bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolutionary dynamics of sex chromosomes of paleognathous birds
Authors: Xu Luohao , Sin Simon Yung Wa , Grayson Phil , Edwards Scott V. , Sackton Timothy B.
Published: April 2018

Standard models of sex chromosome evolution propose that recombination suppression leads to the degeneration of the heterogametic chromosome, as is seen for the Y chromosome in mammals and the W chromosome in most birds. Unlike other birds, paleognaths (ratites and tinamous) possess large non-degenerate regions on their sex chromosomes (PARs or pseudoautosomal regions). It remains unclear why these large PARs are retained over more than 100 MY, and how this retention impacts the evolution of sex chromosomes within this system. To address this puzzle, we analysed Z chromosome evolution and gene expression across 12 paleognaths, several of whose genomes have recently been sequenced. We confirm at the genomic level that most paleognaths retain large PARs. As in other birds, we find that all paleognaths have incomplete dosage compensation on the regions of the Z chromosome homologous to degenerated portions of the W (differentiated regions or DRs), but we find no evidence for enrichments of male-biased genes in PARs. We find limited evidence for increased evolutionary rates (faster-Z) either across the chromosome or in DRs for most paleognaths with large PARs, but do recover signals of faster-Z evolution in tinamou species with mostly degenerated W chromosomes, similar to the pattern seen in neognaths. Unexpectedly, in some species PAR-linked genes evolve faster on average than genes on autosomes, suggested by diverse genomic features to be due to reduced efficacy of selection in paleognath PARs. Our analysis shows that paleognath Z chromosomes are atypical at the genomic level, but the evolutionary forces maintaining largely homomorphic sex chromosomes in these species remain elusive.
Auxiliary subunits keep AMPA receptors compact during activation and desensitization
Authors: Baranovic Jelena , Plested Andrew J.R.
Published: April 2018

Signal transduction at vertebrate excitatory synapses involves the activity of ionotropic glutamate receptors, including the AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionate) receptor. Technical advances in cryo-electron microscopy have brought a slew of full-length structures of AMPA receptors, on their own and in combination with auxiliary subunits. These structures illustrate a wide range of conformations, indicating that individual domains might undergo substantial lateral motions during gating, resulting in an open, “relaxed” extracellular layer. Here, we used bifunctional methanethiosulfonate cross-linkers to calibrate the conformations found in functional AMPA receptors both in the presence and absence of the auxiliary subunit Stargazin. Our data indicate that AMPA receptors have considerable conformational freedom and can get trapped in stable, relaxed conformations, especially upon long exposures to glutamate. In contrast, Stargazin limits this conformational flexibility. Thus, under synaptic conditions, where brief glutamate exposures and the presence of Stargazin dominate, AMPA receptors are unlikely to adopt very relaxed conformations during gating.
Lysosome enlargement during inhibition of the lipid kinase PIKfyve proceeds through lysosome coalescence
Authors: Choy Christopher H. , Saffi Golam , Gray Matthew A. , Wallace Callen , Dayam Roya M. , Ou Zhen-Yi A. , Lenk Guy , Puertollano Rosa , Watkins Simon C. , Botelho Roberto J.
Published: April 2018

Lysosomes receive and degrade cargo from endocytosis, phagocytosis and autophagy. They also play an important role in sensing and instructing cells on their metabolic state. The lipid kinase PIKfyve generates phosphatidylinositol-3,5-bisphosphate to modulate lysosome function. PIKfyve inhibition leads to impaired degradative capacity, ion dysregulation, abated autophagic flux, and a massive enlargement of lysosomes. Collectively, this leads to various physiological defects including embryonic lethality, neurodegeneration and overt inflammation. While being the most dramatic phenotype, the reasons for lysosome enlargement remain unclear. Here, we examined whether biosynthesis and/or fusion-fission dynamics contribute to swelling. First, we show that PIKfyve inhibition activates TFEB, TFE3 and MITF enhancing lysosome gene expression. However, this did not augment lysosomal protein levels during acute PIKfyve inhibition and deletion of TFEB and/or related proteins did not impair lysosome swelling. Instead, PIKfyve inhibition led to fewer but enlarged lysosomes, suggesting that an imbalance favouring lysosome fusion over fission causes lysosome enlargement. Indeed, conditions that abated fusion curtailed lysosome swelling in PIKfyve-inhibited cells.

Summary statement

PIKfyve inhibition causes lysosomes to coalesce, resulting in fewer, enlarged lysosomes. We also show that TFEB-mediated lysosome biosynthesis does not contribute to swelling.
In Silico Benchmarking of Metagenomic Tools for Coding Sequence Detection Reveals the Limits of Sensitivity and Precision
Authors: Golob Jonathan Louis , Minot Samuel Schwartz
Published: April 2018

High-throughput sequencing can establish the functional capacity of a microbial community by cataloging the protein-coding sequences (CDS) present in the metagenome of the community. The relative performance of different computational methods for identifying CDS from whole-genome shotgun sequencing (WGS) is not fully established.

Here we present an automated benchmarking workflow, using synthetic shotgun sequencing reads for which we know the true CDS content of the underlying communities, to determine the relative performance (sensitivity, positive predictive value or PPV, and computational efficiency) of different metagenome analysis tools for extracting the CDS content of a microbial community.

Assembly-based methods are limited by coverage depth, with poor sensitivity for CDS at < 5X depth of sequencing, but have excellent PPV. Mapping-based techniques are more sensitive at low coverage depths, but can struggle with PPV. We additionally describe an expectation maximization based iterative algorithmic approach which we show to successfully improve the PPV of a mapping based technique while retaining improved sensitivity and computational efficiency.
Lipoprotein Signatures of Cholesteryl Ester Transfer Protein and HMG-CoA Reductase Inhibition
Authors: Kettunen Johannes , Holmes Michael V. , Allara Elias , Anufrieva Olga , Ohukainen Pauli , Oliver-Williams Clare , Tillin Therese , Hughes Alun D. , Kähönen Mika , Lehtimäki Terho , Viikari Jorma , Raitakari Olli T. , Salomaa Veikko , Järvelin Marjo-Riitta , Perola Markus , Smith George Davey , Chaturvedi Nish , Danesh John , Angelantonio Emanuele Di , Butterworth Adam S. , AlaKorpela Mika
Published: April 2018

Background

CETP inhibition reduces vascular event rates but confusion surrounds its low-density lipoprotein (LDL)-cholesterol effects. We sought to clarify associations of genetic inhibition of CETP on detailed lipoproteins.

Methods and Results

We used variants associated withCETP(rs247617) andHMGCR(rs12916) expression in 62,400 Europeans with detailed lipoprotein profiling from nuclear magnetic resonance spectroscopy. Genetic associations were scaled to 10% lower risk of coronary heart disease (CHD). Associations of lipoprotein measures with risk of incident CHD in three population-based cohorts (770 cases) were examined.

CETPandHMGCRhad near-identical associations with LDL-cholesterol concentration estimated by Friedewald-equation.HMGCRhad a relatively consistent effect on cholesterol concentrations across all apolipoprotein B-containing lipoproteins.CETPhad stronger effects on remnant and very-low-density lipoprotein cholesterol but no effect on cholesterol concentrations in LDL defined by particle size (diameter 18–26 nm) (-0.02SD 95%CI: -0.10, 0.05 forCETPversus -0.24SD, 95%CI -0.30, -0.18 forHMGCR).CETPhad profound effects on lipid compositions of lipoproteins, with strong reductions in the triglyceride content of all highdensity lipoprotein (HDL) particles. These alterations in triglyceride composition within HDL subclasses were observationally associated with risk of CHD, independently of total cholesterol and triglycerides (strongest HR per 1-SD higher triglyceride composition in very-large HDL 1.35; 95%CI: 1.18, 1.54).

Conclusion

CETP inhibition does not affect size-specific LDL cholesterol but may lower CHD risk by lowering cholesterol in other apolipoprotein-B containing lipoproteins and lowering triglyceride content of HDL particles. Conventional composite lipid assays may mask heterogeneous effects of lipid-altering therapies.
Inversion frequencies and phenotypic effects are modulated by the environment
Authors: Berdan Emma , Rosenquist Hanna , Larson Keith , Wellenreuther Maren
Published: April 2018

Understanding how environmental variation drives phenotypic diversification within species is a major objective in evolutionary biology. The seaweed flyCoelopa frigidaprovides an excellent model for the study of genetically driven phenotypes because it carries an α/β inversion polymorphism that affects body size.Coelopa frigidainhabits highly variable beds of decomposing seaweed on the coast in Scandinavia thus providing a suitable test ground to investigate the genetic effects of substrate on both the frequency of the inversion (directional selection) and on the phenotype (genotype x environment effects). Here we use a reciprocal transplant experiment to test the effect of the α/β inversion on body size traits and development time across four suitable natural breeding substrates from the clinal distribution. We show that while development time is unaffected by GxE effects, both the frequency of the inversion and the relative phenotypic effects of the inversion on body size differ between population x substrate combinations. This indicates that the environment modulates the fitness as well as the phenotypic effects of the inversion karyotypes. It further suggests that the inversion may have accumulated qualitatively different mutations in different populations that interact with the environment. Together our results are consistent with the idea that the inversion inC. frigidalikely evolves via a combination of local mutation, GxE effects, and differential fitness of inversion karyotypes in heterogeneous environments.
Secondary neurulation-fated cells in the tail bud undergo self-renewal and tubulogenesis regulated by a Sox2 gradient
Authors: Kawachi Teruaki , Shimokita Eisuke , Tadokoro Ryosuke , Takahashi Yoshiko
Published: April 2018

During amniote development, anterior and posterior components of the neural tube form by primary neurulation (PN) and secondary neurulation (SN), respectively. Unlike PN, SN proceeds by the mesenchymal-to-epithelial transition of SN precursors in the tail bud, a critical structure for the axial elongation. Our direct cell labeling delineates non-overlapping territories of SN- and mesodermal precursors in the chicken tail bud. SN-fated precursors are further divided into self-renewing and differentiating cells, a decision regulated by graded expression levels of Sox2. Whereas Sox2 is confined to SN precursors, Brachyury (T) is widely and uniformly distributed in the tail bud, indicating that Sox2+/Brachyury+ cells are neural-fated and not mesodermal. These results uncover multiple steps during the neural posterior elongation, including precocious segregation of SN precursors, their self-renewal, and regulation by graded Sox 2.
Target variant detection in leukemia using unaligned RNA-Seq reads
Authors: Audemard Eric Olivier , Gendron Patrick , Lavallée Vincent-Philippe , Hébert Josée , Sauvageau Guy , Lemieux Sébastien
Published: April 2018

Mutations identified in each Acute Myeloid Leukemia (AML) patients are useful for prognosis and to select targeted therapies. Detection of such mutations by the analysis of Next-Generation Sequencing (NGS) data requires a computationally intensive read mapping step and application of several variant calling methods. Targeted mutation identification drastically shifts the usual tradeoff between accuracy and performance by concentrating all computations over a small portion of sequence space. Here, we present km, an efficient approach leveraging k-mer decomposition of reads to identify targeted mutations. Our approach is versatile, as it can detect single-base mutations, several types of insertions and deletions, as well as fusions. We used two independent AML cohorts (The Cancer Genome Atlas and Leucegene), to show that mutation detection bykmis fast, accurate and mainly limited by sequencing depth. Therefore,kmallows to establish fast diagnostics from NGS data, and could be suitable for clinical applications.
Comparative Genome Analysis Reveals Important Genetic Factors Associated with Probiotic Property inEnterococcus faeciumstrains
Authors: Ghattargi Vikas C. , Gaikwad Meghana A. , Meti Bharati S. , Nimonkar Yogesh S. , Dixit Kunal , Prakash Om , Shouche Yogesh S. , Pawar Shrikant S. , Dhotre Dhiraj
Published: April 2018

Enterococcus faeciumthough commensals in human gut, few strains provide beneficial effect to humans as probiotics, few are responsible for nosocomial infection and few as non-pathogens. Comparative genomics ofE. faeciumwill help to reveal the genomic differences responsible for the said properties. In this study, we comparedE. faeciumstrain 17OM39 with a marketed probiotic, non-pathogenic non-probiotic (NPNP) and pathogenic strains. The core genome analysis revealed, 17OM39 was closely related with marketed probiotic strain T110. Strain 17OM39 was found to be devoid of known vancomycin, tetracycline resistance genes and functional virulence genes. Moreover, 17OM39 is „less open‟ due to absence of frequently found transposable elements. Genes imparting beneficial functional properties were observed to be present in marketed probiotic T110 and 17OM39 strains. Additional, genes associated with colonization within gastrointestinal tract were detected across all the strains. Beyond shared genetic features; this study particularly identified genes that are responsible to impart probiotic, non-pathogenic and pathogenic features to the strains ofE. faecium.The study also provides insights into the acquired and intrinsic drug resistance genes, which will be helpful for better understanding of the physiology of antibiotic resistance inE. faeciumstrains. In addition, we could identify genes contributing to the intrinsic ability of 17OM39E. faeciumisolate to be a potential probiotic.

The study has comprehensively characterized genome sequence of each strain to find the genetic variation and understand effects of these on functionality, phenotypic complexity. Further the evolutionary relationship of species along with adaptation strategies have been including in this study.
When more is less: Dual phosphorylation protects signaling off-state against overexpression
Authors: Witzel Franziska , Blüthgen Nils
Published: April 2018

Kinases in signaling pathways are commonly activated by multisite phosphorylation. For example, the mitogen-activated protein kinase Erk is activated by its kinase Mek by two consecutive phosphorylations within its activation loop. In this article, we use kinetic models to study how the activation of Erk is coupled to its abundance. Intuitively, Erk activity should rise with increasing amounts of Erk protein. However, a mathematical model shows that the signaling off-state is robust to increasing amounts of Erk, and Erk activity may even decline with increasing amounts of Erk. This counter-intuitive, bell-shaped response of Erk activity to increasing amounts of Erk arises from the competition of the unmodified and single phosphorylated form of Erk for access to its kinase Mek. This shows that phosphorylation cycles can contain an intrinsic robustness mechanism that protects signaling from aberrant activation e.g. by gene expression noise or kinase overexpression following gene duplication events in diseases like cancer.
A robust MCDM approach for ERP system selection under uncertain environment based on worst case scenario
Authors: Temur Gül Tekin , Bolat Bersam
Published: April 2018

Purpose

ERP selection is a multi-faceted process and needs to be successful in dealing with high uncertainty. The purpose of this paper is to propose a novel multi-criteria decision making (MCDM) approach, titled as cloud-based design optimization (CBDO), for ERP selection problem to handle high uncertainty with a computationally effective way.

Design/methodology/approach

CBDO has been utilized as an alternative method to fuzzy set theory and stochastic programming, and proposes robust findings for worst case scenario. In order to assess the proposed methodology, a numerical study is conducted by taking into account existing state-of-the-art study on the ERP selection problem for the small medium enterprises. The outputs of the existing state-of-the-art study are assumed as uncertain and varying across time as it is expected in real life; therefore, different scenarios are created in order to reveal the effect of uncertainty on decisions.

Findings

In the methodology, the results given under uncertain conditions are compared with the results obtained under stable conditions. It is clearly seen that ERP system selection problem area has high sensitivity to the uncertain environment, and decision makers should not undervalue the unsteadiness of criteria during the ERP system selection process, especially within volatile economies.

Originality/value

This study contributes to the relevant literature by utilizing CBDO as a MCDM tool in the selection of the ERP software as a first time, and validating the impact of unsteadiness on the ERP selection procedure. It is the first CBDO-based study that validates the effect of distributional differences on uncertainties in the ERP selection processes.
Rwanda’s innovation challenges and policies – lessons for Africa
Authors: Aubert Jean-Eric
Published: April 2018

Purpose

The purpose of this paper is to outline the S&T and innovation policy challenges that Rwanda is experiencing in building a knowledge-based economy and draw some more general lessons for African countries.

Design/methodology/approach

The approach is based on methodological framework of country reviews used by international organizations in the field of science, technology and innovation policies.

Findings

The paper presents government policies that have been decisive for the good performance of the country in rebuilding its economy and society since the genocide (1994). It highlights the policy measures that have been taken in the fields of education, information and communication technologies, industry, science and so on with a view to put the country on a knowledge-driven development process. It pinpoints the need for more proactive policies to stimulate the diffusion of new technologies and innovation throughout the economy and the different sectors, including agriculture which employs still 80 percent of the population.

Research limitations/implications

The paper is based on a short field mission (conducted for an international organization) and the collection of published data, in focusing on important messages that should be given to the government, without an in-depth empirical and detailed research.

Practical implications

The paper is a kind of summary of a 80-page report to be published in the course of 2017. It is expected that the analysis will be clear enough to stimulate appropriate action by the Government of Rwanda.

Social implications

There is no direct social implications, but one may expect that the ideas if adopted by the government will help improving the living conditions in the country.

Originality/value

Such country reviews performed by international organizations are unique. They provide key insights on the innovation climate and policy of the nation that is studied, while they offer useful perspectives for countries at similar level of development.
Between Tribute and Unequal Treaties: How China Saw the Sea World in the Early Nineteenth Century
Authors: WANG DONG
Published: April 2018

This article attempts to analyse the Chinese ideology and practice in the sea world from the perspective of the Jiaqing emperor (r. 1796–1820), whose 25‐year reign ushered in modern China in historiography.1 Since the seventeenth century, the Manchu Chinese rulers and civil and military officials had increasingly acknowledged that China was inferior to European naval powers, while at the same time holding fast to their claim to universal greatness as expressed in the tribute system. It took the collusion of all sides involved – including the complicity of foreign powers – to sustain this dual ideology and practice. Qing China did not bear sole responsibility. Contrary to prevailing scholarly interpretations, such duality did not result in abject defeat for China, or total victory for western countries as embodied in the unequal treaties later on, but rather bestowed a measure of success on all parties.
Reproductive performance of cows after fixed‐time artificial insemination with ovulation synchronisation and re‐synchrony in southern Australian dairy herds
Authors: Izzo MM , Humphris M , Pryor L , Perry A , Morton JM
Published: April 2018

Objective

To describe reproductive performance of lactating dairy cows after fixed‐time artificial insemination (FTAI) with ovulation synchronisation and re‐synchrony in Australian dairy herds, and to compare reproductive outcomes with those of conventional mating programs.

Methods

The study was conducted in two seasonally calving dairy herds in which lactating dairy cows (n = 675) were enrolled into three treatment groups: group 1, oestrus detection and AI for 34 days followed by a natural service period; group 2, FTAI on day 1 followed by re‐synchrony of all cows prior to ultrasound pregnancy diagnosis at day 31 and FTAI of cows diagnosed not pregnant at day 34, then a natural service period; group 3, FTAI on day 1 followed by oestrus detection and AI for 34 days, then a natural service period. First‐service conception rate (FSCR), 6‐week in‐calf (6WIC) rate and proportions pregnant at the end of mating were compared using logistic regression with farm fitted as a fixed effect. Times from mating start date to conception were described using survival analysis with Kaplan‐Meier failure functions.

Results

FSCRs (45.3%, 49.1% and 45.6% for groups 1, 2 and 3, respectively) and proportions pregnant at the end of mating (77.6%, 76.0% and 76.8% for groups 1, 2 and 3, respectively) were similar for all groups. The 6WIC rate in group 2 was similar to that in group 3 (70.4% vs. 67.2%; P = 0.486), but tended to be higher than in group 1 (70.4% vs. 62.0%, P = 0.066). The median days to pregnancy for cows that conceived was 1 day in groups 2 and 3 and 10 days in group 1.

Conclusion

Mating plans that use FTAI with ovulation synchronisation and re‐synchrony during the AI period can achieve comparable reproductive performance to conventional mating programs in seasonally calving dairy herds.
A survey of northern Victorian dairy farmers to investigate dairy calf management: colostrum feeding and management
Authors: Phipps AJ , Beggs DS , Murray AJ , Mansell PD , Pyman MF
Published: April 2018

Objectives

To describe colostrum management practices carried out in northern Victorian dairy herds and to identify weaknesses in these areas that may affect calf health and welfare by comparing the results with the current industry recommendations

Methods

A questionnaire to obtain information about colostrum management and calf‐rearing practices was sent to commercial dairy farming clients of Rochester Veterinary Practice between June and September 2013. The questionnaire consisted of a general herd overview and colostrum harvesting practices.

Results

The response rate was 39% (58/150). Many dairy producers were not meeting the current industry recommendations in the following areas: (1) time of removal calf from the dam, (2) relying on calf suckling colostrum from the dam to achieve adequate passive transfer, (3) failing to supplement calves with colostrum, (4) feeding inadequate volumes of colostrum, (5) delayed colostrum harvesting, (6) pooling of colostrum, (7) failing to objectively assess colostrum quality or relying on visual assessment and (8) storing colostrum for a prolonged periods of time at ambient temperatures.

Conclusion

The results from this survey highlight the need for greater awareness of industry standards for colostrum management and feeding hygiene.
A survey of northern Victorian dairy farmers to investigate dairy calf management: calf‐rearing practices
Authors: Phipps AJ , Beggs DS , Murray AJ , Mansell PD , Pyman MF
Published: April 2018

Objectives

To describe the calf‐rearing practices carried out in northern Victorian dairy herds and to identify weaknesses that may affect calf health and welfare by comparing the results with current industry recommendations.

Methods

Survey of dairy farms from Rochester and the surrounding farming area.

Results

The response rate was 39% (58/150). Many dairy producers were not meeting the current industry recommendations in the following areas: (1) delayed access to pellets and roughage, (2) failing to provide access to water from birth, (3) delayed disbudding of calves, (4) delayed timing of booster vaccinations, (5) weaning based on age alone, (6) failing to isolate sick calves and (7) early sale age of excess calves.

Conclusion

The results from this survey highlight the need for greater awareness of industry standards for calf husbandry and weaning.
Zebrafish as a useful model for immunological research with potential applications in aquaculture
Authors: Lee‐Estevez Manuel , Figueroa Elías , Cosson Jacky , Short Stefanía E. , Valdebenito Ivan , Ulloa‐Rodríguez Patricio , Farías Jorge G.
Published: April 2018

The Zebrafish (Danio Rerio) is a Teleost fish, which offers several practical advantages concerning manipulation, maintenance and versatility as well as short life cycle, low cost and physiological similarity with most farmed species. Zebrafish have been used as model for several aquaculture‐relevant infectious agents, since the cost of infections to aquaculture can be great, making failure of immunity a major risk for commercial fish farming. This have allowed scientist to understand pathogens biology as well as fish immune response against infection, and thus have helped to improve disease control in aquaculture. This review summarizes the recent reports and main knowledge concerning the cellular and molecular aspects of the immune response in zebrafish and its potential applications in the fish farming industry. Several research results in zebrafish and other teleosts reveal that mucosal tissues have a strong and well‐structured immune response involving both innate and adaptive components. Together with the advantages of low maintenance cost, easy handling and genetic tools available, zebrafish comes up as a useful and reliable animal model for in vivo study of fish immune response and mechanisms as well as fish‐affecting infectious and inflammatory diseases which are a cause of concern for the aquaculture industry. Also, vaccines development, drugs screening and immunologically focused fish food assessment seem to be promising fields where zebrafish model can be used to generate positive impacts to the aquaculture practice.
How to diagnose renal artery stenosis correctly using ultrasound? Evaluation of results of renal arteries duplex ultrasonography examinations
Authors: Zhu Rong , Xu Zhonghui , QI Zhenhong , YE We , Wang Jian , Kong Jing , Jin Jin , Li Jianchu
Published: April 2018

Aim: Renal artery duplex ultrasonography (RDU) is an effective and non-invasive screening test in diagnosing renal artery stenosis. The discordance of results in multiple RDU is common. We aim to evaluate the discordance and the reasons for discordance between diagnoses and measurements from multiple RDU examinations.Material and method: A retrospective study was performed in 64 examinations of renal arteries from 32 patients that were referred for two or more RDU examinations and renal artery digital subtraction angiography (DSA) within six months, between August 2013 and January 2016. Using DSA as gold standard, we divided the renal arteries into three groups: discordant (one diagnosis of RDU was correct and one was wrong), misdiagnosed (neither RDU diagnosis was correct) and correct (both RDU diagnoses were correct) groups.We evaluated the discordance and reasons for discordance of diagnoses and measurements from multiple RDU examinations. Results: Among 64 renal arteries included in this study, 37 renal arteries had two correct diagnoses, 19 renal arteries had two discordant diagnoses, and eight renal arteries were misdiagnosed twice by RDU. The discordance of peak systolic velocity (PSV), the ratio between PSV in the renal artery with stenosis and PSV in the aorta (RAR), and tardus-parvus waveform measurements were clearly higher in the discordant diagnoses group than in the correctly diagnosed group. The most common reason for a discordant diagnosis was failure in obtaining correct tardus-parvus waveforms of the interlobar artery (26.31%). Themost common reason for misdiagnosis was the presence of an extremely severe stenosis with an atrophic kidney (31.25%). Overall, 87.50% of patients underwent RDU examinations had correct diagnoses of stenosis or occlusion at least once (including location and degree), as confirmed by DSA.Conclusions: Our study indicates that standard operating procedures and improvements in examination technique by ultrasound doctors could reduce the discordance between multiple tests.
Band alignment at the CdTe/InSb (001) heterointerface
Authors: Wang Xingye , Campbell Calli , Zhang Yong-Hang , Nemanich Robert J.
Published: April 2018

CdTe/InSb heterojunctions have attracted considerable attention because of its almost perfect lattice match and the presence of nonoctal interface bonding. This heterojunction is a model heterovalent system to describe band offsets. In this research, molecular beam epitaxy was used to deposit a ∼5 nm epitaxial CdTe (001) layer on an InSb (001) surface. Monochromatic x-ray photoemission spectroscopy and ultraviolet photoemission spectroscopy were used to characterize the electronic states of clean InSb and CdTe surfaces and CdTe/InSb (001) heterostructures. A room temperature remote hydrogen-plasma process was used to clean the surfaces prior to characterization. The results indicate a valence band offset of 0.89 eV and a type-I (straddling gap) alignment for the CdTe/InSb (001) heterostructure interface. In addition, In-Te bonding was observed at the interface. Downward band bending of the InSb is attributed to excess electrons introduced by nonoctal In-Te interface bonding.
Humane studies of octopuses get a boost
Authors: Staaf Danna
Published: April 2018

By identifying effective anesthetics, findings aid compliance with regulations.
Rocky start for China's James Watson center
Authors: Normile Dennis
Published: April 2018

A new center named for the Nobel laureate faces funding and mission challenges.
A delicate balance
Authors: Broadfoot Marla
Published: April 2018

Routinely giving antibiotics to premature babies may do more harm than good.
Convergent evidence for widespread rock nitrogen sources in Earth’s surface environment
Authors: Houlton B. Z. , Morford S. L. , Dahlgren R. A.
Published: April 2018

Freed from a rocky embrace

Nitrogen availability is a central controller of terrestrial plant growth and, thereby, of the carbon cycle and global climate change. It has been widely assumed that the atmosphere is the main source of terrestrial nitrogen input. Surprisingly, Houlton
et al.
now show that bedrock is just as large a nitrogen source across major sectors of the global terrestrial environment. They used three diverse and largely independent assessments of the nitrogen mobility and reactivity of rocks in the surface environment. These approaches yielded convergent estimates pointing to the equal importance of the atmosphere and bedrock as nitrogen sources.

Science
, this issue p.
58
Cell cycle heterogeneity directs the timing of neural stem cell activation from quiescence
Authors: Otsuki L. , Brand A. H.
Published: April 2018

Staging quiescent cells

Tissue-specific stem cells either divide or wait in a quiescent state until needed by the body. Quiescent stem cells have been thought to reside in the G
0
stage before activating to reenter the cell cycle. However, Otsuki and Brand now show that most quiescent stem cells in the
Drosophila
brain are arrested in G
2
. Cells in the two phases display differences; for example, G
2
stem cells awaken more quickly than G
0
stem cells, with the conserved pseudokinase Tribbles playing a regulatory role. Elucidating the different pathways and mechanisms underlying quiescence could help to inform regenerative drug design.

Science
, this issue p.
99
Morphogen gradient reconstitution reveals Hedgehog pathway design principles
Authors: Li Pulin , Markson Joseph S. , Wang Sheng , Chen Siheng , Vachharajani Vipul , Elowitz Michael B.
Published: April 2018

How to build a better morphogen gradient

To translate insights in developmental biology into medical applications, techniques are needed to ensure correct cell localization. Morphogen gradients allow precise and highly reproducible pattern formation during development. Through in vitro experiments and modeling, Li
et al.
tested the effects of unusual properties of Hedgehog (HH) signaling. The HH morphogen's receptor, Patched (PTCH), sends an inhibitory signal when no ligand is bound, which is relieved by ligand binding. PTCH also regulates spatial distribution of the signal by sequestering the HH ligand. Furthermore, signaling through the receptor promotes synthesis of more inhibitory receptor. These characteristics help speed gradient formation and explain the robustness of the system to changes in the rate of morphogen production.

Science
, this issue p.
543
Structure of the herpes simplex virus 1 capsid with associated tegument protein complexes
Authors: Dai Xinghong , Zhou Z. Hong
Published: April 2018

Focusing in on herpesvirus

The herpesvirus family includes herpes simplex virus type 1 (HSV-1), which causes cold sores, and type 2 (HSV-2), which causes genital herpes. Herpesviruses comprise a large DNA genome enclosed in a large and complex protein cage called a capsid (see the Perspective by Heldwein). Dai and Zhou used electron microscopy to determine a high-resolution structure of the HSV-1 capsid bound to the tegument proteins that occupy the space between the capsid and the nuclear envelope. The structure suggests how these components may play a role in viral transport. Yuan
et al.
describe a higher-resolution structure of an HSV-2 capsid, providing insight into how the shell assembles and is stabilized.

Science
, this issue p.
eaao7298
, p.
eaao7283
; see also p.
34
Hepatic thrombopoietin is required for bone marrow hematopoietic stem cell maintenance
Authors: Decker Matthew , Leslie Juliana , Liu Qingxue , Ding Lei
Published: April 2018

Signaling hematopoietic stem cells from afar

Throughout our entire life span, hematopoietic stem cells (HSCs) generate all of our blood cells. The bone marrow microenvironment, or niche, is key to activating stem cell activity. Decker
et al.
now show that thrombopoietin generated in the liver, but not from the local bone marrow niche, maintains HSCs in vivo in mice. Thus, systemic endocrine factors are needed to maintain somatic stem cells from a distance. These findings may be important when considering how to stimulate HSCs for therapeutic use.

Science
, this issue p.
106
Triggered recruitment of ESCRT machinery promotes endolysosomal repair
Authors: Skowyra Michael L. , Schlesinger Paul H. , Naismith Teresa V. , Hanson Phyllis I.
Published: April 2018

A quick fix for leaky endosomes

Cells internalize diverse material through various forms of endocytosis into an extensive endolysosomal network. Protecting the integrity of endolysosomal membranes in both physiological and pathophysiological contexts is critical to cell health. Skowyra
et al.
describe a role for the ESCRT (endosomal sorting complex required for transport) machinery on endolysosomal organelles during membrane repair (see the Perspective by Gutierrez and Carlton). The ESCRTs act as first responders to repair limited membrane damage and thereby restore compartmental integrity and function. This ESCRT activity is distinct from organelle disposal pathways. These findings will be important in understanding cellular responses to invading pathogens and potentially disruptive proinflammatory particulates.

Science
, this issue p.
eaar5078
; see also p.
33
Lattices for fractional Chern insulators
Authors: Repellin Cécile , Regnault Nicolas
Published: April 2018

Topological order beyond Landau levels is seen in encapsulated bilayer graphene
Revisiting a tragedy at Gombe
The Ghosts of Gombe: A True Story of Love and Death in an African Wilderness
Dale Peterson
University of California Press, 2018. 232 pp.
Authors: Stark-Rodenburg Malissa
Published: April 2018

Haunting clues suggest psychological distress preceded a researcher's 1969 death at Goodall's African research center
Science for state legislatures
Authors: Maxon Mary E. , Alberts Bruce
Published: April 2018

Next week on 14 April, the March for Science will once again demonstrate the widespread public support for science around the world. Nowhere is this message more needed than in Washington, D.C., where the federal government continues to ignore the value of independent science advice to inform decision-making. Given this lack of expertise at the national level, it is critical to bolster the role of science in policy-making at the state government level. Here, California can lead by example.
The Protease ClpXP and the PAS Domain Protein DivL Regulate CtrA and Gene Transfer Agent Production in Rhodobacter capsulatus
Authors: Westbye Alexander B. , Kater Lukas , Wiesmann Christina , Ding Hao , Yip Calvin K. , Beatty J. Thomas
Published: April 2018

Several members of the
Rhodobacterales
(
Alphaproteobacteria
) produce a conserved horizontal gene transfer vector, called the gene transfer agent (GTA), that appears to have evolved from a bacteriophage. The model system used to study GTA biology is the
Rhodobacter capsulatus
GTA (RcGTA), a small, tailed bacteriophage-like particle produced by a subset of the cells in a culture. The response regulator CtrA is conserved in the
Alphaproteobacteria
and is an essential regulator of RcGTA production: it controls the production and maturation of the RcGTA particle and RcGTA release from cells. CtrA also controls the natural transformation-like system required for cells to receive RcGTA-donated DNA. Here, we report that dysregulation of the CckA-ChpT-CtrA phosphorelay either by the loss of the PAS domain protein DivL or by substitution of the autophosphorylation residue of the hybrid histidine kinase CckA decreased CtrA phosphorylation and greatly increased RcGTA protein production in
R. capsulatus
. We show that the loss of the ClpXP protease or the three C-terminal residues of CtrA results in increased CtrA levels in
R. capsulatus
and identify ClpX(P) to be essential for the maturation of RcGTA particles. Furthermore, we show that CtrA phosphorylation is important for head spike production. Our results provide novel insight into the regulation of CtrA and GTAs in the
Rhodobacterales
.

IMPORTANCE
Members of the
Rhodobacterales
are abundant in ocean and freshwater environments. The conserved GTA produced by many
Rhodobacterales
may have an important role in horizontal gene transfer (HGT) in aquatic environments and provide a significant contribution to their adaptation. GTA production is controlled by bacterial regulatory systems, including the conserved CckA-ChpT-CtrA phosphorelay; however, several questions about GTA regulation remain. Our identification that a short DivL homologue and ClpXP regulate CtrA in
R. capsulatus
extends the model of CtrA regulation from
Caulobacter crescentus
to a member of the
Rhodobacterales
. We found that the magnitude of RcGTA production greatly depends on DivL and CckA kinase activity, adding yet another layer of regulatory complexity to RcGTA. RcGTA is known to undergo CckA-dependent maturation, and we extend the understanding of this process by showing that the ClpX chaperone is required for formation of tailed, DNA-containing particles.
Borrelia burgdorferi SpoVG DNA- and RNA-Binding Protein Modulates the Physiology of the Lyme Disease Spirochete
Authors: Savage Christina R. , Jutras Brandon L. , Bestor Aaron , Tilly Kit , Rosa Patricia A. , Tourand Yvonne , Stewart Philip E. , Brissette Catherine A. , Stevenson Brian
Published: April 2018

The SpoVG protein of
Borrelia burgdorferi
, the Lyme disease spirochete, binds to specific sites of DNA and RNA. The bacterium regulates transcription of
spoVG
during the natural tick-mammal infectious cycle and in response to some changes in culture conditions. Bacterial levels of
spoVG
mRNA and SpoVG protein did not necessarily correlate, suggesting that posttranscriptional mechanisms also control protein levels. Consistent with this, SpoVG binds to its own mRNA, adjacent to the ribosome-binding site. SpoVG also binds to two DNA sites in the
glpFKD
operon and to two RNA sites in
glpFKD
mRNA; that operon encodes genes necessary for glycerol catabolism and is important for colonization in ticks. In addition, spirochetes engineered to dysregulate
spoVG
exhibited physiological alterations.

IMPORTANCE
B. burgdorferi
persists in nature by cycling between ticks and vertebrates. Little is known about how the bacterium senses and adapts to each niche of the cycle. The present studies indicate that
B. burgdorferi
controls production of SpoVG and that this protein binds to specific sites of DNA and RNA in the genome and transcriptome, respectively. Altered expression of
spoVG
exerts effects on bacterial replication and other aspects of the spirochete's physiology.
Clinical prediction rules for abusive head trauma: a systematic review
Authors: Pfeiffer Helena , Crowe Louise , Kemp Alison Mary , Cowley Laura Elizabeth , Smith Anne S , Babl Franz E
Published: April 2018

Objective

Misdiagnosis of abusive head trauma (AHT) has serious consequences for children and families. This systematic review identifies and compares clinical prediction rules (CPredRs) assisting clinicians in assessing suspected AHT.

Design

We searched MEDLINE, Embase, PubMed and Cochrane databases (January 1996 to August 2016). Externally validated CPredRs focusing on the detection of AHT in the clinical setting were included.

Results

Of 110 potential articles identified, three studies met the inclusion criteria: the Pediatric Brain Injury Research Network (PediBIRN) 4-Variable AHT CPredR, the Predicting Abusive Head Trauma (PredAHT) tool and the Pittsburgh Infant Brain Injury Score (PIBIS). The CPredRs were designed for different populations and purposes: PediBIRN: intensive care unit admissions (<3 years) with head injury, to inform early decisions to launch or forego an evaluation for abuse (sensitivity 0.96); PredAHT: hospital admissions (<3 years) with intracranial injury, to assist clinicians in discussions with child abuse specialists (sensitivity 0.72); and PIBIS: well-appearing children (<1 year) in the emergency department with no history of trauma, temperature <38.3°C, and ≥1 symptom associated with high risk of AHT, to determine the need for a head CT scan (sensitivity 0.93). There was little overlap between the predictive variables.

Conclusion

Three CPredRs for AHT were relevant at different stages in the diagnostic process. None of the CPredRs aimed to diagnose AHT but to act as aids/prompts to clinicians to seek further clinical, social or forensic information. None were widely validated in multiple settings. To assess safety and effectiveness in clinical practice, impact analyses are required and recommended.
Chiari malformation and tuberculous meningitis: aetiology and management
Authors: Diestro Jose Danilo Bengzon , Bautista Jesi Ellen Cueto , Omar Abdelsimar T , Mercado James Garcia , Ramiro Philip Asuncion
Published: April 2018

This is the first reported case of a Chiari 1 malformation in association with tuberculous (TB) meningitis. We present a case of a 23-year-old woman with a 2-week history nocturnal fever, vertigo, headache and projectile vomiting. She had nystagmus, scanning speech, bilateral papilloedema and ataxia. Cranial imaging showed a 10 mm tonsillar herniation. Posterior fossa decompression was done. Because the patient’s gamut of symptoms was highly suspicious for a central nervous system infection, a lumbar tap was done which revealed TB meningitis. Four years later, after anti-TB medications and rehabilitation, all her symptoms except gait instability resolved.
Current detection rates and time-to-detection of all identifiable BRCA carriers in the Greater London population
Authors: Manchanda Ranjit , Blyuss Oleg , Gaba Faiza , Gordeev Vladimir Sergeevich , Jacobs Chris , Burnell Matthew , Gan Carmen , Taylor Rohan , Turnbull Clare , Legood Rosa , Zaikin Alexey , Antoniou Antonis C , Menon Usha , Jacobs Ian
Published: April 2018

Background

BRCA carrier identification offers opportunities for early diagnoses, targeted treatment and cancer prevention. We evaluate BRCA- carrier detection rates in general and Ashkenazi Jewish (AJ) populations across Greater London and estimate time-to-detection of all identifiable BRCA carriers.

Methods

BRCA carrier data from 1993 to 2014 were obtained from National Health Service genetic laboratories and compared with modelled predictions of BRCA prevalence from published literature and geographical data from UK Office for National Statistics. Proportion of BRCA carriers identified was estimated. Prediction models were developed to fit BRCA detection rate data. BRCA carrier identification rates were evaluated for an ‘Angelina Jolie effect’. Maps for four Greater London regions were constructed, and their relative BRCA detection rates were compared. Models developed were used to predict future time-to-identify all detectable BRCA carriers in AJ and general populations.

Results

Until 2014, only 2.6% (3072/111 742 estimated) general population and 10.9% (548/4985 estimated) AJ population BRCA carriers have been identified in 16 696 608 (AJ=190 997) Greater London population. 57% general population and 54% AJ mutations were identified through cascade testing. Current detection rates mirror linear fit rather than parabolic model and will not identify all BRCA carriers. Addition of unselected ovarian/triple-negative breast cancer testing would take >250 years to identify all BRCA carriers. Doubling current detection rates can identify all ‘detectable’ BRCA carriers in the general population by year 2181, while parabolic and triple linear rates can identify ‘detectable’ BRCA carriers by 2084 and 2093, respectively. The linear fit model can identify ‘detectable’ AJ carriers by 2044. We did not find an Angelina Jolie effect on BRCA carrier detection rates. There was a significant difference in BRCA detection rates between geographical regions over time (P<0.001).

Conclusions

The majority of BRCA carriers have not been identified, missing key opportunities for prevention/earlier diagnosis. Enhanced and new strategies/approaches are needed.