bluuebunny/crossref_metadata_2025 huggingface dataset:
Pubertal activation of estrogen receptor α in the medial amygdala is essential for the full expression of male social behavior in mice
Authors: Sano Kazuhiro , Nakata Mariko , Musatov Sergei , Morishita Masahiro , Sakamoto Toshiro , Tsukahara Shinji , Ogawa Sonoko
Published: June 2016

Significance

Testosterone stimulation during the pubertal period is necessary for the full expression of male-type social behaviors. However, it is not known whether estrogen receptor (ER) α may be involved in pubertal organizational action of testosterone on the regulation of male-type social behaviors. In this study, we showed that the prepubertal knockdown of ERα in the medial amygdala (MeA) of gonadally intact male mice reduced both sexual and aggressive behaviors as well as the number of MeA neurons later in adulthood. These results indicate that not only aromatization but also ERα expression in the MeA during the pubertal period is required for organizational action of testosterone to fully masculinize neural circuitry responsible for the expression of male-type social behaviors.
Selective small molecule inhibitor of the
Mycobacterium tuberculosis
fumarate hydratase reveals an allosteric regulatory site
Authors: Kasbekar Monica , Fischer Gerhard , Mott Bryan T. , Yasgar Adam , Hyvönen Marko , Boshoff Helena I. M. , Abell Chris , Barry Clifton E. , Thomas Craig J.
Published: June 2016

Significance

The tricarboxylic acid (TCA) cycle plays a central role in the metabolism of many pathogens, but few inhibitors of this pathway currently exist. Our study describes the first small molecule inhibitor, to our knowledge, of the fumarate hydratase enzyme in the TCA cycle of
Mycobacterium tuberculosis
. We also report the discovery of an allosteric regulatory site that confers selectivity of the inhibitor’s activity over the homologous human enzyme. Our findings illustrate the potential to target vulnerable metabolic enzymes effectively and selectively, despite their high degree of evolutionary conservation.
Placebo effects in cognitive training
Authors: Foroughi Cyrus K. , Monfort Samuel S. , Paczynski Martin , McKnight Patrick E. , Greenwood P. M.
Published: June 2016

Significance

Placebo effects pose problems for some intervention studies, particularly those with no clearly identified mechanism. Cognitive training falls into that category, and yet the role of placebos in cognitive interventions has not yet been critically evaluated. Here, we show clear evidence of placebo effects after a brief cognitive training routine that led to significant fluid intelligence gains. Our goal is to emphasize the importance of ruling out alternative explanations before attributing the effect to interventions. Based on our findings, we recommend that researchers account for placebo effects before claiming treatment effects.
Multiple layers of transcriptional regulation by PLZF in NKT-cell development
Authors: Mao Ai-Ping , Constantinides Michael G. , Mathew Rebecca , Zuo Zhixiang , Chen Xiaoting , Weirauch Matthew T. , Bendelac Albert
Published: June 2016

Significance

Natural killer T (NKT) cells are a specialized population of innate-like T cells that acquire their effector program during development under the control of the transcription factor PLZF (promyelocytic leukemia zinc finger, encoded by
Zbtb16
). To elucidate the mechanisms underlying this unique property of PLZF, we performed ChIP-seq and microarray analysis of NKT cells and PLZF-transgenic T cells, which revealed direct regulation of effector genes and of T-helper–specific transcription factors. Notably, PLZF also bound and repressed
Bach2
, a global repressor of effector differentiation. Thus, multiple layers of positive and negative regulation coordinate the induction of the innate effector program by PLZF.
Decoding and disrupting left midfusiform gyrus activity during word reading
Authors: Hirshorn Elizabeth A. , Li Yuanning , Ward Michael J. , Richardson R. Mark , Fiez Julie A. , Ghuman Avniel Singh
Published: June 2016

Significance

A central issue in the neurobiology of reading is a debate regarding the visual representation of words, particularly in the left midfusiform gyrus (lmFG). Direct neural recordings, electrical brain stimulation, and pre-/postsurgical neuropsychological testing provided strong evidence that the lmFG supports an orthographically specific “visual word form” system that becomes specialized for the representation of orthographic knowledge. Machine learning elucidated the dynamic role lmFG plays with an early processing stage organized by orthographic similarity and a later stage supporting individuation of single words. The results suggest that there is a dynamic shift from gist-level to individuated orthographic representation in the lmFG in service of visual word recognition.
Electrorheology leads to healthier and tastier chocolate
Authors: Tao Rongjia , Tang Hong , Tawhid-Al-Islam Kazi , Du Enpeng , Kim Jeongyoo
Published: June 2016

Significance

Chocolate is one of the most popular food types and flavors in the world. Unfortunately, at present, chocolate products contain too much fat, leading to obesity. Although this issue was called into attention decades ago, no actual solution was found. To bypass this critical outstanding problem, two manufacturers introduced some low-calorie fats to substitute for cocoa butter. Somehow, their fats are forbidden in most countries. Here we show that, by applying an electric field to liquid chocolate in the flow direction, we aggregate the suspended particles into prolate spheroids. This microstructure change reduces the viscosity in the flow direction and enables us to reduce the fat level by 10–20%. A new class of healthier and tastier chocolate should come soon.
Antecedent contained deletions in native and non-native sentence processing
Authors: Boxell Oliver , Felser Claudia , Cunnings Ian
Published: June 2016

We report the results from an eye-movement monitoring study investigating native (L1) and non-native (L2) speakers’ real-time processing of antecedent-contained deletion (ACD), a type of verb phrase ellipsis in which the ellipsis gap forms part of its own antecedent. The resulting interpretation problem is traditionally thought to be solved by quantifier raising, a covert scope-shifting operation that serves to remove the gap from within its antecedent. Our L2 group comprised advanced, native German-speaking L2 learners of English. The analysis of the eye-movement data showed that both L1 and L2 English speakers tried to recover the missing verb phrase after encountering the gap. Only the native speakers showed evidence of ellipsis resolution being affected by quantification, however. No effects of quantification following gap detection were found in the L2 group, by contrast, indicating that recovery of the elided material was accomplished independently from the object’s quantificational status in this group.
Anger and the virtues: a critical study in virtue individuation
Authors: West Ryan
Published: June 2016

Aristotle and others suggest that a single virtue – ‘good temper’ – pertains specifically to anger. I argue that if good temper is a single virtue, it is constituted by aspects of a combination of other virtues. I present three categories of anger-relevant virtues – those that (potentially) dispose one to anger; those that delay, mitigate, and qualify anger; and those required for effortful anger control – and show how virtues in each category make distinct contributions to good temper. In addition to clarifying the relationship between anger and the virtues, my analysis has theoretical implications for virtue individuation more generally, and practical implications for character cultivation.
Un sein d’or et de lait: construire le corps invisible de l’épouse dans la
Première Continuation de Perceval
Authors: Foehr-Janssens Yasmina
Published: June 2016

La
Première Continuation de Perceval
contient, dans sa branche
iii
, le curieux récit de la guérison de Caradoc par l’attrait du corps ‘blanc et tendre’ de son amie Guinier. Le dispositif thérapeutique mis en place afin de débarrasser Caradoc d’un reptile qui s’est enroulé autour de son bras associe de manière explicite la chair de la jeune fille à la douceur du lait, d’autant que c’est vers son sein qu’elle attire l’animal venimeux. Nous tenterons de comprendre la logique de cette scène peu étudiée, contrairement aux autres épisodes du ‘Livre de Caradoc’. Notre lecture s’appuiera sur la version courte de la
Continuation
sans négliger pour autant les autres rédactions. Notre analyse cherche à montrer que ce récit contribue à établir une représentation très normative d’une relation amoureuse entièrement orientée vers la procréation. Tout en magnifiant le corps fécond de l’épouse, le ‘Livre de Caradoc’ affirme une maîtrise masculine sur la reproduction humaine.
Clinical Neurophysiology
Authors: Rubin Devon I. , Daube Jasper R.
Published: June 2016

Clinical neurophysiologic testing is an important component of evaluating patients with complaints that may be attributed to diseases of the central or peripheral nervous system. This classic volume in the Contemporary Neurology Series covers the basic concepts underlying each of the testing techniques and provides comprehensive descriptions of the methods and wide range of electrophysiologic testing available for patients with epilepsy, neuromuscular diseases, movement disorders, demyelinating diseases, sleep disorders, autonomic disorders and those undergoing orthopedic and neurosurgical procedures. This text details the role of each study, the interpretation of findings, and their application clinical problems. This text describes the multiple diagnostic procedures for diverse diseases of the neuromuscular system, including: electroencephalography (EEG); electromyography and nerve conduction studies; single fiber EMG; polysomnography; surface EMG patterns, blood pressure, pulse, sweat measures; vestibular function testing; deep brain stimulator physiology; and intraoperative monitoring. It is a practical textbook for neurologists, physiatrists and clinical neurophysiologists in clinical or research practice or in training. Key features of the new edition include fully updated chapters to reflect new research and techniques in clinical neurophysiology; updated images illustrating key elements of techniques and basic concepts; case examples for practical application.
The Local Group: the ultimate deep field
Authors: Boylan-Kolchin Michael , Weisz Daniel R. , Bullock James S. , Cooper Michael C.
Published: June 2016

Near-field cosmology – using detailed observations of the Local Group and its environs to study wide-ranging questions in galaxy formation and dark matter physics – has become a mature and rich field over the past decade. There are lingering concerns, however, that the relatively small size of the present-day Local Group (∼2 Mpc diameter) imposes insurmountable sample-variance uncertainties, limiting its broader utility. We consider the region spanned by the Local Group's progenitors at earlier times and show that it reaches 3 arcmin ≈ 7 comoving Mpc in linear size (a volume of ≈350 Mpc3) at z = 7. This size at early cosmic epochs is large enough to be representative in terms of the matter density and counts of dark matter haloes with Mvir(z = 7) ≲ 2 × 109 M⊙. The Local Group's stellar fossil record traces the cosmic evolution of galaxies with 103 ≲ M⋆(z = 0)/M⊙ ≲ 109 (reaching M1500 > −9 at z ∼ 7) over a region that is comparable to or larger than the Hubble Ultra-Deep Field (HUDF) for the entire history of the Universe. In the JWST era, resolved stellar populations will probe regions larger than the HUDF and any deep JWST fields, further enhancing the value of near-field cosmology.
Impact of a Telehealth Program That Delivers Remote Consultation and Longitudinal Mentorship to Community HIV Providers
Authors: Wood Brian R. , Unruh Kenton T. , Martinez-Paz Natalia , Annese Mary , Ramers Christian B. , Harrington Robert D. , Dhanireddy Shireesha , Kimmerly Lisa , Scott John D. , Spach David H.
Published: June 2016

Background.  To increase human immunodeficiency virus (HIV) care capacity in our region, we designed a distance mentorship and consultation program based on the Project ECHO (Extension for Community Healthcare Outcomes) model, which uses real-time interactive video to regularly connect community providers with a multidisciplinary team of academic specialists. This analysis will (1) describe key components of our program, (2) report types of clinical problems for which providers requested remote consultation over the first 3.5 years of the program, and (3) evaluate changes in participants′ self-assessed HIV care confidence and knowledge over the study period.

Methods.  We prospectively tracked types of clinical problems for which providers sought consultation. At baseline and regular intervals, providers completed self-efficacy assessments. We compared means using paired-samples t test and examined the statistical relationship between each survey item and level of participation using analysis of variance.

Results.  Providers most frequently sought consultation for changing antiretroviral therapy, evaluating acute symptomatology, and managing mental health issues. Forty-five clinicians completed a baseline and at least 1 repeat assessment. Results demonstrated significant increase (P < .05) in participants' self-reported confidence to provide a number of essential elements of HIV care. Significant increases were also reported in feeling part of an HIV community of practice and feeling professionally connected to academic faculty, which correlated with level of program engagement.

Conclusions.  Community HIV practitioners frequently sought support on clinical issues for which no strict guidelines exist. Telehealth innovation increased providers' self-efficacy and knowledge while decreasing professional isolation. The ECHO model creates a virtual network for peer-to-peer support and longitudinal mentorship, thus strengthening capacity of the HIV workforce.
Is Aerosalization a Problem With Carbapenem-Resistant Acinetobacter baumannii in Thailand Hospital?
Authors: Apisarnthanarak Anucha , Tantajina Ploenpit , Laovachirasuwan Pornpimol , Weber David J. , Singh Nalini
Published: June 2016

We evaluated the presence of air contamination with carbapenem-resistant Acinetobacter baumannii (CRAB) in medical units where patients with CRAB pneumonia were hospitalized, and in Obstetrics and Gynecology units with open-air ventilation in-patient settings. There was no evidence of CRAB contamination in either of the units.
Cefepime Therapy for Cefepime-Susceptible Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae Bacteremia
Authors: Wang Ruibin , Cosgrove Sara E. , Tschudin-Sutter Sarah , Han Jennifer H. , Turnbull Alison E. , Hsu Alice J. , Avdic Edina , Carroll Karen C. , Tamma Pranita D.
Published: June 2016

The role of cefepime for extended-spectrum β-lactamase (ESBL) bacteremia is unclear if susceptible in vitro. In a propensity score-matched study of patients with ESBL bacteremia, risk of death was 2.87 times higher for patients receiving cefepime compared with carbapenems (95% confidence interval [CI], .88–9.41). We compared 14-day mortality of patients with ESBL bacteremia receiving empiric cefepime versus empiric carbapenem therapy in a propensity score-matched cohort. There was a trend towards increased mortality in the cefepime group (hazard ratio, 2.87; 95% CI, .88–9.41), which enhances the existing literature suggesting that cefepime may be suboptimal for invasive ESBL infections.
Gas-to-dust ratios in massive star-forming galaxies at z ∼ 1.4
Authors: Seko Akifumi , Ohta Kouji , Yabe Kiyoto , Hatsukade Bunyo , Aono Yuya , Iono Daisuke
Published: June 2016

We present results of 12CO(J = 2–1) observations toward four massive star-forming galaxies at z ∼ 1.4 with the Nobeyama 45 m radio telescope. The galaxies are detected with Spitzer/MIPS in 24 μm and Herschel/SPIRE in 250 μm and 350 μm, and they mostly reside in the main sequence. Their gas-phase metallicities derived by the N2 method using the Hα and [N ii]λ 6584 emission lines are near the solar value. CO lines are detected toward three galaxies. The molecular-gas masses obtained are (9.6–35) × 1010 M⊙ by adopting the Galactic CO-to-H2 conversion factor and a CO(2–1)/CO(1–0) flux ratio of 3. The dust masses derived from the modified blackbody model (assuming a dust temperature of 35 K and an emissivity index of 1.5) are (2.4–5.4) × 108 M⊙. Resulting gas-to-dust ratios (not accounting for H i mass) at z ∼ 1.4 are 220–1450, which are several times larger than those in local star-forming galaxies. A dependence of the gas-to-dust ratio on the far-infrared luminosity density is not clearly seen.
Acute Babesiosis in Pregnancy
Authors: Gulersen Moti , Brost Brian Charles , Bobrovnikov Vladim , Bornstein Eran
Published: June 2016

BACKGROUND:

Hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome is a serious complication of pregnancy associated with significant maternal and fetal morbidity and mortality. Several medical conditions have been described as imitators of this syndrome, presenting with similar signs and symptoms.

CASE:

A term, multiparous woman with a history of prior pregnancy complicated by preeclampsia developed symptoms and laboratory abnormalities suggestive of HELLP syndrome. After an uncomplicated repeat caesarean delivery of a healthy newborn, infection with Babesia species was diagnosed incidentally on a peripheral blood smear. She was treated with antibiotics postpartum without sequelae for her or her newborn. The laboratory abnormalities normalized by postoperative day 4.

CONCLUSION:

Babesiosis complicating pregnancy may be a novel imitator of HELLP syndrome and should be considered in the differential diagnosis, especially where geographically prevalent infection exists.
Association of Sexual Debut in Adolescents With Microbiota and Inflammatory Markers
Authors: Jespers Vicky , Hardy Liselotte , Buyze Jozefien , Loos Jasna , Buvé Anne , Crucitti Tania
Published: June 2016

OBJECTIVE:

To investigate the association of sexual debut and vaginal, anorectal, and oral microbiota and vaginal inflammatory markers in female adolescents.

METHODS:

We conducted a school-based study in adolescents in Antwerp, Belgium. During three visits over 8 months, participants answered questionnaires and self-collected vaginal, anorectal, and oral swabs. Five Lactobacillus species, Lactobacillus genus, Gardnerella vaginalis, and Atopobium vaginae were quantified; and seven inflammatory markers were measured in the vaginal specimens. In the oral and anorectal specimens, Lactobacillus genus, G vaginalis, and A vaginae were ascertained.

RESULTS:

Of the 93 adolescents (mean age 16.2 years) at the first visit, 41 (44.1%) had passed sexual debut (penile–vaginal intercourse) and five (5.4%) had sexual experience without passing sexual debut. Having sexual experience at the first visit was not found to be associated with species presence or concentrations (acknowledging an underpowered study because the required sample size was not attained). Modeling the longitudinal data on all girls showed that sexual debut was associated with increased odds of vaginal and anorectal G vaginalis (P=.021; P=.030) and A vaginae (P=.041; P=.012) with increments of interleukins (interleukin [IL]-1α P<.001, IL-1β P=.046, IL-8 P=.033) and chemokines (regulated on activation, normal T cell expressed and secreted P<.001; macrophage inflammatory protein-1β P=.040), whereas no difference was seen when modeling (before–after) the girls initiating and girls staying without sexual intercourse. The association of sexual intercourse with IL-1α (P<.001), IL-1β (P=.030), and IL-8 (P=.002) at the first visit was (greater than 70%) mediated by vaginal G vaginalis and A vaginae concentrations.

CONCLUSION:

Sexual debut in adolescents is associated with an inflammatory vaginal reaction and with the presence of bacterial vaginosis–related species. Strategies preventing the colonization of bacterial vaginosis–related organisms during early sexual debut are urgently needed and may prevent acquisition of sexually transmitted infections including human immunodeficiency virus in early life.
The non-uniformity of fossil preservation
Authors: Holland Steven M.
Published: June 2016

The fossil record provides the primary source of data for calibrating the origin of clades. Although minimum ages of clades are given by the oldest preserved fossil, these underestimate the true age, which must be bracketed by probabilistic methods based on multiple fossil occurrences. Although most of these methods assume uniform preservation rates, this assumption is unsupported over geological timescales. On geologically long timescales (more than 10 Myr), the origin and cessation of sedimentary basins, and long-term variations in tectonic subsidence, eustatic sea level and sedimentation rate control the availability of depositional facies that preserve the environments in which species lived. The loss of doomed sediments, those with a low probability of preservation, imparts a secular trend to fossil preservation. As a result, the fossil record is spatially and temporally non-uniform. Models of fossil preservation should reflect this non-uniformity by using empirical estimates of fossil preservation that are spatially and temporally partitioned, or by using indirect proxies of fossil preservation. Geologically, realistic models of preservation will provide substantially more reliable estimates of the origination of clades.

This article is part of the themed issue ‘Dating species divergences using rocks and clocks’.
Conceptual issues in Bayesian divergence time estimation
Authors: Rannala Bruce
Published: June 2016

Bayesian inference of species divergence times is an unusual statistical problem, because the divergence time parameters are not identifiable unless both fossil calibrations and sequence data are available. Commonly used marginal priors on divergence times derived from fossil calibrations may conflict with node order on the phylogenetic tree causing a change in the prior on divergence times for a particular topology. Care should be taken to avoid confusing this effect with changes due to informative sequence data. This effect is illustrated with examples. A topology-consistent prior that preserves the marginal priors is defined and examples are constructed. Conflicts between fossil calibrations and relative branch lengths (based on sequence data) can cause estimates of divergence times that are grossly incorrect, yet have a narrow posterior distribution. An example of this effect is given; it is recommended that overly narrow posterior distributions of divergence times should be carefully scrutinized.

This article is part of the themed issue ‘Dating species divergences using rocks and clocks’.
Closing the gap between rocks and clocks using total-evidence dating
Authors: Ronquist Fredrik , Lartillot Nicolas , Phillips Matthew J.
Published: June 2016

Total-evidence dating (TED) allows evolutionary biologists to incorporate a wide range of dating information into a unified statistical analysis. One might expect this to improve the agreement between rocks and clocks but this is not necessarily the case. We explore the reasons for such discordance using a mammalian dataset with rich molecular, morphological and fossil information. There is strong conflict in this dataset between morphology and molecules under standard stochastic models. This causes TED to push divergence events back in time when using inadequate models or vague priors, a phenomenon we term ‘deep root attraction’ (DRA). We identify several causes of DRA. Failure to account for diversified sampling results in dramatic DRA, but this can be addressed using existing techniques. Inadequate morphological models also appear to be a major contributor to DRA. The major reason seems to be that current models do not account for dependencies among morphological characters, causing distorted topology and branch length estimates. This is particularly problematic for huge morphological datasets, which may contain large numbers of correlated characters. Finally, diversification and fossil sampling priors that do not incorporate all the available background information can contribute to DRA, but these priors can also be used to compensate for DRA. Specifically, we show that DRA in the mammalian dataset can be addressed by introducing a modest extra penalty for ghost lineages that are unobserved in the fossil record, for instance by assuming rapid diversification, rare extinction or high fossil sampling rate; any of these assumptions produces highly congruent divergence time estimates with a minimal gap between rocks and clocks. Under these conditions, fossils have a stabilizing influence on divergence time estimates and significantly increase the precision of those estimates, which are generally close to the dates suggested by palaeontologists.

This article is part of the themed issue ‘Dating species divergences using rocks and clocks’.
Tectonic blocks and molecular clocks
Authors: De Baets Kenneth , Antonelli Alexandre , Donoghue Philip C. J.
Published: June 2016

Evolutionary timescales have mainly used fossils for calibrating molecular clocks, though fossils only really provide minimum clade age constraints. In their place, phylogenetic trees can be calibrated by precisely dated geological events that have shaped biogeography. However, tectonic episodes are protracted, their role in vicariance is rarely justified, the biogeography of living clades and their antecedents may differ, and the impact of such events is contingent on ecology. Biogeographic calibrations are no panacea for the shortcomings of fossil calibrations, but their associated uncertainties can be accommodated. We provide examples of how biogeographic calibrations based on geological data can be established for the fragmentation of the Pangaean supercontinent: (i) for the uplift of the Isthmus of Panama, (ii) the separation of New Zealand from Gondwana, and (iii) for the opening of the Atlantic Ocean. Biogeographic and fossil calibrations are complementary, not competing, approaches to constraining molecular clock analyses, providing alternative constraints on the age of clades that are vital to avoiding circularity in investigating the role of biogeographic mechanisms in shaping modern biodiversity.

This article is part of the themed issue ‘Dating species divergences using rocks and clocks’.
Genomic insights into temperature-dependent transcriptional responses ofKosmotoga olearia, a deep-biosphere bacterium that can grow from 20°C to 79°C
Authors: Pollo Stephen M. J. , Adebusuyi Abigail A. , Straub Timothy J. , Foght Julia M. , Zhaxybayeva Olga , Nesbø Camilla L.
Published: June 2016

Temperature is one of the defining parameters of an ecological niche. Most organisms thrive within a temperature range that rarely exceeds ∼ 30°C, but the deep subsurface bacteriumKosmotoga oleariacan grow over a temperature range of 59°C (20°C -79°C). To identify genes correlated with this flexible phenotype, we compared transcriptomes ofK. oleariacultures grown at its optimal 65°C to those at 30°C, 40°C, and 77°C. The temperature treatments affected expression of 573 of 2,224K. oleariagenes. Notably, this transcriptional response elicits re-modeling of the cellular membrane and changes in metabolism, with increased expression of genes involved in energy and carbohydrate metabolism at high temperatures and up-regulation of amino acid metabolism at lower temperatures. At sub-optimal temperatures, many transcriptional changes were similar to those observed in mesophilic bacteria at physiologically low temperatures, including up-regulation of typical cold stress genes and ribosomal proteins. Comparative genomic analysis of additional Thermotogae genomes, indicate that one ofK. olearia's strategies for low temperature growth is increased copy number of some typical cold response genes through duplication and/or lateral acquisition. At 77°C one third of the up-regulated genes are of hypothetical function, indicating that many features of high temperature growth are unknown.
Evolutionary genomics of peach and almond domestication
Authors: Velasco Dianne , Hough Josh , Aradhya Mallikarjuna , Ross-Ibarra Jeffrey
Published: June 2016

The domesticated almond [Prunus dulcis (L.) Batsch] and peach [P. persica (Mill.) D. A. Webb] originate on opposite sides of Asia and were independently domesticated approximately 5000 years ago. While interfertile, they possess alternate mating systems and differ in a number of morpholog-ical and physiological traits. Here we evaluated patterns of genome-wide diversity in both almond and peach to better understand the impacts of mating system, adaptation, and domestication on the evolution of these taxa. Almond has ∼7X the genetic diversity of peach, and high genome-wide FSTvalues support their status as separate species. We estimated a divergence time of approximately 8 Mya, coinciding with an active period of uplift in the northeast Tibetan Plateau and subsequent Asian climate change. We see no evidence of bottleneck during domestication of either species, but identify a number of regions showing signatures of selection during domestication and a significant overlap in candidate regions between peach and almond. While we expected gene expression in fruit to overlap with candidate selected regions, instead we find enrichment for loci highly differentiated between the species, consistent with recent fossil evidence suggesting fruit divergence long preceded domestication. Taken together this study tells us how closely related tree species evolve and are domesticated, the impact of these events on their genomes, and the utility of genomic information for long-lived species. Further exploration of this data will contribute to the genetic knowledge of these species and provide information regarding targets of selection for breeding application and further the understanding of evolution in these species.
Prioritizing 2nd order interactions via support vector ranking using sensitivity indices on time series Wnt measurements†
Authors: sinha shriprakash
Published: June 2016

It is widely known that the sensitivity analysis plays a major role in computing the strength of the influence of involved factors in any phenomena under investigation. When applied to expression profiles of various intra/extracellular factors that form an integral part of a signaling pathway, the variance and density based analysis yields a range of sensitivity indices for individual as well as various combinations of factors. These combinations denote the higher order interactions among the involved factors, that might be of interest in the working mechanism of the pathway. For example, there are 19 types of WNTs and 10 FZDs with their 2ndorder combinations high enough and it is not possible to know which one to test first (except for those for which wet lab validations have been confirmed). But the effect of these combinations vary over time as measurements of fold changes and deviations in fold changes vary. In this work, after estimating the individual effects of factors for a higher order combination, the individual indices are considered as discriminative features. A combination, then is a multivariate feature set in higher order (>=2). With an excessively large number of factors involved in the pathway, it is difficult to search for important combinations in a wide search space over different orders. Exploiting the analogy of prioritizing webpages using ranking algorithms, for a particular order, a full set of combinations of interactions can then be prioritized based on these features using a powerful ranking algorithm via support vectors. Recording the changing rankings of the combinations over time points and durations, reveals how higher order interactions behave within the pathway and when and where an intervention might be necessary to influence the pathway. This could lead to development of time based therapeutic interventions. Based on a small dataset in time, we were able to generate the rankings of the 2ndorder combinations between WNTs and FZDs at different time snap shots and for different duration or time periods. Code has been made available on Google drive athttps://drive.google.com/folderview?id=0B7Kkv8wlhPU-V1Fkd1dMSTd5ak0&usp=sharing

Significance

The search and wet lab testing of unknown biological hypotheses in the form of combinations of various intra/extracellular factors that are involved in a signaling pathway, costs a lot in terms of time, investment and energy. To reduce this cost of search in a vast combinatorial space, a pipeline has been developed that prioritises these list of combinations so that a biologist can narrow down their investigation. The pipeline uses kernel based sensitivity indices to capture the influence of the factors in a pathway and employs powerful support vector ranking algorithm. The generic workflow and future improvements are bound to cut down the cost for many wet lab experiments and reveal unknown/untested biological hypothesis.
The second decade of 3C technologies: detailed insights into nuclear organization
Authors: Denker Annette , de Laat Wouter
Published: June 2016

The relevance of three-dimensional (3D) genome organization for transcriptional regulation and thereby for cellular fate at large is now widely accepted. Our understanding of the fascinating architecture underlying this function is based on microscopy studies as well as the chromosome conformation capture (3C) methods, which entered the stage at the beginning of the millennium. The first decade of 3C methods rendered unprecedented insights into genome topology. Here, we provide an update of developments and discoveries made over the more recent years. As we discuss, established and newly developed experimental and computational methods enabled identification of novel, functionally important chromosome structures. Regulatory and architectural chromatin loops throughout the genome are being cataloged and compared between cell types, revealing tissue invariant and developmentally dynamic loops. Architectural proteins shaping the genome were disclosed, and their mode of action is being uncovered. We explain how more detailed insights into the 3D genome increase our understanding of transcriptional regulation in development and misregulation in disease. Finally, to help researchers in choosing the approach best tailored for their specific research question, we explain the differences and commonalities between the various 3C-derived methods.
TBR1 regulates autism risk genes in the developing neocortex
Authors: Notwell James H. , Heavner Whitney E. , Darbandi Siavash Fazel , Katzman Sol , McKenna William L. , Ortiz-Londono Christian F. , Tastad David , Eckler Matthew J. , Rubenstein John L.R. , McConnell Susan K. , Chen Bin , Bejerano Gill
Published: June 2016

Exome sequencing studies have identified multiple genes harboring de novo loss-of-function (LoF) variants in individuals with autism spectrum disorders (ASD), including TBR1, a master regulator of cortical development. We performed ChIP-seq for TBR1 during mouse cortical neurogenesis and show that TBR1-bound regions are enriched adjacent to ASD genes. ASD genes were also enriched among genes that are differentially expressed in Tbr1 knockouts, which together with the ChIP-seq data, suggests direct transcriptional regulation. Of the nine ASD genes examined, seven were misexpressed in the cortices of Tbr1 knockout mice, including six with increased expression in the deep cortical layers. ASD genes with adjacent cortical TBR1 ChIP-seq peaks also showed unusually low levels of LoF mutations in a reference human population and among Icelanders. We then leveraged TBR1 binding to identify an appealing subset of candidate ASD genes. Our findings highlight a TBR1-regulated network of ASD genes in the developing neocortex that are relatively intolerant to LoF mutations, indicating that these genes may play critical roles in normal cortical development.
Moss Chloroplasts Are Surrounded by a Peptidoglycan Wall Containing D-Amino Acids
Authors: Hirano Takayuki , Tanidokoro Koji , Shimizu Yasuhiro , Kawarabayasi Yutaka , Ohshima Toshihisa , Sato Momo , Tadano Shinji , Ishikawa Hayato , Takio Susumu , Takechi Katsuaki , Takano Hiroyoshi
Published: June 2016

It is believed that the plastids in green plants lost peptidoglycan (i.e., a bacterial cell wall-containing d-amino acids) during their evolution from an endosymbiotic cyanobacterium. Although wall-like structures could not be detected in the plastids of green plants, the moss Physcomitrella patens has the genes required to generate peptidoglycan (Mur genes), and knocking out these genes causes defects in chloroplast division. Here, we generated P. patens knockout lines (∆Pp-ddl) for a homolog of the bacterial peptidoglycan-synthetic gene encoding d-Ala:d-Ala ligase. ∆Pp-ddl had a macrochloroplast phenotype, similar to other Mur knockout lines. The addition of d-Ala-d-Ala (DA-DA) to the medium suppressed the appearance of giant chloroplasts in ∆Pp-ddl, but the addition of l-Ala-l-Ala (LA-LA), DA-LA, LA-DA, or d-Ala did not. Recently, a metabolic method for labeling bacterial peptidoglycan was established using ethynyl-DA-DA (EDA-DA) and click chemistry to attach an azide-modified fluorophore to the ethynyl group. The ∆Pp-ddl line complemented with EDA-DA showed that moss chloroplasts are completely surrounded by peptidoglycan. Our findings strongly suggest that the moss plastids have a peptidoglycan wall containing d-amino acids. By contrast, no plastid phenotypes were observed in the T-DNA tagged ddl mutant lines of Arabidopsis thaliana.
Antecedents of ERP systems implementation success: a study on Jordanian healthcare sector
Authors: Almajali Dmaithan Abdelkarim , Masa'deh Ra'ed , Tarhini Ali
Published: June 2016

Purpose

– Most small- and medium-sized enterprises (SMEs) use some business management software to manage their daily operations. Ultimately they consider transitioning to an enterprise resources planning (ERP) system. However, implementing ERP system successfully is costly and complex, and often shows high disappointment rates or even abandonment due to need of fit with the business or social culture. In Jordan, large businesses have been using the ERP system for a long time, but SMEs usage of the system is relatively new. The purpose of this paper is to study the effect of ERP implementation success antecedents which consists of training, supportive leadership and ease of use on ERP implementation success itself through a mediating effect of user satisfaction.

Design/methodology/approach

– Empirical data were collected using a survey questionnaire which was distributed to ERP users in Jordanian healthcare organizations. A total of 175 responses were collected and analyzed using structure equation modeling.

Findings

– A significant relationship was found between these antecedents and ERP implementation success. Furthermore, user satisfaction plays a significant mediating role between ease of use and ERP implementation success.

Practical implications

– The outcomes of this study are useful to ERP users as they would be able to strategize future ERP system implementation in different sectors such as education, manufacturing and insurance industry. Finally, the findings may be useful to ERP system adopters in different developing countries.

Originality/value

– This is one of the first studies which adequately covers the relationships between antecedents of user satisfaction and ERP implementation success which consists of training, supportive leadership and ease of use on ERP implementation success itself through a mediating effect of user satisfaction.
Following momentum and avoiding the “Minsky Moment” evidence from investors on the Financial Instability Hypothesis
Authors: Pirie Scott , Chan Ronald King To
Published: June 2016

Purpose

This study aims to find out how institutional investors use momentum in making investment decisions, and whether their actions are consistent with the Financial Instability Hypothesis of Hyman Minsky.

Design/methodology/approach

The study discusses the findings of interviews with 25 professional investors from the Hong Kong offices of five global financial institutions. All of the participants have several years of practical experience in global and regional markets.

Findings

Nearly all the managers interviewed said they use momentum in making investment decisions, and they do this in ways that are consistent with the Financial Instability Hypothesis, in which markets alternate between stable and unstable states. The participants are aware they may contribute to this, but they cannot avoid doing it because of short-term constraints in the present financial system.

Originality/value

This study adds to our knowledge of how professional investors use momentum in their investment strategies. It complements findings of quantitative studies that show momentum strategies have been profitable in many market settings. It also adds evidence that supports the Financial Instability Hypothesis.
Double dissociations in reading comprehension difficulties among Chinese–English bilinguals and their association with tone awareness
Authors: Choi William , Tong Xiuli , Deacon S. Hélène
Published: June 2016

Poor comprehenders have reading comprehension difficulties but normal word recognition ability. Here, we report the first study, which investigated (i) the dissociation and (ii) the prevalence of L1–L2 reading comprehension difficulties, and (iii) the levels of key metalinguistic skills in poor comprehenders among Chinese‐English bilingual children. From a sample of 124 Chinese–English second graders, we identified 18 poor comprehenders (six Chinese, six English, and six in both Chinese and English). We matched these with six average comprehenders of comparable age and word reading abilities. Multivariate analysis of covariance and univariateFtests revealed that poor Chinese comprehenders and poor English comprehenders had significantly lower levels of Chinese lexical tone awareness than average readers even after controlling for nonverbal intelligence. No significant differences emerged on scores for segmental phonological awareness and vocabulary knowledge, either in Chinese and English or on English lexical stress sensitivity. These findings were discussed in relation to the universal view of reading, cross language prosodic transfer and the simple view of reading.
Thin section magnetic resonance diffusion‐weighted imaging in the detection of acute infratentorial stroke
Authors: Entwisle Tom , Perchyonok Yuliya , Fitt Greg
Published: June 2016

Introduction

Magnetic resonance diffusion‐weighted imaging (DWI) is the most accurate technique available for demonstrating acute infarction; however, false‐negative DWI is higher in the infratentorium due to the limited spatial resolution with conventional 5 mm DWI. The aim of this study was to compare 5 mm DWI with 3 mm DWI in the detection of acute infratentorial infarction.

Methods

A 3 mm DWI sequence of the infratentorium was incorporated into the conventional MRI stroke protocol for the evaluation of patients with vertebrobasilar stroke‐like deficits. The 5 mm and 3 mm DWI sequences were assessed by two neuroradiologists who were blinded to the clinical findings. Sensitivity and specificity analysis was then performed against the final clinical diagnosis.

Results

The sensitivity for detection of infratentorial infarction was 81.1% for 5 mm DWI and 94.6% for 3 mm DWI and the specificity was 100% for 5 mm DWI and 97.7% for 3‐mm DWI. The false‐negative rate in detection of infratentorial infarcts was 5.6% for the 5‐mm sequence and 1.6% for the 3‐mm sequence. The six 5‐mm DWI false‐negative cases (4.8%) were less than 9 mm in diameter (3–8 mm, average 4.67 mm) and located in the brainstem. This supports the hypothesis that small lesions may not be detected on 5 mm DWI due to partial volume averaging.

Conclusion

Where there is clinical suspicion of infratentorial infarction, 3 mm DWI of the infratentorium adds sensitivity compared to 5 mm DWI with only a small reduction in specificity.
Significance of different response evaluation criteria in predicting progression‐free survival of lung cancer with certain imaging characteristics
Authors: Yang Dengxia , Woodard Gavitt , Zhou Chan , Wang Xinyue , Liu Zhujun , Ye Zhaoxiang , Li Kai
Published: June 2016

Background

Certain radiographic signs of a treatment response, such as cavitation, changes in density, or tumor change along a short axis, are not considered by Response Evaluation Criteria in Solid Tumors (RECIST). This study evaluates what additional prognostic information can be obtained by including these criteria in tumor assessment.

Methods

Data of 105 patients were included. Tumor cavitation was observed in 51 patients at baseline. An additional 23 patients developed tumor cavitation during treatment. A change in tumor density was the only radiographic treatment response observed in 22 patients. The only measureable treatment response in nine patients was a decrease along the short axis size of the tumor. Tumor response was assessed using various criteria.

Results

In patients with basic tumor cavitation, RECIST1.1 scores accurately predicted differences in progression‐free survival (PFS; P = 0.076) while modified (m) RECIST did not (P = 0.550). mRECIST detected a significant difference between PFS in patients with post‐therapeutic cavitation with different responses, but no significant difference using RECIST1.1 (P = 0.004 vs. P = 0.477). In patients with only tumor density changes, there was no significant difference in PFS when either RECIST1.1 or density criteria were used (P = 0.419). In patients with a change in size along the tumor's short axis, short axis criteria could predict significant difference in PFS (P = 0.004).

Conclusions

RECIST1.1 provides the best assessment of tumor response and prediction of PFS in patients with basic tumor cavitation. mRECIST provides better PFS prognostic information in patients with post‐therapeutic cavitation. Short axis criteria provides better PFS prognostic information in patients with changes in the short axis of tumor diameter. Changes in tumor density were not a useful prognostic sign.
Uniform Service, Uniform Productivity? Regional Efficiency of the Imperial German Postal, Telegraph, and Telephone Service
Authors: Ploeckl Florian
Published: June 2016

Using the regional productivity of the Reichspost, the postal service of the German Empire, I investigate whether a public monopolist operates with uniform regional productivity. Using data envelopment analysis efficiency scores, we derive the relative productivity of the post, telegraph, and telephone sectors from 1891 to 1908. Results show a fairly stable system with substantial raw productivity differences between postal districts, and that the expansion of the service offset technological productivity increases for the mail service.
Handout or Hand‐up: Ongoing Tensions in the Long History of Government Response to Drought in Australia
Authors: Downing Karen , Jones Rebecca , Singley Blake
Published: June 2016

In 2014 the Coalition government announced a 320 million dollar package for drought‐hit farmers. In describing this initiative as a “hand‐up” not a “hand out” Prime Minister Tony Abbott encapsulated more than 150 years of tension over whether government drought response should be unconditional limited relief or conditional longer‐term assistance. This paper considers the long history of drought assistance in Australia as seen through government legislation, year books, newspapers and personal papers. It argues that despite changing political and social circumstances, contradictions in the approach to government drought response, as well as in public and personal reactions to those policies, have remained remarkably consistent. We further suggest that lack of consensus over the inherent nature of drought is not sufficient to explain the dilemma.