Miracle-dz/UniFAR-FTUs huggingface dataset:
The extended GLUT-family of sugar/polyol transport facilitators: nomenclature, sequence characteristics, and potential function of its novel members

During the last 2 years, several novel genes that encode glucose transporter-like proteins have been identified and characterized. Because of their sequence similarity with GLUT1, these genes appear to belong to the family of solute carriers 2A ( SLC2A, protein symbol GLUT). Sequence comparisons of all 13 family members allow the definition of characteristic sugar/polyol transporter signatures: (1) the presence of 12 membrane-spanning helices, (2) seven conserved glycine residues in the helices, (3) several basic and acidic residues at the intracellular surface of the proteins, (4) two conserved tryptophan residues, and (5) two conserved tyrosine residues. On the basis of sequence similarities and characteristic elements, the extended GLUTfamily can be divided intothree subfamilies, namely class I (the previously known glucose transporters GLUT1-4), class II (the previously known fructose transporter GLUT5, the GLUT7, GLUT9 and GLUT11), and class III (GLUT6, 8, 10, 12, and the myoinositol transporter HMIT1). Functional characteristics have been reported for some of the novel GLUTs. Like GLUT1-4, they exhibit a tissue/cell-specific expression (GLUT6, leukocytes, brain; GLUT8, testis, blastocysts, brain, muscle, adipocytes; GLUT9, liver, kidney; GLUT10, liver, pancreas; GLUT11, heart, skeletal muscle). GLUT6 and GLUT8 appear to be regulated by sub-cellular redistribution, because they are targeted to intracellular compartments by dileucine motifs in a dynamin dependent manner. Sugar transport has been reported for GLUT6, 8, and 11; HMIT1 has been shown to be a H + /myo-inositol co-transporter. Thus, the members of the extended GLUT family exhibit a surprisingly diverse substrate specificity, and the definition of sequence elements determining this substrate specificity will require a full functional characterization of all members.
Pulmonary resection for patients with multidrug‐resistant tuberculosis based on survival outcomes: a systematic review and meta‐analysis

Summary We investigated the survival benefit of pulmonary resection for patients with multidrug‐resistant tuberculosis. To weigh the survival benefit of pulmonary resection for patients with multidrug‐resistant tuberculosis who have undergone surgical treatment combined with medical chemotherapy compared with medical chemotherapy alone, we did a meta‐analysis of available studies containing a hazard ratio for pulmonary resection. Among 1726 articles, 6 clinical reports, with a mean sample size of 47 patients per report, met the inclusion criteria. The pooled hazard ratio of 0.68 with a 95% confidence interval of approximately 0.44‐1.07 suggested that the survival benefit of surgical pulmonary resection combined with chemotherapy, in a comparison of the groups ‘with surgery’ and ‘without surgery’, is not significantly greater than that of chemotherapy alone. Selection bias, due to the absence of rigid predetermined indications for pulmonary resection, limited the validity of this analysis. Due to the heterogeneity of the patient groups, greater attention is required to compute additional hazard ratios in future studies with stratification of factors such as cardiopulmonary functions, disease extent and the presence of a cavity. These additional computations in future studies are necessary to determine the survival benefit and to support the rigid surgical indications.
Kinetic and Molecular Analysis of Nuclear Export Factor CRM1 Association with Its Cargo In Vivo

ABSTRACT The nucleocytoplasmic transport receptor CRM1 mediates the export of macromolecules from the nucleus to the cytoplasm by forming a ternary complex with a cargo molecule and RanGTP. The in vivo mechanism of CRM1 export complex formation and its mobility throughout the nucleus have not been fully elucidated. More information is required to fully understand complex formation and the dynamics of CRM1-cargo-RanGTP complexes in space and time. We demonstrate true molecular interaction of CRM1 with its Rev cargo in living cells by using fluorescence resonance energy transfer (FRET). Interestingly, we found that the inhibitory effect of leptomycin B on this CRM1-cargo interaction is Ran dependent. Using fluorescence recovery after photobleaching (FRAP), we show that CRM1 moves at rates similar to that of free green fluorescent protein in the nucleoplasm. A slower mobility was detected on the nuclear membrane, consistent with known CRM1 interactions with nuclear pores. Based on these data, we propose an in vivo model in which CRM1 roams through the nucleus in search of high-affinity binding sites. CRM1 is able to bind Rev cargo in the nucleolus, and upon RanGTP binding a functional export complex is produced that is exported to the cytoplasm.
Community supported agriculture (CSA) as a transformational act—distinct values and multiple motivations among farmers and consumers

ABSTRACT Compared to most other wealthy countries, Norwegian producers and consumers have been somewhat sheltered from the international market, but this has changed over the last decades. As a response to these changes, the number of community supported agriculture (CSA) farms, has grown rapidly in Norway. This article reveals, in depth, why Norwegian producers and consumers engage in CSA and how CSA can be seen as a transformational act toward food system changes. The study reveals that the Norwegian CSA producers, and consumers in general, have distinct values and are motivated by a desire of a production and food system, that safeguards aspects of environment, justice, health, participation, and communication. For them, the farms are an arena for converting societal values into practical actions. The sustainable production methods practiced—and the reallocation of power back to the producers, consumers, and local community—are indicative of the transformational power CSA has had upon the current agri-food system regime. However, the challenge is to upscale these actions, as well as prevent dilution of the core values and agroecological practices seen in the Norwegian CSAs.
Epiregulin (EREG) is upregulated through an IL‐1β autocrine loop in Caco‐2 epithelial cells with reduced CFTR function

CFTR is a cAMP‐regulated chloride channel, whose mutations produce cystic fibrosis. The impairment of CFTR activity increases the intracellular Cl− concentration, which in turn produces an increased interleukin‐1β (IL‐1β) secretion. The secreted IL‐1β then induces an autocrine positive feedback loop, further stimulating IL‐1β priming and secretion. Since IL‐1β can transactivate the epidermal growth factor receptor (EGFR), we study here the levels of expression for different EGFR ligands in Caco‐2/pRS26 cells (expressing shRNA against CFTR resulting in a reduced CFTR expression and activity). The epiregulin (EREG), amphiregulin (AREG), and heparin binding EGF like growth factor (HBEGF) mRNAs, were found overexpressed in Caco‐2/pRS26 cells. The EREG mRNA had the highest differential expression and was further characterized. In agreement with its mRNA levels, Western blots (WB) showed increased EREG levels in CFTR‐impaired cells. In addition, EREG mRNA and protein levels were stimulated by incubation with exogenous IL‐1β and inhibited by the Interleukin 1 receptor type I (IL1R1) antagonist IL1RN, suggesting that the overexpression of EREG is a consequence of the autocrine IL‐1β loop previously described for these cells. In addition, the JNK inhibitor SP600125, and the EGFR inhibitors AG1478 and PD168393, also had an inhibitory effect on EREG expression, suggesting that EGFR, activated in Caco‐2/pRS26 cells, is involved in the observed EREG upregulation. In conclusion, in Caco‐2 CFTR‐shRNA cells, the EGFR ligand EREG is overexpressed due to an active IL‐1β autocrine loop that indirectly activates EGFR, constituting new signaling effectors for the CFTR signaling pathway, downstream of CFTR, Cl−, and IL‐1β.
Disruption of arginase II alters prostate tumor formation in TRAMP mice

Arginase II (AII) is involved in the polyamine synthetic pathway, and elevated levels of expression have been found in a high proportion of prostate cancer samples and patients. However, the biological function of arginase II in prostate cancer still remains to be elucidated. In this study, we utilized the TRAMP mouse prostate cancer model to better understand the contribution of AII on tumor development.
Effects of Tumor Necrosis Factor Alpha on Host Immune Response in Chronic Persistent Tuberculosis: Possible Role for Limiting Pathology

ABSTRACT Reactivation of latent tuberculosis contributes significantly to the incidence of disease caused by Mycobacterium tuberculosis. The mechanisms involved in the containment of latent tuberculosis are poorly understood. Using the low-dose model of persistent murine tuberculosis in conjunction with MP6-XT22, a monoclonal antibody that functionally neutralizes tumor necrosis factor alpha (TNF-α), we examined the effects of TNF-α on the immunological response of the host in both persistent and reactivated tuberculous infections. The results confirm an essential role for TNF-α in the containment of persistent tuberculosis. TNF-α neutralization resulted in fatal reactivation of persistent tuberculosis characterized by a moderately increased tissue bacillary burden and severe pulmonic histopathological deterioration that was associated with changes indicative of squamous metaplasia and fluid accumulation in the alveolar space. Analysis of pulmonic gene and protein expression of mice in the low-dose model revealed that nitric oxide synthase was attenuated during MP6-XT22-induced reactivation, but was not totally suppressed. Interleukin-12p40 and gamma interferon gene expression in TNF-α-neutralized mice was similar to that in control mice. In contrast, interleukin-10 expression was augmented in the TNF-α-neutralized mice. In summary, results of this study suggest that TNF-α plays an essential role in preventing reactivation of persistent tuberculosis, modulates the pulmonic expression of specific immunologic factors, and limits the pathological response of the host.
Relationship of physical activity to eating behaviors and weight loss in women.

PURPOSE To examine whether change in physical activity is associated with compliance to changes in dietary intake and eating behaviors in an 18-month behavioral weight loss program, and to examine the contribution of exercise to weight loss when these other weight loss behaviors are also considered. METHODS Data from 104 subjects who completed an 18-month behavioral weight loss program were analyzed in this study. All subjects were prescribed a reduced energy (1,200-1,500 kcal x d(-1)) and fat (20 to 30%) diet, and exercise progressed from 100 to 200 min x wk(-1). Subjects attended group behavioral lessons throughout the study. Weight, physical activity, energy intake, and weight loss eating behaviors were assessed at 0 and 18 months. RESULTS Body weight decreased 7.8 +/- 7.5 kg and body mass index decreased 2.8 +/- 2.7 kg x m(-2) from 0 to 18 months ( < 0.05). Total energy intake (kcal x d(-1)) and macronutrient intake (g x d(-1)) decreased, whereas physical activity and eating behaviors associated with weight loss increased from 0 to 18 months ( < 0.05). Change in physical activity was significantly correlated with weight loss (r = 0.33), reductions in energy intake (r = 0.20), and improvements in eating behaviors associated with weight loss (r = 0.24) ( < 0.05). Regression analysis indicated that change in physical activity significantly improved weight loss after changes in energy intake and weight loss eating behaviors were considered in the analysis, with R(2)significantly improving by approximately 0.04 ( < 0.05). However, results from multiple regression showed weight loss was influence more by changes in eating behaviors than changes in physical activity (R(2) = 0.17 vs R(2) = 0.04). CONCLUSIONS The combination of changes in eating and physical activity behaviors can improve long-term weight loss compared with either behavior alone. Interventions targeting both behaviors are recommended for improving long-term weight loss.
Biomechanics of the Coracoclavicular Ligament Complex and Augmentations Used in Its Repair and Reconstruction *

Augmentation is a well-accepted and common component of coracoclavicular ligament repairs and reconstructions. The purpose of this study was to examine and compare the strength, stiffness, and mode of failure of the coracoclavicular ligament complex and four different augmentation techniques in cadaveric shoulders. There was no significant difference in the mean failure load between the intact ligament complex (724.9 230.9 N) and augmentations performed with braided polydioxanone (PDS) (676.7 115.4 N) or braided polyethylene placed through (986.1 391.1 N) or around (762.7 218.2 N) the clavicle. The mean failure load for augmentations using a 6.5-mm cancellous screw through the clavicle and into a single cortex of the coracoid (390.1 253.6 N) was significantly lower than that for the intact coracoclavicular ligaments. There was no difference in mean stiffness between the intact coracoclavicular ligament complex (115.9 36.2 N/mm) and the braided polyethylene augmentations placed through (99.8 22.2 N/mm) or around (90.0 25.5 N/mm) the clavicle. Polydioxanone augmentations were significantly less stiff (27.4 3.3 N/mm) than the intact complex, while screw augmentations were significantly stiffer (250.4 88.2 N/mm). There were no significant differences in strength or stiffness of braided polyethylene reconstructions placed around or through a drill hole in the clavicle.
Acute HIV infection transmission among people who inject drugs in a mature epidemic setting

Objective:Estimates for the contribution of transmission arising from acute HIV infections (AHIs) to overall HIV incidence vary significantly. Furthermore, little is known about AHI-attributable transmission among people who inject drugs (PWID), including the extent to which interventions targeting chronic infections (e.g. HAART as prevention) are limited by AHI transmission. Thus, we estimated the proportion of transmission events attributable to AHI within the mature HIV epidemic among PWID in New York City (NYC). Design:Modeling study. Methods:We constructed an interactive sexual and injecting transmission network using an agent-based model simulating the HIV epidemic in NYC between 1996 and 2012. Using stochastic microsimulations, we cataloged transmission from PWID based on the disease stage of index agents to determine the proportion of infections transmitted during AHI (in primary analyses, assumed to last 3 months). Results:Our calibrated model approximated the epidemiological features of the mature HIV epidemic in NYC between 1996 and 2012. Annual HIV incidence among PWID dropped from approximately 1.8% in 1996 to 0.7% in 2012. Over the 16-year period, AHI accounted for 4.9% (10th/90th percentile: 0.1–12.3%) of incident HIV cases among PWID. The annualized contribution of AHI increased over this period from 3.6% in 1996 to 5.9% in 2012. Conclusion:Our results suggest that, in mature epidemics such as NYC, between 3% and 6% of transmission events are attributable to AHI among PWID. Current HIV treatment as prevention strategies are unlikely to be substantially affected by AHI-attributable transmission among PWID populations in mature epidemic settings.
Self-control forecasts better psychosocial outcomes but faster epigenetic aging in low-SES youth

Significance Most childhood outcomes pattern by socioeconomic status (SES). Children from low-SES families complete less education, have worse health, and are convicted of more crimes. To ameliorate these disparities, policymakers are incorporating character-skills training into school curricula and social services. Among other goals, these programs attempt to improve self-control, or the ability to resist temptations that interfere with long-term aspirations. However, data suggest that self-control has unforeseen consequences for the health of low-SES youth. Here, we follow 292 African American teenagers as they transition into adulthood. Among low-SES youth, self-control forecasted better psychosocial outcomes, including less depression, substance use, and aggression. However, it also forecasted more rapid immune cell aging, highlighting the potential health costs of successful adjustment for disadvantaged youth. There are persistent socioeconomic disparities in many aspects of child development in America. Relative to their affluent peers, children of low socioeconomic status (SES) complete fewer years of education, have a higher prevalence of health problems, and are convicted of more criminal offenses. Based on research indicating that low self-control underlies some of these disparities, policymakers have begun incorporating character-skills training into school curricula and social services. However, emerging data suggest that for low-SES youth, self-control may act as a “double-edged sword,” facilitating academic success and psychosocial adjustment, while at the same time undermining physical health. Here, we examine this hypothesis in a five-wave study of 292 African American teenagers from rural Georgia. From ages 17 to 20 y, we assessed SES and self-control annually, along with depressive symptoms, substance use, aggressive behavior, and internalizing problems. At age 22 y, we obtained DNA methylation profiles of subjects’ peripheral blood mononuclear cells. These data were used to measure epigenetic aging, a methylation-derived biomarker reflecting the disparity between biological and chronological aging. Among high-SES youth, better mid-adolescent self-control presaged favorable psychological and methylation outcomes. However, among low-SES youth, self-control had divergent associations with these outcomes. Self-control forecasted lower rates of depressive symptoms, substance use, aggressive behavior, and internalizing problems but faster epigenetic aging. These patterns suggest that for low-SES youth, resilience is a “skin-deep” phenomenon, wherein outward indicators of success can mask emerging problems with health. These findings have conceptual implications for models of resilience, and practical implications for interventions aimed at ameliorating social and racial disparities.
Using cerebral hemovelocity to measure workload during a spatialised auditory vigilance task in novice and experienced observers

This experiment was designed to assess cognitive load using transcranial Doppler sonography during the performance of a 40-min communication vigilance task in which messages were presented in different spatial locations or across a single monaural radio channel. In addition, some observers received 14 hours of practice to determine whether the neurophysiological measure was sensitive to a potential attenuation of workload. Critical messages were detected more frequently in the spatialised audio presentation mode condition, but there were no performance differences between experienced and novice observers. Neurophysiological data show that activation was greater in the novice condition than in the experienced condition, suggesting that novice observers expended greater effort. Furthermore, the neurophysiological measure showed more activation in the monaural radio condition than in the spatialised audio condition. The results support a resource account of vigilance and suggest that cerebral blood flow velocity can be used to diagnose the degree of attentional resource utilisation during vigilance tasks. Practitioner Summary: Due to high workload experienced during vigilance tasks, displays and methods are sought which enhance performance. This study shows that spatialising auditory communications in a monitoring task enhances performance and attenuates mental workload. Also, experience mitigates excessive workload, and cerebral hemovelocity can be used to diagnose attentional resource utilisation.
Cognitive decline precedes late-life longitudinal changes in vascular risk factors

Introduction Although obesity, hypercholesterolaemia and hypertension in midlife are risk factors for dementia in late life, dementia is associated with lower body mass index, cholesterol levels and blood pressures. It is unclear whether declines in these vascular risk factors are preceded by declines in cognitive function or vice versa. Methods Within the Leiden 85-plus Study, a prospective population-based study of 599 subjects aged 85 years, the authors annually measured body mass index, total cholesterol, high-density lipoprotein (HDL) cholesterol, glucose levels and blood pressure, and assessed global cognitive function using the Mini Mental State Examination (MMSE) during a 5-year follow-up. Results For the whole population who survived up to the age of 90 years, strong annual declines in MMSE score, body mass index, total cholesterol levels, glucose levels, and blood pressure, and an annual increase in HDL cholesterol levels were observed during the follow-up period (all p≤0.010). Annual changes in MMSE score from age 85 to 87 years were associated positively with annual changes from age 87 to 90 years in total and HDL cholesterol levels (p=0.002 and p=0.013), systolic and diastolic blood pressure (p=0.008 and p=0.048), but not BMI. Parameter value changes from age 85 to 87 years were not associated with changes in MMSE score from age 87 to 90 years. Discussion In old age, cognitive decline precedes declines in total cholesterol levels, HDL cholesterol levels and blood pressure, and not vice versa. Possibly, brain lesions in metabolic and blood pressure regulation centres cause dysregulation of lipid metabolism and blood pressure.
Second-Line Combination Chemotherapy with Docetaxel for Cisplatin-Pretreated Refractory Metastatic Esophageal Cancer: A Preliminary Report of Initial Experience

Background and Aims: Patients with esophageal cancer often develop metastatic disease after esophageal resection and generally receive cisplatin-based chemotherapy or chemoradiotherapy. The efficacy and toxicity of the combination of docetaxel, 5-fluorouracil (5-FU) and cisplatin (DFC) as a second-line chemotherapy were evaluated in patients with postoperative metastatic esophageal cancer refractory to cisplatin-based chemotherapy. Patients and Methods: Twenty patients with metastatic esophageal cancer after esophagectomy refractory to cispatin-based therapy were included in this study. The DFC regimen consisted of docetaxel (60 mg/m2) on day 1, 5-FU (500 mg/day) on days 1–5 and cisplatin (10 mg/day) on days 1–5, being repeated every 3 weeks. Results: A total of 49 cycles (median 2, range 1–6) was administered to 20 patients. The median follow-up was 8 months (range 3–24). Of the 20 patients, 1 had a complete response, 6 had a partial response, 6 had stable and 7 had progressive disease. Median time to progression for all patients was 4 months (95% Cl 1.7–5.6). The median overall survival for all patients was 8 months (95% CI 5.7–10.3). The major toxicity was myelosuppression. Neutropenia of grade 3 or more occurred in 13 patients (65%), and thrombocytopenia of grade 3 occurred in 1 patient (5%). Febrile neuropenia was observed in 1 patient (5%). There was no treatment-related mortality. Conclusion: DFC is a feasible and promising regimen as a second-line therapy in metastatic/recurrent esophageal cancer refractory to cisplatin-based chemotherapy.