Miracle-dz/UniFAR-FTUs huggingface dataset:
The unfolded protein response regulates hepatic autophagy by sXBP1-mediated activation of TFEB

ABSTRACT Defective macroautophagy/autophagy and a failure to initiate the adaptive unfolded protein response (UPR) in response to the endoplasmic reticulum (ER) stress contributes to obesity-associated metabolic dysfunction. However, whether and how unresolved ER stress leads to defects in the autophagy pathway and to the progression of obesity-associated hepatic pathologies remains unclear. Obesity suppresses the expression of hepatic spliced XBP1 (X-box binding protein 1; sXBP1), the key transcription factor that promotes the adaptive UPR. Our RNA-seq analysis revealed that sXBP1 regulates genes involved in lysosomal function in the liver under fasting conditions. Chromatin immunoprecipitation (ChIP) analyzes of both primary hepatocytes and whole livers further showed that sXBP1 occupies the −743 to −523 site of the promoter of Tfeb (transcription factor EB), a master regulator of autophagy and lysosome biogenesis. Notably, this occupancy was significantly reduced in livers from patients with steatosis. In mice, hepatic deletion of Xbp1 (xbp1 LKO) suppressed the transcription of Tfeb as well as autophagy, whereas hepatic overexpression of sXbp1 enhanced Tfeb transcription and autophagy. Moreover, overexpression of Tfeb in the xbp1 LKO mouse liver ameliorated glucose intolerance and steatosis in mice with diet-induced obesity (DIO). Conversely, loss of TFEB function impaired the protective role of sXBP1 in hepatic steatosis in mice with DIO. These data indicate that sXBP1-Tfeb signaling has direct functional consequences in the context of obesity. Collectively, our data provide novel insight into how two organelle stress responses are integrated to protect against obesity-associated metabolic dysfunction. Abbreviations: AAV8: adeno-associated virus serotype 8; ACTB: actin, beta; ANOVA: analysis of variance; ATF6: activating transcription factor-6; ATG: autophagy related; BECN1: beclin 1; BMI: body mass index; ChIP: chromatin immunoprecipitation; CLEAR: coordinated lysosomal expression and regulation; Cre: cre recombinase; DIO: diet-induced obesity; EBSS: Earle’s balanced salt solution; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; ER: endoplasmic reticulum; ERN1/IRE1: endoplasmic reticulum (ER) to nucleus signaling 1; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; HFD: high-fat diet; h: hours; HSCs: hepatic stellate cells; INS: insulin; L/A: ammonium chloride and leupeptin; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; mRNA: messenger RNA; NAFLD: nonalcoholic fatty liver disease; NASH: nonalcoholic steatohepatitis; RD: regular diet; RFP: red fluorescent protein; SERPINA7/TBG: serpin family A member 7; SQSTM1/p62: sequestome 1; sXbp1 LOE: liver-specific overexpression of spliced Xbp1; TFEB: transcription factor EB; TG: thapsigargin; TN: tunicamycin; UPR: unfolded protein response; wks: weeks; WT: wild type; XBP1: X-box binding protein 1; xbp1 LKO: liver-specific Xbp1 knockout.
Reduced survival after autologous stem cell transplantation in myeloma and lymphoma patients with low vitamin D serum levels

High‐dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) is applied for consolidation in myeloma and relapsing lymphoma patients. Vitamin D (VitD) exerts effects during hematopoietic stem cell proliferation, differentiation and interactions with the immune system. VitD deficiency is frequent in patients with hematological malignancies, but its prognostic relevance after ASCT remains unclear. We investigated the effect of VitD serum levels in patients with lymphomas and myeloma at ASCT on progression‐free (PFS) and overall survival (OS). The cohort (n = 183) was divided into two groups: 81 (44%) had VitD levels >52 nmol/L and 102 (56%) ≤52 nmol/L at ASCT. VitD levels >52 nmol/L were associated with better PFS (P = 0.0194) and OS (P = 0.011). Similarly, when evaluating myeloma patients alone, patients with lower VitD levels (≤52 nmol/L) had inferior PFS (P = 0.0412) and OS (P = 0.049). Finally, the multivariate analysis was consistent that varying VitD levels were significantly associated with OS (P = 0.0167), also when stratifying patients in groups with VitD levels > versus ≤52 nmol/L (P = 0.0421). Our data suggest that reduced serum VitD levels in myeloma and lymphoma patients undergoing HDCT/ASCT are associated with inferior outcome. Optimizing VitD levels before ASCT may be warranted.
Genetic diversity through stability analysis for various fatty acids profile in indigenous Brassica species

A total of 120 locally collected accessions of Brassica napus, Brassica juncea and Brassica rapa were evaluated for two years and three different locations of the country to check the level of stability among these accessions for various fatty acids composition. Combined stability analysis of variance for two years and three locations showed significant genetic variation within brassica accessions for all the fatty acids profile. Season x location, genotype x season, genotypes x locations and genotypes x season x locations were highly significant for all the studied parameters, while the values recorded for regression coefficient (b) and deviation from the regression (S 2 d) also showed high amount of variations. From the observed results, some accessions which produce the values near to the stranded values were recommended for further studies in future breeding programmes.
Feeding behaviour and bone utilization by theropod dinosaurs

Examples of bone exploitation by carnivorous theropod dinosaurs are relatively rare, representing an apparent waste of both mineral and energetic resources. A review of the known incidences and possible ecological implications of theropod bone use concludes that there is currently no definitive evidence supporting the regular deliberate ingestion of bone by these predators. However, further investigation is required as the small bones of juvenile dinosaurs missing from the fossil record may be absent as a result of theropods preferentially hunting and consuming juveniles. We discuss implications for both hunting and feeding in theropods based on the existing data. We conclude that, like modern predators, theropods preferentially hunted and ate juvenile animals leading to the absence of small, and especially young, dinosaurs in the fossil record. The traditional view of large theropods hunting the adults of large or giant dinosaur species is therefore considered unlikely and such events rare. square Behaviour, carnivory, palaeoecology, predation, resource utilization.
The oncogenic role of MUC12 in RCC progression depends on c‐Jun/TGF‐β signalling

Renal cell carcinoma (RCC) is a common kidney cancer worldwide. Even though current treatments show promising therapeutic effectiveness, metastatic RCC still has limited therapeutic options so that novel treatments were urgently needed. Here, we identified that MUC12 was overexpressed in RCC patients and served as poor prognostic factor for RCC progression. Overexpression of MUC12 increased RCC cell growth and cell invasion while deficiency of MUC12 exerted opposite effects on RCC cells. Mechanistic dissection demonstrated that MUC12‐mediated RCC cell growth and cell invasion were dependent of TGF‐β1 signalling because they could be blocked in the presence of TGF‐β1 inhibitor. Moreover, the regulation of TGF‐β1 by MUC12 relied on the transactivation of c‐Jun. MUC12 promoted the recruitment of c‐Jun on the promoter of TGF‐β1, leading to its transcription. Importantly, knockdown of c‐Jun also attenuated MUC12‐mediated TGF‐β1 induction and RCC cell invasion. In summary, our study defines the role of MUC12 in RCC progression and provides rational to develop novel targeted therapy to battle against RCC.
Effects of Forchlorfenuron and Abscisic Acid on the Quality of ‘Flame Seedless’ Grapes

Forchlorfenuron (CPPU), a synthetic cytokinin, applied after fruit set increases the size and firmness of table grapes (Vitis vinifera L.) beyond what is possible without CPPU treatment. However, treatment with CPPU may inhibit coloring of 'Flame Seedless' grapes, limiting its use in growing areas where color has been consistently poor. In contrast, application of abscisic acid (ABA) to 'Flame Seedless' grapes may cause fruit softening, which is undesirable, but its primary effect is to increase anthocyanin content and fruit color. Thus, we hypothesized that application of CPPU followed by ABA might increase the size and firmness of 'Flame Seedless' grapes without excessively inhibiting coloring. Grapes were treated with 0 or 20 gha -1 CPPU (applied at fruit set) and 0, 300, or 600 mgL -1 ABA (applied at veraison) in 2005 and with 0, 5, 10, 15, or 20 gha -1 CPPU and 0, 200, 400, or 600 mgL -1 ABA in 2006. Both plant growth regulators (PGRs) increased berry mass, but grapes treated with CPPU were as firm, or firmer, than nontreated grapes, whereas those treated with ABA were of similar or lesser firmness. Treatment with CPPU generally reduced soluble solids and red berry color, whereas treatment with ABA reduced titratable acidity and increased red color. The PGRs did not interact to affect any of the fruit quality variables measured, so beneficial effects of CPPU or ABA were apparent whether the grapes were treated with either or both PGRs. Thus, the combined use of CPPU and ABA may be a desirable cultural practice for 'Flame Seedless'.
Phenol Biodegradation Kinetics in the Presence of Supplimentary Substrate

Biodegradation of phenol in the presence of glucose as a supplementary substrate was investigated with mixed microbial consortium isolated from waste effluent of coke-steel factory. Batch experiments were carried out at room temperature and pH value of 7. Initial phenol and glucose concentrations were in the range of 25-1000 mg/l and 500-3000 mg/l, respectively. In a dual substrates system the concentration of supplementary source (glucose) was kept constant. It was obvious to find out that glucose as a simple carbon source was initially utilized in the presence of phenol. The rate of phenol degradation started once glucose concentration was significantly depleted. Phenol was known to be an inhibitory substrate, thus Haldane/Andrews kinetic model was applied to evaluate the growth kinetic parameters. The kinetic parameters, μm, Ks and Ki were 0.01 1/h, 27.04 and 127.55 mg/l, respectively. The specific growth rate of the culture in dual substrates system was expressed by SKIP model (R2> 0.951). The values of interaction parameters showed uncompetitive partially inhibition at high phenol concentration.
Nitrogen Requirements of Drip- irrigated Processing Tomatoes

As growers of processing tomato (Lycopersicon esculentum Mill.) adopt drip irrigation, plant vigor and fruit yield typically increase, suggesting a need for re-evaluation of established nitrogen (N) fertilization practices. Trials were conducted in California in 2007-2008 to evaluate growth and N uptake dynamics of drip-irrigated processing tomatoes across N fertigation regimes ranging from deficient to excessive. Whole plants were collected at 2-week intervals for determination of biomass and N content, recently matured whole leaves for total N and petioles for N0 3 -N. Additionally, six commercial fields were sampled at 3- to 4-week intervals to document N uptake and crop N status under conditions representative of the industry. A seasonal N rate of ≈200 kg·ha -1 appeared adequate to maximize fruit yield across the range of field conditions encountered. The four highest-yielding fields (143 Mg·ha -1 mean fresh fruit mass) averaged 14 Mg·ha -1 of above-ground biomass with fruit representing 62%; these fields averaged 296 kg·ha -1 biomass N, of which 71% was in fruit. The rate of biomass development and N uptake peaked during the period between early fruit setting and early red fruit development (a period of ≈6 weeks) during which N uptake averaged 4 to 5 kg·ha -1 ·d -1 . Leaf N concentration was highly correlated with whole plant N (r 2 = 0.83) and provided a reliable indicator of plant N sufficiency throughout the season. Petiole NO 3 -N did not reliably discriminate between crops with adequate or deficient N availability; current petiole N0 3 -N sufficiency guidelines are unrealistically high.
Cerebral Blood Flow Is Associated with Diagnostic Class and Cognitive Decline in Alzheimer's Disease.

BACKGROUND Reliable cerebral blood flow (CBF) biomarkers using a noninvasive imaging technique are sought to facilitate early diagnosis and intervention in early Alzheimer's disease (AD). OBJECTIVE We aim to identify brain regions in which CBF values are affected and related to cognitive decline in early AD using a large cohort. METHODS Perfusion MRIs using continuous arterial spin labeling were acquired at 1.5 T in 58 normal controls (NC), 50 mild cognitive impairments (MCI), and 40 AD subjects from the Cardiovascular Health Study cognition study. Regional absolute CBF and normalized CBF (nCBF) values, without and with correction of partial volume effects, were compared across three groups. Association between regional CBF values and Modified Mini-Mental State Examination (3MSE) were investigated by multiple linear regression analyses adjusted for cardiovascular risk factors. RESULTS After correcting for partial volume effects and cardiovascular risk factors, ADs exhibited decreased nCBF with the strongest reduction in the bilateral posterior cingulate & precuneus region (p < 0.001) compared to NCs, and the strongest reduction in the bilateral superior medial frontal region (p < 0.001) compared to MCIs. MCIs exhibited the strongest nCBF decrease in the left hippocampus and nCBF increase in the right inferior frontal and insular region. The 3MSE scores within the symptomatic subjects were significantly associated with nCBFin the bilateral posterior and middle cingulate & parietal (p < 0.001), bilateral superior medial frontal (p < 0.001), bilateral temporoparietal (p < 0.02), and right hippocampus (p = 0.02) regions. CONCLUSION Noninvasive perfusion MRI can detect functional changes across diagnostic class and serve as staging biomarker of cognitive status.
Experimental Aspergillus fumigatus Infection in Dogs and Treatment with Itraconazole

The aim of this study was to investigate the findings of clinical, haemotological, biochemical, histopathological, mycological and urine analyses and to evaluate the efficiency of itraconazole treatment in dogs experimentally infected with Aspergillus fumigatus. In this study, 25 healthy male dogs were used. The animals were divided into 3 groups: group I (control), group II (infected) and group III (treatment) consisting of 5, 10 and 10 dogs, respectively. Cyclophosphamide was injected into the dogs of groups II and III before the inoculation of A. fumigatus via intravenous (i.v.) route. Clinical findings of aspergillosis were developed after the second day following A. fumigatus inoculation. Three dogs died in group II. On the seventh day after the inoculation of the agent (PI), lymphocytosis, monocytosis, granulocytosis and leucocytosis were determined in groups II and III. However, the percentage of lymphocytes in white blood cells decreased. The red blood cell and platelet counts, haemoglobin and haematocrit values, glucose concentrations and the specific gravity of urine decreased while serum alkaline phosphatase activity, urea nitrogen, total protein, globulin, magnesium and phosphorus concentrations increased. Haematuria was observed in all dogs, and proteinuria, glucosuria and ketonuria were observed in some of them. Leucocyte and erythrocyte counts increased in the urine sediment. Aspergillus fumigatus was isolated from the urine, nasal swabs, lungs, kidney, liver, heart, spleen, nasal concha and lymphoid nodules of some of the dogs, while the hyphae of the agent and granulomatous inflammation were observed only in the lungs and kidneys by histopathological examination. The treatment of the animals started on day 10 PI. Itraconazole, at 5 mg/kg body weight per day, was orally administered for 6 weeks. Four dogs died during the treatment period. At the end of the experiment, all of the clinical signs in the 6 surviving dogs had improved except for exophtalmus, miosis, an absence of pupillary reflexes and blindness in 2 dogs. Haematological, biochemical and urine analysis findings returned to close to normal values. It was determined that itraconazole treatment was effective in 6 dogs.
A fishery-independent assessment of an overfished rockfish stock, cowcod (Sebastes levis), using direct observations from an occupied submersible

A meaningful assessment of cowcod (Sebastes levis) has been conducted using visual, nonextractive, habitat-specific methods. Following the precipitous decline of rockfish (Sebastes spp.) stocks along the Pacific coast, it was evident that more effective methods were needed to assess several species in untrawlable habitats. Cowcod were surveyed within large Cowcod Conservation Areas (CCAs) off southern California using direct observations from the research submersible Delta over eight major offshore rocky banks in depths of 74 to 322 m. Maps of seafloor substratum and bathymetry were used to identify and quantify these areas. A line-transect analysis of fish counts, perpendicular distances of fish from the track line, lengths of survey tracks, and area of each rocky bank was used to estimate abundance. Biomass, calculated from abundance, fish length, and a weight–length relationship, varied with mean size of cowcod on these banks. These fishery-independent results have contributed to the recent assessment .
Assisting Home-Based Resistance Training for Normotensive and Prehypertensive Individuals Using Ambient Lighting and Sonification Feedback: Sensor-Based System Evaluation

Background Physical exercise is an effective lifestyle intervention to improve blood pressure. Although aerobic sports can be performed anywhere, resistance exercises are traditionally performed at the gym; extending the latter to the home setting may promote an increase in the number of practitioners. Objective This study aims to evaluate a sensor-based system that guides resistance exercises through ambient lighting and sonification (A/S) feedback in a home setting in 34 study participants who were normotensive and prehypertensive. Methods Participants took part in a 1.5-hour exercise session in which they experienced the A/S feedback (ie, experimental condition) as well as a control condition (ie, no feedback) and a reference condition (ie, verbal feedback through a human remote coach). The system was evaluated for improving exercise form (range of motion, timing, and breathing patterns) as well as psychophysiological experience (perceived exertion, attentional focus, competence, and motivation). Results A/S feedback was significantly better than the control for concentric (mean 2.48, SD 0.75 seconds; P<.001) and eccentric (mean 2.92, SD 1.05 seconds; P<.001) contraction times, concentric range of motion consistency (mean 15.64, SD 8.31 cm vs mean 17.94, SD 9.75 cm; P<.001), and perceived exertion (mean 3.37, SD 0.78 vs mean 3.64, SD 0.76; P<.001). However, A/S feedback did not outperform verbal feedback on any of these measures. The breathing technique was best in the control condition (ie, without any feedback). Participants did not show more positive changes in perceived competence with A/S feedback or verbal feedback. Conclusions The system seemed to improve resistance exercise execution and perception in comparison with the control, but did not outperform a human tele-coach. Further research is warranted to improve the breathing technique.
An Elasmosaur with Stomach Contents and Gastroliths from the Pierre Shale (Late Cretaceous) of Kansas

Abstract A nearly complete skeleton of an elasmosaurid plesiosaur (NJSM 15435) from the Sharon Springs Member (Middle Campanian) of the Pierre Shale, Logan County, Kansas, is associated intimately with fragmentary fish remains and numerous gastroliths. The fish bones and gastroliths were located just behind the pectoral girdle in the abdominal region. Identifiable prey includes Enchodus and other small clupeomorph fishes. An isolated tooth of the anacoracid shark Squalicorax cf. S. pristodontus also was recovered in this area. Ninety-five gastroliths (6.8 kg) were present, with the largest stone measuring 15.1 × 8.5 × 5.7 cm (5.0 × 3.3 × 2.2 in.) and weighing 1.06 kg (2.3 lb.). Many of the gastroliths are composed of pink or gray Sioux Quartzite, which suggests that the source of these stones was about 600 km (475 mi) to the northeast of where the elasmosaur remains were discovered. The association of fragmentary fish remains and gastroliths within the abdomen of NJSM 15435 supports the contention that the stones aided in the breakdown of food in plesiosaurs.
Avaliação genética de indivíduos e progênies de cupuaçuzeiro no estado do Pará e estimativas de parâmetros genéticos

O presente trabalho relata a avaliacao genotipica de progenies de cupuacuzeiro, no Estado do Para, para os caracteres numero de frutos (NF) em quatro safras, intensidade de ocorrencia de vassoura- de-bruxa na inflorescencia (VBI) e nos frutos (VBF), e peso de vassoura-de-bruxa (PVB). Apresenta tambem estimativas de parâmetros geneticos que permitem inferir sobre o controle genetico e nivel de variabilidade genetica presente no material avaliado. Todos os caracteres apresentaram consideravel variabilidade genetica, com coeficientes de variacao genetica variando de 27% a 88% no âmbito de progenie e de 38% a 123% no âmbito individual. Isto revela excelentes possibilidades para a selecao nessa populacao experimental hibrida. As estimativas de herdabilidade individual no sentido restrito, em uma safra, variaram de 25% a 54%, e as repetibilidades individuais para NF equivaleram a 35%. Com as quatro safras realizadas, a herdabilidade em nivel individual aumentou para 48%, propiciando acuracia seletiva de 70%, para a selecao de individuos. O ganho em eficiencia, quando se usa mais de cinco safras, e praticamente desprezivel. Para NF, ganhos acima de 60% podem ser obtidos com a selecao dos cinco melhores individuos. Poderao ser selecionados individuos com producao anual de 17 frutos, valor muito superior a media geral de 10 frutos, encontrada nos plantios comerciais. Verificam-se ganhos geneticos bastante superiores quando se faz a propagacao clonal dos melhores individuos em relacao ao que se verifica quando se realiza a propagacao sexuada. Para o melhor individuo, o ganho genetico aumenta de 75.5% para 88.3%, ou seja, de 17 para quase 19 frutos por planta. Isto revela um grande potencial para a clonagem comercial de cupuacuzeiro. Para os caracteres VBI e VBF, verificaram-se altas herdabilidades individuais no sentido restrito com valores variando entre 30% e 54%. Isto revela o excelente potencial da selecao recorrente para melhorar, gradativamente, o nivel de resistencia. Parece suficiente considerar na selecao apenas o numero de vassouras, nao sendo necessario considerar o peso. A correlacao entre resistencia no fruto e na inflorescencia foi alta (0.84), indicando algum controle genetico comum aos dois caracteres. Foram identificadas progenies superiores, simultaneamente, para producao de frutos e resistencia a vassoura.