Ontogenetic change in the venom composition of one Mexican black-tailed rattlesnake (Crotalus molossus nigrescens) from Durango, Mexico.

To corroborate the ontogenetic shift in the venom composition of the Mexican Black-tailed Rattlesnake (Crotalus molossus nigrescens) previously reported through the census approach, we evaluated the shift in the protein profile, lethality, and proteolytic and phospholipase activities of four venom samples obtained in 2015, 2018, 2019, and 2021 from one C. m. nigrescens individual (CMN06) collected in Durango, Mexico. We demonstrated that the venom of C. m. nigrescens changed from a myotoxin-rich venom to a phospholipase A2 and snake venom metalloproteinase-rich venom. Additionally, the proteolytic and phospholipase activities increased with age, but the lethality decreased approximately three times.

The impact of anthropogenic pollutants on the distribution of a marine top predator within a coastal estuarine system.

Due to anthropogenic pressures, estuarine systems are among the most broadly impacted areas for marine top predator species. Given this, it is crucial to study the interaction between the vulnerable marine species that inhabit these regions with environmental and anthropogenic variables. This study aims to determine whether nutrient pollution is related to the presence of bottlenose dolphins in a coastal environment. Using a multi-year dataset and GAMs, we studied the relationship between marine pollutants and the presence of bottlenose dolphins in this highly impacted coastal marine environment. We observed that urban fertilizers were linked to the spatial distribution of bottlenose dolphins. There was a higher presence of bottlenose dolphins in areas with high levels of phosphoric acid. In contrast, at higher concentrations of nitrate, the presence of bottlenose dolphins decreased.

Prevalence, causes and impact of TP53-loss phenocopying events in human tumors.

BACKGROUND: TP53 is a master tumor suppressor gene, mutated in approximately half of all human cancers. Given the many regulatory roles of the corresponding p53 protein, it is possible to infer loss of p53 activity - which may occur due to alterations in trans - from gene expression patterns. Several such alterations that phenocopy p53 loss are known, however additional ones may exist, but their identity and prevalence among human tumors are not well characterized. RESULTS: We perform a large-scale statistical analysis on transcriptomes of ~ 7,000 tumors and ~ 1,000 cell lines, estimating that 12% and 8% of tumors and cancer cell lines, respectively, phenocopy TP53 loss: they are likely deficient in the activity of the p53 pathway, while not bearing obvious TP53 inactivating mutations. While some of these cases are explained by amplifications in the known phenocopying genes MDM2, MDM4 and PPM1D, many are not. An association analysis of cancer genomic scores jointly with CRISPR/RNAi genetic screening data identified an additional common TP53-loss phenocopying gene, USP28. Deletions in USP28 are associated with a TP53 functional impairment in 2.9-7.6% of breast, bladder, lung, liver and stomach tumors, and have comparable effect size to MDM4 amplifications. Additionally, in the known copy number alteration (CNA) segment harboring MDM2, we identify an additional co-amplified gene (CNOT2) that may cooperatively boost the TP53 functional inactivation effect of MDM2. An analysis of cancer cell line drug screens using phenocopy scores suggests that TP53 (in)activity commonly modulates associations between anticancer drug effects and various genetic markers, such as PIK3CA and PTEN mutations, and should thus be considered as a drug activity modifying factor in precision medicine. As a resource, we provide the drug-genetic marker associations that differ depending on TP53 functional status. CONCLUSIONS: Human tumors that do not bear obvious TP53 genetic alterations but that phenocopy p53 activity loss are common, and the USP28 gene deletions are one likely cause.

Assessing variability in marine traffic exposure between baleen whale species off the Galician Coast, Spain.

Increases in marine traffic represent a growing issue for marine wildlife, posing threats through the impacts of ship strikes and noise pollution. Baleen whales are especially vulnerable to these impacts, yet regional and species-specific information on exposure to such threats is lacking. This study uses AIS and observational data to provide the first assessment of baleen whale exposure to vessel traffic on the NW coast of Spain. Overlap with vessel traffic was detected for all areas where whales were sighted, indicating that these species may be at risk of vessel exposure and its associated impacts. Level of exposure to vessel traffic experienced by whales was species-specific, with risk of exposure appearing highest for minke whales. Vessel exposure also displayed intra- and inter-annual variability and a significant influence of feeding behaviour highlighting the need for dynamic management tools to minimise interactions between baleen whales and marine traffic off the Galician Coast.

Recent cover crop adoption is associated with small maize and soybean yield losses in the United States.

Cover crops are gaining traction in many agricultural regions, partly driven by increased public subsidies and by private markets for ecosystem services. These payments are motivated by environmental benefits, including improved soil health, reduced erosion, and increased soil organic carbon. However, previous work based on experimental plots or crop modeling indicates cover crops may reduce crop yields. It remains unclear, though, how recent cover crop adoption has affected productivity in commercial agricultural systems. Here we perform the first large-scale, field-level analysis of observed yield impacts from cover cropping as implemented across the US Corn Belt. We use validated satellite data products at sub-field scales to analyze maize and soybean yield outcomes for over 90,000 fields in 2019-2020. Because we lack data on cover crop species or timing, we seek to quantify the yield impacts of cover cropping as currently practiced in aggregate. Using causal forests analysis, we estimate an average maize yield loss of 5.5% on fields where cover crops were used for 3 or more years, compared with fields that did not adopt cover cropping. Maize yield losses were larger on fields with better soil ratings, cooler mid-season temperatures, and lower spring rainfall. For soybeans, average yield losses were 3.5%, with larger impacts on fields with warmer June temperatures, lower spring and late-season rainfall, and, to a lesser extent, better soils. Estimated impacts are consistent with multiple mechanisms indicated by experimental and simulation-based studies, including the effects of cover crops on nitrogen dynamics, water consumption, and soil oxygen depletion. Our results suggest a need to improve cover crop management to reduce yield penalties, and a potential need to target subsidies based on likely yield impacts. Ultimately, avoiding substantial yield penalties is important for realizing widespread adoption and associated benefits for water quality, erosion, soil carbon, and greenhouse gas emissions.

Context-dependent and seasonal fluctuation in bottlenose dolphin (Tursiops truncatus) vocalizations.

A fundamental question in animal behaviour is the role of vocal communication in the regulation of social interactions in species that organise themselves into social groups. Context dependence and seasonality in vocalizations are present in the communication of many species, although very little research has addressed this dependence in marine mammals. The study presented here examined variations in the rate at which free-ranging dyads of bottlenose dolphins emit social-signals in an effort to better understand the relationship between vocal communication and social context. The results demonstrate that changes in the social-signal production in bottlenose dolphins are related to the sex of the partner, mating season and social affiliation between the components of the dyad. In a context of foraging behaviour on the same feeding ground, mixed (male-female) dyads were found to emit more pulsed burst sounds during the mating season. Another relevant aspect of the study seems to be the greater production of agonistic social-signals in the dyads formed by individuals with a lower degree of social affiliation. Overall, this study confirms a clear relationship between dyad composition and context-specific social-signals that could reflect the motivational state of individuals linked to seasonal changes in vocal behaviour.

Thermal imaging of dust hiding the black hole in NGC 1068.

In the widely accepted 'unified model'1 solution of the classification puzzle of active galactic nuclei, the orientation of a dusty accretion torus around the central black hole dominates their appearance. In 'type-1' systems, the bright nucleus is visible at the centre of a face-on torus. In 'type-2' systems the thick, nearly edge-on torus hides the central engine. Later studies suggested evolutionary effects2 and added dusty clumps and polar winds3 but left the basic picture intact. However, recent high-resolution images4 of the archetypal type-2 galaxy NGC 10685,6, suggested a more radical revision. The images displayed a ring-like emission feature that was proposed to be hot dust surrounding the black hole at the radius where the radiation from the central engine evaporates the dust. That ring is too thin and too far tilted from edge-on to hide the central engine, and ad hoc foreground extinction is needed to explain the type-2 classification. These images quickly generated reinterpretations of the dichotomy between types 1 and 27,8. Here we present new multi-band mid-infrared images of NGC 1068 that detail the dust temperature distribution and reaffirm the original model. Combined with radio data (J.F.G. and C.M.V.I., manuscript in preparation), our maps locate the central engine that is below the previously reported ring and obscured by a thick, nearly edge-on disk, as predicted by the unified model. We also identify emission from polar flows and absorbing dust that is mineralogically distinct from that towards the Milky Way centre.

CEST MRI provides amide/amine surrogate biomarkers for treatment-naïve glioma sub-typing.

PURPOSE: Accurate glioma classification affects patient management and is challenging on non- or low-enhancing gliomas. This study investigated the clinical value of different chemical exchange saturation transfer (CEST) metrics for glioma classification and assessed the diagnostic effect of the presence of abundant fluid in glioma subpopulations. METHODS: Forty-five treatment-naïve glioma patients with known isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion status received CEST MRI (B1rms = 2µT, Tsat = 3.5 s) at 3 T. Magnetization transfer ratio asymmetry and CEST metrics (amides: offset range 3-4 ppm, amines: 1.5-2.5 ppm, amide/amine ratio) were calculated with two models: 'asymmetry-based' (AB) and 'fluid-suppressed' (FS). The presence of T2/FLAIR mismatch was noted. RESULTS: IDH-wild type had higher amide/amine ratio than IDH-mutant_1p/19qcodel (p < 0.022). Amide/amine ratio and amine levels differentiated IDH-wild type from IDH-mutant (p < 0.0045) and from IDH-mutant_1p/19qret (p < 0.021). IDH-mutant_1p/19qret had higher amides and amines than IDH-mutant_1p/19qcodel (p < 0.035). IDH-mutant_1p/19qret with AB/FS mismatch had higher amines than IDH-mutant_1p/19qret without AB/FS mismatch ( < 0.016). In IDH-mutant_1p/19qret, the presence of AB/FS mismatch was closely related to the presence of T2/FLAIR mismatch (p = 0.014). CONCLUSIONS: CEST-derived biomarkers for amides, amines, and their ratio can help with histomolecular staging in gliomas without intense contrast enhancement. T2/FLAIR mismatch is reflected in the presence of AB/FS CEST mismatch. The AB/FS CEST mismatch identifies glioma subgroups that may have prognostic and clinical relevance.

Modelling ecosystem dynamics to assess the effect of coastal fisheries on cetacean species.

The expansion of fisheries and its increased efficiency are causing severe detrimental impacts on marine species and ecosystems, that can be categorised into operational and ecological effects. While impacts directly caused by fishing activities have been extensively documented, it is difficult to set an empirical link between fisheries and changes in predator biomass and abundance. Therefore, exploring the functioning of ecosystems as a whole, the interactions between the different species within them and the impact of human activities, is key to understanding the ecological effects of fisheries on top predators and ecosystems, and to develop effective conservation measures, while ensuring a more sustainable exploitation of fishing resources. For instance, mass balance models, such as Ecopath with Ecosim, have proven to be a useful tool to develop more holistic fisheries management and conservation strategies. In this study, Ecopath with Ecosim was used to investigate the temporal dynamics of the Rías Baixas shelf ecosystem (North-West Spain) between 2005 and 2017. Additionally, nine 30-year forward projecting simulations covering the period 2018-2047 were developed to examine the effects of differing fisheries management strategies on common dolphins (Delphinus delphis), bottlenose dolphins (Tursiops truncatus) and harbour porpoises (Phocoena phocoena). Results from these models suggest that when intense fishing increases it poses a major threat to the conservation of these top predators in the area, by reducing the variety of their available prey and potentially enhancing competition amongst them. The study highlights the applicability of Ecopath with Ecosim to develop cetacean conservation measures and despite its small spatial scale, it provides a general framework that can be used to assess cetacean conservation in larger and impacted areas.

Heavy Particle Impact Vibrational Excitation and Dissociation Processes in CO2.

A heavy particle impact vibrational excitation and dissociation model for CO2 is presented. This state-to-state model is based on the forced harmonic oscillator (FHO) theory, which is more accurate than current state-of-the-art kinetic models of CO2 based on first-order perturbation theory. The first excited triplet state 3B2 of CO2, including its vibrational structure, is considered in our model, and a more consistent approach to CO2 dissociation is also proposed. The model is benchmarked against a few academic zero-dimensional (0D) cases and compared to decomposition time measurements in a shock tube. Our model is shown to have reasonable predictive capabilities, and the CO2 + O ↔ CO + O2 reaction is found to have a key influence on the dissociation dynamics of CO2 shocked flows, warranting further theoretical studies. We conclude this study with a discussion on the theoretical improvements that are still required for a more consistent analysis of the vibrational/dissociation dynamics of CO2.

Mitochondrial Signature in Human Monocytes and Resistance to Infection in C. elegans During Fumarate-Induced Innate Immune Training.

Monocytes can develop immunological memory, a functional characteristic widely recognized as innate immune training, to distinguish it from memory in adaptive immune cells. Upon a secondary immune challenge, either homologous or heterologous, trained monocytes/macrophages exhibit a more robust production of pro-inflammatory cytokines, such as IL-1ß, IL-6, and TNF-α, than untrained monocytes. Candida albicans, ß-glucan, and BCG are all inducers of monocyte training and recent metabolic profiling analyses have revealed that training induction is dependent on glycolysis, glutaminolysis, and the cholesterol synthesis pathway, along with fumarate accumulation; interestingly, fumarate itself can induce training. Since fumarate is produced by the tricarboxylic acid (TCA) cycle within mitochondria, we asked whether extra-mitochondrial fumarate has an effect on mitochondrial function. Results showed that the addition of fumarate to monocytes induces mitochondrial Ca2+ uptake, fusion, and increased membrane potential (Δψm), while mitochondrial cristae became closer to each other, suggesting that immediate (from minutes to hours) mitochondrial activation plays a role in the induction phase of innate immune training of monocytes. To establish whether fumarate induces similar mitochondrial changes in vivo in a multicellular organism, effects of fumarate supplementation were tested in the nematode worm Caenorhabditis elegans. This induced mitochondrial fusion in both muscle and intestinal cells and also increased resistance to infection of the pharynx with E. coli. Together, these findings contribute to defining a mitochondrial signature associated with the induction of innate immune training by fumarate treatment, and to the understanding of whole organism infection resistance.

Food-web interactions in a coastal ecosystem influenced by upwelling and terrestrial runoff off North-West Spain.

Ecopath with Ecosim has been used to create mass-balance models of different type of ecosystems around the world to explore and analyse their functioning and structure. This modelling framework has become a key tool in the ecosystem approach to fisheries management, by providing a more comprehensive and holistic understanding of the interactions between the different species. Additionally, Ecopath with Ecosim has provided a useful framework to study ecosystem maturity, changes in the ecosystem functioning over time and the impact of fisheries and aquaculture on the ecosystem, among other aspects. The present work explores the ecosystem functioning and structure in an anthropogenically impacted coastal area, influenced by seasonal coastal upwelling and high input of nutrients from rias (ancient drowned tectonic valleys) off North-West Spain. A mass-balance model with 23 functional groups was created using Ecopath to study the trophic interactions in the ecosystem during the post-upwelling period (August to October) in 2017. The model described an immature, wasp-waist ecosystem, that shared characteristics of ecosystems found in upwelling areas and ecosystems found in fjords or coastal embayments. Deeper analyses highlighted the importance of small planktivorous pelagic fish as a keystone functional group, and of zooplankton, blue whiting (Micromesistius poutassou) and phytoplankton as structuring groups in the ecosystem. Additionally, the study revealed that the existing fishing pressure on species of intermediate-high trophic levels could alter ecosystem functioning and structure, and ultimately affect top predators in the area. Findings of this study provide baseline information in ecosystem functioning and structure in the area and highlight the need to deeper study the effects of fisheries and their potential impacts on top predators.

Mitochondria: An Integrative Hub Coordinating Circadian Rhythms, Metabolism, the Microbiome, and Immunity.

There is currently some understanding of the mechanisms that underpin the interactions between circadian rhythmicity and immunity, metabolism and immune response, and circadian rhythmicity and metabolism. In addition, a wealth of studies have led to the conclusion that the commensal microbiota (mainly bacteria) within the intestine contributes to host homeostasis by regulating circadian rhythmicity, metabolism, and the immune system. Experimental studies on how these four biological domains interact with each other have mainly focused on any two of those domains at a time and only occasionally on three. However, a systematic analysis of how these four domains concurrently interact with each other seems to be missing. We have analyzed current evidence that signposts a role for mitochondria as a key hub that supports and integrates activity across all four domains, circadian clocks, metabolic pathways, the intestinal microbiota, and the immune system, coordinating their integration and crosstalk. This work will hopefully provide a new perspective for both hypothesis-building and more systematic experimental approaches.

First record of atypical pigmentation pattern in fin whale Balaenoptera physalus in the Atlantic Ocean.

Atypical pigmentation, which is rarely observed in the wild, may influence social interactions between animals and can be detrimental for survival. Hypopigmentation, which is the lack of pigment in a part or on the entire body, is a type of atypical pigmentation pattern that can be either acquired (e.g. vitiligo) or congenital resulting from the inheritance of mutations in pigment-related genes (e.g. albinism, leucism and piebaldism). This study documents atypical pigmentation in a fin whale Balaenoptera physalus off the northwestern coast of the Iberian Peninsula (Atlantic Ocean). Photographic and video data collected between 2016 and 2017 on 30 individual fin whales were examined. One fully-grown fin whale exhibited hypopigmentation. Several white patches of different shapes and sizes were present across the body of the fin whale including on the head, body, dorsal fin, flippers, and flukes. The position, shape, and lack of inflammation of the white patches on the whale observed, along with its body length and condition, might indicate that the depigmentation pattern is due to vitiligo. To our knowledge, this is the first case of atypical pigmentation pattern in fin whales described with photographs and video records. As these observations are rare, especially in highly migratory, long-lived, marine mammal species, this study provides valuable information to better understand the occurrence of this phenomenon. Further studies are needed to determine the ecological and physiological implications of atypical colourations, which might have a significant influence on the animal's survival.

Curcumin and α/ß-Adrenergic Antagonists Cotreatment Reverse Liver Cirrhosis in Hamsters: Participation of Nrf-2 and NF-κB.

Liver cirrhosis is the result of an uncontrolled fibrogenetic process, due to the activation and subsequent differentiation into myofibroblasts of the hepatic stellate cells (HSC). It is known that HSC express adrenoreceptors (AR), and the use of AR antagonists protects experimental animals from cirrhosis. However, several studies suggest that the toxicity generated by metabolism of these antagonists would hinder its use in cirrhotic patients. In addition, liver fibrosis may be associated with a decrease of the antioxidant response of the nuclear factor erythroid 2-related factor 2 (Nrf-2) and the overregulation of the proinflammatory pathway of nuclear factor kappa B (NF-κB). Therefore, in the present work, the capacity of doxazosin (α1 antagonist), carvedilol (nonselective beta-adrenoceptor blocker with alpha 1-blocking properties), and curcumin (antioxidant and anti-inflammatory compound) to reverse liver cirrhosis and studying the possible modulation of Nrf-2 and NF-κB were evaluated. Hamsters received CCl4 for 20 weeks, and then treatments were immediately administered for 4 weeks more. The individual administration of doxazosin or carvedilol showed less ability to reverse cirrhosis in relation to concomitantly curcumin administration. However, the best effect was the combined effect of doxazosin, carvedilol, and curcumin, reversing liver fibrosis and decreasing the amount of collagen I (Sirius red stain) without affecting the morphology of hepatocytes (hematoxylin and eosin stain), showing normal hepatic function (glucose, albumin, AST, ALT, total bilirubin, and total proteins). In addition, carvedilol treatment and the combination of doxazosin with curcumin increased Nrf-2/NF-κB mRNA ratio and its protein expression in the inflammatory cells in the livers, possibly as another mechanism of hepatoprotection. Therefore, these results suggest for the first time that α/ß adrenergic blockers with curcumin completely reverse hepatic damage, possibly as a result of adrenergic antagonism on HSC and conceivably by the increase of Nrf-2/NF-κB mRNA ratio.

LprG and PE_PGRS33 Mycobacterium tuberculosis virulence factors induce differential mitochondrial dynamics in macrophages.

The interaction of a pathogen with its host cell takes place at different levels, including the bioenergetics adaptation of both the pathogen and the host cell in the course of an infection. In this regard, Mycobacterium tuberculosis infection of macrophages induces mitochondrial membrane potential (Δψm) changes and cytochrome c release, depending on the bacteria strain's virulence, and the mitochondrial dynamics is modified by pathogens, such as Listeria monocytogenes. Here, we investigated whether two M. tuberculosis virulence factors are able to induce distinguishable bioenergetics traits in human monocyte-derived macrophages (MDMs). Results showed that Rv1411c (LprG, p27) induced mitochondrial fission, lowered the cell respiratory rate and modified the kinetics of mitochondrial Ca2+ uptake in response to agonist stimulation. In contrast, Rv1818c (PE_PGRS33) induced mitochondrial fusion, but failed to induce any appreciable effect on cell respiratory rate or mitochondrial Ca2+ uptake. Overall, these results suggest that two different virulence factors from the same pathogen (M. tuberculosis) induce differential effects on mitochondrial dynamics, cell respiration and mitochondrial Ca2+ uptake in MDMs. The timing of differential mitochondrial activity could ultimately determine the outcome of host-pathogen interactions.

Valor de la comunicación externa en la opinion de la población sobre su hospital / The value of external communications and how they affect a city´s opinion about its hospital

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