bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leg length, skull circumference, and the incidence of dementia in Latin America and China; a 10/66 population-based cohort study
Authors: Prince Martin J. , Acosta Daisy , Guerra Mariella , Huang Yueqin , Jimenez-Velazquez Ivonne Z , Llibre Rodriguez Juan J. , Salas Aquiles , Sosa Ana Luisa , Dewey Michael E. , Guerchet Maelenn M. , Liu Zhaorui , Llibre-Guerra Jorge J. , Prina Matthew A. 
Published: May 2017

AbstractBackgroundAdult leg length is influenced by nutrition in the first few years of life. Adult head circumference is an indicator of brain growth. Cross-sectional studies indicate inverse associations with dementia risk, but there have been few prospective studies.MethodsPopulation-based cohort studies in urban sites in Cuba, Dominican Republic Puerto Rico and Venezuela, and rural and urban sites in Peru, Mexico and China. Sociodemographic and risk factor questionnaires were administered to all participants, and anthropometric measures taken, with ascertainment of incident 10/66 dementia, and mortality, three to five years later.ResultsOf the original at risk cohort of 13,587 persons aged 65 years and over, 2,443 (18.0%) were lost to follow-up; 10,540 persons with skull circumference assessments were followed up for 40,466 person years, and 10,400 with leg length assessments were followed up for 39,954 person years. There were 1,009 cases of incident dementia, and 1,605 dementia free deaths. The fixed effect pooled meta-analysed adjusted subhazard ratio (ASHR) for leg length (highest vs. lowest quarter) was 0.80 (95% CI, 0.66-0.97) and for skull circumference was 1.02 (95% CI, 0.84-1.25), with no heterogeneity of effect between sites (I2=0%). Leg length measurements tended to be shorter at follow-up, particularly for those with baseline cognitive impairment and dementia. However, leg length change was not associated with dementia incidence (ASHR, per cm 1.006, 95% CI 0.992-1.020), and the effect of leg length was little altered after adjusting for baseline frailty (ASHT 0.82, 95% CI 0.67-0.99). A priori hypotheses regarding effect modification by gender or educational level were not supported.ConclusionsConsistent findings across settings provide quite strong support for an association between adult leg length and dementia incidence in late-life. Leg length is a relatively stable marker of early life nutritional programming, which may confer brain reserve and protect against neurodegeneration in later life through mitigation of cardiometabolic risk. Further clarification of these associations could inform predictive models for future dementia incidence in the context of secular trends in adult height, and invigorate global efforts to improve childhood nutrition, growth and development.
Loss oflrrk2impairs dopamine catabolism, cell proliferation, and neuronal regeneration in the zebrafish brain
Authors: Suzzi Stefano , Ahrendt Reiner , Hans Stefan , Semenova Svetlana A. , Bilican Saygın , Sayed Shady , Winkler Sylke , Spieß Sandra , Kaslin Jan , Panula Pertti , Brand Michael 
Published: May 2017

AbstractLRRK2mutations are a major cause of Parkinson’s disease. Pathogenicity of LRRK2 loss-of-function is controversial, as knockout in rodents reportedly induces no brain-specific effects and knockdown studies in zebrafish are conflicting. Here we show that CRISPR/Cas9-engineered deletion of the ~60-kbp-long zebrafishlrrk2locus elicits a pleomorphic, albeit transient brain phenotype in maternal-zygotic mutants (mzLrrk2). Intriguingly, 11-month-old mzLrrk2 adults display increased dopamine and serotonin catabolism. Additionally, we find decreased mitosis in the larval brain and reduced stab injury-induced neuronal regeneration in the adult telencephalon. Finally, hypokinesia associates with loss oflrrk2in larvae. Our results demonstrate thatlrrk2knockout has an early neurodevelopmental effect, and leads to perturbed dopamine and serotonin catabolism in aLRRK2knockout. We propose mzLrrk2 zebrafish as a valuable tool to study LRRK2 loss-of-functionin vivo, and provide a link between LRRK2 and the control of basal cell proliferation in the brain that may become potentially critical upon challenges like brain injury.
Dynamic blue light-inducible T7 RNA polymerases (Opto-T7RNAPs) for precise spatiotemporal gene expression control
Authors: Baumschlager Armin , Aoki Stephanie K. , Khammash Mustafa 
Published: May 2017

ABSTRACTLight has emerged as control input for biological systems due to its precise spatiotemporal resolution. The limited toolset for light control in bacteria motivated us to develop a light-inducible transcription system that is independent from cellular regulation through the use of an orthogonal RNA polymerase. Here, we present our engineered blue light-responsive T7 RNA polymerases (Opto-T7RNAPs) that show properties such as low leakiness of gene expression in the dark-state, high expression strength when induced with blue light, or an inducible range of more than 300-fold. Following optimization of the system to reduce expression variability, we have created a variant, which returns to the inactive dark-state within minutes, once blue light is turned off. This allows for precise dynamic control of gene expression, which is a key aspect for most applications using optogenetic regulation. The regulators were developed and tested in the bacteriumEscherichia coli, which is a crucial cell factory for biotechnology due to its fast and inexpensive cultivation and well understood physiology and genetics. However, minor alterations should be sufficient to allow their use in other species in which the T7 RNAP polymerase and the light-inducible Vivid regulator were shown to be functional, which comprises other bacterial species and eukaryotes such as mammalian cells or yeast. We anticipate that our approach will expand the applicability of using light as an inducer for gene expression independent from cellular regulation, and allow for a more reliable dynamic control of synthetic and natural gene networks.
SUMO E3 ligase Mms21 prevents spontaneous DNA damage induced genome rearrangements
Authors: Liang Jason , Li Bin-zhong , Tan Alexander P. , Kolodner Richard D. , Putnam Christopher D. , Zhou Huilin 
Published: May 2017

AbstractMms21, a subunit of the Smc5/6 complex, possesses an E3 ligase activity for the Small Ubiquitin-like MOdifier (SUMO), which has a major, but poorly understood role in genome maintenance. Here we show mutations that inactivate the E3 ligase activity of Mms21 cause Rad52- and Pol32-dependent break-induced replication (BIR), which specifically requires the Rrm3 DNA helicase. Interestingly, mutations affecting both Mms21 and the Sgs1 helicase, but not sumoylation of Sgs1, cause further accumulation of genome rearrangements, indicating the distinct roles of Mms21 and Sgs1 in suppressing genome rearrangements. Whole genome sequencing further revealed that the Mre11 endonuclease prevents microhomology-mediated translocations and hairpin-mediated inverted duplications in themms21mutant. Consistent with the accumulation of endogenous DNA lesions,mms21cells accumulate spontaneous Ddc2 foci and display a hyper-activated DNA damage checkpoint. Together, these findings support a new paradigm that Mms21 prevents the accumulation of spontaneous DNA lesions that cause diverse genome rearrangements.
Realizing ‘integral control’ in living cells: How to overcome leaky integration due to dilution?
Authors: Qian Yili , Del Vecchio Domitilla 
Published: May 2017

AbstractA major problem in the design of synthetic genetic circuits is robustness to perturbations and uncertainty. Because of this, there have been significant efforts in recent years in finding approaches to implement integral control in genetic circuits. Integral controllers have the unique ability to make the output of a process adapt perfectly to disturbances. However, implementing an integral controller is challenging in living cells. This is because a key aspect of any integral controller is a “memory” element that stores the accumulation (integral) of the error between the output and its desired set-point. The ability to realize such a memory element in living cells is fundamentally challenged by the fact that all biomolecules dilute as cells grow, resulting in a “leaky” memory that gradually fades away. As a consequence, the adaptation property is lost. Here, we propose a general principle for designing integral controllers such that the performance is practically unaffected by dilution. In particular, we mathematically prove that if the reactions implementing the integral controller are all much faster than dilution, then the adaptation error due to integration leakiness becomes negligible. We exemplify this design principle with two synthetic genetic circuits aimed at reaching adaptation of gene expression to fluctuations in cellular resources. Our results provide concrete guidance on the biomolecular processes that are most appropriate for implementing integral controllers in living cells.
Defining marine microbial biomes from environmental and dispersal filtered metapopulations
Authors: Lindh Markus V. 
Published: May 2017

SummaryEnergy and matter fluxes essential for all life1are modulated by spatial and temporal shifts in microbial community structure resulting from environmental and dispersal filtering2,3, emphasizing the continued need to characterize microbial biogeography4,5. Yet, application of metapopulation theory, traditionally used in general ecology for understanding shifts in biogeographical patterns among macroorganisms, has not been tested extensively for defining marine microbial populations filtered by environmental conditions and dispersal limitation at global ocean scales. Here we show, from applying metapopulation theory on two major global ocean datasets6,7, that microbial populations exhibit core- and satellite distributions with cosmopolitan compared to geographically restricted distributions of populations. We found significant bimodal occupancy-frequency patterns (the different number of species occupying different number of patches) at varying spatial scales, where shifts from bimodal to unimodal patterns indicated environmental and dispersal filtering. Such bimodal occupancy-frequency patterns were validated in Longhurst’s classical biogeographical framework andin silicowhere observed bimodal patterns often aligned with specific biomes and provinces described by Longhurst and where found to be non-random in randomized datasets and mock communities. Taken together, our results show that application of metapopulation theory provides a framework for determining distinct microbial biomes maintained by environmental and dispersal filtering.
On growth and form of the distal air exchange surfaces within the lung
Authors: Warburton David , Wigfall Clarence , Pollack Harvey , Koos David , AlAlam Denise , Turcatel Gianluca , Shi Wei , Fraser Scott , Moats Rex 
Published: May 2017

AbstractHerein we show, using several novel imaging and computational approaches, how the air exchange units (AEUs) of the lung develop from the tips and sides of distinct families of tortuous ducts, that themselves ramify as distinct families distal to the bronchoalveolar duct junctions (BADJs), prenatally in humans but postnatally in mice. The mature AEUs thus consist of indented spheroids tightly packed between quite regularly spaced distal ducts. Since the diameter of the BADJs and the distal ducts increases rather than decreasing during the formation of AEUs, we further deduce that the AEUs must form by circular epithelial precursor buckling at their mouths with resulting extrusion of their lumen into the surrounding mesenchyme, stabilized firstly by interlocking rings of elastin and later by rings of elastin and collagen fibers surrounding the mouth of each of the prospective AEUs. Furthermore, we show that the surface of each of the AEUs is highly rugose, being indented by the capillary network that lies close beneath the AES membranes. We propose that, the kissing theorem proposed of Newton that expresses the number of times billiard balls may touch within their frame is a parsimonious solution to achieving optimum packing of the distal AES unit spaces, while allowing sufficient space between them to allow for conducting airways, closely applied pulsatile capillary blood vessels, lymphatics, nerves and other key components of the interstitial mesenchyme.Summary statementEmploying novel imaging and computational approaches we here deduce some new concepts as to how the distal shaping of airway lineage stem and progenitor cells may contribute to the growth and form of the air exchange surface (AES) of the lung, distal to the bronchoalveolar duct junction (BADJ). We then propose that the AES extrudes from the sides and tips of distinct families of small ducts, apparently by buckling of the thinning luminal epithelium into the surrounding mesenchyme, stabilized firstly by rings of elastin and later by rings of collagen and elastin fibers, that surround the mouth of each distal unit of the AES. We propose this mechanism as a parsimonious solution to achieving the optimum form, packing density and functional efficiency of the AES, while allowing sufficient space between for the plumbing of conducting airways, pulsatile capillary blood vessels, lymphatics, nerves and other key matrix and cellular components within the interstitial mesenchyme.
MATAM: reconstruction of phylogenetic marker genes from short sequencing reads in metagenomes
Authors: Pericard Pierre , Dufresne Yoann , Blanquart Samuel , Touzet Hélène 
Published: May 2017

AbstractMotivationAdvances in the sequencing of uncultured environmental samples, dubbed metagenomics, raise a growing need for accurate taxonomic assignment. Accurate identification of organisms present within a community is essential to understanding even the most elementary ecosystems. However, current high-throughput sequencing technologies generate short reads which partially cover full-length marker genes and this poses difficult bioinformatic challenges for taxonomy identification at high resolutionResultsWe designed MATAM, a software dedicated to the fast and accurate targeted assembly of short reads sequenced from a genomic marker of interest. The method implements a stepwise process based on construction and analysis of a read overlap graph. It is applied to the assembly of 16S rRNA markers and is validated on simulated, synthetic and genuine metagenomes. We show that MATAM outperforms other available methods in terms of low error rates and recovered genome fractions and is suitable to provide improved assemblies for precise taxonomic assignments.Availabilityhttps://github.com/bonsai-team/matamContactpierre.pericard@gmail.com,helene.touzet@univ-lille1.fr
High-content protein localization screeningin vivoreveals novel regulators of multiciliated cell development and function
Authors: Tu Fan , Sedzinski Jakub , Ma Yun , Marcotte Edward M. , Wallingford John B. 
Published: May 2017

SUMMARYMulticiliated cells (MCCs) drive fluid flow in diverse tubular organs and are essential for development and homeostasis of the vertebrate central nervous system, airway, and reproductive tracts. These cells are characterized by dozens or hundreds of long, motile cilia that beat in a coordinated and polarized manner (Brooks and Wallingford, 2014). In recent years, genomic studies have not only elucidated the transcriptional hierarchy for MCC specification, but also identified myriad new proteins that govern MCC ciliogenesis, cilia beating, or cilia polarization (e.g. (Choksi et al., 2014b; Chung et al., 2014; Hoh et al., 2012; Ma et al., 2014; Treutlein et al., 2014)). Interestingly, this burst of genomic data has also highlighted the obvious importance of the “ignorome,” that large fraction of vertebrate genes that remain only poorly characterized (Pandey et al., 2014). Understanding the function of novel proteins with little prior history of study presents a special challenge, especially when faced with large numbers of such proteins. Here, we explored the MCC ignorome by defining the subcellular localization of 260 poorly defined proteins in vertebrate MCCsin vivo. Moreover, functional analyses that arose from results of the screen provide novel insights into the mechanisms by which the actin cytoskeleton simultaneously influences diverse aspects of MCC biology, including basal body docking, and ciliogenesis.
Stratified time-course gene preselection shows a pre-diagnostic transcriptomic signal for metastasis in blood cells: a proof of concept from the NOWAC study
Authors: Holsbø Einar , Perduca Vittorio , Bongo Lars Ailo , Lund Eiliv , Birmelé Etienne 
Published: May 2017

AbstractWe investigate whether there is information in gene expression levels in blood that predicts breast cancer metastasis. Our data comes from the NOWAC epidemiological cohort study where blood samples were provided at enrollment. This could be anywhere from years to weeks before any cancer diagnosis. When and if a cancer is diagnosed, it could be so in different ways: at a screening, between screenings, or in the clinic, outside of the screening program. To build predictive models we propose that variable selection should include followup time and stratify by detection method. We show by simulations that this improves the probability of selecting relevant predictor genes. We also demonstrate that it leads to improved predictions and more stable gene signatures in our data. There is some indication that blood gene expression levels hold predictive information about metastasis. With further development such information could be used for early detection of metastatic potential and as such aid in cancer treatment.
Modeling heterogeneous risk preferences
Authors: Guan Zhengfei , Wu Feng 
Published: May 2017

Purpose
The purpose of this paper is to propose a general framework for modeling heterogeneous risk preferences of agricultural producers and identifying the underlying factors that affect risk preferences.

Design/methodology/approach
This paper nests the risk preference function in a general production decision framework to test and model producers’ risk preferences. The framework allows for both production and price risk, and accommodates potential inefficient behavior. Panel data and the GMM method are used in the empirical estimation.

Findings
The results in this study confirmed the hypothesis of heterogeneous risk preferences. Farmers are found to have decreasing absolute risk aversion. Both farmer characteristics and socioeconomic factors have significant impact on producers’ risk preferences. The results suggest that ignoring heterogeneity in risk preferences across individuals and how non-wealth variables could affect farmers’ risk preferences could result in biased economic behavior analysis.

Originality/value
It is generally assumed in the literature that risk preferences are homogeneous among farmers at given wealth. This is a strong assumption and there are abundant evidences that suggest otherwise. This paper makes contributions to the literature by proposing an approach to modeling heterogeneous risk preferences and identifying the factors that affect preferences.
Credit constraints and labour allocation decisions in rural Burkina Faso
Authors: Porgo Mohamed , Kuwornu John K.M. , Zahonogo Pam , Jatoe John Baptist D. , Egyir Irene S. 
Published: May 2017

PurposeCredit is central in labour allocation decisions in smallholder agriculture in developing countries. The purpose of this paper is to analyse the effect of credit constraints on farm households’ labour allocation decisions in rural Burkina Faso.Design/methodology/approachThe study used a direct elicitation approach of credit constraints and applied a farm household model to categorize households into four labour market participation regimes. A joint estimation of both the multinomial logit model and probit model was applied on survey data from Burkina Faso to assess the effect of credit constraint on the probability of choosing one of the four alternatives.FindingsThe results of the probit model showed that households’ endowment of livestock, access to news, and membership to an farmer-based organization were factors lowering the probability of being credit constrained in rural Burkina Faso. The multinomial logit model results showed that credit constraints negatively influenced the likelihood of a farm household to use hired labour in agricultural production and perhaps more importantly it induces farm households to hire out labour off farm. The results also showed that the other components of household characteristics and farm attributes are important factors determining the relative probability of selecting a particular labour market participation regime.Social implicationsFacilitating access to credit in rural Burkina Faso can encourage farm households to use hired labour in agricultural production and thereby positively impacting farm productivity and relieving unemployment pressures.Originality/valueIn order to identify the effect of credit constraints on farm households’ labour decisions, this study examined farm households’ decisions of hiring on-farm labour, supplying labour off-farm or simultaneously hiring on-farm labour and supplying family labour off-farm under credit constraints using the direct elicitation approach of credit constraints. To the best of the authors’ knowledge, this study is the first to examine this problem in Burkina Faso.
The economics and productivity of US dairy farms that use crossbred vs non-crossbred breeding technology (production systems)
Authors: Nehring Richard , Barton Richard , Hallahan Charles 
Published: May 2017

Purpose
The purpose of this paper is to examine the rise in crossbred cow numbers in the US dairy herd. Methods used look at well managed herds to see if crossbreeding provides a management tool that producers are using to maintain profitability.

Design/methodology/approach
The authors estimate a Translog stochastic production frontier (SPF) for US dairy farms to examine the competitiveness of crossbred and non-crossbred dairy herds by system and region.

Findings
The bottom-line conclusion is that WM or highly efficient crossbred herds solidly compete on a financial basis with larger WM Western Holstein herds, the most technically efficient managed group, based on the SPF results in the authors’ study. The study finds that net return on assets for crossbred herds are not different from Western Holstein herds and that there is no significant difference in amount of milk per cow produced annually.

Research limitations/implications
Because of a need to unmask the advantages of crossbreeding as a technology it was necessary to separate WM herds from poorly managed herds. That was done by frontier estimates that robustly ranked operation and corrected for endogeneity, tested for selectivity bias, and incorporated the NASS survey design.

Originality/value
For the first time, the 2010 Dairy Cost and Returns questionnaire version of the Agricultural Resource Management Survey (Dairy CAR) design allows researchers to expand survey observations to represent the vast majority of the US dairy farm population and to sort dairy farms into crossbred/non-crossbred herds.