bluuebunny/crossref_metadata_2025 huggingface dataset:
Nobility or Utility?Zamindars, businessmen, andbhadralokas curators of the Indian nation in Satyajit Ray'sJalsaghar (The Music Room)
Authors: GHOSH GAUTAM
Published: December 2017

The Bengalibhadralokhave had an important impact on Indian nationalism in Bengal and in India more broadly. Their commitment to narratives of national progress has been noted. However, little attention has been given to how ‘earthly paradise’, ‘garden of delights’, and related ideas of refinement and nobility also informed their nationalism. This article excavates the idea of earthly paradise as it is portrayed in Satyajit Ray's 1958 Bengali filmJalsaghar, usually translated asThe Music Room.Jalsagharis typically taken to depict, broadly, the decadence and decline of aristocratic ‘feudal’ landowners (zamindars) who were granted their holdings and, often, noble rank, such as ‘Lord’ or ‘Raja’, during Mughal or British times, representing the languid past of the nobility, and the ascendance of a restless business-oriented class that represents an emerging present and possible future. Thezamindarsare shown as pursuing aesthetic and spiritual delight, ecstasy, and edification through soirées. These soirées are produced for those among the nobility who are sufficiently cultivated and cosmopolitan to appreciate the finer things in life, such as the classical music and dance showcased in this film. The businessmen, too, aspire to host such exceptional events, but are too crass to do so properly and, moreover, they are motivated by a desire to accrue prestige, thus using soirées as a means to an end, rather than to experience aesthetic and spiritual elevation as an end in itself. I argue that the film calls on thebhadralokto value aesthetic cultivation and to actively counter its evanescence. The film thus beckons and authorizes thebhadralokto sustain the value of the timeless past, including nobility and refinement. Yet thebhadralokare also expected to embody and expand a new, progressive, and utilitarian spirit that would modernize India. With the aristocrats gone, and the entrepreneurs eager to assume authority, the film charges thebhadralokto construct a nationalism in which the immortal, character-building values of classical art, for example, can yet be sutured to utilitarian progressivism. I argue that the film conveys this even though it does not explicitly portray or even mention thebhadralok, or feature uniquely Bengali music and art. Accordingly, this article does not focus on the actual aesthetic and political practices ofbhadraloknationalism. The aim is to shed light on one genealogy through which thebhadraloksanctioned themselves as India's stewards along these lines.
Nutrients for neurocognition in health and disease: measures, methodologies and mechanisms
Authors: Scholey Andrew
Published: December 2017

Effective pharmaceutical treatments for age-related cognitive decline have proved elusive. There is, however, compelling evidence that nutritional status and supplementation could play crucial roles in modifying the expression of cognitive change through the lifespan. Subjective memory impairment and mild cognitive impairment can be harbingers of dementia but this is by no means inevitable. Neurocognitive change is influenced by a variety of processes, many of which are involved in other aspects of systemic health, including cardiovascular function. Importantly, many of these processes are governed by mechanisms which may be modified by specific classes of bioactive nutrients. There is increasing, converging evidence from controlled trials that nutritional interventions can improve mood and cognitive function in both clinical and healthy populations. Specific examples include selected botanical extracts such as the flavonoids. Some nutritional supplements (e.g. broad-spectrum micronutrient supplementation) appear to support improved cognitive function, possibly through redressing insufficient nutrient status (i.e. suboptimal but above the threshold for frank deficiency). Recent mechanistic research has unveiled physiologically plausible, modifiable, cognition-relevant targets for nutrition and nutraceuticals. These include processes involved in both systemic and central vascular function, inflammation, metabolism, central activation, improved neural efficiency and angiogenesis. The advent and development of human neuroimaging methodology have greatly aided our understanding of the core central mechanisms of cognitive change. Different imaging modalities can provide insights into modifiable central mechanisms which may be targeted by bioactive nutrients. The latter may contribute to slowing age-related decline through supporting neurocognitive scaffolding mechanisms.
Brain glutamate in medication-free depressed patients: a proton MRS study at 7 Tesla
Authors: Godlewska Beata R. , Masaki Charles , Sharpley Ann L. , Cowen Philip J. , Emir Uzay E.
Published: December 2017

Background

The possible role of glutamate in the pathophysiology and treatment of depression is of intense current interest. Proton magnetic resonance spectroscopy (MRS) enables the detection of glutamate in the living human brain and meta-analyses of previous MRS studies in depressed patients have suggested that glutamate levels are decreased in anterior brain regions. Nevertheless, at conventional magnetic field strengths [1.5–3 Tesla (T)], it is difficult to separate glutamate from its metabolite and precursor, glutamine, with the two often being measured together as Glx. In contrast, MRS at 7 T allows clear spectral resolution of glutamate and glutamine.

Method

We studied 55 un-medicated depressed patients and 50 healthy controls who underwent MRS scanning at 7 T with voxels placed in anterior cingulate cortex, occipital cortex and putamen (PUT). Neurometabolites were calculated using the unsuppressed water signal as a reference.

Results

Compared with controls, depressed patients showed no significant difference in glutamate in any of the three voxels studied; however, glutamine concentrations in the patients were elevated by about 12% in the PUT (p < 0.001).

Conclusions

The increase in glutamine in PUT is of interest in view of the postulated role of the basal ganglia in the neuropsychology of depression and is consistent with elevated activity in the descending cortical glutamatergic innervation to the PUT. The basal ganglia have rarely been the subject of MRS investigations in depressed patients and further MRS studies of these structures in depression are warranted.
Executive function and other cognitive deficits are distal risk factors of generalized anxiety disorder 9 years later
Authors: Zainal Nur Hani , Newman Michelle G.
Published: December 2017

Objective

The cognitive model (Hirsch & Mathews, 2012) and attentional control theory (Eysenck & Derakshan, 2011) postulate that compromised executive function (EF) and other cognitive constructs are negatively linked to increased excessive and uncontrollable worry, the core symptom of generalized anxiety disorder (GAD). However, the prospective link between neuropsychological constructs and GAD are not well understood.

Methods

A nationally representative sample of 2605 community-dwelling adults whose average age was 55.20 (s.d. = 11.41, range 33–84; 56.31% females) participated at baseline and 9-year follow-up. Baseline neuropsychological function and symptoms were measured using the Brief Test of Adult Cognition by Telephone and Composite International Diagnostic Interview – Short Form. Multivariate Poisson and negative binomial regression analyses were conducted with 11 baseline covariates entered simultaneously: age, gender, years of formal education, perceived control, hypertension/diabetes, body mass index, exercise status, as well as GAD severity, panic disorder severity, and depression severity. Those with baseline GAD were also removed.

Results

Lower Time 1 composite global cognition z-score independently predicted higher Time 2 GAD severity and diagnosis [odds ratio (OR) 0.60, 95% confidence interval (CI) 0.40–0.89, p = 0.01]. Poor inhibition, set-shifting, working memory (WM) updating, inductive reasoning, and global cognition sequentially forecasted heightened GAD. However, processing speed, verbal WM, verbal fluency, and episodic memory did not predict future GAD.

Conclusion

Global cognition, inductive reasoning, inhibition, set-shifting, and WM updating EF impairments may be distal risk factors for elevated GAD nearly a decade later.
Legislation for wetland conservation in Brazil: Are existing terms and definitions sufficient?
Authors: MALTCHIK LEONARDO , CALEFFI VANESSA , STENERT CRISTINA , BATZER DAROLD PAUL , FERNANDEZ PIEDADE MARIA TERESA , JUNK WOLFGANG JOHANNES
Published: December 2017

Laws are crucial tools to protect wetlands. How these laws are written has important implications for conservation. We assessed all wetland terms and definitions in Brazilian legislation to identify whether legislation uses any generic terms to represent several or all types of wetlands and to determine if definitions with clear descriptors exist that can easily be used to identify wetland systems. A total of 116 local wetland-related terms and 21 wetland definitions were found in Brazilian legislation. A direct Portuguese translation of the term ‘wetlands’ was found only once in the New Forest Code. The insertion of the term ‘wetlands’ in the New Forest Code has important practical implications for the conservation, since all different Brazilian wetland types would be represented by the generic term ‘wetlands’. The existence of a definition of the term ‘wetlands’ associated with attributes of water and biota in Federal legislation will help environmental technicians to identify wetland systems and to recognize different wetland types. The insertion of this definition in the New Forest Code would make it clear that the drainage of any wetland type – large or small – is prohibited, and those who do so would be breaking Brazilian environmental law.
A rapid review examining purchasing changes resulting from fiscal measures targeted at high sugar foods and sugar-sweetened drinks
Authors: Roberts Katharine E. , Ells Louisa J. , McGowan Victoria J. , Machaira Theodora , Targett Victoria C. , Allen Rachel E. , Tedstone Alison E.
Published: December 2017

To aim of the review was to examine the most recent (2010 onwards) research evidence on the health and behavioural impacts, in adults and children, of fiscal strategies that target high sugar foods and sugar-sweetened drinks (SSDs). A pragmatic rapid review was undertaken using a systematic search strategy. The review was part of a programme of work to support policy development in relation to high sugar food and SSDs. A total of 11 primary research publications were included, describing evidence from France (n = 1), the Netherlands (n = 3), and the United States of America (n = 7), assessed through a variety of study designs, with the majority in adult populations (n = 10). The evidence reviewed focused on consumer behaviour outcomes and suggested that fiscal strategies can influence purchases of high sugar products. Although the majority of studies (n = 10), including three field studies, demonstrated that an increase in the price of high sugar foods and SSDs resulted in a decrease in purchases, eight studies were conducted in a laboratory or virtual setting which may not reflect real-life situations.

Findings from this review support evidence from the broader literature that suggests that fiscal measures can be effective in influencing the purchasing of high sugar foods and SSDs.
Tumor suppressor p53 links ceramide metabolism to DNA damage response through alkaline ceramidase 2
Authors: Xu Ruijuan , Garcia-Barros Monica , Wen Sally , Li Fang , Lin Chih-Li , Hannun Yusuf A. , Obeid Lina M. , Mao Cungui
Published: December 2017

p53 mediates the DNA damage response (DDR) by regulating the expression of genes implicated in cell cycle arrest, senescence, programmed cell death (PCD), and metabolism. Herein we demonstrate that human alkaline ceramidase 2 (ACER2) is a novel transcriptional target of p53 and that its transactivation by p53 mediates the DDR. We found that p53 overexpression or its activation by ionizing radiation (IR) upregulated ACER2 in cells. Two putative p53 responsive elements (p53REs) were found in its first intron of the ACER2 gene, and Chromatin Immunoprecipitation (ChIP) assays in combination with promoter activity assays demonstrated that these p53REs are the bona fide p53 binding sites that mediate ACER2 transactivation by p53. As ACER2 catalyzes the hydrolysis of ceramides into sphingosine, which in turn is phosphorylated to form sphingosine-1-phosphate (S1P), ACER2 upregulation increased the levels of both sphingosine and S1P while decreasing the levels of ceramides in cells. A moderate upregulation of ACER2 inhibited cell cycle arrest and cellular senescence in response to low-level expression of p53 or low-dose IR by elevating S1P, a pro-proliferative and pro-survival bioactive lipid, and/or decreasing ceramides whereas its robust upregulation mediated PCD in response to high-level expression of p53 or high-dose IR likely by accumulating cellular sphingosine, a pro-death bioactive lipid. ACER2 is frequently inactivated in various cancers due to its deletion or mutations, and restoring its expression inhibited the growth of tumor xenografts in mice. These results suggest that p53 mediates DDR and exerts its tumor suppressive role in part by regulating the expression of ACER2, which in turn regulates the bioactive sphingolipid lipids.
SPLICS: a split green fluorescent protein-based contact site sensor for narrow and wide heterotypic organelle juxtaposition
Authors: Cieri Domenico , Vicario Mattia , Giacomello Marta , Vallese Francesca , Filadi Riccardo , Wagner Tina , Pozzan Tullio , Pizzo Paola , Scorrano Luca , Brini Marisa , Calì Tito
Published: December 2017

Contact sites are discrete areas of organelle proximity that coordinate essential physiological processes across membranes, including Ca2+ signaling, lipid biosynthesis, apoptosis, and autophagy. However, tools to easily image inter-organelle proximity over a range of distances in living cells and in vivo are lacking. Here we report a split-GFP-based contact site sensor (SPLICS) engineered to fluoresce when organelles are in proximity. Two SPLICS versions efficiently measured narrow (8–10 nm) and wide (40–50 nm) juxtapositions between endoplasmic reticulum and mitochondria, documenting the existence of at least two types of contact sites in human cells. Narrow and wide ER–mitochondria contact sites responded differently to starvation, ER stress, mitochondrial shape modifications, and changes in the levels of modulators of ER–mitochondria juxtaposition. SPLICS detected contact sites in soma and axons of D. rerio Rohon Beard (RB) sensory neurons in vivo, extending its use to analyses of organelle juxtaposition in the whole animal.
Publisher Correction: Gastric acid suppression promotes alcoholic liver disease by inducing overgrowth of intestinal Enterococcus
Authors: Llorente Cristina , Jepsen Peter , Inamine Tatsuo , Wang Lirui , Bluemel Sena , Wang Hui J. , Loomba Rohit , Bajaj Jasmohan S. , Schubert Mitchell L. , Sikaroodi Masoumeh , Gillevet Patrick M. , Xu Jun , Kisseleva Tatiana , Ho Samuel B. , DePew Jessica , Du Xin , Sørensen Henrik T. , Vilstrup Hendrik , Nelson Karen E. , Brenner David A. , Fouts Derrick E. , Schnabl Bernd
Published: December 2017

In the original PDF version of this Article, which was published on 16 October 2017, the publication date was incorrectly given as 10 October 2017. This has now been corrected in the PDF; the HTML version of the paper was correct from the time of publication.
Author Correction: Improved genome recovery and integrated cell-size analyses of individual uncultured microbial cells and viral particles
Authors: Stepanauskas Ramunas , Fergusson Elizabeth A. , Brown Joseph , Poulton Nicole J. , Tupper Ben , Labonté Jessica M. , Becraft Eric D. , Brown Julia M. , Pachiadaki Maria G. , Povilaitis Tadas , Thompson Brian P. , Mascena Corianna J. , Bellows Wendy K. , Lubys Arvydas
Published: December 2017

The original version of this Article contained errors in the units of concentration of three reagents listed in the Methods. These errors have all been corrected in both the PDF and HTML versions of the Article.
Author Correction: Nanoscale control of competing interactions and geometrical frustration in a dipolar trident lattice
Authors: Farhan Alan , Petersen Charlotte F. , Dhuey Scott , Anghinolfi Luca , Qin Qi Hang , Saccone Michael , Velten Sven , Wuth Clemens , Gliga Sebastian , Mellado Paula , Alava Mikko J. , Scholl Andreas , van Dijken Sebastiaan
Published: December 2017

The original version of this article contained an error in the legend to Figure 4. The yellow scale bar should have been defined as ‘~600 nm’, not ‘~600 µm’. This has now been corrected in both the PDF and HTML versions of the article.
Cell shape information is transduced through tension-independent mechanisms
Authors: Ron Amit , Azeloglu Evren U. , Calizo Rhodora C. , Hu Mufeng , Bhattacharya Smiti , Chen Yibang , Jayaraman Gomathi , Lee Sunwoo , Neves-Zaph Susana R. , Li Hong , Gordon Ronald E. , He John C. , Hone James C. , Iyengar Ravi
Published: December 2017

The shape of a cell within tissues can represent the history of chemical and physical signals that it encounters, but can information from cell shape regulate cellular phenotype independently? Using optimal control theory to constrain reaction-diffusion schemes that are dependent on different surface-to-volume relationships, we find that information from cell shape can be resolved from mechanical signals. We used microfabricated 3-D biomimetic chips to validate predictions that shape-sensing occurs in a tension-independent manner through integrin β3 signaling pathway in human kidney podocytes and smooth muscle cells. Differential proteomics and functional ablation assays indicate that integrin β3 is critical in transduction of shape signals through ezrin–radixin–moesin (ERM) family. We used experimentally determined diffusion coefficients and experimentally validated simulations to show that shape sensing is an emergent cellular property enabled by multiple molecular characteristics of integrin β3. We conclude that 3-D cell shape information, transduced through tension-independent mechanisms, can regulate phenotype.
Evidence for topological type-II Weyl semimetal WTe2
Authors: Li Peng , Wen Yan , He Xin , Zhang Qiang , Xia Chuan , Yu Zhi-Ming , Yang Shengyuan A. , Zhu Zhiyong , Alshareef Husam N. , Zhang Xi-Xiang
Published: December 2017

Recently, a type-II Weyl fermion was theoretically predicted to appear at the contact of electron and hole Fermi surface pockets. A distinguishing feature of the surfaces of type-II Weyl semimetals is the existence of topological surface states, so-called Fermi arcs. Although WTe2 was the first material suggested as a type-II Weyl semimetal, the direct observation of its tilting Weyl cone and Fermi arc has not yet been successful. Here, we show strong evidence that WTe2 is a type-II Weyl semimetal by observing two unique transport properties simultaneously in one WTe2 nanoribbon. The negative magnetoresistance induced by a chiral anomaly is quite anisotropic in WTe2 nanoribbons, which is present in b-axis ribbon, but is absent in a-axis ribbon. An extra-quantum oscillation, arising from a Weyl orbit formed by the Fermi arc and bulk Landau levels, displays a two dimensional feature and decays as the thickness increases in WTe2 nanoribbon.
Spin-momentum locked interaction between guided photons and surface electrons in topological insulators
Authors: Luo Siyuan , He Li , Li Mo
Published: December 2017

The propagation of electrons and photons can respectively have the spin-momentum locking effect which correlates spin with linear momentum. For surface electrons in three-dimensional topological insulators (TIs), their spin is locked to the transport direction. Analogously, photons in optical waveguides carry transverse spin angular momentum which is also locked to the propagation direction. A direct connection between electron and photon spins occurs in TIs due to spin-dependent selection rules of optical transitions. Here we demonstrate an optoelectronic device that integrates a TI with a photonic waveguide. Interaction between photons in the waveguide and surface electrons in a Bi2Se3 layer generates a directional, spin-polarized photocurrent. Because of spin-momentum locking, changing light propagation direction reverses photon spin and thus the direction of the photocurrent. Our device represents a way of implementing coupled spin–orbit interaction between electrons and photons and may lead to applications in opto-spintronics and quantum information processing.
New twinning route in face-centered cubic nanocrystalline metals
Authors: Wang Lihua , Guan Pengfei , Teng Jiao , Liu Pan , Chen Dengke , Xie Weiyu , Kong Deli , Zhang Shengbai , Zhu Ting , Zhang Ze , Ma Evan , Chen Mingwei , Han Xiaodong
Published: December 2017

Twin nucleation in a face-centered cubic crystal is believed to be accomplished through the formation of twinning partial dislocations on consecutive atomic planes. Twinning should thus be highly unfavorable in face-centered cubic metals with high twin-fault energy barriers, such as Al, Ni, and Pt, but instead is often observed. Here, we report an in situ atomic-scale observation of twin nucleation in nanocrystalline Pt. Unlike the classical twinning route, deformation twinning initiated through the formation of two stacking faults separated by a single atomic layer, and proceeded with the emission of a partial dislocation in between these two stacking faults. Through this route, a three-layer twin was nucleated without a mandatory layer-by-layer twinning process. This route is facilitated by grain boundaries, abundant in nanocrystalline metals, that promote the nucleation of separated but closely spaced partial dislocations, thus enabling an effective bypassing of the high twin-fault energy barrier.
Germline TTN variants are enriched in PTEN-wildtype Bannayan–Riley–Ruvalcaba syndrome
Authors: Yehia Lamis , Ni Ying , Eng Charis
Published: December 2017

Bannayan–Riley–Ruvalcaba syndrome (BRRS) is a rare congenital disorder classically characterized by macrocephaly in combination with intestinal hamartomatous polyposis, vascular malformations, lipomas, and genital lentiginosis. Germline PTEN mutations have been reported in up to 60% of BRRS patients. The remaining cases are of unknown genetic etiology. We exome-sequenced 35 unrelated PTEN-wildtype patients with classic presentation of BRRS and identified TTN germline missense variants in 12/35 (34%) patients. TTN encodes TITIN, a key structural and functional muscle protein. Exome and TTN-targeted sequencing in an additional unrelated series of 231 BRRS-like patients revealed 37 (16%) additional patients with germline TTN variants. All variants were predicted to be deleterious and equally distributed between the A-band and I-band protein domains. Rare TTN variants (MAF ≤ 0.0001) are enriched in classic BRRS patients compared to BRRS-like (OR = 2.7, 95% CI 1.21-5.94, p = 1.6 × 10-2) and multiple population controls (OR = 2.2, 95% CI 1.01-4.20, p = 4.7 × 10-2). Germline TTN mutations of different genotypes, inheritance patterns, and protein domain enrichment have been identified in multiple cardiac and/or skeletal muscular disorders. Functional interrogation of I-band variant p.Cys5096Arg identified in one of our classic BRRS patients, using CRISPR-Cas9 genome-edited cell lines, reveals an increased growth and lack of contact inhibition phenotype associated with increased levels of or phosphorylation of focal adhesion kinase (FAK) in mutant cells. These findings suggest that TITIN could play a role in overgrowth-relevant pathways and phenotypes. In summary, our observations suggest TTN as a candidate predisposing gene in classic PTEN-wildtype BRRS patients, perhaps suggesting this syndrome join the growing list of Titinopathies.
Salford Lung Study in chronic obstructive pulmonary disease (SLS COPD): follow-up interviews on patient-centred outcomes
Authors: Doward Lynda , Svedsater Henrik , Whalley Diane , Crawford Rebecca , Leather David , Lay-Flurrie James , Bosanquet Nick
Published: December 2017

This study investigated patient perceptions, experiences and management of COPD throughout the SLS COPD study. Follow-up interviews were conducted with 400 patients who completed SLS COPD; a mixed-methods approach was used to collect quantitative and qualitative information. Structured interviews using closed-ended questions were conducted with 360 patients, detailing aspects of background/lifestyle information and COPD. Extended interviews containing open-ended questions on perceptions of COPD and quality of life (QoL) in addition to the closed-ended questions were completed by 40 further patients. Participants also completed the Adherence Starts with Knowledge-12 (ASK-12) and the COPD and Asthma Sleep Impact Scale (CASIS) questionnaire. Quantitative data were analysed descriptively; qualitative data were analysed using qualitative description. The participants (n = 400) were reasonably representative of the SLS COPD population; mean age was 66.2 years. Breathlessness was the most commonly recalled symptom of/associated with COPD (88.5% of patients) and was the symptom that changed the most (improved, 26.8%/worsened, 20.9%) throughout the study. Participants’ daily functioning and activities were most affected by symptoms of/associated with COPD, followed by relationships and psychological issues. 66.5% of participants experienced exacerbations, 60.5% of whom reported self-management as their first treatment strategy (taking antibiotics, resting and/or corticosteroids). Qualitative analysis revealed COPD symptoms, breathlessness in particular, to have a significant impact on mobility and in turn QoL. In conclusion, breathlessness was cited in these interviews as the COPD symptom with the greatest impact on participants’ daily functioning, activities and self-care. The findings provided significant additional knowledge to the SLS COPD study findings.
Heatwaves diminish the survival of a subtidal gastropod through reduction in energy budget and depletion of energy reserves
Authors: Leung Jonathan Y. S. , Connell Sean D. , Russell Bayden D.
Published: December 2017

Extreme climatic events, such as heatwaves, are predicted to be more prevalent in future due to global climate change. The devastating impacts of heatwaves on the survival of marine organisms may be further intensified by ocean acidification. Here, we tested the hypothesis that prolonged exposure to heatwave temperatures (24 °C, +3 °C summer seawater temperature) would diminish energy budget, body condition and ultimately survival of a subtidal gastropod (Thalotia conica) by pushing close to its critical thermal maximum (CTmax). We also tested whether ocean acidification (pCO2: 1000 ppm) affects energy budget, CTmax and hence survival of this gastropod. Following the 8-week experimental period, mortality was markedly higher at 24 °C irrespective of pCO2 level, probably attributed to energy deficit (negative scope for growth) and concomitant depletion of energy reserves (reduced organ weight to flesh weight ratio). CTmax of T. conica appeared at 27 °C and was unaffected by ocean acidification. Our findings imply that prolonged exposure to heatwaves can compromise the survival of marine organisms below CTmax via disruption in energy homeostasis, which possibly explains their mass mortality in the past heatwave events. Therefore, heatwaves would have more profound effects than ocean acidification on future marine ecosystems.
Host iron status and erythropoietic response to iron supplementation determines susceptibility to the RBC stage of falciparum malaria during pregnancy
Authors: Goheen Morgan M. , Bah Amat , Wegmüller Rita , Verhoef Hans , Darboe Bakary , Danso Ebrima , Prentice Andrew M. , Cerami Carla
Published: December 2017

Anaemia and malaria are both common in pregnant women in Sub-Saharan Africa. Previous evidence has shown that iron supplementation may increase malaria risk. In this observational cohort study, we evaluated P. falciparum pathogenesis in vitro in RBCs from pregnant women during their 2nd and 3rd trimesters. RBCs were collected and assayed before (n = 327), 14 days (n = 82), 49 days (n = 112) and 84 days (n = 115) after iron supplementation (60 mg iron as ferrous fumarate daily). P. falciparum erythrocytic stage growth in vitro is reduced in anaemic pregnant women at baseline, but increased during supplementation. The elevated growth rates parallel increases in circulating CD71-positive reticulocytes and other markers of young RBCs. We conclude that Plasmodium growth in vitro is associated with elevated erythropoiesis, an obligate step towards erythroid recovery in response to supplementation. Our findings support current World Health Organization recommendations that iron supplementation be given in combination with malaria prevention and treatment services in malaria endemic areas.
Culture and Next-generation sequencing-based drug susceptibility testing unveil high levels of drug-resistant-TB in Djibouti: results from the first national survey
Authors: Tagliani Elisa , Hassan Mohamed Osman , Waberi Yacine , De Filippo Maria Rosaria , Falzon Dennis , Dean Anna , Zignol Matteo , Supply Philip , Abdoulkader Mohamed Ali , Hassangue Hawa , Cirillo Daniela Maria
Published: December 2017

Djibouti is a small country in the Horn of Africa with a high TB incidence (378/100,000 in 2015). Multidrug-resistant TB (MDR-TB) and resistance to second-line agents have been previously identified in the country but the extent of the problem has yet to be quantified. A national survey was conducted to estimate the proportion of MDR-TB among a representative sample of TB patients. Sputum was tested using XpertMTB/RIF and samples positive for MTB and resistant to rifampicin underwent first line phenotypic susceptibility testing. The TB supranational reference laboratory in Milan, Italy, undertook external quality assurance, genotypic testing based on whole genome and targeted-deep sequencing and phylogenetic studies. 301 new and 66 previously treated TB cases were enrolled. MDR-TB was detected in 34 patients: 4.7% of new and 31% of previously treated cases. Resistance to pyrazinamide, aminoglycosides and capreomycin was detected in 68%, 18% and 29% of MDR-TB strains respectively, while resistance to fluoroquinolones was not detected. Cluster analysis identified transmission of MDR-TB as a critical factor fostering drug resistance in the country. Levels of MDR-TB in Djibouti are among the highest on the African continent. High prevalence of resistance to pyrazinamide and second-line injectable agents have important implications for treatment regimens.
Nanoimprinted High-Refractive Index Active Photonic Nanostructures Based on Quantum Dots for Visible Light
Authors: Pina-Hernandez Carlos , Koshelev Alexander , Dhuey Scott , Sassolini Simone , Sainato Michela , Cabrini Stefano , Munechika Keiko
Published: December 2017

A novel method to realizing printed active photonic devices was developed using nanoimprint lithography (NIL), combining a printable high-refractive index material and colloidal CdSe/CdS quantum dots (QDs) for applications in the visible region. Active media QDs were applied in two different ways: embedded inside a printable high-refractive index matrix to form an active printable hybrid nanocomposite, and used as a uniform coating on top of printed photonic devices. As a proof-of-demonstration for printed active photonic devices, two-dimensional (2-D) photonic crystals as well as 1D and 2D photonic nanocavities were successfully fabricated following a simple reverse-nanoimprint process. We observed enhanced photoluminescence from the 2D photonic crystal and the 1D nanocavities. Outstandingly, the process presented in this study is fully compatible with large-scale manufacturing where the patterning areas are only limited by the size of the corresponding mold. This work shows that the integration of active media and functional materials is a promising approach to the realization of integrated photonics for visible light using high throughput technologies. We believe that this work represents a powerful and cost-effective route for the development of numerous nanophotonic structures and devices that will lead to the emergence of new applications.
Phospholipid flipping involves a central cavity in P4 ATPases
Authors: Jensen M. S. , Costa S. R. , Duelli A. S. , Andersen P. A. , Poulsen L. R. , Stanchev L. D. , Gourdon P. , Palmgren M. , Günther Pomorski T. , López-Marqués R. L.
Published: December 2017

P4 ATPase flippases translocate phospholipids across biomembranes, thus contributing to the establishment of transmembrane lipid asymmetry, a feature important for multiple cellular processes. The mechanism by which such phospholipid flipping occurs remains elusive as P4 ATPases transport a giant substrate very different from that of other P-type ATPases such as Na+/K+- and Ca2+-ATPases. Based on available crystal structures of cation-transporting P-type ATPases, we generated a structural model of the broad-specificity flippase ALA10. In this model, a cavity delimited by transmembrane segments TM3, TM4, and TM5 is present in the transmembrane domain at a similar position as the cation-binding region in related P-type ATPases. Docking of a phosphatidylcholine headgroupin silicoshowed that the cavity can accommodate a phospholipid headgroup, likely leaving the fatty acid tails in contact with the hydrophobic portion of the lipid bilayer. Mutagenesis data support this interpretation and suggests that two residues in TM4 (Y374 and F375) are important for coordination of the phospholipid headgroup. Our results point to a general mechanism of lipid translocation by P4 ATPases, which closely resembles that of cation-transporting pumps, through coordination of the hydrophilic portion of the substrate in a central membrane cavity.
Myeloid differentiation primary response gene (MyD) 88 signalling is not essential for intestinal fibrosis development
Authors: Lutz C. , Weder B. , Hünerwadel A. , Fagagnini S. , Lang B. , Beerenwinkel N. , Rossel J. B. , Rogler G. , Misselwitz B. , Hausmann M.
Published: December 2017

Dysregulation of the immune response to microbiota is associated with inflammatory bowel disease (IBD), which can trigger intestinal fibrosis. MyD88 is a key component of microbiota signalling but its influence on intestinal fibrosis has not been clarified. Small bowel resections from donor-mice were transplanted subcutaneously into the neck of recipients C57BL/6 B6-MyD88tm1 Aki (MyD88−/−) and C57BL/6-Tg(UBC-green fluorescence protein (GFP))30Scha/J (GFP-Tg). Grafts were explanted up to 21 days after transplantation. Collagen layer thickness was determined using Sirius Red stained slides. In the mouse model of fibrosis collagen deposition and transforming growth factor-beta 1 (TGF-β1) expression was equal in MyD88+/+ and MyD88−/−, indicating that MyD88 was not essential for fibrogenesis. Matrix metalloproteinase (Mmp)9 expression was significantly decreased in grafts transplanted into MyD88−/− recipients compared to MyD88+/+ recipients (0.2 ± 0.1 vs. 153.0 ± 23.1, respectively, p < 0.05), similarly recruitment of neutrophils was significantly reduced (16.3 ± 4.5 vs. 25.4 ± 3.1, respectively, p < 0.05). Development of intestinal fibrosis appears to be independent of MyD88 signalling indicating a minor role of bacterial wall compounds in the process which is in contrast to published concepts and theories. Development of fibrosis appears to be uncoupled from acute inflammation.
New microsatellite markers for population studies of Phytophthora cinnamomi, an important global pathogen
Authors: Engelbrecht J. , Duong T. A. , Berg N. v. d.
Published: December 2017

Phytophthora cinnamomiis the causal agent of root rot, canker and dieback of thousands of plant species around the globe. This oomycete not only causes severe economic losses but also threatens natural ecosystems. In South Africa,P. cinnamomiaffects eucalyptus, avocado, macadamia and indigenous fynbos. Despite being one of the most important plant pathogens with a global distribution, little information is available regarding origin, invasion history and population biology. This is partly due to the limited number of molecular markers available for studyingP. cinnamomi. Using available genome sequences for three isolates ofP. cinnamomi, sixteen polymorphic microsatellite markers were developed as a set of multiplexable markers for both PCR and Gene Scan assays. The application of these markers onP. cinnamomipopulations from avocado production areas in South Africa revealed that they were all polymorphic in these populations. The markers developed in this study represent a valuable resource for studying the population biology and movement ofP. cinnamomiand will aid in the understanding of the origin and invasion history of this important species.
Prevalence of Metabolic Syndrome and its Associated Factors among Multi-ethnic Adults in Rural Areas in Xinjiang, China
Authors: Guo Heng , Gao Xiang , Ma Rulin , Liu Jiaming , Ding Yusong , Zhang Mei , Zhang Jingyu , Mu Lati , He Jia , Yan Yizhong , Ma Jiaolong , Guo Shuxia , Wei Sheng
Published: December 2017

Metabolic syndrome (MetS) has become a global public health problem affecting all nations and races. Few studies on the epidemic of metabolic syndrome (MetS) examined multi-ethnic adults in rural areas in Xinjiang, China. We thus investigated the prevalence and risk factors of MetS there. A cross-sectional study was performed in a representative sample of 15020 rural multi-ethnic adults from 2009 to 2010. Four widely used criteria (ATPIII\IDF\JIS\CDS) were used to measure the prevalence of MetS. Multiple logistic regression analysis was used to explore the risk factors of MetS. The age-adjusted prevalence of MetS was 14.43%, 21.33%, 26.50%, and 19.89% based on the ATP III, IDF, JIS and CDS criterion, respectively. The prevalence of MetS was higher in women and increased with age. According to JIS criterion, the prevalence of components in MetS was 57.75% for abdominal obesity, 44.05% for elevated blood pressure, 40.98% for reduced HDL-cholesterol, 23.33% for elevated triglycerides, 18.95% for raised fasting plasma glucose. Lower consumption of vegetables, milk, and higher consumption of red meat were associated with higher likelihood of having MetS. The prevalence of MetS in Xinjiang rural multi-ethnic adults was high. Diet factors were associated with the prevalence of MetS.
Peripersonal space representation develops independently from visual experience
Authors: Ricciardi Emiliano , Menicagli Dario , Leo Andrea , Costantini Marcello , Pietrini Pietro , Sinigaglia Corrado
Published: December 2017

Our daily-life actions are typically driven by vision. When acting upon an object, we need to represent its visual features (e.g. shape, orientation, etc.) and to map them into our own peripersonal space. But what happens with people who have never had any visual experience? How can they map object features into their own peripersonal space? Do they do it differently from sighted agents? To tackle these questions, we carried out a series of behavioral experiments in sighted and congenitally blind subjects. We took advantage of a spatial alignment effect paradigm, which typically refers to a decrease of reaction times when subjects perform an action (e.g., a reach-to-grasp pantomime) congruent with that afforded by a presented object. To systematically examine peripersonal space mapping, we presented visual or auditory affording objects both within and outside subjects’ reach. The results showed that sighted and congenitally blind subjects did not differ in mapping objects into their own peripersonal space. Strikingly, this mapping occurred also when objects were presented outside subjects’ reach, but within the peripersonal space of another agent. This suggests that (the lack of) visual experience does not significantly affect the development of both one’s own and others’ peripersonal space representation.
An Implantable Micro-Caged Device for Direct Local Delivery of Agents
Authors: Son Alexander I. , Opfermann Justin D. , McCue Caroline , Ziobro Julie , Abrahams John H. , Jones Katherine , Morton Paul D. , Ishii Seiji , Oluigbo Chima , Krieger Axel , Liu Judy S. , Hashimoto-Torii Kazue , Torii Masaaki
Published: December 2017

Local and controlled delivery of therapeutic agents directly into focally afflicted tissues is the ideal for the treatment of diseases that require direct interventions. However, current options are obtrusive, difficult to implement, and limited in their scope of utilization; the optimal solution requires a method that may be optimized for available therapies and is designed for exact delivery. To address these needs, we propose the Biocage, a customizable implantable local drug delivery platform. The device is a needle-sized porous container capable of encasing therapeutic molecules and matrices of interest to be eluted into the region of interest over time. The Biocage was fabricated using the Nanoscribe Photonic Professional GT 3D laser lithography system, a two-photon polymerization (2PP) 3D printer capable of micron-level precision on a millimeter scale. We demonstrate the build consistency and features of the fabricated device; its ability to release molecules; and a method for its accurate, stable delivery in mouse brain tissue. The Biocage provides a powerful tool for customizable and precise delivery of therapeutic agents into target tissues.
Satellite Observations of Imprint of Oceanic Current on Wind Stress by Air-Sea Coupling
Authors: Renault Lionel , McWilliams James C. , Masson Sebastien
Published: December 2017

Mesoscale eddies are present everywhere in the ocean and partly determine the mean state of the circulation and ecosystem. The current feedback on the surface wind stress modulates the air-sea transfer of momentum by providing a sink of mesoscale eddy energy as an atmospheric source. Using nine years of satellite measurements of surface stress and geostrophic currents over the global ocean, we confirm that the current-induced surface stress curl is linearly related to the current vorticity. The resulting coupling coefficient between current and surface stress (sτ [N s m−3]) is heterogeneous and can be roughly expressed as a linear function of the mean surface wind. sτ expresses the sink of eddy energy induced by the current feedback. This has important implications for air-sea interaction and implies that oceanic mean and mesoscale circulations and their effects on surface-layer ventilation and carbon uptake are better represented in oceanic models that include this feedback.
Vitamin K epoxide reductase and its paralogous enzyme have different structures and functions
Authors: Sinhadri Balaji Chandra Sekhar , Jin Da-Yun , Stafford Darrel W. , Tie Jian-Ke
Published: December 2017

Vitamin K epoxide reductase (VKOR) is an essential enzyme for vitamin K-dependent carboxylation, while the physiological function of its paralogous enzyme VKOR-like (VKORL) is yet unknown. Although these two enzymes share approximately 50% protein sequence homology, the membrane topology of VKOR is still in debate. Here, we explored the differences in the membrane topology and disulfide-linked oligomerization of these two enzymes. Results from mutating the critical amino acid residues in the disputed transmembrane (TM) regions revealed that the second TM domain in the proposed 4-TM model of VKOR does not function as an authentic TM helix; supporting VKOR is a 3-TM protein, which is different from VKORL. Additionally, altering the loop sequence between the two conserved cysteine residues of VKORL affects its activity, supporting the notion that the conserved loop cysteines of VKORL are involved in its active site regeneration. However, a similar mutation in VKOR does not affect its enzymatic activity. Finally, our results show that although both VKOR and VKORL form disulfide-linked oligomers, the cysteine residues involved in the oligomerization appear to be different. Overall, the structural and functional differences between VKOR and VKORL shown here indicate that VKORL might have a different physiological function other than recycling vitamin K.
Attribution of recent temperature behaviour reassessed by a neural-network method
Authors: Pasini Antonello , Racca Paolo , Amendola Stefano , Cartocci Giorgio , Cassardo Claudio
Published: December 2017

Attribution studies on recent global warming by Global Climate Model (GCM) ensembles converge in showing the fundamental role of anthropogenic forcings as primary drivers of temperature in the last half century. However, despite their differences, all these models pertain to the same dynamical approach and come from a common ancestor, so that their very similar results in attribution studies are not surprising and cannot be considered as a clear proof of robustness of the results themselves. Thus, here we adopt a completely different, non-dynamical, data-driven and fully nonlinear approach to the attribution problem. By means of neural network (NN) modelling, and analysing the last 160 years, we perform attribution experiments and find that the strong increase in global temperature of the last half century may be attributed basically to anthropogenic forcings (with details on their specific contributions), while the Sun considerably influences the period 1910–1975. Furthermore, the role of sulphate aerosols and Atlantic Multidecadal Oscillation for better catching interannual to decadal temperature variability is clarified. Sensitivity analyses to forcing changes are also performed. The NN outcomes both corroborate our previous knowledge from GCMs and give new insight into the relative contributions of external forcings and internal variability to climate.
Aedes aegypti microRNA miR-2b regulates ubiquitin-related modifier to control chikungunya virus replication
Authors: Dubey Sunil Kumar , Shrinet Jatin , Jain Jaspreet , Ali Shakir , Sunil Sujatha
Published: December 2017

Arboviruses that replicate in mosquitoes activate innate immune response within mosquitoes. Regulatory non-coding microRNAs (miRNA) are known to be modulated in mosquitoes during chikungunya infection. However, information about targets of these miRNAs is scant. The present study was aimed to identify and analyze targets of miRNAs that are regulated during chikungunya virus (CHIKV) replication in Aedes aegypti cells and in the mosquito. Employing next-generation sequencing technologies, we identified a total of 126 miRNAs from the Ae. aegypti cell line Aag2. Of these, 13 miRNAs were found to be regulated during CHIKV infection. Putative targets of three of the most significantly regulated miRNAs- miR-100, miR-2b and miR-989 were also analyzed using quantitative PCRs, in cell lines and in mosquitoes, to validate whether they were the targets of the miRNAs. Our study expanded the list of miRNAs known in Ae. aegypti and predicted targets for the significantly regulated miRNAs. Further analysis of some of these targets revealed that ubiquitin-related modifier is a target of miRNA miR-2b and plays a significant role in chikungunya replication.