bluuebunny/crossref_metadata_2025 huggingface dataset:
A model for reticular dysgenesis shows impaired sensory organ development and hair cell regeneration linked to cellular stress
Authors: Rissone Alberto , Jimenez Erin , Bishop Kevin , Carrington Blake , Slevin Claire , Wincovitch Stephen M. , Sood Raman , Candotti Fabio , Burgess Shawn M.
Published: April 2019

Mutations in the gene AK2 are responsible for Reticular Dysgenesis (RD), a rare and severe form of primary immunodeficiency in children. RD patients have a severely shortened life expectancy and without treatment die a few weeks after birth. The only available therapeutic option for RD is bone marrow transplantation. To gain insight into the pathophysiology of RD, we previously created zebrafish models for an AK2 deficiency. One of the clinical features of RD is hearing loss, but its pathology and causes have not been determined. In adult mammals, sensory hair cells of the inner ear do not regenerate; however, their regeneration has been observed in several non-mammalian vertebrates, including zebrafish. Therefore, we use our RD zebrafish models to determine if AK2 deficiency affects sensory organ development and/or hair cell regeneration. Our studies indicated that AK2 is required for the correct development, survival and regeneration of sensory hair cells. Interestingly, AK2 deficiency induces the expression of several oxidative stress markers and it triggers an increased level of cell death in the hair cells. Finally, we show that glutathione treatment can partially rescue hair cell development in the sensory organs in our RD models, pointing to the potential use of antioxidants as a supportive therapeutic modality for RD patients, not only to increase their chances of survival, but to prevent or ameliorate their sensorineural hearing deficits.
White-nose syndrome restructures bat skin microbiomes
Authors: Ange-Stark Meghan , Cheng Tina L. , Hoyt Joseph R. , Langwig Kate E. , Parise Katy L. , Frick Winifred F. , Kilpatrick A. Marm , MacManes Matthew D. , Foster Jeffrey T.
Published: April 2019

The skin microbiome is an essential line of host defense against pathogens, yet our understanding of microbial communities and how they change when hosts become infected is limited. We investigated skin microbial composition in three North American bat species (Myotis lucifugus,Eptesicus fuscus, andPerimyotis subflavus) that have been impacted by the infectious disease, white-nose syndrome, caused by an invasive fungal pathogen,Pseudogymnoascus destructans. We compared bacterial and fungal composition from 154 skin swab samples and 70 environmental samples using a targeted 16S rRNA and ITS amplicon approach. We found that forM. lucifugus, a species that experiences high mortality from white-nose syndrome, bacterial microbiome diversity was dramatically lower whenP. destructansis present. Key bacterial families—including those potentially involved in pathogen defense—significantly differed in abundance in bats infected withP. destructanscompared to uninfected bats. However, skin bacterial diversity was not lower inE. fuscusorP. subflavuswhenP. destructanswas present, despite populations of the latter species declining sharply from white-nose syndrome. The fungal species present on bats substantially overlapped with the fungal taxa present in the environment at the site where the bat was sampled, but fungal community composition was unaffected by the presence ofP. destructansfor any of the three bat species. This species-specific alteration in bat skin bacterial microbiomes after pathogen invasion may suggest a mechanism for the severity of WNS inM. lucifugus, but not for other bat species impacted by white-nose syndrome.
Genome-wide assessment of genetic risk for systemic lupus erythematosus and disease severity
Authors: Chen Lingyan , Wang Yong-Fei , Liu Lu , Bielowka Adrianna , Ahmed Rahell , Zhang Huoru , Tombleson Phil , Roberts Amy L , Odhams Christopher A , Cunninghame Graham Deborah S , Zhang Xuejun , Yang Wangling , Vyse Timothy J , Morris David L
Published: April 2019

Objective

Using three European and two Chinese genome-wide association studies (GWAS), we investigated the performance of genetic risk scores (GRS) for predicting the susceptibility and severity of Systemic lupus erythematosus (SLE), using renal disease as a proxy for severity.

Methods

We used four GWASs to test the performance of GRS both cross validating within the European population and between European and Chinese populations. The performance of GRS in SLE risk prediction was evaluated by Receiver Operating Characteristic (ROC) curves. We then analyzed the polygenic nature of SLE statistically. We also partitioned patients according to their age-of-onset and evaluated the predictability of GRS in disease severity in each age group.

Results

We found consistently that the best GRS in the prediction of SLE used SNPs associated at the level of P<1e-05 in all GWAS datasets and that SNPs with P-values above 0.2 were inflated for SLE true positive signals. The GRS results in an area under the ROC curve ranging between 0.64 and 0.72, within European and between the European and Chinese populations. We further showed a significant positive correlation between a GRS and renal disease in two independent European GWAS (Pcohort1=2.44e-08; Pcohort2=0.00205) and a significant negative correlation with age of SLE onset (Pcohort1=1.76e-12; Pcohort2=0.00384). We found that the GRS performed better in prediction of renal disease in the ‘later onset’ compared to the ‘earlier onset’ group.

Conclusion

The GRS predicts SLE in both European and Chinese populations and correlates with poorer prognostic factors: young age of onset and lupus nephritis.
Attention Decorrelates Sensory and Motor Signals in the Mouse Visual Cortex
Authors: Abdolrahmani Mohammad , Lyamzin Dmitry R , Aoki Ryo , Benucci Andrea
Published: April 2019

Visually-guided behaviors depend on the activity of cortical networks receiving visual inputs and transforming these signals to guide appropriate actions. However, non-retinal inputs, carrying motor signals as well as cognitive and attentional modulatory signals, also activate these cortical regions. How these networks avoid interference between coincident signals ensuring reliable visual behaviors is poorly understood. Here, we observed neural responses in the dorsal-parietal cortex of mice during a visual discrimination task driven by visual stimuli and movements. We found that visual and motor signals interacted according to two canonical mechanisms: divisive normalization and response demixing. Interactions were contextually modulated by the animal’s state of attention, with attention amplifying visual and motor signals and decorrelating them in a low-dimensional space of neural activations. These findings reveal canonical computational principles operating in dorsal-parietal networks that enable separation of incoming signals for reliable visually-guided behaviors during interactions with the environment.
CreC Sensor Kinase Activation Enhances Growth of Escherichia coli in the Presence of Cephalosporins and Carbapenems
Authors: Takebayashi Yuiko , Taylor Emma S. , Whitwam Sam , Avison Matthew B.
Published: April 2019

Mutants with enhanced growth in the presence of antibiotics but where the antibiotic’s minimum inhibitory concentration does not change, are difficult to identify in mixed populations because they are not amenable to selection. Here we report that activatory mutations in the CreC signal sensor enhance growth of Escherichia coli in the presence of cefoxitin, cefotaxime and meropenem without increasing their minimum inhibitory concentrations. Enhanced growth is dependent on overproduction of the inner-membrane cre-regulon protein CreD.
Distinct changes in morphometric networks in aging versus Alzheimer’s disease dementia
Authors: Binette Alexa Pichet , Gonneaud Julie , Vogel Jacob W. , La Joie Renaud , Rosa-Neto Pedro , Collins D. Louis , Poirier Judes , Breitner John C.S. , Villeneuve Sylvia , Vachon-Presseau Etienne ,   Alzheimer’s Disease Neuroimaging Initiative,   PREVENT-AD Research Group
Published: April 2019

Brain gray matter (GM) morphometric changes are prevalent in both aging and Alzheimers disease (AD), though disentangling these two processes has proved challenging. Using independent component analysis, we derived morphometric networks from a large, multi-cohort dataset, and investigated how GM volume within these networks differs in young adulthood, old adulthood, and AD. Aging and AD contributed additive effects on GM loss in nearly all networks, except frontal lobe networks, where GM reductions were more specific to aging. While no networks show GM loss highly specific to AD, a higher degree of variability in the whole-brain pattern of GM volume characterized AD only. Preservation of the whole-brain GM pattern in cognitively normal older adults was related to better cognition and lower risk of developing cognitive impairment. These results suggest both aging and AD involve widespread atrophy, but that cognitive impairment is uniquely associated with disruption of morphometric organization.
Homeostatic mechanisms may shape the type and duration of oscillatory modulation
Authors: Peterson Erik J. , Voytek Bradley
Published: April 2019

Neural oscillations are observed ubiquitously in the mammalian brain, but their stability is known to be rather variable. Some oscillations are tonic and last for seconds or even minutes. Other oscillations appear as unstable bursts. Likewise, some oscillations rely on excitatory AMPAergic synapses, but others are GABAergic and inhibitory. Why this diversity exists is not clear. We hypothesized Ca 2+ -dependent homeostasis could be important in finding an explanation. We tested this hypothesis in a highly simplified model of hippocampal neurons. In this model homeostasis profoundly alters the modulatory effect of neural oscillations. Under homeostasis, tonic AMPAergic oscillations actually decrease excitability and desynchronize firing. Tonic oscillations that are synaptically GABAergic–like those in real hippocampus–don’t provoke a homeostatic response, however. If our simple model is correct, homeostasis can explain why the theta rhythm in the hippocampus is synaptically inhibitory: GABA has little to no intrinsic homeostatic response, and so can preserve the pyramidal cell’s natural dynamic range. Based on these results we can also speculate that homeostasis may explain why AMPAergic oscillations in cortex, and hippocampus, often appear as bursts. Bursts do not interact with the slow homeostatic time constant, and so retain their normal excitatory effect.

New and Noteworthy

The intricate interplay of neuromodulators, like acetylcholine, with homeostasis is well known. The interplay between oscillatory modulation and homeostasis is not. We studied oscillatory modulation and homeostasis for the first time using a simplified model of hippocampus. We report a paradoxical result: Ca-mediated homeostasis causes AMPAergic oscillations to become effectively inhibitory. This result, along with other new observations, means homeostasis might be just as complex and important for oscillations as it is for other neuromodulators.
The histidine kinase PdtaS is a cyclic di-GMP binding metabolic sensor that controls mycobacterial adaptation to nutrient deprivation
Authors: Hariharan Vignesh Narayan , Thakur Chandrani , Singh Albel , Gopinathan Renu , Singh Devendra Pratap , Sankhe Gaurav , Chandra Nagasuma , Bhatt Apoorva , Saini Deepak Kumar
Published: April 2019

Cell signalling relies on second messengers to transduce signals from the sensory apparatus to downstream components of the signalling pathway. In bacteria, one of the most important and ubiquitous second messengers is the small molecule cyclic diguanosine monophosphate (c-di-GMP). While the biosynthesis, degradation and regulatory pathways controlled by c-di-GMP are well characterized, the mechanisms through which c-di-GMP controls these processes is not completely understood. Here we present the first report of a c-di-GMP regulated sensor histidine kinase previously named PdtaS (Rv3220c), which binds to c-di-GMP at sub-micromolar concentrations, subsequently perturbing signalling of the PdtaS-PdtaR (Rv1626) two component system. Aided by biochemical analysis, molecular docking and structural modelling, we have characterized the binding site of c-di-GMP in the GAF domain of PdtaS. We show that a pdtaS knockout in M. smegmatis is severely compromised in growth on amino acid deficient media and exhibits global transcriptional dysregulation. Perturbation of the c-di-GMP-PdtaS-PdtaR axis results in a cascade of cellular changes recorded by a multi-parametric systems approach of transcriptomics, unbiased metabolomics and lipid analyses.

One-sentence summary

The universal bacterial second messenger cyclic di-GMP controls the mycobacterial nutrient stress response
Microclimate and larval habitat density predict adult Aedes albopictus abundance in urban areas
Authors: Evans Michelle V. , Hintz Carl W. , Jones Lindsey , Shiau Justine , Solano Nicole , Drake John M. , Murdock Courtney C.
Published: April 2019

The Asian tiger mosquito, Aedes albopictus, transmits several arboviruses of public health importance, including chikungunya and Zika. Since its introduction to the United States in 1985, the species has invaded over forty states, including temperate areas not previously at risk of Aedes-transmitted arboviruses. Mathematical models incorporate climatic variables in predictions of site-specific Ae. albopictus abundances to identify human populations at risk of disease. However, these models rely on coarse resolutions of environmental data that may not accurately represent the climatic profile experienced by mosquitoes in the field, particularly in climatically-heterogeneous urban areas. In this study, we pair field surveys of larval and adult Ae. albopictus mosquitoes with site-specific microclimate data across a range of land use types to investigate the relationships between microclimate, density of larval habitat, and adult mosquito abundance and determine whether these relationships change across an urban gradient. We find no evidence for a difference in larval habitat density or adult abundance between rural, suburban, and urban land classes. Adult abundance increases with increasing larval habitat density, which itself is dependent on microclimate. Adult abundance is strongly explained by microclimate variables, demonstrating that theoretically derived, lab-parameterized relationships in ectotherm physiology apply to the field. Our results provide support for the continued use of temperature-dependent models to predict Ae. albopictus abundance in urban areas.
A Cys2/His2 zinc finger protein acts as a repressor of gibberellins biosynthesis by regulating SD1/OsGA20ox2 in rice (Oryza sativa L.)
Authors: Duan Min , Ke Xiao-Juan , Lan Hong-Xia , Yuan Xi , Huang Peng , Xu En-Shun , Gao Xiu-Ying , Wang Ru-Qin , Tang Hai-Juan , Zhang Hong-Sheng , Huang Ji
Published: April 2019

Gibberellins (GAs) play important roles in the regulation of plant growth and development. The green evolution geneSD1encoding gibberellin 20-oxidase 2 (GA20ox2) has been widely used in modern rice breeding. However, the molecular mechanism of howSD1/OsGA20ox2expression is regulated remains unclear. Here we report a Cys2/His2 zinc finger protein ZFP207 acting as a transcriptional repressor ofOsGA20ox2.ZFP207was mainly accumulated in young tissues and more specifically in culm nodes.ZFP207-overexpression (ZFP207OE) plants displayed semi-dwarfism phenotype and small grains by modulating cell length. RNA interference ofZFP207caused higher plant and longer grains. The endogenous bioactive GA levels were significantly reduced inZFP207OEplants and application of exogenous GA3rescued the semi-dwarf phenotype. Thein vivoandin vitrostudies showed that ZFP207 repressed the expression ofOsGA20ox2via binding to its promoter region. Together, ZFP207 acts as a transcriptional repressor of gibberellins biosynthesis and it may play a critical role in plant growth and development through fine-tuning GA biosynthesis in rice.
Targeted transcript quantification in single disseminated cancer cells after whole transcriptome amplification
Authors: Durst Franziska C. , Grujovic Ana , Ganser Iris , Hoffmann Martin , Ugocsai Peter , Klein Christoph A. , Czyż Zbigniew T.
Published: April 2019

Gene expression analysis of rare or heterogeneous cell populations such as disseminated cancer cells (DCCs) requires a sensitive method allowing reliable analysis of single cells. Therefore, we developed and explored the feasibility of a quantitative PCR (qPCR) assay to analyze single-cell cDNA pre-amplified using a previously established whole transcriptome amplification (WTA) protocol. We carefully selected and optimized multiple steps of the protocol, e.g. re-amplification of WTA products, quantification of amplified cDNA yields and final qPCR quantification, to identify the most reliable and accurate workflow for quantitation of gene expression of the ERBB2 gene in DCCs. We found that absolute quantification outperforms relative quantification. We then validated the performance of our method on single cells of established breast cancer cell lines displaying distinct levels of HER2 protein. The different protein levels were faithfully reflected by transcript expression across the tested cell lines thereby proving the accuracy of our approach. Finally, we applied our method on patient-derived breast cancer DCCs. Here, we were able to measure ERBB2 expression levels in all HER2-positive DCCs. In addition, we could detect ERBB2 transcript expression even in HER2-negative DCCs, suggesting post-transcriptional mechanisms of HER2 loss in anti-HER2-treated DCCs. In summary, we developed a reliable single-cell qPCR assay applicable to measure distinct levels of ERBB2 in DCCs.
A simple and versatile microfluidic device for efficient biomacromolecule crystallization and structural analysis by serial crystallography
Authors: de Wijn Raphaël , Hennig Oliver , Roche Jennifer , Engilberge Sylvain , Rollet Kevin , Fernandez-Millan Pablo , Brillet Karl , Betat Heike , Mörl Mario , Roussel Alain , Girard Eric , Mueller-Dieckmann Christoph , Fox Gavin C. , Olieric Vincent , Gavira José A. , Lorber Bernard , Sauter Claude
Published: April 2019

Determining optimal conditions for the production of well diffracting crystals is a key step in every biocrystallography project. Here, a microfluidic device is described that enables the production of crystals by counter-diffusion and their direct on-chip analysis by serial crystallography at room temperature. Nine `non-model' and diverse biomacromolecules, including seven soluble proteins, a membrane protein and an RNA duplex, were crystallized and treated on-chip with a variety of standard techniques including micro-seeding, crystal soaking with ligands and crystal detection by fluorescence. Furthermore, the crystal structures of four proteins and an RNA were determined based on serial data collected on four synchrotron beamlines, demonstrating the general applicability of this multipurpose chip concept.
Competition between cubic and tetragonal phases in all-d-metal Heusler alloys, X
2−x
Mn1+x
V (X = Pd, Ni, Pt, Ag, Au, Ir, Co; x = 1, 0): a new potential direction of the Heusler family
Authors: Han Yilin , Wu Mengxin , Feng Yu , Cheng Zhenxiang , Lin Tingting , Yang Tie , Khenata Rabah , Wang Xiaotian
Published: April 2019

In this work, a series of all-d-metal Heusler alloys, X
2 − x
Mn1 + x
V (X = Pd, Ni, Pt, Ag, Au, Ir, Co; x; = 1, 0), were predicted by first principles. The series can be roughly divided into two categories: XMn2V (Mn-rich type) and X
2MnV (Mn-poor type). Using optimized structural analysis, it is shown that the ground state of these all-d-metal Heusler alloys does not fully meet the site-preference rule for classic full-Heusler alloys. All the Mn-rich type alloys tend to form the L21 structure, where the two Mn atoms prefer to occupy the A (0, 0, 0) and C (0.5, 0.5, 0.5) Wyckoff sites, whereas for the Mn-poor-type alloys, some are stable with XA structures and some are not. The c/a ratio was also changed while maintaining the volume the same as in the cubic state to investigate the possible tetragonal transformation of these alloys. The Mn-rich Heusler alloys have strong cubic resistance; however, all the Mn-poor alloys prefer to have a tetragonal state instead of a cubic phase through tetragonal transformations. The origin of the tetragonal state and the competition between the cubic and tetragonal phases in Mn-poor alloys are discussed in detail. Results show that broader and shallower density-of-states structures at or in the vicinity of the Fermi level lower the total energy and stabilize the tetragonal phases of X
2MnV (X = Pd, Ni, Pt, Ag, Au, Ir, Co). Furthermore, the lack of virtual frequency in the phonon spectra confirms the stability of the tetragonal states of these Mn-poor all-d-metal Heusler alloys. This work provides relevant experimental guidance in the search for possible martensitic Heusler alloys in all-d-metal materials with less Mn and new spintronic and magnetic intelligent materials among all-d-metal Heusler alloys.
Environmental reporting practices and performance of timber firms in Ghana
Authors: Agyei Samuel Kwaku , Yankey Benjamin
Published: April 2019

Purpose

The purpose of this paper is to assess the motivations of timber firms in Ghana to undertake environmental accounting and reporting (EAR) and the perceived benefits from it.

Design/methodology/approach

Survey method involving primary data from a census of 13 timber firms in Kumasi (Ghana) and descriptive statistics including Kendall’s coefficient were used to analyze the perceptions of practitioners on EAR.

Findings

The study offered support for the political economy, legitimacy and stakeholder theories generally applied to the study of EAR. Specifically, the study concluded that EAR is common to timber firms in Ghana. Pressure from government, media, shareholders’ influence and the existence of environmental committee or department in the company are perceived to influence timber firms’ level of environmental disclosure. Meanwhile, perceived benefits from EAR include fostering cordial relationship between timber firms and the society, preventing government fines and improving firm reputation.

Research limitations/implications

The presence of biases in the responses of survey method studies can be difficult to eliminate. However, given the benefits associated with getting practitioners views on EAR and the reliability/validity procedures that the instruments and respondents were subjected to, this weakness was reduced to its barest minimum.

Practical implications

The study recommends that governments should adopt green tax policy to encourage EAR while regulatory bodies make EAR mandatory.

Originality/value

This study contributes to the discussion on EAR from the perspective of practitioners in the timber industry of Ghana, which has been neglected in previous studies.
Supervisors’ experience of delivering individual clinical supervision to qualified therapists: a meta-ethnographic synthesis
Authors: Forshaw Gemma , Sabin-Farrell Rachel , Schröder Thomas
Published: April 2019

Purpose

The purpose of this paper is to systematically identify, appraise and synthesise qualitative literature exploring the experience, both positive and negative, of clinical supervision from the supervisor’s perspective.

Design/methodology/approach

A systematic search of three databases, grey literature, reference lists and citations was conducted. Six articles met the inclusion criteria and their quality was critically appraised by using a modified version of the Critical Appraisal Skills Programme tool. Data extracted from the articles were synthesised using meta-ethnography.

Findings

Four key themes were identified: experiencing difficulties in clinical supervision, responsibility, similarities to therapy and capabilities as a supervisor. These demonstrated that the role of a supervisor has the potential to be both beneficial and harmful to personal and professional development.

Research limitations/implications

The quality of the studies was variable. Further research is required to explore how supervisors manage difficult experiences to ensure personal development and growth.

Practical implications

Clinical implications include the need for employers to consider the additional pressure associated with providing clinical supervision and to ensure that appropriate support is available. Results complement previous research on the bi-directionality of parallel process in clinical supervision.

Originality/value

This review presents an original synthesis of the supervisor’s experience of delivering clinical supervision to qualified therapists. This is achieved by utilising a systematic methodology and appraising the quality of the studies included. The review highlights how the effects of clinical supervision are not limited to the supervisee, but also experienced by the supervisor. The competing demands and responsibilities associated with clinical supervision impact upon the supervisor’s experience, both positively and negatively. When beneficial, delivering clinical supervision can lead to personal and professional growth in addition to the acquisition of new skills.
“I have more support around me to be able to change”: a qualitative exploration of probationers’ and parolees’ experiences living in sober living houses
Authors: DeGuzman Rebecca , Korcha Rachael , Polcin Douglas
Published: April 2019

Purpose

Persons in the USA who are incarcerated for drug offenses are increasingly being released into the community as a way to decrease prison and jail overcrowding. One challenge is finding housing that supports compliance with probation and parole requirements, which often includes abstinence from drugs and alcohol. Sober living houses (SLHs) are alcohol- and drug-free living environments that are increasingly being used as housing options for probationers and parolees. Although a few studies have reported favorable outcomes for residents of SLHs, little is known about resident experiences or the factors that are experienced as helpful or counterproductive. The paper aims to discuss this issue.

Design/methodology/approach

This study conducted qualitative interviews with 28 SLH residents on probation or parole to understand their experiences living in the houses, aspects of the houses that facilitated recovery, ways residence in an SLH affected compliance with probation and parole, and ways the houses addressed HIV risk, a widespread problem among this population. Interviews were audiotaped and coded for dominant themes.

Findings

Study participants identified housing as a critically important need after incarceration. For residents nearing the end of their stay in the SLHs, there was significant concern about where they might live after they left. Residents emphasized that shared experiences and goals, consistent enforcement of rules (especially the requirement of abstinence) and encouragement from probation and parole officers as particularly helpful. There was very little focus in HIV issues, even though risk behaviors were fairly common. For some residents, inconsistent enforcement of house rules was experienced as highly problematic. Research is needed to identify the organizational and operational procedures that enhance factors experienced as helpful.

Research limitations/implications

Data for this study are self-reported views and experiences. Therefore, the study may not tap into a variety of reasons for resident experiences. In addition, the data set was small (n=28) and limited to one city in the USA (Los Angeles), so generalization of results might be limited. However, SLHs represent an important housing option for criminal justice involved persons and knowledge about resident experiences can help guide organization and operation of houses and identify areas for further research.

Originality/value

This paper is the first to document the views and experiences of persons on probation or parole who reside in sober living recovery houses. These data can be used by SLH operators to develop houses that are responsive to factors experienced as helpful and counterproductive. The significance of this paper is evident in the trend toward decreasing incarceration in the USA of persons convicted of drug offenses and the need for alcohol- and drug-free alternative living environments.
A pilin chaperone required for the expression of electrically conductive Geobacter sulfurreducens pili
Authors: Liu Xing , Zhan Ji , Jing Xianyue , Zhou Shungui , Lovley Derek R.
Published: April 2019

Mechanisms controlling the expression of the electrically conductive pili (e‐pili) of Geobacter species are of interest because of the important role of e‐pili in diverse biogeochemical processes, anaerobic digestion and electromicrobiological applications. We investigated the function of the protein, designated Spc (short pilin chaperone), encoded by the gene immediately downstream from the gene for PilA, the monomer that assembles into e‐pili. Multiple lines of evidence suggest that Spc forms an oligomer that is associated with the inner membrane. Mutating the start codon of spc to prevent translation increased the transcript abundance of pilA but greatly diminished the abundance of PilA, and e‐pili could no longer be detected. Cross‐linking, protein capture and two‐hybrid studies demonstrated that Spc and PilA interacted. Two sites in PilA for electrostatic interaction with Spc were identified. The results demonstrate that Spc is required for PilA stability prior to incorporation into e‐pili, suggesting that Spc has a chaperone function that may be specific to the relatively short PilA monomers that assemble into e‐pili. These results are important for identifying microorganisms likely to express e‐pili from (meta)genomic data and for the construction of microbial strains expressing e‐pili.
Sequence capture across large phylogenetic scales by using pooled PCR‐generated baits: A case study of Lepidoptera
Authors: Zhang Yuan , Deng Shaohong , Liang Dan , Zhang Peng
Published: April 2019

Sequence capture across large phylogenetic scales is not easy because hybridization capture is only effective when the genetic distance between the bait and target is small. Here, we propose a simple but effective strategy to tackle this issue: pooling DNA from a number of selected representative species of different clades to prepare PCR‐generated baits to minimize the genetic distance between the bait and target. To demonstrate the utility of this strategy, we newly developed a set of universal nuclear markers (including 94 nuclear protein‐coding genes) for Lepidoptera, a superdiverse insect group. We used a DNA pool from six lepidopteran species (representing six superfamilies) to prepare PCR baits for the 94 markers. These homemade PCR baits were used to capture sequence data from 43 species of 17 lepidopteran families, and 94% of the target loci were recovered. We constructed two data sets from the obtained data (one containing ~90 kb target coding sequences and the other containing ~120 kb target + flanking coding sequences). Both data sets yielded highly similar and well‐resolved trees with 90% of nodes having >95% bootstrap support. Our capture experiment indicated that using DNA mixtures pooled from different clade‐representative species of Lepidoptera to prepare PCR baits can reliably capture a large number of targeted nuclear markers across different Lepidoptera lineages. We hope that this newly developed nuclear marker set will serve as a new phylogenetic tool for Lepidoptera phylogenetics, and the PCR bait preparation strategy can facilitate the application of sequence capture techniques by researchers to accelerate data collection.
Vegetation, land, and wood use at the sites of Bat and Al‐Khashbah in Oman (fourth–third millennium BC)
Authors: Deckers Katleen , Döpper Stephanie , Schmidt Conrad
Published: April 2019

About 4200 charcoal fragments have been identified from the fourth‐ to third‐millennium BC archaeological sites of Bat and Al‐Khashbah in order to gain an understanding of plant resources available at the sites. Acacia sp., Ziziphus sp., and Tamarix sp. were the main taxa identified at both sites and indicate a similar vegetation composition as today. Phoenix sp. (date palm) charcoal also has been found at both sites. Whereas the cultivation of date palm for the 2700–2300 BC layers from Bat was likely, given other circumstantial evidence (i.e. local cereal cultivation and floodwater irrigation), it is unclear whether date palm was cultivated at Al‐Khashbah. Especially for the older periods (3300–2700 BC) it is possible that nomadic pastoralists were exploiting and/or managing wild date palms. The find of Avicennia marina at Al‐Khashbah indicates long‐distance contacts with the coast.
Incidence of chronic pain 6 y after major trauma
Authors: Kolstadbraaten Knut Magne , Spreng Ulrich Johannes , Wisloeff‐Aase Kristin , Gaarder Christine , Naess Paal Aksel , Raeder Johan
Published: April 2019

Background

Life saving measures is the main focus in the initial treatment of major trauma. In surviving patients, chronic pain may be a serious problem, but the long term incidence and potential risk factors are not very well studied.

Methods

All adult trauma patients included in the institutional trauma registry in 2007 were assessed for eligibility. Among exclusion criteria were: Injury Severity Score < 9, endotracheal intubation before or during admission, spinal cord lesion, known chronic drug or substance abuse, major surgery within 3 h after admission. A patient questionnaire was sent out 6 y after injury focusing on frequency and intensity of pain. A subgroup analysis was done in patients with thoracic injuries, comparing patients with epidural analgesia (EDA) and patients without.

Results

Sixty‐eight patients were included in the study. Sixty‐nine percent reported pain 6 y after injury and 24% had severe pain. The severity of the injury was a risk factor for development of chronic pain, whereas pain during initial hospital stay was not. In patients with thoracic injuries there was no correlation between initial treatment with EDA and decreased incidence of chronic pain, however patient numbers were small. Opioids were the main analgesics used initially; no patients received non‐steroidal anti‐inflammatory drugs or peripheral nerve blocks during the first 24 h.

Conclusion

Two thirds of the trauma patients had chronic pain 6 y after injury and one out of four had severe pain. The initial pain treatment was focused on opioids.
Chronic calorie‐dense diet drives differences in motivated food seeking between obesity‐prone and resistant mice
Authors: Inbar Dorrit , Gendelis Shani , Mesner Shanee , Menahem Shira , Kupchik Yonatan M.
Published: April 2019

Obesity results from overconsumption of energy, partly because of the inability to refrain from highly palatable rewarding foods. Even though palatable food is available to everyone, only a fraction of the population develops obesity. We previously showed that following chronic exposure to highly palatable food animals that gained the most weight also showed addictive‐like motivation to seek for palatable food. An important question remains—is this extreme, addictive‐like, motivation to consume palatable food the cause or the consequence of diet‐induced obesity? Here, we show that obesity‐prone (OP) mice exhibit higher motivation for palatable food consumption compared with obesity‐resistant mice even before developing obesity, but that the full manifestation of this high motivation to eat is expressed only after chronic exposure to high‐fat‐high‐sugar (HFHS) diet. HFHS diet also impairs performance in the operant food‐seeking task selectively in OP mice, an impairment that persists even after 2 weeks of abstinence from HFHS food. Overall, our data suggest that while some aspects of food motivation are high in OP mice already before developing obesity, the chronic exposure to HFHS food accentuates it and drives the development of obesity.
Outcomes of universal germline testing for men with prostate cancer in an Australian tertiary center
Authors: Crumbaker Megan , Wong Jean , Joshua Anthony M. , Spigelman Allan D.
Published: April 2019

Aim

The role of germline testing in prostate cancer is evolving and knowledge of an individual's genetic profile may be used to guide not only an assessment of their familial risk but also have prognostic and therapeutic implications. Although international guidelines have incorporated recommendations for germline testing in prostate cancer, there is little Australian data to guide referrals. The aim of this study is to review the frequency of relevant pathogenic mutations in an Australian center, their associated clinical factors and clinical impact.

Methods

We conducted a single‐center retrospective review of men with prostate cancer that undertook prospective germline testing using a targeted next generation sequencing panel.

Results

Results for 100 men were analyzed. Median age at diagnosis was 62 years (range 43–84); 92% had metastatic disease at referral. A pathogenic mutation was confirmed in 9%, a likely pathogenic variant in 2% and a variant of uncertain significance in 15%. Age ≤60 years was associated with an increased risk for a pathogenic germline variant (P = 0.0096). Two of the nine (22%) with pathogenic variants went on to receive targeted treatment.

Conclusions

In this single center study, the incidence of germline mutations in genes associated with DNA‐repair was consistent with rates seen previously published international series of men with metastatic disease. A pathogenic variant was only seen in one patient >60 years of age and no man referred solely on the basis of age or high‐risk localized disease had a relevant finding.
‘Tramline Rescue’: A salvage technique for the failed elliptical excision on the leg
Authors: Coe Alexander , Lyon Matthew
Published: April 2019

We outline an approach to achieve wound closure in the event of a failed elliptical excision on the leg. The various steps are shown, and a clinical example is presented.
Generalised eruptive histiocytosis: Case report
Authors: Costin Adelina , Cerejeira Diogo , Alves João
Published: April 2019

Generalised eruptive histiocytosis is a self‐limited and benign non‐Langerhans cell histiocytic disorder, characterised by recurrent crops of symmetrically distributed skin to red to brown coloured papules on the trunk and proximal extremities. Clinical and pathological correlation is required to establish the diagnosis. We herein present the clinical and histological features of generalised eruptive histiocytosis in a 24‐year‐old female patient.
Development of rear‐impeller axial flow blood pump for realization of axial flow blood pump installed at aortic valve position
Authors: Okamoto Eiji , Yano Tetsuya , Inoue Yusuke , Shiraishi Yasuyuki , Yambe Tomoyuki , Mitamura Yoshinori
Published: April 2019

In this study, rear‐impeller axial flow blood pumps (RIAFBP) were developed to realize a trans‐valve axial ventricular assist device (VAD) which consists of the latter blood pump and a polymer monomembrane aortic valve, such as the jellyfish valve. The motor of the RIAFBP is installed in the left ventricle, and its impeller is placed at the aortic valve position. In the prototype RIAFBP, the rotation of the motor is sustained by polyethylene bushings. The RIAFBP has a length of 50 mm and diameter of 19.6 mm. The miniature RIAFBP has the same construction as that of the prototype; however, it employs a ceramic bearing and fin bearing to improve endurance and to reduce blood stagnation. The miniature RIAFBP has a length of 63 mm and diameter of 12 mm. Both RIAFBPs were examined by an in vitro experiment using a 33% glycerin solution. The prototype RIAFBP achieved a maximum pump outflow of 8.5 L/min against a pump head of 100 mm Hg at a rotational speed of 12 000 rpm. The miniature RIAFBP achieved 7 L/min against a pump head of 70 mm Hg at a rotational speed of 21 600 rpm. In conclusion, the miniature RIAFBP has enough pump performance to realize the trans‐valve axial VAD.
Functional efficacy analysis ofAngelica gigasNakai on chicken myoblast cells through cell‐based in vitro assay
Authors: Lee Jeong Hyo , Park Jeong‐Woong , Seo Eun Sol , Kim Hoy‐Ung , Kim Seo Woo , Han Ji Seon , Jun Hyun Sik , Kim Sung‐Jo , Park Tae Sub , Park Byung‐Chul
Published: April 2019

The value‐added products in livestock industry is one of the key issues in order to maximize the revenue and to create a new business model. Numerous studies have suggested application of herbal plants as feed additives to increase health, productivity, and/or high‐quality product in livestock. In this study, the first experiment was designed to develop in vitro evaluation system by using primary chicken myoblast (pCM) cells isolated from pectoralis major of 10‐day‐old male embryos. Subsequently, to evaluate effects of Korean DangguiAngelica gigasNakai (AGN), we optimized the concentration of AGN root extract for treatment of primary pCM cells. After the treatment of AGN root extract, we compared proliferation and differentiation capacity, and also examined the gene expression. In the second experiment, the next generation sequencing analysis was performed to compare the different patterns of the global gene expression in pCM cells treated with AGN extract. Three up‐regulated (pancreas beta cells, fatty acid metabolism and glycolysis) and one down‐regulated (adipogenesis) gene sets were characterized suggesting that the AGN extract affected the metabolic pathways for the utilization of fat and glucose in chicken muscle cells. Furthermore, we validated the expression patterns of the up‐regulated genes (GCLC,PTPN6,ISL1,SLC25A13,TGFBI, andYWHAH) in the AGN‐treated pCM cells by quantitative RT‐PCR. These results demonstrated that the treatment of AGN extract decreased proliferation and differentiation of pCM cells, and affected the metabolic pathways of glucose and fatty acids. Moreover, AGN extract derived from byproducts such as stem and leaf also showed the reduced proliferation patterns on AGN‐treated pCM cells. Taken together, pCM cell‐based in vitro assay system could be primarily and efficiently applied for evaluating the biofunctional efficacy of various feed additive candidates.
Clinical features and prognosis of microscopic polyangiitis with usual interstitial pneumonia compared with idiopathic pulmonary fibrosis
Authors: Zhao Wen , Dai Huaping , Liu Yan , Zhu Min , Bao Na , Ban Chengjun , Zhang Shu , Ren Yanhong , Ye Qiao , Wang Chen
Published: April 2019

Introduction

Pulmonary involvement in microscopic polyangiitis (MPA) is common, little is known about the clinical features of MPA with interstitial pneumonia (MPA‐IP).

Objectives

This study aimed to explore the prevalence of microscopic polyangiitis associated usual interstitial pneumonia (UIP)(MPA‐UIP) and compare its clinical features and prognosis with those of MPA‐non‐UIP and idiopathic pulmonary fibrosis (IPF).

Methods

A total of 73 patients with MPA‐IP were identified and divided into MPA‐UIP patients and MPA‐non‐UIP patients. The clinical characteristics and survival of MPA‐UIP patients were analysed and compared with those of MPA‐non‐UIP patients and 68 patients with IPF.

Results

The results showed that 34/73 (47%) MPA‐IP patients were classified as MPA‐UIP patients. Compared with MPA‐non‐UIP patients, MPA‐UIP patients tend to have longer duration of symptoms prior to diagnosis and usually have pulmonary involvement as the initial presentation. However, they were less likely to have proteinuria and/or hematuria. Compared with IPF patients, MPA‐UIP patients usually had multisystem damage, positive anti‐neutrophil cytoplasmic autoantibodies and elevated levels of nonspecific inflammatory markers. MPA‐UIP death was concentrated mainly in the first 3 months after diagnosis and resulted in a higher early mortality compared with IPF.

Conclusion

UIP is the most frequent type of MPA‐IP. These patients tend to have longer duration of symptoms prior to diagnosis and usually have pulmonary involvement as the first presentation. However, they are less likely to have proteinuria and/or hematuria. MPA patients with UIP can be differentiated from IPF patients through comprehensive analysis of clinical and laboratory findings.
A Theory of Change to grow numbers of African rhino at a conservation site
Authors: Balfour Dave , Barichievy Chris , Gordon Chris , Brett Rob
Published: April 2019

Rhino horn is highly valued and this drives the illegal hunting of rhino. As a strategy to counter rhino losses incurred through poaching, managers of African protected areas face pressure to increase the number of rhino in their populations by promoting their growth. These efforts are commonly constrained by being balanced against other protected area objectives which seek to manage toward a “natural ecological state”. This is reflected in the draft continental rhino conservation plan as well as many national‐level rhino plans in Africa, but details on how this can be achieved at a site level are limited; indeed a framework for thinking about the problem is lacking. Here we develop a Theory of Change (ToC) which guides management interventions when seeking to grow rhino numbers at a conservation site. We identify four thematic areas for intervention namely; habitat management; range availability; containment and natural attrition; and rhino population management. As many protected areas are underfunded they seek to attract funding, but many donors are uncertain as to best practice and/or are hesitant to dictate how funds should be spent. This ToC can serve as a framework to guide funding. It can also guide policy in this regard.
Half century of protected area dynamism in the country of Gross National Happiness, Bhutan
Authors: Dorji Tshering , Linke Simon , Sheldon Fran
Published: April 2019

Bhutan is recognized for conservation success under its pro‐environmental development philosophy Gross National Happiness (GNH). However, an increase in area coverage alone cannot track the true contribution of protected areas (PAs) to biodiversity conservation. Capturing PA dynamism by tracking PADDD (PA downgrading, downsizing, and degazettement) and gain events can be used as a more comprehensive evaluation method. Based on existing data, we tracked gain events, enacted and proposed PADDD events, proximate causes of PADDD, and gain and PADDD events trends in Bhutan from 1966 to 2016. We also compared PADDD events recorded in www.PADDDtracker.org with the primary data sourced for our study. We discussed the findings in light of four tenets of GNH: good governance, sustainable socioeconomic development, preservation, and promotion of culture, and environmental conservation. We identified 81 gain and 29 PADDD events. All 12 proposed policy downgrading events in 2004 were proximally caused by infrastructure development, while all degazettement (n = 6) in 1993 and all downsizing events (two in 1984 and one in 1993) were proximally caused by conservation planning. Overall the gain and PADDD events were episodic but policy downgrading events occurred only from 2002. Based on our country data, we recorded 4.8 times more PADDD events than was recorded in www.PADDDtracker.org where even some degazetted PAs were not recorded. All gain events and even PADDD events, excluding one enacted and 12 proposed policy downgrading events caused by hydropower projects were aimed to improve conservation thus aligning with tenets of GNH. However, as hydropower is the specific cause for all proposed PADDD, Bhutan should be concerned about PADDD. Our findings provide further evidence for the dynamic nature of PAs, the widespread nature of PADDD and difficulty in detecting it. Furthermore, they also suggest the need to conduct archival case studies to better detect PADDD and PA dynamism.