bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Effects of “Resurrecting” Csp Pseudoproteases duringClostridioides difficileSpore Germination
Authors: Lauren Donnelly M. , Forster Emily R. , Rohlfing Amy E. , Shen Aimee
Published: November 2019

Clostridioides difficileis a spore-forming bacterial pathogen that is the leading cause of hospital-acquired gastroenteritis.C. difficileinfections begin when its spore form germinates in the vertebrate gut upon sensing bile acids. These germinants induce a proteolytic signaling cascade controlled by three members of the subtilisin-like serine protease family, CspA, CspB, and CspC. Notably, even though CspC and CspA are both pseudoproteases, they are nevertheless required to sense germinants and activate the protease, CspB. Thus, CspC and CspA are part of a growing list of pseudoenzymes that play important roles in regulating cellular processes. However, despite their importance, the structural properties of pseudoenzymes that allow them to function as regulators remain poorly understood. Our recently determined crystal structure of CspC revealed that its degenerate site residues align closely with the catalytic triad of CspB, so in this study we tested whether the ancestral protease activity of the CspC and CspA pseudoproteases could be “resurrected.” Restoring the catalytic triad to these pseudoproteases failed to resurrect their protease activity, although the mutations differentially affected the stability and function of these pseudoproteases. Degenerate site mutations destabilized CspC and impaired spore germination without impacting CspA stability or function. Thus, our results surprisingly reveal that the presence of a catalytic triad does not necessarily predict protease activity. Since close homologs ofC. difficileCspA occasionally carry an intact catalytic triad, our results imply that bioinformatics predictions of enzyme activity may overlook pseudoenzymes in some cases.
GFP fusion protein with embedded foreign peptide
Authors: Glukhova K.A. , Klyashtorny V.G. , Melnik B.S.
Published: November 2019

From the point of view structural biology and protein engineering the green fluorescent protein (GFP) is an exceptionally attracting object. The tertiary structure of GFP is quite unique: it reminds a “cylinder” or a “barrel” consisting of beta-layers that contains an alpha-helix inside. The “barrel” is a special container for an alpha-helix serving to protect the latter from the influence of the surroundings. Therefore a reasonable question arises whether the “barrel” can function as a container for preservation and isolation of other peptides. The alpha-helix itself contains hydrophilic amino acids, whereas inside the barrel there are many molecules of bound water. We supposed that the central alpha-helix of green fluorescent protein could be substituted for foreign peptide. In this study we checked the possibility for creation of such a system on base of GFP, where the toxic peptide is isolated from the environment inside the protein. The modification of green fluorescent protein was carried out. An antimicrobial peptide was inserted into the central alpha-helix. The results of our experiments show that such a chimeric protein is compact, soluble and non-toxic for the producing cell culture, but its structure is destabilized. The obtained data show that the idea of use of green fluorescent proteins as a «container» for storing foreign peptides could be realized.
dP75 safeguards oogenesis by preventing H3K9me2 spreading
Authors: Dou Kun , Liu Yanchao , Zhang Yingpei , Wang Chenhui , Huang Ying , Zhang ZZ Zhao
Published: November 2019

Serving as a host factor for HIV integration, LEDGF/p75 has been under extensive study as a potential target for therapy. However, as a highly conserved protein, its physiological function remains to be thoroughly elucidated. Here we characterize the molecular function of dP75, theDrosophilahomolog of p75, during oogenesis. dP75 binds to transcriptionally active chromatin with its PWWP domain. The C-terminus IBD domain-containing region of dP75 physically interacts with the histone kinase Jil-1 and stabilizes itin vivo. Together with Jil-1, dP75 prevents the spreading of the heterochromatin mark–H3K9me2–onto genes required for oogenesis and piRNA production. Without dP75, ectopically silencing of these genes disrupts oogenesis, activates transposons, and causes animal sterility. We propose that dP75, the homolog of an HIV host factor inDrosophila, partners with Jil-1 to ensure gene expression during oogenesis by preventing ectopic heterochromatin spreading.
Contentious politics and democratization in Hong Kong
Authors: Ortmann Stephan
Published: November 2019

Purpose

The purpose of this paper is to explain why many activists in Hong Kong have shifted from demanding democracy to independence while, at least for a short time, there have been more aggressive tactics which culminated in the Fishball Revolution of 2016.

Design/methodology/approach

Based on event analysis, participant observation in recent protests, as well as interviews with participants and non-participants in various pro-democracy protests, this paper traces the changes of the democracy movement from 1997 until 2018.

Findings

The paper demonstrates that the inability of the democracy movement to make progress has contributed to a change in the goals and tactics of some pro-democracy activists. The goals have shifted from moderate democratic reforms to much more revolutionary demands including calls for full autonomy or independence while the approach has shifted from an institutionalized approach toward more aggressive tactics such as illegal forms of resistance. During the Lunar New Year in 2016, the growing frustrations over perceived threats to the local culture have, for the first time since the handover, even led to the use of violence.

Originality/value

This paper views contentious politics in Hong Kong through McAdam’s distinction of reform-oriented and revolutionary goals as well as institutionalized and non-institutionalized tactics. This provides a new perspective for explaining the rise of localism and Hong Kong nationalism.
Expectations do not always hurt! Tying organizational career expectations to employment mode
Authors: Ahmad Bilal , Bilal Ahmad Raza , Hai Mahnoor
Published: November 2019

Purpose

The past decade has witnessed a surge in research focused on universal career development needs. In contrast, the purpose of this paper is to offer a contingency perspective based on self-efficacy theory by examining the relationship between the employees’ perceived mode of employment and expectations of career development opportunities attached to the employer. The authors hypothesized that perceived mode of employment determines employees’ expectations about receiving career development opportunities offered by the employer.

Design/methodology/approach

Responses from 203 banking employees were obtained through a structured questionnaire. Perceived employment mode was identified through Ward’s method of cluster analysis. The proposed hypothesis was tested by using one-way analysis of variance.

Findings

Employees across all modes of employment (knowledge-based, job-based, contract-based and alliance-based) were found to be similar with respect to their need for career development programs. However, employees positioned in knowledge-based and alliance-based modes were also interested in career appraisal and career training.

Originality/value

The study contributes to the existing body of knowledge on career management by imparting preliminary insights into the way employees’ expectations of organizational career management opportunities vary according to their perceived mode of employment based on self-efficacy theory.
Substitute or complementary
Authors: Chen Bo , Saghaian Sayed , Tyler Mark
Published: November 2019

Purpose

The purpose of this paper is to examine the relationship between US farmers’ adoption of organic farming and direct marketing, both of which are increasingly important practices in the US agricultural and food sector. In addition, the effects of the two practices on farm income are evaluated.

Design/methodology/approach

The research uses the Agricultural and Resource Management Survey from the US Department of Agriculture. Farmers’ adoption of the two practices is modeled with a simultaneous linear probability model, which accounts for the possible linkage between the adoption of the two practices in farmers’ decision-making process. Farm income is modeled with a linear regression model, accounting for the possible endogeneity of the adoption of the two practices.

Findings

The main finding is that farmers’ adoption of organic farming decreases their probability of adopting direct marketing, whereas the reverse effect is insignificant. In addition, organic farming helps to improve gross farm income, whereas the effect of direct marketing is insignificant.

Practical implications

These results facilitate better coordination among numerous government programs aimed at promoting organic farming or direct marketing in the US.

Originality/value

This paper extends previous literature by specifically accounting for the possible linkage between farmers’ adoption of organic farming and direct marketing, and demonstrates that farmers do not make the decision to adopt one particular practice in isolation.
Understanding the antecedents of car sharing usage: an empirical study in Italy
Authors: Guglielmetti Mugion Roberta , Toni Martina , Di Pietro Laura , Pasca Maria Giovina , Renzi Maria F.
Published: November 2019

Purpose

Sustainable mobility and collaborative consumption are debated issues in the literature. In this field, car sharing (CS) represents a growing tendency that attracts interest by academicians for its potential positive impact on sustainability. This study aims to understand the main drivers of CS usage, unveiling the role of service quality and the possible inhibitors.

Design/methodology/approach

Based on theoretical assumptions in the literature, the authors developed a theoretical framework that aims at understanding the main antecedents of CS usage. An empirical investigation involving the city of Rome (Italy) was performed. The study presents a qualitative and quantitative survey, while the proposed theoretical model has been tested through structural equation modelling statistical techniques.

Findings

The findings show that usefulness positively affects the intention to use CS services. Moreover, the green attitude and expected service quality indirectly influence the intention to use CS services impacting perceived usefulness. The results show that the expected service quality has a strong influence on usefulness, whereas green attitude has a weaker influence on usefulness. The intention to use CS services is directly influenced by the usefulness and inhibitors that affect it negatively.

Originality/value

The originality of this paper lies in the fact that this study discloses the main antecedents of the intention to use CS services, emphasizing the role of service quality. This study provides fruitful insights to policy and decision-makers to understand how to improve the CS usage in the urban transport system of the city of Rome. It suggests developing a higher level of service quality in the vehicles, suitable technological applications and effective communication as well as on overcoming its main inhibitors.
An investigation into the relationship between materialism and green purchase behavior in Vietnam and Taiwan
Authors: Thi Tuyet Mai Nguyen
Published: November 2019

Purpose

The purpose of this paper is to investigate the impact of materialistic values on purchase intention (PI) toward green products among consumers in Vietnam and Taiwan, two Asian countries with different levels of economic development.

Design/methodology/approach

This research employs the extended theory of planned behavior (TPB) with an integration of materialism. To serve the purpose of this study, two consumer surveys were conducted in Hanoi (Vietnam) and Taipei (Taiwan). The structural equation modeling was employed to test the proposed model and hypotheses.

Findings

This study examined the impact of some antecedents of green PI among consumers in Vietnam and Taiwan, focusing on the indirect impact of materialistic values (through attitude). All five hypotheses received support from the Vietnam data, confirming the significant impacts of materialistic values (i.e. success and happiness) on attitude, and all three antecedents from the TPB model (i.e. attitude, subjective norms and perceived behavioral control) as positive predictors of green PI. For the Taiwan data, the findings were similar to those from the Vietnam data, except insignificant impact of success value on attitude toward buying green products.

Originality/value

This research is expected to contribute to the extant literature by enriching the knowledge of the interesting and important relationship between materialistic values and green purchase behavior among consumers in two Asian markets where, to the author’s best understanding, only modest research effort has been given to explore this topic.
Evolution and decline of MNCs from a leadership-quality perspective- MNCs from the Brazilian market
Authors: Jneid Cherine
Published: November 2019

Purpose

The purpose of this paper is to provide guidelines to IHRM by providing a set of personal and psychological competencies that are relevant to the development of global mindsets in global leaders.

Design/methodology/approach

The authors adopted the qualitative research approach by conducting interviews with 22 top managers and organizing focus groups to 102 expatriated Brazilian global leaders.

Findings

The findings suggest that the language proficiency, the complexity of the global role and the positive psychological traits are highly relevant when developing global mindsets.

Originality/value

The researcher argues that the IHRM must review its practices regarding the management of international assignments which efficiency is overrated by top managers.
Microbial rescue effects: How microbiomes can save hosts from extinction
Authors: Mueller Emmi A. , Wisnoski Nathan I. , Peralta Ariane L. , Lennon Jay T.
Published: November 2019

Rescue effects arise when ecological and evolutionary processes restore positive intrinsic growth rates in populations that are at risk of going extinct. Rescue effects have traditionally focused on the roles of immigration, phenotypic plasticity, gene flow, and adaptation. However, species interactions are also critical for understanding how populations respond to environmental change.

In particular, the fitness of plant and animal hosts is strongly influenced by symbiotic associations with the bacteria, archaea, microeukaryotes and viruses that collectively make up a host's microbiome. While some are pathogenic, many microorganisms confer nutritional, immunological, and developmental benefits that can protect hosts against the effects of rapid environmental change.

Microbial rescue occurs when changes in microbiome abundance, composition, or activity influence host physiology or behaviour in ways that improve host fitness. If these microbial attributes and their beneficial effects are transmitted through a population, it may stabilize growth rates and reduce the probability of extinction.

In addition to providing a framework to guide theoretical and empirical efforts in host‐microbiome research, the principles of microbial rescue may also be useful for adaptively managing at‐risk species. We discuss the risks and rewards of incorporating microbial rescue into conservation strategies such as probiotics, assisted migration, and captive breeding.

A free Plain Language Summary can be found within the Supporting Information of this article.
Explaining the social gradient in smoking and cessation: the peril and promise of social mobility
Authors: Thirlway Frances
Published: November 2019

Smoking in high‐income countries is now concentrated in poor communities whose relatively high smoking prevalence is explained by greater uptake but above all by lower quit rates. Whilst a number of barriers to smoking cessation have been identified, this is the first paper to situate cessation itself as a classed and cultural practice. Drawing on ethnographic research carried out in a working‐class community in the North of England between 2012 and 2015, I theorise smoking cessation as a symbolic practice in relation to the affective experience of class and social mobility. I show that ambivalence about upward mobility as separation and loss translated into ambivalence about smoking cessation. The reason for this was that the social gradient in smoking operated dynamically at the level of the individual life course, i.e. smoking cessation followed upward mobility. A serious health problem was an appropriate reason to quit but older women continued to smoke despite serious health problems. This was linked to historical gender roles leading to women placing a low priority on their own health as well as the intergenerational reproduction of smoking through close affective links with smoking parents.
Effects of Fermentation on Compositions, Color, and Functional Properties of Gelatinized Potato Flours
Authors: Gong Shengxiang , Xie Fan , Lan Xiaohong , Zhang Wei , Gu Xinzhe , Wang Zhengwu
Published: November 2019

This study investigated effects of fermentation on compositions, color, and functional properties of gelatinized potato flours from Atlantic and Kexin No.1 cultivars. Atlantic flour (AF) and Kexin No.1 flour (KF) were fermented using 1% yeast concentration, respectively. Fermentation further improved the nutritional and physicochemical features of gelatinized potato flours by means of increased protein and ash contents, and decreased the levels of moisture, lipid, soluble amylose, amylopectin, and total starch. The lightness and whiteness of potato flours were enhanced with the increase in fermentation time. There are gradual increases in water absorption index, emulsifying capacity and emulsifying stability of potato flours during fermentation. However, bulk density of them slightly reduced with the increase in fermentation time. In addition, fermentation has no significant effect on freeze–thaw stability of gelatinized potato flours. These results indicate that yeast fermentation could enhance certain processing characteristics of potato flours and improve the applicability of them in food formulations.

Practical Application

Lately, China has started national project regarding the use of potato flour in foods. However, due to dark color and low protein content of potato flours, their application in food formulations was limited. This study analyzed the possible mechanisms by which yeast fermentation improved the nutritional and functional characteristics of Atlantic flour (AF) and Kexin No. 1 flour (KF). From applications standpoint, findings of this study could provide knowledge on the selection of potato flours for various food formulations.
Insulin resistance is associated with urinary albumin‐creatinine ratio in normal weight individuals with hypertension and diabetes: The REACTION study
Authors: Gu Shi , Wang Anping , Ning Guang , Zhang Linxi , Mu Yiming
Published: November 2019

Background

The relationship between albuminuria and insulin resistance (IR) has not been clarified in previous studies. This study was conducted to examine whether IR is associated with albuminuria in subjects with diverse blood pressure and glycometabolism statuses.

Methods

This study included 34 136 participants whose data were drawn from a cross‐sectional survey named the 2011 REACTION study. The participants were divided into six groups. The urinary albumin‐creatinine ratio (UACR) and glomerular filtration rate (GFR) were used as markers of chronic kidney disease (CKD). Variance tests and logistic regression models were performed for homeostatic model assessment of insulin resistance (HOMA‐IR) in relation to UACR and eGFR.

Results

First, UACR levels and HOMA‐IR exhibited a positive correlation among participants (P < 0.05), and a negative correlation existed between GFR and HOMA‐IR (P < 0.05). Second, in the hypertension with diabetes group, in individuals whose body mass index (BMI) was 18.5‐24.0 kg/m2, age was 50‐60 years old, low density lipoprotein cholesterol (LDL‐C) was 2.6‐3.4 mmol/L or high density lipoprotein cholesterol (HDL‐C) was 0.9‐1.55 mmol/L, HOMA‐IR was positively associated with UACR (P < 0.05). However, there was a negative correlation between GFR and HOMA‐IR in the hypertension with diabetes group in individuals whose BMI was 18.5‐24.0 kg/m2 or whose age was over 65 years old (P < 0.05).

Conclusions

In the context of different blood pressure and glycometabolism statuses, the positive correlation between UACR levels and HOMA‐IR was affected by BMI, age, LDL‐C, HDL‐C, and GFR. In patients with hypertension and diabetes, the early detection and intervention of IR and related risk factors in patients with normal BMI may reduce the occurrence of microalbuminuria and delay the progression of CKD.
The Psychoactive Surveillance Consortium and Analysis Network (PSCAN): the first year
Authors: Monte Andrew A. , Hopkinson Andrew , Saben Jessica , Shelton Shelby K. , Thornton Stephen , Schneir Aaron , Pomerleau Adam , Hendrickson Robert G. , Arens Ann M. , Cole Jon B. , Chenoweth James , Martin Spencer , Adams Axel , Banister Samuel D. , Gerona Roy R.
Published: November 2019

Background and aims

The Psychoactive Surveillance Consortium and Analysis Network (PSCAN) is a national network of academic emergency departments (ED), analytical toxicologists and pharmacologists that collects clinical data paired with biological samples to identify and improve treatments of medical conditions arising from use of new psychoactive substances (NPS). The aim of this study was to gather clinical data with paired drug identification from NPS users who presented to EDs within PSCAN during its first year (2016–17).

Design

Observational study involving patient records and biological samples.

Setting

Seven academic emergency medical centers across the United States.

Participants

ED patients (n = 127) > 8 years of age with possible NPS use who were identified and enrolled in PSCAN by clinical providers or research personnel.

Measurements

Clinical signs, symptoms and treatments were abstracted from the patients' health records. Biological samples were collected from leftover urine, serum and whole blood. Biological and drug samples, when available, were tested for drugs and drug metabolites via liquid chromatography–quadrupole time‐of‐flight mass spectrometry (LC‐QTOF/MS).

Findings

Patients in whom synthetic opioids were detected (n = 9) showed higher rates of intubation (four of nine), impaired mental status (four of nine) and respiratory acidosis (five of nine) compared with the rest of the cohort (nine of 118, P‐value < 0.05). Patients in whom synthetic cannabinoid (SC) were found (n = 27) had lower median diastolic blood pressures (70.5 versus 77 mmHg, P = 0.046) compared with the rest of the cohort. In 64 cases of single drug ingestion, benzodiazepines were administered in 25 cases and considered effective by the treating physician in 21 (84%) cases.

Conclusions

During its first year of operation, the Psychoactive Surveillance Consortium and Analysis Network captured clinical data on new classes of drugs paired with biological samples over a large geographical area in the United States. Synthetic cannabinoids were the most common new psychoactive drug identified. Synthetic opioids were associated with a high rate of intubation and respiratory acidosis.
Local and Global, but Not national: Citizenship Education of South Asian Migrant Students in Post‐Colonial Hong Kong
Authors: Chee Wai‐chi
Published: November 2019

This article examines how schools in Hong Kong attempt to craft South Asian migrant students into desirable citizens and how the youths understand themselves as members of Hong Kong and of a global community. The contestation has to do both with how South Asians are viewed in Hong Kong and with how post‐colonial Hong Kong is related to China. The process of citizen‐making of transnational youths, I argue, is best understood at the local–national–global intersection.
Associations of sperm telomere length with semen parameters, clinical outcomes and lifestyle factors in human normozoospermic samples
Authors: Berneau Stephane C. , Shackleton Jennifer , Nevin Clare , Altakroni Basher , Papadopoulos George , Horne Gregory , Brison Daniel R. , Murgatroyd Christopher , Povey Andy C. , Carroll Michael
Published: November 2019

Background

Many studies have demonstrated that lifestyle factors can affect sperm quality and fertility. Sperm telomere length (STL) has been reported as potential biomarker or sperm quality. However, no studies have investigated how lifestyle factors can affect STL and associated clinical outcomes.

Objectives

The purpose of this manuscript is to investigate any association between STL with lifestyle factors, semen parameters and clinical outcomes.

Materials and methods

Sperm telomere length was measured using real‐time PCR in normozoospermic male partners (n = 66) of couples undergoing ART treatment. Each participant also completed a detailed questionnaire about general lifestyle. Linear regression univariate analysis and ANCOVA were performed to respectively determine correlations between STL and study parameters or identify statistically significant differences in STL while controlling for age, BMI and other factors.

Results

Using a linear regression model, STL is positively correlated with in vitro fertilization success (n = 65, r = 0.37, P = .004) but not with embryo cleavage rates and post‐implantation clinical outcomes including gestational age‐adjusted birth weight. No associations were observed between STL and sperm count, concentration or progressive motility. We further found that STL did not associate age, BMI, health or lifestyle factors.

Discussion

In somatic cells, the rate of telomere shortening is influenced by a number of lifestyle factors such as smoking, diet and occupation. However, little is known about how lifestyle factors affect STL and subsequently reproductive outcome. Out data suggest that STL might have an important role mechanistically for fertilization rate regardless of sperm parameters and lifestyle factors.

Conclusion

The results of this study demonstrate that STL is associated with in vitro fertilization rates, but not with semen parameters nor lifestyle factors. Further investigations are warranted to identify the potential variation of STL overtime to clarify its significance as a potential biomarker in ART.
Schoolchildren with unilateral or mild to moderate bilateral sensorineural hearing loss should be screened for neurodevelopmental problems
Authors: Stübner Charlotte , Flynn Traci , Gillberg Christopher , Fernell Elisabeth , Miniscalco Carmela
Published: November 2019

Aim

The aim was to assess the rate and overlap of language and other neurodevelopmental problems in children aged 9‐12 years with unilateral or mild to moderate bilateral sensorineural hearing loss.

Methods

Caregivers of 24 of the 58 eligible children, born 2004‐2007, registered at the regional audiology department in Gothenburg, Sweden, with these types of hearing loss completed the Five‐to‐Fifteen questionnaire, a comprehensive screening instrument for neurodevelopmental problems. Of these 24 children, 21 were assessed with the Clinical Evaluation of Language Fundamentals—Fourth Edition (CELF‐4). Children with scores indicating definite problem on the Five‐to‐Fifteen questionnaire and their parents were invited to a clinical neuropaediatric assessment.

Results

Of the 24 children, 13 (54%) screened positive for definite neurodevelopmental problems. Clinical assessments confirmed the presence of at least one neurodevelopmental disorder in eight of these 24, corresponding to 33%. Seven (33%) of the 21 children participating in the CELF‐4 had scores indicating a language disorder, of whom four children had a neurodevelopmental disorder according to the neuropaediatric assessment.

Conclusion

The results support that schoolchildren with unilateral or mild to moderate bilateral sensorineural hearing loss should undergo neurodevelopmental screening to identify possible coexisting neurodevelopmental problems or disorders.
Model‐based approach for methoxy polyethylene glycol‐epoetin beta drug development in paediatric patients with anaemia of chronic kidney disease
Authors: Chanu Pascal , Schaefer Franz , Warady Bradley A. , Schmitt Claus Peter , Reigner Bruno , Schnetzler Gabriel , Meyer Reigner Sylvie , Eisner Mark , Weichert Arlette , Frey Nicolas
Published: November 2019

Aims

Methoxy polyethylene glycol‐epoetin beta (continuous erythropoietin receptor activator, C.E.R.A.) is used for the treatment of anaemia in adults with chronic kidney disease (CKD). Patients treated with shorter‐acting erythropoiesis‐stimulating agents up to three times weekly can be switched to once‐monthly C.E.R.A.. Doses can be adjusted on a monthly basis based on haemoglobin (Hb) levels during the preceding period. A model‐based approach was applied to optimise C.E.R.A. development, more specifically the confirmatory trial of the paediatric plan.

Methods

Pharmacokinetic and pharmacodynamic data from a phase II paediatric study and phase II and III adult studies were analysed together using modelling and simulation to determine the pharmacokinetic/pharmacodynamic characteristics of C.E.R.A. in a broad population. Model‐based simulations of C.E.R.A. treatment outcomes in paediatric patients were performed, notably when administered subcutaneously and compared to clinical and real‐world data.

Results

Age and body weight explained differences in pharmacokinetics, while the pharmacodynamic characteristics of C.E.R.A. were similar between adult and paediatric populations. Simulated Hb levels (mean and 95% prediction interval 10.9 [10.6, 11.2] g dL−1) and C.E.R.A. doses (median and 95% prediction interval 105 [72, 159] μg) 20 weeks after switching to subcutaneous C.E.R.A. were confirmed by observed real‐world data from International Pediatric Dialysis Network registries (mean Hb was 10.8 g dL−1 and median C.E.R.A. dose was 100 μg).

Conclusions

These analyses have facilitated optimisation of the C.E.R.A. development programme in paediatric patients with anaemia of CKD to provide this patient population with faster access to the drug while avoiding unnecessary clinical trial exposure and related monitoring burden in children.
A moral argument for frozen human embryo adoption
Authors: Lovering Rob
Published: November 2019

Some people (e.g., Drs. Paul and Susan Lim) and, with them, organizations (e.g., the National Embryo Donation Center) believe that, morally speaking, the death of a frozen human embryo is a very bad thing. With such people and organizations in mind, the question to be addressed here is as follows: if one believes that the death of a frozen embryo is a very bad thing, ought, morally speaking, one prevent the death of at least one frozen embryo via embryo adoption? By way of a three‐premise argument, one of which is a moral principle first introduced by Peter Singer, my answer to this question is: at least some of those who believe this ought to. (Just who the “some” are is identified in the paper.) If this is correct, then, for said people, preventing the death of a frozen embryo via embryo adoption is not a morally neutral matter; it is, instead, a morally laden one. Specifically, their intentional refusal to prevent the death of a frozen embryo via embryo adoption is, at a minimum, morally criticizable and, arguably, morally forbidden. Either way, it is, to one extent or another, a moral failing.
Butyrate protects against high‐fat diet‐induced atherosclerosis via up‐regulating ABCA1 expression in apolipoprotein E‐deficiency mice
Authors: Du Yu , Li Xingxing , Su Chunyan , Xi Mei , Zhang Xiumin , Jiang Zhibo , Wang Li , Hong Bin
Published: November 2019

Background and Purpose

The gut microbial metabolite butyrate is linked to the modulation of metabolic disease. The mechanism by which butyrate effects in atherosclerosis is unknown. Hence, the present investigation into effects of butyrate on high‐fat diet‐fed ApoE−/− mice after 16 weeks' administration.

Experimental Approach

Gut microbiota composition was analysed via 16S rRNA gene sequencing of caecal contents. The effects of butyrate on atherosclerosis were evaluated in vivo using the ApoE−/− mice model. Serum lipids and glucose were analysed for physiological changes and differentially expressed genes in liver samples were identified by hepatic transcriptome profiling. The proteins involved in reverse cholesterol transport were quantified by Western blot and immunohistochemical staining. Finally, the up‐regulatory effects of butyrate on ATP‐binding cassette sub‐family A member 1 (ABCA1) were further evaluated in RAW 264.7 cells along with role of specificity protein 1 by inhibition and silencing.

Key Results

Oral gavage of butyrate altered microbiota composition and enhanced gut microbial diversity that was decreased by high fat diet (HFD). Butyrate treatment significantly inhibited the HFD‐induced atherosclerosis as well as hepatic steatosis without changing body weight gain in ApoE−/− mice. Butyrate had metabolic effects on the liver by regulation of gene expression involved in lipid/glucose metabolism. Furthermore, ABCA1 was significantly induced by butyrate in vivo, ex vivo and in vitro and Sp1 pathway was identified as a potential mechanism.

Conclusion and Implications

Butyrate ameliorates HFD‐induced atherosclerosis in ApoE−/− mice via ABCA1‐mediated cholesterol efflux in macrophages, which suggesting a promising therapeutic strategy for protecting against atherosclerosis.
Child cash benefits and family expenditures: Evidence from the National Child Benefit
Authors: Jones Lauren E. , Milligan Kevin , Stabile Mark
Published: November 2019

Income may improve child outcomes through two mechanisms: as a direct input into health and education, or indirectly, by reducing household financial stress. We exploit policy‐induced changes in refundable tax benefit income in Canada to study these two potential mechanisms. Our findings suggest that additional income may improve outcomes through both mechanisms: some benefit income is spent on direct education inputs, while some is spent on everyday items likely to improve the general conditions children face. Additionally, some families reduce spending on risky behaviour items. Spending responses to benefit generosity appear to vary by income and by child age.
Contesting cannabis: Indigenous jurisdiction and legalization
Authors: Crosby Andrew
Published: November 2019

In the early days of cannabis legalization, certain Indigenous communities and businesses are asserting jurisdictional authority and refuse to acknowledge federal and provincial sovereignty on their territories. This has led, in some cases, to police intervention. This article examines jurisdictional contestations on Indigenous lands in relation to cannabis legalization, providing insight on the responses of government and law enforcement. The Canadian approach may have lasting implications for reconciliation and Indigenous relations beyond the cannabis field.
Effects of postexercise cooling on heart rate recovery in normotensive and hypertensive men
Authors: Peçanha Tiago , Low David , de Brito Leandro Campos , Fecchio Rafael Yokoyama , de Sousa Patrícia Nascimento , da Silva‐Júnior Natan Daniel , de Abreu Andrea Pio , da Silva Giovanio Vieira , Mion‐Junior Décio , Forjaz Cláudia Lúcia de Moraes
Published: November 2019

Background

Postexercise heart rate recovery (HRR) is determined by cardiac autonomic restoration after exercise and is reduced in hypertension. Postexercise cooling accelerates HRR in healthy subjects, but its effects in a population with cardiac autonomic dysfunction, such as hypertensives (HT), may be blunted. This study assessed and compared the effects of postexercise cooling on HRR and cardiac autonomic regulation in HT and normotensive (NT) subjects.

Methods

Twenty‐three never‐treated HT (43 ± 8 years) and 25 NT (45 ± 8 years) men randomly underwent two exercise sessions (30 min of cycling at 70% VO2peak) followed by 15 min of recovery. In one randomly allocated session, a fan was turned on in front of the subject during the recovery (cooling), while in the other session, no cooling was performed (control). HRR was assessed by heart rate reductions after 60 s (HRR60s) and 300 s (HRR300s) of recovery, short‐term time constant of HRR (T30) and the time constant of the HRR after exponential fitting (HRRτ). HRV was assessed using time‐ and frequency‐domain indices.

Results

HRR and HRV responses in the cooling and control sessions were similar between the HT and NT. Thus, in both groups, postexercise cooling equally accelerated HRR (HRR300s = 39±12 versus 36 ± 10 bpm, P≤0·05) and increased postexercise HRV (lnRMSSD = 1·8 ± 0·7 versus 1·6 ± 0·7 ms, P≤0·05).

Conclusion

Differently from the hypothesis, postexercise cooling produced similar improvements in HRR in HT and NT men, likely by an acceleration of cardiac parasympathetic reactivation and sympathetic withdrawal. These results suggest that postexercise cooling equally accelerates HRR in hypertensive and normotensive subjects.
The long view of epilepsy and depression in pediatrics
Authors: Salpekar Jay A
Published: November 2019

This commentary is on the original article by Rosic et al. on pages 593–599 of this issue.
Value of insoluble PABPN1 accumulation in the diagnosis of oculopharyngeal muscular dystrophy
Authors: Galimberti V. , Tironi R. , Lerario A. , Scali M. , Del Bo R. , Rodolico C. , Brizzi T. , Gibertini S. , Maggi L. , Mora M. , Toscano A. , Comi G. P. , Sciacco M. , Moggio M. , Peverelli L.
Published: November 2019

Background and purpose

The aim was to assess the value of insoluble PABPN1 muscle fibre nuclei accumulation in the diagnosis of atypical cases of oculopharyngeal muscular dystrophy (OPMD).

Methods

Muscle biopsies from a selected cohort of 423 adult patients from several Italian neuromuscular centres were analysed by immunofluorescence: 30 muscle biopsies of genetically proven OPMD, 30 biopsies from patients not affected by neuromuscular disorders, 220 from genetically undiagnosed patients presenting ptosis or swallowing disturbances, progressive lower proximal weakness and/or isolated rimmed vacuoles at muscle biopsy and 143 muscle biopsies of patients affected by other neuromuscular diseases.

Results

The detection of insoluble nuclear PABPN1 accumulation is rapid, sensitive (100%) and specific (96%). The revision of our cohort allowed us to discover 23 new OPMD cases out of 220 patients affected with nonspecific muscle diseases.

Conclusions

Oculopharyngeal muscular dystrophy is often misdiagnosed leading to diagnosis delay, causing waste of time and resources. A great number of these cases present symptoms and histological findings frequently overlapping with other muscle diseases, i.e. inclusion body myositis and progressive external ophthalmoplegia. PABPN1 nuclear accumulation is a reliable method for diagnostic purposes and it is safe and useful in helping pathologists and clinicians to direct genetic analysis in the case of suspected OPMD, even when clinical and histological clues are deceptive.
Automated detection of hippocampal sclerosis using clinically empirical and radiomics features
Authors: Mo Jiajie , Liu Zhenyu , Sun Kai , Ma Yanshan , Hu Wenhan , Zhang Chao , Wang Yao , Wang Xiu , Liu Chang , Zhao Baotian , Zhang Kai , Zhang Jianguo , Tian Jie
Published: November 2019

Objective

Temporal lobe epilepsy is a common form of epilepsy that might be amenable to surgery. However, magnetic resonance imaging (MRI)‐negative hippocampal sclerosis (HS) can hamper early diagnosis and surgical intervention for patients in clinical practice, resulting in disease progression. Our aim was to automatically detect and evaluate the structural alterations of HS.

Methods

Eighty patients with pharmacoresistant epilepsy and histologically proven HS and 80 healthy controls were included in the study. Two automated classifiers relying on clinically empirical and radiomics features were developed to detect HS. Cross‐validation was implemented on all participants, and specificity was assessed in the 80 controls. The performance, robustness, and clinical utility of the model were also evaluated. Structural analysis was performed to investigate the morphological abnormalities of HS.

Results

The computational model based on clinical empirical features showed excellent performance, with an area under the curve (AUC) of 0.981 in the primary cohort and 0.993 in the validation cohort. One of the features, gray‐white matter boundary blurring in the temporal pole, exhibited the highest weight in model performance. Another model based on radiomics features also showed satisfactory performance, with AUC of 0.997 in the primary cohort and 0.978 in the validation cohort. In particular, the model improved the detection rate of MRI‐negative HS to 96.0%. The novel feature of cortical folding complexity of the temporal pole not only played a crucial role in the classifier but also had significant correlation with disease duration.

Significance

Machine learning with quantitative clinical and radiomics features is shown to improve HS detection. HS‐related structural alterations were similar in the MRI‐positive and MRI‐negative HS patient groups, indicating that misdiagnosis originates mainly from empirical interpretation. The cortical folding complexity of the temporal pole is a potentially valuable feature for exploring the nature of HS.
Diagnosis and treatment of mastitis in mares
Authors: Canisso I. F. , Podico G. , Ellerbrock R. E.
Published: November 2019

Infection and inflammation of the udder (mastitis) is a common condition affecting all domestic mammals, but it appears to be less prevalent in mares than in dairy cows and dairy goats. The seemingly reduced incidence of mastitis in mares can be partially explained by the smaller size and relatively concealed location of the mare’s udder, coupled with a smaller storage capacity than cows and goats. Mastitis can affect lactating, peripartum, dry mares, mares at dry‐off or prepubertal foals. Common clinical signs include swollen mammary tissue, abnormal mammary gland secretion, fever and anorexia; less common signs are hindlimb lameness and a swollen mammary vein. On rare occasions, mastitis pathogens can severely affect the nursing foal and mares may develop fibrotic tissue and consequent agalactia in the side(s) or quarter(s) affected. Based on the clinical presentation, mastitis can be classified as acute or chronic, and clinical or subclinical. Diagnosis is based on the clinical signs aided with aerobic culture and cytological evaluation of the gland secretion. In addition, these ancillary tests can also be used to assess prognosis and duration of treatment. Mares suffering from mastitis may present neutrophilia and hyperfibrinogenaemia. Treatment for mastitis includes antimicrobial therapy (systemic and/or locally), nonsteroidal anti‐inflammatory drugs, frequent milking and cold hosing with/without hot‐packing applied on the gland. While the frequent monitoring of mares after weaning and reducing food intake should be part of common practices at weaning, cleaning of the udder, control of insect populations and frequent milking of mares with a foal unable to nurse can also aid in preventing mastitis.
Caveolin‐1 as a possible target in the treatment for acne
Authors: Kruglikov Ilja L. , Scherer Philipp E.
Published: November 2019

Expression of caveolin‐1 (Cav‐1) is an important pathophysiological factor in acne. Cav‐1 strongly interacts with such well‐recognized etiopathogenic factors such as hyperseborrhea, follicular hyperkeratinization and pathogenicity of Cutibacterium acnes. Cav‐1 is a strong negative regulator of transforming growth factor beta (TGF‐β) expression. It acts as a critical determinant of autophagy, which is significantly induced in acne lesions through C. acnes and by absorption of fatty acids. Cav‐1 also demonstrates different correlations with the development of innate immunity. We propose that normalization of Cav‐1 expression can serve as a target in anti‐acne therapy.
Catalytic subunit exchanges in the cellulosomes produced by Ruminiclostridium cellulolyticum suggest unexpected dynamics and adaptability of their enzymatic composition
Authors: Borne Romain , Dao Ti Minh‐Uyen , Fierobe Henri‐Pierre , Vita Nicolas , Tardif Chantal , Pagès Sandrine
Published: November 2019

Cellulosomes are complex nanomachines produced by cellulolytic anaerobic bacteria such as Ruminiclostridium cellulolyticum (formerly known as Clostridium cellulolyticum). Cellulosomes are composed of a scaffoldin protein displaying several cohesin modules on which enzymatic components can bind to through their dockerin module. Although cellulosomes have been studied for decades, very little is known about the dynamics of complex assembly. We have investigated the ability of some dockerin‐bearing enzymes to chase the catalytic subunits already bound onto a miniscaffoldin displaying a single cohesin. The stability of the preassembled enzyme–scaffoldin complex appears to depend on the nature of the dockerin, and we have identified a key position in the dockerin sequence that is involved in the stability of the complex with the cohesin. Depending on the residue occupying this position, the dockerin can establish with the cohesin partner either a nearly irreversible or a reversible interaction, independently of the catalytic domain associated with the dockerin. Site‐directed mutagenesis of this residue can convert a dockerin able to form a highly stable complex with the miniscaffoldin into a reversible complex forming one and vice versa. We also show that refunctionalization can occur with natural purified cellulosomes. Altogether, our results shed light on the dynamics of cellulosomes, especially their capacity to be remodeled even after their assembly is ‘achieved’, suggesting an unforeseen adaptability of their enzymatic composition over time.
Adolescent maturation of the prefrontal cortex: Role of stress and sex in shaping adult risk for compromise
Authors: Shaw Gladys A. , Dupree Jeffrey L. , Neigh Gretchen N.
Published: November 2019

Adolescence is a highly dynamic period of development, which includes the final organizational phases of neural maturation within the prefrontal cortex (PFC). The organizational events of neural pruning and myelination occur in a sex‐specific manner, potentially giving rise to the disparities in mood disorders in adulthood. Because of the extended developmental time period of the PFC, environmental insults, including psychosocial stressors, may play a major role in steering the maturation of this region. In this review, the literature surrounding the sex specific alterations that occur in the PFC in rodent models following adolescent stress will be discussed. This will be complimented by a brief review on the state of human research in PFC sex differences in the development of white matter and cytoarchitecture across the lifespan. Taken together, the impact of developmental psychosocial stress on the circuitry of the PFC and resulting adult phenotypes will be summarized with a focus on the importance of considering sex differences in order to build a better understanding of developmental influences on adult disorders.