bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of essential alphaproteobacterial genes reveals operational variability in conserved developmental and cell cycle systems
Authors: Curtis Patrick D. , Brun Yves V.
Published: June 2014

The cell cycle of Caulobacter crescentus is controlled by a complex signalling network that co‐ordinates events. Genome sequencing has revealed many C. crescentus cell cycle genes are conserved in other Alphaproteobacteria, but it is not clear to what extent their function is conserved. As many cell cycle regulatory genes are essential in C. crescentus, the essential genes of two Alphaproteobacteria, Agrobacterium tumefaciens (Rhizobiales) and Brevundimonas subvibrioides (Caulobacterales), were elucidated to identify changes in cell cycle protein function over different phylogenetic distances as demonstrated by changes in essentiality. The results show the majority of conserved essential genes are involved in critical cell cycle processes. Changes in component essentiality reflect major changes in lifestyle, such as divisome components in A. tumefaciens resulting from that organism's different growth pattern. Larger variability of essentiality was observed in cell cycle regulators, suggesting regulatory mechanisms are more customizable than the processes they regulate. Examples include variability in the essentiality of divJ and divK spatial cell cycle regulators, and non‐essentiality of the highly conserved and usually essential DNA methyltransferase CcrM. These results show that while essential cell functions are conserved across varying genetic distance, much of a given organism's essential gene pool is specific to that organism.
The expression of antibiotic resistance genes in antibiotic‐producing bacteria
Authors: Mak Stefanie , Xu Ye , Nodwell Justin R.
Published: June 2014

Antibiotic‐producing bacteria encode antibiotic resistance genes that protect them from the biologically active molecules that they produce. The expression of these genes needs to occur in a timely manner: either in advance of or concomitantly with biosynthesis. It appears that there have been at least two general solutions to this problem. In many cases, the expression of resistance genes is tightly linked to that of antibiotic biosynthetic genes. In others, the resistance genes can be induced by their cognate antibiotics or by intermediate molecules from their biosynthetic pathways. The regulatory mechanisms that couple resistance to antibiotic biosynthesis are mechanistically diverse and potentially relevant to the origins of clinical antibiotic resistance.
In vitro expression of Candida albicans alcohol dehydrogenase genes involved in acetaldehyde metabolism
Authors: Bakri M.M. , Rich A.M. , Cannon R.D. , Holmes A.R.
Published: June 2014

Alcohol consumption is a risk factor for oral cancer, possibly via its conversion to acetaldehyde, a known carcinogen. The oral commensal yeast Candida albicans may be one of the agents responsible for this conversion intra‐orally. The alcohol dehydrogenase (Adh) family of enzymes are involved in acetaldehyde metabolism in yeast but, for C. albicans it is not known which family member is responsible for the conversion of ethanol to acetaldehyde. In this study we determined the expression of mRNAs from three C. albicans Adh genes (CaADH1, CaADH2 and CaCDH3) for cells grown in different culture media at different growth phases by Northern blot analysis and quantitative reverse transcription polymerase chain reaction. CaADH1 was constitutively expressed under all growth conditions but there was differential expression of CaADH2. CaADH3 expression was not detected. To investigate whether CaAdh1p or CaAdh2p can contribute to alcohol catabolism in C. albicans, each gene from the reference strain C. albicans SC5314 was expressed in Saccharomyces cerevisiae. Cell extracts from an CaAdh1p‐expressing S. cerevisiae recombinant, but not an CaAdh2p‐expressing recombinant, or an empty vector control strain, possessed ethanol‐utilizing Adh activity above endogenous S. cerevisiae activity. Furthermore, expression of C. albicans Adh1p in a recombinant S. cerevisiae strain in which the endogenous ScADH2 gene (known to convert ethanol to acetaldehyde in this yeast) had been deleted, conferred an NAD‐dependent ethanol‐utilizing, and so acetaldehyde‐producing, Adh activity. We conclude that CaAdh1p is the enzyme responsible for ethanol use under in vitro growth conditions, and may contribute to the intra‐oral production of acetaldehyde.
Clinical utility of B‐type natriuretic peptide (NP) in pediatric cardiac surgery – a systematic review
Authors: Afshani Nura , Schülein Simone , Biccard Bruce M. , Thomas Jenny M.
Published: June 2014

Background

NP is a biomarker that has been used in the diagnosis, management, and prognostication of a number of cardiovascular disorders in the pediatric population. The physiological role of this hormone is to allow the myocardium to adapt to stress or strain imposed by a volume and/or pressure load.

Objective

The aim of this study was to determine the utility of preoperative and postoperative NP to predict outcome in pediatric patients undergoing cardiac surgery for structural congenital heart disease.

Method

We conducted a systematic review by searching three electronic databases using the search terms ‘paediatric’ or ‘pediatric’ and ‘B‐type natriuretic peptide’. Twenty peer‐reviewed papers were included in the study.

Results

Preoperative NP levels were associated with the severity of cardiac failure in several studies. Preoperative NPs also correlated with early postoperative outcome measures such as duration of cardiopulmonary bypass, duration of mechanical ventilation, presence of low cardiac output syndrome, length of stay in the intensive care unit and in one study, death. Early (within 24 h) postoperative NPs showed a stronger correlation than preoperative NPs to early postoperative adverse events.

Conclusion

NPs provide a simple, noninvasive and complementary tool to echocardiography that can be used to assist clinicians in the assessment and management of pediatric patients with congenital heart disease in the perioperative period.
Efficacy of aripiprazole augmentation in Japanese patients with major depressive disorder: A subgroup analysis and Montgomery–Åsberg Depression Rating Scale and Hamilton Rating Scale for Depression item analyses of the Aripiprazole Depression Multicenter Efficacy study
Authors: Ozaki Norio , Otsubo Tempei , Kato Masaki , Higuchi Teruhiko , Ono Hiroaki , Kamijima Kunitoshi ,   ADMIRE Study Group
Published: June 2014

Aim

Results from this randomized, placebo‐controlled study of aripiprazole augmentation to antidepressant therapy (ADT) in Japanese patients with major depressive disorder (MDD) (the Aripiprazole Depression Multicenter Efficacy [ADMIRE] study) revealed that aripiprazole augmentation was superior to ADT alone and was well tolerated. In subgroup analyses, we investigated the influence of demographic‐ and disease‐related factors on the observed responses. We also examined how individual symptom improvement was related to overall improvement in MDD.

Methods

Data from the ADMIRE study were analyzed. Subgroup analyses were performed on the primary outcome measures: the mean change in the Montgomery–Åsberg Depression Rating Scale (MADRS) total score from the end of selective serotonin reuptake inhibitor (SSRI)/serotonin norepinephrine reuptake inhibitor (SNRI) treatment to the end of the randomized treatment.

Results

Changes in the MADRS total scores were consistently greater with aripiprazole than placebo in each of the subgroups. Efficacy was not related to sex, age, number of adequate ADT trials in the current episode, MDD diagnosis, number of depressive episodes, duration of the current episode, age at first depressive episode, time since the first depressive episode, type of SSRI/SNRI, or severity at the end of SSRI/SNRI treatment phase. Compared to placebo, aripiprazole resulted in significant and rapid improvement on seven of the 10 MADRS items, including sadness.

Conclusion

These post‐hoc analyses indicated that aripiprazole was effective for a variety of Japanese patients with MDD who had exhibited inadequate responses to ADT. Additionally, we suggest that aripiprazole significantly and rapidly improved the core depressive symptoms.
Comparative profile of circulating antigenic peptides in CSF, serum & urine from patients with neurocysticercosis diagnosed by immunoblotting
Authors: Sahu P. S. , Parija S. , Kumar D. , Jayachandran S. , Narayan S.
Published: June 2014

Traditionally serum and/or CSF specimens have been used for detection of either specific antibodies or antigens as a supportive diagnosis of NCC. However, in recent days, much interest has been shown employing noninvasive specimens such as urine. In our study, we identified and compared a profile of circulating antigenic peptides of parasite origin in three different body fluids (CSF, serum and urine) obtained from confirmed NCC cases and control subjects. The circulating antigenic peptides were resolved by SDS‐PAGE and subjected to immunoblotting. For confirmation of their origin as parasite somatic or excretory secretory (ES) material, immunoreactivity was tested employing affinity purified polyclonal Taenia solium metacestode anti‐somatic or ES antibodies, respectively. Only lower molecular weight antigenic peptides were found circulating in urine in contrast to serum and CSF specimens. Few somatic peptides were identified to be 100% specific for NCC (19·5 kDa in all three specimens; 131, 70 kDa in CSF and serum only; 128 kDa in CSF only). Similarly, the specific ES peptides detected were 32 kDa (in all three specimens), 16·5 kDa (in serum and CSF only), and 15 kDa (urine only). A test format detecting either one or more of these specific peptides would enhance the sensitivity in diagnosis of NCC.
Radiation pathology: From thorotrast to the future beyond radioresistance
Authors: Fukumoto Manabu
Published: June 2014

The effects of radiation on human health have been a major concern, especially after the Fukushima Daiichi Nuclear Power Plant (FNPP) accident. We can determine these effects only from radiological disasters. The radiological contrast medium Thorotrast is known to induce hepatic cancers decades after injection. Using archival materials from Thorotrast patients, we performed molecular pathological studies to elucidate carcinogenic mechanisms of internal radiation exposure. It is emphasized here that radiation‐induced cancers are a complex consequence of biological response to radiation and ingested radionuclides. We further expanded the study to establish clinically relevant radioresistant cancer cells in order to develop more effective and less harmful radiation therapy. We also found that cancer cells can acquire radioresistance by low‐dose fractionated radiation within one month. The FNPP accidents prompted us to collect tissue samples from animals in and around the evacuation zone in order to construct a tissue bank. The final goal of the bank is to enable research that will contribute to the common understanding of radioprotection.
Gastric‐type endocervical glandular neoplasms associated with aberrant p16 expression and K‐RAS gene mutation in Peutz‐Jeghers syndrome
Authors: Ito Shigemi , Tase Toru , Satoh Kennichi , Ueki Miyuki , Sato Ikuro , Sasano Hironobu
Published: June 2014

In this report, unique endocervical glandular lesions exhibiting gastric differentiation were examined in a patient with Peutz‐Jeghers syndrome. The result of the human papillomavirus (HPV) in situ hybridization (ISH) for the hysterectomy specimens was negative, but they demonstrated a papillary mucinous adenocarcinoma at the proximal endocervix continuous to atypical lobular endocervical glandular hyperplasia. Both contained MUC6‐positive neutral mucin in cytoplasm, and showed different immunoreactivity to p16, Ki‐67, and p53. Moreover, they harbored the identical K‐RAS gene mutation suggesting that there was a common origin. Somatic K‐RAS mutation and defective function of p16 may have been involved in the tumorigenesis of these unusual mucinous neoplasms.
Parenchymal cryobiopsies for interstitial lung diseases: A step forward in disease management
Authors: Maldonado Fabien , Moua Teng , Skalski Joseph
Published: June 2014

See article, page 900
Autoantibodies Response to MDM2 and p53 in the Immunodiagnosis of Esophageal Squamous Cell Carcinoma
Authors: Chai Y. , Peng B. , Dai L. , Qian W. , Zhang Y. , Zhang J.‐Y.
Published: June 2014

The human homologue of the mouse double minute 2 (MDM2) is known to be overexpressed in a variety of human malignancies. As one of E3 ubiquitin–protein ligases, MDM2 interacts with the tumour suppressor p53 by mediating ubiquitination and degradation of p53. Since abnormally expressed proteins can induce autoimmune response, to further examine whether sera from patients with esophageal squamous cell carcinoma (ESCC) exhibited immunoreactivity against MDM2 and p53, autoantibody responses to MDM2 and p53 were evaluated by enzyme‐linked immunosorbent assay (ELISA) in sera from patients with ESCC and normal individuals. Positive results were also confirmed by Western blotting and indirect immunofluorescence assay. The results demonstrated that the positive rate of autoantibody against p53 and MDM2 in ESCC sera was 22.9% (36/157) and 14.0% (22/157), whereas this rate was 0% (0/85) and 1.2% (1/85), respectively, in normal individuals. Some of the sera with antibodies specific for MDM2 also contained antibodies against p53. And there was an increase of positive antibody reactions reaching a frequency of 35% (55/157) combination with MDM2 and p53. This was significantly higher than the frequency of antibodies in normal individuals (P < 0.01). Our preliminary results suggest that autoantibodies against MDM2 and p53 may be useful serum biomarkers in the immunodiagnosis of ESCC.
Spin90 Deficiency Increases CXCL13‐Mediated B Cell Migration
Authors: Park S.‐H. , Kim H.‐R. , Jun C.‐D. , Song W. K. , Park S.‐G.
Published: June 2014

SPIN90 regulates actin dynamics, which is important for cell migration control. CXCL13‐mediated B cell migration is essential for B cell immune responses. In this study, we investigated the role of SPIN90 in CXCL13‐mediated B cell migration using Spin90 gene‐deficient mice. Our chemokinesis analysis and transwell cell migration assay showed that SPIN90 is involved in CXCL13‐mediated B cell migration. Moreover, the level of CXCR5, which is CXCL13 receptor, was increased in SPIN90‐deficient B cells compared with wild‐type B cells. Overall, our data suggest that SPIN90 plays an important role in B cell immune responses through the regulation of CXCL13‐mediated B cell migration.
Interferon and Interferon‐Inducible Gene Activation in Patients with Type 1 Diabetes
Authors: Panarina M. , Kisand K. , Alnek K. , Heilman K. , Peet A. , Uibo R.
Published: June 2014

Type 1 diabetes (T1D) is an autoimmune disease that is thought to be triggered by environmental factors in genetically susceptible individuals. Enteroviruses have been mentioned as the most probable induction component of the disease. Nevertheless, the literature is controversial regarding the association of T1D with viral infection and first‐line antiviral defence components, for example type I interferons (IFNs). Our aim was to test the hypothesis that an abnormality in IFN‐stimulated gene patterns may cause a failure in immunological tolerance and, thereby, initiate T1D as an autoimmune disorder. We studied material from 64 T1D and 36 control subjects, divided into two age groups: <10 years and ≥10 years old. Using a relative gene expression method, we observed a lower expression of interferon‐induced helicase 1 (IFIH1) and other type I IFN‐induced genes in the blood cells of T1D subjects, especially subjects under 10 years old, in spite of their higher IFN levels as measured by the pSTAT1‐inducing capacity of their sera. Likewise, freshly purified CpG‐stimulated cells from T1D patients showed significantly lower upregulation of IFN‐induced genes, that is IFIH1 and CXCL10, compared to cells from the control group. The identified dysregulation in the IFN‐α‐induced antiviral response in T1D patients, especially in early childhood, could be one of the factors affecting T1D development.
Antibiotic Treatment of Pregnant Non‐Obese Diabetic Mice Leads to Altered Gut Microbiota and Intestinal Immunological Changes in the Offspring
Authors: Tormo‐Badia N. , Håkansson Å. , Vasudevan K. , Molin G. , Ahrné S. , Cilio C. M.
Published: June 2014

The intestinal microbiota is important for tolerance induction through mucosal immunological responses. The composition of the gut microbiota of an infant is affected by environmental factors such as diet, disease and antibiotic treatment. However, already in utero, these environmental factors can affect the immunological development of the foetus and influence the future gut microbiota of the infant. To investigate the effects of antibiotic treatment of pregnant mothers on the offspring's gut microbiome and diabetes development, we treated non‐obese diabetic (NOD) mice with a cocktail of antibiotics during gestation and the composition of the gut microbiota, diabetes incidence and major gut‐related T lymphocyte populations were investigated in the offspring. We observed a persistent reduction in the general diversity of the gut microbiota in the offspring from NOD mothers treated with antibiotics during gestation compared with offspring from control mothers. In addition, by clustering the present bacterial taxa with principal component analysis, we found a differential clustering of gut microbiota in the offspring from NOD mothers treated with antibiotics during gestation compared with offspring from control mothers. Offspring from NOD mothers treated with antibiotics during gestation also showed some immunological alterations in the gut immune system, which could be related to the diversity of the gut microbiome and influence modulation of diabetes development at 20 weeks. Our data point out maternal derangement of the intestinal microbiota as a potential environmental risk factor for T1D development.
TRPV2 in the Development of Experimental Colitis
Authors: Issa C. M. , Hambly B. D. , Wang Y. , Maleki S. , Wang W. , Fei J. , Bao S.
Published: June 2014

Colitis is still a significant disease challenge in humans, but its underlying mechanism remains to be fully elucidated. The transient receptor potential vanilloid (TRPV) ion channel plays an important pathological role in host immunity, as deficiency of TRPV compromises host defence in vivo and in vitro. Using a DSS‐induced colitis mouse model, the function of TRPV2 in the development of colitis was investigated, utilizing TRPV2−/− and Wt mice. Less severe colitis was observed in TRPV2−/−, compared to that of Wt mice, at the clinical, histopathological and immunohistochemical levels. Compared to Wt mice, reduced severity of colitis in TRPV2−/− mice may be due to less intestinal inflammation via reduced recruitment of macrophages. The TRPV2 pathway contributes to the development of colitis. These data provide useful information for potential therapeutic intervention in colitis patients.
50th Anniversary Article: Comparison Studies of Full Wavefield Signal Processing for Crack Detection
Authors: Ostachowicz W. , Radzieński M. , Kudela P.
Published: June 2014

The signals acquired by measurements of elastic wave propagation have been used for damage detection since the 1970s. The measurements have been carried out mostly by using piezoelectric transducers of various types. Many different sensor configurations and data processing have been proposed to detect and localise structural defects, both for real‐time and off‐line testing.

Nevertheless, in the last decade, significant progress in the measurement techniques such as scanning laser Doppler vibrometry and shearographic interferometry has been made. These techniques enable measurement of a full wavefield of elastic waves. This opens up new possibilities and solutions for the problems of the damage detection in structures. Many researchers successfully applied this type of measurements for the damage detection and localisation in thin‐walled structures. Moreover, advanced signal processing techniques, such as wavenumber filtering, give the possibility of damage size estimation, by filling the gap between damage detection and damage prognosis.

The aim of this paper is to give a comprehensive review of methods used for the full wavefield measurement. It also describes and compares selected signal processing algorithms developed for damage detection and visualisation based on these measuring techniques. Criticism aspects, as well as advantages of each algorithm, are denoted based on the authors' expertise in the field.
Severe infections requiring intensive care unit admission in kidney transplant recipients: impact on graft outcome
Authors: Bige N. , Zafrani L. , Lambert J. , Peraldi M.‐N. , Snanoudj R. , Reuter D. , Legendre C. , Chevret S. , Lemiale V. , Schlemmer B. , Azoulay E. , Canet E.
Published: June 2014

Background

Kidney transplant recipients are at risk for life‐threatening infections, which may affect the long‐term prognosis.

Methods

We retrospectively included all kidney transplant recipients admitted for sepsis, severe sepsis, or septic shock to the medical intensive care unit (ICU) of the Saint‐Louis Hospital, Paris, France, between 2000 and 2010. The main objective was to identify factors associated with survival without graft impairment 90 days after ICU discharge.

Results

Data were available for 83 of 100 eligible patients. The main sites of infection were the lungs (54%), urinary tract (24%), and bloodstream (22%). Among documented infections (55/83), 80% were bacterial. Fungal infections were more common among patients transplanted after 2005 (5% vs. 23%, P = 0.02). Mechanical ventilation was used in 46 (56%) patients, vasopressors in 39 (47%), and renal replacement therapy (RRT) in 34 (41%). In‐hospital and day‐90 mortality rates were 20% and 22%, respectively. On day 90, among the 65 survivors, 39 (47%) had recovered their previous graft function and 26 (31%) had impaired graft function, including 16 (19%) who were dependent on RRT. Factors independently associated with day‐90 survival and graft function recovery were baseline serum creatinine (odds ratio [OR] for a 10 μmol/L increase 0.94, 95% confidence interval [CI] 0.88–1.00) and cyclosporine therapy (OR 0.30, 95% CI 0.11–0.79).

Conclusion

Sepsis was chiefly related to bacterial pneumonia or urinary tract infection. Pneumocystis jirovecii was the leading opportunistic agent, with a trend toward an increase over time. Infections often induced severe graft function impairment. Baseline creatinine and cyclosporine therapy independently predicted the outcome.
Gordonia terrae kidney graft abscess in a renal transplant patient
Authors: Nicodemo A.C. , Odongo F.C.A. , Doi A.M. , Sampaio J.L.M.
Published: June 2014

We present the first report, to our knowledge, of a renal abscess cause by an infection from Gordonia terrae in a kidney transplant patient. The patient simultaneously had pulmonary tuberculosis and a perirenal allograft abscess caused by G. terrae. After treatment with imipenem, in addition to anti‐tuberculous drugs, the patient was cured.
Persistence of Pseudomonas aeruginosa in a pulmonary nodule with late relapse
Authors: Ronkainen S. , Xie Y. , Battiwalla M. , Barrett A.J. , Stock F. , Dekker J.P. , Danner R.L.
Published: June 2014

Lung nodules are common diagnostic challenges in hematopoietic stem cell transplantation and solid organ transplantation. Pseudomonas aeruginosa is a known cause of lung abscess in these patients, but its ability to persist for months in a quiescent lung nodule and later cause recurrent infection is not well known or documented. A patient with a history of acute pre‐B‐cell lymphoblastic leukemia had enlargement and cavitation of a small right upper lobe pulmonary nodule 10 months after allogeneic hematopoietic stem cell transplantation. The nodule was the remnant of a presumed P. aeruginosa septic embolus that occurred 2.5 months after transplantation. With antibiotic treatment, the nodule had shrunk in size to <1 cm and remained stable. Transthoracic needle aspiration grew P. aeruginosa indistinguishable by molecular typing from isolates obtained 7.5 months earlier from blood and bronchoalveolar lavage fluid. Sub‐centimeter pulmonary nodules attributable to previously treated P. aeruginosa may harbor viable organisms and lead to recrudescent infection.
Migration and Career Transitions in Professional Sports: Transnational Athletic Careers in a Psychological and Sociological Perspective
Authors: Agergaard Sine , Ryba Tatiana V.
Published: June 2014

With rising globalization and professionalization within sports, athletes are increasingly migrating across national borders to take up work, and their athletic and nonathletic development is thereby shaped and lived in different countries. Through the analysis of interviews with female professional transnational athletes, this article contextualizes and discusses arguments for developing an interdisciplinary framework to account for lived experiences of the close intertwining between transnational migration and career development in professional sports. By combining our psychological and sociological perspectives, we identify three normative career transitions for transnational athletes. First of all, transnational recruitment that draws on social networks as well as individual agency. Secondly, establishment as a transnational athlete that is connected to cultural and psychological adaptation as well as development of transnational belonging, and thirdly, professional athletic career termination that for transnational athletes is connected to a (re)constitution of one’s transnational network and sense of belonging.
Clustering by fast search and find of density peaks
Authors: Rodriguez Alex , Laio Alessandro
Published: June 2014

Discerning clusters of data points

Cluster analysis is used in many disciplines to group objects according to a defined measure of distance. Numerous algorithms exist, some based on the analysis of the local density of data points, and others on predefined probability distributions. Rodriguez and Laio devised a method in which the cluster centers are recognized as local density maxima that are far away from any points of higher density. The algorithm depends only on the relative densities rather than their absolute values. The authors tested the method on a series of data sets, and its performance compared favorably to that of established techniques.

Science
, this issue p.
1492
Optically measuring force near the standard quantum limit
Authors: Schreppler Sydney , Spethmann Nicolas , Brahms Nathan , Botter Thierry , Barrios Maryrose , Stamper-Kurn Dan M.
Published: June 2014

Measuring tiny forces with atomic clouds

For projects such as detecting gravity waves, physicists need to measure tiny forces precisely. Schreppler
et al.
developed an extremely sensitive method for force measurement. They applied a known force on a cloud of ultracold rubidium atoms in an optical cavity. The force caused the atoms to oscillate, and the researchers used optical measurements to monitor the motion. Under optimal conditions, the authors could measure forces with a level of sensitivity only four times worse than the fundamental limit imposed by the Heisenberg uncertainty principle.

Science
, this issue p.
1486
The valley Hall effect in MoS
2
transistors
Authors: Mak K. F. , McGill K. L. , Park J. , McEuen P. L.
Published: June 2014

Using the valleys in monolayer MoS
2

The electronic structure of the two-dimensional material MoS
2
has two distinct “valleys” of energy that may help to carry information in future electronic devices. Mak
et al.
observed the so-called valley Hall effect in a monolayer of MoS
2
. The electrons from different valleys moved in opposite directions across the sample, with one valley being overrepresented with respect to the other. The scientists achieved this by shining circularly polarized light on the material, which created an imbalance in the population of the two valleys. The findings may enable practical applications in the newly formed field of valleytronics.

Science
, this issue p.
1489
Capturing metastable structures during high-rate cycling of LiFePO
4
nanoparticle electrodes
Authors: Liu Hao , Strobridge Fiona C. , Borkiewicz Olaf J. , Wiaderek Kamila M. , Chapman Karena W. , Chupas Peter J. , Grey Clare P.
Published: June 2014

Watching battery materials in action

When batteries get rapidly charged and discharged repeatedly, they will often stop working. This is especially true when the cycling changes the crystal structure of the battery components. Liu
et al.
examined the structural changes in components of a type of lithium battery (see the Perspective by Owen and Hector). Their findings explain why LiFePO
4
delivers unexpectedly good electrochemical performances, particularly during rapid cycling.

Science
, this issue p.
10.1126/science.1252817
; see also p.
1451
Predicting microbial growth
Authors: Monk Jonathan , Palsson Bernhard O.
Published: June 2014

Integration of a plethora of genomic and biochemical data enables large-scale prediction of cellular functions
Ediacaran metazoan reefs from the Nama Group, Namibia
Authors: Penny A. M. , Wood R. , Curtis A. , Bowyer F. , Tostevin R. , Hoffman K.-H.
Published: June 2014

Building coral reefs in ancient times

540 million years ago, in the dawn before the Cambrian explosion, evolution was setting the stage for the global rise of animals. Before they took over the seas, the earliest animals developed strategies to defend themselves against predators. These strategies, which remain common today, include forming skeletons and building reefs. Penny
et al.
discovered a massive fossil reef deposit in Namibia made up of tiny coneshaped early animals known as
Cloudina.
The reef, which is 20 million years older than other ancient reefs, was probably formed as the
Cloudina
adapted to benefit from reefs, which protect the animals and allow them to feed more efficiently.

Science
, this issue p.
1504
Observing liquid flow in nanotubes by 4D electron microscopy
Authors: Lorenz Ulrich J. , Zewail Ahmed H.
Published: June 2014

Watching lead flow at the nanoscale

Microfluidic devices have recently become useful in commercial chemical synthesis. But what about fluid dynamics at the nanometer scale? Lorenz and Zewail used an electron microscope with nanosecond time resolution to capture images of molten lead flowing through a nanotube. They flash-melted the metal with a laser pulse to begin their flow measurements at a precise time point. The experiments offered insights into viscous friction as well as heat-transfer dynamics in a channel one-thousandth as wide as a strand of hair.

Science
, this issue p.
1496
Nucleoside diphosphate kinases fuel dynamin superfamily proteins with GTP for membrane remodeling
Authors: Boissan Mathieu , Montagnac Guillaume , Shen Qinfang , Griparic Lorena , Guitton Jérôme , Romao Maryse , Sauvonnet Nathalie , Lagache Thibault , Lascu Ioan , Raposo Graça , Desbourdes Céline , Schlattner Uwe , Lacombe Marie-Lise , Polo Simona , van der Bliek Alexander M. , Roux Aurélien , Chavrier Philippe
Published: June 2014

Supplying power: Right time, right place

Cell membranes are very flexible and easily molded to shape; however, to physically pinch off a membrane vesicle from a membrane tube still requires power. A type of molecular machine known as dynamin is involved in this sort of membrane remodeling. Dynamins use guanosine triphosphate (GTP) rather than the more commonly used cellular energy source adenosine triphosphate to work. Boissan
et al.
now show that two separate dynamins found in the cytoplasm or the mitochondria both use the same sort of enzyme—nucleoside diphosphate kinases—to provide GTP at just the right time and the right place to power membrane fission.

Science
, this issue p.
1510
Genomic basis for the convergent evolution of electric organs
Authors: Gallant Jason R. , Traeger Lindsay L. , Volkening Jeremy D. , Moffett Howell , Chen Po-Hao , Novina Carl D. , Phillips George N. , Anand Rene , Wells Gregg B. , Pinch Matthew , Güth Robert , Unguez Graciela A. , Albert James S. , Zakon Harold H. , Samanta Manoj P. , Sussman Michael R.
Published: June 2014

Only one way to make an electric organ?

Electric fish have independently evolved electric organs that help them to communicate, navigate, hunt, and defend themselves. Gallant
et al.
analyzed the genome of the electric eel and the genes expressed in two other distantly related electric fish. The same genes were recruited within the different species to make evolutionarily new structures that function similarly.

Science
, this issue p.
1522
Targeting vascular sprouts
Authors: Rivera Lee B. , Bergers Gabriele
Published: June 2014

Manipulating metabolism could control angiogenesis
Will fracking put too much fizz in your water?
Authors: Stokstad Erik
Published: June 2014

Leaky gas wells loom large in debate over drilling's impact on water quality.
Type I Interferon Mimetics Bypass Vaccinia Virus Decoy Receptor Virulence Factor for Protection of Mice against Lethal Infection
Authors: Ahmed Chulbul M. , Johnson Howard M.
Published: June 2014

The canonical model of interferon (IFN) signaling focuses solely on the activation of STAT transcription factors which, according to the model, are initiated by the singular event of cross-linkage of the receptor extracellular domain by the IFN. The IFN has no further function beyond this. The model thus provides no approach to circumventing poxviruses decoy receptors that compete with the IFN receptors for IFNs. This simple event has allowed smallpox virus to decimate human populations throughout the ages. We have developed a noncanonical model of IFN signaling that has resulted in the development of small peptide mimetics to both types I and II IFNs. In this report, we focus on a type I IFN mimetic at positions 152 to 189, IFN-α1(152–189), which corresponds to the C terminus of human IFN-α1. This mimetic functions intracellularly and is thus not recognized by the B18R vaccinia virus decoy receptor. Mimetic synthesized with an attached palmitate (lipo-) for cell penetration protects mice from a lethal dose of vaccinia virus, while the parent IFN-α1 is ineffective. Unlike IFN-α1, the mimetic does not bind to the B18R decoy receptor. It further differs from the parent IFN in that it lacks the toxicity of weight loss and bone marrow suppression in mice while at the same time possessing a strong adjuvant effect on the immune system. The mimetic is thus an innate and adaptive immune regulator that is evidence of the dynamic nature of the noncanonical model of IFN signaling, in stark contrast to the canonical or classical model of signaling.
Association between Indoor Environmental Contamination by Salmonella enterica and Contamination of Eggs on Layer Farms
Authors: Gole Vaibhav C. , Torok Valeria , Sexton Margaret , Caraguel Charles G. B. , Chousalkar Kapil K.
Published: June 2014

This study involves longitudinal and point-in-time surveys of
Salmonella
carriage and environmental contamination on two commercial cage layer farms positive for
Salmonella enterica
subsp.
enterica
serovar Typhimurium (flock A age, 32 weeks; flock B age, 34 weeks).
Salmonella
-positive fecal, egg belt, and dust samples were all unconditionally associated with eggshells testing positive for
Salmonella
. The odds of an eggshell testing positive for
Salmonella
were 91.8, 61.5, and 18.2 times higher when fecal, egg belt, and dust samples, respectively, tested positive for
Salmonella
. The agreement between the culture-based methods and real-time PCR on preenriched broths for detecting
Salmonella
was almost perfect for eggshell (observed agreement, 99.19%; kappa coefficient, 0.94) and egg belt samples (observed agreement, 95%; kappa coefficient, 0.88), and it was substantial for fecal (observed agreement, 87.14%; kappa coefficient, 0.47) and floor dust samples (observed agreement, 80.61%; kappa coefficient, 0.58). A 1-log increase in the load of
Salmonella
detected in the fecal, egg belt, and floor dust samples resulted in 35%, 43%, and 45% increases, respectively (
P
< 0.001), in the odds of an eggshell testing positive for
Salmonella
. The multilocus variable-number tandem-repeat analysis (MLVA) patterns of the
S
. Typhimurium strains isolated from flock A were distinct from those of flock B.
S
. Typhimurium strains detected from human food poisoning cases exhibited an MLVA pattern similar to those of the strains isolated from flocks A and B.
Microevolution of Burkholderia pseudomallei during an Acute Infection
Authors: Limmathurotsakul Direk , Holden Matthew T. G. , Coupland Paul , Price Erin P. , Chantratita Narisara , Wuthiekanun Vanaporn , Amornchai Premjit , Parkhill Julian , Peacock Sharon J.
Published: June 2014

We used whole-genome sequencing to evaluate 69 independent colonies of
Burkholderia pseudomallei
isolated from seven body sites of a patient with acute disseminated melioidosis. Fourteen closely related genotypes were found, providing evidence for the rapid
in vivo
diversification of
B. pseudomallei
after inoculation and systemic spread.
Predicting the Impact of CD8+T Cell Polyfunctionality on HIV Disease Progression
Authors: Graw Frederik , Regoes Roland R.
Published: June 2014

During the chronic phase of HIV-1 infection, polyfunctional CD8+T cell responses, which are characterized by a high frequency of cells able to secrete multiple cytokines simultaneously, are associated with lower virus loads and slower disease progression. This relationship may arise for different reasons. Polyfunctional responses may simply be stronger. Alternatively, it could be that the increased functional diversity in polyfunctional responses leads to lower virus loads and slower disease progression. Lastly, polyfunctional responses could contain more CD8+T cells that mediate a specific key function that is primarily responsible for viral control. Disentangling the influences of overall strength, functional diversity, and specific function on viral control and disease progression is very relevant for the rational design of vaccines and immunotherapy using cellular immune responses. We developed a mathematical model to study how polyfunctional CD8+T cell responses mediating lytic and nonlytic effector functions affect the CD4+T cell count and plasma viral load. We based our model onin vitrodata on the efficacy of gamma interferon (IFN-γ) and macrophage inflammatory protein 1β (MIP-1β)/RANTES against HIV. We find that the strength of the response is a good predictor of disease progression, while functional diversity has only a minor influence. In addition, our model predicts for realistic levels of cytotoxicity that immune responses dominated by nonlytic effector functions most positively influence disease outcome.

IMPORTANCEIt is an open question in HIV research why polyfunctional CD8+T cell responses are associated with better viral control, while individual functional correlates of protection have not been identified so far. Identifying the role of CD8+T cells in HIV-1 infection has important implications for the potential development of effective T cell-based vaccines. Our analysis provides new ways to think about a causative role of CD8+T cells by studying different hypotheses regarding why polyfunctional CD8+T cells might be more advantageous. We identify measurements that have to be obtained in order to evaluate the role of CD8+T cells in HIV-1 infection. In addition, our method shows how individual cell functionality data can be used in population-based virus dynamics models.
Three-Dimensional Imaging of HIV-1 Virological Synapses Reveals Membrane Architectures Involved in Virus Transmission
Authors: Do Thao , Murphy Gavin , Earl Lesley A. , Del Prete Gregory Q. , Grandinetti Giovanna , Li Guan-Han , Estes Jacob D. , Rao Prashant , Trubey Charles M. , Thomas James , Spector Jeffrey , Bliss Donald , Nath Avindra , Lifson Jeffrey D. , Subramaniam Sriram
Published: June 2014

HIV transmission efficiency is greatly increased when viruses are transmitted at virological synapses formed between infected and uninfected cells. We have previously shown that virological synapses formed between HIV-pulsed mature dendritic cells (DCs) and uninfected T cells contain interdigitated membrane surfaces, with T cell filopodia extending toward virions sequestered deep inside invaginations formed on the DC membrane. To explore membrane structural changes relevant to HIV transmission across other types of intercellular conjugates, we used a combination of light and focused ion beam scanning electron microscopy (FIB-SEM) to determine the three-dimensional (3D) architectures of contact regions between HIV-1-infected CD4
+
T cells and either uninfected human CD4
+
T cells or human fetal astrocytes. We present evidence that in each case, membrane extensions that originate from the uninfected cells, either as membrane sheets or filopodial bridges, are present and may be involved in HIV transmission from infected to uninfected cells. We show that individual virions are distributed along the length of astrocyte filopodia, suggesting that virus transfer to the astrocytes is mediated, at least in part, by processes originating from the astrocyte itself. Mechanisms that selectively disrupt the polarization and formation of such membrane extensions could thus represent a possible target for reducing viral spread.

IMPORTANCE
Our findings lead to new insights into unique aspects of HIV transmission in the brain and at T cell-T cell synapses, which are thought to be a predominant mode of rapid HIV transmission early in the infection process.
Host Factors That Interact with the Pestivirus N-Terminal Protease, N
pro
, Are Components of the Ribonucleoprotein Complex
Authors: Jefferson Matthew , Donaszi-Ivanov Andras , Pollen Sean , Dalmay Tamas , Saalbach Gerhard , Powell Penny P.
Published: June 2014

The viral N-terminal protease N
pro
of pestiviruses counteracts cellular antiviral defenses through inhibition of IRF3. Here we used mass spectrometry to identify a new role for N
pro
through its interaction with over 55 associated proteins, mainly ribosomal proteins and ribonucleoproteins, including RNA helicase A (DHX9), Y-box binding protein (YBX1), DDX3, DDX5, eIF3, IGF2BP1, multiple myeloma tumor protein 2, interleukin enhancer binding factor 3 (IEBP3), guanine nucleotide binding protein 3, and polyadenylate-binding protein 1 (PABP-1). These are components of the translation machinery, ribonucleoprotein particles (RNPs), and stress granules. Significantly, we found that stress granule formation was inhibited in MDBK cells infected with a noncytopathic bovine viral diarrhea virus (BVDV) strain, Kyle. However, ribonucleoproteins binding to N
pro
did not inhibit these proteins from aggregating into stress granules. N
pro
interacted with YBX1 though its TRASH domain, since the mutant C112R protein with an inactive TRASH domain no longer redistributed to stress granules. Interestingly, RNA helicase A and La autoantigen relocated from a nuclear location to form cytoplasmic granules with N
pro
. To address a proviral role for N
pro
in RNP granules, we investigated whether N
pro
affected RNA interference (RNAi), since interacting proteins are involved in RISC function during RNA silencing. Using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) silencing with small interfering RNAs (siRNAs) followed by Northern blotting of GAPDH, expression of N
pro
had no effect on RNAi silencing activity, contrasting with other viral suppressors of interferon. We propose that N
pro
is involved with virus RNA translation in the cytoplasm for virus particle production, and when translation is inhibited following stress, it redistributes to the replication complex.

IMPORTANCE
Although the pestivirus N-terminal protease, N
pro
, has been shown to have an important role in degrading IRF3 to prevent apoptosis and interferon production during infection, the function of this unique viral protease in the pestivirus life cycle remains to be elucidated. We used proteomic mass spectrometry to identify novel interacting proteins and have shown that N
pro
is present in ribosomal and ribonucleoprotein particles (RNPs), indicating a translational role in virus particle production. The virus itself can prevent stress granule assembly from these complexes, but this inhibition is not due to N
pro
. A proviral role to subvert RNA silencing through binding of these host RNP proteins was not identified for this viral suppressor of interferon.
Role of Electrostatics in the Assembly Pathway of a Single-Stranded RNA Virus
Authors: Garmann Rees F. , Comas-Garcia Mauricio , Koay Melissa S. T. , Cornelissen Jeroen J. L. M. , Knobler Charles M. , Gelbart William M.
Published: June 2014

We have recently discovered (R. D. Cadena-Nava et al., J. Virol.
86:
3318–3326, 2012, doi:10.1128/JVI.06566-11) that the
in vitro
packaging of RNA by the capsid protein (CP) of cowpea chlorotic mottle virus is optimal when there is a significant excess of CP, specifically that complete packaging of all of the RNA in solution requires sufficient CP to provide charge matching of the N-terminal positively charged arginine-rich motifs (ARMS) of the CPs with the negatively charged phosphate backbone of the RNA. We show here that packaging results from the initial formation of a charge-matched protocapsid consisting of RNA decorated by a disordered arrangement of CPs. This protocapsid reorganizes into the final, icosahedrally symmetric nucleocapsid by displacing the excess CPs from the RNA to the exterior surface of the emerging capsid through electrostatic attraction between the ARMs of the excess CP and the negative charge density of the capsid exterior. As a test of this scenario, we prepare CP mutants with extra and missing (relative to the wild type) cationic residues and show that a correspondingly smaller and larger excess, respectively, of CP is needed for complete packaging of RNA.

IMPORTANCE
Cowpea chlorotic mottle virus (CCMV) has long been studied as a model system for the assembly of single-stranded RNA viruses. While much is known about the electrostatic interactions within the CCMV virion, relatively little is known about these interactions during assembly, i.e., within intermediate states preceding the final nucleocapsid structure. Theoretical models and coarse-grained molecular dynamics simulations suggest that viruses like CCMV assemble by the bulk adsorption of CPs onto the RNA driven by electrostatic attraction, followed by structural reorganization into the final capsid. Such a mechanism facilitates assembly by condensing the RNA for packaging while simultaneously concentrating the local density of CP for capsid nucleation. We provide experimental evidence of such a mechanism by demonstrating that efficient assembly is initiated by the formation of a disordered protocapsid complex whose stoichiometry is governed by electrostatics (charge matching of the anionic RNA and the cationic N termini of the CP).