Miracle-dz/UniFAR-FTUs huggingface dataset:
Spin-labeled nanobodies as protein conformational reporters for electron paramagnetic resonance in cellular membranes

Significance Small fragments of antibodies, called nanobodies, are emerging tools in structural biology, cell imaging, and drug discovery. Here we pioneer the use of their biocompatible spin-labeled variants as reporters of conformational dynamics of membrane proteins using DEER spectroscopy. Our study shows that it is possible to monitor the fraction of outward-facing conformation of a wild-type ABC transporter not only under turnover conditions in vitro but also in isolated cellular membranes with no need of purification or labeling of the target transporter. This paves the way for in-cell EPR on membrane proteins, a challenging task in the field. Nanobodies are emerging tools in a variety of fields such as structural biology, cell imaging, and drug discovery. Here we pioneer the use of their spin-labeled variants as reporters of conformational dynamics of membrane proteins using DEER spectroscopy. At the example of the bacterial ABC transporter TM287/288, we show that two gadolinium-labeled nanobodies allow us to quantify, via analysis of the modulation depth of DEER traces, the fraction of transporters adopting the outward-facing state under different experimental conditions. Additionally, we quantitatively follow the interconversion from the outward- to the inward-facing state in the conformational ensemble under ATP turnover conditions. We finally show that the specificity of the nanobodies for the target protein allows the direct attainment of structural information on the wild-type TM287/288 expressed in cellular membranes without the need to purify or label the investigated membrane protein.
Electronic Transport in Alloys with Phase Separation (Composites)

A measure for the efficiency of a thermoelectric material is the figure of merit defined by ZT = S2T/ρκ, where S, ρ and κ are the electronic transport coefficients, Seebeck coefficient, electrical resistivity and thermal conductiviy, respectively. T is the absolute temperature. Large values for ZT have been realized in nanostructured materials such as superlattices, quantum dots, nanocomposites, and nanowires. In order to achieve further progress, (1) a fundamental understanding of the carrier transport in nanocomposites is necessary, and (2) effective experimental methods for designing, producing and measuring new material compositions with nanocomposite-structures are to be applied. During the last decades, a series of formulas has been derived for calculation of the electronic transport coefficients in composites and disordered alloys. Along the way, some puzzling phenomenons have been solved as why there are simple metals with positive thermopower? and what is the reason for the phenomenon of the “Giant Hall effect”? and what is the reason for the fact that amorphous composites can exist at all? In the present review article, (1), formulas will be presented for calculation of σ = (-1/ρ), κ, S, and R in composites. R, the Hall coefficient, provides additional informations about the type of the dominant electronic carriers and their densities. It will be shown that these formulas can also be applied successfully for calculation of S, ρ, κ and R in nanocomposites if certain conditions are taken into account. Regarding point (2) we shall show that the combinatorial development of materials can provide unfeasible results if applied noncritically.
Single-cell RNA sequencing of Trypanosoma brucei from tsetse salivary glands unveils metacyclogenesis and identifies potential transmission blocking antigens

Significance African trypanosomes, Trypanosoma brucei spp. , are transmitted by the bite of infected tsetse flies. Mammalian vaccines are not available, and diagnosis and treatment remain difficult in the affected remote areas. The transcriptomic analysis of individual parasites from infected tsetse salivary glands provides insight into the developmental processes that give rise to infective metacyclic parasites transmitted to the host bite site. We describe proteins associated with the different parasite developmental stages in salivary glands and specifically highlight a family of nonvariant surface proteins associated with metacyclic parasites. Immunization with one member of this family reduced parasitemia early in the infection in mice, promising to be a potential candidate antigen for a transmission blocking vaccine approach. Tsetse-transmitted African trypanosomes must develop into mammalian-infectious metacyclic cells in the fly’s salivary glands (SGs) before transmission to a new host. The molecular mechanisms that underlie this developmental process, known as metacyclogenesis, are poorly understood. Blocking the few metacyclic parasites deposited in saliva from further development in the mammal could prevent disease. To obtain an in-depth perspective of metacyclogenesis, we performed single-cell RNA sequencing (scRNA-seq) from a pool of 2,045 parasites collected from infected tsetse SGs. Our data revealed three major cell clusters that represent the epimastigote, and pre- and mature metacyclic trypanosome developmental stages. Individual cell level data also confirm that the metacyclic pool is diverse, and that each parasite expresses only one of the unique metacyclic variant surface glycoprotein (mVSG) coat protein transcripts identified. Further clustering of cells revealed a dynamic transcriptomic and metabolic landscape reflective of a developmental program leading to infectious metacyclic forms preadapted to survive in the mammalian host environment. We describe the expression profile of proteins that regulate gene expression and that potentially play a role in metacyclogenesis. We also report on a family of nonvariant surface proteins (Fam10) and demonstrate surface localization of one member (named SGM1.7) on mature metacyclic parasites. Vaccination of mice with recombinant SGM1.7 reduced parasitemia early in the infection. Future studies are warranted to investigate Fam10 family proteins as potential trypanosome transmission blocking vaccine antigens. Our experimental approach is translationally relevant for developing strategies to prevent other insect saliva-transmitted parasites from infecting and causing disease in mammalian hosts.
Neurofilaments: The C-Reactive Protein of Neurology

Neurofilaments (NFs) are quickly becoming the biomarkers of choice in the field of neurology, suggesting their use as an unspecific screening marker, much like the use of elevated plasma C-reactive protein (CRP) in other fields. With sensitive techniques being readily available, evidence is growing regarding the diagnostic and prognostic value of NFs in many neurological disorders. Here, we review the latest literature on the structure and function of NFs and report the strengths and pitfalls of NFs as markers of neurodegeneration in the context of neurological diseases of the central and peripheral nervous systems.
Epidemiology, Treatment, and Prevention of Nosocomial Bacterial Pneumonia

Septicaemia likely results in high case-fatality rates in the present multidrug-resistant (MDR) era. Amongst them are hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), two frequent fatal septicaemic entities amongst hospitalised patients. We reviewed the PubMed database to identify the common organisms implicated in HAP/VAP, to explore the respective risk factors, and to find the appropriate antibiotic choice. Apart from methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, extended-spectrum β-lactamase-producing Enterobacteriaceae spp. , MDR or extensively drug-resistant (XDR)-Acinetobacter baumannii complex spp. , followed by Stenotrophomonas maltophilia, Chryseobacterium indologenes, and Elizabethkingia meningoseptica are ranked as the top Gram-negative bacteria (GNB) implicated in HAP/VAP. Carbapenem-resistant Enterobacteriaceae notably emerged as an important concern in HAP/VAP. The above-mentioned pathogens have respective risk factors involved in their acquisition. In the present XDR era, tigecycline, colistin, and ceftazidime-avibactam are antibiotics effective against the Klebsiella pneumoniae carbapenemase and oxacillinase producers amongst the Enterobacteriaceae isolates implicated in HAP/VAP. Antibiotic combination regimens are recommended in the treatment of MDR/XDR-P. aeruginosa or A. baumannii complex isolates. Some special patient populations need prolonged courses (>7-day) and/or a combination regimen of antibiotic therapy. Implementation of an antibiotic stewardship policy and the measures recommended by the United States (US) Institute for Healthcare were shown to decrease the incidence rates of HAP/VAP substantially.
Impact of transition in metabolic health and obesity on the incident chronic kidney disease: A nationwide cohort study.

CONTEXT Metabolically healthy obesity (MHO) is a dynamic condition. OBJECTIVE To evaluate the risk of chronic kidney disease (CKD) among people with MHO according to its longitudinal change. DESIGN Observational study. SETTING A nationwide population-based cohort. PARTICIPANTS 514,866 people from the Korean National Health Insurance Service-National Sample Cohort. INTERVENTION The initial presence and changes of obesity [using body mass index (BMI) and waist circumference (WC)] and metabolic health status. MAIN OUTCOME MEASURE Incident CKD from 2011 to 2015. RESULTS Of the people classified as MHO at baseline (BMI criteria), 47.6% remained as MHO in 2011-2012, whereas 12.1%, 5.5%, and 34.8% were classified as metabolically healthy, non-obese (MHNO), metabolically unhealthy, non-obese (MUNO), and metabolically unhealthy, obese (MUO), respectively. The risk of incident CKD in the baseline MHO group was higher than that in the MHNO group (HR, 1.23; 95% CI, 1.12-1.36). However, when transition was taken into account, people who converted to MHNO were not at increased risk (HR, 0.98; 95% CI, 0.72-1.32), whereas the stable MHO group and the groups that evolved to metabolically unhealthy status had a higher risk of incident CKD than the stable MHNO group. When the risk was analyzed using WC criteria, it showed a similar pattern to BMI criteria except for the stable MHO group. CONCLUSIONS MHO was a dynamic condition, and people with MHO constituted a heterogeneous group. Although the MHO phenotype was generally associated with incident CKD, maintenance of metabolic health and weight reduction might alleviate the risk of CKD.
Title Clinical efficacy of adalimumab in Crohn ’ s disease : a real practiceobservational study in Japan

Background: There are few reports of the efficacy of adalimumab (ADA) for clinical remission and preventing postoperative recurrence in Crohn's disease (CD) in Asian real practice settings. We conducted a Japanese multicenter retrospective observational study. Methods: We evaluated patients with CD who were treated with ADA at 11 medical institutions in Japan to investigate the clinical efficacy of remission up to 52 weeks and the associated factors to achieve remission with a CD Activity Index (CDAI) < 150. The effects of preventing postoperative recurrence were also evaluated. Results: In 62 patients, the remission rates were 33.9, 74.2, 75.8, 77.4, and 66.1 % at 0, 4, 12, 26, and 52 weeks, respectively. Although 10 patients discontinued treatment due to primary nonresponse, secondary nonresponse, or adverse events, the ongoing treatment rate at 52 weeks was 83.9 %. Comparison of remission and non-remission on univariate analysis identified colonic type and baseline CDAI value as significant associated factors (P < 0.05). In 16 patients who received ADA to prevent postoperative recurrence, the clinical remission maintenance rate was 93.8 % and the mucosal healing rate was 64.3 % during a mean postoperative follow-up period of 32.3 months. Conclusions: ADA effectively induced remission and prevented postoperative recurrence in patients with CD in a real practice setting.
Mowing Height, Nitrogen Rate, and Biostimulant Influence Root Development of Field-grown `TifEagle' Bermudagrass

As golfers demand higher quality golf green putting surfaces, researchers continue to seek improved turfgrass cultivars. One such improved cultivar is 'TifEagle' bermudagrass [Cynodon dactylon (L.) Pers. × C. transvaalensis Burtt-Davy], which is an improvement over traditional bermudagrass cultivars such as 'Tifgreen' and 'Tifdwarf' due to its ability to tolerate mowing heights of 11%, RSA by >11%, and TQ by >17%. Increasing N rates from 12 to 24 kg N ha -1 week -1 increased RLD by >17%, RSA by >26% and TQ by >16%. No effect on RLD was observed after the first year of biostimulant use, however, after the second year, BIO1 increased RLD by >11% when applied with the lowest rate of N (12 kg N/ha/week). Higher mowing heights (4.8 and 4.0 mm) increased TLD >6% compared to the lowest mowing height (3.2 mm), and higher N rates (48 and 24 kg N/ha/week) increased TLD >3% compared to the lowest N rate (12 kg N/ha/week). Overall, a mowing heights >4.0 mm, N rates ≥24 kg N/ha/week, and long-term use of a cytokinins-containing biostimulant had a positive effect on 'TifEagle' rooting.
Co-circulation of multiple enterovirus D68 subclades, including a novel B3 cluster, across Europe in a season of expected low prevalence, 2019/20

Enterovirus D68 (EV-D68) was detected in 93 patients from five European countries between 1 January 2019 and 15 January 2020, a season with expected low circulation. Patients were primarily children (n = 67, median age: 4 years), 59 patients required hospitalisation and five had severe neurologic manifestations. Phylogenetic analysis revealed two clusters in the B3 subclade and subclade A2/D. This circulation of EV-D68 associated with neurological manifestations stresses the importance of surveillance and diagnostics beyond expected peak years.
VISION OF A NEW STATE

The establishment of a Jewish homeland is central to many aspects of Judaism, and from any standard of newsworthiness, the events in Palestine in the late 1940s and early 1950s were a major development. Still, journalistic texts are not created in a vacuum. To fully understand the meaning of these texts, the cultural context in which they are created and the viewpoint embodied in the producer's work must be examined. The work of Robert Capa represents an excellent case study for examining the construction and recapitulation of myth through “objective” news coverage. Photojournalist Robert Capa's images of the birth of the State of Israel argue for a specific reading, one that celebrates a presumed rightness/naturalness of the Jewish state and embraces dominant Israeli cultural myths related to its founding. Further, his photographs argue that the Israelis were creating a state ex nihilo by turning a desolate, unpopulated strip of land into both an urban and agricultural oasis. Capa's images tap into the reclamation myth of the land that settlers believed was rightly theirs and their spiritual connection to that land. This analysis gives insight into the practice of photojournalism as a human craft, rather than a mechanical one.
Keap1 deletion accelerates mutant K-ras/p53-driven cholangiocarcinoma.

The activation of the Kelch-like ECH-associated protein 1 (Keap1)-NF-E2-related factor 2 (Nrf2) pathway contributes to cancer progression in addition to oxidative stress responses. Loss-of-function Keap1 mutations were reported to activate Nrf2, leading to cancer progression. We examined the effects of Keap1 deletion in a cholangiocarcinoma mouse model using a mutant K-ras/p53 mouse. Introduction of the Keap1 deletion into liver-specific mutant K-ras/p53 expression resulted in the formation of invasive cholangiocarcinoma. Comprehensive analyses of the gene expression profiles identified broad up-regulation of Nrf2-target genes such as Nqo1 and Gstm1 in the Keap1-deleted mutant K-ras/p53 expressing livers, accompanied by up-regulation of cholangiocyte-related genes. Among these genes, the transcriptional factor Sox9 was highly expressed in the dysplastic bile duct. The Keap-Nrf2-Sox9 axis might serve as a novel therapeutic target for cholangiocarcinoma.
Manager skills of long/short equity hedge funds : the factor model dependency

Performance analysis of hedge funds has proven to be challenging in the past since these entities have the flexibility to choose between a wide variety of dynamic trading strategies without being compelled to report their holdings. That being said, using bootstrap procedures, some authors in the academic literature have succeeded in quantifying the proportion of funds which demonstrates persistent performance. Yet, these methodologies are based on an extensive range of multifactor models to estimate the performance of hedge funds. Four different models which seem particularly adapted to assess hedge fund returns will be replicated, with both buyand-hold and optional factors incorporated. The research aims at demonstrating the potential bias and/or outperformance brought by some factor models used when defining hedge fund manager skills. Using robust bootstrap simulations, evidence was found that superior hedge fund performance cannot be explained by luck alone and that, regardless of the multifactor model used.
A Complex Interplay between Nitric Oxide, Quorum Sensing, and the Unique Secondary Metabolite Tundrenone Constitutes the Hypoxia Response in Methylobacter

Here, we describe a novel and complex hypoxia response system in a methanotrophic bacterium that involves modules of central carbon metabolism, denitrification, quorum sensing, and a secondary metabolite, tundrenone. This intricate stress response system, so far unique to Methylobacter species, may be responsible for the persistence and activity of these species across gradients of dioxygen tensions and for the cosmopolitan distribution of these organisms in freshwater and soil environments in the Northern Hemisphere, including the fast-melting permafrosts. ABSTRACT Methylobacter species, members of the Methylococcales, have recently emerged as some of the globally widespread, cosmopolitan species that play a key role in the environmental consumption of methane across gradients of dioxygen tensions. In this work, we approached the question of how Methylobacter copes with hypoxia, via laboratory manipulation. Through comparative transcriptomics of cultures grown under high dioxygen partial pressure versus cultures exposed to hypoxia, we identified a gene cluster encoding a hybrid cluster protein along with sensing and regulatory functions. Through mutant analysis, we demonstrated that this gene cluster is involved in the hypoxia stress response. Through additional transcriptomic analyses, we uncovered a complex interconnection between the NO-mediated stress response, quorum sensing, the secondary metabolite tundrenone, and methanol dehydrogenase functions. This novel and complex hypoxia stress response system is so far unique to Methylobacter species, and it may play a role in the environmental fitness of these organisms and in their cosmopolitan environmental distribution. IMPORTANCE Here, we describe a novel and complex hypoxia response system in a methanotrophic bacterium that involves modules of central carbon metabolism, denitrification, quorum sensing, and a secondary metabolite, tundrenone. This intricate stress response system, so far unique to Methylobacter species, may be responsible for the persistence and activity of these species across gradients of dioxygen tensions and for the cosmopolitan distribution of these organisms in freshwater and soil environments in the Northern Hemisphere, including the fast-melting permafrosts.
The role of L 1 durational correlates in L 2 acquisition : A production study of Japanese geminates by Italian , French and English L 2 learners

This study explores experimentally some of the characteristics of durational production cues in nonnative pronunciation of the Japanese consonantal length contrast for three learner groups: Italian, French and English native speakers, based on the different phonological properties of their L1 regarding the presence/absence of such a contrast. Specifically, this paper investigates whether the phonetic implementation of this contrast is based on the same cues as native speakers, or on their L1 production cues. Previous studies have pointed out the crucial role of the presence of a consonantal length contrast in the learner’s L1 in L2 acquisition of a similar contrast. However, the present results suggest that although this might be the case when building separate phonemic categories for short and long consonants, in terms of phonetic implementation, the presence of a consonantal length contrast in the L1 might hinder the acquisition of a native-like timing control.
Potential Role of Tocotrienols on Non-Communicable Diseases: A Review of Current Evidence

Tocotrienol (T3) is a subfamily of vitamin E known for its wide array of medicinal properties. This review aimed to summarize the health benefits of T3, particularly in prevention or treatment of non-communicable diseases (NCDs), including cardiovascular, musculoskeletal, metabolic, gastric, and skin disorders, as well as cancers. Studies showed that T3 could prevent various NCDs, by suppressing 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in the mevalonate pathway, inflammatory response, oxidative stress, and alternating hormones. The efficacy of T3 in preventing/treating these NCDs is similar or greater compared to tocopherol (TF). TF may lower the efficacy of T3 because the efficacy of the combination of TF and T3 was lower than T3 alone in some studies. Data investigating the effects of T3 on osteoporosis, arthritis, and peptic ulcers in human are limited. The positive outcomes of T3 treatment obtained from the preclinical studies warrant further validation from clinical trials.
Stock Market Wealth and the Real Economy: A Local Labor Market Approach

We provide evidence of the stock market consumption wealth effect by using a local labor market analysis. An increase in local stock wealth driven by aggregate stock prices increases local employment and payroll in nontradable industries and in total, with no effect on employment in tradable industries. In a model of geographic heterogeneity in stock wealth, these responses imply an MPC of 3.2 cents per year and that a 20 percent increase in stock valuations, unless countered by monetary policy, increases the aggregate labor bill by at least 1.7 percent and aggregate hours by at least 0.7 percent two years after the shock. (JEL E21, E24, E52, G12, G51, R22, R23 )
Leaching of sulfentrazone herbicide in soils with different textures

The objective of this study was to evaluate the leaching potential of sulfentrazone herbicide through bioindicator plants after the occurrence of natural rainfall in soils with clayey and sandy textures. The experimental design was completely randomized in a 3 x 8 factorial with four replications, with three levels of rainfall (30-40, 60-80 and 100-120 mm) and eight depth of soil profile (0-3, 3-6, 6-9, 9-12, 12-15, 15-20, 20-25 and 25-30 cm). The collections of samples occurred after sulfentrazone application at doses of 800 g ha -1 and 600 g ha -1 for the clayey and sandy soils, respectively, and subsequent accumulation of rainfalls. For the collection of soil sam­ples, PVC columns with 30 cm and 15 cm in diameter were introduced in soil profile. The columns were care­fully removed by digging around him and maintaining the original soil integrity during the collection. Subsequently, the columns were sepa­rated with cross section for the sowing of bioindicator species, sorghum and Bidens pilosa . After sowing, for eval­uations of bioindicator plants in columns, it was adopted range of 0% to 100% of phytotoxicity, at 5, 7, 10 and 12 days after sowing. Leaching of sulfentrazone was dependent on rain accumulation and soil texture. In larger rain accumulations, sulfentrazone can be found deeper in soils of sandy textures. Sorghum was more suitable as bioindicator plant to demonstrate the herbicide presence at greater depths.