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Abstract Endothelial cells (ECs) are highly glycolytic, but whether they generate glycolytic intermediates via gluconeogenesis (GNG) in glucose-deprived conditions remains unknown. Here, we report that glucose-deprived ECs upregulate the GNG enzyme PCK2 and rely on a PCK2-dependent truncated GNG, whereby lactate and glutamine are used for the synthesis of lower glycolytic intermediates that enter the serine and glycerophospholipid biosynthesis pathways, which can play key roles in redox homeostasis and phospholipid synthesis, respectively. Unexpectedly, however, even in normal glucose conditions, and independent of its enzymatic activity, PCK2 silencing perturbs proteostasis, beyond its traditional GNG role. Indeed, PCK2-silenced ECs have an impaired unfolded protein response, leading to accumulation of misfolded proteins, which due to defective proteasomes and impaired autophagy, results in the accumulation of protein aggregates in lysosomes and EC demise. Ultimately, loss of PCK2 in ECs impaired vessel sprouting. This study identifies a role for PCK2 in proteostasis beyond GNG.

ABSTRACT: During the first 3 wk of life, the immune system of newborn ruminants starts to work, as indicated by fluctuations in the concentrations of proinflammatory cytokines and acute phase proteins (APP). They have been shown to be markers for short and long-term weight gain in ruminants. This observational study investigated these proteins as possible indicators of first lactation performance of dairy cows. A total of 117 dairy calves from a single farm were enrolled in the study. Serum and fecal samples were taken once a week for the first 3 wk of life. Cryptosporidium spp. infection and its treatment were monitored and accounted for in statistical analysis. The concentrations of the APP serum amyloid A (SAA) and haptoglobin (Hp), and the proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) were analyzed in serum. After the first lactation, health and performance data of the cows were retrieved, and associations between APP and cytokine concentrations with first lactation outcomes were investigated through linear and logistic regression. This study found a negative association between the concentration of Hp in the second week of life and average daily weight gain at one year. The SAA concentration measured during the second and third weeks of life was positively associated with age at first calving. IL-6, SAA, and Hp measured in the second week of life were positively associated with calving to conception interval. The concentrations of IL-6 and TNF-α during the first week of life were associated with higher odds of reproductive issues during the first lactation period. These markers can be used to help understand underlying processes that influence animal health and production. In conclusion, inflammatory responses during the first week of life are related to reproductive success, whereas the second and third weeks of life seem to influence the future productive performance in dairy cows.

La enfermedad de Graves representa la principal causa de hipertiroidismo durante el embarazo. Aunque su prevalencia es baja, resulta esencial su manejo precoz y seguimiento oportuno. El abordaje diagnóstico se realiza con las pruebas de función tiroidea, correlacionando sus rangos de referencia con los cambios fisiológicos presentes durante el embarazo, además de la identificación de anticuerpos antireceptor de TSH (TRAb) en suero materno. La base del tratamiento radica en el uso de tionamidas, teniendo consideraciones especiales en su empleo durante las distintas etapas de la gestación y el periodo de lactancia. La tiroidectomía puede estar indicada bajo circunstancias muy específicas. Por otra parte, la enfermedad de Graves puede cursar con complicaciones maternas, obstétricas, fetales y neonatales las cuales se presentan en relación con la tirotoxicosis, los fenómenos autoinmunes y los efectos de los fármacos antitiroideos. Finalmente, el seguimiento postparto también es fundamental para minimizar el riesgo de recaídas y morbilidad asociada.

Abstract Open Science enhances information sharing and makes scientific results of transport research more transparent and accessible at all levels and to everyone allowing integrity and reproducibility. However, what future impacts will Open Science have on the societal, environmental and economic development within the transport sector? Using the Future Wheel methodology, we conducted a workshop with transport experts from both industry and academia to answer this question. The main findings of this study point in the direction of previous studies in other fields, in terms of increased innovation, increased efficiency, economic savings, more equality, and increased participation of citizens. In addition, we found several potential transport specific impacts: lower emission, faster travel times, improved traffic safety, increased awareness for transport policies, artificial intelligence improving mobility services. Several potential negative outcomes of Open Science were also identified by the expert group: job loss, new types of risks, increased cost, increased conflicts, time delays, increased inequality and increased energy consumption. If we know the negative outcomes it is much easier to put in place strategies that are sustainable for a broader stakeholder group, which also increase the probability of taking advantage of all the positive impacts of Open Science.

ABSTRACT: The core part of the mammal innate immune system is the acute-phase response (APR), during which acute-phase proteins (APP) are synthesized. Colostrum contains immunomodulating factors such as proinflammatory cytokines and APP in large quantities. We looked at proinflammatory cytokines [IL-1β, IL-6, and tumor necrosis factor-α (TNF-α)] and APP [serum amyloid A (SAA) and haptoglobin (Hp)] in colostrum and in calves' serum. The aim of this study was to evaluate the effects of colostrum on the calves' systemic APR and the associations of the calves' serum APR with short- and long-term weight gain (at the age of 1, 3, and 9 mo). A total of 143 female dairy calves were studied during their first 3 wk of life. The calves were separated from their mothers immediately after birth and bottle-fed 3 L of quality-controlled colostrum once within 2 h after birth. Serum samples were collected once a week during the first 3 wk of life (a total of 1–3 samples per calf). Mean sampling age (±standard deviation) was 4.3 (±2.0) d in the first week, 11.0 (±2.0) d in the second week, and 18.0 (±2.0) d in the third week. Linear regression models were used to study associations of colostrum APP and cytokine concentration with serum APR markers and for studying associations of colostrum and serum APR markers with calves' average daily weight gain (ADWG). Mixed linear regression models were used to compare serum concentrations of APR markers by study weeks. The colostrum IL-6 concentrations were positively associated with serum IL-6 in the first 3 wk of life. Colostrum IL-1β was positively associated with calves' serum IL-1β during the first week of life, and colostrum TNF-α was positively associated with calves' serum TNF-α during the first 2 wk of life. Serum IL-1β concentrations differed over the 3 wk, being the highest during the first week and the lowest during the second week. For IL-6, the concentration during the first week was the highest, and for TNF-α, a steady decline in the concentration was observed. Serum SAA concentrations were elevated during the first 2 wk of life and subsequently declined during the third week. Albumin concentrations were lowest in the first week, whereas Hp concentrations were highest during the second week. Serum concentrations of SAA, Hp, IL-6, and TNF-α during the second week were negatively associated with ADWG at 9 mo of age. The SAA concentrations during the third week of age had a negative association with 9-mo ADWG. Serum Hp concentrations in the third week were negatively associated with 3-mo ADWG. The results of our study suggest that colostrum cytokines influence calf serum cytokine concentrations. Thus, they influence the newborn calves' adaptation to the environment and the development of their immune system. Factors that activate an APR during the second and third week of life have a long-term influence on calves' development.

IntroductionStimulant use is an important health issue. In the US in 2018, 2.8% of males and 1.5% of females older than 18 had used cocaine in the preceding 12 months.ObjectiveTo intervene in a specific targeted group of Stimulant Use Disorder (SUD) patients according to CBT and relapse prevention theories, and to determine the program’s feasibility and attendance.MethodStimulant Use Disorder patients in addiction care were evaluated for addictive, psychological and psychiatric dimensions at baseline and conclusion in a 9-session CBT group program with several themes: define SUD, enhance motivation, involve close companions, cope with craving, decline a proposal, solve problems, invite expert patients, invest time and money, and review content.ResultsIn total, 41 patients attended at least one session. They were mainly poly dependent, primarily cocaine users. Sixty percent of the population also suffered from another psychiatric comorbidity. Median attendance for participants was 7/9 sessions.ConclusionA specific targeted CBT group for stimulant dependent highly comorbid patients is feasible. These findings suggest that peers should be included in addiction care services.

Aesthetic aspects of drinking water, such as Taste and Odor (T&O), have significant effects on consumer perceptions and acceptability. Solving unpleasant water T&O episodes in water supplies is challenging, since it requires expertise and know-how in diagnosis, evaluation of impacts and implementation of control measures. We present gaps, challenges and perspectives to advance water T&O science and technology, by identifying key areas in sensory and chemical analysis, risk assessment and water treatment, as articulated by WaterTOP (COST Action CA18225), an interdisciplinary European and international network of researchers, experts, and stakeholders.

This paper describes the nature of home-school value discrepancies perceived by students, and tests associations between such value discrepancies and teacher-student relationships with student generational status as a moderator. Using a sample of 1,551 students from grades 10 and 11, chi-square tests and ANOVAs were used to describe the nature of discrepancies, while hierarchical linear regressions were conducted to test associations. Second-generation students generally perceived more differences between family-school values. When experiencing less value discrepancies, students reported closer teacher-student relationships. Value discrepancies were also associated with conflict, third-plus-generation standing out. Practitioners should mitigate value discrepancies to improve teacher-student relationships.

Computational models are an essential tool for the design, characterization, and discovery of novel materials. Computationally hard tasks in materials science stretch the limits of existing high-performance supercomputing centers, consuming much of their resources for simulation, analysis, and data processing. Quantum computing, on the other hand, is an emerging technology with the potential to accelerate many of the computational tasks needed for materials science. In order to do that, the quantum technology must interact with conventional high-performance computing in several ways: approximate results validation, identification of hard problems, and synergies in quantum-centric supercomputing. In this paper, we provide a perspective on how quantum-centric supercomputing can help address critical computational problems in materials science, the challenges to face in order to solve representative use cases, and new suggested directions.

Photoautotrophic picoplankton (0.2-2 μm) can be a major contributor to primary production and play a significant part in the ecosystem carbon flow. However, the understanding about the dynamics of both eukaryotic and prokaryotic components of picoplankton in shallow eutrophic freshwater environments is still poor. Very few studies in these ecosystems reveal the taxonomic composition of picoeukaryotes. The main objective of this study was to investigate the seasonal dynamics of phototrophic picoplankton with the emphasis on the eukaryote community composition in a large shallow, eutrophic lake of the northern temperate zone (Lake Võrtsjärv). Phytoplankton pigments were employed to determine the taxonomic composition of photoautotrophic picoplankton. We found out that photoautotrophic picoplankton constitutes an important part of the phytoplankton community in Lake Võrtsjärv and its contribution can be highly variable (from ~9.3% to ~39%) in different years. The eukaryotic photoautotrophic picoplankton was dominated by diatoms followed by chrysophytes and other minor groups. Picoeukaryotes were prevailing in low-light conditions and low temperatures as their predominance in the picoplankton community was tightly linked to the presence or absence of ice cover. Ice cover strongly suppressed the growth of picocyanobacteria. Total phosphorus, turbidity and metazooplankton abundance had a clear relationship with photoautotrophic picoplankton chlorophyll a.

The tissue microenvironment in the mouse pancreas has been shown to promote very different polarizations of resident macrophages with islet-resident macrophages displaying an inflammatory “M1” profile and macrophages in the exocrine tissue mostly displaying an alternatively activated “M2” profile. The impact of this polarization on tissue homeostasis and diabetes development is unclear. In this study, the ability of pancreas-resident macrophages to phagocyte bacterial and endogenous debris was investigated. Mouse endocrine and exocrine tissues were separated, and tissue-resident macrophages were isolated by magnetic immunolabeling. Isolated macrophages were subjected to flow cytometry for polarization markers and qPCR for phagocytosis-related genes. Functional in vitro investigations included phagocytosis and efferocytosis assays using pH-sensitive fluorescent bacterial particles and dead fluorescent neutrophils, respectively. Intravital confocal imaging of in situ phagocytosis and efferocytosis in the pancreas was used to confirm findings in vivo. Gene expression analysis revealed no significant overall difference in expression of most phagocytosis-related genes in islet-resident vs. exocrine-resident macrophages included in the analysis. In this study, pancreas-resident macrophages were shown to differ in their ability to phagocyte bacterial and endogenous debris depending on their microenvironment. This difference in abilities may be one of the factors polarizing islet-resident macrophages to an inflammatory state since phagocytosis has been found to imprint macrophage heterogeneity. It remains unclear if this difference has any implications in the development of islet dysfunction or autoimmunity.

AbstractIntroduction Bleaching teeth to have a whiter and bright smile is a popular trend and currently one can do it at home, without technical support from dentists. However, whitening products are not innocuous and the European legislation is clear limiting the content in hydrogen peroxide (H2O2), present or released, to 6%, still, products containing up to 40% of H2O2 are commercially available. In fact, the contact time of live tissues with H2O2 agents is usually small, which may restrict side effects, but on the other hand, successively applications as well as at-home careless applications may be harmful. This work aims to verify how whitening products commercialised in Portugal impact on fibroblasts viability.Materials and methods We used fibroblasts, the main cells of both pulp and gingivae that contact with whitening gels. Mouse embryo fibroblasts (NIH/3T3) were incubated with serial dilutions of Opalescence PF boost 40%, Opalescent PF 16%, Opalescent PF 10% from Ultradent (USA) and Bbryance 0.095% (France) in culture medium for 1-hour. After that period, the culture medium was removed and cell viability was determined using MTT assay.Results Our results showed a huge decrease in fibroblasts viability after exposure to both product types: containing H2O2 or carbamide peroxide. To achieve conditions considered non-toxic, i.e. showing a reduction in cell viability 70%).[Table: see text]Discussion and conclusions Although we cannot extrapolate this effect directly to human teeth, because the concentration of H2O2 arriving at the pulp depends on diffusion through dentinal tubules, our observations are of great concern in particular for gingivae health. Moreover, the whitening products sold for at-home use are as cytotoxic as the in-office product to be applied under the supervision of the dental professional independently of the product type. Since we found that at-home products have similar toxicities, we anticipated that the BBRYANCE gel will induce less severe effects due to his lower H2O2 concentration.

COVID-19 containment measures brought many changes in our lives and forced teachers all around the world to adopt various new practices. Given its specific education requirements and numerous school boards, the province of Quebec, Canada, was chosen to study the effects of the pandemic on music teaching in schools in the spring and fall of 2020. An electronic survey was distributed, to which 517 elementary and high school music teachers responded. Teachers reported on the transformation of teaching modes from an exclusively in-person practice to an online or bimodal approach. Continuation and interruption of music programs varied greatly from school to school and, for those who were allowed musical activities, different protective health measures were implemented. Teachers working with large ensembles (e.g. band and orchestra) experienced more interruptions in their music programs. Teachers also reported how their planning was affected by the new modes of instruction, but no matter which modes were used, most of them experienced less motivation for teaching during the spring of 2020. In addition, they perceived that it was more motivating for students to receive an education in person. Finally, positive outcomes of the pandemic on education included the development of new skills in the use of digital resources and online teaching, as well as a renewed sense of solidarity between teachers.

Abstract Background The CD4-induced (CD4i) epitopes in gp120 includes the co-receptor binding site, which are formed and exposed after interaction with CD4. Monoclonal antibodies (mAbs) to the CD4i epitopes exhibit limited neutralizing activity because of restricted access to their epitopes. However, small fragment counterparts such as single-chain variable fragments (scFvs) have been reported to neutralize a broad range of viruses compared with the full-size IgG molecule. To identify the CD4i epitope site responsible for this broad neutralization we constructed three scFvs of anti-CD4i mAbs from a human immunodeficiency virus type 1 (HIV-1)-infected elite controller, and investigated the neutralization coverage and precise binding site in the CD4i epitopes. Results We constructed scFvs from the anti-CD4i mAbs, 916B2, 4E9C, and 25C4b and tested their neutralization activity against a panel of 66 viruses of multi-subtype. Coverage of neutralization by the scFvs against this panel of pseudoviruses was 89% (59/66) for 4E9C, 95% (63/66) for 25C4b and 100% (66/66) for 916B2. Analysis using a series of envelope glycoprotein mutants revealed that individual anti-CD4i mAbs showed various dependencies on the hairpin 1 (H1) and V3 base. The binding profiles of 25C4b were similar to those of 17b, and 25C4b bound the region spanning multiple domains of H1 and hairpin 2 (H2) of the bridging sheet and V3 base. For 4E9C, the V3-base dependent binding was apparent from no binding to mutants containing the ΔV3 truncation. In contrast, binding of 916B2 was dependent on the H1 region, which is composed of β2 and β3 strands, because mutants containing the H1 truncation did not show any reactivity to 916B2. Although the H1 region structure is affected by CD4 engagement, the results indicate the unique nature of the 916B2 epitope, which may be structurally conserved before and after conformational changes of gp120. Conclusions Identification of a unique structure of the H1 region that can be targeted by 916B2 may have an important implication in the development of small molecules to inhibit infection by a broad range of HIV-1 for the purpose of HIV treatment and prevention.