Miracle-dz/UniFAR-FTUs huggingface dataset:
The TDP‐43 N‐terminal domain structure at high resolution

Transactive response DNA‐binding protein 43 kDa (TDP‐43) is an RNA transporting and processing protein whose aberrant aggregates are implicated in neurodegenerative diseases. The C‐terminal domain of this protein plays a key role in mediating this process. However, the N‐terminal domain (residues 1–77) is needed to effectively recruit TDP‐43 monomers into this aggregate. In the present study, we report, for the first time, the essentially complete 1H, 15N and 13C NMR assignments and the structure of the N‐terminal domain determined on the basis of 26 hydrogen‐bond, 60 torsion angle and 1058 unambiguous NOE structural restraints. The structure consists of an α‐helix and six β‐strands. Two β‐strands form a β‐hairpin not seen in the ubiquitin fold. All Pro residues are in the trans conformer and the two Cys are reduced and distantly separated on the surface of the protein. The domain has a well defined hydrophobic core composed of F35, Y43, W68, Y73 and 17 aliphatic side chains. The fold is topologically similar to the reported structure of axin 1. The protein is stable and no denatured species are observed at pH 4 and 25 °C. At 4 kcal·mol−1, the conformational stability of the domain, as measured by hydrogen/deuterium exchange, is comparable to ubiquitin (6 kcal·mol−1). The β‐strands, α‐helix, and three of four turns are generally rigid, although the loop formed by residues 47–53 is mobile, as determined by model‐free analysis of the 15N{1H}NOE, as well as the translational and transversal relaxation rates.
Contrary Effects of Octopamine Receptor Ligands on Behavioral and Neuronal Changes in Locomotion of Lymnaea

The pond snail Lymnaea stagnalis moves along the sides and bottom of an aquarium, but it can also glide upside down on its back below the water's surface. We have termed these two forms of locomotion “standard locomotion” and “upside-down gliding,” respectively. Previous studies showed that standard locomotion is produced by both cilia activity on the foot and peristaltic contraction of the foot muscles, whereas upside-down gliding is mainly caused by cilia activity. The pedal A neurons are thought to receive excitatory octopaminergic input, which ultimately results in increased cilia beating. However, the relationship between locomotory speed and the responses of these neurons to octopamine is not known. We thus examined the effects of both an agonist and an antagonist of octopamine receptors on locomotory speed and the firing rate of the pedal A neurons. We also examined, at the electron and light-microscopic levels, whether structural changes occur in cilia following the application of either an agonist or an antagonist of octopamine receptors to the central nervous system (CNS). We found that the application of an octopamine antagonist to the CNS increased the speed of both forms of locomotion, whereas application of octopamine increased only the firing rate of the pedal A neurons. Microscopic examination of the cilia proved that there were no changes in their morphology after application of octopamine ligands. These data suggest that there is an unidentified octopaminergic neuronal network in the CNS whose activation reduces cilia movement and thus locomotory speed.
DeNovo Infection with Rhesus Monkey Rhadinovirus Leads to theAccumulation of Multiple Intranuclear Capsid Species during LyticReplication but Favors the Release of Genome-ContainingVirions

ABSTRACT Rhesus monkey rhadinovirus (RRV) is one of the closest phylogenetic relatives to the human pathogen Kaposi's sarcoma-associated herpesvirus (KSHV), yet it has the distinct experimental advantage of entering efficiently into lytic replication and growing to high titers in culture. RRV therefore holds promise as a potentially attractive model with which to study gammaherpesvirus structure and assembly. We have isolated RRV capsids, determined their molecular composition, and identified the genes encoding five of the main capsid structural proteins. Our data indicate that, as with other herpesviruses, lytic infection with RRV leads to the synthesis of three distinct intranuclear capsid species. However, in contrast to the inefficiency of KSHV maturation following reactivation from latently infected B-cell lines (K. Nealon, W. W. Newcomb, T. R. Pray, C. S. Craik, J. C. Brown, and D. H. Kedes, J. Virol. 75:2866-2878, 2001), de novo infection of immortalized rhesus fibroblasts with RRV results in the release of high levels of infectious virions with genome-containing C capsids at their center. Together, our findings argue for the use of RRV as a powerful model with which to study the structure and assembly of gammaherpesviruses and, specifically, the human rhadinovirus,KSHV.
Influence of high glucose concentrations on the expression of glycosaminoglycans and N-deacetylase/N-sulphotransferase mRNA in cultured skin fibroblasts from diabetic patients with or without nephropathy.

BACKGROUND The Steno hypothesis postulates that a genetic defect in the regulation of the production of heparan sulphate by renal and non-renal cells determines susceptibility for the development of proteinuria and macro-angiopathy in patients with diabetic nephropathy (DN). METHODS To test this hypothesis, skin fibroblasts isolated from type II diabetic patients with overt DN, micro-albuminuria, or without DN and from non-diabetic patients (n=8 for each group) were cultured in the presence of 5 or 25 mM D-glucose or in 25 mM L-glucose, and tested for the expression of N-deacetylase/N-sulphotransferase (NDST) 1 and 2 by semi-quantitative RT--PCR. Proteoglycan production was measured by means of metabolic labelling. RESULTS In each group of patients, 25 mM D-glucose significantly reduced the incorporation of [3H]glucosamine (P<0.01), but not [35S]sulphate. The quantity of NDST 1 mRNA expression did not differ between the four groups. In the non-diabetic group only, 25 mM D-glucose significantly increased NDST 1 mRNA expression (P<0.01). In contrast, NDST 2 mRNA expression was reduced by 25 mM D-glucose in all groups (P<0.01). In the diabetic patients, NDST 2 mRNA was significantly reduced compared with the non-diabetic patients. No differences were found between patients with or without nephropathy. In mesangial cells (MC), NDST expression was not influenced by glucose. CONCLUSIONS Since NDST 1 and 2 are not differentially expressed in patients with or without nephropathy and, in MC, the mRNA expression hereof is not influenced by glucose as in skin fibroblasts, our data do not support the Steno hypothesis.
Transport of IgG across the Blood-Luminal Barrier of the Male Reproductive Tract of the Rat and the Effect of Estradiol Administration on Reabsorption of Fluid and IgG by the Epididymal Ducts1

Abstract In rats immunized systemically with tetanus toxoid the concentration of specific anti-tetanus-toxoid-specific IgG in fluid from the rete testis and cauda epididymidis were respectively 0.6% and 1.4% the concentration in blood serum. The extratesticular duct system reabsorbed 97% of the IgG and 99% of the fluid leaving the rete, but estradiol administration affected the site of reabsorption. In untreated rats, the ductuli efferentes reabsorbed 94% of the IgG and 96% of the fluid leaving the rete, whereas estradiol-treated rats reabsorbed 83% of the IgG and 86% of the fluid, and the ductus epididymidis fully compensated for these different effects of estradiol on the ductuli efferentes. The concentrations of IgG in secretions of the seminal vesicles and prostate gland were lower (0.1% and 0.3% respectively of the titers in blood serum) than in fluids from the extratesticular ducts, and were not affected by the administration of estradiol. RT-PCR showed that Fcgrt (neonatal Fc receptor, also known as FcRn) is expressed in the reproductive ducts, where IgG is probably transported across epithelium, being particularly strong in the ductuli efferentes (where most IgG was reabsorbed) and distal caput epididymidis. It is concluded that IgG enters the rete testis and is concentrated only 2.5-fold along the extratesticular duct system, unlike spermatozoa, which are concentrated 95-fold. Further, the ductus epididymidis can recognize and compensate for changes in function of the ductuli efferentes.
‘One Big Playground for Kids’: A Contextual Appraisal of Some 1970s Photographs of Children Hanging Out on a Post-Second-World-War British Council Estate

ABSTRACT This article gives a broad assessment of a selection of photographs taken in the early 1970s of children on a post-Second-World-War British council estate in Gainsborough, Lincolnshire. As one of the cornerstones of postwar social reconstruction in Britain, the provision and design of new public housing often had the well-being of the future citizen – the child – in mind, and the photography of these estates at the time often included children as a way to promote a sense of well-being and community. This article offers a reading of these photographs as a representation of the child’s day-to-day life in this particular environment, and to present an understanding of how the planning and layout of the estate was intended to function as a crucial influence on the development of the children who lived there.
Fostering Creativity Through Critical Thinking: The Case of Business Start‐Up Simulations

Research suggests a positive link between critical thinking and creativity. However, this relationship has not been measured in an empirical study. This study aims to explore whether critical thinking can serve to enhance creativity and whether creativity positively mediates the relationship between critical thinking and business performance. In this study, we analyse these relationships within the entrepreneurial context of a web-based business start-up simulation. We examined data from 26 teams of three to four senior business students and found partial support for our hypotheses. Critical thinking positively influenced creativity, measured as the total number of unique product designs. Creativity (unique product designs) also positively mediated the link between critical thinking and performance. This effect, however, did not exist when creativity was assessed through advertisement designs. This research contributes to entrepreneurship and innovation management by demonstrating the importance of critical thinking as a basis for creativity and testing this relationship in a business start-up simulation context.
Spatial and temporal correlation between leukocyte behavior and cell injury in postischemic rat skeletal muscle microcirculation.

BACKGROUND Although leukocyte adhesion and capillary plugging are postulated to play a role in postischemic tissue injury, there is only limited evidence demonstrating the relationship between tissue leukocyte accumulation and cell injury in terms of their temporal sequence and spatial distribution. EXPERIMENTAL DESIGN This study was designed to study in vivo neutrophil behavior and its correlation with cell injury in postischemic skeletal muscle microcirculation. The microcirculation of the rat spinotrapezius muscle was observed in vivo using dual-color digital microfluorography to simultaneously visualize leukocyte traffic and cell death (irreversible nuclear damage) on the basis of carboxyfluorescein diacetate succinimidyl ester and propidium iodide, respectively. A 1-hour period of hemorrhagic hypotension (40 mm Hg) followed by reperfusion was carried out to induce muscle injury. RESULTS Hypotension was followed by an increase in leukocyte recruitment in two different ways: capillary obstruction and venular adhesion. Upon reperfusion, a majority of the leukocytes were initially dispersed from the muscle capillaries and venules, but then the number of leukocytes plugging capillaries and adherent to venules increased again in a time-dependent manner. The number of leukocytes obstructing capillaries was closely correlated with the postischemic systemic blood pressure. The cell injury became detectable initially at the end of the hypotensive period and then increased explosively after reperfusion before a significant leukocyte accumulation. Reperfusion-induced early nuclear injury was seen predominantly in reperfused capillaries without plugging leukocytes. A majority of the initially damaged nuclei were those of myocytes in the pericapillary space, but no nuclei of capillary endothelium was involved. Sodium (-)-8-(3-methoxy-4-phenylsulfinylphenyl) pyrazolo [1,5-a]-1,3,5-triazine-4-olate monohydrate, a novel inhibitor of xanthine oxidase, significantly attenuated the early increase in muscle injury and subsequent venular leukocyte adhesion after reperfusion. CONCLUSIONS These results suggest the involvement of an endothelium-dependent mechanism involving xanthine oxidase in postischemic irreversible myocyte injury. It is conceivable that leukocytes adherent to venules as well as those plugging capillaries play only minor roles in the initial mechanism of reperfusion injury.
The influence of obesity on response to tumour necrosis factor-α inhibitors in psoriatic arthritis: results from the DANBIO and ICEBIO registries.

OBJECTIVES To investigate the impact of obesity on response to the first TNF-α inhibitor (TNFI) treatment course in patients with PsA followed in routine care. METHODS We performed an observational cohort study based on the Danish and Icelandic biologics registries. Kaplan-Meier plots, Cox and logistic regression analyses were performed to study the impact of obesity (BMI ⩾30 kg/m2) on TNFI adherence and response after 6 months (according to 20/50/70% improvement in ACR criteria and EULAR criteria). Subanalyses studied the impact of obesity according to gender, TNFI type and nationality. RESULTS Among 1943 PsA patients (193 Icelandic/1750 Danish) identified in the registries, 1271 (65%) had available BMI and 408 (32%) were obese. The median follow-up-time was 1.5 years [interquartile range (IQR) 0.5-3.9]. Obese patients had higher baseline disease activity, for example, 28-joint DAS [mean 4.6 (sd 1.2) vs 4.4 (1.2)]; CRP [median 9 mg/l (IQR 5-19) vs 7 (3-18)] and visual analogue scale-pain [66 mm (IQR 48-76) vs 60 (38-74)], compared with non-obese patients (all P < 0.05). TNFI adherence was shorter in obese patients, especially among men, where the median TNFI duration was 2.5 years (95% CI 1.7, 3.2) in obese vs 5.9 (4.1, 7.7) in non-obese patients (P < 0.01). A EULAR good or moderate (EGOM) response was achieved by 55% of obese vs 65% of non-obese patients after 6 months (P = 0.02). In multivariable analyses, obesity increased the risk of TNFI withdrawal [hazard ratio 1.6 (95% CI 1.3, 2.0)] and reduced odds for EGOM response [odds ratio 0.47 (95% CI 0.29, 0.72)]. The impact of obesity was significant across genders, TNFI types and nationality. CONCLUSION Obesity was associated with higher disease activity and seemed to diminish response and adherence to TNFIs in PsA.
European integration (theory) in times of crisis. A comparison of the euro and Schengen crises

ABSTRACT The European Union has gone through major crises of its two flagship integration projects of the 1990s: the euro and Schengen. Both crises had structurally similar causes and beginnings: exogenous shocks exposed the functional shortcomings of both integration projects and produced sharp distributional conflict among governments, as well as an unprecedented politicization of European integration in member state societies. Yet they have resulted in significantly different outcomes: whereas the euro crisis has brought about a major deepening of integration, the Schengen crisis has not. I put forward a neofunctionalist explanation of these different outcomes, which emphasizes variation in transnational interdependence and supranational capacity across the two policy areas.
Characteristics of young colorectal cancer in Brunei Darussalam: an epidemiologic study of 29 years (1986-2014).

BACKGROUND Colorectal cancer (CRC) is the most common gastrointestinal cancer and the incidence is increasing. CRC is more common with increasing age, but a proportion occurs in young adults, termed young CRC. This study assessed the incidence and the demographic of young CRC in Brunei Darussalam. MATERIALS AND METHODS All histologically proven CRC between 1986 and 2014 registered with the Department of Pathology cancer registry were reviewed and data extracted for analyses. Young CRC was defined as cancer in patients aged less than 45 years. The various population groups were categorized into locals (Malays, Chinese and Indigenous) and expatriates. RESULTS Over the study period, there were 1,126 histologically proven CRC (mean age 59.1 ± 14.7 years, Male 58.0%, Locals 91.8% and 8.2% expatriates). Young CRC accounted for 15.1% with the proportion declining over the years, from 29% (1986-1990) to 13.2% (2011-2014). The proportion of young CRC was highest among the indigenous (30.8%), followed by the expatriates (29.3%), Malays (14.3%) and lowest among the Chinese (10.8%). The mean age of young CRC was 35.9 ± 6.2; lowest among the indigenous (33.5 ± 6.7), expatriate (34.9 ± 6.0) groupd and the Malays (35.6 ± 6.5) compared to the Chinese (38.6 ± 4.6), a similar trend being observed in the non-young CRC groups. There were no difference between the genders and tumor locations (rectum or colon) between the young and the non-young CRC cases. Female young CRC was significantly younger than male (p<0.05) without any significant variation between the various population groups (p>0.05). CONCLUSIONS Our study showed that the young CRC accounted for 15.1% of all CRC with declining trend observed over recent years. Young CRC was more common among indigenous, expatriates and Malays and least common among the Chinese. There were no differences in the gender and tumor locations.
Sporulation of Fusarium oxysporum f. sp. lycopersici on Stem Surfaces of Tomato Plants and Aerial Dissemination of Inoculum.

ABSTRACT Plants exhibiting symptoms of wilt and xylem discoloration typical of Fusarium wilt caused by Fusarium oxysporum f. sp. lycopersici were observed in greenhouses of cherry tomatoes at various sites in Israel. However, the lower stems of some of these plants were covered with a pink layer of macroconidia of F. oxysporum. This sign resembles the sporulating layer on stems of tomato plants infected with F. oxysporum f. sp. radicis-lycopersici, which causes the crown and root rot disease. Monoconidial isolates of F. oxysporum from diseased plants were assigned to vegetative compatibility group 0030 of F. oxysporum f. sp. lycopersici and identified as belonging to race 1 of F. oxysporum f. sp. lycopersici. The possibility of coinfection with F. oxysporum f. sp. lycopersici and F. oxysporum f. sp. radicis-lycopersici was excluded by testing several macroconidia from each plant. Airborne propagules of F. oxysporum f. sp. lycopersici were trapped on selective medium in greenhouses in which plants with a sporulating layer had been growing. Sporulation on stems was reproduced by inoculating tomato plants with races 1 and 2 of F. oxysporum f. sp. lycopersici. This phenomenon has not been reported previously with F. oxysporum f. sp. lycopersici and might be connected to specific environmental conditions, e.g., high humidity. The sporulation of F. oxysporum f. sp. lycopersici on plant stems and the resultant aerial dissemination of macroconidia may have serious epidemiological consequences. Sanitation of the greenhouse structure, as part of a holistic disease management approach, is necessary to ensure effective disease control.
Quantifying the risks of hypertension, age, sex and smoking in patients with abdominal aortic aneurysm

The prevalence of abdominal aortic aneurysm (AAA) in a community‐based sample of men and women aged 65–79 years was correlated with known risk factors. In addition, the effect of high blood pressure and the use of antihypertensive medication on growth of AAAs were studied.
Prevalence and Hospital Resource Utilization in Tympanoplasty and Revision Tympanoplasty: A Population-Based Comparative Study

Objective To compare trends, risk factors, prevalence rates, and hospital resource utilization between tympanoplasty and revision tympanoplasty. Study Design Retrospective review. Setting All hospitals. Patients This study analyzed 58,038 tympanoplasty procedures and 953 revision tympanoplasty procedures performed in Taiwan from 1996 to 2007. Main Outcome Measures Administrative claims data from the Bureau of National Health Insurance of Taiwan. Odds ratio and 95% confidence intervals were calculated to assess the relative change rate. Regression models were used to predict length of stay (LOS) and hospital treatment costs. Results The number of tympanoplasties performed per 100,000 patients was 22.97 in 1996. It gradually increased to 26.7 in 2001 and then gradually decreased to 16.61 in 2007. The number of revision tympanoplasties per 100,000 patients during the same period, however, was 0.29 to 0.48. During the study period, the LOS associated with both tympanoplasty and revision tympanoplasty decreased, whereas hospital treatment costs associated with the 2 procedures increased. Considerably decreased LOS and increased hospital treatment costs were associated with age, sex, number of comorbidities, hospital level, hospital volume, surgeon volume, and LOS. Conclusion High-volume hospitals and surgeons obtained the largest improvements in tympanoplasty outcomes, particularly in LOS and hospital treatment costs. Health care providers and patients should recognize that hospital resource utilization may depend on hospital attributes as well as patient attributes.
Bitcoin: Speculative Bubble or Future Value?

Created in 2009, bitcoin reaches record heights every week, having hit $17,000 on 11 December 2017 - the first day a bitcoin futures contract traded at the CBOE - versus $1,000 in early 2017 and $1 in 2001. Yet there is still no consensus among economists whether bitcoin comprises a new decentralised currency free of central bank influence, or is a purely speculative instrument.
Effect of Central Bank Intervention in Estimating Exchange Rate Exposure: Evidence from an Emerging Market

This study examines the relationship between the value of the firm and unanticipated changes in exchange rate. Using a sample of 651 Indian firms over the period from 2001 to 2013, this study finds that unanticipated changes in exchange rates are more appropriate than actual changes to discover statistically significant and economically important exchange rate exposure. Using a vector error correction model (VECM) to generate unanticipated exchange rate changes, this study provides new evidence that the intervention by central bank has a major impact on the level of Indian firms’ exchange rate exposure.