Miracle-dz/UniFAR-FTUs huggingface dataset:
Two familial ALS proteins function in prevention/repair of transcription-associated DNA damage

Significance Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which progressive dysfunction of motor neurons leads to paralysis and death. There is currently no known pathway of disease pathogenesis. However, many genes with varying functions have been linked to familial and sporadic forms of ALS suggesting multiple possible disease mechanisms. One set of gene products, including ALS-linked FUS and TDP43, functions in transcription and RNA processing. We find that defects in transcription due to loss of function of FUS or TDP43 can lead to DNA damage, including in primary human neuronal cells, and hypothesize that dysfunction in their RNA processing roles leads to DNA damage in motor neurons that, if incompletely resolved, could contribute to motor neuron death and ALS. Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron dysfunction disease that leads to paralysis and death. There is currently no established molecular pathogenesis pathway. Multiple proteins involved in RNA processing are linked to ALS, including FUS and TDP43, and we propose a disease mechanism in which loss of function of at least one of these proteins leads to an accumulation of transcription-associated DNA damage contributing to motor neuron cell death and progressive neurological symptoms. In support of this hypothesis, we find that FUS or TDP43 depletion leads to increased sensitivity to a transcription-arresting agent due to increased DNA damage. Thus, these proteins normally contribute to the prevention or repair of transcription-associated DNA damage. In addition, both FUS and TDP43 colocalize with active RNA polymerase II at sites of DNA damage along with the DNA damage repair protein, BRCA1, and FUS and TDP43 participate in the prevention or repair of R loop-associated DNA damage, a manifestation of aberrant transcription and/or RNA processing. Gaining a better understanding of the role(s) that FUS and TDP43 play in transcription-associated DNA damage could shed light on the mechanisms underlying ALS pathogenesis.
Effects of diet, physical activity and performance, and body weight on incident gout in ostensibly healthy, vigorously active men.

BACKGROUND Physical activity and cardiorespiratory fitness are not currently recognized as factors related to preventing gout, nor are risk factors for gout in physically active men well understood. OBJECTIVE The objective was to identify risk factors for gout in ostensibly healthy, vigorously active men. DESIGN Incident self-reported gout was compared with baseline diet, body mass index (BMI; in kg/m(2)), physical activity (in km/d run), and cardiorespiratory fitness (in m/s during 10-km footrace) prospectively in 28,990 male runners. RESULTS Men (n = 228; 0.79%) self-reported incident gout during 7.74 y of follow-up. The risk of gout increased with higher alcohol intake [per 10 g/d; relative risk (RR): 1.19; 95% CI: 1.12, 1.26; P < 0.0001], meat consumption (per servings/d; RR: 1.45; 95% CI: 1.06, 1.92; P = 0.002), and BMI (RR: 1.19; 95% CI: 1.15, 1.23; P < 0.0001) and declined with greater fruit intake (per pieces/d; RR: 0.73; 95% CI: 0.62, 0.84; P < 0.0001), running distance (per km/d; RR: 0.92; 95% CI: 0.88, 0.97; P < 0.001), and fitness (per m/s; RR: 0.55; 95% CI: 0.41, 0.75; P < 0.0001). The RR per 10 g alcohol/d consumed as wine (1.27; P = 0.002), beer (1.19; P < 0.0001), and mixed drinks (1.13; P = 0.18) was not significantly different from each other. Men who consumed > 15 g alcohol/d had 93% greater risk than abstainers, and men who averaged > 2 pieces fruit/d had 50% less risk than those who ate < 0.5 fruit/d. Risk of gout was 16-fold greater for BMI > 27.5 than < 20. Compared with the least active or fit men, those who ran > or = 8 km/d or > 4.0 m/s had 50% and 65% lower risk of gout, respectively. Lower BMI contributed to the risk reductions associated with distance run and fitness. CONCLUSION These findings, based on male runners, suggest that the risk of gout is lower in men who are more physically active, maintain ideal body weight, and consume diets enriched in fruit and limited in meat and alcohol.
Drosophila female-specific Ilp7 motoneurons are generated by Fruitless-dependent cell death in males and by a double-assurance survival role for Transformer in females

ABSTRACT Female-specific Ilp7 neuropeptide-expressing motoneurons (FS-Ilp7 motoneurons) are required in Drosophila for oviduct function in egg laying. Here, we uncover cellular and genetic mechanisms underlying their female-specific generation. We demonstrate that programmed cell death (PCD) eliminates FS-Ilp7 motoneurons in males, and that this requires male-specific splicing of the sex-determination gene fruitless (fru) into the FruMC isoform. However, in females, fru alleles that only generate FruM isoforms failed to kill FS-Ilp7 motoneurons. This blockade of FruM-dependent PCD was not attributable to doublesex gene function but to a non-canonical role for transformer (tra), a gene encoding the RNA splicing activator that regulates female-specific splicing of fru and dsx transcripts. In both sexes, we show that Tra prevents PCD even when the FruM isoform is expressed. In addition, we found that FruMC eliminated FS-Ilp7 motoneurons in both sexes, but only when Tra was absent. Thus, FruMC-dependent PCD eliminates female-specific neurons in males, and Tra plays a double-assurance function in females to establish and reinforce the decision to generate female-specific neurons. Summary: In Drosophila, Tra antagonizes the function of male-specific Fru (FruM) to prevent FruM-dependent cell death of a subset of female-specific motoneurons that control egg laying.
A new species of Sigmaxinella Dendy, 1897 (Demospongiae, Poecilosclerida, Desmacellidae) from the Tasman Sea

Sigmaxinella hipposiderus sp. nov. is described from morphological and molecular datasets, based on a single known specimen collected from the upper margin of a submarine canyon on the edge of the continental shelf, south-east of coastal Victoria (Tasman Sea), Australia. Morphologically, the species is clearly assigned to the genus Sigmaxinella, and preliminary molecular data (COI mt DNA) support the close relationship of this new species to other specimens attributed to Desmacellidae. This is the thirteenth species of Sigmaxinella and the seventh described for the Australian EEZ. Remarkably, 12 of the 13 known species are recorded predominantly from temperate or subantarctic Australian, New Zealand or South African waters, with only a single species described so far from the temperate Atlantic Ocean.
Neural responses to reward in childhood: relations to early behavioral inhibition and social anxiety

Behavioral inhibition (BI) is an early temperamental profile characterized by negative reactivity to novelty, withdrawal from social situations, and increased risk for social anxiety. Previous research associated BI assessed in early childhood to striatal hypersensitivity in mid-to-late adolescence. The present study examined this association among 10 year-olds, characterized with BI at ages 24 and 36 months on measures of temperamental reactivity. Participants (n = 40) were studied at age 10 using a reward processing task during functional magnetic resonance imaging (fMRI). Child- and maternal-report of social anxiety symptoms was collected at ages 10 and 13. Findings indicate greater caudate activation and stronger striatal connectivity in high, compared to low, behaviorally inhibited children. Caudate activation related to social anxiety symptoms at both ages. These findings suggest that enhanced striatal responsivity reliably manifests among high behaviorally inhibited children as early as age 10. This may reflect hyper-sensitivity to reward or excessive motivation to avoid errors.
Iron deficiency anemia: higher prevalence in Mexican American than in non-Hispanic white females in the third National Health and Nutrition Examination Survey, 1988-1994.

BACKGROUND Mexican American females have a higher prevalence of iron deficiency than do non-Hispanic white females. OBJECTIVE The objective was to estimate the prevalence of iron deficiency anemia and examine potential reasons for this difference between Mexican American (n = 1194) and non-Hispanic white (n = 1183) females aged 12-39 y. DESIGN We used data from the third National Health and Nutrition Examination Survey (1988-1994). Iron deficiency anemia was defined as abnormal results from >/=2 of 3 tests (erythrocyte protoporphyrin, transferrin saturation, and serum ferritin) and a low hemoglobin concentration. We used multiple logistic regression to adjust for factors that were more prevalent in Mexican American females and significantly associated with iron deficiency anemia. RESULTS The prevalence of iron deficiency anemia was 6.2 +/- 0.8% (f1.gif" BORDER="0"> +/- SE) in Mexican American females and 2.3 +/- 0.4% in non-Hispanic white females. Mean dietary iron intake, mean serum vitamin C concentrations, and the proportion of females using oral contraceptives were similar in the 2 groups. Age <20 y and education were not associated with iron deficiency anemia. After adjustment for poverty level, parity, and iron supplement use, the prevalence of iron deficiency anemia was 2.3 times higher in Mexican American than in non-Hispanic white females (95% CI: 1.4, 3.9). In those with a poverty income ratio (based on household income) >3.0, however, the prevalence of iron deficiency anemia was 2.6 +/- 0.9% in Mexican American and 1.9 +/- 0.6% in non-Hispanic white females (NS). CONCLUSION Although much of the ethnic disparity in iron deficiency anemia remains unexplained, factors associated with household income may be involved.
Prospective study of major dietary patterns and risk of coronary heart disease in men.

BACKGROUND Previous studies on diet and coronary heart disease (CHD) focused primarily on individual nutrients or foods. OBJECTIVE We examined whether overall dietary patterns derived from a food-frequency questionnaire (FFQ) predict risk of CHD in men. DESIGN This was a prospective cohort study of 44875 men aged 40-75 y without diagnosed cardiovascular disease or cancer at baseline in 1986. RESULTS During 8 y of follow-up, we documented 1089 cases of CHD (nonfatal myocardial infarction and fatal CHD). Using factor analysis, we identified 2 major dietary patterns using dietary data collected through a 131-item FFQ. The first factor, which we labeled the "prudent pattern," was characterized by higher intake of vegetables, fruit, legumes, whole grains, fish, and poultry, whereas the second factor, the "Western pattern," was characterized by higher intake of red meat, processed meat, refined grains, sweets and dessert, French fries, and high-fat dairy products. After adjustment for age and CHD risk factors, the relative risks from the lowest to highest quintiles of the prudent pattern score were 1.0, 0. 87, 0.79, 0.75, and 0.70 (95% CI: 0.56, 0.86; P: for trend = 0.0009). In contrast, the relative risks across increasing quintiles of the Western pattern score were 1.0, 1.21, 1.36, 1.40, and 1.64 (95% CI: 1.24, 2.17; P: for trend < 0.0001). These associations persisted in subgroup analyses according to cigarette smoking, body mass index, and parental history of myocardial infarction. CONCLUSIONS These data suggest that major dietary patterns derived from the FFQ predict risk of CHD, independent of other lifestyle variables.
Business Model Analysis Applied to Mobile Business

Mobile business is a young promising industry created by the emergence of wireless data networks. Similar to other emerging industries, it is characterized by a large number of uncertainties at different levels concerning technology, demand and strategy. This paper focuses on the strategic uncertainties, where a large number of actors are trying a number of strategic approaches to position themselves in the most favourable position in the value system. As a consequence, they are experimenting with a number of innovating business models. We argue that successful business models are likely to be the ones that best address the economic peculiarities underlying this industry, like mobility, network effects and natural monopolies. The paper presents the principal classes of actors that will participate in the mobile business industry and give an overview of their business models based on a formalized ontology.
Employment, Wages and Optimal Monetary Policy

We study optimal monetary policy when the empirical evidence leaves the policymaker uncertain whether the true data-generating process is given by a model with sticky wages or a model with search and matching frictions in the labor market. Unless the policymaker is almost certain about the search and matching model being the correct data-generating process, the policymaker chooses to stabilize wage inflation at the expense of price inflation, a policy resembling the policy that is optimal in the sticky wage model, regardless of the true model. This finding reflects the greater sensitivity of welfare losses to deviations from the model-specific optimal policy in the sticky wage model. Thus, uncertainty about important aspects of the structure of the economy does not necessarily translate into uncertainty about the features of good monetary policy.
Protonation-dependent conformational dynamics of the multidrug transporter EmrE

Significance Small multidrug resistance (SMR) transporters play an important role in the protection of prokaryotes from cytotoxic molecules. They exploit the proton electrochemical gradient to drive the transport of these molecules out of the cell against their concentration gradient. This work investigated how binding of protons power the conformational changes that enable substrate binding and subsequent alternating access of the Escherichia coli SMR transporter EmrE. The results show that protonation induces large-scale reconfiguration of the structure, including helical rotation and tilt and repacking of loops. A highly conserved charged residue primarily accounts for proton sensing, but other acidic residues control local structures. Our findings stimulate a structural model of transport, offering a novel perspective on proton-coupled multidrug transport. The small multidrug transporter from Escherichia coli, EmrE, couples the energetically uphill extrusion of hydrophobic cations out of the cell to the transport of two protons down their electrochemical gradient. Although principal mechanistic elements of proton/substrate antiport have been described, the structural record is limited to the conformation of the substrate-bound state, which has been shown to undergo isoenergetic alternating access. A central but missing link in the structure/mechanism relationship is a description of the proton-bound state, which is an obligatory intermediate in the transport cycle. Here we report a systematic spin labeling and double electron electron resonance (DEER) study that uncovers the conformational changes of EmrE subsequent to protonation of critical acidic residues in the context of a global description of ligand-induced structural rearrangements. We find that protonation of E14 leads to extensive rotation and tilt of transmembrane helices 1–3 in conjunction with repacking of loops, conformational changes that alter the coordination of the bound substrate and modulate its access to the binding site from the lipid bilayer. The transport model that emerges from our data posits a proton-bound, but occluded, resting state. Substrate binding from the inner leaflet of the bilayer releases the protons and triggers alternating access between inward- and outward-facing conformations of the substrate-loaded transporter, thus enabling antiport without dissipation of the proton gradient.
Triadic gaze intervention for young children with physical disabilities.

PURPOSE This randomized controlled study investigated whether a supplemental treatment designed to teach triadic gaze (TG) as a signal of coordinated joint attention would yield a significantly greater increase in TG in the experimental versus control group. METHOD Eighteen 10- to 24-month-old children with severe motor impairments were randomly assigned to an experimental ( n = 9) or control group ( n = 9). For approximately 29 sessions over 17 weeks, experimental participants received TG treatment twice weekly with a speech-language pathologist in addition to standard practice. Control participants received only standard practice from birth-to-three therapists. Coders who were masked to group assignment coded TG productions with an unfamiliar speech-language pathologist at baseline, every 3 weeks during the experimental phase, and at the final measurement session. RESULTS TG increased across groups from baseline to final measurement, with the experimental group showing slightly greater change. Performance trends were examined using experimental phase moving averages. Comparisons revealed significant differences between groups at 2 time points (at 12 weeks, r = .30, a medium effect, and at the end of the phase, r = .50, a large effect). CONCLUSION The results suggest the promise of a short-term, focused treatment to teach TG as a behavioral manifestation of coordinated joint attention to children with severe physical disabilities.
Prospective evaluation of hematocrit in gender‐affirming hormone treatment: results from European Network for the Investigation of Gender Incongruence

In trans persons on gender‐affirming hormonal treatment, a decrease (in trans women) or increase (in trans men) in hematocrit is often observed. Reference ranges for evaluation of hematocrit levels in trans persons have not been established. This prospective cohort study is part of the European Network for the Investigation of Gender Incongruence (ENIGI). At the Ghent and Amsterdam sites, we included 625 hormone‐naïve trans persons. Gender‐affirming hormonal treatment was initiated at the first visit. In trans men, serum hematocrit (Hct) levels increased during the first year (+4.9 Hct %, 95% CI 3.82–5.25), with the most pronounced increase during the first 3 months (+2.7 Hct %, 95% CI 1.94–3.29). Trans men receiving testosterone esters had a larger increase in serum hematocrit levels compared to trans men receiving testosterone undecanoate (Δ 0.8 Hct %). Of 192 trans men, 22 (11.5%) developed serum hematocrit levels ≥50.0%. Trans men on testosterone undecanoate were less likely to develop hematocrit levels ≥50% or ≥52%, compared to trans men on testosterone esters, and were less likely to develop hematocrit levels ≥50%, compared to trans men on testosterone gel. In trans women, serum hematocrit had dropped by 4.1 Hct % (95% CI 3.50–4.37) after 3 months, after which only small decreases were observed. In conclusion, serum hematocrit levels can be found in the reference range of the perceived gender as from 3 months after the initiation of gender‐affirming hormonal treatment.
SHARP MINIMAX ESTIMATION OF THE VARIANCE OF BROWNIAN MOTION CORRUPTED WITH GAUSSIAN NOISE

Let Wt be a Brownian motion with ² in i.i. d. ∼ N (0, 1), i = 1, . , n, in- dependent of Wt. σ, τ > 0 are real, unknown parameters. Suppose we observe Yi,n = σWi/n + τ ² in. In this paper we establish sharp estimators for σ 2 and τ 2 in minimax sense, i.e. they attain the minimax constant asymptotically. A short and direct proof for the minimax lower bound is given. These estimators are based on a spectral decomposition of the underlying process Yi,n and can be computed explicitly taking O(n log n) operations. We outline how these estimators can be gen- eralized from Brownian motion to processes with independent increments. Further we show that the spectral estimators presented are asymptotically normal.
Compressible Carbon Nanotube–Graphene Hybrid Aerogels with Superhydrophobicity and Superoleophilicity for Oil Sorption

Spilled oil represents a menace to the aquatic ecosystem and the whole environment in general and requires timely cleanup. Among all the avaliable technologies, oil sorption has attracted the most attention because of its simplicity and high level of effectiveness. The key for the development of this technology is convenient fabrication of high-performance oil sorbents that can be used repeatedly. In this work, a fast microwave irradiation-mediated approach has been proposed for manufacturing multiwall carbon nanotube (MWCNT)–graphene hybrid aerogels, in which MWCNTs are vertically anchored on the surface of cell walls of graphene aerogels. The hybrid monoliths show superhydrophobicity and superoleophilicity, a large pore volume, a large pore size, and excellent compressibility, demonstrating outstanding performance for recyclable oil sorption.
Geometrical Theory of Diffraction for Modeling Acoustics in Virtual Environments

Realistic modeling of reverberant sound is crucial in 3D virtual worlds, providing users important cues for localizing sound sources and understanding the geometric and material properties of the environment. Unfortunately, current geometric acoustic modeling systems do not accurately simulate reverberant sound. Instead, they model only direct transmission and specular reflection, while diffraction is either ignored or modeled through statistical approximation. However, diffraction is extremely important for correct interpretation of acoustic environments, especially where the direct path between sound source and receiver is often occluded. The Geometrical Theory of Diffraction (GTD) extends geometrical optics with diffraction phenomena. When a ray hits a wedge, it produces diffracted rays. Thus, wedges become secondary sources of diffracted rays that in turn may be reflected and diffracted. In this paper, we extend earlier beam-tracing methods to include diffraction, using the GTD for deriving secondary diffracted rays and associated diffraction coefficients. Our main contributions are: 1) a beam tracing algorithm that uses adjacencies stored in a spatial subdivision to find diffracting edges and trace diffraction beams; 2) a method for computing reverberation paths, incorporating specular reflection, transmission, and diffraction; and 3) a real-time auralization system demonstrating that diffraction improves dramatically the audio quality in virtual environments.