bluuebunny/crossref_metadata_2025 huggingface dataset:
Unstructural biology of the dengue virus proteins
Authors: Meng Fanchi , Badierah Reaid A. , Almehdar Hussein A. , Redwan Elrashdy M. , Kurgan Lukasz , Uversky Vladimir N.
Published: June 2015

In this study, we used a wide spectrum of bioinformatics techniques to evaluate the extent of intrinsic disorder in the complete proteomes of genotypes of four human dengue virus (DENV), to analyze the peculiarities of disorder distribution within individual DENV proteins, and to establish potential roles for the structural disorder with respect to their functions. We show that several proteins (ER, E, 1, 2A and 4A) are predicted to be mostly ordered, whereas four proteins (C, 2k, NS3 and NS5) are expected to have high disorder levels. The profiles of disorder propensities are similar across the four genotypes, except for the NS5 protein. Cleavage sites are depleted in polymorphic sites, and have a high propensity for disorder, especially relative to neighboring residues. Disordered regions are highly polymorphic in type 1 DENV but have a relatively low number of polymorphic sites in the type 4 virus. There is a high density of polymorphisms in proteins 2A and 4A, which are depleted in disorder. Thus, a high density of polymorphism is not unique to disordered regions. Analysis of disorder/function association showed that the predominant function of the disordered regions in the DENV proteins is protein–protein interaction and binding of nucleic acids, metals and other small molecules. These regions are also associated with phosphorylation, which may regulate their function.
A novel mixed‐mode brittle fracture criterion for crack growth path prediction under static and fatigue loading
Authors: Sajjadi S. H. , Ostad Ahmad Ghorabi M. J. , Salimi‐Majd D.
Published: June 2015

In this paper, in order to predict the crack growth direction and fracture load under mixed modes I and II loading, a new criterion is proposed. For this purpose, after reviewing existing criteria, an effective stress is defined so as to include the influential stress components in fracture and exclude insignificant ones. Moreover, investigations show that most criteria predict a certain angle of fracture in pure mode II independent of material properties, although the experimental results are noticeably different for various materials. To solve this problem, effects of the ratio of fracture toughness for pure mode II to that of pure mode I are considered by defining a new material parameter. To verify the suggested criterion, after characterization of the newly defined material parameter, the predicted values using this criterion for the mixed‐mode conditions are computed. The predicted results show a good agreement with the experimental results.
Changes in soil moisture drive soil methane uptake along a fire regeneration chronosequence in a eucalypt forest landscape
Authors: Fest Benedikt , Wardlaw Tim , Livesley Stephen J. , Duff Thomas J. , Arndt Stefan K.
Published: June 2015

Disturbance associated with severe wildfires (WF) and WF simulating harvest operations can potentially alter soil methane (CH4) oxidation in well‐aerated forest soils due to the effect on soil properties linked to diffusivity, methanotrophic activity or changes in methanotrophic bacterial community structure. However, changes in soil CH4 flux related to such disturbances are still rarely studied even though WF frequency is predicted to increase as a consequence of global climate change. We measured in‐situ soil–atmosphere CH4 exchange along a wet sclerophyll eucalypt forest regeneration chronosequence in Tasmania, Australia, where the time since the last severe fire or harvesting disturbance ranged from 9 to >200 years. On all sampling occasions, mean CH4 uptake increased from most recently disturbed sites (9 year) to sites at stand ‘maturity’ (44 and 76 years). In stands >76 years since disturbance, we observed a decrease in soil CH4 uptake. A similar age dependency of potential CH4 oxidation for three soil layers (0.0–0.05, 0.05–0.10, 0.10–0.15 m) could be observed on incubated soils under controlled laboratory conditions. The differences in soil CH4 uptake between forest stands of different age were predominantly driven by differences in soil moisture status, which affected the diffusion of atmospheric CH4 into the soil. The observed soil moisture pattern was likely driven by changes in interception or evapotranspiration with forest age, which have been well described for similar eucalypt forest systems in south‐eastern Australia. Our results imply that there is a large amount of variability in CH4 uptake at a landscape scale that can be attributed to stand age and soil moisture differences. An increase in severe WF frequency in response to climate change could potentially increase overall forest soil CH4 sinks.
Clinical Pain Catastrophizing in Women With Migraine and Obesity
Authors: Bond Dale S. , Buse Dawn C. , Lipton Richard B. , Thomas J. Graham , Rathier Lucille , Roth Julie , Pavlovic Jelena M. , Evans E. Whitney , Wing Rena R.
Published: June 2015

Objective/Background

Obesity is related to migraine. Maladaptive pain coping strategies (eg, pain catastrophizing) may provide insight into this relationship. In women with migraine and obesity, we cross‐sectionally assessed: (1) prevalence of clinical catastrophizing; (2) characteristics of those with and without clinical catastrophizing; and (3) associations of catastrophizing with headache features.

Methods

Obese women migraineurs seeking weight loss treatment (n = 105) recorded daily migraine activity for 1 month via smartphone and completed the Pain Catastrophizing Scale (PCS). Clinical catastrophizing was defined as total PCS score ≥30. The six‐item Headache Impact Test (HIT‐6), 12‐item Allodynia Symptom Checklist (ASC‐12), Headache Management Self‐Efficacy Scale (HMSE), and assessments for depression (Centers for Epidemiologic Studies Depression Scale) and anxiety (seven‐item Generalized Anxiety Disorder Scale) were also administered. Using PCS scores and body mass index (BMI) as predictors in linear regression, we modeled a series of headache features (ie, headache days, HIT‐6, etc) as outcomes.

Results

One quarter (25.7%; 95% confidence interval [CI] = 17.2‐34.1%) of participants met criteria for clinical catastrophizing: they had higher BMI (37.9 ± 7.5 vs 34.4 ± 5.7 kg/m2, P = .035); longer migraine attack duration (160.8 ± 145.0 vs 97.5 ± 75.2 hours/month, P = .038); higher HIT‐6 scores (68.7 ± 4.6 vs 64.5 ± 3.9, P < .001); more allodynia (7.0 ± 4.1 vs 4.5 ± 3.5, P < .003), depression (25.4 ± 12.4 vs 13.3 ± 9.2, P < .001), and anxiety (11.0 ± 5.2 vs 5.6 ± 4.1, P < .001); and lower self‐efficacy (80.1 ± 25.6 vs 104.7 ± 18.9, P < .001) compared with participants without clinical catastrophizing. The odds of chronic migraine were nearly fourfold greater in those with (n = 8/29.6%) vs without (n = 8/10.3%) clinical catastrophizing (odds ratio = 3.68; 95%CI = 1.22‐11.10, P = .021). In all participants, higher PCS scores were related to more migraine days (β = 0.331, P = .001), longer attack duration (β = 0.390, P < .001), higher HIT‐6 scores (β = 0.425, P < .001), and lower HMSE scores (β = −0.437, P < .001). Higher BMI, but not higher PCS scores, was related to more frequent attacks (β = −0.203, P = .044).

Conclusions

One quarter of participants with migraine and obesity reported clinical catastrophizing. These individuals had more frequent attacks/chronicity, longer attack duration, higher pain sensitivity, greater headache impact, and lower headache management self‐efficacy. In all participants, PCS scores were related to several migraine characteristics, above and beyond the effects of obesity. Prospective studies are needed to determine sequence and mechanisms of relationships between catastrophizing, obesity, and migraine.
Cloaked in ubiquitin, a killer hides in plain sight: the molecular regulation of RIPK1
Authors: Justus Scott J. , Ting Adrian T.
Published: June 2015

In the past decade, studies have shown how instrumental programmed cell death (PCD) can be in innate and adaptive immune responses. PCD can be a means to maintain homeostasis, prevent or promote microbial pathogenesis, and drive autoimmune disease and inflammation. The molecular machinery regulating these cell death programs has been examined in detail, although there is still much to be explored. A master regulator of programmed cell death and innate immunity is receptor‐interacting protein kinase 1 (RIPK1), which has been implicated in orchestrating various pathologies via the induction of apoptosis, necroptosis, and nuclear factor‐κB‐driven inflammation. These and other roles for RIPK1 have been reviewed elsewhere. In a reflection of the ability of tumor necrosis factor (TNF) to induce either survival or death response, this molecule in the TNF pathway can transduce either a survival or a death signal. The intrinsic killing capacity of RIPK1 is usually kept in check by the chains of ubiquitin, enabling it to serve in a prosurvival capacity. In this review, the intricate regulatory mechanisms responsible for restraining RIPK1 from killing are discussed primarily in the context of the TNF signaling pathway and how, when these mechanisms are disrupted, RIPK1 is free to unveil its program of cellular demise.
Nanomechanics of Refractory Transition‐Metal Carbides: A Path to Discovering Plasticity in Hard Ceramics
Authors: Kiani Sara , Yang Jenn‐Ming , Kodambaka Suneel
Published: June 2015

Refractory carbides of transition metals (Zr, Ta, etc.), owing to a mixture of ionic, covalent, and metallic bonding, exhibit high hardness (10s of GPa), high elastic moduli (100s of GPa), good resistance to wear, ablation, and corrosion, high‐temperature mechanical strength, along with good electrical conductivities. They are attractive as high‐temperature structural components in aerospace vehicles. Although these materials are exceptionally hard, their structural applications at low temperatures have been limited because of their brittleness. The design of ceramic materials possessing both high hardness and enhanced ductility has been a long‐standing challenge. Various research studies have focused on this topic with limited success. Here, we present a brief review of our recent results obtained from direct observations of mechanical deformation during uniaxial compression of group IV and group V transition‐metal carbide (ZrC and TaC) single crystals inside a transmission electron microscope. Our studies provide new insights into the mechanical deformation mechanisms and help to identify strategies for enhancing room‐temperature plasticity in this class of materials.
Damage Tolerance and Extensive Plastic Deformation of β‐Yb2Si2O7 from Room to High Temperatures
Authors: Tian Zhilin , Zheng Liya , Wang Jiemin , Yang Jinbo , Yang Guang , Wang Jingyang
Published: June 2015

β‐Yb2Si2O7 is a promising environmental barrier coating (EBC) material and recently attracted attention for its damage tolerance. To investigate the mechanisms of its damage tolerance and possible plasticity, dense β‐Yb2Si2O7 sample was synthesized by in situ reaction/hot‐pressing method, and its mechanical properties were measured from room to high temperatures. The low magnitudes of hardness to Young's modulus ratio HV/E, shear modulus to bulk modulus ratio G/B, and high fracture toughness to strength ratio KIC/σ provide evidences of damage tolerance of β‐Yb2Si2O7. β‐Yb2Si2O7 exhibits extensive plastic deformation in Hertzian contact tests at both room and high temperatures. Transmission electron microscopy (TEM) observations show that the deformation mechanisms are different at low and high temperatures. Deformation twinning and parallel dislocation arrangement occur in plastic deformation at room temperature. Above the brittle‐to‐ductile transition temperature (between 1200°C and 1300°C), plastic deformation brings out extensive slip and climb of dislocations, while twinning is seldom observed. Measurement of temperature‐dependent dynamic Young's modulus demonstrates excellent elastic stiffness retention up to 1300°C.
Zinc deficiency impairs the renewal of hippocampal neural stem cells in adult rats: involvement of FoxO3a activation and downstream p27kip1 expression
Authors: Han Jingling , Zhao Jianya , Jiang Junkang , Ma Xia , Liu Xinhang , Wang Cheng , Jiang Shengyang , Wan Chunhua
Published: June 2015

Zinc plays an important role in the development and maintenance of central neural system. Zinc deficiency has been known to alter normal brain function, whose molecular mechanism remains largely elusive. In the present study, we established a zinc deficiency‐exposed rat model, and, using western blot and immunohistochemical analyses, found that the expression of FoxO3a and p27kip1 was remarkably up‐regulated in the rat brain hippocampus. Immunofluorescence assay showed that FOXO3a and p27kip1 were significantly co‐localized with nestin, the marker of neural stem cells (NSCs). Furthermore, we identified that the proportion of proliferating NSCs was markedly decreased in zinc‐deficient rat hippocampaus. Using C17.2 neural stem cells, it was revealed that exposure to zinc chelator N,N,N’,N’‐tetrakis‐(2‐pyridylmethy) ethylenediamine induced the expression of FoxO3a and p27kip1, which coincided with reduced NSC proliferation. Furthermore, depletion of FoxO3a inhibited p27kip1 expression and restored the growth of NSCs. On the basis of these data, we concluded that FoxO3a/p27kip1 signaling might play a significant role in zinc deficiency‐induced growth impairment of NSCs and consequent neurological disorders.

image

We describe here that zinc deficiency induces the proliferative impairment of hippocampal neural stem cells partially through the activation of FOXO3a‐p27 axis in rats. Neural progenitor cells exhibited significantly up‐regulated expression of FOXO3a and p27 after zinc deficiency in vivo and in vitro. Depletion of FOXO3a ameliorates zinc deficiency‐induced expression of p27 and growth impairment of neural stem cells. We provide novel insight into the mechanisms underlying zinc deficiency‐induced neurological deficits.
Transcatheter Closure of Coronary Artery Fistulae: Considerations and Approaches Based on Fistula Origin
Authors: Xiao Yunbin , Gowda Srinath T. , Chen Zhi , Delaney Jeffrey W. , Amin Zahid , Latson Larry A. , Kutty Shelby
Published: June 2015

Objectives

To investigate technical approaches for transcatheter closure of coronary artery fistula based on anatomic type of the fistula.

Background

The variability in coronary artery fistulae (CAF) anatomy that necessitates different transcatheter closure (TCC) approaches has not been well documented.

Methods

Records of patients with CAF who underwent TCC at 2 centers were reviewed for technical details and procedural outcome. CAF were classified as proximal and distal. TCC approaches employed were arterio‐venous or arterio‐arterial loop, retrograde arterial, and antegrade venous.

Results

Eighteen patients with CAF, mean age 12.6 years (0.07–60), 11 male (61%), underwent TCC. All CAF drained predominantly into the right side of the heart. Types of CAF were proximal in 15 and distal in 3 patients. CAF calibers were large in 7, medium in 9, and small in 2 patients. The arterio‐venous loop approach was used in the majority of the cases (11 patients) and the CAF size were medium to large. The retrograde arterial approach was used in 4; of these, 3 patients had small to medium sized CAF. In 2 patients with long tortuous CAF an antegrade venous approach was employed. TCC was successful in 17 of the 18 patients (94.4%). There were no peri‐procedural deaths or vascular complications.

Conclusions

This study documents transcatheter closure approaches for CAF and device selection based on fistula origin. The choices of TCC technique and device selection vary, and are primarily determined by the heterogeneous anatomic characteristics of the fistulae.
Genetic association between VEGF polymorphisms and BRONJ in the Korean population
Authors: Choi H , Lee JH , Lee J‐H , Kim J‐H
Published: June 2015

Objectives

The purpose of this study was to evaluate the association between vascular endothelial growth factor (VEGF) polymorphisms and bisphosphonate‐related osteonecrosis of the jaw (BRONJ) in the Korean population.

Subjects and Methods

Forty‐five individuals (2 men, 43 women; mean age: 68.7 ± 12.3 years) were recruited for this study. All visited the Yonsei University Dental Hospital for surgical intervention from January 2012 to January 2013 and had a history of bisphosphonate (BP) administration (oral and/or intravenous). Patients were allocated to case (n = 26) or control (n = 19) groups according to the patients' selection criteria. Association between three VEGF single nucleotide polymorphisms (rs699947 (‐2578 C>A), rs2010963 (‐634 G>C) and rs3025039 (+936 C>T)) and BRONJ were investigated using multiple logistic regression analysis and Fisher's exact test where appropriate (α = 0.05).

Results

The CC homozygotes of rs2010963 and rs3025039 of VEGF gene were associated with an increased risk of BRONJ (P = 0.04, 0.03, respectively). In haplotype analysis, no differences in haplotype C‐C (‐2578/‐634) and haplotype C‐C‐C (‐2578/‐634/+936) were observed.

Conclusion

The CC homozygotes of rs2010963 and rs3025039 polymorphisms in the VEGF gene were associated with an increased risk of BRONJ in the Korean population. Further epidemiological cohort studies with a larger sample size would be required to confirm the suggestive correlations.
Time constraint effects on phenology and life history synchrony in a damselfly along a latitudinal gradient
Authors: Śniegula Szymon , Gołąb Maria J. , Johansson Frank
Published: June 2015

In organisms with complex life cycles living in seasonal environments, the synchronisation of phenological events is important from the ecological and evolutionary perspectives. Life history transitions should be synchronised to a greater degree at northern latitudes. We quantified hatching and emergence timing and synchrony in the obligate univoltine damselfly Lestes sponsa along a latitudinal gradient covering its entire north–south range in Europe. In our first experiment, populations from different latitudes were grown in separate climate chambers simulating temperature and photoperiod conditions occurring at their sites of origin. Northern populations expressed early and high synchronous hatching and emergence, central populations intermediate, and southern populations late and low synchronous hatching and emergence. This pattern was expressed at both population and full‐sibling family levels, indicating stronger selection for timing and synchronisation in the north compared to the south. In our second experiment, populations from all latitudes were reared in conditions simulating an average temperature and photoperiod over the latitudinal gradient. Interestingly, the pattern of timing and synchronisation was reversed with respect to latitude when compared to the pattern shown in the first experiment, indicating the importance of environmental factors in shaping phenological events. Our results indicate strong selection for timing and synchronisation of life history events at northern latitudes, caused by time constraints. Our results also show that it is important to use as natural conditions as possible in experiments on life history shifts in organisms with complex life cycles in order to achieve a correct understanding of these shifts.
Basipetal auxin versus acropetal cytokinin transport, and their interaction with NO3 fertilisation in cotyledon senescence and sink:source relationships in cucumber (Cucumis sativus L.)
Authors: Bangerth K.‐F.
Published: June 2015

The paramount role of cytokinins (CKs) in initiation, as well as prevention, of senescence is well established. In recent years, experimental methods have become available to raise and lower the CK concentration and experimentally manipulate senescence. Decapitating the apical shoot and adding the synthetic auxin naphthylacetic acid to the cut stem reduced endogenous CKs to low levels. Conversely, if no auxin was applied, xylem and leaf CK levels increased dramatically, indicating that basipolar auxin transport is a key determinant in the synthesis of CKs and is potentially more important than NO3. Manipulating the concentration of applied NO3 caused considerable variation in leaf CK levels and concomitant changes in senescence. These and other results suggest that the frequently discussed decrease in nitrogen use efficiency (NUE) may be more highly regulated by CKs than by NO3. Analysis of the re‐metabolisation and re‐allocation of chlorophyll, proteins, amino acids and starch in three different cucumber cultivars indirectly showed that these metabolites were significantly affected by the concentration of CKs in the leaves. Further research in this area may allow leaf senescence and plant yield to be more efficiently regulated by manipulating CKs and/or basipolar auxin transport instead of nitrate.
Cryopreservation and In Vitro culture of Preimplantation Embryos in Djungarian Hamster (Phodopus sungorus)
Authors: Brusentsev EYu , Abramova TO , Rozhkova IN , Igonina TN , Naprimerov VA , Feoktistova NYu , Amstislavsky SYa
Published: June 2015

Contents

Although embryo cryobanking was applied to Syrian golden and to Campbell's hamsters, no attempt has been made at freezing embryos in Djungarian hamsters. Four‐cell stage embryos were flushed from the reproductive ducts of pregnant females before noon of the third‐day post coitum and frozen in 0.25‐ml straws according to standard procedures of slow cooling. A mixture of permeating (ethylene glycol) and non‐permeating (sucrose) cryoprotectants was used. The thawing was performed by incubating at RT for 40 s followed by 40 s in a water bath at 30.0°C. Most (66.7%) of the non‐frozen four‐cell embryos developed up to the morula stage in rat one‐cell embryo culture medium (R1ECM). The use of hamster embryo culture medium (HECM) yielded fewer morulas (18.2%) during the same 24‐h period of culture. The rate of embryo's surviving the freezing–thawing procedures, as estimated by light microscopy, was 60.7–68.8%. After 24‐h culturing in R1ECM, 64.7% of frozen–thawed four‐cell embryos developed and all of them reached the morula stage. Supplementation of R1ECM with GM‐CSF (2 ng/ml) improved the rate of Djungarian hamster frozen–thawed embryo development: 100% of the four‐cell stage embryos developed, 50% of them achieved the morula stage, and 50% developed even further and reached the blastocyst stage within 24 h of culturing. This study reports the world's first successful transfer of frozen–thawed Djungarian hamster embryos yielding term pups. Taken together, the results of this study demonstrate the possibility of applying some key reproductive technologies, that is, embryo freezing/cryopreservation and in vitro culture, to Djungarian hamsters.
Simulation of the Collection of Catch Crops for the Recovery of Agricultural Resources using Geographic and Statistical Data
Authors: Matsuoka Masayuki , Nagare Hideaki , Fujiwara Taku
Published: June 2015

The cultivation of catch crops has great potential in agricultural areas for the recovery of nutrients, mitigation of groundwater contamination, and secondary utilization of harvestry. To estimate the potential volume of catch crops that can be collected at prospective locations, we simulated the cultivation and collection process at a regional scale using geographic and statistical data. Three types of geographic data, namely the locations of greenhouses, collecting stations and road networks, were used in a geographic information system to compute the volume of collected catch crops and carrying distance between greenhouses and collecting stations. Carbon emission from transportation of the catch crop was calculated using an improved ton‐km method, and the results were compared with the carbon content of the catch crop to evaluate the carbon balance. We found that the total fresh weight of the collected catch crops was 67900 t, of which 70% was collected at the top 15 of 73 stations. Carbon emissions from transportation ranged from >1 to 12% of the carbon content of the catch crop. The analytical method used in this study can readily be applied to other environmental studies concerning the collection of agricultural products and other biomass resources.
Effects of intravenous administration of tranexamic acid on hematological, hemostatic, and thromboelastographic analytes in healthy adult dogs
Authors: Kelmer Efrat , Segev Gilad , Papashvilli Victoria , Rahimi‐Levene Naomi , Bruchim Yaron , Aroch Itamar , Klainbart Sigal
Published: June 2015

Objective

To assess the effects of tranexamic acid (TA) on hematological, hemostatic, and thromboelastographic analytes in healthy adult dogs.

Design

Prospective study.

Setting

University teaching hospital.

Animals

Eleven healthy, staff‐owned, adult dogs.

Measurements and Main Results

Dogs were administered TA as an IV bolus, followed by a 3‐hour constant rate infusion (CRI). Complete blood count, prothrombin time, activated partial thromboplastin time, D‐dimer, antithrombin, fibrinogen, and thromboelastography (TEG) were measured prior to, and immediately after TA administration. Vomiting occurred transiently in the first 2 treated dogs, immediately after 20 and 15 mg/kg IV boluses, but not during the CRI. In all other dogs the TA IV bolus dose was reduced to 10 mg/kg, and administered slower, and vomiting did not occur. All measured hemostatic and hematological analytes remained within their reference intervals, however, following TA treatment, significant decreases were recorded in prothrombin time, TEG R and A30 values, Hct, and hemoglobin concentration, while the TEG LY30 significantly increased.

Conclusions

Administration of TA as a slow IV bolus at 10 mg/kg, followed by a 10 mg/kg/h CRI over 3 hours to healthy dogs is safe; however, its effect on TEG A30, A60, LY30, and LY60 values was inconsistent with its expected anti‐fibrinolytic properties.
Implementation of the floods directive in selected EU member states
Authors: Nones Michael
Published: June 2015

To reduce the flood risk at European scale, the Floods Directive (FD) became into force in 2007. Each member state had transposed the directive in national laws and guidelines, generating a quite spotted situation. This work is intended to compare and briefly assess the implementation process on rivers in selected European countries by means of the available literature and a specific questionnaire. Different structures, methodologies and data conditions used for preliminary flood risk assessment, flood hazard maps, flood risk maps and flood risk management plans are here presented and analysed. To minimise the flood risk, the technical differences between the EU countries need to be reduced in the next implementation cycles of the FD.
Hierarchical and symmetric infant image registration by robust longitudinal‐example‐guided correspondence detection
Authors: Wu Yao , Wu Guorong , Wang Li , Munsell Brent C. , Wang Qian , Lin Weili , Feng Qianjin , Chen Wufan , Shen Dinggang
Published: June 2015

Purpose:

To investigate anatomical differences across individual subjects, or longitudinal changes in early brain development, it is important to perform accurate image registration. However, due to fast brain development and dynamic tissue appearance changes, it is very difficult to align infant brain images acquired from birth to 1‐yr‐old.

Methods:

To solve this challenging problem, a novel image registration method is proposed to align two infant brain images, regardless of age at acquisition. The main idea is to utilize the growth trajectories, or spatial‐temporal correspondences, learned from a set of longitudinal training images, for guiding the registration of two different time‐point images with different image appearances. Specifically, in the training stage, an intrinsic growth trajectory is first estimated for each training subject using the longitudinal images. To register two new infant images with potentially a large age gap, the corresponding images patches between each new image and its respective training images with similar age are identified. Finally, the registration between the two new images can be assisted by the learned growth trajectories from one time point to another time point that have been established in the training stage. To further improve registration accuracy, the proposed method is combined with a hierarchical and symmetric registration framework that can iteratively add new key points in both images to steer the estimation of the deformation between the two infant brain images under registration.

Results:

To evaluate image registration accuracy, the proposed method is used to align 24 infant subjects at five different time points (2‐week‐old, 3‐month‐old, 6‐month‐old, 9‐month‐old, and 12‐month‐old). Compared to the state‐of‐the‐art methods, the proposed method demonstrated superior registration performance.

Conclusions:

The proposed method addresses the difficulties in the infant brain registration and produces better results compared to existing state‐of‐the‐art registration methods.
Segment Kinematics Differ Between Jump and Drop Landings Regardless of Practice
Authors: Chiu Loren Z.F. , Moolyk Amy N.
Published: June 2015

Joint kinematics differ between jump and drop landings and there is evidence that segment kinematics may also be different. The purpose of this research was to compare lower extremity segment kinematics for jump and drop landings, and to examine if multiple days of practice would influence these kinematics. Men (n = 9) and women (n = 15) performed 4 sessions of jump and drop landings (40 cm and 60 cm) in a motion-capture laboratory. Segment kinematics at initial contact, foot flat, and peak knee flexion were compared between landing types and across visits. At initial contact, foot plantar flexion was greater in jump versus drop landings (P < .05). At initial contact and foot flat, forward leg inclination and pelvis flexion were greater in jump landing (P < .05), while thigh flexion was greater in drop landings (P > .05). The differences in leg and thigh angles at initial contact and foot flat altered lower extremity posture. These results are in contrast to a previous study; this suggests that drop landing can be modified to have the same mechanics as jump landing. As practice did not influence drop landing mechanics (P > .05), specific control strategies and instructions need to be identified.
The return of Philae
Authors: Hand Eric , Clery Daniel
Published: June 2015

Revived after hibernation, comet lander awaits orders.
Research chimps will soon be listed as ‘endangered’
Authors: Grimm David
Published: June 2015

Ruling could disrupt biomedical research.
Republicans split on climate, social science spending
Authors: Mervis Jeffrey
Published: June 2015

House calls for cuts, Senate favors status quo.
Last dance?
Authors: Lavelle Marianne
Published: June 2015

An urgent effort to save the West's iconic lesser prairie chicken could point the way to a truce in other endangered-species battles.
Topological defect dynamics in operando battery nanoparticles
Authors: Ulvestad A. , Singer A. , Clark J. N. , Cho H. M. , Kim J. W. , Harder R. , Maser J. , Meng Y. S. , Shpyrko O. G.
Published: June 2015

Watching defects during battery cycling

Dislocations affect the mechanical properties of a material. Ulvestad
et al.
studied the influence of dislocations on a nanoparticle undergoing charge and discharge cycles in a lithium ion battery. The defects influenced the way the material expanded and contracted during cycling. In the future, it may be possible to tune the properties of a material through controlled defect engineering.

Science
, this issue p.
1344
Long-lived photoinduced polaron formation in conjugated polyelectrolyte-fullerene assemblies
Authors: Huber Rachel C. , Ferreira Amy S. , Thompson Robert , Kilbride Daniel , Knutson Nicholas S. , Devi Lekshmi Sudha , Toso Daniel B. , Challa J. Reddy , Zhou Z. Hong , Rubin Yves , Schwartz Benjamin J. , Tolbert Sarah H.
Published: June 2015

Photoinduction of long-lived polarons

Photosynthetic complexes and organic photovoltaics can rapidly create separated charges upon photoexcitation. However, unproductive charge recombination often occurs in the human-made system. This is in part because the charge acceptor and donor structures are much larger. Huber
et al.
created aqueous micelles that pair conjugated polyelectrolyte charge donors with fullerene acceptors at a much smaller interface. They observed the photoinduced formation of polarons—stable pairs of separated charges—with lifetimes of several days.

Science
, this issue p.
1340
A mucosal vaccine against
Chlamydia trachomatis
generates two waves of protective memory T cells
Authors: Stary Georg , Olive Andrew , Radovic-Moreno Aleksandar F. , Gondek David , Alvarez David , Basto Pamela A. , Perro Mario , Vrbanac Vladimir D. , Tager Andrew M. , Shi Jinjun , Yethon Jeremy A. , Farokhzad Omid C. , Langer Robert , Starnbach Michael N. , von Andrian Ulrich H.
Published: June 2015

The right combination for protection

Despite its prevalence, no vaccine exists to protect against infection with the sexually transmitted bacterium
Chlamydia trachomatis
. Stary
et al.
now report on one potential vaccine candidate (see the Perspective by Brunham). Vaccinating with an ultraviolet light-inactivated
C. trachomatis
linked to adjuvant-containing charged nanoparticles protected female conventional and humanized mice against
C. trachomatis
infection. The vaccine conferred protection only when delivered through mucosal routes. Protection relied on targeting the bacteria to a particular population of immunogenic dendritic cells and inducing memory T cells that resided in the female genital tract.

Science
, this issue
10.1126/science.aaa8205
; see also p.
1322
Endocytic sites mature by continuous bending and remodeling of the clathrin coat
Authors: Avinoam Ori , Schorb Martin , Beese Carsten J. , Briggs John A. G. , Kaksonen Marko
Published: June 2015

Bend me, shape me: Clathrin in action

Endocytic clathrin-coated pits were among the first cellular structures described by electron microscopy over five decades ago. Despite this, the question remains: Does clathrin bind to the membrane as a flat lattice and then bend during coated pit invagination, or does clathrin assemble with a defined curvature as membranes invaginate? Avinoam
et al.
applied two state-of-the-art imaging approaches to resolve this conflict. They suggest that clathrin assembles into a defined flat lattice early in endocytosis, which predetermines the size of the vesicle. The assembled clathrin coat then rearranges through dynamic exchange of clathrin with the cytosolic pool to wrap around the forming vesicle.

Science
, this issue p.
1369
Pneumococcal Capsules and Their Types: Past, Present, and Future
Authors: Geno K. Aaron , Gilbert Gwendolyn L. , Song Joon Young , Skovsted Ian C. , Klugman Keith P. , Jones Christopher , Konradsen Helle B. , Nahm Moon H.
Published: June 2015

Streptococcus pneumoniae(the pneumococcus) is an important human pathogen. Its virulence is largely due to its polysaccharide capsule, which shields it from the host immune system, and because of this, the capsule has been extensively studied. Studies of the capsule led to the identification of DNA as the genetic material, identification of many different capsular serotypes, and identification of the serotype-specific nature of protection by adaptive immunity. Recent studies have led to the determination of capsular polysaccharide structures for many serotypes using advanced analytical technologies, complete elucidation of genetic basis for the capsular types, and the development of highly effective pneumococcal conjugate vaccines. Conjugate vaccine use has altered the serotype distribution by either serotype replacement or switching, and this has increased the need to serotype pneumococci. Due to great advances in molecular technologies and our understanding of the pneumococcal genome, molecular approaches have become powerful tools to predict pneumococcal serotypes. In addition, more-precise and -efficient serotyping methods that directly detect polysaccharide structures are emerging. These improvements in our capabilities will greatly enhance future investigations of pneumococcal epidemiology and diseases and the biology of colonization and innate immunity to pneumococcal capsules.
Evaluation of the Long-Term Anti-Human Papillomavirus 6 (HPV6), 11, 16, and 18 Immune Responses Generated by the Quadrivalent HPV Vaccine
Authors: Nygård Mari , Saah Alfred , Munk Christian , Tryggvadottir Laufey , Enerly Espen , Hortlund Maria , Sigurdardottir Lara G. , Vuocolo Scott , Kjaer Susanne K. , Dillner Joakim
Published: June 2015

This quadrivalent human papillomavirus (qHPV) (HPV6, -11, -16, and -18) vaccine long-term follow-up (LTFU) study is an ongoing extension of a pivotal clinical study (FUTURE II) taking place in the Nordic region. The LTFU study was designed to evaluate the effectiveness, immunogenicity, and safety of the qHPV vaccine (Gardasil) for at least 10 years following completion of the base study. The current report presents immunogenicity data from testing samples of the year 5 LTFU visit (approximately 9 years after vaccination). FUTURE II vaccination arm subjects, who consented to being followed in the LTFU, donated serum at regular intervals and in 2012. Anti-HPV6, -11, -16, and -18 antibodies were detected by the competitive Luminex immunoassay (cLIA), and in addition, serum samples from 2012 were analyzed by the total IgG Luminex immunoassay (LIA) (
n
= 1,598). cLIA geometric mean titers (GMTs) remained between 70% and 93% of their month 48 value depending on HPV type. For all HPV types, the lower bound of the 95% confidence interval (CI) for the year 9 GMTs remained above the serostatus cutoff value. The proportion of subjects who remained seropositive based on the IgG LIA was higher than the proportion based on cLIA, especially for anti-HPV18. As expected, the anti-HPV serum IgG and cLIA responses were strongly correlated for all HPV types. Anti-HPV GMTs and the proportion of vaccinated individuals who are seropositive remain high for up to 9 years of follow-up after vaccination.
Rapidec Carba NP Test for Rapid Detection of Carbapenemase Producers
Authors: Poirel Laurent , Nordmann Patrice
Published: June 2015

Performances of the Rapidec Carba NP test (bioMérieux) were evaluated for detection of all types of carbapenemases in
Enterobacteriaceae
,
Acinetobacter baumannii
, and
Pseudomonas aeruginosa
. In less than 2 h after sample preparation, it showed a sensitivity and specificity of 96%. This ready-to-use test is well adapted to the daily need for detection of carbapenemase producers in any laboratory worldwide.
Biology of Zika Virus Infection in Human Skin Cells
Authors: Hamel Rodolphe , Dejarnac Ophélie , Wichit Sineewanlaya , Ekchariyawat Peeraya , Neyret Aymeric , Luplertlop Natthanej , Perera-Lecoin Manuel , Surasombatpattana Pornapat , Talignani Loïc , Thomas Frédéric , Cao-Lormeau Van-Mai , Choumet Valérie , Briant Laurence , Desprès Philippe , Amara Ali , Yssel Hans , Missé Dorothée
Published: June 2015

Zika virus (ZIKV) is an emerging arbovirus of the
Flaviviridae
family, which includes dengue, West Nile, yellow fever, and Japanese encephalitis viruses, that causes a mosquito-borne disease transmitted by the
Aedes
genus, with recent outbreaks in the South Pacific. Here we examine the importance of human skin in the entry of ZIKV and its contribution to the induction of antiviral immune responses. We show that human dermal fibroblasts, epidermal keratinocytes, and immature dendritic cells are permissive to the most recent ZIKV isolate, responsible for the epidemic in French Polynesia. Several entry and/or adhesion factors, including DC-SIGN, AXL, Tyro3, and, to a lesser extent, TIM-1, permitted ZIKV entry, with a major role for the TAM receptor AXL. The ZIKV permissiveness of human skin fibroblasts was confirmed by the use of a neutralizing antibody and specific RNA silencing. ZIKV induced the transcription of Toll-like receptor 3 (TLR3), RIG-I, and MDA5, as well as several interferon-stimulated genes, including OAS2, ISG15, and MX1, characterized by strongly enhanced beta interferon gene expression. ZIKV was found to be sensitive to the antiviral effects of both type I and type II interferons. Finally, infection of skin fibroblasts resulted in the formation of autophagosomes, whose presence was associated with enhanced viral replication, as shown by the use of Torin 1, a chemical inducer of autophagy, and the specific autophagy inhibitor 3-methyladenine. The results presented herein permit us to gain further insight into the biology of ZIKV and to devise strategies aiming to interfere with the pathology caused by this emerging flavivirus.

IMPORTANCE
Zika virus (ZIKV) is an arbovirus belonging to the
Flaviviridae
family. Vector-mediated transmission of ZIKV is initiated when a blood-feeding female
Aedes
mosquito injects the virus into the skin of its mammalian host, followed by infection of permissive cells via specific receptors. Indeed, skin immune cells, including dermal fibroblasts, epidermal keratinocytes, and immature dendritic cells, were all found to be permissive to ZIKV infection. The results also show a major role for the phosphatidylserine receptor AXL as a ZIKV entry receptor and for cellular autophagy in enhancing ZIKV replication in permissive cells. ZIKV replication leads to activation of an antiviral innate immune response and the production of type I interferons in infected cells. Taken together, these results provide the first general insights into the interaction between ZIKV and its mammalian host.
Molecular Signatures of Immune Activation and Epithelial Barrier Remodeling Are Enhanced during the Luteal Phase of the Menstrual Cycle: Implications for HIV Susceptibility
Authors: Birse Kenzie , Arnold Kelly B. , Novak Richard M. , McCorrister Stuart , Shaw Souradet , Westmacott Garrett R. , Ball Terry B. , Lauffenburger Douglas A. , Burgener Adam
Published: June 2015

The variable infectivity and transmissibility of HIV/SHIV has been recently associated with the menstrual cycle, with particular susceptibility observed during the luteal phase in nonhuman primate models and
ex vivo
human explant cultures, but the mechanism is poorly understood. Here, we performed an unbiased, mass spectrometry-based proteomic analysis to better understand the mucosal immunological processes underpinning this observed susceptibility to HIV infection. Cervicovaginal lavage samples (
n
= 19) were collected, characterized as follicular or luteal phase using days since last menstrual period, and analyzed by tandem mass spectrometry. Biological insights from these data were gained using a spectrum of computational methods, including hierarchical clustering, pathway analysis, gene set enrichment analysis, and partial least-squares discriminant analysis with LASSO feature selection. Of the 384 proteins identified, 43 were differentially abundant between phases (
P
< 0.05, ≥2-fold change). Cell-cell adhesion proteins and antiproteases were reduced, and leukocyte recruitment (interleukin-8 pathway,
P
= 1.41E–5) and extravasation proteins (
P
= 5.62E–4) were elevated during the luteal phase. LASSO/PLSDA identified a minimal profile of 18 proteins that best distinguished the luteal phase. This profile included cytoskeletal elements and proteases known to be involved in cellular movement. Gene set enrichment analysis associated CD4
+
T cell and neutrophil gene set signatures with the luteal phase (
P
< 0.05). Taken together, our findings indicate a strong association between proteins involved in tissue remodeling and leukocyte infiltration with the luteal phase, which may represent potential hormone-associated mechanisms of increased susceptibility to HIV.

IMPORTANCE
Recent studies have discovered an enhanced susceptibility to HIV infection during the progesterone-dominant luteal phase of the menstrual cycle. However, the mechanism responsible for this enhanced susceptibility has not yet been determined. Understanding the source of this vulnerability will be important for designing efficacious HIV prevention technologies for women. Furthermore, these findings may also be extrapolated to better understand the impact of exogenous hormone application, such as the use of hormonal contraceptives, on HIV acquisition risk. Hormonal contraceptives are the most widely used contraceptive method in sub-Saharan Africa, the most HIV-burdened area of the world. For this reason, research conducted to better understand how hormones impact host immunity and susceptibility factors important for HIV infection is a global health priority.
ERdj5 Reductase Cooperates with Protein Disulfide Isomerase To Promote Simian Virus 40 Endoplasmic Reticulum Membrane Translocation
Authors: Inoue Takamasa , Dosey Annie , Herbstman Jeffrey F. , Ravindran Madhu Sudhan , Skiniotis Georgios , Tsai Billy
Published: June 2015

The nonenveloped polyomavirus (PyV) simian virus 40 (SV40) traffics from the cell surface to the endoplasmic reticulum (ER), where it penetrates the ER membrane to reach the cytosol before mobilizing into the nucleus to cause infection. Prior to ER membrane penetration, ER lumenal factors impart structural rearrangements to the virus, generating a translocation-competent virion capable of crossing the ER membrane. Here we identify ERdj5 as an ER enzyme that reduces SV40's disulfide bonds, a reaction important for its ER membrane transport and infection. ERdj5 also mediates human BK PyV infection. This enzyme cooperates with protein disulfide isomerase (PDI), a redox chaperone previously implicated in the unfolding of SV40, to fully stimulate membrane penetration. Negative-stain electron microscopy of ER-localized SV40 suggests that ERdj5 and PDI impart structural rearrangements to the virus. These conformational changes enable SV40 to engage BAP31, an ER membrane protein essential for supporting membrane penetration of the virus. Uncoupling of SV40 from BAP31 traps the virus in ER subdomains called foci, which likely serve as depots from where SV40 gains access to the cytosol. Our study thus pinpoints two ER lumenal factors that coordinately prime SV40 for ER membrane translocation and establishes a functional connection between lumenal and membrane events driving this process.

IMPORTANCE
PyVs are established etiologic agents of many debilitating human diseases, especially in immunocompromised individuals. To infect cells at the cellular level, this virus family must penetrate the host ER membrane to reach the cytosol, a critical entry step. In this report, we identify two ER lumenal factors that prepare the virus for ER membrane translocation and connect these lumenal events with events on the ER membrane. Pinpointing cellular components necessary for supporting PyV infection should lead to rational therapeutic strategies for preventing and treating PyV-related diseases.
Immunoglobulin with High-Titer
In Vitro
Cross-Neutralizing Hepatitis C Virus Antibodies Passively Protects Chimpanzees from Homologous, but Not Heterologous, Challenge
Authors: Bukh Jens , Engle Ronald E. , Faulk Kristina , Wang Richard Y. , Farci Patrizia , Alter Harvey J. , Purcell Robert H.
Published: June 2015

The importance of neutralizing antibodies (NAbs) in protection against hepatitis C virus (HCV) remains controversial. We infused a chimpanzee with H06 immunoglobulin from a genotype 1a HCV-infected patient and challenged with genotype strains efficiently neutralized by H06
in vitro
. Genotype 1a NAbs afforded no protection against genotype 4a or 5a. Protection against homologous 1a lasted 18 weeks, but infection emerged when NAb titers waned. However, 6a infection was prevented. The differential
in vivo
neutralization patterns have implications for HCV vaccine development.