bluuebunny/crossref_metadata_2025 huggingface dataset:
Reversal of dopamine‐mediated firing inhibition through activation of the dopamine transporter in substantia nigra pars compacta neurons
Authors: Aversa Daniela , Martini Alessandro , Guatteo Ezia , Pisani Antonio , Mercuri Nicola Biagio , Berretta Nicola
Published: June 2018

Background and Purpose

One of the hallmarks of ventral midbrain dopamine‐releasing neurons is membrane hyperpolarization in response to stimulation of somato‐dendritic D2 receptors. At early postnatal age, under sustained dopamine, this inhibitory response is followed by a slow recovery, resulting in dopamine inhibition reversal (DIR). In the present investigation, we aimed to get a better insight into the cellular mechanisms underlying DIR.

Experimental Approach

We performed single‐unit extracellular recordings with a multi‐electrode array device and conventional patch‐clamp recordings on midbrain mouse slices.

Key Results

While continuous dopamine (100 μM) perfusion gave rise to firing inhibition that recovered in 10 to 15 min, the same effect was not obtained with the D2 receptor agonist quinpirole (100 nM). Moreover, firing inhibition caused by the GABAB receptor agonist baclofen (300 nM) was reversed by dopamine (100 μM), albeit D2 receptors had been blocked by sulpiride (10 μM). Conversely, the block of the dopamine transporter (DAT) with cocaine (30 μM) prevented firing recovery by dopamine under GABAB receptor stimulation. Accordingly, in whole‐cell recordings from single cells, the baclofen‐induced outward current was counteracted by dopamine (100 μM) in the presence of sulpiride (10 μM), and this effect was prevented by the DAT antagonists cocaine (30 μM) and GBR12909 (2 μM).

Conclusions and Implications

Our results indicate that the DAT plays a major role in DIR, mediating it under conditions of sustained dopamine exposure, and point to DAT as an important target for pharmacological therapies leading to prolonged enhancement of the dopaminergic signal.
Modulation of sonic hedgehog‐induced mouse embryonic stem cell behaviours through E‐cadherin expression and integrin β1‐dependent F‐actin formation
Authors: Oh Ji Young , Suh Han Na , Choi Gee Euhn , Lee Hyun Jik , Jung Young Hyun , Ko So Hee , Kim Jun Sung , Chae Chang Woo , Lee Chang‐Kyu , Han Ho Jae
Published: June 2018

Background and Purpose

The sonic hedgehog pathway (Shh) plays a central role in maintaining stem cell function and behaviour in various processes related to self‐renewal and tissue regeneration. However, the therapeutic effect of Shh on mouse embryonic stem cells (mESCs) has not yet been clearly elucidated. Thus, we investigated the effect of Shh on the regulation of mESC behaviour as well as the effect of Shh‐pretreated mESCs in skin wound healing.

Experimental Approach

The underlying mechanisms of Shh signalling pathway in growth and motility of mESCs were investigated using Western blot analysis, a cell proliferation assay and cell migration assay. In addition, the effect of Shh‐pretreated mESCs in skin wound healing was determined using a mouse excisional wound splinting model.

Key Results

Shh disrupted the adherens junction through proteolysis by activating MMPs. In addition, the release of β‐catenin from adherens junctions mediated by Shh led to cell cycle‐dependent mESC proliferation. Shh‐mediated Gli1 expression led to integrin β1 up‐regulation, followed by FAK and Src phosphorylation. Furthermore, among the Rho‐GTPases, Rac1 and Cdc42 were activated in a Shh‐dependent manner while F‐actin expression was suppressed by Rac1 and Cdc42 siRNA transfection. Consistent with the in vitro results, the skin wound healing assay revealed that Shh‐treated mESCs increased angiogenesis and skin wound repair compared to that in Shh‐treated mESCs transfected with integrin β1 siRNA in vivo.

Conclusions and Implications

Our results imply that Shh induces adherens junction disruption and integrin β1‐dependent F‐actin formation by a mechanism involving FAK/Src and Rac1/Cdc42 signalling pathways in mESCs.
Selection‐based design of in silico dengue epitope ensemble vaccines
Authors: Murphy David , Reche Pedro , Flower Darren R.
Published: June 2018

Dengue virus affects approximately 130 countries. Twenty‐five percentage of infections result in febrile, self‐limiting illness; heterotypic infection results in potentially fatal dengue haemorrhagic fever or dengue shock syndrome. Only one vaccine is currently available. Its efficacy is very variable. Thus, to target dengue, we used an innovative immunoinformatics protocol to design a putative epitope ensemble vaccine by selecting an optimal set of highly conserved epitopes with experimentally verified immunogenicity. From 1597 CD4+ and MHC II epitopes, six MHC Class I epitopes (RAVHADMGYW, GPWHLGKLEM, GLYGNGVVTK, NMIIMDEAHF, KTWAYHGSY and WAYHGSYEV) and nine MHC Class II epitopes (LAKAIFKLTYQNKVV, GKIVGLYGNGVVTTS, AAIFMTATPPGSVEA, AAIFMTATPPGTADA, GKTVWFVPSIKAGND, KFWNTTIAVSMANIF, RAIWYMWLGARYLEF, VGTYGLNTFTNMEVQ and WTLMYFHRRDLRLAA) were selected; this candidate vaccine achieved a world population coverage of 92.49%.
Next‐generation sequencing improves treatment efficacy and reduces hospitalization in children with drug‐resistant epilepsy
Authors: Peng Jing , Pang Nan , Wang Ying , Wang Xiao‐Le , Chen Jian , Xiong Juan , Peng Pan , Zhu Can‐Hui , Kessi Miriam Barakael , He Fang , Yin Fei
Published: June 2018

Background

The purposes of this study were three‐fold: (i) to determine the contribution of known genes to the causation of a broad‐spectrum of pediatric drug‐resistant epilepsy (DRE), (ii) to compare the diagnostic yield and cost among different next‐generation sequencing (NGS) approaches, and especially (iii) to assess how NGS approaches can benefit patients by improving diagnosis and treatment efficiency.

Methods

This study enrolled 273 pediatric DRE patients with no obvious acquired etiology. Seventy‐four patients underwent whole‐exome sequencing (WES), 141 patients had epilepsy‐related gene panel testing, and another 58 patients had clinical WES gene panel testing. We obtained these patients’ seizure and hospitalization frequency by periodic follow‐up phone calls and outpatient visits.

Results

Genetic diagnosis was achieved in 86 patients (31.5%) and involved 93 likely disease‐causing mutations in 33 genes. In this study, the detection rates of the epilepsy‐related gene panel, the clinical WES gene panel, and WES were 32.6% (46/141), 44.8% (26/58), and 17.3% (13/74), respectively. Moreover, 34 patients accepted corrective therapy according to their mutant genes, after which 52.9% (18/34) became seizure‐free and 38.2% (13/34) achieved seizure reduction. In the end, patients with either positive or negative genetic results had significantly fewer hospitalization incidents (times/half year) than before (positive genetic results group 0.58 ± 1.14 vs 0.10 ± 0.26; negative genetic results group 0.72 ± 1.65 vs 0.12 ± 0.33).

Conclusions

These results offer further proof that NGS approaches represent powerful tools for establishing a definitive diagnosis. Moreover, this study indicated how NGS can improve treatment efficacy and reduce hospitalization in children with DRE.
Generic names and mislabeling conceal high species diversity in global fisheries markets
Authors: Cawthorn Donna‐Mareè , Baillie Charles , Mariani Stefano
Published: June 2018

Consumers have the power to influence conservation of marine fishes by selectively purchasing sustainably harvested species. Yet, this power is hindered by vague labeling and seafood fraud, which may mask market biodiversity and lead to inadvertent consumption of threatened species. Here, we investigate the repercussions of such labeling inaccuracies for one of the world's most highly prized families of fishes‐–the snappers (Family: Lutjanidae). By DNA barcoding 300 “snapper” samples collected from six countries, we show that the lax application of this umbrella term and widespread mislabeling (40%) conceal the identities of at least 67 species from 16 families in global marketplaces, effectively lumping taxa for sale that derive from an array of disparately managed fisheries and have markedly different conservation concerns. Bringing this trade into the open should compel a revision of international labeling and traceability policies, as well as enforcement measures, which currently allow such extensive biodiversity to be consumed unknowingly.
Improving outcomes in gestational diabetes: does gestational weight gain matter?
Authors: Aiken C. E. M. , Hone L. , Murphy H. R. , Meek C. L.
Published: June 2018

Aim

Excessive gestational weight gain increases risk of gestational diabetes mellitus (GDM) but it remains unclear whether weight control after GDM diagnosis improves outcomes. We assessed whether: (1) total gestational weight gain during pregnancy (0–36 weeks); (2) early gestational weight gain (0–28 weeks, before GDM diagnosis); or (3) late gestational weight gain (28–36 weeks, after diagnosis) are associated with maternal–fetal outcomes.

Methods

Some 546 women with GDM who delivered viable singleton infants at a single UK obstetric centre (October 2014 to March 2017) were included in this retrospective observational study.

Results

Higher total gestational weight gain was associated with Caesarean section [n = 376; odds ratio (OR) 1.05; confidence intervals (CI) 1.02–1.08, P < 0.001] and large for gestational age (OR 1.08; CI 1.03–1.12, P < 0.001). Higher late gestational weight gain (28–36 weeks; n = 144) was associated with large for gestational age (OR 1.17; CI 1.01–1.37, P < 0.05), instrumental deliveries (OR 1.26; CI 1.03–1.55, P < 0.01), higher total daily insulin doses (36 weeks; beta coefficient 4.37; CI 1.92–6.82, P < 0.001), and higher post‐partum 2‐h oral glucose tolerance test concentrations (beta coefficient 0.12; CI 0.01–0.22, P < 0.05). Women who avoided substantial weight gain after GDM diagnosis had 0.7 mmol/l lower postnatal 2‐h glucose and needed half the amount of insulin/day at 36 weeks compared with women with substantial weight gain after diagnosis. There were no significant associations between early gestational weight gain (0–28 weeks) and pregnancy outcomes.

Conclusions

These findings suggest that controlling gestational weight gain should be a priority following GDM diagnosis to optimize pregnancy outcomes and improve maternal postnatal glucose homeostasis. The period after diagnosis of GDM (often 28 weeks gestation) is not too late to offer lifestyle advice or intervention to improve weight management and pregnancy outcomes.
Cognitive reserve maps the core loci of neurodegeneration in corticobasal degeneration
Authors: Isella V. , Grisanti S. G. , Ferri F. , Morzenti S. , Crivellaro C. , Musarra M. , Ferrarese C.
Published: June 2018

Background and purpose

Cognitively stimulating life experiences and activities are deemed to moderate the clinical impact of brain damage progressively building a neural and cognitive reserve (CR). CR has been studied extensively in various neurodegenerative disorders, but not in corticobasal degeneration (CBD).

Methods

Using Statistical Parametric Mapping 8, years of education, as a determinant of CR, was correlated with tracer uptake on positron emission tomography with 18F‐fluorodeoxyglucose, as a marker of neurodegeneration, in 35 patients with various phenotypes of CBD, including a cognitive–motor composite score or symptoms duration as covariates for controlling disease stage.

Results

A cluster of relative hypometabolism was found associated with higher education in the left inferior regions of pre‐ and post‐rolandic gyri and insula, which represent typical loci of neurodegeneration in CBD regardless of clinical presentation.

Conclusions

The present findings extend to CBD the evidence gathered in other neurodegenerative disorders that a higher CR has a protective effect against the clinical manifestations of brain degeneration.
Measurement of the biomechanical function and structure of ex vivo drying skin using raman spectral analysis and its modulation with emollient mixtures
Authors: Biniek Krysta , Tfayli Ali , Vyumvuhore Raoul , Quatela Alessia , Galliano Marie‐Florence , Delalleau Alexandre , Baillet‐Guffroy Arlette , Dauskardt Reinhold H. , Duplan Helene
Published: June 2018

An important aspect of the biomechanical behaviour of the stratum corneum (SC) is the drying stresses that develop with water loss. These stresses act as a driving force for damage in the form of chapping and cracking. Betasitosterol is a plant sterol with a structure similar to cholesterol, a key component in the intercellular lipids of the outermost layer of human skin, the SC. Cholesterol plays an important role in stabilizing the SC lipid structure, and altered levels of cholesterol have been linked with SC barrier abnormalities. Betasitosterol is currently applied topically to skin for treatment of wounds and burns. However, it is unknown what effect betasitosterol has on the biomechanical barrier function of skin. Here, by analysing the drying stress profile of SC generated during a kinetics of dehydration, we show that betasitosterol, in combination with two emollient molecules, isocetyl stearoyl stearate (ISS) and glyceryl tri‐2‐ethylhexanoate (GTEH), causes a significant modulation of the drying stress behaviour of the SC by reducing both the maximal peak stress height and average plateau of the drying stress profile. Raman spectra analyses demonstrate that the combination of betasitosterol with the two emollients, ISS and GTEH, allows a high water retention capacity within the SC, while the lipid conformational order by increasing the amount of trans conformers. Our study highlights the advantage of combining a biomechanical approach together with Raman spectroscopy in engineering a suitable combination of molecules for alleviating dryness and dry skin damage.
A Cu2+ complex induces the aggregation of human papillomavirus oncoprotein E6 and stabilizes p53
Authors: Kumar Amit , Kuhn Lars T. , Balbach Jochen
Published: June 2018

Papillomavirus oncoprotein E6 is a critical factor in the modulation of cervical cancer in humans. At the molecular level, formation of the E6–E6AP‐p53 ternary complex, which directs p53's degradation, is the key instigator of cancer transforming properties. Herein, a Cu2+ anthracenyl‐terpyridine complex is described which specifically induces the aggregation of E6 in vitro and in cultured cells. For a hijacking mechanism, both E6 and E6AP are required for p53 ubiquitination and degradation. The Cu2+ complex interacts with E6 at the E6AP and p53 binding sites. We show that E6 function is suppressed by aggregation, rendering it incapable of hijacking p53 and thus increasing its cellular level. Therapeutic treatments of cervical cancer are currently unavailable to infected individuals. We anticipate that this Cu2+ complex might open up a new therapeutic avenue for the design and development of new chemical entities for the diagnosis and treatment of HPV‐induced cancers.
BCCIP binds to and activates its promoter in a YY1‐dependent fashion in HCT116 cells
Authors: Sui Yi , Li Fuqiang , Wu Tingting , Ding Jian , Lu Zeming , Wang Lingyao , Yang Yang , Wang Fei , Zhao Linhong , Zhu Huihui , Wei Tao , Jin Jingji , Cai Yong
Published: June 2018

The restriction of Yin Yang 1 (YY1) at BRCA2 and CDKN1A/p21‐interacting protein (BCCIP) transcriptional start site (TSS) proximal region in several human cancer cell lines was found by analyzation of ChIP‐Seq database from UCSC Genome Browser (http://genome.ucsc.edu). However, whether the stabilization of YY1 by BCCIP impacts its recruitment in the BCCIP promoter region is unclear. Here, we present evidence that transcriptional regulation of YY1 on BCCIP is closely related to YY1 stability in HCT116 human colon cancer cells. YY1 stabilization was in turn regulated by BCCIP, suggesting the existence of a BCCIP–YY1 feedback loop in regulating BCCIP transcription by the YY1. Overexpression of BCCIP stabilized YY1 while knockdown of BCCIP reduced YY1 protein level. In addition, direct interaction between YY1 and BCCIP was confirmed by coimmunoprecipitation approach. Also, the N‐terminus region of BCCIP, including the internal conserved domain (ICD), was responsible for binding with the amino acid 146–270 of YY1. More importantly, YY1 stability was related to the BCCIP/ICD domain‐mediated YY1 ubiquitination pathway. Moreover, a limited BCCIP promoter region containing YY1 binding site (CCGCCATC) was tightly associated with the pGL4‐BCCIP‐Luc luciferase activity. In ChIP assays, shBCCIP lentiviral‐mediated YY1 instability decreased recruitment of the YY1 at BCCIP TSS proximal region, which could not be restored by YY1 overexpression. Furthermore, knockdown of YY1 inhibited the binding of BCCIP itself at BCCIP promoter region proximal to TSS, demonstrating that transcriptional regulation of the YY1 on BCCIP can be modulated by BCCIP itself in a YY1‐dependent fashion.
Controlled synthesis of Bi2O3/BiOBr/Zn2GeO4 heterojunction photocatalysts with enhanced photocatalytic activity
Authors: Zhang Qiang , Pang Kuan , Xu Yan
Published: June 2018

BiOBr/Zn2GeO4 heterojunctions decorated by Bi2O3 quantum dots (QDs; named as Bi2O3/BiOBr/Zn2GeO4 hereafter) with intriguing micro/nanostructures have been constructed via a two‐step hydrothermal route. The compositions, phases, and morphologies of Bi2O3/BiOBr/Zn2GeO4 were investigated in detail. The light absorption ability, photocurrent responses, and photocatalytic degradation of methylene blue (MB) experiments were performed to evaluate the photocatalytic activity of the micro/nanoheterostructured Bi2O3/BiOBr/Zn2GeO4, which present a degradation efficiency of 88% after 240 minutes under light irradiation (λ = 300‐600 nm) over 100 mg Bi2O3/BiOBr/Zn2GeO4 in a 100 mL, 4 mg/L MB solution. The photocatalytic performance could be retained for at least four runs, indicating its excellent reusability for the degradation of MB in aqueous solution. It is found that the photodegradation of MB over Bi2O3/BiOBr/Zn2GeO4 is mainly ascribed to a hole oxidation mechanism in combination with a superoxide oxidation process. The high photocatalytic performance of Bi2O3/BiOBr/Zn2GeO4 upon UV light irradiation can be attributed to the effective charge separation and smoothly transferring of the photogenerated charge carriers throughout the heterojunction. The feasible strategy of preparing Bi2O3/BiOBr/Zn2GeO4 ternary composites is also of benefit to fabricate other efficient heterojunction catalysts with specific morphologies and properties.
Oxygen stoichiometry, chemical expansion or contraction, and electrical properties of rutile, TiO2±δ ceramics
Authors: Dang Yun , West Anthony R.
Published: June 2018

Rutile, TiO2 is increasingly oxygen‐deficient on heating in air above ~700°C. The weight loss is generally too small for accurate measurement, but the electrical properties of quenched samples provide a sensitive qualitative indicator of oxygen content since their conductivity can vary by many orders of magnitude. The oxygen lost at high temperature is fully recovered if samples are cooled slowly. With rapid quenching, by dropping samples into liquid N2, the oxygen stoichiometry at high temperature is preserved to ambient and the resulting materials are kinetically stable but thermodynamically metastable. The lattice parameters of quenched samples showed an unusual dependence on quench temperature and, by implication, on oxygen stoichiometry. Lattice parameters increased with a small oxygen loss, δ; chemical expansion of the lattice occurred and is attributed to reduction in average Ti oxidation state and increase in Ti–O bond lengths. At higher δ, lattice parameters started to decrease giving a chemical contraction effect attributed to partial collapse of columns of edge‐sharing TiO6 octahedra in the rutile structure and elimination of oxygen vacancies by crystallographic shear plane formation. Oxygen‐deficient samples quenched from above 700°C were n‐type, as were samples annealed and measured at 650 and 700°C. Samples measured at 450‐500°C were p‐type and believed to be slightly oxygen‐rich; it is suggested that holes located on oxide ions at or near the sample surface arose from redox electron transfer between underbonded surface oxide ions and adsorbed O2 molecules. Samples annealed between 550 and 600°C showed cross‐over between n‐ and p‐type behavior.
Transition from school to adult services for young people with severe or profound intellectual disability: A systematic review utilizing framework synthesis
Authors: Jacobs Paula , MacMahon Kenneth , Quayle Ethel
Published: June 2018

Background

The transition to adulthood has been described as a difficult time in the lives of young people with intellectual disability. There has been little emphasis on young people with severe or profound intellectual disability specifically, even though their pathways may differ, due to greater support needs across the life course.

Methods

A systematic review was conducted utilising Bronfenbrenner's ecological model to inform framework analysis to synthesise qualitative findings.

Results

Taking an ecological perspective proved valuable. The transition process was described as stressful and barriers were identified across the ecological levels. Parents accounted for the majority of participants in studies, and the needs of young people and their parents emerged as highly interdependent.

Conclusion

Themes reflect the complex nature of the question what adulthood should look like for individuals with severe or profound intellectual disability. There is a lack of involvement of multiple stakeholders and young people themselves within studies.
Invasive round goby Neogobius melanostomus has sex‐dependent locomotor activity and is under‐represented in catches from passive fishing gear compared with seine catches
Authors: Žák Jakub , Jůza Tomáš , Blabolil Petr , Baran Roman , Bartoň Daniel , Draštík Vladislav , Frouzová Jaroslava , Holubová Michaela , Ketelaars Henk A. M. , Kočvara Luboš , Kubečka Jan , Mrkvička Tomáš , Muška Milan , Říha Milan , Sajdlová Zuzana , Šmejkal Marek , Tušer Michal , Vašek Mojmír , Vejřík Lukáš , Vejříková Ivana , Wagenvoort Arco J.
Published: June 2018

The higher proportion of males of the invasive round goby Neogobius melanostomus in samples from two activity selective passive fishing gears compared with one activity non‐selective fishing gear in three Dutch lakes is related to higher male locomotory activity and is a sex‐dependent trait. This difference in activity reflects the different ecology of male and female N. melanostomus.
Assessment of the timing and degree of smolt development in southern populations of masu salmon Oncorhynchus masou
Authors: Inatani Yu , Ineno Toshinao , Sone Shiori , Matsumoto Naoto , Uchida Katsuhisa , Shimizu Munetaka
Published: June 2018

The present study assessed whether non‐anadromous masu salmon Oncorhynchus masou in Miyazaki, southern Japan, smoltify, and if so, at what time of the year. Yearling O. masou of Miyazaki and an anadromous population from Hokkaido, northern Japan, were reared in hatcheries in their respective regions and sampled monthly from February to June to examine the spring smoltification period. The Hokkaido population showed a peak of gill Na+–K+‐ATPase (NKA) activity in May, which was accompanied with an increase in mRNA levels of the seawater (SW)‐type NKA alpha subunit, nkaα1b. Increases in gill NKA activity and nkaa1b levels were not seen in Miyazaki populations. Transferring yearling Miyazaki population to 70% SW (salinity of 23) in mid‐April resulted in an increased serum osmolality over 4 days. These results suggest that they do not smoltify in their second spring. Next, profiles of gill NKA activity and its subunit mRNA levels in under‐yearling Miyazaki population in the autumn were examined. Two phenotypes differing in body color during this period were categorized as parr and smolt‐like fish. Smolt‐like fish had higher gill NKA activity than parr in December while there was no significant difference in gill nkaα1b levels. Smolt‐like fish acclimated to 70% SW better than parr as judged by lower serum osmolality. However, serum osmolality in smolt‐like fish did not return to the basal level 7 days after transfer to 70% SW, suggesting that their hypo‐osmoregulatory ability was not fully developed to a level comparable to anadromous populations of this species. The present study suggests that, if O. masou in Miyazaki go though a smoltification process, it occurs in its first autumn instead of the second spring and is less pronounced compared with anadromous populations.
Experimental evidence of masculinization by continuous illumination in a temperature sex determination teleost (Atherinopsidae) model: is oxidative stress involved?
Authors: Corona‐Herrera Guillermo A. , Arranz Silvia E. , Martínez‐Palacios Carlos A. , Navarrete‐Ramírez Pamela , Toledo‐Cuevas Elva M. , Valdez‐Alarcón Juan J. , Martínez‐Chávez Carlos C.
Published: June 2018

The present study evaluates the influence of continuous light on phenotypic sex ratios in Chirostoma estor, a temperature sex determination animal model. Relative gene expression levels of 5 day old larvae were performed on two early gonad differentiation genes (sox9 and foxl2), two stress axis activation genes (gcr1 and crf) and four reactive oxygen species (ROS) antagonist effector genes (sod2, ucp2, gsr and cat). Two light treatments were applied from fertilization; control (12L:12D) simulated natural photoperiod and a continuous illumination photoperiod. By the end of the trial (12 weeks after hatching), differentiated and normal gonads were clearly identifiable in both treatments by histological observations. Regarding sex ratio, 73% of phenotypic males were found in continuous illumination compared with 40% in controls. Consistently, the sox9 gene (involved in early testis differentiation) showed an over expression in 64% of the individual larvae analysed compared with foxl2 (ovarian differentiation) suggesting a masculinization tendency in continuous illumination. On the other hand, only 36% of individuals showed the same tendency in the control treatment consistent with phenotypic sex ratios found under normal culture conditions. Relative gene expression results did not show significant difference in sod2, ucp2 and gcr1 levels, but cat, gsr and crf showed significantly higher expression levels in the continuous illumination treatment suggesting that both, the stress axis and ROS response mechanisms were activated at this time. This study suggests, a link between continuous light, oxidative stress and environmental sex determination in vertebrates. However, further research is necessary to describe this possible upstream mechanism that may drive some aspects of sexual plasticity in vertebrates.
Estimating fish swimming metrics and metabolic rates with accelerometers: the influence of sampling frequency
Authors: Brownscombe Jacob W. , Lennox Robert J. , Danylchuk Andy J. , Cooke Steven J.
Published: June 2018

Accelerometry is growing in popularity for remotely measuring fish swimming metrics, but appropriate sampling frequencies for accurately measuring these metrics are not well studied. This research examined the influence of sampling frequency (1–25 Hz) with tri‐axial accelerometer biologgers on estimates of overall dynamic body acceleration (ODBA), tail‐beat frequency, swimming speed and metabolic rate of bonefish Albula vulpes in a swim‐tunnel respirometer and free‐swimming in a wetland mesocosm. In the swim tunnel, sampling frequencies of ≥ 5 Hz were sufficient to establish strong relationships between ODBA, swimming speed and metabolic rate. However, in free‐swimming bonefish, estimates of metabolic rate were more variable below 10 Hz. Sampling frequencies should be at least twice the maximum tail‐beat frequency to estimate this metric effectively, which is generally higher than those required to estimate ODBA, swimming speed and metabolic rate. While optimal sampling frequency probably varies among species due to tail‐beat frequency and swimming style, this study provides a reference point with a medium body‐sized sub‐carangiform teleost fish, enabling researchers to measure these metrics effectively and maximize study duration.
Under what circumstances does the capture and tagging of wild Atlantic salmon Salmo salar smolts affect probability of return as adults?
Authors: Riley William D. , Ibbotson Anton T. , Gregory Stephen D. , Russell Ian C. , Lauridsen Rasmus B. , Beaumont William R. C. , Cook Alastair C. , Maxwell David L.
Published: June 2018

Adult return rates for wild Atlantic salmon Salmo salar smolts captured in a rotary screw trap and tagged with coded wire (CW) tags were compared with a control group, using detections from passive integrated transponder (PIT) antennae systems over 7 years in a small chalk stream in southern England, U.K. Compared with control smolts, capture and CW‐tagging of experimental smolts affected detected return rates only under certain conditions, with a decreased return probability for smolts caught and tagged following mild winter river temperature anomalies and during the night. Similarly, analysis of the experimental smolts revealed that capture and CW‐tagging following mild winters decreased their probability of return as adults. There were also marginal positive effects of length at PIT‐tagging as parr and length at CW‐tagging as smolts, on individual probability of return as adult. The results support the hypothesis that the effect of procedures involving the capture and tagging of migrating wild S. salar smolts will vary with the circumstances under which they are performed. The implications of the findings are considered in the context of ongoing investigations to derive and report marine return rates for S. salar in support of national and international stock assessments and in developing best practice.
Risk factors for advanced colorectal neoplasms in the proximal colon in 6218 subjects undergoing complete colonoscopy
Authors: Hirai Hoyee W , Ching Jessica Y L , Wu Justin C Y , Sung Joseph J Y , Chan Francis K L , Ng Siew C
Published: June 2018

Background and Aim

Proximal migration of colonic lesion has been observed; however, risk factors of lesions in the proximal colon remain uncertain. This study aimed to investigate risk factors of lesions in the proximal colon.

Methods

Consecutive subjects with complete colonoscopy were included. The primary outcome was risk factors associated with advanced neoplasm (AN) and serrated lesion in the proximal colon. Age, gender, first‐degree relative (FDR) with colorectal cancer (CRC), smoking, alcohol consumption, body mass index, hypertension, diabetes, ischemic heart disease, and the use of aspirin, non‐steroidal anti‐inflammatory drug, and anticoagulants were fitted into a regression model, with reference to subjects without colonic finding. Results were measured by odds ratio (OR) with 95% confidence interval (CI).

Results

Among 6218 subjects (mean age 56.65 ± 6.15 years; 46.8% male), 352 (5.7%) had AN; 809 (13.0%) had serrated lesions, and 3648 (58.7%) had no colonic finding. There were 148 (2.4%) and 235 (3.8%) subjects having AN and serrated lesion in the proximal colon. Age ≥ 50 (OR: 13.30; 95% CI: 1.85–95.76), male gender (OR: 1.82; 95% CI: 1.26–2.62), FDR with CRC (OR: 2.12; 95% CI: 1.43–3.15), and hypertension (OR: 1.86; 95% CI: 1.30–2.68) were associated with AN in the proximal colon. Age ≥ 50 (OR: 5.72; 95% CI: 2.10–15.53), male gender (OR: 1.54; 95% CI: 1.15–2.05), and smoking (OR: 1.85; 95% CI: 1.23–2.79) increased risk of serrated lesions in the proximal colon.

Conclusion

Age ≥ 50 and male gender were associated with both proximally located AN and serrated lesion; FDR with CRC and hypertension increased the risk of proximal AN, while ever smoking increased the risk of proximal serrated lesion. FDR with CRC was not associated with serrated lesion.
Nutrition‐Related Cardiovascular Risk Factors in Older People: Results from the Third National Health and Nutrition Examination Survey
Authors: Erlinger Thomas P. , Pollack Harold , Appel Lawrence J.
Published: June 2018

SETTING

In view of the recognized potential benefits of nutritional therapy in older persons, Congress is evaluating the coverage of nutritional services for Medicare beneficiaries.

OBJECTIVE

To estimate the number of older persons in the US who have one or more cardiovascular risk factors (hypertension, increased low density lipoprotein (LDL) cholesterol, and diabetes mellitus), for which nutritional therapy is recommended.

DESIGN

Cross‐sectional analysis of adults, aged ≥65, participating in the Third National Health and Nutrition Examination Survey (NHANES III).

MAIN OUTCOMES

The authors estimated the proportion of adults, aged ≥65, with diabetes mellitus, increased LDL cholesterol, and/or hypertension. Efforts were made to assess whether obesity status, gender, race, and/or socioeconomic factors were associated with the prevalence of any or all three conditions.

RESULTS

Approximately 86% (20 million persons) in the US, aged ≥65, have at least one of the index conditions. Whereas a higher body mass index (BMI) increased the likelihood of having any or all three conditions, 81% of persons of average body weight (BMI <25 kg/m2) had at least one condition. After adjusting for age, gender, BMI, marital status, and poverty index, blacks were more likely than whites to have any one condition (odds ratio (OR) = 3.0, P < .01) or all three conditions (OR = 2.3, P = .05).

CONCLUSIONS

Almost 90% of Americans ≥aged have one or more nutrition‐related cardiovascular risk factors. Improved nutritional interventions may be valuable especially for blacks, who have a higher prevalence of conditions requiring nutritional therapy.
A Case‐Oriented Web‐Based Curriculum in Geriatrics for Third‐Year Medical Students
Authors: Swagerty Daniel , Studenski Stephanie , Laird Rosemary , Rigler Sally
Published: June 2018

OBJECTIVES

This paper describes the development, implementation, and evaluation of a case‐oriented, web‐based curriculum in geriatric medicine for third‐year medical students.

DESIGN

Single cohort, pre/post trial.

SETTING

University of Kansas School of Medicine, Kansas City, Kansas.

PARTICIPANTS

Third‐year medical students (n = 130).

INTERVENTION

A web‐rbased curriculum, offered during a clinical geriatrics clerkship, is composed of 13 case‐oriented, web‐based modules spanning key topics in geriatric medicine. Each module topic is also reviewed in a post‐module, faculty‐led discussion session.

MEASUREMENTS

A pre‐and post‐rotation test of knowledge was completed. Student feedback about the curriculum was collected through web‐based and written evaluation.

MAIN RESULTS

Pre‐and post‐rotation comparison of examination scores demonstrated an average increase of 13 correct items on a 40‐item exam. Seventy‐five percent of students rated each module favorably at the time of completion (range 53–89%). Most modules (10/13) were rated as excellent or good after all modules had been completed.

CONCLUSIONS

A case‐oriented web‐based curriculum in geriatrics was rated favorably by third‐year medical students. Students' knowledge increased in key geriatric topics. Student feedback allows for continuous improvement of the curriculum. This model of curricular innovation may be useful for other institutions seeking to develop or enhance geriatric medicine content in the medical school curriculum.
Analysis of Stigma and Bank Credit Provision
Authors: VOSSMEYER ANGELA
Published: June 2018

Bank rescue programs are designed to provide assistance to struggling financial intermediaries during financial crises. A complicating factor is that participating banks are often stigmatized by accepting assistance from the government. This paper investigates stigma in two ways: (i) it examines how stigma changes a bank's decision to seek assistance from the rescue program, and (ii) it analyzes how stigma affects a bank's ability to operate as a financial intermediary using a joint model for bank‐level application, approval, and lending decisions. The empirical results indicate that stigma hinders the objectives of the rescue program and slows the production of credit.
Remote focusing in confocal microscopy by means of a modified Alvarez lens
Authors: BAWART M. , JESACHER A. , BERNET S. , RITSCH‐MARTE M.
Published: June 2018

Alvarez lenses are actuated lens‐pairs which allow one to tune the optical power by mechanical displacement of subelements. Here, we show that a recently realized modified Alvarez lens design which does not require mechanical actuation can be integrated into a confocal microscope. Instead of mechanically moving them, the sublenses are imaged onto each other in a 4f‐configuration, where the lateral image shift leading to a change in optical power is created by a galvo‐mirror. The avoidance of mechanical lens shifts leads to a large speed gain for axial (and hence also 3D) image scans compared to classical Alvarez lenses. We demonstrate that the suggested operation principle is compatible with confocal microscopy. In order to optimize the system, we have drawn advantage of the flexibility a liquid‐crystal spatial light modulator offers for the implementation. For given specifications, dedicated diffractive optical elements or freeform elements can be used in combination with resonant galvo‐scanners or acousto‐optic beam deflectors, to achieve even faster z‐scans than reported here, reaching video rate.
Hyaluronic acid-modified cationic niosomes for ocular gene delivery: improving transfection efficiency in retinal pigment epithelium
Authors: Qin Yanmei , Tian Yongfeng , Liu Yang , Li Dong , Zhang Hua , Yang Yeqian , Qi Jianping , Wang Hao , Gan Li
Published: June 2018

Objectives

Recent years, gene therapy to treat retinal diseases has been paid much attention. The key to successful therapy is utilizing smart delivery system to achieve efficient gene delivery and transfection. In this study, hyaluronic acid (HA) modified cationic niosomes (HA-C-niosomes) have been designed in order to achieve retinal pigment epithelium (RPE) cells targeted gene delivery and efficient gene transfection.

Methods

Cationic niosomes composed of tween 80/squalene/1, 2-dioleoyl-3-trimethylammonium-propane (DOTAP) were prepared by the ethanol injection method. After that, HA-DOPE was further added into cationic niosomes to form HA-C-niosomes. Cellular uptake and transfection have been investigated in ARPE-19 cells. In vivo pEGFP transfection efficiency was evaluated in rats.

Key findings

Twenty percentage HA-C-niosomes were about 180 nm, with −30 mV, and showing spherical shape in TEM. 2 times higher transfection efficiency was found in the group of HA-C-niosomes with 20% HA modification. No toxicity was found in niosome preparations. In vivo evaluation in Sprague Dawley (SD) rats revealed that HA-C-niosomes could specifically target to the retina layer. In the group of pEGFP-loaded HA-C-niosomes, 6–6.5 times higher gene transfection has been achieved, compared with naked pEGFP.

Conclusions

Hyaluronic acid-C-niosomes might provide a promising gene delivery system for successful retinal gene therapy.
Impacts of domestication on population genetics of a traditional Chinese medicinal herb, Atractylodes macrocephala (Asteraceae)
Authors: Chen Chuan , Zheng Li , Ma Qing , Zhou Wen‐Bin , Lu Yin , Zhao Yun‐Peng , Fu Cheng‐Xin
Published: June 2018

As a medicinal herb, Atractylodes macrocephala Koidz. experienced centuries of cultivation in China, and germplasm resources of all cultivated populations have degraded over time as a consequence of domestication processes. This study used chloroplast DNA and microsatellites to clarify not only the effects of domestication on population genetics, but also determine the geographic origins of landraces. The results revealed that cultivated populations (except the “Pingzhu” landrace) showed higher genetic diversity than their wild counterparts and low levels of genetic differentiation occurred between cultivated and wild groups. Furthermore, STRUCTURE and UPGMA analyses grouped all wild populations into three genotypic clusters, two of which (in Shaanxi and Hunan Province) shared the same gene pool with cultivated A. macrocephala, suggesting that wild populations in Central China have been involved in the origin of cultivated A. macrocephala. Moreover, the wild population from Qimen, Anhui Province and the cultivated “Pingzhu” landrace harbor unique gene pools and rare alleles that could be useful in future breeding efforts. This large‐scale analysis of population genetics on a medicinal herb that has a centuries‐long history of human‐mediated selection will facilitate utilization and conservation of the valuable genetic resources of medicinal species.
Age, courtship and senescence: sexual ornaments are larger in older great crested newts
Authors: Palau Daval N. , Gardette V. , Joly P.
Published: June 2018

Patterns of senescence are highly diverse and the underlying mechanisms are controversial. Most studies have focused on endothermic tetrapods, who usually exhibit both actuarial (e.g. the increase in mortality rate with age) and reproductive senescence. However, senescence patterns are less clear in ectothermic vertebrates since these animals exhibit undetermined growth and often increase their reproductive potential throughout their life history. We contribute to this topic by investigating the relationship between age and relative size of sexual ornaments in a urodele amphibian, the great crested newt, Triturus cristatus. We found that the relative sizes of sexual ornaments (crest height, crest area, area of the white caudal spot) were correlated with an individual's age in a population monitored in the wild. These sexual ornaments constitute honest signals reflecting male quality. Thus, the crested newt appeared to undergo negligible reproductive senescence in our population, although further experiments on reproductive success are needed to confirm this hypothesis.
Prevention of the mother‐to‐child transmission of Hepatitis B virus
Authors: Pol Stanislas , Jourdain Gonzague
Published: June 2018

See Article on Page 1212
The state of global capitalism today
Authors: Gindin Sam , Panitch Leo
Published: June 2018

Will the US sustain its imperial role in the wake of the fourth great crisis of capitalism?
A question of leadership?
Authors: Curtice John
Published: June 2018

In both domestic and foreign policy, having the right policies is not enough; Labour must prove its capability to lead if it is to win the next election
Turning back the Doomsday Clock
Authors: Hudson Kate
Published: June 2018

There is a dynamic in world politics towards greater global tension, conflict and war, including nuclear war. Britain must work to end the possibility of nuclear disaster
The uncomfortable history of Britain in Europe
Authors: Owen David
Published: June 2018

Why an increasingly federal Europe has never been right for the UK
An Accuracy‐Dominance Argument for Conditionalization
Authors: Briggs R.A. , Pettigrew Richard
Published: June 2018

Epistemic decision theorists aim to justify Bayesian norms by arguing that these norms further the goal of epistemic accuracy—having beliefs that are as close as possible to the truth. The standard defense of Probabilism appeals to accuracy dominance: for every belief state that violates the probability calculus, there is some probabilistic belief state that is more accurate, come what may. The standard defense of Conditionalization, on the other hand, appeals to expected accuracy: before the evidence is in, one should expect to do better by conditionalizing than by following any other rule. We present a new argument for Conditionalization that appeals to accuracy‐dominance, rather than expected accuracy. Our argument suggests that Conditionalization is a rule of coherence: plans that conflict with Conditionalization don't just prescribe bad responses to the evidence; they also give rise to inconsistent attitudes.
Malate valves: old shuttles with new perspectives
Authors: Selinski J. , Scheibe R.
Published: June 2018

Malate valves act as powerful systems for balancing the ATP/NAD(P)H ratio required in various subcellular compartments in plant cells. As components of malate valves, isoforms of malate dehydrogenases (MDHs) and dicarboxylate translocators catalyse the reversible interconversion of malate and oxaloacetate and their transport. Depending on the co‐enzyme specificity of the MDH isoforms, either NADH or NADPH can be transported indirectly. Arabidopsis thaliana possesses nine genes encoding MDH isoenzymes. Activities of NAD‐dependent MDHs have been detected in mitochondria, peroxisomes, cytosol and plastids. In addition, chloroplasts possess a NADP‐dependent MDH isoform. The NADP‐MDH as part of the ‘light malate valve’ plays an important role as a poising mechanism to adjust the ATP/NADPH ratio in the stroma. Its activity is strictly regulated by post‐translational redox‐modification mediated via the ferredoxin‐thioredoxin system and fine control via the NADP+/NADP(H) ratio, thereby maintaining redox homeostasis under changing conditions. In contrast, the plastid NAD‐MDH (‘dark malate valve’) is constitutively active and its lack leads to failure in early embryo development. While redox regulation of the main cytosolic MDH isoform has been shown, knowledge about regulation of the other two cytosolic MDHs as well as NAD‐MDH isoforms from peroxisomes and mitochondria is still lacking. Knockout mutants lacking the isoforms from chloroplasts, mitochondria and peroxisomes have been characterised, but not much is known about cytosolic NAD‐MDH isoforms and their role in planta. This review updates the current knowledge on MDH isoforms and the shuttle systems for intercompartmental dicarboxylate exchange, focusing on the various metabolic functions of these valves.
Re‐investigation of Gymnodinium natalense (Dinophyceae), a tidal pool dinoflagellate from South Africa and the proposal of a new combination Ansanella natalensis
Authors: Dawut Mahmutjan , Sym Stuart D. , Horiguchi Takeo
Published: June 2018

A small tidal pool bloom‐forming dinoflagellate, Gymnodinium natalense T. Horiguchi & Pienaar, sampled from its type locality in South Africa, was re‐investigated and a new combination Ansanella natalensis (T. Horiguchi & Pienaar) Dawut, Sym & T. Horiguchi comb. nov. was proposed. The species was originally described as a new species of the genus Gymnodinium, and later, Moestrup et al. (2009a) transferred it to their new genus Biecheleria based on morphological resemblance. However, no molecular data were available at that time, making confirmation of its phylogenetic affinities impossible. An organism more‐recently isolated from the type locality was confirmed as G. natalense based on its morphological features. In addition, we were able to characterize details of its surface structure, which were lacking in the original description. Cells were covered with small, mostly hexagonal, amphiesmal vesicles (AV) arranged in 11–13 latitudinal rows. The episome contained an elongated amphiesmal vesicle (EAV) enclosing approximately 25 knobs in linear array. A phylogenetic analysis based on SSU rDNA sequences revealed that this dinoflagellate was closely related to Ansanella granifera the only member of the genus. The G. natalense shared numerous characteristics with A. granifera, such as the arrangement of AVs in a similar number of latitudinal rows, the shape and position of the EAV, the possession of a type E eyespot, a similar type of pyrenoid, the absence of a peduncle and nuclear chambers, the lack of a nuclear fibrous connective and no resting cyst‐like cells. Yet, it also showed some morphological differences, i.e. the possession of a single chloroplast that lacks grana‐like thylakoids, which separate it from A. granifera. These morphological features, along with its highly supported molecular affinity with A. granifera, led to the conclusion that this dinoflagellate represents a new member of this genus, i.e. A. natalensis comb. nov. The phylogenetic analysis showed no support for a close relationship with members of the genus Biecheleria.