Mechanism of RanGTP priming H2A-H2B release from Kap114 in an atypical RanGTP•Kap114•H2A-H2B complex.

Previously, we showed that the nuclear import receptor Importin-9 wraps around the H2A-H2B core to chaperone and transport it from the cytoplasm to the nucleus. However, unlike most nuclear import systems where RanGTP dissociates cargoes from their importins, RanGTP binds stably to the Importin-9•H2A-H2B complex, and formation of the ternary RanGTP•Importin-9•H2A-H2B complex facilitates H2A-H2B release to the assembling nucleosome. It was unclear how RanGTP and the cargo H2A-H2B can bind simultaneously to an importin, and how interactions of the three components position H2A-H2B for release. Here, we show cryo-EM structures of Importin-9•RanGTP and of its yeast homolog Kap114, including Kap114•RanGTP, Kap114•H2A-H2B, and RanGTP•Kap114•H2A-H2B, to explain how the conserved Kap114 binds H2A-H2B and RanGTP simultaneously and how the GTPase primes histone transfer to the nucleosome. In the ternary complex, RanGTP binds to the N-terminal repeats of Kap114 in the same manner as in the Kap114/Importin-9•RanGTP complex, and H2A-H2B binds via its acidic patch to the Kap114 C-terminal repeats much like in the Kap114/Importin-9•H2A-H2B complex. Ran binds to a different conformation of Kap114 in the ternary RanGTP•Kap114•H2A-H2B complex. Here, Kap114 no longer contacts the H2A-H2B surface proximal to the H2A docking domain that drives nucleosome assembly, positioning it for transfer to the assembling nucleosome or to dedicated H2A-H2B chaperones in the nucleus.

Levels of Angiopoietin 2 Are Predictive for Mortality in Patients Infected With Yellow Fever Virus.

In 2018 there was a large yellow fever outbreak in São Paulo, Brazil, with a high fatality rate. Yellow fever virus can cause, among other symptoms, hemorrhage and disseminated intravascular coagulation, indicating a role for endothelial cells in disease pathogenesis. Here, we conducted a case-control study and measured markers related to endothelial damage in plasma and its association with mortality. We found that angiopoietin 2 is strongly associated with a fatal outcome and could serve as a predictive marker for mortality. This could be used to monitor severe cases and provide care to improve disease outcome.

Viral Kinetics in Sylvatic Yellow Fever Cases.

BACKGROUND: Yellow fever is a mosquito-borne zoonotic disease caused by yellow fever virus (YFV). Between 2017 and 2019, more than 504 human cases and 176 deaths were confirmed in the outskirts of São Paulo city. Throughout this outbreak, studies suggested a potential association between YFV viremia and mortality. METHODS: Viral ribonucleic acid was measured using reverse-transcription quantitative polymerase chain reaction in plasma samples collected at up to 5 time points, between 3 and 120 days after symptoms onset. RESULTS: Eighty-four patients with confirmed YFV infection were included. Most were males, median age was 42, and 30 (36%) died. Deceased patients were older than survivors (P = .003) and had a higher viremia across all time points (P = .0006). Mean values of viremia had a positive, statistically significant correlation with peak values of neutrophils, indirect bilirubin, aspartate transaminase, international normalized ratio, and creatinine. Finally, a Cox proportional hazards model adjusted for age and laboratory variables showed that viremia is independently associated with death, with a mean 1.84-fold increase (84%) in the hazard of death (P < .001) for each unit increase in mean log10 viremia. CONCLUSIONS: Our results raise the importance of monitoring YFV viremia and suggest a potential benefit of antiviral drugs or neutralizing monoclonal antibodies early in the course of this infection to improve disease outcomes.

Levels of angiopoietin-2 are predictive for mortality in yellow fever virus infected patients.

In 2018 there was a large yellow fever outbreak in São Paulo, Brazil, with a high fatality rate. Yellow fever virus can cause, among other symptoms, haemorrhage and disseminated intravascular coagulation, indicating a role for endothelial cells in the disease pathogenesis. Here, we conducted a case-control study and measured markers related to endothelial damage in plasma and its association with mortality. We found that angiopoietin-2 is strongly associated with a fatal outcome and could serve as a predictive marker for mortality. This could be used to monitor severe patients and provide care to improve disease outcome.

Autologous stem cell transplantation improves cardiopulmonary exercise testing outcomes in systemic sclerosis patients.

OBJECTIVES: Autologous haematopoietic stem cell transplantation (AHSCT) is a disease-modifying treatment for patients with severe SSc. Here, we aimed at assessing cardiopulmonary function outcomes of SSc patients after AHSCT. METHODS: Twenty-seven SSc adult patients treated with AHSCT were included in this retrospective study. Most had the diffuse cutaneous subset (93%) and pulmonary involvement (85%). Before and 12 months after AHSCT, patients underwent cardiopulmonary exercise testing, transthoracic echocardiography, pulmonary function test with diffusing capacity for carbon monoxide (DLCO), 6-min walk test (6MWT) and quality of life evaluations. RESULTS: After AHSCT, the peak VO2 increased from 954 to 1029 ml/min (P = 0.02), the percentage of predicted peak VO2 increased from 48.9 to 53.5 m (P = 0.01), and the distance measured by the 6MWT increased from 445 to 502 m (P = 0.01), compared with baseline. Improvements in peak VO2 correlated positively with improvements in 6MWT distance, and negatively with a decrease in resting heart rate. At baseline, patients with DLCO >70% had higher peak VO2 values than those with DLCO <70% (P = 0.04), but after AHSCT all patients showed improved VO2 values, regardless of baseline DLCO levels. Increases in VO2 levels after AHSCT positively correlated with increases in the physical component scores of the Short Form-36 quality of life questionnaire (r = 0.70; P = 0.0003). CONCLUSION: AHSCT improves the aerobic capacity of SSc patients probably reflecting combined increments in lungs, skeletal muscle and cardiac function.

Release Assays and Potency Assays for CAR T-Cell Interventions.

Chimeric antigen receptor (CAR) T-cells are considered "living drugs" and offer a compelling alternative to conventional anticancer therapies. Briefly, T-cells are redirected, using gene engineering technology, toward a specific cancer cell surface target antigen via a synthetic chimeric antigen receptor (CAR) protein. CARs have a modular design comprising four main structures: an antigen-binding domain, a hinge region, a transmembrane domain, and one or more intracellular signaling domains for T-cell activation. A major challenge in the CAR T-cell manufacturing field is balancing product quality with scalability and cost-effectiveness, especially when transitioning from an academic clinical trial into a marketed product, to be implemented across many collection, manufacturing, and treatment sites. Achieving product consistency while circumnavigating the intrinsic variability associated with autologous products is an additional barrier. To overcome these limitations, a robust understanding of the product and its biological actions is crucial to establish a target product profile with a defined list of critical quality attributes to be assessed for each batch prior to product certification. Additional challenges arise as the field progresses, such as new safety considerations associated with the use of allogenic T-cells and genome editing tools. In this chapter, we will discuss the release and potency assays required for CAR T-cell manufacturing, covering their relevance, current challenges, and future perspectives.

Experimental validation of a computational fluid dynamics model using micro-particle image velocimetry of the irrigation flow in confluent canals.

AIM: This study aimed to experimentally validate a computational fluid dynamics (CFD) model, using micro-particle image velocimetry (micro-PIV) measurements of the irrigation flow velocity field developed in confluent canals during irrigation with a side-vented needle. METHODOLOGY: A microchip with confluent canals, manufactured in polydimethylsiloxane was used in a micro-PIV analysis of the irrigation flow using a side-vented needle placed 3 mm from the end of the confluence of the canals. Velocity fields and profiles were recorded for flow rates of 0.017 and 0.1 ml/s and compared with those predicted in CFD numerical simulations (using a finite volume commercial code - FLUENT) for both laminar and turbulent regimes. RESULTS: The overall flow pattern, isovelocity and vector maps as well as velocity profiles showed a close agreement between the micro-PIV experimental and CFD predicted data. No relevant differences were observed between the results obtained with the laminar and turbulent flow models used. CONCLUSIONS: Results showed that the laminar CFD modelling is reliable to predict the flow in similar domains.

Evaluation of an EPID in vivo monitoring system using local and external independent audit measurements.

PURPOSE: The aim of this work was to evaluate the SunCHECK PerFRACTION, the software for in vivo monitoring using EPID images. MATERIALS/METHODS: First, the PerFRACTION ability to detect errors was investigated simulating two situations: (1) variation of LINAC output and (2) variation of the phantom thickness. An ionization chamber was used as reference to measure the introduced dose variations. Both tests used EPID in integrated mode (absolute dose). Second, EPID measurements in integrated mode were carried out during an independent Brazilian governmental audit that provided four phantoms and TLDs. PerFRACTION calculated the absolute dose on EPID plane, and it compared with predicted calculated dose for every delivered plan. The dose deviations reported using PerFRACTION were compared with dose deviations reported by the independent audit. Third, an end-to-end test using a heterogeneous phantom was performed. A VMAT plan with EPID in cine mode was delivered. PerFRACTION calculated the mean dose on CBCT using EPID information and log files. The calculated doses at four different points were compared with ionization chambers measurements. RESULTS: About the first test, the largest difference found was 1.2%. Considering the audit results, the variations detected by TLD measurements and by PerFRACTION dose calculation on EPID plane were close: 12 points had variations less than 2%, 2 points with variation between 2% and 3%, and 2 points with deviations greater than 3% (max 3.7%). The end-to-end tests using a heterogeneous phantom achieved dose deviation less than 1.0% in the water-equivalent region. In the mimicking lung region, the deviations were higher (max 7.3%), but in accordance with what is expected for complex situations. CONCLUSION: The tests results indicate that PerFRACTION dose calculations in different situations have good agreement with standard measurements. Action levels were suggested for absolute dose on EPID plane as well as 3D dose calculation on CBCT using PerFRACTION.

Continuous Production of Highly Tuned Silk/Calcium-Based Composites: Exploring New Pathways for Skin Regeneration.

Calcium plays an important role in barrier function repair and skin homeostasis. In particular, calcium phosphates (CaPs) are well established materials for biomedical engineering due to their biocompatibility. To generate biomaterials with a more complete set of biological properties, previously discarded silk sericin (SS) has been recovered and used as a template to grow CaPs. Crucial characteristics for skin applications, such as antibacterial activity, can be further enhanced by doping CaPs with cerium (Ce) ions. The effectiveness of cell attachment and growth on the materials highly depends on their morphology, particle size distribution, and chemical composition. These characteristics can be tailored through the application of oscillatory flow technology, which provides precise mixing control of the reaction medium. Thus, in the present work, CaP/SS and CaP/SS/Ce particles were fabricated for the first time using a modular oscillatory flow plate reactor (MOFPR) in a continuous mode. Furthermore, the biological behavior of both these composites and of previously produced pure CaPs was assessed using human dermal fibroblasts (HDFs). It was demonstrated that both CaP based with plate-shaped nanoparticles and CaP-SS-based composites significantly improved cell viability and proliferation over time. The results obtained represent a first step towards the reinvention of CaPs for skin engineering.

Rotavirus F and G circulating in chickens in Southeastern Brazil.

Rotavirus (RV) infections represent a significant cause of enteritis and diarrhea in avian species and pose a major concern for the poultry industry. However, the prevalence of rotavirus infections among birds is poorly understood. Stool samples were collected from laying and broiler hens from commercial poultry farms in the states of Rio de Janeiro and Espírito Santo, Southwest region of Brazil, for detection of rotavirus species F and G (RVF and RVG, respectively) by reverse transcription polymerase chain reaction. RV was detected in 11.7% (38/325) of samples: 35 samples were positive for RVF and 3 for RVG. RVF was detected in 15 samples from Rio de Janeiro and 23 samples from Espírito Santo. RVG was detected in 3 samples from Espírito Santo. All the positive samples were from asymptomatic broiler chickens. The prevalence of RV infection in these flocks was high, especially considering that the birds had no apparent clinical disease. Silent circulation in the herds signifies the need for a continuous surveillance program to guide measures to control and prevent this viral infection. Continuous monitoring of pathogens is crucial to ensure greater productivity on poultry farms.

Autologous haematopoietic stem cell transplantation restores the suppressive capacity of regulatory B cells in systemic sclerosis patients.

OBJECTIVES: The rationale of autologous haematopoietic stem cell transplantation (AHSCT) for autoimmune diseases is that high-dose immunosuppression eradicates autoreactive T and B cells and the infused autologous haematopoietic stem cells promote reconstitution of a naïve and self-tolerant immune system. The aim of this study was to evaluate the reconstitution of different B cell subsets, both quantitatively and functionally, in SSc patients treated with AHSCT. METHODS: Peripheral blood was harvested from 22 SSc patients before transplantation and at 30, 60, 120, 180 and 360 days post-AHSCT. Immunophenotyping of B cell subsets, B cell cytokine production, signalling pathways and suppressive capacity of regulatory B cells (Bregs) were assessed by flow cytometry. RESULTS: Naïve B cell frequencies increased from 60 to 360 days post-AHSCT compared with pre-transplantation. Conversely, memory B cell frequencies decreased during the same period. Plasma cell frequencies transiently decreased at 60 days post-AHSCT. IL-10-producing Bregs CD19+CD24hiCD38hi and CD19+CD24hiCD27+ frequencies increased at 180 days. Moreover, the phosphorylation of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase increased in B cells reconstituted post-AHSCT. Notably, CD19+CD24hiCD38hi Bregs recovered their ability to suppress production of Th1 cytokines by CD4+ T cells at 360 days post-AHSCT. Finally, IL-6 and TGF-ß1-producing B cells decreased following AHSCT. CONCLUSION: Taken together, these results suggest improvements in immunoregulatory and anti-fibrotic mechanisms after AHSCT for SSc, which may contribute to re-establishment of self-tolerance and clinical remission.

Efficacy and Safety of 2 Injection Techniques for Hand Biostimulatory Treatment With Diluted Calcium Hydroxylapatite.

BACKGROUND: Calcium hydroxylapatite (CaHA) is effective for dorsal hand rejuvenation. Higher dilutions are used for biostimulation with fewer side effects. OBJECTIVE: To evaluate the efficacy and safety of 2 techniques of diluted CaHA injection for dorsal hand treatment. METHODS: A prospective, evaluator-blinded study was performed to compare (side-to-side) techniques for treating the dorsum of the hands with diluted CaHA: deep fat lamina or subdermal injection. Fifteen women with aging grades between 1 and 3 on the MHGS (Merz hand grading scale) were enrolled and followed up for 24 weeks. The outcomes were a histological analysis of collagen, skin viscoelasticity, high-frequency ultrasound parameters, MHGS score, and the global aesthetic improvement scale (GAIS) score. RESULTS: Improvement in the MHGS and GAIS scores (p < .01) was observed, with no difference between techniques (p > .05). Skin viscoelasticity measures and ultrasonography for dermal parameters improved for both treatments (p < .01). The mean total collagen density increased from the baseline for both techniques (p < .01). Pain during the procedure as well as adverse effects within the follow-up did not differ between treatments (p > .4). The overall satisfaction was 12% greater for the subdermal technique (p < .05). CONCLUSION: Diluted CaHA improves the skin quality of aging hands with a safe profile, without substantial differences between the techniques.

Effects of grape juice, red wine and resveratrol on liver parameters of rat submitted high-fat diet.

This work evaluated the effect of grape juice, red wine and resveratrol in liver parameters of rats submitted to high-fat diet. Experimental model was conducted with groups of adult females Rattus norvegicus: control (CG); high-fat (HG); grape juice (JG); red wine (RW) and resveratrol solution (RG). The high-fat diet significantly altered hepatocytes and Kupffer cells in all treated groups. HG group presented severe steatosis followed hepatocyte ballooning and tissue damages. JG group minimized hepatic histological lesion caused by high-fat diet and WG group also induced steatosis and inflammation in hepatocytes, similar to HG. Still, resveratrol protected the tissue against fatty liver disease by reducing fat infiltration and inflammation, indicating possible therapeutic effects on the liver. Cell cycle analysis showed that HG promoted damage to the tissue, reducing the viable cell content and increasing apoptosis, even when associated with wine consumption or isolated resveratrol. However, JG protected the liver against cell damage generated by the diet. Consumption of grape juice, even associated with a high-fat diet, represents a promising protection of the liver against cellular damage, but red wine further affects the tissue, and resveratrol alone was able to reduce damage but did not minimize cellular damage to the liver.

Automatic Quantitative Computed Tomography Evaluation of the Lungs in Patients With Systemic Sclerosis Treated With Autologous Stem Cell Transplantation.

BACKGROUND/OBJECTIVE: Interstitial lung disease stands among the leading causes of death in systemic sclerosis (SSc) patients. Autologous hematopoietic stem cell transplantation (AHSCT) has been proven superior to conventional immunosuppressive therapy in severe and progressive SSc. Here, pulmonary quantitative measurements were obtained in high-resolution computed tomography (HRCT) scans of patients with SSc before and after AHSCT. METHODS: The medical records of thirthy-three patients who underwent AHSCT between 2011 and 2017 were evaluated for clinical and tomographic features at baseline (pre-AHCST) and 18 months after the procedure. Quantitative analysis of HRCT images by a fully automated program calculated lung volumes, densities, attenuation percentiles, and vascular volume. Patients were divided into 2 groups, according to changes in forced vital capacity (FVC). The "best response" group included patients that had an increased FVC of 10% or greater, and the "stable response" group included those who had a decreased or an increased FVC of less than 10%. RESULTS: In the best response group (15 patients), there was reduction (p < 0.05) of mean lung density and density percentile values after AHSCT. In the stable response group (18 patients), there were no significant changes in lung volumes and pulmonary densities after AHSCT. Pulmonary HRCT densities showed moderate/strong correlation with function. CONCLUSIONS: Quantitative HRCT analysis identified significant reduction in pulmonary densities in patients with improved pulmonary function after AHSCT. Lung density, as evaluated by the quantitative HRCT analysis tool, has potential to become a biomarker in the evaluation of interstitial lung disease treatment in patients with SSc.

Hematopoietic Stem Cell Transplantation Improves Functional Outcomes of Systemic Sclerosis Patients.

BACKGROUND/OBJECTIVE: We sought to evaluate if autologous hematopoietic stem cell transplantation (AHSCT) influences the functional status of systemic sclerosis (SSc) patients. METHODS: From 2014 to 2018, a cohort of 27 SSc patients was assessed before, and at 6 and 12 months after AHSCT for modified Rodnan's skin score (mRSS), mouth opening, hand grip strength, range of motion (ROM), functional ability of upper limbs (DASH questionnaire and Cochin hand function scale-CHFS), 6-minute walk test (6MWT), and quality of life (SF-36 questionnaire). Linear regression models with random effects and Spearman's test were used for statistical analysis. RESULTS: At 6 and 12 months after AHSCT, respectively, we observed significant improvement of mRSS (p < 0.01 and p < 0.01), mouth opening (p = 0.02 and p < 0.01), hand function (DASH, p < 0.01 and p < 0.01; CHFS, p < 0.01 and p < 0.01; strength, p < 0.01 and p < 0.01), physical capacity (6MWT, p = 0.02 and p = 0.03) and physical (p < 0.01 and p < 0.01) and mental (ns and p = 0.02) component scores of SF-36. At 12 months after AHSCT, ROM measurements improved (p < 0.05) in five out of six evaluated joints in both hands, compared to baseline. Correlation was significant between physical capacity and quality of life (R = 0.62; p < 0.01), between DASH and quality of life (R = -0.48; p = 0.03), and between skin involvement and wrist ROM measures (dominant hand, R = -0.65, p < 0.01; non-dominant hand, R = -0.59; p < 0.01). CONCLUSIONS: AHSCT enhances the functional status of SSc patients in the first year of follow-up, significantly improving hand function, physical capacity and quality of life. These results are interpreted as positive outcomes of AHSCT for SSc.

Vascular endothelial cell expression of JAK2V617F is sufficient to promote a pro-thrombotic state due to increased P-selectin expression.

Thrombosis is the main cause of morbidity and mortality in patients with JAK2V617F myeloproliferative neoplasms. Recent studies have reported the presence of JAK2V617F in endothelial cells of some patients with myeloproliferative neoplasms. We investigated the role of endothelial cells that express JAK2V617F in thrombus formation using an in vitro model of human endothelial cells overexpressing JAK2V617F and an in vivo model of mice with endothelial-specific JAK2V617F expression. Interestingly, these mice displayed a higher propensity for thrombus. When deciphering the mechanisms by which JAK2V617F-expressing endothelial cells promote thrombosis, we observed that they have a pro-adhesive phenotype associated with increased endothelial P-selectin exposure, secondary to degranulation of Weibel-Palade bodies. We demonstrated that P-selectin blockade was sufficient to reduce the increased propensity of thrombosis. Moreover, treatment with hydroxyurea also reduced thrombosis and decreased the pathological interaction between leukocytes and JAK2V617F-expressing endothelial cells through direct reduction of endothelial P-selectin expression. Taken together, our data provide evidence that JAK2V617F-expressing endothelial cells promote thrombosis through induction of endothelial P-selectin expression, which can be reversed by hydroxyurea. Our findings increase our understanding of thrombosis in patients with myeloproliferative neoplasms, at least those with JAK2V617F-positive endothelial cells, and highlight a new role for hydroxyurea. This novel finding provides the proof of concept that an acquired genetic mutation can affect the pro-thrombotic nature of endothelial cells, suggesting that other mutations in endothelial cells could be causal in thrombotic disorders of unknown cause, which account for 50% of recurrent venous thromboses.

Food intake of women with gestational diabetes mellitus, in accordance with two methods of dietary guidance: a randomised controlled clinical trial.

The aim of the study was to evaluate the food intake of pregnant women with gestational diabetes mellitus (GDM) according to two methods of dietary guidance. A randomised controlled clinical trial was conducted by appointment with a nutritionist and by using data from hospital records (2011-2014). The study population comprised adult women diagnosed with GDM treated in a public maternity hospital in Rio de Janeiro, Brazil. The control group (CG) received nutritional advice by the traditional method and the intervention group (IG) were instructed on carbohydrate counting. The analysis of food intake and the consumption of processed foods (PF) and ultra-processed foods (UPF) were evaluated in the second and third trimester. A total of 286 pregnant women were initially assessed (145 in the CG and 141 in the IG). It was observed that 89/120 (74·2 %) and 183/229 (79·9 %) consumed PF daily in the second and third trimesters, respectively, whereas 117/120 (97·5 %) and 225/231 (97·4 %) consumed UPF daily in the second and third trimesters, respectively. When analysing the intake of macronutrients (%) by quartiles, women who had fat intake in the third quartile had the highest average postprandial blood glucose compared with those who consumed fat in the second quartile (P=0·02). The consumption of PF and UPF was high and dietary intake was similar in both groups, regardless of dietary guidance method deployed, suggesting that both methods tested in the study can be used for monitoring the nutritional status of pregnant women with GDM.

Bacterial Community Dynamics across the Gastrointestinal Tracts of Dairy Calves during Preweaning Development.

Microbial communities play critical roles in the gastrointestinal tracts (GIT) of preruminant calves by influencing performance and health. However, little is known about the establishment of microbial communities in the calf GIT or their dynamics during development. In this study, next-generation sequencing was used to assess changes in the bacterial communities of the rumen, jejunum, cecum, and colon in 26 crossbred calves at four developmental stages (7, 28, 49, and 63 days old). Alpha diversity differed among GIT regions with the lowest diversity and evenness in the jejunum, whereas no changes in alpha diversity were observed across developmental stage. Beta diversity analysis showed both region and age effects, with low numbers of operational taxonomic units (OTUs) shared between regions within a given age group or between ages in a given region. Taxonomic analysis revealed that several taxa coexisted in the rumen, jejunum, cecum, and colon but that their abundances differed considerably by GIT region and age. As calves aged, we observed lower abundances of taxa such as Bacteroides, Parabacteroides, and Paraprevotella with higher abundances of Bulleidia and Succiniclasticum in the rumen. The jejunum also displayed taxonomic changes with increases in Clostridiaceae and Turicibacter taxa in older calves. In the lower gut, taxa such as Lactobacillus, Blautia, and Faecalibacterium decreased and S24-7, Paraprevotella, and Prevotella increased as calves aged. These data support a model whereby early and successive colonization by bacteria occurs across the GIT of calves and provides insights into the temporal dynamics of the GIT microbiota of dairy calves during preweaning development.IMPORTANCE The gastrointestinal tracts (GIT) of ruminants, such as dairy cows, house complex microbial communities that contribute to their overall health and support their ability to produce milk. For example, the rumen microbiota converts feed into usable nutrients, while the jejunal microbiota provides access to protein. Thus, establishing a properly functioning GIT microbiota in dairy calves is critical to their productivity as adult cows. However, little is known about the establishment, maintenance, and dynamics of the calf GIT microbiota in early life. In this study, we evaluated the bacterial communities in the rumen, jejunum, cecum, and colon in dairy calves across preweaning development and show that they are highly variable early on in life before transitioning to a stable community. Understanding the dairy calf GIT microbiota has implications for ensuring proper health during early life and will aid in efforts to develop strategies for improving downstream production.

Common and Rare Taxa of Planktonic Ciliates: Influence of Flood Events and Biogeographic Patterns in Neotropical Floodplains.

After much discussion about the cosmopolitan nature of microbes, the great issue nowadays is to identify at which spatial extent microorganisms may display biogeographic patterns and if temporal variation is important in altering those patterns. Here, planktonic ciliates were sampled from shallow lakes of four Neotropical floodplains, distributed over a spatial extent of ca. 3000 km, during high and low water periods, along with several abiotic and biotic variables potentially affecting the ciliate community. We found that common ciliate species were more associated with environmental gradients and rare species were more related to spatial variables; however, this pattern seemed to change depending on the temporal and spatial scales considered. Environmental gradients were more important in the high waters for both common and rare species. In low waters, common species continued to be mainly driven by environmental conditions, but rare species were more associated with the spatial component, suggesting dispersal limitation likely due to differences in dispersal ability and ecological tolerance of species. We also found that common and rare species were related to different environmental variables, suggesting different ecological niches. At the largest spatial extents, rare species showed clear biogeographic patterns.

Proteomics of cell-cell interactions in health and disease.

The mechanisms of cell-cell communications are now under intense study by proteomic approaches. Proteomics has unraveled changes in protein profiling as the result of cell interactions mediated by ligand/receptor, hormones, soluble factors, and the content of extracellular vesicles. Besides being a brief overview of the main and profitable methodologies now available (evaluating theory behind the methods, their usefulness, and pitfalls), this review focuses on-from a proteome perspective-some signaling pathways and post-translational modifications (PTMs), which are essential for understanding ischemic lesions and their recovery in two vital organs in mammals, the heart, and the kidney. Knowledge of misdirection of the proteome during tissue recovery, such as represented by the convergence between fibrosis and cancer, emerges as an important tool in prognosis. Proteomics of cell-cell interaction is also especially useful for understanding how stem cells interact in injured tissues, anticipating clues for rational therapeutic interventions. In the effervescent field of induced pluripotency and cell reprogramming, proteomic studies have shown what proteins from specialized cells contribute to the recovery of infarcted tissues. Overall, we conclude that proteomics is at the forefront in helping us to understand the mechanisms that underpin prevalent pathological processes.