bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolved, Selective Erasers of Distinct Lysine Acylations
Authors: Spinck Martin , Ecke Maria , Gasper Raphael , Neumann Heinz
Published: August 2019

Lysine acetylation, including related lysine modifications such as butyrylation and crotonylation, is a widespread post-translational modification with important roles in many important physiological processes. However, uncovering the regulatory mechanisms that govern the reverse process, deacylation, has been challenging to address, in great part because the small set of lysine deacetylases (KDACs) that remove the modifications are promiscuous in their substrate and acylation-type preference. This lack of selectivity hinders a broader understanding of how deacylation is regulated at the cellular level and how it is correlated with lysine deacylation-related diseases. To facilitate the dissection of KDACs with respect to substrate specificity and modification type, it would be beneficial to re-engineer KDACs to be selective towards a given substrate and/or modification. To dissect the differential contributions of various acylations to cell physiology, we developed a novel directed evolution approach to create selective KDAC variants that are up to 400-fold selective towards butyryl- over crotonyl-lysine substrates. Structural analyses of this non-promiscuous KDAC revealed unprecedented insights regarding the conformational changes mediating the gain in specificity. As a second case study to illustrate the power of this approach, we re-engineer the human SirT1 to increase its selectivity towards acetylated versus crotonylated substrates. These new enzymes, as well as the generic approach that we report here, will greatly facilitate the dissection of the differential roles of lysine acylation in cell physiology.

Significance Statement

Acetylation of lysine residues features numerous roles in diverse physiological processes and correlates with the manifestation of metabolic diseases, cancer and ageing. The already huge diversity of the acetylome is multiplied by variations in the types of acylation. This complexity is in stark contrast to the small set of lysine deacetylases (KDACs) present in human cells, anticipating a pronounced substrate promiscuity.

We device a strategy to tackle this disarray by creating KDAC variants with increased selectivity towards particular types of lysine acylations using a novel selection system. The variants facilitate the dissection of the differential contributions of particular acylations to gene expression, development and disease. Our structural analyses shed light on the mechanism of substrate discrimination by Sirtuin-type KDACs.
Global priorities for conservation of reptilian phylogenetic diversity in the face of human impacts
Authors: Gumbs Rikki , Gray Claudia L. , Böhm Monika , Hoffmann Michael , Grenyer Richard , Jetz Walter , Meiri Shai , Roll Uri , Owen Nisha R. , Rosindell James
Published: August 2019

Phylogenetic Diversity (PD) is increasingly recognised as an important measure that can provide information on evolutionary and functional aspects of biodiversity for conservation planning that are not readily captured by species diversity. Here we develop and analyse two new metrics that combine the effects of PD and human encroachment on species range size — one metric valuing regions and another enabling species prioritisation. We evaluate these metrics for reptiles, which have been largely neglected in previous studies, and contrast these results with equivalent calculations for all terrestrial vertebrate groups. We find that high human impacted areas unfortunately coincide with the most valuable areas of reptilian diversity, more than expected by chance. We also find that, under our species-level metric, the highest priority reptile species score far above the top mammal and bird species, and they include a disproportionate number of species with insufficient information on potential threats. Such Data Deficient species are, in terms of our metric, comparable to Critically Endangered species and may require urgent conservation attention.
Digital Natives and Dual Task: Handling It But Not Immune Against Cognitive-Locomotor Interferences
Authors: Frédéric Dierick , Fabien Buisseret , Mathieu Renson , Mae Luta Adèle
Published: August 2019

Digital natives developed in an electronic dual tasking world. This paper addresses two questions. Do digital natives respond differently under a cognitive load realized during a locomotor task in a dual-tasking paradigm and how does this address the concept of safety? We investigate the interplay between cognitive (talking and solving Raven’s matrices) and locomotor (walking on a treadmill) tasks in a sample of 17 graduate level participants. The costs of dual-tasking on gait were assessed by studying changes in stride interval time and its variability at long-range. A safety index was designed and computed from total relative change between the variability indices in the single walking and dual-task conditions. As expected, results indicate high Raven’s scores with gait changes found between the dual task conditions compared to the single walking task. Greater changes are observed in the talking condition compared to solving Raven’s matrices, resulting in high safety index values observed in 5 participants. We conclude that, although digital natives are efficient in performing the dual tasks when they are not emotional-based, modification of gait are observable. Due to the variation within participants and the observation of high safety index values in several of them, individuals that responded poorly to low cognitive loads should be encouraged to not perform dual task when executing a primate task of safety to themselves or others.
Increased soluble amyloid-beta causes early aberrant brain network hypersynchronisation in a mature-onset mouse model of amyloidosis
Authors: Ben-Nejma Inès R.H. , Keliris Aneta J. , Daans Jasmijn , Ponsaerts Peter , Verhoye Marleen , Van der Linden Annemie , Keliris Georgios A.
Published: August 2019

Background

Alzheimer’s disease (AD) is the most common form of dementia in the elderly population. Currently, no effective cure is available for AD. According to the amyloid hypothesis, the accumulation and deposition of the amyloid-beta (Aβ) peptides plays a key role in AD pathology. Soluble Aβ (sAβ) oligomers were shown to be synaptotoxic and involved in pathological hypersynchronisation of brain resting-state networks in different transgenic developmental-onset mouse models of amyloidosis. However, the impact of protein overexpression during brain postnatal development may cause additional phenotypes unrelated to AD. To address this concern, we investigated sAβ effects on functional resting-state networks in transgenic mature-onset amyloidosis Tet-Off APP (TG) mice.

Methods

TG mice and control littermates were raised on doxycycline (DOX) diet from 3d up to 3m of age to suppress transgenic Aβ production. Thereafter, longitudinal resting-state functional MRI was performed on a 9.4T MR-system starting from week 0 (3m old mice) up to 28w post DOX treatment. Ex vivo immunohistochemistry and ELISA analysis (additional mice cohort) was performed to address the development of amyloid pathology.

Results

Functional Connectivity (FC) analysis demonstrated early abnormal hypersynchronisation in the TG mice compared to the controls at 8w post DOX treatment. This effect was observed particularly across regions of the default mode-like network, known to be affected in AD. Ex vivo analyses performed at this time point confirmed a 20-fold increase in total sAβ levels and the absence of Aβ plaques in the TG mice compared to the controls. On the contrary at week 28, TG mice showed an overall hypoconnectivity, coinciding with a widespread deposition of Aβ plaques in the brain.

Conclusions

By preventing developmental influence of APP and/or sAβ during brain postnatal development, we demonstrated FC abnormalities driven by sAβ synaptotoxicity on resting state neuronal networks in mature-induced TG mice. Thus, the Tet-Off APP mouse model could be a powerful tool while used as a mature-onset model to shed light into amyloidosis mechanisms in AD. Therefore, this inducible APP expression model used in combination with early non-invasive in vivo rsfMRI readout for sAβ synaptotoxicity sets the stage for future Aβ targeting preventative treatment studies.
A theoretical model for focal seizure initiation, propagation, termination, and progression
Authors: Liou Jyun-you , Smith Elliot H. , Bateman Lisa M. , Bruce Samuel L. , McKhann Guy M. , Goodman Robert R. , Emerson Ronald G. , Schevon Catherine A. , Abbott L. F.
Published: August 2019

We developed a neural network model that can account for the major elements common to human focal seizures. These include the tonic-clonic transition, slow advance of clinical semiology and corresponding seizure territory expansion, widespread EEG synchronization, and slowing of the ictal rhythm as the seizure approaches termination. These were reproduced by incorporating usage-dependent exhaustion of inhibition in an adaptive neural network that receives global feedback inhibition in addition to local recurrent projections. Our model proposes mechanisms that may underline common EEG seizure onset patterns and status epilepticus and postulates a role for synaptic plasticity in emergence of epileptic foci. Complex patterns of seizure activity and bi-stable seizure evolution end-points arise when stochastic noise is included. With the rapid advancement of clinical and experimental tools, we believe that this can provide a roadmap and potentially a testbed for future explorations of seizure mechanisms and clinical therapies.
Essential role of Bone morphogenetic protein 15 in porcine ovarian and follicular development and ovulation
Authors: Qin Yufeng , Tang Tao , Li Wei , Liu Zhiguo , Yang Xiaoliang , Shi Xuan , Sun Guanjie , Liu Xiaofeng , Wang Min , Liang Xinyu , Cong Peiqing , Mo Delin , Liu Xiaohong , Chen Yaosheng , He Zuyong
Published: August 2019

Bone morphogenetic protein 15 (BMP15) is a multifunctional oocyte-specific secreted factor. It controls female fertility and follicular development in both species-specific and dosage-sensitive manners. Previous studies found that BMP15 played a critical role on follicular development and ovulation rate of mono-ovulatory mammalian species, but has minimal impact on poly-ovulatory mice. However, whether this is true in non-rodent poly-ovulatory species need to be validated. To investigate this question, we generated a BMP15 knockdown pig model. We found that BMP15 knockdown gilts showed markedly reduced fertility accompanied with phenotype of dysplastic ovaries containing significantly declined number of follicles, increased number of abnormal follicles, and abnormally enlarged antral follicles resulting in disordered ovulation. Molecular and transcriptome analysis revealed that knockdown of BMP15 significantly suppressed cell proliferation, differentiation, Fshr expression, leading to premature luteinization and reduced estradiol production in GCs, and simultaneously decreased the quality and meiotic maturation of oocyte. Our results provide in vivo evidences for the essential role of BMP15 in porcine ovarian and follicular development, and new insight into the complicated regulatory function of BMP15 in female fertility of poly-ovulatory species.
Locomotor suppression by a monosynaptic amygdala to brainstem circuit
Authors: Roseberry Thomas K. , Lalive Arnaud L. , Margolin Benjamin D. , Kreitzer Anatol C.
Published: August 2019

The control of locomotion is fundamental to vertebrate animal survival. Defensive situations require an animal to rapidly decide whether to run away or suppress locomotor activity to avoid detection. While much of the neural circuitry involved in defensive action selection has been elucidated, top-down modulation of brainstem locomotor circuitry remains unclear. Here we provide evidence for the existence and functionality of a monosynaptic connection from the central amygdala (CeA) to the mesencephalic locomotor region (MLR) that inhibits locomotion in unconditioned and conditioned defensive behavior in mice. We show that locomotion stimulated by airpuff coincides with increased activity of MLR glutamatergic neurons. Using retrograde tracing and ex vivo electrophysiology, we find that the CeA makes a monosynaptic connection with the MLR. In the open field, in vivo stimulation of this projection suppressed spontaneous locomotion, whereas inhibition of this projection had no effect. However, inhibiting CeA terminals within the MLR increased both neural activity and locomotor responses to airpuff. Finally, using a conditioned avoidance paradigm known to activate CeA neurons, we find that inhibition of the CeA projection increased successful escape, whereas activating the projection reduced escape. Together these results provide evidence for a new circuit substrate influencing locomotion and defensive behaviors.
Relating visual production and recognition of objects in human visual cortex
Authors: Fan Judith E. , Wammes Jeffrey D. , Gunn Jordan B. , Yamins Daniel L. K. , Norman Kenneth A. , Turk-Browne Nicholas B.
Published: August 2019

Drawing is a powerful tool that can be used to convey rich perceptual information about objects in the world. What are the neural mechanisms that enable us to produce a recognizable drawing of an object, and how does this visual production experience influence how this object is represented in the brain? Here we evaluate the hypothesis that producing and recognizing an object recruit a shared neural representation, such that repeatedly drawing the object can enhance its perceptual discriminability in the brain. We scanned participants using fMRI across three phases of a training study: during training, participants repeatedly drew two objects in an alternating sequence on an MR-compatible tablet; before and after training, they viewed these and two other control objects, allowing us to measure the neural representation of each object in visual cortex. We found that: (1) stimulus-evoked representations of objects in visual cortex are recruited during visually cued production of drawings of these objects, even throughout the period when the object cue is no longer present; (2) the object currently being drawn is prioritized in visual cortex during drawing production, while other repeatedly drawn objects are suppressed; and (3) patterns of connectivity between regions in occipital and parietal cortex supported enhanced decoding of the currently drawn object across the training phase, suggesting a potential substrate for learning how to transform perceptual representations into representational actions. Taken together, our study provides novel insight into the functional relationship between visual production and recognition in the brain.

Significance Statement

Humans can produce simple line drawings that capture rich information about their perceptual experiences. However, the mechanisms that support this behavior are not well understood. Here we investigate how regions in visual cortex participate in the recognition of an object and the production of a drawing of it. We find that these regions carry diagnostic information about an object in a similar format both during recognition and production, and that practice drawing an object enhances transmission of information about it to downstream regions. Taken together, our study provides novel insight into the functional relationship between visual production and recognition in the brain.
Chance and Necessity in the Pleiotropic Consequences of Adaptation for Budding Yeast
Authors: Jerison Elizabeth R. , Nguyen Ba Alex N. , Desai Michael M. , Kryazhimskiy Sergey
Published: August 2019

Mutations that a population accumulates during evolution in one (“home”) environment may cause fitness gains or losses in other conditions. Such pleiotropic fitness effects determine the evolutionary fate of the population in variable environments and can lead to ecological specialization. It is unclear how the pleiotropic outcomes of evolution are shaped by the intrinsic randomness of the evolutionary process and by the deterministic variation in selection pressures across environments. To address this question, we evolved 20 replicate populations of the yeastSaccharomyces cerevisiaein 11 laboratory environments and measured their fitness across multiple other conditions. We found that evolution in all home environments led to a diversity of patterns of pleiotropic fitness gains and losses, driven by multiple types of mutations. Approximately 60% percent of this variation are explained by clone’s home environment and the most common parallel genetic changes, while about 40% are attributed to the stochastic accumulation of mutations whose pleiotropic effects are unpredictable. On average, populations specialized to their home environment, but generalists also evolved in almost all conditions. Our results suggest that the mutations accumulating in a home environment incur a variety of pleiotropic effects, from costs to benefits, with different probabilities. Therefore, whether a population evolves towards a specialist or a generalist phenotype is heavily influenced by chance.
Hummingbirds budget energy flexibly in response to changing resources
Authors: Shankar Anusha , Graham Catherine H. , Canepa Joseph R. , Wethington Susan M. , Powers Donald R.
Published: August 2019

A key component of individual fitness is the ability to manage energy stores in response to variable resource availability, but because directly measuring energy budgets is difficult, daily energy management is rarely measured.

Hummingbirds' energy management is relatively simple to model compared to other endotherms because they have high mass‐specific metabolic rates and store little fat.

We determined which aspects of the hummingbird daily energy budget (i.e. thermoregulation, daytime activity costs, night‐time costs) change at the individual level in response to environmental variation.

We found that daily energy expenditure varied threefold in two populations of broad‐billed hummingbirds (Cynanthus latirostris).

Our model indicated the energy budget was distributed in the following proportions: daytime activity, 59% (range 22%–84%); thermoregulation, 23% (11%–32%); basal metabolism, 7% (3%–16%); and night‐time energy, 17% (6%–37%). Activity costs were higher at the hotter, homogeneous site and during the early‐wet season at both sites.

Increased daily energy expenditure was related to decreased nectar availability and not significantly related to temperature or bird mass. With climate change, the indirect energetic costs of shifting resources could have greater impacts on endotherm energy budgets than direct costs such as thermoregulation. Increased foraging and activity costs could decrease the energy available to birds for somatic repair and reproduction, potentially causing differential fitness across seasons and sites.

A free Plain Language Summary can be found within the Supporting Information of this article.
Linking epigenetics and biological conservation: Towards a conservation epigenetics perspective
Authors: Rey Olivier , Eizaguirre Christophe , Angers Bernard , Baltazar‐Soares Miguel , Sagonas Kostas , Prunier Jérôme G. , Blanchet Simon
Published: August 2019

Biodiversity conservation is a global issue where the challenge is to integrate all levels of biodiversity to ensure the long‐term evolutionary potential and resilience of biological systems. Genetic approaches have largely contributed to conservation biology by defining “conservation entities” accounting for their evolutionary history and adaptive potential, the so‐called evolutionary significant units (ESUs). Yet, these approaches only loosely integrate the short‐term ecological history of organisms.

Here, we argue that epigenetic variation, and more particularly DNA methylation, represents a molecular component of biodiversity that directly links the genome to the environment. As such, it provides the required information on the ecological background of organisms for an integrative field of conservation biology.

We synthesize knowledge about the importance of epigenetic mechanisms in (a) orchestrating fundamental development alternatives in organisms, (b) enabling individuals to respond in real‐time to selection pressures and (c) improving ecosystem stability and functioning.

Using practical examples in conservation biology, we illustrate the relevance of DNA methylation (a) as biomarkers of past and present environmental stress events as well as biomarkers of physiological conditions of individuals; (b) for documenting the ecological structuring/clustering of wild populations and hence for better integrating ecology into ESUs; (c) for improving conservation translocations; and (d) for studying landscape functional connectivity.

We conclude that an epigenetic conservation perspective will provide environmental managers the possibility to refine ESUs, to set conservation plans taking into account the capacity of organisms to rapidly cope with environmental changes, and hence to improve the conservation of wild populations.

A free Plain Language Summary can be found within the Supporting Information of this article.
Alternative functional trajectories along succession after different land uses in central Amazonia
Authors: Fernandes Neto Jose G. , Costa Flavia R. C. , Williamson G. Bruce , Mesquita Rita C. G.
Published: August 2019

The recovery capacity and the successional pathways of tropical forests after anthropogenic disturbance vary considerably and may depend on prior land‐use type and intensity. It is still unclear if forests subjected to high intensity impact, such as periodically burned pastures, are capable of restoring their original functional properties.

This study analysed the functional trait dynamics of the dominant species in successional trajectories following two land uses, pasture or clear‐cut, north of Manaus. Fourteen years of demographic data from the Biological Dynamics of Forest Fragments Project were used to determine the dominant species of the two successional trajectories, for which leaf area, leaf dry mass content, specific leaf area and wood density were collected, whereas seed mass was obtained from literature. Community weighted mean of each trait was weighted by basal area determined annually along succession. Prinicpal components analysis was used to analyse the extension and direction of the functional trajectories of plots.

Forests regenerating from pastures increased in wood density through successional time, but other traits did not change significantly. Succession after clear‐cut exhibited increasing leaf dry mass content and seed mass, and decreasing leaf area over time, but no change in wood density. Functional trajectories of plots after clear‐cut were more extensive and directional than those of pasture‐derived plots.

Synthesis and applications. We demonstrate how central Amazonian secondary forests subjected to different land uses show differences in functional trait trajectories, in ways parallel to previously shown changes in biomass, floristic diversity and forest structure. These results indicate that natural recovery of forest functional traits is affected by prior land‐use history, with implications for management and restoration. Thus, natural recovery of forests on abandoned pastures is much slower than clear‐cuts, even though seed sources from mature forests are very close to these areas, and the former may need intervention to counteract the diverted succession.
Deep microbial analysis of multiple placentas shows no evidence for a placental microbiome
Authors: Kuperman AA , Zimmerman A , Hamadia S , Ziv O , Gurevich V , Fichtman B , Gavert N , Straussman R , Rechnitzer H , Barzilay M , Shvalb S , Bornstein J , Ben‐Shachar I , Yagel S , Haviv I , Koren O
Published: August 2019

Objectives

To resolve the controversy regarding the presence of a microbiota in the placenta.

Design

Classical and molecular microbiological study.

Setting

All samples were collected during caesarean section.

Population

A total of 28 human placentas and six murine placentas.

Methods

All 28 human placentas were checked for 16S rRNA gene amplification products. Three locations from four selected human placentas and three ‘environmental controls’ for each placenta were placed in seven culture media. The four selected human placentas were further analysed using Gram stain, immunohistochemistry for bacteria, electron microscopy, and TaqMan RT‐qPCR. Six placentas from three SPF mice were cut into four pieces each, and further analysed for 16S rRNA gene amplification.

Main outcome measures

Microbiological and molecular evidence of bacteria.

Results

None of the placental cultures used for the full analysis, or their environmental cultures, was positive for bacterial growth. None of the other methods showed any evidence of bacteria. Immunohistochemistry showed negligible bacterial counts. None of the murine placentas showed evidence of 16S rRNA gene amplification.

Conclusions

Our results support that the fetal environment in the womb is sterile. Based on the immunohistochemistry and the limit of detection of the other methods used, if a placental microbiome exists, it is of extreme low biomass, and thus its effect on clinical phenotypes is probably minor, if it exists at all.

Tweetable abstract

Using several microbiological and molecular methods in parallel, we found no compelling evidence of bacteria in human and mouse placentas.
Body mass index, abdominal fatness, weight gain and the risk of urinary incontinence: a systematic review and dose–response meta‐analysis of prospective studies
Authors: Aune D , Mahamat‐Saleh Y , Norat T , Riboli E
Published: August 2019

Background

Adiposity has been associated with elevated risk of urinary incontinence in epidemiological studies; however, the strength of the association has differed between studies.

Objectives

To conduct a systematic literature review and dose–response meta‐analysis of prospective studies on adiposity and risk of urinary incontinence.

Search strategy

We searched PubMed and Embase databases up to 19 July 2017.

Selection criteria

Prospective cohort studies were included.

Data collection and analysis

Data were extracted by one reviewer and checked for accuracy by a second reviewer. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random effects models.

Main results

Twenty‐four prospective studies were included. The summary RR per 5 kg/m2 increment in body mass index (BMI) was 1.20 (95% CI 1.16–1.25, I2 = 62%, n = 11) for population‐based studies and 1.19 (95% CI 1.08–1.30, I2 = 87.1%, n = 8) for pregnancy‐based studies, 1.18 (95% CI 1.14–1.22, I2 = 0%, n = 2) per 10 cm increase in waist circumference and 1.34 (95% CI 1.11–1.62, I2 = 90%, n = 2) per 10 kg of weight gain. Although the test for nonlinearity was significant for BMI, P = 0.04, the association was approximately linear. For subtypes of urinary incontinence the summary RR per 5 BMI units was 1.45 (95% CI 1.25–1.68, I2 = 85%, n = 3) for frequent incontinence, 1.52 (95% CI 1.37–1.68, I2 = 34%, n = 4) for severe incontinence, 1.33 (95% CI 1.26–1.41, I2 = 0%, n = 8) for stress incontinence, 1.26 (95% CI 1.14–1.40, I2 = 70%, n = 7) for urge incontinence, and 1.52 (95% CI 1.36–1.69, I2 = 0%, n = 3) for mixed incontinence.

Conclusion

These results suggest excess weight may increase risk of urinary incontinence.

Tweetable abstract

Overweight and obesity increase the risk of urinary incontinence.
Radiation Oncology Quality Assessment Tool: A proposal for a new audit tool in modern radiation oncology
Authors: Atwell Daisy B , Booth Clemency , Vignarajah Dinesh D , Knesl Marcel , Buddle Nicole , Hoozer Marshall , Min Myo
Published: August 2019

Introduction

As a consequence of the development of improved treatment techniques and utilisation of digital records in radiation oncology, the RANZCR Peer Review Audit Tool has become outdated. The aim of this internal audit was to objectively evaluate the practice of our radiation oncology department to ensure that patients are being treated according to evidence‐based national guidelines through the use of a new self‐audit algorithm, the Radiation Oncology Quality Assessment Tool (ROQAT).

Methods

Using ROQAT, a retrospective audit was conducted of patients who received definitive treatment within the first six months (June 2017–November 2017) of opening a new radiation oncology department at the Sunshine Coast University Hospital. Data were collected from MOSAIQ® and electronic medical records.

Results

Two hundred and six patients were included. The median age was 65 years. Most commonly treated tumour streams included: breast (n = 62), skin (n = 31), colorectal (n = 25), genitourinary (n = 21) and head and neck (n = 21). Documentation was complete for all patients. Seventy‐four per cent of patients were discussed in a multidisciplinary team meeting. Fifty‐five per cent of patients were treated with inverse planning techniques. Treatment with radiation therapy was indicated in 97% of patients. Dose and fractionation were concordant with protocols in 83% of cases. Thirty‐nine per cent received concurrent chemotherapy, and of these, 93% were in accordance with protocols. More than 50% were treated according to published delineation protocols.

Conclusion

The ROQAT is a proposal for a new audit tool that reflects modern radiation therapy practice, with emphasis on compliance with evidence‐based guidelines.
Measuring Real Activity Management
Authors: Cohen Daniel , Pandit Shailendra , Wasley Charles E. , Zach Tzachi
Published: August 2019

To test hypotheses about earnings management, many studies investigate managers' manipulation of real activities (real earnings management, REM). Tests using measures of abnormal REM hinge critically on the measurement of normal real activities. Yet, there is no systematic evidence on the statistical properties of commonly used REM measures. We provide such evidence by documenting the Type I error rates and power of the test of the REM measures commonly used in the literature. We find these measures are often misspecified with Type I error rates that deviate from the nominal significance level of the test, especially in samples of firms with extreme performance or firm characteristics. We also compare the specification and power of traditional REM measures with performance‐matched REM measures to see if the latter provide better specified and more powerful tests. While performance‐matched REM measures are not immune from misspecification in all settings, in general they are better specified under the null hypothesis (i.e., in terms of Type I errors) than are traditional REM measures. Comparisons of the power to detect abnormal REM reveal that neither approach, traditional or performance‐matched, is consistently more powerful than the other in terms of detecting abnormal REM ranging from 1 to 10 percent of (lagged) total assets. The absence of a dominant approach to measure abnormal REM leads us to recommend that future researchers report results using both traditional and performance‐matched measures, so that readers are able to clearly assess the reliability of the inferences drawn about the magnitude and significance of the abnormal REM documented in a given study.
Short Sellers and Long‐Run Management Forecasts
Authors: Chen Xia , Cheng Qiang , Luo Ting , Yue Heng
Published: August 2019

We examine how short sellers affect long‐run management forecasts using a natural experiment (Regulation SHO) that relaxes short‐selling constraints on a group of randomly selected firms (referred to as pilot firms). We find that compared to other firms, the pilot firms issue more long‐run good news forecasts but do not change the frequency of long‐run bad news forecasts. The increase in good news forecasts is greater when the pilot firms have higher‐quality forecasts, greater uncertainty about firm value, or higher manager equity incentives. Overall, these results and the results of additional analyses indicate that the reduction in short‐selling constraints and the increase in short‐selling threat induce managers to enhance disclosures through more long‐run good news forecasts to discourage short sellers.
Bold Stock Recommendations: Informative or Worthless?
Authors: Palmon Dan , Sarath Bharat , Xin Hua C.
Published: August 2019

We select a small set of recommendations that lie in the upper and lower tail of the empirical distribution of divergences between a recommendation, and the consensus over the window (−30, −1) days prior to that recommendation. We classify these extremely divergent recommendations as bold, and then subdivide them into informative bold recommendations that lead other analysts (leading‐bold) and those that are ignored by other analysts (contra‐bold) based on the consensus change in the 30 days after the announcement. We focus on the information conveyed to the market by these bold, leading‐bold, and contra‐bold recommendations through their effects on cumulative abnormal returns (CAR). We find that bold recommendations are not anticipated by market participants (CARs are negative before a bold buy and positive before a bold sell). The next finding is that the market responds strongly to both leading and contra‐bold recommendations over the (0, +4)‐day window and that these reactions are stronger than that to nonbold recommendations. In contrast, over the longer (0, +30)‐day window, leading‐bold recommendations earn additional returns whereas contra‐bold ones reverse significantly due to lack of confirmation. The overall pattern is one of rational market reaction both in the short and long windows. We support the rationality of the market reaction by showing that the percentage of leading‐bold recommendations exceeds that of contra‐bold recommendations, and that these two types of recommendations cannot be separated using observable analyst characteristics such as experience or brokerage size.
Early‐onset fetal growth restriction: A systematic review on mortality and morbidity
Authors: Pels Anouk , Beune Irene M. , van Wassenaer‐Leemhuis Aleid G. , Limpens Jacqueline , Ganzevoort Wessel
Published: August 2019

Introduction

Severe early‐onset fetal growth restriction is an obstetric condition with significant risks of perinatal mortality, major and minor neonatal morbidity, and long‐term health sequelae. The prognosis of a fetus is influenced by the extent of prematurity and fetal weight. Clinical care is individually adjusted. In literature, survival rates vary and studies often only include live‐born neonates with missing rates of antenatal death. This systematic review aims to summarize the literature on mortality and morbidity.

Material and methods

A broad literature search was conducted in OVID MEDLINE from 2000 to 26 April 2019 to identify studies on fetal growth restriction and perinatal death. Studies were excluded when all included children were born before 2000 because (neonatal) health care has considerably improved since this period. Studies were included that described fetal growth restriction diagnosed before 32 weeks of gestation and antenatal mortality and neonatal mortality and/or morbidity as outcome. Quality of evidence was rated with the GRADE instrument.

Results

Of the 2604 publications identified, 25 studies, reporting 2895 pregnancies, were included in the systematic review. Overall risk of bias in most studies was judged as low. The quality of evidence was generally rated as very low to moderate, except for 3 large well‐designed randomized controlled trials. When combining all data on mortality, in 355 of 2895 pregnancies (12%) the fetus died antenatally, 192 died in the neonatal period (8% of live‐born neonates) and 2347 (81% of all pregnancies) children survived. Of the neonatal morbidities recorded, respiratory distress syndrome (34% of the live‐born neonates), retinopathy of prematurity (13%) and sepsis (30%) were most common. Of 476 children that underwent neurodevelopmental assessment, 58 (12% of surviving children, 9% of all pregnancies) suffered from cognitive impairment and/or cerebral palsy.

Conclusions

When combining the data of 25 included studies, survival in fetal growth restriction pregnancies, diagnosed before 32 weeks of gestation, was 81%. Neurodevelopmental impairment was assessed in a minority of surviving children. Individual prognostic counseling on the basis of these results is hampered by differences in patient and pregnancy characteristics within the included patient groups.
Hardscape floristics: Functional and phylogenetic diversity of parking‐lot plants
Authors: Frazee Lauren J. , Aronson Myla F. J. , Kattge Jens , Struwe Lena
Published: August 2019

Questions

The study of organisms living in extreme environments has shaped our knowledge of the deterministic and stochastic factors that contribute to community assembly. With hardscape habitats (HH), humans have created a novel land‐cover type that is physically analogous to extreme terrestrial environments such as deserts, barrens, and rocky outcrops and may harbor rare or specialist species and communities. We addressed the following questions: (a) which plant species inhabit hardscapes; (b) do hardscapes serve as a refuge for rare or specialist species; (c) how taxonomically similar are hardscape plant communities to one another and the regional species pool; (d) is phylogenetic diversity of hardscape communities different from that of the regional species pool; and (e) which functional traits and life history strategies are filtered for or against in hardscape plant communities?

Location and Methods

We surveyed the vascular plant communities of 17 asphalt parking lots in New Jersey, USA, to use as a focal hardscape habitat for this study.

Results

Parking‐lot plant communities contained 119 vascular plant taxa out of the 2,199 regional species and had a lower beta and phylogenetic diversity than the regional species pool. The parking‐lot flora had significantly higher frequencies of annuals, biennials, C4 plants, ruderal strategists, non‐natives, herbaceous plants, self‐compatible species, and species from the Caryophyllales, Asterales, Ulmaceae, and Plantaginaceae clades compared to the regional pool and contained no New Jersey threatened or endangered species.

Conclusions

Hardscape habitats may be similar to naturally occurring, extreme terrestrial environments in that they impose stringent filters on ecological communities leading to increased proportions of short‐lived and C4 plant species compared to the regional pool. Nevertheless, hardscapes are unlikely to serve as biodiversity refuges in the Northeastern USA as they create novel abiotic conditions that may be hostile to many native, rare, and specialist species.
A qualitative analysis of psychologists' views of bereavement among children with intellectual disability in Ireland
Authors: McClean Katie , Guerin Suzanne
Published: August 2019

Accessible Summary

Twelve psychologists were asked about supporting children with intellectual disabilities when a member of their family dies.

Psychologists said that these children were often left out when a family member dies.

Explanations of what had happened were often vague. People often try to protect children with intellectual disabilities by not upsetting them.

Children with intellectual disabilities often express their sadness using challenging behaviours or by going quiet.

The psychologists worked mainly with the parents of the child.

The psychologists wanted to see more education on emotions for children with intellectual disabilities.

Background

The present study investigated psychologists’ views of the experience of death and bereavement among children with intellectual disabilities.

Materials and Methods

Twelve psychologists with experience of working with children with intellectual disabilities (Educational = 2, Clinical = 8, and Behavioural analysts = 2; average years of experience = 24 years, SD = 10.4) completed semi‐structured interviews and thematic analysis was conducted on the data.

Results

The results indicated that psychologists were in favour of concrete and factual explanations of death for children with intellectual disabilities, as opposed to metaphorical or vague explanations. Psychologists reported that intellectual disability did not prevent the child from experiencing grief, but did impact their expression of grief. The challenges identified by psychologists included overcoming assumptions about the capabilities of a child with intellectual disability to understand and experience grief, enabling and encouraging families to includethe child in the bereavement process. Finally, the psychologists emphasised the need to normalise grief and make it part of life.

Conclusion

This study benefitted from a sample rich in relevant experience and from the rigorous process of thematic analysis. However, this project can only be considered a proxy study as there is no way to be certain the views of the psychologists actually reflect the experiences of grieving children. This is an area for further research.
P2X7 activation enhances skeletal muscle metabolism and regeneration in SOD1G93A mouse model of amyotrophic lateral sclerosis
Authors: Fabbrizio Paola , Apolloni Savina , Bianchi Andrea , Salvatori Illari , Valle Cristiana , Lanzuolo Chiara , Bendotti Caterina , Nardo Giovanni , Volonté Cinzia
Published: August 2019

Muscle weakness plays an important role in neuromuscular disorders comprising amyotrophic lateral sclerosis (ALS). However, it is not established whether muscle denervation originates from the motor neurons, the muscles or more likely both. Previous studies have shown that the expression of the SOD1G93A mutation in skeletal muscles causes denervation of the neuromuscular junctions, inability to regenerate and consequent atrophy, all clear symptoms of ALS. In this work, we used SOD1G93A mice, a model that best mimics some pathological features of both familial and sporadic ALS, and we investigated some biological effects induced by the activation of the P2X7 receptor in the skeletal muscles. The P2X7, belonging to the ionotropic family of purinergic receptors for extracellular ATP, is abundantly expressed in the healthy skeletal muscles, where it controls cell duplication, differentiation, regeneration or death. In particular, we evaluated whether an in vivo treatment in SOD1G93A mice with the P2X7 specific agonist 2′(3′)‐O‐(4‐Benzoylbenzoyl) adenosine5′‐triphosphate (BzATP) just before the onset of a pathological neuromuscular phenotype could exert beneficial effects in the skeletal muscles. Our findings indicate that stimulation of P2X7 improves the innervation and metabolism of myofibers, moreover elicits the proliferation/differentiation of satellite cells, thus preventing the denervation atrophy of skeletal muscles in SOD1G93A mice. Overall, this study suggests that a P2X7‐targeted and site‐specific modulation might be a strategy to interfere with the complex multifactorial and multisystem nature of ALS.
Pterostilbene restores carbapenem susceptibility in New Delhi metallo‐β‐lactamase‐producing isolates by inhibiting the activity of New Delhi metallo‐β‐lactamases
Authors: Liu Shui , Zhang Jian , Zhou Yonglin , Hu Naiyu , Li Jiyun , Wang Yang , Niu Xiaodi , Deng Xuming , Wang Jianfeng
Published: August 2019

Background and Purpose

Bacteria producing New Delhi metallo‐β‐lactamase‐1 (NDM‐1) are an increasing clinical threat. NDM‐1 can inactivate almost all β‐lactams and is not sensitive to any existing β‐lactamase inhibitors. To identify effective inhibitors of the NDM‐1 enzyme and clarify the mechanism of action, a “lead compound” for developing more potent NDM‐1 inhibitors needs to be provided.

Experimental Approach

Natural compounds were tested by enzyme inhibition screening to find potential inhibitors. MIC assays, growth curve assays, and time‐kill assays were conducted to evaluate the in vitro antibacterial activity of pterostilbene and the combination of pterostilbene and meropenem. A murine thigh model and a mouse pneumonia model were used to evaluate the in vivo efficacy of combined therapy. Molecular modelling and a mutational analysis were used to clarify the mechanism of action.

Key Results

Pterostilbene significantly inhibited NDM‐1 hydrolysis activity in enzyme inhibition screening assays and effectively restored the effectiveness of meropenem in vitro with NDM‐expressing isolates in antibacterial activity assays. In addition, the combined therapy effectively reduced the bacterial burden in a murine thigh model and protected mice from pneumonia caused by Klebsiella pneumoniae. By means of molecular dynamics simulation, we observed that pterostilbene localized to the catalytic pocket of NDM‐1, hindering substrate binding to NDM‐1 and reducing NDM‐1 activity.

Conclusions and Implications

These findings indicated that pterostilbene combined with meropenem may offer a new safe and potential “lead compound” for the further development of NDM‐1 inhibitors.
Role of diet and gut microbiota in multiple sclerosis: New findings on the role of high‐salt intake in induction of neuroinflammation
Authors: Abdoli Amir , Mofazzal Jahromi Mirza Ali , Roustazadeh Abazar
Published: August 2019

Multiple etiological factors are involved in the pathogenesis of multiple sclerosis (MS). The recent study by Okuno et al. provides an insight into the interaction of gut microbiota and immune cells in MS. However, new findings showed that a high‐salt diet is involved in the induction of severe neuroinflammation through the aggravation of T helper 17 pathways and their inflammatory cytokines. The synergistic effects of high‐salt and high‐fat intake in the induction of inflammatory reactions are also plausible. This article is a snapshot of the recent findings about the putative role of high‐salt intake in the pathogenesis of MS.
The Principles and Ethics of Including Children with Disability in Child Research
Authors: Jenkin Elena , Wilson Erin , Campain Robert , Clarke Matthew
Published: August 2019

This paper provides a set of principles and ethics, developed in collaboration between Pacific‐ and Australian‐based researchers, to guide research practice in a project enabling the self‐reporting of children with disability in Vanuatu and Papua New Guinea (PNG). The paper presents both a summary of academic literature relating to these principles and ethics, as well as their succinct ‘translation’ into a set of action statements for researchers working with children with disability. The paper offers a base for further development by others to guide research practice and foster the autonomous participation of children with disability in developing countries.