bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell Surface THY-1 Contributes to Human Cytomegalovirus Entry via a Macropinocytosis-Like Process
Authors: Li Qingxue , Fischer Elizabeth , Cohen Jeffrey I.
Published: August 2016

Previously we showed that THY-1 has a critical role in the initial stage of infection of certain cell types with human cytomegalovirus (HCMV) and that THY-1 is important for HCMV-mediated activation of phosphatidylinositol 3-kinase (PI3K)/Akt during virus entry. THY-1 is known to interact with integrins and is a major cargo protein of clathrin-independent endocytic vesicles. Since macropinocytosis involves integrin signaling, is PI3K/Akt dependent, and is a clathrin-independent endocytic process, we determined whether THY-1 has a role in HCMV entry by macropinocytosis. Using electron microscopy in two cell lines that support HCMV infection in a THY-1-dependent manner, we found that HCMV enters these cells by a macropinocytosis-like process. THY-1 associated with HCMV virions on the cell surface and colocalized with virus inside macropinosomes. 5-(
N
-Ethyl-
N
-isopropyl)amiloride (EIPA) and soluble THY-1 blocked HCMV infection in the cell lines by ≥80% and 60%, respectively. HCMV entry into the cells triggered increased influx of extracellular fluid, a marker of macropinocytosis, and this increased fluid uptake was inhibited by EIPA and by soluble THY-1. Blocking actin depolymerization, Na
+
/H
+
exchange, PI3K, and Pak1 kinase, which are critical for macropinocytosis, impaired HCMV infection. Neither internalized HCMV virions nor THY-1 in virus-infected cells colocalized with transferrin as determined by confocal microscopy, indicating that clathrin-mediated endocytosis was not involved in THY-1-associated virus entry. These results suggest that HCMV has adapted to utilize THY-1, a cargo protein of clathrin-independent endocytotic vesicles, to facilitate efficient entry into certain cell types by a macropinocytosis-like process.

IMPORTANCE
Human cytomegalovirus (HCMV) infects over half of the population and is the most common infectious cause of birth defects. The virus is the most important infection occurring in transplant recipients. The mechanism of how HCMV enters cells is controversial. In this study, we show that THY-1, a cell surface protein that is critical for the early stage of entry of HCMV into certain cell types, contributes to virus entry by macropinocytosis. Our findings suggest that HCMV has adapted to utilize THY-1 to facilitate entry of HCMV into macropinosomes in certain cell types. Further knowledge about the mechanism of HCMV entry into cells may facilitate the development of novel inhibitors of virus infection.
A Single Mutation at Position 190 in Hemagglutinin Enhances Binding Affinity for Human Type Sialic Acid Receptor and Replication of H9N2 Avian Influenza Virus in Mice
Authors: Teng Qiaoyang , Xu Dawei , Shen Weixia , Liu Qinfang , Rong Guangyu , Li Xuesong , Yan Liping , Yang Jianmei , Chen Hongjun , Yu Hai , Ma Wenjun , Li Zejun
Published: August 2016

H9N2 avian influenza virus (AIV) has an extended host range, but the molecular basis underlying H9N2 AIV transmission to mammals remains unclear. We isolated more than 900 H9N2 AIVs in our 3-year surveillance in live bird markets in China from 2009 to 2012. Thirty-seven representative isolates were selected for further detailed characterization. These isolates were categorized into 8 genotypes (B64 to B71) and formed a distinct antigenic subgroup. Three isolates belonging to genotype B69, which is a predominant genotype circulating in China, replicated efficiently in mice, while the viruses tested in parallel in other genotypes replicated poorly, although they, like the three B69 isolates, have a leucine at position 226 in the hemagglutinin (HA) receptor binding site, which is critical for binding human type sialic acid receptors. Further molecular and single mutation analysis revealed that a valine (V) residue at position 190 in HA is responsible for efficient replication of these H9N2 viruses in mice. The 190V in HA does not affect virus receptor binding specificity but enhances binding affinity to human cells and lung tissues from mouse and humans. All these data indicate that the 190V in HA is one of the important determinants for H9N2 AIVs to cross the species barrier to infect mammals despite multiple genes conferring adaptation and replication of H9N2 viruses in mammals. Our findings provide novel insights on understanding host range expansion of H9N2 AIVs.

IMPORTANCE
Influenza virus hemagglutinin (HA) is responsible for binding to host cell receptors and therefore influences the viral host range and pathogenicity in different species. We showed that the H9N2 avian influenza viruses harboring 190V in the HA exhibit enhanced virus replication in mice. Further studies demonstrate that 190V in the HA does not change virus receptor binding specificity but enhances virus binding affinity of the H9N2 virus to human cells and attachment to lung tissues from humans and mouse. Our findings suggest that more attention should be given to the H9N2 AIVs with HA-190V during surveillance due to their potential threat to mammals, including humans.
HIV-1-Neutralizing IgA Detected in Genital Secretions of Highly HIV-1-Exposed Seronegative Women on Oral Preexposure Prophylaxis
Authors: Lund Jennifer M. , Broliden Kristina , Pyra Maria N. , Thomas Katherine K. , Donnell Deborah , Irungu Elizabeth , Muwonge Timothy R. , Mugo Nelly , Manohar Madhuri , Jansson Marianne , Mackelprang Romel , Marzinke Mark A. , Baeten Jared M. , Lingappa Jairam R.
Published: August 2016

Although nonhuman primate studies have shown that simian immunodeficiency virus/simian-human immunodeficiency virus (SIV/SHIV) exposure during preexposure prophylaxis (PrEP) with oral tenofovir can induce SIV immunity without productive infection, this has not been documented in humans. We evaluated cervicovaginal IgA in Partners PrEP Study participants using a subtype C primary isolate and found that women on PrEP had IgA with higher average human immunodeficiency virus type 1 (HIV-1)-neutralizing magnitude than women on placebo (33% versus 7%;
P
= 0.008). Using a cutoff of ≥90% HIV-1 neutralization, 19% of women on-PrEP had HIV-1-neutralizing IgA compared to 0% of women on placebo (
P
= 0.09). We also estimated HIV-1 exposure and found that the proportion of women with HIV-1-neutralizing IgA was associated with the level of HIV-1 exposure (
P
= 0.04). Taken together, our data suggest that PrEP and high levels of exposure to HIV may each enhance mucosal HIV-1-specific humoral immune responses in sexually exposed but HIV-1-uninfected individuals.

IMPORTANCE
Although there is not yet an effective HIV-1 vaccine, PrEP for at-risk HIV-1-uninfected individuals is a highly efficacious intervention to prevent HIV-1 acquisition and is currently being recommended by the CDC and WHO for all individuals at high risk of HIV-1 acquisition. We previously demonstrated that PrEP use does not enhance peripheral blood HIV-1-specific T-cell responses in HIV-exposed individuals. Here, we evaluate for cervicovaginal HIV-neutralizing IgA responses in genital mucosal secretions of HIV-exposed women, which is likely a more relevant site than peripheral blood for observation of potentially protective immune events occurring in response to sexual HIV-1 exposure for various periods. Furthermore, we assess for host response in the context of longitudinal quantification of HIV-1 exposure. We report that HIV-neutralizing IgA is significantly correlated with higher HIV-1 exposure and, furthermore, that there are more women with HIV-1-neutralizing IgA in the on-PrEP group than in the placebo group.
Glycan Specificity of P[19] Rotavirus and Comparison with Those of Related P Genotypes
Authors: Liu Yang , Ramelot Theresa A. , Huang Pengwei , Liu Yan , Li Zhen , Feizi Ten , Zhong Weiming , Wu Fang-Tzy , Tan Ming , Kennedy Michael A. , Jiang Xi
Published: August 2016

The P[19] genotype belongs to the P[II] genogroup of group A rotaviruses (RVs). However, unlike the other P[II] RVs, which mainly infect humans, P[19] RVs commonly infect animals (pigs), making P[19] unique for the study of RV diversity and host ranges. Through
in vitro
binding assays and saturation transfer difference (STD) nuclear magnetic resonance (NMR), we found that P[19] could bind mucin cores 2, 4, and 6, as well as type 1 histo-blood group antigens (HBGAs). The common sequences of these glycans serve as minimal binding units, while additional residues, such as the A, B, H, and Lewis epitopes of the type 1 HBGAs, can further define the binding outcomes and therefore likely the host ranges for P[19] RVs. This complex binding property of P[19] is shared with the other three P[II] RVs (P[4], P[6], and P[8]) in that all of them recognized the type 1 HBGA precursor, although P[4] and P[8], but not P[6], also bind to mucin cores. Moreover, while essential for P[4] and P[8] binding, the addition of the Lewis epitope blocked P[6] and P[19] binding to type 1 HBGAs. Chemical-shift NMR of P[19] VP8* identified a ligand binding interface that has shifted away from the known RV P-genotype binding sites but is conserved among all P[II] RVs and two P[I] RVs (P[10] and P[12]), suggesting an evolutionary connection among these human and animal RVs. Taken together, these data are important for hypotheses on potential mechanisms for RV diversity, host ranges, and cross-species transmission.

IMPORTANCE
In this study, we found that our P[19] strain and other P[II] RVs recognize mucin cores and the type 1 HBGA precursors as the minimal functional units and that additional saccharides adjacent to these units can alter binding outcomes and thereby possibly host ranges. These data may help to explain why some P[II] RVs, such as P[6] and P[19], commonly infect animals but rarely humans, while others, such as the P[4] and P[8] RVs, mainly infect humans and are predominant over other P genotypes. Elucidation of the molecular bases for strain-specific host ranges and cross-species transmission of these human and animal RVs is important to understand RV epidemiology and disease burden, which may impact development of control and prevention strategies against RV gastroenteritis.
Adoptive Transfer of Engineered Rhesus Simian Immunodeficiency Virus-Specific CD8+T Cells Reduces the Number of Transmitted/Founder Viruses Established in Rhesus Macaques
Authors: Ayala Victor I. , Trivett Matthew T. , Barsov Eugene V. , Jain Sumiti , Piatak Michael , Trubey Charles M. , Alvord W. Gregory , Chertova Elena , Roser James D. , Smedley Jeremy , Komin Alexander , Keele Brandon F. , Ohlen Claes , Ott David E.
Published: August 2016

AIDS virus infections are rarely controlled by cell-mediated immunity, in part due to viral immune evasion and immunodeficiency resulting from CD4+T-cell infection. One likely aspect of this failure is that antiviral cellular immune responses are either absent or present at low levels during the initial establishment of infection. To test whether an extensive, timely, and effective response could reduce the establishment of infection from a high-dose inoculum, we adoptively transferred large numbers of T cells that were molecularly engineered with anti-simian immunodeficiency virus (anti-SIV) activity into rhesus macaques 3 days following an intrarectal SIV inoculation. To measurein vivoantiviral activity, we assessed the number of viruses transmitted using SIVmac239X, a molecularly tagged viral stock containing 10 genotypic variants, at a dose calculated to transmit 12 founder viruses. Single-genome sequencing of plasma virus revealed that the two animals receiving T cells expressing SIV-specific T-cell receptors (TCRs) had significantly fewer viral genotypes than the two control animals receiving non-SIV-specific T cells (means of 4.0 versus 7.5 transmitted viral genotypes;P= 0.044). Accounting for the likelihood of transmission of multiple viruses of a particular genotype, the calculated means of the total number of founder viruses transmitted were 4.5 and 14.5 in the experimental and control groups, respectively (P= 0.021). Thus, a large antiviral T-cell response timed with virus exposure can limit viral transmission. The presence of strong, preexisting T-cell responses, including those induced by vaccines, might help prevent the establishment of infection at the lower-exposure doses in humans that typically transmit only a single virus.

IMPORTANCEThe establishment of AIDS virus infection in an individual is essentially a race between the spreading virus and host immune defenses. Cell-mediated immune responses induced by infection or vaccination are important contributors in limiting viral replication. However, in human immunodeficiency virus (HIV)/SIV infection, the virus usually wins the race, irreversibly crippling the immune system before an effective cellular immune response is developed and active. We found that providing an accelerated response by adoptively transferring large numbers of antiviral T cells shortly after a high-dose mucosal inoculation, while not preventing infection altogether, limited the number of individual viruses transmitted. Thus, the presence of strong, preexisting T-cell responses, including those induced by vaccines, might prevent infection in humans, where the virus exposure is considerably lower.
Heparan Sulfate Binding Promotes Accumulation of Intravitreally Delivered Adeno-associated Viral Vectors at the Retina for Enhanced Transduction but Weakly Influences Tropism
Authors: Woodard Kenton T. , Liang Katharine J. , Bennett William C. , Samulski R. Jude
Published: August 2016

Many adeno-associated virus (AAV) serotypes efficiently transduce the retina when delivered to the subretinal space but show limited success when delivered to the vitreous due to the inner limiting membrane (ILM). Subretinal delivery of AAV serotype 2 (AAV2) and its heparan sulfate (HS)-binding-deficient capsid led to similar expression, indicating transduction of the outer retina occurred by HS-independent mechanisms. However, intravitreal delivery of HS-ablated recombinant AAV2 (rAAV2) led to a 300-fold decrease in transduction compared to AAV2. Fluorescence
in situ
hybridization of AAV transgenes was used to identify differences in retinal trafficking and revealed that HS binding was responsible for AAV2 accumulation at the ILM. This mechanism was tested on human
ex vivo
retinas and showed similar accumulation with HS-binding AAV2 capsid only. To evaluate if HS binding could be applied to other AAV serotypes to enhance their transduction, AAV1 and AAV8 were modified to bind HS with a single-amino-acid mutation and tested in mice. Both HS-binding mutants of AAV1 and AAV8 had higher intravitreal transduction than their non-HS-binding parent capsid due to increased retinal accumulation. To understand the influence that HS binding has on tropism, chimeric AAV2 capsids with dual-glycan usage were tested intravitreally in mice. Compared to HS binding alone, these chimeric capsids displayed enhanced transduction that was correlated with a change in tropism. Taken together, these data indicate that HS binding serves to sequester AAV capsids from the vitreous to the ILM but does not influence retinal tropism. The enhanced retinal transduction of HS-binding capsids provides a rational design strategy for engineering capsids for intravitreal delivery.

IMPORTANCE
Adeno-associated virus (AAV) has become the vector of choice for viral gene transfer and has shown great promise in clinical trials. The need for development of an easy, less invasive injection route for ocular gene therapy is met by intravitreal delivery, but delivery of AAV by this route results in poor transduction outcomes. The inner limiting membrane (ILM) creates a barrier separating the vitreous and the retina. Binding of AAV to heparan sulfate proteoglycan (HSPG) at the ILM may allow the virus to traverse this barrier for better retinal transduction. We show that HSPG binding is correlated with greater accumulation and penetration of AAV in the retina. We demonstrated that this accumulation is conserved across mouse and human retinas and that the addition of HSPG binding to other AAV capsids can increase the number of vectors accumulating at the ILM without dictating tropism.
High-risk glycated hemoglobin trajectories established by mid-20s: findings from a birth cohort study
Authors: Shearer Dara M , Thomson W Murray , Broadbent Jonathan M , McLean Rachael , Poulton Richie , Mann Jim
Published: August 2016

Objective

To describe the natural history of glycemia (as measured by glycated hemoglobin (HbA1c)) over 12 years using group-based trajectory modeling (GBTM), and to examine baseline predictors of trajectory.

Research design and methods

HbA1c data collected at ages 26, 32 and 38 in the long-running, prospective Dunedin Multidisciplinary Health and Development Study were used to assign study members (n=893) to trajectories applying GBTM. A generalization of the model allowed the statistical linking of baseline demographic, smoking and anthropometric characteristics to group membership probability.

Results

Mean HbA1c increased with age, as did prevalence of prediabetes, diabetes and dysglycemia. The greatest increase occurred between ages 26 and 32. Glycemic health status at age 26 predicted glycemic health status at age 38. 3 HbA1c trajectory groups were identified: ‘low’ (n=98, 11.0%); ‘medium’ (n=482, 54.0%); and ‘high’ (n=313, 35.0%) with mean HbA1c of 29.6, 34.1, and 38.7 mmol/mol, respectively, at age 38. High waist circumference (≥880 mm for women and ≥1020 mm for men), high waist-height ratio (≥0.50), and being a smoker at age 26 predicted membership of the least favorable trajectory over the next 12 years. High body mass index (≥30) at age 26 did not predict of trajectory.

Conclusions

Trajectories of HbA1c are established relatively early in adulthood. HbA1c levels, waist circumference, waist-height ratio, and smoking status at age 26 are valid clinical predictors for future dysglycemic risk. The identification of HbA1c trajectories and their predictors introduces the possibility of an individualized approach to prevention at an earlier stage than is currently done.
Demographic and socioeconomic inequalities in the risk of emergency hospital admission for violence: cross-sectional analysis of a national database in Wales
Authors: Long Sara Jayne , Fone David , Gartner Andrea , Bellis Mark A
Published: August 2016

Objectives

To investigate the risk of emergency hospital admissions for violence (EHAV) associated with demographic and socioeconomic factors in Wales between 2007/2008 and 2013/2014, and to describe the site of injury causing admission.

Design

Database analysis of 7 years’ hospital admissions using the Patient Episode Database for Wales (PEDW).

Setting and participants

Wales, UK, successive annual populations ∼2.8 million aged 0–74 years.

Primary outcome

The first emergency admission for violence in each year of the study, defined by the International Classification of Diseases V.10 (ICD-10) codes for assaults (X85-X99, Y00-Y09) in any coding position.

Results

A total of 11 033 admissions for assault. The majority of admissions resulted from head injuries. The overall crude admission rate declined over the study period, from 69.9 per 100 000 to 43.2 per 100 000, with the largest decrease in the most deprived quintile of deprivation. A generalised linear count model with a negative binomial log link, adjusted for year, age group, gender, deprivation quintile and settlement type, showed the relative risk was highest in age group 18–19 years (RR=6.75, 95% CI 5.88 to 7.75) compared with the reference category aged 10–14 years. The risk decreased with age after 25 years. Risk of admission was substantially higher in males (RR=4.55, 95% CI 4.31 to 4.81), for residents of the most deprived areas of Wales (RR=3.60, 95% CI 3.32 to 3.90) compared with the least deprived, and higher in cities (RR=1.37, 95% CI 1.27 to 1.49) and towns (RR=1.32, 95% CI 1.21 to 1.45) compared with villages.

Conclusions

Despite identifying a narrowing in the gap between prevalence of violence in richer and poorer communities, violence remains strongly associated with young men living in areas of socioeconomic deprivation. There is potential for a greater reduction, given that violence is mostly preventable. Recommendations for reducing inequalities in the risk of admission for violence are discussed.
OPAL: a randomised, placebo-controlled trial of opioid analgesia for the reduction of pain severity in people with acute spinal pain. Trial protocol
Authors: Lin Chung-Wei Christine , McLachlan Andrew J , Latimer Jane , Day Ric O , Billot Laurent , Koes Bart W , Maher Chris G
Published: August 2016

Introduction

Low back pain and neck pain are extremely prevalent and are responsible for an enormous burden of disease globally. Strong analgesics, such as opioid analgesics, are recommended by clinical guidelines for people with acute low back pain or neck pain who are slow to recover and require more pain relief. Opioid analgesics are widely and increasingly used, but there are no strong efficacy data supporting the use of opioid analgesics for acute low back pain or neck pain. Concerns regarding opioid use are further heightened by the risks of adverse events, some of which can be serious (eg, dependency, misuse and overdose).

Methods and analysis

OPAL is a randomised, placebo-controlled, triple-blinded trial that will investigate the judicious use of an opioid analgesic in 346 participants with acute low back pain and/or neck pain who are slow to recover. Participants will be recruited from general practice and randomised to receive the opioid analgesic (controlled release oxycodone plus naloxone up to 20 mg per day) or placebo in addition to guideline-based care (eg, reassurance and advice of staying active) for up to 6 weeks. Participants will be followed-up for 3 months for effectiveness outcomes. The primary outcome will be pain severity. Secondary outcomes will include physical functioning and time to recovery. Medication-related adverse events will be assessed and a cost-effectiveness analysis will be conducted. We will additionally assess long-term use and risk of misuse of opioid analgesics for up to 12 months.

Ethics and dissemination

Ethical approval has been obtained. Trial results will be disseminated by publications and conference presentations, and via the media.

Trial registration number

ACTRN12615000775516: Pre-results.
Zombie tapeworms in late capitalism: accelerating clinical and reproductive labour in Mira Grant'sParasitologyTrilogy
Authors: Attebery Stina
Published: August 2016

Biomedicine is increasingly shaped by the speculative economical values of neoliberal capitalism. A key feature of this new bioeconomical regime is the patenting and circulation of organisms and tissue samples, allowing rapid commercialisation of bacterial, animal and human biomedical materials. When thinking about this trend towards commercialisation, we must consider the ways by which biomedicine has been shaped by economics to better address these exploitative relationships between medical researchers and subjects. These fraught questions of agency and exploitation can be addressed through the concept of clinical labour, a term Melinda Cooper and Catherine Waldby coined to discuss embodied forms of labour, including surrogacy, clinical trials and tissue economies, that dominate the post-Fordist biomedical economy. As a genre that extrapolates from contemporary technoscientific practices, science fiction is uniquely positioned to explore the ethics of biomedical research in this neoliberal speculative economy. Science fiction can give human-like agency and affect to microbial, animal and alien life, allowing modified organisms to speak and interact with their creators. Creating these dialogues between commercialised organisms and biomedical researchers makes clear the connections between contemporary clinical practice and exploitative labour relations, illuminating the more troubling aspects of the new bioeconomy and imagining alternatives to this system.
Rescue mechanical thrombectomy using a retrievable stent for thromboembolic occlusion occurring during coil embolization of ruptured intracranial aneurysms
Authors: Ahn Jun Hyong , Jun Hyo Sub , Song Joon Ho , Cho Byung Moon , Lee Ho Kook , Kim Byong-Cheol , Hyun Dong-Keun , Chang In Bok
Published: August 2016

Objective

To examine the safety and efficacy of mechanical thrombectomy using a retrievable stent for thromboembolic occlusion occurring during coil embolization of ruptured intracranial aneurysms.

Methods

Between June 2011 and June 2015, 631 consecutive patients with ruptured intracranial aneurysms underwent coil embolization at 6 hospitals. Among 53 patients who had thromboembolic complications, 15 patients harboring 15 aneurysms underwent rescue mechanical thrombectomy with a retrievable stent for the treatment of thromboembolic occlusion during the coiling of ruptured aneurysms. The patients' clinical and radiologic outcomes were retrospectively reviewed.

Results

Of the 15 aneurysms, coiling alone was used for 13 (86.7%), and stent-assisted coiling was performed for 2 (13.3%). Thromboembolic occlusion most frequently occurred distal to the aneurysm (n=10, 66.7%), followed by proximal to the aneurysm (n=3, 20%), and at the coil−parent vessel interface (n=2, 13.3%). All patients underwent mechanical thrombectomy with a retrievable stent, including 5 patients who were initially treated with an IA tirofiban infusion. Complete recanalization (Thrombolysis in Cerebral Infarction (TICI) 3) was obtained in 13 (86.7%) and partial recanalization (TICI 2b) in 2 (13.3%). Two patients who had received IA tirofiban before mechanical thrombectomy had hemorrhagic complications. At 6 months after discharge, 9 patients had a modified Rankin Scale (mRS) score of 1, 3 patients were mRS 2, 1 patient was mRS 3, 1 patient was mRS 4, and 1 patient was mRS 6.

Conclusions

Rescue mechanical thrombectomy using a retrievable stent can be a useful treatment for thromboembolic occlusion occurring during coil embolization of ruptured intracranial aneurysms.
Endovascular treatment of complex intracranial aneurysms using Acandis Acclino stents
Authors: Brassel Friedhelm , Grieb Dominik , Meila Dan , Schlunz-Hendann Martin , Greling Björn , Melber Katharina
Published: August 2016

Objective

To determine the safety and effectiveness of a new low-profile, laser-cut, closed-cell stent system in the treatment of complex intracranial aneurysms.

Methods

A total number of 43 patients with complex intracranial aneurysms were treated using 60 Acandis Acclino stent systems (follow-up 2012–2016; mean 11 months). 36 patients presented with wide-necked intracranial aneurysms, dissecting aneurysms were seen in 7 patients. 39 patients received stent-assisted coiling. We analyzed demographic data and follow-up results.

Results

Sixty stents were successfully deployed. In one paraophthalmic internal carotid artery aneurysm the stent could not be placed. Thirty-three wide necked aneurysms were treated by single or multiple stent-assisted coiling. Complete occlusion was achieved in 31 of those cases (94% Raymond−Roy occlusion classification, RROC 1). Two patients showed stable residual aneurysmal filling (RROC 3). In three wide-necked aneurysms, sole stenting was the preferred treatment. For dual stent-assisted procedures the kissing-Y stenting technique was successfully performed in 11 aneurysms. In all dissecting aneurysms constructive therapy with stenting and preservation of the affected parent artery was achieved. Additional subsequent coil embolization was intentionally planned and successfully performed in 6 of the 7 dissecting aneurysms. The overall directly procedure-related complication rate was 7%, including one death.

Conclusions

Endovascular treatment of complex intracranial aneurysms using Acclino stents is a feasible and safe procedure with low complication rates. Even severe cases can be treated among others using the kissing-Y stenting technique, with good mid-term results.
Radiographic anatomy of juvenile bovine limbs
Authors: Hoey S. E. , Biedrzycki A. H. , Livesey M. J. , Drees R.
Published: August 2016

Juvenile bovine patients who present with clinical signs of lameness are commonly evaluated using radiographic techniques both within a hospital setting and in a farm environment. The radiographic development of the juvenile bovine skeleton is currently poorly documented. In this study, the limbs of four heifer calves were sequentially radiographed to assess development of the juvenile bovine appendicular skeleton in the first 12 months of life. Images were acquired at three weeks, three months, six months, nine months and one year of age. The normal radiographic anatomy of the fore limbs and hindlimbs and the changes over the first 12 months are described. The majority of physes remain open throughout this period, with the exception of the proximal physes of the proximal and middle phalanges, the proximal radial physis, and the proximal humeral physis which close radiographically between 9 months and 12 months of age, and fusion of the fourth and central tarsal bones occurs between 9 months and 12 months of age. The results of this study may aid in differentiating normal and abnormal anatomy in the juvenile bovine limb.
Molecular dynamics studies of a β-sheet blocking peptide with the full-length amyloid beta peptide of Alzheimer’s disease
Authors: Amini Zohreh , Fatemi Mohammad Hossein , Rauk Arvi
Published: August 2016

The region encompassing residues 13–23 of the amyloid beta peptide (Aβ(13–23)) of Alzheimer’s disease is the self-recognition site that initiates toxic oligomerization and fibrillization. A number of pseudopeptides have been designed to bind to Aβ(13–23) and been computationally shown to do so with high affinity. More interactions are available in full-length Aβ than are available in the shorter peptide. We describe herein a study by molecular dynamics (MD) of nine distinct complexes formed by one such pseudopeptide, SGA1, with full-length beta amyloid, Aβ(1–42). The relative stabilities of the Aβ–SGA1 complexes were estimated by a combination of MD and ab initio methods. The most stable complex, designated AB1, was found to be one in which SGA1 is bound to the self-recognition site of Aβ(1–42) in an antiparallel β-sheet fashion. Another complex, designated AB3, also involved SGA1 binding to the self-recognition region of Aβ(1–42), albeit with lower affinity. In both AB1 and AB3, SGA1 formed antiparallel β-sheets but to opposite edges of Aβ. A complex, AB4, with similar stability to AB3, was found with a parallel β-sheet in the self-recognition site. A fourth complex, AB7, also with similar stability, formed a parallel β-sheet in the hydrophobic central region of Aβ. In all cases, complexation of SGA1 induced extensive β-sheet structure in Aβ(1–42).
Insights from molecular dynamics on substrate binding and effects of active site mutations in Δ1-pyrroline-5-carboxylate dehydrogenase
Authors: Ion Bogdan F. , Aboelnga Mohamed M. , Gauld James W.
Published: August 2016

The NAD+-dependent enzyme, Δ1-pyrroline-5-carboxylate dehydrogenase (P5CDH), has an important role in proline and hydroxyproline catabolism for humans. Specifically, this aldehyde dehydrogenase is responsible for the oxidation of both l-glutamate-γ-semialdehyde (GSA) and 4-erythro-hydroxy-l-glutamate-γ-semialdehyde (4-OH-GSA) to their respective l-glutamate product forms. We have performed a detailed molecular dynamics (MD) study of both the reactant and product complex structures of P5CDH to gain insights into ligand binding (i.e., GSA, 4-OH-GSA, NAD+, GLU) in the active site. Moreover, our investigations were further extended to examine the structural impact of S352L, S352A, and E314A mutations on the deficiency in the P5CDH enzymatic activity. Our in silico mutation analysis indicated that the conserved Glu447 has significantly shifted in both the S352L and E314A mutants, causing NAD+ to be displaced from its predictive orientation in the binding site and hence forming a catalytically inactive enzyme. However in the case of S352A, the catalytic site including the oxyanion hole and Cys348 remain virtually unchanged, and the coenzyme maintains its binding position.
Suppressing Wind-Induced Oscillations of Prismatic Structures by Dynamic Vibration Absorbers
Authors: Liu W. B. , Dai H. L. , Wang L.
Published: August 2016

The suppression of oscillations of an elastically mounted prism under galloping by a dynamic vibration absorber (DVA) with linear damping and stiffness is investigated. A model considering the dynamic coupling of the prism and the DVA is constructed, with the aerodynamic loads acting on the system represented by a quasi-steady approximation. Based on the coupled nonlinear governing equations of motion, a linear analysis is first conducted to explore the coupled frequency and damping, and the onset speed of galloping in the presence of the DVA. Subsequently, the normal form of the Hopf bifurcation for the coupled system near the onset of galloping is derived to characterize the type of instability (supercritical or subcritical), while evaluating the effects of the DVA parameters. The results show that with appropriate parametric values, the DVA has great impact on the onset speed of galloping and can significantly alleviate the oscillation amplitude of the prism.
Ca2+-activated Cl− channel currents in mammary secretory cells from lactating mouse
Authors: Kamikawa Akihiro , Ichii Osamu , Sakazaki Junpei , Ishikawa Toru
Published: August 2016

The Cl− secretion via Ca2+-activated Cl− channel (CaCC) is critical for fluid secretion in exocrine glands like the salivary gland. Also in the mammary gland, it has been hypothesized that CaCC plays an important role in the secretion of Cl− and aqueous phase of milk. However, there has been no evidence for the functional expression of CaCC in native mammary secretory (MS) cells of lactating animals. We therefore assessed membrane current in MS cells that were freshly isolated from lactating mice using whole cell patch-clamp techniques. In MS cells, we detected CaCC current that exhibited the following characteristics: 1) Ca2+-dependent activation at the concentrations of submicromolar range; 2) voltage-dependent activation; 3) slow kinetics for activation and deactivation; 4) outward rectification of the steady-state current; 5) anion permeability in the sequence of I− > NO3− > Br− > Cl− >> glutamate; 6) inhibition by Cl− channel blockers (niflumic acid, DIDS, and CaCCinh-A01). These characteristics of native CaCC current were similar to reported characteristics of heterologously expressed TMEM16A. RT-PCR analyses showed the expression of multiple CaCC channels including TMEM16A, Best1, and Best3 in the mammary glands of lactating mice. Immunohistochemical staining revealed the localization of TMEM16A protein at the apical membrane of the MS cells. Collectively, our data strongly suggest that MS cells functionally express CaCC, which is at least partly constituted by TMEM16A. The CaCC such as TMEM16A at the apical membrane of the MS cells may influence the quantity and/or quality of milk.
Targeting cytokine signaling in salt-sensitive hypertension
Authors: Crowley Steven D. , Jeffs Alexander D.
Published: August 2016

Activated immune cell populations contribute to hypertension in part through inciting damage to the kidney and by provoking inappropriate sodium reabsorption in the nephron. Inflammatory mediators called cytokines produced by T lymphocytes and macrophages act on specific sodium transporters in the kidney, augmenting their activity or expression, with consequent expansion of intravascular fluid volume and cardiac output. The overlapping functions of these cytokines, each of which may activate multiple receptors, present challenges in precisely targeting inflammatory signaling cascades in hypertension. Moreover, broad immune suppression could expose the hypertensive patient to disproportional risks of infection or malignancy. Nevertheless, the possibility that incisive immunomodulatory therapies could provide cardiovascular and renal protection through both blood pressure-dependent and -independent mechanisms justifies comprehensive investigation into the relevant signaling pathways and tissue sites in which inflammatory cytokines function to exaggerate blood pressure elevation and target organ damage in hypertension.
A systematic analysis of neurons with large somatosensory receptive fields covering multiple body regions in the secondary somatosensory area of macaque monkeys
Authors: Taoka M. , Toda T. , Hihara S. , Tanaka M. , Iriki A. , Iwamura Y.
Published: August 2016

Previous neurophysiological studies performed in macaque monkeys have revealed complex somatosensory responses in the secondary somatosensory area (SII), such as large receptive fields (RFs), as well as bilateral ones. However, systematic analyses of neurons with large RFs have not been performed. In the present study, we recorded single-unit activities in SII of awake macaque monkeys to investigate systematically large RFs by dividing the whole body into four body regions (head, trunk, forelimb, and hindlimb). Recorded neurons were classified into two types, according to whether the RFs were confined to one body region: single ( n = 817) and combined ( n = 282) body-region types. These two types were distinct in terms of the percentage of bilateral RFs: 55% in the single-region type and 90% in the combined type, demonstrating that two types of RF enlargement occur simultaneously in the combined type, namely, RF convergence from different body regions and RF convergence from both hemibodies. Among the combined-type RFs, two tendencies of RF convergence were found: 1) the distal parts of the limbs (i.e., hand and foot) and the mouth are interconnected, and 2) the trunk RFs extend continuously toward the distal parts of the limb and head to cover the entire body surface. Our distribution analysis on unfolded maps clarified that neurons having RFs with these two tendencies were distributed within specific subregions in SII.
GDF-15 and Hepcidin Levels in Nonanemic Patients with Impaired Glucose Tolerance
Authors: Yalcin Mehmet Muhittin , Altinova Alev Eroglu , Akturk Mujde , Gulbahar Ozlem , Arslan Emre , Ors Sendogan Damla , Yetkin Ilhan , Toruner Fusun Balos
Published: August 2016

Aims. Growth Differentiation Factor-15 (GDF-15) has been suggested as one of the regulators of hepcidin, an important regulatory peptide for iron deposition. Current data is conflicting about the relationship between hepcidin and disorders of glucose metabolism. We aimed to investigate serum hepcidin and GDF-15 concentrations and their associations with each other, in nonanemic subjects with impaired glucose tolerance (IGT) in comparison with the nonanemic subjects with normal glucose tolerance (NGT).Methods. Thirty-seven subjects with IGT and 32 control subjects with NGT, who were age-, gender-, and body mass index- (BMI-) matched, were included in the study.Results. Serum GDF-15 levels were significantly higher in IGT compared to NGT. There were no differences in hepcidin, interleukin-6, and high sensitive C-reactive protein levels between the groups. We found a positive correlation between GDF-15 and hepcidin levels. There were also positive correlations between GDF-15 and age, uric acid, creatinine, and area under the curve for glucose (AUC-G). Hepcidin was correlated positively with ferritin levels. In the multiple regression analysis, GDF-15 concentrations were independently associated with age, uric acid, and AUC-G.Conclusions. Impaired glucose tolerance is associated with increased GDF-15 levels even in the absence of anemia, but the levels of hepcidin are not significantly altered in prediabetic state.
Differential Regulation of the Extracellular Cysteine/Cystine Redox State (EhCySS) by Lung Fibroblasts from Young and Old Mice
Authors: Watson Walter H. , Burke Tom J. , Zelko Igor N. , Torres-González Edilson , Ritzenthaler Jeffrey D. , Roman Jesse
Published: August 2016

Aging is associated with progressive oxidation of plasma cysteine (Cys)/cystine (CySS) redox state, expressed as EhCySS. Cultured cells condition their media to reproduce physiological EhCySS, but it is unknown whether aged cells produce a more oxidized extracellular environment reflective of that seen in vivo. In the current study, we isolated primary lung fibroblasts from young and old female mice and measured the media EhCySS before and after challenge with Cys or CySS. We also measured expression of genes related to redox regulation and fibroblast function. These studies revealed that old fibroblasts produced a more oxidizing extracellular EhCySS than young fibroblasts and that old fibroblasts had a decreased capacity to recover from an oxidative challenge due to a slower rate of reduction of CySS to Cys. These defects were associated with 10‐fold lower expression of the Slc7a11 subunit of the xCT cystine‐glutamate transporter. Extracellular superoxide dismutase (Sod3) was the only antioxidant or thiol‐disulfide regulating enzyme among 36 examined that was downregulated in old fibroblasts by more than 2‐fold, but there were numerous changes in extracellular matrix components. Thus, aging fibroblasts not only contribute to remodeling of the extracellular matrix but also have a profound effect on the extracellular redox environment.
The Relationship between Branched-Chain Amino Acid Related Metabolomic Signature and Insulin Resistance: A Systematic Review
Authors: Zhao Xue , Han Qing , Liu Yujia , Sun Chenglin , Gang Xiaokun , Wang Guixia
Published: August 2016

Recent studies have shown the positive association between increased circulating BCAAs (valine, leucine, and isoleucine) and insulin resistance (IR) in obese or diabetic patients. However, results seem to be controversial in different races, diets, and distinct tissues. Our aims were to evaluate the relationship between BCAA and IR as well as later diabetes risk and explore the phenotypic and genetic factors influencing BCAA level based on available studies. We performed systematic review, searching MEDLINE, EMASE, ClinicalTrials.gov, the Cochrane Library, and Web of Science from inception to March 2016. After selection, 23 studies including 20,091 participants were included. Based on current evidence, we found that BCAA is a useful biomarker for early detection of IR and later diabetic risk. Factors influencing BCAA level can be divided into four parts: race, gender, dietary patterns, and gene variants. These factors might not only contribute to the elevated BCAA level but also show obvious associations with insulin resistance. Genes related to BCAA catabolism might serve as potential targets for the treatment of IR associated metabolic disorders. Moreover, these factors should be controlled properly during study design and data analysis. In the future, more large-scale studies with elaborate design addressing BCAA and IR are required.
A Temperature Compensation Model for Low Cost Quartz Accelerometers and Its Application in Tilt Sensing
Authors: Yang Weibin , Fang Bin , Tang Yuan Yan , Qin Xudong
Published: August 2016

Although the quartz accelerometer has made great advances, the performance, in some specific applications such as tilt sensing, needs to be well compensated in high temperature environment. Based on the high temperature testing of low cost quartz accelerometers, we found that the normalized positive and negative parts are asymmetrical at high temperature and the temperature curve of zero sensor output is related to the roll angle of the sensor. Traditional temperature compensation method only considers the temperature factor and ignores the roll sensitivity, which leads to deteriorated accuracy. To solve this problem, this paper proposes a novel and simple mathematical model to obtain a more accurate expression of zero sensor output, which makes the sensor output more robust at high temperature. Experimental results on two low cost quartz accelerometers demonstrate that the proposed model is feasible and effective, which could reduce the temperature drift error of the sensor output typically from 0.01 g to 0.001 g. Furthermore, we introduce the compensated sensors in the three-axis inclinometer system for tilt sensing, and the evaluation results show that the temperature drift error of the inclination in the range (20∘C,150∘C) is reduced typically from0.4∘to0.1∘compared to the traditional method.
The Robot Path Planning Based on Improved Artificial Fish Swarm Algorithm
Authors: Zhang Yi , Guan Guolun , Pu Xingchen
Published: August 2016

Path planning is critical to the efficiency and fidelity of robot navigation. The solution of robot path planning is to seek a collision-free and the shortest path from the start node to target node. In this paper, we propose a new improved artificial fish swarm algorithm (IAFSA) to process the mobile robot path planning problem in a real environment. In IAFSA, an attenuation function is introduced to improve the visual of standard AFSA and get the balance of global search and local search; also, an adaptive operator is introduced to enhance the adaptive ability of step. Besides, a concept of inertia weight factor is proposed in IAFSA inspired by PSO intelligence algorithm to improve the convergence rate and accuracy of IAFSA. Five unconstrained optimization test functions are given to illustrate the strong searching ability and ideal convergence of IAFSA. Finally, the ROS (robot operation system) based experiment is carried out on a Pioneer 3-DX mobile robot; the experiment results also show the superiority of IAFSA.
Progressive FastICA Peel-Off and Convolution Kernel Compensation Demonstrate High Agreement for High Density Surface EMG Decomposition
Authors: Chen Maoqi , Holobar Ales , Zhang Xu , Zhou Ping
Published: August 2016

Decomposition of electromyograms (EMG) is a key approach to investigating motor unit plasticity. Various signal processing techniques have been developed for high density surface EMG decomposition, among which the convolution kernel compensation (CKC) has achieved high decomposition yield with extensive validation. Very recently, a progressive FastICA peel-off (PFP) framework has also been developed for high density surface EMG decomposition. In this study, the CKC and PFP methods were independently applied to decompose the same sets of high density surface EMG signals. Across 91 trials of 64-channel surface EMG signals recorded from the first dorsal interosseous (FDI) muscle of 9 neurologically intact subjects, there were a total of 1477 motor units identified from the two methods, including 969 common motor units. On average,10.6±4.3common motor units were identified from each trial, which showed a very high matching rate of97.85±1.85% in their discharge instants. The high degree of agreement of common motor units from the CKC and the PFP processing provides supportive evidence of the decomposition accuracy for both methods. The different motor units obtained from each method also suggest that combination of the two methods may have the potential to further increase the decomposition yield.
Myocardial Infarction and Aortic Root Mycotic Aneurysm Complicating Aortic Valve Endocarditis: Utility of Cardiac CT
Authors: Moores Aimee E. , Cahill Michael S. , Villines Todd C.
Published: August 2016

Aortic mycotic aneurysms are a rare but life-threatening potential complication of infective endocarditis. Rapid deterioration of the vascular wall in highly focal areas makes these pseudoaneurysms particularly prone to rupture, resulting in uncontrolled aortic hemorrhage. While computed tomography angiography (CTA) is the imaging modality of choice for the evaluation of mycotic aneurysms, it is not routinely performed in patients with known or suspected infective endocarditis (IE). However, current valvular heart disease guidelines support the use of cardiac CTA in cases of IE and suspected perivalvular extension when there is inadequate or ambiguous visualization on echocardiography. Here, we describe a case of IE in which cardiac CTA was used for two purposes: to assess perivalvular complications and to define coronary anatomy in a patient with a suspected embolic myocardial infarction. Subsequent detection of an aortic root mycotic aneurysm not previously demonstrated on transthoracic or transesophageal echocardiography allowed for timely and uncomplicated surgical intervention, while avoiding invasive coronary angiography.