Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Characterization of Arabinoxylan from Wheat Beer, Beer Foam and Defoamed Beer

This research was to explore the distribution and some molecular characterization of arabinoxylan in wheat beer (B), beer foam (BF) and defoamed beer (DB) because of the crucial influences of arabinoxylan on wheat beer and its foam. The purified arabinoxylan from B, BF, and DB were fractionated by ethanol of 50%, 67%, 75%, and 80%. The monosaccharide composition, substitution degree (Ara/Xyl ratio, A/X), and average degrees of polymerization (avDP) of arabinoxylan were investigated. Molecular weight and microstructure were also involved in this study by GPC-LLS and SEM, respectively. Under the same ethanol concentration, the arabinoxylan content in the BF was higher than the other two, respectively, and it was precipitated in BF fraction with 50% ethanol which accounted for 80.84% of the total polysaccharides. Meanwhile, the greatest substitution degree (A/X) and highest value of avDP of the arabinoxylan was found in all beer foam fractions regardless of the concentration of ethanol used. The average degrees of polymerization (avDP) of arabinoxylan displayed a significant difference (p < 0.05) among B, BF, and DB. Furthermore, arabinoxylan presented varied microstructure with irregular lamellas and spherical structures and the weight-average molecular weight (Mw) of arabinoxylan showed the lowest values in BF, while the largest values were shown in DB. Therefore, arabinoxylan was more accumulated in beer foam, especially in 50% ethanol, characterised by greater value of A/X and avDP, as well as lower Mw. It was suggested that the arabinoxylan played important roles in maintaining wheat beer foam characteristics.
A catalytic domain variant of mitofusin requiring a wildtype paralog for function uncouples mitochondrial outer-membrane tethering and fusion

Mitofusins (Mfns) are dynamin-related GTPases that mediate mitochondrial outer-membrane fusion, a process that is required for mitochondrial and cellular health. In Mfn1 and Mfn2 paralogs, a conserved phenylalanine (Phe-202 (Mfn1) and Phe-223 (Mfn2)) located in the GTPase domain on a conserved β strand is part of an aromatic network in the core of this domain. To gain insight into the poorly understood mechanism of Mfn-mediated membrane fusion, here we characterize a Mitofusin mutant variant etiologically linked to Charcot–Marie–Tooth syndrome. From analysis of mitochondrial structure in cells and mitochondrial fusion in vitro, we found that conversion of Phe-202 to leucine in either Mfn1 or Mfn2 diminishes the fusion activity of heterotypic complexes with both Mfn1 and Mfn2 and abolishes fusion activity of homotypic complexes. Using coimmunoprecipitation and native gel analysis, we further dissect the steps of mitochondrial fusion and demonstrate that the mutant variant has normal tethering activity but impaired higher-order nucleotide-dependent assembly. The defective coupling of tethering to membrane fusion observed here suggests that nucleotide-dependent self-assembly of Mitofusin is required after tethering to promote membrane fusion.
Serum Calcification Propensity and Coronary Artery Calcification Among Patients With CKD: The CRIC (Chronic Renal Insufficiency Cohort) Study.

RATIONALE & OBJECTIVE Coronary artery calcification (CAC) is prevalent among patients with chronic kidney disease (CKD) and increases risks for cardiovascular disease events and mortality. We hypothesized that a novel serum measure of calcification propensity is associated with CAC among patients with CKD stages 2 to 4. STUDY DESIGN Prospective cohort study. SETTING & PARTICIPANTS Participants from the Chronic Renal Insufficiency Cohort (CRIC) Study with baseline (n=1,274) and follow-up (n=780) CAC measurements. PREDICTORS Calcification propensity, quantified as transformation time (T50) from primary to secondary calciprotein particles, with lower T50 corresponding to higher calcification propensity. Covariates included age, sex, race/ethnicity, clinical site, estimated glomerular filtration rate, proteinuria, diabetes, systolic blood pressure, number of antihypertensive medications, current smoking, history of cardiovascular disease, total cholesterol level, and use of statin medications. OUTCOMES CAC prevalence, severity, incidence, and progression. ANALYTICAL APPROACH Multivariable-adjusted generalized linear models. RESULTS At baseline, 824 (65%) participants had prevalent CAC. After multivariable adjustment, T50 was not associated with CAC prevalence but was significantly associated with greater CAC severity among participants with prevalent CAC: 1-SD lower T50 was associated with 21% (95% CI, 6%-38%) greater CAC severity. Among 780 participants followed up an average of 3 years later, 65 (20%) without baseline CAC developed incident CAC, while 89 (19%) with baseline CAC had progression, defined as annual increase≥100 Agatston units. After multivariable adjustment, T50 was not associated with incident CAC but was significantly associated with CAC progression: 1-SD lower T50 was associated with 28% (95% CI, 7%-53%) higher risk for CAC progression. LIMITATIONS Potential selection bias in follow-up analyses; inability to distinguish intimal from medial calcification. CONCLUSIONS Among patients with CKD stages 2 to 4, higher serum calcification propensity is associated with more severe CAC and CAC progression.
Feeding Diets Moderate in Physically Effective Fibre Alters Eating and Feed Sorting Patterns without Improving Ruminal pH, but Impaired Liver Health in Dairy Cows

Simple Summary This study tested the hypothesis that the content of physically effective fibre in the diet modifies eating and feed sorting patterns of cows, which is reflected in rumen and systemic health variables. We observed that switching cows from a diet high to a diet moderate in physically effective fibre (17.8%; 28% starch on dry matter basis) in an attempt to stabilize rumen pH variations altered eating, sorting, and chewing behaviour. However, this attempt did not prevent ruminal pH drop and the impairment of liver health variables. Therefore, our study emphasizes the importance of increasing the level of physically effective fibre for particles >8 mm beyond 17%–18% of the diet when (barley grain-based) starch content is at a 28% level. Abstract The main challenge in dairy cattle feeding is to find a balance between the energy and physically effective fibre (peNDF), required to maintain rumen health. In an attempt to regulate the balance between energy intake and rumen buffering, we hypothesized that the content of peNDF in the diet modifies eating and feed sorting patterns of the cows. Sixteen lactating Simmental cows were switched from a diet high in peNDF, with which they were fed for one week, to a diet moderate in peNDF for four weeks. Data showed that during the moderate peNDF feeding the cows increased sorting for medium-sized particles and avoided both long and very fine particles. In addition, cows decreased their eating time per meal, but increased the number of meals per day, obviously attempting to decrease the amount of fermentable substrate per time unit while maintaining high levels of nutrient/energy intake. Although these changes during the moderate peNDF feeding went along with a lower diurnal variation of ruminal pH, feeding of the latter diet did not prevent ruminal pH drop and increased the level of all liver enzymes, indicating liver tissue damage. In conclusion, the altered eating, chewing, and sorting behaviour of the cows during the moderate peNDF feeding could not alleviate the deficiency in peNDF, which resulted in ruminal pH depression and impairment of liver health variables.
The NOD-scid IL2rγnull Mouse Model Is Suitable for the Study of Osteoarticular Brucellosis and Vaccine Safety

Osteoarticular brucellosis is the most common complication in Brucella-infected humans regardless of age, sex, or immune status. The mechanism of bone destruction caused by Brucella species remained partially unknown due to the lack of a suitable animal model. ABSTRACT Osteoarticular brucellosis is the most common complication in Brucella-infected humans regardless of age, sex, or immune status. The mechanism of bone destruction caused by Brucella species remained partially unknown due to the lack of a suitable animal model. Here, to study this complication, we explored the suitability of the use of the NOD-scid IL2rγnull mouse to study osteoarticular brucellosis and examined the potential use of this strain to evaluate the safety of live attenuated vaccine candidates. Mice were inoculated intraperitoneally with a single dose of 1 × 104, 1 × 105, or 1 × 106 CFU of B. abortus S19 or the vaccine candidate B. abortus S19ΔvjbR and monitored for the development of side effects, including osteoarticular disease, for 13 weeks. Decreased body temperature, weight loss, splenomegaly, and deformation of the tails were observed in mice inoculated with B. abortus S19 but not in those inoculated with S19ΔvjbR. Histologically, all S19-inoculated mice had a severe dose-dependent inflammatory response in multiple organs. The inflammatory response at the tail was characterized by the recruitment of large numbers of neutrophils, macrophages, and osteoclasts with marked bone destruction. These lesions histologically resembled what is typically observed in Brucella-infected patients. In contrast, mice inoculated with B. abortus S19ΔvjbR did not show significant bone changes. Immunofluorescence, in situ hybridization, and confocal imaging demonstrated the presence of Brucella at the sites of inflammation, both intra- and extracellularly, and large numbers of bacteria were observed within mature osteoclasts. These results demonstrate the potential use of the NOD-scid IL2rγnull mouse model to evaluate vaccine safety and further study osteoarticular brucellosis.
Adoptive Immunotherapy with Antigen-Specific T Cells Expressing a Native TCR

Although T cells genetically modified with chimeric antigen receptors became the first immune effector product to obtain FDA approval, T-cell products that recognize their antigenic targets through their native receptors have also produced encouraging responses. For instance, T cells recognizing immunogenic viral antigens are effective when infused in immunosuppressed patients. A large number of tumor antigens are also expressed on nonviral tumors, but these antigens are less immunogenic. Many tumors can evade a transferred immune response by producing variants, which have lost the targeted antigens, or inhibitory molecules that recruit suppressive cells, impeding persistence and function of immune effectors. Nevertheless, infusion of antigen-specific T cells has been well-tolerated, and clinical responses have been consistently associated with immune activity against tumor antigens and epitope spreading. To overcome some of the obstacles mentioned above, current research is focused on defining ex vivo culture conditions that promote in vivo persistence and activity of infused antigen-specific T cells. Combinations with immune checkpoint inhibitors or epigenetic modifiers to improve T-cell activity are also being evaluated in the clinic. Antigen-specific T cells may also be manufactured to overcome tumor evasion mechanisms by targeting multiple antigens and engineered to be resistant to inhibitory factors, such as TGFβ, or to produce the cytokines that are essential for T-cell expansion and sustained antitumor activity. Here, we discuss the use of T cells specific to tumor antigens through their native receptors and strategies under investigation to improve antitumor responses.
Osteosarcopenic Obesity: Current Knowledge, Revised Identification Criteria and Treatment Principles

Osteosarcopenic obesity (OSO) syndrome describes the simultaneous deterioration of bone, muscle and excess fat, resulting in reduced functionality and systemic metabolic dysregulation. The key component contributing to this may be ectopic fat in the viscera, bone and muscle. OSO research to date is summarized, and the revised criteria for its identification for research purposes are reviewed and proposed, including new criteria to assess visceral fat in males and females. Finally, nutritional and physical activity recommendations are consolidated into a treatment algorithm, which can be validated in future studies and which may also be applied to preventative management.
I Can But I Shall Not Always Be Empathic

Empathy, a core process for social interactions, is the capacity to understand and share others’ mental states and emotions. Each individual is thought to have a maximum level of empathy (empathic ability) and a spontaneous tendency to express it (empathic propensity), which can be affected by multiple factors. Two within-subject studies were conducted to assess the malleability of empathy by modulating contextual factors and measuring their interaction with psychological characteristics. In Study 1, 59 healthy adults evaluated their empathy for people showing facial expressions of pain following different instructions: Passive Observation and Instruction to Actively Empathize. In Study 2, 56 healthy adults performed a similar task under two conditions: Passive Observation and Observation under a Cognitive Load. The results revealed that empathy was significantly increased in the actively empathizing condition (Study 1) and under a cognitive load, but more importantly for men (Study 2). The level of change between the two conditions was associated with self-reported empathy, autistic, alexithymia and psychopathic traits (Study 1), as well as with working memory capacities and the level of empathy reported in the passive observation condition (Study 2). These findings suggest that an instruction to actively empathize and, surprisingly, a cognitive load can both increase empathy, but not for the same individuals. An instruction to actively empathize seems to increase empathy for individuals with good empathic dispositions, while a cognitive load enhances empathy in people for which empathic propensity is sub-optimal.
Multi-omics analysis unravels a segregated metabolic flux network that tunes co-utilization of sugar and aromatic carbons in Pseudomonas putida

Pseudomonas species thrive in different nutritional environments and can catabolize divergent carbon substrates. These capabilities have important implications for the role of these species in natural and engineered carbon processing. However, the metabolic phenotypes enabling Pseudomonas to utilize mixed substrates remain poorly understood. Here, we employed a multi-omics approach involving stable isotope tracers, metabolomics, fluxomics, and proteomics in Pseudomonas putida KT2440 to investigate the constitutive metabolic network that achieves co-utilization of glucose and benzoate, respectively a monomer of carbohydrate polymers and a derivative of lignin monomers. Despite nearly equal consumption of both substrates, metabolite isotopologues revealed nonuniform assimilation throughout the metabolic network. Gluconeogenic flux of benzoate-derived carbons from the tricarboxylic acid cycle did not reach the upper Embden–Meyerhof–Parnas pathway nor the pentose–phosphate pathway. These latter two pathways were populated exclusively by glucose-derived carbons through a cyclic connection with the Entner–Doudoroff pathway. We integrated the 13C-metabolomics data with physiological parameters for quantitative flux analysis, demonstrating that the metabolic segregation of the substrate carbons optimally sustained biosynthetic flux demands and redox balance. Changes in protein abundance partially predicted the metabolic flux changes in cells grown on the glucose:benzoate mixture versus on glucose alone. Notably, flux magnitude and directionality were also maintained by metabolite levels and regulation of phosphorylation of key metabolic enzymes. These findings provide new insights into the metabolic architecture that affords adaptability of P. putida to divergent carbon substrates and highlight regulatory points at different metabolic nodes that may underlie the high nutritional flexibility of Pseudomonas species.
The Effect of Rotavirus Vaccine on Socioeconomic Differentials of Paediatric Care Due to Gastroenteritis in Swedish Infants

Background: Previous Swedish studies have shown a social gradient on paediatric care for viral gastroenteritis. Aim: To study the effect of a free rotavirus vaccine programme on hospital care for viral gastroenteritis. Method: A register-based national cohort study of paediatric in- and outpatient care for viral gastroenteritis in children <2 years old in two Swedish counties in 2014–2017, with the rest of the country as comparison. Adjusted hazard ratios were estimated by the differences-in-differences (DiD) estimator in Cox regression in the entire cohort and by social indicators. Results: Reductions of 37% and 24% for inpatient care, and 11 % and 21% for outpatient care for viral gastroenteritis were found in the Stockholm and Jönköping counties, respectively, after adjusting for time trends and social indicators. For inpatient care, the change was similar over social groups in both counties. In the larger county of Stockholm, smaller reductions in outpatient care were detected for children in socially disadvantaged families. Conclusions: A free rotavirus vaccination programme moderately reduced paediatric care for viral gastroenteritis. There were indications of an increase in socioeconomic differences in paediatric outpatient care for viral gastroenteritis, but further studies are needed to confirm this result in a broader health care perspective.
Macrolides Inhibit Capsule Formation of Highly Virulent Cryptococcus gattii and Promote Innate Immune Susceptibility

Cryptococcus gattii is a fungal pathogen, endemic in tropical and subtropical regions, the west coast of Canada, and the United States, that causes a potentially fatal infection in otherwise healthy individuals. Because the cryptococcal polysaccharide capsule is a leading virulence factor due to its resistance against innate immunity, the inhibition of capsule formation may be a promising new therapeutic strategy for C. gattii. ABSTRACT Cryptococcus gattii is a fungal pathogen, endemic in tropical and subtropical regions, the west coast of Canada, and the United States, that causes a potentially fatal infection in otherwise healthy individuals. Because the cryptococcal polysaccharide capsule is a leading virulence factor due to its resistance against innate immunity, the inhibition of capsule formation may be a promising new therapeutic strategy for C. gattii. Macrolides have numerous nonantibiotic effects, including immunomodulation of mammalian cells and suppression of bacterial (but not fungal) pathogenicity. Thus, we hypothesized that a macrolide would inhibit cryptococcal capsule formation and improve the host immune response. Coincubation with clarithromycin (CAM) and azithromycin significantly reduced the capsule thickness and the amount of capsular polysaccharide of both C. gattii and C. neoformans. CAM-treated C. gattii cells were significantly more susceptible to H2O2 oxidative stress and opsonophagocytic killing by murine neutrophils. In addition, more C. gattii cells were phagocytosed by murine macrophages, resulting in increased production of tumor necrosis factor alpha (TNF-α) by CAM exposure. After CAM exposure, dephosphorylation of Hog1, one of the mitogen-activated protein kinase (MAPK) signaling pathways of Cryptococcus, was observed in Western blot analysis. In addition, CAM exposure significantly reduced the mRNA expression of LAC1 and LAC2 (such mRNA expression is associated with cell wall integrity and melanin production). These results suggest that CAM may aid in inhibiting capsular formation via the MAPK signaling pathway and by suppressing virulent genes; thus, it may be a useful adjunctive agent for treatment of refractory C. gattii infection.
Polyphenols Modulate Alzheimer’s Amyloid Beta Aggregation in a Structure-Dependent Manner

Some polyphenols, which are common natural compounds in fruits, vegetables, seeds, and oils, have been considered as potent inhibitors of amyloid beta (Aβ) aggregation, one critical pathogenic event in Alzheimer’s disease (AD). However, the mechanisms by which polyphenols affect aggregation are not fully understood. In this study, we aimed to investigate the effect of two classes of polyphenols (flavonoids and stilbenes) on the self-assembly of Aβ_42, in particular, how this relates to structure. We found that the flavonoids gallocatechin gallate (GCG) and theaflavin (TF) could completely inhibit Aβ aggregation, while two stilbenes, resveratrol and its glucoside derivative piceid, could also suppress Aβ aggregation, but to a much lesser extent. Intriguingly, resveratrol accelerated the formation of Aβ fibrils before its decreasing effect on fibrillation was detected. Atomic force microscopy (AFM) images showed a huge mass of long and thin Aβ fibrils formed in the presence of resveratrol. Although the morphology was the same in the presence of piceid, the fibrils were sparse in the presence of picead. In the presence of flavonoids, Aβ morphology was unchanged from prior to incubation (0 h), in agreement with amyloid beta kinetics analysis using thioflavin-T fluorescence assay. The electrochemical data showed a higher ability of GCG and TF to interact with Aβ than resveratrol and piceid, which could be attributed to the presence of more aromatic rings and hydroxyl groups. In addition, the two flavonoids exhibited a similar propensity for Aβ aggregation, despite having some differences in their structure. However, in the case of stilbenes, the addition of a glucoside at C-7 slightly decreased anti-Aβ aggregation property compared to resveratrol. These findings contribute to a better understanding of the essential structural features of polyphenols required for inhibiting Aβ aggregation, and the possible mechanisms for modulating aggregation.
The triglyceride synthesis enzymes DGAT1 and DGAT2 have distinct and overlapping functions in adipocytes[S]

Mammals store metabolic energy as triacylglycerols (TGs) in adipose tissue. TG synthesis is catalyzed by the evolutionarily unrelated acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes DGAT1 and DGAT2, which catalyze the same reaction and account for nearly all TG synthesis. The reasons for their convergent evolution to synthesize TGs remain unclear. Mice lacking DGAT1 are viable with reduced fat stores of TGs, whereas DGAT2 KO mice die postnatally just after birth with >90% reduction of TGs, suggesting that DGAT2 is the predominant enzyme for TG storage. To better understand the functional differences between the DGATs, we studied mice fed chow or high-fat diets lacking either enzyme in adipose tissue. Unexpectedly, mice lacking DGAT2 in adipocytes have normal TG storage and glucose metabolism on regular or high-fat diets, indicating DGAT2 is not essential for fat storage. In contrast, mice lacking DGAT1 in adipocytes have normal TG storage on a chow diet but moderately decreased body fat accompanied by glucose intolerance when challenged with a high-fat diet. The latter changes were associated with the activation of ER stress pathways. We conclude that DGAT1 and DGAT2 can largely compensate for each other for TG storage but that DGAT1 uniquely has an important role in protecting the ER from the lipotoxic effects of high-fat diets.