Miracle-dz/UniFAR-FTUs huggingface dataset:
Sequence Analysis and Structural Predictions of Lipid Transfer Bridges in the Repeating Beta Groove (RBG) Superfamily Reveal Past and Present Domain Variations Affecting Form, Function and Interactions of VPS13, ATG2, SHIP164, Hobbit and Tweek

Lipid transfer between organelles requires proteins that shield the hydrophobic portions of lipids as they cross the cytoplasm. In the last decade a new structural form of lipid transfer protein (LTP) has been found: long hydrophobic grooves made of beta-sheet that bridge between organelles at membrane contact sites. Eukaryotes have five families of bridge-like LTPs: VPS13, ATG2, SHIP164, Hobbit and Tweek. These are unified into a single superfamily through their bridges being composed of just one domain, called the repeating beta groove (RBG) domain, which builds into rod shaped multimers with a hydrophobic-lined groove and hydrophilic exterior. Here, sequences and predicted structures of the RBG superfamily were analyzed in depth. Phylogenetics showed that the last eukaryotic common ancestor contained all five RBG proteins, with duplicated VPS13s. The current set of long RBG protein appears to have arisen in even earlier ancestors from shorter forms with 4 RBG domains. The extreme ends of most RBG proteins have amphipathic helices that might be an adaptation for direct or indirect bilayer interaction, although this has yet to be tested. The one exception to this is the C-terminus of SHIP164, which instead has a coiled-coil. Finally, the exterior surfaces of the RBG bridges are shown to have conserved residues along most of their length, indicating sites for partner interactions almost all of which are unknown. These findings can inform future cell biological and biochemical experiments.
ReactionsAmplification Loop of Inflammatory Skin Keratinocytes: A Novel Autocrine Induction of C3 and CCL2 by C3a in

The complement fragment-3a (C3a) acts via a G protein-coupled C3aR and is of importance in allergic and inﬂammatory diseases. Recent studies suggest the presence of complement proteins in the epidermal compartment and synthesis of some of these proteins (C3, factor B, and factor H) by human primary keratinocytes (KCs) during inﬂammation. However, expression of C3aR and its role in human KCs is not elucidated thus far. In this study, we demonstrate the expression of C3aR on KCs as detected by quantitative real-time RT-PCR and ﬂow cytometry. IFN- (cid:1) and IFN- (cid:2) strongly up-regulated the surface expression of C3aR on KCs among all other cytokines tested. After up-regulation of C3aR by IFN- (cid:1) and IFN- (cid:2) , we observed the induction of ﬁve genes ( CCL2 , CCL5 , CXCL8 , CXCL10 , and C3 ) after stimulation of KCs with C3a in microarray analysis. We conﬁrmed the induction of C3 and CCL2 at RNA and protein levels. Furthermore, incubation of C3 with skin mast cells tryptase resulted in the generation of C3 fragments with C3a activity. In conclusion, our data illustrate that epidermal KCs express functional C3aR. The increases of C3 and CCL2 synthesis by C3a and C3 activation by skin mast cell tryptase delineates a novel ampliﬁcation loop of complement activation and inﬂammatory responses that may inﬂuence the pathogenesis of allergic/inﬂammatory skin diseases. The Journal of Immunology, 2006, 177: 4444–4450.
Use of survival analysis to assess management options for ray blight in Australian pyrethrum ﬁelds

The effects of fungicide, cultivar and plant density on the time-to-death of pyrethrum ﬂowers affected by ray blight (caused by Phoma ligulicola var. inoxydablis ) in Australia were analysed using nonparametric Kaplan–Meier (KM) estimates and accelerated failure time (AFT) models with a Weibull probability distribution. Analyses using KM estimates and AFT models yielded similar results. The median survival time ( T ) for all ﬂowers in the fungicide trial was estimated at 53 days [95% conﬁdence interval (CI) = 43–53] in 2000 and 60 days (CI = 51–60) in 2001. In both years, all fungicides tested except copper oxychloride signiﬁcantly ( P £ 0 Æ 0495) increased the duration of ﬂower survival compared with nontreated plots. Signiﬁcant variation ( P < 0 Æ 0001) was noted between years and among four cultivars in terms of ﬂower survival, with T values for different cultivars ranging from 41 to 81 days, and averaging 69 days (CI = 60–69) in 2005 and 64 days (CI = 56–64) in 2006 for all cultivars. Planting at a quarter the density currently recommended increased ﬂower survival by 41 Æ 8% ( v 2 = 29 Æ 19; P < 0 Æ 0001), but did not increase yield. Linear regression indicated that defoliation severity accounted for at least 94% of variation in median survival time. Improved management may be achieved via an integrated strategy incorporating these factors.
Alloimmunity and nonimmunologic risk factors in cardiac allograft vasculopathy

Graft vasculopathy is an accelerated form of coronary artery disease that occurs in transplanted hearts. Despite major advances in immunosuppression, the prevalence of the disease has remained substantially unchanged during the last two decades. According to the ‘response to injury’ paradigm, graft vasculopathy is the result of a continuous inflammatory response to tissue injury initiated by both alloantigen-dependent and independent stress responses. Experimental evidence suggests that these responses may become self-sustaining, as allograft re-transplantation into the donor strain at a later stage fails to prevent disease progression. Histological evidence of endothelitis and arteritis, in association with intima fibrosis and atherosclerosis, reflects the central role of alloimmunity and inflammation in the development of arterial lesions. Experimental results in gene-targeted mouse models indicate that cellular and humoral immune responses are both involved in the pathogenesis of graft vasculopathy. Circulating antibodies against donor endothelium are found in a significant number of patients, but their pathogenic role is still controversial. Alloantigen-independent factors include donor-transmitted coronary artery disease, surgical trauma, ischaemia-reperfusion injury, viral infections, hyperlipidaemia, hypertension, and glucose intolerance. Recent therapeutic advances include the use of novel immunosuppressive agents such as sirolimus (rapamycin), HMG-CoA reductase inhibitors, calcium channel blockers, and angiotensin converting enzyme inhibitors. Optimal treatment of cardiovascular risk factors remains of paramount importance.
Other race effect onamygdala response during affective facial processing in major depression Other race effect on amygdala response in depression

Objective: The other race effect, also known as own race bias, refers to the enhanced ability to recognize faces belonging to one’s own race relative to faces from another race. The other race effect is associated with increased amygdala response in healthy individuals. The amygdala is a key node in emotion processing which shows impaired functioning in depression and has been proposed to be a marker of depressive state. We investigated the impact of the other race effect on amygdala responses in depression. Methods: Participants were 30 individuals with major depression (mean age 39.4 years) and 23 healthy individuals (mean age: 38.8 years) recruited from the community. Participants were Asian, Black/African American and Caucasian. During a functional MRI scan, participants viewed Caucasian faces which displayed a range of sad expressions. A region of interest analysis of left and right amygdala responses was performed. Results: Increased bilateral amygdala responses were observed in response to the Caucasian face stimuli in participants who were Asian or Black/African American as compared to Caucasian participants in both healthy individuals and individuals with major depression. There was no significant group by race interaction effect. Conclusions: Increased amygdala responses associated with the other race effect were evident in both individuals with major depression and in healthy participants. Increased amygdala responses with the other race effect is a potential confound of the neural correlates of facial processing in healthy participants and in mental health disorders. The implications of the other race effect on impairments in interpersonal functioning in depression require further investigation.
Enhancement of Mat Nursery Management and Planting Pattern (Using Rolling Markers) in System of Rice Intensification (SRI) Technique

Nursery and field experiments were conducted at Madurai from July to November 2006 to evaluate the response of hybrid rice in modified mat nursery and transplanting single seedling in different planting patterns in main field (using rolling markers) under System of Rice Intensification (SRI) technique. Rice seedlings grown from seeds fortified with 1% KCl + 6 g m Pseudomonas + DAP 50 g m powdered DAP + 2 2 0.5% DAP drenching on 9 day + 20 g m Azophos + 50 g m VAM + 0.5 kg m vermicompost exhibited the th 2 2 2 best seedling characteristics AND it was found suitable for mat nursery at 14 days producing seedlings with more root length (12.9 cm), seedling height (21.7 cm), chlorophyll meter (SPAD) value (32.9), seedling dry weight (18.1 g) and seedling vigour index (15.8). Grain yield was influenced by manuring. Higher plant height, more number of tillers hill , greater quantity of dry matter production, higher leaf area index AND root characters 1 were observed at all growth stages with oblong pattern of planting (30 x 25 cm). The results of the study indicated the potential benefits of integrated approach to raising seedlings in mat nursery (organic, inorganic, biofertiliser) which includes seed fortification with 1% KCl + 6 g m Pseudomonas + 50 g m powdered DAP 2 2 + 0.5% DAP drenching on 9 day + 20 g m Azophos + 50 g m VAM + 0.5 kg m vermicompost along with th 2 2 2 zig zag pattern of planting adopted by using triangular rolling markers was found to be the best option for getting higher productivity in hybrid rice under System of Rice Intensification technique.
Rural and Urban Land Tourism and Destination Image: A Dual-Case Study Approach Examining Energy-Saving Behavior and Loyalty

: Although the signiﬁcance of destination image is acknowledged, its effect on tourist reactions, especially energy-saving behavior, remains unknown. This research aimed to explore tourist energy-saving behavior (TESB) and loyalty (TL) in a rural land context by using the cognition-affect-behavior (CAB) model. The ﬁndings indicated: (1) destination image positively and directly inﬂuenced TESB and TL; (2) relationship quality variables, i.e., tourist satisfaction and destination trust, positively and separately mediated the associations of destination image with TESB and TL; and (3) a cross-validation approach of rural and urban cases documented support for the research ﬁndings. This study extends the destination image literature by introducing the CAB model and the cross-validation approach to examine energy-saving behavior and loyalty. It offers guidance and a reference for tourism destination practitioners to promote energy-saving behavior and loyalty through the enhancement of destination image and relationship quality.
Risk of dementia hospitalization associated with cardiovascular risk factors in midlife and older age: the Atherosclerosis Risk in Communities (ARIC) study

Background— Cardiovascular risk factors are associated with a higher risk of developing dementia. Studies in older populations, however, have often failed to show this relationship. We assessed the association between cardiovascular risk factors measured in midlife and risk of being hospitalized with dementia and determined whether this association was modified by age and ethnicity. Methods— We studied 11,151 participants in the population-based Atherosclerosis Risk in Communities cohort, aged 46-70 (23% African Americans) in 1990-1992, when participants underwent a physical exam and cognitive testing. Hospitalizations with dementia were ascertained through December 2004. Results— During follow-up, 203 cases of hospitalization with dementia were identified. Smoking (hazard ratio (HR), 95% confidence interval (CI): 1.7, 1.2-2.5), hypertension (HR, 95% CI: 1.6, 1.2-2.2) and diabetes (HR, 95% CI: 2.2, 1.6-3.0) were strongly associated with dementia, both in whites and African-Americans. These associations were stronger when risk factors were measured at younger age than at older age. In analyses including updated information on risk factors during follow-up, the HR of dementia in hypertensive versus non-hypertensive participants was 1.8 at age <55 years compared to 1.0 at age 70+ years. Parallel results were observed for diabetes (HR 3.4 in <55, 2.0 in ≥ 70), Conclusion— In this prospective study, smoking, hypertension, and diabetes were strongly associated with subsequent risk of hospitalization with dementia, particularly in middle aged individuals. Our results emphasize the importance of early lifestyle modification and risk factor treatment to prevent dementia.
The sapphirine-bearing rocks in contact with the Lherz peridotite body: new mineralogical data, age and attempt at interpretation

– Sapphirine-bearing rocks are described in the Aulus Basin (Ariège, France) in a contact zone between the Lherz peridotitic body and Mesozoic metasediments which underwent the Pyrenean Cretaceous high-temperature, low-pressure metamorphic event (Monchoux, 1970, 1972a, 1972b). Sapphirine crystals occur in layered clastic deposits characterized by an uncommon suite of Al-Mg-rich minerals. A detailed petrographic study of sixteen samples representative of the diversity of the Lherz sapphirine-bearing rocks is presented. These rocks include breccias and microbreccias with various compositions. Some samples are composed of polymineralic clasts and isolated minerals that derive from regionally well-known protoliths such as ultrama ﬁ c rocks, meta-ophites, “ micaceous hornfels ” , and very scarce Paleozoic basement rocks. Nevertheless, a large portion of the sapphirine-bearing clastic suite is composed of mono- and polymineralic debris that derive from unknown protolith(s). We de ﬁ ne a "sapphirine-bearing mineral suite ” (SBMS) composed of monomineralic debris including: þ aluminous spinel þ Mg-amphiboles þ Ca-amphiboles þ kornerupine þ accessory minerals (apatite, diopside, rutile, serpentine, smectite, tourmaline, vermiculite and a white mica). We highlight the dominance of metamorphic Keuper clastic materials in the studied rocks and the presence of inclusions of anhydrite and F-, Cl-, Sr-rich apatite in minerals of the Al-Mg-rich suite. The brecciated texture and the presence of unequivocal sedimentary features suggest that the sapphirine-bearing rocks were mechanically disaggregated and then experienced winnowing in underwater conditions with poor mixing between the different sources. We measured U-Pb rutile age data in order to provide constraints on the age of (one of) the protolith(s) of those clastic deposits. The obtained age (98.6 þ 1.2 Ma) is interpreted as the age of metamorphism of this protolith of the SBMS. Previous works interpreted the Lherz sapphirine-bearing rocks as crustal protoliths modi ﬁ ed at depth along the contact with the ultrama ﬁ c rocks of the Lherz body during their ascent towards shallower depths. These new data imply: (i) an Upper Triassic to Lower Jurassic origin for the main protolith of the sapphirine-bearing rocks; (ii) the metamorphism of this protolith along an active hot crust – mantle detachment during Cenomanian times with the involvement of metasomatic, brine-type ﬂ uids; and (iii) its brecciation during the exhumation of the material due to the evolution of the detachment, followed by subsequent sedimentary reworking of the metamorphic material.
Stochastic Route Planning for Electric Vehicles

Electric Vehicle routing is often modeled as a generalization of the energy-constrained shortest path problem, taking travel times and energy consumptions on road network edges to be deterministic. In practice, however, energy consumption and travel times are stochastic distributions, typically estimated from real-world data. Consequently, real-world routing algorithms can make only probabilistic feasibility guarantees. Current stochastic route planning methods either fail to ensure that routes are energy-feasible, or if they do, have not been shown to scale well to large graphs. Our work bridges this gap by finding routes to maximize on-time arrival probability and the set of non-dominated routes under two criteria for stochastic route feasibility: E -feasibility and p -feasibility. Our E -feasibility criterion ensures energy-feasibility in expectation, using expected energy values along network edges. Our p -feasibility criterion accounts for the actual distribution along edges, and keeps the stranding probability along the route below a user-specified threshold p . We generalize the charging function propagation algorithm to accept stochastic edge weights to find routes that maximize the probability of on-time arrival, while maintaining E - or p -feasibility. We also extend multi-criteria Contraction Hierarchies to accept stochastic edge weights and offer heuristics to speed up queries. Our experiments on a real-world road network instance of the Los Angeles area show that our methods answer stochastic queries in reasonable time, that the two criteria produce similar routes for longer deadlines, but that E -feasibility queries can be much faster than p -feasibility queries.
Pharmacodynamic Target Assessment and PK/PD Cutoff Determination for Gamithromycin Against Streptococcus suis in Piglets

Gamithromycin is a long-acting azalide antibiotic that has been developed recently for the treatment of swine respiratory diseases. In this study, the pharmacokinetic/pharmacodynamic (PK/PD) targets, PK/PD cutoff, and optimum dosing regimen of gamithromycin were evaluated in piglets against Streptococcus suis in China, including a subset with capsular serotype 2. Short post-antibiotic effects (PAEs) (0.5–2.6 h) and PA-SMEs (2.4–7.7 h) were observed for gamithromycin against S. suis. The serum matrix dramatically facilitated the intracellular uptake of gamithromycin by S. suis strains, thus contributing to the potentiation effect of serum on their susceptibilities, with a Mueller-Hinton broth (MHB)/serum minimum inhibitory concentration (MIC) ratio of 28.86 for S. suis. Dose-response relationship demonstrated the area under the concentration (AUC)/MIC ratio to be the predictive PK/PD index closely linked to activity (R2 > 0.93). For S. suis infections, the net stasis, 1–log10, and 2–log10 kill effects were achieved at serum AUC24h/MIC targets of 17.9, 49.1, and 166 h, respectively. At the current clinical dose of 6.0 mg/kg, gamithromycin PK/PD cutoff value was determined to be 8 mg/L. A PK/PD-based dose assessment demonstrated that the optimum dose regimen of gamithromycin to achieve effective treatments for the observed wild-type MIC distribution of S. suis in China with a probability of target attainment (PTA) ≥ 90% was 2.53 mg/kg in this study. These results will aid in the development of clinical dose-optimization studies and the establishment of clinical breakpoints for gamithromycin in the treatment of swine respiratory infections due to S. suis.
Clinical and Pulmonary CT Characteristics of Patients Infected With the SARS-CoV-2 Omicron Variant Compared With Those of Patients Infected With the Alpha Viral Strain

Background Omicron has become the dominant variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) globally. We aimed to compare the clinical and pulmonary computed tomography (CT) characteristics of the patients infected with SARS-CoV-2 Omicron with those of patients infected with the Alpha viral strain. Methods Clinical profiles and pulmonary CT images of 420 patients diagnosed with coronavirus disease-2019 (COVID-19) at Ningbo First Hospital between January 2020 and April 2022 were collected. Demographic characteristics, symptoms, and imaging manifestations of patients infected with the SARS-CoV-2 Omicron variant were compared with those of patients infected with the Alpha strain. Results A total of 38 patients were diagnosed to be infected with the Alpha strain of SARS-CoV-2, whereas 382 patients were thought to be infected with the Omicron variant. Compared with patients infected with the Alpha strain, those infected with the Omicron variant were younger, and a higher proportion of men were infected (P < 0.001). Notably, 93 (24.3%) of the patients infected with Omicron were asymptomatic, whereas only two (5.3%) of the patients infected with the Alpha strain were asymptomatic. Fever (65.8%), cough (63.2%), shortness of breath (21.1%), and diarrhea (21.1%) were more common in patients infected with the SARS-CoV-2 Alpha strain, while runny nose (24.1%), sore throat (31.9%), body aches (13.6%), and headache (12.3%) were more common in patients with the Omicron variant. Compared with 33 (86.84%) of 38 patients infected with the Alpha strain, who had viral pneumonia on pulmonary CT images, only 5 (1.3%) of 382 patients infected with the Omicron variant had mild foci. In addition, the distribution of opacities in the five patients was unilateral and centrilobular, whereas most patients infected with the Alpha strain had bilateral involvement and multiple lesions in the peripheral zones of the lung. Conclusion The SARS-CoV-2 Alpha strain mainly affects the lungs, while Omicron is confined to the upper respiratory tract in patients with COVID-19.
Association of Mesoscale Auroral Structures and Breakups With Energetic Particle Injections at Geosynchronous Orbit

Geomagnetic substorms are associated with characteristic energetic particle injection signatures at geosynchronous orbit that are often dispersionless in both electrons and ions near the magnetic local time sector of auroral onset locations and are dispersed farther away from this region. Although the precise mechanism responsible for the coherent injection signatures at geosynchronous orbit have been the topic on considerable ongoing debate for decades, recent work on bursty bulk flows (BBFs) in the tail have led to the hypothesis that they may be the result of multiple, overlapping flow bursts penetrating into the inner magnetosphere from more distant downtail reconnection sites. Since auroral streamers are thought to be ionospheric signatures of BBFs in the tail, they can be used as proxies for testing this hypothesis. Using high resolution auroral imagery from the POLAR/VIS instrument combined with multi-spacecraft observations of energetic particle injections at geosynchronous orbit, we examine the association of mesoscale auroral structures with particle injection signatures over many hours during the 9 November 1998 storm. We find that the explosive types of auroral activations, such as pseudo-breakups and substorm onset breakups, are associated with the more intense and well-defined dispersed injection signatures, while intervals of isolated streamer activity appear to be associated with smaller dispersed “injectionlet” signatures. Furthermore, intervals of sustained, intense, and late expansion phase/recovery phase streamer activity appear to be associated with sustained elevated dispersed particle fluxes. These results are consistent with the hypothesis that it is the overlapping effects of sustained, intense multiple flow bursts penetrating toward the Earth that result in classical substorm particle injection signatures at geosynchronous orbit. However, it is also suggested that torches/omega-band tongues are the prime fate of braking isolated flow bursts (streamers) rather than the development of breakups, bulges, and substorm current wedge formation. A statistical analysis is presented showing that 93% of the observed torches evolved from streamers, 93% of streamers arriving in the equatorward regions of the bulge led to torches, 10.5% of such streamers led to breakups (either pseudo-breakups or substorm onsets), and only 3.5% of such streamers led to substorm onsets.