bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasmepsin II–III copy number accounts for bimodal piperaquine resistance among Cambodian Plasmodium falciparum
Authors: Bopp Selina , Magistrado Pamela , Wong Wesley , Schaffner Stephen F. , Mukherjee Angana , Lim Pharath , Dhorda Mehul , Amaratunga Chanaki , Woodrow Charles J. , Ashley Elizabeth A. , White Nicholas J. , Dondorp Arjen M. , Fairhurst Rick M. , Ariey Frederic , Menard Didier , Wirth Dyann F. , Volkman Sarah K.
Published: April 2018

Multidrug resistant Plasmodium falciparum in Southeast Asia endangers regional malaria elimination and threatens to spread to other malaria endemic areas. Understanding mechanisms of piperaquine (PPQ) resistance is crucial for tracking its emergence and spread, and to develop effective strategies for overcoming it. Here we analyze a mechanism of PPQ resistance in Cambodian parasites. Isolates exhibit a bimodal dose–response curve when exposed to PPQ, with the area under the curve quantifying their survival in vitro. Increased copy number for plasmepsin II and plasmepsin III appears to explain enhanced survival when exposed to PPQ in most, but not all cases. A panel of isogenic subclones reinforces the importance of plasmepsin II–III copy number to enhanced PPQ survival. We conjecture that factors producing increased parasite survival under PPQ exposure in vitro may drive clinical PPQ failures in the field.
Representation of multiple objects in macaque category-selective areas
Authors: Bao Pinglei , Tsao Doris Y.
Published: April 2018

Object recognition in the natural world usually occurs in the presence of multiple surrounding objects, but responses of neurons in inferotemporal (IT) cortex, the large brain area responsible for object recognition, have mostly been studied only to isolated objects. We study rules governing responses to multiple objects by cells in two category-selective regions of macaque IT cortex, the middle lateral face patch (ML) and the middle body patch (MB). We find that responses of single ML and MB cells to pairs of objects can be explained by the widely accepted framework of normalization, with one added ingredient: homogeneous category selectivity of neighboring neurons forming the normalization pool. This rule leads to winner-take-all, contralateral-take-all, or weighted averaging behavior in single cells, depending on the category, spatial configuration, and relative contrast of the two objects. The winner-take-all behavior suggests a potential mechanism for clutter-invariant representation of face and bodies under certain conditions.
Structures of chaperone-substrate complexes docked onto the export gate in a type III secretion system
Authors: Xing Qiong , Shi Ke , Portaliou Athina , Rossi Paolo , Economou Anastassios , Kalodimos Charalampos G.
Published: April 2018

The flagellum and the injectisome enable bacterial locomotion and pathogenesis, respectively. These nanomachines assemble and function using a type III secretion system (T3SS). Exported proteins are delivered to the export apparatus by dedicated cytoplasmic chaperones for their transport through the membrane. The structural and mechanistic basis of this process is poorly understood. Here we report the structures of two ternary complexes among flagellar chaperones (FliT and FliS), protein substrates (the filament-capping FliD and flagellin FliC), and the export gate platform protein FlhA. The substrates do not interact directly with FlhA; however, they are required to induce a binding-competent conformation to the chaperone that exposes the recognition motif featuring a highly conserved sequence recognized by FlhA. The structural data reveal the recognition signal in a class of T3SS proteins and provide new insight into the assembly of key protein complexes at the export gate.
P53 and mTOR signalling determine fitness selection through cell competition during early mouse embryonic development
Authors: Bowling Sarah , Di Gregorio Aida , Sancho Margarida , Pozzi Sara , Aarts Marieke , Signore Massimo , D. Schneider Michael , Martinez-Barbera Juan Pedro , Gil Jesús , Rodríguez Tristan A.
Published: April 2018

Ensuring the fitness of the pluripotent cells that will contribute to future development is important both for the integrity of the germline and for proper embryogenesis. Consequently, it is becoming increasingly apparent that pluripotent cells can compare their fitness levels and signal the elimination of those cells that are less fit than their neighbours. In mammals the nature of the pathways that communicate fitness remain largely unknown. Here we identify that in the early mouse embryo and upon exit from naive pluripotency, the confrontation of cells with different fitness levels leads to an inhibition of mTOR signalling in the less fit cell type, causing its elimination. We show that during this process, p53 acts upstream of mTOR and is required to repress its activity. Finally, we demonstrate that during normal development around 35% of cells are eliminated by this pathway, highlighting the importance of this mechanism for embryonic development.
CE-BLAST makes it possible to compute antigenic similarity for newly emerging pathogens
Authors: Qiu Tianyi , Yang Yiyan , Qiu Jingxuan , Huang Yang , Xu Tianlei , Xiao Han , Wu Dingfeng , Zhang Qingchen , Zhou Chen , Zhang Xiaoyan , Tang Kailin , Xu Jianqing , Cao Zhiwei
Published: April 2018

Major challenges in vaccine development include rapidly selecting or designing immunogens for raising cross-protective immunity against different intra- or inter-subtypic pathogens, especially for the newly emerging varieties. Here we propose a computational method, Conformational Epitope (CE)-BLAST, for calculating the antigenic similarity among different pathogens with stable and high performance, which is independent of the prior binding-assay information, unlike the currently available models that heavily rely on the historical experimental data. Tool validation incorporates influenza-related experimental data sufficient for stability and reliability determination. Application to dengue-related data demonstrates high harmonization between the computed clusters and the experimental serological data, undetectable by classical grouping. CE-BLAST identifies the potential cross-reactive epitope between the recent zika pathogen and the dengue virus, precisely corroborated by experimental data. The high performance of the pathogens without the experimental binding data suggests the potential utility of CE-BLAST to rapidly design cross-protective vaccines or promptly determine the efficacy of the currently marketed vaccine against emerging pathogens, which are the critical factors for containing emerging disease outbreaks.
Identification of a pyrophosphate-dependent kinase and its donor selectivity determinants
Authors: Nagata Ryuhei , Fujihashi Masahiro , Sato Takaaki , Atomi Haruyuki , Miki Kunio
Published: April 2018

Almost all kinases utilize ATP as their phosphate donor, while a few kinases utilize pyrophosphate (PPi) instead. PPi-dependent kinases are often homologous to their ATP-dependent counterparts, but determinants of their different donor specificities remain unclear. We identify a PPi-dependent member of the ribokinase family, which differs from known PPi-dependent kinases, and elucidate its PPi-binding mode based on the crystal structures. Structural comparison and sequence alignment reveal five important residues: three basic residues specifically recognizing PPi and two large hydrophobic residues occluding a part of the ATP-binding pocket. Two of the three basic residues adapt a conserved motif of the ribokinase family for the PPi binding. Using these five key residues as a signature pattern, we discover additional PPi-specific members of the ribokinase family, and thus conclude that these residues are the determinants of PPi-specific binding. Introduction of these residues may enable transformation of ATP-dependent ribokinase family members into PPi-dependent enzymes.
Precisely timed inhibition facilitates action potential firing for spatial coding in the auditory brainstem
Authors: Beiderbeck Barbara , Myoga Michael H. , Müller Nicolas I. C. , Callan Alexander R. , Friauf Eckhard , Grothe Benedikt , Pecka Michael
Published: April 2018

The integration of excitatory and inhibitory synaptic inputs is fundamental to neuronal processing. In the mammalian auditory brainstem, neurons compare excitatory and inhibitory inputs from the ipsilateral and contralateral ear, respectively, for sound localization. However, the temporal precision and functional roles of inhibition in this integration process are unclear. Here, we demonstrate by in vivo recordings from the lateral superior olive (LSO) that inhibition controls spiking with microsecond precision throughout high frequency click trains. Depending on the relative timing of excitation and inhibition, neuronal spike probability is either suppressed or—unexpectedly—facilitated. In vitro conductance-clamp LSO recordings establish that a reduction in the voltage threshold for spike initiation due to a prior hyperpolarization results in post-inhibitory facilitation of otherwise sub-threshold synaptic events. Thus, microsecond-precise differences in the arrival of inhibition relative to excitation can facilitate spiking in the LSO, thereby promoting spatial sensitivity during the processing of faint sounds.
Exceptional point engineered glass slide for microscopic thermal mapping
Authors: Zhao Han , Chen Zhaowei , Zhao Ruogang , Feng Liang
Published: April 2018

Thermal sensing with fine spatial resolution is important to the study of many scientific areas. While modern microscopy systems allow optical detection at high spatial resolution, their intrinsic functions are mainly focused on imaging but limited in detecting other physical parameters, for example, mapping thermal variations. Here, with a coating of an optical exceptional point structure, we demonstrate a low-cost but efficient multifunctional microscope slide, supporting real-time monitoring and mapping of temperature distribution and heat transport in addition to conventional microscopic imaging. The square-root dependency associated with an exceptional point leads to enhanced thermal sensitivity for precise temperature measurement. With a microscale resolution, real-time thermal mapping is conducted, showing dynamic temperature variation in a spatially defined area. Our strategy of integrating low-cost and efficient optical sensing technologies on a conventional glass slide enables simultaneous detection of multiple environmental parameters, producing improved experimental control at the microscale in various scientific disciplines.
Incorporating epilepsy genetics into clinical practice: a 360°evaluation
Authors: Oates Stephanie , Tang Shan , Rosch Richard , Lear Rosalie , Hughes Elaine F. , Williams Ruth E. , Larsen Line H. G. , Hao Qin , Dahl Hans Atli , Møller Rikke S. , Pal Deb K.
Published: April 2018

We evaluated a new epilepsy genetic diagnostic and counseling service covering a UK population of 3.5 million. We calculated diagnostic yield, estimated clinical impact, and surveyed referring clinicians and families. We costed alternative investigational pathways for neonatal onset epilepsy. Patients with epilepsy of unknown aetiology onset < 2 years; treatment resistant epilepsy; or familial epilepsy were referred for counseling and testing. We developed NGS panels, performing clinical interpretation with a multidisciplinary team. We held an educational workshop for paediatricians and nurses. We sent questionnaires to referring paediatricians and families. We analysed investigation costs for 16 neonatal epilepsy patients. Of 96 patients, a genetic diagnosis was made in 34% of patients with seizure onset < 2 years, and 4% > 2 years, with turnaround time of 21 days. Pathogenic variants were seen in SCN8A, SCN2A, SCN1A, KCNQ2, HNRNPU, GRIN2A, SYNGAP1, STXBP1, STX1B, CDKL5, CHRNA4, PCDH19 and PIGT. Clinician prediction was poor. Clinicians and families rated the service highly. In neonates, the cost of investigations could be reduced from £9362 to £2838 by performing gene panel earlier and the median diagnostic delay of 3.43 years reduced to 21 days. Panel testing for epilepsy has a high yield among children with onset < 2 years, and an appreciable clinical and financial impact. Parallel gene testing supersedes single gene testing in most early onset cases that do not show a clear genotype-phenotype correlation. Clinical interpretation of laboratory results, and in-depth discussion of implications for patients and their families, necessitate multidisciplinary input and skilled genetic counseling.
Printed microelectrode arrays on soft materials: from PDMS to hydrogels
Authors: Adly Nouran , Weidlich Sabrina , Seyock Silke , Brings Fabian , Yakushenko Alexey , Offenhäusser Andreas , Wolfrum Bernhard
Published: April 2018

Microelectrode arrays (MEAs) provide promising opportunities to study electrical signals in neuronal and cardiac cell networks, restore sensory function, or treat disorders of the nervous system. Nevertheless, most of the currently investigated devices rely on silicon or polymer materials, which neither physically mimic nor mechanically match the structure of living tissue, causing inflammatory response or loss of functionality. Here, we present a new method for developing soft MEAs as bioelectronic interfaces. The functional structures are directly deposited on PDMS-, agarose-, and gelatin-based substrates using ink-jet printing as a patterning tool. We demonstrate the versatility of this approach by printing high-resolution carbon MEAs on PDMS and hydrogels. The soft MEAs are used for in vitro extracellular recording of action potentials from cardiomyocyte-like HL-1 cells. Our results represent an important step toward the design of next-generation bioelectronic interfaces in a rapid prototyping approach.
Meteorological Controls on Local and Regional Volcanic Ash Dispersal
Authors: Poulidis Alexandros P. , Phillips Jeremy C. , Renfrew Ian A. , Barclay Jenni , Hogg Andrew , Jenkins Susanna F. , Robertson Richard , Pyle David M.
Published: April 2018

Volcanic ash has the capacity to impact human health, livestock, crops and infrastructure, including international air traffic. For recent major eruptions, information on the volcanic ash plume has been combined with relatively coarse-resolution meteorological model output to provide simulations of regional ash dispersal, with reasonable success on the scale of hundreds of kilometres. However, to predict and mitigate these impacts locally, significant improvements in modelling capability are required. Here, we present results from a dynamic meteorological-ash-dispersion model configured with sufficient resolution to represent local topographic and convectively-forced flows. We focus on an archetypal volcanic setting, Soufrière, St Vincent, and use the exceptional historical records of the 1902 and 1979 eruptions to challenge our simulations. We find that the evolution and characteristics of ash deposition on St Vincent and nearby islands can be accurately simulated when the wind shear associated with the trade wind inversion and topographically-forced flows are represented. The wind shear plays a primary role and topographic flows a secondary role on ash distribution on local to regional scales. We propose a new explanation for the downwind ash deposition maxima, commonly observed in volcanic eruptions, as resulting from the detailed forcing of mesoscale meteorology on the ash plume.
A new phylogeny-based tribal classification of subfamily Detarioideae, an early branching clade of florally diverse tropical arborescent legumes
Authors: de la Estrella Manuel , Forest Félix , Klitgård Bente , Lewis Gwilym P. , Mackinder Barbara A. , de Queiroz Luciano P. , Wieringa Jan J. , Bruneau Anne
Published: April 2018

Detarioideae (81 genera, c. 760 species) is one of the six Leguminosae subfamilies recently reinstated by the Legume Phylogeny Working Group. This subfamily displays high morphological variability and is one of the early branching clades in the evolution of legumes. Using previously published and newly generated sequences from four loci (matK-trnK, rpL16, trnG-trnG2G and ITS), we develop a new densely sampled phylogeny to assess generic relationships and tribal delimitations within Detarioideae. The ITS phylogenetic trees are poorly resolved, but the plastid data recover several strongly supported clades, which also are supported in a concatenated plastid + ITS sequence analysis. We propose a new phylogeny-based tribal classification for Detarioideae that includes six tribes: re-circumscribed Detarieae and Amherstieae, and the four new tribes Afzelieae, Barnebydendreae, Saraceae and Schotieae. An identification key and descriptions for each of the tribes are also provided.
Relationship between body mass index and renal function deterioration among the Taiwanese chronic kidney disease population
Authors: Chang Tian-Jong , Zheng Cai-Mei , Wu Mei-Yi , Chen Tzu-Ting , Wu Yun-Chun , Wu Yi-Lien , Lin Hsin-Ting , Zheng Jing-Quan , Chu Nain-Feng , Lin Yu-Me , Su Sui-Lung , Lu Kuo-Cheng , Chen Jin-Shuen , Sung Fung-Chang , Lee Chien-Te , Yang Yu , Hwang Shang-Jyh , Wang Ming-Cheng , Hsu Yung-Ho , Chiou Hung-Yi , Kao Senyeong , Lin Yuh-Feng
Published: April 2018

This study investigated the characteristics of patients with different chronic kidney disease (CKD) stages according to various body mass index (BMI) categories and determined the influence of BMI in renal function deterioration. We conducted a multicenter, longitudinal cohort study based on the Epidemiology and Risk Factors Surveillance of CKD project (2008–2013) and National Health Insurance Research Database (2001–2013). A total of 7357 patients with CKD aged 20–85 years from 14 hospitals were included in the study. A higher male sex, diabetes mellitus (DM) and hypertension were noted among overweight and obese CKD patients, while more cancer prevalence was noted among underweight CKD patients. Charlson comorbidity index was significantly higher and correlated with BMI among late CKD patients. Patients with BMI < 18.5 kg/m2 exhibited non-significantly higher events of eGFR decline events in both early and late CKD stages than other BMI groups. BMI alone is not a determinant of CKD progression among our Taiwanese CKD patients. Obesity should be re-defined and body weight manipulation should be individualized in CKD patients.
Satiety behavior is regulated by ASI/ASH reciprocal antagonism
Authors: Davis Kristen C. , Choi Young-In , Kim Jeongho , You Young-Jai
Published: April 2018

Appropriate decision-making is essential for ensuring survival; one such decision is whether to eat. Overall metabolic state and the safety of food are the two factors we examined using C. elegans to ask whether the metabolic state regulates neuronal activities and corresponding feeding behavior. We monitored the activity of sensory neurons that are activated by nutritious (or appetitive) stimuli (ASI) and aversive stimuli (ASH) in starved vs. well-fed worms during stimuli presentation. Starvation reduces ASH activity to aversive stimuli while increasing ASI activity to nutritious stimuli, showing the responsiveness of each neuron is modulated by overall metabolic state. When we monitored satiety quiescence behavior that reflects the overall metabolic state, ablation of ASI and ASH produce the opposite behavior, showing the two neurons interact to control the decision to eat or not. This circuit provides a simple approach to how neurons handle sensory conflict and reach a decision that is translated to behavior.
Interfacial magnetic-phase transition mediated large perpendicular magnetic anisotropy in FeRh/MgO by a heavy transition-metal capping
Authors: Odkhuu Dorj
Published: April 2018

Stacking a magnetic memory junction in spintronic devices necessarily involves making contacts with a transitional-metal capping electrode. Herein, by means of first-principles calculations, we reveal the importance of heavy transition-metal capping on magnetic-phase transition from antiferromagnetic (AFM) to ferromagnetic (FM) order and the large perpendicular magnetic anisotropy (PMA) found in Ta-capped FeRh films on MgO substrate. While magnetization of FeRh films reorients from in-plane to PMA when in contact with MgO, the presence of Ta capping further enhances the magnitude of the PMA energy by at least five times. This large PMA is associated with the AFM-FM transition at the interface, which in turn modifies the out-of-plane Fe 3d orbital states through the hybridization with the strong spin-orbit coupled Ta 5d orbitals. Furthermore, the magnetic-phase transition at the interface is the result of the mutual mechanisms of the capping-induced volume/tetragonal expansion in the interfacial FeRh layers and the competition between the direct and indirect exchange interactions. These findings suggest that Ta/FeRh/MgO multilayers may represent highly favourable memory materials with net interfacial ferromagnetism and large PMA in antiferromagnet spintronics.
Spectroscopic features of ultrahigh-pressure impact glasses of the Kara astrobleme
Authors: Shumilova T. G. , Lutoev V. P. , Isaenko S. I. , Kovalchuk N. S. , Makeev B. A. , Lysiuk A. Yu. , Zubov A. A. , Ernstson K.
Published: April 2018

The state of substances under ultrahigh pressures and temperatures (UHPHT) now raises a special interest as a matter existing under extreme conditions and as potential new material. Under laboratory conditions only small amounts of micrometer-sized matter are produced at a pressure up to 100 GPa and at room temperature. Simultaneous combination of ultrahigh pressures and temperatures in a lab still requires serious technological effort. Here we describe the composition and structure of the UHPHT vein-like impact glass discovered by us in 2015 on the territory of the Kara astrobleme (Russia) and compare its properties with impact glass from the Ries crater (Germany). A complex of structural and spectroscopic methods presents unusual high pressure marks of structural elements in 8-fold co-ordination that had been described earlier neither in synthetic nor natural glasses. The Kara natural UHPHT glasses being about 70 Ma old have well preserved initial structure, presenting some heterogeneity as a result of partial liquation and crystallization differentiation where an amorphous component is proposed to originate from low level polymerization. Homogeneous parts of the UHPHT glasses can be used to deepened fundamental investigation of a substance under extreme PT conditions and to technological studies for novel material creations.
In silico assessment of the conduction mechanism of the Ryanodine Receptor 1 reveals previously unknown exit pathways
Authors: Heinz Leonard P. , Kopec Wojciech , de Groot Bert L. , Fink Rainer H. A.
Published: April 2018

The ryanodine receptor 1 is a large calcium ion channel found in mammalian skeletal muscle. The ion channel gained a lot of attention recently, after multiple independent authors published near-atomic cryo electron microscopy data. Taking advantage of the unprecedented quality of structural data, we performed molecular dynamics simulations on the entire ion channel as well as on a reduced model. We calculated potentials of mean force for Ba2+, Ca2+, Mg2+, K+, Na+and Cl−ions using umbrella sampling to identify the key residues involved in ion permeation. We found two main binding sites for the cations, whereas the channel is strongly repulsive for chloride ions. Furthermore, the data is consistent with the model that the receptor achieves its ion selectivity by over-affinity for divalent cations in a calcium-block-like fashion. We reproduced the experimental conductance for potassium ions in permeation simulations with applied voltage. The analysis of the permeation paths shows that ions exit the pore via multiple pathways, which we suggest to be related to the experimental observation of different subconducting states.
Namib Desert primary productivity is driven by cryptic microbial community N-fixation
Authors: Ramond Jean-Baptiste , Woodborne Stephan , Hall Grant , Seely Mary , Cowan Don A.
Published: April 2018

Carbon exchange in drylands is typically low, but during significant rainfall events (wet anomalies) drylands act as a C sink. During these anomalies the limitation on C uptake switches from water to nitrogen. In the Namib Desert of southern Africa, the N inventory in soil organic matter available for mineralisation is insufficient to support the observed increase in primary productivity. The C4 grasses that flourish after rainfall events are not capable of N fixation, and so there is no clear mechanism for adequate N fixation in dryland ecosystems to support rapid C uptake. Here we demonstrate that N fixation by photoautotrophic hypolithic communities forms the basis for the N budget for plant productivity events in the Namib Desert. Stable N isotope (δ15N) values of Namib Desert hypolithic biomass, and surface and subsurface soils were measured over 3 years across dune and gravel plain biotopes. Hypoliths showed significantly higher biomass and lower δ15N values than soil organic matter. The δ15N values of hypoliths approach the theoretical values for nitrogen fixation. Our results are strongly indicative that hypolithic communities are the foundation of productivity after rain events in the Namib Desert and are likely to play similar roles in other arid environments.
Monitoring voltage fluctuations of intracellular membranes
Authors: Sepehri Rad Masoud , Cohen Lawrence B. , Braubach Oliver , Baker Bradley J.
Published: April 2018

In eukaryotic cells, the endoplasmic reticulum (ER) is the largest continuous membrane-enclosed network which surrounds a single lumen. Using a new genetically encoded voltage indicator (GEVI), we applied the patch clamp technique to cultured HEK293 cells and neurons and found that there is a very fast electrical interaction between the plasma membrane and internal membrane(s). This discovery suggests a novel mechanism for interaction between the external membrane and internal membranes as well as mechanisms for interactions between the various internal membranes. The ER may transfer electrical signals between the plasma membrane and other internal organelles. The internal membrane optical signal is reversed in polarity but has a time course similar to that of the plasma membrane signal. The optical signal of the GEVI in the plasma membrane is consistent from trial to trial. However, the internal signal decreases in size with repeated trials suggesting that the electrical coupling is degrading and/or the resistance of the internal membrane is decaying.
The stage of seed development influences iron bioavailability in pea (Pisum sativum L.)
Authors: Moore Katie L. , Rodríguez-Ramiro Ildefonso , Jones Eleanor R. , Jones Emily J. , Rodríguez-Celma Jorge , Halsey Kirstie , Domoney Claire , Shewry Peter R. , Fairweather-Tait Susan , Balk Janneke
Published: April 2018

Pea seeds are widely consumed in their immature form, known as garden peas and petit pois, mostly after preservation by freezing or canning. Mature dry peas are rich in iron in the form of ferritin, but little is known about the content, form or bioavailability of iron in immature stages of seed development. Using specific antibodies and in-gel iron staining, we show that ferritin loaded with iron accumulated gradually during seed development. Immunolocalization and high-resolution secondary ion mass spectrometry (NanoSIMS) revealed that iron-loaded ferritin was located at the surface of starch-containing plastids. Standard cooking procedures destabilized monomeric ferritin and the iron-loaded form. Iron uptake studies using Caco-2 cells showed that the iron in microwaved immature peas was more bioavailable than in boiled mature peas, despite similar levels of soluble iron in the digestates. By manipulating the levels of phytic acid in the digestates we demonstrate that phytic acid is the main inhibitor of iron uptake from mature peas in vitro. Taken together, our data show that immature peas and mature dry peas contain similar levels of ferritin-iron, which is destabilized during cooking. However, iron from immature peas is more bioavailable because of lower phytic acid levels compared to mature peas.
Elevated leptin and decreased adiponectin independently predict the post-thrombotic syndrome in obese and non-obese patients
Authors: Mrozinska Sandra , Cieslik Joanna , Broniatowska Elżbieta , Undas Anetta
Published: April 2018

Post-thrombotic syndrome (PTS) is a common complication of deep vein thrombosis (DVT). Little is known about the involvement of adipokines in the pathogenesis of DVT. We evaluated whether adipokines can predict PTS. In a prospective cohort study, 320 DVT patients aged 70 years or less were enrolled. Serum adiponectin, leptin and resistin levels were measured three months since the index first-ever DVT. After 2 years’ follow-up PTS was diagnosed in 83 of 309 available patients (26.9%) who had 13.9% lower adiponectin and 16% higher leptin levels compared with the remainder (both p < 0.0001). No PTS-associated differences in C-reactive protein, fibrinogen, D-dimer, plasminogen activator inhibitor-1 and resistin were observed. The multivariable logistic regression adjusted for age, sex, obesity and tissue plasminogen activator (tPa) showed that lower adiponectin (odds ratio [OR], 0.42; 95% confidence interval [CI], 0.31–0.56) and higher leptin levels (OR, 1.49; 95% CI, 1.31–1.69) are independent predictors for PTS. Obesity-stratified logistic regression analysis confirmed that lower adiponectin (OR, 0.49; 95% CI, 0.38–0.64) and higher leptin (OR, 1.41; 95% Cl, 1.25–1.58) levels predicted PTS. Our findings showed that lower adiponectin and higher leptin measured 3 months after DVT, regardless of obesity, can independently predict PTS, which suggests novel links between adipokines and thrombosis.
Recurrent complex spinal tuberculosis accompanied by sinus tract formation: causes of recurrence and clinical treatments
Authors: Wang Biao , Kong Lingbo , Zhu Ziqi , Gao Wenjie , Guo Hua , Wang Xiaodong , Li Hui , Zhao Qinpeng , Zhang Haiping , Hao Dingjun
Published: April 2018

Recurrent complex spinal tuberculosis accompanied by sinus tract formation is one of the most common and complex types of recurrent tuberculosis. To date, only very few studies have reported the strategies and effectiveness of surgical treatments on postoperative recurrent spinal tuberculosis accompanied by sinus tract formation. In this study, 21 recurrent patients out of 87 patients with complex spinal tuberculosis were reviewed. The data of the patients, including age, gender, existence of drug-resistant mycobacterium tuberculosis, postoperative standard chemotherapy, completeness of lesion debridement, reconstruction of the spinal stability, nutritional status, accompaniment by tuberculosis in other regions, timing of the operations, and areas of the lesions, were collected for single- and multiple-factor analyses. The clinical outcomes were evaluated by long-term follow-ups. The results showed that 7 factors were significantly associated with postoperative recurrence of complex spinal tuberculosis accompanied by sinus tract formation. This suggested that when we treat complex spinal tuberculosis, we should pay more attention to these seven indicators to avoid postoperative recurrence, and our clinical outcomes suggested that it is difficult to treat recurrent complicated spinal tuberculosis combined with sinus tract formation. The key for successful surgical treatment includes effective chemotherapy, radical debridement and proper reconstruction of spinal stability.
The behavioral and neural binding phenomena during visuomotor integration of angry facial expressions
Authors: Coll Sélim Yahia , Ceravolo Leonardo , Frühholz Sascha , Grandjean Didier
Published: April 2018

Different parts of our brain code the perceptual features and actions related to an object, causing a binding problem, in which the brain has to integrate information related to an event without any interference regarding the features and actions involved in other concurrently processed events. Using a paradigm similar to Hommel, who revealed perception-action bindings, we showed that emotion could bind with motor actions when relevant, and in specific conditions, irrelevant for the task. By adapting our protocol to a functional Magnetic Resonance Imaging paradigm we investigated, in the present study, the neural bases of the emotion-action binding with task-relevant angry faces. Our results showed that emotion bound with motor responses. This integration revealed increased activity in distributed brain areas involved in: (i) memory, including the hippocampi; (ii) motor actions with the precentral gyri; (iii) and emotion processing with the insula. Interestingly, increased activations in the cingulate gyri and putamen, highlighted their potential key role in the emotion-action binding, due to their involvement in emotion processing, motor actions, and memory. The present study confirmed our previous results and point out for the first time the functional brain activity related to the emotion-action association.
Si Nanocrystal-Embedded SiO
x
nanofoils: Two-Dimensional Nanotechnology-Enabled High Performance Li Storage Materials
Authors: Yoo Hyundong , Park Eunjun , Bae Juhye , Lee Jaewoo , Chung Dong Jae , Jo Yong Nam , Park Min-Sik , Kim Jung Ho , Dou Shi Xue , Kim Young-Jun , Kim Hansu
Published: April 2018

Silicon (Si) based materials are highly desirable to replace currently used graphite anode for lithium ion batteries. Nevertheless, its usage is still a big challenge due to poor battery performance and scale-up issue. In addition, two-dimensional (2D) architectures, which remain unresolved so far, would give them more interesting and unexpected properties. Herein, we report a facile, cost-effective, and scalable approach to synthesize Si nanocrystals embedded 2D SiO
x
nanofoils for next-generation lithium ion batteries through a solution-evaporation-induced interfacial sol-gel reaction of hydrogen silsesquioxane (HSiO1.5, HSQ). The unique nature of the thus-prepared centimeter scale 2D nanofoil with a large surface area enables ultrafast Li+ insertion and extraction, with a reversible capacity of more than 650 mAh g−1, even at a high current density of 50 C (50 A g−1). Moreover, the 2D nanostructured Si/SiO
x
nanofoils show excellent cycling performance up to 200 cycles and maintain their initial dimensional stability. This superior performance stems from the peculiar nanoarchitecture of 2D Si/SiO
x
nanofoils, which provides short diffusion paths for lithium ions and abundant free space to effectively accommodate the huge volume changes of Si during cycling.
Mineral dust as a driver of carbon accumulation in northern latitudes
Authors: Kylander Malin E. , Martínez-Cortizas A. , Bindler Richard , Kaal Joeri , Sjöström Jenny K. , Hansson Sophia V. , Silva-Sánchez Noemí , Greenwood Sarah L. , Gallagher Kerry , Rydberg Johan , Mörth Carl-Magnus , Rauch Sebastien
Published: April 2018

Peatlands in northern latitudes sequester one third of the world’s soil organic carbon. Mineral dusts can affect the primary productivity of terrestrial systems through nutrient transport but this process has not yet been documented in these peat-rich regions. Here we analysed organic and inorganic fractions of an 8900-year-old sequence from Store Mosse (the “Great Bog”) in southern Sweden. Between 5420 and 4550 cal yr BP, we observe a seven-fold increase in net peat-accumulation rates corresponding to a maximum carbon-burial rate of 150 g C m−2 yr−1 – more than six times the global average. This high peat accumulation event occurs in parallel with a distinct change in the character of the dust deposited on the bog, which moves from being dominated by clay minerals to less weathered, phosphate and feldspar minerals. We hypothesize that this shift boosted nutrient input to the bog and stimulated ecosystem productivity. This study shows that diffuse sources and dust dynamics in northern temperate latitudes, often overlooked by the dust community in favour of arid and semi-arid regions, can be important drivers of peatland carbon accumulation and by extension, global climate, warranting further consideration in predictions of future climate variability.
Concurrent micro- to macro-cardiac electrophysiology in myocyte cultures and human heart slices
Authors: Chowdhury Rasheda A. , Tzortzis Konstantinos N. , Dupont Emmanuel , Selvadurai Shaun , Perbellini Filippo , Cantwell Chris D. , Ng Fu Siong , Simon Andre R. , Terracciano Cesare M. , Peters Nicholas S.
Published: April 2018

The contact cardiac electrogram is derived from the extracellular manifestation of cellular action potentials and cell-to-cell communication. It is used to guide catheter based clinical procedures. Theoretically, the contact electrogram and the cellular action potential are directly related, and should change in conjunction with each other during arrhythmogenesis, however there is currently no methodology by which to concurrently record both electrograms and action potentials in the same preparation for direct validation of their relationships and their direct mechanistic links. We report a novel dual modality apparatus for concurrent electrogram and cellular action potential recording at a single cell level within multicellular preparations. We further demonstrate the capabilities of this system to validate the direct link between these two modalities of voltage recordings.
Publisher Correction: A smartphone app to reduce excessive alcohol consumption: Identifying the effectiveness of intervention components in a factorial randomised control trial
Authors: Crane David , Garnett Claire , Michie Susan , West Robert , Brown Jamie
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
EAAC1 gene deletion reduces adult hippocampal neurogenesis after transient cerebral ischemia
Authors: Choi Bo Young , Won Seok Joon , Kim Jin Hee , Sohn Min , Song Hong Ki , Chung Tae Nyoung , Kim Tae Yul , Suh Sang Won
Published: April 2018

Several studies have demonstrated that excitatory amino acid carrier-1 (EAAC1) gene deletion exacerbates hippocampal and cortical neuronal death after ischemia. However, presently there are no studies investigating the role of EAAC1 in hippocampal neurogenesis. In this study, we tested the hypothesis that reduced cysteine transport into neurons by EAAC1 knockout negatively affects adult hippocampal neurogenesis under physiological or pathological states. This study used young mice (aged 3–5 months) and aged mice (aged 11–15 months) of either the wild-type (WT) or EAAC1
−/−
genotype. Ischemia was induced through the occlusion of bilateral common carotid arteries for 30 minutes. Histological analysis was performed at 7 or 30 days after ischemia. We found that both young and aged mice with loss of the EAAC1 displayed unaltered cell proliferation and neuronal differentiation, as compared to age-matched WT mice under ischemia-free conditions. However, neurons generated from EAAC1
−/−
mice showed poor survival outcomes in both young and aged mice. In addition, deletion of EAAC1 reduced the overall level of neurogenesis, including cell proliferation, differentiation, and survival after ischemia. The present study demonstrates that EAAC1 is important for the survival of newly generated neurons in the adult brain under physiological and pathological conditions. Therefore, this study suggests that EAAC1 plays an essential role in modulating hippocampal neurogenesis.
Electrochemical detection of NGF using a reduced graphene oxide- titanium nitride nanocomposite
Authors: Wei Zheng , Wang Yanchun , Zhang Junping
Published: April 2018

There is a correlation between the severity of neurological impairment in patients that have suffered a cerebrovascular accident and the nerve growth factor (NGF) level. This study addressed the fabrication of a titanium nitride (TiN) and reduced graphene oxide (RGO)-based composite with remarkable electrocatalytic activity towards NGF oxidation in a phosphate buffer solution (PB, 0.1 M). The proposed electrochemical sensor was linearly related to the NGF concentration in the range of 10 nM-5 μM with a detection limit of 2.6 nM.
Chalcogen passivation: an in-situ method to manipulate the morphology and electrical property of GaAs nanowires
Authors: Yang Zai-xing , Yin Yanxue , Sun Jiamin , Bian Luozhen , Han Ning , Zhou Ziyao , Shu Lei , Wang Fengyun , Chen Yunfa , Song Aimin , Ho Johnny C.
Published: April 2018

Recently, owing to the large surface-area-to-volume ratio of nanowires (NWs), manipulation of their surface states becomes technologically important and being investigated for various applications. Here, an in-situ surfactant-assisted chemical vapor deposition is developed with various chalcogens (e.g. S, Se and Te) as the passivators to enhance the NW growth and to manipulate the controllable p-n conductivity switching of fabricated NW devices. Due to the optimal size effect and electronegativity matching, Se is observed to provide the best NW surface passivation in diminishing the space charge depletion effect induced by the oxide shell and yielding the less p-type (i.e. inversion) or even insulating conductivity, as compared with S delivering the intense p-type conductivity for thin NWs with the diameter of ~30 nm. Te does not only provide the surface passivation, but also dopes the NW surface into n-type conductivity by donating electrons. All of the results can be extended to other kinds of NWs with similar surface effects, resulting in careful device design considerations with appropriate surface passivation for achieving the optimal NW device performances.
Explicit size distributions of failure cascades redefine systemic risk on finite networks
Authors: Burkholz Rebekka , Herrmann Hans J. , Schweitzer Frank
Published: April 2018

How big is the risk that a few initial failures of nodes in a network amplify to large cascades that span a substantial share of all nodes? Predicting the final cascade size is critical to ensure the functioning of a system as a whole. Yet, this task is hampered by uncertain and missing information. In infinitely large networks, the average cascade size can often be estimated by approaches building on local tree and mean field approximations. Yet, as we demonstrate, in finite networks, this average does not need to be a likely outcome. Instead, we find broad and even bimodal cascade size distributions. This phenomenon persists for system sizes up to 107 and different cascade models, i.e. it is relevant for most real systems. To show this, we derive explicit closed-form solutions for the full probability distribution of the final cascade size. We focus on two topological limit cases, the complete network representing a dense network with a very narrow degree distribution, and the star network representing a sparse network with a inhomogeneous degree distribution. Those topologies are of great interest, as they either minimize or maximize the average cascade size and are common motifs in many real world networks.
Cryptic species in a well-known habitat: applying taxonomics to the amphipod genus Epimeria (Crustacea, Peracarida)
Authors: Beermann Jan , Westbury Michael V. , Hofreiter Michael , Hilgers Leon , Deister Fabian , Neumann Hermann , Raupach Michael J.
Published: April 2018

Taxonomy plays a central role in biological sciences. It provides a communication system for scientists as it aims to enable correct identification of the studied organisms. As a consequence, species descriptions should seek to include as much available information as possible at species level to follow an integrative concept of ‘taxonomics’. Here, we describe the cryptic speciesEpimeria frankeisp. nov. from the North Sea, and also redescribe its sister species,Epimeria cornigera. The morphological information obtained is substantiated by DNA barcodes and complete nuclear 18S rRNA gene sequences. In addition, we provide, for the first time, full mitochondrial genome data as part of a metazoan species description for a holotype, as well as the neotype. This study represents the first successful implementation of the recently proposed concept of taxonomics, using data from high-throughput technologies for integrative taxonomic studies, allowing the highest level of confidence for both biodiversity and ecological research.
Inherent flexibility of CLIC6 revealed by crystallographic and solution studies
Authors: Ferofontov Alisa , Strulovich Roi , Marom Milit , Giladi Moshe , Haitin Yoni
Published: April 2018

Chloride intracellular channels (CLICs) are a family of unique proteins, that were suggested to adopt both soluble and membrane-associated forms. Moreover, following this unusual metamorphic change, CLICs were shown to incorporate into membranes and mediate ion conductionin vitro, suggesting multimerization upon membrane insertion. Here, we present a 1.8 Å resolution crystal structure of the CLIC domain of mouse CLIC6 (mCLIC6). The structure reveals a monomeric arrangement and shows a high degree of structural conservation with other CLICs. Small-angle X-ray scattering (SAXS) analysis of mCLIC6 demonstrated that the overall solution structure is similar to the crystallographic conformation. Strikingly, further analysis of the SAXS data using ensemble optimization method unveiled additional elongated conformations, elucidating high structural plasticity as an inherent property of the protein. Moreover, structure-guided perturbation of the inter-domain interface by mutagenesis resulted in a population shift towards elongated conformations of mCLIC6. Additionally, we demonstrate that oxidative conditions induce an increase in mCLIC6 hydrophobicity along with mild oligomerization, which was enhanced by the presence of membrane mimetics. Together, these results provide mechanistic insights into the metamorphic nature of mCLIC6.
Seasonal dynamics of typhoid and paratyphoid fever
Authors: Saad Neil J. , Lynch Victoria D. , Antillón Marina , Yang Chongguang , Crump John A. , Pitzer Virginia E.
Published: April 2018

Typhoid and paratyphoid fever may follow a seasonal pattern, but this pattern is not well characterized. Moreover, the environmental drivers that influence seasonal dynamics are not fully understood, although increasing evidence suggests that rainfall and temperature may play an important role. We compiled a database of typhoid, paratyphoid, or enteric fever and their potential environmental drivers. We assessed the seasonal dynamics by region and latitude, quantifying the mean timing of peak prevalence and seasonal variability. Moreover, we investigated the potential drivers of the seasonal dynamics and compared the seasonal dynamics for typhoid and paratyphoid fever. We observed a distinct seasonal pattern for enteric and typhoid fever by latitude, with seasonal variability more pronounced further from the equator. We also found evidence of a positive association between preceding rainfall and enteric fever among settings 35°–11°N and a more consistent positive association between temperature and enteric fever incidence across most regions of the world. In conclusion, we identified varying seasonal dynamics for enteric or typhoid fever in association with environmental factors. The underlying mechanisms that drive the seasonality of enteric fever are likely dependent on the local context and should be taken into account in future control efforts.