Miracle-dz/UniFAR-FTUs huggingface dataset:
A QUICK Screen for Lrrk2 Interaction Partners – Leucine-rich Repeat Kinase 2 is Involved in Actin Cytoskeleton Dynamics*

Mutations in human leucine-rich repeat kinase 2 (Lrrk2), a protein of yet unknown function, are linked to Parkinson's disease caused by degeneration of midbrain dopaminergic neurons. The protein comprises several domains including a GTPase and a kinase domain both affected by several pathogenic mutations. To elucidate the molecular interaction network of endogenous Lrrk2 under stoichiometric constraints, we applied QUICK (quantitative immunoprecipitation combined with knockdown) in NIH3T3 cells. The identified interactome reveals actin isoforms as well as actin-associated proteins involved in actin filament assembly, organization, rearrangement, and maintenance, suggesting that the biological function of Lrrk2 is linked to cytoskeletal dynamics. In fact, we demonstrate Lrrk2 de novo binding to F-actin and its ability to modulate its assembly in vitro. When tested in intact cells, knockdown of Lrrk2 causes morphological alterations in NIH3T3 cells. In developing dopaminergic midbrain primary neurons, Lrrk2 knockdown results in shortened neurite processes, indicating a physiological role of Lrrk2 in cytoskeletal organization and dynamics of dopaminergic neurons. Hence, our results demonstrate that molecular interactions as well as the physiological function of Lrrk2 are closely related to the organization of the actin-based cytoskeleton, a crucial feature of neuronal development and neuron function.
Ecological determinants of parenting.

An ecological model of human development was used to assess the interrelationship between psychological determinants of parenting parental age and parenting skill for a sample of 210 parents. Parents race was found to be significantly related to attitudes toward childrearing knowledge of child development and perceived social support. Punitive attitudes toward childrearing and parental race were significant predictors of the quality of parenting with more punitive and younger parents having less supportive and less nurturant home environments. The subjects were recruited from 3 agencies in the Midwest. Data were collected between March 1984 and March 1985. Each subject was interviewed and a HOME instrument was administered to each one. The HOME is a 45 item interview/observation scale which contains 6 subscales: emotional and verbal responsivity avoidance of restriction and punishment organization of the environment provision of play materials maternal involvement and variety in daily stimulation. The apparent unimportance of parental age as a predictor of parenting raises doubts about the appropriateness of equating chronological age with poor caretaking. The results do not give an indication of the cause-effect relationship between depression knowledge expectations attitudes and perceived social support. Low income participants with relatively little education were high in reported levels of social support.
Pilot Designs for Channel Estimation of OFDM Systems with Frequency-Dependent I/Q Imbalances

Multiple input multiple output (MIMO) orthogonal frequency division multiplexing (OFDM) systems facilitate high data rate wireless communications, and require reliable channel estimates to fully materialize their advantages. The semiconductor downscaling trend has exacerbated device impairments such as inphase and quadrature (I/Q) imbalances which cause inter-carrier interferences in OFDM systems which cannot be remedied by increasing signal power. Different RF chains of MIMO branches can cause different I/Q imbalances which further complicates MIMO OFDM channel estimation. This paper proposes several pilot designs for the estimation of the combined responses of MIMO frequency-selective channels and frequency-dependent I/Q imbalances. The proposed designs require much smaller pilot overhead than the existing designs, and also provide estimation mean-squares error optimality (under white noise) and general applicability to preamble as well as pilot-data-multiplexed symbols in MIMO systems with or without null guard tones. Performance analyses and simulation results corroborate advantages of the proposed designs.
Paraquat neurotoxicity is mediated by the dopamine transporter and organic cation transporter-3

The herbicide paraquat (PQ) has increasingly been reported in epidemiological studies to enhance the risk of developing Parkinson's disease (PD). Furthermore, case-control studies report that individuals with genetic variants in the dopamine transporter (DAT, SLC6A) have a higher PD risk when exposed to PQ. However, it remains a topic of debate whether PQ can enter dopamine (DA) neurons through DAT. We report here a mechanism by which PQ is transported by DAT: In its native divalent cation state, PQ2+ is not a substrate for DAT; however, when converted to the monovalent cation PQ+ by either a reducing agent or NADPH oxidase on microglia, it becomes a substrate for DAT and is accumulated in DA neurons, where it induces oxidative stress and cytotoxicity. Impaired DAT function in cultured cells and mutant mice significantly attenuated neurotoxicity induced by PQ+. In addition to DAT, PQ+ is also a substrate for the organic cation transporter 3 (Oct3, Slc22a3), which is abundantly expressed in non-DA cells in the nigrostriatal regions. In mice with Oct3 deficiency, enhanced striatal damage was detected after PQ treatment. This increased sensitivity likely results from reduced buffering capacity by non-DA cells, leading to more PQ+ being available for uptake by DA neurons. This study provides a mechanism by which DAT and Oct3 modulate nigrostriatal damage induced by PQ2+/PQ+ redox cycling.
Competing obesity discourses and critical challenges for health and physical educators

Health and physical education teachers have become subject to epistemological and ethical tensions associated with competing obesity and physical activity discourses. The dominating obesity discourse, underpinned by truth claims from science, encourages educators to pathologise fatness, treat exercise as a medicine and survey student activity levels. A reverse obesity discourse, however, argues that obesity concerns are socially constructed in response to a moral panic surrounding youth lifestyles and these concerns are, of themselves, harmful for health. Educators, accordingly, are drawn in different directions with respect to how to manage their governance role of student bodies and the dissemination of health and physical activity knowledge. In this paper, we discuss this dilemma and draw from Foucauldian and Derridian theorising to offer one potential educational strategy. This strategy rests on the idea that knowledge is not fixed but fluid and, therefore, critical education is less about the transmission of knowledge and more about equipping students with skills so that they can critically engage with uncertainty and negotiate the complexities of social life.
Acid sensitive background potassium channels K2P3.1 and K2P9.1 undergo rapid dynamin-dependent endocytosis

Acid-sensitive, two-pore domain potassium channels, K2P3.1 and K2P9.1, are implicated in cardiac and nervous tissue responses to hormones, neurotransmitters and drugs. K2P3.1 and K2P9.1 leak potassium from the cell at rest and directly impact membrane potential. Hence altering channel number on the cell surface drives changes in cellular electrical properties. The rate of K2P3.1 and K2P9.1 delivery to and recovery from the plasma membrane determines both channel number at the cell surface and potassium leak from cells. This study examines the endocytosis of K2P3.1 and K2P9.1. Plasma membrane biotinylation was used to follow the fate of internalized GFP-tagged rat K2P3.1 and K2P9.1 transiently expressed in HeLa cells. Confocal fluorescence images were analyzed using Imaris software, which revealed that both channels are endocytosed by a dynamin-dependent mechanism and over the course of 60 min, move progressively toward the nucleus. Endogenous endocytosis of human K2P3.1 and K2P9.1 was examined in the lung carcinoma cell line, A549. Endogenous channels are endocytosed over a similar time-scale to the channels expressed transiently in HeLa cells. These findings both validate the use of recombinant systems and identify an endogenous model system in which K2P3.1 and K2P9.1 trafficking can be further studied.
Dissociation of Object and Spatial Vision in Human Extrastriate Cortex: Age-Related Changes in Activation of Regional Cerebral Blood Flow Measured with [15 O]Water and Positron Emission Tomography

We previously reported selective activation of regional cerebral blood flow (rCBF) in occipitotemporal cortex during a face matching task (object vision) and activation in superior parietal cortex during a dot-location matching task (spatial vision) in young subjects, The purpose of the present study was to determine the effects of aging on these extrastriate visual processing systems. Eleven young (mean age 27 4 years) and nine old (mean age 72 7 years) male subjects were studied. Positron emission tomographic scans were performed using a Scanditronix PC10247B tomograph and H215O to measure rCBF. To locate brain areas that were activated by the visual tasks, pixel-by-pixel difference images were computed between images from a control task and images from the face and dot-location matching tasks. Both young and old subjects showed rCBF activation during face matching primarily in occipitotemporal cortex, and activation of superior parietal cortex during dot-location matching. Statistical comparisons of these activations showed that the old subjects had more activation of occipitotemporal cortex during the spatial task and more activation of superior parietal cortex during the object task than did the young subjects. These results show less functional separation of the dorsal and ventral visual pathways in older subjects, and may reflect an age-related reduction in the processing efficiency of these visual cortical areas.
Identifying an indoor air exposure limit for formaldehyde considering both irritation and cancer hazards

Formaldehyde is a well-studied chemical and effects from inhalation exposures have been extensively characterized in numerous controlled studies with human volunteers, including asthmatics and other sensitive individuals, which provide a rich database on exposure concentrations that can reliably produce the symptoms of sensory irritation. Although individuals can differ in their sensitivity to odor and eye irritation, the majority of authoritative reviews of the formaldehyde literature have concluded that an air concentration of 0.3 ppm will provide protection from eye irritation for virtually everyone. A weight of evidence–based formaldehyde exposure limit of 0.1 ppm (100 ppb) is recommended as an indoor air level for all individuals for odor detection and sensory irritation. It has recently been suggested by the International Agency for Research on Cancer (IARC), the National Toxicology Program (NTP), and the US Environmental Protection Agency (US EPA) that formaldehyde is causally associated with nasopharyngeal cancer (NPC) and leukemia. This has led US EPA to conclude that irritation is not the most sensitive toxic endpoint and that carcinogenicity should dictate how to establish exposure limits for formaldehyde. In this review, a number of lines of reasoning and substantial scientific evidence are described and discussed, which leads to a conclusion that neither point of contact nor systemic effects of any type, including NPC or leukemia, are causally associated with exposure to formaldehyde. This conclusion supports the view that the equivocal epidemiology studies that suggest otherwise are almost certainly flawed by identified or yet to be unidentified confounding variables. Thus, this assessment concludes that a formaldehyde indoor air limit of 0.1 ppm should protect even particularly susceptible individuals from both irritation effects and any potential cancer hazard.
What's New in New Forms of Organizing? On the Construction of Gender in Project-Based Work

In several industries, projects are now the normal form of work for individuals. The consequences of project work have not so far been subject to critical inquiry, however. This implies inquiry not only on how people handle project work at work, it also means inquiring into how they live their lives when working by projects. In this paper, we study this from a constructionist gender perspective, in which project work is seen as an ongoing construction of patterns of femininity and masculinity in society. The aim of the paper is to contribute to an understanding of how project work is related to the ongoing construction of femininity and masculinity in the work and lives of human beings. From a narrative study of individuals in the same project team in an IT-consultancy company, we discuss masculinization and femininization in project-based work. It appears that current project work practices imply reproduction of masculinities such as rationality, efficiency, control, devotion to work etc, while femininization is instead found in the rhetoric of the organizational context and the expectations on newly recruited women. The organization was in the process of femininization through rhetoric on 'family friendliness', but everyday life for consultants was not spent at the organization but in project teams in the customers' offices. Projects are special in the sense that they are clearly delimited episodes of work in which it is possible to apply entirely different norms than 'outside' the project - which makes the tendency to reproduce traditional masculinities even stronger.
Altered Thermal Selection Behavior in Mice Lacking Transient Receptor Potential Vanilloid 4

Transient receptor potential vanilloid 4 (TRPV4), a cation channel responsive to hypotonicity, can also be activated by warm temperatures. Moreover, TRPV4-/- mice reportedly exhibit deficits in inflammation-induced thermal hyperalgesia. However, it is unknown whether TRPV4 or related transient receptor potential channels account for warmth perception under injury-free conditions. We therefore investigated the contribution of TRPV4 to thermosensation and thermoregulation in vivo. On a thermal gradient, TRPV4-/- mice selected warmer floor temperatures than wild-type littermates. In addition, whereas wild-type mice failed to discriminate between floor temperatures of 30 and 34°C, TRPV4-/- mice exhibited a strong preference for 34°C. TRPV4-/- mice also exhibited prolonged withdrawal latencies during acute tail heating. TRPV4-/- and wild-type mice exhibited similar changes in behavior on a thermal gradient after paw inflammation. Circadian body temperature fluctuations and thermoregulation in a warm environment were also indistinguishable between genotypes. These results demonstrate that TRPV4 is required for normal thermal responsiveness in vivo.
Deep phylogeographic break among white croaker Pennahia argentata (Sciaenidae, Perciformes) populations in North-western Pacific

The Quaternary cold periods in the North-western Pacific are thought to have greatly influenced the genetic structures of marine species. One hundred and thirty-two individuals of white croaker Pennahia argentata were sampled from 12 localities throughout its distribution range to estimate the demographic history and genetic structure based on mitochondrial DNA cytochrome b gene and control region sequences. Two distinct clades with net genetic divergence of 3% in the control region were detected, one in Chinese coastal waters and the other in Japanese coastal waters. These clades may have been isolated and diverged during Pleistocene low sea levels. Nucleotide diversity was much higher in the Chinese clade than in the Japanese clade. The demographic history of the two clades was examined using neutrality tests and mismatch analyses, and the results indicated Pleistocene population expansion in both clades. Molecular variance and pairwise FST analyses revealed significant differentiation between two Japanese populations and lack of genetic structure in the Chinese populations. The significant geographic structure in white croaker suggests a low level of dispersal in this species. The lack of phylogeographic structure in Chinese coastal waters may reflect a recent range expansion after the last glacial maximum and insufficient time to attain migration-drift equilibrium.
DNA synthesis generally initiates outside the simian virus 40 core origin in vitro

The nucleotide positions at which DNA synthesis initiates in vitro, in the vicinity of the simian virus 40 origin, have been determined. Start sites for DNA synthesis are greatly suppressed over the simian virus 40 core origin. Relatively weak start sites are detected over the 21-bp repeats and T-antigen-binding site I; distal to these regions, stronger start sites are detected. Thus, studies using a model system for eukaryotic DNA replication indicate that DNA synthesis events initiate, in general, outside the core origin.
Complexity Comparison of Non-Binary LDPC Decoders

This paper presents a detailed complexity study of the existing non-binary LDPC decoding algorithms in order to rigorously compare them from a hardware perspective. The Belief Propagation algorithm is first considered as well as its derivative versions in the frequency and logarithm domains. We then focus on the Extended Min-Sum and its recent simplified version. For each algorithm, the number of operations in an elementary step of the check and variable nodes is determined. Finally we evaluate the interest of the application of the simplified Extended Min- Sum algorithm to a new family of non-binary LDPC codes designed in the framework of the DaVinci project 1 .
A Moment Bound for Multi-hinge Classifiers

The success of support vector machines in binary classification relies on the fact that hinge loss employed in the risk minimization targets the Bayes rule. Recent research explores some extensions of this large margin based method to the multicategory case. We show a moment bound for the socalled multi-hinge loss minimizers based on two kinds of complexity constraints: entropy with bracketing and empirical entropy. Obtaining such a result based on the latter is harder than finding one based on the former. We obtain fast rates of convergence that adapt to the unknown margin.
Buprenorphine versus Methadone Maintenance for Opioid Dependence

Buprenorphine at 2 mg and 6 mg daily was compared with methadone at 35 mg and 65 mg during 24 weeks of maintenance among 125 opioid-dependent patients. As hypothesized, 6 mg of buprenorphine were superior to 2 mg of buprenorphine in reducing illicit opioid use, but higher dosage did not improve treatment retention. Self-reported illicit opioid use declined substantially in all groups, but by the third month, significantly more heroin abuse was reported at 2 mg than at 6 mg of buprenorphine or of methadone. From an initial average of $1860/month, month 3 usage dropped to $41 (methadone 65 mg), $73 (methadone 35 mg), $118 (buprenorphine 6 mg), and $35I/month (buprenorphine 2 mg). Days of use also dropped from 29 days to 1.7 (methadone 65 mg), 2.8 (methadone 35 mg), 4.0 (buprenorphine 6 mg), and 6.6 days/month (buprenorphine 2 mg). This relatively low efficacy for 2 mg of buprenorphine persisted through month 6 of the trial, with 7.2 days/month and $235/month of use for buprenorphine at 2 mg versus 1.9 days/month and $65/month for the other three groups. Increased opioid abuse also was associated with significantly greater and persistent opioid withdrawal symptoms. Our secondary hypothesis, that buprenorphine would be equivalent to methadone in efficacy, was not supported. Treatment retention was significantly better on methadone (20 us. 16 weeks), and methadone patients had significantly more opioid-free urines (51% vs. 26%). Abstinence for at least 3 weeks was also more common on methadone than buprenorphine (65% vs. 27%). Thus, methadone was clearly superior to these two buprenorphine doses, but illicit opioid use was reduced more by higher than lower buprenorphine dosage. Future studies need to examine higher sublingual buprenorphine doses of 12 mg to 20 mg daily for potential efficacy.
Social deprivation and prognostic benefits of cardiac surgery: observational study of 44 902 patients from five hospitals over 10 years

Objective To assess the effects of social deprivation on survival after cardiac surgery and to examine the influence of potentially modifiable risk factors. Design Analysis of prospectively collected data. Prognostic models used to examine the additional effect of social deprivation on the end points. Setting Birmingham and north west England. Participants 44 902 adults undergoing cardiac surgery, 1997-2007. Main outcome measures Social deprivation with census based 2001 Carstairs scores. All cause mortality in hospital and at mid-term follow-up. Results In hospital mortality for all cardiac procedures was 3.25% and mid-term follow-up (median 1887 days; range 1180-2725 days) mortality was 12.4%. Multivariable analysis identified social deprivation as an independent predictor of mid-term mortality (hazard ratio 1.024, 95% confidence interval 1.015 to 1.033; P<0.001). Smoking (P<0.001), body mass index (BMI, P<0.001), and diabetes (P<0.001) were associated with social deprivation. Smoking at time of surgery (1.294, 1.191 to 1.407, P<0.001) and diabetes (1.305, 1.217 to 1.399, P<0.001) were independent predictors of mid-term mortality. The relation between BMI and mid-term mortality was non-linear and risks were higher in the extremes of BMI (P<0.001). Adjustment for smoking, BMI, and diabetes reduced but did not eliminate the effects of social deprivation on mid-term mortality (1.017, 1.007 to 1.026, P<0.001). Conclusions Smoking, extremes of BMI, and diabetes, which are potentially modifiable risk factors associated with social deprivation, are responsible for a significant reduction in survival after surgery, but even after adjustment for these variables social deprivation remains a significant independent predictor of increased risk of mortality.
Introduction to the Special Issue of Social Development: Emotion Socialization in Childhood and Adolescence

This Special Issue of Social Development focuses on social contextual influences that shape emotional repertoires for those in middle childhood and adolescence. Acknowledging a broad array of potential influences, the emphasis of this issue is on family emotional processes. Research advances over the past two decades have contributed considerably to our knowledge of maternal practices in shaping emotion in infants and young children (for recent reviews refer to Denham, Bassett, & Wyatt, 2006 and Eisenberg, Cumberland, & Spinrad, 1998; and a special issue of Marriage and Family Review edited by Fabes,Valiente, & Leonard, 2002). Yet, there continues to be a paucity of research examining parents’ role in socializing emotional behavior in older children, particularly during the adolescent years. The collection of manuscripts in this Special Issue represents a significant step in addressing this gap in our knowledge. In this Introduction we provide an overview of some of the central themes that unify this body of research including salient adaptive and maladaptive developmental processes relevant to emotion socialization with older children and the conceptual and methodological issues that are centrally relevant to this topic of inquiry. Recent empirical advances and conceptual developments in the field are highlighted with recommendations for future research integrated throughout.