bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase Engineering of 2D Tin Sulfides
Authors: Mutlu Zafer , Wu Ryan J. , Wickramaratne Darshana , Shahrezaei Sina , Liu Chueh , Temiz Selcuk , Patalano Andrew , Ozkan Mihrimah , Lake Roger K. , Mkhoyan K. A. , Ozkan Cengiz S.
Published: April 2016

Tin sulfides can exist in a variety of phases and polytypes due to the different oxidation states of Sn. A subset of these phases and polytypes take the form of layered 2D structures that give rise to a wide host of electronic and optical properties. Hence, achieving control over the phase, polytype, and thickness of tin sulfides is necessary to utilize this wide range of properties exhibited by the compound. This study reports on phase‐selective growth of both hexagonal tin (IV) sulfide SnS2 and orthorhombic tin (II) sulfide SnS crystals with diameters of over tens of microns on SiO2 substrates through atmospheric pressure vapor‐phase method in a conventional horizontal quartz tube furnace with SnO2 and S powders as the source materials. Detailed characterization of each phase of tin sulfide crystals is performed using various microscopy and spectroscopy methods, and the results are corroborated by ab initio density functional theory calculations.
Glycogen storage disease type III: diagnosis, genotype, management, clinical course and outcome
Authors: Sentner Christiaan P. , Hoogeveen Irene J. , Weinstein David A. , Santer René , Murphy Elaine , McKiernan Patrick J. , Steuerwald Ulrike , Beauchamp Nicholas J. , Taybert Joanna , Laforêt Pascal , Petit François M. , Hubert Aurélie , Labrune Philippe , Smit G. Peter A. , Derks Terry G. J.
Published: April 2016

Glycogen storage disease type III (GSDIII) is a rare disorder of glycogenolysis due to AGL gene mutations, causing glycogen debranching enzyme deficiency and storage of limited dextrin. Patients with GSDIIIa show involvement of liver and cardiac/skeletal muscle, whereas GSDIIIb patients display only liver symptoms and signs. The International Study on Glycogen Storage Disease (ISGSDIII) is a descriptive retrospective, international, multi‐centre cohort study of diagnosis, genotype, management, clinical course and outcome of 175 patients from 147 families (86 % GSDIIIa; 14 % GSDIIIb), with follow‐up into adulthood in 91 patients. In total 58 AGL mutations (non‐missense mutations were overrepresented and 21 novel mutations were observed) were identified in 76 families. GSDIII patients first presented before the age of 1.5 years, hepatomegaly was the most common presenting clinical sign. Dietary management was very diverse and included frequent meals, uncooked cornstarch and continuous gastric drip feeding. Chronic complications involved the liver (hepatic cirrhosis, adenoma(s), and/or hepatocellular carcinoma in 11 %), heart (cardiac involvement and cardiomyopathy, in 58 % and 15 %, respectively, generally presenting in early childhood), and muscle (pain in 34 %). Type 2 diabetes mellitus was diagnosed in eight out of 91 adult patients (9 %). In adult patients no significant correlation was detected between (non‐) missense AGL genotypes and hepatic, cardiac or muscular complications. This study demonstrates heterogeneity in a large cohort of ageing GSDIII patients. An international GSD patient registry is warranted to prospectively define the clinical course, heterogeneity and the effect of different dietary interventions in patients with GSDIII.
2016 Alzheimer's disease facts and figures
Authors:   Alzheimer's Association
Published: April 2016

This report describes the public health impact of Alzheimer's disease, including incidence and prevalence, mortality rates, costs of care, and the overall impact on caregivers and society. It also examines in detail the financial impact of Alzheimer's on families, including annual costs to families and the difficult decisions families must often make to pay those costs. An estimated 5.4 million Americans have Alzheimer's disease. By mid‐century, the number of people living with Alzheimer's disease in the United States is projected to grow to 13.8 million, fueled in large part by the aging baby boom generation. Today, someone in the country develops Alzheimer's disease every 66 seconds. By 2050, one new case of Alzheimer's is expected to develop every 33 seconds, resulting in nearly 1 million new cases per year. In 2013, official death certificates recorded 84,767 deaths from Alzheimer's disease, making it the sixth leading cause of death in the United States and the fifth leading cause of death in Americans age ≥65 years. Between 2000 and 2013, deaths resulting from stroke, heart disease, and prostate cancer decreased 23%, 14%, and 11%, respectively, whereas deaths from Alzheimer's disease increased 71%. The actual number of deaths to which Alzheimer's disease contributes is likely much larger than the number of deaths from Alzheimer's disease recorded on death certificates. In 2016, an estimated 700,000 Americans age ≥65 years will die with Alzheimer's disease, and many of them will die because of the complications caused by Alzheimer's disease. In 2015, more than 15 million family members and other unpaid caregivers provided an estimated 18.1 billion hours of care to people with Alzheimer's and other dementias, a contribution valued at more than $221 billion. Average per‐person Medicare payments for services to beneficiaries age ≥65 years with Alzheimer's disease and other dementias are more than two and a half times as great as payments for all beneficiaries without these conditions, and Medicaid payments are 19 times as great. Total payments in 2016 for health care, long‐term care and hospice services for people age ≥65 years with dementia are estimated to be $236 billion. The costs of Alzheimer's care may place a substantial financial burden on families, who often have to take money out of their retirement savings, cut back on buying food, and reduce their own trips to the doctor. In addition, many family members incorrectly believe that Medicare pays for nursing home care and other types of long‐term care. Such findings highlight the need for solutions to prevent dementia‐related costs from jeopardizing the health and financial security of the families of people with Alzheimer's and other dementias.
Testing and disclosures related to amyloid imaging and Alzheimer's disease: Common questions and fact sheet summary
Authors: Rabinovici Gil D. , Karlawish Jason , Knopman David , Snyder Heather M. , Sperling Reisa , Carrillo Maria C.
Published: April 2016

Alzheimer's disease research has often focused on the molecular brain changes that promote memory loss and other dementia‐related cognitive impairments. Many studies, for example, have used positron emission tomography (PET) imaging to measure brain levels of the beta‐amyloid protein, a key molecular suspect in Alzheimer's. In recent years, PET scans have become more prominent in clinical settings. Clinicians may use a positive PET scan—that is, a significant presence of beta‐amyloid plaques in the brain—to help determine a diagnosis of Alzheimer's disease. Yet, because beta‐amyloid PET remains a fairly new diagnostic tool, physicians and patients still have many basic questions about how and why it is used. This article addresses some of those questions. It explains what PET scans actually show, how they are employed in research and clinical trials, and when they should and should not be used to help diagnose Alzheimer's in everyday patients. The article also discusses whether cognitively healthy people should request PET scans to assess their risk for developing dementia. Information in the text will be updated in future years, as diagnostic imaging techniques for Alzheimer's disease continue to evolve.
Gamma glutamyltransferase and risk of future dementia in middle‐aged to older Finnish men: A new prospective cohort study
Authors: Kunutsor Setor K. , Laukkanen Jari A.
Published: April 2016

Introduction

We assessed the association of gamma glutamyltransferase (GGT) with risk of dementia.

Methods

Serum GGT activity was assessed at baseline in the Kuopio Ischemic Heart Disease prospective cohort of 2415 relatively healthy men with good cognitive function. Correction was made for within‐person variability in GGT levels.

Results

During an average follow‐up of 22 years, 219 new cases of dementia were recorded. Serum GGT was log‐linearly associated with risk of dementia. The hazard ratio (HR) (95% CIs) for dementia per 1 standard deviation (SD) higher baseline loge GGT values was 1.33 (95% CI = 1.14–1.55) after adjustment for several established and emerging risk factors. The corresponding HR was 1.52 (95% CI = 1.22–1.89) after correction for within‐person variability.

Discussion

GGT is positively, log‐linearly, and independently associated with future risk of dementia in the general male population. Further research is needed to unravel the mechanistic pathways of GGT in the pathogenesis of dementia.
Closer caregiver and care‐recipient relationships predict lower informal costs of dementia care: The Cache County Dementia Progression Study
Authors: Rattinger Gail B. , Fauth Elizabeth B. , Behrens Stephanie , Sanders Chelsea , Schwartz Sarah , Norton Maria C. , Corcoran Chris , Mullins C. Daniel , Lyketsos Constantine G. , Tschanz JoAnn T.
Published: April 2016

Introduction

Identifying factors associated with lower dementia care costs is essential. We examined whether two caregiver factors were associated with lower costs of informal care.

Methods

A total of 271 care dyads of the Cache County Dementia Study were included. Estimates of informal costs were based on caregiver reports of time spent in care‐related activities and inflation‐adjusted 2012 Utah median hourly wages. Caregiver coping and emotional closeness with the care‐recipient were assessed using the Ways of Coping Checklist–Revised and Relationship Closeness Scale, respectively.

Results

Higher closeness was associated with 24% lower costs (expβ = 0.763 [95% confidence interval: 0.583–0.999]) in linear mixed models controlling for demographics and baseline dementia severity and duration. Problem‐focused coping was not associated with informal costs (P = .354).

Discussion

Caregiver closeness, a potentially modifiable factor, predicted lower dementia informal care costs over time. Future studies examining the care environment in closer dyads may identify specific care‐related behaviors or strategies that are associated with lower costs.
Detailed Chromospheric Activity Nature of KIC 9641031
Authors: Yoldaş Ezgi , Dal Hasan Ali
Published: April 2016

This study depends on KIC 9641031 eclipsing binary with a chromospherically active component. There are three type variations, such as geometrical variations due to eclipses, sinusoidal variations due to the rotational modulations, and also flares, in the light curves. Taking into account results obtained from observations in the Kepler Mission Database, we discuss the details of chromospheric activity. The sinusoidal light variations due to rotational modulation and the flare events were modelled. 92 different data subsets separated using the analytic models were modelled separately to obtain the cool spot configuration. Acording to the model, there are two active regions separated by about 180° longitudinally between the latitudes of +50° and +100°. 240 flares, whose parameters were computed, were detected. Using these parameters, the OPEA model was derived, in which the Plateau value was found to be 1.232±0.069 s, and half-life parameter was found as 2291.7 s. The flare frequency N1 was found as 0.41632 h−1, while the flare frequency N2 was found as 0.00027. Considering these parameters together with the orbital period variations demonstrates that the period variations depend on chromospheric activity. Comparing the system with its analogue, the activity level of KIC 9641031 is remarkably lower than the others.
Effect of fat type in baked bread on amylose–lipid complex formation and glycaemic response
Authors: Lau Evelyn , Zhou Weibiao , Henry Christiani Jeyakumar
Published: April 2016

The formation of amylose–lipid complexes (ALC) had been associated with reduced starch digestibility. A few studies have directly characterised the extent of ALC formation with glycaemic response. The objectives of this study were to investigate the effect of using fats with varying degree of saturation and chain length on ALC formation as well as glycaemic and insulinaemic responses after consumption of bread. Healthy men consumed five test breads in a random order: control bread without any added fats (CTR) and breads baked with butter (BTR), coconut oil (COC), grapeseed oil (GRP) or olive oil (OLV). There was a significant difference in glycaemic response between the different test breads (P=0·002), primarily due to COC having a lower response than CTR (P=0·016), but no significant differences between fat types were observed. Insulinaemic response was not altered by the addition of fats/oils. Although BTR was more insulinotropic than GRP (P<0·05), postprandialβ-cell function did not differ significantly. The complexing index (CI), a measure of ALC formation, was significantly higher for COC and OLV compared with BTR and GRP (P<0·05). CI was significantly negatively correlated with incremental AUC (IAUC) of change in blood glucose concentrations over time (IAUCglucose) (r–0·365,P=0·001). Linear regression analysis showed that CI explained 13·3 % of the variance and was a significant predictor of IAUCglucose(β=–1·265,P=0·001), but IAUCinsulindid not predict IAUCglucose. Our study indicated that a simple way to modulate glycaemic response in bread could lie in the choice of fats/oils, with coconut oil showing the greatest attenuation of glycaemic response.
Reconciling Nations and Citizenship: Meaning, Creativity, and the Performance of a North Korean Troupe in South Korea
Authors: Koo Sunhee
Published: April 2016

Since 2000, a number of performing troupes have been established in South Korea, made up largely of musicians and dancers who were professionally trained in North Korea prior to their migration and presenting a range of music and dances related to both the North and South. Combining ethnographic data with performance analysis of one such troupe, the Pyŏngyang Minsok Yesultan, I show how the nation and the state intersect in the space of performing arts as the troupe's creative culture reflects the settlement experiences of North Koreans in the South. While the troupe's organization, membership, and performance culture delineate migrant adaptation and understanding of their new citizenship, the performance of these Koreans is a complex terrain in which the two Koreas converge and are contested as the performers enact a constant negotiation between “being” and “negating” North Korean-ness, expressing their cultural hybridity as emergent citizens of the South.
INSTITUTIONS, RULE-FOLLOWING AND GAME THEORY
Authors: Hédoin Cyril
Published: April 2016

Most game-theoretic accounts of institutions reduce institutions to behavioural patterns the players are incentivized to implement. An alternative account linking institutions to rule-following behaviour in a game-theoretic framework is developed on the basis of David Lewis’s and Ludwig Wittgenstein's respective accounts of conventions and language games. Institutions are formalized as epistemic games where the players share some forms of practical reasoning. An institution is a rule-governed game satisfying three conditions: common understanding, minimal awareness and minimal practical rationality. Common understanding has a strong similarity with Ludwig Wittgenstein's concept of lebensform while minimal awareness and minimal practical rationality capture the idea that rule-following is community-based.
Data before models
Authors: POPLACK SHANA , TORRES CACOULLOS RENA
Published: April 2016

New theories are a constant of the now vast literature on code-mixing (CM). The Gradient Symbolic Computation model proposed by Goldrick, Putnam and Schwartz (Goldrick, Putnam & Schwartz) will appeal to many, especially those who already espouse constraint-based approaches to grammar. As variationist sociolinguists, we particularly welcome the model's incorporation of “relative probabilities of certain structures”, a feature we believe can enhance our chances of capturing actual CM behavior. We also applaud Goldrick et al.’s efforts to integrate experimental findings on co-activation with grammatical principles. Our questions concern the utility of “doubling constructions” to showcase the model, and by extension, the degree to which it can account for bilinguals’ spontaneous production of CM. A historical perspective on the field shows that none of the myriad theories of CM, often inspired by competing sets of grammatical principles, has yet achieved broad acceptance. In the absence of any widely endorsed evaluation metric – still sadly lacking -– how are we to decide amongst them?
He Said, She Said: The Impact of Candidate Gender in Negative Campaigns
Authors: Craig Stephen C. , Rippere Paulina S.
Published: April 2016

Although there is evidence that negative advertising “works” at least some of the time, it has been suggested that going negative poses a special risk for female candidates because it violates expectations about appropriate behavior that are rooted in the traditional gender stereotypes still held by many voters. In this paper, we employ data from a survey experiment to examine gender differences in the effectiveness of one particular attack made by a challenger against an incumbent of the opposite sex in a hypothetical race for the U.S. House of Representatives. Our interest is not limited to the attack itself, however, but extends to the question of how candidates should respond when they are attacked and whether certain types of responses/rebuttals (including counterattacks) work better for men than they do for women, and vice versa, in terms of mitigating the damage inflicted by an initially successful negative ad. Overall, we find little support for the idea that the effectiveness of either attack or response (denial, counterattack, counterimaging, justification, accusing one's opponent of mudslinging) varies significantly according to candidate gender. Further, shared partisanship matters more than shared gender in shaping how voters react to the campaign messages of male and female candidates.
Psychometric Properties of the Spanish Adaptation of the Anger Rumination Scale: Evidence of Reliability and Validity in the General Population
Authors: Magán Uceda Inés , Lozano Bleda José Héctor , Pérez Nieto Miguel Ángel , Sukhodolsky Denis G. , Escalona Martínez Amalia
Published: April 2016

The key role of rumination and perseveration processes in anger experience has been empirically supported. The tendency to ruminate has been demonstrated to be crucial in understanding pathological and adaptive behaviours. The Anger Rumination Scale (ARS) was developed to assess anger rumination frequency when people are angry, showing adequate levels of reliability and validity. However, although it has been adapted to several languages, the development of the Spanish version was still pending. The aim of this study, therefore, was to develop the Spanish adaptation of the ARS and to validate it in a general population sample (N = 388). Participants were asked to complete the ARS as well as other measures of anger (STAXI-2), anxiety (STAI-T), depression (BDI-II short form), rumination (PSWQ), and thought self-regulation (TCQ). A confirmatory factor analysis replicated the four-factor structure obtained with the original version (S-B χ2(145) = 323.26, p < .00005; CFI = .92; TLI = .90; RMSEA = .06; SRMR = .05). The resulting subscales (i.e., Angry Afterthoughts, Angry Memories, Thoughts of Revenge, and Understanding of Causes) met psychometric criteria of reliability (α = .89) and validity. In conclusion, a psychometrically sound Spanish adaptation of the ARS is now available.
The Attrition of the Common Fan: Class, Spectatorship, and Major League Stadiums in Postwar America
Authors: Dinces Sean
Published: April 2016

This study examines how changes in the growth model of the US sports business since World War II—namely, changes in stadium design and ticket sales strategies—have transformed the accessibility of major league stadiums and the class composition of the fans inside. While survey data show an overrepresentation of wealthy fans in stadiums at the end of the twentieth century, they reveal little about whether or not this was a new phenomenon. I use ticket sales data to demonstrate that the displacement of working-class fans by the relatively affluent began in earnest at least as early as the 1950s. Before “premium-seating” options like luxury boxes became the norm, the expanded sale of season-ticket packages requiring large up-front payments made it more difficult for wage earners to attend games. While this crowding out of working-class fans has a longer history than very recent outcries over “stadium gentrification” suggest, it has intensified significantly over the last quarter century. Using an original data set containing information on seating arrangements at both the current and previous facilities of 73 of 91 active Major League Baseball, National Basketball Association, and National Football League franchises, this article offers the first systematic evidence in support of claims that the proliferation of luxury suites and other exclusive seating options has resulted in the subtraction of large numbers of relatively affordable seats. This research not only deepens our understanding of the history of urban gentrification and postwar consumption, but also has important implications for the ongoing debate over public stadium subsidies.
You Will Attain My Goal
Authors: Hollmann Jelena , Gorges Julia , Wild Elke
Published: April 2016

Abstract. This paper deals with parental goals for children, that is, goals parents want their children to attain by the time they reach adulthood. Presenting an adaption of the German Aspirations Index to assess parental goals for children (AI-PG), factorial structure and psychometric properties in a nonclinical sample of German parents of children between 10 and 15 years of age were investigated. Parents (NT1 = 948; NT2 = 670) rated the importance of different parental goals for children. The AI-PG structure was first examined in a subsample of mothers using confirmatory factor analyses. Main results provided support for the hypothesized hierarchical factorial structure. Accordingly, the given 21 items can be assigned to seven first-order factors that reflect goal-contents, and two second-order factors that reflect goals’ motivational orientation as either intrinsic or extrinsic. The questionnaire shows good psychometric properties (i.e., homogeneity, model-based reliability, and stability). Multiple-group analyses confirmed measurement invariance across informants (mothers and fathers), gender of target children (daughters and sons), and measurement time points. Small but significant relationships of the scales with need-threatened environment, parenting practices, and child internalizing behavior problems added to the scale’s construct validity. Results are discussed in terms of the fruitfulness of a concept of parental goals for children within self-determination theory.
Development and Psychometric Evaluation of a Revised Sense of	Coherence Scale
Authors: Bachem Rahel , Maercker Andreas
Published: April 2016

Abstract. The present study introduces a revised Sense of Coherence (SOC) scale, a new conceptualization and operationalization of the resilience indicator SOC. It outlines the scale development and aims for testing its reliability, factor structure, and validity. Literature on Antonovsky’s SOC (SOC-A) was critically reviewed to identify needs for improving the scale. The scale was investigated in two samples. Sample 1 consisted of 334 bereaved participants, Sample 2 of 157 healthy controls. The revised SOC Scale, SOC-A, and theoretically relevant questionnaires were applied. Explorative and confirmatory factor analyses established a three-factor structure in both samples. The revised SOC Scale showed significant but discriminative associations with related constructs, including self-efficacy, posttraumatic growth, and neuroticism. The revised measure was significantly associated with psychological health indicators, including persistent grief, depression, and anxiety, but not to the extent as the previous SOC-A. Stability over time was sufficient. The study provides psychometric support for the revised SOC conceptualization and scale. It has several advantages over the previous SOC-A scale (unique variance, distinct factor structure, stability). The scale could be used for clinical and health psychological testing or research into the growing field of studies on resilience over the life span.
The Role of Job and Family Involvement for Satisfaction in Job and	Family
Authors: Konradt Udo , Garbers Yvonne
Published: April 2016

Abstract. Job and family involvement have been shown to have important implications for job and family satisfaction. While most theoretical considerations and research imply that each type of involvement will be beneficial for participation and satisfaction in each particular domain, their joint impact is not well understood. Moreover, little is known of how overall involvement may predict changes in job and family satisfaction across time. This study empirically examines the effect of both involvement in job and family on job and family satisfaction trajectories. Self-report data were collected from 460 employees at three time points over a 12-month period. Using latent growth curve modeling, results demonstrate that people who are highly involved overall (i.e., have high levels in job and family involvement) show higher initial scores in latent job and family satisfaction trajectories, compared to people who have very little involvement. In turn, people who are highly involved overall show a decline in family satisfaction across time. Our results provide insight into the beneficial and detrimental effects that might arise when employees place high importance on both job and family involvement. The findings also suggest that research should address the joint operation of the two types of involvement in order to predict changes in job and family satisfaction over time.
Gypsum Forms in an Unexpected Way
Authors: Joel Lucas
Published: April 2016

Scientists spot the "stem cell" building blocks that lay the foundation for gypsum's formation.
Naïve and memory B cells exhibit distinct biochemical responses following BCR engagement
Authors: Moens Leen , Kane Alisa , Tangye Stuart G
Published: April 2016

Immunological memory is characterized by the rapid reactivation of memory B cells that produce large quantities of high‐affinity antigen‐specific antibodies. This contrasts the response of naïve B cells, and the primary immune response, which is much slower and of lower affinity. Memory responses are critical for protection against infectious diseases and form the basis of most currently available vaccines. Although we have known about the phenomenon of long‐lived memory for centuries, the biochemical differences underlying these diverse responses of naïve and memory B cells is incompletely resolved. Here we investigated the nature of B‐cell receptor (BCR) signaling in human splenic naïve, IgM+ memory and isotype‐switched memory B cells following multivalent BCR crosslinking. We observed comparable rapid and transient phosphorylation kinetics for proximal (phosphotyrosine and spleen tyrosine kinase) and propagation (B‐cell linker, phospholipase Cγ2) signaling components in these different B‐cell subsets. However, the magnitude of activation of downstream components of the BCR signaling pathway were greater in memory compared with naïve cells. Although no differences were observed in the magnitude of Ca2+ mobilization between subsets, IgM+ memory B cells exhibited a more rapid Ca2+ mobilization and a greater depletion of the Ca2+ endoplasmic reticulum stores, while IgG+ memory B cells had a prolonged Ca2+ uptake. Collectively, our findings show that intrinsic signaling features of B‐cell subsets contribute to the robust response of human memory B cells over naïve B cells. This has implications for our understanding of memory B‐cell responses and provides a framework to modulate these responses in the setting of vaccination and immunopathologies, such as immunodeficiency and autoimmunity.
Competition within the virus‐specific CD4 T‐cell pool limits the T follicular helper response after influenza infection
Authors: Olson Matthew R , Chua Brendon Y , Good‐Jacobson Kim L , Doherty Peter C , Jackson David C , Turner Stephen J
Published: April 2016

CD4 T follicular helper cells (TFH) are critical in the generation of potent and long‐lived B‐cell responses after viral infection. However, the factors that dictate the generation and maintenance of these cells are not fully understood. Here we use adoptive transfer of OTII T‐cell receptor transgenic CD4 T cells, followed by infection with recombinant influenza A virus (IAV), as a means of identifying and tracking virus‐specific CD4+ T‐cell responses. We show that T‐cell competition within the virus‐specific CD4 T‐cell pool induced by IAV infection limits the proliferation and differentiation of IAV‐specific CD4+ TFH responses. In particular, increased T‐cell competition for antigen results in a diminished IAV‐specific TFH CD4 T‐cell responses, particularly germinal center TFH responses. Strikingly, competition in the form of preexisting cellular immunity generated by heterosubtypic IAV immunization limits de novo CD4 T‐cell responses in secondary lymphoid tissue. Taken together, these data show a profound linkage between antigen availability and promotion of TFH CD4+ T‐cell responses in response to infection. These data suggest that competition within the CD4 T‐cell pool limits TFH responses and may be an important regulatory mechanism for controlling immunity.
A mobile genetic element profoundly increases heat resistance of bacterial spores
Authors: Berendsen Erwin M , Boekhorst Jos , Kuipers Oscar P , Wells-Bennik Marjon H J
Published: April 2016

Bacterial endospores are among the most resilient forms of life on earth and are intrinsically resistant to extreme environments and antimicrobial treatments. Their resilience is explained by unique cellular structures formed by a complex developmental process often initiated in response to nutrient deprivation. Although the macromolecular structures of spores from different bacterial species are similar, their resistance to environmental insults differs widely. It is not known which of the factors attributed to spore resistance confer very high-level heat resistance. Here, we provide conclusive evidence that in Bacillus subtilis, this is due to the presence of a mobile genetic element (Tn1546-like) carrying five predicted operons, one of which contains genes that encode homologs of SpoVAC, SpoVAD and SpoVAEb and four other genes encoding proteins with unknown functions. This operon, named spoVA2mob, confers high-level heat resistance to spores. Deletion of spoVA2mob in a B. subtilis strain carrying Tn1546 renders heat-sensitive spores while transfer of spoVA2mob into B. subtilis 168 yields highly heat-resistant spores. On the basis of the genetic conservation of different spoVA operons among spore-forming species of Bacillaceae, we propose an evolutionary scenario for the emergence of extremely heat-resistant spores in B. subtilis, B. licheniformis and B. amyloliquefaciens. This discovery opens up avenues for improved detection and control of spore-forming bacteria able to produce highly heat-resistant spores.
Comparative analysis of ear-hole closure identifies epimorphic regeneration as a discrete trait in mammals
Authors: Gawriluk Thomas R. , Simkin Jennifer , Thompson Katherine L. , Biswas Shishir K. , Clare-Salzler Zak , Kimani John M. , Kiama Stephen G. , Smith Jeramiah J. , Ezenwa Vanessa O. , Seifert Ashley W.
Published: April 2016

Why mammals have poor regenerative ability has remained a long-standing question in biology. In regenerating vertebrates, injury can induce a process known as epimorphic regeneration to replace damaged structures. Using a 4-mm ear punch assay across multiple mammalian species, here we show that several Acomys spp. (spiny mice) and Oryctolagus cuniculus completely regenerate tissue, whereas other rodents including MRL/MpJ ‘healer’ mice heal similar injuries by scarring. We demonstrate ear-hole closure is independent of ear size, and closure rate can be modelled with a cubic function. Cellular and genetic analyses reveal that injury induces blastema formation in Acomys cahirinus. Despite cell cycle re-entry in Mus musculus and A. cahirinus, efficient cell cycle progression and proliferation only occurs in spiny mice. Together, our data unite blastema-mediated regeneration in spiny mice with regeneration in other vertebrates such as salamanders, newts and zebrafish, where all healthy adults regenerate in response to injury.
Insights into the activation mechanism of class I HDAC complexes by inositol phosphates
Authors: Watson Peter J. , Millard Christopher J. , Riley Andrew M. , Robertson Naomi S. , Wright Lyndsey C. , Godage Himali Y. , Cowley Shaun M. , Jamieson Andrew G. , Potter Barry V. L. , Schwabe John W. R.
Published: April 2016

Histone deacetylases (HDACs) 1, 2 and 3 form the catalytic subunit of several large transcriptional repression complexes. Unexpectedly, the enzymatic activity of HDACs in these complexes has been shown to be regulated by inositol phosphates, which bind in a pocket sandwiched between the HDAC and co-repressor proteins. However, the actual mechanism of activation remains poorly understood. Here we have elucidated the stereochemical requirements for binding and activation by inositol phosphates, demonstrating that activation requires three adjacent phosphate groups and that other positions on the inositol ring can tolerate bulky substituents. We also demonstrate that there is allosteric communication between the inositol-binding site and the active site. The crystal structure of the HDAC1:MTA1 complex bound to a novel peptide-based inhibitor and to inositol hexaphosphate suggests a molecular basis of substrate recognition, and an entropically driven allosteric mechanism of activation.
Rifampin phosphotransferase is an unusual antibiotic resistance kinase
Authors: Stogios Peter J. , Cox Georgina , Spanogiannopoulos Peter , Pillon Monica C. , Waglechner Nicholas , Skarina Tatiana , Koteva Kalinka , Guarné Alba , Savchenko Alexei , Wright Gerard D.
Published: April 2016

Rifampin (RIF) phosphotransferase (RPH) confers antibiotic resistance by conversion of RIF and ATP, to inactive phospho-RIF, AMP and Pi. Here we present the crystal structure of RPH from Listeria monocytogenes (RPH-Lm), which reveals that the enzyme is comprised of three domains: two substrate-binding domains (ATP-grasp and RIF-binding domains); and a smaller phosphate-carrying His swivel domain. Using solution small-angle X-ray scattering and mutagenesis, we reveal a mechanism where the swivel domain transits between the spatially distinct substrate-binding sites during catalysis. RPHs are previously uncharacterized dikinases that are widespread in environmental and pathogenic bacteria. These enzymes are members of a large unexplored group of bacterial enzymes with substrate affinities that have yet to be fully explored. Such an enzymatically complex mechanism of antibiotic resistance augments the spectrum of strategies used by bacteria to evade antimicrobial compounds.
Structural correlates of affinity in fetal versus adult endplate nicotinic receptors
Authors: Nayak Tapan Kumar , Chakraborty Srirupa , Zheng Wenjun , Auerbach Anthony
Published: April 2016

Adult-type nicotinic acetylcholine receptors (AChRs) mediate signalling at mature neuromuscular junctions and fetal-type AChRs are necessary for proper synapse development. Each AChR has two neurotransmitter binding sites located at the interface of a principal and a complementary subunit. Although all agonist binding sites have the same core of five aromatic amino acids, the fetal site has ∼30-fold higher affinity for the neurotransmitter ACh. Here we use molecular dynamics simulations of adult versus fetal homology models to identify complementary-subunit residues near the core that influence affinity, and use single-channel electrophysiology to corroborate the results. Four residues in combination determine adult versus fetal affinity. Simulations suggest that at lower-affinity sites, one of these unsettles the core directly and the others (in loop E) increase backbone flexibility to unlock a key, complementary tryptophan from the core. Swapping only four amino acids is necessary and sufficient to exchange function between adult and fetal AChRs.
Network dynamics in nanofilled polymers
Authors: Baeza Guilhem P. , Dessi Claudia , Costanzo Salvatore , Zhao Dan , Gong Shushan , Alegria Angel , Colby Ralph H. , Rubinstein Michael , Vlassopoulos Dimitris , Kumar Sanat K.
Published: April 2016

It is well accepted that adding nanoparticles (NPs) to polymer melts can result in significant property improvements. Here we focus on the causes of mechanical reinforcement and present rheological measurements on favourably interacting mixtures of spherical silica NPs and poly(2-vinylpyridine), complemented by several dynamic and structural probes. While the system dynamics are polymer-like with increased friction for low silica loadings, they turn network-like when the mean face-to-face separation between NPs becomes smaller than the entanglement tube diameter. Gel-like dynamics with a Williams–Landel–Ferry temperature dependence then result. This dependence turns particle dominated, that is, Arrhenius-like, when the silica loading increases to ∼31 vol%, namely, when the average nearest distance between NP faces becomes comparable to the polymer’s Kuhn length. Our results demonstrate that the flow properties of nanocomposites are complex and can be tuned via changes in filler loading, that is, the character of polymer bridges which ‘tie’ NPs together into a network.
The HSP70 co-chaperone DNAJC14 targets misfolded pendrin for unconventional protein secretion
Authors: Jung Jinsei , Kim Jiyoon , Roh Shin Hye , Jun Ikhyun , Sampson Robert D. , Gee Heon Yung , Choi Jae Young , Lee Min Goo
Published: April 2016

Mutations in SLC26A4, which encodes pendrin, are responsible for hearing loss with an enlarged vestibular aqueduct and Pendred syndrome. The most prevalent mutation in East Asia is p.H723R (His723Arg), which leads to defects in protein folding and cell-surface expression. Here we show that H723R-pendrin can be rescued to the cell surface by an HSP70 co-chaperone DNAJC14-dependent unconventional trafficking pathway. Blockade of ER-to-Golgi transport or activation of ER stress signals induced Golgi-independent cell-surface expression of H723R-pendrin and restored its cell-surface Cl−/HCO3− exchange activity. Proteomic and short interfering RNA screenings with subsequent molecular analyses showed that Hsc70 and DNAJC14 are required for the unconventional trafficking of H723R-pendrin. Moreover, DNAJC14 upregulation was able to induce the unconventional cell-surface expression of H723R-pendrin. These results indicate that Hsc70 and DNAJC14 play central roles in ER stress-associated unconventional protein secretion and are potential therapeutic targets for diseases such as Pendred syndrome, which arise from transport defects of misfolded proteins.
Host gene constraints and genomic context impact the expression and evolution of human microRNAs
Authors: França Gustavo S. , Vibranovski Maria D. , Galante Pedro A. F.
Published: April 2016

Increasing evidence has shown that recent miRNAs tend to emerge within coding genes. Here we conjecture that human miRNA evolution is tightly influenced by the genomic context, especially by host genes. Our findings show a preferential emergence of intragenic miRNAs within old genes. We found that miRNAs within old host genes are significantly more broadly expressed than those within young ones. Young miRNAs within old genes are more broadly expressed than their intergenic counterparts, suggesting that young miRNAs have an initial advantage by residing in old genes, and benefit from their hosts’ expression control and from the exposure to diverse cellular contexts and target genes. Our results demonstrate that host genes may provide stronger expression constraints to intragenic miRNAs in the long run. We also report associated functional implications, highlighting the genomic context and host genes as driving factors for the expression and evolution of human miRNAs.
Correction: Corrigendum: Establishment of a cone photoreceptor transplantation platform based on a novel cone-GFP reporter mouse line
Authors: Smiley Sheila , Nickerson Philip E. , Comanita Lacrimioara , Daftarian Narsis , El-Sehemy Ahmed , Tsai En Leh Samuel , Matan-Lithwick Stuart , Yan Keqin , Thurig Sherry , Touahri Yacine , Dixit Rajiv , Aavani Tooka , De Repentigny Yves , Baker Adam , Tsilfidis Catherine , Biernaskie Jeff , Sauvé Yves , Schuurmans Carol , Kothary Rashmi , Mears Alan J. , Wallace Valerie A.
Published: April 2016

Scientific Reports 6: Article number: 22867 ; published online: 11 March 2016; updated: 22 April 2016 The original version of this Article contained a typographical error in the spelling of the author Yves De Repentigny, which was incorrectly given as Yves De Repentingy. This has now been corrected in the PDF and HTML versions of the Article.
Correction: Corrigendum: N-terminal domain of Bothrops asper Myotoxin II Enhances the Activity of Endothelin Converting Enzyme-1 and Neprilysin
Authors: Smith A. Ian , Rajapakse Niwanthi W. , Kleifeld Oded , Lomonte Bruno , Sikanyika Nkumbu L. , Spicer Alexander J. , Hodgson Wayne C. , Conroy Paul J. , Small David H. , Kaye David M. , Parkington Helena C. , Whisstock James C. , Kuruppu Sanjaya
Published: April 2016

Scientific Reports 6: Article number: 22413; published online: 02 March 2016; updated: 22 April 2016 The Acknowledgements section in this Article is incomplete. “We wish to thank William He and Steven Fernandez for technical support. This research was supported by funding from the J.o. & J.R. Wicking Trust & Mason Foundation; a strategic rant awarded to Dr.
Correction: Corrigendum: Gene profiling of embryonic skeletal muscle lacking type I ryanodine receptor Ca2+ release channel
Authors: Filipova Dilyana , Walter Anna M. , Gaspar John A. , Brunn Anna , Linde Nina F. , Ardestani Mostafa A. , Deckert Martina , Hescheler Jürgen , Pfitzer Gabriele , Sachinidis Agapios , Papadopoulos Symeon
Published: April 2016

Scientific Reports 6: Article number: 20050; published online: 01 February 2016; updated: 22 April 2016 This Article contains a typographical error in the Methods section under subheading ‘Animals and skeletal muscle preparation’. “All experimental protocols were approved by the local governmental authorities (Landesamt für Natur, Umwelt und Verbraucherschutz, North Rhine-Westphalia, AZ84-02.
Snapshot Hyperspectral Volumetric Microscopy
Authors: Wu Jiamin , Xiong Bo , Lin Xing , He Jijun , Suo Jinli , Dai Qionghai
Published: April 2016

The comprehensive analysis of biological specimens brings about the demand for capturing the spatial, temporal and spectral dimensions of visual information together. However, such high-dimensional video acquisition faces major challenges in developing large data throughput and effective multiplexing techniques. Here, we report the snapshot hyperspectral volumetric microscopy that computationally reconstructs hyperspectral profiles for high-resolution volumes of ~1000 μm × 1000 μm × 500 μm at video rate by a novel four-dimensional (4D) deconvolution algorithm. We validated the proposed approach with both numerical simulations for quantitative evaluation and various real experimental results on the prototype system. Different applications such as biological component analysis in bright field and spectral unmixing of multiple fluorescence are demonstrated. The experiments on moving fluorescent beads and GFP labelled drosophila larvae indicate the great potential of our method for observing multiple fluorescent markers in dynamic specimens.
Role of Berberine in the Treatment of Methicillin-Resistant Staphylococcus aureus Infections
Authors: Chu Ming , Zhang Ming-bo , Liu Yan-chen , Kang Jia-rui , Chu Zheng-yun , Yin Kai-lin , Ding Ling-yu , Ding Ran , Xiao Rong-xin , Yin Yi-nan , Liu Xiao-yan , Wang Yue-dan
Published: April 2016

Berberine is an isoquinoline alkaloid widely used in the treatment of microbial infections. Recent studies have shown that berberine can enhance the inhibitory efficacy of antibiotics against clinical multi-drug resistant isolates of methicillin-resistantStaphylococcus aureus(MRSA). However, the underlying mechanisms are poorly understood. Here, we demonstrated that sub-minimum inhibitory concentrations (MICs) of berberine exhibited no bactericidal activity against MRSA, but affected MRSA biofilm development in a dose dependent manner within the concentration ranging from 1 to 64 μg/mL. Further study indicated that berberine inhibited MRSA amyloid fibrils formation, which consist of phenol-soluble modulins (PSMs). Molecular dynamics simulation revealed that berberine could bind with the phenyl ring of Phe19 in PSMα2 through hydrophobic interaction. Collectively, berberine can inhibit MRSA biofilm formationviaaffecting PSMs’ aggregation into amyloid fibrils and thereby enhance bactericidal activity of antibiotics. These findings will provide new insights into the multiple pharmacological properties of berberine in the treatment of microbial-generated amyloid involved diseases.
Coherent Charge Transport in Ballistic InSb Nanowire Josephson Junctions
Authors: Li S. , Kang N. , Fan D. X. , Wang L. B. , Huang Y. Q. , Caroff P. , Xu H. Q.
Published: April 2016

Hybrid InSb nanowire-superconductor devices are promising for investigating Majorana modes and topological quantum computation in solid-state devices. An experimental realisation of ballistic, phase-coherent superconductor-nanowire hybrid devices is a necessary step towards engineering topological superconducting electronics. Here, we report on a low-temperature transport study of Josephson junction devices fabricated from InSb nanowires grown by molecular-beam epitaxy and provide a clear evidence for phase-coherent, ballistic charge transport through the nanowires in the junctions. We demonstrate that our devices show gate-tunable proximity-induced supercurrent and clear signatures of multiple Andreev reflections in the differential conductance, indicating phase-coherent transport within the junctions. We also observe periodic modulations of the critical current that can be associated with the Fabry-Pérot interference in the nanowires in the ballistic transport regime. Our work shows that the InSb nanowires grown by molecular-beam epitaxy are of excellent material quality and hybrid superconducting devices made from these nanowires are highly desirable for investigation of the novel physics in topological states of matter and for applications in topological quantum electronics.
Correction: Corrigendum: Panel-based NGS Reveals Novel Pathogenic Mutations in Autosomal Recessive Retinitis Pigmentosa
Authors: Perez-Carro Raquel , Corton Marta , Sánchez-Navarro Iker , Zurita Olga , Sanchez-Bolivar Noelia , Sánchez-Alcudia Rocío , Lelieveld Stefan H. , Aller Elena , Lopez-Martinez Miguel Angel , López-Molina Mª Isabel , Fernandez-San Jose Patricia , Blanco-Kelly Fiona , Riveiro-Alvarez Rosa , Gilissen Christian , Millan Jose M , Avila-Fernandez Almudena , Ayuso Carmen
Published: April 2016

Scientific Reports 6: Article number: 19531; published online: 25 January 2016; updated: 22 April 2016 This Article contains errors. In Table 1, for Family RP-1929 the nucleotide change ‘c.9079dupA’ and protein change ‘p.Arg3027Lysfs*9’ were incorrectly given as ‘c.9142dupA’ and ‘p.Arg3048Lysfs*9’ respectively.