bluuebunny/crossref_metadata_2025 huggingface dataset:
Capsid-CPSF6 Interaction Is Dispensable for HIV-1 Replication in Primary Cells but Is Selected during Virus Passage
In Vivo
Authors: Saito Akatsuki , Henning Matthew S. , Serrao Erik , Dubose Brittany N. , Teng Samantha , Huang Jing , Li Xiangming , Saito Namiko , Roy Saumendra Prasad , Siddiqui Mohammad Adnan , Ahn Jinwoo , Tsuji Moriya , Hatziioannou Theodora , Engelman Alan N. , Yamashita Masahiro
Published: June 2016

Cleavage and polyadenylation specificity factor subunit 6 (CPSF6), a host factor that interacts with the HIV-1 capsid (CA) protein, is implicated in diverse functions during the early part of the HIV-1 life cycle, including uncoating, nuclear entry, and integration targeting. Preservation of CA binding to CPSF6
in vivo
suggests that this interaction is fine-tuned for efficient HIV-1 replication in physiologically relevant settings. Nevertheless, this possibility has not been formally examined. To assess the requirement for optimal CPSF6-CA binding during infection of primary cells and
in vivo
, we utilized a novel CA mutation, A77V, that significantly reduced CA binding to CPSF6. The A77V mutation rendered HIV-1 largely independent from TNPO3, NUP358, and NUP153 for infection and altered the integration site preference of HIV-1 without any discernible effects during the late steps of the virus life cycle. Surprisingly, the A77V mutant virus maintained the ability to replicate in monocyte-derived macrophages, primary CD4
+
T cells, and humanized mice at a level comparable to that for the wild-type (WT) virus. Nonetheless, revertant viruses that restored the WT CA sequence and hence CA binding to CPSF6 emerged in three out of four A77V-infected animals. These results suggest that the optimal interaction of CA with CPSF6, though not absolutely essential for HIV-1 replication in physiologically relevant settings, confers a significant fitness advantage to the virus and thus is strictly conserved among naturally circulating HIV-1 strains.

IMPORTANCE
CPSF6 interacts with the HIV-1 capsid (CA) protein and has been implicated in nuclear entry and integration targeting. Preservation of CPSF6-CA binding across various HIV-1 strains suggested that the optimal interaction between CA and CPSF6 is critical during HIV-1 replication
in vivo
. Here, we identified a novel HIV-1 capsid mutant that reduces binding to CPSF6, is largely independent from the known cofactors for nuclear entry, and alters integration site preference. Despite these changes, virus carrying this mutation replicated in humanized mice at levels indistinguishable from those of the wild-type virus. However, in the majority of the animals, the mutant virus reverted back to the wild-type sequence, hence restoring the wild-type level of CA-CPSF6 interactions. These results suggest that optimal binding of CA to CPSF6 is not absolutely essential for HIV-1 replication
in vivo
but provides a fitness advantage that leads to the widespread usage of CPSF6 by HIV-1
in vivo
.
Repair of a Mutation Disrupting the Guinea Pig Cytomegalovirus Pentameric Complex Acquired during Fibroblast Passage Restores Pathogenesis in Immune-Suppressed Guinea Pigs and in the Context of Congenital Infection
Authors: McVoy Michael A. , Wang Jian Ben , Dittmer Dirk P. , Bierle Craig J. , Swanson Elizabeth C. , Fernández-Alarcón Claudia , Hernandez-Alvarado Nelmary , Zabeli Jason C. , Schleiss Mark R.
Published: June 2016

Guinea pig cytomegalovirus (GPCMV) provides a valuable model for congenital cytomegalovirus transmission. Salivary gland (SG)-passaged stocks of GPCMV are pathogenic, while tissue culture (TC) passage in fibroblasts results in attenuation. Nonpathogenic TC-derived virus N13R10 (cloned as a bacterial artificial chromosome [BAC]) has a 4-bp deletion that disrupts
GP129
, which encodes a subunit of the GPCMV pentameric complex (PC) believed to govern viral entry into select cell types, and
GP130
, an overlapping open reading frame (ORF) of unknown function. To determine if this deletion contributes to attenuation of N13R10, markerless gene transfer in
Escherichia coli
was used to construct virus r129, a variant of N13R10 in which the 4-bp deletion is repaired. Virions from r129 were found to contain GP129 as well as two other PC subunit proteins, GP131 and GP133, whereas these three PC subunits were absent from N13R10 virions. Replication of r129 in fibroblasts appeared unaltered compared to that of N13R10. However, following experimental challenge of immunocompromised guinea pigs, r129 induced significant weight loss, longer duration of viremia, and dramatically higher (up to 1.5 × 10
6
-fold) viral loads in blood and end organs compared to N13R10. In pregnant guinea pigs, challenge with doses of r129 virus of ≥5 × 10
6
PFU resulted in levels of maternal viremia, congenital transmission, pup viral loads, intrauterine growth restriction, and pup mortality comparable to that induced by pathogenic SG virus, although higher doses of r129 were required. These results suggest that the
GP129-GP130
mutation is a significant contributor to attenuation of N13R10, likely by abrogating expression of a functional PC.

IMPORTANCE
Tissue culture adaptation of cytomegaloviruses rapidly selects for mutations, deletions, and rearrangements in the genome, particularly for viruses passaged in fibroblast cells. Some of these mutations are focused in the region of the genome encoding components of the pentameric complex (PC), in particular homologs of human cytomegalovirus (HCMV) proteins UL128, UL130, and UL131A. These mutations can attenuate the course of infection when the virus is reintroduced into animals for vaccine and pathogenesis studies. This study demonstrates that a deletion that arose during the process of tissue culture passage can be repaired, with subsequent restoration of pathogenicity, using BAC-based mutagenesis. Restoration of pathogenicity by repair of a frameshift mutation in GPCMV gene
GP129
using this approach provides a valuable genetic platform for future studies using the guinea pig model of congenital CMV infection.
Macrophages in Progressive Human Immunodeficiency Virus/Simian Immunodeficiency Virus Infections
Authors: DiNapoli Sarah R. , Hirsch Vanessa M. , Brenchley Jason M.
Published: June 2016

The cells that are targeted by primate lentiviruses (HIV and simian immunodeficiency virus [SIV]) are of intense interest given the renewed effort to identify potential cures for HIV. These viruses have been reported to infect multiple cell lineages of hematopoietic origin, including all phenotypic and functional CD4 T cell subsets. The two most commonly reported cell types that become infected
in vivo
are memory CD4 T cells and tissue-resident macrophages. Though viral infection of CD4 T cells is routinely detected in both HIV-infected humans and SIV-infected Asian macaques, significant viral infection of macrophages is only routinely observed in animal models wherein CD4 T cells are almost entirely depleted. Here we review the roles of macrophages in lentiviral disease progression, the evidence that macrophages support viral replication
in vivo
, the animal models where macrophage-mediated replication of SIV is thought to occur, how the virus can interact with macrophages
in vivo
, pathologies thought to be attributed to viral replication within macrophages, how viral replication in macrophages might contribute to the asymptomatic phase of HIV/SIV infection, and whether macrophages represent a long-lived reservoir for the virus.
Recapitulating Cross-Species Transmission of Simian Immunodeficiency Virus SIVcpz to Humans by Using Humanized BLT Mice
Authors: Yuan Zhe , Kang Guobin , Ma Fangrui , Lu Wuxun , Fan Wenjin , Fennessey Christine M. , Keele Brandon F. , Li Qingsheng
Published: June 2016

The origins of human immunodeficiency virus type 1 (HIV-1) have been widely accepted to be the consequences of simian immunodeficiency viruses from wild chimpanzees (SIVcpz) crossing over to humans. However, there has not been any
in vivo
study of SIVcpz infection of humans. Also, it remains largely unknown why only specific SIVcpz strains have achieved cross-species transmission and what transmission risk might exist for those SIVcpz strains that have not been found to infect humans. Closing this knowledge gap is essential for better understanding cross-species transmission and predicting the likelihood of additional cross-species transmissions of SIV into humans. Here we show that humanized bone marrow, thymus, and liver (hu-BLT) mice are susceptible to all studied strains of SIVcpz, including the inferred ancestral viruses of pandemic and nonpandemic HIV-1 groups M (SIVcpzMB897) and N (SIVcpzEK505) as well as strains that have not been found in humans (SIVcpzMT145 and SIVcpzBF1167). Importantly, the ability of SIVcpz to cross the interspecies barrier to infect humanized mice correlates with their phylogenetic distance to pandemic HIV-1. We also identified mutations of SIVcpzMB897 (Env G411R and G413R) and SIVcpzBF1167 (Env H280Q and Q380R) at 14 weeks postinoculation. Together, our results have recapitulated the events of SIVcpz cross-species transmission to humans and identified mutations that occurred during the first 16 weeks of infection, providing
in vivo
experimental evidence that the origins of HIV-1 are the consequence of SIVcpz crossing over to humans. This study also revealed that SIVcpz viruses whose inferred descendants have not been found in humans still have the potential to cause an HIV-1-like zoonosis.

IMPORTANCE
It is believed that the origins of HIV-1 are the consequence of SIV from wild chimpanzees crossing over to humans. However, the origins of HIV-1 have been linked back to only specific SIVcpz strains. There have been no experiments that directly test the
in vivo
cross-species transmissibility of SIVcpz strains to humans. This is the first
in vivo
study of SIVcpz cross-species transmission. With the humanized-BLT mouse model, we have provided
in vivo
experimental evidence of multiple SIVcpz strains crossing over to humans and identified several important mutations of divergent SIVcpz strains after long-term replication in human cells. We also found that the cross-species transmission barrier of SIVcpz to humans correlates with their phylogenetic distance to pandemic HIV-1 group M. Importantly, this work provides evidence that SIVcpz viruses, whose inferred descendants have not been found in humans, still have the potential to cause a future HIV-1-like zoonotic outbreak.
Characterization of a Novel Conformational GII.4 Norovirus Epitope: Implications for Norovirus-Host Interactions
Authors: Carmona-Vicente Noelia , Vila-Vicent Susana , Allen David , Gozalbo-Rovira Roberto , Iturriza-Gómara Miren , Buesa Javier , Rodríguez-Díaz Jesús
Published: June 2016

Human noroviruses (NoVs) are the main etiological agents of acute gastroenteritis worldwide. While NoVs are highly diverse (more than 30 genotypes have been detected in humans), during the last 40 years most outbreaks and epidemics have been caused by GII.4 genotype strains, raising questions about their persistence in the population. Among other potential explanations, immune evasion is considered to be a main driver of their success. In order to study antibody recognition and evasion in detail, we analyzed a conformational epitope recognized by a monoclonal antibody (3C3G3) by phage display, site-directed mutagenesis, and surface plasmon resonance. Our results show that the predicted epitope is composed of 11 amino acids within the P domain: P245, E247, I389, Q390, R397, R435, G443, Y444, P445, N446, and D448. Only two of them, R397 and D448, differ from the homologous variant (GII.4 Den-Haag_2006b) and from a previous variant (GII.4 VA387_1996) that is not recognized by the antibody. A double mutant derived from the VA387_1996 variant containing both changes, Q396R and N447D, is recognized by the 3C3G3 monoclonal antibody, confirming the participation of the two sites in the epitope recognized by the antibody. Furthermore, a single change, Q396R, is able to modify the histo-blood group antigen (HBGA) recognition pattern. These results provide evidence that the epitope recognized by the 3C3G3 antibody is involved in the virus-host interactions, both at the immunological and at the receptor levels.

IMPORTANCE
Human noroviruses are the main cause of viral diarrhea worldwide in people of all ages. Noroviruses can infect individuals who had been previously exposed to the same or different norovirus genotypes. Norovirus genotype GII.4 has been reported to be most prevalent during the last 40 years. In the present study, we describe a novel viral epitope identified by a monoclonal antibody and located within the highly diverse P domain of the capsid protein. The evolution of this epitope along with sequential GII.4 variants has allowed noroviruses to evade previously elicited antibodies, thus explaining how the GII.4 genotype can persist over long periods, reinfecting the population. Our results also show that the epitope participates in the recognition of host receptors that have evolved over time, as well.
Uranium irradiation history of carbonado diamond; implications for Paleoarchean oxidation in the São Francisco craton
Authors: Magee Charles W. , Teles Guilherme , Vicenzi Edward P. , Taylor Wayne , Heaney Peter
Published: June 2016

Carbonado is a porous polycrystalline diamond rock found in central African and Brazilian placer deposits. It contains unsupported radiogenic isotopes of He, Ne, Kr, Xe, and Pb. Here we show that these, and the radiation-related defects introduced to the diamond structure, are a result of uranium precipitation, with no isotopic or spectroscopic evidence of Th enrichment. The daughter products are unsupported due to Proterozoic U remobilization. Combining existing carbonado Pb isotope data with recent studies of the geochronology of the tectonic evolution of the São Francisco craton (eastern South America) reveals that the most likely scenario is Paleoarchean uranium enrichment of carbonado, followed by Mesoproterozoic uranium dissolution. Under all possible scenarios, the carbonado radiation damage history requires U mobilization in the Mesoarchean or late Paleoarchean. This is consistent with recent studies of South Africa and India Mesoarchean paleosols, which also show evidence for local oxygen activity greater than that of the Archean atmosphere and ocean. While those studies rely on whole-rock trace element and transition metal stable isotope measurements, this combination of crystallographic defects, sedimentary geochronology, and radiogenic isotopes supports the same conclusions of nonmarine, near-surface Archean oxygen enhancement.
Vegetation control allows autocyclic formation of multiple dunes on prograding coasts
Authors: Moore Laura J. , Vinent Orencio Durán , Ruggiero Peter
Published: June 2016

We investigate the formation of multiple dunes using a >15 yr record of dune growth from Long Beach Peninsula, Washington State (USA), and a recently published coastal dune model modified to include a feedback between vegetation growth and local dune slope. In the presence of shoreline progradation, we find that multiple dune ridge formation can be autocyclic, arising purely from internal dune dynamics rather than requiring variations in external conditions. Our results suggest that the ratio of the shoreline progradation rate and the lateral dune growth rate is critical in determining the height, number, and form of multiple dunes, allowing the development of testable predictions. Our findings are consistent with observations and imply that caution is required when using dune ridges as proxies for past changes in climate, sea level, land use, and tectonic activity because the relationship between external events and the formation of multiple dunes may not be one to one as previously thought.
Effects of seafloor diagenesis on planktic foraminiferal radiocarbon ages
Authors: Wycech Jody , Kelly D. Clay , Marcott Shaun
Published: June 2016

Radiocarbon (14C) ages obtained from planktic foraminiferal calcite are a mainstay for reconstructing ocean-climate change and carbon cycle dynamics of the past 30 k.y., yet the effects of diagenesis on this vital chronometer are poorly constrained. Here, we address this shortcoming by comparing 14C ages and trace element ratios (Mg/Ca, Mn/Ca) of planktic foraminifera with white, opaque shells deemed well preserved by traditional standards to those with exquisitely preserved translucent shells. Results support a diagenetic mechanism as opaque shells yield 14C ages invariably older and trace element ratios consistently higher than those of translucent shells. Radiocarbon age offsets are particularly pronounced in mono-specific samples taken from stratigraphic horizons proximal to the δ18O maximum marking the Last Glacial Maximum (LGM) and the subsequent deglacial. Radiocarbon-based calendar ages of translucent shells from the two intervals are congruent with the established age ranges for these climate events, whereas those of co-occurring opaque shells overestimate the LGM and deglacial by 8–15 k.y. and 14–22 k.y., respectively. These results demonstrate that the use of translucent foraminifera enhances reproducibility and accuracy of 14C ages by minimizing the deleterious effects of diagenesis. This study serves as a cautionary tale since white, opaque foraminifera are common in pelagic sediments, and 14C ages derived from their ostensibly well-preserved shells can lead to discrepancies in the timing of Quaternary climate events and ocean circulation reconstructions.
Rectal adenocarcinoma infiltrating the bulbar urethra and metastasising to the penis
Authors: James Mathews , Amaranathan Anandhi , Nelamangala Ramakrishnaiah Vishnu Prasad , Toi Pampa Chakrabarty
Published: June 2016

Secondary penile tumours from rectal carcinoma is a known clinical entity but can be missed unless carefully evaluated. We report a case of rectal adenocarcinoma with synchronous painless penile nodules. A patient presented with constipation and rectal bleeding. He had an anorectal growth as well as palpable nodules on his penis. Rectal biopsy yielded adenocarcinoma. Imaging revealed direct infiltration of tumour into the bulb of the penis as well as distal shaft lesions. Fine-needle aspiration cytology of the penile nodule showed metastatic adenocarcinoma. Diversion colostomy was performed and the patient referred for chemoradiation. Since he did not have any urinary symptoms, the penile lesions were left unaltered. Repeat imaging after concurrent chemoradiotherapy showed no response. The prognosis was explained and the patient was given palliative clinic care.
High incidence of injury at the Sochi 2014 Winter Paralympic Games: a prospective cohort study of 6564 athlete days
Authors: Derman W , Schwellnus M P , Jordaan E , Runciman P , Van de Vliet P , Blauwet C , Webborn N , Willick S , Stomphorst J
Published: June 2016

Objective

To describe the epidemiology of injuries at the Sochi 2014 Winter Paralympic Games.

Methods

A total of 547 athletes from 45 countries were monitored daily for 12 days during the Sochi 2014 Winter Paralympic Games (6564 athlete days). Daily injury data were obtained from teams with their own medical support (32 teams, 510 athletes) and teams without their own medical support (13 teams, 37 athletes) through electronic data capturing systems.

Results

There were 174 total injuries reported, with an injury incidence rate (IR) of 26.5 per 1000 athlete days (95% CI 22.7% to 30.8%). There was a significantly higher IR recorded in alpine skiing/snowboarding (IR of 41.1 (95% CI 33.7% to 49.6%) p=0.0001) compared to cross-country skiing/biathlon, ice sledge hockey or wheelchair curling. Injuries in the shoulder region were the highest single-joint IR (IR of 6.4 (95% CI 4.6% to 8.6%)), although total upper and lower body IR were similar (IR 8.5 vs 8.4 (95% CI 6.4% to 11.1%)). Furthermore, the IR of acute injuries was significantly higher than other types of injury onset (IR of 17.8 (95% CI 14.7% to 21.4%)).

Conclusions

In a Winter Paralympic Games setting, athletes report higher injury incidence than do Olympic athletes or athletes in a Summer Paralympic Games setting. The highest incidence of injury was reported in the alpine skiing/snowboarding sporting category. There was a similar incidence of injury in the upper and lower limbs. The joint with the greatest rate of injury reported was the shoulder joint. Our data can inform injury prevention programmes and policy considerations regarding athlete safety in future Winter Paralympic Games.
The anticoagulation choices of internal medicine residents for stroke prevention in non-valvular atrial fibrillation
Authors: Moulson Nathaniel , McIntyre William F , Oqab Zardasht , Yazdan-Ashoori Payam , Quinn Kieran L , van Oosten Erik , Hopman Wilma M , Baranchuk Adrian
Published: June 2016

Purpose of the study

To explore the oral anticoagulation (OAC) prescribing choices of Canadian internal medicine residents, at different training levels, in comparison with the Canadian Cardiovascular Society (CCS) guidelines for non-valvular atrial fibrillation (NVAF).

Study design

Cross-sectional, web-based survey, involving clinical scenarios designed to favour the use of non-vitamin K antagonists (NOACs) as per the 2014 CCS NVAF guidelines. Additional questions were also designed to determine resident attitudes towards OAC prescribing.

Results

A total of 518 internal medicine responses were analysed, with 196 postgraduate year (PGY)-1s, 169 PGY-2s and 153 PGY-3s. The majority of residents (81%) reported feeling comfortable choosing OAC, with 95% having started OAC in the past 3 months. In the initial clinical scenario involving an uncomplicated patient with a CHADS2 score of 3, warfarin was favoured over any of the NOACs by PGY-1s (81.6% vs 73.9%), but NOACs were favoured by PGY-3s (88.3% vs 83.7%). This was the only scenario where OAC choices varied by PGY year, as each of the subsequent clinical scenarios residents generally favoured warfarin over NOACs irrespective of level of training. The majority of residents stated that they would no longer prescribe warfarin once NOAC reversal agents are available, and residents felt risk of adverse events was the most important factor when choosing OAC.

Conclusions

Canadian internal medicine residents favoured warfarin over NOACs for patients with NVAF, which is in discordance with the evidence-based CCS guidelines. This finding persisted throughout the 3 years of core internal medicine training.
Antibiotic resistance: in the news, and staying there
Authors: Gibbens Nigel
Published: June 2016

In his latest update for Veterinary Record, Nigel Gibbens, the UK's Chief Veterinary Officer, discusses antimicrobial resistance and the UK's approach to tackling this global issue
Part of the global livestock industry
Authors: Tice George
Published: June 2016

As an undergraduate, George Tice developed an interest in farm animal medicine and planned to work in this area after qualifying, but he also wanted to experience working in Africa. Having achieved both, he joined Elanco and has worked in a variety of roles in Europe and the USA. So as not to lose direct contact with animals, however, he keeps a selection at home
Systematic review of the relationships between objectively measured physical activity and health indicators in school-aged children and youth
Authors: Poitras Veronica Joan , Gray Casey Ellen , Borghese Michael M. , Carson Valerie , Chaput Jean-Philippe , Janssen Ian , Katzmarzyk Peter T. , Pate Russell R. , Connor Gorber Sarah , Kho Michelle E. , Sampson Margaret , Tremblay Mark S.
Published: June 2016

Moderate-to-vigorous physical activity (MVPA) is essential for disease prevention and health promotion. Emerging evidence suggests other intensities of physical activity (PA), including light-intensity activity (LPA), may also be important, but there has been no rigorous evaluation of the evidence. The purpose of this systematic review was to examine the relationships between objectively measured PA (total and all intensities) and health indicators in school-aged children and youth. Online databases were searched for peer-reviewed studies that met the a priori inclusion criteria: population (apparently healthy, aged 5–17 years), intervention/exposure/comparator (volumes, durations, frequencies, intensities, and patterns of objectively measured PA), and outcome (body composition, cardiometabolic biomarkers, physical fitness, behavioural conduct/pro-social behaviour, cognition/academic achievement, quality of life/well-being, harms, bone health, motor skill development, psychological distress, self-esteem). Heterogeneity among studies precluded meta-analyses; narrative synthesis was conducted. A total of 162 studies were included (204 171 participants from 31 countries). Overall, total PA was favourably associated with physical, psychological/social, and cognitive health indicators. Relationships were more consistent and robust for higher (e.g., MVPA) versus lower (e.g., LPA) intensity PA. All patterns of activity (sporadic, bouts, continuous) provided benefit. LPA was favourably associated with cardiometabolic biomarkers; data were scarce for other outcomes. These findings continue to support the importance of at least 60 min/day of MVPA for disease prevention and health promotion in children and youth, but also highlight the potential benefits of LPA and total PA. All intensities of PA should be considered in future work aimed at better elucidating the health benefits of PA in children and youth.
Associations between sleep duration, sedentary time, physical activity, and health indicators among Canadian children and youth using compositional analyses
Authors: Carson Valerie , Tremblay Mark S. , Chaput Jean-Philippe , Chastin Sebastien F.M.
Published: June 2016

The purpose of this study was to examine the relationships between movement behaviours (sleep duration, sedentary time, physical activity) and health indicators in a representative sample of children and youth using compositional analyses. Cross-sectional findings are based on 4169 children and youth (aged 6–17 years) from cycles 1 to 3 of the Canadian Health Measures Survey. Sedentary time (SB), light-intensity physical activity (LPA), and moderate- to vigorous-intensity physical activity (MVPA) were accelerometer-derived. Sleep duration was subjectively measured. Body mass index z scores, waist circumference, blood pressure, behavioural strengths and difficulties, and aerobic fitness were measured in the full sample. Triglycerides, high-density lipoprotein-cholesterol, C-reactive protein, and insulin were measured in a fasting subsample. The composition of movement behaviours was entered into linear regression models via an isometric log ratio transformation and was found to be associated with all health indicators (p < 0.01). Relative to other movement behaviours, time spent in SB or LPA was positively associated (p < 0.04) and time spent in MVPA or sleep was negatively associated (p < 0.02) with obesity risk markers. Similarly, LPA was positively associated (p < 0.005) and sleep was negatively associated (p < 0.03) with unfavourable behavioural strengths and difficulties scores and systolic blood pressure. Relative to other movement behaviours, time spent in SB was negatively associated (p < 0.001) and time spent in MVPA (p < 0.001) was positively associated with aerobic fitness. Likewise, MVPA was also negatively associated with several cardiometabolic risk markers (p < 0.008). Compositional data analyses provide novel insights into collective health implications of 24-h movement behaviours and can facilitate interesting avenues for future investigations.
A mathematical analysis of the GW0 method for computing electronic excited energies of molecules
Authors: Cancés Eric , Gontier David , Stoltz Gabriel
Published: June 2016

This article is concerned with the GW method for finite electronic systems. In the first step, we provide a mathematical framework for the usual one-body operators that appear naturally in many-body perturbation theory. We then give a rigorous mathematical formulation of the [Formula: see text] equations, and study the well-posedness of these equations, proving the existence of a unique solution in a perturbative regime.
Nonaxial hexadecapole deformation effects on the fission barrier
Authors: Kardan A. , Nejati S.
Published: June 2016

Fission barrier of the heavy nucleus [Formula: see text]Cf is analyzed in a multi-dimensional deformation space. This space includes two quadrupole ([Formula: see text]) and three hexadecapole deformation ([Formula: see text]) parameters. The analysis is performed within an unpaired macroscopic–microscopic approach. Special attention is given to the effects of the axial and non-axial hexadecapole deformation shapes. It is found that the inclusion of the nonaxial hexadecapole shapes does not change the fission barrier heights, so it should be sufficient to minimize the energy in only one degree of freedom in the hexadecapole space [Formula: see text]. The role of hexadecapole deformation parameters is also discussed on the Lublin–Strasbourg drop (LSD) macroscopic and the Strutinsky shell energies.
Design and Implementation of a Low Cost Mini Quadrotor for Vision Based Maneuvers in GPS Denied Environments
Authors: Liu Chang , Prior Stephen D. , Scanlan James P.
Published: June 2016

This paper presents the design and implementation detail of an advanced mini quadrotor system, including the low cost commercial-off-the-shelf (COTS) electronics and advanced control algorithm. The proposed quadrotor has a gross takeoff weight of 758[Formula: see text]g and 360[Formula: see text]mm frame diagonal size. It is capable of semi-autonomous maneuver in GPS denied environments, solely relying on onboard sensors and computers. A globally defined quadrotor model is formularized, and a nonlinear velocity tracking controller is implemented on the special Euclidean group SE(3). An optical flow and ultrasonic-based onboard downward-facing camera is used as the primary sensor to provide velocity and altitude measurement feedback for the controller. The control and sensor fusion algorithm is developed under Arduino compatible open source electronics.
MultiLanes
Authors: Kang Junbin , Hu Chunming , Wo Tianyu , Zhai Ye , Zhang Benlong , Huai Jinpeng
Published: June 2016

OS-level virtualization is often used for server consolidation in data centers because of its high efficiency. However, the sharing of storage stack services among the colocated containers incurs contention on shared kernel data structures and locks within I/O stack, leading to severe performance degradation on manycore platforms incorporating fast storage technologies (e.g., SSDs based on nonvolatile memories).

This article presents MultiLanes, a virtualized storage system for OS-level virtualization on manycores. MultiLanes builds an isolated I/O stack on top of a virtualized storage device for each container to eliminate contention on kernel data structures and locks between them, thus scaling them to manycores. Meanwhile, we propose a set of techniques to tune the overhead induced by storage-device virtualization to be negligible, and to scale the virtualized devices to manycores on the host, which itself scales poorly. To reduce the contention within each single container, we further propose SFS, which runs multiple file-system instances through the proposed virtualized storage devices, distributes all files under each directory among the underlying file-system instances, then stacks a unified namespace on top of them.

The evaluation of our prototype system built for Linux container (LXC) on a 32-core machine with both a RAM disk and a modern flash-based SSD demonstrates that MultiLanes scales much better than Linux in micro- and macro-benchmarks, bringing significant performance improvements, and that MultiLanes with SFS can further reduce the contention within each single container.
Progress in the Analysis of Complex Atmospheric Particles
Authors: Laskin Alexander , Gilles Mary K. , Knopf Daniel A. , Wang Bingbing , China Swarup
Published: June 2016

This article presents an overview of recent advances in field and laboratory studies of atmospheric particles formed in processes of environmental air-surface interactions. The overarching goal of these studies is to advance predictive understanding of atmospheric particle composition, particle chemistry during aging, and their environmental impacts. The diversity between chemical constituents and lateral heterogeneity within individual particles adds to the chemical complexity of particles and their surfaces. Once emitted, particles undergo transformation via atmospheric aging processes that further modify their complex composition. We highlight a range of modern analytical approaches that enable multimodal chemical characterization of particles with both molecular and lateral specificity. When combined, these approaches provide a comprehensive arsenal of tools for understanding the nature of particles at air-surface interactions and their reactivity and transformations with atmospheric aging. We discuss applications of these novel approaches in recent studies and highlight additional research areas to explore the environmental effects of air-surface interactions.
Advanced Multidimensional Separations in Mass Spectrometry: Navigating the Big Data Deluge
Authors: May Jody C. , McLean John A.
Published: June 2016

Hybrid analytical instrumentation constructed around mass spectrometry (MS) is becoming the preferred technique for addressing many grand challenges in science and medicine. From the omics sciences to drug discovery and synthetic biology, multidimensional separations based on MS provide the high peak capacity and high measurement throughput necessary to obtain large-scale measurements used to infer systems-level information. In this article, we describe multidimensional MS configurations as technologies that are big data drivers and review some new and emerging strategies for mining information from large-scale datasets. We discuss the information content that can be obtained from individual dimensions, as well as the unique information that can be derived by comparing different levels of data. Finally, we summarize some emerging data visualization strategies that seek to make highly dimensional datasets both accessible and comprehensible.
Recent Progress in Monolithic Silica Columns for High-Speed and High-Selectivity Separations
Authors: Ikegami Tohru , Tanaka Nobuo
Published: June 2016

Monolithic silica columns have greater (through-pore size)/(skeleton size) ratios than particulate columns and fixed support structures in a column for chemical modification, resulting in high-efficiency columns and stationary phases. This review looks at how the size range of monolithic silica columns has been expanded, how high-efficiency monolithic silica columns have been realized, and how various methods of silica surface functionalization, leading to selective stationary phases, have been developed on monolithic silica supports, and provides information on the current status of these columns. Also discussed are the practical aspects of monolithic silica columns, including how their versatility can be improved by the preparation of small-sized structural features (sub-micron) and columns (1 mm ID or smaller) and by optimizing reaction conditions for in situ chemical modification with various restrictions, with an emphasis on recent research results for both topics.
Vascular CaMKII: heart and brain in your arteries
Authors: Toussaint Fanny , Charbel Chimène , Allen Bruce G. , Ledoux Jonathan
Published: June 2016

First characterized in neuronal tissues, the multifunctional calcium/calmodulin-dependent protein kinase II (CaMKII) is a key signaling component in several mammalian biological systems. Its unique capacity to integrate various Ca2+ signals into different specific outcomes is a precious asset to excitable and nonexcitable cells. Numerous studies have reported roles and mechanisms involving CaMKII in brain and heart tissues. However, corresponding functions in vascular cell types (endothelium and vascular smooth muscle cells) remained largely unexplored until recently. Investigation of the intracellular Ca2+ dynamics, their impact on vascular cell function, the regulatory processes involved and more recently the spatially restricted oscillatory Ca2+ signals and microdomains triggered significant interest towards proteins like CaMKII. Heteromultimerization of CaMKII isoforms (four isoforms and several splice variants) expands this kinase's peculiar capacity to decipher Ca2+ signals and initiate specific signaling processes, and thus controlling cellular functions. The physiological functions that rely on CaMKII are unsurprisingly diverse, ranging from regulating contractile state and cellular proliferation to Ca2+ homeostasis and cellular permeability. This review will focus on emerging evidence of CaMKII as an essential component of the vascular system, with a focus on the kinase isoform/splice variants and cellular system studied.
Demonstration of the functional impact of vasopressin signaling in the thick ascending limb by a targeted transgenic rat approach
Authors: Mutig Kerim , Borowski Tordis , Boldt Christin , Borschewski Aljona , Paliege Alexander , Popova Elena , Bader Michael , Bachmann Sebastian
Published: June 2016

The antidiuretic hormone vasopressin (AVP) regulates renal salt and water reabsorption along the distal nephron and collecting duct system. These effects are mediated by vasopressin 2 receptors (V2R) and release of intracellular Gs-mediated cAMP to activate epithelial transport proteins. Inactivating mutations in the V2R gene lead to the X-linked form of nephrogenic diabetes insipidus (NDI), which has chiefly been related with impaired aquaporin 2-mediated water reabsorption in the collecting ducts. Previous work also suggested the AVP-V2R-mediated activation of Na+-K+-2Cl−-cotransporters (NKCC2) along the thick ascending limb (TAL) in the context of urine concentration, but its individual contribution to NDI or, more generally, to overall renal function was unclear. We hypothesized that V2R-mediated effects in TAL essentially determine its reabsorptive function. To test this, we reevaluated V2R expression. Basolateral membranes of medullary and cortical TAL were clearly stained, whereas cells of the macula densa were unreactive. A dominant-negative, NDI-causing truncated V2R mutant (Ni3-Glu242stop) was then introduced into the rat genome under control of the Tamm-Horsfall protein promoter to cause a tissue-specific AVP-signaling defect exclusively in TAL. Resulting Ni3-V2R transgenic rats revealed decreased basolateral but increased intracellular V2R signal in TAL epithelia, suggesting impaired trafficking of the receptor. Rats displayed significant baseline polyuria, failure to concentrate the urine in response to water deprivation, and hypercalciuria. NKCC2 abundance, phosphorylation, and surface expression were markedly decreased. In summary, these data indicate that suppression of AVP-V2R signaling in TAL causes major impairment in renal fluid and electrolyte handling. Our results may have clinical implications.
Active sensing without efference copy: referent control of perception
Authors: Feldman Anatol G.
Published: June 2016

Although action and perception are different behaviors, they are likely to be interrelated, as implied by the notions of perception-action coupling and active sensing. Traditionally, it has been assumed that the nervous system directly preprograms motor commands required for actions and uses a copy of them called efference copy (EC) to also influence our senses. This review offers a critical analysis of the EC concept by identifying its limitations. An alternative to the EC concept is based on the experimentally confirmed notion that sensory signals from receptors are perceived relative to referent signals specified by the brain. These referents also underlie the control of motor actions by predetermining where, in the spatial domain, muscles can work without preprogramming how they should work in terms of motor commands or EC. This approach helps solve several problems of action and explain several sensory experiences, including position sense and the sense that the world remains stationary despite changes in its retinal image during eye or body motion (visual space constancy). The phantom limb phenomenon and other kinesthetic illusions are also explained within this framework.
α1- and α2-adrenergic receptors in the retrotrapezoid nucleus differentially regulate breathing in anesthetized adult rats
Authors: Oliveira Luiz M. , Moreira Thiago S. , Kuo Fu-Shan , Mulkey Daniel K. , Takakura Ana C.
Published: June 2016

Norepinephrine (NE) is a potent modulator of breathing that can increase/decrease respiratory activity by α1-/α2-adrenergic receptor (AR) activation, respectively. The retrotrapezoid nucleus (RTN) is known to contribute to central chemoreception, inspiration, and active expiration. Here we investigate the sources of catecholaminergic inputs to the RTN and identify respiratory effects produced by activation of ARs in this region. By injecting the retrograde tracer Fluoro-Gold into the RTN, we identified back-labeled catecholaminergic neurons in the A7 region. In urethane-anesthetized, vagotomized, and artificially ventilated male Wistar rats unilateral injection of NE or moxonidine (α2-AR agonist) blunted diaphragm muscle activity (DiaEMG) frequency and amplitude, without changing abdominal muscle activity. Those inhibitory effects were reduced by preapplication of yohimbine (α2-AR antagonist) into the RTN. Conversely, unilateral RTN injection of phenylephrine (α1-AR agonist) increased DiaEMGamplitude and frequency and facilitated active expiration. This response was blocked by prior RTN injection of prazosin (α1-AR antagonist). Interestingly, RTN injection of propranolol (β-AR antagonist) had no effect on respiratory inhibition elicited by applications of NE into the RTN; however, the combined blockade of α2- and β-ARs (coapplication of propranolol and yohimbine) revealed an α1-AR-dependent excitatory response to NE that resulted in increase in DiaEMGfrequency and facilitation of active expiration. However, blockade of α1-, α2-, or β-ARs in the RTN had minimal effect on baseline respiratory activity, on central or peripheral chemoreflexes. These results suggest that NE signaling can modulate RTN chemoreceptor function; however, endogenous NE signaling does not contribute to baseline breathing or the ventilatory response to central or peripheral chemoreceptor activity in urethane-anesthetized rats.
Morphine-induced synaptic plasticity in the VTA is reversed by HDAC inhibition
Authors: Authement Michael E. , Langlois Ludovic D. , Kassis Haifa , Gouty Shawn , Dacher Matthieu , Shepard Ryan D. , Cox Brian M. , Nugent Fereshteh S.
Published: June 2016

Dopamine (DA) dysfunction originating from the ventral tegmental area (VTA) occurs as a result of synaptic abnormalities following consumption of drugs of abuse and underlies behavioral plasticity associated with drug abuse. Drugs of abuse can cause changes in gene expression through epigenetic mechanisms in the brain that underlie some of the lasting neuroplasticity and behavior associated with addiction. Here we investigated the function of histone acetylation and histone deacetylase (HDAC)2 in the VTA in recovery of morphine-induced synaptic modifications following a single in vivo exposure to morphine. Using a combination of immunohistochemistry, Western blot, and whole cell patch-clamp recording in rat midbrain slices, we show that morphine increased HDAC2 activity in VTA DA neurons and reduced histone H3 acetylation at lysine 9 (Ac-H3K9) in the VTA 24 h after the injection. Morphine-induced synaptic changes at glutamatergic synapses involved endocannabinoid signaling to reduce GABAergic synaptic strength onto VTA DA neurons. Both plasticities were recovered by in vitro incubation of midbrain slices with a class I-specific HDAC inhibitor (HDACi), CI-994, through an increase in acetylation of histone H3K9. Interestingly, HDACi incubation also increased levels of Ac-H3K9 and triggered GABAergic and glutamatergic plasticities in DA neurons of saline-treated rats. Our results suggest that acute morphine-induced changes in VTA DA activity and synaptic transmission engage HDAC2 activity locally in the VTA to maintain synaptic modifications through histone hypoacetylation.
Synaptic and intrinsic homeostasis cooperate to optimize single neuron response properties and tune integrator circuits
Authors: Cannon Jonathan , Miller Paul
Published: June 2016

Homeostatic processes that provide negative feedback to regulate neuronal firing rate are essential for normal brain function, and observations suggest that multiple such processes may operate simultaneously in the same network. We pose two questions: why might a diversity of homeostatic pathways be necessary, and how can they operate in concert without opposing and undermining each other? To address these questions, we perform a computational and analytical study of cell-intrinsic homeostasis and synaptic homeostasis in single-neuron and recurrent circuit models. We demonstrate analytically and in simulation that when two such mechanisms are controlled on a long time scale by firing rate via simple and general feedback rules, they can robustly operate in tandem to tune the mean and variance of single neuron's firing rate to desired goals. This property allows the system to recover desired behavior after chronic changes in input statistics. We illustrate the power of this homeostatic tuning scheme by using it to regain high mutual information between neuronal input and output after major changes in input statistics. We then show that such dual homeostasis can be applied to tune the behavior of a neural integrator, a system that is notoriously sensitive to variation in parameters. These results are robust to variation in goals and model parameters. We argue that a set of homeostatic processes that appear to redundantly regulate mean firing rate may work together to control firing rate mean and variance and thus maintain performance in a parameter-sensitive task such as integration.
Self-reinnervated muscles lose autogenic length feedback, but intermuscular feedback can recover functional connectivity
Authors: Lyle Mark A. , Prilutsky Boris I. , Gregor Robert J. , Abelew Thomas A. , Nichols T. Richard
Published: June 2016

In this study, we sought to identify sensory circuitry responsible for motor deficits or compensatory adaptations after peripheral nerve cut and repair. Self-reinnervation of the ankle extensor muscles abolishes the stretch reflex and increases ankle yielding during downslope walking, but it remains unknown whether this finding generalizes to other muscle groups and whether muscles become completely deafferented. In decerebrate cats at least 19 wk after nerve cut and repair, we examined the influence of quadriceps (Q) muscles' self-reinnervation on autogenic length feedback, as well as intermuscular length and force feedback, among the primary extensor muscles in the cat hindlimb. Effects of gastrocnemius and soleus self-reinnervation on intermuscular circuitry were also evaluated. We found that autogenic length feedback was lost after Q self-reinnervation, indicating that loss of the stretch reflex appears to be a generalizable consequence of muscle self-reinnervation. However, intermuscular force and length feedback, evoked from self-reinnervated muscles, was preserved in most of the interactions evaluated with similar relative inhibitory or excitatory magnitudes. These data indicate that intermuscular spinal reflex circuitry has the ability to regain functional connectivity, but the restoration is not absolute. Explanations for the recovery of intermuscular feedback are discussed, based on identified mechanisms responsible for lost autogenic length feedback. Functional implications, due to permanent loss of autogenic length feedback and potential for compensatory adaptations from preserved intermuscular feedback, are discussed.