Miracle-dz/UniFAR-FTUs huggingface dataset:
Minimum energy compact structures in force-quench polyubiquitin folding are domain swapped

Single molecule experiments that initiate folding using mechanical force are uniquely suited to reveal the nature of populated states in the folding process. Using a strategy proposed on theoretical grounds, which calls for repeated cycling of force from high to low values using force pulses, it was demonstrated in atomic force spectroscopy (AFM) experiments that an ensemble of minimum energy compact structures (MECS) are sampled during the folding of polyubiquitin. The structures in the ensemble are mechanically resistant to a lesser extent than the native state. Remarkably, forced unfolding of the populated intermediates reveals a broad distribution of extensions including steps up to 30 nm and beyond. We show using molecular simulations that favorable interdomain interactions leading to domain swapping between adjacent ubiquitin modules results in the formation of the ensemble of MECS, whose unfolding leads to an unusually broad distribution of steps. We obtained the domain-swapped structures using coarse-grained ubiquitin dimer models by exchanging native interactions between two monomeric ubiquitin molecules. Brownian dynamics force unfolding of the proposed domain-swapped structures, with mechanical stability that is approximately 100-fold lower than the native state, gives rise to a distribution of extensions from 2 to 30 nm. Our results, which are in quantitative agreement with AFM experiments, suggest that domain swapping may be a general mechanism in the assembly of multi-sub-unit proteins.
Recent insights into cerebral cavernous malformations: the molecular genetics of CCM

Cerebral cavernous malformations (CCM) are vascular lesions which can occur as a sporadic (80% of the cases) or familial autosomal dominant form (20%). Three CCM genes have been identified: CCM1/KRIT1, CCM2/MGC4607 and CCM3/PDCD10. Almost 80% of CCM patients affected with a genetic form of the disease harbor a heterozygous germline mutation in one of these three genes. Recent work has shown that a two‐hit mechanism is involved in CCM pathogenesis which is caused by a complete loss of any of the three CCM proteins within endothelial cells lining the cavernous capillary cavities. These data were an important step towards the elucidation of the mechanisms of this condition.
Autoregulation of SafA Assembly through Recruitment of a Protein Cross-Linking Enzyme

ABSTRACT The coat of Bacillus subtilis spores is a multiprotein protective structure that also arbitrates many of the environmental interactions of the spore. The coat assembles around the cortex peptidoglycan layer and is differentiated into an inner and an outer layer and a crust. SafA governs assembly of the inner coat, whereas CotE drives outer coat assembly. SafA localizes to the cortex-coat interface. Both SafA and its short form C30 are substrates for Tgl, a coat-associated transglutaminase that cross-links proteins through ε-(γ-glutamyl)lysyl isopeptide bonds. We show that SafA and C30 are distributed between the coat and cortex layers. The deletion of tgl increases the extractability of SafA, mainly from the cortex. Tgl itself is mostly located in the inner coat and cortex. The localization of Tgl-cyan fluorescent protein (Tgl-CFP) is strongly, but not exclusively, dependent on safA. However, the association of Tgl with the cortex requires safA. Together, our results suggest an assembly pathway in which Tgl is first recruited to the forming spore in a manner that is only partially dependent on SafA and then is drafted to the cortex by SafA. Tgl, in turn, promotes the conversion of coat- and cortex-associated SafA into forms that resist extraction, possibly by catalyzing the cross-linking of SafA to other coat proteins, to the cortex, and/or to cortex-associated proteins. Therefore, the final assembly state of SafA relies on an autoregulatory pathway that requires the subcellular localization of a protein cross-linking enzyme. Tgl most likely exerts a “spotwelding” activity, cross-linking preformed complexes in the cortex and inner coat layers of spores. IMPORTANCE In this work, we show how two proteins work together to determine their subcellular location within the coat of bacterial endospores. Bacillus subtilis endospores are surrounded by a multilayer protein coat composed of over 80 proteins, which surrounds an underlying peptidoglycan layer (the spore cortex) protecting it from lytic enzymes. How specific coat proteins are targeted to specific layers of the coat is not well understood. We found that the protein SafA recruits a protein-cross-linking enzyme (a transglutaminase) to the cortex and inner layers of the coat, where both are cemented, by cross-linking, into macromolecular complexes.
Impact of intraoperative stimulation brain mapping on glioma surgery outcome: a meta-analysis.

PURPOSE Surgery for infiltrative gliomas aims to balance tumor removal with preservation of functional integrity. The usefulness of intraoperative stimulation mapping (ISM) has not been addressed in randomized trials. This study addresses glioma surgery outcome on the basis of a meta-analysis of observational studies. METHODS A systematic search retrieved 90 reports published between 1990 and 2010 with 8,091 adult patients who had resective surgery for supratentorial infiltrative glioma, with or without ISM. Quality criteria consisted of postoperative neurologic examination details and follow-up timing. New postoperative neurologic deficits were categorized on the basis of timing and severity. Meta-analysis with a Bayesian random effects model determined summary event rates of deficits as well as gross total resection rate and eloquent locations. Meta-regression analysis explored heterogeneity among studies. RESULTS Late severe neurologic deficits were observed in 3.4% (95% CI, 2.3% to 4.8%) of patients after resections with ISM, and in 8.2% (95% CI, 5.7% to 11.4%) of patients after resections without ISM (adjusted odds ratio, 0.39; 95% CI, 0.23 to 0.64). The percentages of radiologically confirmed gross total resections were 75% (95% CI, 66% to 82%) with ISM and 58% (95% CI, 48% to 69%) without ISM. Eloquent locations were involved in 99.9% (95% CI, 99.9% to 100%) of resections with ISM and in 95.8% (95% CI, 73.1% to 99.8%) of resections without ISM. Relevant sources of heterogeneity among studies were ISM, continent, and academic setting. CONCLUSION Glioma resections using ISM are associated with fewer late severe neurologic deficits and more extensive resection, and they involve eloquent locations more frequently. This indicates that ISM should be universally implemented as standard of care for glioma surgery.
Automatic classification of trees using a UAV onboard camera and deep learning

Automatic classification of trees using remotely sensed data has been a dream of many scientists and land use managers. Recently, Unmanned aerial vehicles (UAV) has been expected to be an easy-to-use, cost-effective tool for remote sensing of forests, and deep learning has attracted attention for its ability concerning machine vision. In this study, using a commercially available UAV and a publicly available package for deep learning, we constructed a machine vision system for the automatic classification of trees. In our method, we segmented a UAV photography image of forest into individual tree crowns and carried out object-based deep learning. As a result, the system was able to classify 7 tree types at 89.0% accuracy. This performance is notable because we only used basic RGB images from a standard UAV. In contrast, most of previous studies used expensive hardware such as multispectral imagers to improve the performance. This result means that our method has the potential to classify individual trees in a cost-effective manner. This can be a usable tool for many forest researchers and managements.
Fault Detection in Parity Preserving Reversible Circuits

Motivated by its variety of applications in several (emerging) technologies, the design of reversible circuits received significant attention in the recent past. With the emergence of physical realizations, also the consideration of faults and fault-tolerance became important. It has been suggested that parity preserving circuits would be ideal for fault detection, since here the parity of the inputs is the same as the parity of the outputs. Hence, if there is a fault on any single output, the parity should be flipped which would make the fault easy to detect. This paper however shows that this is not always the case. In fact, we provide and discuss examples showing that it is not sufficient to have parity preserving circuits when considering established fault models for reversible logic. As a result of our investigations, we can conclude that, even if a reversible circuit is parity preserving, it has to be checked against a particular fault model.
Synthesis and Characterization of pH and Thermo Dual-Responsive Hydrogels with a Semi-IPN Structure Based on N-Isopropylacrylamide and Itaconamic Acid

A series of semi-interpenetrating polymer network (semi-IPN) hydrogels were synthesized and investigated in this study. Linear copolymer poly(N-isopropylacrylamide-co-itaconamic acid) p(NIPAM-co-IAM), which is formed by copolymerization of N-isopropylacrylamide (NIPAM) and itaconamic acid (IAM, 4-amino-2-ethylene-4-oxobutanoic acid), was introduced into a solution of NIPAM to form a series of pH and thermo dual-responsive p(NIPAM-co-IAM)/pNIPAM semi-IPN hydrogels by free radical polymerization. The structural, morphological, chemical, and physical properties of the linear copolymer and semi-IPN hydrogels were investigated. The semi-IPN hydrogel showed high thermal stability according to thermal gravimetric analyzer (TGA). Scanning electronic microscopy (SEM) images showed that the pore size was in the range of 119~297 µm and could be controlled by the addition ratio of the linear copolymer in the semi-IPN structure. The addition of linear copolymer increased the fracture strain from 57.5 ± 2.9% to 91.1 ± 4.9% depending on the added amount, while the compressive modulus decreased as the addition increased. Moreover, the pH and thermo dual-responsive properties were investigated using differential scanning calorimetry (DSC) and monitoring the swelling behavior of the hydrogels. In deionized (DI) water, the equilibrium swelling ratio of the hydrogels decreased as the temperature increased from 20 °C to 50 °C, while it varied in various pH buffer solutions. In addition, the swelling and deswelling rates of the hydrogels also significantly increased. The results indicate that the novel pH-thermo dual-responsive semi-IPN hydrogels were synthesized successfully and may be a potential material for biomedical, drug delivery, or absorption application.
Opportunistic infections in relation to antiretroviral status among AIDS patients from south India.

BACKGROUND There is a need to generate data from India on relative frequencies of specific opportunistic infections (OIs) in different regions and their relation to the choice of commonly used generic highly active anti-retroviral therapy (HAART) regimens. OBJECTIVES To document the prevailing prevalence pattern of OIs both before and after HAART, to look for reduction in OIs following HAART, to assess the risk of developing new OIs within 6 months of HAART initiation and to see if there is any difference in the risk of developing a new OI within 6 months of HAART initiation, for those on Efavirenz (EFV)-based regimens and Nevirapine (NVP)-based regimens. MATERIALS AND METHODS In a prospective observational cohort study conducted in South India involving 108 ART-naive AIDS patients, different pathogens were isolated and identified using standard laboratory techniques. Data analysis was done using SPSS software (version 16.0). Risk of developing an OI after HAART initiation was assessed using the likelihood ratio test from Cox regression models. RESULTS Tuberculosis (53.4%), oral Candidiasis (27.2%) and Herpes Zoster (14.7%) were the common infections seen. There was a drastic reduction of 96.59% in OI events after 6 months of HAART. The risk of developing an OI within 6 months of HAART initiation was 5.56%. Time to development of an OI in the first 6 months of HAART was shorter for the NVP-based regimens than with EFV-based regimens, but this difference was not statistically significant (HR=0.891, 95% CI: 0.179-4.429; P=0.888). CONCLUSION Tuberculosis is the most important OI before initiation of HAART. Both EFV and NVP-based regimens are equally efficacious in controlling OIs.
Association of HLA-DR, -DQ Genotype and CTLA-4 Gene Polymorphism with Graves’ Disease in Japanese Children

Objective: Childhood onset Graves’ disease (GD) has been documented to be clinically distinct from adult onset GD, and an association with the genes encoding HLA and CTLA-4 (cytotoxic T lymphocyte antigen-4) has been reported in both Caucasian and Japanese adult GD patients. The aim of this study was to determine whether HLA-DR, -DQ and CTLA-4 are associated with childhood onset GD in Japanese individuals. Methods: We investigated the genotype of HLA class II (DRB1, DQB1) and the A/G transition polymorphism of CTLA-4 exon 1 position 49 in 43 GD patients and in healthy controls for comparison. The CTLA-4 alleles were identified by the polymerase chain reaction (PCR) of genomic DNA and restriction fragment-length polymorphism analysis (PCR-RFLP) with Ita1. Results: The frequency of both HLA-DRB1*0405 and DQB1*0401 was increased in the patient group (DRB1*0405: 26.7%, p < 0.001; DQB1*0401: 25.6%, p < 0.005) compared with the controls. Patients with GD had a significantly lower frequency of the AA genotype of CTLA-4 than the controls, but there was no difference in allele frequency between the G and A allele. Conclusions: the association of HLA-DRB1 and DQB1 genotype with susceptibility to childhood onset GD differs from that in adult onset GD, whereas the association between CTLA-4 gene polymorphism and childhood onset GD is similar to that in adult onset GD in Japanese individuals, but the association is weak.
Laying Eggs in a Neighbor's Nest: Benefit and Cost of Colonial Nesting in Swallows

Intraspecific brood parasitism (laying eggs in another's nest) occurs widely in colonial cliff swallows (Passeriformes: Hirundinidae: Hirundo pyrrhonota). In colonies consisting of more than ten nests, up to 24 percent of the nests were sometimes parasitized by colony members. Laying eggs in a conspecific's nest may be a benefit of coloniality for parasitic individuals and simultaneously may represent a cost to host individuals within the same colony.
A novel method of comparing the healing properties of two hydrogels in chronic leg ulcers

Skin ulcers on the legs have a chronic, relapsing course and are often a significant management challenge. Novel methods of measuring and comparing the effects of different treatments can be of assistance in addressing this situation. A clinical pilot study using original methods was undertaken to compare the healing properties of the alginate gel Flaminal® (test) and the hydrocolloid gel Intrasite® (control) on chronic leg ulcers. The study was performed over a period of 28 days with two parallel groups of 10 patients. Both the surface (acetate tracing and planimetry) and the volume (Jeltrate® mould impression and weighting) of each wound were measured at baseline and after 7, 14 and 28 days of treatment. On both parameters results were superior with the test product compared to the control, with volume reduction being the first parameter to change. Between groups, difference in wound volume reduction was detected as early as day 7 whereas difference in surface reduction was clearly apparent only at day 28. Correlation between wound surface and volume reductions was also better in the test group (r = 0.843 vs. 0.421) than in the control. In conclusion, this pilot study suggests that combining wound surface and volume evaluations allows a more precise analysis of the healing process in venous leg ulcers and that this method is able to detect very early differences in treatments even with limited sample size.
Consent behind the counter: aspiring citizens and labour control under precarious (im)migration schemes

Abstract ‘Managed migration’ schemes promote mobility of labour across international borders, diversifying worksites and introducing new systems of enacting labour consent. This article examines how Canadian franchisees are recruiting Filipino migrants to staff their restaurants, facilitating employers’ access to new, flexible subjects. These workers covet their employment as pathways to Canadian citizenship. Some are unaware, however, that they are recruited under a precarious immigration scheme, one that neither directly denies nor facilitates access to legal incorporation. Instead, migrants are (transnationally) encouraged to compete in the worksite for employer-nominated citizenship, a highly productive system for engendering consent. This draws attention to new challenges ‘managed migration’ schemes pose for resisting downward pressures on work and employment conditions.
Design of New Competitive Dengue Ns2b/Ns3 Protease Inhibitors—A Computational Approach

Dengue is a serious disease which has become a global health burden in the last decade. Currently, there are no approved vaccines or antiviral therapies to combat the disease. The increasing spread and severity of the dengue virus infection emphasizes the importance of drug discovery strategies that could efficiently and cost-effectively identify antiviral drug leads for development into potent drugs. To this effect, several computational approaches were applied in this work. Initially molecular docking studies of reference ligands to the DEN2 NS2B/NS3 serine protease were carried out. These reference ligands consist of reported competitive inhibitors extracted from Boesenbergia rotunda (i.e., 4-hydroxypanduratin A and panduratin A) and three other synthesized panduratin A derivative compounds (i.e., 246DA, 2446DA and 20H46DA). The design of new lead inhibitors was carried out in two stages. In the first stage, the enzyme complexed to the reference ligands was minimized and their complexation energies (i.e., sum of interaction energy and binding energy) were computed. New compounds as potential dengue inhibitors were then designed by putting various substituents successively on the benzyl ring A of the reference molecule. These substituted benzyl compounds were then computed for their enzyme-ligand complexation energies. New enzyme-ligand complexes, exhibiting the lowest complexation energies and closest to the computed energy for the reference compounds, were then chosen for the next stage manipulation and design, which involved substituting positions 4 and 5 of the benzyl ring A (positions 3 and 4 for 2446DA) with various substituents.
NarJ Chaperone Binds on Two Distinct Sites of the Aponitrate Reductase of Escherichia coli to Coordinate Molybdenum Cofactor Insertion and Assembly*

Understanding when and how metal cofactor insertion occurs into a multisubunit metalloenzyme is of fundamental importance. Molybdenum cofactor insertion is a tightly controlled process that involves specific interactions between the proteins that promote cofactor delivery, enzyme-specific chaperones, and the apoenzyme. In the assembly pathway of the multisubunit molybdoenzyme, membrane-bound nitrate reductase A from Escherichia coli, a NarJ-assisted molybdenum cofactor (Moco) insertion step, must precede membrane anchoring of the apoenzyme. Here, we have shown that the NarJ chaperone interacts at two distinct binding sites of the apoenzyme, one interfering with its membrane anchoring and another one being involved in molybdenum cofactor insertion. The presence of the two NarJ-binding sites within NarG is required to ensure productive formation of active nitrate reductase. Our findings supported the view that enzyme-specific chaperones play a central role in the biogenesis of multisubunit molybdoenzymes by coordinating subunits assembly and molybdenum cofactor insertion.
Comparison of Clinical Outcomes in Patients Undergoing Coronary Intervention with Drug-Eluting Stents or Bare-Metal Stents: A Nationwide Population Study.

BACKGROUND The aim of this propensity score-matched cohort study was to investigate the prognostic impacts of drug-eluting stents (DES) and bare-metal stents (BMS) in patients undergoing percutaneous coronary intervention (PCI). METHODS We conducted a retrospective cohort study based on the National Health Insurance program. Patients who had undergone coronary stenting between Jan. 2007 and Dec. 2008 were recruited and monitored until the end of 2010. Subjects with either BMS or DES were matched 2:1 by propensity score, which adjusted for age, sex, stent number and Charlson comorbidity index (CCI). The Kaplan-Meier method and Cox regression models were used for prognostic analyses. RESULTS Among a total of 966 patients with a mean age of 66 years, 644 subjects had BMS and 322 subjects had DES. The incidence of myocardial infarction (MI) and death were significantly lower in the DES group as compared with the BMS group for the three-year follow-up duration. With adjustments for age, sex, premium-based monthly salary, levels of hospital care, stent number, CCI, medications, and acute coronary syndrome presentation in the index hospitalization, use of DES rather than BMS was associated with reduced adverse coronary events (hazard ratio and 95% confidence interval: 0.55, 0.38-0.81 in the whole population, and 0.44, 0.26-0.73 in the subgroup patients with stable coronary artery disease). CONCLUSIONS Implantation of DES was related to better outcomes than for BMS, in terms of reducing MI and mortality after PCI. The survival benefit for patients with DES was even greater in patients with stable coronary artery disease.
Drug-induced infiltrative lung disease with weekly paclitaxel in breast cancer: Case series

Drug-induced infiltrative lung disease (DI-ILD) can be caused by chemotherapeutic agents, antibiotics, antiarrhythmic drugs, and immunosuppressive agents. Common chemotherapeutic drugs causing DI-ILD include bleomycin, mitomycin C, bis (2-chloroethyl)-l-nitrosourea, cyclophosphamide, busulfan, and methotrexate. Taxanes and trastuzumab are also associated with lung injury. Estimated incidence of paclitaxel-induced lung injury is 0.73%–12%. Although cases of paclitaxel-induced lung injury have been reported previously, we found only one published case report of fatal lung injury caused by paclitaxel use. We are reporting the largest case series of seven patients who developed paclitaxel-induced lung injury along with review of literature.