bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and Validation of a Clinical Prediction Rule to Predict Transmission of Methicillin-Resistant Staphylococcus aureus in Nursing Homes
Authors: Jackson Sarah S , Lydecker Alison D , Magder Laurence S , Roghmann Mary-Claire
Published: September 2018

The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) colonization among nursing home residents is high. Health-care workers (HCWs) often serve as a vector in MRSA transmission. The ability to identify residents who are likely to transmit MRSA to HCWs’ hands and clothing during clinical care is important so that infection control measures, such as Contact Precautions, can be employed. Using data on demographic and clinical characteristics collected from residents of community nursing homes in Maryland and Michigan between 2012 and 2014, we developed a clinical prediction rule predicting the probability of MRSA transmission to HCWs’ gowns. We externally validated this model in a cohort of Department of Veterans Affairs nursing home residents from 7 states between 2012 and 2016. The prediction model, which included sex, race, resident dependency on HCWs for care, the presence of any medical device, diabetes mellitus, and chronic skin breakdown, showed good performance (C statistic = 0.70; sensitivity = 76%, specificity = 49%) in the development set. The decision curve analysis indicated that this model has greater clinical utility than use of a nares surveillance culture for MRSA colonization, which is current clinical practice for placing hospital inpatients on Contact Precautions. The prediction rule demonstrated less utility in the validation cohort, suggesting that a separate rule should be developed for residents of Veterans Affairs nursing homes.
MSPminer: abundance-based reconstitution of microbial pan-genomes from shotgun metagenomic data
Authors: Plaza Oñate Florian , Le Chatelier Emmanuelle , Almeida Mathieu , Cervino Alessandra C L , Gauthier Franck , Magoulès Frédéric , Ehrlich S Dusko , Pichaud Matthieu
Published: September 2018

Motivation

Analysis toolkits for shotgun metagenomic data achieve strain-level characterization of complex microbial communities by capturing intra-species gene content variation. Yet, these tools are hampered by the extent of reference genomes that are far from covering all microbial variability, as many species are still not sequenced or have only few strains available. Binning co-abundant genes obtained from de novo assembly is a powerful reference-free technique to discover and reconstitute gene repertoire of microbial species. While current methods accurately identify species core parts, they miss many accessory genes or split them into small gene groups that remain unassociated to core clusters.

Results

We introduce MSPminer, a computationally efficient software tool that reconstitutes Metagenomic Species Pan-genomes (MSPs) by binning co-abundant genes across metagenomic samples. MSPminer relies on a new robust measure of proportionality coupled with an empirical classifier to group and distinguish not only species core genes but accessory genes also. Applied to a large scale metagenomic dataset, MSPminer successfully delineates in a few hours the gene repertoires of 1661 microbial species with similar specificity and higher sensitivity than existing tools. The taxonomic annotation of MSPs reveals microorganisms hitherto unknown and brings coherence in the nomenclature of the species of the human gut microbiota. The provided MSPs can be readily used for taxonomic profiling and biomarkers discovery in human gut metagenomic samples. In addition, MSPminer can be applied on gene count tables from other ecosystems to perform similar analyses.

Availability and implementation

The binary is freely available for non-commercial users at www.enterome.com/downloads.

Supplementary information

Supplementary data are available at Bioinformatics online.
Using electronic health records to characterize prescription patterns: focus on antidepressants in nonpsychiatric outpatient settings
Authors: Deferio Joseph J , Levin Tomer T , Cukor Judith , Banerjee Samprit , Abdulrahman Rozan , Sheth Amit , Mehta Neel , Pathak Jyotishman
Published: September 2018

Objective

To characterize nonpsychiatric prescription patterns of antidepressants according to drug labels and evidence assessments (on-label, evidence-based, and off-label) using structured outpatient electronic health record (EHR) data.

Methods

A retrospective analysis was conducted using deidentified EHR data from an outpatient practice at a New York City-based academic medical center. Structured “medication–diagnosis” pairs for antidepressants from 35 325 patients between January 2010 and December 2015 were compared to the latest drug product labels and evidence assessments.

Results

Of 140 929 antidepressant prescriptions prescribed by primary care providers (PCPs) and nonpsychiatry specialists, 69% were characterized as “on-label/evidence-based uses.” Depression diagnoses were associated with 67 233 (48%) prescriptions in this study, while pain diagnoses were slightly less common (35%). Manual chart review of “off-label use” prescriptions revealed that on-label/evidence-based diagnoses of depression (39%), anxiety (25%), insomnia (13%), mood disorders (7%), and neuropathic pain (5%) were frequently cited as prescription indication despite lacking ICD-9/10 documentation.

Conclusions

The results indicate that antidepressants may be prescribed for off-label uses, by PCPs and nonpsychiatry specialists, less frequently than believed. This study also points to the fact that there are a number of off-label uses that are efficacious and widely accepted by expert clinical opinion but have not been included in drug compendia. Despite the fact that diagnosis codes in the outpatient setting are notoriously inaccurate, our approach demonstrates that the correct codes are often documented in a patient’s recent diagnosis history. Examining both structured and unstructured data will help to further validate findings. Routinely collected clinical data in EHRs can serve as an important resource for future studies in investigating prescribing behaviors in outpatient clinics.
Socioeconomic Differences in Smoking and Cessation Across a Period of Rapid Economic Growth in an Upper-Middle-Income Country
Authors: Mariapun Jeevitha , Hairi Noran N , Ng Chiu-Wan
Published: September 2018

Introduction

Higher smoking rates and lower cessation rates among the poor compared to the rich are evident in high-income countries. In low and middle-income countries (LMICs), many of which are in the early stages of tackling the tobacco epidemic, more knowledge is required of the socioeconomic inequalities in smoking. This is especially the case for upper-middle-income countries, where smoking prevalence is highest. This study examines trends in the socioeconomic gradient in smoking and cessation among adults across a period of rapid economic development in Malaysia, an LMIC with an upper-middle-income economy.

Methods

The socioeconomic trends in smoking were analyzed using data from cross-sectional National Health and Morbidity Surveys for the years 1996, 2006, and 2011. Household per capita income was used as a measure of socioeconomic position. As a measure of inequality, the concentration index that quantified the degree of socioeconomic inequality in a health outcome was computed. Smoking was assessed in current and former smokers. The study population was examined by gender, region, and age group.

Results

This study found a trend of an increasingly higher smoking prevalence among the poor and higher cessation rates among the rich. With the exception of younger women in Peninsular Malaysia, the socioeconomic gradient in current smoking is concentrated among the poor. For former smokers, especially men, distributions across the years were mostly concentrated among the rich.

Conclusion

It is important to ensure that health policies, programs, and interventions consider the potential impact of the socioeconomic patterning in smoking on equity in health.

Implications

Findings on the socioeconomic gradient in smoking and cessation from Malaysia across a period of rapid economic development will contribute to addressing the paucity of knowledge on the socioeconomic gradient of smoking and cessation in other progressing LMICs. This study provides evidence from an upper-middle-income country, of an increasing trend of smoking among the poor and an increasing trend of cessation rates among the rich, particularly for men. We found opposing trends for younger adult women in the more developed, Peninsular Malaysia. More rich young women were found to have taken up smoking compared to socioeconomically less advantaged young women.
“Electronic Cigarettes” Are Not Cigarettes, and Why That Matters
Authors: Olonoff Matthew , Niaura Raymond , Hitsman Brian
Published: September 2018

As the prevalence rates of cigarette use have declined over the past decade, use of electronic cigarettes (e-cigarettes) continues to increase, and companies are heavily invested in manufacturing new e-cigarette products. Scientists are therefore studying e-cigarette use at a rapid rate, generally by conceptualizing e-cigarettes as similar to traditional cigarettes in their use and effects. Thinking of e-cigarettes as largely comparable with cigarettes, however, fails to capture the unique e-cigarette capabilities, user experiences, and effects on nicotine dependence and even health. Assuming that e-cigarette users puff on their devices as they do cigarettes to attain doses of nicotine comparable in magnitude and asking questions about e-cigarette use modeled after how smoking behavior has been usually assessed (eg, puff number, duration, number of cigarettes per day) may miss important differences. A greater appreciation of the distinct uniqueness of e-cigarettes, as compared with cigarettes, will help to accelerate innovative research on e-cigarettes and other electronic devices, leading to new theoretical models and behavioral measures.

Implications

With research about electronic cigarettes (e-cigarettes) rapidly increasing, this commentary addresses the conceptualization of e-cigarettes as similar to traditional cigarettes. The more we attempt to understand and measure e-cigarettes as equivalent to cigarettes, the more likely research may err in conclusions about these unique devices. Our commentary notes how using unique conceptualizations and measures for e-cigarettes will help accelerate new research.
Jesuits and Islam in Early Modern Europe
Authors: Colombo Emanuele
Published: September 2018

This chapter discusses Jesuit narratives of Islam and the Jesuits’ approaches to Muslims in early modern Europe. It argues that the Jesuits’ interaction with Islam was a key component of the Society’s identity, despite the fact that the order was not celebrated for the success of this interaction. It explores the desire of Ignatius of Loyola and the first Jesuits to convert Muslims; the history of Muslims who converted to Catholicism and joined the Society of Jesus; the Jesuits’ tension between a polemical attitude and a missionary approach to Muslims; and, finally, the Jesuits’ willingness to engage Islam and their attempts to study Arabic during this period. The chapter sheds new light on the presence of Islam in early modern Europe and helps our understanding of views that also influenced early modern Jesuit missionaries overseas, most of whom undertook their formation in Europe.
Israel’s Global Perspective
Authors: Shindler Colin
Published: September 2018

Zionism set out not only to establish a state of the Jews, but also to create a Jewish society, one profoundly different from the ones the immigrants had been born into. The genocide of the Nazis, the abandonment of internationalism by the Soviet Union, and the hostility of Arab nationalism moved Zionism toward a position more concerned with national survival. Israel was forced to abandon a nonaligned status after 1950 and, when diplomatically isolated after the 1973 Yom Kippur War, to cultivate relations with regimes that were considered pariah states, such as South Africa, Chile, and Argentina. The ascendancy of the Israeli Right after 1977 accentuated this approach. The demise of the USSR, the end of the Cold War, and the signing of the Oslo Accords in the 1990s all contributed to the establishment of diplomatic relations with major states such as India and China and Arab neighbors such as Jordan, as well as to unofficial contacts with others such as Cuba. In the twenty-first century many states relegated ideology to a secondary position, assisting Israel’s policy of survivalism.
Interpersonal Processes and the Development of Emotion Dysregulation
Authors: Stoycos Sarah A. , Corner Geoffrey W. , Khaled Mona , Saxbe Darby
Published: September 2018

Emotion regulation and dysregulation often unfold within interpersonal contexts. Parent–child relationships provide early scaffolding of emotion regulation processes. Parents attune to, and influence, their children’s emotions, through pathways such as physical touch, infant cry, facial expressions, and stress physiology. Interpersonal emotion regulation and dysregulation processes continue to evolve within other close relationship contexts such as romantic couple relationships in adulthood. Partners shape each other’s emotion regulation through stress contagion and physiological interconnection, and through interactions that can be conflictual or supportive. This chapter reviews the theoretical foundations and the existing literature describing how emotion regulation and dysregulation take place within interpersonal relationships.
Neuroimaging of Emotion Dysregulation
Authors: Leshin Joseph C. , Lindquist Kristen A.
Published: September 2018

Affective neuroscience, the study of neural mechanisms that give rise to emotional experiences in humans and animals, has a short but rich history. Almost three decades old, affective neuroscience has predominantly taken two theoretical approaches to understanding the brain bases of human emotions, and thus, two stances on the brain bases of emotion dysregulation. One approach, the traditional approach, argues that specific emotions are hardwired in human biology with specific neural underpinnings or signatures for said emotions. The second approach, a psychological constructionist approach, argues that each experienced emotion emerges not from a specific, dedicated anatomical circuit, but from an interplay of broad networks in the brain that are involved in general operations of the mind. This chapter provides an overview of these two theoretical approaches with a specific focus on functional magnetic resonance imaging (fMRI) findings. It concludes with evidence suggesting how emotion dysregulation may arise and links this work to clinical fMRI investigations of anxiety disorders. It closes by suggesting future directions affective neuroscience may take to better understand processes underlying dysregulated emotions.
Emotion Dysregulation and Eating Disorders
Authors: Racine Sarah E. , Horvath Sarah A.
Published: September 2018

This chapter reviews evidence for the role of emotion dysregulation in the etiology and maintenance of eating disorders. It examines theoretical models that describe functional relations between emotions and eating disorder behaviors. Data from self-report questionnaire studies, ecological momentary assessment, and experimental research designs are considered, with a focus on identifying similarities and differences in emotion dysregulation across eating disorders. The chapter concludes by describing a model in which stable (i.e., trait) emotion regulation difficulties increase the likelihood of using maladaptive strategies, such as eating disorder behaviors, to regulate emotions. Future work must identify factors that predict whether someone will express trait emotion dysregulation as an eating disorder versus another psychiatric disorder, and whether emotion dysregulation maintains eating disorders and can be targeted in treatment.
Perinatal Development of the Medial Nucleus of the Trapezoid Body
Authors: Sivaramakrishnan Shobhana , Brandebura Ashley , Holcomb Paul , Heller Daniel , Kolson Douglas , Jackson Dakota , Mathers Peter H. , Spirou George A.
Published: September 2018

Bushy cells (BC) of the cochlear nucleus mono-innervate their target neuron, the principal cell of the medial nucleus of the trapezoid body (MNTB), via the calyx of Held (CH) terminal, which is a typically mammalian structure and perhaps the largest nerve terminal in the brain. CH:MNTB innervation has become an attractive model to study neural circuit formation because it forms quickly, passing through stages of competition in mice within 2–4 days. BCs innervate MNTB neurons by E17, but CHs do not begin to grow for another five days (P3). Progress has been made to identify molecular factors for axon guidance, CH growth, and physiological maturation of synaptic partners, but important details remain to be discovered. We summarize key events in CH formation and highlight unresolved issues in molecular and physiological signaling, roles for non-neural cells, and the nature of competition during the first postnatal week.
The Criminalization of Migration in Canada and Its Unintended Policy Consequences
Authors: Atak Idil
Published: September 2018

This chapter examines the criminalization of asylum seekers arriving irregularly into Canada and the human rights implications of this process, in particular the Designated Foreign National (DFN) policy established in 2012 and the increased role of the Canada Border Services Agency (CBSA) in the refugee system. These changes exemplify the crisis-led management by the previous Conservative government as a reaction to the 2009 and 2010 boat arrivals of nearly 600 Tamil asylum seekers from Sri Lanka. The specific objectives of the policy amendments are scrutinized to determine whether their stated goals are being achieved. The chapter draws on interviews conducted between October 2015 and May 2017 in three major provinces (Quebec, Ontario, and British Columbia) that host the majority of asylum seekers in Canada.
Exceptional Italy? The Many Ends of the Italian Colonial Empire
Authors: Labanca Nicola
Published: September 2018

Both the history of Italian colonialismand its end have often been seen as exceptional. Depending on the opinions of different historians, the Italian colonial empire was either built too late or remained too small to be compared to the large overseas possessions of other European imperial powers, such as Portugal, Spain, France, and the United Kingdom. Focusing on the particularities of an Italian Empire built in East Africa and in Libya, this chapter surveys the motivating factors of, the geopolitical obstacles to, and popular cultural engagement with colonial expansion in Italy before, during, and after the country’s turn to fascism.
The Life-World of the Obsessive-Compulsive Person
Authors: Bürgy Martin
Published: September 2018

Taking up the work of Karl Jaspers, we develop a phenomenological method, which has not been fully used in clinical practice. We describe three levels of understanding of psychiatric symptoms: the static understanding as a description of symptoms in the here and now; the genetic understanding of symptom development; and the hermeneutic understanding as an interpretation of meaning and sense. This phenomenological method is illustrated using its application in obsessive-compulsive disorder. Previous findings are thus organized and illustrated on the basis of a case study. This leads us to a deeper understanding of obsessive-compulsive disorder, both from the disturbance side, as well as from the defending and coping side, to a deeper understanding, too, of its development and of the world- and self-experiencing.
Hans-Georg Gadamer
Authors: Wiercinski Andrzej
Published: September 2018

Hermeneutics as the art of understanding concerns the totality of being a human being in the world. By thematizing health in its unstable equilibrium, Gadamer’s phenomenological hermeneutics of medicine offers an alternative to the predominantly scientific modes of understanding health and illness. Gadamer advocates embracing the truth of lived experience without silencing what seems to be incomprehensible, unpredictable, and inexplicable. Hermeneutics promotes an understanding of the art of healing, which overcomes the overwhelming tendency in contemporary medicine to interpret phenomenological descriptions of the human condition into the language of clinical and pathophysiological processes that require pharmacological intervention. The hermeneutic task of the doctor is to learn together with the patient about our self-understanding by thinking about and dealing with the medical condition. Clinical medicine can be practiced as hermeneutics by addressing the phenomena of health and illness as the first-person human experience that calls for understanding.
Understanding Empathy
Authors: Duan Changming , Sager Kristen
Published: September 2018

Empathy, one of the most studied and most multidisciplinary theoretical constructs, has garnered the attention of scholars from psychology as well as the social and biological sciences. The scholarship of empathy has developed significantly in the past century, with the most notable knowledge emerging in the areas of the neuroscience of empathy and the interplay between race/culture and empathy in recent decades. The positive psychology of empathy also continues to occupy researchers, as the links between empathy and individual and societal health abound. Future empathy research by socially and scholastically responsible scientists must overcome a long history of Euro-ethnocentric biases and integrate social justice into the understanding of this important construct. The scholarship and application of empathy will continue to be an important source of positivity for humans and for society as a whole.
The History of Clinical Neuropsychology in the Nordic Countries
Authors: Hessen Erik , Hokkanen Laura , Bartfai Aniko , Nyman Håkan , Gade Anders
Published: September 2018

This chapter presents views on the history of clinical neuropsychology in the Nordic countries. These countries have fostered significant contributors to clinical neuropsychology and produced a steady output of respectable clinical research. Nordic Conferences in Neuropsychology have facilitated mutual inspiration and collaboration since 1982 and have influenced training models in clinical neuropsychology. Unlike the training models in the United States and United Kingdom, which require a doctoral degree, those in the Nordic region are comparable to the training of medical specialists, requiring minimum of 9–11 years in psychology and neuropsychology education and practice before obtaining a specialty in clinical neuropsychology. This model produces high-quality specialists who are able to take responsibility in diagnostics, treatment, and rehabilitation. Such specialists have contributed to significant change in diagnostic and rehabilitation practices regarding disorders with cognitive symptoms.
Anterior-Segment Optical Coherence Tomography and Scanning Electron Microscopy to Evaluate Corneal Epithelial Changes in Patients Undergoing Glaucoma Therapy
Authors: Cennamo Gilda , Montorio Daniela , Del Prete Salvatore , Del Prete Antonio , Cennamo Giovanni
Published: September 2018

Purpose:

To measure corneal epithelial thickness (CET) in patients with glaucoma using anterior-segment optical coherence tomography and to evaluate CET changes in relation to corneal epithelial microvilli analyzed by scanning electron microscopy (SEM).

Methods:

Twenty-two eyes (16 patients) being treated with preservative-containing topical medications and 12 normal eyes underwent anterior-segment optical coherence tomography imaging using RTVue-100. The CET maps generated corresponded to a 6-mm diameter area of cornea that was divided into 17 sectors. We compared the CETs of each sector obtained in the glaucomatous group with those obtained in the control group.

Results:

Glaucomatous eyes were divided into 2 groups based on the number of microvilli on SEM: group 1 (6 eyes) = grades 1 and 2 at SEM (range: 500–3000) and group 2 (10 eyes) = grades 3 and 4 at SEM (range: 0–500). Four CET sectors were significantly thinner in group 1 than in normal eyes: central (P = 0.012), superior (P = 0.005), temporal paracentral (P = 0.003), and temporal midperipheral (P = 0.023). No significant differences were observed between group 2 and normal eyes. CET sectors were significantly thinner in group 1 than in group 2 only in the superior (P = 0.024) and superior-temporal paracentral (P = 0.020) sectors. CET progressively increased in patients with glaucoma as the number of corneal epithelial microvilli decreased.

Conclusions:

CET and corneal epithelial microvilli are new parameters with which to evaluate early stages of corneal epithelial changes during glaucoma therapy. In advanced stages of corneal epithelial damage, SEM evaluation reveals ultrastructural epithelial changes that may not be observed on CET measurements.
Does Same-Day Postoperative Increased Intraocular Pressure Affect Endothelial Cell Density After Descemet Membrane Endothelial Keratoplasty?
Authors: Fajgenbaum Mark A. P. , Hollick Emma J.
Published: September 2018

Purpose:

High intraocular pressure (IOP) is common in association with intracameral air and gas tamponade after Descemet membrane endothelial keratoplasty (DMEK); yet its influence on endothelial cell survival is unknown. Our aim was to determine the effect of high IOP measured 2 hours after DMEK on 1-month endothelial cell density (ECD). The influence of other potentially relevant factors was also investigated.

Methods:

Retrospective, consecutive series. Inclusions: low-to-moderate risk DMEK surgery alone or combined with phacoemulsification. Exclusions: previous penetrating keratoplasty or glaucoma surgery; grafts with any of the following in the first month: rebubble, rejection, or graft failure.

Results:

Sixty-two grafts met inclusion with 60 having IOP recorded at 2 hours. Thirty-eight percent (23/60) had IOP >30 mm Hg and 22% (13/60) had IOP >40 mm Hg at 2 hours. All grafts with IOP >30 mm Hg had air released and immediate normalization of pressure. One-month ECD (mean ± standard error of mean) was 1872 ± 58 cells/mm2, representing cell loss of 29.8 ± 2.0%. Two-hour IOP was highly insignificant against 1-month ECD when tested as a continuous variable (P = 0.78). Lower 1-month ECD was statistically correlated with lower donor count (P = 0.002) and combined DMEK-phaco surgery (P = 0.01) on univariate and multivariate analysis. Insignificant factors (P > 0.05) against 1-month ECD included patient age, sex and race, surgical indication (Fuchs endothelial dystrophy vs. non-Fuchs endothelial dystrophy), and donor age.

Conclusions:

Increased IOP at 2 hours is common after DMEK, but does not seem to influence early endothelial cell survival. One-month ECD was influenced by donor counts and combined cataract surgery.
Upper Eyelid Approach for the Reconstruction of Isolated Fractures of the Anterior Wall of the Frontal Sinus
Authors: Nguyen David , Hakimi Michael , Sinha Sumedha R. , Martin Mark
Published: September 2018

The management of frontal sinus fractures can vary widely depending on involvement of the anterior wall, the posterior wall, and the frontonasal duct. The main morbidity associated with isolated anterior wall fractures is an aesthetic deformity. Treatment includes coronal, endoscopic, and transcutaneous approaches. However, each has reported limitations and associated risks of iatrogenic injuries. In this paper, the authors discuss a novel approach through the upper eyelid crease and examine 4 cases where it is utilized for anterior frontal sinus wall, superior orbital rim, and orbital roof fracture repair.
Morphometric Analysis of the Facial Profile: Contour of the Side Face and its Variations
Authors: Li Haijun , Wu Xianzhu , Zhang Yidan , Chen Feng
Published: September 2018

Much research has been conducted on the morphological characteristics of the Chinese. However, very few facial measurements have been documented, especially of the side face. This study uses geometirc morphometric method to analyze the contour and variations of the side face in Bai and Yi ethnic minorities from Yunnan province, China. The mark collection proves that for the Bai ethnicity, the variations of the nose are comparatively large, while the forehead variations are small. Variations around the lips and the chin are the largest. For the Yi ethnicity, the forehead also witnesses small variations and the nose again has large variations. The area around the glabella has large variations. Through the comparisons, the area around the glabella tends to extrude more in males both in Bai and Yi. The situation, however, is much more different when it comes to the trichion landmark collection where we see an apparent intrusion in males. For the trichion, Yi people are more intruded than the Bai. Similarities between Bai and Yi are demonstrated by principal component analysis: one can roughly set the males apart from the females using the vertical axis. Profile at the end of horizontal axis suggests that the female facial profile has the following features: the nose is not so prominent as the male, the forehead and the nose are linked by an noticeable arc, the forehead is comparatively steep and is almost in a vertical plane with the lips and the chin. By comparison, the male has a flatter forehead, a more prominent nose, an obvious sellion, and an intruded chin. The common morphologic features of the Chinese face may be reflected through these similarities.
Blocking mechanosensitive ion channels eliminates the effects of applied mechanical loading on chick joint morphogenesis
Authors: Parisi Cristian , Chandaria Vikesh V. , Nowlan Niamh C.
Published: September 2018

Abnormalities in joint shape are increasingly considered a critical risk factor for developing osteoarthritis in life. It has been shown that mechanical forces during prenatal development, particularly those due to fetal movements, play a fundamental role in joint morphogenesis. However, how mechanical stimuli are sensed or transduced in developing joint tissues is unclear. Stretch-activated and voltage-gated calcium ion channels have been shown to be involved in the mechanoregulation of chondrocytes
in vitro
. In this study, we analyse, for the first time, how blocking these ion channels influences the effects of mechanical loading on chick joint morphogenesis. Using
in vitro
culture of embryonic chick hindlimb explants in a mechanostimulation bioreactor, we block stretch-activated and voltage-gated ion channels using, respectively, gadolinium chloride and nifedipine. We find that the administration of high doses of either drug largely removed the effects of mechanical stimulation on growth and shape development
in vitro
, while neither drug had any effect in static cultures. This study demonstrates that, during joint morphogenesis, mechanical cues are transduced—at least in part—through mechanosensitive calcium ion channels, advancing our understanding of cartilage development and mechanotransduction.

This article is part of the Theo Murphy meeting issue ‘Mechanics of development’.
From mechanobiology to developmentally inspired engineering
Authors: Ingber Donald E.
Published: September 2018

The field of mechanobiology emerged based on the recognition of the central role that physical forces play in development and physiology. In this article, which is based on a lecture I presented at the 2018 Royal Society meeting on Mechanics of Development, I review work from my laboratory carried out over the 40 years which helped to birth this field. I will also describe how we are leveraging the fundamental design principles that govern mechanoregulation to develop new experimental tools and organ-engineering approaches as well as novel mechanotherapeutics.

This article is part of the Theo Murphy meeting issue ‘Mechanics of development’.
Pathway maps enable straightforward yet customized and semi-automated yet insightful analyses of omics data
Authors: Möller Steffen , Barrantes Israel , Jaster Robert , Henze Larissa , Escobar Hugo Murua , Junghanss Christian , Hakenberg Oliver , Weber Marc-André , Krause Bernd J. , Wolkenhauer Olaf , Ibrahim Saleh , Köhling Rüdiger , Lange Falko , Walter Uwe , Hamed Mohamed , Kowald Axel , Fuellen Georg
Published: September 2018

To explore the molecular processes underlying some biological theme of interest based on public data, gene lists are used herein as input for the construction of annotated pathway maps, employing Cytoscape apps, and then high-throughput (“omics”) gene expression data are overlaid onto these maps. Seeded with a published set of marker genes of the senescence-associated secretory phenotype and the genes of the cellular senescence KEGG pathway, a gene/protein interaction network and annotated clusters (a “pathway map”) of cellular senescence are derived. The map can be amended, by adding some application-specific genes, and overlaid with gene expression data describing cellular senescence of fibroblasts and with disease-related gene expression data associated with prostate and pancreatic cancer, and with ischemic stroke, allowing insights into the role of cellular senescence in disease. Some gene expression data are derived from the “Biomarker Benchmark repository”. The pathway map approach can be followed in principle for any biological theme of interest, fostering much-needed independence from the investigator-biased expert networks usually used for overlaying gene expression data.
Isolation and Characterization of a Novel Alkaline Lipase/Esterase Lip-1420 from a Metagenomic Library
Authors: Lim Hee Kyung , Kim Dal Rye , Woo Min Woo , Hahm Moon-Sun , Hwang In Taek
Published: September 2018

A novel lipase gene, Lip-1420, was isolated from a metagenomics library constructed from soil samples from reed marshes and from Mt. Jumbong in Korea consisting of 112,500 recombinant plasmids. A selected recombinant plasmid, Lip-1420, was further analyzed which exhibited the maximum lipolytic activity among 18 recombinant fosmids that showed lipolytic activity. Among them, DNA sequence analysis of a 5,513 bp subclone in pUC119 Lip-1420-sub revealed that 11 ORFs were included in the gene according to the blast search from GenBank. The transformant of Lip-1420-ORF3 exhibited lipolytic activity, and plasmid pET21a(+)-Lipase-6H was constructed and transferred to the expression hostE. coliBL21(DE3). Finally, the lipase Lip1420 was purified from a FPLC system, and the recombinant enzyme was kept in a −70 ºC freezer at a concentration of 1 mg/mL in a buffer solution (50 mM Tris-HCl and 0.15 M NaCl, pH 7.4). The Lip-1420 gene was registered in GenBank (MH628529), and the purified enzyme had an optimal activity at 40 °C and pH 8.0. Kinetic analysis of the Lip-1420 lipase with the substratep-nitrophenyl palmitate was performed at 40°C and pH 8.0, and theKmandVmaxvalues of the protein were determined to be 0.268 mM and 1.821 units, respectively. The purified Lip-1420 exhibited the maximum enzymatic activity towardsp-nitrophenyl palmitate, indicating that it is an esterase.

IMPORTANCE

This study provides the knowledge to develop a new lipase from the metagenomics library of rhizosphere in Korea using an activity-based method. In addition, the knowledge gained from this study has allowed us to understand that the natural ecosystems are still an unknown genetic material storage report in relation to industrially useful biocatalysts, which are still rich in biodiversity. Moreover, alkaline lipase has great potential for applications in the detergent industry. Especially in the major part of the global industrial enzyme market with high growth potential. It is used, for example, in detergent additives, biopolymer synthesis, and biodiesel production, synthesis of optically pure compounds and food additives as well as in the paper industry, perfume and fragrance blends, biological purification and waste treatment.
Strategies of host resistance to pathogens in spatially structured populations: An agent-based evaluation
Authors: Boëte Christophe , Seston Morgan , Legros Mathieu
Published: September 2018

There is growing theoretical evidence that spatial structure can affect the ecological and evolutionary outcomes of host-parasite interactions. Locally restricted interactions have been shown in particular to affect host resistance and tolerance. In this study we investigate the evolution of several types of host disease resistance strategies, alone or in combination, in spatially structured populations. We construct a spatially explicit, individual-based stochastic model where hosts and parasites interact with each other in a spatial lattice, and interactions are restricted to a given neighbourhood of varying size. We investigate several host resistance strategies, including constitutive (expressed in all resistant hosts), induced (expressed only upon infection), and combinations thereof. We show that the specific resistance mechanism against a pathogen as well as the size of the neighbourhood both affect resistance spread and parasite dynamics, an effect modulated by the level of the cost of resistance. Our results shed new light on the dynamics of disease resistance in a spatially-structured host-pathogen system, and illustrate the conditions in which a variety of resistance mechanisms can be maintained, including when they are costly. Overall these results advance our theoretical understanding of the evolutionary dynamics of disease resistance, a necessary step to elaborate more efficient and sustainable strategies for disease management.
Facial masculinity is only weakly correlated with handgrip strength in young adult women
Authors: Hahn Amanda C , Holzleitner Iris J , Lee Anthony J , Kandrik Michal , O’Shea Kieran J , DeBruine Lisa M , Jones Benedict C
Published: September 2018

Objectives

Ancestrally, strength is likely to have played a critical role in determining the ability to obtain and retain resources and the allocation of social status among humans. Responses to facial cues of strength are therefore thought to play an important role in human social interaction. Although many researchers have proposed that sexually dimorphic facial morphology is reliably correlated with physical strength, evidence for this hypothesis is somewhat mixed. Moreover, to date, only one study has investigated the putative relationship between facial masculinity and physical strength in women. Consequently, we tested for correlations between handgrip strength and objective measures of face-shape masculinity.

Methods

531 women took part in the study. We measured each participant’s handgrip strength (dominant hand). Sexual dimorphism of face shape was objectively measured from each face photograph using two methods: discriminant analysis and vector analysis. These methods use shape components derived from principal component analyses of facial landmarks to measure the probability of the face being classified as male (discriminant analysis method) or to locate the face on a female-male continuum (vector analysis method).

Results

Our analyses revealed that handgrip strength is, at best, only weakly correlated with facial masculinity in women. There was a weak significant association between handgrip strength and one measure of women’s facial masculinity. The relationship between handgrip strength and our other measure of women’s facial masculinity was not significant.

Discussion

Together, these results do not support the hypothesis that face-shape masculinity is an important cue of physical strength, at least in women.
Functional importance of JMY expression by Sertoli cells in mediating mouse spermatogenesis
Authors: Liu Yue , Fan Jiaying , Yan Yan , Dang Xuening , Zhao Ran , Xu Yimei , Ding Zhide
Published: September 2018

Sertoli cells are crucial for spermatogenesis in the seminiferous epithelium because their actin cytoskeleton supports vesicle transport, cell junction, protein anchoring and spermiation. Here, we show that junction-mediating and regulatory protein (JMY), an actin regulating protein, also affects endocytic vesicle trafficking and Sertoli cell junction remodeling since disruption of these functions induced male subfertility in Sertoli cell-specificJmyknockout mice. Specifically, these mice have: a) impaired BTB integrity and spermatid adhesion in the seminiferous tubules; b) high incidence of sperm structural deformity; c) reduced sperm count and poor sperm motility. Moreover, the cytoskeletal integrity in Sertoli cell-specificJmyknockout mice was compromised along with endocytic vesicular trafficking. These effects impaired junctional protein recycling and reduced Sertoli cell junctions. In addition, JMY interaction with α-actinin1 and Sorbs2 was related to JMY activity and in turn actin cytoskeletal organization. In summary, JMY affects control of spermatogenesis through regulating actin filament organization and endocytic vesicle trafficking in Sertoli cells.
Illustrating phylogenetic placement of fossils using RoguePlots: An example from ichneumonid parasitoid wasps (Hymenoptera, Ichneumonidae) and an extensive morphological matrix
Authors: Klopfstein Seraina , Spasojevic Tamara
Published: September 2018

The fossil record constitutes the primary source of information about the evolutionary history of extant and extinct groups, and many analyses of macroevolution rely on fossils that are accurately placed within phylogenies. To avoid misinterpretation of the fossil record, especially by non-palaeontologists, the proper assessment and communication of uncertainty in fossil placement is crucial. We here use Bayesian morphological phylogenetics to evaluate the classifications of fossil parasitoid wasps (Hymenoptera, Ichneumonidae) and introduce ‘RoguePlots’ to illustrate placement uncertainty on the phylogeny of extant taxa. Based on an extensive, newly constructed morphological matrix of 222 characters in 24 fossil and 103 extant taxa, we test three different aspects of models of morphological evolution. We find that a model that includes ordered characters, among-character rate variation, and a state-space restricted to observed states achieves the highest marginal likelihoods. The individual RoguePlots reveal large differences in confidence in the placement of the different fossils and allow some refinements to their classification:Polyhelictes bipolarusandIchninsum appendicrassumare moved from an uncertain subfamily placement to Pimplinae,Plectiscidea lanhamiis transferred toAllomacrusin Cylloceriinae (Allomacrus lanhami, comb. nov.),Lithotorus cressoniis moved from Diplazontinae to Orthocentrinae, and we note uncertainty in the generic placement ofXanthopimpla?messelensis. We discuss potential artefacts that might result in biased posterior probabilities in Bayesian morphological phylogenetic analyses, pertaining to character and taxon sampling, fossilization biases, and model misspecification. Finally, we suggest future directions both in ichneumonid palaeontology, in the modelling of morphological evolution, and in the way Bayesian phylogenetics can improve both assessment and representation of fossil placement uncertainty.
Dynamics of contrast decrement and increment responses in human visual cortex
Authors: Norcia Anthony M. , Yakovleva Alexandra , Hung Bethany , Goldberg Jeffrey L.
Published: September 2018

The goal of the present experiments was to determine whether electrophysiological response properties of the ON and OFF visual pathways observed in animal experimental models can be observed in human. Visual Evoked Potentials (VEPs) were recorded in response to equivalent magnitude contrast increments and decrements presented using sawtooth temporal waveforms at a temporal frequency of 2.73 Hz. VEP response waveforms and response spectra for incremental and decremental stimuli were analyzed as a function of stimulus size and visual field location in 68 healthy adult participants. VEP response were larger in amplitude and shorter in latency for contrast decrements than for contrast increments. The spatial tuning was narrower for contrast decrements than for contrast increments and responses were larger for displays that were scaled for cortical magnification. VEPs recorded at the scalp differ between contrast decrements and increments of equal Weber contrast in a fashion that parallels results from the early visual system of cats and monkeys. Because our assay allows differential detection of ON and OFF pathway activity in human, the approach may be useful in future work on disease detection and treatment monitoring.
Indole Pulse Signalling Regulates the Cytoplasmic pH ofE. coliin a Memory-Like Manner
Authors: Zarkan Ashraf , Muñiz Santiago Caño , Zhu Jinbo , Al Nahas Kareem , Cama Jehangir , Keyser Ulrich F. , Summers David K.
Published: September 2018

Bacterial cells are critically dependent upon pH regulation. Most proteins function over a limited pH range and the pH gradient across the bacterial cell membrane is central to energy production and transduction1. Here we demonstrate that indole plays a critical role in the regulation of the cytoplasmic pH ofE. coli. Indole is an aromatic molecule with diverse signalling roles that in bacteria is produced from tryptophan by the enzyme tryptophanase (TnaA)2. Two modes of indole signalling have been described: persistent and pulse signalling. The latter is illustrated by the brief but intense elevation of intracellular indole during stationary phase entry3,4. We show thatE. colicells growing under conditions where no indole is produced maintain their cytoplasmic pH at 7.8 ± 0.2. In contrast, under conditions permitting indole production, pH is maintained at 7.2 ± 0.2. Experiments where indole was added experimentally to non-producing cultures showed that pH regulation results from pulse, rather than persistent, indole signalling. Furthermore, the application of an artificial pulse of either of two non-biological proton ionophores (DNP or CCCP) caused a similar effect, suggesting that the relevant property of indole in this context is its ability to conduct protons across the cytoplasmic membrane5. Additionally, we show that the effect of the indole pulse that occurs normally during stationary phase entry in rich medium remains as a “memory” to maintain the correct cytoplasmic pH until entry into the next stationary phase. The indole-mediated reduction in cytoplasmic pH may explain why indole providesE. coliwith a degree of protection against stresses, including some bactericidal antibiotics.
Vegfaexpression is activated through positive and negative transcriptional regulatory networks controlled by the ETS factor Etv6in vivo
Authors: Li Lei , Rispoli Rossella , Patient Roger , Ciau-Uitz Aldo , Porcher Catherine
Published: September 2018

VEGFA signaling is crucial for physiological and pathological angiogenesis and hematopoiesis. Although many context-dependent signaling pathways downstream of VEGFA have been uncovered, vegfa transcriptional regulation in vivo remains unclear. Here we show that the ETS transcription factor, Etv6, positively regulates vegfa expression during Xenopus blood stem cell development through multiple transcriptional inputs. In agreement with its established repressive functions, Etv6 directly inhibits the expression of the vegfa repressor, foxo3. Surprisingly, it also directly activates the expression of the vegfa activator, klf4. Finally, it indirectly binds to the vegfa promoter where it co-localizes with Klf4. Klf4 deficiency downregulates vegfa expression and significantly decreases Etv6 binding to the vegfa promoter, indicating that Klf4 recruits Etv6 to the vegfa promoter. Thus, our work uncovers a dual function for Etv6, as both a transcriptional repressor and activator, in controlling a major signaling pathway involved in blood and endothelial development in vivo. Given the established relationships between development and cancer, this elaborate gene regulatory network may inform new strategies for the treatment of VEGFA-dependent tumorigenesis.