucity of hominin remains, the lack of comparative hominoid data, and the destructive nature of many life history approaches have limited our understanding of the relationship between dental development (eruption) and weaning in primates. Alternatively, the rate of dental wear in early-forming teeth has been suggested a good proxy for the timing of weaning. Here we test this hypothesis on an ontogenetic series of Gorilla gorilla gorilla and Pan troglodytes troglodytes, using geographic information systems-based shape descriptors of M1s in relation to the nitrogen (δ15N) and carbon (δ13C) isotope composition of their associated hair. Results show that Gorilla g. gorilla are fully weaned considerably later than Pan t. troglodytes, that is, after M1s had been in full functional occlusion for some time. Yet, throughout ontogeny, gorilla dental wear rates are greater than they are in chimpanzees. This refutes the hypothesis that the rates of wear of early-forming teeth inform the time of weaning (i.e., nutritional independence). Instead, dietary breadth and seasonal variation in resource availability are implicated. This finding has implications for interpreting the hominin fossil record and raises questions about the triggers for, and the mechanisms of, life history change in hominin evolution. As a case in point, commonalities in life history patterns between early hominins and Western lowland gorillas seem to be a means to mitigate the effects of recurrent (i.e., seasonal) resource limitations and-conceivably-to prevent high infant mortality rates. Taken further, difference between hominid life histories are likely to be of degree, not kind.

Associations of paternal serum dioxin-like polychlorinated biphenyl concentrations with IVF success: A pilot study.

Dioxin-like polychlorinated biphenyls (DL-PCBs) are environmental pollutants that have been associated with impaired semen quality. However, research on the potential impact of paternal exposure to DL-PCBs and the risk of adverse pregnancy outcomes are limited. We examine the relationship between serum DL-PCB concentrations and IVF outcomes among 42 males seeking fertility treatment. Concentrations of 12 serum DL-PCBs were analyzed by high-resolution gas chromatography coupled to high-resolution mass spectrometry. Modified Poisson regressions, adjusted for confounders, were used to assess bivariate associations and to estimate risk ratios (RRs) between DL-PCBs and binary IVF outcomes. The median concentration (25th-75th percentiles) of the sum of the 12 DL-PCBs (∑DL-PCBs) obtained for the patients was 5.42 (3.78-7.78) ng/g lipid. No statistically significant association between DL-PCB levels and embryo quality was found. However, men with high serum PCB-77 concentrations present more probability of high-quality embryos (RR: 0.292; 95% CI: 0.090-0.942), whereas the opposite trend is observed for men with lower serum levels of PCB-156 (RR: 7.960; 95% CI: 1.020-62.100), who present increased odds of high-quality embryos. Serum concentrations of PCB-126 and PCB-114 were associated with decreased implantation rates (p < 0.05). Moreover, PCB-77 and ∑non-ortho PCBs were significantly associated with a lower likelihood of clinical pregnancy (p < 0.05). A lower likelihood of live birth was associated with higher levels of PCB-77, PCB-105, PCB-118, and recording significant differences for ∑non-ortho PCBs, ∑mono-ortho PCBs, and ∑DL-PCBs (p < 0.05). These findings suggest that paternal DL-PCB exposure before conception may be related to pregnancy endpoints. However, DL-PCB measurement were limited to male partners. Therefore, we propose that future studies with larger population sizes should include both maternal and paternal factors.

In Silico Prediction of the Toxic Potential of Neuroprotective Bifunctional Molecules Based on Chiral N-Propargyl-1,2-amino Alcohol Derivatives.

N-Propargylamines are useful synthetic scaffolds for the synthesis of bioactive molecules, and in addition, they possess important pharmacological activities. We obtained several neuroprotective molecules, chiral 1,2-amino alcohols and 1,2-diamines, able to reduce by almost 70% the rotenone and oligomycin A-induced damage in SH-SY5Y cells. Furthermore, some molecules assessed also counteracted the toxicity evoked by the Ser/Thr phosphatase inhibitor okadaic acid. Before extrapolating these data to preclinical studies, we analyze the molecules through an in silico prediction system to detect carcinogenicity risk or other toxic effects. In light of these promising results, these molecules may be considered as a lead family of neuroprotective and relatively safe compounds.

Ecological quality assessement of marinas: An integrative approach combining biological and environmental data.

The importance of marinas as infrastructures for recreational boating is increasing substantially. However, information on their soft-bottom benthic communities, a key tool for managing programmes, is still scarce. We combined environment features with macro- and meiofaunal soft-bottom community information for assessing the ecological status of marinas with an integrative approach. To address this issue, we focused on eight marinas of the Southern Iberian Peninsula. Macro- and meiofauna data revealed high benthic heterogeneity at a spatial scale. The environmental variables which correlated best with macrofauna were mainly phosphorus, granulometry, and total organic carbon, and secondarily important variables were faecal coliforms, the biocide Irgarol, and heavy metals; total hydrocarbon concentration was also significant for meiofauna. Annelida was the dominant phylum in terms of number of species (37%) and abundance (66%) and were better descriptors of the environmental conditions than Arthropoda and Mollusca. Although identification to the species level is desirable and mandatory for assessing biological pollution, significant differences among marinas and correlations between fauna and abiotic variables were already detected at the level of family and order. This implies that biota assessment at higher levels may still be useful in monitoring programmes limited by time and budget constraints. The major novelty of this study lies in the development of an integrative assessment method based on the following selected ecological indicators: Marinas Environmental Pollution Index (MEPI), Biocontamination Index (BCI), macrofaunal biotic indices (AMBI, M-AMBI, BENTIX, MEDOCC and BENFES), macrofaunal taxa richness and Shannon-Wiener's diversity, and nematode:copepod index. This approach was able to discriminate marinas of the Southern Iberian Peninsula based on their ecological status, which ranged from poor to good. The method can be useful to design standards for assigning "sustainable quality seals" to those marinas with better values of ecological indicators.

Melatonin's efficacy in stroke patients; a matter of dose? A systematic review.

There is a lack of effective therapies for stroke patients; its treatment is even more difficult considering the unexpected onset of the disease. In the last decade, melatonin has emerged as a promising neuroprotective agent which is able to cross the blood-brain-barrier (BBB) and with a low toxicity profile. The aim of this systematic review was to summarize and critically review clinical and pre-clinical evidence related to melatonin's effectiveness as a stroke treatment. Together with a comparative dose extrapolation with those used in the selected randomized controlled trials (RCTs), and based on these data to discuss whether the administered doses correlate with those advisable in human patients. To address this purpose, we performed a systematic review of the available literature. A total of 529 records were screened with the selecting of six full articles containing RCTs that met the inclusion/exclusion criteria. The evidence drawn from these six reports was analyzed to identify remaining gaps, treatment efficacy, and to suggest future directions. The primary outcome reported was the reduction of the oxidative response; the secondary outcome was the increase of the survival rate of the patients in the intervention groups. Calculations derived from animal studies revealed that the translational doses to humans were substantially higher than those employed in the RCTs. The findings of this systematic review revealed that there are insufficient RCTs to prove melatonin's value in stroke patients. Nevertheless, the evidence is promising, and further clinical research may support the benefits of melatonin in stroke patients, if the adequate dose is administered.

Three-dimensional dental topography and feeding ecology in the extinct cave bear.

The cave bear (Ursus spelaeus s.l.) was an iconic extinct bear that inhabited the Pleistocene of Eurasia. The cause of extinction of this species is unclear and to identify the actual factors, it is crucial to understand its feeding preferences. Here, we quantified the shape descriptor metrics in three-dimensional (3D) models of the upper teeth (P4-M2) of the cave bear to make inferences about its controversial feeding behaviour. We used comparative samples, including representatives of all living bear species with known diets, as a template. Our topographic analyses show that the complexity of upper tooth rows in living bears is more clearly associated with the mechanical properties of the items consumed than with the type of food. Cave bears exhibit intermediate values on topographic metrics compared with the bamboo-feeder giant panda (Ailuropoda melanoleuca) and specialists in hard mast consumption (Ursus arctos and Ursus thibetanus). The crown topography of cave bear upper teeth suggests that they could chew on tough vegetal resources of low quality with high efficiency, a characteristic that no living bear currently displays. Our results align with a climate-driven hypothesis to explain the extinction of cave bear populations during the Late Pleistocene.

Prevalence and genotypic diversity of ostreid herpesvirus type 1 in Crassostrea gigas cultured in the Gulf of California, Mexico.

In bivalve mollusk aquaculture, massive disease outbreaks with high mortality and large economic losses can occur, as in northwest Mexico in the 1990s. A range of pathogens can affect bivalves; one of great concern is ostreid herpesvirus 1 (OsHV-1), of which there are several strains. This virus has been detected in the Gulf of California in occasional or sporadic samplings, but to date, there have been few systematic studies. Monthly samples of Crassostrea gigas, water, and sediment were taken in the La Cruz coastal lagoon and analyzed by PCR. The native mollusk, Dosinia ponderosa, which lives outside the lagoon, was sampled as a control. The virus was found throughout the year only in C. gigas, with prevalence up to 60%. In total, 9 genotype variants were detected, and genetic analysis suggests that linear genotypic evolution has occurred from strain JF894308, present in La Cruz in 2011. There has been no evidence of the entry of new viral genotypes in the recent past, thus confinement of the virus within the lagoons of the Gulf of California could promote a native genotypic diversity in the short term.

FE-SEM Characterization of α-Mannose Density and Surface Mapping Changes in Human Sperm Head During In Vitro Capacitation.

Sperm capacitation includes the reorganization of plasma membrane components and the outstanding modification of the glycocalyx. The α-mannose presence and location during in vitro capacitation have been commonly described in human spermatozoa using Concanavalin A (Con A) lectin. However, it is still unclear to date how in vitro capacitation time affects the α-mannose residues and their topographic spatial distribution on sperm membrane. Here, we characterized the α-mannose density and specific membrane domain locations before and after in vitro capacitation (1­4 h) using high-resolution field emission scanning electron microscopy (FE-SEM). Results showed that α-mannose residues were present preferably on the acrosome domains for all physiological conditions. Uncapacitated sperm comparatively exhibits significant highest labeling densities of α-mannose residues. In addition, as in vitro capacitation takes place, significant and progressive decreasing of sugar residues was combined with their relocation mostly affecting acrosomal domain apical areas. Our findings reveal that combined approach using FE-SEM and gold nanoparticle topographical mapping offers new human sperm biomolecular and structural details during capacitation events.

The emergence of melatonin in oncology: Focus on colorectal cancer.

Within the last few decades, melatonin has increasingly emerged in clinical oncology as a naturally occurring bioactive molecule with substantial anticancer properties and a pharmacological profile optimal for joining the currently available pharmacopeia. In addition, extensive experimental data shows that this chronobiotic agent exerts oncostatic effects throughout all stages of tumor growth, from initial cell transformation to mitigation of malignant progression and metastasis; additionally, melatonin alleviates the side effects and improves the welfare of radio/chemotherapy-treated patients. Thus, the support of clinicians and oncologists for the use of melatonin in both the treatment and proactive prevention of cancer is gaining strength. Because of its epidemiological importance and symptomatic debut in advanced stages of difficult clinical management, colorectal cancer (CRC) is a preferential target for testing new therapies. In this regard, the development of effective forms of clinical intervention for the improvement of CRC outcome, specifically metastatic CRC, is urgent. At the same time, the need to reduce the costs of conventional anti-CRC therapy results is also imperative. In light of this status quo, the therapeutic potential of melatonin, and the direct and indirect critical processes of CRC malignancy it modulates, have aroused much interest. To illuminate the imminent future on CRC research, we focused our attention on the molecular mechanisms underlying the multiple oncostatic actions displayed by melatonin in the onset and evolution of CRC and summarized epidemiological evidence, as well as in vitro, in vivo and clinical findings that support the broadly protective potential demonstrated by melatonin.

The effects of male social environment on sperm phenotype and genome integrity.

Sperm function and quality are primary determinants of male reproductive performance and hence fitness. The presence of rival males has been shown to affect ejaculate and sperm traits in a wide range of taxa. However, male physiological conditions may not only affect sperm phenotypic traits but also their genetic and epigenetic signatures, affecting the fitness of the resulting offspring. We investigated the effects of male-male competition on sperm quality using TUNEL assays and geometric morphometrics in the zebrafish, Danio rerio. We found that the sperm produced by males exposed to high male-male competition had smaller heads but larger midpiece and flagellum than sperm produced by males under low competition. Head and flagella also appeared less sensitive to the osmotic stress induced by activation with water. In addition, more sperm showed signals of DNA damage in ejaculates of males under high competition. These findings suggest that the presence of a rival male may have positive effects on sperm phenotypic traits but negative effects on sperm DNA integrity. Overall, males facing the presence of rival males may produce faster swimming and more competitive sperm but this may come at a cost for the next generation.

Age-related tooth wear in African rainforest hunter-gatherers.

OBJECTIVES: Central African small-scale foragers subsist primarily on hunting game activities and wild plant-food gathering. Starch-rich tubers are underground storage organs (USOs) and staple food resources in savanna and tropical rainforests. However, little is known about the effect of USO consumption on tooth wear development in living hunter-gatherers. We report age- and sex-dependent tooth wear rates in forest-dwelling Baka Pygmies with well-documented wild-yam-tuber-based diet to explore the long-term impact of USO mechanical hardness and abrasiveness on the wearing down of the teeth. MATERIALS AND METHODS: Percentages of dentine exposure (PDEs) of permanent left mandibular first molars (M1 ) were recorded using in vivo high-resolution replicas of Baka individuals (aged 8-33 years), inhabiting Le Bosquet district in Cameroon (Western Africa). Regression and covariance analyses were used to test the effect of individual aging by sex on PDE rates. RESULTS: We found a strong increase of PDE by age among Baka individuals. No evidence of sexual dimorphism in wear patterns suggests similar sex-related dietary and masticatory demands during growth. Overall, greatest dentine exposure values ≈4% denote unexpected slow wear down rates for foraging diets relying on USO consumption. DISCUSSION: The low molar wear rates with age found in Baka Pygmies contrast with extensive wear rates in savanna-dwelling foragers, reflecting differences in thermal processing techniques affecting fracture toughness and grittiness of mechanically challenging foods. Our findings reveal that culture-specific dietary proclivities influence tooth wear among foraging behaviors with important implications in hominin dietary versatility and abrasive stress on chewing surfaces.

New flavonoid - N,N-dibenzyl(N-methyl)amine hybrids: Multi-target-directed agents for Alzheimer´s disease endowed with neurogenic properties.

The design of multi-target directed ligands (MTDLs) is a valid approach for obtaining effective drugs for complex pathologies. MTDLs that combine neuro-repair properties and block the first steps of neurotoxic cascades could be the so long wanted remedies to treat neurodegenerative diseases (NDs). By linking two privileged scaffolds with well-known activities in ND-targets, the flavonoid and the N,N-dibenzyl(N-methyl)amine (DBMA) fragments, new CNS-permeable flavonoid - DBMA hybrids (1-13) were obtained. They were subjected to biological evaluation in a battery of targets involved in Alzheimer's disease (AD) and other NDs, namely human cholinesterases (hAChE/hBuChE), ß-secretase (hBACE-1), monoamine oxidases (hMAO-A/B), lipoxygenase-5 (hLOX-5) and sigma receptors (σ1R/σ2R). After a funnel-type screening, 6,7-dimethoxychromone - DBMA (6) was highlighted due to its neurogenic properties and an interesting MTD-profile in hAChE, hLOX-5, hBACE-1 and σ1R. Molecular dynamic simulations showed the most relevant drug-protein interactions of hybrid 6, which could synergistically contribute to neuronal regeneration and block neurodegeneration.

Tooth dimensions and body size in a Pygmy population.

Background: The relationship between tooth size and stature has been analysed extensively at the interspecies level but has received less attention at the intraspecies level. The relationship between these two parameters does not seem to be the same among modern human populations.Aim: The aim of this study is to analyse the relationship between tooth dimensions and body measurements in the Baka Pygmies.Subjects and methods: Height, weight, and tooth dimensions were obtained for 45 adult Baka females and 17 males from Le Bosquet (Cameroon). Correlations were obtained between the variables and compared to results for other human populations.Results: The Baka population is distinctive in the small number of significant correlations. Only two buccolingual diameters among Baka females show any significant correlation with height. The lack of significant correlations between tooth dimensions and body dimensions among the Baka means that changes in body size are accompanied by random variations in tooth dimensions.Conclusion: The absence of correlations may be accounted for by the impact of environmental effects on the somatic growth of the Baka producing a Pygmy phenotype adapted to live in the forest. It is worth noting that many correlations become significant when sexes are pooled.

QuinoxalineTacrine QT78, a Cholinesterase Inhibitor as a Potential Ligand for Alzheimer's Disease Therapy.

We report the synthesis and relevant pharmacological properties of the quinoxalinetacrine (QT) hybrid QT78 in a project targeted to identify new non-hepatotoxic tacrine derivatives for Alzheimer's disease therapy. We have found that QT78 is less toxic than tacrine at high concentrations (from 100 µM to 1 mM), less potent than tacrine as a ChE inhibitor, but shows selective BuChE inhibition (IC50 (hAChE) = 22.0 ± 1.3 µM; IC50 (hBuChE) = 6.79 ± 0.33 µM). Moreover, QT78 showed effective and strong neuroprotection against diverse toxic stimuli, such as rotenone plus oligomycin-A or okadaic acid, of biological significance for Alzheimer's disease.

Modulation of Heat Shock Response Proteins by ASS234, Targeted for Neurodegenerative Diseases Therapy.

ASS234 is a new multitarget molecule with multiple neuroprotective actions that significantly elevate mRNA levels of NRF2 and HSF1 transcriptional factors and of HSP105, HSP90AB1, HSPA1A, HSPA1B, HSPA5, HSPA8, HSPA9, HSP60, DNAJA1, DNAJB1, DNAJB6, DNAJC3, DNAJC5, DNAJC6, HSPB1, HSPB2, HSPB5, HSPB6, HSPB8, and HSP10 heat shock proteins (HSPs) family members in SH-SY5Y cells. This NRF2 and HSF1 overexpression may explain the upregulation of both the antioxidant enzymes previously described and the members of the HSPs family observed. These findings suggest that ASS234 is a potent HSPs inductor, which might be beneficial for preventing protein misfolding aggregation and cell death in Alzheimer's disease and other neurodegenerative diseases.

Analysis of mycobacterial infection-induced changes to host lipid metabolism in a zebrafish infection model reveals a conserved role for LDLR in infection susceptibility.

Changes to lipid metabolism are well-characterised consequences of human tuberculosis infection but their functional relevance are not clearly elucidated in these or other host-mycobacterial systems. The zebrafish-Mycobacterium marinum infection model is used extensively to model many aspects of human-M. tuberculosis pathogenesis but has not been widely used to study the role of infection-induced lipid metabolism. We find mammalian mycobacterial infection-induced alterations in host Low Density Lipoprotein metabolism are conserved in the zebrafish model of mycobacterial pathogenesis. Depletion of LDLR, a key lipid metabolism node, decreased M. marinum burden, and corrected infection-induced altered lipid metabolism resulting in decreased LDL and reduced the rate of macrophage transformation into foam cells. Our results demonstrate a conserved role for infection-induced alterations to host lipid metabolism, and specifically the LDL-LDLR axis, across host-mycobacterial species pairings.