bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergistic defects in pre-rRNA processing from mutations in the U3-specific protein Rrp9 and U3 snoRNA
Authors: Clerget Guillaume , Bourguignon-Igel Valérie , Marmier-Gourrier Nathalie , Rolland Nicolas , Wacheul Ludivine , Manival Xavier , Charron Christophe , Kufel Joanna , Méreau Agnès , Senty-Ségault Véronique , Tollervey David , Lafontaine Denis L J , Branlant Christiane , Rederstorff Mathieu 
Published: January 2020

Abstract
U3 snoRNA and the associated Rrp9/U3-55K protein are essential for 18S rRNA production by the SSU-processome complex. U3 and Rrp9 are required for early pre-rRNA cleavages at sites A0, A1 and A2, but the mechanism remains unclear. Substitution of Arg 289 in Rrp9 to Ala (R289A) specifically reduced cleavage at sites A1 and A2. Surprisingly, R289 is located on the surface of the Rrp9 β-propeller structure opposite to U3 snoRNA. To understand this, we first characterized the protein-protein interaction network of Rrp9 within the SSU-processome. This identified a direct interaction between the Rrp9 β-propeller domain and Rrp36, the strength of which was reduced by the R289A substitution, implicating this interaction in the observed processing phenotype. The Rrp9 R289A mutation also showed strong synergistic negative interactions with mutations in U3 that destabilize the U3/pre-rRNA base-pair interactions or reduce the length of their linking segments. We propose that the Rrp9 β-propeller and U3/pre-rRNA binding cooperate in the structure or stability of the SSU-processome. Additionally, our analysis of U3 variants gave insights into the function of individual segments of the 5′-terminal 72-nt sequence of U3. We interpret these data in the light of recently reported SSU-processome structures.
Cas3/I-C mediated target DNA recognition and cleavage during CRISPR interference are independent of the composition and architecture of Cascade surveillance complex
Authors: Nimkar Siddharth , Anand B 
Published: January 2020

AbstractIn type I CRISPR-Cas system, Cas3—a nuclease cum helicase—in cooperation with Cascade surveillance complex cleaves the target DNA. Unlike the Cascade/I-E, which is composed of five subunits, the Cascade/I-C is made of only three subunits lacking the CRISPR RNA processing enzyme Cas6, whose role is assumed by Cas5. How these differences in the composition and organization of Cascade subunits in type I-C influence the Cas3/I-C binding and its target cleavage mechanism is poorly understood. Here, we show that Cas3/I-C is intrinsically a single-strand specific promiscuous nuclease. Apart from the helicase domain, a constellation of highly conserved residues—which are unique to type I-C—located in the uncharacterized C-terminal domain appears to influence the nuclease activity. Recruited by Cascade/I-C, the HD nuclease of Cas3/I-C nicks the single-stranded region of the non-target strand and positions the helicase motor. Powered by ATP, the helicase motor reels in the target DNA, until it encounters the roadblock en route, which stimulates the HD nuclease. Remarkably, we show that Cas3/I-C supplants Cas3/I-E for CRISPR interference in type I-E in vivo, suggesting that the target cleavage mechanism is evolutionarily conserved between type I-C and type I-E despite the architectural difference exhibited by Cascade/I-C and Cascade/I-E.
A prospective study of pre-employment psychological testing amongst police recruits
Authors: Marshall R E , Milligan-Saville J S , Steel Z , Bryant R A , Mitchell P B , Harvey S B 
Published: January 2020

Abstract

Background
Pre-employment psychological screening to detect psychological vulnerability is common amongst emergency service organizations worldwide, yet the evidence for its ability to predict poor mental health outcomes is limited with published studies looking at post-recruitment research data rather than data collected by the organizations themselves.

Aims
The present study sought to investigate the ability of pre-employment screening to predict later psychological injury-related absenteeism amongst police officers.

Methods
A nested case–control study using prospective data was conducted. One hundred and fifty police officers with a liability-accepted psychological injury were matched to a control group of 150 psychologically healthy officers. Conditional logistic regression was used to examine associations between Minnesota Multiphasic Personality Inventory-2 (MMPI-2) scales measuring factors research has shown to predict psychological injury (Neuroticism, Psychoticism, Introversion, Disconstraint and Aggressiveness) and psychopathology (Depression, Anxiety and post-traumatic stress disorder [PTSD]) with subsequent psychological injury.

Results
Contrary to expectations, we were unable to demonstrate any association between validated pre-employment measures of personality and psychopathology with mental health outcomes amongst newly recruited police officers over a 7-year follow-up.

Conclusions
Other measures may be better able to predict future mental health problems in police recruits.
Public versus private equity
Authors: Stulz René M 
Published: January 2020

AbstractThe last 20 years or so have seen a sharp decline in public equity. I present a framework that explains the forces that cause the listing propensity of firms to change over time. This framework highlights the benefits and costs of a public listing compared to the benefits and costs of financing with private equity. With this framework, the decline in public equity is explained by the increased supply of funds for private equity and changes in the nature of firms. The increase in the importance of intangible assets makes it costlier for young firms to be public when the alternative is funding through private equity from investors who have specialized knowledge that enables them to better understand the business model of young firms and contribute to the development of that business model in contrast to passive public equity investors.
Preparing for CBME: How often are faculty observing residents?
Authors: George Sheenagh J K , Manos Sarah , Wong Kenny K 
Published: January 2020

Abstract

Background
The Royal College of Physicians and Surgeons of Canada officially launched ‘Competence by Design’ in July 2017, moving from time-based to outcomes-based training. Transitioning to competency-based medical education (CBME) necessitates change in resident assessment. A greater frequency of resident observation will likely be required to adequately assess whether entrustable professional activities have been achieved.

Purpose
Characterize faculty and resident experiences of direct observation in a single paediatric residency program, pre-CBME implementation. Qualitatively describe participants’ perceived barriers and incentives to participating in direct observation.

Methods
Surveys were sent to paediatric residents and faculty asking for demographics, the frequency of resident observation during an average 4-week rotation, perceived ideal frequency of observation, and factors influencing observation frequency. Descriptive data were analyzed. Institutional research ethics board approval was received.

Results
The response rate was 54% (34/68 faculty and 16/25 residents). When asked the MAXIMUM frequency FACULTY observed a resident take a history, perform a physical examination, or deliver a plan, the median faculty reply was 1, 2, and 3, for outpatient settings and 0, 1, and 2, for inpatient settings. The median RESIDENT reply was 2, 4, and 10 for outpatient settings and 1, 2, and 20 for inpatient settings. When asked the MINIMUM frequency for each domain, the median FACULTY and RESIDENT reply was 0, except for delivering a plan in the inpatient setting. Faculty reported observing seniors delivering the plan more frequently than junior residents. Faculty and resident median replies for how frequently residents should be observed for each domain were the same, three to four, three to four, and five to six times. Four per cent of faculty reported regularly scheduling observations, and 77% of residents regularly ask to be observed. The most common barriers to observation were too many patients to see and both faculty and residents were seeing patients at the same time. Most faculty and resident responders felt that observation frequency could be improved if scheduled at the start of the rotation; faculty were provided a better tool for assessment; and if residents asked to be observed.

Conclusions
This study provides baseline data on how infrequent faculty observation is occurring and at a frequency lower than what faculty and residents feel is necessary. The time needed for observation competes with clinical service demands, but better scheduling strategies and assessment tools may help.
Plasma Membrane Aquaporin Members PIPs Act in Concert to Regulate Cold Acclimation and Freezing Tolerance Responses in Arabidopsis thaliana
Authors: Rahman Arifa , Kawamura Yukio , Maeshima Masayoshi , Rahman Abidur , Uemura Matsuo 
Published: January 2020

AbstractAquaporins play a major role in plant water uptake at both optimal and environmentally stressed conditions. However, the functional specificity of aquaporins under cold remains obscure. To get a better insight to the role of aquaporins in cold acclimation and freezing tolerance, we took an integrated approach of physiology, transcript profiling and cell biology in Arabidopsis thaliana. Cold acclimation resulted in specific upregulation of PIP1;4 and PIP2;5 aquaporin (plasma membrane intrinsic proteins) expression, and immunoblotting analysis confirmed the increase in amount of PIP2;5 protein and total amount of PIPs during cold acclimation, suggesting that PIP2;5 plays a major role in tackling the cold milieu. Although single mutants of pip1;4 and pip2;5 or their double mutant showed no phenotypic changes in freezing tolerance, they were more sensitive in root elongation and cell survival response under freezing stress conditions compared with the wild type. Consistently, a single mutation in either PIP1;4 or PIP2;5 altered the expression of a number of aquaporins both at the transcriptional and translational levels. Collectively, our results suggest that aquaporin members including PIP1;4 and PIP2;5 function in concert to regulate cold acclimation and freezing tolerance responses.
The Price of Twin Earth
Authors: Ashby Brandon James 
Published: January 2020

AbstractLiberals about perceptual contents claim that perceptual experiences can represent kinds and specific, familiar individuals as such; they also claim that the representation of an individual or kind as such by a perceptual experience will be reflected in the phenomenal character of that experience. Conservatives always deny the latter and sometimes also the former claim. I argue that neither liberals nor conservatives have adequately appreciated how the content internalism/externalism debate bears on their views. I show that perceptual content internalism entails conservativism when conjoined with one other, extremely plausible premise. Hence, liberals are committed to perceptual contents externalism, yet they have failed to fully address the consequences that this has for their view. Moreover, the argument is easily adapted to perceptual experiences of Twin Earthable properties, like colour and shape. I use this last result to show why existing conservative arguments that appeal to Twin Earth plausibly overgeneralize.
CP violations in a predictive A4 symmetry model
Authors: Nguyen T Phong , Hue L T , Si D T , Thuc T T 
Published: January 2020

Abstract
We will investigate numerically a seesaw model with $A_4$ flavor symmetry to find allowed regions satisfying the current experimental neutrino oscillation data, then use them to predict physical consequences. Namely, the lightest active neutrino mass is of the order of $\mathcal{O}(10^{-2})$ eV. The effective neutrino mass $|\langle m\rangle|$ associated with neutrinoless double beta decay is in the range $[0.002 \,\mathrm{eV},0.038\,\mathrm{eV}]$ and $[0.048\,\mathrm{eV},0.058\,\mathrm{eV}]$, corresponding to the normal and the inverted hierarchy schemes, respectively. Other relations among relevant physical quantities are shown, so that they can be determined if some of them are confirmed experimentally. The recent data of the baryon asymmetry of the Universe ($\eta_B$) can be explained via leptogenesis caused by the effect of the renormalization group evolution on the Dirac Yukawa couplings, provided the right-handed neutrino mass scale $M_0$ ranges from $\mathcal{O}(10^8)$ GeV to $\mathcal{O}(10^{12})$ GeV for $\tan\beta =3$. This allowed $M_0$ range is different from the scale of $\mathcal{O}(10^{13})$ GeV for other effects that also generate a consistent $\eta_B$ from leptogenesis. The branching ratio of the decay $ \mu \rightarrow\,e\gamma$ may reach future experimental sensitivity for very light values of $M_0$. Hence, it will be inconsistent with the $M_0$ range predicted from the $\eta_B$ data whenever this decay is detected experimentally.
GAMMA SPECTRUM STABILIZATION FOR ENVIRONMENTAL RADIATION MONITORING STATIONS USING NAI(TL) DETECTOR
Authors: Hung Dinh Tien , Van Hiep Cao , Khang Pham Dinh , Hai Nguyen Xuan , Anh Nguyen Ngoc , Dinh D A , Hao T V Nhan , Pham V 
Published: January 2020

Abstract
Gamma spectrum measured by an NaI(Tl) detector is known to be unstable with the in situ temperature. In the present work, an advanced method has been applied to stabilize the gamma spectrum measured by the NaI(Tl) detector at environmental radiation monitoring (ERM) stations. The method is based on experimental data obtained under controlled conditions in laboratory. In the temperature range from 4 to 45°C, the relative deviation of the peak positions within the stabilized gamma spectrum is less than 2%. To test this method in a real scenario, it has been integrated into the ERM station at the Military Institute of Chemical and Environmental Engineering in Hanoi, Vietnam. The results show that the proposed method is ready for a real application.
Physical Illnesses Before Diagnosed as Schizophrenia: A Nationwide Case-Control Study
Authors: Chen Yi-Lung , Pan Chun-Hung , Chang Chi-Kang , Chen Pao-Huan , Chang Hu-Ming , Tai Ming-Hong , Su Sheng-Shiang , Tsai Shang-Ying , Chen Chiao-Chicy , Kuo Chian-Jue 
Published: January 2020

AbstractSome physical illnesses are potentially associated with the development of schizophrenia. However, few studies have investigated these associations. Here, we examined physical illnesses and medical utilization patterns existing before patients received a diagnosis of schizophrenia. We enrolled a large representative cohort of the general population in Taiwan (N = 1 000 000) and identified 1969 young patients with a new diagnosis of schizophrenia from January 1, 2000 to December 31, 2013. We conducted a nested case-control study based on risk-set sampling. Each case was age-matched and sex-matched with 4 controls selected from the general population. The case and control groups were compared on the basis of various clinical characteristics. Conditional logistic regression was used to estimate the magnitude of risk associated with newly diagnosed schizophrenia. Within the 1 year before the schizophrenia diagnosis, the cases were most likely to visit the psychiatry department, followed by internal medicine and family medicine departments. According to multivariate analysis, compared with the controls, the cases had substantially higher risk of physical conditions in the prodromal phase, including hypertension (adjusted risk ratio [aRR] = 1.93, P = .001), other forms of heart disease (aRR = 2.07, P &lt; .001), cerebrovascular diseases (aRR = 2.96, P = .001), chronic obstructive pulmonary disease (aRR = 1.50, P = .005), asthma (aRR = 1.76, P = .003), and irritable bowel syndrome (aRR = 2.00, P &lt; .001). A wide range of psychiatric diseases and concomitant use of medications were significantly associated with schizophrenia development. In conclusion, several physical illnesses were identified to be associated with schizophrenia development, indicating that people with these illnesses could be vulnerable to schizophrenia.
Localization of Early-Stage Visual Processing Deficits at Schizophrenia Spectrum Illness Onset Using Magnetoencephalography
Authors: Sklar Alfredo L , Coffman Brian A , Salisbury Dean F 
Published: January 2020

AbstractImpairments in early-stage visual processing are observed in chronic psychosis. However, their presence, localization within the brain, and contribution to cognitive symptoms remain less well established early in disease course. The present study utilized magnetoencephalography (MEG) to examine sensory responses within primary visual cortex (V1). MEG was recorded from 38 individuals diagnosed with a schizophrenia spectrum illness at first psychotic episode (FESz) and 38 matched healthy controls (HC) during visual search tasks. The inverse solution for cortical activity contributing to the M100 visual evoked field was derived. Task performance and V1 activation were compared between groups. FESz exhibited a reduced V1 response relative to HC. This group deficit, however, was selective for the left hemisphere (LH). A similar interaction was observed for response time with FESz exhibiting slower responses to right visual field targets, a difference not observed among HC. Among FESz, larger LH V1 activity was associated with larger hallucination subscale scores on the Scale for the Assessment of Positive Symptoms. Early-stage visual processing deficits localized to V1 are present at disease onset in the schizophrenia spectrum. This impairment appears to be restricted to the LH, consistent with previous reports detailing a predominantly LH disease process in early psychosis, and activity within this region was associated with an increased experience of hallucinations. These findings detail the cortical responses contributing to visual processing impairments and their relationship with symptoms at disease onset, advancing our understanding of their developmental trajectory over the course of psychotic illness.
High-Throughput Functional Evaluation ofBRCA2Variants of Unknown Significance
Authors: Ikegami Masachika , Kohsaka Shinji , Ueno Toshihide , Momozawa Yukihide , Tamura Kenji , Shimomura Akihiko , Hosoya Noriko , Kobayashi Hiroshi , Tanaka Sakae , Mano Hiroyuki 
Published: January 2020

ABSTRACTNumerous nontruncating missense variants of theBRCA2gene have been identified, but there is a lack of convincing evidence, such as familial data, demonstrating their clinical relevance and they thus remain unactionable. To assess the pathogenicity of variants of unknown significance (VUSs) withinBRCA2, we developed a novel method, the MANO-B method, for high-throughput functional evaluation utilizingBRCA2-deficient cells and poly(ADP-ribose) polymerase (PARP) inhibitors. The estimated sensitivity and specificity of this assay compared to those of the International Agency for Research on Cancer (IARC) classification system were 95% and 95%, respectively. We classified the pathogenicity of 186BRCA2VUSs with our original computational pipeline, resulting in the classification of 126 mutations as “neutral/likely neutral”, 23 as “intermediate”, and 37 as “deleterious/likely deleterious”. We further invented a simplified, on-demand annotation system, the Accurate BRCA Companion Diagnostic (ABCD) test, as a companion diagnostic for PARP inhibitors in patients with unknownBRCA2VUSs. The ABCD test classification was reproducible and consistent with that of a large-scale MANO-B method.
Structural determinants of dynamic fluctuations between segregation and integration on the human connectome
Authors: Fukushima Makoto , Sporns Olaf 
Published: January 2020

AbstractWhile segregation and integration of neural information in the neocortex are thought to be important for human behavior and cognition, the neural substrates enabling their dynamic fluctuations remain elusive. To tackle this problem, we aim to identify specific network features of the connectome (the complete set of structural brain connections) that are responsible for the emergence of dynamic fluctuations between segregated and integrated patterns in human resting-state fMRI functional connectivity. The contributions of network features to the dynamic fluctuations were examined by constructing randomly rewired surrogate connectome data in which network features of interest were selectively preserved, and then by assessing the magnitude of fluctuations simulated with these surrogates. Our analysis demonstrates significant contributions from spatial geometry and network topology of the connectome, as well as from localized structural connections involving visual areas. By providing a structural account of dynamic fluctuations in functional connectivity, this study offers new insights into generative mechanisms driving temporal changes in segregation and integration in the brain.
Is cathodal prefrontal transcranial direct current stimulation capable of affecting inhibitory control and sustained attention? A single-blind, crossover, sham-controlled study
Authors: Sá Canabarro Soraya Lage de , Karolina Paniago Cássia , Magalhães Santos Priscilla , Rosa Lorena da Silva , Espíndola Leite Borges Vitória , McManus Daniel Pimentel , Garcia Ana , Satler Corina , Brasil-Neto Joaquim P. , Tavares Maria Clotilde Henriques 
Published: January 2020

AbstractBackgroundAnodal transcranial direct current stimulation (a-tDCS) has been shown to promote performance improvement of normal individuals in tests of executive function, including tasks that demand sustained attention and inhibitory control. The presumed mechanism is facilitation of prefrontal cortex activation, since a-tDCS is thought to increase cortical excitability. Only a few studies, however, have investigated the effects of inhibitory, cathodal tDCS (c-tDCS) on cognitive tasks, and reported results are often inconsistent. Studies about the effects of c-tDCS upon accuracy and reaction times are particularly scant.Objective/HypothesisThis study assessed the effects of inhibitory c-tDCS over the left dorsolateral prefrontal cortex (l-DLPFC) on the performance of neurologically intact young adults in Stroop and reaction time tests.MethodsSeventeen healthy undergraduate students (ten women) performed Stroop and reaction time tasks after delivery of c-tDCS (1 mA, 20 min) over l-DLFPC or a sham session. All subjects underwent both real and sham sessions, which were separated by an interval of one week. We hypothesized that c-tDCS might lead to an impairment of inhibitory control and attention abilities.ResultsWe found an interference effect on the Stroop task and also a ceiling effect on the reaction Time task. There were no statistically significant performance differences in any of the neuropsychological tests as a function of stimulation condition and/or subject gender.ConclusionsC-tDCS over the l-DLPFC of neurologically intact young individuals did not affect performance in Stroop Test accuracy or in reaction times, irrespective of subject gender. These results raise the possibility that c-tDCS inhibitory effects, well documented for the primary motor area, do not necessarily apply to higher order associative areas. The assumption that c-tDCS has inhibitory effects upon any cortical area, common in clinical trials, should be made with caution.