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Obesity is a chronic disease associated with impaired physical and mental health. A widespread view in the treatment of obesity is that the goal is to normalize the individual's body mass index (BMI). However, a modest weight loss (usually above 5%) is already associated with clinical improvement, while weight losses of 10%-15% bring even further benefits, independent from the final BMI. The percentage of weight reduction is accepted as a treatment goal since a greater decrease in weight is frequently difficult to achieve due to metabolic adaptation along with environmental and lifestyle factors. In this document, the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Society for the Study of Obesity and Metabolic Syndrome (ABESO) propose a new obesity classification based on the maximum weight attained in life (MWAL). In this classification, individuals losing a specific proportion of weight are classified as having “reduced” or “controlled” obesity. This simple classification – which is not intended to replace others but to serve as an adjuvant tool – could help disseminate the concept of clinical benefits derived from modest weight loss, allowing individuals with obesity and their health care professionals to focus on strategies for weight maintenance instead of further weight reduction. In future studies, this proposed classification can also be an important tool to evaluate possible differences in therapeutic outcomes between individuals with similar BMIs but different weight trajectories.

Glycerol is the by-product of biodiesel production and its utilisation in fish feed has recently gained relevance. As an important metabolic intermediate and structural component of triacylglycerol (TAG), it is still unclear whether its supplementation affects lipid utilisation and/or deposition in different tissues. Accordingly, a set of studies was aimed to evaluate how increasing levels of dietary glycerol (0, 2.5 and 5%) affect lipid synthesis in the liver, muscle and adipose tissue. After a growth trial with rainbow trout (8 weeks) and European seabass (6 weeks) fish were sampled at 6 and 24 h to assess mRNA levels of lipid metabolism-related enzymes. The remaining fish were subjected to a metabolic trial consisting of a 6-day residence in deuterated water (2H2O) for metabolic flux calculations. This study stands as the second part of a broader experiment that also aimed at evaluating the carbohydrate metabolism (Viegas et al., 2022). Dietary supplementation at 5% glycerol significantly increased plasma TAG levels in both species and liver TAG levels in seabass, with no repercussions on the perivisceral fat index. Despite responding as expected in a postprandial setting, only fas and Δ6-fad in trout and Δ6-fad in seabass responded significantly by increasing with the dietary supplementation of glycerol. In trout, the observed differences in the regulation of these enzymes were not reflected in the de novo lipogenic fluxes. The fractional synthetic rates (FSR) were overall low in all tissues with an average of 0.04, 0.02 and 0.01% d–1, for liver, muscle and perivisceral fat, respectively. In seabass on the other hand, and despite increased mRNA levels in Δ6-fad, the overall lipid profile in the liver muscle and perivisceral fat was higher in MUFA at the expense of lower PUFA. Moreover, glycerol supplementation altered the lipogenic capacity of seabass with hepatic fractional synthetic rates for TAG-bound FA increasing with increasing glycerol levels (0.32 ± 0.18, 0.57 ± 0.18, and 0.82 ± 0.24 for 0%, 2.5% and 5% glycerol supplementation, respectively). The findings of the present study suggest that supplementation up to 2.5% of glycerol did not severely impact the lipid metabolism nor increased lipogenic potential in liver, muscle and perivisceral fat accumulation. This work was supported by Fundação para a Ciência e ̂Tecnologia (FCT; Portugal) through national funds with cofunding from ERDF/FEDER, within the PT2020 Partnership Agreement, and COMPETE 2020: research grant to IV (PTDC/CVT-NUT/2851/2014, PTDC/BAA-AGR/3550/2020); individual grant to MP through Centro2020 (ReNATURE; Centro-01-0145-FEDER-000007); and structural funds to Center for Neuroscience and Cell Biology (UID/NEU/04539/2013) and Centre for Functional Ecology (UID/BIA/04004/2019) and Interdisciplinary Centre of Marine and Environmental Research (UID/Multi/04423/2019; UIDB/04423/2020; UIDP/ 04423/2020). UC- NMR facilities (REEQ/481/QUI/2006, RECI/QEQ-QFI/0168/2012, Centro-07-CT62-FEDER-002012) and Rede Nacional de Ressonância Magnética Nuclear (RNRMN).

Glycerol is the by-product of biodiesel production and its utilisation in fish feed has recently gained relevance. As an important metabolic intermediate and structural component of triacylglycerol (TAG), it is still unclear whether its supplementation affects lipid utilisation and/or deposition in different tissues. Accordingly, a set of studies was aimed to evaluate how increasing levels of dietary glycerol (0, 2.5 and 5%) affect lipid synthesis in the liver, muscle and adipose tissue. After a growth trial with rainbow trout (8 weeks) and European seabass (6 weeks) fish were sampled at 6 and 24 h to assess mRNA levels of lipid metabolism-related enzymes. The remaining fish were subjected to a metabolic trial consisting of a 6-day residence in deuterated water (2H2O) for metabolic flux calculations. This study stands as the second part of a broader experiment that also aimed at evaluating the carbohydrate metabolism (Viegas et al., 2022). Dietary supplementation at 5% glycerol significantly increased plasma TAG levels in both species and liver TAG levels in seabass, with no repercussions on the perivisceral fat index. Despite responding as expected in a postprandial setting, only fas and Δ6-fad in trout and Δ6-fad in seabass responded significantly by increasing with the dietary supplementation of glycerol. In trout, the observed differences in the regulation of these enzymes were not reflected in the de novo lipogenic fluxes. The fractional synthetic rates (FSR) were overall low in all tissues with an average of 0.04, 0.02 and 0.01% d–1, for liver, muscle and perivisceral fat, respectively. In seabass on the other hand, and despite increased mRNA levels in Δ6-fad, the overall lipid profile in the liver muscle and perivisceral fat was higher in MUFA at the expense of lower PUFA. Moreover, glycerol supplementation altered the lipogenic capacity of seabass with hepatic fractional synthetic rates for TAG-bound FA increasing with increasing glycerol levels (0.32 ± 0.18, 0.57 ± 0.18, and 0.82 ± 0.24 for 0%, 2.5% and 5% glycerol supplementation, respectively). The findings of the present study suggest that supplementation up to 2.5% of glycerol did not severely impact the lipid metabolism nor increased lipogenic potential in liver, muscle and perivisceral fat accumulation. This work was supported by Fundação para a Ciência e Tecnologia (FCT; Portugal) through national funds with co-funding from ERDF/FEDER, within the PT2020 Partnership Agreement, and COMPETE 2020: research grant to IV (PTDC/CVT-NUT/2851/2014, PTDC/BAA-AGR/3550/2020); individual grant to MP through Centro2020 (ReNATURE; Centro-01-0145-FEDER-000007); and structural funds to Center for Neuroscience and Cell Biology (UID/NEU/04539/2013) and Centre for Functional Ecology (UID/BIA/04004/2019) and Interdisciplinary Centre of Marine and Environmental Research (UID/Multi/04423/2019). UC-NMR facilities (REEQ/481/QUI/2006, RECI/QEQ-QFI/0168/2012, Centro-07-CT62-FEDER-002012) and Rede Nacional de Ressonância Magnética Nuclear (RNRMN).

International audience; This work investigates batch and continuous-flow heterogeneous catalytic hydrogenation of a mixture of cafestol and kahweol (C&K) to obtain pure cafestol. These diterpenes were extracted from green coffee beans, and hydrogenation was performed using well-established palladium catalysts (Pd/C, Pd/CaCO3, Pd/BaSO4, and Pd/Al2O3) and a carbon black-supported Pd catalyst coated by a covalently tethered SiO2 shell with mesoporous texture (Pd/CB@SiO2), all partially deactivated with quinoline. Pd/C 10% poisoned with 1 wt % quinoline gave the best result for batch reaction, producing cafestol from kahweol with high selectivity (>99%) after 10 min. Excellent selectivity was also obtained with the catalyst Pd/CB@SiO2 with only 1% Pd. In addition, Pd/C-quinoline adapted for continuous-flow experiments exhibited the best catalytic activity, also providing cafestol with excellent selectivity (>99%) after 9.8 s.

Dietary glycerol supplementation in aquaculture feed is seen as an alternative and inexpensive way to fuel fish metabolism, attenuate metabolic utilization of dietary proteins and, subsequently, reduce nitrogen excretion. In this study, we evaluated the impact of dietary glycerol supplementation on nitrogen excretion of European seabass (Dicentrarchus labrax) and its effects on metabolite profile and bacterial community composition of gut digesta. These effects were evaluated in a 60-day trial with fish fed diets supplemented with 2.5% or 5% (w/w) refined glycerol and without glycerol supplementation. Nuclear magnetic resonance spectroscopy and high-throughput 16S rRNA gene sequencing were used to characterize the effects of glycerol supplementation on digesta metabolite and bacterial community composition of 6-h postprandial fish. Our results showed that ammonia excretion was not altered by dietary glycerol supplementation, and the highest glycerol dosage was associated with significant increases in amino acids and a decrease of ergogenic creatine in digesta metabolome. Concomitantly, significant decreases in putative amino acid degradation pathways were detected in the predicted metagenome analysis, suggesting a metabolic shift. Taxon-specific analysis revealed significant increases in abundance of some specific genera (e.g., Burkholderia and Vibrio) and bacterial diversity. Overall, our results indicate glycerol supplementation may decrease amino acid catabolism without adversely affecting fish gut bacterial communities. Key points • Glycerol can be an inexpensive and energetic alternative in fish feed formulations. • Glycerol did not affect nitrogen excretion and gut bacteriome composition. • Glycerol reduced uptake of amino acids and increased uptake of ergogenic creatine. • Glycerol reduced putative amino acid degradation pathways in predicted metagenome.

Benzocaine (ethyl p-aminobenzoate), ethyl ester of p-aminobenzoic acid, is an anesthetic acting as a blocker of the nerve impulses and reducing the permeability of neuronal membrane to sodium iodide, it has become widespread in the pharmaceutical industry having applications as an anesthetic prior to exams such as endoscopy or as a “retarding” agent when inserted in condom. Due to the wide insertion in the pharmaceutical market, the methodologies for obtaining this molecule have already been elucidated and published in the literature, however the application of traditional reactions in refined systems, such as continuous flow are a technological bottleneck that allow approaches aimed at the optimization of productivity. Thus, the present work aimed to apply the reduction and esterification of p-nitrobenzoic acid in one step continuous flow systems, optimizing the reaction time and sequences, in order to add relevance and technology to the process as a whole. The model applied in a continuous flow system generated extremely positive values ​​compared to the present literature, which include results with high conversion (> 99%) and selectivity (> 99%), in residence times that reach up to a minimum of 12 s.

Studying the causes of technical debt (TD) could aid in TD prevention, thus easing the job of TD management. On the other hand, better understanding of the effects of TD could also aid in TD management by facilitating more informed decisions about incurring and paying off debt. Create a deeper understanding, and confirming existing evidence, of the causes and effects of TD by collecting new evidence from real-world TD examples. InsighTD is a globally distributed family of industrial surveys on the causes and effects of TD. It is designed to run as a large-scale study based on continuous and independent replications in different countries. The survey instrument asks practitioners to describe in detail a real example of TD from their experience. We present in this paper the design of InsighTD, which has the primary goal of replication at a large-scale, with the results of the study in Brazil as a small part of the larger puzzle. The first iteration of the InsighTD survey, carried out in Brazil, yielded 107 responses. We identified a total of 78 causes and 66 effects, which confirm and also extend the current knowledge on causes and effects of TD. Then, we organized the identified set of causes and effects in probabilistic cause-effect diagrams. The proposed diagrams highlight the causes that can most contribute to the occurrence of TD as well as the most common effects that occur as a result of debt. We intend to reduce the problem of isolated TD investigations that are not yet representative and build a continuous and generalizable empirical basis for understanding practical problems and challenges of TD.

Programmed cell death-1 (PD-1)/programmed death ligand-1 blockade may potentially augment graft-vs-tumor effects following allogeneic hematopoietic cell transplantation (alloHCT), but retrospective studies of anti–PD-1 therapy reported substantial toxicity from graft-versus-host-disease (GVHD). Here, we report the results of a prospective clinical trial of PD-1 blockade for relapsed hematologic malignancies (HMs) after alloHCT (NCT01822509). The primary objective in this phase 1 multicenter, investigator-initiated study was to determine maximum tolerated dose and safety. Secondary objectives were to assess efficacy and immunologic activity. Patients with relapsed HMs following alloHCT were eligible. Nivolumab was administered every 2 weeks until progression or unacceptable toxicity, starting with a 1-mg/kg cohort, with planned deescalation based on toxicity to a 0.5-mg/kg cohort. Twenty-eight patients were treated (n = 19 myeloid, n = 9 lymphoid). Median age was 57 years (range 27-76), and median time from alloHCT to enrollment was 21 months (range 5.6-108.5). Two of 6 patients treated at 1 mg/kg experienced dose-limiting toxicity (DLT) from immune-related adverse events (irAEs). Twenty-two patients were treated at 0.5 mg/kg, and 4 DLTs occurred, including 2 irAEs and 2 with fatal GVHD. The overall response rate in efficacy-evaluable patients was 32% (8/25). With a median follow-up of 11 months, the 1-year progression-free survival and overall survival were 23% and 56%, respectively. In this first prospective clinical trial of an anti–PD-1 antibody for post–alloHCT relapse, GVHD and irAEs occurred, requiring dose deescalation, with only modest antitumor activity. Further studies of anti–PD-1 therapy post–alloHCT may require specific toxicity mitigation strategies. This trial was registered at www.clinicaltrials.gov as #NCT 01822509.

SummaryFoam increases sweep efficiency during gas injection in enhanced oil recovery processes. Surfactant alternating gas (SAG) is the preferred method to inject foam for both operational and injectivity reasons. Dynamic SAG corefloods are unreliable for direct scaleup to the field because of core-scale artifacts. In this study, we report fit and scaleup local-equilibrium (LE) data at very-low injected-liquid fractions in a Bentheimer core for different surfactant concentrations and total superficial velocities.We fit LE data to an implicit-texture foam model for scaleup to a dynamic foam process on the field scale using fractional-flow theory. We apply different parameter-fitting methods (least-squares fit to entire foam-quality scan and the method of Rossen and Boeije 2015) and compare their fits to data and predictions for scaleup. We also test the implications of complete foam collapse at irreducible water saturation for injectivity.Each set of data predicts a shock front with sufficient mobility control at the leading edge of the foam bank. Mobility control improves with increasing surfactant concentration. In every case, scaleup injectivity is much better than with coinjection of gas and liquid. The results also illustrate how the foam model without the constraint of foam collapse at irreducible water saturation (Namdar Zanganeh et al. 2014) can greatly underestimate injectivity for strong foams.For the first time, we examine how the method of fitting the parameters to coreflood data affects the resulting scaleup to field behavior. The method of Rossen and Boeije (2015) does not give a unique parameter fit, but the predicted mobility at the foam front is roughly the same in all cases. However, predicted injectivity does vary somewhat among the parameter fits. Gas injection in a SAG process depends especially on behavior at low injected-water fraction and whether foam collapses at the irreducible water saturation, which may not be apparent from a conventional scan of foam mobility as a function of gas fraction in the injected foam. In two of the five cases examined, this method of fitting the whole scan gives a poor fit for the shock in gas injection in SAG. We also test the sensitivity of the scaleup to the relative permeability krw(Sw) function assumed in the fit to data.There are many issues involved in scaleup of laboratory data to field performance: reservoir heterogeneity, gravity, interactions between foam and oil, and so on. This study addresses the best way to fit model parameters without oil for a given permeability, an essential first step in scaleup before considering these additional complications.

Background Chile is the second largest avocado producer in the world. However, there have been few studies on interactions between native bees and avocado pollination in a Chilean environment. The flowering period of avocado is very sensitive to temperature fluctuations and so environmental conditions, particularly cool temperatures, can have a strong influence on its floral behaviour. Thus, we aimed to determine whether temperature also influences bee visitation rates to avocado flowers or if this was due to the number of available flowers. Moreover, we proposed to verify the attractiveness of avocado flowers to native bees and compare flower handling time and type of floral resource collected between managed and native bees. Methods An avocado orchard of “Hass” cultivar located in the Mediterranean region of Chile was studied during the flowering season of 2016. The frequency of exotic and native bee species in flowers, floral phenology, and environmental temperature were analysed, and the foraging behaviours of exotic and native bee species in avocado flowers compared. Results Five Chilean native and two exotic species were recorded visiting avocado flowers at the studied orchard. The bees generally sought nectar rather than pollen. The European honeybee (Apis mellifera) was the most frequent flower visitor, followed by the native species Colletes cyanescens and Cadeguala occidentalis. There was a strong positive correlation between temperature and number of visits, but no significant correlation between number of open flowers and number of visits. Conclusions Native Chilean bees visited avocado flowers and some of them were frequent floral visitors. They generally sought for nectar rather than pollen and were as fast as honeybees handling avocado flowers. The environmental temperature plays a key role in the frequency of bees in avocado flowers. The warmer weather is related to the higher number of bees visits to avocado flowers.

We have investigated the synthesis of p-mentha-2,8-dien-1-ol (1) as a cannabidiol precursor by photochemical oxidation of (R)-limonene (2) with singlet oxygen (1O2) using meso-tetraphenylporphyrin ...

Wang S, Zhang H, Liu Y, Li L, Guo Y, Jiao F, Fang X, Jefferson JR, Li M, Gao W, Gonzalez-Fernandez E, Maranon RO, Pabbidi MR, Liu R, Alexander BT, Roman RJ, Fan F. Sex differences in the structure and function of rat middle cerebral arteries. Am J Physiol Heart Circ Physiol 318: H1219 –H1232, 2020. First published March 27, 2020; doi:10.1152/ajpheart.00722.2019.—Epidemiological studies demonstrate that there are sex differences in the incidence, prevalence, and outcomes of cerebrovascular disease (CVD). The present study compared the structure and composition of the middle cerebral artery (MCA), neurovascular coupling, and cerebrovascular function and cognition in young Sprague-Dawley (SD) rats. Wall thickness and the inner diameter of the MCA were smaller in females than males. Female MCA exhibited less vascular smooth muscle cells (VSMCs), diminished contractile capability, and more collagen in the media, and a thicker internal elastic lamina with fewer fenestrae compared with males. Female MCA had elevated myogenic tone, lower distensibility, and higher wall stress. The stress/strain curves shifted to the left in female vessels compared with males. The MCA of females failed to constrict compared with a decrease of 15.5 ± 1.9% in males when perfusion pressure was increased from 40 to 180 mmHg. Cerebral blood flow (CBF) rose by 57.4 ± 4.4 and 30.1 ± 3.1% in females and males, respectively, when perfusion pressure increased from 100 to 180 mmHg. The removal of endothelia did not alter the myogenic response in both sexes. Functional hyperemia responses to whisker-barrel stimulation and cognition examined with an eight-arm water maze were similar in both sexes. These results demonstrate that there are intrinsic structural differences in the MCA between sexes, which are associated with diminished myogenic response and CBF autoregulation in females. The structural differences do not alter neurovascular coupling and cognition at a young age; however, they might play a role in the development of CVD after menopause. NEW & NOTEWORTHY Using perfusion fixation of the middle cerebral artery (MCA) in calcium-free solution at physiological pressure and systematically randomly sampling the sections prepared from the same M2 segments of MCA, we found that there are structural differences that are associated with altered cerebral blood flow (CBF) autoregulation but not neurovascular coupling and cognition in young, healthy Sprague-Dawley (SD) rats. Understanding the intrinsic differences in cerebrovascular structure and function in males and females is essential to develop new pharmaceutical treatments for cerebrovascular disease (CVD). Fil: Wang, Shaoxun. University Of Mississippi Medical Center; Estados Unidos Fil: Zhang, Huawei. University Of Mississippi Medical Center; Estados Unidos Fil: Liu, Yedan. University Of Mississippi Medical Center; Estados Unidos Fil: Li, Longyang. University Of Mississippi Medical Center; Estados Unidos Fil: Guo, Ya. University Of Mississippi Medical Center; Estados Unidos Fil: Jiao, Feng. Peking University People's Hospital; China. University Of Mississippi Medical Center; Estados Unidos Fil: Fang, Xing. University Of Mississippi Medical Center; Estados Unidos Fil: Jefferson, Joshua R.. University Of Mississippi Medical Center; Estados Unidos Fil: Li, Man. University Of Mississippi Medical Center; Estados Unidos Fil: Gao, Wenjun. University Of Mississippi Medical Center; Estados Unidos Fil: Gonzalez Fernandez, Ezekiel. University Of Mississippi Medical Center; Estados Unidos Fil: Marañón, Rodrigo Oscar. University Of Mississippi Medical Center; Estados Unidos. Universidad Nacional de Tucumán. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; Argentina Fil: Pabbidi, Mallikarjuna R.. University Of Mississippi Medical Center; Estados Unidos Fil: Liu, Ruen. Peking University People's Hospital; China Fil: Alexander, Barbara T.. University Of Mississippi Medical Center; Estados Unidos Fil: Roman, Richard J.. University Of Mississippi Medical Center; Estados Unidos Fil: Fan, Fan. University Of Mississippi Medical Center; Estados Unidos

Development of positron emission tomography (PET) imaging agents capable of quantifying tau aggregates in neurodegenerative disorders such as Alzheimer's disease (AD) is of enormous importance in the field of dementia research. The aim of the present study was to conduct first-in-man imaging studies with the potential novel tau imaging agent [18F]N-methyl lansoprazole ([18F]NML). Herein we report validation of the synthesis of [18F]NML for clinical use by labeling the trifluoromethyl group via radiofluorination of the corresponding gem-difluoro enol ether precursor. This is the first use of this method for clinical production of PET radiotracers and confirmed that it can be readily implemented at multiple production facilities to provide [18F]NML in good noncorrected radiochemical yield (3.4 ± 1.5 GBq, 4.6% ± 2.6%) and molar activity (120.1 ± 186.3 GBq/μmol), excellent radiochemical purity (>97%), and suitable for human use (n = 15). With [18F]NML in hand, we conducted rodent biodistribution, estimates of human dosimetry, and preliminary evaluation of [18F]NML in human subjects at two imaging sites. Healthy controls (n = 4) and mildly cognitively impaired (MCI) AD patients (n = 6) received [18F]NML (tau), [18F]AV1451 (tau), and [18F]florbetaben or [18F]florbetapir (amyloid) PET scans. A single progressive supranuclear palsy (PSP) patient also received [18F]NML and [18F]AV1451 PET scans. [18F]NML showed good brain uptake, reasonable pharmacokinetics, and appropriate imaging characteristics in healthy controls. The mean ± SD of the administered mass of [18F/19F]NML was 2.01 ± 2.17 μg (range, 0.16-8.27 μg) and the mean administered activity was 350 ± 62 MBq (range, 199-403 MBq). There were no adverse or clinically detectable pharmacologic effects in any of the 11 subjects, and no significant changes in vital signs were observed. However, despite high affinity for tau in vitro, brain retention in MCI/AD and PSP patients was low, and there was no evidence of specific signals in vivo that corresponded to tau. Although it is still unclear why clinical translation of the radiotracer was unsuccessful, we nevertheless conclude that further development of [18F]NML as a tau PET imaging agent is not warranted at this time.

Background: Oxidative stress plays an essential role in the vascular tone in hypertension; however, the mechanisms remain unclear. Aim: This study aimed to determine the antioxidant effect of tempol and vitamin C (Vit-C) on the basal tone and vascular remodeling of the aorta in nitric oxide (NO) deficiency-induced hypertensive rats. Method: Male Sprague-Dawley rats were induced to hypertension by Nω-nitro-L-arginine methyl ester (L-NAME). Animals were randomized as follows: vehicle (Control: CR), CR-tempol, CR-Vit-C, L-NAME, L-NAME-tempol, and L-NAME-Vit-C. After 6 weeks of treatment, the basal aortic tone was evaluated by sodium nitroprusside (SNP) and calcium-free medium. Endothelial function, NO, reduced-to-oxidized glutathione (GSH/GSSG) ratio, resting membrane potential (mP), and vascular remodeling were also measured. Results: L-NAME rats showed an increased basal tone that was blunted by both SNP (−547 ± 69; n = 7 vs. CR: −7.5 ± 6.7 mg; n = 7; p < 0.001) and calcium-free medium. Tempol or Vit-C did not reverse hypertension, and the high basal tone was decreased only with tempol. In L-NAME rats, only tempol partially improved endothelial function, GSH-to-GSSG ratio, mP values, and vascular remodeling. Conclusions: Tempol decreased calcium-dependent basal aortic tone and improved vascular homeostasis in L-NAME rats. Vit-C did not lead to a similar effect, suggesting that alterations in the superoxide dismutase pathway may play a role in the basal aortic tone.

In this study of 400 patients with early-onset rectal cancer, 12.5 per cent demonstrated microsatellite instability (MSI). MSI was associated with a reduced likelihood of nodal positivity, an increased rate of pathological complete response, and improved disease-specific survival.

International audience; Studies involving the transformation of lignocellulosic biomass into high value-added chemical products have been intensively conducted in recent years. Its matrix is mainly composed of cellulose, hemicellulose and lignin, being, therefore, an abundant and renewable source for obtaining several platform molecules, with levoglucosan (LG) standing out. This anhydrous carbohydrate can be acylated to obtain carbohydrate fatty acid esters (CFAEs). Here, these compounds were obtained via enzymatic acylation of LG, commercially obtained (Start BioScience®), with different acyl donors in continuous flow. Through the experimental design using a model reaction, it was possible to optimize the reaction conditions, temperature and residence time, obtaining a maximum conversion at 61 C and 77 min. In addition, there was a productivity gain of up to 100 times in all comparisons made with the batch system. Finally, CFAEs were applied in tests of interfacial tension and biological activity. For a mixture of 4-and 2-O-lauryl-1,6-anhydroglucopyranose (MONLAU), the minimum interfacial tension (IFT min) obtained was 96 mN m À1 and the critical micelle concentration (CMC) was 50 mM. Similar values were obtained for a mixture of 4-and 2-O-palmitoyl-1,6-anhydroglucopyranose (MONPAL), not yet reported in the literature, of 88 mN m À1 in 50 mM. For a mixture of 4-and 2-O-estearyl-1,6anhydroglucopyranose (MONEST) and 4-and 2-O-oleoyl-1,6-anhydroglucopyranose (MONOLE), CMC was higher than 60 mM and IFT min of 141 mN m À1 and 102 mN m À1 , respectively. Promising data were obtained for minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of MONLAU against Staphylococcus aureus strains at 0.25 mM.

SummaryChromatin-based mechanisms regulating developmental transitions during meiosis are fundamental but understudied aspects of male gametogenesis. Indeed, chromatin undergoes extensive remodeling during meiosis, leading to specific patterns of gene expression and chromosome organization, which ultimately controls fundamental meiotic processes such as recombination and homologous chromo-some associations. Recent game-changing advances have been made by analysis of chromatin binding sites of meiotic specific proteins genome-wide in mouse spermatocytes. However, further progress is still highly dependent on the reliable isolation of sufficient quantities of spermatocytes at specific stages of prophase I. Here, we describe a combination of methodologies adapted for rapid and reliable isolation of synchronized fixed mouse spermatocytes. We show that chromatin isolated from these cells can be used to study chromatin binding sites by ChIP-seq. High quality data we obtained from INO80 ChIP-seq in zygotene cells was used for functional analysis of chromatin binding sites.

Made available in DSpace on 2022-04-28T19:49:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-01 Universidade Federal do Rio de Janeiro Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Amine transaminases (ATAs) are pyridoxal-5′-phosphate (PLP)-dependent enzymes that catalyze the transfer of an amino group from an amino donor to an aldehyde and/or ketone. In the past decade, the enzymatic reductive amination of prochiral ketones catalyzed by ATAs has attracted the attention of researchers, and more traditional chemical routes were replaced by enzymatic ones in industrial manufacturing. In the present work, the influence of the presence of an α,β-unsaturated system in a methylketone model substrate was investigated, using a set of five wild-type ATAs, the (R)-selective from Aspergillus terreus (Atr-TA) and Mycobacterium vanbaalenii (Mva-TA), the (S)-selective from Chromobacterium violaceum (Cvi-TA), Ruegeria pomeroyi (Rpo-TA), V. fluvialis (Vfl-TA) and an engineered variant of V. fluvialis (ATA-256 from Codexis). The high conversion rate (80 to 99%) and optical purity (78 to 99% ee) of both (R)-and (S)-ATAs for the substrate 1-phenyl-3-butanone, using isopropylamine (IPA) as an amino donor, were observed. However, the double bond in the α,β-position of 4-phenylbut-3-en-2-one dramatically reduced wild-type ATA reactivity, leading to conversions of 99% ee. Computational docking simulations showed the differences in orientation and intermolecular interactions in the active sites, providing insights to rationalize the observed experimental results. Institute of Chemistry UNESP-São Paulo State University, SP Institute of Chemistry Federal University of Rio de Janeiro, RJ Department of Biotechnology & Enzyme Catalysis Institute of Biochemistry Greifswald University Institute of Chemistry UNESP-São Paulo State University, SP FAPESP: 2014/50249-8 FAPESP: 2014/50926-0 FAPESP: 2019/15230-8 CNPq: 465637/2014-0 CNPq: 490278/2013-2

Fear memory generalisation is a central hallmark in the broad range of anxiety and trauma-related disorders. Recent findings suggest that fear generalisation is closely related to hippocampal dependency during retrieval. In this review, we describe the current understanding about memory generalisation and its potential influence in fear attenuation through pharmacological and behavioural interventions. In light of systems consolidation framework, we propose that keeping memory precision could be a key step to enhance therapeutic outcomes.

Additional file 2: Figure S2. Spermatogonia enrichment. Analysis of Thy1+ and c-Kit+ fractions. Cells were attached to coverslips and immunostained with the indicated antibodies. A Quantification of germ cell shows that spermatogonia represents 61.5% (± 3.7%) from Thy1+ fractions (Plzf positive cells) and 65.4% (± 11%) from c-Kit fractions (Ddx4 positive cells). B Flow-through fraction obtained after use of the Thy1 and c-Kit columns is composed of 60.6% ± 3.6% Sertoli cells. A minor fraction of Sertoli cells was also detected in Thy1+ (28.1 ± 6.3%) and c-Kit+ (25.4% ± 7.4%) fractions. Numbers represent average ± standard deviation from 2 biological replicates and 4 technical replicates.

Additional file 4: Figure S4. Ablation of both chd4 alleles are required for a Sertoli-only phenotype and Chd3 is dispensable for gametogenesis. A Histological sections of 2 months of old mice testis stained with H&E shows no differences between homozygous (chd4wt/wt) and the heterozygous (ddx4-chd4wt/−) mice controls, while ddx4-chd4−/− mouse results in absence of germ cells. B H&E stained histological sections of wild type and ddx4-chd3−/− testis. No differences in type or number of germ cell at any stage of development are observed between wild type and ddx4-chd3−/− knockouts.

Additional file 6: Figure S6. Deficient spermatogonia cell survival and differentiation in chd4−/− mice. Histological sections of wild type and ddx4-chd4−/− testis cords from 1, 3, 4, 7, 9, 14, and 21 dpp mice stained with Tra98 antibodies. See quantification in Fig. 4C.

Additional file 1: Figure S1. Chd4 expression during gametogenesis. Expression of Chd4 monitored by immunofluorescence in paraffin embedded testis sections of 1, 3, 4, 7, 9, 14, and 120 dpp mice. Spermatogonia cells are positive for Plzf and Sertoli cells are positive for Sox9.

Made available in DSpace on 2022-04-28T19:50:14Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-03-15 Secondary forests (SFs) growing on previously cleared land could be a low-cost climate change mitigation strategy due to their potential to sequester CO2. However, given widespread changes in climate and land-use in the Amazon in the past 20 years, it is not clear whether current rates of carbon uptake by SFs reflect estimates based on dividing the carbon stock by the estimated age of the forest. This is important, as differences between methodological approaches could lead to important discrepancies in estimates of carbon accumulation. Furthermore, we know little about how carbon uptake rates of secondary forests vary across some of the most deforested regions of the Amazon, where reforestation actions are most needed. Here, we compare the rates of carbon accumulation estimated over the lifetime of a stand (by stand age) with the contemporary rates estimated by recensus data, based on 28 permanent SFs plots distributed across four regions. Then, we compare how carbon uptakes rates vary across regions and how they compare to previous studies. The average rates of contemporary (1.23 ± 0.57 Mg C ha−1 yr−1) and lifetime (1.14 ± 0.63 Mg C ha−1 yr−1) carbon accumulation were strongly correlated (r = 0.78) and similar between regions. Overall, our carbon accumulation rates were much lower than other estimates of Amazonian SFs, which suggests that regions with the greatest opportunities for large-scale implementation of SFs have some of the slowest rates of carbon accumulation. Contrary to predictions from chronosequence analysis, the lack of difference between lifetime and contemporary rates of carbon accumulation suggests forests are maintaining a consistent rate of growth in the first decades after abandonment. These results—combined with the high rates of ongoing environmental change - highlight the importance of continuing to monitor the rate of carbon accumulation in secondary forests. This is necessary to support the implementation and monitoring of large-scale passive restoration in the highly-deforested Amazon. Universidade Federal do Pará Instituto de Ciências Biológicas Programa de Pós-Graduação em Ecologia, Campus Guamá Embrapa Amazônia Oriental Rede Amazônia Sustentável Environmental Change Institute University of Oxford Lancaster Environment Centre Lancaster University School of Biological Sciences University of Bristol Universidade Estadual Paulista Departamento de Ecologia Universidade Federal Rural da Amazônia, Campus Capitão Poço Universidade Estadual Paulista Departamento de Ecologia

Additional file 5: Figure S5. Chd4 deletion results in deficient spermatogonia cell development and near absence of spermatocytes. A Histological sections of 9 dpp wild type and ddx4-chd4−/− testis showing seminiferous tubules immunolabeled with Tra98 (a marker of germ cells) and Sycp3 and γH2AX (markers of primary spermatocytes). Arrows indicate examples of positive cells. B Quantitation of cell number per positive tubule shown in A. Tra98 positive cells in wild type (45 ± 10, n = 66) and ddx4-chd4−/− (4.6 ± 3, n = 60, P