bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rift Valley Fever Virus Strain MP-12 Enters Mammalian Host Cells via Caveola-Mediated Endocytosis
Authors: Harmon Brooke , Schudel Benjamin R. , Maar Dianna , Kozina Carol , Ikegami Tetsuro , Tseng Chien-Te Kent , Negrete Oscar A. 
Published: September 2012

ABSTRACT

Rift Valley fever virus (RVFV) is a zoonotic pathogen capable of causing serious morbidity and mortality in both humans and livestock. The lack of efficient countermeasure strategies, the potential for dispersion into new regions, and the pathogenesis in humans and livestock make RVFV a serious public health concern. The receptors, cellular factors, and entry pathways used by RVFV and other members of the family
Bunyaviridae
remain largely uncharacterized. Here we provide evidence that RVFV strain MP-12 uses dynamin-dependent caveola-mediated endocytosis for cell entry. Caveolae are lipid raft domains composed of caveolin (the main structural component), cholesterol, and sphingolipids. Caveola-mediated endocytosis is responsible for the uptake of a wide variety of host ligands, as well as bacteria, bacterial toxins, and a number of viruses. To determine the cellular entry mechanism of RVFV, we used small-molecule inhibitors, RNA interference (RNAi), and dominant negative (DN) protein expression to inhibit the major mammalian cell endocytic pathways. Inhibitors and RNAi specific for macropinocytosis and clathrin-mediated endocytosis had no effect on RVFV infection. In contrast, inhibitors of caveola-mediated endocytosis, and RNAi targeted to caveolin-1 and dynamin, drastically reduced RVFV infection in multiple cell lines. Expression of DN caveolin-1 also reduced RVFV infection significantly, while expression of DN EPS15, a protein required for the assembly of clathrin-coated pits, and DN PAK-1, an obligate mediator of macropinocytosis, had no significant impact on RVFV infection. These results together suggest that the primary mechanism of RVFV MP-12 uptake is dynamin-dependent, caveolin-1-mediated endocytosis.
Manual aspiration thrombectomy for cerebral venous sinus thrombosis
Authors: Jankowitz Brian Thomas , Bodily Lance Matukas , Jumaa Mouhammad , Syed Zaidi F , Jovin Tudor G 
Published: September 2012

BackgroundHydration and anticoagulation are the standard of care for cerebral venous sinus thrombosis (CVST) but some patients remain refractory to medical management and warrant more aggressive therapy. Here we present the technique of endovascular transvenous manual aspiration thrombectomy (MAT) in six patients.ObjectivePresent an alternative technique for endovascular transvenous thrombectomy in a series of CVST patients.MethodsWe reviewed the records of six patients with medically refractory CVST. Transvenous access via the femoral vein was used to advance an aspiration catheter of varying internal diameter (0.044, 0.054, 0.057, 0.070, 0.072) up to and through the thrombus. Tissue plasminogen activator was administered in select cases. Manual aspiration with a 20 ml syringe applied to the catheter hub was applied as the catheter was slowly retracted. Presentation, technique, and outcome were evaluated.ResultsClinical presentation included vomiting, dehydration, mental status changes, headaches, and acute motor deficits. On imaging, four of the six patients had hemorrhage, edema, and mass effect present before treatment, while two had edema only. All patients demonstrated continued deterioration despite early and aggressive medical anticoagulation therapy, warranting aggressive intervention. Aspiration of the superior sagittal sinus, transverse sinuses, straight sinus, sigmoid sinus, and internal jugular vein were performed in this series. There were no procedural complications. Revascularization was achieved in all instances. A modified Rankin Scale score of 1–3 was attained in 5/6 patients, while one patient died.ConclusionsIn this series, transvenous MAT was a safe, simple, and effective revascularization technique to treat patients with CVST who remained refractory to medical management.
Aryl Hydrocarbon Receptor-Induced Adrenomedullin Mediates Cigarette Smoke Carcinogenicity in Humans and Mice
Authors: Portal-Nuñez Sergio , Shankavaram Uma T. , Rao Mahadev , Datrice Nicole , Atay Scott , Aparicio Marta , Camphausen Kevin A. , Fernández-Salguero Pedro M. , Chang Han , Lin Pinpin , Schrump David S. , Garantziotis Stavros , Cuttitta Frank , Zudaire Enrique 
Published: September 2012

Abstract
Cigarette smoking (CS) is a leading cause of death worldwide. The aryl hydrocarbon receptor (AHR) is partially responsible for tobacco-induced carcinogenesis although the underlying mechanisms involving early effector genes have yet to be determined. Here, we report that adrenomedullin (ADM) significantly contributes to the carcinogenicity of tobacco-activated AHR. CS and AHR activating ligands induced ADM in vitro and in vivo but not in AHR-deficient fibroblasts and mice. Ectopic transfection of AHR rescued ADM expression in AHR−/− fibroblasts whereas AHR blockage with siRNA in wild type cells significantly decreased ADM expression. AHR regulates ADM expression through two intronic xenobiotic response elements located close to the start codon in the ADM gene. Using tissue microarrays we showed that ADM and AHR were coupregulated in lung tumor biopsies from smoker patients. Microarray meta-analysis of 304 independent microarray experiments showed that ADM is elevated in smokers and smokers with cancer. In addition, ADM coassociated with a subset of AHR responsive genes and efficiently differentiated patients with lung cancer from nonsmokers. In a novel preclinical model of CS-induced tumor progression, host exposure to CS extracts significantly elevated tumor ADM although systemic treatment with the ADM antagonist NSC16311 efficiently blocked tobacco-induced tumor growth. In conclusion, ADM significantly contributes the carcinogenic effect of AHR and tobacco combustion products. We suggest that therapeutics targeting the AHR/ADM axis may be of clinical relevance in the treatment of tobacco-induced pulmonary malignancies. Cancer Res; 72(22); 5790–800. ©2012 AACR.
Microphysical Processes Evident in Aerosol Forcing of Tropical Deep Convective Clouds
Authors: Storer Rachel L. , van den Heever Susan C. 
Published: September 2012

AbstractThis study investigates the effects of aerosols on tropical deep convective clouds (DCCs). A series of large-scale, two-dimensional cloud-resolving model simulations was completed, differing only in the concentration of aerosols available to act as cloud condensation nuclei (CCN). Polluted simulations contained more DCCs, wider storms, higher cloud tops, and more convective precipitation domainwide. Differences in warm cloud microphysics were largely consistent with the first and second aerosol indirect effects. The average surface precipitation produced in each DCC column decreased with increasing aerosol concentration. A detailed microphysical budget analysis showed that the reduction in collision and coalescence largely dominated the trend in average precipitation. The production of rain from ice, though it also decreased, became a more important contribution to precipitation as the aerosol concentration increased. The DCCs in polluted simulations contained more frequent extreme values of vertical velocity, but the average updraft speed decreased with increasing aerosols in DCCs above 6 km. An examination of the buoyancy term of the vertical velocity equation demonstrates that the drag associated with condensate loading is an important factor in determining the average updraft strength. The largest contributions to latent heating in DCCs were cloud nucleation and vapor deposition onto water and ice, but changes in latent heating were, on average, an order of magnitude smaller than those in the condensate loading term. The average updraft speed was largely affected by increased drag from condensate loading in more mature updrafts, while early storm updrafts experienced convective invigoration from increased latent heating.
Three-Dimensional UAV-Based Atmospheric Tomography
Authors: Rogers Kevin , Finn Anthony 
Published: September 2012

Abstract
This paper presents a method for tomographically reconstructing spatially varying three-dimensional atmospheric temperature profiles and wind velocity fields based on passive acoustic travel time measurements between a small unmanned aerial vehicle (UAV) and ground-based microphones. A series of simulations are presented to provide an indication of the performance of the technique. The parametric fields are modeled as the weighted sum of radial basis functions (RBFs) or Fourier series, which also allow local meteorological measurements made at the UAV and ground receivers to supplement any time delay observations. The technique has potential for practical applications such as boundary layer meteorology and theories of atmospheric turbulence and wave propagation through a turbulent atmosphere.
Representing Absences in the Postdictatorial Documentary Cinema of Patricio Guzmán
Authors: Blaine Patrick 
Published: September 2012

For nearly 40 years, Patricio Guzmán has explored the complex relationships between time, memory, and absence in postdictatorial Chile while infusing his documentaries with personal narrative and devices more commonly seen in literary fiction. His films have redefined the genre from the advent of the New Latin American Cinema through the 2010s and are characterized by marked subjectivity and the representation of absence in the postdictatorial context. His filmmaking, beginning in the early 1970s and ending with his latest film, Nostalgia de la luz (2010), constitutes the most complete attempt in any medium to document Chilean national life before, during, and after the Pinochet dictatorship (1973–1990). Por casi 40 años, Patricio Guzmán ha explorado la compleja relación entre el tiempo, la memoria, y la ausencia en el Chile de la posdictadura, mientras infundía sus documentales con narrativas personales y recursos mas bien vistos comúnmente en la ficción literaria. Sus películas han vuelto a definir el ge’nero desde el avenimiento del nuevo cine latinoamericano en su transcurso hasta los 2010, y se destacan por una subjetividad marcada y la representación de la ausencia en el contexto de la posdictadura. Su obra cinematográfica, comenzando con los principios de la década 1970 y acabando con su film mas reciente, Nostalgia de la luz (2010), constituye el esfuerzo mas completo en cualquier medio para documentar la vida nacional chilena antes, durante, y luego de la dictadura de Pinochet (1973–1990).
Infection control in United Kingdom neonatal units: variance in practice and the need for an evidence base
Authors: Francis S , Khan H , Kennea NL 
Published: September 2012

Infection prevention is a cornerstone of good neonatal care. There are, however, few research data to support infection control approaches in this population. Through a structured telephone interview we surveyed all neonatal units in the United Kingdom to identify infection control issues, practices and policies. Eighty seven percent of the 198 neonatal units participated. Twenty one units (12.2%) had closed with infection control issues in the last year; 14.1% had current infection control concerns; 81.5% of units decolonised MRSA positive infants, but over 15 regimens were used. Wide variations in hygiene measures were identified; 22.1% of units used theatre scrubs for all staff, 7.6% used aprons and 5.8% required gloves to be worn when entering clinical areas. Only 54% required hand washing and alcohol gel before entry to a patient care area; 11.6% required only the use of alcohol gel. Although infection control issues are resulting in neonatal unit closures and risks to patients, there are considerable variations in hygiene and screening practices. There is little data to support the safety or efficacy of decolonisation in neonatal populations, but this is widely practised. Research needs to be carried out to evaluate the effectiveness of screening practices and decolonisation in order that a consistent evidence-based approach can be applied.
Copy Number Amplification of the PIK3CA Gene Is Associated with Poor Prognosis in Non-lymph node metastatic Head and Neck Squamous Cell Carcinoma
Authors: Suda Toshihito , Hama Takanori , Kondo Shu , Yuza Yuki , Yoshikawa Mamoru , Urashima Mitsuyoshi , Kato Takakuni , Moriyama Hiroshi 
Published: September 2012

Abstract

Background
Deregulation of the EGFR signaling pathway is one of the most frequently observed genetic abnormalities that drives cancer development. Although mutations in the downstream components of the EGFR signaling pathway, including KRAS, BRAF and PIK3CA, have been reported in numerous cancers, extensive mutation and copy number analysis of these genes in clinical samples has not been performed for head and neck squamous cell carcinoma (HNSCC).

Methods
We examined the mutations and copy number alterations of KRAS, BRAF and PIK3CA in 115 clinical specimens of HNSCC obtained from surgically treated patients.
We used DNA sequencing to detect mutations and the copy number changes were evaluated by qPCR and array comparative genomic hybridization (CGH) analysis.

Results
We examined the mutations and copy number alterations of KRAS, BRAF and PIK3CA in 115 clinical specimens of HNSCC obtained from surgically treated patients. We identified 3 mutations (2.6%) in K-RAS and 3 mutations (2.6%) in PIK3CA. Copy number amplification was found in 37 cases (32.2%) for PIK3CA, 10 cases (8.7%) for K-RAS and 2 cases (1.7%) for BRAF. Kaplan-Meier survival analysis revealed that copy-number amplification of PIK3CA was markedly associated with cancer relapse in patients without lymph node metastasis. (Log-rank test, p = 0.026)

Conclusions
Copy number amplification of the PIK3CA gene is associated with poor prognosis in HNSCC patients without lymph node metastasis. The PIK3CA copy number status will serve as a marker of poor prognosis in patients with HNSCC.
The role of basic health insurance on depression: an epidemiological cohort study of a randomized community sample in Northwest China
Authors: Tian Donghua , Qu Zhiyong , Wang Xiaohua , Guo Jing , Xu Fan , Zhang Xiulan , Chan Cecilia Lai-Wan 
Published: September 2012

Abstract

Background
Little research has focused on the relationship between health insurance and mental health in the community. The objective of this study is to determine how the basic health insurance system influences depression in Northwest China.

Methods
Participants were selected from 32 communities in two northwestern Chinese cities through a three-stage random sampling. Three waves of interviews were completed in April 2006, December 2006, and January 2008. The baseline survey was completed by 4,079 participants. Subsequently, 2,220 participants completed the first follow-up, and 1,888 completed the second follow-up. Depression symptoms were measured by the Center for Epidemiologic Studies Depression Scale (CES-D).

Results
A total of 40.0% of participants had at least one form of health insurance. The percentages of participants with severe depressive symptoms in the three waves were 21.7%, 22.0%, and 17.6%. Depressive symptoms were found to be more severe among participants without health insurance in the follow-up surveys. After adjusting for confounders, participants without health insurance were found to experience a higher risk of developing severe depressive symptoms than participants with health insurance (7 months: OR, 1.40; 95% CI, 1.09-1.82; p = 0.01; 20 months: OR, 1.89; 95% CI, 1.37-2.61; p < 0.001).

Conclusion
A lack of basic health insurance can dramatically increase the risk of depression based on northwestern Chinese community samples.
HIV-1 subtype C superinfected individuals mount low autologous neutralizing antibody responses prior to intrasubtype superinfection
Authors: Basu Debby , Kraft Colleen S , Murphy Megan K , Campbell Patricia J , Yu Tianwei , Hraber Peter T , Irene Carmela , Pinter Abraham , Chomba Elwyn , Mulenga Joseph , Kilembe William , Allen Susan A , Derdeyn Cynthia A , Hunter Eric 
Published: September 2012

Abstract

Background
The potential role of antibodies in protection against intra-subtype HIV-1 superinfection remains to be understood. We compared the early neutralizing antibody (NAb) responses in three individuals, who were superinfected within one year of primary infection, to ten matched non-superinfected controls from a Zambian cohort of subtype C transmission cases. Sequence analysis of single genome amplified full-length envs from a previous study showed limited diversification in the individuals who became superinfected with the same HIV-1 subtype within year one post-seroconversion. We hypothesized that this reflected a blunted NAb response, which may have made these individuals more susceptible to superinfection.

Results
Neutralization assays showed that autologous plasma NAb responses to the earliest, and in some cases transmitted/founder, virus were delayed and had low to undetectable titers in all three superinfected individuals prior to superinfection. In contrast, NAbs with a median IC50 titer of 1896 were detected as early as three months post-seroconversion in non-superinfected controls. Early plasma NAbs in all subjects showed limited but variable levels of heterologous neutralization breadth. Superinfected individuals also exhibited a trend toward lower levels of gp120- and V1V2-specific IgG binding antibodies but higher gp120-specific plasma IgA binding antibodies.

Conclusions
These data suggest that the lack of development of IgG antibodies, as reflected in autologous NAbs as well as gp120 and V1V2 binding antibodies to the primary infection virus, combined with potentially competing, non-protective IgA antibodies, may increase susceptibility to superinfection in the context of settings where a single HIV-1 subtype predominates.
Deciphering the differential response of two human fibroblast cell lines following Chikungunya virus infection
Authors: Thon-Hon Vincent G , Denizot Melanie , Li-Pat-Yuen Ghislaine , Giry Claude , Jaffar-Bandjee Marie-Christine , Gasque Philippe 
Published: September 2012

Abstract

Background
Chikungunya virus (CHIKV) is an arthritogenic member of the Alphavirus genus (family Togaviridae) transmitted by Aedes mosquitoes. CHIKV is now known to target non hematopoietic cells such as epithelial, endothelial cells, fibroblasts and to less extent monocytes/macrophages. The type I interferon (IFN) response is an early innate immune mechanism that protects cells against viral infection. Cells express different pattern recognition receptors (including TLR7 and RIG-I) to sense viruses and to induce production of type I IFNs which in turn will bind to their receptor. This should result in the phosphorylation and translocation of STAT molecules into the nucleus to promote the transcription of IFN-stimulated antiviral genes (ISGs). We herein tested the capacity of CHIKV clinical isolate to infect two different human fibroblast cell lines HS 633T and HT-1080 and we analyzed the resulting type I IFN innate immune response.

Methods
Indirect immunofluorescence and quantitative RT-PCR were used to test for the susceptibility of both fibroblast cell lines to CHIKV.

Results
Interestingly, the two fibroblast cell lines HS 633T and HT-1080 were differently susceptible to CHIKV infection and the former producing at least 30-fold higher viral load at 48 h post-infection (PI). We found that the expression of antiviral genes (RIG-I, IFN-β, ISG54 and ISG56) was more robust in the more susceptible cell line HS 633T at 48 h PI. Moreover, CHIKV was shown to similarly interfere with the nuclear translocation of pSTAT1 in both cell lines.

Conclusion
Critically, CHIKV can control the IFN response by preventing the nuclear translocation of pSTAT1 in both fibroblast cell lines. Counter-intuitively, the relative resistance of HT-1080 cells to CHIKV infection could not be attributed to more robust innate IFN- and ISG-dependent antiviral responses. These cell lines may prove to be valuable models to screen for novel mechanisms mobilized differentially by fibroblasts to control CHIKV infection, replication and spreading from cell to cell.
A simple protocol for the subcellular fractionation of skeletal muscle cells and tissue
Authors: Dimauro Ivan , Pearson Timothy , Caporossi Daniela , Jackson Malcolm J 
Published: September 2012

Abstract

Background
We describe a method for subcellular fractionation of mouse skeletal muscle, myoblast and myotubes to obtain relatively pure fractions of nuclear, cytosolic and mitochondrial compartments. Fractionation allows the analysis of a protein of interest (or other cellular component) based on its subcellular compartmental distribution and can also generate molecular information about the state of a cell and/or tissue and how the distribution of a protein may differ between different cellular compartments, tissues or cell types, in response to treatments or ageing.

Findings
The described method was specifically developed for skeletal muscle and proliferating/differentiated muscle cells. The purity of the different fractions, representing the cytoplasmic, mitochondrial and nuclear subcellular compartments was validated by western blot analysis of “house-keeper” marker proteins specific for each cellular compartment.

Conclusion
This low cost method allowed the mitochondrial, cytoplasmic and nuclear subcellular compartments from the same starting muscle samples to be rapidly and simultaneously isolated with good purity and without the use of an ultracentrifuge. This method permits samples to be frozen at −80°C for future analysis and/or additional processing at a later date.
Clinical Heterogeneity in two patients with Noonan-like Syndrome associated with the same SHOC2 mutation
Authors: Capalbo Donatella , Scala Maria Giuseppa , Melis Daniela , Minopoli Giorgia , Improda Nicola , Palamaro Loredana , Pignata Claudio , Salerno Mariacarolina 
Published: September 2012

Abstract
Noonan-like syndrome with loose anagen hair (NS/LAH; OMIM #607721) has been recently related to the invariant c.4A > G missense change in SHOC2. It is characterized by features reminiscent of Noonan syndrome. Ectodermal involvement, short stature associated to growth hormone (GH) deficiency (GHD), and cognitive deficits are common features. We compare in two patients with molecularly confirmed NS/LAH diagnosis, the clinical phenotype and pathogenetic mechanism underlying short stature. In particular, while both the patients exhibited a severe short stature, GH/IGFI axis functional evaluation revealed a different pathogenetic alteration, suggesting in one patient an upstream alteration (typical GHD) and in the other one a peripheral GH insensitivity.
Since only a few cases of NS/LAH associated to SHOC2 mutations have been so far described, the complex phenotype of the syndrome and the exact mechanism impairing GH/IGFI axis still remain to be elucidated and studies on larger cohort of subjects are needed to better delineate this syndrome.