bluuebunny/crossref_metadata_2025_split huggingface dataset:
A metal-organic framework–based splitter for separating propylene from propane
Authors: Cadiau A. , Adil K. , Bhatt P. M. , Belmabkhout Y. , Eddaoudi M. 
Published: July 2016

Separating one organic from another
Separating closely related organic molecules is a challenge (see the Perspective by Lin).The separation of acetylene from ethylene is needed in high-purity polymer production. Cui et al. developed a copper-based metal-organic framework with hexafluorosilicate and organic linkers designed to have a high affinity for acetylene. These materials, which capture four acetylene molecules in each pore, successfully separated acetylene from mixtures with ethylene. Propane and propylene are both important feedstock chemicals. Their physical and chemical similarity, however, requires energy-intense processes to separate them. Cadiau et al. designed a fluorinated porous metal-organic framework material that selectively adsorbed propylene, with the complete exclusion of propane.

Science
, this issue pp.
141
and
137
; see also p.
121
Antimicrobial Stewardship in the Microbiology Laboratory: Impact of Selective Susceptibility Reporting on Ciprofloxacin Utilization and Susceptibility of Gram-Negative Isolates to Ciprofloxacin in a Hospital Setting
Authors: Langford B. J. , Seah J. , Chan A. , Downing M. , Johnstone J. , Matukas L. M. 
Published: July 2016

ABSTRACT

The objective of this study was to determine the impact of selective susceptibility reporting on ciprofloxacin utilization and Gram-negative susceptibility to ciprofloxacin in a hospital setting. Historically at our institution, the microbiology laboratory practice was to report ciprofloxacin susceptibility for all
Enterobacteriaceae
regardless of susceptibility to other agents. A selective reporting policy was implemented which involved the suppression of ciprofloxacin susceptibility to
Enterobacteriaceae
when there was lack of resistance to the antibiotics on the Gram-negative panel. Ciprofloxacin utilization (measured in defined daily doses [DDD] per 1,000 patient days) was collected before and after the intervention and compared to moxifloxacin, trimethoprim-sulfamethoxazole, nitrofurantoin, and amoxicillin-clavulanate. Monthly susceptibility of
Pseudomonas aeruginosa
and
Escherichia coli
to ciprofloxacin was tabulated. An interrupted time series analysis using segmented regression was performed. The mean monthly ciprofloxacin utilization decreased from 87 (95% CI, 83.7 to 91.2) to 39 (95% CI, 35.0 to 44.0) DDD per 1,000 patient days before and after the implementation of selective reporting, respectively. There was an immediate and sustained reduction in ciprofloxacin usage at 1, 3, 6, 12, and 24 months postintervention (
P
< 0.001). A compensatory increase in amoxicillin-clavulanate use was noted starting at 6 months postintervention and persisted for the study period (
P
< 0.027). Susceptibility of
E. coli
, but not that of
P. aeruginosa
, to ciprofloxacin was higher than predicted starting 12 months after the intervention (
P
< 0.05). In conclusion, selective reporting of ciprofloxacin susceptibly may be a useful intervention to reduce targeted antimicrobial utilization and improve Gram-negative susceptibility to ciprofloxacin. This approach should be considered as part of a broader multimodal antimicrobial stewardship program.
Comprehensive Characterization of HIV-1 Molecular Epidemiology and Demographic History in the Brazilian Region Most Heavily Affected by AIDS
Authors: Gräf Tiago , Machado Fritsch Hegger , de Medeiros Rúbia Marília , Maletich Junqueira Dennis , Esteves de Matos Almeida Sabrina , Pinto Aguinaldo Roberto 
Published: July 2016

ABSTRACT

The high incidence of AIDS cases and the dominance of HIV-1 subtype C infections are two features that distinguish the HIV-1 epidemic in the two southernmost Brazilian states (Rio Grande do Sul [RS] and Santa Catarina [SC]) from the epidemic in other parts of the country. Nevertheless, previous studies on HIV molecular epidemiology were conducted mainly in capital cities, and a more comprehensive understanding of factors driving this unique epidemic in Brazil is necessary. Blood samples were collected from individuals in 13 municipalities in the Brazilian southern region. HIV-1
env
and
pol
genes were submitted to phylogenetic analyses for assignment of subtype, and viral population phylodynamics were reconstructed by applying Skygrid and logistic coalescent models in a Bayesian analysis. A high prevalence of subtype C was observed in all sampled locations; however, an increased frequency of recombinant strains was found in RS, with evidence for new circulating forms (CRFs). In the SC state, subtype B and C epidemics were associated with distinct exposure groups. Although logistic models estimated similar growth rates for HIV-1 subtype C (HIV-1C) and HIV-1B, a Skygrid plot reveals that the former epidemic has been expanding for a longer time. Our results highlight a consistent expansion of HIV-1C in south Brazil, and we also discuss how heterosexual and men who have sex with men (MSM) transmission chains might have impacted the current prevalence of HIV-1 subtypes in this region.

IMPORTANCE
The AIDS epidemic in south Brazil is expanding rapidly, but the circumstances driving this condition are not well known. A high prevalence of HIV-1 subtype C was reported in the capital cities of this region, in contrast to the subtype B dominance in the rest of the country. This study sought to comparatively investigate the HIV-1 subtype B and C epidemics by sampling individuals from several cities in the two states with the highest AIDS incidences in Brazil. Our analyses showed distinct epidemic growth curves for the two epidemics, and we also found evidence suggesting that separate transmission chains may be impacting the viral phylodynamics and the emergence of new recombinant forms.
The Interferon-Stimulated GeneIfitm3Restricts West Nile Virus Infection and Pathogenesis
Authors: Gorman Matthew J. , Poddar Subhajit , Farzan Michael , Diamond Michael S. 
Published: July 2016

ABSTRACTThe interferon-induced transmembrane protein (IFITM) family of proteins inhibit infection of several different enveloped viruses in cell culture by virtue of their ability to restrict entry and fusion from late endosomes. As few studies have evaluated the importance ofIfitm3 in vivoin restricting viral pathogenesis, we investigated its significance as an antiviral gene against West Nile virus (WNV), an encephalitic flavivirus, in cells and mice.Ifitm3−/−mice were more vulnerable to lethal WNV infection, and this was associated with greater virus accumulation in peripheral organs and central nervous system tissues. As no difference in viral burden in the brain or spinal cord was observed after direct intracranial inoculation, Ifitm3 likely functions as an antiviral protein in nonneuronal cells. Consistent with this,Ifitm3−/−fibroblasts but not dendritic cells resulted in higher yields of WNV in multistep growth analyses. Moreover, transcomplementation experiments showed that Ifitm3 inhibited WNV infection independently of Ifitm1, Ifitm2, Ifitm5, and Ifitm6. Beyond a direct effect on viral infection in cells, analysis of the immune response in WNV-infectedIfitm3−/−mice showed decreases in the total number of B cells, CD4+T cells, and antigen-specific CD8+T cells. Finally, bone marrow chimera experiments demonstrated that Ifitm3 functioned in both radioresistant and radiosensitive cells, as higher levels of WNV were observed in the brain only when Ifitm3 was absent from both compartments. Our analyses suggest that Ifitm3 restricts WNV pathogenesis likely through multiple mechanisms, including the direct control of infection in subsets of cells.IMPORTANCEAs part of the mammalian host response to viral infections, hundreds of interferon-stimulated genes (ISGs) are induced. The inhibitory activity of individual ISGs varies depending on the specific cell type and viral pathogen. Among ISGs, the genes encoding interferon-induced transmembrane protein (IFITM) have been reported to inhibit multiple families of viruses in cell culture. However, few reports have evaluated the impact ofIFITMgenes on viral pathogenesisin vivo. In this study, we characterized the antiviral activity of Ifitm3 against West Nile virus (WNV), an encephalitic flavivirus, using mice with a targeted gene deletion ofIfitm3. Based on extensive virological and immunological analyses, we determined that Ifitm3 protects mice from WNV-induced mortality by restricting virus accumulation in peripheral organs and, subsequently, in central nervous system tissues. Our data suggest that Ifitm3 restricts WNV pathogenesis by multiple mechanisms and functions in part by controlling infection in different cell types.
CD25+FoxP3+Memory CD4 T Cells Are Frequent Targets of HIV InfectionIn Vivo
Authors: Chachage Mkunde , Pollakis Georgios , Kuffour Edmund Osei , Haase Kerstin , Bauer Asli , Nadai Yuka , Podola Lilli , Clowes Petra , Schiemann Matthias , Henkel Lynette , Hoffmann Dieter , Joseph Sarah , Bhuju Sabin , Maboko Leonard , Sarfo Fred Stephen , Eberhardt Kirsten , Hoelscher Michael , Feldt Torsten , Saathoff Elmar , Geldmacher Christof 
Published: July 2016

ABSTRACTInterleukin 2 (IL-2) signaling through the IL-2 receptor alpha chain (CD25) facilitates HIV replicationin vitroand facilitates homeostatic proliferation of CD25+FoxP3+CD4+T cells. CD25+FoxP3+CD4+T cells may therefore constitute a suitable subset for HIV infection and plasma virion production. CD25+FoxP3+CD4+T cell frequencies, absolute numbers, and the expression of CCR5 and cell cycle marker Ki67 were studied in peripheral blood from HIV+and HIV−study volunteers. Different memory CD4+T cell subsets were then sorted for quantification of cell-associated HIV DNA and phylogenetic analyses of the highly variable EnvV1V3 region in comparison to plasma-derived virus sequences. In HIV+subjects, 51% (median) of CD25+FoxP3+CD4+T cells expressed the HIV coreceptor CCR5. Very high frequencies of Ki67+cells were detected in CD25+FoxP3+memory CD4+T cells (median, 27.6%) in comparison to CD25−FoxP3−memory CD4+T cells (median, 4.1%;P< 0.0001). HIV DNA content was 15-fold higher in CD25+FoxP3+memory CD4+T cells than in CD25−FoxP3−T cells (P= 0.003). EnvV1V3 sequences derived from CD25+FoxP3+memory CD4+T cells did not preferentially cluster with plasma-derived sequences. Quasi-identical cell-plasma sequence pairs were rare, and their proportion decreased with the estimated HIV infection duration. These data suggest that specific cellular characteristics of CD25+FoxP3+memory CD4+T cells might facilitate efficient HIV infectionin vivoand passage of HIV DNA to cell progeny in the absence of active viral replication. The contribution of this cell population to plasma virion production remains unclear.IMPORTANCEDespite recent advances in the understanding of AIDS virus pathogenesis, which cell subsets support HIV infection and replicationin vivois incompletely understood.In vitro, the IL-2 signaling pathway and IL-2-dependent cell cycle induction are essential for HIV infection of stimulated T cells. CD25+FoxP3+memory CD4 T cells, often referred to as regulatory CD4 T cells, depend on IL-2 signaling for homeostatic proliferationin vivo. Our results show that CD25+FoxP3+memory CD4+T cells often express the HIV coreceptor CCR5, are significantly more proliferative, and contain more HIV DNA than CD25−FoxP3−memory CD4 T cell subsets. The specific cellular characteristics of CD25+FoxP3+memory CD4+T cells probably facilitate efficient HIV infectionin vivoand passage of HIV DNA to cell progeny in the absence of active viral replication. However, the contribution of this cell subset to plasma viremia remains unclear.
Endogenous Gibbon Ape Leukemia Virus Identified in a Rodent (Melomys burtoni subsp.) from Wallacea (Indonesia)
Authors: Alfano Niccolò , Michaux Johan , Morand Serge , Aplin Ken , Tsangaras Kyriakos , Löber Ulrike , Fabre Pierre-Henri , Fitriana Yuli , Semiadi Gono , Ishida Yasuko , Helgen Kristofer M. , Roca Alfred L. , Eiden Maribeth V. , Greenwood Alex D. 
Published: July 2016

ABSTRACT

Gibbon ape leukemia virus (GALV) and koala retrovirus (KoRV) most likely originated from a cross-species transmission of an ancestral retrovirus into koalas and gibbons via one or more intermediate as-yet-unknown hosts. A virus highly similar to GALV has been identified in an Australian native rodent (
Melomys burtoni
) after extensive screening of Australian wildlife. GALV-like viruses have also been discovered in several Southeast Asian species, although screening has not been extensive and viruses discovered to date are only distantly related to GALV. We therefore screened 26 Southeast Asian rodent species for KoRV- and GALV-like sequences, using hybridization capture and high-throughput sequencing, in the attempt to identify potential GALV and KoRV hosts. Only the individuals belonging to a newly discovered subspecies of
Melomys
burtoni
from Indonesia were positive, yielding an endogenous provirus very closely related to a strain of GALV. The sequence of the critical receptor domain for GALV infection in the Indonesian
M. burtoni
subsp. was consistent with the susceptibility of the species to GALV infection. The second record of a GALV in
M. burtoni
provides further evidence that
M. burtoni
, and potentially other lineages within the widespread subfamily
Murinae
, may play a role in the spread of GALV-like viruses. The discovery of a GALV in the most western part of the Australo-Papuan distribution of
M. burtoni
, specifically in a transitional zone between Asia and Australia (Wallacea), may be relevant to the cross-species transmission to gibbons in Southeast Asia and broadens the known distribution of GALVs in wild rodents.

IMPORTANCE
Gibbon ape leukemia virus (GALV) and the koala retrovirus (KoRV) are very closely related, yet their hosts neither are closely related nor overlap geographically. Direct cross-species infection between koalas and gibbons is unlikely. Therefore, GALV and KoRV may have arisen via a cross-species transfer from an intermediate host whose range overlaps those of both gibbons and koalas. Using hybridization capture and high-throughput sequencing, we have screened a wide range of rodent candidate hosts from Southeast Asia for KoRV- and GALV-like sequences. Only a
Melomys
burtoni
subspecies from Wallacea (Indonesia) was positive for GALV. We report the genome sequence of this newly identified GALV, the critical domain for infection of its potential cellular receptor, and its phylogenetic relationships with the other previously characterized GALVs. We hypothesize that
Melomys
burtoni
, and potentially related lineages with an Australo-Papuan distribution, may have played a key role in cross-species transmission to other taxa.
Roles of the Rabies Virus Phosphoprotein Isoforms in Pathogenesis
Authors: Okada Kazuma , Ito Naoto , Yamaoka Satoko , Masatani Tatsunori , Ebihara Hideki , Goto Hideo , Nakagawa Kento , Mitake Hiromichi , Okadera Kota , Sugiyama Makoto 
Published: July 2016

ABSTRACT

Rabies virus (RABV) P gene mRNA encodes five in-frame start codons, resulting in expression of full-length P protein (P1) and N-terminally truncated P proteins (tPs), designated P2, P3, P4, and P5. Despite the fact that some tPs are known as interferon (IFN) antagonists, the importance of tPs in the pathogenesis of RABV is still unclear. In this study, to examine whether tPs contribute to pathogenesis, we exploited a reverse genetics approach to generate CE(NiP)ΔP2-5, a mutant of pathogenic CE(NiP) in which the P gene was mutated by replacing all of the start codons (AUG) for tPs with AUA. We confirmed that while CE(NiP) expresses detectable levels of P2 and P3, CE(NiP)ΔP2-5 has an impaired ability to express these tPs. After intramuscular inoculation, CE(NiP)ΔP2-5 caused significantly lower morbidity and mortality rates in mice than did CE(NiP), indicating that tPs play a critical role in RABV neuroinvasiveness. Further examinations revealed that this less neuroinvasive phenotype of CE(NiP)ΔP2-5 correlates with its impaired ability to replicate in muscle cells, indicative of the importance of tPs in viral replication in muscle cells. We also demonstrated that CE(NiP)ΔP2-5 infection induced a higher level of
Ifn-β
gene expression in muscle cells than did CE(NiP) infection, consistent with the results of an IFN-β promoter reporter assay suggesting that all tPs function to antagonize IFN induction in muscle cells. Taken together, our findings strongly suggest that tPs promote viral replication in muscle cells through their IFN antagonist activities and thereby support infection of peripheral nerves.

IMPORTANCE
Despite the fact that previous studies have demonstrated that P2 and P3 of RABV have IFN antagonist activities, the actual importance of tPs in pathogenesis has remained unclear. Here, we provide the first evidence that tPs contribute to the pathogenesis of RABV, especially its neuroinvasiveness. Our results also show the mechanism underlying the neuroinvasiveness driven by tPs, highlighting the importance of their IFN antagonist activities, which support viral replication in muscle cells.
Mapping Murine Corneal Neovascularization and Weight Loss Virulence Determinants in the Herpes Simplex Virus 1 Genome and the Detection of an Epistatic Interaction between the UL and IRS/US Regions
Authors: Lee Kyubin , Kolb Aaron W. , Larsen Inna , Craven Mark , Brandt Curtis R. 
Published: July 2016

ABSTRACTHerpes simplex virus 1 (HSV-1) most commonly causes recrudescent labial ulcers; however, it is also the leading cause of infectious blindness in developed countries. Previous research in animal models has demonstrated that the severity of HSV-1 ocular disease is influenced by three main factors: host innate immunity, host immune response, and viral strain. We have previously shown that mixed infection with two avirulent HSV-1 strains (OD4 and CJ994) results in recombinants with a wide range of ocular disease phenotype severity. Recently, we developed a quantitative trait locus (QTL)-based computational approach (vQTLmap) to identify viral single nucleotide polymorphisms (SNPs) predicted to influence the severity of the ocular disease phenotypes. We have now applied vQTLmap to identify HSV-1 SNPs associated with corneal neovascularization and mean peak percentage weight loss (MPWL) using 65 HSV-1 OD4-CJ994 recombinants. The vQTLmap analysis using Random Forest for neovascularization identified phenotypically meaningful nonsynonymous SNPs in the ICP4, UL41 (VHS), UL42, UL46 (VP11/12), UL47 (VP13/14), UL48 (VP22), US3, US4 (gG), US6 (gD), and US7 (gI) coding regions. The ICP4 gene was previously identified as a corneal neovascularization determinant, validating the vQTLmap method. Further analysis detected an epistatic interaction for neovascularization between a segment of the unique long (UL) region and a segment of the inverted repeat short (IRS)/unique short (US) region. Ridge regression was used to identify MPWL-associated nonsynonymous SNPs in the UL1 (gL), UL2, UL4, UL49 (VP22), UL50, and ICP4 coding regions. The data provide additional insights into virulence gene and epistatic interaction discovery in HSV-1.IMPORTANCEHerpes simplex virus 1 (HSV-1) typically causes recurrent cold sores; however, it is also the leading source of infectious blindness in developed countries. Corneal neovascularization is critical for the progression of blinding ocular disease, and weight loss is a measure of infection severity. Previous HSV-1 animal virulence studies have shown that the severity of ocular disease is partially due to the viral strain. In the current study, we used a recently described computational quantitative trait locus (QTL) approach in conjunction with 65 HSV-1 recombinants to identify viral single nucleotide polymorphisms (SNPs) involved in neovascularization and weight loss. Neovascularization SNPs were identified in the ICP4, VHS, UL42, VP11/12, VP13/14, VP22, gG, US3, gD, and gI genes. Further analysis revealed an epistatic interaction between the UL and US regions. MPWL-associated SNPs were detected in the UL1 (gL), UL2, UL4, VP22, UL50, and ICP4 genes. This approach will facilitate future HSV virulence studies.
Prevailing PA Mutation K356R in Avian Influenza H9N2 Virus Increases Mammalian Replication and Pathogenicity
Authors: Xu Guanlong , Zhang Xuxiao , Gao Weihua , Wang Chenxi , Wang Jinliang , Sun Honglei , Sun Yipeng , Guo Lu , Zhang Rui , Chang Kin-Chow , Liu Jinhua , Pu Juan 
Published: July 2016

ABSTRACT

Adaptation of the viral polymerase complex comprising PB1, PB2, and PA is necessary for efficient influenza A virus replication in new host species. We found that PA mutation K356R (PA-K356R) has become predominant since 2014 in avian H9N2 viruses in China as with seasonal human H1N1 viruses. The same mutation is also found in most human isolates of emergent avian H7N9 and H10N8 viruses whose six internal gene segments are derived from the H9N2 virus. We further demonstrated the mammalian adaptive functionality of the PA-K356R mutation. Avian H9N2 virus with the PA-K356R mutation in human A549 cells showed increased nuclear accumulation of PA and increased viral polymerase activity that resulted in elevated levels of viral transcription and virus output. The same mutant virus in mice also enhanced virus replication and caused lethal infection. In addition, combined mutation of PA-K356R and PB2-E627K, a well-known mammalian adaptive marker, in the H9N2 virus showed further cooperative increases in virus production and severity of infection
in vitro
and
in vivo
. In summary, PA-K356R behaves as a novel mammalian tropism mutation, which, along with other mutations such as PB2-E627K, might render avian H9N2 viruses adapted for human infection.

IMPORTANCE
Mutations of the polymerase complex (PB1, PB2, and PA) of influenza A virus are necessary for viral adaptation to new hosts. This study reports a novel and predominant mammalian adaptive mutation, PA-K356R, in avian H9N2 viruses and human isolates of emergent H7N9 and H10N8 viruses. We found that PA-356R in H9N2 viruses causes significant increases in virus replication and severity of infection in human cells and mice and that PA-K356R cooperates with the PB2-E627K mutation, a well-characterized human adaptive marker, to exacerbate mammalian infection
in vitro
and
in vivo
. Therefore, the PA-K356R mutation is a significant adaptation in H9N2 viruses and related H7N9 and H10N8 reassortants toward human infectivity.