bluuebunny/crossref_metadata_2025 huggingface dataset:
UbiFast, a rapid and deep-scale ubiquitylation profiling approach for biology and translational research
Authors: Udeshi Namrata D. , Mani Deepak C. , Satpathy Shankha , Fereshetian Shaunt , Gasser Jessica A. , Svinkina Tanya , Ebert Benjamin L. , Mertins Philipp , Carr Steven A.
Published: September 2019

Protein ubiquitylation is involved in a plethora of cellular processes. Defects in the ubiquitin system are at the root of many acquired and hereditary diseases. While antibodies directed at ubiquitin remnants (K-ε-GG) have improved the ability to monitor ubiquitylation using mass spectrometry, methods for highly-multiplexed measurement of ubiquitylation in tissues and primary cells using sub-milligram amounts of sample remains a challenge. Here we present a highly-sensitive, rapid and multiplexed protocol for quantifying ∼10,000 ubiquitylation sites from as little as 500 ug peptide per sample from cells or tissue in a TMT10 plex in ca. 5 hr. High-field Asymmetric Ion Mobility Spectrometry (FAIMS) is used to improve quantitative accuracy for posttranslational modification analysis. We use the approach to rediscover substrates of the E3 ligase targeting drug lenalidomide and to identify proteins modulated by ubiquitylation in models of basal and luminal human breast cancer. The sensitivity and speed of the UbiFast method makes it suitable for large-scale studies in primary tissue samples.
The RNA helicase DDX3 induces neural crest by promoting AKT activity
Authors: Perfetto Mark , Xu Xiaolu , Yousaf Natasha , Li Jiejing , Wei Shuo
Published: September 2019

Mutations in the RNA helicase DDX3 have emerged as a frequent cause of intellectual disability in humans. Because many patients carrying DDX3 mutations have additional defects in craniofacial structures and other tissues containing neural crest (NC)-derived cells, we hypothesized that DDX3 is also important for NC development. UsingXenopus tropicalisas a model, we show that DDX3 is required for normal NC induction and craniofacial morphogenesis by regulating AKT kinase activity. Depletion of DDX3 decreases AKT activity and AKT-dependent inhibitory phosphorylation of GSK3β, leading to reduced levels of β-catenin and Snai1, two GSK3β substrates that are critical for NC induction. DDX3 function in regulating these downstream signaling events during NC induction is likely mediated by RAC1, a small GTPase whose translation depends on the RNA helicase activity of DDX3. These results suggest an evolutionarily conserved role of DDX3 in NC development by promoting AKT activity, and provide a potential mechanism for the NC-related birth defects displayed by patients harboring mutations in DDX3 and its downstream effectors in this signaling cascade.
The origin of physiological local mGluR1 supralinear Ca2+ signals in cerebellar Purkinje neurons
Authors: Ouares Karima Ait , Canepari Marco
Published: September 2019

In Purkinje neurons, the climbing fibre (CF) input provides a signal to parallel fibre (PF) synapses triggering PF synaptic plasticity. This supralinear Ca2+ signal, co-localised with the PF Ca2+ influx, occurs when PF activity precedes the CF input. Using membrane potential (Vm) and Ca2+ imaging, we identified the biophysical determinants of these supralinear Ca2+ signals. The CF-associated Ca2+ influx is mediated by T-type or by P/Q-type Ca2+ channels, depending on whether the dendritic Vm is hyperpolarised or depolarised. The resulting Ca2+ elevation is locally amplified by saturation of the endogenous Ca2+ buffer produced by the PF-associated Ca2+ influx, in particular by the slow Ca2+ influx mediated by type-1 metabotropic glutamate receptors (mGluR1s). When the dendrite is hyperpolarised, mGluR1s boost neighbouring T-type channels providing a mechanism for local coincident detection of PF-CF activity. In contrast, when the dendrite is depolarised, mGluR1s increase dendritic excitability by inactivating A-type K+ channels, but this phenomenon is not restricted to the activated PF synapses. Thus, Vm is likely a crucial parameter in determining PF synaptic plasticity and the occurrence of hyperpolarisation episodes is expected to play an important role in motor learning.
Rapid and Sustained Homeostatic Control of Presynaptic Exocytosis at a Central Synapse
Authors: Delvendahl Igor , Kita Katarzyna , Müller Martin
Published: September 2019

Animal behavior is remarkably robust despite constant changes in neural activity. Homeostatic plasticity stabilizes central nervous system (CNS) function on time scales of hours to days. If and how CNS function is stabilized on more rapid time scales remains unknown. Here we discovered that mossy fiber synapses in the mouse cerebellum homeostatically control synaptic efficacy within minutes after pharmacological glutamate receptor impairment. This rapid form of homeostatic plasticity is expressed presynaptically. We show that modulations of readily-releasable vesicle pool size and release probability normalize synaptic strength in a hierarchical fashion upon acute pharmacological and prolonged genetic receptor perturbation. Presynaptic membrane capacitance measurements directly demonstrate regulation of vesicle pool size upon receptor impairment. Moreover, presynaptic voltage-clamp analysis revealed increased calcium-current density under specific experimental conditions. Thus, homeostatic modulation of presynaptic exocytosis through specific mechanisms stabilizes synaptic transmission in a CNS circuit on time scales ranging from minutes to months. Rapid presynaptic homeostatic plasticity may ensure stable neural circuit function in light of rapid activity-dependent plasticity.
Genetic interactions derived from high-throughput phenotyping of 7,350 yeast cell cycle mutants
Authors: Gallegos Jenna E. , Adames Neil R. , Rogers Mark F. , Kraikivski Pavel , Ibele Aubrey , Nurzynski-Loth Kevin , Kudlow Eric , Murali T.M. , Tyson John J. , Peccoud Jean
Published: September 2019

Over the last 30 years, computational biologists have developed increasingly realistic mathematical models of the regulatory networks controlling the division of eukaryotic cells. These models capture data resulting from two complementary experimental approaches: low-throughput experiments aimed at extensively characterizing the functions of small numbers of genes, and large-scale genetic interaction screens that provide a systems-level perspective on the cell division process. The former is insufficient to capture the interconnectivity of the genetic control network, while the latter is fraught with irreproducibility issues. Here, we describe a hybrid approach in which the genetic interactions between 36 cell-cycle genes are quantitatively estimated by high-throughput phenotyping with an unprecedented number of biological replicates. Using this approach, we identify a subset of high-confidence genetic interactions, which we use to refine a previously published mathematical model of the cell cycle. We also present a quantitative dataset of the growth rate of these mutants under six different media conditions in order to inform future cell cycle models.

Author Summary

The process of cell division, also called the cell cycle, is controlled by a highly complex network of interconnected genes. If this process goes awry, diseases such as cancer can result. In order to unravel the complex interactions within the cell cycle control network, computational biologists have developed mathematical models that describe how different cell cycle genes are related. These models are built using large datasets describing the effect of mutating one or more genes within the network. In this manuscript, we present a novel method for producing such datasets. Using our method, we generate 7,350 yeast mutants to explore the interactions between key cell cycle genes. We measure the effect of the mutations by monitoring the growth rate of the yeast mutants under different environmental conditions. We use our mutants to revise an existing model of the yeast cell cycle and present a dataset of ∼44,000 gene by environment combinations as a resource to the yeast genetics and modeling communities.
A PUF hub drives self-renewal inC. elegansgermline stem cells
Authors: Haupt Kimberly A. , Law Kimberley T. , Enright Amy L. , Kanzler Charlotte R. , Shin Heaji , Wickens Marvin , Kimble Judith
Published: September 2019

Stem cell regulation relies on extrinsic signaling from a niche plus intrinsic factors that respond and drive self-renewal within stem cells. Apriori,loss of niche signaling and loss of the intrinsic self-renewal factors might be expected to have equivalent stem cell defects. Yet this simple prediction has not been borne out for most stem cells, includingC. elegansgermline stem cells (GSCs). The central regulators ofC. elegansGSCs include extrinsically-acting GLP-1/Notch signaling from the niche, intrinsically-acting RNA binding proteins in the PUF family, termed FBF-1 and FBF-2 (collectively FBF), and intrinsically-acting PUF partner proteins that are direct Notch targets. Abrogation of either GLP-1/Notch signaling or its targets yields an earlier and more severe GSC defect than loss of FBF-1 and FBF-2, suggesting that additional intrinsic regulators must exist. Here, we report that those missing regulators are two additional PUF proteins, PUF-3 and PUF-11. Remarkably, anfbf-1 fbf-2; puf-3 puf-11quadruple null mutant has a GSC defect virtually identical to that of aglp-1/Notch null mutant. PUF-3 and PUF-11 both affect GSC maintenance; both are expressed in GSCs; and epistasis experiments place them at the same position as FBF within the network. Therefore, action of PUF-3 and PUF-11 explains the milder GSC defect infbf-1 fbf-2mutants. We conclude that a “PUF hub”, comprising four PUF proteins and two PUF partners, constitutes the intrinsic self-renewal node of theC. elegansGSC RNA regulatory network. Discovery of this hub underscores the significance of PUF RNA-binding proteins as key regulators of stem cell maintenance.
Heterogeneous T cell motility behaviors emerge from a coupling between speed and turningin vivo
Authors: Jerison Elizabeth R. , Quake Stephen R.
Published: September 2019

T cellsin vivomigrate primarily via undirected random walks, but it remains unresolved how these random walks generate an efficient search. Here, we use light sheet microscopy of T cells in the larval zebrafish as a model system to study motility across large populations of cells over hours in their native context. We show that cell-to-cell variability is amplified by a correlation between speed and directional persistence, generating a characteristic cell behavioral manifold that is preserved under a perturbation to cell speeds, and seen in Mouse T cells andDictyostelium. These results suggest that there is a single variable underlying ameboid cell motility that jointly controls speed and turning. This coupling explains behavioral heterogeneity in diverse systems and allows cells to access a broad range of length scales.
Exposure to predator models during the fertile period leads to higher levels of extra‐pair paternity in blue tits
Authors: Santema Peter , Valcu Mihai , Kempenaers Bart
Published: September 2019

The perceived risk of predation can affect breeding behaviour and reduce reproductive success in prey species. Individuals exposed to predators may also adopt different mating tactics with potential consequences for the distribution of paternity in socially monogamous species that engage in extra‐pair copulations.

We experimentally increased perceived predation risk during the fertile period in blue tits Cyanistes caeruleus. Every morning between nest completion and the onset of egg laying, we presented a model of either a predator or a non‐predator (control) near active nestboxes.

Broods from pairs exposed to predators had higher levels of extra‐pair paternity than control broods. This mainly resulted from a higher proportion of extra‐pair offspring in broods with at least one extra‐pair young.

Females exposed to predators first emerged from the nestbox later in the morning, stayed away from the nestbox for longer and were less likely to be visited at the nest by their social mate, but we detected no behavioural differences once the model was removed.

Our results suggest that the higher rates of extra‐pair paternity resulted from the disruption of morning routines, which may have inhibited within‐pair copulations or increased opportunities for females to engage in extra‐pair copulations. We conclude that the perceived risk of predation can have substantial effects on levels of extra‐pair paternity.
Seeking compromise across competing goals in conservation translocations: The case of the ‘extinct’ Floreana Island Galapagos giant tortoise
Authors: Hunter Elizabeth A. , Gibbs James P. , Cayot Linda J. , Tapia Washington , Quinzin Maud C. , Miller Joshua M. , Caccone Adalgisa , Shoemaker Kevin T.
Published: September 2019

Conservation translocation projects must carefully balance multiple, potentially competing objectives (e.g. population viability, retention of genetic diversity, delivery of key ecological services) against conflicting stakeholder values and severe time and cost constraints. Advanced decision support tools would facilitate identifying practical solutions.

We examined how to achieve compromise across competing objectives in conservation translocations via an examination of giant tortoises in the Galapagos Islands with ancestry from the extinct Floreana Island species (Chelonoidis niger). Efforts have begun to populate Floreana Island with tortoises genetically similar to its historical inhabitants while balancing three potentially competing objectives – restoring ecosystem services (sustaining a high tortoise population size), maximizing genome representation of the extinct C. niger species and maintaining a genetically diverse population – under realistic cost constraints.

We developed a novel approach to this conservation decision problem by coupling an individual‐based simulation model with generalized additive models and global optimization. We identified several incompatibilities among programme objectives, with quasi‐optimal single‐objective solutions (sets of management actions) differing substantially in programme duration, translocation age, incubation temperature (determinant of sex ratio) and the number of individuals directly translocated from the source population.

Quasi‐optimal single‐objective solutions were able to produce outcomes (i.e. population size and measures of genetic diversity and C. niger genome representation) to within 75% of their highest simulated outcomes (e.g. highest population size achieved across all simulations) within a cost constraint of c. $2m USD, but these solutions resulted in severe declines (up to 74% reduction) in outcomes for non‐focal objectives. However, when all programme objectives were equally weighted to produce a multi‐objective solution, all objectives were met to within 90% of the highest achievable mean values across all cost constraints.

Synthesis and applications. Multi‐objective conservation translocations are likely to encounter complex trade‐offs and conflicts among programme objectives. Here, we developed a novel combination of modelling approaches to identify optimal management strategies. We found that solutions that simultaneously addressed multiple, competing objectives performed better than single‐objective solutions. Our model‐based decision support tool demonstrates that timely, cost‐effective solutions can be identified in cases where management objectives appear to be incompatible.
Shrub encroachment decreases soil inorganic carbon stocks in Mongolian grasslands
Authors: Liu Shangshi , Zhou Luhong , Li He , Zhao Xia , Yang Yuanhe , Zhu Yankun , Hu Huifeng , Chen Leiyi , Zhang Pujin , Shen Haihua , Fang Jingyun
Published: September 2019

Widespread shrub encroachment in global drylands may increase plant biomass and change soil organic carbon stocks of grassland ecosystems. However, the response of soil inorganic carbon (SIC), which is a major component of dryland carbon pools, to this vegetation shift remains unknown.

We conducted a systematic field survey in 75 pairs of shrub‐encroached grassland (SEG) and control plots at 25 sites in the grasslands of the Inner Mongolia Plateau to evaluate how shrub encroachment affects SIC density (SICD) in these ecosystems.

We found that shrub encroachment significantly reduced SICD in the upper 100 cm (3.85 vs. 4.74 kg C m−2, p < .05), especially in the subsurface soil (20–50 cm layer). The magnitude of SICD changes was related to the change in soil pH, shrub patch size and initial SICD, reflecting that the reduction in SICD might be attributed to the shrub encroachment‐related soil acidification. Our results also revealed that the lost SIC was mainly released into the atmosphere rather than redistributed into deeper soil layers.

Synthesis. We provide the first evidence for the soil acidification‐induced SIC loss caused by shrub encroachment. Our findings highlight the non‐negligible role of SIC dynamics in the C budget of SEG ecosystems and the need to consider these dynamics in terrestrial C cycle research.
Rhizosphere and litter feedbacks to range‐expanding plant species and related natives
Authors: Manrubia Marta , van der Putten Wim H. , Weser Carolin , Veen Ciska (G. F.)
Published: September 2019

Plant–soil feedback (PSF) results from the net legacy effect that plants leave in the composition of soil communities and abiotic soil properties. PSF is induced by the rhizosphere and by litter inputs into the soil, however, we have little understanding of their individual contributions. Here, we examine feedback effects from the rhizosphere of living plants, decomposing litter and their combination.

We used four pairs of climate warming‐induced range‐expanding plant species and congeneric natives, and examined PSF effects on plant biomass production, as well as on decomposition in their new range.

We tested the hypothesis that the plant rhizosphere provides less negative feedback to range‐expanders than to the congeneric natives, and that feedback mediated by litter decomposition does not provide such a difference because decomposers might be less specialized than pathogens. To determine PSF, we used soil from the congener species within each pair as an ‘away’ soil to indicate whether range‐expanders may have lost their specialized soil biota upon arrival in the novel range.

Our results show that although range‐expanding plant species and their congeneric natives developed neutral PSF in both rhizosphere‐ and litter‐conditioned soils, two of the four range‐expanders produced more biomass than natives in soils conditioned by litter, that is, soils with high nutrient content. Shoot litter from two out of four range‐expanding species decomposed more than that of natives, but decomposition was unaffected by soil conditioning.

Synthesis. We compared PSF effects of range‐expanders and congeneric natives mediated via both the rhizosphere and litter using the congeneric species as a control. Under those conditions, PSF effects were neutral and not affected by plant origin. Therefore, we conclude that studies not comparing within plant genera may overestimate the impact of plant origin on PSF. Still, even under those conditions range‐expanders appeared to benefit more from high soil nutrient availability than natives, thus providing a possible advantage over congeneric natives.
Quinazolinone derivative BNUA‐3 ameliorated [NDEA+2‐AAF]‐induced liver carcinogenesis in SD rats by modulating AhR‐CYP1B1‐Nrf2‐Keap1 pathway
Authors: Bose Pritha , Siddique Mohd. Usman M. , Acharya Reetuparna , Jayaprakash Venkatesan , Sinha Barij Nayan , Lapenna Antonio , Pattanayak Shakti P
Published: September 2019

Cytochrome P450 1B1, considered as one of the novel chemotherapeutic targets involved in cancer prevention and therapy is also associated with the conversion of procarcinogens into their active metabolites. The aryl hydrocarbon receptor (AhR) is responsible for mediating different biological responses to a wide variety of environmental pollutants and also causes transcriptional activation of cytochrome P450 enzymes including CYP1B1 and thus plays a pivotal role for initiating cancer and its progression. On the other hand, active carcinogenic metabolites and reactive oxygen species‐mediated stress alter different molecular signalling pathways and gene expressions. Quinazoline derivatives are recognized for their diversified biological activities including anticancer properties. The current study was designed for evaluation of chemotherapeutic efficacy of a synthetic quinazolinone derivative BNUA‐3 against hepatocellular cancer in Sprague‐Dawley (SD) rats. A detailed in vivo analysis was performed by administrating BNUA‐3 (15, 30 mg/kg b.w. for 28 days, i.p.) in N‐Nitrosodiethylamine + 2‐Acetylaminofluorene induced partially hepatectomized liver cancer in SD rats. This was followed by morphological evaluations, biochemical estimations and analysis of different mRNA and protein expressions. The results demonstrated the potency of BNUA‐3 in efficient restoration of the altered morphology of liver, its protective effect against lipid peroxidation, enzymic and non‐enzymic antioxidants levels in liver tissue which was disrupted after cancer induction. The study also demonstrated downregulation of AhR, CYP1B1 and Keap1 expressions with subsequent augmentation of protective Nrf2, HO‐1, NQO1 and GSTA1 expressions thus, revealing the chemotherapeutic potency of BNUA‐3 in inhibiting liver carcinogenesis through AhR/CYP1B1/Nrf2/Keap1 pathway.
(In)visible materialities in the context of dementia care
Authors: Cleeve Helena , Borell Lena , Rosenberg Lena
Published: September 2019

Seemingly mundane materialities are intertwined with important, but often neglected, care interactions. It has been argued that if healthcare professionals paid more attention to the roles materialities can have, everyday routines could become important occasions for care. In response to such proposals, we argue that it is relevant to examine how materialities are currently understood. In this article, we explore materialities as part of work in a dementia unit. Using abstracted illustrations of everyday materialities to elicit reflections, we conducted 11 individual interviews with certified nursing assistants. Through phenomenographic analysis we explain our findings as three different categories conceptualising understandings of materialities as: ‘tools for care’, ‘a set of principles for care’ and ‘caring relationships’. Our analysis indicates that understanding materialities as instruments was reinforced and made visible through the healthcare organisation while understanding materialities as part of specific relationships with residents appeared informal and less visible. How materialities were understood seemed to have several implications for residents. While care practices could benefit from nursing assistants’ abilities to alternate between ways of understanding materialitites, such competence seemed dependent on how professional care was organised, structured and materialised.
Embracing a ‘new normal’: the construction of biographical renewal in young adults’ narratives of living with a stoma
Authors: Polidano Kay , Chew‐Graham Carolyn A. , Bartlam Bernadette , Farmer Adam D. , Saunders Benjamin
Published: September 2019

Stoma surgery can be a life‐changing procedure due to bodily changes and related psychological responses. Despite previous literature identifying unique challenges for young adults living with a long‐term condition, no studies have explored the biographical implications of stoma formation. Drawing on interviews with 13 young adults, aged 18–29 years, with a stoma resulting from inflammatory bowel disease, this article aims to generate new theoretical insights in understanding the process of biographical (re)construction and the wider implications of stoma formation among this group. Data analysis combined constructivist grounded theory and narrative analysis. Whilst two narratives display ‘biographical suspension’ characterised by a distancing of self from their stoma, the majority of narratives highlight positive transformations in the young adults’ conceptions of self; which we explain through the concept of ‘biographical renewal’. The liberating effects of stoma surgery allowed young adults to reclaim aspects of their pre‐illness selves, yet also reconfigure a new, altered sense of self, culminating in a ‘new normal’. However, psychological distress also co‐existed alongside these positive representations, revealing a tension that young adults attempt to reconcile through narrativising their experiences. Our findings have implications for the identification and management of the psychological needs of young people with a stoma.
Differentiation of Commercially Available Kratom by Purported Country of Origin using Inductively Coupled Plasma–Mass Spectrometry,
Authors: Braley Cody , Hondrogiannis Ellen M.
Published: September 2019

Kratom is a plant material exhibiting both analgesic and stimulant effects and is also forensically relevant since it is abused as a “legal high.” It is regulated in several countries but not scheduled in the United States at the federal level. This study used inductively coupled plasma–mass spectrometry (ICP–MS) to measure the concentrations of 13 elements in 19 kratom samples obtained from an online distributor selling kratom, from Borneo, Malaysia, Indonesia, Thailand, and Vietnam, for the purpose of using the elements to discriminate among purported country of origin, “suborigin,” and strain. Analysis of variance revealed statistical differences in concentrations of elements from each group, while discriminant function analysis (using leave‐one‐out classification) successfully classified kratom samples by their purported country of origin (100%), “suborigin,” (100%), and strain (86%). Our method illustrates the possibility of utilizing ICP–MS for determination of commercially available kratom samples by purported origin, “subororign,” or by product line.
Microbial communities of the Mediterranean rocky shore: ecology and biotechnological potential of the sea‐land transition
Authors: Molina‐Menor Esther , Tanner Kristie , Vidal‐Verdú Àngela , Peretó Juli , Porcar Manuel
Published: September 2019

Microbial communities from harsh environments hold great promise as sources of biotechnologically relevant strains and compounds. In the present work, we have characterized the microorganisms from the supralittoral and splash zone in three different rocky locations of the Western Mediterranean coast, a tough environment characterized by high levels of irradiation and large temperature and salinity fluctuations. We have retrieved a complete view of the ecology and functional aspects of these communities and assessed the biotechnological potential of the cultivable microorganisms. All three locations displayed very similar taxonomic profiles, with the genus Rubrobacter and the families Xenococcaceae, Flammeovirgaceae, Phyllobacteriaceae, Rhodobacteraceae and Trueperaceae being the most abundant taxa; and Ascomycota and halotolerant archaea as members of the eukaryotic and archaeal community respectively. In parallel, the culture‐dependent approach yielded a 100‐isolates collection, out of which 12 displayed high antioxidant activities, as evidenced by two in vitro (hydrogen peroxide and DPPH) and confirmed in vivo with Caenorhabditis elegans assays, in which two isolates, CR22 and CR24, resulted in extended survival rates of the nematodes. This work is the first complete characterization of the Mediterranean splash‐zone coastal microbiome, and our results indicate that this microbial niche is home of an extremophilic community that holds biotechnological potential.
Financial applications of semidefinite programming: a review and call for interdisciplinary research
Authors: Gepp Adrian , Harris Geoff , Vanstone Bruce
Published: September 2019

Optimisation problems in finance commonly have non‐linear constraints for which previous solutions have required unrealistic assumptions. However, many of these can be efficiently solved as semidefinite programming (SDP) problems, which have less restrictive assumptions. Through review of the literature that uses SDP in finance, two major research streams are identified: portfolio optimisation and option pricing. Nevertheless, many finance researchers are unaware of SDP. One possible reason is that this research is often published in non‐finance journals. This paper aims to better integrate the SDP research to promote wider use of current findings and further interdisciplinary research, particularly in environmental finance.
Behavioral and physiological stress responses to local spatial disturbance and human activities by howler monkeys at Los Tuxtlas, Mexico
Authors: Cañadas Santiago S. , Dias P. A. D. , Garau S. , Coyohua Fuentes A. , Chavira Ramírez D. R. , Canales Espinosa D. , Rangel Negrín A.
Published: September 2019

To develop effective conservation and management actions, it is important to examine anthropogenic disturbance patterns and their impact on wildlife. We examined variation in the behavioral and physiological stress response of the Critically Endangered Mexican mantled howler monkeys Alouatta palliata mexicana in relation to two types of anthropogenic disturbance, habitat spatial patterns and presence of humans or their livestock (noise and presence nearby primates). We studied four groups (42 individuals) in two forest fragments at the Los Tuxtlas Biosphere Reserve for a total of 1100 observation hours, during which we recorded the howler monkeys’ vocalizations, locomotion and vigilance. We additionally collected fecal samples to determine the concentrations of glucocorticoid metabolites (fGCM). Howler monkeys vocalized less and moved more when in more spatially disturbed locations and when exposed more time to nearby noise but spent less time in locomotion when humans were present. fGCM were only related to human presence, suggesting that habitat spatial patterns are less of a challenge than human presence. This may be related to the generally unpredictable nature of the latter. Although our study does not allow determining whether the behavioral and physiological responses of howler monkeys to disturbance are costly, from a conservation standpoint it may be more prudent to assume that they are and design strategies to mitigate them. In this sense, actions aimed at reducing anthropogenic noise could benefit the conservation of Mexican mantled howler monkeys.
Spatial niche modelling of five endemic cacti from the Brazilian Caatinga: Past, present and future
Authors: Simões Silvana dos Santos , Zappi Daniela , Costa Grênivel Mota da , de Oliveira Guilherme , Aona Lidyanne Yuriko Saleme
Published: September 2019

Climate change, together with human activities, impacts on natural and human systems on all continents and poses a major threat to biodiversity, especially in environments with a high rate of endemism and where species are profoundly adapted to specific environmental conditions, as is the case of the seasonally dry tropical forests, noticeably the Caatinga, an exclusively Brazilian biome. The objective of this study was to build spatial niche models of five species of Cactaceae (Arrojadoa penicillata, Brasilicereus phaeacanthus, Pereskia aureiflora, Stephanocereus leucostele and Tacinga inamoena) endemic to the Caatinga and with different traits, to evaluate the impact of climate change on their geographical distribution. The species records and environmental variable values were overlaid on a grid of 6818 cells with 0.5° spatial resolution. Niche models were obtained for five types of general circulation models between ocean and atmosphere and 12 different ecological models. The ensemble ecological niche model was calculated at present and projected to past (last glacial maximum – LGM, 21 000; and mid‐Holocene – Hol, 6000 years ago) and future climate conditions (average of 2080), under the effect of climate change, in the greenhouse gas emission scenario RCP4.5. The distribution pattern of the studied species indicates an area with less environmental suitability in the LGM, followed by an expansion that began in the Hol and continued until the present period. In the future (2080), the models predicted a retraction of areas of environmental suitability, in which P. aureiflora and B. phaeacanthus, given their more restricted, marginal habitat and woody habit, present a great risk of extinction, whilst S. leucostele, A. penicillata and T. inamoena present a smaller reduction in suitable area, partly reflecting their spreading, less woody habit. Regional conservation actions for Cactaceae species and their habitat need to take these findings into account if we are to ensure the survival of these species.
Resistance to cyclic fatigue of reciprocating instruments determined at body temperature and phase transformation analysis
Authors: Scott Raymond , Arias Ana , Macorra José C. , Govindjee Sanjay , Peters Ove A.
Published: September 2019

The purpose of this study was to compare cyclic fatigue (CF) resistance of reciprocating instruments at body temperature and relate the findings to their martensitic transformation temperatures. Contemporary nickel‐titanium (NiTi) reciprocating instruments WaveOne Primary, WaveOne Gold Primary and EdgeFile X1 (n = 20 each and #25 tip diameter) were tested for CF resistance at body temperature (37 ± 1°C). Instruments were actioned according to manufacturer guidelines until fracture occurred in a simulated canal (angle of curvature = 60°, radius of curvature = 3 mm and centre of curvature = 5 mm from the tip). Time to fracture was recorded, and data analysed using Weibull analysis. Two instruments of each were tested using differential scanning calorimetry (DSC) to assess phase transformation temperatures. Reciprocating instruments manufactured with new alloys seem to be safer to CF than those manufactured with traditional M‐Wire at body temperature. Martensitic transformation temperatures seem not to relate with fatigue behaviour for reciprocating motions.
Early‐stage endometrial cancer, CTNNB1 mutations, and the relation between lymphovascular space invasion and recurrence
Authors: Imboden Sara , Tapia Coya , Scheiwiller Nadja , Kocbek Vida , Altermatt Hans J. , Janzen Jan , Mueller Michael D. , McKinnon Brett
Published: September 2019

Introduction

Women diagnosed with early‐stage (FIGO 1) endometrial cancer, grade 1 and 2 can have a good prognosis. Most of these women can be treated successfully with a hysterectomy and bilateral salpingo‐oophorectomy and without the additional adjuvant treatment that is accompanied by more risks for complications. However, when recurrence does occur, the consequences can be dire. Accurate decisions must therefore be made by surgeons to avoid either under‐ or over‐treatment. Risk and patient stratification for tailoring treatment still need further improvement. Both histopathology and genetic variants could be integrated into the decision process if relevant factors were identified.

Material and methods

Morphological features and the presence of selected genetic mutations in isolated malignant endometrial epithelial cells from these tumors were analyzed in a strictly defined cohort of FIGO 1, grade 1 and 2 low‐risk endometrial cancer. Their presence in this cohort, their relation to recurrence, and the association between histopathological features and mutations were determined. This analysis was performed using archival formalin‐fixed paraffin‐embedded tissue, complete re‐evaluation of histopathological features, laser capture microdissection of epithelial cells, and a polymerase chain reaction‐based mutational screening assay.

Results

Twenty‐one women with recurrence, after initial identification as low‐risk endometrial cancer, were compared with 20 matched control women. The histological marker of lymphovascular invasion was significantly associated with recurrence. There was also a very high prevalence of mutations in CTNNB1 gene, occurring in 50% of this cohort. PTEN mutations were also observed in 27.8% of cases and PIK3CA mutations in 22.2%; none of these mutations were significantly related to recurrence.

Conclusions

This study supports the importance of lymphovascular space invasion to identify women with significant risk for recurrence in initially low‐risk, early‐stage endometrial cancer. It also identifies CTNNB1 as a significant mutation in early‐stage disease, and although it may not represent a marker for recurrence its high prevalence in early stage disease could have relevance for both pathogenesis and early treatment.
Histological chorioamnionitis is predicted by early infant C‐reactive protein in preterm infants and correlates with neonatal outcomes
Authors: Ryan Emer , Eves Doireann , Menon Poornima Jayadev , Alnafisee Sarah , Mooney Eoghan E. , Downey Paul , Culliton Marie , Murphy John F. A. , Vavasseur Claudine , Molloy Eleanor J.
Published: September 2019

Aim

Histological chorioamnionitis (HCA) is associated with preterm birth and adverse neonatal outcomes. We evaluated the rise in C‐reactive protein (CRP) in preterm infants as a predictor of HCA severity and outcomes.

Methods

Consecutive preterm infants, born January 2009 to January 2014 in the National Maternity Hospital, Dublin, under 32 weeks' gestation or <1.5 kg birthweight, were included. Histological chorioamnionitis was staged as maternal inflammatory response, foetal inflammatory response and non‐HCA.

Results

Preterm infants (n = 518) were included with a mean gestational age 28.5 ± 2.8 weeks, birthweight 1.1 ± 0.3 kg, and 53.5% were male. Histological chorioamnionitis was found in 25.4%. Histological chorioamnionitis was present in 93.7% when CRP > 5 mg/L, 65.2% when CRP 1‐5 mg/L and in 19.4% when CRP < 1 mg/L. When both the immature to total neutrophil (IT) ratio was >0.2 and the CRP > 1 mg/L the positive predictive value and negative predictive value for HCA were 92.5% and 84.9%, respectively. Histological chorioamnionitis was associated with more resuscitation and respiratory distress syndrome (both P < .001). A CRP > 10 mg/L was associated with a foetal inflammatory response and increased early‐onset sepsis.

Conclusion

Higher early CRP was a surrogate predictor of HCA and correlated with the severity of HCA. Higher CRP and HCA were associated with adverse early outcomes.
High prevalence of attention‐deficit/hyperactivity disorder in adolescents with severe obesity seeking bariatric surgery
Authors: Leib Shiran , Gilon Mann Tal , Stein Daniel , Vusiker Irena , Tokatly Latzer Itay , Ben‐Ami Michal , Feigin Anya , Dubnov‐Raz Gal
Published: September 2019

Aim

To examine the prevalence of attention‐deficit/hyperactivity disorder (ADHD) and related post‐surgical weight loss in adolescents with severe obesity seeking bariatric surgery.

Methods

The study population included 84 adolescents (age 13‐19 years; 44 males, 40 females) with severe obesity who sought bariatric surgery at the Sheba Medical Centre in Israel during the years 2011‐2017. Anthropometric and clinical data were collected from medical records. A subgroup of 20 participants filled questionnaires that evaluated ADHD‐like symptoms, eating behaviours and quality of life. Data on adolescents that ultimately underwent surgery (n = 45) were also obtained.

Results

The prevalence of ADHD was 28.6% in adolescents seeking bariatric surgery, much higher than that of the general adolescent population of Israel (17.1%, P < .001). There were no significant differences in reductions of weight, body mass index, body mass index standard deviation scores and body fat percent between participants with or without ADHD. In the subgroup that filled questionnaires, higher scores on ADHD‐Rating Scale at baseline were associated with greater excess weight loss.

Conclusion

The prevalence of ADHD in adolescents seeking bariatric surgery was very high. Diagnosed ADHD was not related to post‐surgical weight loss, whereas baseline ADHD‐related behaviour was associated with higher post‐surgical weight loss.
Detrimental Effects of Newcomer Person‐Job Misfit on Actual Turnover and Performance: The Buffering Role of Multidimensional Person‐Environment Fit
Authors: Chi Nai‐Wen , Fang Li‐Chun , Shen Chi‐Tai , Fan Hsiao‐Ling
Published: September 2019

Researchers of person–job (P‐J) misfit have suggested that newcomers who “misfit” with their job often perform poorly and eventually leave the organization. However, no known studies have examined ways to alleviate the negative impacts of newcomers’ P‐J misfit. Based on the theory of work adjustment and the spillover model of person–environment fit, we explore whether newcomers’ fit with the social context (i.e. person–group [P‐G] and person–organization [P‐O] fit) and interpersonal relationships (i.e. person–mentor [P‐M] and person–supervisor [P‐S] fit) can buffer the detrimental outcomes of newcomers’ P‐J misfit. Using data from two field studies with time‐lag and multi‐source research designs, the results consistently show that: (1) newcomers’ P‐G fit buffered the positive relationship between their initial N–S misfit and subsequent actual turnover, (2) newcomers’ P‐M fit buffered the negative relationship between their initial D‐A misfit and subsequent task performance. Theoretical and practical implications are also discussed.
Empathy choice in physicians and non‐physicians
Authors: Cameron C. Daryl , Inzlicht Michael
Published: September 2019

Empathy in medical care has been one of the focal points in the debate over the bright and dark sides of empathy. Whereas physician empathy is sometimes considered necessary for better physician–patient interactions, and is often desired by patients, it also has been described as a potential risk for exhaustion among physicians who must cope with their professional demands of confronting acute and chronic suffering. The present study compared physicians against demographically matched non‐physicians on a novel behavioural assessment of empathy, in which they choose between empathizing or remaining detached from suffering targets over a series of trials. Results revealed no statistical differences between physicians and non‐physicians in their empathy avoidance, though physicians were descriptively more likely to choose empathy. Additionally, both groups were likely to perceive empathy as cognitively challenging, and perceived cognitive costs of empathy associated with empathy avoidance. Across groups, there were also no statistically significant differences in self‐reported trait empathy measures and empathy‐related motivations and beliefs. Overall, these results suggest that physicians and non‐physicians were more similar than different in terms of their empathic choices and in their assessments of the costs and benefits of empathy for others.
Astrocyte–microglial association and matrix composition are common events in the natural history of primary familial brain calcification
Authors: Nahar Khayrun , Lebouvier Thibaud , Andaloussi Mäe Maarja , Konzer Anne , Bergquist Jonas , Zarb Yvette , Johansson Bengt , Betsholtz Christer , Vanlandewijck Michael
Published: September 2019

Primary familial brain calcification (PFBC) is an age‐dependent and rare neurodegenerative disorder characterized by microvascular calcium phosphate deposits in the deep brain regions. Known genetic causes of PFBC include loss‐of‐function mutations in genes involved in either of three processes—platelet‐derived growth factor (PDGF) signaling, phosphate homeostasis or protein glycosylation—with unclear molecular links. To provide insight into the pathogenesis of PFBC, we analyzed murine models of PFBC for the first two of these processes in Pdgfbret/ret and Slc20a2−/− mice with regard to the structure, molecular composition, development and distribution of perivascular calcified nodules. Analyses by transmission electron microscopy and immunofluorescence revealed that calcified nodules in both of these models have a multilayered ultrastructure and occur in direct contact with reactive astrocytes and microglia. However, whereas nodules in Pdgfbret/ret mice were large, solitary and smooth surfaced, the nodules in Slc20a2−/− mice were multi‐lobulated and occurred in clusters. The regional distribution of nodules also differed between the two models. Proteomic analysis and immunofluorescence stainings revealed a common molecular composition of the nodules in the two models, involving proteins implicated in bone homeostasis, but also proteins not previously linked to tissue mineralization. While the brain vasculature of Pdgfbret/ret mice has been reported to display reduced pericyte coverage and abnormal permeability, we found that Slc20a2−/− mice have a normal pericyte coverage and no overtly increased permeability. Thus, lack of pericytes and increase in permeability of the blood–brain barrier are likely not the causal triggers for PFBC pathogenesis. Instead, gene expression and spatial correlations suggest that astrocytes are intimately linked to the calcification process in PFBC.
Ki‐67 and MCM6 labeling indices are correlated with overall survival in anaplastic oligodendroglioma, IDH1‐mutant and 1p/19q‐codeleted: a multicenter study from the French POLA network
Authors: Pouget Celso , Hergalant Sébastien , Lardenois Emilie , Lacomme Stéphanie , Houlgatte Rémi , Carpentier Catherine , Dehais Caroline , Rech Fabien , Taillandier Luc , Sanson Marc , Appay Romain , Colin Carole , Figarella‐Branger Dominique , Battaglia‐Hsu Shyue‐Fang , Gauchotte Guillaume
Published: September 2019

Anaplastic oligodendroglioma (AO), IDH‐mutant and 1p/19q codeleted (IDHmut+/1p19qcodel), is a high‐grade glioma with only limited prognostic markers. The primary objective of this study was to evaluate, by immunohistochemistry, the prognostic value of two proliferation markers, MCM6 and Ki‐67, in a large series of IDHmut+/1p19qcodel AO included in the POLA (“Prise en charge des Oligodendrogliomes Anaplasiques”) French national multicenter network. We additionally examined the transcriptome obtained from this series to understand the functional pathways dysregulated with the mRNA overexpression of these two markers. The labeling indices (LI) of MCM6 and Ki‐67 were obtained via computer‐assisted color image analyses on immunostained AO tissues of the cohort (n = 220). Furthermore, a subgroup of AO (n = 68/220) was used to perform transcriptomic analyses. A high LI of either MCM6 (≥50%) or Ki‐67 (≥15%) correlated with shorter overall survival, both in univariate (P = 0.013 and P = 0.004, respectively) and multivariate analyses (P = 0.027; multivariate Cox model including age, mitotic index, MCM6 and Ki‐67). MCM6 and Ki‐67 LI also correlated with overall survival in an additional retrospective cohort of 30 grade II IDHmut+/1p19qcodel oligodendrogliomas. The prognostic value of MCM6 mRNA level was confirmed in The Cancer Genome Atlas (TCGA) IDHmut+/1p19qcodel gliomas. The transcriptomic approach revealed that high transcriptional expressions of MCM6 and MKI67 were both linked positively with cell cycle progression, DNA replication, mitosis, pro‐neural phenotype as well as neurogenesis, and negatively with microglial cell activation, immune response, positive regulation of myelination, oligodendrocyte development, beta‐amyloid binding and postsynaptic specialization. In conclusion, the overexpression of MCM6 and/or Ki‐67 is independently associated to shorter overall survival in IDHmut+/1p19qcodel AO. These two easy‐to‐use and cost‐effective markers could thus be used concurrently in routine pathology practice. Additionally, the transcriptomic analyses showed that AO with high proliferation index have down‐regulated immune response and lower microglial cells activation, and bears pro‐neural phenotype.