bluuebunny/crossref_metadata_2025 huggingface dataset:
Incorporating Specific Functional Strength Integration Techniques to Improve Functional Performance for Veterans After Total Hip Arthroplasty: Protocol for a Randomized Clinical Trial
Authors: Judd Dana L , Cheuy Victor A , Forster Jeri E , Christiansen Cory L , Stevens-Lapsley Jennifer E
Published: July 2019

Background

Total hip arthroplasty (THA) is a common procedure, yet persistent deficits in functional performance exist after surgery. These deficits may be related to movement compensations observed after THA, which negatively affect quality of life and may increase morbidity and health care utilization, including in the veteran population. However, the best rehabilitative approach to remediating movement compensations and physical function deficits has not been determined.

Objective

The objective is to determine if a functional strength integration intervention (FSI), as part of a post-THA rehabilitation program, improves movement compensation, physical function, muscle strength, and self-reported outcome measures more than a control group (CON) undergoing a standard of care exercise program.

Design

This is a 2-arm randomized, controlled clinical trial.

Setting

The Veteran Affairs outpatient physical therapy clinics and academic research laboratory will be the settings.

Participants

One hundred veterans undergoing THA for hip osteoarthritis will be included in the study.

Interventions

Participants will be randomized to either the FSI or CON group and participate in visits of physical therapy over 8 weeks. The FSI protocol will include targeted exercise to improve muscular control and stability around the hip and trunk to minimize movement compensation during daily activity combined with progressive resistance exercise. The CON protocol will include patient education, flexibility activity, and low load resistance exercise.

Measurements

Functional performance, muscle strength and endurance, and self-reported outcomes will be measured at baseline (prior to surgery), midway through intervention (6 weeks after surgery), at the end of intervention (10 weeks after surgery), and 26 weeks after THA.

Limitations

The inability to blind treating therapists to study arm allocation is a limitation.

Conclusions

The proposed study aims to determine if targeted FSI can affect movement compensation to improve functional outcomes after THA more than traditional rehabilitation paradigms.
From Depletion to Regeneration: Addressing Structural and Physical Violence in Post-Conflict Economies
Authors: Rai Shirin M , True Jacqui , Tanyag Maria
Published: July 2019

Drawing on depletion through social reproduction and political economy of violence against women (PEVAW) approaches, we show how the context of violence intensifies the depletion of women’s lives as they labor to meet their household needs; and how this depletion heightens their vulnerability to violence in conflict-affected contexts and inhibits their roles in peacebuilding. We propose the concept of the “regenerative state,” as a post-conflict moment of openness when state policy underpinned by attention to issues of depletion, social reproduction, and violence against women can help reshape gendered power relations in post-conflict transitions.
Morpho-Pathological and Global Transcriptomic Analysis Reveals the Robust Nonhost Resistance Responses in Chickpea Interaction with Alternaria brassicae
Authors: Fatima Urooj , Bhorali Priyadarshini , Senthil-Kumar Muthappa
Published: July 2019

Alternaria blight, caused by Alternaria brassicae, causes considerable yield loss in Brassica crops. While several blight-resistant varieties have been developed using resistance sources from host germplasm, none of them are entirely successful in imparting durable resistance. This has prompted the exploration of novel gene pools of nonhost plant species. Nonhost resistance (NHR) is a durable form of resistance, comprising pre- and postinvasion layers of defense. We aimed to identify the molecular basis of NHR to A. brassicae and identify the layers of NHR operating in a nonhost, chickpea (Cicer arietinum). To elucidate the layers of NHR operating against A. brassicae, we compared the histopathology and infection patterns of A. brassicae in C. arietinum and Brassica juncea. Delayed conidial germination, impeded hyphal growth, suppressed appressorium formation, and limited hyphal penetration occurred in the nonhost plant compared with the host plant, implying the involvement of the preinvasion layer of NHR in C. arietinum. Next, we investigated the molecular basis of robust NHR, in C. arietinum challenged with A. brassicae, by microarray-based global transcriptome profiling. Genes involved in stomatal closure, cuticular wax biosynthesis, cell-wall modification, and secondary metabolite production (contributing to preinvasion NHR) as well as reactive oxygen species (ROS) and cell death (contributing to postinvasion NHR) were found to be upregulated. Consistent with transcriptomic analysis, the morpho-pathological analysis revealed stomatal closure, ROS accumulation, and localized cell death in C. arietinum as the defense strategies against A. brassicae. Thus, we identified NHR-contributing genes with potential applications in blight resistance gene transfer to B. juncea.
Distribution and Pathogenicity of Colletotrichum Species Associated With Mango Anthracnose in Mexico
Authors: Tovar-Pedraza J. M. , Mora-Aguilera J. A. , Nava-Díaz C. , Lima N. B. , Michereff S. J. , Sandoval-Islas J. S. , Câmara M. P. S. , Téliz-Ortiz D. , Leyva-Mir S. G.
Published: July 2019

Mango anthracnose, caused by Colletotrichum spp., is the most significant disease of mango (Mangifera indica L.) in almost all production areas around the world. In Mexico, mango anthracnose has only been attributed to C. asianum and C. gloeosporioides. The aims of this study were to identify the Colletotrichum species associated with mango anthracnose symptoms in Mexico by phylogenetic inference using the ApMat marker, to determine the distribution of these species, and to test their pathogenicity and virulence on mango fruits. Surveys were carried out from 2010 to 2012 in 59 commercial orchards in the major mango growing states of Mexico, and a total of 118 isolates were obtained from leaves, twigs, and fruits with typical anthracnose symptoms. All isolates were tentatively identified in the C. gloeosporioides species complex based on morphological and cultural characteristics. The Bayesian inference phylogenetic tree generated with Apn2/MAT intergenic spacer sequences of 59 isolates (one per orchard) revealed that C. alienum, C. asianum, C. fructicola, C. siamense, and C. tropicale were associated with symptoms of mango anthracnose. In this study, C. alienum, C. fructicola, C. siamense, and C. tropicale are reported for the first time in association with mango tissues in Mexico. This study represents the first report of C. alienum causing mango anthracnose worldwide. The distribution of Colletotrichum species varied among the mango growing states from Mexico. Chiapas was the only state in which all five species were found. Pathogenicity tests on mango fruit cultivar Manila showed that all Colletotrichum species from this study could induce anthracnose lesions. However, differences in virulence were evident among species. C. siamense and C. asianum were the most virulent, whereas C. alienum and C. fructicola were considered the least virulent species.
Bacteria Associated with Onion Foliage in Michigan and Their Copper Sensitivity
Authors: Tho Kim E. , Brisco-McCann Elizabeth , Wiriyajitsomboon Prissana , Sundin George W. , Hausbeck Mary K.
Published: July 2019

Bacterial stalk and leaf necrosis of onion, Allium cepa L., is a concern of Michigan producers. Plants with symptoms of bacterial stalk and leaf necrosis were collected in 2013 and 2014 from 17 fields in six Michigan counties. Bacterial isolates were identified using Biolog and confirmed by sequencing the 16s rDNA gene. From a total of 414 isolates, 10 bacterial species were identified. Pantoea agglomerans (42.5%), Pantoea ananatis (17.4%), and Enterobacter cowanii (7.5%) were most prevalent and were tested for pathogenicity on onion foliage and bulbs. More P. ananatis isolates (92%) were pathogenic on seedlings than P. agglomerans or E. cowanii isolates (approximately 50%). When 197 bacterial isolates were tested for sensitivity to copper hydroxide (200 µg/ml), 41% of P. agglomerans isolates were found to be tolerant to copper hydroxide, whereas 19 and 22% of P. ananatis and E. cowanii isolates were tolerant, respectively. Identifying the bacterial species associated with foliar disease symptoms on onions in Michigan, their pathogenicity and tolerance to copper is an important step in developing improved disease management strategies.
Phyllachora maydis, Causal Agent of Tar Spot on Corn, Can Overwinter in Northern Illinois
Authors: Kleczewski Nathan M. , Donnelly James , Higgins Russ
Published: July 2019

Tar spot on corn (Zea mays L.), caused by the obligate fungal pathogen Phyllachora maydis Maubl., was first detected in the United States in 2015. Currently, the disease has been detected in 172 counties across Florida, Illinois, Indiana, Iowa, Michigan, Ohio, and Wisconsin. Although observations indicate that P. maydis likely overwinters in the region, this has not been conclusively proven. Samples of corn foliage heavily infected with P. maydis were recovered from two fields in northern Illinois in March 2019. Ascospores were extracted and were applied to corn seedlings under controlled greenhouse conditions. Symptoms of tar spot were observed 17 days after inoculation, and ascospores were extracted from stromata to confirm P. maydis. This is the first conclusive proof that P. maydis can overwinter the United States. We also present a preliminary greenhouse method that, if optimized, may be used to study this pathosystem under controlled conditions.
Attitudes Towards Physicians Requiring Remediation: One-of-Us or Not-Like-Us?
Authors: Bourgeois-Law Gisèle , Teunissen Pim W. , Varpio Lara , Regehr Glenn
Published: July 2019

Purpose

The data for this paper were collected as part of a larger project exploring how the medical profession conceptualizes the task of supporting physicians struggling with clinical competency issues. In this paper, the authors focus on a topic that has been absent in the literature thus far—how physicians requiring remediation are perceived by those responsible for organizing remediation and by their peers in general.

Method

Using a constructivist grounded theory approach, the authors conducted semistructured interviews with 17 remediation stakeholders across Canada. Given that in Canada health is a provincial responsibility, the authors purposively sampled stakeholders from across provincial and language borders and across the full range of organizations that could be considered as participating in the remediation of practicing physicians.

Results

Interviewees expressed mixed, sometimes contradictory, emotions toward and perceptions of physicians requiring remediation. They also noted that their colleagues, including physicians in training, were not always sympathetic to their struggling peers.

Conclusions

The medical profession’s attitude toward those who struggle with clinical competency—as individuals and as a whole—is ambivalent at best. This ambivalence grows out of psychological and cultural factors and may be an undiscussed factor in the profession’s struggle to deal adequately with underperforming members. To contend with the challenge of remediating practicing physicians, the profession needs to address this ambivalence and its underlying causes.
Reconsidering Basic: Integrating Social and Behavioral Sciences to Support Learning
Authors: Chaudhary Zarah K. , Mylopoulos Maria , Barnett Rachael , Sockalingam Sanjeev , Hawkins Michael , O’Brien J. Darcy , Woods Nicole N.
Published: July 2019

Purpose

The integration of basic science mechanistic knowledge (pathophysiology and etiology) with clinical features (signs and symptoms) during learning leads to robust cognitive representations in novices and supports the development of clinical reasoning, including better diagnostic accuracy and later learning of related concepts. However, previous studies have used a limited scope of traditional biomedical sciences, including biochemistry, anatomy, and physiology. The use of extended forms of foundational knowledge, including behavioral and sociological sciences, that have been proposed to support learning and performance in complex health systems remains unexplored.

Method

Thirty-three first-year medical students from the University of Toronto MD Program participated in the study. The effect of integrated extended basic science (EBS) learning was compared with that of clinically focused instruction on an initial assessment of diagnosis using clinical vignettes and a “preparation for future learning” assessment (PFLA) to assess learning of new related content in medical psychiatry (co-occurring physical and mental health conditions).

Results

Both forms of instruction supported the development of diagnostic ability on initial assessment (t[30] = 1.20, P = .24). On the PFLA, integrated instruction of extended forms of basic science led to superior performance on assessing complex patients’ health care needs (t[30] = 2.70, P < .05).

Conclusions

Similar to previous studies using integration of biomedical sciences, the integration of EBS can enhance later learning of new related concepts. These results have implications for curriculum design to support development of expert clinical reasoning.
Determination of Perampanel in Dried Plasma Spots: Applicability to Therapeutic Drug Monitoring
Authors: Franco Valentina , Baruffi Katia , Marchiselli Roberto , Crema Francesca , Fattore Cinzia , Romigi Andrea , De Giorgis Valentina , Tartara Elena , Elia Maurizio , D'Avolio Antonio , Perucca Emilio
Published: July 2019

Background:

Although therapeutic drug monitoring of antiepileptic drugs is typically based on the analysis of plasma samples, alternative matrices, such as dried plasma spots (DPSs), may offer specific advantages. The aims of this work were to (1) develop and validate a bioanalytical method for the quantitative determination of the second-generation antiepileptic drug perampanel in DPSs; (2) assess short- and long-term stability of perampanel in DPSs; and (3) test the clinical applicability of the developed method.

Methods:

Two hundred microliters of plasma were dispensed on a glass paper filter and dried. Glass paper filter discs were then inserted into clean tubes. After addition of the internal standard (ie, promethazine), the analytes were extracted with 5-mL methanol, dried at room temperature (23 ± 2°C), and reconstituted. Separation and quantification were achieved on 2 serial reverse-phase monolithic columns connected to an UV detector (λ = 320 nm).

Results:

Calibration curves were linear in the validated concentration range (25–1000 ng/mL). Intraday and interday accuracy were in the range of 99.2%–111.4%, whereas intraday and interday precision (coefficient of variation) ranged from 2.8% to 8.6%. The lowest limit of quantitation was 25 ng/mL. The stability of the analyte in DPSs was assessed and confirmed under different storage conditions. Perampanel concentrations estimated in DPS samples from patients receiving therapeutic doses were equivalent to those measured in plasma samples.

Conclusions:

This simple method enables the quantitation of perampanel in DPSs with adequate accuracy, precision, specificity, and sensitivity. The short- and long-term stabilities of perampanel in DPSs are highly beneficial for sample shipment or storage at ambient temperature. Moreover, DPSs decreases the costs associated with storage and transportation compared with conventional wet samples.
Idiopathic Conjunctival Calcinosis Associated With an Intradermal and Subepithelial Nevus of the Eyelid Margin.
Authors: Charles Norman C. , Belinsky Irina
Published: July 2019

A 37-year-old woman underwent excision of a congenital melanocytic nevus of the right lower eyelid margin for cosmetic reasons. She suffered from a severe dry eye syndrome which was partially alleviated with various topical eye drops. Histopathology of the excised tissue displayed flecks of calcium that were present within the immediate subepithelial conjunctival fibrous tissue but not the nevocytes or the cutaneous surface. Unlike calcinosis cutis, wherein calcium is deposited within the cutaneous dermis, calcification of the conjunctival substantia propria is rare and may be related to the dry eye state.
Dacryoadenitis Caused by Blastomycosis: A Case Report
Authors: Kwan Changyow C. , Prager Alisa J. , Huang Russell M. , Bryar Paul J. , Thyparampil Preeti J.
Published: July 2019

This is the first case of histopathologically proven blastomycosis involving the lacrimal gland. A 51-year-old woman with a history of disseminated blastomycosis involving her lungs and skin, on oral itraconazole, presented with 3 days of right upper eyelid swelling, erythema, and pain concerning for recurrent dacryoadenitis. MRI showed enlargement of the right lacrimal gland with a cystic lesion at the anterior aspect of the gland with a radiographic differential diagnosis of abscess versus cyst. After no improvement with intravenous antibiotics, orbitotomy with lacrimal gland biopsy and incision and drainage of the cystic lesion were performed. Culture and pathology of the drained fluid demonstrated an abscess with both viable and nonviable broad-based budding yeast consistent with partially treated blastomycosis. The patient’s symptoms improved after the surgery and continued itraconazole therapy.
Esophageal Capsule Endoscopy in Children and Young Adults With Portal Hypertension
Authors: Pai Anita K. , Jonas Maureen M. , Fox Victor L.
Published: July 2019

Objectives:

Variceal hemorrhage (VH) is a serious complication of portal hypertension (PH). We evaluated the feasibility, safety, and clinical impact of esophageal capsule endoscopy (ECE) in pediatric and young adult patients with known or suspected PH.

Methods:

Children and young adults with PH at Boston Children's Hospital (2005–2017) were offered ECE for variceal screening or surveillance. Patient histories, ECE findings, and clinical outcomes were reviewed retrospectively.

Results:

One hundred and forty‐nine ECE studies were performed in 98 patients (57.1% male patients) using 3 ECE devices for variceal screening (66.5%) or surveillance (33.5%). Three readers interpreted the studies (88.3%, 10.3%, and 1.4%, respectively). Median age was 16 years (IQR 13.7–18.5). One hundred and three ECE studies involved patients <18 years (69.1%). Fifteen patients (29 ECE studies) had a gastrointestinal (GI) bleeding (GIB) history, 5 in the preceding 12 months.

Sixty‐two ECE studies (44.9%) detected varices: 59 esophageal (40 small, 19 medium/large), 17 gastric, 6 duodenal. Other findings included: portal gastropathy (25, 18.1%), esophagitis (20, 14.5%), ulcers (5, 3.6%), erosions (31, 22.5%), heterotopic tissue (13, 9.4%), blood flecks (23, 16.7%), and mucosal scars (17, 12.3%). There were 2 transient capsule retentions and no major adverse events.

ECE led to follow‐up EGD in 11 (7 variceal banding) and medication initiation in 12 (4 proton‐pump inhibitor, 7 nonselective beta blocker, 2 other) cases. Four patients had GIB within 12 months of ECE.

Conclusion:

ECE is a feasible alternative to EGD for screening and surveillance of esophageal varices in children and young adults.
Further Exploration of Personal and Social Functioning
Authors: Talevi Dalila , Pacitti Francesca , Costa Manuela , Rossi Alessandro , Collazzoni Alberto , Crescini Claudio , Rossi Rodolfo
Published: July 2019

Social functioning (SF) has mainly been studied in major psychoses in relation to symptom severity, but other factors may interfere with the achievement of a functional remission. The aim of this study is to explore interpersonal violence (IV), service engagement (SE), and social network (SN), together with demographics, as predictors of SF in a sample of subjects with severe mental illness (SMI). Consecutive adult inpatients were evaluated using self-report and clinician-rated questionnaires. Findings suggest that IV, SE, SN, male sex, and illness duration explained 39.1% of SF variance in people affected by SMI. IV was the strongest predictor, followed by sex and duration of illness. Lifetime expression of violence is a stronger predictor than lifetime exposure to violence. Positive SE and SN were found to predict SF, whereas age was not associated. This study underlines the need of other non-symptom-related variables for the comprehension of SF in mental disorders.
Coping Among Parents of Teens With Inflammatory Bowel Disease
Authors: Carlsen Katrine , Phan Becky L. , Pittman Nanci , Benkov Keith , Dubinsky Marla C. , Keefer Laurie
Published: July 2019

Parents of teens with inflammatory bowel disease must prepare their children for independent disease self-management. This study characterizes the stressors and coping strategies adopted among parents of teens with inflammatory bowel disease. Teens aged 16–22 years with inflammatory bowel disease who were consecutively seen by a pediatric gastroenterologist prior to transition to adult-centered care and their parents completed sociodemographic data, and two validated questionnaires for coping (Coping Health Inventory for Parents) and stress (Pediatric Inventory for Parents). Sixty-six patient–parent pairs were enrolled in this study—impairment was highest in role function (e.g., trying to attend to the needs of other family members, being unable to go to work, and feeling uncertain about how to maintain consistent discipline). These concerns seemed to be most pronounced among parents of children 18 years and older (χ2 (df) = 1, p = .04) with Crohn disease (χ2 (df) = 1, p = .02). The top five listed concerns differed depending on the caregiver's gender. Parents of teens with inflammatory bowel disease are concerned about parenting role function. Parents of teens 18 years and older with Crohn disease reported the highest stress. Caregiver gender differences were noted.
The ecological and epidemiological consequences of reproductive interference between the vectors
Aedes aegypti
and
Aedes albopictus
Authors: Paton Robert S. , Bonsall Michael B.
Published: July 2019

Vector ecology is integral to understanding the transmission of vector-borne diseases, with processes such as reproduction and competition pivotal in determining vector presence and abundance. The arbovirus vectors
Aedes aegypti
and
Aedes albopictus
compete as larvae, but this mechanism is insufficient to explain patterns of coexistence and exclusion. Inviable interspecies matings—known as reproductive interference—is another candidate mechanism. Here, we analyse mathematical models of mosquito population dynamics and epidemiology which include two
Aedes
-specific features of reproductive interference. First, as these mosquitoes use hosts to find mates, reproductive interference will only occur if the same host is visited. Host choice will, in turn, be determined by behavioural responses to host availability. Second, females can become sterilized after mis-mating with heterospecifics. We find that a species with an affinity for a shared host will suffer more from reproductive interference than a less selective competitor. Costs from reproductive interference can be ‘traded-off’ against costs from larval competition, leading to competitive outcomes that are difficult to predict from empirical evidence. Sterilizations of a self-limiting species can counterintuitively lead to
higher
densities than a competitor suffering less sterilization. We identify that behavioural responses and reproductive interference mediate a concomitant relationship between vector ecological dynamics and epidemiology. Competitors with opposite behavioural responses can maintain disease where human hosts are rare, due to vector coexistence facilitated by a reduced cost from reproductive interference. Our work elucidates the relative roles of the competitive mechanisms governing
Aedes
populations and the associated epidemiological consequences.
Convolution quadrature methods for time-domain scattering from unbounded penetrable interfaces
Authors: Labarca Ignacio , Faria Luiz M. , Pérez-Arancibia Carlos
Published: July 2019

This paper presents a class of boundary integral equation methods for the numerical solution of acoustic and electromagnetic time-domain scattering problems in the presence of unbounded penetrable interfaces in two spatial dimensions. The proposed methodology relies on convolution quadrature (CQ) schemes and the recently introduced windowed Green function (WGF) method. As in standard time-domain scattering from bounded obstacles, a CQ method of the user's choice is used to transform the problem into a finite number of (complex) frequency-domain problems posed, in our case, on the domains containing unbounded penetrable interfaces. Each one of the frequency-domain transmission problems is then formulated as a second-kind integral equation that is effectively reduced to a bounded interface by means of the WGF method—which introduces errors that decrease super-algebraically fast as the window size increases. The resulting windowed integral equations can then be solved by means of any (accelerated or unaccelerated) off-the-shelf Nyström or boundary element Helmholtz integral equation solvers capable of handling complex wavenumbers with large imaginary part. A high-order Nyström method based on Alpert's quadrature rules is used here. A variety of CQ schemes and numerical examples, including wave propagation in open waveguides as well as scattering from multiple layered media, demonstrate the capabilities of the proposed approach.
Possible adverse impact of contaminants on Atlantic cod population dynamics in coastal ecosystems
Authors: Ono Kotaro , Knutsen Halvor , Olsen Esben M. , Ruus Anders , Hjermann Dag Ø. , Chr. Stenseth Nils
Published: July 2019

While many in-laboratory ecotoxicological studies have shown the adverse impact of pollutants to the fitness of an individual, direct evidence from the field on the population dynamics of wildlife animals has been lacking. Here, we provide empirical support for a negative effect of pollution on Atlantic cod (
Gadus morhua
) population dynamics in coastal waters of Norway by combining unique time series of juvenile cod abundance, body size, environmental concentration of toxic contaminants and a spatially structured population dynamics model. The study shows that mercury concentration might have decreased the reproductive potential of cod in the region despite the general decline in the environmental concentration of mercury, cadmium and hexachlorobenzene since the implementation of national environmental laws. However, some cod populations appeared to be more resistant to mercury pollution than others, and the strength and shape of mercury effect on cod reproductive potential was fjord-specific. Additionally, cod growth rate changed at scales smaller than fjords with a gradient related to the exposure to the open ocean and offshore cod. These spatial differences in life-history traits emphasize the importance of local adaptation in shaping the dynamics of local wildlife populations. Finally, this study highlights the possibility to mitigate pollution effects on natural populations by reducing the overall pollution level, but also reveals that pollution reduction alone is not enough to rebuild local cod populations. Cod population recovery probably requires complementary efforts on fishing regulation and habitat restoration.
Genetic inheritance and environment determine endocrine plasticity to urban living
Authors: Ouyang Jenny Q. , Baldan Davide , Munguia Crystal , Davies Scott
Published: July 2019

As urban areas continue to expand globally, understanding how and why species respond to novel habitats becomes increasingly important. Knowledge of the mechanisms behind observed phenotypic changes in urban animals will enable us to better evaluate the impact of urbanization on current and future generations of wildlife. Physiological changes, such as those involved in the endocrine stress response, may allow individuals to inhabit and thrive in urbanized areas, but it is currently unknown how these changes arise in natural populations. In this study, we performed a four-way cross-foster experiment in free-living house wren chicks,Troglodytes aedon, to disentangle whether differences in baseline corticosterone between urban and rural individuals are a result of genetic and/or plastic mechanisms during development. We found that urban chicks already had higher corticosterone levels than their rural counterparts on the day they hatched, which suggests a possible genetic component to the corticosterone phenotype. However, rural offspring that were moved to an urban environment significantly increased their corticosterone levels, mimicking those of urban offspring. Our findings suggest that, although differences in baseline corticosterone concentrations between urban and rural individuals may have a genetic component, plasticity plays a pivotal role and can modify the corticosterone phenotype in response to the environment experienced in the first two weeks of life.
Lifestyle-intervention-induced reduction of abdominal fat is reflected by a decreased circulating glycerol level and an increased HDL diameter
Authors: Beekman Marian , Schutte Bianca A.M. , van den Akker Erik B. , Noordam Raymond , Dibbets-Schneider Petra , de Geus-Oei Lioe-Fee , Deelen Joris , van de Rest Ondine , van Heemst Diana , Feskens Edith J.M. , Slagboom P. Eline
Published: July 2019

SCOPE

Abdominal obesity is one of the main modifiable risk factors of age-related cardiometabolic disease. Cardiometabolic disease risk and its associated high abdominal fat mass, high cholesterol and glucose concentrations can be reduced by a healthier lifestyle. Hence, our aim is to understand the relation between lifestyle-induced changes in body composition, and specifically abdominal fat, and accompanying changes in circulating metabolic biomarkers.

Methods and results

We used the data from the Growing Old Together (GOTO) study, in which 164 older adults (mean age 63 years, BMI 23-35 kg/m2) changed their lifestyle during 13 weeks by 12.5% caloric restriction plus 12.5% increase in energy expenditure. We show that levels of circulating metabolic biomarkers, even after adjustment for body mass index, specifically associate with abdominal fat mass. Next, we show that the applied lifestyle intervention mainly reduces abdominal fat mass (−2.6%, SD=3.0) and that this reduction, when adjusted for general weight loss, is highly associated with decreased circulating glycerol concentrations and increased HDL diameter.

Conclusions

The lifestyle-induced reduction of abdominal fat mass is particularly associated, independent of body mass index or general weight loss, with associated with decreased circulating glycerol concentrations and increased HDL diameter.
Intraspecific genetic variation underlying postmating reproductive barriers between species in the wild tomato clade (Solanumsect.Lycopersicon)
Authors: Jewell Cathleen P , Zhang Simo , Gibson Matthew J. S. , Tovar-Méndez Alejandro , McClure Bruce , Moyle Leonie C
Published: July 2019

A goal of speciation genetics is to understand how the genetic components underlying interspecific reproductive barriers originate within species. Unilateral incompatibility (UI) is a postmating prezygotic barrier in which pollen rejection in the female reproductive tract (style) occurs in only one direction of an interspecific cross. Natural variation in the strength of UI has been observed among populations within species in the wild tomato clade. In some cases, molecular loci underlying self-incompatibility (SI) are associated with this variation in UI, but the mechanistic connection between these intra- and inter-specific pollen rejection behaviors is poorly understood in most instances. We generated an F2population between SI and SC genotypes of a single species,Solanum pennellii, to examine the genetic basis of intraspecific variation in the strength of UI against other species, and to determine whether loci underlying SI are genetically associated with this variation. We found that F2individuals vary in the rate at which UI rejection occurs. One large effect QTL detected for this trait co-localized with the SI-determiningS-locus. Moreover, individuals that expressed S-RNase—theS-locus protein involved in SI pollen rejection—in their styles had much more rapid UI responses compared to those without S-RNase protein. Our analysis shows that intraspecific variation at mate choice loci—in this case at loci that prevent self-fertilization—can contribute to variation in the strength of interspecific isolation, including postmating prezygotic barriers. Understanding the nature of such standing variation can provide insight into the accumulation of these barriers between diverging lineages.
WITHDRAWN: Complementary functions of the mechanosensitive factorsegr1,klf2bandklf2ainstruct the endocardial program
Authors: Faggianelli-Conrozier Nathalie , Polyzou Aikaterini , Chow Renee , Roth Stéphane , Trompouki Eirini , Vermot Julien
Published: July 2019

Withdrawal Statement

The authors would like to withdraw this manuscript because they have been unable to reproduce a key finding of the preprint showing thategr1mutants have a valve phenotype. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding authors.
Differential lipid dynamics in stocked and wild juvenile lake trout
Authors: Sorrentino Madelyn G. , Stewart Taylor R. , Marsden J. Ellen , Stockwell Jason D.
Published: July 2019

After more than 40 years of stocking, lake trout (Salvelinus namaycush) in Lake Champlain have started to exhibit strong, natural recruitment. The abrupt surge in recruitment suggests a change in limiting factors such as prey availability or overwinter survival. The distribution of juvenile wild lake trout varies in relative abundance among regions of Lake Champlain. The differences suggest the prey base, or foraging success, may vary geographically within the lake. Stocked and wild lake trout may differ in their ability to use resources and in overwinter survival. One metric that can indicate differences in resources across regions is lake trout lipid content, which reflects the quality of available food and serves as an important energy reserve for overwinter survival. We quantified total lipid content of stocked and wild juvenile lake trout across spatial (lake regions) and temporal (seasonal) scales. No spatial differences in lipid content were apparent. Wild fish had greater lipid content than stocked fish. Seasonally, stocked fish showed a continuous drop in lipid content from pre-winter levels at stocking to the following autumn. Wild fish showed a cyclical summer increase in lipids following winter depletion, which plateaued by autumn. The high lipid content of hatchery lake trout may be necessary as they acclimate to foraging in the wild. Hatcheries would benefit from evaluating whether post-stocking survival could be improved by altering feeding or rearing regimes.
Lifespan-increasing drug nordihydroguaiaretic acid inhibits p300 and activates autophagy
Authors: Tezil Tugsan , Chamoli Manish , Ng Che-Ping , Simon Roman P. , Butler Victoria J. , Jung Manfred , Andersen Julie , Kao Aimee W. , Verdin Eric
Published: July 2019

Aging is characterized by the progressive loss of physiological function in all organisms. Remarkably, the aging process can be modulated by environmental modifications, including diet and small molecules. The natural compound nordihydroguaiaretic acid (NDGA) robustly increases lifespan in flies and mice, but its mechanism of action remains unclear. Here, we report that NDGA is an inhibitor of the epigenetic regulator p300. We find that NDGA inhibits p300 acetyltransferase activityin vitroand suppresses acetylation of a key p300 target in histones (i.e., H3K27) in cells. We use the cellular thermal shift assay to uniquely demonstrate NDGA binding to p300 in cells. Finally, in agreement with recent findings indicating that p300 is a potent blocker of autophagy, we show that NDGA treatment induces autophagy. These findings identify p300 as a novel target of NDGA and provide mechanistic insight into its role in longevity.
Systems-level analysis of monocyte responses in inflammatory bowel disease identifies IL-10 and IL-1 cytokine networks that regulate IL-23
Authors: Aschenbrenner Dominik , Quaranta Maria , Banerjee Soumya , Ilott Nicholas , Jansen Joanneke , Steere Boyd A. , Chen Yin-Huai , Ho Stephen , Cox Karen ,   Oxford IBD Cohort Investigators, Arancibia-Cárcamo Carolina V. , Coles Mark , Gaffney Eamonn , Travis Simon , Denson Lee A. , Kugathasan Subra , Schmitz Jochen , Powrie Fiona , Sansom Stephen , Uhlig Holm H.
Published: July 2019

BACKGROUND & AIMS

Dysregulated immune responses are the cause of inflammatory bowel diseases. Studies in both mice and humans suggest a central role of IL-23 producing mononuclear phagocytes in disease pathogenesis. Mechanistic insights into the regulation of IL-23 are prerequisite for select IL-23 targeting therapies as part of personalized medicine.

METHODS

We performed transcriptomic analysis to investigate IL-23 expression in human mononuclear phagocytes and peripheral blood mononuclear cells. We investigated the regulation of IL-23 expression and used single-cell RNA-sequencing to derive a transcriptomic signature of hyper-inflammatory monocytes. Using gene network correlation analysis, we deconvolve this signature into components associated with homeostasis and inflammation in patient biopsy samples.

RESULTS

We characterized monocyte subsets of healthy individuals and patients with inflammatory bowel disease that express IL-23. We identified auto- and paracrine sensing of IL-1α/IL-1β and IL-10 as key cytokines that control IL-23-producing monocytes. Whereas Mendelian genetic defects in IL-10 receptor signalling induced IL-23 secretion, uptake of whole bacteria induced IL-23 production via acquired IL-10 signalling resistance. We found a transcriptional signature of IL-23-producing inflammatory monocytes that predicted both disease and resistance to anti-TNF therapy and differentiated that from an IL-23-associated lymphocyte differentiation signature that was present in homeostasis and in disease.

CONCLUSION

Our work identifies IL-10 and IL-1 as critical regulators of monocyte IL-23 production. We differentiate homeostatic IL-23 production from hyper-inflammation-associated IL-23 production in patients with severe ulcerating active Crohn’s disease and anti-TNF treatment non-responsiveness. Altogether, we identify subgroups of patients with inflammatory bowel disease that might benefit from IL-23p19 and/or IL-1α/IL-1β-targeting therapies upstream of IL-23.
Criticality as a determinant of integrated information Φ in human brain networks
Authors: Kim Hyoungkyu , Hudetz Anthony G. , Mashour George A. , Lee UnCheol
Published: July 2019

Integrated information theory (IIT) postulates that consciousness arises from the cause-effect structure of a system but the optimal network conditions for this structure have not been elucidated. In the study, we test the hypothesis that network criticality, a dynamically balanced state between a large variation of functional network configurations and a large constraint of structural network configurations, is a necessary condition for the emergence of a cause-effect structure that results in a large Φ, a surrogate of integrated information. We also hypothesized that if the brain deviates from criticality, the cause-effect structure is obscured and Φ diminishes. We tested these hypotheses with a large-scale brain network model and high-density electroencephalography (EEG) acquired during various levels of human consciousness during general anesthesia. In the modeling study, maximal criticality coincided with maximal Φ. The constraint of the structural network on the functional network is maximized in the maximal criticality. The EEG study demonstrated an explicit relationship between Φ, criticality, and level of consciousness. Functional brain network significantly correlated with structural brain network only in conscious states. The results support the hypothesis that network criticality maximizes Φ.
The human canonical core histone catalogue
Authors: Susano Pinto David Miguel , Flaus Andrew
Published: July 2019

Core histone proteins H2A, H2B, H3, and H4 are encoded by a large family of genes distributed across the human genome. Canonical core histones contribute the majority of proteins to bulk chromatin packaging, and are encoded in 4 clusters by 65 coding genes comprising 17 for H2A, 18 for H2B, 15 for H3, and 15 for H4, along with at least 17 total pseudogenes. The canonical core histone genes display coding variation that gives rise to 11 H2A, 15 H2B, 4 H3, and 2 H4 unique protein isoforms. Although histone proteins are highly conserved overall, these isoforms represent a surprising and seldom recognised variation with amino acid identity as low as 77% between canonical histone proteins of the same type. The gene sequence and protein isoform diversity also exceeds commonly used subtype designations such as H2A.1 and H3.1, and exists in parallel with the well-known specialisation of variant histone proteins. RNA sequencing of histone transcripts shows evidence for differential expression of histone genes but the functional significance of this variation has not yet been investigated. To assist understanding of the implications of histone gene and protein diversity we have catalogued the entire human canonical core histone gene and protein complement. In order to organise this information in a robust, accessible, and accurate form, we applied software build automation tools to dynamically generate the canonical core histone repertoire based on current genome annotations and then to organise the information into a manuscript format. Automatically generated values are shown with a light grey background. Alongside recognition of the encoded protein diversity, this has led to multiple corrections to human histone annotations, reflecting the flux of the human genome as it is updated and enriched in reference databases. This dynamic manuscript approach is inspired by the aims of reproducible research and can be readily adapted to other gene families.
Lattice arrangement of myosin filaments correlates with fiber type in rat skeletal muscle
Authors: Ma Weikang , Lee Kyoung Hwan , Yang Shixin , Irving Thomas , Craig Roger
Published: July 2019

The thick (myosin-containing) filaments of vertebrate skeletal muscle are arranged in a hexagonal lattice, interleaved with an array of thin (actin-containing) filaments with which they interact to produce contraction. X-ray diffraction and electron microscopy have shown that there are two types of thick filament lattice. In the simple lattice, all filaments have the same orientation about their long axis, while in the super lattice, nearest neighbors have rotations differing by 60°. Tetrapods (amphibians, reptiles, birds, mammals) typically have only a super lattice, while the simple lattice is confined to fish. We have carried out X-ray diffraction and electron microscopy of the soleus (SOL) and extensor digitorum longus (EDL) muscles of the rat and found that while the EDL has a super-lattice, as expected, the SOL has a simple lattice. The EDL and SOL of the rat are unusual in being essentially pure fast and slow muscles respectively. The mixed fiber content of most tetrapod muscles and/or lattice disorder may explain why the simple lattice has not been apparent in these vertebrates before. This is supported by only weak simple lattice diffraction in the X-ray pattern of mouse SOL, which has a greater mix of fiber types than rat. We conclude that the simple lattice might be common in tetrapods. The correlation between fiber type and filament lattice arrangement suggests that the lattice arrangement may contribute to the functional properties of a muscle.

The three-dimensional arrangement of thick filaments in skeletal muscle is studied by X-ray diffraction and electron microscopy. A correlation is found between thick filament lattice type (simple or super lattice) and fiber type (fast/slow). This suggests that lattice organization contributes to muscle functional properties
S-Acylation of plant immune receptors mediates immune signaling in plasma membrane nanodomains
Authors: Chen Dongqin , Ahsan Nagib , Thelen Jay J. , Stacey Gary
Published: July 2019

S-Acylation is a reversible protein post-translational modification mediated by Protein S-acyltransferases (PATs). Here, we demonstrate that three plant immune receptors P2K1 (DORN1), FLS2 and CERK1, representing three distinct families of receptor like-kinases, are S-acylated by Arabidopsis PAT5 and PAT9 on the plasma membrane (PM). Mutations in Atpat5 and Atpat9 resulted in an elevated plant immune response, increased phosphorylation and decreased degradation of FLS2, P2K1 and CERK1 during immune signaling. Mutation of key cysteine residues S-acylated in these receptors resulted in a similar phenotype as exhibited by Atpat5/Atpat9 mutant plants. The data indicate that S-acylation also controls localization of the receptors in distinct PM nanodomains and, thereby, controls the formation of specific protein-protein interactions. Our study reveals that S-acylation plays a critical role in mediating spatiotemporal dynamics of plant receptors within PM nanodomains, suggesting a key role for this modification in regulating the ability of plants in respond to external stimuli.
The Ufm1 system is upregulated by ER stress during osteogenic differentiation
Authors: Dudek Michal , Wallis Gillian A.
Published: July 2019

Objective

Mutations in the catalytic site of the ubiquitin-fold modifier 1(UFM1)-specific peptidase 2 (UFSP2) gene have been identified to cause autosomal dominant Beukes hip dysplasia in a large multigenerational family and a novel form of autosomal dominant spondyloepimetaphyseal dysplasia in a second family. We investigated the expression of the UFSP2/UFM1 system during mouse joint development the connection to ER stress induced during osteogenic differentiation.

Methods

The pattern of expression of Ufsp2 was determined by radioactive RNA in situ hybridisation on mouse tissue sections. qPCR was used to monitor expression during in vitro osteogenic differentiation and chemically induced ER stress. Affinity purification and mass spectrometry was used for isolation and identification of Ufm1 conjugation targets. Luciferase reporter assay was used to investigate the activity of Ufm1 system genes’ promoters.

Results

We found that Ufsp2 was predominantly expressed in the bone and secondary ossification centres of 10-day old mice. The Ufm1 system was upregulated during in vitro osteogenic differentiation and in response to chemically induced ER stress. We identified unfolded protein response elements in the upstream sequences of Uba5, Ufl1, Ufm1and Lzap. We identified putative Ufm1 conjugation targets where conjugation was increased in response to ER stress.

Conclusion

Higher expression of Ufsp2 in bone and secondary ossification centres as well as upregulation of components of the Ufm1system in response to ER stress suggests that the molecular pathway between the UFSP2 mutations and form of skeletal dysplasia may relate to abnormal ER stress responses during osteoblast differentiation.