bluuebunny/crossref_metadata_2025 huggingface dataset:
Bimodal coupling of ripples and slower oscillations during sleep in patients with focal epilepsy
Authors: Song Inkyung , Orosz Iren , Chervoneva Inna , Waldman Zachary J. , Fried Itzhak , Wu Chengyuan , Sharan Ashwini , Salamon Noriko , Gorniak Richard , Dewar Sandra , Bragin Anatol , Engel Jerome , Sperling Michael R. , Staba Richard , Weiss Shennan A.
Published: September 2017

Objective

Differentiating pathologic and physiologic high‐frequency oscillations (HFOs) is challenging. In patients with focal epilepsy, HFOs occur during the transitional periods between the up and down state of slow waves. The preferred phase angles of this form of phase‐event amplitude coupling are bimodally distributed, and the ripples (80–150 Hz) that occur during the up‐down transition more often occur in the seizure‐onset zone (SOZ). We investigated if bimodal ripple coupling was also evident for faster sleep oscillations, and could identify the SOZ.

Methods

Using an automated ripple detector, we identified ripple events in 40–60 min intracranial electroencephalography (iEEG) recordings from 23 patients with medically refractory mesial temporal lobe or neocortical epilepsy. The detector quantified epochs of sleep oscillations and computed instantaneous phase. We utilized a ripple phasor transform, ripple‐triggered averaging, and circular statistics to investigate phase event‐amplitude coupling.

Results

We found that at some individual recording sites, ripple event amplitude was coupled with the sleep oscillatory phase and the preferred phase angles exhibited two distinct clusters (p < 0.05). The distribution of the pooled mean preferred phase angle, defined by combining the means from each cluster at each individual recording site, also exhibited two distinct clusters (p < 0.05). Based on the range of preferred phase angles defined by these two clusters, we partitioned each ripple event at each recording site into two groups: depth iEEG peak‐trough and trough‐peak. The mean ripple rates of the two groups in the SOZ and non‐SOZ (NSOZ) were compared. We found that in the frontal (spindle, p = 0.009; theta, p = 0.006, slow, p = 0.004) and parietal lobe (theta, p = 0.007, delta, p = 0.002, slow, p = 0.001) the SOZ incidence rate for the ripples occurring during the trough‐peak transition was significantly increased.

Significance

Phase‐event amplitude coupling between ripples and sleep oscillations may be useful to distinguish pathologic and physiologic events in patients with frontal and parietal SOZ.
Using fuzzy logic to determine the vulnerability of marine species to climate change
Authors: Jones Miranda C. , Cheung William W. L.
Published: September 2017

Marine species are being impacted by climate change and ocean acidification, although their level of vulnerability varies due to differences in species' sensitivity, adaptive capacity and exposure to climate hazards. Due to limited data on the biological and ecological attributes of many marine species, as well as inherent uncertainties in the assessment process, climate change vulnerability assessments in the marine environment frequently focus on a limited number of taxa or geographic ranges. As climate change is already impacting marine biodiversity and fisheries, there is an urgent need to expand vulnerability assessment to cover a large number of species and areas. Here, we develop a modelling approach to synthesize data on species‐specific estimates of exposure, and ecological and biological traits to undertake an assessment of vulnerability (sensitivity and adaptive capacity) and risk of impacts (combining exposure to hazards and vulnerability) of climate change (including ocean acidification) for global marine fishes and invertebrates. We use a fuzzy logic approach to accommodate the variability in data availability and uncertainties associated with inferring vulnerability levels from climate projections and species' traits. Applying the approach to estimate the relative vulnerability and risk of impacts of climate change in 1074 exploited marine species globally, we estimated their index of vulnerability and risk of impacts to be on average 52 ± 19 SD and 66 ± 11 SD, scaling from 1 to 100, with 100 being the most vulnerable and highest risk, respectively, under the ‘business‐as‐usual' greenhouse gas emission scenario (Representative Concentration Pathway 8.5). We identified 157 species to be highly vulnerable while 294 species are identified as being at high risk of impacts. Species that are most vulnerable tend to be large‐bodied endemic species. This study suggests that the fuzzy logic framework can help estimate climate vulnerabilities and risks of exploited marine species using publicly and readily available information.
Novel KIR genotypes and gene copy number variations in northeastern Thais
Authors: Chaisri Suwit , Traherne James A. , Jayaraman Jyothi , Romphruk Amornrat , Trowsdale John , Leelayuwat Chanvit
Published: September 2017

KIR (Killer Immunoglobulin‐like Receptor) variants influence immune responses and are genetic factors in disease susceptibility. Using sequence‐specific priming PCR, we have previously described the diversity of KIR genes in term of presence/absence in northeastern Thais (NETs). To provide additional resolution beyond conventional methods, quantitative PCR was applied to determine KIR copy number profiles. Novel expanded and contracted KIR copy number profiles were identified at cumulatively high frequencies. These all comprise haplotypes with duplication (6·9%) or deletion (2·7%) of KIR3DL1/S1 along with adjacent genes. Five expanded KIR profiles comprised haplotypes with duplications of KIR2DP1, 2DL1, 3DP1, 2DL4, 3DL1/S1 and 2DS1/4, whereas two contracted profiles contained only a single copy of KIR3DP1, 3DL1/S1 and 2DL4. Using a KIR haplotype prediction program (KIR Haplotype Identifier), 14% of NET haplotypes carried atypical haplotypes based on the gene copy number data.
Context matters: Explicit and implicit reminders of ingroup privilege increase collective guilt among foreigners in a developing country
Authors: Greenaway Katharine H. , Fisk Kylie , Branscombe Nyla R.
Published: September 2017

We test three ways context matters in the study of intergroup inequality: where participants are approached, who interacts with participants, and how researchers ask participants questions. Regarding how, we replicate a finding that framing intergroup inequality as outgroup disadvantage rather than ingroup privilege reduces collective guilt in a novel context. Regarding where, we go beyond the laboratory to test foreigners in Nepal—a country where inequality is highly salient. Regarding who, we had participants approached by an ingroup (foreign) experimenter or an outgroup (Nepalese) experimenter. We found an outgroup disadvantage framing reduced collective guilt relative to ingroup privilege framing, but only when delivered by an ingroup member. This highlights the importance of taking where, who, and how into account to fully understand the contextual nature of intergroup emotion.
Impact of diabetes mellitus and hepatitis B virus coinfection on patients with chronic hepatitis C: A territory‐wide cohort study
Authors: Subramaniam Shreenidhi , Wong Vincent Wai‐Sun , Tse Yee‐Kit , Yip Terry Cheuk‐Fung , Chan Henry Lik‐Yuen , Wong Grace Lai‐Hung
Published: September 2017

Background and Aim

Studies have demonstrated a higher prevalence of diabetes mellitus (DM) in patients with chronic hepatitis C (CHC). Furthermore, coinfection with hepatitis B virus (HBV) is common because of its endemicity in Asian–Pacific regions. The aim of the present study was to investigate the impact of DM and HBV coinfection on the clinical outcomes in Chinese CHC patients.

Methods

A territory‐wide cohort study was conducted using the database from Hospital Authority, the sole public medical service provider in Hong Kong. CHC patients were identified by the International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes, diagnosed between 2000 and 2012. The primary outcome was overall mortality.

Results

A total of 7149 CHC patients were included. Seven hundred twenty‐two (10.1%) patients were coinfected with HBV. Their mean age was 56 years; 69.0% were men. The prevalence of DM was similar in mono‐infection and coinfection cohorts (22.3% and 21.3%, respectively). Multivariable analysis identified DM as an independent risk factor for death and antiviral treatment for hepatitis C virus (HCV) as an independent protective factor against death. The 5‐year survival of CHC patients with mono‐infection was better than that of HBV coinfected patients (62.5% vs 57.0%; P = 0.001). The 5‐year survival of patients who did or did not receive antiviral treatment for HCV was 94.7% and 55.2%, respectively (P < 0.001).

Conclusions

Hepatitis B virus coinfection and DM were independent risk factors for death in Hong Kong CHC patients. Antiviral treatment for HCV but not HBV was a protective factor against death.
Clinical significance of nutritional risk screening tool for hospitalised children with acute burn injuries: a cross‐sectional study
Authors: Bang Y. K. , Park M. K. , Ju Y. S. , Cho K. Y.
Published: September 2017

Background

We assessed the nutritional risks among children hospitalised with acute burn injuries and their associated clinical outcomes using three nutritional risk screening (NRS) tools: Screening Tool for Risk of Impaired Nutritional Status and Growth (STRONGKIDS), Pediatric Yorkhill Malnutrition Score (PYMS) and Screening Tool for the Assessment for Malnutrition in Pediatrics (STAMP).

Methods

This prospective cross‐sectional study was conducted from October 2015 to November 2016, in a regional burn centre. Patients were screened by two independent observers, using the three NRS tools.

Results

A total of 100 children aged 3 months to 16.5 years were included. STRONGKIDS identified 16% of patients as having high risk, with being identified 45% by PYMS and 44% by STAMP. After adjustment for confounding factors in multivariate regression analysis, patients in the high‐risk group had significantly longer median (SD) lengths of stay [medium versus high risk: STRONGKIDS, 9.5 (6.6) versus 15.0 (24.2) days; PYMS, 8.5 (4.4) versus 13.0 (16.1) days; STAMP, 9.0 (5.7) versus 11.0 (17.4) days] and greater median (SD) weight loss [medium versus high risk: STRONGKIDS, 0.15 (0.8) versus ‐0.35 (0.8) kg; STAMP, 0.5 (0.7) versus 0 (0.1) kg] than patients in the medium‐risk group (P < 0.05). The strengths of agreement in the nutritional risk classification between the two observers were good (κ for STRONGKIDS = 0.61; PYMS = 0.79; STAMP = 0.75) (P < 0.01).

Conclusions

The STRONGKIDS, PYMS and STAMP tools could be useful and practical for determining which hospitalised children with acute burn injuries will need additional nutritional intervention.
Benefits to Children Who Participate in Family Therapy with their Substance‐Using Mother
Authors: Bartle‐Haring Suzanne , Slesnick Natasha , Murnan Aaron
Published: September 2017

It is rare that family members other than the identified patient are followed over time in studies of therapy effectiveness. Family therapy is believed to be effective because it targets processes within the system that maintain symptoms. If these processes are changed, then all family members can benefit. Using a sample of 183 mother–child dyads from a study comparing family therapy for adult substance use versus an attention control, change in child's substance use (tobacco, alcohol, and marijuana) was estimated. Children who participated in family therapy with their mothers showed greater decreases in alcohol and tobacco use and were less likely to begin using compared to children whose mothers participated in the attention control condition.
Does pathology of small venules contribute to cerebral microinfarcts and dementia?
Authors: Hartmann David A. , Hyacinth Hyacinth I. , Liao Francesca‐Fang , Shih Andy Y.
Published: September 2017

Microinfarcts are small, but strikingly common, ischemic brain lesions in the aging human brain. There is mounting evidence that microinfarcts contribute to vascular cognitive impairment and dementia, but the origins of microinfarcts are unclear. Understanding the vascular pathologies that cause microinfarcts may yield strategies to prevent their occurrence and reduce their deleterious effects on brain function. Current thinking suggests that cortical microinfarcts arise from the occlusion of penetrating arterioles, which are responsible for delivering oxygenated blood to small volumes of tissue. Unexpectedly, pre‐clinical studies have shown that the occlusion of penetrating venules, which drain deoxygenated blood from cortex, lead to microinfarcts that appear identical to those resulting from arteriole occlusion. Here we discuss the idea that cerebral venule pathology could be an overlooked source for brain microinfarcts in humans.

image

This article is part of the Special Issue “Vascular Dementia”.

Cover Image for this Issue: doi: 10.1111/jnc.14167.
Diagnostic Expectations and Credit Cycles
Authors: BORDALO PEDRO , GENNAIOLI NICOLA , SHLEIFER ANDREI
Published: September 2017

We present a model of credit cycles arising from diagnostic expectations—a belief formation mechanism based on Kahneman and Tversky's representativeness heuristic. Diagnostic expectations overweight future outcomes that become more likely in light of incoming data. The expectations formation rule is forward looking and depends on the underlying stochastic process, and thus is immune to the Lucas critique. Diagnostic expectations reconcile extrapolation and neglect of risk in a unified framework. In our model, credit spreads are excessively volatile, overreact to news, and are subject to predictable reversals. These dynamics can account for several features of credit cycles and macroeconomic volatility.
Both modular and single‐domain Type I polyketide synthases are expressed in the brevetoxin‐producing dinoflagellate, Karenia brevis (Dinophyceae)
Authors: Van Dolah Frances M. , Kohli Gurjeet S. , Morey Jeanine S. , Murray Shauna A.
Published: September 2017

Dinoflagellates are prolific producers of polyketide compounds, many of which are potent toxins with adverse impacts on human and marine animal health. To identify polyketide synthase (PKS) genes in the brevetoxin‐producing dinoflagellate, Karenia brevis, we assembled a transcriptome from 595 million Illumina reads, sampled under different growth conditions. The assembly included 125,687 transcripts greater than 300 nt in length, with over half having >100× coverage. We found 121 transcripts encoding Type I ketosynthase (KS) domains, of which 99 encoded single KS domains, while 22 contained multiple KS domains arranged in 1–3 protein modules. Phylogenetic analysis placed all single domain and a majority of multidomain KSs within a monophyletic clade of protist PKSs. In contrast with the highly amplified single‐domain KSs, only eight single‐domain ketoreductase transcripts were found in the assembly, suggesting that they are more evolutionarily conserved. The multidomain PKSs were dominated by trans‐acyltransferase architectures, which were recently shown to be prevalent in other algal protists. Karenia brevis also expressed several hybrid nonribosomal peptide synthetase (NRPS)/PKS sequences, including a burA‐like sequence previously reported in a wide variety of dinoflagellates. This contrasts with a similarly deep transcriptome of Gambierdiscus polynesiensis, which lacked NRPS/PKS other than the burA‐like transcript, and may reflect the presence of amide‐containing polyketides in K. brevis and their absence from G. polynesiensis. In concert with other recent transcriptome analyses, this study provides evidence for both single domain and multidomain PKSs in the synthesis of polyketide compounds in dinoflagellates.
Neurobiological bases of reading disorder part II: The importance of developmental considerations in typical and atypical reading
Authors: Black Jessica M. , Xia Zhichao , Hoeft Fumiko
Published: September 2017

Decoding‐based reading disorder (RD; aka developmental dyslexia) is one of the most common neurodevelopmental disorders, affecting approximately 5–10% of school‐aged children across languages. Even though neuroimaging studies suggest an impairment of the left reading network in RD, the onset of this deficit and its developmental course, which may include constancy and change, are largely unknown. There is now growing evidence that the recruitment of brain networks underlying perceptual, cognitive, and linguistic processes relevant to reading acquisition varies with age. These age‐dependent changes may in turn impact the neurocognitive characteristics of RD observed at specific developmental stages. Here, we synthesize findings from functional and structural magnetic resonance imaging studies to increase our understanding of the developmental time course of the neural bases underlying (a)typical reading. We first provide an overview of the brain bases of typical and atypical (impaired) reading. Next, we describe how the understanding of RD can be deepened through scientific attention to age effects, for example, by integrating findings from cross‐sectional studies of RD at various ages. Finally, we accent findings from extant longitudinal studies that directly examined developmental reading trajectories beginning in the preliterate stage at both group and individual levels. Although science is at the very early stage of understanding developmental aspects of neural deficits in RD, evidence to date characterizes RD by atypical brain maturation. We contend that exploring the developmental trajectories of RD will contribute to a greater understanding of how neural systems support reading acquisition. Further, we propose and cite evidence that the etiology of RD can be better investigated by distinguishing primary deficits from secondary impairments unfolding along development. These exciting and modern investigatory efforts can also indirectly contribute to a centered practice of early and accurate identification and optimal intervention to support the development of foundational pre‐literacy skills and fluent reading. In sum, integrating a developmental understanding into the science and practice of reading acquisition and intervention is both possible and necessary.
Long‐chain polyunsaturated fatty acids in infant formula and cardiovascular markers in childhood
Authors: Pluymen Linda P. M. , Dalmeijer Geertje W. , Smit Henriëtte A. , Uiterwaal Cuno S. P. M. , van der Ent Cornelis K. , van Rossem Lenie
Published: September 2017

To investigate whether children who consumed infant formula supplemented with long‐chain polyunsaturated fatty acids (LCPUFAs) had a more favourable cardiovascular profile than children who consumed formula without these fatty acids, we used the Wheezing Illnesses Study Leidsche Rijn, a birth cohort that included 2,468 newborns between 2001 and 2014. Data on infant feeding were obtained by questionnaires. At age 5, blood pressure, carotid intima‐media thickness (CIMT), and carotid distension were measured. We used multivariable linear regression analysis to compare levels of cardiovascular markers in formula‐fed children born before and after the LCPUFA supplementation. To account for secular trends, we compared levels of cardiovascular markers in a control group of breastfed children from the same cohort born before and after the supplementation. Formula‐fed children born after the LCPUFA supplementation (n = 48) had no different systolic blood pressure (−2.58 mmHg, 95% confidence interval, CI [−5.5, 0.30]), diastolic blood pressure (−0.13 mmHg, 95% CI [−2.3, 2.1]), or carotid distension (24.8 MPa−1, 95% CI [−47.1, 96.6]) and had a higher CIMT (18.6 μm, 95% CI [3.7, 33.5]) than formula‐fed children born before the supplementation (n = 163). In the control group, children born after the LCPUFA supplementation (n = 98) had no different systolic‐ or diastolic‐blood pressure, or CIMT, and a higher carotid distension than children born before the supplementation (n = 142).

In conclusion, children who consumed infant formula supplemented with LCPUFAs did not have a more favourable cardiovascular profile in early childhood than children who consumed formula without LCPUFAs.
The HLA‐B landscape of Africa: Signatures of pathogen‐driven selection and molecular identification of candidate alleles to malaria protection
Authors: Sanchez‐Mazas Alicia , Černý Viktor , Di Da , Buhler Stéphane , Podgorná Eliška , Chevallier Elodie , Brunet Lydie , Weber Stephan , Kervaire Barbara , Testi Manuela , Andreani Marco , Tiercy Jean‐Marie , Villard Jean , Nunes José Manuel
Published: September 2017

Human leukocyte antigen (HLA) genes play a key role in the immune response to infectious diseases, some of which are highly prevalent in specific environments, like malaria in sub‐Saharan Africa. Former case–control studies showed that one particular HLA‐B allele, B*53, was associated with malaria protection in Gambia, but this hypothesis was not tested so far within a population genetics framework. In this study, our objective was to assess whether pathogen‐driven selection associated with malaria contributed to shape the HLA‐B genetic landscape of Africa. To that aim, we first typed the HLA‐A and ‐B loci in 484 individuals from 11 populations living in different environments across the Sahel, and we analysed these data together with those available for 29 other populations using several approaches including linear modelling on various genetic, geographic and environmental parameters. In addition to relevant signatures of populations’ demography and migrations history in the genetic differentiation patterns of both HLA‐A and ‐B loci, we found that the frequencies of three HLA alleles, B*53, B*78 and A*74, were significantly associated with Plasmodium falciparum malaria prevalence, suggesting their increase through pathogen‐driven selection in malaria‐endemic environments. The two HLA‐B alleles were further identified, by high‐throughput sequencing, as B*53:01:01 (in putative linkage disequilibrium with one HLA‐C allele, C*04:01:01:01) and B*78:01 in all but one individuals tested, making them appropriate candidates to malaria protection. These results highlight the role of environmental factors in the evolution of the HLA polymorphism and open key perspectives for functional studies focusing on HLA peptide‐binding properties.
Integration of genetic and seed fitness data to the conservation of isolated subpopulations of the Mediterranean plantMalcolmia littorea
Authors: De Vitis M. , Mattioni C. , Mattana E. , Pritchard H. W. , Seal C. E. , Ulian T. , Cherubini M. , Magrini S.
Published: September 2017

Plant autoecology and population genetics provide a perspective on the likelihood of natural regeneration, which is critical when designing conservation strategies for endangered species. The threatened coastal plantMalcolmia littorea(Brassicaceae) was sampled across its European distribution and studied for genetic diversity and seed fitness, with the aim of providing information for the conservation of isolated and declining populations.

Nine microsatellite markers (five chloroplast and four nuclear) were analysed to assess population genetic diversity and structure and to conduct a spatial analysis using the software DIVA‐GIS. Germination percentages and rates were assessed by incubating the seeds under eight constant temperatures (0–27 °C).

The genetic diversity was found to be similar among subpopulations (chloroplastH = 0.04–0.17; nuclearHo = 0.20–0.37), with no correlation between subpopulation diversity and the area of occupancy (AOO). The subpopulations were found to be clustered in three genetic groups, and three of them were identified as conservation priorities due to their unique genetic composition. The germination study revealed a significant influence of the maternal environment and AOO on seed germination, with the smaller subpopulations showing lower germination percentages (P < 0.05).

These results highlight the importance of obtaining information on isolated subpopulations through different experimental approaches (e.g. seed germination plus population genetics) to enable planning of effective conservation actions. ForM. littorea, seed collection for bothin situandex situconservation should take into account the local adaptation of the subpopulation and the genetic structure of the species.
A role for glutathione reductase and glutathione in the tolerance of Chlamydomonas reinhardtii to photo‐oxidative stress
Authors: Lin Tsen‐Hung , Rao Meng‐Yuan , Lu Hao‐Wen , Chiou Chih‐Wen , Lin Shu‐Tseng , Chao Hung‐Wei , Zheng Zhao‐Liang , Cheng Hao‐Chien , Lee Tse‐Min
Published: September 2017

The role of glutathione reductase (GR; EC 1.6.4.2) in the tolerance of Chlamydomonas reinhardtii P.A. Dangeard to high‐intensity light stress (HL, 1400 μmol m−2 s−1) was examined. Cells survived under high light (HL) stress, although their growth was inhibited after long‐term treatment (9‐24 h). GR activity increased 1 h after HL treatment. The contents of total glutathione, reduced glutathione (GSH) and glutathione disulfide (GSSG) increased 1‐3 h after HL treatment and then decreased after 24 h, while the GSH:GSSG ratio (glutathione redox potential) decreased after 3–9 h and recovered after 24 h. The transcript abundance of GR, CrGR1 (Cre06.g262100) and CrGR2 (Cre09.g396252) as well as glutathione synthesis‐related genes, CrGSH1 (Cre02g077100.t1.1) and CrGSH2 (Cre17.g70800.t1.1), increased with a peak near 1 h after HL treatment. Except for enhanced glutathione synthesis, the GR‐mediated glutathione redox machinery is also critical for the tolerance of C. reinhardtii cells to HL stress. Therefore, GR was downregulated or upregulated to investigate the importance of GR in HL tolerance. The CrGR1 knockdown amiRNA line exhibited low GR transcript abundance, GR activity and GSH:GSSG ratio and could not survive under HL conditions. Over‐expression of CrGR1 or CrGR2 driven by a HSP70A:RBCS2 fusion promoter resulted in a higher GR transcript abundance, GR activity and GSH:GSSG ratio and led to cell survival when exposed to high‐intensity illumination, i.e. 1800 μmol m−2 s−1. In conclusion, GR‐mediated modulation of the glutathione redox potential plays a role in the tolerance of Chlamydomonas cells to photo‐oxidative stress.
Contraceptive methods and issues around the menopause: an evidence update
Authors: Bakour Shagaf H , Hatti Archana , Whalen Susan
Published: September 2017

Key content

There have been a number of recent advances and an increase in the number of contraceptive methods available to perimenopausal women.

Other relevant issues, including transition to and diagnosis of menopause, the use of hormone replacement therapy with contraception, and when to stop contraception, are discussed.

Some hormonal contraceptives have added benefits in the management of common perimenopausal gynaecological problems.

Research and development into intrauterine contraception, microchip drug release technology, progesterone receptor modulators, male contraception and vaccines is currently underway.

Learning objectives

Understand that, although women's natural fertility declines after their mid‐30s, effective contraception is required until menopause to prevent unintended pregnancies.

Be aware that the risks of fetal chromosomal abnormalities, miscarriage, pregnancy complications and maternal morbidity and mortality increase for women aged 40 years and over.

No contraceptive method is contraindicated on the basis of age alone.

Clinicians must carefully consider comorbidities when prescribing women the most suitable contraception.

Ethical issues

Return of fertility can be delayed for up to 1 year after discontinuing progestogen‐only injectable contraceptives; therefore, these contraceptives are not suitable for perimenopausal women considering future pregnancies.

Contraceptive methods with a recognised post‐fertilisation, pre‐implantation effect may not be acceptable to some women.

Women should be given information about all suitable contraceptive methods to make an informed choice.
A functional zeaxanthin epoxidase from red algae shedding light on the evolution of light‐harvesting carotenoids and the xanthophyll cycle in photosynthetic eukaryotes
Authors: Dautermann Oliver , Lohr Martin
Published: September 2017

The epoxy‐xanthophylls antheraxanthin and violaxanthin are key precursors of light‐harvesting carotenoids and participate in the photoprotective xanthophyll cycle. Thus, the invention of zeaxanthin epoxidase (ZEP) catalyzing their formation from zeaxanthin has been a fundamental step in the evolution of photosynthetic eukaryotes. ZEP genes have only been found in Viridiplantae and chromalveolate algae with secondary plastids of red algal ancestry, suggesting that ZEP evolved in the Viridiplantae and spread to chromalveolates by lateral gene transfer. By searching publicly available sequence data from 11 red algae covering all currently recognized red algal classes we identified ZEP candidates in three species. Phylogenetic analyses showed that the red algal ZEP is most closely related to ZEP proteins from photosynthetic chromalveolates possessing secondary plastids of red algal origin. Its enzymatic activity was assessed by high performance liquid chromatography (HPLC) analyses of red algal pigment extracts and by cloning and functional expression of the ZEP gene from Madagascaria erythrocladioides in leaves of the ZEP‐deficient aba2 mutant of Nicotiana plumbaginifolia. Unlike other ZEP enzymes examined so far, the red algal ZEP introduces only a single epoxy group into zeaxanthin, yielding antheraxanthin instead of violaxanthin. The results indicate that ZEP evolved before the split of Rhodophyta and Viridiplantae and that chromalveolates acquired ZEP from the red algal endosymbiont and not by lateral gene transfer. Moreover, the red algal ZEP enables engineering of transgenic plants incorporating antheraxanthin instead of violaxanthin in their photosynthetic machinery.
Use of urinary bladder measurements from a point‐of‐care cysto‐colic ultrasonographic view to estimate urinary bladder volume in dogs and cats
Authors: Lisciandro Gregory R. , Fosgate Geoffrey T.
Published: September 2017

Objective

To develop a point‐of‐care ultrasound‐derived formula to estimate urinary bladder volume noninvasively in dogs and cats.

Design

Prospective case series.

Setting

Private 24‐hour veterinary emergency center.

Animals

Client‐owned dogs and cats requiring urethral catheterization.

Interventions

Ultrasound measurements of length, width, and height of balloons filled with known water volumes were used to develop a formula to estimate urinary bladder volume using linear regression. The formula was then applied to point‐of‐care ultrasound‐derived cysto‐colic view measurements, and calculations were compared to total aspirated urine volume.

Measurements and Main Results

Fifteen balloons with known volumes (median, 126 mL [range, 27–689 mL]) were used to identify length × width × height (cm) × 0.2 × π as the best formula to estimate urinary bladder volume in milliliters. Fourteen cats and 14 dogs were used for comparison of formula‐derived volume estimate to actual urinary bladder volume. Median aspirated urine volume, bias (formula‐derived minus actual aspirated), and percentage difference were 80 mL, –4.1 mL, and –6.6% for cats, respectively. For dogs, the results were 78 mL, 3.4 mL, and 3.6%, respectively.

Conclusions and Clinical Relevance

The point‐of‐care ultrasound‐derived formula may be useful to estimate urine volume noninvasively in dogs and cats.
Export Diversification and Economic Growth in Morocco: An Econometric Analysis
Authors: Lotfi Bilal , Karim Mohamed
Published: September 2017

Since the work of Imbs and Wacziarg (2003), most recent studies confirm a positive relationship between export diversification and income per capita (Cadot et al., 2011; Agosin et al., 2012). Therefore, export diversification appears as an important lever for economic growth. This type of export strategy contradicts the conventional theories of international trade, such as ricardien model, which considers that countries should specialize in the production of goods for which they have a comparative advantage. However, recent literature and international experience have shown that more diversified countries tend to have faster and inclusive economic growth (Hesse, 2009). Thereby, export diversification can also help to improve international competitiveness, especially in developing contries. For the case of Morocco, this conclusion suggests that greater stage of export diversification would lead to a higher level of economic development.
Traders as Diplomats: Trade and Sino-American Rapprochement, 1971-78
Authors: Lin Mao
Published: September 2017

During the 1970s, U.S.-China relations went through a major strategic transformation. To oppose their common enemy, the Soviet Union, the two countries ended hostilities which lasted for more than two decades and became Cold War allies. Many scholars have discussed this major historic turning point, however, most scholars have focused exclusively on the strategic relations between the two countries, while ignoring bilateral economic and trade relations. This paper argues that trade relations actually constituted an important aspect of American foreign policy towards China. And the development of trade relations in the 1970s was mainly promoted by American businessmen. These American businessmen not only hoped to open the Chinese market, but also consciously regarded themselves as “unofficial ambassadors”, because they believed that trade will contribute to the improvement of the relations between the two countries. By developing trade with China, the United States expected to transform China into a market-oriented economy, and eventually change the political nature of the Chinese regime.
Calcium influx through TRPV4 channels modulates the adherens contacts between retinal microvascular endothelial cells
Authors: Phuong Tam T. T. , Redmon Sarah N. , Yarishkin Oleg , Winter Jacob M. , Li Dean Y. , Križaj David
Published: September 2017

Key points

Endothelial cells employ transient receptor potential isoform 4 (TRPV4) channels to sense ambient mechanical and chemical stimuli.

In retinal microvascular endothelial cells, TRPV4 channels regulate calcium homeostasis, cytoskeletal signalling and the organization of adherens junctional contacts.

Intracellular calcium increases induced by TRPV4 agonists include a significant contribution from calcium release from internal stores.

Activation of TRPV4 channels regulates retinal endothelial barriersin vitroandin vivo.

TRPV4 sensing may provide a feedback mechanism between sensing shear flow and eicosanoid modulators, vascular permeability and contractility at the inner retinal endothelial barrier.

The identity of microvascular endothelial (MVE) mechanosensors that sense blood flow in response to mechanical and chemical stimuli and regulate vascular permeability in the retina is unknown. Using immunohistochemistry, calcium imaging, electrophysiology, impedance measurements and vascular permeability assays, we show that the transient receptor potential isoform 4 (TRPV4) plays a major role in Ca2+/cation signalling, cytoskeletal remodelling and barrier function in retinal microvasculaturein vitroandin vivo. Human retinal MVE cells (HrMVECs) predominantly expressedTrpv1andTrpv4transcripts, and TRPV4 was broadly localized to the plasma membrane of cultured cells and intact blood vessels in the inner retina. Treatment with the selective TRPV4 agonist GSK1016790A (GSK101) activated a nonselective cation current, robustly elevated [Ca2+]iand reversibly increased the permeability of MVEC monolayers. This was associated with disrupted organization of endothelial F‐actin, downregulated expression of occludin and remodelling ofadherenscontacts consisting of vascular endothelial cadherin (VE‐cadherin) and β‐catenin.In vivo, GSK101 increased the permeability of retinal blood vessels in wild type but not in TRPV4 knockout mice. Agonist‐evoked effects on barrier permeability and cytoskeletal reorganization were antagonized by the selective TRPV4 blocker HC 067047. Human choroidal endothelial cells expressed lower TRPV4 mRNA/protein levels and showed less pronounced agonist‐evoked calcium signals compared to MVECs. These findings indicate a major role for TRPV4 in Ca2+homeostasis and barrier function in human retinal capillaries and suggest that TRPV4 may differentially contribute to the innervs. outer blood–retinal barrier function.
Measured and modeled acoustic propagation underneath the rough Arctic sea-ice
Authors: Hope Gaute , Sagen Hanne , Storheim Espen , Hobæk Halvor , Freitag Lee
Published: September 2017

A characteristic surface duct beneath the sea-ice in the Marginal Ice Zone causes acoustic waves to be trapped and continuously interact with the sea-ice. The reflectivity of the sea-ice depends on the thickness, the elastic properties, and its roughness. This work focuses on the influence of sea-ice roughness on long-range acoustic propagation, and on how well the arrival structure can be predicted by the full wave integration model OASES. In 2013, acoustic signals centered at 900 Hz were transmitted every hour for three days between ice-tethered buoys in a drifting network in the Fram Strait. The experiment was set up to study the signal stability in the surface channel below the sea-ice. Oceanographic profiles were collected during the experiment, while a statistical description of the rough sea-ice was established based on historical ice-draft measurements. This environmental description is used as input to the range independent version of OASES. The model simulations correspond fairly well with the observations, despite that a flat bathymetry is used and the sea-ice roughness cannot be fully approximated by the statistical representation used in OASES. Long-range transmissions around 900 Hz are found to be more sensitive to the sea-ice roughness than the elastic parameters.
Protecting cognition from antipsychotics
Authors: Ferrarelli Leslie K.
Published: September 2017

Inhibiting a mechanism that mediates cognitive deficits caused by antipsychotic drugs may improve clinical outcomes for schizophrenia patients.
Papers of note in
Science Translational Medicine
9
(408)
Authors: Ferrarelli Leslie K.
Published: September 2017

This week’s articles describe new therapeutic strategies for cancer, lung inflammation, and graft-versus-host disease.
The Staphylococcus aureus Cell Wall-Anchored Protein Clumping Factor A Is an Important T Cell Antigen
Authors: Lacey Keenan A. , Leech John M. , Lalor Stephen J. , McCormack Niamh , Geoghegan Joan A. , McLoughlin Rachel M.
Published: September 2017

Staphylococcus aureus
has become increasingly resistant to antibiotics, and vaccines offer a potential solution to this epidemic of antimicrobial resistance. Targeting of specific T cell subsets is now considered crucial for next-generation anti-
S. aureus
vaccines; however, there is a paucity of information regarding T cell antigens of
S. aureus
. This study highlights the importance of cell wall-anchored proteins as human CD4
+
T cell activators capable of driving antigen-specific Th1 and Th17 cell activation. Clumping factor A (ClfA), which contains N1, N2, and N3 binding domains, was found to be a potent human T cell activator. We further investigated which subdomains of ClfA were involved in T cell activation and found that the full-length ClfA N123 and N23 were potent Th1 and Th17 activators. Interestingly, the N1 subdomain was capable of exclusively activating Th1 cells. Furthermore, when these subdomains were used in a model vaccine, N23 and N1 offered Th1- and Th17-mediated systemic protection in mice upon intraperitoneal challenge. Overall, however, full-length ClfA N123 is required for maximal protection both locally and systemically.
The Capsular Polysaccharide of Acinetobacter baumannii Is an Obstacle for Therapeutic Passive Immunization Strategies
Authors: Wang-Lin Shun Xin , Olson Ruth , Beanan Janet M. , MacDonald Ulrike , Balthasar Joseph P. , Russo Thomas A.
Published: September 2017

Acinetobacter baumannii
has become an important concern for human health due to rapid development and wide spread of antimicrobial-resistant strains and high mortality associated with the infection. Passive immunizations with antisera targeting outer membrane proteins (OMPs) have shown encouraging results in protecting mice from
A. baumannii
infection, but monoclonal anti-OMP antibodies have not been developed, and their potential therapeutic properties have not been explored. The goal of this report is to evaluate the antibacterial activity of monoclonal antibodies (MAbs) targeting outer membrane protein A (OmpA) of
A. baumannii
. Five anti-OmpA MAbs were developed using hybridoma technology and showed strong binding to strain ATCC 19606. However, low antibody binding was observed when they were tested against six clinical isolates, which included extensively drug-resistant strains. In contrast, high binding to an isogenic K1 capsule-negative mutant (AB307.30) was shown, suggesting that capsular polysaccharide mediated the inhibition of MAb binding to OmpA. Anti-OmpA MAbs increased the macrophage-mediated bactericidal activity of AB307.30 but failed to increase phagocytic killing of capsule-positive strains. Capsular polysaccharide was also protective against complement-mediated bactericidal activity in human ascites in the presence and absence of opsonization. Lastly, passive immunization with anti-OmpA MAbs did not confer protection against challenge with AB307-0294, the encapsulated parent strain of AB307.30, in a mouse sepsis infection model. These results reveal the important role of capsule polysaccharide in shielding OmpA and thereby inhibiting anti-OmpA MAb binding to clinical isolates. This property of capsule hindered the therapeutic utility of anti-OmpA MAbs, and it may apply to other conserved epitopes in
A. baumannii
.
Interleukin 1α Is Critical for Resistance against Highly Virulent Aspergillus fumigatus Isolates
Authors: Caffrey-Carr Alayna K. , Kowalski Caitlin H. , Beattie Sarah R. , Blaseg Nathan A. , Upshaw Chanell R. , Thammahong Arsa , Lust Hannah E. , Tang Yi-Wei , Hohl Tobias M. , Cramer Robert A. , Obar Joshua J.
Published: September 2017

Heterogeneity among
Aspergillus fumigatus
isolates results in unique virulence potential and inflammatory responses. How these isolates drive specific immune responses and how this affects fungally induced lung damage and disease outcome are unresolved. We demonstrate that the highly virulent CEA10 strain is able to rapidly germinate within the immunocompetent lung environment, inducing greater lung damage, vascular leakage, and interleukin 1α (IL-1α) release than the low-virulence Af293 strain, which germinates with a lower frequency in this environment. Importantly, the clearance of CEA10 was consequently dependent on IL-1α, in contrast to Af293. The release of IL-1α occurred by a caspase 1/11- and P2XR7-independent mechanism but was dependent on calpain activity. Our finding that early fungal conidium germination drives greater lung damage and IL-1α-dependent inflammation is supported by three independent experimental lines. First, pregermination of Af293 prior to
in vivo
challenge drives greater lung damage and an IL-1α-dependent neutrophil response. Second, the more virulent EVOL20 strain, derived from Af293, is able to germinate in the airways, leading to enhanced lung damage and IL-1α-dependent inflammation and fungal clearance. Third, primary environmental
A. fumigatus
isolates that rapidly germinate under airway conditions follow the same trend toward IL-1α dependency. Our data support the hypothesis that
A. fumigatus
phenotypic variation significantly contributes to disease outcomes.
Increased cholestatic enzymes in two patients with long-term history of ulcerative colitis: consider primary biliary cholangitis not always primary sclerosing cholangitis
Authors: Polychronopoulou Erietta , Lygoura Vasiliki , Gatselis Nikolaos K , Dalekos George N
Published: September 2017

Several hepatobiliary disorders have been reported in ulcerative colitis (UC) patients with primary sclerosing cholangitis (PSC) being the most specific. Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, rarely occurs in UC. We present two PBC cases of 67 and 71 years who suffered from long-standing UC. Both patients were asymptomatic but they had increased cholestatic enzymes and high titres of antimitochondrial antibodies (AMA)—the laboratory hallmark of PBC. After careful exclusion of other causes of cholestasis by MRI/magnetic resonance cholangiopancreatography (MRCP), virological and microbiological investigations, a diagnosis of PBC associated with UC was established. The patients started ursodeoxycholic acid (13 mg/kg/day) with complete response. During follow-up, both patients remained asymptomatic with normal blood biochemistry. Although PSC is the most common hepatobiliary manifestation among patients with UC, physicians must keep also PBC in mind in those with unexplained cholestasis and repeatedly normal MRCP. In these cases, a reliable AMA testing can help for an accurate diagnosis.
Medical school predictors of later perceived mastery of clinical work among Norwegian doctors: a cohort study with 10-year and 20-year follow-up
Authors: Belfrage Anna , Grotmol Kjersti Støen , Lien Lars , Moum Torbjørn , Wiese Ragna Veslemøy , Tyssen Reidar
Published: September 2017

Objective

Doctors’ self-perceived mastery of clinical work might have an impact on their career and patient care, in addition to their own health and well-being. The aim of this study is to identify predictors at medical school of perceived mastery later in doctors’ careers.

Design

A cohort of medical students (n=631) was surveyed in the final year of medical school in 1993/1994 (T1), and 10 (T2) and 20 (T3) years later.

Setting

Nationwide healthcare institutions.

Participants

Medical students from all universities in Norway.

Main outcome measures

Perceived mastery of clinical work was measured at T2 and T3. The studied predictors measured at T1 included personality traits, medical school stress, perceived medical recording skills, identification with the role of doctor, hazardous drinking and drinking to cope, in addition to age and gender. Effects were studied using multiple linear regression models.

Results

Response rates: T1, 522/631 (83%); T2, 390/522 (75%); and T3, 303/522 (58%). Mean scores at T2 and T3 were 22.3 (SD=4.2) and 24.5 (3.0) (t=8.2, p<0.001), with no gender difference. Adjusted associations at T2 were: role identification (β=0.16; p=0.006; 95% CI 0.05 to 0.28), perceived medical recording skills (β=0.13; p=0.02; 95% CI 0.02 to 0.24) and drinking to cope (β=–2.45; p=0.001; 95% CI –3.88 to –1.03). Adjusted association at T3 was perceived medical recording skills (β=0.11; p=0.015; 95% CI 0.02 to 0.21).

Conclusions

Perceived medical recording skills and role identification were associated with higher perceived mastery. Medical schools should provide experiences, teaching and assessment to enhance students’ physician role identification and confidence in their own skills. Drinking to cope was associated with lower perceived mastery, which indicates the importance of acquiring healthier coping strategies in medical school.