Miracle-dz/UniFAR-FTUs huggingface dataset:
Phosphosite charge rather than shootward localization determines OCTOPUS activity in root protophloem

Significance The evolution of plant vasculature was a key event in earth history because it enabled plants to effectively colonize land. The phloem vasculature was particularly important in this process. In angiosperms, the dominant group of extant terrestrial plants, phloem is assembled from specific conductive cells, the sieve elements. Here we provide evidence that a master regulator of the commitment to sieve element fate in Arabidopsis is strongly conserved and already present in the most basal extant angiosperms. We demonstrate the exquisite dosage-sensitive action of this polar-localized protein and show that its activity is in part regulated through the charge in a phosphorylation site. Surprisingly, however, its shootward polar localization does not appear to be essential for its function. Polar cellular localization of proteins is often associated with their function and activity. In plants, relatively few polar-localized factors have been described. Among them, the plasma membrane-associated Arabidopsis proteins OCTOPUS (OPS) and BREVIS RADIX (BRX) display shootward and rootward polar localization, respectively, in developing root protophloem cells. Both ops and brx null mutants exhibit defects in protophloem differentiation. Here we show that OPS and BRX act genetically in parallel in this process, although OPS dosage increase mends defects caused by brx loss-of-function. OPS protein function is ancient and conserved in the most basal angiosperms; however, many highly conserved structural OPS features are not strictly required for OPS function. They include a BRASSINOSTEROID INSENSITIVE 2 (BIN2) interaction domain, which supposedly mediates gain-of-function effects obtained through ectopic OPS overexpression. However, engineering an increasingly positive charge in a critical phosphorylation site, S318, progressively amplifies OPS activity. Such hyperactive OPS versions can even complement the severe phenotype of brx ops double mutants, and the most active variants eventually trigger gain-of-function phenotypes. Finally, BRX-OPS as well as OPS-BRX fusion proteins localize to the rootward end of developing protophloem cells, but complement ops mutants as efficiently as shootward localized OPS. Thus, our results suggest that S318 phosphorylation status, rather than a predominantly shootward polar localization, is a primary determinant of OPS activity.
Physical activity and colorectal cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population.

OBJECTIVE Higher levels of physical activity have been consistently associated with a decreased risk of colon cancer, but not rectal cancer, in Western populations. The present study systematically evaluated epidemiologic evidence on the association between physical activity and colorectal cancer risk among the Japanese population. METHODS Original data were obtained from MEDLINE searched using PubMed or from searches of the Ichushi database, complemented by manual searches. The associations were evaluated based on the strength of evidence, the magnitude of association and biologic plausibility. RESULTS Two cohort studies and six case-control studies were identified. A weak to strong protective association between physical activity and colon cancer risk was observed in both cohort studies, showing a graded relationship, and among the majority of case-control studies, with some showing a dose-response relationship. The association observed in cohort studies was more consistent and stronger in men than in women and for proximal colon cancer than for distal colon cancer. A protective association with rectal cancer was found only in case-control studies, but the evidence was less consistent and weaker than that observed for colon cancer. CONCLUSIONS Physical activity probably decreases the risk of colorectal cancer among the Japanese population. More specifically, the evidence for the colon is probable, whereas that for the rectum is insufficient.
Neural substrates underlying fear-evoked freezing: the periaqueductal grey–cerebellar link

At the heart of the brain circuitry underlying fear behaviour is the periaqueductal grey (PAG). We address an important gap in understanding regarding the neural pathways and mechanisms that link the PAG to distinct patterns of motor response associated with survival behaviours. We identify a highly localised part of the cerebellum (lateral vermal lobule VIII, pyramis) as a key supraspinal node within a chain of connections that links the PAG to the spinal cord to elicit fear‐evoked freezing behaviour. Expression of fear‐evoked freezing behaviour, both conditioned and innate, is dependent on cerebellar pyramis neural input–output pathways. We also address an important controversy in the literature, namely whether or not ventrolateral PAG (vlPAG) increases muscle tone. We provide evidence that activation of the vlPAG causes an increase in α‐motoneurone excitability, consistent with a role in generating muscle tone associated with fear‐evoked freezing.
Individuals at high risk for type 2 diabetes invited to a lifestyle program: characteristics of participants versus non-participants (the HUNT Study) and 24-month follow-up of participants (the VEND-RISK Study)

Objective Prevention of type 2 diabetes mellitus is possible through lifestyle programs, but the effect depends on the program's content, resources, and setting. Lifestyle programs are often confronted with high rates of non-participation and attrition. This study invited individuals at high risk for type 2 diabetes to a lifestyle program in the Norwegian primary healthcare setting. The aims were to investigate possible differences in characteristics between participants and non-participants and to study the effect of the lifestyle program at 24-month follow-up for participants. Research design and methods Individuals identified at high risk for type 2 diabetes during the third survey of the Nord-Trøndelag Health Study (HUNT3) from two municipalities (n=332) were invited to a lifestyle program (the VEND-RISK Study). A cross-sectional design was used to explore if the participants’ characteristics differed from non-participants. A non-randomized, single-arm, pre–post examination was used to examine the effect of the lifestyle program on participants’ characteristics at 24-month follow-up. Results Of all individuals at high risk for type 2 diabetes invited to the lifestyle program, 86% (287/332) declined to participate. Non-participating women had fewer years of education (p<0.001), compared with participating women. For men, no differences were seen between non-participants and participants. Among all participants (n=45) at 24-month follow-up, none had developed type 2 diabetes, and HbA1c (p<0.001) had decreased significantly. There was a small reduction in mean body mass index from baseline to 24 months that was not statistically significant. For women, waist circumference (−4.0 cm, p<0.001) decreased significantly. Conclusions Future research regarding individuals at high risk for type 2 diabetes in the primary healthcare lifestyle program should focus on how to promote recruitment of women with low education. Participants attending this study's lifestyle program improved their cardiometabolic markers. Clinical trials registration NCT01135901; Results.
Young Offspring at Genetic Risk of Adult Psychoses: The Form of the Trajectory of IQ or Memory May Orient to the Right Dysfunction at the Right Time

Objective Neurocognitive dysfunctions analogous to those of adult patients have been detected in children at risk of schizophrenia and bipolar disorder. This led to the following developmental question: Do IQ and memory impairments exhibit different developmental courses from childhood to young adulthood in terms of stability or fluctuations? Methods In a high risk sample, we used a step by step sampling approach to narrow-down the early disease mechanisms. Upstream, we started with a 20-year follow-up of 48 densely affected multigenerational kindreds, including 1500 clinically characterized adult members. We then identified 400 adult members affected by a DSM-IV schizophrenia or bipolar disorder. Downstream, we finally focused on 65 offspring (of an affected parent) aged 7 to 22, who were administered a neuropsychological battery. We then constructed cross-sectional trajectories that were compared to those of controls. Results The childhood IQ deficit displayed a stability until young adulthood. The delay in visual memory exhibited a non-linear two-stage trajectory: a lagging period during childhood followed by a recuperation period from adolescence until adulthood, as supported by a significant Group x Age Periods interaction. No data suggested deterioration between 7 and 22. Conclusion In these offspring at genetic risk, the developmental trajectory of global IQ impairment may not apply to specific domains of cognition such as episodic memory. Different cognitive dysfunctions would mark different developmental courses. The shape of the trajectories might itself have a meaning and provide empirical leads for targeting the right dysfunction at the right time in future prevention research.
Angiogenic Imbalance and Residual Myocardial Injury in Recovered Peripartum Cardiomyopathy Patients

Background—Recent studies suggest that angiogenic imbalance during pregnancy may lead to acute peripartum cardiomyopathy (PPCM). We propose that angiogenic imbalance and residual cardiac dysfunction may exist even after recovery from PPCM. Methods and Results—Twenty-nine women at least 12 months after presentation with PPCM, who exhibited recovery of left ventricular (LV) ejection fraction (≥50%), were included in the study (mean age 35±6 years, LV ejection fraction 61.0±3.9%). The number of circulating endothelial progenitor cells (EPCs) and plasma levels of proangiogenic vascular endothelial growth factor and of soluble vascular endothelial growth factor receptor Flt1 (sFlt1) were measured. All patients underwent comprehensive cardiac function assessment, including tissue Doppler imaging and 2-dimensional (2D) strain echocardiography. All measurements were compared with healthy controls. Patients with a history of PPCM have significantly higher sFlt1 concentrations (median [25th–75th percentile]; 149.57, [63.14–177.89] versus 20.29, [15.00–53.89] pg/mL, P<0.001) and significantly decreased vascular endothelial growth factor/sFlt1 ratio (P=0.012) compared with controls, with a trend toward lower concentration of circulating CD34+/KDR+ levels. In addition, patients with PPCM had lower early velocities E′ septal (9.9±2.1 versus 11.0±1.5 cm/s, P=0.02), with a significantly lower systolic velocity S′ septal (7.6±1.2 versus 8.5±1.2 cm/s, P=0.003) by tissue Doppler imaging. Significantly lower LV global longitudinal (−19.1±3.3 versus −22.7±2.2%, P<0.001) and apical circumferential 2D strain (−16.6±4.9 versus −21.2±7.9, P=0.02) were present in patients with PPCM compared with controls. Conclusions—Higher concentration of sFlt1 with concomitant decreased circulating endothelial progenitor cell levels along with inappropriate attenuated vascular endothelial growth factor levels may imply an angiogenic imbalance that exists even after recovery and may thus predispose to PPCM. In addition, tissue Doppler imaging and 2D strain were able to identify residual myocardial injury in post-PPCM women with apparent recovery of LV systolic function. Both angiogenic imbalance and residual myocardial injury may play an important role in the recurrence of LV dysfunction during subsequent pregnancies.
Report of Recombinant Norovirus GII.g/GII.12 in Beijing, China

Background Norovirus (NoV) has been recognized as the most important cause of nonbacterial acute gastroenteritis affecting all age group people in the world. Genetic recombination is a common occurance in RNA viruses and many recombinant NoV strains have been described since it was first reported in 1997. However, the knowledge of recombinant NoV in China is extremely limited. Methods A total of 685 stool specimens were tested for NoV infection from the acute gastroenteritis patients who visited one general hospital in Beijing from April 2009 to November 2011. The virus recombination was identified by constructing phylogenetic trees of two genes, further SimPlot and the maximum chi-square analysis. Results The overall positive rate was 9.6% (66/685). GII.4 New Orleans 2009 and GII.4 2006b variants were the dominant genotype. Four GII.g/GII.12 and one GII.12/GII.3 recombinant strains were confirmed, and all derived from adult outpatients. The predictive recombination point occurred at the open reading frame (ORF)1/ORF2 overlap. Conclusions The GII.g ORF1/GII.12ORF2 recombinant has been reported in several countries and it was the first report of this recombinant in China.
Adenosine 3',5'-phosphate phosphodiesterase and pheromone response in the yeast Saccharomyces cerevisiae

Theophylline, aminophylline, and isobutylmethylxanthine, compounds reported to be inhibitors of adenosine 3',5'-phosphate (cAMP) phosphodiesterase, prevented the alpha-factor-induced cell cycle arrest of Saccharomyces cerevisiae a cells. To determine whether the in vivo effect of these methylxanthines on yeast pheromone response was related to their known biochemical mode of action, two assays for cAMP phosphodiesterase based on affinity of the product of the reaction (5'-AMP) for boronate groups were developed and were used to monitor the activity of the low Km cAMP phosphodiesterase present in yeast extracts. It was found that the relative efficacy of the methylxanthines as inhibitors of this enzyme in vitro was correlated with the degree to which they antagonized alpha-factor action in vivo. These results were consistent with our previous proposal that pheromone action involves a lowering of cAMP level in the target cell.
Is Structural Equation Modeling Advantageous for the Genetic Improvement of Multiple Traits?

Structural equation models (SEMs) are multivariate specifications capable of conveying causal relationships among traits. Although these models offer insights into how phenotypic traits relate to each other, it is unclear whether and how they can improve multiple-trait selection. Here, we explored concepts involved in SEMs, seeking for benefits that could be brought to breeding programs, relative to the standard multitrait model (MTM) commonly used. Genetic effects pertaining to SEMs and MTMs have distinct meanings. In SEMs, they represent genetic effects acting directly on each trait, without mediation by other traits in the model; in MTMs they express overall genetic effects on each trait, equivalent to lumping together direct and indirect genetic effects discriminated by SEMs. However, in breeding programs the goal is selecting candidates that produce offspring with best phenotypes, regardless of how traits are causally associated, so overall additive genetic effects are the matter. Thus, no information is lost in standard settings by using MTM-based predictions, even if traits are indeed causally associated. Nonetheless, causal information allows predicting effects of external interventions. One may be interested in predictions for scenarios where interventions are performed, e.g., artificially defining the value of a trait, blocking causal associations, or modifying their magnitudes. We demonstrate that with information provided by SEMs, predictions for these scenarios are possible from data recorded under no interventions. Contrariwise, MTMs do not provide information for such predictions. As livestock and crop production involves interventions such as management practices, SEMs may be advantageous in many settings.
Virtual Reality Cues for Binge Drinking in College Students

We investigated the ability of virtual reality (VR) cue exposure to trigger a desire for alcohol among binge-drinking students. Fifteen binge-drinking college students and eight students who were nonbingers were immersed into a neutral-cue environment or room (underwater scenes), followed by four alcohol-cue rooms (bar, party, kitchen, argument), followed by a repeat of the neutral room. The virtual rooms were computer generated via head-mounted visual displays with associated auditory and olfactory stimuli. In each room, participants reported their subjective cravings for alcohol, the amount of attention given to the sight and smell of alcohol, and how much they were thinking of drinking. A 2 x 6 (type of drinker by VR room) repeated measures ANOVA was conducted on the responses to each question. After alcohol exposure, binge drinkers reported significantly higher cravings for and thoughts of alcohol than nonbinge drinkers, whereas differences between the groups following the neutral rooms were not significant.
The effectiveness of combining information retrieval strategies for European languages

Building an effective Information Retrieval system requires various design choices, ranging from the weighting scheme of the type of morphological normalization. The combination of runs has become a standard technique to reap the benefits of different run types. Until now, systematic studies of the effectiveness of combination strategies have only been carried out for English. This paper provides an exploratory overview of the effectiveness of combination methods in nine European languages. We demonstrate that the combination of effective information retrieval strategies can lead to significant improvements of retrieval effectiveness. Furthermore, we analyze the relative impact of retrieving more relevant documents and of improved ranking of relevant documents. The experimental evidence is obtained using the 2003 testsuite of the cross-language evaluation forum (CLEF).
Quotient Equations and Integrals of Motion for Vector Massless Field

In this article a group-theoretical aspect of the method of dimensional reduction is presented. Then, on the base of symmetry analysis of an anisotropic space geometrical description of dimensional reduction of equations for vector massless field is given. Formula for calculating components of the energymomentum tensor from the variables of the field factor-equations is derived.
Optical Models for Direct Volume Rendering

This tutorial survey paper reviews several different models for light interaction with volume densities of absorbing, glowing, reflecting, and/or scattering material. They are, in order of increasing realism, absorption only, emission only, emission and absorption combined, single scattering of external illumination without shadows, single scattering with shadows, and multiple scattering. For each model the paper provides the physical assumptions, describes the applications for which it is appropriate, derives the differential or integral equations for light transport, presents calculation methods for solving them, and shows output images for a data set representing a cloud. Special attention is given to calculation methods for the multiple scattering model. >
A lidar perception scheme for intelligent vehicle navigation

In urban environments, detection of moving obstacles and free space determination are key issues for driving assistance systems or autonomous vehicles. This paper presents a lidar-based perception system for passenger-cars, able to do simultaneously mapping and moving obstacles detection. Nowadays, many lidars provide multi-layer and multi-echo measurements. A smart way to handle this multi-modality is to use grids projected on the road surface in both global and local frames. The global one generates the mapping and the local is used to deal with moving objects. An approach based on both positive and negative accumulation has been developed to address the remnant problem of quickly moving obstacles. This method is also well suited for multi-layer and multi-echo sensors. Experimental results carried out with an IBEO Alasca and an Applanix positioning system show the performance of such a perception strategy.
Oxidative stress induced in E. coli by the human antimicrobial peptide LL-37

Antimicrobial peptides (AMPs) are thought to kill bacterial cells by permeabilizing their membranes. However, some antimicrobial peptides inhibit E. coli growth more efficiently in aerobic than in anaerobic conditions. In the attack of the human cathelicidin LL-37 on E. coli, real-time, single-cell fluorescence imaging reveals the timing of membrane permeabilization and the onset of oxidative stress. For cells growing aerobically, a CellROX Green assay indicates that LL-37 induces rapid formation of oxidative species after entry into the periplasm, but before permeabilization of the cytoplasmic membrane (CM). A cytoplasmic Amplex Red assay signals a subsequent burst of oxidative species, most likely hydrogen peroxide, shortly after permeabilization of the CM. These signals are much stronger in the presence of oxygen, a functional electron transport chain, and a large proton motive force (PMF). They are much weaker in cells growing anaerobically, by either fermentation or anaerobic respiration. In aerobic growth, the oxidative signals are attenuated in a cytochrome oxidase–bd deletion mutant, but not in a –bo3 deletion mutant, suggesting a specific effect of LL-37 on the electron transport chain. The AMPs melittin and LL-37 induce strong oxidative signals and exhibit O2-sensitive MICs, while the AMPs indolicidin and cecropin A do not. These results suggest that AMP activity in different tissues may be tuned according to the local oxygen level. This may be significant for control of opportunistic pathogens while enabling growth of commensal bacteria.
Laboratory Diagnosis of Tuberculous Meningitis – Is There a Scope for Further Improvement?

Aims: Tuberculous meningitis (TBM) still remains a diagnostic challenge because of inconsistent clinical presentation and lack of rapid, sensitive and specific tests. This study was carried out to diagnose TBM by a combination of direct microscopy on Ziehl-Neelsen (ZN) staining, culture by conventional Lowenstein Jensen (LJ) media and Bactec MGIT 960 system in clinically suspected cases, supported by laboratory parameters. Materials and Methods: A total of 164 cerebrospinal fluid (CSF) samples from suspected cases of TBM were processed for direct acid fast bacilli (AFB) smear examination, and culture on Bactec MGIT 960 and LJ media. Results: AFB were detected on direct smears in 13 of 164 (7.9%) specimens and Mycobacterium tuberculosis was isolated by at least one of the culture methods from 49 (29.8%) CSF samples of which 45 (27.4%) were detected positive for M. tuberculosis by MGIT 960 culture and 18 (10.9%) by culture on LJ medium. The mean time of detection in MGIT and LJ media for M. tuberculosis were 18 and 38 days, respectively. Conclusions: A combination of laboratory parameters like smear microscopy, conventional culture and automated method like Bactec MGIT increases the sensitivity of diagnosing TBM as compared to any single method.