bluuebunny/crossref_metadata_2025 huggingface dataset:
The evolution of symbiont preference traits in the model legume Medicago truncatula
Authors: Batstone Rebecca T. , Dutton Emily M. , Wang Donglin , Yang Molly , Frederickson Megan E.
Published: November 2016

Many hosts preferentially associate with or reward better symbionts, but how these symbiont preference traits evolve is an open question. Legumes often form more nodules with or provide more resources to rhizobia that fix more nitrogen (N), but they also acquire N from soil via root foraging. It is unclear whether root responses to abiotically and symbiotically derived N evolve independently.

Here, we measured root foraging and both preferential allocation of root resources to and preferential association with an effective vs an ineffective N‐fixing Ensifer meliloti strain in 35 inbred lines of the model legume Medicago truncatula.

We found that M. truncatula is an efficient root forager and forms more nodules with the effective rhizobium; root biomass increases with the number of effective, but not ineffective, nodules, indicating preferential allocation to roots harbouring effective rhizobia; root foraging is not genetically correlated with either preferential allocation or association; and selection favours plant genotypes that form more effective nodules.

Root foraging and symbiont preference traits appear to be genetically uncoupled in M. truncatula. Rather than evolving to exclude ineffective partners, our results suggest that preference traits probably evolve to take better advantage of effective symbionts.
‘We can only request what's in our protocol’: technology and work autonomy in healthcare
Authors: Petrakaki Dimitra , Kornelakis Andreas
Published: November 2016

This article explores the tension between standardization and autonomy raised by the implementation of new technology in healthcare organizations. The theoretical frame of this study is grounded in the impact of new technologies on work organization, routinization and autonomy across settings. Empirically it presents evidence from twoNHSTrusts in England that implemented a national Electronic Patient Record (EPR). The paper aims to reinvigorate the debate on the tension between standardization and autonomy in professional workplaces such as healthcare. It argues that the implication of technology in professional work conditions processes of task routinization that constrain autonomy, and enables reallocation of discretion between professional groups. We argue that routinization is not restricted to low‐skill work but may travel across contexts and be evidenced in high‐skill work environments. The interplay between routinization and autonomy is also useful in drawing insights concerning the dynamics of change that occur in professional work.
Family Planning Vouchers in Low and Middle Income Countries: A Systematic Review
Authors: Bellows Ben , Bulaya Carol , Inambwae Sophie , Lissner Craig L. , Ali Moazzam , Bajracharya Ashish
Published: November 2016

Family planning (FP) vouchers have targeted subsidies to disadvantaged populations for quality reproductive health services since the 1960s. To summarize the effect of FP voucher programs in low‐ and middle‐income countries, a systematic review was conducted, screening studies from 33 databases through three phases: keyword search, title and abstract review, and full text review. Sixteen articles were selected including randomized control trials, controlled before‐and‐after, interrupted time series analyses, cohort, and before‐and‐after studies. Twenty‐three study outcomes were clustered around contraceptive uptake, with study outcomes including fertility in the early studies and equity and discontinuation in more recent publications. Research gaps include measures of FP quality, unintended outcomes, clients’ qualitative experiences, FP voucher integration with health systems, and issues related to scale‐up of the voucher approach.
Leadership behavior changes following a theory‐based leadership development intervention: A longitudinal study of subordinates’ and leaders’ evaluations
Authors: Larsson Gerry , Sandahl Christer , Söderhjelm Teresa , Sjövold Endre , Zander Ann
Published: November 2016

The aim was to evaluate effects of leadership courses based on the developmental leadership model at the leadership behavioral level. A longitudinal design was employed with assessments before, one and six months after the leadership courses. The sample consisted of 59 leaders who made self‐ratings and were rated by at least three subordinates on each occasion. Leadership behaviors were measured with the Developmental Leadership Questionnaire (DLQ). A limited increase of favorable leadership behaviors and a significant reduction of unfavorable leadership behaviors were found, particularly according to the subordinates’ ratings. A cluster analysis yielded three meaningful leader profiles and showed that this pattern was found in all three profiles, irrespective of how favorably they were rated before the onset of the intervention.
High spatial resolution mass spectrometry imaging reveals the genetically programmed, developmental modification of the distribution of thylakoid membrane lipids among individual cells of maize leaf
Authors: Dueñas Maria Emilia , Klein Adam T. , Alexander Liza E. , Yandeau‐Nelson Marna D. , Nikolau Basil J. , Lee Young Jin
Published: November 2016

Metabolism in plants is compartmentalized among different tissues, cells and subcellular organelles. Mass spectrometry imaging (MSI) with matrix‐assisted laser desorption ionization (MALDI) has recently advanced to allow for the visualization of metabolites at single‐cell resolution. Here we applied 5‐ and 10 μm high spatial resolution MALDI‐MSI to the asymmetric Kranz anatomy of Zea mays (maize) leaves to study the differential localization of two major anionic lipids in thylakoid membranes, sulfoquinovosyldiacylglycerols (SQDG) and phosphatidylglycerols (PG). The quantification and localization of SQDG and PG molecular species, among mesophyll (M) and bundle sheath (BS) cells, are compared across the leaf developmental gradient from four maize genotypes (the inbreds B73 and Mo17, and the reciprocal hybrids B73 × Mo17 and Mo17 × B73). SQDG species are uniformly distributed in both photosynthetic cell types, regardless of leaf development or genotype; however, PG shows photosynthetic cell‐specific differential localization depending on the genotype and the fatty acyl chain constituent. Overall, 16:1‐containing PGs primarily contribute to the thylakoid membranes of M cells, whereas BS chloroplasts are mostly composed of 16:0‐containing PGs. Furthermore, PG 32:0 shows genotype‐specific differences in cellular distribution, with preferential localization in BS cells for B73, but more uniform distribution between BS and M cells in Mo17. Maternal inheritance is exhibited within the hybrids, such that the localization of PG 32:0 in B73 × Mo17 is similar to the distribution in the B73 parental inbred, whereas that of Mo17 × B73 resembles the Mo17 parent. This study demonstrates the power of MALDI‐MSI to reveal unprecedented insights on metabolic outcomes in multicellular organisms at single‐cell resolution.
Value of calcium and phosphate in a bicarbonate‐containing platelet additive solution with low plasma levels in maintaining key in vitro platelet storage parameters
Authors: Skripchenko Andrey , Turgeon Annette , Thompson‐Montgomery Dedeene , Awatefe Helen , Wagner Stephen J.
Published: November 2016

BACKGROUND

Use of recently developed platelet (PLT) additive solutions (PAS) with 5% plasma levels may reduce the frequency and/or severity of transfusion reactions attributed to plasma. PLTs suspended in bicarbonate‐containing PAS‐5 with 5% plasma levels can maintain key PLT parameters during 7‐day storage. This study evaluates the role of calcium and phosphate, as constituents of PAS‐5, in maintaining PLT parameters.

STUDY DESIGN AND METHODS

An Amicus apheresis PLT unit (n = 13) was equally divided into four 60‐mL aliquots in CF‐250 polyolefin bags. Four different formulations of PAS‐5 were prepared: PAS‐5, PAS‐5 without phosphate (−PO4), PAS‐5 without calcium (−Ca), and PAS‐5 without Ca and phosphate (−Ca/−PO4). PLTs were centrifuged, and the supernatant was expressed and replaced with the respective PAS, yielding PLTs suspended in 95% PAS and 5% plasma. PLTs were stored at 20 to 24ºC with agitation for 7 days. PLT in vitro parameters were evaluated on Days 1, 5, and 7.

RESULTS

In PLT PAS‐5 aliquots, pH levels were maintained better compared with those in −Ca and –Ca/−PO4 aliquots. Glycolysis was greater in −Ca and –Ca/−PO4 PLT aliquots compared with PAS‐5 aliquots. Hypotonic stress response and morphology were less and p‐selectin (CD62P) binding was greater in –Ca/−PO4 PLT aliquots. The accumulation of reactive oxygen species was greater in –Ca/−PO4 PLTs. Phosphorylation of p38 mitogen‐activated protein kinase (MAPK) was greater in –Ca and −Ca/−PO4 PLT aliquots during storage.

CONCLUSION

The removal of calcium and phosphate from PAS‐5 leads to the activation of p38 MAPK and deterioration of key PLT storage parameters.
The Photo Essay
Authors: Sutherland Patrick
Published: November 2016

This invited essay reflects upon the use of the photo essay within documentary photography. In particular, it compares Righteous Dopefiend, the much‐lauded anthropological text by Philippe Bourgois with photographs by Jeff Schonberg, to work by photographers exploring similar subject matter. It aims to tease out some of the essential elements of the photo essay as well as the connections between the practices of visual anthropology, documentary photography, and photojournalism. It is accompanied by a separate online article that describes an approach to shooting, editing, and constructing a photo essay and offers guidelines for the submission of photo essays to VAR.
Post‐translational cleavage of Hv1 in human sperm tunes pH‐ and voltage‐dependent gating
Authors: Berger Thomas K. , Fußhöller David M. , Goodwin Normann , Bönigk Wolfgang , Müller Astrid , Dokani Khesroshahi Nasim , Brenker Christoph , Wachten Dagmar , Krause Eberhard , Kaupp U. Benjamin , Strünker Timo
Published: November 2016

Key points

In human sperm, proton flux across the membrane is controlled by the voltage‐gated proton channel Hv1.

We show that sperm harbour both Hv1 and an N‐terminally cleaved isoform termed Hv1Sper.

The pH‐control of Hv1Sper and Hv1 is distinctively different.

Hv1Sper and Hv1 can form heterodimers that combine features of both constituents.

Cleavage and heterodimerization of Hv1 might represent an adaptation to the specific requirements of pH control in sperm.

In human sperm, the voltage‐gated proton channel Hv1 controls the flux of protons across the flagellar membrane. Here, we show that sperm harbour Hv1 and a shorter isoform, termed Hv1Sper. Hv1Sper is generated from Hv1 by removal of 68 amino acids from the N‐terminus by post‐translational proteolytic cleavage. The pH‐dependent gating of the channel isoforms is distinctly different. In both Hv1 and Hv1Sper, the conductance–voltage relationship is determined by the pH difference across the membrane (∆pH). However, simultaneous changes in intracellular and extracellular pH that leave ΔpH constant strongly shift the activation curve of Hv1Sper but not that of Hv1, demonstrating that cleavage of the N‐terminus tunes pH sensing in Hv1. Moreover, we show that Hv1 and Hv1Sper assemble as heterodimers that combine features of both constituents. We suggest that cleavage and heterodimerization of Hv1 represents an adaptation to the specific requirements of pH control in sperm.
Inwardly rectifying K+ channels are major contributors to flow‐induced vasodilatation in resistance arteries
Authors: Ahn Sang Joon , Fancher Ibra S. , Bian Jing‐Tan , Zhang Chong Xu , Schwab Sarah , Gaffin Robert , Phillips Shane A. , Levitan Irena
Published: November 2016

Key points

Endothelial inwardly rectifying K+ (Kir2.1) channels regulate flow‐induced vasodilatation via nitric oxide (NO) in mouse mesenteric resistance arteries.

Deficiency of Kir2.1 channels results in elevated blood pressure and increased vascular resistance.

Flow‐induced vasodilatation in human resistance arteries is also regulated by inwardly rectifying K+ channels.

This study presents the first direct evidence that Kir channels play a critical role in physiological endothelial responses to flow.

Inwardly rectifying K+ (Kir) channels are known to be sensitive to flow, but their role in flow‐induced endothelial responses is not known. The goal of this study is to establish the role of Kir channels in flow‐induced vasodilatation and to provide first insights into the mechanisms responsible for Kir signalling in this process. First, we establish that primary endothelial cells isolated from murine mesenteric arteries express functional Kir2.1 channels sensitive to shear stress. Then, using the Kir2.1+/− heterozygous mouse model, we establish that downregulation of Kir2.1 results in significant decrease in shear‐activated Kir currents and inhibition of endothelium‐dependent flow‐induced vasodilatation (FIV) assayed in pressurized mesenteric arteries pre‐constricted with endothelin‐1. Deficiency in Kir2.1 also results in the loss of flow‐induced phosphorylation of eNOS and Akt, as well as inhibition of NO generation. All the effects are fully rescued by endothelial cell (EC)‐specific overexpression of Kir2.1. A component of FIV that is Kir independent is abrogated by blocking Ca2+‐sensitive K+ channels. Kir2.1 has no effect on endothelium‐independent and K+‐induced vasodilatation in denuded arteries. Kir2.1+/− mice also show increased mean blood pressure measured by carotid artery cannulation and increased microvascular resistance measured using a tail‐cuff. Importantly, blocking Kir channels also inhibits flow‐induced vasodilatation in human subcutaneous adipose microvessels. Endothelial Kir channels contribute to FIV of mouse mesenteric arteries via an NO‐dependent mechanism, whereas Ca2+‐sensitive K+ channels mediate FIV via an NO‐independent pathway. Kir2 channels also regulate vascular resistance and blood pressure. Finally, Kir channels also contribute to FIV in human subcutaneous microvessels.
Study of Starting Problem of Axisymmetric Divergent Dual Throat Nozzle
Authors: Wang Yangsheng , Xu Jinglei , Huang Shuai
Published: November 2016

Compared to the conventional axisymmetric dual throat nozzle, the axisymmetric divergent dual throat nozzle (ADDTN) can offer larger thrust vector angles. However, the starting problem maybe exists in the ADDTN and results in a huge thrust loss. In this paper, the ADDTN starting problem has been studied by steady and unsteady numerical simulations. The effects of nozzle geometric parameters on internal nozzle performance have been discussed in detail, including cavity divergence angle, cavity convergence angle, cavity length, expansion ratio, rounding radius at the nozzle throat, and rounding radius at the cavity bottom. And, the shock oscillation phenomenon is found inside the recessed cavity in some high-expansion ratio configurations. In addition, a bypass is proposed in this study to solve the ADDTN starting problem. The main numerical simulation results show that the expansion ratio is the most sensitive parameter affecting the starting characteristic of ADDTN, followed by the cavity divergence angle and the cavity length. And, among these parameters, the parameters of cavity convergence angle and rounding radius at the cavity bottom contribute the least to the starting problem. Besides, the ADDTN configurations of large rounding radius at the nozzle throat tend to start.
Plasma polymerization of poly(3,4-ethylenedioxyethene) films: The influence of plasma gas phase chemistry
Authors: Liu Caroline , Goeckner Matthew J. , Walker Amy V.
Published: November 2016

Poly(3,4-ethylenedioxythiophene) (PEDOT) is a conducting polymer and so has many technological applications. Plasma polymerization is an attractive technique by which to form PEDOT because it does not require solvents and can be performed at low substrate temperatures. However to date, plasma polymerized PEDOT have electrical conductivities that are at least 4 orders of magnitude lower than PEDOT synthesized using other methods. In this paper, the authors investigate the influence of the plasma gas phase chemistry on the conductivity of plasma polymerized films using infrared spectroscopy and complementary density functional theory calculations. The authors show that the monomer of PEDOT, 3,4-ethylenedioxythiophene (EDOT), begins to decompose at very low energies per molecule (<1 eV/n) with its weakest bonds, the C–O bonds of the dioxy ring, breaking first. Little, or no, fragmentation of the aromatic (thiophene) ring is observed. Since reactions can now occur at the 3,4-positions of the thiophene ring as well as the 2,5 positions, the resulting film is composed of low-molecular weight species, and there is not sufficient bond conjugation for electrical conduction. Finally, at very low plasma powers, significant variations in the decomposition of EDOT suggest that there are changes in the electron energy density function.
Physical constraints of cultural evolution of dialects in killer whales
Authors: Filatova Olga A. , Samarra Filipa I. P. , Barrett-Lennard Lance G. , Miller Patrick J. O. , Ford John K. B. , Yurk Harald , Matkin Craig O. , Hoyt Erich
Published: November 2016

Odontocete sounds are produced by two pairs of phonic lips situated in soft nares below the blowhole; the right pair is larger and is more likely to produce clicks, while the left pair is more likely to produce whistles. This has important implications for the cultural evolution of delphinid sounds: the greater the physical constraints, the greater the probability of random convergence. In this paper the authors examine the call structure of eight killer whale populations to identify structural constraints and to determine if they are consistent among all populations. Constraints were especially pronounced in two-voiced calls. In the calls of all eight populations, the lower component of two-voiced (biphonic) calls was typically centered below 4 kHz, while the upper component was typically above that value. The lower component of two-voiced calls had a narrower frequency range than single-voiced calls in all populations. This may be because some single-voiced calls are homologous to the lower component, while others are homologous to the higher component of two-voiced calls. Physical constraints on the call structure reduce the possible variation and increase the probability of random convergence, producing similar calls in different populations.
Single-particle mapping of nonequilibrium nanocrystal transformations
Authors: Ye Xingchen , Jones Matthew R. , Frechette Layne B. , Chen Qian , Powers Alexander S. , Ercius Peter , Dunn Gabriel , Rotskoff Grant M. , Nguyen Son C. , Adiga Vivekananda P. , Zettl Alex , Rabani Eran , Geissler Phillip L. , Alivisatos A. Paul
Published: November 2016

Watching it all fall apart

The control of the shape and size of metal nanoparticles can be very sensitive to the growth conditions of the particles. Ye
et al.
studied the reverse process: They tracked the dissolution of gold nanoparticles in a redox environment inside a liquid cell within an electron microscope, controlling the particle dissolution with the electron beam. Tracking short-lived particle shapes revealed structures of greater or lesser stability. The findings suggest kinetic routes to particle sizes and shapes that would otherwise be difficult to generate.

Science
, this issue p.
874
The formation of peak rings in large impact craters
Authors: Morgan Joanna V. , Gulick Sean P. S. , Bralower Timothy , Chenot Elise , Christeson Gail , Claeys Philippe , Cockell Charles , Collins Gareth S. , Coolen Marco J. L. , Ferrière Ludovic , Gebhardt Catalina , Goto Kazuhisa , Jones Heather , Kring David A. , Le Ber Erwan , Lofi Johanna , Long Xiao , Lowery Christopher , Mellett Claire , Ocampo-Torres Rubén , Osinski Gordon R. , Perez-Cruz Ligia , Pickersgill Annemarie , Poelchau Michael , Rae Auriol , Rasmussen Cornelia , Rebolledo-Vieyra Mario , Riller Ulrich , Sato Honami , Schmitt Douglas R. , Smit Jan , Tikoo Sonia , Tomioka Naotaka , Urrutia-Fucugauchi Jaime , Whalen Michael , Wittmann Axel , Yamaguchi Kosei E. , Zylberman William
Published: November 2016

Drilling into Chicxulub's formation

The Chicxulub impact crater, known for its link to the demise of the dinosaurs, also provides an opportunity to study rocks from a large impact structure. Large impact craters have “peak rings” that define a complex crater morphology. Morganet al.looked at rocks from a drilling expedition through the peak rings of the Chicxulub impact crater (see the Perspective by Barton). The drill cores have features consistent with a model that postulates that a single over-heightened central peak collapsed into the multiple-peak-ring structure. The validity of this model has implications for far-ranging subjects, from how giant impacts alter the climate on Earth to the morphology of crater-dominated planetary surfaces.

Science, this issue p.878; see also p.836
Diamond defects cooperate via light
Authors: Hanson Ronald
Published: November 2016

Silicon-vacancy centers in diamond show single-photon switching and superradiance
Neural circuitry gets rewired
Authors: Adameyko Igor
Published: November 2016

Former parasympathetic innervations of organs are now claimed sympathetic
Plant metabolons assembled on demand
Authors: Dastmalchi Mehran , Facchini Peter J.
Published: November 2016

Proteins interact at an intracellular membrane to form dynamic metabolons that increase metabolic flux
Elucidating the interplay between IgG-Fc valency and FcγR activation for the design of immune complex inhibitors
Authors: Ortiz Daniel F. , Lansing Jonathan C. , Rutitzky Laura , Kurtagic Elma , Prod’homme Thomas , Choudhury Amit , Washburn Nathaniel , Bhatnagar Naveen , Beneduce Christopher , Holte Kimberly , Prenovitz Robert , Child Matthew , Killough Jason , Tyler Steven , Brown Julia , Nguyen Stephanie , Schwab Inessa , Hains Maurice , Meccariello Robin , Markowitz Lynn , Wang Jing , Zouaoui Radouane , Simpson Allison , Schultes Birgit , Capila Ishan , Ling Leona , Nimmerjahn Falk , Manning Anthony M. , Bosques Carlos J.
Published: November 2016

An engineered trivalent Fc drug candidate is a potent inhibitor of FcγR-driven immune cell activation and autoimmune diseases in animal models.
Reloadable multidrug capturing delivery system for targeted ischemic disease treatment
Authors: Wu Jasmine P. J. , Cheng Bill , Roffler Steve R. , Lundy David J. , Yen Christopher Y. T. , Chen Peilin , Lai James J. , Pun Suzie H. , Stayton Patrick S. , Hsieh Patrick C. H.
Published: November 2016

A reloadable drug capture system facilitates multidrug therapy for neovascularization after limb ischemia.
Boosting dopamine to lift depression?
Authors: Etkin Amit
Published: November 2016

The brain reward circuit that is dysfunctional in depression can be targeted pharmacologically.
Detection of Clostridium difficile in Feces of Asymptomatic Patients Admitted to the Hospital
Authors: Terveer Elisabeth M. , Crobach Monique J. T. , Sanders Ingrid M. J. G. , Vos Margreet C. , Verduin Cees M. , Kuijper Ed J.
Published: November 2016

Recent evidence shows that patients asymptomatically colonized with
Clostridium difficile
may contribute to the transmission of
C. difficile
in health care facilities. Additionally, these patients may have a higher risk of developing
C. difficile
infection. The aim of this study was to compare a commercially available PCR directed to both toxin A and B (
artus
C. difficile
QS-RGQ kit CE; Qiagen), an enzyme-linked fluorescent assay to glutamate dehydrogenase (GDH ELFA) (Vidas, bioMérieux), and an in-house-developed PCR to
tcdB
, with (toxigenic) culture of
C. difficile
as the gold standard to detect asymptomatic colonization. Test performances were evaluated in a collection of 765 stool samples obtained from asymptomatic patients at admission to the hospital. The
C. difficile
prevalence in this collection was 5.1%, and 3.1% contained toxigenic
C. difficile
. Compared to
C. difficile
culture, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the
C. difficile
GDH ELFA were 87.2%, 91.2%, 34.7%, and 99.3%, respectively. Compared with results of toxigenic culture, the sensitivity, specificity, PPV, and NPV of the commercially available PCR and the in-house PCR were 95.8%, 93.4%, 31.9%, 99.9%, and 87.5%, 98.8%, 70%, and 99.6%, respectively. We conclude that in a low-prevalence setting of asymptomatically colonized patients, both GDH ELFA and a nucleic acid amplification test can be applied as a first screening test, as they both display a high NPV. However, the low PPV of the tests hinders the use of these assays as stand-alone tests.
Progress in Quantitative Viral Load Testing: Variability and Impact of the WHO Quantitative International Standards
Authors: Hayden R. T. , Sun Y. , Tang L. , Procop G. W. , Hillyard D. R. , Pinsky B. A. , Young S. A. , Caliendo A. M.
Published: November 2016

It has been hoped that the recent availability of WHO quantitative standards would improve interlaboratory agreement for viral load testing; however, insufficient data are available to evaluate whether this has been the case. Results from 554 laboratories participating in proficiency testing surveys for quantitative PCR assays of cytomegalovirus (CMV), Epstein-Barr virus (EBV), BK virus (BKV), adenovirus (ADV), and human herpesvirus 6 (HHV6) were evaluated to determine overall result variability and then were stratified by assay manufacturer. The impact of calibration to international units/ml (CMV and EBV) on variability was also determined. Viral loads showed a high degree of interlaboratory variability for all tested viruses, with interquartile ranges as high as 1.46 log
10
copies/ml and the overall range for a given sample up to 5.66 log
10
copies/ml. Some improvement in result variability was seen when international units were adopted. This was particularly the case for EBV viral load results. Variability in viral load results remains a challenge across all viruses tested here; introduction of international quantitative standards may help reduce variability and does so more or less markedly for certain viruses.
Coat Protein Regulation by CK2, CPIP, HSP70, and CHIP Is Required for Potato Virus A Replication and Coat Protein Accumulation
Authors: Lõhmus Andres , Hafrén Anders , Mäkinen Kristiina
Published: November 2016

We demonstrate here that both coat protein (CP) phosphorylation by protein kinase CK2 and a chaperone system formed by two heat shock proteins, CP-interacting protein (CPIP) and heat shock protein 70 (HSP70), are essential for potato virus A (PVA; genus
Potyvirus
) replication and that all these host proteins have the capacity to contribute to the level of PVA CP accumulation. An E3 ubiquitin ligase called carboxyl terminus Hsc70-interacting protein (CHIP), which may participate in the CPIP-HSP70-mediated CP degradation, is also needed for robust PVA gene expression. Residue Thr
243
within the CK2 consensus sequence of PVA CP was found to be essential for viral replication and to regulate CP protein stability. Substitution of Thr
243
either with a phosphorylation-mimicking Asp (CP
ADA
) or with a phosphorylation-deficient Ala (CP
AAA
) residue in CP expressed from viral RNA limited PVA gene expression to the level of nonreplicating PVA. We found that both the CP
AAA
mutant and CK2 silencing inhibited, whereas CP
ADA
mutant and overexpression of CK2 increased, PVA translation. From our previous studies, we know that phosphorylation reduces the RNA binding capacity of PVA CP and an excess of CP fully blocks viral RNA translation. Together, these findings suggest that binding by nonphosphorylated PVA CP represses viral RNA translation, involving further CP phosphorylation and CPIP-HSP70 chaperone activities as prerequisites for PVA replication. We propose that this mechanism contributes to shifting potyvirus RNA from translation to replication.

IMPORTANCE
Host protein kinase CK2, two host chaperones, CPIP and HSP70, and viral coat protein (CP) phosphorylation at Thr
243
are needed for potato virus A (PVA) replication. Our results show that nonphosphorylated CP blocks viral translation, likely via binding to viral RNA. We propose that this translational block is needed to allow time and space for the formation of potyviral replication complex around the 3′ end of viral RNA. Progression into replication involves CP regulation by both CK2 phosphorylation and chaperones CPIP and HSP70.
Hepatitis C Virus-Induced Rab32 Aggregation and Its Implications for Virion Assembly
Authors: Pham Tu M. , Tran Si C. , Lim Yun-Sook , Hwang Soon B.
Published: November 2016

Hepatitis C virus (HCV) is highly dependent on cellular factors for viral propagation. Using high-throughput next-generation sequencing, we analyzed the host transcriptomic changes and identified 30 candidate genes which were upregulated in cell culture-grown HCV (HCVcc)-infected cells. Of these candidates, we selected Rab32 for further investigation. Rab32 is a small GTPase that regulates a variety of intracellular membrane-trafficking events in various cell types. In this study, we demonstrated that both mRNA and protein levels of Rab32 were increased in HCV-infected cells. Furthermore, we showed that HCV infection converted the predominantly expressed GTP-bound Rab32 to GDP-bound Rab32, contributing to the aggregation of Rab32 and thus making it less sensitive to cellular degradation machinery. In addition, GDP-bound Rab32 selectively interacted with HCV core protein and deposited core protein into the endoplasmic reticulum (ER)-associated Rab32-derived aggregated structures in the perinuclear region, which were likely to be viral assembly sites. Using RNA interference technology, we demonstrated that Rab32 was required for the assembly step but not for other stages of the HCV life cycle. Taken together, these data suggest that HCV may modulate Rab32 activity to facilitate virion assembly.

IMPORTANCE
Rab32, a member of the Ras superfamily of small GTPases, regulates various intracellular membrane-trafficking events in many cell types. In this study, we showed that HCV infection concomitantly increased Rab32 expression at the transcriptional level and altered the balance between GDP- and GTP-bound Rab32 toward production of Rab32-GDP. GDP-bound Rab32 selectively interacted with HCV core protein and enriched core in the ER-associated Rab32-derived aggregated structures that were probably necessary for viral assembly. Indeed, we showed that Rab32 was specifically required for the assembly of HCV. Collectively, our study identifies that Rab32 is a novel host factor essential for HCV particle assembly.
A Transformation-Defective Polyomavirus Middle T Antigen with a Novel Defect in PI3 Kinase Signaling
Authors: Denis Deborah , Rouleau Cecile , Schaffhausen Brian S.
Published: November 2016

Middle T antigen (MT), the principal oncoprotein of murine polyomavirus, transforms by association with cellular proteins. Protein phosphatase 2A (PP2A), YAP, Src family tyrosine kinases, Shc, phosphatidylinositol 3-kinase (PI3K), and phospholipase C-γ1 (PLCγ1) have all been implicated in MT transformation. Mutant dl1015, with deletion of residues 338 to 347 in the C-terminal region, has been an enigma, because the basis for its transformation defect has not been apparent. This work probes the dl1015 region of MT. Because the region is proline rich, the hypothesis that it targets Src homology domain 3 (SH3) domains was tested, but mutation of the putative SH3 binding motif did not affect transformation. During this work, two point mutants, W348R and E349K, were identified as transformation defective. Extensive analysis of the E349K mutant is described here. Similar to wild-type MT, the E349K mutant associates with PP2A, YAP, tyrosine kinases, Shc, PI3 kinase, and PLCγ1. The E349K mutant was examined to determine the mechanism for its transformation defect. Assays of cell localization and membrane targeting showed no obvious difference in localization. Src association was normal as assayed by
in vitro
kinase and MT phosphopeptide mapping. Shc activation was confirmed by its tyrosine phosphorylation. Association of type 1 PI3K with MT was demonstrated by coimmunoprecipitation, showing both PI3K subunits and
in vitro
activity. Nonetheless, expression of the mutants failed to lead to the activation of two known downstream targets of PI3K, Akt and Rac-1. Strikingly, despite normal association of the E349K mutant with PI3K, cells expressing the mutant failed to elevate phosphatidylinositol (3,4,5)-trisphosphate (PIP3) in mutant-expressing cells. These results indicate a novel unsuspected aspect to PI3K control.

IMPORTANCE
The gene coding for middle T antigen (MT) is the murine polyomavirus oncogene most responsible for tumor formation. Its study has a history of uncovering novel aspects of mammalian cell regulation. The importance of PI3K activity and tyrosine phosphorylation are two examples of insights coming from MT. This study describes new mutants unable to transform like the wild type that point to novel regulation of PI3K signaling. Previous mutants were defective in PI3K because they failed to bind the enzyme and bring the activity to the membrane. These mutants recruit PI3K activity like the wild type, but fail to elevate the cellular level of PIP3, the product used to signal downstream of PI3K. As a result, they fail to activate either Akt or Rac1, explaining the transformation defect.
Identification of Human Anti-HIV gp160 Monoclonal Antibodies That Make Effective Immunotoxins
Authors: Pincus Seth H. , Song Kejing , Maresh Grace A. , Hamer Dean H. , Dimitrov Dimiter S. , Chen Weizao , Zhang Mei-Yun , Ghetie Victor F. , Chan-Hui Po-Ying , Robinson James E. , Vitetta Ellen S.
Published: November 2016

The envelope (Env) glycoprotein of HIV is the only intact viral protein expressed on the surface of both virions and infected cells. Env is the target of neutralizing antibodies (Abs) and has been the subject of intense study in efforts to produce HIV vaccines. Therapeutic anti-Env Abs can also exert antiviral effects via Fc-mediated effector mechanisms or as cytotoxic immunoconjugates, such as immunotoxins (ITs). In the course of screening monoclonal antibodies (MAbs) for their ability to deliver cytotoxic agents to infected or Env-transfected cells, we noted disparities in their functional activities. Different MAbs showed diverse functions that did not correlate with each other. For example, MAbs against the external loop region of gp41 made the most effective ITs against infected cells but did not neutralize virus and bound only moderately to the same cells that they killed so effectively when they were used in ITs. There were also differences in IT-mediated killing among transfected and infected cell lines that were unrelated to the binding of the MAb to the target cells. Our studies of a well-characterized antigen demonstrate that MAbs against different epitopes have different functional activities and that the binding of one MAb can influence the interaction of other MAbs that bind elsewhere on the antigen. These results have implications for the use of MAbs and ITs to kill HIV-infected cells and eradicate persistent reservoirs of HIV infection.

IMPORTANCEThere is increased interest in using antibodies to treat and cure HIV infection. Antibodies can neutralize free virus and kill cells already carrying the virus. The virus envelope (Env) is the only HIV protein expressed on the surfaces of virions and infected cells. In this study, we examined a panel of human anti-Env antibodies for their ability to deliver cell-killing toxins to HIV-infected cells and to perform other antiviral functions. The ability of an antibody to make an effective immunotoxin could not be predicted from its other functional characteristics, such as its neutralizing activity. Anti-HIV immunotoxins could be used to eliminate virus reservoirs that persist despite effective antiretroviral therapy.
Remote multifocal bleeding points producing a Sylvian subpial hematoma during endovascular coiling of an acutely ruptured cerebral aneurysm
Authors: Hilditch Christopher Alan , Sonwalkar Hemant , Wuppalapati Siddhartha
Published: November 2016

Subpial hematoma is a rare type of intracranial hemorrhage with a poor prognosis. A new mechanism to explain subpial Sylvian hematoma formation in acute post-aneurysmal subarachnoid hemorrhage (SAH) was observed during coiling of a posterior communicating artery aneurysm. Multiple small bleeding points from pial branches of the left middle cerebral artery, which were remote from the ruptured aneurysm, were observed on conventional angiography. This bleeding led to the formation of a large expanding subpial Sylvian hematoma. Similar observations have been recently demonstrated on 4D CT angiography (4D CTA). We present a case that adds evidence to the literature in support of a new mechanism of subpial hematoma formation in the setting of acute SAH. This may advocate the early use of 4D CTA and conveys a poor prognosis, which might influence treatment decisions.
Management of Hermansky-Pudlak syndrome in pregnancy and review of literature
Authors: Van Avermaete Freya , Muys Joke , Jacquemyn Yves
Published: November 2016

We report on the obstetric outcome of a woman aged 27 years with Hermansky-Pudlak syndrome (HPS). She underwent a caesarean section after failed induction of labour. Platelet transfusion was administered in a set schedule for 36 hours, starting 2 hours before delivery. The child had good Apgar scores and there were no significant problems of prolonged bleeding during the procedure. 72 hours postpartum, a haematoma developed at the site of the wound, subsequently complicated by a secondary infection for which she received antibiotics. Wound care was provided in an outpatient setting during 2 weeks, in which the infection stabilised and responded to the treatment. Mother and child could leave the hospital after 6 days.
Neurogenic fever in a patient with a chordoid glioma
Authors: García Carretero Rafael , Romero Brugera Marta , Vazquez-Gomez Oscar , Rebollo-Aparicio Noelia
Published: November 2016

Chordoid gliomas are rare tumours. Despite being considered low-grade neoplasms, recent reviews have reported generally poor prognosis due to complications involving severe hypothalamic symptoms. We report a patient aged 30 years with chordoid glioma. What makes this case report interesting is the presence of neurogenic fever, which was already present before the final diagnosis of the brain tumour and also several months after the surgical removal. Since the patient underwent a subtotal resection of the tumour, it remains unclear whether the fever was due to hypothalamic dysfunction or remnants of the tumour. We also performed temperature logging with a continuous-monitoring recording device.
Association of psychological variables and outcome in tendinopathy: a systematic review
Authors: Mallows Adrian , Debenham James , Walker Tom , Littlewood Chris
Published: November 2016

Objective

Fear, anxiety, depression, distress and catastrophisation are all factors known to affect pain and disability levels. To date, the association of such psychological factors has yet to be established in tendinopathy. Therefore, the purpose of this paper was to determine if psychological variables are associated with tendinopathy and whether any such variables may be associated with pain and disability outcomes in conservative management of tendinopathy.

Design

A systematic review was undertaken and included studies were appraised for risk of bias using the Newcastle-Ottawa Scale. Owing to heterogeneity of studies, a qualitative synthesis was undertaken.

Data sources

An electronic search of MEDLINE, CiNAHL, SPORTDiscus, PsycINFO, EMBASE and PsycARTICLES was undertaken from their inception to April 2016.

Eligibility criteria for selecting studies

Any study design that incorporated psychological measures and clinical outcomes using participants with tendinopathy.

Results

Ten articles describing nine studies and 1108 participants were included. Conflicting evidence exists regarding the association of anxiety, depression and lateral epicondylalgia (LE). Strong evidence suggests LE is not associated with kinesiophobia. Moderate evidence links catastrophisation and distress with LE. Moderate evidence suggests distress is not associated with rotator cuff tendinopathy, but kinesiophobia and catastrophisation are. Limited evidence suggests patellar tendinopathy is not associated with anxiety or depression and kinesiophobia may be linked with suboptimal outcomes in Achilles tendinopathy.

Summary/conclusions

Tendinopathy requires an individualised approach to management. Clinicians should consider using validated screening tools for the presence of psychological variables as a part of their holistic management.
Perceived barriers to accessing mental health services among black and minority ethnic (BME) communities: a qualitative study in Southeast England
Authors: Memon Anjum , Taylor Katie , Mohebati Lisa M , Sundin Josefin , Cooper Max , Scanlon Thomas , de Visser Richard
Published: November 2016

Objective

In most developed countries, substantial disparities exist in access to mental health services for black and minority ethnic (BME) populations. We sought to determine perceived barriers to accessing mental health services among people from these backgrounds to inform the development of effective and culturally acceptable services to improve equity in healthcare.

Design and setting

Qualitative study in Southeast England.

Participants

26 adults from BME backgrounds (13 men, 13 women; aged >18 years) were recruited to 2 focus groups. Participants were identified through the registers of the Black and Minority Ethnic Community Partnership centre and by visits to local community gatherings and were invited to take part by community development workers. Thematic analysis was conducted to identify key themes about perceived barriers to accessing mental health services.

Results

Participants identified 2 broad themes that influenced access to mental health services. First, personal and environmental factors included inability to recognise and accept mental health problems, positive impact of social networks, reluctance to discuss psychological distress and seek help among men, cultural identity, negative perception of and social stigma against mental health and financial factors. Second, factors affecting the relationship between service user and healthcare provider included the impact of long waiting times for initial assessment, language barriers, poor communication between service users and providers, inadequate recognition or response to mental health needs, imbalance of power and authority between service users and providers, cultural naivety, insensitivity and discrimination towards the needs of BME service users and lack of awareness of different services among service users and providers.

Conclusions

People from BME backgrounds require considerable mental health literacy and practical support to raise awareness of mental health conditions and combat stigma. There is a need for improving information about services and access pathways. Healthcare providers need relevant training and support in developing effective communication strategies to deliver individually tailored and culturally sensitive care. Improved engagement with people from BME backgrounds in the development and delivery of culturally appropriate mental health services could facilitate better understanding of mental health conditions and improve access.
Tutorial: The quantum finite square well and the Lambert W function
Authors: Roberts Ken , Valluri S.R.
Published: November 2016

We present a solution of the quantum mechanics problem of the allowable energy levels of a bound particle in a one-dimensional finite square well. The method is a geometric-analytic technique utilizing the conformal mapping w → z = wew between two complex domains. The solution of the finite square well problem can be seen to be described by the images of simple geometric shapes, lines, and circles, under this map and its inverse image. The technique can also be described using the Lambert W function. One can work in either of the complex domains, thereby obtaining additional insight into the finite square well problem and its bound energy states. This suggests interesting possibilities for the design of materials that are sensitive to minute changes in their environment such as nanostructures and the quantum well infrared photodetector.
Use of online resources by physics students in Canada: A cross sectional study
Authors: Terrana Alexandra , Leung Anthony C.K. , Jerzak Stanislaw
Published: November 2016

With the main goal of understanding how and why university physics majors use educational internet resources, we conducted a cross-sectional survey of undergraduate and graduate physics students attending 20 universities across Canada. The survey probes how intensively students at different academic levels rely on various forms of internet resources, such as online texts, videos, and online courses to supplement their physics education. The results imply that the internet can effectively facilitate autonomous, self-driven learning, but submersion into completely online courses is not popular. This report presents the survey results, interpretations, and ideas for how university instructors can take advantage of the growing volume and quality of online physics resources.
From Structure to Activity: Using Centrality Measures to Predict Neuronal Activity
Authors: Fletcher Jack McKay , Wennekers Thomas
Published: November 2016

It is clear that the topological structure of a neural network somehow determines the activity of the neurons within it. In the present work, we ask to what extent it is possible to examine the structural features of a network and learn something about its activity? Specifically, we consider how the centrality (the importance of a node in a network) of a neuron correlates with its firing rate. To investigate, we apply an array of centrality measures, including In-Degree, Closeness, Betweenness, Eigenvector, Katz, PageRank, Hyperlink-Induced Topic Search (HITS) and NeuronRank to Leaky-Integrate and Fire neural networks with different connectivity schemes. We find that Katz centrality is the best predictor of firing rate given the network structure, with almost perfect correlation in all cases studied, which include purely excitatory and excitatory–inhibitory networks, with either homogeneous connections or a small-world structure. We identify the properties of a network which will cause this correlation to hold. We argue that the reason Katz centrality correlates so highly with neuronal activity compared to other centrality measures is because it nicely captures disinhibition in neural networks. In addition, we argue that these theoretical findings are applicable to neuroscientists who apply centrality measures to functional brain networks, as well as offer a neurophysiological justification to high level cognitive models which use certain centrality measures.