Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased PLEKHO1 within osteoblasts suppresses Smad‐dependent BMP signaling to inhibit bone formation during aging

Emerging evidence indicates that the dysregulation of protein ubiquitination plays a crucial role in aging‐associated diseases. Smad‐dependent canonical BMP signaling pathway is indispensable for osteoblastic bone formation, which could be disrupted by the ubiquitination and subsequent proteasomal degradation of Smad1/5, the key molecules for BMP signaling transduction. However, whether the dysregulation of Smad1/5 ubiquitination and disrupted BMP signaling pathway is responsible for the age‐related bone formation reduction is still underexplored. Pleckstrin homology domain‐containing family O member 1 (PLEKHO1) is a previously identified ubiquitination‐related molecule that could specifically target the linker region between the WW domains of Smurf1 to promote the ubiquitination of Smad1/5. Here, we found an age‐related increase in the expression of PLEKHO1 in bone specimens from either fractured patients or aging rodents, which was associated with the age‐related reduction in Smad‐dependent BMP signaling and bone formation. By genetic approach, we demonstrated that loss of Plekho1 in osteoblasts could promote the Smad‐dependent BMP signaling and alleviated the age‐related bone formation reduction. In addition, osteoblast‐specific Smad1 overexpression had beneficial effect on bone formation during aging, which could be counteracted after overexpressing Plekho1 within osteoblasts. By pharmacological approach, we showed that osteoblast‐targeted Plekho1 siRNA treatment could enhance Smad‐dependent BMP signaling and promote bone formation in aging rodents. Taken together, it suggests that the increased PLEKHO1 could suppress Smad‐dependent BMP signaling to inhibit bone formation during aging, indicating the translational potential of targeting PLEKHO1 in osteoblast as a novel bone anabolic strategy for reversing established osteoporosis during aging.
PERCHED AT THE MITO‐NUCLEAR CROSSROADS: DIVERGENT MITOCHONDRIAL LINEAGES CORRELATE WITH ENVIRONMENT IN THE FACE OF ONGOING NUCLEAR GENE FLOW IN AN AUSTRALIAN BIRD

Relationships among multilocus genetic variation, geography, and environment can reveal how evolutionary processes affect genomes. We examined the evolution of an Australian bird, the eastern yellow robin Eopsaltria australis, using mitochondrial (mtDNA) and nuclear (nDNA) genetic markers, and bioclimatic variables. In southeastern Australia, two divergent mtDNA lineages occur east and west of the Great Dividing Range, perpendicular to latitudinal nDNA structure. We evaluated alternative scenarios to explain this striking discordance in landscape genetic patterning. Stochastic mtDNA lineage sorting can be rejected because the mtDNA lineages are essentially distinct geographically for > 1500 km. Vicariance is unlikely: the Great Dividing Range is neither a current barrier nor was it at the Last Glacial Maximum according to species distribution modeling; nuclear gene flow inferred from coalescent analysis affirms this. Female philopatry contradicts known female‐biased dispersal. Contrasting mtDNA and nDNA demographies indicate their evolutionary histories are decoupled. Distance‐based redundancy analysis, in which environmental temperatures explain mtDNA variance above that explained by geographic position and isolation‐by‐distance, favors a nonneutral explanation for mitochondrial phylogeographic patterning. Thus, observed mito‐nuclear discordance accords with environmental selection on a female‐linked trait, such as mtDNA, mtDNA–nDNA interactions or genes on W‐chromosome, driving mitochondrial divergence in the presence of nuclear gene flow.
Hearing and vision impairment and the 5-year incidence of falls in older adults.

BACKGROUND concurrent vision and hearing loss are common in older adults; however, epidemiological data on their relationship with the incidence of falls are lacking. OBJECTIVE we assessed the association between dual sensory impairment (DSI) and incidence of falls. We examined the influence of self-perceived hearing handicap and hearing aid use and risk of falls. DESIGN a population-based, cohort study of participants followed over 5 years. SETTING Blue Mountains, west of Sydney, Australia. SUBJECTS one thousand four hundred and seventy-eight participants aged 55 and older at baseline were included in longitudinal analyses. METHODS visual impairment was defined as presenting or best-corrected visual acuity less than 20/40 (better eye), and hearing impairment as average pure-tone air conduction threshold >25 dB HL (500-4,000 Hz, better ear). The shortened version of the hearing handicap inventory for the elderly was administered. Incident falls were assessed over the 12 months before each visit. Cognitive impairment was determined using the Mini-Mental State Examination. RESULTS five-year incidence of falls was 10.4%. Participants with severe self-perceived hearing handicap versus no hearing handicap had increased risk of incident falls, multivariable-adjusted OR 1.93 (95% confidence intervals, CI, 1.02-3.64). Hearing aid users versus non-users had 75% increased likelihood of incident falls. Participants with co-existing best-corrected visual impairment and mild hearing loss (>25 to ≤40 dB HL) had higher odds of incident falls, OR 2.19 (95% CI 1.03-4.67). After excluding persons with cognitive impairment, this association did not persist. CONCLUSION these epidemiological data show that DSI in older adults could significantly increase their risk of falling.
Substance P in the anterior thalamic paraventricular nucleus: promotion of ethanol drinking in response to orexin from the hypothalamus

The paraventricular nucleus of the thalamus (PVT) appears to participate in drug addiction. Recent evidence in rats shows that ethanol drinking is increased by orexin/hypocretin (OX) afferents from the hypothalamus, acting specifically in the anterior (aPVT) rather than posterior (pPVT) PVT subregion. The present study sought to identify neuropeptides transcribed within the PVT, which themselves might contribute to ethanol drinking and possibly mediate the actions of OX. We discovered that substance P (SP) in the aPVT can stimulate intermittent‐access ethanol drinking, similar to OX, and that SP receptor [neurokinin 1 receptor/tachykinin receptor 1 (NK1R)] antagonists in this subregion reduce ethanol drinking. As with OX, this effect is site specific, with SP in the pPVT or dorsal third ventricle having no effect on ethanol drinking, and it is behaviorally specific, with SP in the aPVT reducing the drinking of sucrose and stimulating it in the pPVT. A close relationship between SP and OX was demonstrated by a stimulatory effect of local OX injection on SP mRNA and peptide levels, specifically in the aPVT but not pPVT, and a stimulatory effect of OX on SP expression in isolated thalamic neurons, reflecting postsynaptic actions. A functional relationship between OX and SP in the aPVT is suggested by our additional finding that ethanol drinking induced by OX is blocked by a local NK1R antagonist administered at a sub‐threshold dose. These results, suggesting that SP in the aPVT mediates the stimulatory effect of OX on ethanol drinking, identify a new role for SP in the control of this behavior.
ARTHUR: Retrieving Orchestral Music by Long-Term Structure

We introduce an audio retrieval-by-example system for orchestral music. Unlike many other approaches, this system is based on analysis of the audio waveform and does not rely on symbolic or MIDI representations. ARTHUR retrieves audio on the basis of long-term structure, specifically the variation of soft and louder passages. The longterm structure is determined from envelope of audio energy versus time in one or more frequency bands. Similarity between energy profiles is calculated using dynamic programming. Given an example audio document, other documents in a collection can be ranked by similarity of their energy profiles. Experiments are presented for a modest corpus that demonstrate excellent results in retrieving different performances of the same orchestral work, given an example performance or short excerpt as a query.
Spotting-and treating-PTSD in primary care.

CASE. Maureen S,* a patient in her late 50s with chronic pain due to severe degenerative disc disease and early-stage chronic obstructive pulmonary disease (COPD) from years of smoking, was referred to me (JRF) 5 years ago after her physician relocated. Because of her chronic health problems, I began scheduling monthly visits. But she rarely followed through on my recommendations, whether for smoking cessation, physical therapy, pain management, or mammography screening. As I got to know Maureen, it was clear that she was chronically depressed and anxious. I began asking her why she didn’t take better care of herself. Gradually, she provided the answers. Throughout her childhood, Maureen confi ded, her mother had subjected her to severe corporal punishment. From the time she was 7 until she reached her teens, Maureen’s “uncle” had sexually abused her. As an adult, she’d had a series of abusive relationships. The patient’s poor health and failure to care for herself, I suspected, were related to chronic post-traumatic stress disorder (PTSD).
Effect of sleep on breathing - Why recurrent apneas are only seen during sleep.

In the past four decades, respiration during sleep has intrigued clinicians and basic scientists, probably owing to a better recognition of the clinical significance of sleep apnea syndrome. Sleep apnea syndrome is characterized by repetitive episodes of cessation of airflow at the nose and mouth lasting at least 10 seconds during sleep in association with one or more of the following symptoms: habitual snoring, restless sleep, morning headache, excessive daytime sleepiness and intellectual impairment (1). Although the phenomenon of sleep disordered breathing (SDB) has long been noticed (2,3), the first polysomnographic recording of frequent respiratory pauses during sleep in humans dates back to 1965 (4).
LIG at MediaEval 2015 Multimodal Person Discovery in Broadcast TV Task

In this working notes paper the contribution of the LIG team (partnership between Univ. Grenoble Alpes and Ozyegin University) to the Multimodal Person Discovery in Broadcast TV task in MediaEval 2015 is presented. The task focused on unsupervised learning techniques. Two dierent approaches were submitted by the team. In the rst one, new features for face and speech modalities were tested. In the second one, an alternative way to calculate the distance between face tracks and speech segments is presented. It also had a competitive MAP score and was able to beat the baseline.
Cesarean Section and Chronic Immune Disorders

OBJECTIVES: Immune diseases such as asthma, allergy, inflammatory bowel disease, and type 1 diabetes have shown a parallel increase in prevalence during recent decades in westernized countries. The rate of cesarean delivery has also increased in this period and has been associated with the development of some of these diseases. METHODS: Mature children born by cesarean delivery were analyzed for risk of hospital contact for chronic immune diseases recorded in the Danish national registries in the 35-year period 1977–2012. Two million term children participated in the primary analysis. We studied childhood diseases with a suspected relation to a deviant immune-maturation and a debut at young age. The effect of cesarean delivery on childhood disease incidences were estimated by means of confounder-adjusted incidence rate ratios with 95% confidence intervals obtained in Poisson regression analyses. RESULTS: Children delivered by cesarean delivery had significantly increased risk of asthma, systemic connective tissue disorders, juvenile arthritis, inflammatory bowel disease, immune deficiencies, and leukemia. No associations were found between cesarean delivery and type 1 diabetes, psoriasis, or celiac disease. CONCLUSIONS: Cesarean delivery exemplifies a shared environmental risk factor in early life associating with several chronic immune diseases. Understanding commonalities in the underlying mechanisms behind chronic diseases may give novel insight into their origin and allow prevention.
Functional Response of a Near-Surface Soil Microbial Community to a Simulated Underground CO2 Storage Leak

Understanding the impacts of leaks from geologic carbon sequestration, also known as carbon capture and storage, is key to developing effective strategies for carbon dioxide (CO2) emissions management and mitigation of potential negative effects. Here, we provide the first report on the potential effects of leaks from carbon capture and storage sites on microbial functional groups in surface and near-surface soils. Using a simulated subsurface CO2 storage leak scenario, we demonstrate how CO2 flow upward through the soil column altered both the abundance (DNA) and activity (mRNA) of microbial functional groups mediating carbon and nitrogen transformations. These microbial responses were found to be seasonally dependent and correlated to shifts in atmospheric conditions. While both DNA and mRNA levels were affected by elevated CO2, they did not react equally, suggesting two separate mechanisms for soil microbial community response to high CO2 levels. The results did not always agree with previous studies on elevated atmospheric (rather than subsurface) CO2 using FACE (Free-Air CO2 Enrichment) systems, suggesting that microbial community response to CO2 seepage from the subsurface might differ from its response to atmospheric CO2 increases.
Update on optimal use of lisdexamfetamine in the treatment of ADHD

Lisdexamfetamine (LDX) has been a recent addition to the treatment armamentarium for Attention Deficit Hyperactivity Disorder (ADHD). It is unique among stimulants as it is a prodrug, and has been found to be safe and well-tolerated medication in children older than 6 years, adolescents and adults. It has a smooth onset of action, exerts its action up to 13 hours and may have less rebound symptoms. LDX has proven to be effective in the treatment of ADHD in placebo controlled trials, and improved performance in simulated academic and work environments have been noticed. Both stimulant-naïve and stimulant-exposed patients with ADHD appear to benefit from LDX. It has also shown some promise in improving emotional expression and executive function of patients with ADHD. Adverse effects such as decrease in sleep, loss of appetite and others have been reported with LDX use, just as with other stimulant formulations. Since most such studies exclude subjects with preexisting cardiac morbidity, prescribing precautions should be taken with LDX in such subjects, as with any other stimulant. Study subjects on LDX have been reported to have low scores on drug likability scales, even with intravenous use; as a result, LDX may have somewhat less potential for abuse and diversion. There is a need for future studies comparing other long acting stimulants with LDX in ADHD; in fact clinical trials comparing LDX with OROS (osmotic controlled-release oral delivery system) methylphenidate are currently underway. Furthermore, the utility of this medication in other psychiatric disorders and beyond ADHD is being investigated.
Hierarchical visualization with treemaps: making sense of pro basketball data

ABSTRACT Treemaps support visualization of large hierarchical information spaces. The treemap generation algorithm is straightforward and application prototypes have only minimal hardware requirements. Given primary graphical encodings of area, color and enclosure, treemaps are best suited for the tasks of outlier detection, cause-effect analysis and location of specific nodes—satisfying user-specified criteria—in their hierarchical context. Distortion effects extend treemap capabilities by emphasizing node relationships in the diagram.
Steklov Geometry Processing: An Extrinsic Approach to Spectral Shape Analysis

We propose Steklov geometry processing, an extrinsic approach to spectral geometry processing and shape analysis. Intrinsic approaches, usually based on the Laplace-Beltrami operator, cannot capture the spatial embedding of a shape up to rigid motion, while many previous extrinsic methods lack theoretical justification. Instead, we propose a systematic approach by considering the Steklov eigenvalue problem, computing the spectrum of the Dirichlet-to-Neumann operator of a surface bounding a volume. A remarkable property of this operator is that it encodes the volumetric geometry. We use the boundary element method (BEM) to discretize the operator, accelerated by hierarchical numerical schemes and preconditioning; this pipeline allows us to solve eigenvalue and linear problems on large-scale meshes despite the density of the Dirichlet-to-Neumann discretization. We further demonstrate that our operators naturally fit into existing frameworks for geometry processing, making a shift from intrinsic to extrinsic geometry as simple as substituting the Laplace-Beltrami operator with the Dirichlet-to-Neumann operator.
Privacy Preserving Vehicle Purchase Marketplace

The car customer in the U.S. market has come to expect many incentives during her purchase process. Many of these incentives are based on the private profile information of the customer, which she would not want to disclose to the set of all possible dealers. On the other hand, the dealers want to keep the exact information on various incentives on offer private as well due to various business reasons. In this paper, we present design of a privacy preserving marketplace that executes control on information disclosure while enabling the purchasing process. Marketplace designs pertaining to both single dealer and multiple dealer participation are dealt with
Personality and Social Psychology Review How People Explain Behavior: a New Theoretical Framework

This article presents a theoretical framework of how people explain behavior. The framework, based on the folk concept of intentionality, distinguishes two major modes of explanation—reason explanation and cause explanation—as well as two minor modes and identifies conditions under which they occur. Three studies provide empirical support for these distinctions. As part of the framework, a detailed model of people's reason explanations is developed, which emphasizes the unique conceptual and linguistic features of reasons. This model points to limitations of traditional at-tribution concepts, which are examined theoretically and empirically. Finally, the theoretical framework incorporates attribution concepts, which apply to some but not all modes of explanation. Several paths for future research are outlined—on novel topics such as the roles of rationality and subjectivity in explanations and on classic topics such as the actor-observer asymmetry and the self-serving bias. Folk explanations of behavior guide people's perceptions , attitudes, and actions towards each other; they affect impressions, sway sympathies, and alter the paths of relationships. By explaining behavior, people make sense of the social world, adapt to it, and shape it. Behavior explanations are thus themselves a social behavior that must be described and explained. Attribution theory has been the predominant psychological account of people's behavior explanations, focusing on the various causes that people assign to behavior (e. This article has benefited from many critical minds. It has its roots in a term paper for Lee Ross and Mark Lepper's 1990 graduate social psychology course. Subsequent rewrites were shaped significantly by feedback from planations that attribution theory has painted, however, differs markedly from the picture that philosophers, developmental psychologists, and sociologists have These disciplines suggest that people explain intentional behavior differently from unintentional behavior , and these different explanations have typically been called reason explanations and causal explanations , respectively. Some authors have criticized attri-bution theory for ignoring the difference between peo-ple's reason explanations and causal explanations that attribution theory has not delivered an adequate account of how people explain behavior. Despite the gravity of this implication, the cause-reason distinction has not been systematically studied and is surprisingly rarely discussed—never in textbooks and only occasionally in comprehensive reviews (e. This article offers an account of the cause–reason distinction within a larger framework of how people explain behavioral events. 1 In short, the framework identifies cause and reason explanations as two among several modes of explanation with which people clarify 1 I use …
Age-Related Deficits of Dual-Task Walking: A Review

This review summarizes our present knowledge about elderly people's problems with walking. We highlight the plastic changes in the brain that allow a partial compensation of these age-related deficits and discuss the associated costs and limitations. Experimental evidence for the crucial role of executive functions and working memory is presented, leading us to the hypothesis that it is difficult for seniors to coordinate two streams of visual information, one related to navigation through visually defined space, and the other to a visually demanding second task. This hypothesis predicts that interventions aimed at the efficiency of visuovisual coordination in the elderly will ameliorate their deficits in dual-task walking.
Arabidopsis Kelch Repeat F-Box Proteins Regulate Phenylpropanoid Biosynthesis via Controlling the Turnover of Phenylalanine Ammonia-Lyase[C][W][OPEN]

Phenylalanine ammonia-lyase (PAL) catalyzes the first rate-limiting step in the phenylpropanoid pathway. Both in vitro and in vivo biochemical and genetic evidence demonstrated that a group of Kelch repeat F-box proteins physically interact with PAL isozymes, mediating their degradation via the ubiquitination-26S proteasome system, thus affecting phenylpropanoid biosynthesis. Phenylalanine ammonia-lyase (PAL) catalyzes the first rate-limiting step in the phenylpropanoid pathway, which controls carbon flux to a variety of bioactive small-molecule aromatic compounds, and to lignin, the structural component of the cell wall. PAL is regulated at both the transcriptional and translational levels. Our knowledge about the transcriptional regulation of PAL is relatively comprehensive, but our knowledge of the molecular basis of the posttranslational regulation of PAL remains limited. Here, we demonstrate that the Arabidopsis thaliana Kelch repeat F-box (KFB) proteins KFB01, KFB20, and KFB50 physically interact with four PAL isozymes and mediate their proteolytic turnover via the ubiquitination-26S proteasome pathway. The KFB genes are differentially expressed in Arabidopsis tissues and respond to developmental and environmental cues. Up- or downregulation of their expression reciprocally affects the stability of the PAL enzymes, consequently altering the levels of phenylpropanoids. These data suggest that the KFB-mediated protein ubiquitination and degradation regulates the proteolysis of PALs, thus posttranslationally regulating phenylpropanoid metabolism. Characterizing the KFB-mediated proteolysis of PAL enzymes may inform future strategies for manipulating the synthesis of bioactive phenolics.