Assessment of the adaptive capacity of Morada Nova ewes with different coat coloration.

Coat color is a factor affecting heat tolerance in tropical ruminant and a particular coat color can determine which is more resilient to environmental changes. The aim of this study was to measure the level of adaptation of Morada Nova sheep with different coat color by using an Adaptability Index (AI). Adult ewes were used, including two different coat colors of Morada Nova sheep (red and white) with mean of body weight of 28.02 ± 5.70 kg and 31.47 ± 3.41 kg, respectively. Physiology parameters, hematology, electrolytes, acid-base status, mineral, renal functions, metabolites, enzymes, and proteins were measured. AI was designed using a multivariate approach (principal component analysis) to "weigh" the influence of each variable in the animal responses. The variables more important for adaptive aspects of Red Morada Nova were: haematology, electrolytes and acid-base status. The hemoglobin (HG), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), sodium (Na+), oxygen pressure (PO2), glucose (GLU) and albumin (ALB) were significantly higher in Red Morada Nova sheep and hydrogen carbonate (HCO3), base excess (BE), total carbon dioxide concentration (TCO2) and URE were significantly higher in the white phenotype. The variables more important for adaptive aspects of White Morada Nova sheep were: (K+), total protein (TP), PO2, HG, cholesterol (CHO), rectal temperature (RT) and glucose (GLU). Both phenotypes showed a high adaptation level, however, a higher value was generated for the Red Morada Nova sheep (81.97). This study concludes that both phenotypes of the Morada Nova sheep breed are well adapted to the climatic condition of the Brazilian tropical region using different adaptive mechanisms.

Compilations and updates on residual feed intake in sheep.

The increasing global demand for food and the strong effect of climate change have forced animal science to advance regarding new methods of selection in search of more efficient animals in production systems. Feed consumption represents more than 70% of the costs of sheep farms, and more efficient animals can increase the farmers' profitability. One of the main measures of feed efficiency is estimated residual feed intake (RFI), created in 1963 by Robert Koch for estimation in cattle and later adapted for sheep. Animals with negative RFI values (RFI-) are more efficient than animals with positive values (RFI+), with influence on the variables of performance, carcass quality and production of enteric gases. The RFI is the most common and accepted metric of the feed efficiency trait for genetic selection, since it is independent of growth traits, unlike the feed conversion ratio. The purpose of this review article was to present updated literature information on the relationship of RFI estimates with performance measures, molecular markers, greenhouse gas production and feed efficiency, the technical aspects and physiological basis of metabolic in sheep.

Performance, feed efficiency, feeding behavior, and cortisol concentration of lambs ranked for Residual Feed Intake and Residual Intake and Gain.

This study aimed to evaluate the performance, feed efficiency, feeding behavior, and cortisol concentrations of lambs ranked into different groups of Residual Feed Intake (RFI) and Residual Intake and Gain (RIG). Forty Santa Inês lambs with a mean initial age of 120 ± 30 days and mean initial (IBW) and final body weight (FBW) of 28.9 ± 3.2 and 43.7 ± 3.9 kg, respectively, were used. The animals were fed at an automatic feed and water station (Intergado®) for 60 days and classified at the end of the experiment as low-RFI/RIG, medium-RFI/RIG, and high-RFI/RIG according to RFI and RIG. Performance, feed efficiency measures, ingestive behavior, temperament, and cortisol concentrations were measured, and Pearson's correlation analysis was performed to evaluate the relationship between the variables studied. The variables that differed most between RFI groups were dry matter intake, feed conversion, and feed efficiency, with better values in efficient animals (RFI-). Regarding the RGI groups, the average daily gain of animals classified as RIG- was 19.37% lower than that of animals classified as RIG± and 39.28% lower than that of animals classified as RIG+. Only the hourly feeding rate per day (p = 0.04) differed significantly between RFI and RIG classes, while no differences were observed for the ingestive behavior variables or cortisol. The number of visits to the feed bunk (total, with or without intake) showed no correlation with any performance or efficiency measure. Identifying animals ranked into different RFI and RIG classes shows that more efficient animals have a lower feed intake for the same weight gain and spend less time at the feed bunk.

Clinical and Prognostic Impact of the Warburg Effect in Esophageal Carcinoma: Monocarboxylate Transporters as Candidates for Therapeutic Targeting.

INTRODUCTION: Esophageal cancer (EC) seems to display increased glycolytic activity, but clinical studies on the expression/prognostic significance of glycometabolism-related proteins, as well as functional assays, are missing. METHODS: Expression of 10 glycolytic biomarkers was evaluated by immunohistochemistry in tissue sections from 95 patients. Two esophageal squamous cell carcinoma (ESCC) cell lines were used to assess the effect of monocarboxylate transporter (MCT) downregulation on cell viability and extracellular lactate/glucose accumulation. RESULTS: Expression of MCT1, MCT4, CD147, and GLUT1 was significantly associated with an ESCC histopathology, while a poor clinicopathological profile was seen in GLUT1- and LDHA-positive EC cases. In the ESCC group, MCT1 immunoreactivity is associated with high TNM stage and metastasis. The 3-year overall survival (OS) rate was significantly influenced by MCT4 and CAIX positivity and HKII negativity. Those biomarkers were considered independent prognostic factors of OS in multivariate analysis. Dual inhibition of MCT1/4 expression decreased cell viability and extracellular lactate accumulation in ESCC cells. CONCLUSION: Elevated glycolytic rates correlate with a poor clinicopathological profile in EC patients. MCT4 and CAIX positivity independently predict a worse prognosis. Due to the lack of information on treatment modalities, we could not further infer the role of these biomarkers in predicting response to therapy, which needs to be assessed in future studies. In addition, MCT1/4 targeting should be performed both "in vitro" and "in vivo" to further explore its impact on tumor growth and response to classical therapies. HKII expression and function, particularly in the tumor stroma, should be investigated.

Sarcopenia in Children With Wilms Tumor: A Marker of Undernutrition Which May Impact Adversely on Clinical Outcomes.

The therapeutic approach to Wilms tumor (WT) is multidisciplinary and leads to significant patient impairment, increasing the risk of nutritional compromise and malnutrition. Children with cancer are vulnerable to sarcopenia which has been recognized as a negative impact of anticancer therapy. Recent studies have highlighted the reduction in the total psoas muscle area (TPMA) to be associated with a poor prognosis in many pediatric diseases, including cancer. This study aims to evaluate changes in the TPMA compartment during the treatment of children with WT. An observational, longitudinal, and retrospective study was undertaken in a single institution evaluating children (1 to 14 y, n=38) with WT between 2014 and 2020. TPMA was assessed by the analysis of previously collected, electronically stored computed tomography images of the abdomen obtained at 3 time points: diagnosis, preoperatively, and 1 year after surgery. For all patients, TPMA/age were calculated with a specific online calculator. Our data show a high incidence of sarcopenia (55.3%) at diagnosis which increased after 4 to 6 weeks of neoadjuvant chemotherapy (73.7%) and remained high (78.9%) 1 year after the surgical procedure. Using TPMA/age Z-score curves we have found significant and rapid muscle loss in children with WT, with little or no recovery in the study period.

Effects of adding aerobic physical activity to strengthening exercise on hip osteoarthritis symptoms: protocol for the PHOENIX randomised controlled trial.

BACKGROUND: Hip osteoarthritis (OA) is a leading cause of musculoskeletal pain. Exercise is a core recommended treatment. Most evidence is based on muscle-strengthening exercise, but aerobic physical activity has potential to enhance clinical benefits. The primary aim of this study is to test the hypothesis that adding aerobic physical activity to a muscle strengthening exercise leads to significantly greater reduction in hip pain and improvements in physical function, compared to a lower-limb muscle strengthening exercise program alone at 3 months. METHODS: This is a superiority, 2-group, parallel randomised controlled trial including 196 people with symptomatic hip OA from the community. Following baseline assessment, participants are randomly allocated to receive either i) aerobic physical activity and muscle strengthening exercise or; ii) muscle strengthening exercise only. Participants in both groups receive 9 consultations with a physiotherapist over 3 months. Both groups receive a progressive muscle strengthening exercise program in addition to advice about OA management. The aerobic physical activity plan includes a prescription of moderate intensity aerobic physical activity with a goal of attaining 150 min per week. Primary outcomes are self-reported hip pain assessed on an 11-point numeric rating scale (0 = 'no pain' and 10 = 'worst pain possible') and self-reported physical function (Western Ontario and McMaster Universities Osteoarthritis Index physical function subscale) at 3 months. Secondary outcomes include other measures of self-reported pain (assessed at 0, 3, 9 months), self-reported physical function (assessed at 0, 3, 9 months), performance-based physical function (assessed at 0, 3 months), joint stiffness (assessed at 0, 3, 9 months), quality of life (assessed at 0, 3, 9 months), muscle strength (assessed at 0, 3 months), and cardiorespiratory fitness (assessed at 0, 3 months). Other measures include adverse events, co-interventions, and adherence. Measures of body composition, serum inflammatory biomarkers, quantitative sensory measures, anxiety, depression, fear of movement and self-efficacy are included to explore causal mechanisms. DISCUSSION: Findings will assist to provide an evidence-based recommendation regarding the additional effect of aerobic physical activity to lower-limb muscle strengthening on hip OA pain and physical function. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry reference: ACTRN 12619001297112. Registered 20th September 2019.

Valorisation Potential of Invasive Acacia dealbata, A. longifolia and A. melanoxylon from Land Clearings.

Acacia spp. are invasive in Southern Europe, and their high propagation rates produce excessive biomass, exacerbating wildfire risk. However, lignocellulosic biomass from Acacia spp. may be utilised for diverse biorefinery applications. In this study, attenuated total reflectance Fourier transform infrared spectroscopy (FTIR-ATR), high-performance anion-exchange chromatography pulsed amperometric detection (HPAEC-PAD) and lignin content determinations were used for a comparative compositional characterisation of A. dealbata, A. longifolia and A. melanoxylon. Additionally, biomass was treated with three white-rot fungi species (Ganoderma lucidum, Pleurotus ostreatus and Trametes versicolor), which preferentially degrade lignin. Our results showed that the pre-treatments do not significantly alter neutral sugar composition while reducing lignin content. Sugar release from enzymatic saccharification was enhanced, in some cases possibly due to a synergy between white-rot fungi and mild alkali pretreatments. For example, in A. dealbata stems treated with alkali and P. ostreatus, saccharification yield was 702.3 nmol mg-1, which is higher than the samples treated only with alkali (608.1 nmol mg-1), and 2.9-fold higher than the non-pretreated controls (243.9 nmol mg-1). By characterising biomass and pretreatments, generated data creates value for unused biomass resources, contributing to the implementation of sustainable biorefining systems. In due course, the generated value will lead to economic incentives for landowners to cut back invasive Acacia spp. more frequently, thus reducing excess biomass, which exacerbates wildfire risk.

Brain state monitoring for the future prediction of migraine attacks.

BACKGROUND: Migraine attacks are unpredictable, precluding preemptive interventions and leading to lack of control over individuals' lives. Although there are neurophysiological changes 24-48 hours before migraine attacks, so far, they have not been used in patients' management. This study evaluates the applicability and the ability to identify pre-attack changes of daily "at home" electroencephalography obtained with a portable system for migraine patients. METHODS: Patients with episodic migraine fulfilling ICHD-3 beta criteria used a mobile system composed of a wireless EEG device (BrainStation®, Neuroverse®, Inc., USA) and mobile application (BrainVitalsM®, Neuroverse®, Inc., USA) to self-record their neural activity daily at home while resting and while performing an attention task, over the course of 2 weeks. Standard EEG spectral analysis and event-related brain potentials (ERP) methods were used and recordings were grouped by time from migraine attacks (i.e. "Interictal day", "24 h Before Migraine", "Migraine day" and "Post Migraine"). RESULTS: Twenty-four patients (22 women) recorded an average of 13.3 ± 1.9 days and had 2 ± 0.9 attacks. Twenty-four hours before attack onset, there was a statistically significant modulation of relative power in the delta (decrease) and beta (increase) frequency bands, at rest, and a significant reduction of the amplitude and inter-trial coherence measures of an attention event-related brain potential (P300). CONCLUSIONS: This proof-of-concept study shows that brain state monitoring, utilising an easy-to-use wearable EEG system to track neural modulations at home, can identify physiological changes preceding a migraine attack enabling valuable pre-symptom prediction and subsequent early intervention.

Evaluation of a cattle rapid test for early pregnancy diagnosis in sheep.

The early pregnancy diagnosis allows optimizing production and timely management correction, with a greater reproductive output of livestock. The Idexx Rapid Visual Pregnancy Test® consists of an ELISA for visual reading which does not require the use of readers in the laboratory, with satisfactory pregnancy diagnoses at 28 days of pregnancy in cattle. Therefore, the aim of this study was to evaluate this rapid test and to verify the most appropriate day for the diagnosis of pregnancy in the ovine species. For this purpose, 98 serum samples from pregnant sheep and 36 from non-pregnant were used, with duplicate samples, and diagnosis was confirmed by ultrasound examination, used as the gold standard. The numbers of positive samples obtained at 26, 28, and 30 days of pregnancy were 26, 27, and 45, respectively. The Rapid Visual Pregnancy Test correctly identified 100% of the samples as positive at pregnancy of days 26, 28, and 30. The sensitivity and specificity of the test were also 100%. The Idexx Rapid Visual Pregnancy Test, initially indicated for cattle, is effective for the detection of pregnancy in the ovine species, enabling diagnosis of pregnant sheep from the 26th day of pregnancy.

Uterine hemodynamics during a short-term progesterone synchronization protocol in ewes.

Twenty-eight pluriparous and non-lactating Santa Inês sheep were synchronized with vaginal sponge and an intramuscular (IM) injection of 37.5 µg of cloprostenol on random days of the estrous cycle (D0); day 6 (D6), at 7:00 am, the devices were removed, and after 24 h (D7), GnRH analog (25 µg of lecirelin) was administrated. Fixed-time artificial insemination (FTAI) with cervical traction by the transcervical route was performed 52 to 58 h after sponge removal. Doppler velocimetry of both uterine arteries was performed on D0, D2, D4, and the morning of D6 (every 48 h), and then every 12 h from D6 to D8 (7:00 a.m. and 7:00 p.m.). We analyzed the peak systolic velocity (PSV), end-diastolic velocity (EVD), time-averaged maximum and mean velocity (TAMAX, TAMEAN), pulsatility index (PI), resistance index (RI), systolic/diastolic ratio (S/D), arterial diameter (AD), and blood flow volume (BFV), with the objective of evaluating the hemodynamic behavior of blood flow velocity parameters of the uterine artery during a short-term progesterone synchronization protocol in ewes. With respect to phases, we noted increases in the means of TAMAX and TAMEAN and decreases of EDV, PI, and RI (P < 0.05). S/D, EDV, TAMEAN, PI, RI, SD, AD, and BFV showed differences between the time of progesterone insertion and the estimated time of ovulation (which was considered the last evaluation) (P < 0.05). The PI and RI values were different when comparing the times of insertion and withdrawal of the progesterone device (PI 2.53-1.54 and RI 0.76-0.68) (P < 0.05). The PI was different with respect to side (P < 0.001), but no side effect was seen in the RI. In conclusion, the two uterine arteries behave differently under the effect of progesterone (intravaginal sponges) and the effect of estradiol during the follicular phase, and estrous phase was responsible for increasing uterine blood flow.

CAIX is a predictor of pathological complete response and is associated with higher survival in locally advanced breast cancer submitted to neoadjuvant chemotherapy.

BACKGROUND: Locally advanced breast cancer often undergoes neoadjuvant chemotherapy (NAC), which allows in vivo evaluation of the therapeutic response. The determination of the pathological complete response (pCR) is one way to evaluate the response to neoadjuvant chemotherapy. However, the rate of pCR differs significantly between molecular subtypes and the cause is not yet determined. Recently, the metabolic reprogramming of cancer cells and its implications for tumor growth and dissemination has gained increasing prominence and could contribute to a better understanding of NAC. Thus, this study proposed to evaluate the expression of metabolism-related proteins and its association with pCR and survival rates. METHODS: The expression of monocarboxylate transporters 1 and 4 (MCT1 and MCT4, respectively), cluster of differentiation 147 (CD147), glucose transporter-1 (GLUT1) and carbonic anhydrase IX (CAIX) was analyzed in 196 locally advanced breast cancer samples prior to NAC. The results were associated with clinical-pathological characteristics, occurrence of pCR, disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS). RESULTS: The occurrence of pCR was higher in the group of patients whith tumors expressing GLUT1 and CAIX than in the group without expression (27.8% versus 13.1%, p = 0.030 and 46.2% versus 13.5%, p = 0.007, respectively). Together with regional lymph nodes staging and mitotic staging, CAIX expression was considered an independent predictor of pCR. In addition, CAIX expression was associated with DFS and DSS (p = 0.005 and p = 0.012, respectively). CONCLUSIONS: CAIX expression was a predictor of pCR and was associated with higher DFS and DSS in locally advanced breast cancer patients subjected to NAC.

Nutrient and drought stress: implications for phenology and biomass quality in miscanthus.

BACKGROUND AND AIMS: The cultivation of dedicated biomass crops, including miscanthus, on marginal land provides a promising approach to the reduction of dependency on fossil fuels. However, little is known about the impact of environmental stresses often experienced on lower-grade agricultural land on cell-wall quality traits in miscanthus biomass crops. In this study, three different miscanthus genotypes were exposed to drought stress and nutrient stress, both separately and in combination, with the aim of evaluating their impact on plant growth and cell-wall properties. METHODS: Automated imaging facilities at the National Plant Phenomics Centre (NPPC-Aberystwyth) were used for dynamic phenotyping to identify plant responses to separate and combinatorial stresses. Harvested leaf and stem samples of the three miscanthus genotypes (Miscanthus sinensis, Miscanthus sacchariflorus and Miscanthus × giganteus) were separately subjected to saccharification assays, to measure sugar release, and cell-wall composition analyses. KEY RESULTS: Phenotyping showed that the M. sacchariflorus genotype Sac-5 and particularly the M. sinensis genotype Sin-11 coped better than the M. × giganteus genotype Gig-311 with drought stress when grown in nutrient-poor compost. Sugar release by enzymatic hydrolysis, used as a biomass quality measure, was significantly affected by the different environmental conditions in a stress-, genotype- and organ-dependent manner. A combination of abundant water and low nutrients resulted in the highest sugar release from leaves, while for stems this was generally associated with the combination of drought and nutrient-rich conditions. Cell-wall composition analyses suggest that changes in fine structure of cell-wall polysaccharides, including heteroxylans and pectins, possibly in association with lignin, contribute to the observed differences in cell-wall biomass sugar release. CONCLUSIONS: The results highlight the importance of the assessment of miscanthus biomass quality measures in addition to biomass yield determinations and the requirement for selecting suitable miscanthus genotypes for different environmental conditions.

Evaluation of Parasitological Homeopathic Complex in the Control of Gastrointestinal Nematodes in Peripartum Sheep.

BACKGROUND: The appearance of anthelmintic resistance has made it difficult to control verminosis in sheep, leading to increased research to find alternative nematode control. The use of homeopathy in veterinary medicine has been studied as an alternative for the treatment and control of some diseases. In this study, ewes received an anti-parasitic homeopathic complex medicine during the critical peripartum period of increased susceptibility to nematodes. METHODS: Three randomized groups containing 16 animals each were assigned as follows: 'H10' received 10 g homeopathic complex added to concentrated food per day; 'H20' received 20 g homeopathic complex added to concentrated food per day; 'C' (control group) did not receive a homeopathic complex. Animals were tested to evaluate the effect of homeopathy on several health parameters during a period of 110 days. RESULTS: The parasite that prevailed in the copro-cultures of both treatments throughout the experiment was Haemonchus contortus (78.26%). Packed cell volume averages did not present statistically significant differences between the treatments (24.5, 24.4 and 23.9% to C, H10 and H20, respectively; p < 0.05). For total white cell count, lower mean values ( ± standard error of mean) were observed for the H20 treatment (5,490.9 ± 0.02/µL; p < 0.05), whereas the H10 (5,919.4 ± 0.02/µL) and control (6,098.5 ± 0.02/µL) presented higher and similar averages (p > 0.05). The values for erythrocytes, monocytes, and lymphocytes did not show differences between treatments (p > 0.05). Body weight was greater in the H10-treated animals compared with control. For the fecal egg count (FEC) of Trichostrongylidae and Strongyloides spp., respectively, the averages of the H20 treatment (1,523.0 and 30.6) were not different from control (1,616.0 and 31.6) and H10 (1,038.0 and 27.6); for Trichostrongylidae, however, H10 presented a lower FEC than the control (p = 0.02). For Cooperia, H10- and H20-treated animals showed FEC reductions of 97% and 98%, respectively. CONCLUSIONS: H20 treatment in peripartum sheep resulted in greater body weight and lower leukocyte count. H10 was associated with lower FEC for Trichostrongylidae. Both H10 and H20 justify a label of 'effective anthelmintic' for Cooperia.

A cell wall reference profile for Miscanthus bioenergy crops highlights compositional and structural variations associated with development and organ origin.

Miscanthus spp. are promising lignocellulosic energy crops, but cell wall recalcitrance to deconstruction still hinders their widespread use as bioenergy and biomaterial feedstocks. Identification of cell wall characteristics desirable for biorefining applications is crucial for lignocellulosic biomass improvement. However, the task of scoring biomass quality is often complicated by the lack of a reference for a given feedstock. A multidimensional cell wall analysis was performed to generate a reference profile for leaf and stem biomass from several miscanthus genotypes harvested at three developmentally distinct time points. A comprehensive suite of 155 monoclonal antibodies was used to monitor changes in distribution, structure and extractability of noncellulosic cell wall matrix glycans. Glycan microarrays complemented with immunohistochemistry elucidated the nature of compositional variation, and in situ distribution of carbohydrate epitopes. Key observations demonstrated that there are crucial differences in miscanthus cell wall glycomes, which may impact biomass amenability to deconstruction. For the first time, variations in miscanthus cell wall glycan components were comprehensively characterized across different harvests, organs and genotypes, to generate a representative reference profile for miscanthus cell wall biomass. Ultimately, this portrait of the miscanthus cell wall will help to steer breeding and genetic engineering strategies for the development of superior energy crops.

Nonhuman primate model of schizophrenia using a noninvasive EEG method.

There is growing evidence that impaired sensory-processing significantly contributes to the cognitive deficits found in schizophrenia. For example, the mismatch negativity (MMN) and P3a event-related potentials (ERPs), neurophysiological indices of sensory and cognitive function, are reduced in schizophrenia patients and may be used as biomarkers of the disease. In agreement with glutamatergic theories of schizophrenia, NMDA antagonists, such as ketamine, elicit many symptoms of schizophrenia when administered to normal subjects, including reductions in the MMN and the P3a. We sought to develop a nonhuman primate (NHP) model of schizophrenia based on NMDA-receptor blockade using subanesthetic administration of ketamine. This provided neurophysiological measures of sensory and cognitive function that were directly comparable to those recorded from humans. We first developed methods that allowed recording of ERPs from humans and rhesus macaques and found homologous MMN and P3a ERPs during an auditory oddball paradigm. We then investigated the effect of ketamine on these ERPs in macaques. As found in humans with schizophrenia, as well as in normal subjects given ketamine, we observed a significant decrease in amplitude of both ERPs. Our findings suggest the potential of a pharmacologically induced model of schizophrenia in NHPs that can pave the way for EEG-guided investigations into cellular mechanisms and therapies. Furthermore, given the established link between these ERPs, the glutamatergic system, and deficits in other neuropsychiatric disorders, our model can be used to investigate a wide range of pathologies.

Genetic basis of congenital erythrocytosis: mutation update and online databases.

Congenital erythrocytosis (CE), or congenital polycythemia, represents a rare and heterogeneous clinical entity. It is caused by deregulated red blood cell production where erythrocyte overproduction results in elevated hemoglobin and hematocrit levels. Primary congenital familial erythrocytosis is associated with low erythropoietin (Epo) levels and results from mutations in the Epo receptor gene (EPOR). Secondary CE arises from conditions causing tissue hypoxia and results in increased Epo production. These include hemoglobin variants with increased affinity for oxygen (HBB, HBA mutations), decreased production of 2,3-bisphosphoglycerate due to BPGM mutations, or mutations in the genes involved in the hypoxia sensing pathway (VHL, EPAS1, and EGLN1). Depending on the affected gene, CE can be inherited either in an autosomal dominant or recessive mode, with sporadic cases arising de novo. Despite recent important discoveries in the molecular pathogenesis of CE, the molecular causes remain to be identified in about 70% of the patients. With the objective of collecting all the published and unpublished cases of CE the COST action MPN&MPNr-Euronet developed a comprehensive Internet-based database focusing on the registration of clinical history, hematological, biochemical, and molecular data (http://www.erythrocytosis.org/). In addition, unreported mutations are also curated in the corresponding Leiden Open Variation Database.

Transcriptional response to cardiac injury in the zebrafish: systematic identification of genes with highly concordant activity across in vivo models.

BACKGROUND: Zebrafish is a clinically-relevant model of heart regeneration. Unlike mammals, it has a remarkable heart repair capacity after injury, and promises novel translational applications. Amputation and cryoinjury models are key research tools for understanding injury response and regeneration in vivo. An understanding of the transcriptional responses following injury is needed to identify key players of heart tissue repair, as well as potential targets for boosting this property in humans. RESULTS: We investigated amputation and cryoinjury in vivo models of heart damage in the zebrafish through unbiased, integrative analyses of independent molecular datasets. To detect genes with potential biological roles, we derived computational prediction models with microarray data from heart amputation experiments. We focused on a top-ranked set of genes highly activated in the early post-injury stage, whose activity was further verified in independent microarray datasets. Next, we performed independent validations of expression responses with qPCR in a cryoinjury model. Across in vivo models, the top candidates showed highly concordant responses at 1 and 3 days post-injury, which highlights the predictive power of our analysis strategies and the possible biological relevance of these genes. Top candidates are significantly involved in cell fate specification and differentiation, and include heart failure markers such as periostin, as well as potential new targets for heart regeneration. For example, ptgis and ca2 were overexpressed, while usp2a, a regulator of the p53 pathway, was down-regulated in our in vivo models. Interestingly, a high activity of ptgis and ca2 has been previously observed in failing hearts from rats and humans. CONCLUSIONS: We identified genes with potential critical roles in the response to cardiac damage in the zebrafish. Their transcriptional activities are reproducible in different in vivo models of cardiac injury.

Genotype, development and tissue-derived variation of cell-wall properties in the lignocellulosic energy crop Miscanthus.

BACKGROUND AND AIMS: Species and hybrids of the genus Miscanthus contain attributes that make them front-runners among current selections of dedicated bioenergy crops. A key trait for plant biomass conversion to biofuels and biomaterials is cell-wall quality; however, knowledge of cell-wall composition and biology in Miscanthus species is limited. This study presents data on cell-wall compositional changes as a function of development and tissue type across selected genotypes, and considers implications for the development of miscanthus as a sustainable and renewable bioenergy feedstock. METHODS: Cell-wall biomass was analysed for 25 genotypes, considering different developmental stages and stem vs. leaf compositional variability, by Fourier transform mid-infrared spectroscopy and lignin determination. In addition, a Clostridium phytofermentans bioassay was used to assess cell-wall digestibility and conversion to ethanol. KEY RESULTS: Important cell-wall compositional differences between miscanthus stem and leaf samples were found to be predominantly associated with structural carbohydrates. Lignin content increased as plants matured and was higher in stem tissues. Although stem lignin concentration correlated inversely with ethanol production, no such correlation was observed for leaves. Leaf tissue contributed significantly to total above-ground biomass at all stages, although the extent of this contribution was genotype-dependent. CONCLUSIONS: It is hypothesized that divergent carbohydrate compositions and modifications in stem and leaf tissues are major determinants for observed differences in cell-wall quality. The findings indicate that improvement of lignocellulosic feedstocks should encompass tissue-dependent variation as it affects amenability to biological conversion. For gene-trait associations relating to cell-wall quality, the data support the separate examination of leaf and stem composition, as tissue-specific traits may be masked by considering only total above-ground biomass samples, and sample variability could be mostly due to varying tissue contributions to total biomass.

Effect of Personalized Sodium Replacement on Fluid and Sodium Balance and Thermophysiological Strain During and After Ultraendurance Running in the Heat.

PURPOSE: To investigate the effect of personalized sweat sodium replacement on drinking behavior, sodium and water balance, and thermophysiological responses during and after ultraendurance running in hot conditions. METHODS: Nine participants (7 male, 2 female) completed two 5-hour treadmill runs (60% maximum oxygen uptake, 30°C ambient temperature), in a double-blind randomized crossover design, consuming sodium chloride (SODIUM) capsules to replace 100% of previously assessed losses or placebo (PLACEBO). Fluid was consumed ad libitum. RESULTS: No effect of SODIUM was observed for ad libitum fluid intake or net fluid balance (P > .05). Plasma sodium concentration increased in both trials, but to a greater extent in SODIUM at 2.5 hours (mean [SD]: 4 [4] mmol·L-1 vs 1 [5] mmol·L-1; P < .05) and postexercise (4 [3] mmol·L-1 vs 1 [5] mmol·L-1; P < .05). Plasma volume change was not different between trials (P > .05) but was strongly correlated with sodium balance in SODIUM (r = .880, P < .01). No effect of sodium replacement was observed for heart rate, rectal temperature, thermal comfort, perceived exertion, or physiological strain index. During the 24 hours postexercise, ad libitum fluid intake was greater following SODIUM (2541 [711] mL vs 1998 [727] mL; P = .04), as was urinary sodium excretion (NaCl: 66 [35] mmol, Pl: 21 [12] mmol; P < .01). CONCLUSIONS: Personalized sweat sodium replacement during ultraendurance running in hot conditions, with ad libitum fluid intake, exacerbated the rise in plasma sodium concentration compared to no sodium replacement but did not substantially influence overall body-water balance or thermophysiological strain. A large sodium deficit incurred during exercise leads to substantial renal sodium conservation postexercise.

Traditional herbal compounds as candidates to inhibit the SARS-CoV-2 main protease: an in silico study.

COVID-19, a disease caused by the SARS-CoV-2 virus, is responsible for a pandemic since March 2020 and it has no cure. Therefore, herein, different theoretical methods were used to obtain potential candidates from herbal compounds to inhibit the SARS-CoV-2 main protease (Mpro). Initially, the 16 best-scored compounds were selected from a library containing 4066 ligands using virtual screening by molecular docking. Among them, six molecules (physalin B 5,6-epoxide (PHY), methyl amentoflavone (MAM), withaphysalin C (WPC), daphnoline or trilobamine (TRI), cepharanoline (CEP) and tetrandrine (TET)) were selected based on Lipinski's rule and ADMET analysis as criteria. These compounds complexed with the Mpro were submitted to triplicate 100 ns molecular dynamics simulations. RMSD, RMSF, and radius of gyration results show that the overall protein structure is preserved along the simulation time. The average ΔGbinding values, calculated by the MM/PBSA method, were -41.7, -55.8, -45.2, -38.7, -49.3, and -57.9 kcal/mol for the PHY-Mpro, MAM-Mpro, WPC-Mpro, CEP-Mpro, TRI-Mpro, and TET-Mpro complexes, respectively. Pairwise decomposition analyses revealed that the binding pocket is formed by His41-Val42, Met165-Glu166-Leu167, Asp187, and Gln189. The PLS regression model generated by QSPR analysis indicated that non-polar and polar groups with the presence of hydrogen bond acceptors play an important role in the herbal compounds-Mpro interactions. Overall, we found six potential candidates to inhibit the SARS-CoV-2 Mpro and highlighted key residues from the binding pocket that can be used for future drug design. Communicated by Ramaswamy H. Sarma.