bluuebunny/crossref_metadata_2025 huggingface dataset:
NIST’s Digital Library of Mathematical Functions
Authors: Schneider Barry I. , Miller Bruce R. , Saunders Bonita V.
Published: February 2018

The half-century-old handbook commonly known as Abramowitz and Stegun enters the 21st century.
Tropical forage legumes provide large nitrogen benefits to maize except when fodder is removed
Authors: Traill Skye , Bell Lindsay W. , Dalgliesh Neal P. , Wilson Ainsleigh , Ramony Lina-May , Guppy Chris
Published: February 2018

Integration of tropical forage legumes into cropping systems may improve subsequent crop nitrogen (N) supply, but removal of legume biomass for forage is likely to diminish these benefits. This study aimed to determine: (i) under irrigated conditions, the potential N inputs that can be provided by different tropical forage legumes to a subsequent cereal crop; and (ii) the residual N benefits once fodder had been removed. Available soil mineral N following tropical forage legumes lablab (Lablab purpureus), centro (Centrosema pascuorum), butterfly pea (Clitoria ternatea) and burgundy bean (Macroptilium bracteatum) and grain legume soybean (Glycine max) was compared with a maize (Zea mays) control when legume biomass was retained or cut and removed (phase 1). An oat (Avena sativa) cover crop was then grown to ensure consistent soil-water across treatments (phase 2), followed by a maize grain crop (phase 3) in which N uptake, biomass production and grain yield were compared among the phase 1 treatments. To determine N-fertiliser equivalence values for subsequent maize crop yields, different rates of fertiliser (0–150 kg urea-N/ha) were applied in phase 3. Retained biomass of butterfly pea, centro and lablab increased phase 3 unfertilised maize grain yield by 6–8 t/ha and N uptake by 95–200 kg N/ha compared with a previous cereal crop, contributing the equivalent of 100–150 kg urea-N/ha. When legume biomass was cut and removed, grain yield in the phase 3 maize crop did not increase significantly. When butterfly pea, centro and lablab biomass was retained rather than removed, the maize accumulated an additional 80–132 kg N/ha. After fodder removal, centro was the only legume that provided N benefits to the phase 3 maize crop (equivalent of 33 kg urea-N/ha). Burgundy bean did not increase subsequent crop production when biomass was either retained or removed. The study found that a range of tropical forage legumes could contribute large amounts of N to subsequent crops, potentially tripling maize grain yield. However, when these legumes were cut and removed, the benefits were greatly diminished and the legumes provided little residual N benefit to a subsequent crop. Given the large N trade-offs between retaining and removing legume biomass, quantification of N inputs under livestock grazing or when greater residual biomass is retained may provide an alternative to achieving dual soil N–fodder benefits.
Molecular and phenotypic diversity among chickpea (Cicer arietinum) genotypes as a function of drought tolerance
Authors: Sachdeva Supriya , Bharadwaj C. , Sharma Vinay , Patil B. S. , Soren K. R. , Roorkiwal Manish , Varshney Rajeev , Bhat K. V.
Published: February 2018

Diversity as a function of drought tolerance may be identified by morphological characters, and molecular tools used to find the most divergent genotypes for breeding programs for drought tolerance in future. The narrow genetic base of chickpea can be circumvented by using diverse lines in breeding programs. Forty chickpea genotypes were studied for their morphological and molecular diversity with an objective of identifying the most diverse drought-tolerant lines. In total, 90 alleles were detected with 3.6 alleles per locus. Polymorphism information content (PIC) values ranged from 0.155 to 0.782 with an average value of 0.4374 per locus. The size of amplified products ranged from 160 bp to 390 bp. Primer TA136 with eight alleles showed the highest PIC value of 0.7825, indicating its ability to differentiate the genotypes at molecular level. DARwin neighbour-joining tree analysis based on dissimilarity estimates was done for the molecular data and sequential agglomerative hierarchical non-overlapping (SAHN) grouping for the morphological data. It could clearly discriminate the tolerance and the sensitivity of genotypes. Two-dimensional principal coordinates analysis (PCoA) plot indicated good diversity for drought tolerance. The genetic similarity coefficients ranged from 0.115 (genotypes BGD72 to ICCV 5308) to 0.828 (genotypes ICCV 10316 to ICCV 92337).
Time on hands
Authors: Li Heng
Published: February 2018

The present study investigates deliberate and spontaneous temporal gestures in
Mandarin speakers. The results of our analysis show that when asked to gesture
about past and future events deliberately (Study 1), Mandarin speakers tend to
mimic space-time mappings in their spoken metaphors or graphic conventions for
time in Chinese culture, including sagittal mappings (front/past, back/future),
vertical mappings (up/past, down/future), and lateral mappings (left/past,
right/future). However, in their spontaneous co-speech gestures about time
(Study 2), more congruent gestures were produced on the lateral axis than on the
vertical axis. This suggests that although Mandarin speakers could think about
time vertically, they still showed a horizontal bias in their conceptions of
time. Speakers were also more likely to gesture according to future-in-front
mappings despite more past-in-front mappings found in spoken Chinese, suggesting
a dissociation of temporal language and temporal thought. These results
demonstrate that gesture is useful for revealing the spatial conceptualization
of time.
Effects of gesture restriction on quality of narrative
production
Authors: Jenkins Theodore , Coppola Marie , Coelho Carl
Published: February 2018

Hand gestures have been found to provide both semantic information and cognitive
facilitative effects in language tasks. These benefits, however, have typically
been linked to micro-levels of word and sentence production, and little
attention has been paid to the macro-levels of narrative production and
organization. In this study, we examined the length, content, syntactic
complexity, and organization of narratives of ten typically developing adults
under two conditions: (i) Free Gesture, in which participants were allowed to
gesture freely while retelling a story, and (ii) Restricted Gesture, where the
participants were prevented from moving their hands freely. Results indicated
that although narrative length and content did not vary significantly between
conditions, narratives produced in the Free Gesture condition were significantly
more grammatically complex and better organized than those produced in the
Restricted Gesture condition. The findings are discussed with respect to the
potential facilitative cognitive effects of gesture for discourse planning.
Interactional functions of lip funneling gestures
Authors: Mihas Elena
Published: February 2018

Based on extensive ethnographic fieldwork in lowland Peru, this study examines interactional functions of Northern Kampa (Arawak) lip funneling gestures. The study has shown that lip funnels have two functions, spatial deictic and upgrading. Spatial deictic lip funnels orient the addressee to a referential target in acts of direct and deferred ostension and abstract pointing; they are accompanied with aligned gaze and coupled with a variety of lexical items (although they need not be). Spatial deictic lip funnels are intense, sometimes held for the duration of the entire utterance. The second function of lip funnels is to amplify the speaker’s claim to epistemic authority in upgraded responses. In the upgrading function, lip funnels are paired with a limited range of grammatical constructions (negative-interrogative, polar focus and exhaustive focus); the gesturer’s gaze is directed at the recipient, or eyes are shut. Nasalization of vowels is in complementary distribution with eye shutting. ‘Upgrading’ lip funnels are transitory facial actions, normally lasting a split second.
Some effects of tool geometric features on friction stir weld response parameters
Authors: Reza-E-Rabby Md. , Reynolds Anthony P.
Published: February 2018

Pin geometries (shape, dimensions, and surface features) have significant effects on friction stir welding, dictating, to some extent, the material flow which in turn affects process variables and joint quality. In this paper, volumetric defect content and process response variables (in-plane forces, torque, power, and temperature) as a function of pin thread forms and features (thread/flat/flute) on mildly tapered conical pins were examined in AA6061-T6 for a range of welding parameters. The coarser thread pitch with different pin features performed better for producing good quality welds compared to finer threaded pins. Forge force requirements can be minimised using counter-flow flutes in threaded pin. Variations of nugget geometry, torque, power, and temperature were reported to correlate their dependence on pin features.
ARGs-OAP v2.0 with an expanded SARG database and Hidden Markov Models for enhancement characterization and quantification of antibiotic resistance genes in environmental metagenomes
Authors: Yin Xiaole , Jiang Xiao-Tao , Chai Benli , Li Liguan , Yang Ying , Cole James R , Tiedje James M , Zhang Tong
Published: February 2018

Motivation

Much global attention has been paid to antibiotic resistance in monitoring its emergence, accumulation and dissemination. For rapid characterization and quantification of antibiotic resistance genes (ARGs) in metagenomic datasets, an online analysis pipeline, ARGs-OAP has been developed consisting of a database termed Structured Antibiotic Resistance Genes (the SARG) with a hierarchical structure (ARGs type-subtype-reference sequence).

Results

The new release of the database, termed SARG version 2.0, contains sequences not only from CARD and ARDB databases, but also carefully selected and curated sequences from the latest protein collection of the NCBI-NR database, to keep up to date with the increasing number of ARG deposited sequences. SARG v2.0 has tripled the sequences of the first version and demonstrated improved coverage of ARGs detection in metagenomes from various environmental samples. In addition to annotation of high-throughput raw reads using a similarity search strategy, ARGs-OAP v2.0 now provides model-based identification of assembled sequences using SARGfam, a high-quality profile Hidden Markov Model (HMM), containing profiles of ARG subtypes. Additionally, ARGs-OAP v2.0 improves cell number quantification by using the average coverage of essential single copy marker genes, as an option in addition to the previous method based on the 16S rRNA gene.

Availability and implementation

ARGs-OAP can be accessed through http://smile.hku.hk/SARGs. The database could be downloaded from the same site. Source codes for this study can be downloaded from https://github.com/xiaole99/ARGs-OAP-v2.0.

Supplementary information

Supplementary data are available at Bioinformatics online.
Suppression of globular cluster formation in metal-poor gas clouds by Lyman α radiation feedback
Authors: Abe Makito , Yajima Hidenobu
Published: February 2018

We study the impact of Ly α radiation feedback on globular cluster (GC) formation. In this Letter, we analytically derive the relation between star formation efficiency (SFE) and metallicity in spherical clouds with the Ly α radiation feedback. Our models show that the SFE becomes small as the metallicity decreases. In metal-poor gas clouds, Ly α photons are trapped for a long time and exert strong radiation force to the gas, resulting in the suppression of star formation. We find that bound star clusters (SFE ≳ 0.5) form only for the metallicity higher than ∼ 10− 2.5 Z⊙ in the case with the initial cloud mass 105 M⊙ and the radius 5 pc. Our models successfully reproduce the lower bound of observed metallicity of GCs. Thus, we suggest that the Ly α radiation feedback can be essential in understanding the formation of GCs.
The Increase in Hospitalizations for Urinary Tract Infections and the Associated Costs in the United States, 1998–2011
Authors: Simmering Jacob E. , Tang Fan , Cavanaugh Joseph E. , Polgreen Linnea A. , Polgreen Philip M.
Published: February 2018

Background

Outpatient therapies for urinary tract infections (UTIs) are becoming limited due to antimicrobial resistance. The purpose of this paper is to report how the incidence of hospitalizations for UTIs have varied over time in both men and women and across age groups. We also explore how the severity for UTI hospitalizations has changed and describe the seasonality of UTI hospitalizations.

Methods

Using the Nationwide Inpatient Sample, we compute a time-series of UTI incidence and subdivide the series by age and sex. We fit a collection of time-series models to explore how the trend and seasonal intensity varies by age and sex. We modeled changes in severity using regression with available confounders.

Results

In 2011, there were approximately 400000 hospitalizations for UTIs with an estimated cost of $2.8 billion. Incidence increased by 52% between 1998 and 2011. The rate of increase was larger among both women and older patients. We found that the seasonal intensity (summer peaks and winter troughs) increased over time among women while decreasing among men. For both men and women, seasonality decreased with advancing age. Relative to controls and adjusted for demographics, we found that costs among UTI patients grew more slowly, patients left the hospital earlier, and patients had lower odds of death.

Conclusions

Incidence of UTI hospitalization is increasing and is seasonal, peaking in the summer. However, the severity of UTI admissions seems to be decreasing, indicating that patients previously treated as outpatients may now be admitted to the hospital due to increasing antimicrobial resistance.
Therapeutic drug monitoring of biologicals in rheumatoid arthritis: a disconnect between beliefs and facts
Authors: den Broeder Alfons A. , van Herwaarden Noortje , van den Bemt Bart J.F.
Published: February 2018

Purpose of review

To give an overview of recently published articles covering therapeutic drug monitoring (TDM) of biological DMARDs (bDMARDs) in rheumatoid arthritis.

Recent findings

In the last 18 months, two clinical studies and nine reviews were found after a systematic literature search. Most (narrative) reviews conclude that TDM should be used to improve biological treatment in rheumatoid arthritis patients, whereas most of the clinical studies (including 13 studies identified earlier) whenever scrutinized do not support this conclusion. This disconnect between sobering data from prediction studies and test-treatment diagnostic studies and optimistic TDM beliefs in reviews is caused by failure to recognize incorrect study designs, false positives because of lack of validation after explorative multiple testing, cherry picking of studies, and incorrect interpretation of test characteristics.

Serum (anti)-drug level monitoring has been extensively studied in rheumatoid arthritis, but correctly designed and executed interventional prediction studies or test-treatment intervention studies are sparse and mostly negative. In contrast, many reviews advocate use of biological TDM in rheumatoid arthritis. On the basis of current evidence, therapeutic drug monitoring of biologicals cannot be recommended in the treatment of rheumatoid arthritis patients, although two clinical scenarios deserve further study.
Early Electroencephalography Findings in Cardiogenic Shock Patients Treated by Venoarterial Extracorporeal Membrane Oxygenation
Authors: Sinnah Fabrice , Dalloz Marie-Amélie , Magalhaes Eric , Wanono Ruben , Neuville Mathilde , Smonig Roland , Radjou Aguila , Mourvillier Bruno , Bouadma Lila , Timsit Jean-François , d’Ortho Marie-Pia , Rouvel-Tallec Any , Sonneville Romain
Published: February 2018

Objectives:

We aimed to assess early electroencephalography findings in patients treated by venoarterial extracorporeal membrane oxygenation and their association with neurologic outcome.

Design:

Single-center observational study.

Setting:

Medical ICU of a university hospital.

Patients:

An early standardized electroencephalography assessment, that is, standard electroencephalography followed by continuous electroencephalography, was performed in consecutive cardiogenic shock patients requiring venoarterial extracorporeal membrane oxygenation. Associations between electroencephalography findings and outcome, defined as a composite of acute brain injury or death at 14 days, were investigated.

Measurements and Main Results:

Twenty-two patients with a median Full Outline of Unresponsiveness score of 4 (interquartile range, 3–6) were studied. Pupillary light reflex, corneal reflex, and cough reflex were preserved in 20 (90%), 17 (77%), and 17 (77%) patients, respectively. Overall, standard electroencephalography findings consisted of diffuse slowing in 21 patients (95%) and severe background abnormalities in 13 patients (59%) (i.e., a discontinuous [n= 5; 23%] and/or an unreactive background [n= 9; 41%]). Severe background abnormalities on standard electroencephalography (poor outcome rate: 69% vs 22%;p= 0.03) and absence of sleep transients on continuous electroencephalography (poor outcome rate: 67% vs 14%;p= 0.02) were associated with a poor outcome, whereas neurologic findings and doses of sedation were not. Patients without sleep transients on continuous electroencephalography tended to have lower Full Outline of Unresponsiveness scores than patients with preserved sleep transients-appearing patterns.

Conclusions:

In patients treated by venoarterial extracorporeal membrane oxygenation, early severe background abnormalities on standard electroencephalography provide important information on neurologic outcome. The lack of sleep transients on continuous electroencephalography reflects the severity of brain dysfunction and might represent an additional prognostic marker.
Detection of Cytomegalovirus in Liver Tissue by Polymerase Chain Reaction in Infants With Neonatal Cholestasis
Authors: Goel Akshat , Chaudhari Sneha , Sutar Jyoti , Bhonde Gauri , Bhatnagar Sushmita , Patel Vainav , Bhor Vikrant , Shah Ira
Published: February 2018

Aim:

Cytomegalovirus (CMV) is associated with neonatal cholestasis (NC). Diagnosis of CMV infection is most often based on either positive blood CMV IgM or CMV blood polymerase chain reaction (PCR). Isolation of CMV in liver tissues in patients with NC has rarely been reported. This study was undertaken to see if CMV is present in liver tissues of patients with NC and evaluate the correlation between positive CMV PCR in liver tissue with the serology and blood PCR.

Methods:

This study was conducted in 31 infants with NC from June 2015 to December 2016. All patients underwent blood CMV IgM, blood CMV PCR and liver CMV PCR. Prevalence of CMV in NC based on positive liver CMV PCR was calculated. Sensitivity and specificity of the serologic markers and blood CMV PCR to identify CMV infection in the liver was determined.

Results:

CMV IgM was positive in 13 (42%) patients, CMV IgG was positive in 26 (84%) patients and blood CMV PCR was positive in 23 (74%) patients. Liver CMV PCR was positive in 16 (52%) patients. Fifteen (48%) patients had biliary atresia (BA), 10 (32%) patients had neonatal hepatitis, 5 (16%) had paucity of bile ducts and 1 (3%) had ascending cholangitis. Of the 16 patients with positive liver CMV PCR, 8 (50%) had BA, 4 (25%) had neonatal hepatitis, 3 (19%) had paucity of bile ducts and 1 (6%) had ascending cholangitis. Sensitivity of blood CMV IgM in relation to liver CMV PCR was 69% and specificity was 61%. Sensitivity of blood CMV PCR was 61% and specificity was 71% when compared with liver CMV PCR.

Conclusion:

CMV is present in the liver tissues of more than half the patients with NC. Serology or blood CMV PCR is apparently not an accurate marker of CMV in the liver tissue. Also, CMV infection in children seems to be associated equally with BA or non-BA neonatal hepatitis.
Symptoms, Signs and Long-term Prognosis of Vertically Transmitted Chlamydia trachomatis Infections
Authors: Honkila Minna , Renko Marjo , Pokka Tytti , Wikström Erika , Uhari Matti , Tapiainen Terhi
Published: February 2018

Background:

Although Chlamydia trachomatis infection is common in pregnant women, such infections are rarely encountered in infants. To clarify the recognition of C. trachomatis infections in infants, we analyzed symptoms and signs of perinatally acquired chlamydial infection, together with its long-term prognosis in a large population-based patient series.

Methods:

A search through 2 national health registries covering 1996–2011, a cohort of 933,823 births, yielded 124 children with a microbiologically confirmed C. trachomatis infection. We then reviewed copies of the children’s medical records up to 16 years of age.

Results:

One-third of the infants with chlamydial conjunctivitis (33/110) had spontaneous blood-stained discharge from the infected eye. The infants with C. trachomatis lower respiratory tract infection were mostly afebrile (30/32), and 15/32 of them had wheezing. Staccato cough was not recorded in any of the infants. The median diagnostic delay from the onset of the symptoms was 13 (range 4–374) days for conjunctivitis and 25 (range 10–149) days for lower respiratory tract infection. One neglected child developed bilateral corneal scars because of an untreated C. trachomatis infection.

Conclusions:

Blood-stained discharge was a typical finding in C. trachomatis conjunctivitis. The C. trachomatis–infected infants had severe and prolonged symptoms, but long-term consequences were rare. The diagnostic delay was long, especially among the infants with a C. trachomatis lower respiratory tract infection.
Is acute kidney injury a harbinger for chronic kidney disease?
Authors: Selewski David T. , Hyatt Dylan M. , Bennett Kevin M. , Charlton Jennifer R.
Published: February 2018

Purpose of review

Despite abundant evidence in adults, the relationship between acute kidney injury (AKI) and chronic kidney disease (CKD) remains unanswered in pediatrics. Obstacles to overcome include the challenges defining these entities and the lack of long-term follow-up studies. This review focuses on pediatric populations at high-risk for AKI, the evidence of the long-term effect of AKI on renal health, and biomarkers to detect renal disease.

Recent findings

AKI in critically ill children and neonates is common and independently associated with adverse outcomes. Patients with diabetes and sickle cell disease along with neonates with necrotizing enterocolitis have been identified as high-risk for AKI. Preterm birth and neonates with AKI have signs of renal dysfunction early in childhood. Urinary biomarkers may identify AKI and CKD earlier than traditional biomarkers, but more work is necessary to determine their clinical utility. Promising technological advances including the ability to determine nephron number noninvasively will expand our ability to characterize the AKI to CKD transition.

AKI is common and associated with poor outcomes. It is probable that AKI is a harbinger to CKD in pediatric populations. However, we currently lack the tools to definitely answer this question and more research is needed.
Eosinophil Counts in the Small Intestine and Colon of Children Without Apparent Gastrointestinal Disease
Authors: Kiss Zoltán , Tél Bálint , Farkas Nelli , Garami András , Vincze Áron , Bajor Judit , Sarlós Patrícia , Márta Katalin , Erős Adrienn , Mikó Alexandra , Szakács Zsolt , Pécsi Dániel , Mátrai Péter , Hegyi Péter , Veres Gábor
Published: February 2018

The aim of the current study was to review the available data regarding eosinophil density in healthy tissue specimen originating from lower gastrointestinal segments to support suggested diagnostic cutoffs widely used in clinical practice. A systematic search was performed in 3 different databases. Calculations were made with Comprehensive MetaAnalysis software using random‐effects model. Cell number measurements were pooled using the random‐effects model and displayed on forest plots. Summary point estimations, 95% confidence intervals (CIs), and 95% prediction intervals (PIs) were calculated. The cumulative mean cell numbers were 8.26 (95% CI 4.71‐11.80) with PI of 0‐25.32 for the duodenum, 11.52 (95% CI 7.21‐15.83) with PI 0‐60.64 for the terminal ileum, and 11.10/ high‐power field (HPF) (95% CI 9.11–13.09) with PI of 0.96 to 21.23 in the large intestine and the rectum (HPF area = 0.2 mm2). Previous studies included control patients with irritable bowel syndrome and functional gastrointestinal disorders. As mucosal eosinophils have a role in their pathomechanism, those patients should have been excluded. A critical point of interpreting reported data is that HPF is relative to the technical parameters of the microscopes; therefore, it is important to report findings in cell/mm2. The present meta‐analysis does not support the higher (>20) or lower (<10) cutoff values for healthy tissue eosinophil number. In contrast to the esophagus, there is no normal cutoff eosinophil density in the small intestine and the colon. A prospective, multicenter study to establish normal mucosal eosinophil density is clearly needed.
The Value of Regional Cerebral Blood Flow SPECT and FDG PET in Operculoinsular Epilepsy
Authors: Fei Phillip , Soucy Jean-Paul , Obaid Sami , Boucher Olivier , Bouthillier Alain , Nguyen Dang Khoa
Published: February 2018

Purpose

Operculoinsular epilepsy (OIE) can be challenging to diagnose. While the value of SPECT cerebral blood flow and PET 18F-FDG studies for presurgical evaluation of patients with medial temporal lobe epilepsy (MTLE) is well established, it remains unclear whether they can help identify an operculoinsular epileptic focus. This study assesses the value of interictal/ictal regional cerebral blood flow (rCBF) SPECT and FDG PET for OIE diagnosis.

Methods

Eighteen patients with proven OIE who underwent interictal/ictal rCBF SPECT and/or FDG-PET prior to epilepsy surgery were identified from our clinical database and were compared with a group of 18 patients who underwent MTLE surgery. Regional cerebral blood flow SPECT and FDG PET images were reevaluated visually by an expert reader blind to clinical data.

Results

Interictal/ictal rCBF SPECT correctly identified an operculoinsular focus in 11 (65%) of 17 OIE patients and was misleading in 3 cases (18%). Secondary activation in areas connected to the insula was often observed. In the MTLE group, the area of maximal increased perfusion was congruent in 12 (75%) of 16 patients and extended to the ipsilateral insula in 1 patient. FDG PET findings were concordant with the epileptic focus in 8 (47%) of 17 OIE patients and were misleading in 4 (24%), whereas they were concordant in all MTLE patients.

Conclusions

Interictal/ictal rCBF SPECT can identify a concordant operculoinsular focus in a significant proportion of OIE patients and offers a valuable diagnostic tool in nonlesional cases. By contrast, the value of interictal FDG PET in this population is more equivocal.
Same or Different
Authors: Terry Nicole Patton , Gatlin Brandy , Johnson Lakeisha
Published: February 2018

Reading achievement gaps are prominent in U.S. schools, most notably when comparing the performance of African American and Latino/Hispanic children to their White peers. Among the many reasons offered to explain and address these achievement gaps, language differences and language proficiency are primary considerations because many African American children are bidialectal and many Latino/Hispanic children are bilingual. A review of research findings on the relations between language and reading development and performance in these two distinct student populations suggests that bidialectalism and bilingualism are not risks to be remedied. Rather, they are unique language experiences that have different implications for children's English language knowledge and, therefore, reading development and achievement. Moreover, there is evidence that, when provided with rich and robust language interactions, bidialectalism and bilingualism can be leveraged as strengths to support literacy learning.
Professional Development Aimed at Increasing the Quality of Language Input During Storybook Interactions
Authors: O'Keefe Casey
Published: February 2018

This article provides a review of problems associated with teachers' talk and indicators of higher quality teachers' talk for use with lower socioeconomic status (SES) Head Start students. Then it shows how one Head Start teacher, called Michele in this article, responded to professional development that was aimed at increasing the quality of language input during storybook interactions, especially for children from low SES communities. Michele's attempts to modify her classroom discourse in her response to her experiences may inform future efforts to work with teachers to improve their classroom interactions with children in inner city Head Start programs, including those who are bilingual and bidialectal. In addition, the article describes the methods that were used to increase Michele's awareness of her language use and draws examples from her experiences in attempting to translate them into higher quality of language input for her Head Start students in actual practice. This qualitative case study shows one teacher's journey and highlights several turning points along the way, perhaps serving as evidence that the intense effort required for this type of change is worth it.
A survey on information sources used by academic researchers to evaluate scientific instruments
Authors: Bergenholtz Carsten , MacAulay Samuel C. , Kolympiris Christos , Seim Inge
Published: February 2018

Most scientific research is fueled by research equipment (instruments); typically hardware purchased to suit a particular research question. Examples range from 17thcentury microscopes to modern particle colliders and high-throughput sequencers. Here, we studied the information sources used by academic researchers to assess scientific instruments, and reveal evidence of a worrying confluence of incentives similar to those that drove the biopharmaceutical industry to adopt controversial practices such as ghostwriting and hidden sponsorship. Our findings suggest there are little understood incentives against disclosure in the peer-reviewed literature on scientific instruments; constituting an underappreciated threat to scientific standards of trustworthiness and transparency. We believe that a public debate and subsequent editorial policy action are urgently required.
Genome-wide translating mRNA analysis following ketamine reveals novel targets for antidepressant treatment
Authors: Miller Oliver H. , Grabole Nils , Wells Isabelle , Hall Benjamin J.
Published: February 2018

Low-dose ketamine is an efficacious antidepressant for treatment-resistant unipolar and bipolar depressed patients. Major Depression Disorder patients receiving a single infusion report elevated mood within two hours, and ketamine’s antidepressant effects have been observed as long as seven days post-treatment. In light of this remarkable observation, efforts have been undertaken to “reverse-translate” ketamine’s effects to understand its mechanism of action. Major advances have been achieved in understanding the molecular, cellular, and circuit level changes that are initiated by low-dose ketamine. Although enhancement of protein synthesis clearly plays a role, the field lacks a comprehensive understanding of the protein synthesis program initiated after ketamine treatment. Here, using ribosome-bound mRNA footprinting and deep sequencing (RiboSeq), we uncover a genome-wide set of actively translated mRNAs (the translatome) in medial prefrontal cortex after an acute antidepressant-like dose of ketamine. Gene Ontology analysis confirmed that initiation of protein synthesis is a defining feature of antidepressant-dose ketamine in mice and Gene Set Enrichment Analysis points to a role for GPCR signaling, metabolism, vascularization, and structural plasticity in ketamine’s effects. One gene, VIPR2, whose protein product VPAC2 acts as a GPCR for the neuropeptide vasoactive intestinal peptide, was characterized in cortex and identified as a potential novel target for antidepressant action.
Ecological advantages and evolutionary limitations of aggregative multicellular development
Authors: Pentz Jennifer T. , Márquez-Zacarías Pedro , Yunker Peter J. , Libby Eric , Ratcliff William C.
Published: February 2018

All multicellular organisms develop through one of two basic routes: they either aggregate from free-living cells, creating potentially-chimeric multicellular collectives, or they develop clonally via mother-daughter cellular adhesion. While evolutionary theory makes clear predictions about trade-offs between these developmental modes, these have never been experimentally tested in otherwise genetically-identical organisms. We engineered unicellular baker’s yeast (Saccharomyces cerevisiae) to develop either clonally (‘snowflake’, Δace2), or aggregatively (‘floc’,GAL1p::FLO1), and examined their fitness in a fluctuating environment characterized by periods of growth and selection for rapid sedimentation. When cultured independently, aggregation was far superior to clonal development, providing a 35% advantage during growth, and a 2.5-fold advantage during settling selection. Yet when competed directly, clonally-developing snowflake yeast rapidly displaced aggregative floc. This was due to unexpected social exploitation: snowflake yeast, which do not produce adhesive FLO1, nonetheless become incorporated into flocs at a higher frequency than floc cells themselves. Populations of chimeric clusters settle much faster than floc alone, providing snowflake yeast with a fitness advantage during competition. Mathematical modeling suggests that such developmental cheating may be difficult to circumvent; hypothetical ‘choosy floc’ that avoid exploitation by maintaining clonality pay an ecological cost when rare, often leading to their extinction. Our results highlight the conflict at the heart of aggregative development: non-specific cellular binding provides a strong ecological advantage – the ability to quickly form groups – but this very feature leads to its exploitation.
Relationships between Human Brain Structural Connectomes and Traits
Authors: Zhang Zhengwu , Allen Genevera I. , Zhu Hongtu , Dunson David
Published: February 2018

Advanced brain imaging techniques make it possible to measure individuals’ structural connectomes in large cohort studies non-invasively. However, due to limitations in image resolution and pre-processing, questions remain about whether reconstructed connectomes are measured accurately enough to detect relationships with human traits and behaviors. Using a state-of-the-art structural connectome processing pipeline and a novel dimensionality reduction technique applied to data from the Human Connectome Project (HCP), we show strong relationships between connectome structure and various human traits. Our dimensionality reduction approach uses a tensor characterization of the connectomes and relies on a generalization of principal components analysis. We analyze over 1100 scans for 1076 subjects from the HCP and the Sherbrooke test-retest data set as well as 175 human traits that measure domains including cognition, substance use, motor, sensory and emotion. We find that brain connectomes are associated with many traits. Specifically, fluid intelligence, language comprehension, and motor skills are associated with increased cortical-cortical brain connectivity, while the use of alcohol, tobacco, and marijuana are associated with decreased cortical-cortical connectivity.
The evolutionary dynamics of microRNAs in domestic mammals
Authors: Penso-Dolfin Luca , Moxon Simon , Haerty Wilfried , Di Palma Federica
Published: February 2018

MicroRNAs are crucial regulators of gene expression found across both the plant and animal kingdoms. While the numberof annotated microRNAs deposited in miRBase has greatly increased in recent years, few studies provided comparative analyses across sets of related species, or investigated the role of microRNAs in the evolution of gene regulation.

We generated small RNA libraries across 5 mammalian species (cow, dog, horse, pig and rabbit) from 4 different tissues (brain, heart, kidney and testis). We identified 1675 miRBase and 413 novel microRNAs by manually curating the set of computational predictions obtained frommiRCatandmiRDeep2.

Our dataset spanning five species has enabled us to investigate the molecular mechanisms and selective pressures driving the evolution of microRNAs in mammals. We highlight the important contributions of intronic sequences (366 orthogroups), duplication events (135 orthogroups) and repetitive elements (37 orthogroups) in the emergence of new microRNA loci.

We use this framework to estimate the patterns of gains and losses across the phylogeny, and observe high levels of microRNA turnover. Additionally, the identification of lineage-specific losses enables the characterisation of the selective constraints acting on the associated target sites.

Compared to the miRBase subset, novel microRNAs tend to be more tissue specific. 20 percent of novel orthogroups are restricted to the brain, and their target repertoires appear to be enriched for neuron activity and differentiation processes. These findings may reflect an important role for young microRNAs in the evolution of brain expression plasticity.

Many seed sequences appear to be specific to either the cow or the dog. Analyses on the associated targets highlightthe presence of several genes under artificial positive selection, suggesting an involvement of these microRNAs in the domestication process.

Altogether, we provide an overview on the evolutionary mechanisms responsible for microRNA turnover in 5 domestic species, and their possible contribution to the evolution of gene regulation.
A Survey of Orbitrap All Ion Fragmentation Analysis Assessed by an R MetaboList Package to Study Small-molecule Metabolites
Authors: Sentandreu Enrique , Peris-Díaz Manuel D , Sweeney Shannon R , Chiou Jennifer , Muñoz Nathalie , Tiziani Stefano
Published: February 2018

Leukemia cell and melanoma tumor tissue extracts were studied for small (mostly m/z <250) polar metabolites by LC-ESI-HRMSn analysis powered by a hybrid Quadrupole-Orbitrap. MS data was simultaneously acquired in fast polarity switching mode operating in MS1 and MS/MS (All Ion Fragmentation, AIF) full-scan analyses at high mass resolution. Positive assignments were achieved by AIF analysis considering at least two characteristic transitions of metabolites. A targeted metabolite profiling was achieved by the relative quantification of 18 metabolites through spiking their respective deuterated counterparts. Manual data processing of MS1 and AIF scans were compared for accurate determination of natural metabolites and their deuterated analogs by chromatographic alignment and peak area integration. Evaluation of manual and automated (MetaboList R package) AIF data processing yielded comparable results. The versatility of AIF analysis also enabled the untargeted metabolite profiling of leukemia and melanoma samples in which 22 and 53 compounds were respectively identified outside those studied by labeling. The main limitation of the method was that low abundance metabolites with scan rates below 8 scans/peak could not be accurately quantified by AIF analysis. Combination of AIF analysis with MetaboList R package represents an opportunity to move towards automated, faster and more global metabolomics approaches supported by an entirely flexible open source automated data processing platform freely available from Comprehensive R Archive Network (CRAN, https://CRAN.R-project.org/package=MetaboList).
Rapid multiplex small DNA sequencing on the MinION nanopore sequencing platform
Authors: Wei Shan , Weiss Zachary R. , Williams Zev
Published: February 2018

Real-time sequencing of short DNA reads has a wide variety of clinical and research applications including screening for mutations, target sequences and aneuploidy. We recently demonstrated that MinION, a nanopore-based DNA sequencing device the size of a USB drive, could be used for short-read DNA sequencing. In this study, an ultra-rapid multiplex library preparation and sequencing method for the MinION is presented and applied to accurately test normal diploid and aneuploidy samples’ genomic DNA in under three hours, including library preparation and sequencing. This novel method shows great promise as a clinical diagnostic test for applications requiring rapid short-read DNA sequencing.
Anatomical, Physiological, and Functional Heterogeneity of the Dorsal Raphe Serotonin System
Authors: Ren Jing , Friedmann Drew , Xiong Jing , Liu Cindy D. , DeLoach Katherine E. , Ran Chen , Pu Albert , Sun Yanwen , Weissbourd Brandon , Neve Rachael L. , Horowitz Mark , Luo Liqun
Published: February 2018

The dorsal raphe (DR) constitutes a major serotonergic input to the forebrain, and modulates diverse functions and brain states including mood, anxiety, and sensory and motor functions. Most functional studies to date have treated DR serotonin neurons as a single, homogeneous population. Using viral-genetic methods, we found that subcortical-vs. cortical-projecting serotonin neurons have distinct cell body distributions within the DR and different degrees of coexpressing a vesicular glutamate transporter. Further, the amygdala-and frontal cortex-projecting DR serotonin neurons have largely complementary whole-brain collateralization patterns, receive biased inputs from presynaptic partners, and exhibit opposite responses to aversive stimuli. Gain-and loss-of-function experiments suggest that amygdala-projecting DR serotonin neurons promote anxiety-like behavior, whereas frontal cortex-projecting neurons promote active coping in face of challenge. These results provide compelling evidence that the DR serotonin system contains parallel sub-systems that differ in input and output connectivity, physiological response properties, and behavioral functions.
N6-methyladenosine binding proteins negatively regulate HIV-1 infectivity and viral production
Authors: Lu Wuxun , Tirumuru Nagaraja , Koneru Pratibha C. , Liu Chang , Kvaratskhelia Mamuka , He Chuan , Wu Li
Published: February 2018

Background

The internalN6-methyladenosine (m6A) modification of cellular mRNA regulates post-transcriptional gene expression. The YTH domain family proteins (YTHDF1-3, or Y1-3) bind to m6A-modified cellular mRNA and modulate its metabolism and processing, thereby affecting protein translation in cells. We previously reported that HIV-1 RNA contains m6A modification and that Y1-3 proteins inhibit HIV-1 infection by decreasing HIV-1 reverse transcription. Here we extended our studies to further understand the mechanisms of Y1-3-mediated inhibition of HIV-1 infection and viral production.

Results

Overexpression of Y1-3 proteins in HIV-1 target cells decreased viral genome RNA (gRNA) levels and inhibited early and late reverse transcription. Purified recombinant Y1-3 proteins preferentially bound to the m6A-modified 5’ leader sequence of gRNA compared with its unmodified RNA counterpart, consistent with the strong binding of Y1-3 to HIV-1 gRNA in infected cells. HIV-1 mutants with two altered m6A modification sites in the 5’ leader sequence of gRNA demonstrated significantly lower infectivity compared with wild-type HIV-1, confirming that these sites are important for viral infection. HIV-1 produced from cells with knockdown of endogenous Y1, Y3, or Y1-3 proteins together showed increased viral infectivity compared with HIV-1 produced from control cells. Interestingly, we found that Y1-3 proteins and HIV-1 Gag formed a complex with RNA in HIV-1-infected target cells.

Conclusions

Our results suggest the inhibitory effects of Y1-3 proteins on HIV-1 infection and provide new insight into the mechanisms of m6A modification of HIV-1 RNA in regulating viral replication, which clarify some discrepancies in the previously published studies in this area.
A stable mode of bookmarking by TBP recruits RNA Polymerase II to mitotic chromosomes
Authors: Teves Sheila S. , An Luye , Bhargava-Shah Aarohi , Xie Liangqi , Darzacq Xavier , Tjian Robert
Published: February 2018

How a cell maintains transcriptional fidelity across mitosis has remained an enduring mystery in biology. One challenge arises during mitosis when chromatin becomes condensed and transcription is shut off. How do the daughter cells re-establish the original transcription program? Here, we report that the TATA-binding protein (TBP), a key component of the core transcriptional machinery, remains bound globally to active promoters in ES cells during mitosis. Using live-cell single-molecule imaging, we observed that TBP mitotic binding is highly stable, with an average residence time of minutes. This stable binding is in stark contrast to typical TFs with residence times of seconds. To test the functional effect of mitotic TBP binding, we used a drug-inducible degron system and found that TBP promotes the association of RNA Polymerase II with mitotic chromosomes, and facilitates transcriptional reactivation following mitosis. These results suggest that the core transcriptional machinery maintains global transcriptional memory during mitosis.
Crystal structure of chromo barrel domain of RBBP1
Authors: Lei Ming , Feng Yue , Zhou Mengqi , Yang Yuan , Loppnau Peter , Li Yanjun , Yang Yi , Liu Yanli
Published: February 2018

RBBP1 is a retinoblastoma protein (pRb) binding protein acting as a repressor of gene transcription. RBBP1 is a multidomain protein including a chromo barrel domain, and its chromo barrel domain has been reported to recognize histone H4K20me3 weakly, and this binding is enhanced by the simultaneous binding of DNA. However, the molecular basis of this DNA-mediated histone binding by the chromo barrel domain of RBBP1 is unclear. Here we attempted to co-crystallize the chromo barrel domain of RBBP1 with either a histone H4K20me3 peptide alone or with both a histone H4K20me3 peptide and DNA, but only solved the peptide/DNA unbound crystal structure. Our structural analysis indicates that RBBP1 could interact with histone H4K20me3 similar to other histone binding chromo barrel domains, and the surface charge representation analysis of the chromo barrel domain of RBBP1 suggests that the chromo barrel domain of RBBP1 does not have a typical DNA binding surface, indicating that it might not bind to DNA. Consistently, our ITC assays also showed that DNA does not significantly enhance the histone binding ability of the chromo barrel domain of RBBP1.
Mechanistic analysis of the SERK3 elongated allele defines a role for BIR ectodomains in brassinosteroid signaling
Authors: Hohmann Ulrich , Nicolet Joël , Moretti Andrea , Hothorn Ludwig A. , Hothorn Michael
Published: February 2018

The leucine-rich repeat receptor kinase (LRR-RK) BRI1 requires a shape-complementary SERK co-receptor for brassinosteroid sensing and receptor activation. Interface mutations that weaken the interaction between receptor and co-receptor in vitro reduce brassinosteroid signaling responses. The SERK3 elongated (elg) allele maps to the complex interface and shows enhanced brassinosteroid signaling, but surprisingly no tighter binding to the BRI1 ectodomain in vitro. Here, we report that rather than promoting the interaction with BRI1, the elg mutation disrupts the ability of the co-receptor to interact with the ectodomains of BIR receptor pseudokinases, negative regulators of LRR-RK signaling. A conserved lateral surface patch in BIR LRR domains is required for targeting SERK co-receptors and the elg allele maps to the core of the complex interface in a 1.25 Å BIR3 - SERK1 structure. Collectively, our structural, quantitative biochemical and genetic analyses suggest that brassinosteroid signaling complex formation is negatively regulated by BIR receptor ectodomains.