bluuebunny/crossref_metadata_2025 huggingface dataset:
Fine particle sources and cognitive function in an older Puerto Rican cohort in Greater Boston
Authors: Wurth Renee , Kioumourtzoglou Marianthi-Anna , Tucker Katherine L. , Griffith John , Manjourides Justin , Suh Helen
Published: August 2018

Background:

Puerto Ricans living in the mainland US have substantially higher rates of impairment to cognitive performance as compared to non-Hispanic Whites, with air pollutant exposures a potential risk factor. We investigated whether exposures to specific air pollution sources were associated with performance across several cognitive domains in a cohort of Puerto Rican older adults.

Objectives:

To investigate the association between sources of fine particulate matter (PM2.5) and cognitive performance in each of five cognitive domains.

Methods:

We obtained demographic, health, and cognitive function data for 1500 elderly participants of the Boston Puerto Rican Health Study. Cognitive function was assessed in each of two waves for five domains: verbal memory, recognition, mental processing, and executive and visuospatial function. To these data, we linked concentrations of PM2.5and its components, black carbon (BC), nickel, sulfur, and silicon, as tracers for PM2.5from traffic, oil combustion, coal combustion, and resuspended dust, respectively. Associations between each PM2.5component and cognitive domain were examined using linear mixed models.

Results:

One year moving average exposures to BC were significantly associated with decreased verbal memory (−0.38; 95% confidence interval [CI] = −0.46, −0.30), recognition (−0.35; 95% CI = −0.46, −0.25), mental processing (−1.14; 95% CI = −1.55, −0.74), and executive function (−0.94; 95% CI = −1.31, −0.56). Similar associations were found for nickel. Associations for sulfur, and silicon, and PM2.5were generally null, although sulfur (−0.51; 95% CI = −0.75, −0.28), silicon (−0.25; 95% CI = −0.36, −0.13), and PM2.5(−0.35; 95% CI = −0.57, −0.12) were associated with decreased recognition.

Conclusion:

Long-term exposures to BC and nickel, tracers of traffic and oil combustion, respectively, were associated with decreased cognitive function across all domains, except visuospatial function.
To Shave or Not to Shave? A Series of Periclitoral Masses Associated With Depilatory Techniques and a Review of the Literature
Authors: Stenson Amy L. , Leclair Catherine
Published: August 2018

Periclitoral masses are uncommon disorders in gynecology often leading to pain and distress. With the popularity of female genital hair grooming and depilation, the vulva has been exposed to new insults including contact dermatitis and folliculitis. The unique anatomy of the protective covering of the clitoral hood may subject hair fragments to trapping, inflammation, irritation, and in some cases abscess formation.
Building Meaningful Patient Engagement in Research
Authors: Warren Nathaniel T. , Gaudino James A. , Likumahuwa-Ackman Sonja , Dickerson Kristin , Robbins Lynn , Norman Kathy , Lind John , D’Amato Sele , Foley Perry , Gold Rachel , Bauer Vance , Fields Scott A. , Cohen Deborah J. , Clark Khaya D. , DeVoe Jennifer E.
Published: August 2018

Background:

Strategies to engage patients to improve and enhance research and clinical care are increasingly being implemented in the United States, yet little is known about best practices for or the impacts of meaningful patient engagement.

Objective:

We describe and reflect on our patient stakeholder groups, engagement framework, experiences, and lessons learned in engaging patients in research, from generating proposal ideas to disseminating findings.

Setting:

The ADVANCE (Accelerating Data Value Across a National Community Health Center Network) clinical data research network is the nation’s largest clinical dataset on the safety net, with outpatient clinical data from 122 health systems (1109 clinics) in 23 states.

Results:

Patients stakeholders codeveloped the ADVANCE engagement framework and its implementation in partnership with network leaders. In phase I of ADVANCE, patients were involved with designing studies (input on primary outcome measures and methods) and usability testing (of the patient portal). In phase II, the network is prioritizing research training, dissemination opportunities, an “ambassador” program to pair more experienced patient stakeholders with those less experienced, and evaluation of engagement activities and impacts.

Discussion:

The ADVANCE framework for patient engagement has successfully involved a diverse group of patients in the design, implementation, and interpretation of comparative effectiveness research. Our experience and framework can be used by other organizations and research networks to support patient engagement activities.
Novel targeted drug delivery systems to minimize systemic immunosuppression in vascularized composite allotransplantation
Authors: Taddeo Adriano , Tsai Catherine , Vögelin Esther , Rieben Robert
Published: August 2018

Purpose of review

The long-term adverse effects of immunosuppressive treatment, the high rate of acute rejection and the development of chronic rejection are the main factors preventing a wider clinical application of vascularized composite allotransplantation (VCA). Targeted immunosuppression using innovative drug delivery systems (DDS) may help to overcome these hurdles, increasing therapeutic efficacy while reducing systemic toxicity. This review provides a summary of the recently developed strategies for targeted delivery of immunosuppressive drugs in VCA.

Recent findings

Currently, several innovative strategies for targeted immunosuppression have been designed based on the anatomy and function of the target organ. Site-specific DDS have been developed both for directly accessible organs (i.e. skin, eye and lung) and internal organs (i.e. lymph nodes, liver, nervous system, etc.). In preclinical models, DDS designed for sustained, ‘on demand,’ or ‘on cue’ drug release has been shown to promote VCA survival while reducing systemic toxicity. These findings suggest that targeted delivery could increase patient compliance and potentially decrease toxicity in VCA recipients.

Targeted immunosuppression in VCA represents a promising approach for improving patient compliance and graft survival while reducing off-target toxicity, intensity and frequency of acute rejection episodes and risk of chronic rejection.

Video Abstract

http://links.lww.com/COOT/A1
Long-Term Survivors of Pancreatic Cancer
Authors: Kardosh Adel , Lichtensztajn Daphne Y. , Gubens Matthew A. , Kunz Pamela L. , Fisher George A. , Clarke Christina A.
Published: August 2018

Objectives

Pancreatic cancer continues to carry a poor prognosis with survival rates that have had minimal improvement over the past 4 decades. We report a population-based, comprehensive analysis of long-term survivors of pancreatic adenocarcinoma diagnosed in the diverse population of California.

Methods

Data from the California Cancer Registry were used to evaluate long-term survival. A total of 70,442 patients diagnosed with pancreatic adenocarcinoma between 1988 and 2009 were identified. Logistic regression was used to identify factors associated with achieving 5-year survival.

Results

The overall 5-year survival was 2.5%, with minimal incremental improvements throughout the 3 decades. Age, stage, degree of differentiation, and surgical resection were associated with 5-year survival. Furthermore, younger age and receiving care at a National Cancer Institute–designated cancer center were similarly correlated with 5-year survival regardless of surgical intervention. In addition, we identified stage, differentiation, and adjuvant chemotherapy as significant factors for long-term survival in surgically resected patients. In the unresectable patients, Asian/Pacific islanders and Hispanics were significantly more likely to reach the 5-year milestone than non-Hispanic whites.

Conclusions

Although pancreatic cancer mortality remains high, our study highlights baseline characteristics, treatment, biological factors, and ethnicity that are associated with long-term survival. These findings may serve as a springboard for further investigation.
Application of a Frailty Modeling Approach to Correlated Breastfeeding Duration Data
Authors: Zhao Jian , Zhao Yun , Khanal Vishnu , Lee Andy H. , Binns Colin W.
Published: August 2018

Background

Correlated breastfeeding duration data are very common in infant feeding research using cohort designs. Intracluster correlation within the same clustering group is expected and needs to be taken into account in statistical analysis; otherwise, the corresponding statistical inferences may be subject to an increased Type I error.

Objectives

The aims of this study were to illustrate the necessity of adjusting for the intracluster correlation in correlated breastfeeding duration data analysis and to demonstrate different frailty modeling approaches.

Methods

An introduction to shared frailty models was presented under the assumption of proportional hazards (PH). Then, two different approaches—the Cox frailty model (semiparametric approach) and the parametric frailty model (parametric approach)—were used to fit the data from a maternal cohort in Nepal as an illustrative example.

Results

For the semiparametric approach, random effects denoting the variations in the hazard of breastfeeding cessation shared by mothers living in the 27 distinct communities were estimated and graphically presented. Compared with the conventional Cox model, Cox frailty model reduced the chance of Type I error occurring, providing a better model fit in the presence of correlated survival data. Among candidate parametric approaches, a Weibull PH model with a gamma frailty term was selected as an appropriate model fitting the breastfeeding data.

Discussion

Shared frailty models can be used in other research areas in the presence of correlated time-to-event data. Model selection depends on the assumption of PH, the specification of the baseline hazard function, and also the study purpose.
PTGER2-β-Catenin Axis Links High Salt Environments to Autoimmunity by Balancing IFNγ and IL-10 in FoxP3+Regulatory T cells
Authors: Sumida Tomokazu , Lincoln Matthew R. , Ukeje Chinonso M. , Rodriguez Donald M. , Akazawa Hiroshi , Noda Tetsuo , Naito Atsuhiko T. , Komuro Issei , Dominguez-Villar Margarita , Hafler David A.
Published: August 2018

Foxp3+regulatory T cells (Tregs) are the central component of peripheral immune tolerance. While dysregulation of the Treg cytokine signature has been observed in autoimmune diseases such as multiple sclerosis (MS) and type 1 diabetes, the regulatory mechanisms balancing pro- and anti-inflammatory cytokine production are not known. Here, we identify imbalance between IFNγ and IL-10 as a shared Treg signature, present in patients with MS and under high salt conditions. By performing RNA-seq analysis on human Treg subpopulations, we identify β-catenin as a key regulator that controls the expression of IFNγ and IL-10. The activated β-catenin signature is enriched specifically in IFNγ+Tregs in humans, and this was confirmedin vivowith Treg-specific β-catenin-stabilized mice exhibiting lethal autoimmunity with a dysfunctional, IFNγ-producing, Treg phenotype. Moreover, we identify PTGER2 as a major factor balancing IFNγ and IL-10 production in the context of a high salt environment, with skewed activation of the β-catenin/SGK1/Foxo axis in IFNγ+Tregs. These findings identify a novel molecular mechanism underlying inflammatory Tregs in human autoimmune disease and reveal a new role for a PTGER2-β-catenin loop in Tregs linking environmental high salt conditions to autoimmunity.
Profiling the surface proteome identifies actionable biology for TSC1 mutant cells beyond mTORC1 signaling
Authors: Wei Junnian , Leung Kevin K. , Truillet Charles , Ruggero Davide , Wells James A. , Evans Michael J.
Published: August 2018

Loss of the TSC1/TSC2 complex leads to constitutively high mTORC1 signaling; however, pharmacological inhibition of mTORC1 in this setting produces a broad spectrum of clinical responses. We report herein several cell surface proteins upregulated by inactivation of TSC1 that present therapeutic alternatives or adjuvants to direct mTORC1 inhibition. A proteomics screen revealed that TSC1 loss most dramatically induced the expression of neprilysin (NEP/CD10) and aminopeptidase N (APN/CD13). The survival of TSC1 null human cancer cells was dependent on NEP expression, and TSC1 mutation sensitized cells to biochemical inhibition of APN. Remarkably, NEP and APN upregulation occurred via a TSC2- and mTORC1-independent mechanism; therefore, the antiproliferative effects of mTORC1 inhibition could be augmented by co-suppression of APN activity.

Statement of significance

These data introduce a non-canonical biological role for TSC1 beyond regulating mTORC1 signaling, which also enabled several immediately translatable therapeutic strategies for clinically problematic cells with TSC1 mutations.
Large-Scale plurimodal networks common to listening, production and reading word-lists: an fmri study combining tasks-induced activation and intrinsic connectivity in 144 right-handers
Authors: Hesling I , Labache L , Joliot M , Tzourio-Mazoyer N
Published: August 2018

Even if speech perception and production have been revealed to share a common recruitment of both discrete auditory and motor areas, this overlap being also common to reading and listening, no study has investigated the involvement of larger networks in the three tasks yet. So, we first identified the multimodal bilateral brain areas conjointly activated and asymmetrical during listening, production and reading of word-list using fMRI in 144 healthy right-handers (27 years ± 6 years). Such a selection made it possible to unravel 14 regions of the left hemisphere including motor, premotor and inferior parietal cortical areas. On the right, 7 regions were selected, including the posterior Human Voice Area (pHVA). To characterize the network organization within these 21 regions, we then analysed resting-state functional connectivity in 138 of the same participants. It allowed us to segregate a network of executive areas in relation with task completion from a bilateral WORD_CORE network composed of (1) all left areas supporting the action-perception cycle, in which articulatory gestures are the central motor units on which word perception, production, but also reading, would develop and act together according to the motor theory of speech; (2) the right pHVA, acting as a prosodic integrative area, underpinning the intertwining across hemispheres between prosodic (pHVA) and phonemic (left SMG) processing. The present results show that word processing, whatever the language modality involved, is based on a network of plurimodal areas hosting processes specific to each hemisphere and on their cooperation built upon synchronisation at rest.
A non-canonical chemical feedback self-limits nitric oxide-cyclic GMP signaling in health and disease
Authors: Dao Vu Thao-Vi , Elbatreek Mahmoud H. , Deile Martin , Nedvetsky Pavel I. , Güldner Andreas , Ibarra-Alvarado César , Gödecke Axel , Schmidt Harald H.H.W.
Published: August 2018

Nitric oxide (NO)-cyclic GMP (cGMP) signaling is a vasoprotective pathway therapeutically targeted for example in pulmonary hypertension. Its dysregulation in disease is incompletely understood. Here we show in pulmonary artery endothelial cells that feedback inhibition by NO of the NO receptor, the cGMP forming soluble guanylate cyclase (sGC), may contribute to this. Both endogenous NO from endothelial NO synthase or exogenous NO from NO donor compounds decreased sGC protein and activity. This was not mediated by cGMP as the NO-independent sGC stimulator or direct activation of cGMP-dependent protein kinase did not mimic it. Thiol-sensitive mechanisms were also not involved as the thiol-reducing agent, N-acetyl-L-cysteine did not prevent this feedback. Instead, bothin-vitroandin-vivoand in health and acute respiratory lung disease, chronically elevated NO led to the inactivation and degradation of sGC whilst leaving the heme-free isoform, apo-sGC, intact or even increasing its levels. Thus, NO regulates sGC in a bimodal manner, acutely stimulating and chronically inhibiting, as part of self-limiting direct feedback that is cGMP-independent. In high NO disease conditions, this is aggravated but can be functionally recovered in a mechanism-based manner by apo-sGC activators that re-establish cGMP formation.
The fitness consequences of genetic variation in wild populations of mice
Authors: Barrett Rowan D.H. , Laurent Stefan , Mallarino Ricardo , Pfeifer Susanne P. , Xu Charles C.Y. , Foll Matthieu , Wakamatsu Kazumasa , Duke-Cohan Jonathan S. , Jensen Jeffrey D. , Hoekstra Hopi E.
Published: August 2018

Adaptive evolution can occur when genetic change affects traits subject to natural selection. Although selection is a deterministic process, adaptation can be difficult to predict in finite populations because the functional connections between genotype, phenotype, and fitness are complex. Here, we make these connections using a combination of field and laboratory experiments. We conduct a large-scale manipulative field experiment with wild populations of deer mice in distinct habitats to directly estimate natural selection on pigmentation traits and next test whether this selection drives changes in allele frequency at an underlying pigment locus. We find that divergent cryptic phenotypes are repeatedly favoured in each habitat, leaving footprints of selection in the Agouti gene. Next, using transgenic experiments in Mus, we functionally test one of the Agouti mutations associated with survival, a Serine deletion in exon 2, and find that it causes lighter coat colour via changes in its protein binding properties. Finally, we show significant change in the frequency of this mutation in our field experiment. Together, our findings demonstrate how a sequence variant alters phenotype and show the ensuing ecological consequences that drive changes in population allele frequency, thereby revealing the full process of evolution by natural selection.
Drosophilasmall ovarygene ensures germline stem cell maintenance and differentiation by silencing transposons and organising heterochromatin
Authors: Jankovics Ferenc , Bence Melinda , Sinka Rita , Faragó Anikó , Bodai László , Pettkó-Szandtner Aladár , Ibrahim Karam , Takács Zsanett , Szarka-Kovács Alexandra Brigitta , Erdélyi Miklós
Published: August 2018

Self-renewal and differentiation of stem cells is one of the fundamental biological phenomena relying on proper chromatin organisation. In our study, we describe a novel chromatin regulator encoded by theDrosophila small ovary (sov)gene. We demonstrate thatsovis required in both the germline stem cells (GSCs) and the surrounding somatic niche cells to ensure GSC survival and differentiation.Sovmaintains niche integrity and function by repressing transposon mobility, not only in the germline, but also in the soma. Protein interactome analysis of Sov revealed a physical interaction between Sov and HP1a. In the germ cell nuclei, Sov co-localises with HP1a, suggesting that Sov affects transposon repression as a component of the heterochromatin. In a position effect variegation assay, we found a dominant genetic interaction betweensovand HP1a, indicating their functional cooperation in promoting the spread of heterochromatin. Anin vivotethering assay and FRAP analysis revealed that Sov enhances heterochromatin formation by supporting the recruitment of HP1a to the chromatin. We propose a model in whichsovmaintains GSC niche integrity by regulating piRNA-mediated transposon silencing as a heterochromatin regulator.

Summary statement

Small ovarymaintains the integrity of the stem cell niche by regulating piRNA-mediated transposon silencing acting as a key component of the heterochromatin.
DOT1L inhibition reveals a distinct class of enhancers dependent on H3K79 methylation
Authors: Godfrey Laura , Crump Nicholas T. , Thorne Ross , Lau I-Jun , Repapi Emmanouela , Dimou Dimitra , Telenius Jelena M. , Oudelaar A. Marieke , Downes Damien J. , Vyas Paresh , Hughes Jim R. , Milne Thomas A.
Published: August 2018

Enhancer elements are a key regulatory feature of many important genes. Several general features including the presence of specific histone modifications are used to identify and subcategorize enhancers. Here we identify a distinct subset of enhancers in leukemia cells that are functionally dependent upon H3K79me3. Using the DOT1L inhibitor, EPZ-5676, we show that loss of H3K79me3 at these H3K79me3 enhancer elements (KEEs) leads to reduced chromatin accessibility, histone acetylation and transcription factor binding. We then use Capture-C, a high-resolution chromosome conformation capture technique, to show that H3K79me3 is required for KEE interactions with the promoter as well as transcription of the associated genes. Together these data implicate H3K79me3 in having a functional role at a subset of active enhancers where it helps maintain histone acetylation and chromatin accessibility, potentially by promoting phase-separated condensates.
(-)-Epigallocatechin-3-gallate inhibition of Epstein-Barr virus lytic replication involves latent membrane protein 1-mediated MAPK signaling pathways
Authors: Li Hongde , Luo Xiangjian , Hu Jianmin , Liu Sufang , Li Namei , Tang Min , Weng Xinxiang , Yi Wei , Gao Jinghe , Bode Ann M. , Dong Zigang , Cao Ya
Published: August 2018

EBV lytic replication has been shown to be important for carcinogenesis. Latent membrane protein 1 (LMP1) plays an important role in the viral latent infection and is abundantly expressed after EBV entry into the lytic cycle. However, the biological significance of LMP1 continuous expression in EBV lytic cycle is still not completely understood. We found that LMP1 promotes EBV reactivation by activating the downstream MAPK signaling in both AGS-EBV and B95.8 cells. In AGS-EBV cells, LMP1 induces EBV the initiation of the EBV lytic cycle in a p53 dependent manner. Activation of c-Jun by LMP1 through JNKs appears to be involved in EBV reactivation in p53 mutant B95.8 cells. We also demonstrated that EGCG, an anti-EBV agent, inhibits LMP1 expression and the activation of the downstream MAPK signaling pathways, followed by downregulation of EBV lytic protein expression level. Together, this study provides the first evidence that LMP1 promotes EBV reactivation via activation of the MAPK signaling pathways. Our findings further demonstrate that the mechanisms underlying EGCG inhibition of the EBV lytic replication involve the suppression of LMP1-mediated MAPK signaling pathways.

Summary statement

This study definitely confirms the role of LMP1 in EBV reactivation and further explores the mechanism by which EGCG inhibits EBV lytic replication.
Alteration of the social and spatial organization of the vector of Chagas disease,Triatoma infestans, by the parasiteTrypanosoma cruzi
Authors: Depickère Stéphanie , Ramírez-Ávila Gonzalo Marcelo , Deneubourg Jean-Louis
Published: August 2018

Insects of Triatominae subfamily are vectors of the parasiteTrypanosoma cruzi, the etiological agent of Chagas disease affecting millions of people in Latin America. Some of these vector species, likeTriatoma infestans, live in the human neighborhood, aggregating in walls or roof cracks during the day and going out to feed on animal or human blood at night. Except for their feeding specialization, these insects share this cycle of activities with many gregarious arthropod species. The understanding of how sex andT. cruziinfection affect their aggregation and geotaxis behavior is essential for understanding the spatial organization of the insects and the parasite dispersion. Experiments with non-infected and infected adults ofT. infestansshow that the insects presented a high negative geotaxis and aggregative behavior. Males had a higher negative geotaxis and a higher aggregation level than females. The aggregation level and the negative geotaxis were stronger in infected insects than in non-infected ones, the difference between sexes being maintained. The importance of these results is discussed in term of parasitic manipulation, dispersion of the vector and strategy of its monitoring.
Accurate Reference-Free Somatic Variant-Calling by Integrating Genomic, Sequencing and Population Data
Authors: Sun Ren X. , Lalansingh Christopher M. , Espiritu Shadrielle Melijah G. , Yao Cindy Q. , Yamaguchi Takafumi N. , Prokopec Stephenie D. , Szyca Lesia , Houlahan Kathleen E. , Heisler Lawrence E. , Black Morgan , Li Constance H. , Barrett John W. , Nichols Anthony C. , Boutros Paul C.
Published: August 2018

The detection of somatic single nucleotide variants (SNVs) is critical in both research and clinical applications. Studies of human cancer typically use matched normal (reference) samples from a distant tissue to increase SNV prediction accuracy. This process both doubles sequencing costs and poses challenges when reference samples are not readily available, such as for many cell-lines. To address these challenges, we created S22S: an approach for the prediction of somatic mutations without need for matched reference tissue. S22S takes underlying sequence data, augments them with genomic background context and population frequency information, and classifies SNVs as somatic or non-somatic. We validated S22S using primary tumor/normal pairs from four tumor types, spanning two different sequencing technologies. S22S robustly identifies somatic SNVs, with the area under the precision recall curve reaching 0.97 in kidney clear cell carcinoma, comparable to the best tumor/normal analysis pipelines. S22S is freely available at http://labs.oicr.on.ca/Boutros-lab/software/s22s.
Rift Valley fever virus induces fetal demise through direct placental infection
Authors: McMillen Cynthia M. , Arora Nitin , Boyles Devin A. , Albe Joseph R. , Kujawa Michael R. , Bonadio Jeffrey F. , Coyne Carolyn B. , Hartman Amy L.
Published: August 2018

Rift Valley fever virus (RVFV) infections in pregnant livestock are associated with high rates of fetal demise and have been linked to miscarriage in pregnant women. To address how acute RVFV infection during pregnancy causes detrimental effects on the fetus, we developed an immunocompetent pregnant rodent model of RVFV infection. We found that pregnant rats were more susceptible to RVFV-induced death than their non-pregnant counterparts and that RVFV infection resulted in intrauterine fetal death and severe congenital abnormalities, even in pups from infected asymptomatic pregnant rats. Virus distribution in infected dams was widespread, with a previously unrecognized preference for infection, replication, and tissue damage in the placenta. In human mid-gestation placental tissue, RVFV directly infected placental chorionic villi, with replication detected in the outermost syncytial layer. Our work identifies direct placental infection by RVFV as a mechanism for vertical transmission and points to the teratogenic potential of this virus in humans. This is the first time vertical transmission of RVFV has been shown in species other than livestock. This study highlights the potential impact of a future epidemic of this emerging mosquito-borne virus.
Genetic deletion of genes in the cerebellar rhombic lip lineage can stimulate compensation through adaptive reprogramming of ventricular zone-derived progenitors
Authors: Wojcinski Alexandre , Morabito Morgane , Lawton Andrew K. , Stephen Daniel N. , Joyner Alexandra L.
Published: August 2018

Background

The cerebellum is a foliated posterior brain structure involved in coordination of motor movements and cognition. The cerebellum undergoes rapid growth postnataly due to Sonic Hedgehog (SHH) signaling-dependent proliferation of ATOH1+ granule cell precursors (GCPs) in the external granule cell layer (EGL), a key step for generating cerebellar foliation and the correct number of granule cells. Due to its late development, the cerebellum is particularly vulnerable to injury from preterm birth and stress around birth. We recently uncovered an intrinsic capacity of the developing cerebellum to replenish ablated GCPs via adaptive reprogramming of Nestin-expressing progenitors (NEPs). However, whether this compensation mechanism occurs in mouse mutants affecting the developing cerebellum and could lead to mis-interpretation of phenotypes was not known.

Methods

We used two different approaches to remove the main SHH signaling activator GLI2 in GCPs: 1) our mosaic mutant analysis with spatial and temporal control of recombination (MASTR) technique to deleteGli2in a small subset of GCPs; 2) AnAtohl-Cretransgene to deleteGli2in most of the EGL. Genetic Inducible Fate Mapping (GIFM) and live imaging were used to analyze the behavior of NEPs afterGli2deletion.

Results

Mosaic analysis demonstrated that SHH-GLI2 signaling is critical for generating the correct pool of granule cells by maintaining GCPs in an undifferentiated proliferative state and promoting their survival. Despite this, inactivation ofGLI2in a large proportion of GCPs in the embryo did not lead to the expected dramatic reduction in the size of the adult cerebellum. GIFM uncovered that NEPs do indeed replenish GCPs inGli2conditional mutants, and then expand and partially restore the production of granule cells. Furthermore, the SHH signaling-dependent NEP compensation requiresGli2, demonstrating that the activator side of the pathway is involved.

Conclusion

We demonstrate that a mouse conditional mutation that results in loss of SHH signaling in GCPs is not sufficient to induce long term severe cerebellum hypoplasia. The ability of the neonatal cerebellum to regenerate after loss of cells via a response by NEPs must therefore be considered when interpreting the phenotypes of conditional mutants affecting GCPs.
Emergence of trait variability through the lens of nitrogen assimilation in Prochlorococcus
Authors: Berube Paul M. , Rasmussen Anna , Braakman Rogier , Stepanauskas Ramunas , Chisholm Sallie W.
Published: August 2018

Intraspecific trait variability has important consequences for the function and stability of marine ecosystems. The marine cyanobacterium Prochlorococcus is a useful model system for understanding how trait variability emerges within microbial species: Its functional diversity is overlaid on measurable environmental gradients, providing a powerful lens into large-scale evolutionary processes. Here we examine variation in the ability to use nitrate across hundreds of Prochlorococcus genomes to better understand the modes of evolution influencing the allocation of ecologically important functions within microbial species. We find that nitrate assimilation genes are absent in basal lineages of Prochlorococcus but occur at an intermediate frequency that is randomly distributed within recently emerged clades. The distribution of nitrate assimilation genes within clades appears largely governed by vertical inheritance, stochastic gene loss, and homologous recombination among closely related cells. By mapping this process onto a model of Prochlorococcus’ macroevolution, we propose that niche-constructing adaptive radiations and subsequent niche partitioning set the stage for loss of nitrate assimilation genes from basal lineages as they specialized to lower light levels. Retention of these genes in recently emerged lineages has likely been facilitated by selection as they sequentially partitioned into niches where nitrate assimilation conferred a fitness benefit.
Tracing human stem cell lineage during development using DNA methylation
Authors: Salas Lucas A. , Wiencke John K. , Koestler Devin C. , Zhang Ze , Christensen Brock C. , Kelsey Karl T.
Published: August 2018

Stem cell maturation is a fundamental, yet poorly understood aspect of human development. We devised a DNA methylation signature deeply reminiscent of embryonic stem cells (a fetal cell origin signature, FCO) to interrogate the evolving character of multiple human tissues. The cell fraction displaying this FCO signature was highly dependent upon developmental stage (fetal versus adult), and in leukocytes, it described a dynamic transition during the first 5 yr of life. Significant individual variation in the FCO signature of leukocytes was evident at birth, in childhood, and throughout adult life. The genes characterizing the signature included transcription factors and proteins intimately involved in embryonic development. We defined and applied a DNA methylation signature common among human fetal hematopoietic progenitor cells and have shown that this signature traces the lineage of cells and informs the study of stem cell heterogeneity in humans under homeostatic conditions.
Characterization and on-line adjustment of the sagittal-bent Laue crystal profile
Authors: Dong Weiwei , Cai Quan , Yang Fugui , Liu Xu , Yang Jiaowang , Diao Qianshun , Liu Peng , Zhang Xiaowei , Hu Lingfei
Published: August 2018

The sagittal-bent Laue monochromator can provide an ideal way to focus high-energy X-ray beams. However, the anticlastic curvature induced by sagittal bending has a great influence on the crystal performance. Thus, characterizing the bent-crystal shape is very important for predicting the performance of the bent-crystal monochromator. In this paper the crystal profile is measured by off-line optical metrology and on-line X-ray experiments. The off-line results showed that the bent-crystal surface could be well fitted to a saddle surface apart from a redundant cubic term which was related to the different couples applied on the crystal. On-line characterization of the meridional and the sagittal radius of the bent crystal includes double-crystal topography and ray-tracing measurement. In addition, the double-crystal topography experiment could be used as a quick diagnostic method for the bending condition adjustment. The sagittal radius of the bent crystal was characterized through a ray-tracing experiment by using a particularly designed tungsten mask. Moreover, rocking curves under different bending conditions were measured as well. The results were highly consistent with analytical results derived from the elastic theory. Furthermore, radii along different vertical positions under various bending conditions were measured and showed a quadratic relationship between the vertical positions and the meridional radii.
HAXPES beamline PES-BL14 at the Indus-2 synchrotron radiation source
Authors: Jagannath  , Goutam U. K. , Sharma R. K. , Singh J. , Dutta K. , Sule U. S. , Pradeep R. , Gadkari S. C.
Published: August 2018

The Hard X-ray Photo-Electron Spectroscopy (HAXPES) beamline (PES-BL14), installed at the 1.5 T bending-magnet port at the Indian synchrotron (Indus-2), is now available to users. The beamline can be used for X-ray photo-emission electron spectroscopy measurements on solid samples. The PES beamline has an excitation energy range from 3 keV to 15 keV for increased bulk sensitivity. An in-house-developed double-crystal monochromator [Si (111)] and a platinum-coated X-ray mirror are used for the beam monochromatization and manipulation, respectively. This beamline is equipped with a high-energy (up to 15 keV) high-resolution (meV) hemispherical analyzer with a microchannel plate and CCD detector system with SpecsLab Prodigy and CasaXPS software. Additional user facilities include a thin-film laboratory for sample preparation and a workstation for on-site data processing. In this article, the design details of the beamline, other facilities and some recent scientific results are described.
XMCD studies of magnetic polarization at Mo atoms in CoMo alloy and magnetically coupled Co/Mo multilayers
Authors: Wawro Andrzej , Milińska Ewelina , Kurant Zbigniew , Pietruczik Aleksiej , Kanak Jarosław , Ollefs Katharina , Wilhelm Fabrice , Rogalev Andrei , Maziewski Andrzej
Published: August 2018

Magnetic polarization of Mo atoms in Co96Mo4 alloy film and Co/Mo multilayered structures has been studied by X-ray magnetic circular dichroism. Samples with Mo spacers of two different thicknesses (0.9 nm and 1.8 nm) were investigated. Mo atoms receive a magnetic moment of −0.21μB in the alloy. In the multilayer with the thinner Mo spacer (d
Mo = 0.9 nm) the magnetic moment is much smaller (−0.03μB). In both cases the measured induced moment at the Mo site is oriented antiparallel to the moment at the Co atoms. The presence of the induced moment in the Mo spacer coincides with antiferromagnetic coupling between the Co component slabs. In contrast, neither measurable induced moment at the Mo site nor interlayer coupling between the Co layers has been found for the multilayer with the thicker Mo spacer. Possible mechanisms of the coupling associated with the induced moment are discussed in detail.
CAMP@FLASH: an end-station for imaging, electron- and ion-spectroscopy, and pump–probe experiments at the FLASH free-electron laser
Authors: Erk Benjamin , Müller Jan P. , Bomme Cédric , Boll Rebecca , Brenner Günter , Chapman Henry N. , Correa Jonathan , Düsterer Stefan , Dziarzhytski Siarhei , Eisebitt Stefan , Graafsma Heinz , Grunewald Sören , Gumprecht Lars , Hartmann Robert , Hauser Günter , Keitel Barbara , von Korff Schmising Clemens , Kuhlmann Marion , Manschwetus Bastian , Mercadier Laurent , Müller Erland , Passow Christopher , Plönjes Elke , Ramm Daniel , Rompotis Dimitrios , Rudenko Artem , Rupp Daniela , Sauppe Mario , Siewert Frank , Schlosser Dieter , Strüder Lothar , Swiderski Angad , Techert Simone , Tiedtke Kai , Tilp Thomas , Treusch Rolf , Schlichting Ilme , Ullrich Joachim , Moshammer Robert , Möller Thomas , Rolles Daniel
Published: August 2018

The non-monochromatic beamline BL1 at the FLASH free-electron laser facility at DESY was upgraded with new transport and focusing optics, and a new permanent end-station, CAMP, was installed. This multi-purpose instrument is optimized for electron- and ion-spectroscopy, imaging and pump–probe experiments at free-electron lasers. It can be equipped with various electron- and ion-spectrometers, along with large-area single-photon-counting pnCCD X-ray detectors, thus enabling a wide range of experiments from atomic, molecular, and cluster physics to material and energy science, chemistry and biology. Here, an overview of the layout, the beam transport and focusing capabilities, and the experimental possibilities of this new end-station are presented, as well as results from its commissioning.
The impact of autonomy on the relationship between mentoring and entrepreneurial intentions among youth in Germany, Kenya, and Uganda
Authors: Baluku Martin Mabunda , Leonsio Matagi , Bantu Edward , Otto Kathleen
Published: August 2018

Purpose

The purpose of this paper is to investigate how autonomy, moderated by employment status, impacts the relationship between entrepreneurial mentoring (EM) and entrepreneurial intentions (EI) among three countries (Germany, Kenya, and Uganda); as informed by both theory of planned behavior and self-determination theory.

Design/methodology/approach

A convenient sample of 1,509 youth from Germany, Kenya, and Uganda consisting of final-year university students, wage-employed, and unemployed was identified and studied. A multi-group analysis was conducted to test for differences in the impact of EM and autonomy on EI.

Findings

The findings indicate that mentoring and autonomy are positively correlated with EI. EM and intentions were lower among German participants than for the East African countries. The moderated moderation results revealed that EM is related to higher EI among students and the unemployed, and when individuals have higher levels of autonomy. Country-level analysis showed the effects of EM and autonomy are highest in Germany and lowest in Uganda.

Practical implications

Mentoring and self-determination play an important role in the development of EI. Entrepreneurship mentors should specifically support their protégées to develop the ability to act autonomously as an important entrepreneurial competence. The results further indicate that effectiveness of EM varies according to employment status and among countries. This is particularly important for targeting and designing of EM interventions. EM resources should be applied to youth with high autonomy, who are in either in insecure wage employment or who have no jobs. Protégés with low levels of autonomy should be supported to appreciate autonomy and develop the ability for autonomous action. Future EI research should also examine the impact of the availability of attractive positions in wage employment; and the effects of the availability of social safety nets on the need for autonomy.

Originality/value

A major challenge in EI research is the predominant focus on student populations. Using a multi-group analysis, the present paper tested for differences in the impact of EM and autonomy on EI. EM and EI were lower in German participants that in Kenyan and Ugandan participants. Whereas EM was generally positively correlated to EI, the moderated results showed that EM is related to higher EI among students and the unemployed, and when participants have higher autonomy. The study implies that EM and EI are highly correlated when participants need to work but have not or cannot find work or whey they do not need salaried employment to survive.
Residential segregation of same-sex partnered households in the US
Authors: Morales Danielle Xiaodan
Published: August 2018

Purpose

Quantitative research on the segregation of same-sex partners in the USA is new, and limited by challenges related to the accurate measurement of segregation and data errors. The purpose of this paper is to provide a novel approach to re-examine residential segregation between same-sex partners and different-sex partners in the USA.

Design/methodology/approach

Two versions of the dissimilarity index and corrected same-sex partners data from the 2010 decennial census were used. Effects of different geographic scales were examined.

Findings

Results reveal that the levels of segregation of both male and female same-sex partners were higher at metropolitan- vs state-levels; the levels of segregation was lower when measured using the unbiased as compared to the conventional version of the D-index; and male same-sex partnered households were more segregated from different-sex partnered households than were female same-sex partnered households.

Research limitations/implications

Future studies should be attuned to geographic scale effects and should not ignore the bias of the D-index.

Originality/value

This study provides a better test of the differences between the two versions of the D-index and contributes to the literature by examining the segregation of both male same-sex partners and female same-sex partners across different geographic scales.
Feeding the bottleneck: airport congestion during relief operations
Authors: Veatch Michael , Goentzel Jarrod
Published: August 2018

Purpose

Scheduling the airlift of relief supplies into a damaged or small airport during a crisis is complex yet crucial. The volume of cargo and flights can temporarily overwhelm the airport’s capacity and the mix of flights adds complexity. The purpose of this paper is to better characterize airport operations during a crisis, to develop a model that can assess strategies for scheduling flights and to draw implications for decision makers.

Design/methodology/approach

First, empirical data are analyzed to characterize airport operations. Previously unreported data from the 2010 Haiti earthquake response in the form of a “flight log” are analyzed to provide new insights and parameters. Alternate scheduling strategies are drawn from review of the literature and After Action Reports. Second, a queuing model is developed to understand operations in past crises and predict the impact of alternate scheduling strategies. Empirical data provide the parameters for airport scenarios evaluated.

Findings

Unloading capacity is seen to be the bottleneck but also to not be fully utilized, suggesting that a more aggressive flight schedule is needed. Scheduling flights is shown to be a tradeoff between volume of aid delivered and flights that must be diverted. The proper mix of aircraft and prioritized divert policies also provide benefits. Finally, it is beneficial, though perhaps counterintuitive, to create a parking buffer upstream from the unloading bottleneck.

Originality/value

Analysis of previously unreported data from the Haiti earthquake provides new insights regarding airport parking and unloading operations. A new model of airport scheduling for disaster response is proposed. The model differs from other humanitarian airlift models in that it focuses on aircraft parking and unloading. It differs from commercial aircraft scheduling and gate assignment in the objective used.
The signalling role of audit committee characteristics and the cost of equity capital
Authors: Appuhami Ranjith
Published: August 2018

Purpose

The purpose of this study is to examine whether audit committee characteristics influence the cost of equity capital.

Design/methodology/approach

Drawing on signalling theory, this study hypothesises that the presence of an AC with adequate characteristics serves as a market “signal” of the credibility of the effective monitoring process and hence affects the perception of capital providers on the cost of equity capital. The study uses a multiple regression analysis on data collected from a sample of top Australian listed firms.

Findings

The study finds that audit committee characteristics such as size, meeting frequency and independence are significantly and negatively associated with the cost of equity capital. However, there is no significant evidence that the financial qualifications of audit committee directors are associated with the cost of equity capital.

Originality/value

While there have been several studies examining the cost of equity capital, there is very limited research on the cost of capital in Australian firms. The study aims to fill this gap, in part, and contribute to the literature on corporate governance and signalling theory.
National identity on the Portuguese‐Spanish frontier
Authors: SILVA LUÍS
Published: August 2018

This article gives an ethnographic account of national identity in the day‐to‐day lives of villagers who face one another across the Portuguese‐Spanish frontier along the Guadiana River on the Iberian Peninsula. The article shows that despite European integration, the symbolic boundaries of culture and identity in these nation states persist.
Boys who work on the streets of Iraq are exposed to more traumatic events such as torture than schoolboys of the same age
Authors: Taib Nezar Ismet , Ahmad Abdulbaghi
Published: August 2018

Aim

Information is scarce about the issues faced by street working. This study examined traumatic events experienced by boys working on the streets of Iraq compared to schoolboys.

Methods

We compared 100 street working boys aged 8–16 years who were attending a drop‐in centre for street working children in Duhok City, Kurdistan, Iraq, in 2004/2005 with 100 age‐matched schoolboys randomly selected from six local schools. The instruments that were used included the Harvard–Uppsala Trauma Questionnaire for Children.

Results

Most of the street working boys were involved in activities such as selling goods or shoe shining, and some were stealing or begging. None were involved in drugs or prostitution. The street working boys showed a significantly higher rate of traumatic events than the control group (96% versus 64%, p < 0.001) and higher rates of moderate to severe trauma levels (78% versus 25%, p < 0.001). A varying degree of association was found for reporting different traumatic events. The largest effect size was found for torture, with an odds ratio of 28.4, and the smallest for maltreatment or assault (2.7).

Conclusion

Street working boys in Iraq faced a higher risk of exposure to traumatic events than age‐matched schoolboys.