bluuebunny/crossref_metadata_2025_split huggingface dataset:
The dark side of amyloid aggregation: Exploring the productive and non-productive pathways with multi-scale modeling
Authors: Jia Zhiguang , Schmit Jeremy D. , Chen Jianhan 
Published: June 2019

ABSTRACTAtomistic description of protein fibril formation has remained prohibitive due to the complexity and long timescales of the conformational search problem. Here, we develop a multi-scale approach that combines a large number of atomistic molecular dynamics simulations in explicit solvent to derive Markov State Models (MSMs) for simulation of fibril growth. The search for the in-registered fully bound fibril state is modeled as a random walk on a rugged 2D energy landscape along enumerated β-sheet registry and hydrogen bonding states, whereas interconversions among nonspecific bound states and between nonspecific and hydrogen-bounded states are derived from kinetic clustering analysis. The reversible association/dissociation of an incoming peptide and overall growth kinetics are then computed from MSM trajectories. This approach is applied to derive a comprehensive description of fibril elongation of wild-type Aβ16-22 and how it is modulated by phenylalanine to cyclohexane (CHA) mutations. The resulting models recapitulate the experimental observation that mutants CHA19 and CHA1920 accelerate fibril elongation, but have a relatively minor effect on the critical concentration for fibril growth. Importantly, the kinetic consequences of mutations arise from a complex perturbation of the network of productive and non-productive pathways of fibril grown. This is consistent with the expectation that non-functional states will not have evolved efficient folding pathways and, therefore, will require a random search of configuration space. This study highlights the importance of describing the complete energy landscape when studying the elongation mechanism and kinetics of protein fibrils.
Energetic and Environmental Constraints on the Community Structure of Benthic Microbial Mats in Lake Fryxell, Antarctica
Authors: Dillon Megan L. , Hawes Ian , Jungblut Anne D. , Mackey Tyler J. , Eisen Jonathan A. , Doran Peter T. , Sumner Dawn Y. 
Published: July 2019

AbstractEcological communities are commonly thought to be controlled by the dynamics of energy flow through environments. Two of the most important energetic constraints on all communities are photosynthetically active radiation (PAR) and oxygen concentration ([O2]). Microbial mats growing on the bottom of Lake Fryxell, Antarctica, span environmental gradients in PAR and [O2], which we used to test the extent to which each controls community structure. Metagenomic analyses showed variation in the diversity and relative abundances of Archaea, Bacteria, and Eukaryotes across three [O2] and PAR conditions. Where [O2] saturated the mats or was absent from the overlying water, PAR structured the community. Where [O2] varied within mats, microbial communities changed across covarying PAR and [O2] gradients. Diversity negatively correlated with [O2] and PAR through mat layers in each habitat suggesting that, on the millimeter-scale, communities are structured by the optimization of energy use. In contrast, [O2] positively correlated with diversity and affected the distribution of dominant populations across the three habitats, suggesting that meter-scale diversity is structured by energy availability. The benthic microbial communities in Lake Fryxell are thus structured by energy flow in a scale-dependent manner.
Tissue mechanics regulate mitotic nuclear dynamics during epithelial development
Authors: Kirkland Natalie J. , Yuen Alice C. , Tozluoglu Melda , Hui Nancy , Paluch Ewa K. , Mao Yanlan 
Published: July 2019

SummaryCell divisions are essential for tissue growth. In pseudostratified epithelia, where nuclei are staggered across the tissue, each nucleus migrates apically before undergoing mitosis. Successful apical nuclear migration is critical to preserve tissue integrity during cell division. Most previous investigations have focused on the local cellular mechanisms controlling nuclear migration. Yet, inter-species and inter-organ comparisons of different pseudostratified epithelia suggest global tissue architecture may influence nuclear dynamics, but the underlying mechanisms remain elusive. Here, we use the developing Drosophila wing disc to systematically investigate, in a single epithelial type, how changes in tissue architecture during growth influence mitotic nuclear migration. We observe distinct nuclear dynamics at discrete developmental stages, as epithelial morphology changes. We then use genetic and physical perturbations to show a direct effect of cell density on mitotic nuclear positioning. We also find Rho kinase and Diaphanous, which facilitate mitotic cell rounding in confined cell conditions, are essential for efficient apical nuclear movement. Strikingly, perturbation of Diaphanous causes increasing defects in apical nuclear migration as the tissue grows, and these defects can be reversed by acute physical reduction of cell density. Our findings reveal how the mechanical environment imposed on cells within a tissue alters the molecular and cellular mechanisms adopted by single cells for mitosis. We speculate that mechanical regulation of apical mitotic positioning could be a global mechanism for tissue growth control.
Coexpression of CCR7 and CXCR4 during B cell development controls CXCR4 responsiveness and bone marrow homing
Authors: Mcheik Saria , Van Eeckhout Nils , De Poorter Cédric , Galés Céline , Parmentier Marc , Springael Jean-Yves 
Published: July 2019

AbstractG protein-coupled receptors (GPCR) constitute the largest family of plasma membrane proteins involved in cell signaling. Besides their canonical role in signaling, GPCR can also act as allosteric modulator of one another through receptor oligomerization. However, only few studies have investigated the relevance of GPCR oligomerization, and the role of GPCR interaction in physiological processes remains largely unknown. By using chemokine receptors and B cell development as a model system, we unveil in this study a novel role for CCR7 as a selective endogenous allosteric modulator of CXCR4. We show that the upregulation of CCR7 expression naturally occurring in late stages of B cell development contributes to the functional inactivation of CXCR4, and that B cell populations from CCR7-/-mice display higher responsiveness to CXCL12 and improved retention in the bone marrow parenchyma. We also provide molecular evidences supporting a model in which upregulation of CCR7 favors the formation of CXCR4-CCR7 heteromers wherein CXCR4 is selectively impaired in its ability to activate some G protein complexes.
Surface-induced formation and redox-dependent staining of outer membrane extensions inShewanella oneidensisMR-1
Authors: Chong Grace W. , Pirbadian Sahand , El-Naggar Mohamed Y. 
Published: July 2019

AbstractThe metal-reducing bacteriumShewanella oneidensisMR-1 produces extensions of its outer membrane (OM) and periplasm that contain cytochromes responsible for extracellular electron transfer (EET) to external redox-active surfaces, including minerals and electrodes. While the role of multi-heme cytochromes in transporting electrons across the cell wall is well established, their distribution alongS. oneidensisOM extensions is also thought to allow lateral electron transport along these filaments. These proposed bacterial nanowires, which can be several times the cell length, would thereby extend EET to more distant electron acceptors. However, it is still unclear why these extensions form, and to what extent they contribute to respiration in living cells. Here, we investigate physical contributors to their formation usingin vivofluorescence microscopy. While previous studies focused on the display ofS. oneidensisouter membrane extensions (OMEs) as a response to oxygen limitation, we find that cell-to-surface contact is sufficient to trigger the production of OMEs, including some that reach >100 µm in length, irrespective of medium composition, agitation, or aeration. To visualize the extent of heme redox centers along OMEs, and help distinguish these structures from other extracellular filaments, we also performed histochemical redox-dependent staining with transmission electron microscopy on wild type and cytochrome-deficient strains. We demonstrate that redox-active components are limited to OMEs and not present on other extracellular appendages, such as pili and flagella. We also observed that the loss of 8 functional periplasmic and outer membrane cytochromes significantly decreased both the frequency and intensity of redox-dependent staining found widespread on OMEs. These results will improve our understanding of the environmental conditions that influence the formation ofS. oneidensisOMEs, as well as the distribution and functionality of EET components along extracellular appendages.
The potential for polyphosphate metabolism in Archaea and anaerobic polyphosphate formation inMethanosarcina mazei
Authors: Paula Fabiana S. , Chin Jason , Schnurer Anna , Muller Bettina , Manesiotis Panagiotis , Waters Nicholas , Macintosh Katrina A. , Quinn John P. , Connolly Jasmine , Abram Florence , McGrath John , O’Flaherty Vincent 
Published: July 2019

AbstractInorganic polyphosphate (polyP) is ubiquitous across all forms of life, but the study of its metabolism has been mainly confined to bacteria and yeasts. Few reports detail the presence and accumulation of polyP in Archaea, and little information is available on its functions and regulation. Here, we report that homologs of bacterial polyP metabolism proteins are present across the major taxa in the Archaea, suggesting that archaeal populations may have a greater contribution to global phosphorus cycling than has previously been recognised. We also demonstrate that polyP accumulation can be induced under strictly anaerobic conditions, in response to changes in phosphate (Pi) availability, i.e. Pi starvation, followed by incubation in Pi replete media (overplus), in cells of the methanogenic archaeonMethanosarcina mazei. Pi-starvedM. mazeicells increased transcript abundance of the PHO-regulated alkaline phosphatase (phoA) gene and of the high-affinity phosphate transport (pstSCAB-phoU) operon: no increase in polyphosphate kinase 1 (ppk1) transcript abundance was observed. Subsequent incubation of Pi-starvedM. mazeicells under Pi replete conditions, led to a 237% increase in intracellular polyphosphate content and a >5.7-fold increase inppk1gene transcripts.Ppk1expression inM. mazeithus appears not to be under classical PHO regulon control.
Brain connectivity during Alzheimer’s disease progression and its cognitive impact in a transgenic rat model
Authors: Muñoz-Moreno Emma , Tudela Raúl , López-Gil Xavier , Soria Guadalupe 
Published: July 2019

ABSTRACTThe research of Alzheimer’s disease (AD) in their early stages and its progression till symptomatic onset is essential to understand the pathology and investigate new treatments. Animal models provide a helpful approach to this research, since they allow for controlled follow-up during the disease evolution. In this work, transgenic TgF344-AD rats were longitudinally evaluated starting at 6 months of age. Every 3 months, cognitive abilities were assessed by a memory-related task and magnetic resonance imaging (MRI) was acquired. Structural and functional brain networks were estimated and characterized by graph metrics to identify differences between the groups in connectivity, its evolution with age, and its influence on cognition. Structural networks of transgenic animals were altered since the earliest stage. Likewise, aging significantly affected network metrics in TgF344-AD, but not in the control group. In addition, while the structural brain network influenced cognitive outcome in transgenic animals, functional network impacted how control subjects performed. TgF344-AD brain network alterations were present from very early stages, difficult to identify in clinical research. Likewise, the characterization of aging in these animals, involving structural network reorganization and its effects on cognition, opens a window to evaluate new treatments for the disease.AUTHOR SUMMARYWe have applied magnetic resonance image based connectomics to characterize TgF344-AD rats, a transgenic model of Alzheimer’s disease (AD). This represents a highly translational approach, what is essential to investigate potential treatments. TgF344-AD animals were evaluated from early to advanced ages to describe alterations in brain connectivity and how brain networks are affected by age. Results showed that aging had a bigger impact in the structural connectivity of the TgF344-AD than in control animals, and that changes in the structural network, already observed at early ages, significantly influenced cognitive outcome of transgenic animals. Alterations in connectivity were similar to the described in AD human studies, and complement them providing insights into earlier stages and a plot of AD effects throughout the whole life span.
Elevated temperatures translate into reduced dispersal abilities in a natural population of an aquatic insect
Authors: Jourdan Jonas , Baranov Viktor , Wagner Rüdiger , Plath Martin , Haase Peter 
Published: July 2019

Abstract

Rising global temperatures force many species to shift their distribution ranges. However, whether or not (and how fast) such range shifts occur depends on species' dispersal capacities. In most ecological studies, dispersal‐related traits (such as the wing size or wing loading in insects) are treated as fixed, species‐specific characteristics, ignoring the important role of phenotypic plasticity during insect development.

We tested the hypothesis that dispersal‐related traits themselves vary in dependence of ambient environmental conditions (temperature regimes, discharge patterns and biotic interactions during individual development).

We collected data over 8 years from a natural population of the crane fly Tipula maxima in central Germany. Using linear mixed‐effect models, we analysed how phenotypic traits, phenological characteristics and population densities are affected by environmental conditions during the preceding 3, 6 and 12 months.

We found a moderate (5.6%) increase in wing length per 1°C increase in mean annual temperatures during the previous year. At the same time, body weight increased by as much as 17.8% in females and 26.9% in males per 1°C, likely driven by increased habitat productivity, which resulted in a 16.4% (female) and 19.3% (male) increased wing loading. We further found a shorter, more synchronized emergence period (i.e. a narrower time frame for dispersal) with increasing temperatures.

Altogether, our results suggest that dispersal abilities of T. maxima were negatively affected by elevated temperatures, and we discuss how similar patterns might affect the persistence of populations of other aquatic insects, especially stenoecious taxa with narrow distribution ranges. Our study calls for integration of information on temperature‐induced phenotypic plasticity of dispersal‐related traits into models forecasting range shifts in the face of climate change. Furthermore, the patterns reported here are likely to affect metapopulation dynamics of aquatic insects under climate change conditions and may contribute to the ongoing decline of insect biomass and diversity.
Climate and Land Use Effects on Hydrologic Processes in a Primarily Rain‐Fed, Agricultural Watershed
Authors: Phung Quang A. , Thompson Allen L. , Baffaut Claire , Costello Christine , Sadler E. John , Svoma Bohumil M. , Lupo Anthony , Gautam Sagar 
Published: July 2019

AbstractAnticipating changes in hydrologic variables is essential for making socioeconomic water resource decisions. This study aims to assess the potential impact of land use and climate change on the hydrologic processes of a primarily rain‐fed, agriculturally based watershed in Missouri. A detailed evaluation was performed using the Soil and Water Assessment Tool for the near future (2020–2039) and mid‐century (2040–2059). Land use scenarios were mapped using the Conversion of Land Use and its Effects model. Ensemble results, based on 19 climate models, indicated a temperature increase of about 1.0°C in near future and 2.0°C in mid‐century. Combined climate and land use change scenarios showed distinct annual and seasonal hydrologic variations. Annual precipitation was projected to increase from 6% to 7%, which resulted in 14% more spring days with soil water content equal to or exceeding field capacity in mid‐century. However, summer precipitation was projected to decrease, a critical factor for crop growth. Higher temperatures led to increased potential evapotranspiration during the growing season. Combined with changes in precipitation patterns, this resulted in an increased need for irrigation by 38 mm representing a 10% increase in total irrigation water use. Analysis from multiple land use scenarios indicated converting agriculture to forest land can potentially mitigate the effects of climate change on streamflow, thus ensuring future water availability.
The Influence of Firms' Emissions Management Strategy Disclosures on Investors' Valuation Judgments
Authors: Johnson Joseph A. , Theis Jochen , Vitalis Adam , Young Donald 
Published: June 2019

ABSTRACTRecent accounting research indicates that capital markets price firms' greenhouse gas (GHG) emissions and that disclosed emissions levels are negatively associated with firms' market values. The departure point for this study is to investigate whether investors value firms differently based on the strategies firms use to mitigate GHG emissions. These strategies include making operational changes, which reduces emissions attributable to the firm, and purchasing offsets, which reduces emissions unattributable to the firm. Using an experiment, we hold constant a firm's financial performance, investment in emissions mitigation, and net emissions, and find evidence that nonprofessional investors perceive the firm to be more valuable when it primarily uses an operational change strategy versus an offsets strategy. However, consistent with theory, this result only occurs when the firm's prior sustainability performance is below the industry average and not when it is above the industry average. This difference in firm value is consistent with the notion that nonprofessional investors believe information about a firm's emissions management strategy is material. Supplemental exploratory analyses reveal that our results are mediated by investors' perception that an operational change strategy is more socially and environmentally responsible than an offsets strategy for below industry average firms. Implications for our findings on theory and practice are discussed.
Patterns and predictors of e‐cigarette, cigarette and dual use uptake in UK adolescents: evidence from a 24‐month prospective study
Authors: Conner Mark , Grogan Sarah , Simms‐Ellis Ruth , Scholtens Keira , Sykes‐Muskett Bianca , Cowap Lisa , Lawton Rebecca , Armitage Christopher J. , Meads David , Schmitt Laetitia , Torgerson Carole , West Robert , Siddiqi Kamran 
Published: June 2019

AbstractBackground and AimsTo assess prevalence and predictors of e‐cigarettes/cigarettes patterns of use in adolescents in England.DesignProspective study with 24‐month follow‐up of e‐cigarette/cigarette ever/regular use with data from an intervention evaluation.SettingForty‐five schools in England (Staffordshire and Yorkshire).ParticipantsA total of 3210 adolescents who, at baseline, were aged 13–14 years and had never used e‐cigarettes/cigarettes.MeasurementsBased on e‐cigarette/cigarette ever use at follow‐up, six groups were created: (a) never user, (b) e‐cigarette only, (c) cigarette only, (d) dual use—order of use unclear, (e) dual use—e‐cigarettes used first and (f) dual use—cigarettes used first. Baseline measures were: gender, ethnicity, socio‐economic status, impulsivity, family plus friend smoking and smoking‐related beliefs (attitude and perceived behavioural control).FindingsIn groups (a) to (f), there were 71.5, 13.3, 3.3, 5.7, 2.9 and 3.4% adolescents, respectively. Among groups using cigarettes, regular smoking was more prevalent in group (f) (dual use—cigarettes used first) [17.6%, 95% confidence interval (CI) = 10.4, 24.8] than in groups (c), (d) and (e) combined (7.3%, 95% CI = 4.7, 9.9). Among groups using e‐cigarettes, regular use was less prevalent in group (b) (e‐cigarette only) (1.9%, 95% CI = 0.6, 3.2) than in groups (d), (e) and (f) combined (12.2%, 95% CI = 8.9, 15.5). Higher impulsivity plus friends and family smoking were predictive of being in groups (b) to (f) compared with group (a) (never users). Males were more likely to be in group (b) compared to group (a); females were more likely to be in groups (c) to (f) compared to group (a).ConclusionsRegular use of e‐cigarettes/cigarettes varies across groups defined by ever use of e‐cigarettes/cigarettes. Interventions targeted at tackling impulsivity or adolescents whose friends and family members smoke may represent fruitful avenues for future research.
A review of the law of consent in dentistry
Authors: Holden ACL , Stewart C 
Published: July 2019

AbstractThe development of the law of consent has led to much discussion within the dental literature as to how these changes might impact practice. The move from a practitioner‐focused standard of consent to a patient‐focused standard has altered the nature of the framework required to support a patient's decision‐making to avoid an allegation or finding of a negligent consent process. Contrastingly, there has been little in the way of exploration as to how the law of battery (in civil matters) and assault (in criminal cases), where consent is entirely absent, might apply to dentistry and the practice of the profession. This article considers the law of consent, using several key examples from dentistry, as well as providing an update of recent case law of relevance to dental practice.
Geriatricians’ attitudes towards voluntary assisted dying: A survey of Australian and New Zealand Society for Geriatric Medicine members
Authors: Munday Tanya , Poon Peter 
Published: June 2019

AbstractObjectiveTo identify the attitudes of Australian and New Zealand geriatricians to legalisation of voluntary assisted dying.MethodsAn anonymous, voluntary, online survey of Australian and New Zealand Society for Geriatric Medicine (ANZSGM) members.ResultsA total of 226 members completed the survey equating to a 20% response rate. About 24% of respondents supported legalisation of voluntary assisted dying, whilst 53% opposed. If voluntary assisted dying was legalised, 12% would be willing to prescribe to an appropriate patient, and 61% would be willing to refer them onto a third party. Risk to vulnerable patients was the most important concern identified.ConclusionsSupport for voluntary assisted dying among surveyed ANZSGM members is low, but varies according to patient circumstances. Key areas of concern highlighted were risk to vulnerable patients, estimating prognosis, and capacity assessments. Further training is required for doctors on discussing voluntary assisted dying options, estimating prognosis, and capacity assessments prior to implementation.
Atypical severe progressive perioral ulceration due to herpes simplex virus on the background of undiagnosed HIV/AIDS
Authors: Howard Matthew David , Poon Flora , Milne Olivia Jean , Kelmann Anthony , Chong Alvin H 
Published: July 2019

AbstractPerioral ulcerative plaques have a broad list of differential diagnoses. We describe an unusual presentation of chronic progressive perioral ulceration due to herpes simplex type (HSV)‐1 on a background of undiagnosed human immunodeficiency virus infection with acquired immunodeficiency syndrome. Whilst chronic mucocutaneous HSV is an AIDS‐defining condition with both HSV‐1 and HSV‐2 implicated, typical reported cases describe vesicular eruptions rather than perioral ulcerative plaques. This case highlights that common infections may present atypically in immunocompromised individuals and may be a clue to underlying systemic illness.