bluuebunny/crossref_metadata_2025 huggingface dataset:
Rates and predictors of remission, recurrence and conversion to bipolar disorder after the first lifetime episode of depression – a prospective 5-year follow-up study
Authors: Bukh J. D. , Andersen P. K. , Kessing L. V.
Published: January 2016

Background

In depression, non-remission, recurrence of depressive episodes after remission and conversion to bipolar disorder are crucial determinants of poor outcome. The present study aimed to determine the cumulative incidences and clinical predictors of these long-term outcomes after the first lifetime episode of depression.

Method

A total of 301 in- or out-patients aged 18–70 years with a validated diagnosis of a single depressive episode were assessed from 2005 to 2007. At 5 years of follow-up, 262 patients were reassessed by means of the life chart method and diagnostic interviews from 2011 to 2013. Cumulative incidences and the influence of clinical variables on the rates of remission, recurrence and conversion to bipolar disorder, respectively, were estimated by survival analysis techniques.

Results

Within 5 years, 83.3% obtained remission, 31.5% experienced recurrence of depression and 8.6% converted to bipolar disorder (6.3% within the first 2 years). Non-remission increased with younger age, co-morbid anxiety and suicidal ideations. Recurrence increased with severity and treatment resistance of the first depression, and conversion to bipolar disorder with treatment resistance, a family history of affective disorder and co-morbid alcohol or drug abuse.

Conclusions

The identified clinical characteristics of the first lifetime episode of depression should guide patients and clinicians for long-term individualized tailored treatment.
Taxometric evidence of a dimensional latent structure for depression in an epidemiological sample of children and adolescents
Authors: Liu R. T.
Published: January 2016

Background

A basic phenomenological question of much theoretical and empirical interest is whether the latent structure of depression is dimensional or categorical in nature. Prior taxometric studies of youth depression have yielded mixed findings. In a step towards resolving these contradictory findings, the current taxometric investigation is the first to utilize a recently developed objective index, the comparison curve fit index, to evaluate the latent structure of major depression in an epidemiological sample of children and adolescents.

Method

Data were derived from Mental Health of Children and Young People in Great Britain surveys. Participants were administered a structured diagnostic interview to assess for current depression. Parents (n= 683) were interviewed for children aged 5–16 years, and child interviews (n= 605) were conducted for those aged 11–16 years.

Results

MAMBAC (mean above minus below a cut), MAXEIG (maximum eigenvalue) and L-Mode (latent mode) analyses provided convergent support for a dimensional latent structure.

Conclusions

The current findings suggest that depression in youth is more accurately conceptualized as a continuous syndrome rather than a discrete diagnostic entity.
Work Enforcement in Liberal Democracies
Authors: RAFFASS TANIA
Published: January 2016

The paper aims to contribute to the normative debate concerning work enforcement in liberal democracies. In the late 1980s, OECD countries began to revert to the pre-welfare-state tradition of attributing unemployment to personal failure. The new welfare-to-work policies emphasised individual responsibility for securing employment. Stepping up job search requirements and sanctions for failure to meet them was presented as a public intervention that helps unemployed individuals return from dependency to autonomy. Jobseekers have been made to believe that success in obtaining employment depends on how doggedly they search for work and how adaptable they become to employer needs. These presumptions are challenged in the paper. Contracts that jobseekers are forced to sign with providers of employment services curtail their autonomy not only to the extent that they cannot avoid unproductive activity tests imposed on them, but also from a lifetime perspective in cases where they are forced into inferior jobs. In job-short economies, employers are also certain to discriminate against disadvantaged jobseekers notwithstanding the intensity of their effort or openness to occupational change.
A trend towards increasing viral load in newly diagnosed HIV-infected inpatients in southeast China
Authors: CHEN Y. , WANG Z. , HUANG A. , YUAN J. , WEI D. , YE H.
Published: January 2016

Peripheral blood viral load is an important indicator of viral production and clearance. Previous studies have suggested that viral load might predict the rate of decrease in CD4+cell count and progression to AIDS and death. Here, we conducted a retrospective analysis of the trends in HIV-1 viral load in southeast China. Among inpatients newly diagnosed with HIV infection, we found that viral load has increased over the past decade from 4·20 log10copies/ml in 2002 to 6·61 log10copies/ml in 2014, with a mean increase of 0·19 log10copies/ml each year. However, the CD4+cell count was stable and insensitive to changes in viral load. Thus, increasing viral load appears to be an emerging trend in newly diagnosed HIV-infected inpatients.
Health and health-related quality of life in pig farmers carrying livestock-associated methicillin-resistantStaphylococcus aureus
Authors: VAN CLEEF B. A. G. L , VAN BENTHEM B. H. B. , VERKADE E. J. M. , VAN RIJEN M. M. L. , KLUYTMANS-VAN DEN BERGH M. F. Q. , GRAVELAND H. , BOSCH T. , VERSTAPPEN K. M. H. W. , WAGENAAR J. A. , HEEDERIK D. , KLUYTMANS J. A. J. W.
Published: January 2016

There is limited knowledge about the effect of livestock-associated methicillin-resistantStaphylococcus aureus(LA-MRSA) carriage on health-related quality of life (QoL). With this study, we explored whether LA-MRSA causes infections or affects health-related QoL in pig farmers. This prospective cohort study surveyed persons working on 49 farrowing pig farms in The Netherlands for 1 year (2010–2011). On six sampling moments, nasal swabs, environmental samples and questionnaires on activities and infections were collected. At the end of the study year, persons were asked about their QoL using the validated SF-36 and EQ-5D questionnaires. Of 120 persons, 44 (37%) were persistent MRSA carriers. MRSA carriage was not associated with infections, use of antimicrobials, healthcare contact and health-related QoL items in univariate or multivariate analysis, most likely due to the ‘healthy worker effect’. Despite high carriage rates, the impact of LA-MRSA carriage in this population of relatively healthy pig farmers on health and health-related QoL appears limited; more research is needed for confirmation.
Virology and epidemiology analyses of global adenovirus-associated conjunctivitis outbreaks, 1953–2013
Authors: ZHANG L. , ZHAO N. , SHA J. , WANG C. , JIN X. , AMER S. , LIU S.
Published: January 2016

This study aimed to compare the virology and epidemiology of epidemic keratoconjunctivitis (EKC), pharyngoconjunctival fever (PCF) and acute haemorrhagic conjunctivitis (AHC) outbreaks worldwide caused by the human adenovirus (HAdV) from 1953 to 2013. Eighty-three hexon sequences from 76 conjunctivitis outbreaks were analysed and subtyped using Mega 5.05, Clustal X and SimPlot software. Epidemiology was performed for the area, age and seasonal distribution. A phylogenetic analysis indicated that all the isolates could be divided into three subgenetic lineages, without a common ancestor. The major causes of the outbreaks were Ad8, Ad7 and Ad2 co-infection with enterovirus 70 (EV70) in EKC, PCF and AHC, respectively. The epidemiological findings suggested that EKC and AHC were circulating predominantly in Asia during the early winter and spring, whereas PCF was circulating mainly in China, Australia and the United States during the summer. This study suggests that EKC, AHC and PCF outbreaks have different circulating patterns throughout the world and are caused by different adenovirus serotypes. A global surveillance system should be established to monitor conjunctivitis outbreaks in the future.
Phenotypic and genotypic characterization of twoToxoplasma gondiiisolates in free-range chickens from Uberlândia, Brazil
Authors: LOPES C. S. , FRANCO P. S. , SILVA N. M. , SILVA D. A. O. , FERRO E. A. V. , PENA H. F. J. , SOARES R. M. , GENNARI S. M. , MINEO J. R.
Published: January 2016

The aim of this study was to determine the seroprevalence ofToxoplasma gondiiinfection in free-range chickens from Uberlândia, Minas Gerais state, Brazil, and characterize the genotypic and phenotypic features of two isolates of this parasite, considering the importance of these hosts in the epidemiology of toxoplasmosis. Serum samples from 108 free-range chickens were obtained from ten different districts, and submitted to the modified agglutination test (MAT) for the presence of anti-T. gondiiantibodies, and brain and heart tissue samples from infected chickens were processed for mouse bioassay. An overall seroprevalence of 71·3% was found and antibody titres ranged from 16 to 4096. After confirmation of seropositivity by mouse bioassay, the determination of theT. gondiigenotypes of two isolates was performed by PCR–RFLP, using primers for the following markers: SAG1, SAG2, SAG3, BTUB, GRA6, c22–8, c29–2, L358, PK1, new SAG2, Apico and CS3. TheseT. gondiiisolates, designated TgChBrUD1and TgChBrUD2, were obtained from heart samples of free-range chickens. The TgChBrUD1 isolate belonged to ToxoDB PCR–RFLP genotype 11 and the TgChBrUD2 isolate belonged to ToxoDB PCR–RFLP genotype 6. Both isolates demonstrated high virulence in a rodent model, with the TgChBrUD1 isolate able to induce brain cysts, in accord with its pattern of multiplication rates in human fibroblast culture. Taken together, these results reveal high prevalence ofT. gondiiinfection in free-range chickens throughout Uberlândia, indicating an important degree of oocyst environmental contamination and the existence of considerable risk forT. gondiitransmission to humans by consumption of free-range chicken as a food source.
An assessment of the gravity signature of the Windmill Islands, East Antarctica
Authors: Bailey Brad T. , Morgan Peter J. , Lackie Mark A.
Published: January 2016

A gravity survey was conducted on the Windmill Islands, East Antarctica, during the 2004–05 summer season. The aim of the study was to investigate the subsurface geology of the Windmill Islands area. Ninety-seven gravity stations were established. Additionally, 49 observations from a survey in 1993–94 were re-reduced and merged with the 2004–05 data. A three-dimensional subsurface model was constructed from the merged gravity dataset to determine the subsurface geology of the Windmill Islands. The main country rock in the Windmill Islands is a Garnet-bearing Granite Gneiss. A relatively dense intrusive charnockite unit, the Ardery Charnockite, generates the dominant gravity high of the study area and has been modelled to extend to depths of 7–13 km. It has moderate to steep contacts against the surrounding Garnet-bearing Granite Gneiss. The Ardery Charnockite surrounds a less dense granite pluton, the Ford Granite, which is modelled to a depth of 6–12 km and creates a localized gravity low. This granitic pluton extends at depth towards the east. The modelling process has also shown that Mitchell Peninsula is linked to the adjacent Law Dome ice cap by an ‘ice ramp’ of approximately 100 m thickness.
On the IAA version of the Doi–Edwards model versus the K-BKZ rheological model for polymer fluids: A global existence result for shear flows with small initial data
Authors: CIUPERCA IONEL SORIN , HEIBIG ARNAUD , PALADE LIVIU IULIAN
Published: January 2016

This paper establishes the existence of smooth solutions for the Doi–Edwards rheological model of viscoelastic polymer fluids in shear flows. The problem turns out to be formally equivalent to a K-BKZ equation but with constitutive functions spanning beyond the usual mathematical framework. We prove, for small enough initial data, that the solution remains in the domain of hyperbolicity of the equation for all t≥0.
Effect of simulated rainfall during wheat seed development and maturation on subsequent seed longevity is reversible
Authors: Ellis Richard H. , Yadav Gajender
Published: January 2016

Poor wheat seed quality in temperate regions is often ascribed to wet production environments. We investigated the possible effect of simulated rain during seed development and maturation on seed longevity in wheat (Triticum aestivum L.) cv. Tybalt grown in the field (2008, 2009) or a polythene tunnel house (2010). To mimic rain, the seed crops were wetted from above with the equivalent of 30 mm (2008, 2009) or 25 mm rainfall (2010) at different stages of seed development and maturation (17–58 DAA, days after 50% anthesis), samples were harvested serially, and subsequent air-dry seed longevity estimated. No pre-harvest sprouting occurred. Seed longevity (p50, 50% survival period in experimental hermetic storage at 40°C with c. 15% moisture content) in field-grown controls increased during seed development and maturation, attaining maxima at 37 (2008) or 44 DAA (2009); it declined thereafter. Immediate effects of simulated rain at 17–58 DAA in field studies (2008, 2009) on subsequent seed longevity were negative but small, e.g. a 1–4 d delay in seed quality improvement for treatments early in development, but with no damage detected at final harvests. In rainfall-protected conditions (2010), simulated rain close to harvest maturity (55–56 DAA) reduced longevity immediately and substantially, with greater damage from two sequential days of wetting than one; again, later harvests provided evidence of recovery in subsequent longevity. In the absence of pre-harvest sprouting, the potentially deleterious effects of rainfall to wheat seed crops on subsequent seed longevity may be reversible in full or in part.
Quantification of diabetes consultations by the main primary health care nurse groups in Auckland, New Zealand
Authors: Daly Barbara , Arroll Bruce , Sheridan Nicolette , Kenealy Timothy , Scragg Robert
Published: January 2016

Background:Diabetes prevalence continues to increase, with most diabetes patients managed in primary care.Aim:This report quantifies the number of diabetes consultations undertaken by primary healthcare nurses in Auckland, New Zealand.Methods:Of 335 primary healthcare nurses randomly selected, 287 (86%) completed a telephone interview in 2006–2008.Findings:On a randomly sampled day (from the past seven) for each nurse, 42% of the nurses surveyed (n=120) consulted 308 diabetes patients. From the proportion of nurses sampled in the study, it is calculated that the number of diabetes patients consulted by primary healthcare nurses per week in Auckland between September 2006 and February 2008 was 4210, with 61% consulted by practice, 23% by specialist and 16% by district nurses. These findings show that practice nurses carry out the largest number of community diabetes consultations by nurses. Their major contribution needs to be incorporated into future planning of the community management of diabetes.
A comparison of Geriatric Depression Scale scores in older Australian and Japanese women
Authors: Campbell K. E. , Dennerstein L. , Tacey M. , Fujise N. , Ikeda M. , Szoeke C.
Published: January 2016

Aims:

The aim of this study was to compare the prevalence of depressive symptoms in Australian and Japanese populations of community-dwelling older women using the Geriatric Depression Scale (GDS-15). In addition, the relationship between lifestyle and health factors and higher ratings of depressive symptoms was also examined to determine if there were culturally consistent risk factors associated with higher depressive symptom scores.

Methods:

A total of 444 community based women aged between 65 and 77 years completed a depressive symptom measure (GDS-15) and provided information on common lifestyle factors. The Australian sample (n = 222) were drawn from the Women's Healthy Ageing Project and the age-matched, Japanese sample from the Kumamoto Ageing Study of Mental Health (n = 222). The GDS was chosen to; (1) reduce the impact of physical symptoms associated with old age and, (2) reduce the inflation in scores that may result from the Japanese tendency to endorse somatic items more often than Western adults.

Results:

Mean GDS total scores were significantly higher for the Japanese population 3.97 ± 3.69 compared with 1.73 ± 2.7 for Australian women. The percentages of women scoring in the normal; mild and moderate ranges for depression were 91, 7 and 2% for Australia and 67, 24 and 9% for Japan. Scores remained significantly higher for the Japanese cohort when controlling for lifestyle and health factors associated with depression. The analysis of lifestyle and health characteristics showed that the greatest difference between cohorts was in the area of living status, with more Australian women living with their partner and more than three times as many Japanese women living with their children. When the data for the countries was considered independently employment status affected the likelihood of higher depression scores in the Australian sample while heart disease and poor sleep impacted the risk for the Japanese population.

Conclusions:

Significantly more Japanese women scored within the mild and moderate ranges on the GDS compared with their Australian peers, even when controlling for possible confounding factors. Of the lifestyle and health factors assessed in this analysis no single variable was a common risk factor for higher depressive scores for both countries. The presence of cultural influences that may impact the risk of experiencing depressive symptoms, and culture specific patterns of item endorsement on depressive symptom measures, needs to be explored in more detail.
Haaranalyse zum retrospektiven und prospektiven Konsum-Monitoring: Substanzmissbrauch, Abstinenz- und Compliancekontrolle
Authors: Binz Tina M. , Baumgartner Markus R.
Published: January 2016

Zusammenfassung. Die Möglichkeiten und Anwendungen moderner Haaranalytik haben sich in den letzten Jahren stark weiterentwickelt. Die in Haaren nachweisbaren Substanzen umfassen neben einer Vielzahl an Drogen auch zahlreiche Medikamente, Alkoholmarker oder körpereigene Substanzen wie z.B. das Stresshormon Cortisol. Die Haaranalytik ist sowohl für forensische als auch für klinische Fragestellungen relevant, da durch diese Analyse ein retrospektiver Überblick über das Konsum- und Einnahmeverhalten während eines grösseren Zeitraums ermöglicht wird.
Treg activation defect in type 1 diabetes: correction with TNFR2 agonism
Authors: Okubo Yoshiaki , Torrey Heather , Butterworth John , Zheng Hui , Faustman Denise L
Published: January 2016

Activated T‐regulatory cells (aTregs) prevent or halt various forms of autoimmunity. We show that type 1 diabetics (T1D) have a Treg activation defect through an increase in resting Tregs (rTregs, CD4+CD25+Foxp3+CD45RA) and decrease in aTregs (CD4+CD25+Foxp3+CD45RO) (n= 55 T1D, n=45 controls, P=0.01). The activation defect persists life long in T1D subjects (T1D=45, controls=45, P=0.01, P=0.04). Lower numbers of aTregs had clinical significance because they were associated with a trend for less residual C‐peptide secretion from the pancreas (P=0.08), and poorer HbA1C control (P=0.03). In humans, the tumor necrosis factor receptor 2 (TNFR2) is obligatory for Treg induction, maintenance and expansion of aTregs. TNFR2 agonism is a method for stimulating Treg conversion from resting to activated. Using two separate in vitro expansion protocols, TNFR2 agonism corrected the T1D activation defect by triggering conversion of rTregs into aTregs (n=54 T1D, P<0.001). TNFR2 agonism was superior to standard protocols and TNF in proliferating Tregs. In T1D, TNFR2 agonist‐expanded Tregs were homogeneous and functionally potent by virtue of suppressing autologous cytotoxic T cells in a dose‐dependent manner comparable to controls. Targeting the TNFR2 receptor for Treg expansion in vitro demonstrates a means to correct the activation defect in T1D.
A shear gradient-activated microfluidic device for automated monitoring of whole blood haemostasis and platelet function
Authors: Jain Abhishek , Graveline Amanda , Waterhouse Anna , Vernet Andyna , Flaumenhaft Robert , Ingber Donald E.
Published: January 2016

Accurate assessment of blood haemostasis is essential for the management of patients who use extracorporeal devices, receive anticoagulation therapy or experience coagulopathies. However, current monitoring devices do not measure effects of haemodynamic forces that contribute significantly to platelet function and thrombus formation. Here we describe a microfluidic device that mimics a network of stenosed arteriolar vessels, permitting evaluation of blood clotting within small sample volumes under pathophysiological flow. By applying a clotting time analysis based on a phenomenological mathematical model of thrombus formation, coagulation and platelet function can be accurately measured in vitro in patient blood samples. When the device is integrated into an extracorporeal circuit in pig endotoxemia or heparin therapy models, it produces real-time readouts of alterations in coagulation ex vivo that are more reliable than standard clotting assays. Thus, this disposable device may be useful for personalized diagnostics and for real-time surveillance of antithrombotic therapy in clinic.
Nanopore sensing at ultra-low concentrations using single-molecule dielectrophoretic trapping
Authors: Freedman Kevin J. , Otto Lauren M. , Ivanov Aleksandar P. , Barik Avijit , Oh Sang-Hyun , Edel Joshua B.
Published: January 2016

Single-molecule techniques are being developed with the exciting prospect of revolutionizing the healthcare industry by generating vast amounts of genetic and proteomic data. One exceptionally promising route is in the use of nanopore sensors. However, a well-known complexity is that detection and capture is predominantly diffusion limited. This problem is compounded when taking into account the capture volume of a nanopore, typically 108–1010 times smaller than the sample volume. To rectify this disproportionate ratio, we demonstrate a simple, yet powerful, method based on coupling single-molecule dielectrophoretic trapping to nanopore sensing. We show that DNA can be captured from a controllable, but typically much larger, volume and concentrated at the tip of a metallic nanopore. This enables the detection of single molecules at concentrations as low as 5 fM, which is approximately a 103 reduction in the limit of detection compared with existing methods, while still maintaining efficient throughput.
Genetically engineering self-organization of human pluripotent stem cells into a liver bud-like tissue using Gata6
Authors: Guye Patrick , Ebrahimkhani Mohammad R. , Kipniss Nathan , Velazquez Jeremy J. , Schoenfeld Eldi , Kiani Samira , Griffith Linda G. , Weiss Ron
Published: January 2016

Human induced pluripotent stem cells (hiPSCs) have potential for personalized and regenerative medicine. While most of the methods using these cells have focused on deriving homogenous populations of specialized cells, there has been modest success in producing hiPSC-derived organotypic tissues or organoids. Here we present a novel approach for generating and then co-differentiating hiPSC-derived progenitors. With a genetically engineered pulse of GATA-binding protein 6 (GATA6) expression, we initiate rapid emergence of all three germ layers as a complex function of GATA6 expression levels and tissue context. Within 2 weeks we obtain a complex tissue that recapitulates early developmental processes and exhibits a liver bud-like phenotype, including haematopoietic and stromal cells as well as a neuronal niche. Collectively, our approach demonstrates derivation of complex tissues from hiPSCs using a single autologous hiPSCs as source and generates a range of stromal cells that co-develop with parenchymal cells to form tissues.
Three-dimensional controlled growth of monodisperse sub-50 nm heterogeneous nanocrystals
Authors: Liu Deming , Xu Xiaoxue , Du Yi , Qin Xian , Zhang Yuhai , Ma Chenshuo , Wen Shihui , Ren Wei , Goldys Ewa M. , Piper James A. , Dou Shixue , Liu Xiaogang , Jin Dayong
Published: January 2016

The ultimate frontier in nanomaterials engineering is to realize their composition control with atomic scale precision to enable fabrication of nanoparticles with desirable size, shape and surface properties. Such control becomes even more useful when growing hybrid nanocrystals designed to integrate multiple functionalities. Here we report achieving such degree of control in a family of rare-earth-doped nanomaterials. We experimentally verify the co-existence and different roles of oleate anions (OA−) and molecules (OAH) in the crystal formation. We identify that the control over the ratio of OA− to OAH can be used to directionally inhibit, promote or etch the crystallographic facets of the nanoparticles. This control enables selective grafting of shells with complex morphologies grown over nanocrystal cores, thus allowing the fabrication of a diverse library of monodisperse sub-50 nm nanoparticles. With such programmable additive and subtractive engineering a variety of three-dimensional shapes can be implemented using a bottom–up scalable approach.
Genome-wide association study identifies variation at 6q25.1 associated with survival in multiple myeloma
Authors: Johnson David C. , Weinhold Niels , Mitchell Jonathan S. , Chen Bowang , Kaiser Martin , Begum Dil B. , Hillengass Jens , Bertsch Uta , Gregory Walter A. , Cairns David , Jackson Graham H. , Försti Asta , Nickel Jolanta , Hoffmann Per , Nöethen Markus M. , Stephens Owen W. , Barlogie Bart , Davis Faith E. , Hemminki Kari , Goldschmidt Hartmut , Houlston Richard S. , Morgan Gareth J.
Published: January 2016

Survival following a diagnosis of multiple myeloma (MM) varies between patients and some of these differences may be a consequence of inherited genetic variation. In this study, to identify genetic markers associated with MM overall survival (MM-OS), we conduct a meta-analysis of four patient series of European ancestry, totalling 3,256 patients with 1,200 MM-associated deaths. Each series is genotyped for ∼600,000 single nucleotide polymorphisms across the genome; genotypes for six million common variants are imputed using 1000 Genomes Project and UK10K as the reference. The association between genotype and OS is assessed by Cox proportional hazards model adjusting for age, sex, International staging system and treatment. We identify a locus at 6q25.1 marked by rs12374648 associated with MM-OS (hazard ratio=1.34, 95% confidence interval=1.22–1.48, P=4.69 × 10–9). Our findings have potential clinical implications since they demonstrate that inherited genotypes can provide prognostic information in addition to conventional tumor acquired prognostic factors.
Negative magnetoresistance in Dirac semimetal Cd3As2
Authors: Li Hui , He Hongtao , Lu Hai-Zhou , Zhang Huachen , Liu Hongchao , Ma Rong , Fan Zhiyong , Shen Shun-Qing , Wang Jiannong
Published: January 2016

A large negative magnetoresistance (NMR) is anticipated in topological semimetals in parallel magnetic fields, demonstrating the chiral anomaly, a long-sought high-energy-physics effect, in solid-state systems. Recent experiments reveal that the Dirac semimetal Cd3As2 has the record-high mobility and positive linear magnetoresistance in perpendicular magnetic fields. However, the NMR has not yet been unveiled. Here we report the observation of NMR in Cd3As2 microribbons in parallel magnetic fields up to 66% at 50 K and visible at room temperatures. The NMR is sensitive to the angle between magnetic and electrical fields, robust against temperature and dependent on the carrier density. The large NMR results from low carrier densities in our Cd3As2 samples, ranging from 3.0 × 1017 cm−3 at 300 K to 2.2 × 1016 cm−3 below 50 K. We therefore attribute the observed NMR to the chiral anomaly. In perpendicular magnetic fields, a positive linear magnetoresistance up to 1,670% at 14 T and 2 K is also observed.
Interplay of active processes modulates tension and drives phase transition in self-renewing, motor-driven cytoskeletal networks
Authors: Mak Michael , Zaman Muhammad H. , Kamm Roger D. , Kim Taeyoon
Published: January 2016

The actin cytoskeleton—a complex, nonequilibrium network consisting of filaments, actin-crosslinking proteins (ACPs) and motors—confers cell structure and functionality, from migration to morphogenesis. While the core components are recognized, much less is understood about the behaviour of the integrated, disordered and internally active system with interdependent mechano-chemical component properties. Here we use a Brownian dynamics model that incorporates key and realistic features—specifically actin turnover, ACP (un)binding and motor walking—to reveal the nature and underlying regulatory mechanisms of overarching cytoskeletal states. We generate multi-dimensional maps that show the ratio in activity of these microscopic elements determines diverse global stress profiles and the induction of nonequilibrium morphological phase transition from homogeneous to aggregated networks. In particular, actin turnover dynamics plays a prominent role in tuning stress levels and stabilizing homogeneous morphologies in crosslinked, motor-driven networks. The consequence is versatile functionality, from dynamic steady-state prestress to large, pulsed constrictions.
Correction: Corrigendum: Bub1 is required for maintaining cancer stem cells in breast cancer cell lines
Authors: Han Jeong Yoon , Han Yu Kyeong , Park Ga-Young , Kim Sung Dae , Lee Chang Geun
Published: January 2016

Breast cancer is a leading cause of death among women worldwide due to therapeutic resistance and cancer recurrence. Cancer stem cells are believed to be responsible for resistance and recurrence. Many efforts to overcome resistance and recurrence by regulating cancer stem cells are ongoing. Bub1 (Budding uninhibited by benzimidazoles 1) is a mitotic checkpoint serine/threonine kinase that plays an important role in chromosome segregation. Bub1 expression is correlated with a poor clinical prognosis in patients with breast cancer. We identified that depleting Bub1 using shRNAs reduces cancer stem cell potential of the MDA-MB-231 breast cancer cell line, resulting in inhibited formation of xenografts in immunocompromised mice. These results suggest that Bub1 may be associated with cancer stem cell potential and could be a target for developing anti-breast cancer stem cell therapies.
Rational design of ultrastable and reversibly photoswitchable fluorescent proteins for super-resolution imaging of the bacterial periplasm
Authors: El Khatib Mariam , Martins Alexandre , Bourgeois Dominique , Colletier Jacques-Philippe , Adam Virgile
Published: January 2016

Phototransformable fluorescent proteins are central to several nanoscopy approaches. As yet however, there is no available variant allowing super-resolution imaging in cell compartments that maintain oxidative conditions. Here, we report the rational design of two reversibly switchable fluorescent proteins able to fold and photoswitch in the bacterial periplasm, rsFolder and rsFolder2. rsFolder was designed by hybridisation of Superfolder-GFP with rsEGFP2 and inherited the fast folding properties of the former together with the rapid switching of the latter, but at the cost of a reduced switching contrast. Structural characterisation of the switching mechanisms of rsFolder and rsEGFP2 revealed different scenarios for chromophore cis-trans isomerisation and allowed designing rsFolder2, a variant of rsFolder that exhibits improved switching contrast and is amenable to RESOLFT nanoscopy. The rsFolders can be efficiently expressed in the E. coli periplasm, opening the door to the nanoscale investigation of proteins localised in hitherto non-observable cellular compartments.
Diversity and interactions of microbial functional genes under differing environmental conditions: insights from a membrane bioreactor and an oxidation ditch
Authors: Xia Yu , Hu Man , Wen Xianghua , Wang Xiaohui , Yang Yunfeng , Zhou Jizhong
Published: January 2016

The effect of environmental conditions on the diversity and interactions of microbial communities has caused tremendous interest in microbial ecology. Here, we found that with identical influents but differing operational parameters (mainly mixed liquor suspended solid (MLSS) concentrations, solid retention time (SRT) and dissolved oxygen (DO) concentrations), two full-scale municipal wastewater treatment systems applying oxidation ditch (OD) and membrane bioreactor (MBR) processes harbored a majority of shared genes (87.2%) but had different overall functional gene structures as revealed by two datasets of 12-day time-series generated by a functional gene array-GeoChip 4.2. Association networks of core carbon, nitrogen and phosphorus cycling genes in each system based on random matrix theory (RMT) showed different topological properties and the MBR nodes showed an indication of higher connectivity. MLSS and DO were shown to be effective in shaping functional gene structures of the systems by statistical analyses. Higher MLSS concentrations resulting in decreased resource availability of the MBR system were thought to promote positive interactions of important functional genes. Together, these findings show the differences of functional potentials of some bioprocesses caused by differing environmental conditions and suggest that higher stress of resource limitation increased positive gene interactions in the MBR system.
The Influence of Doping on the Optoelectronic Properties of PbS Colloidal Quantum Dot Solids
Authors: Papagiorgis P. , Stavrinadis A. , Othonos A. , Konstantatos G. , Itskos G.
Published: January 2016

We report on an extensive spectroscopic investigation of the impact of substitutional doping on the optoelectronic properties of PbS colloidal quantum dot (CQD) solids. N-doping is provided by Bi incorporation during CQD synthesis as well as post-synthetically via cation exchange reactions. The spectroscopic data indicate a systematic quenching of the excitonic absorption and luminescence and the appearance of two dopant-induced contributions at lower energies to the CQD free exciton. Temperature-dependent photoluminescence indicates the presence of temperature-activated detrapping and trapping processes of photoexcitations for the films doped during and after synthesis, respectively. The data are consistent with a preferential incorporation of the dopants at the QDs surface in the case of the cation-exchange treated films versus a more uniform doping profile in the case of in-situ Bi incorporation during synthesis. Time-resolved experiments indicate the presence of fast dopant- and excitation-dependent recombination channels attributed to Auger recombination of negatively charged excitons, formed due to excess of dopant electrons. The data indicate that apart from dopant compensation and filling of dopant induced trap states, a fraction of the Bi ionized electrons feeds the QD core states resulting in n-doping of the semiconductor, confirming reported work on devices based on such doped CQD material.
Overexpression of ThVHAc1 and its potential upstream regulator, ThWRKY7, improved plant tolerance of Cadmium stress
Authors: Yang Guiyan , Wang Chao , Wang Yucheng , Guo Yucong , Zhao Yulin , Yang Chuanping , Gao Caiqiu
Published: January 2016

As one of the most toxic heavy metals in the environment, cadmium (Cd) poses a severe threat to plant growth. We previously reported that overexpression of the Tamarix hispida V-ATPase c subunit (ThVHAc1) improved the Cd tolerance of Saccharomyces cerevisiae. In the current study, we further explored the Cd tolerance conferred by ThVHAc1 in Arabidopsis and T. hispida. ThVHAc1 transgenic Arabidopsis had higher seed germination, biomass and chlorophyll content under CdCl2 treatment. In Cd-stressed plants, overexpression of ThVHAc1 significantly improved V-ATPase activity and affected the expression of other V-ATPase subunit-encoding genes. Intriguingly, the lower level of ROS accumulation in ThVHAc1-overexpressing lines under CdCl2 treatment demonstrated that ThVHAc1 may modulate Cd stress tolerance by regulating ROS homeostasis. Transient expression of ThVHAc1 in T. hispida further confirmed these findings. Furthermore, promoter analysis and yeast one-hybrid assay revealed that the transcription factor ThWRKY7 can specifically bind to the WRKY cis-element in the ThVHAc1 promoter. ThWRKY7 exhibited similar expression patterns as ThVHAc1 under CdCl2 treatment and improved Cd tolerance, suggesting that ThWRKY7 may be an upstream regulatory gene of ThVHAc1. Therefore, our results show that the combination of ThVHAc1 and its upstream regulator could be used to improve Cd stress tolerance in woody plants.
Exceptional preservation reveals gastrointestinal anatomy and evolution in early actinopterygian fishes
Authors: Argyriou Thodoris , Clauss Marcus , Maxwell Erin E. , Furrer Heinz , Sánchez-Villagra Marcelo R.
Published: January 2016

Current knowledge about the evolutionary morphology of the vertebrate gastrointestinal tract (GIT) is hindered by the low preservation potential of soft tissues in fossils. Exceptionally preserved cololites of individual †Saurichthys from the Middle Triassic of Switzerland provide unique insights into the evolutionary morphology of the GIT. The GIT of †Saurichthys differed from that of other early actinopterygians and was convergent to that of some living sharks and rays, in exhibiting up to 30 turns of the spiral valve. Dissections and literature review demonstrate the phylogenetic diversity of GIT features and signs of biological factors that influence its morphology. A phylogenetically informed analysis of a dataset containing 134 taxa suggests that body size and phylogeny are important factors affecting the spiral valve turn counts. The high number of turns in the spiral valve of †Saurichthys and some recent sharks and rays reflect both energetically demanding lifestyles and the evolutionary histories of the groups.
Hybridization following population collapse in a critically endangered antelope
Authors: Vaz Pinto Pedro , Beja Pedro , Ferrand Nuno , Godinho Raquel
Published: January 2016

Population declines may promote interspecific hybridization due to the shortage of conspecific mates (Hubb’s ‘desperation’ hypothesis), thus greatly increasing the risk of species extinction. Yet, confirming this process in the wild has proved elusive. Here we combine camera-trapping and molecular surveys over seven years to document demographic processes associated with introgressive hybridization between the critically endangered giant sable antelope (Hippotragus niger variani) and the naturally sympatric roan antelope (H. equinus). Hybrids with intermediate phenotypes, including backcrosses with roan, were confirmed in one of the two remnant giant sable populations. Hybridization followed population depletion of both species due to severe wartime poaching. In the absence of mature sable males, a mixed herd of sable females and hybrids formed and grew progressively over time. To prevent further hybridization and recover this small population, all sable females were confined to a large enclosure, to which sables from the other remnant population were translocated. Given the large scale declines in many animal populations, hybridization and introgression associated with the scarcity of conspecific mates may be an increasing cause of biodiversity conservation concern. In these circumstances, the early detection of hybrids should be a priority in the conservation management of small populations.
Macroevolution of hyperdiverse flightless beetles reflects the complex geological history of the Sunda Arc
Authors: Tänzler Rene , Van Dam Matthew H. , Toussaint Emmanuel F. A. , Suhardjono Yayuk R. , Balke Michael , Riedel Alexander
Published: January 2016

The Sunda Arc forms an almost continuous chain of islands and thus a potential dispersal corridor between mainland Southeast Asia and Melanesia. However, the Sunda Islands have rather different geological histories, which might have had an important impact on actual dispersal routes and community assembly. Here, we reveal the biogeographical history of hyperdiverse and flightless Trigonopterus weevils. Different approaches to ancestral area reconstruction suggest a complex east to west range expansion. Out of New Guinea, Trigonopterus repeatedly reached the Moluccas and Sulawesi transgressing Lydekker′s Line. Sulawesi repeatedly acted as colonization hub for different segments of the Sunda Arc. West Java, East Java and Bali are recognized as distinct biogeographic areas. The timing and diversification of species largely coincides with the geological chronology of island emergence. Colonization was not inhibited by traditional biogeographical boundaries such as Wallace’s Line. Rather, colonization patterns support distance dependent dispersal and island age limiting dispersal.
Enhancement of hepatocyte differentiation from human embryonic stem cells by Chinese medicine Fuzhenghuayu
Authors: Chen Jiamei , Gao Wei , Zhou Ping , Ma Xiaocui , Tschudy-Seney Benjamin , Liu Chenghai , Zern Mark A , Liu Ping , Duan Yuyou
Published: January 2016

Chinese medicine, Fuzhenghuayu (FZHY), appears to prevent fibrosis progression and improve liver function in humans. Here we found that FZHY enhanced hepatocyte differentiation from human embryonic stem cells (hESC). After treatment with FZHY, albumin expression was consistently increased during differentiation and maturation process and expression of metabolizing enzymes and transporter were also increased. Importantly, expression of mesenchymal cell and cholangiocyte marker was significantly reduced by treatment with FZHY, indicating that one possible mechanism of FZHY’s role is to inhibit the formation of mesenchymal cells and cholangiocytes. Edu-labelled flow cytometric analysis showed that the percentage of the Edu positive cells was increased in the treated cells. These results indicate that the enhanced proliferation involved hepatocytes rather than another cell type. Our investigations further revealed that these enhancements by FZHY are mediated through activation of canonical Wnt and ERK pathways and inhibition of Notch pathway. Thus, FZHY not only promoted hepatocyte differentiation and maturation, but also enhanced hepatocyte proliferation. These results demonstrate that FZHY appears to represent an excellent therapeutic agent for the treatment of liver fibrosis and that FZHY treatment can enhance our efforts to generate mature hepatocytes with proliferative capacity for cell-based therapeutics and for pharmacological and toxicological studies.
Impaired encoding of rapid pitch information underlies perception and memory deficits in congenital amusia
Authors: Albouy Philippe , Cousineau Marion , Caclin Anne , Tillmann Barbara , Peretz Isabelle
Published: January 2016

Recent theories suggest that the basis of neurodevelopmental auditory disorders such as dyslexia or specific language impairment might be a low-level sensory dysfunction. In the present study we test this hypothesis in congenital amusia, a neurodevelopmental disorder characterized by severe deficits in the processing of pitch-based material. We manipulated the temporal characteristics of auditory stimuli and investigated the influence of the time given to encode pitch information on participants’ performance in discrimination and short-term memory. Our results show that amusics’ performance in such tasks scales with the duration available to encode acoustic information. This suggests that in auditory neuro-developmental disorders, abnormalities in early steps of the auditory processing can underlie the high-level deficits (here musical disabilities). Observing that the slowing down of temporal dynamics improves amusics’ pitch abilities allows considering this approach as a potential tool for remediation in developmental auditory disorders.
CrossNorm: a novel normalization strategy for microarray data in cancers
Authors: Cheng Lixin , Lo Leung-Yau , Tang Nelson L. S. , Wang Dong , Leung Kwong-Sak
Published: January 2016

Normalization is essential to get rid of biases in microarray data for their accurate analysis. Existing normalization methods for microarray gene expression data commonly assume a similar global expression pattern among samples being studied. However, scenarios of global shifts in gene expressions are dominant in cancers, making the assumption invalid. To alleviate the problem, here we propose and develop a novel normalization strategy, Cross Normalization (CrossNorm), for microarray data with unbalanced transcript levels among samples. Conventional procedures, such as RMA and LOESS, arbitrarily flatten the difference between case and control groups leading to biased gene expression estimates. Noticeably, applying these methods under the strategy of CrossNorm, which makes use of the overall statistics of the original signals, the results showed significantly improved robustness and accuracy in estimating transcript level dynamics for a series of publicly available datasets, including titration experiment, simulated data, spike-in data and several real-life microarray datasets across various types of cancers. The results have important implications for the past and the future cancer studies based on microarray samples with non-negligible difference. Moreover, the strategy can also be applied to other sorts of high-throughput data as long as the experiments have global expression variations between conditions.
Tooth loss is associated with increased risk of esophageal cancer: evidence from a meta-analysis with dose-response analysis
Authors: Chen Qi-Lin , Zeng Xian-Tao , Luo Zhi-Xiao , Duan Xiao-Li , Qin Jie , Leng Wei-Dong
Published: January 2016

Epidemiological studies have revealed the association between tooth loss and the risk of esophageal cancer (EC); however, consistent results were not obtained from different single studies. Therefore, we conducted the present meta-analysis to evaluate the association between tooth loss and EC. We conducted electronic searches of PubMed until to February 10, 2015 to identify relevant observational studies that examined the association between tooth loss and the risk of EC. Study selection and data extraction from eligible studies were independently performed by two authors. The meta-analysis was conducted using Stata 12.0 software. Finally eight eligible publications with ten studies involving 3 cohort studies, 5 case-control studies and 1 cross-sectional study were yielded. Meta-analysis identified tooth loss increased risk of EC 1.30 times (Relative risk = 1.30, 95% confidence interval = 1.06–1.60, I2 = 13.5%). Dose-response analysis showed linear relationship between tooth loss and risk of EC (RR = 1.01, 95%CI = 1.00–1.03; P for non-linearity test was 0.45). Subgroup analysis proved similar results and publication bias was not detected. In conclusion, tooth loss could be considered to be a significant and dependent risk factor for EC based on the current evidence.
Novel mutations in CRYGD are associated with congenital cataracts in Chinese families
Authors: Yang Guoxing , Chen Zhimin , Zhang Wulin , Liu Zhiqiang , Zhao Jialiang
Published: January 2016

Congenital cataract disease is a clinically and genetically heterogeneous lens disorder. The purpose of this study was to identify the genetic defects and to investigate the relationships between disease-causing genes and lens morphology in congenital cataracts. Patients were given a physical examination and their blood samples were collected for DNA extraction. Mutation analysis was performed by direct sequencing of the following candidate genes: CRYGC, CRYGD, CRYGS, GJA8, GJA3 and CRYAA. Mutational analysis of CRYGD identified a recurrent (p.P24T) mutation in two unrelated families with congenital coralliform cataracts and three novel (p.Q101X, p.E104fsX4 and p.E135X) mutations in three families with congenital nuclear cataracts. The p.E135X mutation is a de novo mutation. Haplotype analysis showed patients inherited the same CRYGD allele originated from father. The p.E135X mutation seen in two siblings suggests a mechanism of gonadal mosaicism in the father.