bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution and dispersal of mammoths across the Northern Hemisphere
Authors: Lister A. M. , Sher A. V.
Published: November 2015

Moving mammoths

Mammoths are a particularly charismatic example of our Pleistocene megafuana. Lister and Sher took a detailed look at mammoth fossils globally and suggest that the North American Columbian mammoth, thought to have arisen from a European species, probably evolved from a more advanced Asian species. Similar dispersal events of Asian mammoths led to later colonization events in Europe and North America.

Science, this issue p.805
Climate change and marine vertebrates
Authors: Sydeman William J. , Poloczanska Elvira , Reed Thomas E. , Thompson Sarah Ann
Published: November 2015

Climate change impacts on vertebrates have consequences for marine ecosystem structures and services. We review marine fish, mammal, turtle, and seabird responses to climate change and discuss their potential for adaptation. Direct and indirect responses are demonstrated from every ocean. Because of variation in research foci, observed responses differ among taxonomic groups (redistributions for fish, phenology for seabirds). Mechanisms of change are (i) direct physiological responses and (ii) climate-mediated predator-prey interactions. Regional-scale variation in climate-demographic functions makes range-wide population dynamics challenging to predict. The nexus of metabolism relative to ecosystem productivity and food webs appears key to predicting future effects on marine vertebrates. Integration of climate, oceanographic, ecosystem, and population models that incorporate evolutionary processes is needed to prioritize the climate-related conservation needs for these species.
Imaging resonances in low-energy NO-He inelastic collisions
Authors: Vogels Sjoerd N. , Onvlee Jolijn , Chefdeville Simon , van der Avoird Ad , Groenenboom Gerrit C. , van de Meerakker Sebastiaan Y. T.
Published: November 2015

Watching collisions in the slow lane

Quantum mechanics aims to “micromanage” the details of collisions between atoms and molecules. However, it's hard to discern all the subtleties under high-energy conditions. Vogels
et al.
slowed down two intersecting beams of helium atoms and nitric oxide (NO) molecules to a relative crawl in order to characterize the collisions precisely. The data revealed short-lived resonances that matched theoretical predictions remarkably well—a striking feat on both sides, given the challenge of accurately modeling NO's unpaired electron. The study highlights chemists' increasingly sophisticated understanding of collision dynamics.

Science
, this issue p.
787
Torque-mixing magnetic resonance spectroscopy
Authors: Losby J. E. , Sani F. Fani , Grandmont D. T. , Diao Z. , Belov M. , Burgess J. A. J. , Compton S. R. , Hiebert W. K. , Vick D. , Mohammad K. , Salimi E. , Bridges G. E. , Thomson D. J. , Freeman M. R.
Published: November 2015

Mechanically detected spin resonances

The interaction of spins in a sample with a magnetic field can generate forces that can be sensed with cantilever probes. Losby
et al.
measured the resonance signals at room temperature with a micromechanical torque magnetometer. The difference between two applied radio-frequency signals corresponded to the mechanical frequency of the resonator. This approach revealed the vortex core dynamics of the ferri-toferro–magnetic transition in a micrometer-sized yttrium-iron-garnet single-crystal disk.

Science
, this issue p.
798
To catch and smash charge on the hop
Authors: Ueda Kiyoshi
Published: November 2015

High-harmonic spectroscopy can probe charge migration controlled by a laser field

[Also see Report by

Kraus
et al
.

]
Breaching the gut-vascular barrier
Authors: Bouziat Romain , Jabri Bana
Published: November 2015

A vascular barrier in the intestinal tract controls pathogen dissemination

[Also see Report by

Spadoni
et al
.

]
Persistence of Antibody to Influenza A/H5N1 Vaccine Virus: Impact of AS03 Adjuvant
Authors: Chen Wilbur H. , Jackson Lisa A. , Edwards Kathryn M. , Keitel Wendy A. , Hill Heather , Noah Diana L. , Creech C. Buddy , Patel Shital M. , Mangal Brian , Kotloff Karen L.
Published: November 2015

The adjuvant AS03 is stockpiled for future formulations with new and existing vaccines for the control of pandemic influenza virus. We previously reported the immunogenicity of an A/H5N1 vaccine extemporaneously mixed with the AS03 adjuvant for 42 days following vaccination. This report extends those findings to 1 year after vaccination.
Whole-Genome Sequence of Mycobacterium bovis BCG-1 (Russia)
Authors: Ludannyy R. , Alvarez Figueroa M. , Levi D. , Markelov M. , Dedkov V. , Aleksandrova N. , Shipulin G.
Published: November 2015

BCG vaccine (
Mycobacterium bovis
BCG-1 [Russia]) is the most important component of tuberculosis prophylaxis in Russia. This study represents the complete genome sequence and genetic characteristics of
M. bovis
BCG-1 (Russia), which has been used to manufacture BCG vaccine in Russia and in some other countries.
Draft Genome Sequence of
Halostagnicola
sp. A56, an Extremely Halophilic Archaeon Isolated from the Andaman Islands
Authors: Kanekar Sagar P. , Saxena Neha , Pore Soham D. , Arora Preeti , Kanekar P. P. , Dhakephalkar P. K.
Published: November 2015

The first draft genome of
Halostagnicola
sp. A56, isolated from the Andaman Islands is reported here. The A56 genome comprises 3,178,490 bp in 26 contigs with a G+C content of 60.8%. The genome annotation revealed that A56 could have potential applications for the production of polyhydroxyalkanoate or bioplastics.
Epidemiology Analysis of Streptococcus pyogenes in a Hospital in Southern Taiwan by Use of the Updated
emm
Cluster Typing System
Authors: Chiang-Ni Chuan , Zheng Po-Xing , Wang Shu-Ying , Tsai Pei-Jane , Chuang Woei-Jer , Lin Yee-Shin , Liu Ching-Chuan , Wu Jiunn-Jong
Published: November 2015

emm
typing is the most widely used molecular typing method for the human pathogen
Streptococcus pyogenes
(group A streptococcus [GAS]).
emm
typing is based on a small variable region of the
emm
gene; however, the
emm
cluster typing system defines GAS types according to the nearly complete sequence of the
emm
gene. Therefore,
emm
cluster typing is considered to provide more information regarding the functional and structural properties of M proteins in different
emm
types of GAS. In the present study, 677 isolates collected between 1994 and 2008 in a hospital in southern Taiwan were analyzed by the
emm
cluster typing system.
emm
clusters A-C4, E1, E6, and A-C3 were the most prevalent
emm
cluster types and accounted for 67.4% of total isolates.
emm
clusters A-C4 and E1 were associated with noninvasive diseases, whereas E6 was significantly associated with both invasive and noninvasive manifestations. In addition,
emm
clusters D4, E2, and E3 were significantly associated with invasive manifestations. Furthermore, we found that the functional properties of M protein, including low fibrinogen-binding and high IgG-binding activities, were correlated significantly with invasive manifestations. In summary, the present study provides updated epidemiological information on GAS
emm
cluster types in southern Taiwan.
Commentary: Peaks of Promise and Peril: Screening for Antibiotic Resistance by Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry
Authors: Anderson Neil W.
Published: November 2015

An article in this issue of the
Journal of Clinical Microbiology
(J.-H. Youn, S. K. Drake, R. A. Weingarten, K. M. Frank, J. P. Dekker, and A. F. Lau, J Clin Microbiol 53:35–42, 2015,
http://dx.doi.org/10.1128/JCM.01643-15
) describes the use of matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry for the detection of organisms carrying a
bla
KPC
-containing plasmid. This powerful and promising application highlights the challenges of using MALDI-TOF mass spectrometry for purposes other than organism identification.
Epstein-Barr Virus (EBV) Tegument Protein BGLF2 Promotes EBV Reactivation through Activation of the p38 Mitogen-Activated Protein Kinase
Authors: Liu XueQiao , Cohen Jeffrey I.
Published: November 2015

Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus associated with both B cell and epithelial cell malignancies. EBV infection of B cells triggers activation of several signaling pathways that are critical for cell survival, virus latency, and growth transformation. To identify EBV proteins important for regulating cell signaling, we used a proteomic approach to screen viral proteins for AP-1 and NF-κB promoter activity in AP-1– and NF-κB–luciferase reporter assays. We found that EBV BGLF2 activated AP-1 but not NF-κB reporter activity. Expression of EBV BGLF2 in cells activated p38 and c-Jun N-terminal kinase (JNK), both of which are important for mitogen-activated protein kinase (MAPK) signaling. Deletion of the carboxyl-terminal 66 amino acids of BGLF2 reduced the ability of BGLF2 to activate JNK and p38. Expression of BGLF2 enhanced BZLF1 expression in latently EBV-infected lymphoblastoid cell lines, and knockdown of BGLF2 reduced EBV reactivation induced by IgG cross-linking. Expression of BGLF2 induced BZLF1 expression and virus production in EBV-infected gastric carcinoma cells. BGLF2 enhanced BZLF1 expression and EBV production by activating p38; chemical inhibition of p38 and MAPK/ERK kinases 1 and 2 (MEK1/2) reduced expression of BZLF1 and virus production induced by BGLF2. In summary, the EBV tegument protein BGLF2, which is delivered to the cell at the onset of virus infection, activates the AP-1 pathway and enhances EBV reactivation and virus production.

IMPORTANCE
Epstein-Barr virus (EBV) is associated with both B cell and epithelial cell malignancies, and the virus activates multiple signaling pathways important for its persistence in latently infected cells. We identified a viral tegument protein, BGLF2, which activates members of the mitogen-activated protein kinase signaling pathway. Expression of BGLF2 increased expression of EBV BZLF1, which activates a switch from latent to lytic virus infection, and increased production of EBV. Inhibition of BGFL2 expression or inhibition of p38/MAPK, which is activated by BGLF2, reduced virus reactivation from latency. These results indicate that a viral tegument protein which is delivered to cells upon infection activates signaling pathways to enhance virus production and facilitate virus reactivation from latency.
Four Amino Acid Changes in HIV-2 Protease Confer Class-Wide Sensitivity to Protease Inhibitors
Authors: Raugi Dana N. , Smith Robert A. , Gottlieb Geoffrey S. ,   for the University of Washington-Dakar HIV-2 Study Group
Published: November 2015

Protease is essential for retroviral replication, and protease inhibitors (PI) are important for treating HIV infection. HIV-2 exhibits intrinsic resistance to most FDA-approved HIV-1 PI, retaining clinically useful susceptibility only to lopinavir, darunavir, and saquinavir. The mechanisms for this resistance are unclear; although HIV-1 and HIV-2 proteases share just 38 to 49% sequence identity, all critical structural features of proteases are conserved. Structural studies have implicated four amino acids in the ligand-binding pocket (positions 32, 47, 76, and 82). We constructed HIV-2ROD9molecular clones encoding the corresponding wild-type HIV-1 amino acids (I32V, V47I, M76L, and I82V) either individually or together (clone PRΔ4) and compared the phenotypic sensitivities (50% effective concentration [EC50]) of mutant and wild-type viruses to nine FDA-approved PI. Single amino acid replacements I32V, V47I, and M76L increased the susceptibility of HIV-2 to multiple PI, but no single change conferred class-wide sensitivity. In contrast, clone PRΔ4 showed PI susceptibility equivalent to or greater than that of HIV-1 for all PI. We also compared crystallographic structures of wild-type HIV-1 and HIV-2 proteases complexed with amprenavir and darunavir to models of the PRΔ4 enzyme. These models suggest that the amprenavir sensitivity of PRΔ4 is attributable to stabilizing enzyme-inhibitor interactions in the P2 and P2′ pockets of the protease dimer. Together, our results show that the combination of four amino acid changes in HIV-2 protease confer a pattern of PI susceptibility comparable to that of HIV-1, providing a structural rationale for intrinsic HIV-2 PI resistance and resolving long-standing questions regarding the determinants of differential PI susceptibility in HIV-1 and HIV-2.

IMPORTANCEProteases are essential for retroviral replication, and HIV-1 and HIV-2 proteases share a great deal of structural similarity. However, only three of nine FDA-approved HIV-1 protease inhibitors (PI) are active against HIV-2. The underlying reasons for intrinsic PI resistance in HIV-2 are not known. We examined the contributions of four amino acids in the ligand-binding pocket of the enzyme that differ between HIV-1 and HIV-2 by constructing HIV-2 clones encoding the corresponding HIV-1 amino acids and testing the PI susceptibilities of the resulting viruses. We found that the HIV-2 clone containing all four changes (PRΔ4) was as susceptible as HIV-1 to all nine PI. We also modeled the PRΔ4 enzyme structure and compared it to existing crystallographic structures of HIV-1 and HIV-2 proteases complexed with amprenavir and darunavir. Our findings demonstrate that four positions in the ligand-binding cleft of protease are the primary cause of HIV-2 PI resistance.
Sequential Infection in Ferrets with Antigenically Distinct Seasonal H1N1 Influenza Viruses Boosts Hemagglutinin Stalk-Specific Antibodies
Authors: Kirchenbaum Greg A. , Carter Donald M. , Ross Ted M.
Published: November 2015

Broadly reactive antibodies targeting the conserved hemagglutinin (HA) stalk region are elicited following sequential infection or vaccination with influenza viruses belonging to divergent subtypes and/or expressing antigenically distinct HA globular head domains. Here, we demonstrate, through the use of novel chimeric HA proteins and competitive binding assays, that sequential infection of ferrets with antigenically distinct seasonal H1N1 (sH1N1) influenza virus isolates induced an HA stalk-specific antibody response. Additionally, stalk-specific antibody titers were boosted following sequential infection with antigenically distinct sH1N1 isolates in spite of preexisting, cross-reactive, HA-specific antibody titers. Despite a decline in stalk-specific serum antibody titers, sequential sH1N1 influenza virus-infected ferrets were protected from challenge with a novel H1N1 influenza virus (A/California/07/2009), and these ferrets poorly transmitted the virus to naive contacts. Collectively, these findings indicate that HA stalk-specific antibodies are commonly elicited in ferrets following sequential infection with antigenically distinct sH1N1 influenza virus isolates lacking HA receptor-binding site cross-reactivity and can protect ferrets against a pathogenic novel H1N1 virus.

IMPORTANCE
The influenza virus hemagglutinin (HA) is a major target of the humoral immune response following infection and/or seasonal vaccination. While antibodies targeting the receptor-binding pocket of HA possess strong neutralization capacities, these antibodies are largely strain specific and do not confer protection against antigenic drift variant or novel HA subtype-expressing viruses. In contrast, antibodies targeting the conserved stalk region of HA exhibit broader reactivity among viruses within and among influenza virus subtypes. Here, we show that sequential infection of ferrets with antigenically distinct seasonal H1N1 influenza viruses boosts the antibody responses directed at the HA stalk region. Moreover, ferrets possessing HA stalk-specific antibody were protected against novel H1N1 virus infection and did not transmit the virus to naive contacts.
HIV-1 Virion Production from Single Inducible Proviruses following T-Cell Activation
Ex Vivo
Authors: Bui John K. , Mellors John W. , Cillo Anthony R.
Published: November 2015

Quantifying induced virion production from single proviruses is important for assessing the effects of HIV-1 latency reversal agents. Limiting dilution
ex vivo
cultures of resting CD4
+
T cells from 14 HIV-positive volunteers revealed that virion production after T-cell activation from individual proviruses varies by 10,000-fold to 100,000-fold. High-producing proviruses were associated with increases in cell-associated HIV-1 DNA levels, suggesting that reactivated proviruses proliferate. Single-cell analyses are needed to investigate differences in proviral expansion and virus production following latency reversal.
Crystal Structure of the Core Region of Hantavirus Nucleocapsid Protein Reveals the Mechanism for Ribonucleoprotein Complex Formation
Authors: Guo Yu , Wang Wenming , Sun Yuna , Ma Chao , Wang Xu , Wang Xin , Liu Pi , Shen Shu , Li Baobin , Lin Jianping , Deng Fei , Wang Hualin , Lou Zhiyong
Published: November 2015

Hantaviruses, which belong to the genusHantavirusin the familyBunyaviridae, infect mammals, including humans, causing either hemorrhagic fever with renal syndrome (HFRS) or hantavirus cardiopulmonary syndrome (HCPS) in humans with high mortality. Hantavirus encodes a nucleocapsid protein (NP) to encapsidate the genome and form a ribonucleoprotein complex (RNP) together with viral polymerase. Here, we report the crystal structure of the core domains of NP (NPcore) encoded by Sin Nombre virus (SNV) and Andes virus (ANDV), which are two representative members that cause HCPS in the New World. The constructs of SNV and ANDV NPcoreexclude the N- and C-terminal portions of full polypeptide to obtain stable proteins for crystallographic study. The structure features an N lobe and a C lobe to clamp RNA-binding crevice and exhibits two protruding extensions in both lobes. The positively charged residues located in the RNA-binding crevice play a key role in RNA binding and virus replication. We further demonstrated that the C-terminal helix and the linker region connecting the N-terminal coiled-coil domain and NPcoreare essential for hantavirus NP oligomerization through contacts made with two adjacent protomers. Moreover, electron microscopy (EM) visualization of native RNPs extracted from the virions revealed that a monomer-sized NP-RNA complex is the building block of viral RNP. This work provides insight into the formation of hantavirus RNP and provides an understanding of the evolutionary connections that exist among bunyaviruses.

IMPORTANCEHantaviruses are distributed across a wide and increasing range of host reservoirs throughout the world. In particular, hantaviruses can be transmitted via aerosols of rodent excreta to humans or from human to human and cause HFRS and HCPS, with mortalities of 15% and 50%, respectively. Hantavirus is therefore listed as a category C pathogen. Hantavirus encodes an NP that plays essential roles both in RNP formation and in multiple biological functions. NP is also the exclusive target for the serological diagnoses. This work reveals the structure of hantavirus NP, furthering the knowledge of hantavirus RNP formation, revealing the relationship between hantavirus NP and serological specificity and raising the potential for the development of new diagnosis and therapeutics targeting hantavirus infection.
A Comprehensive RNA Sequencing Analysis of the Adeno-Associated Virus (AAV) Type 2 Transcriptome Reveals Novel AAV Transcripts, Splice Variants, and Derived Proteins
Authors: Stutika Catrin , Gogol-Döring Andreas , Botschen Laura , Mietzsch Mario , Weger Stefan , Feldkamp Mirjam , Chen Wei , Heilbronn Regine
Published: November 2015

Adeno-associated virus (AAV) is recognized for its bipartite life cycle with productive replication dependent on coinfection with adenovirus (Ad) and AAV latency being established in the absence of a helper virus. The shift from latent to Ad-dependent AAV replication is mostly regulated at the transcriptional level. The current AAV transcription map displays highly expressed transcripts as found upon coinfection with Ad. So far, AAV transcripts have only been characterized on the plus strand of the AAV single-stranded DNA genome. The AAV minus strand is assumed not to be transcribed. Here, we apply Illumina-based RNA sequencing (RNA-Seq) to characterize the entire AAV2 transcriptome in the absence or presence of Ad. We find known and identify novel AAV transcripts, including additional splice variants, the most abundant of which leads to expression of a novel 18-kDa Rep/VP fusion protein. Furthermore, we identify for the first time transcription on the AAV minus strand with clustered reads upstream of the p5 promoter, confirmed by 5ˈ rapid amplification of cDNA ends and RNase protection assays. The p5 promoter displays considerable activity in both directions, a finding indicative of divergent transcription. Upon infection with AAV alone, low-level transcription of both AAV strands is detectable and is strongly stimulated upon coinfection with Ad.

IMPORTANCE
Next-generation sequencing (NGS) allows unbiased genome-wide analyses of transcription profiles, used here for an in depth analysis of the AAV2 transcriptome during latency and productive infection. RNA-Seq analysis led to the discovery of novel AAV transcripts and splice variants, including a derived, novel 18-kDa Rep/VP fusion protein. Unexpectedly, transcription from the AAV minus strand was discovered, indicative of divergent transcription from the p5 promoter. This finding opens the door for novel concepts of the switch between AAV latency and productive replication. In the absence of a suitable animal model to study AAV
in vivo
, combined
in cellulae
and
in silico
studies will help to forward the understanding of the unique, bipartite AAV life cycle.
Atypical CML with massive splenic infarct: an extremely rare presentation
Authors: Bandyopadhyay Dhrubajyoti , Manna Satyaki , Hajra Adrija , Bhattacharya Tanima Das
Published: November 2015

We report a case of a 47-year-old man who presented with hepatosplenomegaly, anaemia and massive splenic infarct. A series of investigations led us to a diagnosis of atypical chronic myeloid leucaemia, a rare variety of a mixed myelodysplastic/myeloproliferative neoplasm. This is the first case of atypical CML presenting with massive splenic infarction.
VIPoma with multiple endocrine neoplasia type 1 identified as an atypical gene mutation
Authors: Fujiya Atsushi , Kato Makoto , Shibata Taiga , Sobajima Hiroshi
Published: November 2015

A 47-year-old man presented with persistent diarrhoea and hypokalaemia. CT revealed 4 pancreatic tumours that appeared to be VIPomas, because the patient had an elevated plasma vasoactive intestinal polypeptide level. MRI showed a low-intensity area in the pituitary suggestive of a pituitary tumour, and a parathyroid tumour was detected by ultrasonography and 99Tc-MIBI scintigraphy. Given these results, the patient was diagnosed with multiple endocrine neoplasia type 1 (MEN1) and scheduled for surgery. MEN1 is an autosomal dominant disorder associated withMEN1mutations. Genetic testing indicated that the patient had aMEN1gene mutation; his 2 sons had the same mutations. Most MEN1 tumours are benign, but some pancreatic and thymic tumours could become malignant. Without treatment, such tumours would result in earlier mortality. Despite its rarity, we should perform genetic testing for family members of patients with MEN1 to identify mutation carriers and improve the patients’ prognosis.
Injury rate and injury patterns in FIS World Cup Alpine skiing (2006–2015): have the new ski regulations made an impact?
Authors: Haaland Bjørnar , Steenstrup Sophie E , Bere Tone , Bahr Roald , Nordsletten Lars
Published: November 2015

Background

New regulations for ski equipment were implemented prior to the 2012/2013 season in the International Ski Federation (FIS) Alpine World Cup (WC).

Objective

To investigate the effect of the new ski regulations on the rate and pattern of injuries by comparing data before (2006–2012) and after the implementation (2012–2015).

Methods

Injuries were recorded on the basis of the FIS Injury Surveillance System (FIS ISS) through retrospective interviews at the end of each of the nine WC seasons. All acute injuries that required medical attention were registered. Exposure was calculated on the basis of the official result lists.

Results

The absolute injury rate (injuries/100 athletes/season) was lower in the three seasons after the new ski regulations compared with the six seasons before (risk ratio (RR) 0.74, 95% CI 0.63 to 0.87). This was also the case for the relative injury rate (injuries/1000 runs) (RR 0.76, 95% CI 0.59 to 0.98). These changes were evident for male skiers, not for female skiers. There was a lower absolute injury rate for upper body injuries (RR 0.56, 95% CI 0.43 to 0.77), while no difference was found for lower extremity injuries (RR 0.84, 95% CI 0.70 to 1.01).

Conclusions

We found a lower rate of injuries in the three seasons after the new ski regulation compared with the six seasons before. However, the ability to draw conclusions on the effects of the equipment change in subgroups of sex, discipline or body part is restricted by the limited statistical power.
Analysis of HLA-B15 and HLA-B27 in spondyloarthritis with peripheral and axial clinical patterns
Authors: Londono John , Santos Ana Maria , Peña Paola , Calvo Enrique , Espinosa Luis R , Reveille John D , Vargas-Alarcon Gilberto , Jaramillo Carlos A , Valle-Oñate Rafael , Avila Mabel , Romero Consuelo , Medina Juan F
Published: November 2015

Objective

Human leucocyte antigen (HLA) B27 and HLA-B15 are associated with spondyloarthritis (SpA). Recent Assessment of SpondyloArthritis international Society (ASAS) criteria emphasise a distinction between SpA with axial and peripheral patterns. We analysed whether HLA-A, HLA-B and HLA-DRB1 alleles could associate with these patterns.

Methods

We studied 100 healthy individuals and 178 patients with SpA according to European Spondyloarthropathy Study Group (ESSG) criteria. Patients were then classified according to ASAS criteria, the axial spondyloarthritis pattern (axSpA) being defined by ascertained sacroiliitis and the peripheral pattern (pSpA) by enthesitis and/or arthritis in extremities. A combined ax/p pattern was also considered.

Results

Only HLA-B27 and HLA-B15 alleles were associated with SpA. ASAS criteria for axSpA were met in 152 patients (12 with isolated axSpA and 140 with a combined ax/p patterns). When the ASAS peripheral criteria were applied, 161 patients met these criteria (13 with isolated pSpA and 148 with a combined ax/p pattern). HLA-B27 was found in 83% of patients with axSpA and 43% of ax/pSpA patients according to axASAS. HLA-B27 occurred in 7% controls but not in any patient with isolated pSpA. HLA-B15 was encountered in 31% of patients with isolated pSpA and 20% of ax/pSpA patients according to pASAS criteria. Moreover, 2 healthy controls, but none of our patients with isolated axSpA were positive for HLA-B15.

Conclusions

Our data suggest that the presence of HLA-B15 favours the development of isolated/combined peripheral rather than isolated axSpA, while HLA-B27 promotes an isolated/combined axial disease and excludes a peripheral pattern. HLA-B15 should be considered in addition to HLA-B27 when diagnosing patients with SpA according to ASAS criteria.
Europium-doped boro-bismuth-tellurite glasses for multicolor phosphor applications
Authors: Keshavamurthy K. , Eraiah B.
Published: November 2015

The glass system (50–x)B2O3–30Bi2O3–20TeO2–xEu2O3 (x = 0, 0.1, 0.5, 1.0, 1.5, and 2.0 mol%) having been prepared using the conventional melt quenching method, is investigated in terms of physical, optical, and luminescence properties. The density of these glasses is measured and the corresponding molar volume is also calculated. The (αhν)1/n versus hν graph was plotted and it is well fitted to both direct (n = 1/2) and indirect (n = 2) band gaps. The direct and indirect band gap values range from 2.57 to 2.94 eV and 1.74 to 2.58 eV, respectively. The Urbach energy of the glass system was calculated to have values ranging from 0.29 to 0.62 eV. Yellow, orange, and red emissions have been observed through photoluminescence (PL) spectroscopy excited at 464 nm and the obtained multicolor emissions have been demonstrated according to the Commission International de l’Eclairage de France 1931 standards. The results of PL studies indicated the possibility towards the development of multicolor phosphor applications.
Nanoindentation response of Fe-10%Cr bi-crystal structures with Σ5〈001〉 and Σ3〈110〉 tilt boundaries: An atomistic study
Authors: Shabib Ishraq , Abu-Shams Mohammad , Khan Mujibur R.
Published: November 2015

In this research, nanoindentation responses of Fe-10%Cr bi-crystal structures containing [Formula: see text][Formula: see text] and [Formula: see text][Formula: see text] tilt grain boundaries (GBs) have been investigated using atomistic simulation technique. Deformation analyses identify the nucleation of [Formula: see text], [Formula: see text] and [Formula: see text] types of dislocations within the material. The [Formula: see text] slip planes are found to be more active than the [Formula: see text] and [Formula: see text] slip planes. Load-displacement response and corresponding changes in contact area have been recorded and used to measure material hardness and reduced modulus. The lengths of the nucleated dislocations are measured and used to estimate dislocation density within the plastic zone beneath the indenter. Dislocation motion has been found to be much easier in model with [Formula: see text]3 boundary and the early interaction of the dislocation with the boundary affects the shape of the load-displacement curve, contact area on the indented surface, and the volume of the plastic zone. The hardness of the material has been found to be affected primarily by the interaction of the dislocation with the boundary, rather than by the dislocation density within the plastic zone. Both the boundaries exhibit maximum resistance to slip transmission even at the maximum indentation depth.
Glial cell line-derived neurotrophic factor protects against high-fat diet-induced hepatic steatosis by suppressing hepatic PPAR-γ expression
Authors: Mwangi Simon Musyoka , Peng Sophia , Nezami Behtash Ghazi , Thorn Natalie , Farris Alton B. , Jain Sanjay , Laroui Hamed , Merlin Didier , Anania Frank , Srinivasan Shanthi
Published: November 2015

Glial cell line-derived neurotrophic factor (GDNF) protects against high-fat diet (HFD)-induced hepatic steatosis in mice, however, the mechanisms involved are not known. In this study we investigated the effects of GDNF overexpression and nanoparticle delivery of GDNF in mice on hepatic steatosis and fibrosis and the expression of genes involved in the regulation of hepatic lipid uptake and de novo lipogenesis. Transgenic overexpression of GDNF in liver and other metabolically active tissues was protective against HFD-induced hepatic steatosis. Mice overexpressing GDNF had significantly reduced P62/sequestosome 1 protein levels suggestive of accelerated autophagic clearance. They also had significantly reduced peroxisome proliferator-activated receptor-γ (PPAR-γ) and CD36 gene expression and protein levels, and lower expression of mRNA coding for enzymes involved in de novo lipogenesis. GDNF-loaded nanoparticles were protective against short-term HFD-induced hepatic steatosis and attenuated liver fibrosis in mice with long-standing HFD-induced hepatic steatosis. They also suppressed the liver expression of steatosis-associated genes. In vitro, GDNF suppressed triglyceride accumulation in Hep G2 cells through enhanced p38 mitogen-activated protein kinase-dependent signaling and inhibition of PPAR-γ gene promoter activity. These results show that GDNF acts directly in the liver to protect against HFD-induced cellular stress and that GDNF may have a role in the treatment of nonalcoholic fatty liver disease.
Properties of pattern and component direction-selective cells in area MT of the macaque
Authors: Wang Helena X. , Movshon J. Anthony
Published: November 2015

Neurons in area MT/V5 of the macaque visual cortex encode visual motion. Some cells are selective for the motion of oriented features (component direction-selective, CDS); others respond to the true direction of complex patterns (pattern-direction selective, PDS). There is a continuum of selectivity in MT, with CDS cells at one extreme and PDS cells at the other; we compute a pattern index that captures this variation. It is unknown how a neuron's pattern index is related to its other tuning characteristics. We therefore analyzed the responses of 792 MT cells recorded in the course of other experiments from opiate-anesthetized macaque monkeys, as a function of the direction, spatial frequency, drift rate, size, and contrast of sinusoidal gratings and of the direction and speed of random-dot textures. We also compared MT responses to those of 718 V1 cells. As expected, MT cells with higher pattern index tended to have stronger direction selectivity and broader direction tuning to gratings, and they responded better to plaids than to gratings. Strongly PDS cells also tended to have smaller receptive fields and stronger surround suppression. Interestingly, they also responded preferentially to higher drift rates and higher speeds of moving dots. The spatial frequency preferences of PDS cells depended strongly on their preferred temporal frequencies, whereas these preferences were independent in component-selective cells. Pattern direction selectivity is statistically associated with many response properties of MT cells but not strongly associated with any particular property. Pattern-selective signals are thus available in association with most other signals exported by MT.
CaV3.2 T-type Ca2+channels mediate the augmented calcium influx in carotid body glomus cells by chronic intermittent hypoxia
Authors: Makarenko Vladislav V. , Ahmmed Gias U. , Peng Ying-Jie , Khan Shakil A. , Nanduri Jayasri , Kumar Ganesh K. , Fox Aaron P. , Prabhakar Nanduri R.
Published: November 2015

Chronic intermittent hypoxia (CIH) is a hallmark manifestation of sleep apnea. A heightened carotid body activity and the resulting chemosensory reflex mediate increased sympathetic nerve activity by CIH. However, the mechanisms underlying heightened carotid body activity by CIH are not known. An elevation of intracellular calcium ion concentration ([Ca2+]i) in glomus cells, the primary oxygen-sensing cells, is an essential step for carotid body activation by hypoxia. In the present study, we examined the effects of CIH on the glomus cell [Ca2+]iresponse to hypoxia and assessed the underlying mechanisms. Glomus cells were harvested from adult rats or wild-type mice treated with 10 days of either room air (control) or CIH (alternating cycles of 15 s of hypoxia and 5 min of room air; 9 episodes/h; 8 h/day). CIH-treated glomus cells exhibited an enhanced [Ca2+]iresponse to hypoxia, and this effect was absent in the presence of 2-(4-cyclopropylphenyl)- N-((1R)-1-[5-[(2,2,2-trifluoroethyl)oxo]-pyridin-2-yl]ethyl)acetamide (TTA-A2), a specific inhibitor of T-type Ca2+channels, and in voltage-gated calcium channel, type 3.2 (CaV3.2), null glomus cells. CaV3.2 knockout mice exhibited an absence of CIH-induced hypersensitivity of the carotid body. CIH increased reactive oxygen species (ROS) levels in glomus cells. A ROS scavenger prevented the exaggerated TTA-A2-sensitive [Ca2+]iresponse to hypoxia. CIH had no effect on CaV3.2 mRNA levels. CIH augmented Ca2+currents and increased CaV3.2 protein in plasma membrane fractions of human embryonic kidney-293 cells stably expressing CaV3.2, and either a ROS scavenger or brefeldin-A, an inhibitor of protein trafficking, prevented these effects. These findings suggest that CIH leads to an augmented Ca2+influx via ROS-dependent facilitation of CaV3.2 protein trafficking to the plasma membrane.
Balanced ionotropic receptor dynamics support signal estimation via voltage-dependent membrane noise
Authors: Marcoux Curtis M. , Clarke Stephen E. , Nesse William H. , Longtin Andre , Maler Leonard
Published: November 2015

Encoding behaviorally relevant stimuli in a noisy background is critical for animals to survive in their natural environment. We identify core biophysical and synaptic mechanisms that permit the encoding of low-frequency signals in pyramidal neurons of the weakly electric fish Apteronotus leptorhynchus, an animal that can accurately encode even miniscule amplitude modulations of its self-generated electric field. We demonstrate that slow NMDA receptor (NMDA-R)-mediated excitatory postsynaptic potentials (EPSPs) are able to summate over many interspike intervals (ISIs) of the primary electrosensory afferents (EAs), effectively eliminating the baseline EA ISI correlations from the pyramidal cell input. Together with a dynamic balance of NMDA-R and GABA-A-R currents, this permits stimulus-evoked changes in EA spiking to be transmitted efficiently to target electrosensory lobe (ELL) pyramidal cells, for encoding low-frequency signals. Interestingly, AMPA-R activity is depressed and appears to play a negligible role in the generation of action potentials. Instead, we hypothesize that cell-intrinsic voltage-dependent membrane noise supports the encoding of perithreshold sensory input; this noise drives a significant proportion of pyramidal cell spikes. Together, these mechanisms may be sufficient for the ELL to encode signals near the threshold of behavioral detection.
13C NMR and ESR Characterization of Humic Substances Isolated from Soils of Two Siberian Arctic Islands
Authors: Abakumov E. , Lodygin E. , Tomashunas V.
Published: November 2015

Humic acids (HAs) and fulvic acids (FAs) of two Polar soils were investigated by13C NMR and ESR spectroscopies, investigating the degree of humification and the molecular structure. One soil, from Bolshoi Lyakhovsky Island, contains two humus horizons: modern and buried. The other soil, from Wrangel Island, had only one modern humus horizon. The HAs and FAs of the two soils investigated show essential differences. The HAs show fewer oxygen-containing groups in comparison with the FAs, whereas the degree of aromaticity is two or three times higher in the HAs. The13C NMR data also show that HAs are very different from FAs in terms of their molecular composition and hydrophobicity. Humification in the Arctic is limited by the very low content of lignin-derived compounds, due to the restricted vascular flora. As a result, the HAs, isolated from Polar soils, are more similar to the corresponding FAs than to the typical HAs of temperate soils. This was confirmed by ESR data, which show similar levels of free radical concentration for HAs and FAs and are related to the low level of aromaticity of both materials investigated. Apparently, the humification process in the soils of Polar Arctic deserts is in an initial stage.
Characterization and Compatibility Studies of Different Rate Retardant Polymer Loaded Microspheres by Solvent Evaporation Technique: In Vitro-In Vivo Study of Vildagliptin as a Model Drug
Authors: Dewan Irin , Islam Swarnali , Rana Md. Sohel
Published: November 2015

The present study has been performed to microencapsulate the antidiabetic drug of Vildagliptin to get sustained release of drug. The attempt of this study was to formulate and evaluate the Vildagliptin loaded microspheres by emulsion solvent evaporation technique using different polymers like Eudragit RL100, Eudragit RS100, Ethyl cellulose, and Methocel K100M. In vitro dissolution studies were carried out in 0.1 N HCl for 8 hours according to USP paddle method. The maximum and minimum drug release were observed as 92.5% and 68.5% from microspheres, respectively, after 8 hours. Release kinetics were studied in different mathematical release models to find out the linear relationship and release rate of drug. The SEM, DSC, and FTIR studies have been done to confirm good spheres and smooth surface as well as interaction along with drug and polymer. In this experiment, it is difficult to explain the exact mechanism of drug release. But the drug might be released by both diffusion and erosion as the correlation coefficient (R2) best fitted with Korsmeyer model and release exponent (n) was 0.45–0.89. At last it can be concluded that all in vitro and in vivo experiments exhibited promising result to treat type II diabetes mellitus with Vildagliptin microspheres.
AspergillusThyroiditis after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Ataca Pinar , Atilla Erden , Saracoglu Pelin , Yilmaz Gulden , Civriz Bozdag Sinem , Toprak Selami Kocak , Yuksel Meltem Kurt , Ceyhan Koray , Topcuoglu Pervin
Published: November 2015

Aspergillusthyroiditis is a rare disorder detected in immunocompromised patients during disseminated infections. Early management is essential to prevent high mortality. A 61-year-old allogeneic stem cell male recipient presented with painful thyroid nodular enlargement. He had low TSH and low free T4 levels. The thyroid ultrasound showed a hypoechoic nodule; biopsy indicated suppurativeAspergillusthyroiditis. He was successfully treated by amphotericin B.
Onychomycosis due toCunninghamella bertholletiaein an Immunocompetent Male from Central India
Authors: Tadepalli Karuna , Gupta Pradeep Kumar , Asati Dinesh P. , Biswas Debasis
Published: November 2015

Onychomycosis is a fungal infection of nails seen frequently in immune competent and immune compromised patients due to dermatophytes,Candidaspp.,Fusariumspp.,Scopulariopsis brevicaulis,Penicilliumspp., andAspergillusspp. We report a case of onychomycosis in a young immunocompetent male who presented onycholysis of a solitary nail without inflammation. The etiological agent was diagnosed to beCunninghamella bertholletiae, a fungus pertaining to the order Mucorales (subdivision Mucoromycotina) and known for some of the invasive lesions among immunocompromised patients. This case demonstrates the association of onychomycosis withCunninghamella bertholletiaein an immune competent individual, not reported so far.
Atypical Parathyroid Adenoma Complicated with Protracted Hungry Bone Syndrome after Surgery: A Case Report and Literature Review
Authors: Juárez-León Óscar Alfredo , Gómez-Sámano Miguel Ángel , Cuevas-Ramos Daniel , Almeda-Valdés Paloma , López-Flores A La Torre Manuel Alejandro , Reza-Albarrán Alfredo Adolfo , Gómez-Pérez Francisco Javier
Published: November 2015

Hungry Bone Syndrome refers to the severe and prolonged hypocalcemia and hypophosphatemia, following parathyroidectomy in patients with hyperparathyroidism. We present the case of an eighteen-year-old woman with a four-year history of hyporexia, polydipsia, weight loss, growth retardation, and poor academic performance. The diagnostic work-up demonstrated primary hyperparathyroidism with hypercalcemia of 13.36 mg/dL, a PTH level of 2551 pg/mL, bone brown tumors, and microcalcifications within pancreas and kidneys. Neck ultrasonography revealed a parathyroid adenoma of 33 × 14 × 14 mm, also identified on99Tc-sestamibi scan. Bone densitometry showed decreasedZ-Score values (total lumbarZ-Score of −4.2). A right hemithyroidectomy and right lower parathyroidectomy were performed. Pathological examination showed an atypical parathyroid adenoma, of 3.8 g of weight and 2.8 cm in diameter. After surgery she developed hypocalcemia with tetany and QTc interval prolongation. The patient required 3 months of oral and intravenous calcium supplementation due to Hungry Bone Syndrome (HBS). After 42 months, she is still under oral calcium. Usually HBS lasts less than 12 months. Therefore we propose the term “Protracted HBS” in patients with particularly long recovery of 1 year. We present a literature review of the diagnosis, pathophysiology, and treatment of HBS.
Nanoplugging Performance of Hyperbranched Polyamine as Nanoplugging Agent in Oil‐Based Drilling Fluid
Authors: Xie Gang , Luo Pingya , Deng Mingyi , Wang Zheng
Published: November 2015

A hyperbranched polyamine was synthesized by self‐condensing vinyl polymerization with divinyl sulfone, N‐phenyl‐p‐phenylenediamine, by A2 + approach. The hyperbranched polyamine was characterized by FT‐IR, TGA, and phase analysis light scanning. Average grain diameter of hyperbranched polyamine was 36.7 nm. Hyperbranched polyamine has good thermal stability. Hyperbranched polyamine (HBPA) was employed successfully as nanoplugging agent in oil‐based drilling fluid system, which could plug nanopore formation in shale formation. HBPA has a little effect on rheological properties of oil‐based drilling fluid and the FLAPI and FLHTHP decreased dramatically with an increase of hyperbranched polyamine. Emulsion‐breaking voltage has a slight increase, which is beneficial to maintain stability of oil‐based drilling fluid. When the HBPA concentration is greater than 1 wt%, plugging rate of oil‐based drilling fluid for artificial core is close to 100% and the permeability recovery value can reach 99.7% after adding 1 wt% HBPA, which prove that HBPA has an excellent plugging performance.
Autocrine Human Urotensin II Enhances Macrophage-Derived Foam Cell Formation in Transgenic Rabbits
Authors: Zhao Sihai , Li Yafeng , Gao Shoucui , Wang Xiaojing , Sun Lijing , Cheng Daxing , Bai Liang , Guan Hua , Wang Rong , Fan Jianglin , Liu Enqi
Published: November 2015

Circulating urotensin II (UII) is involved in the development of atherosclerosis. However, the role of autocrine UII in the development of atherosclerosis remains unclear. Here, we tested the hypothesis that autocrine UII would promote atherosclerosis. Transgenic rabbits were created as a model to study macrophage-specific expressing human UII (hUII) and used to investigate the role of autocrine UII in the development of atherosclerosis. Transgenic rabbits and their nontransgenic littermates were fed a high cholesterol diet to induce atherosclerosis. Comparing the transgenic rabbits with their nontransgenic littermates, it was observed that hUII expression increased the macrophage-positive area in the atherosclerotic lesions by 45% and the positive area ratio by 56% in the transgenic rabbits. Autocrine hUII significantly decreased the smooth muscle cell-positive area ratio in transgenic rabbits (by 54%), without affecting the plasma levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and glucose and adipose tissue contents. These results elucidated for the first time that autocrine UII plays an important role in the development of atherosclerosis by increasing the accumulation of macrophage-derived foam cell.