bluuebunny/crossref_metadata_2025 huggingface dataset:
Motor Proficiency and Generalized Self‐Efficacy Toward Physical Activity in Children With Intestinal Failure
Authors: So Stephanie , Patterson Catherine , Evans Cathy , Wales Paul W.
Published: July 2018

Objective:

Survival rates of children with intestinal failure have increased; however, associated co‐morbidities may affect long‐term motor developmental outcomes. This study evaluates motor proficiency and generalized self‐efficacy toward physical activity (PA) in children ages 6 to 12 years with intestinal failure.

Methods:

This is an observational, cross‐sectional study of children followed in a multidisciplinary intestinal rehabilitation program. Motor proficiency was assessed using the Bruininks‐Oseretsky Test of Motor Proficiency‐2 Short Form (BOT‐2 SF) and the Scales of Independent Behavior (parent‐proxy report). Children completed the Children's Self‐Perceptions of Adequacy in and Predilection for Physical Activity (CSAPPA) and a PA questionnaire. Relevant demographic and medical variables were correlated with assessment results.

Results:

Participants include 30 children (18 males), median age 7 years (interquartile range [IQR] 6–9) with gestational age 35 weeks (IQR 32–39) and birth weight 2.13 kg (IQR 1.68–2.77). Thirteen (43%) were dependent on parenteral nutrition. Fifteen (50%) scored below average on the BOT‐2 SF. Lower BOT‐2 SF scores were significantly associated with lower CSAPPA scores (r = 0.480, P = 0.01), with a common barrier to PA being the presence of a central line or enterostomy tube. Gestational age, height z scores, length of hospital admissions, and number of septic events were all significantly correlated with lower scores in motor proficiency. Number of septic events and total parenteral nutrition days were significant predictors of lower BOT‐2 SF scores, when adjusting for birth weight.

Conclusions:

Multiple medical variables related to intestinal failure may affect motor proficiency and PA self‐efficacy. Developmental follow‐up is important to optimize motor skill development and promote PA participation.
Enhancing the Outcome of Traumatic Sensory Nerve Lesions of the Hand by Additional Use of a Chitosan Nerve Tube in Primary Nerve Repair: A Randomized Controlled Bicentric Trial
Authors: Neubrech Florian , Sauerbier Michael , Moll Wibke , Seegmüller Jessica , Heider Sina , Harhaus Leila , Bickert Berthold , Kneser Ulrich , Kremer Thomas
Published: July 2018

Background:

Peripheral sensory nerve injuries present a significant yet common challenge in acute hand trauma surgery. Standard treatment remains microsurgical end-to-end nerve repair where appropriate. Permanent loss of sensitivity and painful neuroma formation are typical sequelae of unsuccessful surgery. The objective of this study was to evaluate whether the additional use of a chitosan nerve tube in primary nerve repair positively influences sensory recovery.

Methods:

A randomized, controlled, two-center trial with parallel group design and double-blind assessment was conducted to demonstrate the superiority of the additional use of a chitosan nerve tube compared with microsurgical nerve repair alone. Seventy-four participants were enrolled. The primary outcome parameter used was degree of static two-point discrimination at 6 months after surgery. Additional secondary outcome parameters included filament recognition testing (Semmes-Weinstein); pain; neuroma development; and the Disabilities of the Arm, Shoulder and Hand score.

Results:

Nerve repair with additional use of chitosan nerve tubes (intervention group) significantly increased both tactile gnosis (expressed by two-point discrimination) and sensitivity (expressed by Semmes-Weinstein testing). The mean two-point discrimination at 6-month follow-up was 8 mm (range, 2 to 20 mm) in the control group and 6.3 mm (range, 1 to 15 mm) in the intervention group, respectively (p = 0.029). Two-point discrimination correlated with the Disabilities of the Arm, Shoulder and Hand score. In the control and intervention groups, respectively, three versus zero neuromas were found.

Conclusions:

Peripheral sensory nerve regeneration can be improved significantly by additional use of a chitosan nerve tube. An improved ability of static two-point discrimination is clinically relevant.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, I.
Anti-CTGF Oligonucleotide Reduces Severity of Postsurgical Hypertrophic Scars in a Randomized, Double-Blind, Within-Subject, Placebo-Controlled Study
Authors: Jensen Jeff , Gentzkow Gary , Berman Gabe , Senne Lane , Jewell Mark , Connall Timothy P. , Miller Scott R. , Galiano Robert D. , Young Leroy
Published: July 2018

Background:

Connective tissue growth factor (CTGF) levels are up-regulated in wounded skin and are thought to play a major role in scar formation. An antisense oligonucleotide targeting CTGF was evaluated in adult patients undergoing hypertrophic scar revision surgery, to determine effects on reducing the severity of subsequent scars.

Methods:

In a randomized, double-blind, within-subject, placebo-controlled study, 23 female subjects (aged 28 to 55 years) with bilateral, symmetric, hypertrophic surgical scars of the breast underwent scar revision surgery. The resulting breast incisions were randomized to receive EXC 001 (5 mg/cm) or placebo injected intradermally at postsurgery weeks 2, 5, 8, and 11. Scar severity assessments were performed at weeks 12 and 24 by an expert panel using blinded photographs, and by physicians and subjects using a scar scoring scale, the Patient and Observer Scar Assessment Scale. An assumption of the design is that within-subject variance would be small and that whatever within-subject variance there was would be controlled through the randomization process.

Results:

EXC 001 significantly reduced scar severity at both 12 and 24 weeks after scar revision surgery in all three measures (expert panel and physician Patient and Observer Scar Assessment Scale, p < 0.001; Patient and Observer Scar Assessment Scale, p < 0.003).

Conclusions:

This study provided positive preliminary data that intradermal injection of EXC 001 produced a significant reduction in severity of postsurgical skin scars, as measured by physicians, subjects, and an expert panel. This study provided evidence that suppression of CTGF could be a viable strategy for hypertrophic scar reduction therapy and that further study of the antisense oligonucleotide EXC 001 was indicated.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, II.
Social Media and the Dissemination of Research: Insights from the Most Widely Circulated Articles in Plastic Surgery
Authors: Zhou Joy Z. , Lemelman Benjamin T. , Done Nicolae , Henderson Macey L. , Macmillan Alexandra , Song David H. , Dorafshar Amir H.
Published: July 2018

Background:

The purpose of this study is to quantify the relationship between social media use and the dissemination of research across nontraditional channels.

Methods:

Between June and August of 2016, the authors identified 10 plastic surgery journals with the highest impact factor and their 10 most widely circulated articles. Article age; journal impact factor; “distinguished” article designation; and social media metadata of the first authors, last authors, and journals were incorporated into a multivariate regression model to predict the Altmetric Attention Score, a quantitative measure of popularity across Web-based media platforms.

Results:

A total of 100 articles, 181 authors, and 10 journals were identified. Older articles tended to be less popular. The article’s popularity was associated with the journal’s audience size, but not with the author’s social media activity. For each 1000 additional Twitter followers of the journal of publication, the Altmetric score is greater by a factor of 1.72 (95 percent CI, 1.076 to 2.749), which is the equivalent of 72 percent more Tweets. There is also a small but statistically significant negative association between the author’s social media audience size and the popularity of his or her articles: for every 1000 additional followers, the Altmetric score is lower by a factor of 0.822 (95 percent CI, 0.725 to 0.932), which is the equivalent of 17.8 percent fewer Tweets.

Conclusion:

The popularity of an article across social media platforms is associated with the journal’s audience on social media, not with the magnitude of the author’s social media activity.
Cross-Face Nerve Grafting versus Masseteric-to-Facial Nerve Transposition for Reanimation of Incomplete Facial Paralysis: A Comparative Study Using the FACIAL CLIMA Evaluating System
Authors: Hontanilla Bernardo , Olivas Jesús , Cabello Álvaro , Marré Diego
Published: July 2018

Background:

Incomplete facial paralysis is still a challenge because we must restore what is missing without causing damage to what has recovered. The current literature is insufficient, with a small number of cases. The use of nerve transfers has gained recent popularity for reanimating facial palsy. The authors present a comparative study between cross-face nerve grafting and masseteric-to-facial nerve transposition for incomplete facial paralysis.

Methods:

Twenty-eight patients with incomplete unilateral facial paralysis were reanimated with either cross-face nerve grafting (group I, n = 10) or masseteric nerve transfer (group II, n = 18). Commissural displacement and commissural contraction velocity were measured using the FACIAL CLIMA dystem. Spontaneity of the movement and satisfaction were also assessed.

Results:

When comparing the reconstructed and the healthy sides, statistical differences were found in group I but not in group II, suggesting that the resulting movement was symmetrical in group II but not in group I. Intergroup comparison showed that both commissural displacement and commissural contraction velocity were higher in group II. Spontaneity in group I was higher than in group II, but patients in group II showed more satisfaction, both without being statistically significant.

Conclusions:

Reanimation of incomplete facial paralysis can be satisfactorily achieved with both cross-face nerve grafting and direct masseteric-to-facial nerve transposition. However, with the masseteric nerve, better symmetry, a higher degree of recovery, and an increased level of satisfaction are achieved in a one-stage operation. Furthermore, both nerve sources are able to restore spontaneity in more than 50 percent of the patient’s daily life, with no significant differences between them.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Combined 68Ga-NOTA-PRGD2 and 18F-FDG PET/CT Can Discriminate Uncommon Meningioma Mimicking High-Grade Glioma
Authors: Li Deling , Zhang Jingjing , Ji Nan , Zhao Xiaobin , Zheng Kun , Qiao Zhen , Li Fang , Lang Lixin , Iagaru Andrei , Niu Gang , Zhu Zhaohui , Chen Xiaoyuan
Published: July 2018

Objectives

Uncommon pathological subtypes of meningioma may present with severe peritumoral brain edema and mimic high-grade glioma (HGG). In a prospective cohort study of 68Ga-NOTA-PRGD2 PET/CT to evaluate glioma, we occasionally observed that a combination of 68Ga-NOTA-PRGD2 and 18F-FDG was able to differentiate these 2 lesion types.

Methods

From 2013 to 2016, 21 patients suspected of HGG by MRI were recruited for evaluation using 68Ga-NOTA-PRGD2 PET/CT. Brain 18F-FDG PET/CT was performed within 3 days for comparison, and the tumor was surgically removed. The PET results were compared with integrin αvβ3 expression and microvascular density quantification of tumor samples.

Results

Of the 21 recruited patients, 5 patients were finally pathologically diagnosed as uncommon meningioma with severe peritumoral brain edema, including chordoid meningioma (n = 1), angiomatous meningioma (n = 1), and mixed angiomatous and microcystic meningioma (n = 3). Sixteen were diagnosed as HGG. All the meningioma lesions (n = 5) exhibited intense and homogeneous 68Ga-NOTA-PRGD2 uptake with higher SUVmax on 68Ga-NOTA-PRGD2 PET (1.64–7.86; mean ± SD, 4.23 ± 2.48) than the HGG lesions (0.81–2.99; mean ± SD, 1.57 ± 0.33; P = 0.0047). Moreover, the uptake ratios of 68Ga-NOTA-PRGD2 over 18F-FDG, normalized as lg100 * SUVmax (RGD / FDG), in the uncommon meningiomas were significantly higher than those in HGG (1.87 ± 1.36 vs 1.04 ± 0.87, P = 0.0001). A cutoff value of 1.58 was able to discriminate between these lesion types. There were positive correlations among the expression level of integrin αvβ3, microvascular density, and the tumor-to-background ratio derived from 68Ga-NOTA-PRGD2 PET (P < 0.05).

Conclusions

This study reveals a specific imaging pattern of uncommon meningioma mimicking HGG, in which 68Ga-NOTA-PRGD2 PET provided added value to 18F-FDG PET.
Prospective Pilot Evaluation of Radiologists and Computer-aided Pulmonary Nodule Detection on Ultra–low-Dose CT With Tin Filtration
Authors: Takahashi Edwin A. , Koo Chi Wan , White Darin B. , Lindell Rebecca M. , Sykes Anne-Marie G. , Levin David L. , Kuzo Ronald S. , Wolf Matthias , Bogoni Luca , Carter Rickey E. , McCollough Cynthia H. , Fletcher Joel G.
Published: July 2018

Purpose:

The aim of this study was to evaluate the ability of computer-aided detection (CAD) and human readers to detect pulmonary nodules ≥5 mm using 100 kV ultra–low-dose computed tomography (ULDCT) utilizing a tin filter.

Materials and Methods:

After informed consent, 55 patients prospectively underwent standard-dose chest CT (SDCT) using 120 kV followed by ULDCT using 100 kV/tin. Reference nodules ≥5 mm were identified by a thoracic radiologist using SDCT. Four thoracic radiologists marked detected nodules on SDCT and ULDCT examinations using a dedicated computer workstation. After a 6-month memory extinction, readers were shown the same ULDCT cases with all CAD markings as well as their original detections, and characterized CAD detections as true positive or false positive.

Results:

Volume CT Dose index (CTDIvol) for SDCT and ULDCT were 5.3±2 and 0.4±0.2 mGy (P<0.0001), respectively. Forty-five reference nodules were detected in 30 patients. Reader sensitivity varied widely but similarly for SDCT (ranging from 45% to 87%) and ULDCT (45% to 83%). CAD sensitivity was 76% (34/45) for SDCT and 71% (32/45) for ULDCT. After CAD, reader sensitivity substantially improved by 19% and 18% for 2 readers, and remained nearly unchanged for the other 2 readers (0% and 2%), despite reader perception that many more nodules were identified with CAD. There was a mean of 2 false-positive CAD detections/case.

Conclusions:

ULDCT with 100 kV/tin reduced patient dose by over 90% without compromising pulmonary nodule detection sensitivity. CAD can substantially improve nodule detection sensitivity at ULDCT for some readers, maintaining interobserver performance.
Reduced Risk of BK Polyomavirus Infection in HLA-B51–positive Kidney Transplant Recipients
Authors: Wunderink Herman F. , Haasnoot Geert W. , de Brouwer Caroline S. , van Zwet Erik W. , Kroes Aloysius C. M. , de Fijter Johan W. , Rotmans Joris I. , Claas Frans H. J. , Feltkamp Mariet C. W.
Published: July 2018

Background.

Identification of specific HLA alleles and T-cell epitopes that influence the course of BK polyomavirus (BKPyV) infection after kidney transplantation (KTx), including development of BKPyV-associated nephropathy (BKPyVAN), can be useful for patient risk stratification and possibly vaccine development.

Methods.

In a retrospective cohort of 407 living kidney donor-recipient pairs, donor and recipient HLA class I and II status were correlated with the occurrence of recipient BKPyV viremia and BKPyVAN in the first year after KTx. Relevant HLA alleles were systematically analyzed for candidate peptide epitopes in silico.

Results.

Although none of the 78 HLA alleles analyzed increased the risk of BKPyV viremia and BKPyVAN, a considerable reduction of BKPyV viremia and BKPyVAN cases was observed in HLA-B51–positive KTx recipients. Multivariate analysis showed that HLA-B51 positivity, found in 36 (9%) recipients, reduced the risk of viremia approximately fivefold (hazard ratio, 0.18; 95% confidence interval, 0.04–0.73; P = 0.017). Four HLA-B51-restricted putative cytotoxic T lymphocyte epitopes were identified, including a previously described HLA-B supermotif-containing peptide (LPLMRKAYL), encoded by 2 relevant T-antigens (small T and large T) and previously shown to be highly immunogenic.

Conclusions.

In conclusion, HLA-B51-positive kidney transplant recipients were less susceptible to BKPyV infection, which might be explained by efficient presentation of a particular BKPyV-derived immunogenic peptide.
The Impact of Deceased Donor Liver Extraction Time on Early Allograft Function in Adult Liver Transplant Recipients
Authors: Adelmann Dieter , Roll Garrett R. , Kothari Rishi , Syed Shareef , Burdine Lyle J. , Tavakol Mehdi , Niemann Claus U.
Published: July 2018

Background

In liver transplantation, both cold and warm ischemia times are known to impact early graft function. The extraction time is a period during the initial phase of organ cooling which occurs during deceased donor procurement. During this time, the organ is at risk of suboptimal cooling. Whether donor extraction time, the time from donor aortic cross-clamp to removal of the donor organ from the body cavity has an effect on early graft function is not known.

Methods

We investigated the effect of donor extraction time on early graft function in 292 recipients of liver grafts procured locally and transplanted at our center between June 2012 and December 2016. Early graft function was assessed using the model of early allograft function score in a multivariable regression model including donor extraction time, cold ischemia time, warm ischemia time, donor risk index, and terminal donor sodium.

Results

Donor extraction time had an independent effect on early graft function measured by the model of early allograft function score (coefficient, 0.021; 95% confidence interval, 0.007-0.035; P < 0.01; for each minute increase of donor extraction time). Besides donor extraction time, cold ischemia time, warm ischemia time, and donor risk index had a significant effect on early graft function.

Conclusions

We demonstrate an independent effect of donor extraction time on graft function after liver transplantation. Efforts to minimize donor extraction time could improve early graft function in liver transplantation.
Towards clinical outcome measures in myotonic dystrophy type 2: a systematic review
Authors: Rastelli Emanuele , Montagnese Federica , Massa Roberto , Schoser Benedikt
Published: July 2018

Purpose of review

Myotonic dystrophies are the most frequent muscular dystrophies in adulthood; however, myotonic dystrophy type 2 (DM2) is by far less prevalent than myotonic dystrophy type 1 (DM1). Consequently, studies on large cohorts are lacking and disease-specific outcome measures have not been developed (see video abstract, Supplemental Digital Content 1, http://links.lww.com/CONR/A44).

The aim of this review is to systematically evaluate the outcome measures applied in patients with DM2 and to identify tests adopted from other neuromuscular disorders potentially suitable for DM2.

A systematic review of functional tests and patient reported outcomes (PROs) previously used in DM2 has been performed. In addition, we reviewed functional tests and PROs previously used in neuromuscular diseases (NMDs). Based on this approach, we propose a battery of tests to be validated in DM2.

Recent findings:

No outcome measures or PROs have been validated in DM2. The most used PROs in DM2 were INQoL, SF-36, MPQ, and BPI. It is not clear whether it is better to use MMT or QMT to assess muscle strength. The algometer seems to be a useful tool to assess myalgia. No currently adopted tests or PROs seem effective to assess the mild myotonia of DM2. Several outcome measures used in other NMDs (e.g. 6MWT, QMFT, GSGC) might be suitable for DM2; however, their disease-specific validity needs to be explored.

Although DM2 has a milder and more heterogeneous phenotype than DM1, there is an urgent need to develop validated outcome measures in DM2. The current lack of validated DM2 tests will delay the start of therapeutic trials.
Neuroinflammatory mechanisms in amyotrophic lateral sclerosis pathogenesis
Authors: Thonhoff Jason R. , Simpson Ericka P. , Appel Stanley H.
Published: July 2018

Purpose of review

Neuroinflammation is increasingly recognized as an important mediator of disease progression in patients with amyotrophic lateral sclerosis (ALS), and is characterized by reactive central nervous system (CNS) microglia and astroglia as well as infiltrating peripheral monocytes and lymphocytes. Anti-inflammatory and neuroprotective factors sustain the early phase of the disease whereas inflammation becomes proinflammatory and neurotoxic as disease progression accelerates. Initially, motor neurons sustain injuries through multiple mechanisms resulting from harmful mutations causing disruptions of critical intracellular pathways. Injured motor neurons release distress signal(s), which induce inflammatory processes produced by surrounding glial cells in the CNS as well as peripheral innate and adaptive immune cells. This review will focus on mechanisms of neuroinflammation and their essential contributions in ALS pathogenesis.

Recent findings

Regulatory T lymphocytes (Tregs) are a subpopulation of immunosuppressive T lymphocytes that become reduced and dysfunctional as the disease progresses in ALS patients. Their degree of dysfunction correlates with the extent and rapidity of the disease. Treg numbers are boosted in transgenic mutant SOD1 (mSOD1) mice through the passive transfer of Tregs or through treatment with an interleukin-2/ interleukin-2 monoclonal antibody complex and rapamycin. Treating the transgenic mice with either of these modalities delays disease progression and prolongs survival. In addition, Treg function is restored when dysfunctional Tregs are isolated from ALS patients and expanded ex vivo in the presence of interleukin-2 and rapamycin. Based on these findings, a first-in-human phase 1 trial has been completed in which expanded autologous Tregs were infused back into ALS patients as a potential treatment. The infusions were safe and shown to ‘hit target’ by enhancing both Treg numbers and suppressive functions.

A delicate balance between anti-inflammatory and proinflammatory factors modulates the rates of disease progression and survival times in ALS. Tipping the balance toward the anti-inflammatory mediators shows promise in slowing the progression of this devastating disease.
Is it actionable? An Evaluation of the Rapid PCR-Based Blood Culture Identification Panel on the Management of Gram-Positive and Gram-Negative Blood Stream Infections
Authors: Tseng Andrew S. , Kasule Sabirah N. , Rice Felicia , Mi Lanyu , Chan Lynn , Seville Maria T. , Grys Thomas E.
Published: July 2018

Background

There is growing interest in the use of rapid blood culture identification (BCID) panels in antimicrobial stewardship programs (ASP). While many studies have looked at its clinical and economic utility, its comparative utility in gram-positive and gram-negative blood stream infections (BSI) have not been as well characterized.

Methods

The study was a quasi-experimental retrospective study at the Mayo Clinic in Phoenix, Arizona. All adult patients with positive blood cultures before BCID implementation (June 2015 to December 2015) and after BCID implementation (June 2016 to December 2016) were included. The outcomes of interest included: time to first appropriate antibiotic escalation, time to first appropriate antibiotic de-escalation, time to organism identification, LOS, infectious disease consultation, discharge disposition, and in-hospital mortality.

Results

In total, 203 patients were included in this study. There was a significant difference in the time to organism identification between pre- and post-BCID cohorts (27.1h vs. 3.3h, p<0.0001). BCID did not significantly reduce the time to first appropriate antimicrobial escalation or de-escalation for either GP-BSIs or GN-BSIs. Providers were more likely to escalate antimicrobial therapy in GP-BSIs after gram stain and more likely to de-escalate therapy in GN-BSIs after susceptibilities. While there were no significant differences in changes in antimicrobial therapy after organism identification by BCID, over a quarter of providers (28.1%) made changes after organism identification.

Conclusions

While BCID significantly reduced the time to identification for both GP-BSIs and GN-BSIs, BCID did not reduce the time to first appropriate antimicrobial escalation and de-escalation.
A nonlinear simulation framework supports adjusting for age when analyzing BrainAGE
Authors: Le Trang T. , Kuplicki Rayus , McKinney Brett A. , Yeh Hung-wen , Thompson Wesley K. ,   Tulsa 1000 Investigators, Paulus Martin P.
Published: July 2018

Several imaging modalities, including T1-weighted structural imaging, diffusion tensor imaging, and functional MRI can show chronological age related changes. Employing machine learning algorithms, an individual’s imaging data can predict their age with reasonable accuracy. While details vary according to modality, the general strategy is to: 1) extract image-related features, 2) build a model on a training set that uses those features to predict an individual’s age, 3) validate the model on a test dataset, producing a predicted age for each individual, 4) define the “Brain Age Gap Estimate” (BrainAGE) as the difference between an individual’s predicted age and his/her chronological age, and 5) estimate the relationship between BrainAGE and other variables of interest, and 6) make inferences about those variables and accelerated or delayed brain aging. For example, a group of individuals with overall positive BrainAGE may show signs of accelerated aging in other variables as well. There is inevitably an overestimation of the age of younger individuals and an underestimation of the age of older individuals due to ‘regression to the mean’. The correlation between chronological age and BrainAGE may significantly impact the relationship between BrainAGE and other variables of interest when they are also related to age. In this study, we examine the detectability of variable effects under different assumptions. We use empirical results from two separate datasets [training=475 healthy volunteers, aged 18 – 60 years (259 female); testing=489 participants including people with mood/anxiety, substance use, eating disorders and healthy controls, aged 18 – 56 years (312 female)] to inform simulation parameter selection. Outcomes in simulated and empirical data strongly support the proposal that models incorporating BrainAGE should include chronological age as a covariate. We propose either including age as a covariate in step 5 of the above framework, or employing a multistep procedure where age is regressed on BrainAGE prior to step 5, producing BrainAGE Residualized (BrainAGER) scores.
PIF transcription factors link a neighbor threat cue to accelerated reproduction in Arabidopsis
Authors: Galvāo V.C. , Fiorucci A.S , Trevisan M. , Franco-Zorrilla J.M. , Goyal A. , Schmid-Siegert E. , Solano R. , Fankhauser C.
Published: July 2018

Changes in light quality indicative of competition for this essential resource influence plant growth and developmental transitions. Little is known about neighbor proximity-induced acceleration of reproduction. phytochrome B (phyB) senses light cues from plant competitors ultimately leading to the expression of the floral inducers FLOWERING LOCUS (FT) and TWIN SISTER of FT (TSF). Here we show that three PHYTOCHROME INTERACTING FACTOR (PIF) transcriptional regulators act directly downstream of phyB to promote expression of FT and TSF. Neighbor proximity enhances PIF accumulation towards the end of the day coinciding with enhanced floral inducer expression. We present evidence for direct PIF-mediated TSF expression. The relevance of our findings is illustrated by the prior identification of FT, TSF and PIF4 as loci underlying flowering time regulation in nature.

One Sentence Summary

PIF transcription factors mediate reproductive transition in response to neighbor proximity light cues in Arabidopsis.
A low resolution epistasis mapping approach to identify chromosome arm interactions in allohexaploid wheat
Authors: Santantonio Nicholas , Jannink Jean-Luc , Sorrells Mark E.
Published: July 2018

1

Epistasis is an important contributor to genetic variance, even in inbred populations where it is present as additive by additive interactions. Testing for epistasis presents a multiple testing problem as the search space for modest numbers of markers is large. Additionally, single markers do not necessarily track functional units of interacting chromatin as well as haplotype based methods do. To harness the power of multiple markers while drastically minimizing the number of tests conducted, we present a low resolution test for epistatic interactions across whole chromosome arms. Two additive genetic covariance matrices are constructed from markers on two different chromosome arms. The Hadamard product of these additive covariance matrices is then used to produce the additive by additive epistasis covariance matrix between the two chromosome arms. The covariance matrices are subsequently used to estimate an epistatic interaction variance parameter in a mixed model framework, while correcting for background additive and epistatic effects. We find significant epistatic interactions for 2% of interactions tested for four agronomic traits in a population of winter wheat. Interactions across homeologous chromosome arms were identified, but were less abundant than other interaction chromosome arm pairs. Of these, homeologous chromosome arm pair 4BL and 4DL showed a strong relationship between the product of their additive effects and the interaction effect that may be indicative of functional redundancy. Several chromosome arms were involved in many interactions across the genome, suggesting that they may contain important large effect regulatory factors. The differential patterns of epistasis across different traits suggests that detection of epistatic interactions is robust when correcting for background additive and epistatic effects in the population. The low resolution epistasis mapping method presented here identifies important epistatic interactions with a limited number of statistical tests at the cost of relatively lower precision.
Dynamic multifactor hubs interact transiently with sites of active transcription inDrosophilaembryos
Authors: Mir Mustafa , Stadler Michael R. , Ortiz Stephan A. , Harrison Melissa M. , Darzacq Xavier , Eisen Michael B.
Published: July 2018

The regulation of transcription requires the coordination of numerous activities on DNA, yet it remains poorly understood how transcription factors facilitate these multiple functions. Here we use lattice light-sheet microscopy to integrate single-molecule and high-speed 4D imaging in developingDrosophilaembryos to study the nuclear organization and interactions of the key patterning factors Zelda and Bicoid. In contrast to previous studies suggesting stable, cooperative binding, we show that both factors interact with DNA with surprisingly high off-rates. We find that both factors form dynamic subnuclear hubs, and that Bicoid binding is enriched within Zelda hubs. Remarkably, these hubs are both short lived and interact only transiently with sites of active Bicoid dependent transcription. Based on our observations we hypothesize that, beyond simply forming bridges between DNA and the transcription machinery, transcription factors can organize other proteins into hubs that transiently drive multiple activities at their gene targets.
Auditory and Language Contributions to Neural Encoding of Speech Features in Noisy Environments
Authors: Zou Jiajie , Feng Jun , Xu Tianyong , Jin Peiqing , Luo Cheng , Chen Feiyan , Zhang Jianfeng , Ding Nai
Published: July 2018

Recognizing speech in noisy environments is a challenging task that involves both auditory and language mechanisms. Previous studies have demonstrated noise-robust neural tracking of the speech envelope, i.e., fluctuations in sound intensity, in human auditory cortex, which provides a plausible neural basis for noise-robust speech recognition. The current study aims at teasing apart auditory and language contributions to noise-robust envelope tracking by comparing 2 groups of listeners, i.e., native listeners of the testing language and foreign listeners who do not understand the testing language. In the experiment, speech is mixed with spectrally matched stationary noise at 4 intensity levels and the neural responses are recorded using electroencephalography (EEG). When the noise intensity increases, an increase in neural response gain is observed for both groups of listeners, demonstrating auditory gain control mechanisms. Language comprehension creates no overall boost in the response gain or the envelope-tracking precision but instead modulates the spatial and temporal profiles of envelope-tracking activity. Based on the spatio-temporal dynamics of envelope-tracking activity, the 2 groups of listeners and the 4 levels of noise intensity can be jointly decoded by a linear classifier. All together, the results show that without feedback from language processing, auditory mechanisms such as gain control can lead to a noise-robust speech representation. High-level language processing, however, further modulates the spatial-temporal profiles of the neural representation of the speech envelope.
Stavudine Reduces NLRP3 Inflammasome Activation and Upregulates Aβ-Autophagy
Authors: Rosa Francesca La , Saresella Marina , Marventano Ivana , Piancone Federica , Ripamonti Enrico , Zoia Chiara Paola , Conti Elisa , Ferrarese Carlo , Clerici Mario
Published: July 2018

Alzheimer’s disease (AD) is associated with amyloid-beta (Aβ) deposition and neuroinflammation, possibly driven by activation of the NLRP3 inflammasome. Nucleoside reverse transcriptase inhibitors (NRTI) hamper the assembly of the NLRP3 inflammasome; we analyzed whether stavudine (D4T), a prototypical NRTI, modulates Aβ-mediated inflammasome activation; because neuroinflammation impairs Aβ clearance by phagocytes, phagocytosis and autophagy were examined as well. THP-1-derived macrophages were stimulated in vitro with Aβ42 alone or after LPS priming with/without D4T. NLRP3 and TREM2 expression was analyzed by RT-PCR, phagocytosis and ASC-Speck by AmnisFlowSight, NLRP3-produced cytokines by ELISA, authophagy by P-ELISA evaluation of P-ERK and P-AKT. Results showed that IL1β, IL18 and caspase-1 were increased whereas Aβ-phagocytosis and TREM2 were reduced in LPS+Aβ42-stimulated cells. D4T reduced NLRP3 assembly as well as IL18 and caspase-1 production, but not IL1β, phagocytosis, and TREM2. P-AKT expression was augmented and P-ERK was reduced by D4T, suggesting a stimulatory effect on autophagy. D4T reduces NLRP3 inflammasome-associated inflammation, possibly restoring autophagy, in an in vitro model of AD; it will be interesting to verify its possibly beneficial effects in the clinical scenario.
Opposing effects of impulsivity and mindset on sources of science selfefficacy and STEM interest in adolescents
Authors: Marriott L.K. , Coppola L. , S.H. Mitchell , Bouwma-Gearhart J. , Chen Z. , Shifrer D. , Shannon J.S.
Published: July 2018

Impulsivity has been linked to academic performance in the context of Attention Deficit Hyperactivity Disorder, though its influence on a wider spectrum of students remains largely unexplored, particularly in the context of STEM learning (i.e. science, technology, engineering, and math). STEM learning was hypothesized to be more challenging for impulsive students, since it requires the practice and repetition of tasks as well as concerted attention to task performance. Impulsivity was assessed in a cross-sectional sample of 2,476 students in grades 6-12. Results show impulsivity affects a larger population of students, not limited to students with learning disabilities. Impulsivity was associated with lower sources of science self-efficacy (SSSE) scores, interest in all STEM domains (particularly math), and self-reported STEM skills. The large negative effect observed for impulsivity was opposed by “growth” mindset, which describes a student’s belief in the importance of effort when learning is difficult. Mindset had a large positive effect, which was associated with greater SSSE, STEM interest, and STEM skills. When modeled together, results suggest that mindset interventions may benefit impulsive students who struggle with STEM. Together, these data suggest important interconnected roles for impulsivity and mindset that can influence secondary students’ STEM trajectories.
Desensitization of NMDA receptors depends of their association with plasma membrane sodium-calcium exchangers in lipid nanoclasters
Authors: Sibarov Dmitry A. , Poguzhelskaya Ekaterina E. , Antonov Sergei M.
Published: July 2018

The plasma membrane Na+/Ca2+-exchanger (NCX) has recently been shown to regulate Ca2+-dependent N-methyl-d-aspartate receptor (NMDAR) desensitization, suggesting tight interaction of NCXs and NMDARs in lipid nanoclaster or “rafts”. To evaluate possible role of this interaction we studied effects of Li+ on NMDA-elicited whole-cell currents and Ca2+ responses of rat cortical neurons in vitro before and after cholesterol extraction by methyl-β-cyclodextrin (MβCD). Substitution Li+ for Na+ in the external solution caused a concentration-dependent decrease of steady-state NMDAR currents from 440 ± 71 pA to 111 ± 29 pA in 140 mM Na+ and 140 mM Li+, respectively. Li+ inhibition of NMDAR currents disappeared in the absence of Ca2+ in the external solution (Ca2+-free), suggesting that Li+ enhanced Ca2+-dependent NMDAR desensitization. Whereas the cholesterol extraction with MβCD induced NMDAR current decrease to 136 ± 32 pA in 140 mM Na+ and 46 ± 15 pA in 140 mM Li+, the IC50 values for the Li+ inhibition were similar (about 44 mM Li+) before and after this procedure. In Ca2+-free Na+ solution steady-state NMDAR currents after the cholesterol extraction were 47 ± 6 % of control currents. Apparently this amplitude decrease was not Ca2+-dependent. In 1 mM Ca2+ Na+ solution the Ca2+-dependent NMDAR desensitization was greater when cholesterol was extracted. Obviously, this procedure promoted its development. In agreement, Li+ and KB-R7943, an inhibitor of NCX, both considerably reduced NMDAR-mediated Ca2+ responses. The cholesterol extraction itself caused a decrease of NMDAR-mediated Ca2+ responses and, in addition, abolished the effects of Li+ and KB-R7943. Taken together our data suggest that NCXs downregulate the Ca2+-dependent NMDAR desensitization. Most likely, this is determined by co-localization and tight functional interaction of NCX and NMDAR molecules in membrane lipid rafts. Their destruction is accompanied by an enhancement of NMDAR desensitization and a loss of NCX-selective agent effects on NMDARs.
On the impact of the pangenome and annotation discrepancies while building protein sequence databases for bacteria proteogenomics
Authors: Machado K.C.T. , Fortuin S. , Tomazella G.G. , Fonseca A.F. , Warren R. , Wiker H.G. , de Souza S.J. , de Souza G.A.
Published: July 2018

In proteomics, peptide information within mass spectrometry data from a specific organism sample is routinely challenged against a protein sequence database that best represent such organism. However, if the species/strain in the sample is unknown or poorly genetically characterized, it becomes challenging to determine a database which can represent such sample. Building customized protein sequence databases merging multiple strains for a given species has become a strategy to overcome such restrictions. However, as more genetic information is publicly available and interesting genetic features such as the existence of pan- and core genes within a species are revealed, we questioned how efficient such merging strategies are to report relevant information. To test this assumption, we constructed databases containing conserved and unique sequences for ten different species. Features that are relevant for probabilistic-based protein identification by proteomics were then monitored. As expected, increase in database complexity correlates with pangenomic complexity. However, Mycobacterium tuberculosis and Bortedella pertusis generated very complex databases even having low pangenomic complexity or no pangenome at all. This suggests that discrepancies in gene annotation is higher than average between strains of those species. We further tested database performance by using mass spectrometry data from eight clinical strains from Mycobacterium tuberculosis, and from two published datasets from Staphylococcus aureus. We show that by using an approach where database size is controlled by removing repeated identical tryptic sequences across strains/species, computational time can be reduced drastically as database complexity increases.
Tiling light sheet selective plane illumination microscopy using discontinuous light sheets
Authors: Gao Liang
Published: July 2018

Tiling light sheet selective plane illumination microscopy (TLS-SPIM) improves 3D imaging ability of SPIM by using a real-time optimized tiling light sheet. However, the imaging speed decreases, and size of the raw image data increases proportionally to the number of tiling positions in TLS-SPIM. The decreased imaging speed and the increased raw data size could cause significant problems when TLS-SPIM is used to image large specimens at high spatial resolution. Here, we present a novel method to solve the problem. Discontinuous light sheets created by scanning coaxial beam arrays synchronized with camera exposures are used for 3D imaging to decrease the number of tiling positions required at each image plane without sacrificing the spatial resolution. We investigate the performance of the method via numerical simulation and discuss the technical details of the method.
Lamin A/C controls nuclear matrin-3 levels and localization, but not alternative splicing of cassette exons
Authors: Rajgor Dipen , Gooding Clare , Hayward Robert , Coelho Miguel B , Smith Christopher WJ , Shanahan Catherine M
Published: July 2018

Disruptions in connections between the nuclear lamina and nuclear matrix occur in myopathic disorders. However, the biological significance of nuclear lamina - nuclear matrix coupling still remains largely undetermined. Previously it has been demonstrated that the nuclear matrix protein, matrin-3, binds to lamin A/C and this interaction is disrupted in laminopathies resulting in enhanced separation between the lamina and matrix. Matrin-3 has recently been identified as a core regulator of alternative splicing, whereas the involvement of lamin A/C in splicing still remains controversial. In this study, we demonstrate that lamin A/C is not only required for maintaining the nuclear organization of matrin-3, but also of other splicing activators and small nuclear ribonucleoproteins (snRNP) components. Interestingly, mis-localization of these splicing components did not appear to significantly disrupt alternative splicing events of cassette exons regulated by matrin-3. Thus, the lamin A/C-matrin3 interaction is unlikely to be involved in controlling alternative splicing but could be important in coordinating other nuclear activities. Interestingly, matrin-3 knock-down results in misshapen nuclei suggesting its interaction with lamin A/C maybe important in maintaining nuclear structural integrity.
LOPIT-DC: A simpler approach to high-resolution spatial proteomics
Authors: Geladaki Aikaterini , Britovšek Nina Kočevar , Breckels Lisa M. , Smith Tom S. , Mulvey Claire M. , Crook Oliver M. , Gatto Laurent , Lilley Kathryn S.
Published: July 2018

Hyperplexed Localisation of Organelle Proteins by Isotope Tagging (hyperLOPIT) is a well-established method for studying protein subcellular localisation in complex biological samples. As a simpler alternative we developed a second workflow named Localisation of Organelle Proteins by Isotope Tagging after Differential ultraCentrifugation (LOPIT-DC) which is faster and less resource-intensive. We present the most comprehensive high-resolution mass spectrometry-based human dataset to date and deliver a flexible set of subcellular proteomics protocols for sample preparation and data analysis. For the first time, we methodically compare these two different mass spectrometry-based spatial proteomics methods within the same study and also apply QSep, the first tool that objectively and robustly quantifies subcellular resolution in spatial proteomics data. Using both approaches we highlight suborganellar resolution and isoform-specific subcellular niches as well as the locations of large protein complexes and proteins involved in signalling pathways which play important roles in cancer and metabolism. Finally, we showcase an extensive analysis of the multilocalising proteome identified via both methods.
GrapeTree: visualization of core genomic relationships among 100,000 bacterial pathogens
Authors: Zhou Zhemin , Alikhan Nabil-Fareed , Sergeant Martin J. , Luhmann Nina , Vaz Cátia , Francisco Alexandre P. , Carriço João André , Achtman Mark
Published: July 2018

Current methods struggle to reconstruct and visualize the genomic relationships of large numbers of bacterial genomes. GrapeTree facilitates the analyses of large numbers of allelic profiles by a static “GrapeTree Layout” algorithm that supports interactive visualizations of large trees within a web browser window. GrapeTree also implements a novel minimum spanning tree algorithm (MSTree V2) to reconstruct genetic relationships despite high levels of missing data. GrapeTree is a stand-alone package for investigating phylogenetic trees plus associated metadata and is also integrated into EnteroBase to facilitate cutting edge navigation of genomic relationships among bacterial pathogens.
A slow-cooling-rate in situ cell for long-duration studies of mineral precipitation in cold aqueous environments on Earth and other planetary bodies
Authors: Thompson Stephen P. , Kennedy Hilary , Day Sarah J. , Baker Annabelle R. , Butler Benjamin M. , Safi Emmal , Kelly Jon , Male Andrew , Potter Jonathan , Cobb Tom , Murray Claire A. , Tang Chiu C. , Evans Aneurin , Mercado Ronaldo
Published: July 2018

Liquid oceans and ice caps, along with ice crusts, have long been considered defining features of the Earth, but space missions and observations have shown that they are in fact common features among many of the solar system's outer planets and their satellites. Interactions with rock-forming materials have produced saline oceans not dissimilar in many respects to those on Earth, where mineral precipitation within frozen seawater plays a significant role in both determining global properties and regulating the environment in which a complex ecosystem of extremophiles exists. Since water is considered an essential ingredient for life, the presence of oceans and ice on other solar system bodies is of great astrobiological interest. However, the details surrounding mineral precipitation in freezing environments are still poorly constrained, owing to the difficulties of sampling and ex situ preservation for laboratory analysis, meaning that predictive models have limited empirical underpinnings. To address this, the design and performance characterization of a transmission-geometry sample cell for use in long-duration synchrotron X-ray powder diffraction studies of in situ mineral precipitation from aqueous ice–brine systems are presented. The cell is capable of very slow cooling rates (e.g. 0.3°C per day or less), and its performance is demonstrated with the results from a year-long study of the precipitation of the hydrated magnesium sulfate phase meridianiite (MgSO4·11H2O) from the MgSO4–H2O system. Evidence from the Mars Rover mission suggests that this hydrated phase is widespread on the present-day surface of Mars. However, as well as the predicted hexagonal ice and meridianiite phases, an additional hydrated sulfate phase and a disordered phase are observed.