bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative effectiveness and safety study of triple therapy with simeprevir or telaprevir for non‐cirrhotic patients with chronic hepatitis C virus genotype 1b infection
Authors: Ogawa Eiichi , Furusyo Norihiro , Kajiwara Eiji , Nomura Hideyuki , Kawano Akira , Takahashi Kazuhiro , Dohmen Kazufumi , Satoh Takeaki , Azuma Koichi , Nakamuta Makoto , Koyanagi Toshimasa , Kotoh Kazuhiro , Shimoda Shinji , Hayashi Jun
Published: June 2015

Background and Aim

The addition of hepatitis C virus (HCV) NS3/4A protease inhibitors to pegylated‐interferon alpha (PEG‐IFNα) and ribavirin (triple therapy) has greatly improved treatment outcome. The aim of this study was to compare the effectiveness and safety of simeprevir‐based or telaprevir‐based triple therapy for non‐cirrhotic patients in real‐world clinical practice.

Methods

This multicenter study consisted of 835 consecutive Japanese HCV genotype 1b patients treated in a clinical setting, 716 of whom were enrolled (simeprevir = 256 and telaprevir = 460). Logistic regression was carried out after propensity score matching to assess the sustained virological response at week 12 after the end of treatment (SVR12).

Results

In the propensity‐matched cohort (253 matched pairs), the SVR12 rates of the patients who underwent simeprevir‐based or telaprevir‐based triple therapy were 85.0% and 84.2%, respectively, by intention‐to‐treat analysis. Prior treatment response to PEG‐IFNα/ribavirin and IL28B genotype was independently associated with SVR12 in both groups. No significant differences in the SVR12 rates stratified by prior treatment response to PEG‐IFNα/ribavirin were found between the simeprevir (treatment‐naïve 89.1%, prior relapse 94.3%, prior partial response 65.0%, and prior null response 33.3%) and telaprevir (treatment‐naïve 87.8%, prior relapse 90.1%, prior partial response 68.4%, and prior null response 50.0%) groups. The incidence of adverse effects, such as anemia, severe rash, and the elevation of serum creatinine, was markedly higher in the telaprevir group.

Conclusions

Considering the effectiveness and safety, simeprevir‐based triple therapy will continue to be a useful treatment option in Japan for treatment‐naïve or prior relapse patients with a favorable IL28B genotype.
Lymphocyte activation gene 3 negatively regulates the function of intrahepatic hepatitis C virus‐specific CD8+ T cells
Authors: Chen Na , Liu Yehong , Guo Yonghong , Chen Yunru , Liu Xiaojing , Liu Min
Published: June 2015

Background and Aim:

Chronic hepatitis C (CHC) in humans caused by persistent hepatitis C virus (HCV) infection is a global public health problem. The functional exhaustion of HCV‐specific CD8+ T cells regulated by several inhibitory receptors has been shown to contribute to chronic HCV infection. Lymphocyte activation gene 3 (LAG‐3), which is an inhibitory receptor, plays an important role in several chronic viral infections. However, its effect on the function of HCV‐specific CD8+ T cells is unclear.

Methods:

The expression of LAG‐3 on the CD8+ T cells in intrahepatic and peripheral lymphocytes from 17 CHC patients and 15 HCV‐negative patients was analyzed by flow cytometry. The LAG‐3 expression in CD8+ T cells was downregulated or upregulated by lentivirus LAG‐3 shRNA or lentivirus overexpressing LAG‐3. After HCV peptide stimulation, flow cytometry was used to detect cell proliferation and cytokine (γ‐interferon [IFN‐γ], tumor necrosis factor‐α [TNF‐α], granzyme B, and perforin) production of CD8+ T cells. Cytotoxicity functions of HCV‐specific CD8+ T cells were measured using a 51Cr release assay.

Results:

The frequency of LAG‐3‐positive intrahepatic and peripheral CD8+ T cells was higher in CHC patients, compared with HCV‐negative patients. The cell proliferation, cytokine (IFN‐γ, TNF‐α, granzyme B, and perforin) expression and cytotoxicity function of HCV‐specific CD8+ T cells in CHC patients were increased by the knocking down and blockade of LAG‐3. In the LAG‐3 overexpressed CD8+ T cells, cell proliferation, cytokine (IFN‐γ, TNF‐α, granzyme B, and perforin) expression, and cytotoxicity function were inhibited, while the LAG‐3 blocking antibody reversed the inhibition.

Conclusion:

LAG‐3 negatively regulated the function of HCV‐specific CD8+ T cells in CHC patients.
Improvement of liver function and non‐invasive fibrosis markers in hepatitis B virus‐associated cirrhosis: 2 years of entecavir treatment
Authors: Shin Seung Kak , Kim Jeong Han , Park Hyeonsu , Kwon Oh Sang , Lee Hyun Jung , Yeon Jong Eun , Byun Kwan Soo , Suh Sang Jun , Yim Hyung Joon , Kim Yun Soo , Kim Ju Hyun
Published: June 2015

Background and Aim

Entecavir (ETV) induces biochemical and histologic improvement of the liver in patients with chronic hepatitis B. This study aimed to confirm that 2 years of ETV treatment improves liver function and non‐invasive fibrosis markers in patients with hepatitis B virus (HBV)‐associated cirrhosis.

Methods

A total 472 naïve patients with HBV‐associated cirrhosis was treated with ETV for at least 2 years, between March 2007 and December 2012. Model for end‐stage liver disease and Child‐Pugh (CP) score were used to evaluate the improvement of liver function. Aspartate transaminase to platelet ratio index, FIB‐4 index, and fibrosis index were used to evaluate the improvement of fibrosis.

Results

The final 370 of 472 patients with HBV‐associated cirrhosis were enrolled. Mean age was 51 ± 10 years, and 240 patients (64.9%) were men. The distribution of CP class was 71.1% in A, 24.6% in B, and 4.3% in C. Mean end‐stage liver disease and CP score changed over the study period from 8.5 ± 4.6 to 6.2 ± 4.2 (P < 0.001) and from 6.2 ± 1.6 to 5.6 ± 0.9 (P < 0.001), respectively. Aspartate transaminase to platelet ratio index, FIB‐4 index, and fibrosis index changed from 3.6 ± 4.5 to 1.5 ± 1.5 (P < 0.001), from 7.0 ± 6.2 to 3.9 ± 2.8 (P < 0.001), and from 3.3 ± 0.9 to 2.5 ± 1.1 (P < 0.001), respectively.

Conclusions

After 2 years of treatment, ETV improves liver function and non‐invasive fibrosis markers in patients with HBV‐associated cirrhosis.
Is Self‐Reported Sleep Duration Associated with Osteoporosis? Data from a 4‐Year Aggregated Analysis from the National Health and Nutrition Examination Survey
Authors: Cunningham Tina D. , Di Pace Brian S.
Published: June 2015

Objectives

To examine the association between self‐reported sleep duration and osteoporosis in a national sample of the U.S. elderly population.

Design

Population‐based cross‐sectional study.

Setting

Four‐year National Health and Nutrition Examination Survey data from two survey cycles between 2005–06 and 2007–08.

Participants

Men and women aged 50 and older with data in the surveys and medical examination data files (N = 5,288).

Measurements

Osteoporosis diagnosis was based on bone mineral density measurement and self‐report. Sleep duration was ascertained from the sleep survey. Simple and multiple logistic regression models were used to evaluate the association between these two factors.

Results

Shorter sleep duration (<6 hours) was found to be significantly associated with osteoporosis after adjusting for potential covariates (odds ratio (OR) = 1.59, 95% confidence interval (CI) = 1.07–2.37). After stratifying according to age group, this association remained significant (OR = 1.80, 95% CI = 1.20–2.68) only in the older age group (>65).

Conclusion

These results underscore the possible linkage between sleep and osteoporosis and the need for additional research on this topic.
Analysis of High‐Resolution Utility Data for Understanding Energy Use in Urban Systems: The Case of Los Angeles, California
Authors: Pincetl Stephanie , Graham Robert , Murphy Sinnott , Sivaraman Deepak
Published: June 2015

Urban metabolism provides a framework to understand resource flows into cities and waste flows out. Its potential has been hampered by the lack of good disaggregated data. This article presents energy‐use findings for the residential sector for the city of Los Angeles based on census‐block–level aggregation of address‐level electricity use obtained from the Los Angeles Department of Water and Power. City or county billing data by customer class over time can enable empirical tracking of energy conservation and efficiency programs by different customer classes, and matched to census information and county tax assessor data about building vintage, size, and type can provide information important for rate setting, for example, or energy conservation and efficiency program investments. We report on median electricity demand and corresponding greenhouse gas emissions and expenditures at three geographical aggregations: city council district (15 in total); neighborhood (114 in total); and census block group (2,538 in total). We find that the ratio of median annual demand between highest‐ and lowest‐tier users is 26 at the census‐block group level, but only 2.2 at the city council district level, demonstrating that spatial aggregation significantly masks the degree of variation that may be observed. We also show how such data can enable the description of energy to develop energy disclosure thresholds that reflect a city's morphology. In contrast to New York City's 50,000‐square‐foot reporting threshold, to capture half of Los Angeles’ electricity consumption, the threshold for reporting would have to be 5,000 square feet.
“Mental Health” Power and Its Effects: A Commentary on Battling Against Inter‐Faith Relations in Israel
Authors: Sparks Jacqueline A.
Published: June 2015

Hakak () provides an opportunity to examine how mental health and therapy systems in the United States operate to maintain current social and political structures. This commentary suggests that practitioners, including family therapists, participate in and support practices that do not serve the interests of marginalized social groups, despite our best intentions. Discourse theory offers a lens through which such practices become visible and thus open to revision.
Effects of the amount of rice in meals on postprandial blood pressure in older people with postprandial hypotension: a within‐subjects design
Authors: Son Jung Tae , Lee Eunjoo
Published: June 2015

Aims and objectives

To determine the effect of the amount of rice carbohydrates consumed during mealtime on the extent of decrease in postprandial blood pressure in older people with postprandial hypotension.

Background

The incidence of postprandial hypotension is as high as 74% in older people with hypertension.

Design

A within‐subjects repeated measures design was used.

Methods

Thirty‐nine older people in nursing homes received a full serving and a half‐serving of rice on two separate days, in random order blood pressure and heart rate were measured before each meal and every 15 minutes for a total of 120 minutes after each meal. Data were analysed using repeated measures analysis of variance and the paired t‐test with a Bonferroni adjustment using IBM spss version 19.0.

Results

The control and intervention conditions yielded significantly different patterns in systolic blood pressure and diastolic blood pressure. Postprandial hypotension was less frequent under the intervention condition; however, decrease in rice intake did not significantly affect heart rate.

Conclusion

Reducing the amount of rice intake per meal prevents postprandial blood pressure decreases in the older people. Small and frequent meals with decreased carbohydrate content are recommended to prevent postprandial hypotension and its complications in the older people.

Relevance to clinical practice

Patients, dieticians and caregivers of older patients should be aware of the importance of diet, especially of decreasing the amount of carbohydrate in a meal. Smaller and more frequent meals are recommended for older people to slow gastric emptying.
Nonmarital Relationships and Changing Perceptions of Marriage Among African American Young Adults
Authors: Barr Ashley B. , Simons Ronald L. , Simons Leslie Gordon
Published: June 2015

Cohabitation has become increasingly widespread over the past decade. Such trends have given rise to debates about the relation between cohabitation and marriage in terms of what cohabitation means for individual relationship trajectories and for the institution of marriage more generally. Using recent data from a sample of almost 800 African Americans and fixed effects modeling procedures, in the present study the authors shed some light on these debates by exploring the extent to which cohabitation, relative to both singlehood and dating, was associated with within‐individual changes in African Americans' marital beliefs during the transition to adulthood. The findings suggest that cohabitation is associated with changes in marital beliefs, generally in ways that repositioned partners toward marriage, not away from it. This was especially the case for women. These findings suggest that, for young African American women, cohabitation holds a distinct place relative to dating and, in principle if not practice, relative to marriage.
Management of sleep bruxism in adults: a qualitative systematic literature review
Authors: Manfredini Daniele , Ahlberg Jari , Winocur Ephraim , Lobbezoo Frank
Published: June 2015

This paper updates the bruxism management review published by Lobbezoo et al. in 2008 (J Oral Rehabil 2008; 35: 509–23). The review focuses on the most recent literature on management of sleep bruxism (SB) in adults, as diagnosed with polysomnography (PSG) with audio–video (AV) recordings, or with any other approach measuring the sleep‐time masticatory muscles' activity, viz., PSG without AV recordings or electromyography (EMG) recorded with portable devices. Fourteen (N = 14) papers were included in the review, of which 12 were randomised controlled trials (RCTs) and 2 were uncontrolled before–after studies. Structured reading of the included articles showed a high variability of topics, designs and findings. On average, the risk of bias for RCTs was low‐to‐unclear, whilst the before–after studies had several methodological limitations. The studies’ results suggest that (i) almost every type of oral appliance (OA) (seven papers) is somehow effective to reduce SB activity, with a potentially higher decrease for devices providing large extent of mandibular advancement; (ii) all tested pharmacological approaches [i.e. botulinum toxin (two papers), clonazepam (one paper) and clonidine (one paper)] may reduce SB with respect to placebo; (iii) the potential benefit of biofeedback (BF) and cognitive–behavioural (CB) approaches to SB management is not fully supported (two papers); and (iv) the only investigation providing an electrical stimulus to the masseter muscle supports its effectiveness to reduce SB. It can be concluded that there is not enough evidence to define a standard of reference approach for SB treatment, except for the use of OA. Future studies on the indications for SB treatment are recommended.
Thin Images Reflected in the Water: Narcissism and Girls’ Vulnerability to the Thin‐Ideal
Authors: Thomaes Sander , Sedikides Constantine
Published: June 2015

The purpose of this research is to test how adolescent girls’ narcissistic traits—characterized by a need to impress others and avoid ego‐threat—influence acute adverse effects of thin‐ideal exposure. Participants (11–15 years; total N = 366; all female) reported their narcissistic traits. Next, in two experiments, they viewed images of either very thin or average‐sized models, reported their wishful identification with the models (Experiment 2), and tasted high‐calorie foods in an alleged taste test (both experiments). Narcissism kept girls from wishfully identifying with thin models, which is consistent with the view that narcissistic girls are prone to disengage from thin‐ideal exposure. Moreover, narcissism protected vulnerable girls (those who experience low weight‐esteem) from inhibiting their food intake, and led other girls (those who consider their appearance relatively unimportant) to increase their food intake. These effects did not generalize to conceptually related traits of self‐esteem and perfectionism, and were not found for a low‐calorie foods outcome, attesting to the specificity of findings. These experiments demonstrate the importance of narcissism at reducing girls’ thin‐ideal vulnerability. Girls high in narcissism disengage self‐protectively from threats to their self‐image, a strategy that renders at least subsets of them less vulnerable to the thin‐ideal.
Melatonin alleviates brain injury in mice subjected to cecal ligation and puncture via attenuating inflammation, apoptosis, and oxidative stress: the role of SIRT1 signaling
Authors: Zhao Lei , An Rui , Yang Yang , Yang Xiangmin , Liu Haixiao , Yue Liang , Li Xia , Lin Yan , Reiter Russel J. , Qu Yan
Published: June 2015

Sepsis is a systemic inflammatory response to infection that causes severe neurological complications. Previous studies have suggested that melatonin is protective during sepsis. Additionally, silent information regulator 1 (SIRT1) was reported to be beneficial in sepsis. However, the role of SIRT1 signaling in the protective effect of melatonin against septic encephalopathy remains unclear. This study aimed to investigate the role of SIRT1 in the protective effect of melatonin. EX527, a SIRT1 inhibitor, was used to reveal the role of SIRT1 in melatonin's action. Cecal ligation and puncture or sham operation was performed in male C57BL/6J mice. Melatonin was administrated intraperitoneally (30 mg/kg). The survival rate of mice was recorded for the 7‐day period following the sham or CLP operation. The blood–brain barrier (BBB) integrity, brain water content, levels of inflammatory cytokines (TNF‐α, IL‐1β, and HMGB1), and the level of oxidative stress (superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA)) and apoptosis were assessed. The expression of SIRT1, Ac‐FoxO1, Ac‐p53, Ac‐NF‐κB, Bcl‐2, and Bax was detected by Western blot. The results suggested that melatonin improved survival rate, attenuated brain edema and neuronal apoptosis, and preserved BBB integrity. Melatonin decreased the production of TNF‐α, IL‐1β, and HMGB1. Melatonin increased the activity of SOD and CAT and decreased the MDA production. Additionally, melatonin upregulated the expression of SIRT1 and Bcl‐2 and downregulated the expression of Ac‐FoxO1, Ac‐p53, Ac‐NF‐κB, and Bax. However, the protective effects of melatonin were abolished by EX527. In conclusion, our results demonstrate that melatonin attenuates sepsis‐induced brain injury via SIRT1 signaling activation.
Nutrient limitation of algal periphyton in streams along an acid mine drainage gradient
Authors: DeNicola Dean M. , Lellock Amber J.
Published: June 2015

Metal oxyhydroxide precipitates that form from acid mine drainage (AMD) may indirectly limit periphyton by sorbing nutrients, particularly P. We examined effects of nutrient addition on periphytic algal biomass (chl a), community structure, and carbon and nitrogen content along an AMD gradient. Nutrient diffusing substrata with treatments of +P, +NP and control were placed at seven stream sites. Conductivity and SO4 concentration ranged over an order of magnitude among sites and were used to define the AMD gradient, as they best indicate mine discharge sources of metals that create oxyhydroxide precipitates. Aqueous total phosphorous (TP) ranged from 2 to 23 μg · L−1 and significantly decreased with increasing SO4. Mean chl a concentrations at sites ranged from 0.2 to 8.1 μg · cm−2. Across all sites, algal biomass was significantly higher on +NP than control treatments (Co), and significantly increased with +NP. The degree of nutrient limitation was determined by the increase in chl a concentration on +NP relative to Co (response ratio), which ranged from 0.6 to 9.7. Response to nutrient addition significantly declined with increasing aqueous TP, and significantly increased with increasing SO4. Thus, nutrient limitation of algal biomass increased with AMD impact, indicating metal oxyhydroxides associated with AMD likely decreased P availability. Algal species composition was significantly affected by site but not nutrient treatment. Percent carbon content of periphyton on the Co significantly increased with AMD impact and corresponded to an increase in the relative abundance of Chlorophytes. Changes in periphyton biomass and cellular nutrient content associated with nutrient limitation in AMD streams may affect higher trophic levels.
Novel psychrotolerant picocyanobacteria isolated from Chesapeake Bay in the winter
Authors: Xu Yongle , Jiao Nianzhi , Chen Feng
Published: June 2015

Picocyanobacteria are major primary producers in the ocean, especially in the tropical or subtropical oceans or during warm seasons. Many “warm” picocyanobacterial species have been isolated and characterized. However, picocyanobacteria in cold environments or cold seasons are much less studied. In general, little is known about the taxonomy and ecophysiology of picocyanobacteria living in the winter. In this study, 17 strains of picocyanobacteria were isolated from Chesapeake Bay, a temperate estuarine ecosystem, during the winter months. These winter isolates belong to five distinct phylogenetic lineages, and are distinct from the picocyanobacteria previously isolated from the warm seasons. The vast majority of the winter isolates were closely related to picocyanobacteria isolated from other cold environments like Arctic or subalpine waters. The winter picocyanobacterial isolates were able to maintain slow growth or prolonged dormancy at 4°C. Interestingly, the phycoerythrin‐rich strains outperformed the phycocyanin‐rich strains at cold temperature. In addition, winter picocyanobacteria changed their morphology when cultivated at 4°C. The close phylogenetic relationship between the winter picocyanobacteria and the picocyanobacteria living in high latitude cold regions indicates that low temperature locations select specific ecotypes of picocyanobacteria.
Effects of lunar phase on sleep in men and women in Surrey
Authors: Della Monica Ciro , Atzori Giuseppe , Dijk Derk‐Jan
Published: June 2015

Recently, evidence has emerged that the phases of the moon may modulate subjective sleep quality and polysomnographically assessed sleep structure in humans. We aimed to explore further the putative effects of circa‐lunar periodicity (~29.5 days) on subjective and objective parameters of human sleep in a retrospective analysis. The baseline sleep recordings of 205 (91 males and 114 females; mean age = 47.47 years, standard deviation =19.01; range: 20–84 years) healthy and carefully screened participants who participated in two clinical trials in the Surrey Clinical Research Centre were included in the analyses. Sleep was recorded in windowless sleep laboratories. For each study night, we calculated the distance, in days, to the date of the closest full moon phase and based on this distance, classified sleep records in three lunar classes. Univariate analysis of variance with factors lunar class, age and sex was applied to each of 21 sleep parameters. No significant main effect for the factor lunar class was observed for any of the objective sleep parameters and subjective sleep quality but some significant interactions were observed. The interaction between lunar class and sex was significant for total sleep time, Stage 4 sleep and rapid eye movement (REM) sleep. Separate analyses for men and women indicated that in women total sleep time, Stage 4 sleep and REM sleep were reduced when sleep occurred close to full moon, whereas in men REM duration increased around full moon. These data provide limited evidence for an effect of lunar phase on human sleep.
MEAN‐VARIANCE POLICY FOR DISCRETE‐TIME CONE‐CONSTRAINED MARKETS: TIME CONSISTENCY IN EFFICIENCY AND THE MINIMUM‐VARIANCE SIGNED SUPERMARTINGALE MEASURE
Authors: Cui Xiangyu , Li Duan , Li Xun
Published: June 2015

The discrete‐time mean‐variance portfolio selection formulation, which is a representative of general dynamic mean‐risk portfolio selection problems, typically does not satisfy time consistency in efficiency (TCIE), i.e., a truncated precommitted efficient policy may become inefficient for the corresponding truncated problem. In this paper, we analytically investigate the effect of portfolio constraints on the TCIE of convex cone‐constrained markets. More specifically, we derive semi‐analytical expressions for the precommitted efficient mean‐variance policy and the minimum‐variance signed supermartingale measure (VSSM) and examine their relationship. Our analysis shows that the precommitted discrete‐time efficient mean‐variance policy satisfies TCIE if and only if the conditional expectation of the density of the VSSM (with respect to the original probability measure) is nonnegative, or once the conditional expectation becomes negative, it remains at the same negative value until the terminal time. Our finding indicates that the TCIE property depends only on the basic market setting, including portfolio constraints. This motivates us to establish a general procedure for constructing TCIE dynamic portfolio selection problems by introducing suitable portfolio constraints.
Possible melting produced chondrule destruction in NWA 6604 CK4 chondrite
Authors: Kereszturi A. , Ormandi S. , Jozsa S.
Published: June 2015

In analyzing a thin section of the NWA 6604 CK4 meteorite, only altered chondrules and various components that are probably left behind the destruction of former chondrules can be observed. We suggest that melting, grain size decrease, resorption of the original chondrules, and crystallization of opaque minerals were the main processes that destroyed the chondrules. Four different events could be identified as having occurred during this alteration. First, opaques crystallized along former fractures producing chains of separated grains. Later, opaques and Ca‐rich minerals crystallized together in veins and large melt pockets; this was the strongest recrystallization phase involving the largest volume of melt. This occurred along different fractures than the first phase above. During the third phase, only Ca‐rich plagioclase crystallized along thin veins, and in a fourth phase, fractures formed again, partly along those formed during the second phases but without substantial mineral infill. Two simple possible case models should be considered for this meteorite: alteration by purely impact‐driven processes or mainly by melt‐driven processes. Although for CK4 chondrites, the shock‐produced alteration driven by impact is the more accepted and widespread approach, melting is also compatible with the observed textural characteristics of chondrule destruction. During melting, recrystallization took place producing iron‐rich minerals earlier and Ca‐Si‐rich ones later. The penetration of melts into veins contributed in the chondrule destruction. The stress directions also changed during these alterations, and minerals that formed later filled differently oriented fractures than the earlier ones. From our observations, we favor a view where heat‐driven melting and recrystallization produced the destruction and uniform mineralogy in the sample.
The instrumentally recorded fall of the Križevci meteorite, Croatia, February 4, 2011
Authors: Borovička J. , Spurný P. , Šegon D. , Andreić Ž. , Kac J. , Korlević K. , Atanackov J. , Kladnik G. , Mucke H. , Vida D. , Novoselnik F.
Published: June 2015

The Križevci H6 meteorite was recovered on the basis of fireball data obtained by the cameras of the Croatian Meteor Network. The fireball, which occurred on February 4, 2011, 23:20:40 UT, was also observed by meteor cameras in Slovenia and by the Autonomous Fireball Observatory in Martinsberg, Austria, which belongs to the European Fireball Network. Here, we present detailed data on fireball trajectory, velocity, deceleration, light curve, and orbit. We also modeled the atmospheric fragmentation of the meteoroid on the basis of the light curve and deceleration. The initial mass of the meteoroid was between 25–100 kg, most probably about 50 kg. Severe fragmentation occurred at heights of approximately 60 and 31 km, under dynamic pressures of 0.1 and 3 MPa, respectively. The peak absolute magnitude of −13.7 was reached during the second severe fragmentation event. The recovered 291 g meteorite was probably the only fragment with a terminal mass exceeding 100 g. The orbit had a low inclination of 0.6 degrees, perihelion distance 0.74 AU, and semimajor axis 1.54 AU. Križevci can be ranked among the 10 best documented meteorite falls.
Phylogeny and biogeography of the American live oaks (QuercussubsectionVirentes): a genomic and population genetics approach
Authors: Cavender‐Bares Jeannine , González‐Rodríguez Antonio , Eaton Deren A. R. , Hipp Andrew A. L. , Beulke Anne , Manos Paul S.
Published: June 2015

The nature and timing of evolution of niche differentiation among closely related species remains an important question in ecology and evolution. The American live oak clade,Virentes,which spans the unglaciated temperate and tropical regions of North America and Mesoamerica, provides an instructive system in which to examine speciation and niche evolution. We generated a fossil‐calibrated phylogeny ofVirentesusingRADseq data to estimate divergence times and used nuclear microsatellites, chloroplast sequences and an intron region of nitrate reductase (NIA‐i3) to examine genetic diversity within species, rates of gene flow among species and ancestral population size of disjunct sister species. Transitions in functional and morphological traits associated with ecological and climatic niche axes were examined across the phylogeny. We found theVirentesto be monophyletic with three subclades, including a southwest clade, a southeasternUSclade and a Central American/Cuban clade. Despite high leaf morphological variation within species and transpecific chloroplast haplotypes,RADseq and nuclearSSRdata showed genetic coherence of species. We estimated a crown date forVirentesof 11 Ma and implicated the formation of the Sea of Cortés in a speciation event ~5 Ma. Tree height at maturity, associated with fire tolerance, differs among the sympatric species, while freezing tolerance appears to have diverged repeatedly across the tropical–temperate divide. Sympatric species thus show evidence of ecological niche differentiation but share climatic niches, while allopatric and parapatric species conserve ecological niches, but diverge in climatic niches. The mode of speciation and/or degree of co‐occurrence may thus influence which niche axis plants diverge along.
A prezygotic transmission distorter acting equally in female and male zebra finchesTaeniopygia guttata
Authors: Knief Ulrich , Schielzeth Holger , Ellegren Hans , Kempenaers Bart , Forstmeier Wolfgang
Published: June 2015

The two parental alleles at a specific locus are usually inherited with equal probability to the offspring. However, at least three processes can lead to an apparent departure from fair segregation: early viability selection, biased gene conversion and various kinds of segregation distortion. Here, we conduct a genome‐wide scan for transmission distortion in a captive population of zebra finches (Taeniopygia guttata) using 1302 single‐nucleotide polymorphisms (SNPs) followed by confirmatory analyses on independent samples from the same population. In the initial genome‐wide scan, we found significant distortion at three linked loci on chromosomeTgu2and we were able to replicate this finding in each of two follow‐up data sets [overall transmission ratio = 0.567 (95%CI = 0.536–0.600), based on 1101 informative meioses]. Although the driving allele was preferentially transmitted by both heterozygous females [ratio = 0.560 (95%CI = 0.519–0.603)] and heterozygous males [ratio = 0.575 (95%CI = 0.531–0.623)], we could rule out postzygotic viability selection and biased gene conversion as possible mechanisms. Early postzygotic viability selection is unlikely, because it would result in eggs with no visible embryo and hence no opportunity for genotyping, and we confirmed that both females and males heterozygous for the driving allele did not produce a larger proportion of such eggs than homozygous birds. Biased gene conversion is expected to be rather localized, while we could trace transmission distortion in haplotypes of several megabases in a recombination desert. Thus, we here report the rare case of a prezygotically active transmission distorter operating equally effectively in female and male meioses.
Evolution of egg coats: linking molecular biology and ecology
Authors: Shu Longfei , Suter Marc J.‐F. , Räsänen Katja
Published: June 2015

One central goal of evolutionary biology is to explain how biological diversity emerges and is maintained in nature. Given the complexity of the phenotype and the multifaceted nature of inheritance, modern evolutionary ecological studies rely heavily on the use of molecular tools. Here, we show how molecular tools help to gain insight into the role of egg coats (i.e. the extracellular structures surrounding eggs and embryos) in evolutionary diversification. Egg coats are maternally derived structures that have many biological functions from mediating fertilization to protecting the embryo from environmental hazards. They show great molecular, structural and functional diversity across species, but intraspecific variability and the role of ecology in egg coat evolution have largely been overlooked. Given that much of the variation that influences egg coat function is ultimately determined by their molecular phenotype, cutting‐edge molecular tools (e.g. proteomics, glycomics and transcriptomics), combined with functional assays, are needed for rigorous inferences on their evolutionary ecology. Here, we identify key research areas and highlight emerging molecular techniques that can increase our understanding of the role of egg coats in the evolution of biological diversity, from adaptation to speciation.
Regulation of DNA phosphorothioate modifications by the transcriptional regulator DptB in Salmonella
Authors: Cheng Qiuxiang , Cao Bo , Yao Fen , Li Jinli , Deng Zixin , You Delin
Published: June 2015

DNA phosphorothioate (PT) modifications, with one non‐bridging phosphate oxygen replaced with sulfur, are widely but sporadically distributed in prokaryotic genomes. Short consensus sequences surround the modified linkage in each strain, although each site is only partially modified. The mechanism that maintains this low‐frequency modification status is still unknown. In Salmonella enterica serovar Cerro 87, PT modification is mediated by a four‐gene cluster called dptBCDE. Here, we found that deletion of dptB led to a significant increase in intracellular PT modification level. In this deletion, transcription of downstream genes was elevated during rapid cell growth. Restoration of dptB on a plasmid restored wild‐type levels of expression of downstream genes and PT modification. In vitro, DptB directly protected two separate sequences within the dpt promoter region from DNase I cleavage. Each protected sequence contained a direct repeat (DR). Mutagenesis assays of the DRs demonstrated that each DR was essential for DptB binding. The observation of two shifted species by gel‐shift analysis suggests dimer conformation of DptB protein. These DRs are conserved among the promoter regions of dptB homologs, suggesting that this regulatory mechanism is widespread. These findings demonstrate that PT modification is regulated at least in part at the transcriptional level.
Long‐term interspecies association patterns of Atlantic bottlenose dolphins, Tursiops truncatus, and Atlantic spotted dolphins, Stenella frontalis, in the Bahamas
Authors: Elliser Cindy R. , Herzing Denise L.
Published: June 2015

With the exception of primates, detailed interspecies behavioral studies are rare in mammalian species and for cetaceans, most are anecdotal descriptions. This study is the first long‐term study on interspecies associations of regularly interacting groups. In the Bahamas Atlantic bottlenose (Tursiops truncatus) and spotted dolphins (Stenella frontalis) regularly form mixed species encounters (MSE). Both species show strong site fidelity with high resighting rates. During MSE, the majority (>65%) of spotted dolphins (especially males) were continually resighted; however bottlenose dolphins had comparatively low resighting rates (<17%). During MSE group size was significantly larger for spotted dolphins (13.0 ± 11.0) than bottlenose dolphins (4.8 ± 3.5) (F = 93.803, df = 1, P < 0.001). This difference was largest during aggressive encounters, due to the increased spotted dolphin group size (t‐test, t = 4.75, df = 184, P < 0.0001), but no difference in bottlenose dolphin group size. Strong associations (greater than twice the community average) were primarily between male spotted dolphins. Male alliances were prevalent for spotted dolphins but rare for bottlenose dolphins. These species differences were also observed in lagged association rates. These results highlight the differences involved in alliance formation and function for regularly interacting sympatric species and reveal insights into possible ecological and social reasons for these group formations.
Use of enhancer trapping to identify pathogen‐induced regulatory events spatially restricted to plant–microbe interaction sites
Authors: Schroeder Mercedes , Tsuchiya Tokuji , He Shuilin , Eulgem Thomas
Published: June 2015

Plant genes differentially expressed during plant–pathogen interactions can be important for host immunity or can contribute to pathogen virulence. Large‐scale transcript profiling studies, such as microarray‐ or mRNA‐seq‐based analyses, have revealed hundreds of genes that are differentially expressed during plant–pathogen interactions. However, transcriptional responses limited to a small number of cells at infection sites can be difficult to detect using these approaches, as they are under‐represented in the whole‐tissue datasets typically generated by such methods. This study examines the interactions between Arabidopsis thaliana (Arabidopsis) and the pathogenic oomycete Hyaloperonospora arabidopsidis (Hpa) by enhancer trapping to uncover novel plant genes involved in local infection responses. We screened a β‐glucuronidase (GUS) reporter‐based enhancer‐trap population for expression patterns related to Hpa infection. Several independent lines exhibited GUS expression in leaf mesophyll cells surrounding Hpa structures, indicating a regulatory response to pathogen infection. One of these lines contained a single enhancer‐trap insertion in an exon of At1g08800 (MyoB1, Myosin Binding Protein 1) and was subsequently found to exhibit reduced susceptibility to Hpa. Two additional Arabidopsis lines with T‐DNA insertions in exons of MyoB1 also exhibited approximately 30% fewer spores than wild‐type plants. This study demonstrates that our enhancer‐trapping strategy can result in the identification of functionally relevant pathogen‐responsive genes. Our results further suggest that MyoB1 either positively contributes to Hpa virulence or negatively affects host immunity against this pathogen.
Brain weight in sudden unexpected death in infancy: experience from a large single‐centre cohort
Authors: Bamber Andrew R. , Paine Simon M. L. , Ridout Deborah A. , Pryce Jeremy W. , Jacques Thomas S. , Sebire Neil J.
Published: June 2015

Aims

Published reports of brain weight in sudden infant death syndrome (SIDS) are contradictory, although several have concluded that brain weight is increased in SIDS compared with controls or reference data. This is important as, if brain weight is significantly different, it may be of diagnostic use or provide insights into the aetiology of SIDS. The aim of this study was to use a large series of well‐characterized sudden unexpected infant deaths from a single centre to provide definitive data regarding this issue.

Methods

A retrospective review identified 1100 infants who had died suddenly and undergone a comprehensive autopsy at Great Ormond Street Hospital between 1996 and 2011. They were split into two groups: those in whom death could be explained and those whose deaths remained unexplained despite full investigation (SIDS/unexplained sudden unexpected death in infancy).

Results

There were 1100 cases of whom 573 (52%) were unexplained and 527 (48%) explained. Multiple regression analysis, which adjusted for sex, age and post‐mortem interval, showed no difference in the ratio of brain weight : body weight between those infants dying of explained causes and those in whom no cause could be found. This finding remained true when restricting analysis to those with macroscopically normal brains.

Conclusions

In this large series of infants dying of both explained and unexplained causes, brain weight, once corrected for body weight, did not vary consistently with the cause of death. Brain weight cannot be used as a diagnostic indicator of the cause of death or to inform hypothetical models of the pathogenesis of SIDS.
Motor neurone disease/amyotrophic lateral sclerosis associated with intermediate‐length CAG repeat expansions in Ataxin‐2 does not have 1C2‐positive polyglutamine inclusions
Authors: Highley John Robin , Lorente Pons Alejandro , Cooper‐Knock Johnathan , Wharton Stephen B. , Ince Paul G. , Shaw Pamela J. , Wood Jon , Kirby Janine
Published: June 2015

Background

Intermediate‐length cytosine‐adenine‐guanine repeat expansions in the ATXN2 gene (which encodes for Ataxin‐2 protein) have been linked to increased risk for motor neurone disease/amyotrophic lateral sclerosis (ALS). We screened DNA from cases for which we had post‐mortem brain tissue to enable characterization of the neuropathology associated with this mutation.

Methods

Polymerase chain reaction and sequencing of DNA from frozen brain tissue on a cohort of 178 amyotrophic lateral sclerosis (ALS) autopsy cases from the north of England and 159 controls was performed. This was followed by tinctorial staining and immunohistochemistry (including for Ataxin‐2) on selected blocks from ALS cases with intermediate‐length expansions (ATXN2‐ALS), sporadic ALS cases and neurologically healthy controls.

Results

Four ALS cases with intermediate‐length CAG repeat expansions within ATXN2 were identified. One such case also had a mutation of the C9ORF72 gene. All had lower motor neurone depletion, and three out of four cases had transactive response DNA binding protein 43 (TDP‐43)‐positive neuronal cytoplasmic inclusions (predominantly skein‐like). No inclusions of aggregated polyglutamine proteins were identified. Ataxin‐2 protein expression was largely granular and cytoplasmic with the most prominent staining observed in larger neurones. Ataxin‐2 staining was variable both within and between cases, but no staining pattern that was specific for cases with ATXN2 mutations was seen.

Conclusions

Intermediate expansions of the CAG repeat in ATXN2 are associated with ALS. They are mostly associated with TDP‐43 proteinopathy, but not with 1C2‐positive polyglutamine inclusions. In the nervous system, Ataxin‐2 protein expression is predominantly seen in large neurones. There is no consistent histopathological hallmark that is unique to ATXN2‐ALS.
EZH2 expression in gliomas: Correlation with CDKN2A gene deletion/ p16 loss and MIB‐1 proliferation index
Authors: Purkait Suvendu , Sharma Vikas , Jha Prerana , Sharma Mehar Chand , Suri Vaishali , Suri Ashish , Sharma BS , Sarkar Chitra
Published: June 2015

Enhancer of zeste homolog 2 (EZH2) mediated down‐regulation of CDKN2A/p16 has been observed in cell lines as well as in a few carcinomas. However, there is no study correlating EZH2 expression with CDKN2A/p16 status in gliomas. Hence, the present study was conducted to evaluate EZH2 expression in astrocytic and oligodendroglial tumors and correlate with CDKN2A/p16 status as well as MIB‐1 labeling index (LI). Gliomas of all grades (n = 118) were studied using immunohistochemistry to assess EZH2, p16 and MIB‐1 LI and fluorescence in situ hybrization to evaluate CDKN2A gene status. EZH2 expression and CDKN2A homozygous deletion (HD) were both significantly more frequent in high‐grade gliomas (HGG). Further, strong EZH2 expression (LI ≥ 25%) was significantly more common in HGGs without CDKN2A HD (48.7%; 19/39) as compared to cases with deletion (15.8%; 3/19). Loss of p16 expression was noted in 100% and 51.3% of CDKN2A deleted and non‐deleted tumors, respectively. Notably, 80% (16/20) of the CDKN2A non‐deleted HGGs with p16 loss had strong EZH2 expression, in contrast to only 15.8% (3/19) in the deleted group. Loss of p16 expression significantly correlated with MIB‐1 LI, irrespective of EZH2 status. Thus, this study shows that EZH2 expression correlates with tumor grade in both astrocytic and oligodendroglial tumors and hence can be used as a diagnostic marker to differentiate between low and HGGs. Further, this is the first report demonstrating an inverse correlation of strong EZH2 expression with CDKN2A HD in HGGs. Loss of p16 protein expression is mostly attributable to CDKN2A HD and correlates significantly with MIB‐1 LI. Notably, our study for the first time suggests a possible epigenetic mechanism of p16 loss in CDKN2A non‐deleted HGGs mediated by strong EZH2 expression. A hypothetical model for control of proliferative activity in low versus HGGs is therefore proposed.
Complex sarcolemmal invaginations mimicking myotendinous junctions in a case of Laing early‐onset distal myopathy
Authors: Reis Gerald F. , de la Motte Grant , Gooding Rebecca , Laing Nigel G. , Margeta Marta
Published: June 2015

Distal myopathies are a group of clinically and pathologically overlapping muscle diseases that are genetically complex and can represent a diagnostic challenge. Laing early‐onset distal myopathy (MPD1) is a form of distal myopathy caused by mutations in the MYH7 gene, which encodes the beta myosin heavy chain protein expressed in type 1 skeletal muscle fibers and cardiac myocytes. Here, we present a case of genetically confirmed MPD1 with a typical clinical presentation but distinctive light microscopic and ultrastructural findings on muscle biopsy. A 39‐year‐old professional male cellist presented with a bilateral foot drop that developed by age 8; analysis of the family pedigree showed an autosomal dominant pattern of inheritance. The physical exam demonstrated bilateral weakness of ankle dorsiflexors, toe extensors and finger extensors; creatine kinase level was normal. Biopsy of the quadriceps femoris muscle showed predominance and hypotrophy of type 1 fibers, hybrid fibers with co‐expression of slow and fast myosin proteins (both in highly atrophic and normal size range), moth‐eaten fibers and mini‐cores, lack of rimmed vacuoles and rare desmin‐positive eosinophilic sarcoplasmic inclusions. In addition to these abnormalities often observed in MPD1, the biopsy demonstrated frequent clefted fibers with complex sarcolemmal invaginations; on ultrastructural examination, these structures closely mimicked myotendinous junctions but were present away from the tendon and were almost exclusively found in type 1 fibers. Sequencing analysis of the MYH7 gene in the index patient and other affected family members demonstrated a previously described heterozygous c.4522_4524delGAG (p.Glu1508del) mutation. This case widens the pathologic spectrum of MPD1 and highlights the pathologic and clinical variability that can accompany the same genetic mutation, suggesting a significant role for modifier genes in MPD1 pathogenesis.