bluuebunny/crossref_metadata_2025 huggingface dataset:
Ikaros Imposes a Barrier to CD8+ T Cell Differentiation by Restricting Autocrine IL-2 Production
Authors: O’Brien Shaun , Thomas Rajan M. , Wertheim Gerald B. , Zhang Fuqin , Shen Hao , Wells Andrew D.
Published: April 2014

Naive CD4+ T cells require signals from the TCR and CD28 to produce IL-2, expand, and differentiate. However, these same signals are not sufficient to induce autocrine IL-2 production by naive CD8+ T cells, which require cytokines provided by other cell types to drive their differentiation. The basis for failed autocrine IL-2 production by activated CD8+ cells is unclear. We find that Ikaros, a transcriptional repressor that silences IL-2 in anergic CD4+ T cells, also restricts autocrine IL-2 production by CD8+ T cells. We find that CD8+ T cell activation in vitro in the absence of exogenous cytokines and CD4 help leads to marked induction of Ikaros, a known repressor of the Il2 gene. Naive murine CD8 T cells haplo-insufficient for Ikzf1 failed to upregulate Ikaros, produced autocrine IL-2, and differentiated in an IL-2–dependent manner into IFN-γ–producing CTLs in response to TCR/CD28 stimulation alone. Furthermore, Ikzf1 haplo-insufficient CD8+ T cells were more effective at controlling Listeria infection and B16 melanoma growth in vivo, and they could provide help to neighboring, non-IL-2–producing cells to differentiate into IFN-γ–producing effectors. Therefore, by repressing autocrine IL-2 production, Ikaros ensures that naive CD8+ T cells remain dependent on licensing by APCs and CD4+ T cells, and it may therefore act as a cell-intrinsic safeguard against inappropriate CTL differentiation and immunopathology.
Longitudinal Requirement for CD4+ T Cell Help for Adenovirus Vector–Elicited CD8+ T Cell Responses
Authors: Provine Nicholas M. , Larocca Rafael A. , Penaloza-MacMaster Pablo , Borducchi Erica N. , McNally Anna , Parenteau Lily R. , Kaufman David R. , Barouch Dan H.
Published: April 2014

Despite the widespread use of replication-incompetent recombinant adenovirus (Ad) vectors as candidate vaccine platforms, the mechanism by which these vectors elicit CD8+ T cell responses remains poorly understood. Our data demonstrate that induction and maintenance of CD8+ T cell responses by Ad vector immunization is longitudinally dependent on CD4+ T cell help for a prolonged period. Depletion of CD4+ T cells in wild type mice within the first 8 d following Ad immunization resulted in dramatically reduced induction of Ag-specific CD8+ T cells, decreased T-bet and eomesodermin expression, impaired KLRG1+ effector differentiation, and atypical expression of the memory markers CD127, CD27, and CD62L. Moreover, these CD8+ T cells failed to protect against a lethal recombinant Listeria monocytogenes challenge. Depletion of CD4+ T cells between weeks 1 and 4 following immunization resulted in increased contraction of memory CD8+ T cells. These data demonstrate a prolonged temporal requirement for CD4+ T cell help for vaccine-elicited CD8+ T cell responses in mice. These findings have important implications in the design of vaccines aimed at eliciting CD8+ T cell responses and may provide insight into the impaired immunogenicity of vaccines in the context of AIDS and other CD4+ T cell immune deficiencies.
Cross-Desensitization of CCR1, but Not CCR2, following Activation of the Formyl Peptide Receptor FPR1
Authors: Bednar Filip , Song Changcheng , Bardi Giuseppe , Cornwell William , Rogers Thomas J.
Published: April 2014

The cross-regulation of G protein–coupled receptors (GPCRs) plays an important role in the immune response. Studies from several laboratories have suggested that a hierarchy of sensitivities to cross-desensitization exists for the chemoattractant GPCRs. We carried out experiments to study the capacity of the formyl peptide receptor-1 (FPR1) to desensitize chemokine receptors CCR1 and CCR2. Our results show that activation of FPR1 resulted in the desensitization and partial internalization of CCR1, but not CCR2, in both primary human monocytes and HEK293 cells coexpressing CCR1, CCR2, and FPR1 (HR1R2F cells). The desensitization of CCR1 by FPR1 stimulation was not due to the simple depletion of the Ca2+ stores, but was dependent on activation of protein kinase C. Furthermore, we found that the cross-desensitization of CCR1 by FPR1 was associated with CCR1 phosphorylation and moderate reduction of CCR1 cell-surface expression. In contrast, CCR2 was not phosphorylated or internalized after FPR1 activation. Additional studies showed that optimal cross talk between FPR1 and CCR1 was dependent on the functional activity of protein kinase Cβ. These results provide a mechanistic basis for the capacity of certain GPCR ligands to exert rapid and selective cross-inactivation of other chemoattractant receptors, and suggest that FPR1 is able to exert “traffic control” in the migration of inflammatory cells by rapidly inhibiting the cell responses to potentially “low-priority” chemoattractants such as CCR1 agonists without inhibiting the response to “higher priority” CCR2 chemoattractants.
Recombinant Human Hyaluronidase PH20 Does Not Stimulate an Acute Inflammatory Response and Inhibits Lipopolysaccharide-Induced Neutrophil Recruitment in the Air Pouch Model of Inflammation
Authors: Huang Zhongdong , Zhao Chunmei , Chen Yanling , Cowell Jessica A. , Wei Ge , Kultti Anne , Huang Lei , Thompson Curtis B. , Rosengren Sanna , Frost Gregory I. , Shepard H. Michael
Published: April 2014

Hyaluronidase (Hyal) and low m.w. hyaluronan (LMW HA) fragments have been widely reported to stimulate the innate immune response. However, most hyaluronidases used were purified from animal tissues (e.g., bovine testis Hyal [BTH]), and contain endotoxin and other unrelated proteins. We tested a highly purified recombinant human Hyal (rHuPH20) and endotoxin-free HA fragments from Mr 5,000 to 1,500,000 in the rodent air pouch model of inflammation to determine their potential for stimulation of the innate immune response. Exogenous LMW HA fragments (average Mr 200,000) failed to induce either cytokine/chemokine production or neutrophil infiltration into the air pouch. Challenging the air pouch with LPS or BTH stimulated production of cytokines and chemokines but rHuPH20 did not, suggesting that neither PH20 nor generation of LMW HA fragments in situ stimulates cytokine and chemokine production. LPS and BTH also induced neutrophil infiltration into the air pouch, which was not observed with rHuPH20 treatment. Endotoxin-depleted BTH had much reduced proinflammatory activity, suggesting that the difference in inflammatory responses between rHuPH20 and BTH is likely due to endotoxin contaminants in BTH. When rHuPH20 was dosed with LPS, the induction of cytokines and chemokines was the same as LPS alone, but neutrophil infiltration was inhibited, likely by interrupting HA–CD44 interaction. Our results indicate that neither rHuPH20 nor its directly generated HA catabolites have inflammatory properties in the air pouch model, and rHuPH20 can instead inhibit some aspects of inflammation, such as neutrophil infiltration into the air pouch.
Increased Immunoaccessibility of MOMP Epitopes in a Vaccine Formulated with Amphipols May Account for the Very Robust Protection Elicited against a Vaginal Challenge with Chlamydia muridarum
Authors: Tifrea Delia F. , Pal Sukumar , Popot Jean-Luc , Cocco Melanie J. , de la Maza Luis M.
Published: April 2014

There is a need to implement a vaccine to protect against Chlamydia trachomatis infections. To test a new vaccine, mice were immunized with the Chlamydia muridarum native major outer membrane protein (nMOMP) solubilized with either amphipol A8-35 or the detergent Z3-14. OVA was used as a negative control, and mice were inoculated intranasally with C. muridarum as positive controls. Animals vaccinated with nMOMP mounted strong Chlamydia-specific humoral and cell-mediated immune responses. Mice vaccinated with nMOMP/A8-35 had a higher ratio of Abs to denatured elementary bodies (EB) over live EB, recognized more synthetic MOMP peptides and had higher neutralizing titers than sera from mice immunized with nMOMP/Z3-14. T cell lymphoproliferative responses and levels of IFN-γ were also higher in mice vaccinated with nMOMP/A8-35 than with nMOMP/Z3-14. Following immunization, animals were challenged intravaginally with C. muridarum. On the basis of the number of mice with positive vaginal cultures, length of vaginal shedding, total number of positive vaginal cultures, and number of Chlamydia inclusion forming units recovered, nMOMP/A8-35 elicited a more robust protection than nMOMP/Z3-14. By depleting T cells with Abs, we determined that CD4+ and not CD8+ T cells mediated the protection elicited by nMOMP/A8-35. Mice were subsequently mated, and based on the number of pregnant mice and number of embryos, animals that were vaccinated with nMOMP/A8-35 or nMOMP/Z3-14 had fertility rates equivalent to the positive control group immunized with live EB and the fertility controls. In conclusion, increased accessibility of epitopes in the nMOMP/A8-35 preparation may account for the very robust protection against infection and disease elicited by this vaccine.
Endothelial PINK1 Mediates the Protective Effects of NLRP3 Deficiency during Lethal Oxidant Injury
Authors: Zhang Yi , Sauler Maor , Shinn Amanda S. , Gong Huan , Haslip Maria , Shan Peiying , Mannam Praveen , Lee Patty J.
Published: April 2014

High levels of inspired oxygen, hyperoxia, are frequently used in patients with acute respiratory failure. Hyperoxia can exacerbate acute respiratory failure, which has high mortality and no specific therapies. We identified novel roles for PTEN-induced putative kinase 1 (PINK1), a mitochondrial protein, and the cytosolic innate immune protein NLRP3 in the lung and endothelium. We generated double knockouts (PINK1−/−/NLRP3−/−), as well as cell-targeted PINK1 silencing and lung-targeted overexpression constructs, to specifically show that PINK1 mediates cytoprotection in wild-type and NLRP3−/− mice. The ability to resist hyperoxia is proportional to PINK1 expression. PINK1−/− mice were the most susceptible; wild-type mice, which induced PINK1 after hyperoxia, had intermediate susceptibility; and NLRP3−/− mice, which had high basal and hyperoxia-induced PINK1, were the least susceptible. Genetic deletion of PINK1 or PINK1 silencing in the lung endothelium increased susceptibility to hyperoxia via alterations in autophagy/mitophagy, proteasome activation, apoptosis, and oxidant generation.
Test and Treat in Washington, DC: Evaluating the Costs and Benefits of a Comprehensive Strategy to Fight HIV/AIDS
Authors: Raimondo Estelle R.
Published: April 2014

This paper assesses the economic implications of an innovative approach to preventing the spread of HIV/AIDS in Washington, DC. “Test & Treat” is premised on the idea that the epidemic can ultimately be eliminated by testing people widely and regularly and by putting all infected persons on antiretroviral medicines upon diagnosis. The relative costs and benefits of Test & Treat are quantified, monetized, and compared to the status quo, which can be characterized as a ‘test and wait’ approach. This cost-benefit analysis concludes that under a plausible set of circumstances, and with a conservative estimate of the number of infections averted, the benefits of Test & Treat in Washington, DC would outweigh the costs of implementation.
The Nature of the Original "Firm": A Coasean Cost-Benefit Analysis of Legalizing Prostitution
Authors: Dalesandry Malia
Published: April 2014

Though there have been many studies of prostitution from the legal perspective, the feminist perspective, the societal perspective, and the moral, ethical, and religious perspective, the current breadth of literature does not include a cost-benefit analysis from which to examine its economic effects. This paper attempts a comprehensive analysis of legalizing prostitution while noting deficiencies in data and recognizing variations when interpreting existing data. The most salient monetary costs and benefits are discussed and calculated, and many others are included for the sake of a more developed examination. After a sensitivity analysis and a brief discussion of how Coase’s theorem may be utilized to determine economic efficiency, the conclusion and final recommendation is that, because economic benefits vastly outweigh economic costs, all states could benefit economically from legalizing prostitution.
Red Ink: Inside the High-Stakes Politics of the Federal Budget
Authors: Veselik Michael
Published: April 2014

No abstract available.
Cytomorphologic spectrum of Hashimoto's thyroiditis and its clinical correlation: A retrospective study of 52 patients
Authors: Chandanwale Shirish S. , Gore Charusheela R. , Bamanikar Sunita A. , Gupta Nidhi , Gupta Kanika
Published: April 2014

Background:

Hashimoto's thyroiditis (HT) is an autoimmune disease and it is more prevalent in Asians. The incidence of HT seems to be increasing in the recent times. It is one of the most common cause of hypothyroidism. The purpose of this study is to review the cytomorphologic spectrum of HT and correlate it with clinical findings including thyroid function and antibody profile.

Materials and Methods:

We retrospectively analyzed the fine-needle aspiration (FNA) features of 52 HT patients. Based on cytomorphologic features patients were categorized into three groups. Clinical findings including thyroid function and thyroid peroxidase (TPO) antibody profile were correlated with cytomorphologic features in all three groups.

Results:

Majority of the patients were females and in 2nd, 3rd and 4th decades. Diffuse goiter and thyroid hypofunction were the common findings. Significant number of patients had thyroid hyperfunction. Increased lymphocytes on the background and lymphocytic infiltration of thyroid follicular cell clusters in cytology smears were diagnostic of HT. The 32 patients showed elevated titers of TPO antibodies. In the early stages and mild form of the disease, results of thyroid function and anti TPO antibodies are quite variable.

Conclusions:

HT is a disease of young and middle age and mostly occur in females. Clinical findings alone may not be adequate for definitive diagnosis. FNA is the gold standard for diagnosis. In the presence of abundant colloid, follicular hyperplasia or co-existing neoplasm, careful interpretation of cytology smears should be done. Aspiration from more than one site minimizes the diagnostic pitfalls.
Cancerogenesis Risks between 64 and 320 Row Detector CT for Coronary CTA Screening
Authors: Khan Atif N. , Khosa Faisal , Nikolic Boris , Shuaib Waqas , Lin Pei-Jan Paul , Khan Mohammad K.
Published: April 2014

Objectives:

This study compares cancerogenesis risks posed by the 64 row detector and the 320 row detector computed tomography scanners used during coronary computed tomography angiography (CCTA) following decennial screening guidelines.

Material and Methods:

Data of the radiation absorbed after CCTA by lung, thyroid, and female breast in patients between 50 and 70 years of age obtained from prior published literature for the 64 row CT scanner were compared with data from our study using 320 row detector CT scanner. Data from the 64 row and the 320 row detector CT scanners was used to determine lifetime attributable risks (LAR) of cancer based on the biological effects of ionizing radiation (BEIR) VII report.

Results:

The relative reduction of LAR (%) for 50-, 60-, and 70-year-old patients undergoing scanning with the 320 row detector CT scanner was 30% lower for lung, and more than 50% lower for female breast when compared with results from 64 row detector CT scanner. The use of 320 row detector CT would result in a combined cumulative cancer incidence of less than 1/500 for breast in women and less than 1/1000 for lung in men; By comparison, this is much lower than other more common risk factors: 16-fold for lung cancer in persistent smokers, 2-fold for breast cancer with a first degree family member history of breast cancer, and 10-fold for thyroid cancer with a family member with thyroid cancer. Decennial screening would benefit at least 355,000 patients from sudden cardiac death each year, 94% of whom have significant coronary artery disease, with at least one stenosis >75%. LAR for thyroid cancer was negligible for both scanners.

Conclusion:

Lung and female breast LAR reductions with 320 row detector compared with 64 row detector CT are substantial, and the benefits would outweigh increased cancer risks with decennial screening in the age group of 50-70 years.
Imaging Features of AlloDerm®Used in Postmastectomy Breast Reconstructions
Authors: Lee Christine U. , Clapp Allison J. , Jacobson Steven R.
Published: April 2014

The purpose of this pictorial essay is to demonstrate the imaging features (ultrasound, mammogram, and magnetic resonance imaging (MRI)) of AlloDerm®(LifeCell Corp.; Branchburg, NJ), an acellular dermal matrix sometimes used in both primary and reconstructive breast surgeries. AlloDerm®is derived from cadaveric dermis and provides an immunologically inert scaffold in tissue reconstruction. Since there is little literature on the imaging of this substance, radiologists may be unfamiliar with its appearance in breast imaging. For this manuscript,ex vivoandin vivoimages of AlloDerm®in postmastectomy patients were evaluated using different imaging modalities. The appearance of AlloDerm®can vary based on length of time postsurgery and incorporation into the host. AlloDerm®appears as an isodense to glandular tissue on a mammogram and isoechoic to glandular tissue on ultrasound imaging. On MRI, in comparison with normal breast parenchyma, AlloDerm®is hyperintense on T2-weighted imaging and isointense on T1-weighted imaging and demonstrates mild enhancement. To the best of the authors’ knowledge, this is the first multimodality imaging description of AlloDerm®used in postmastectomy patients. The conformation of AlloDerm®at surgical placement and the degree of host cell migration and neoangiogenesis are factors to take into consideration when performing diagnostic evaluations; and, familiarity with the various imaging appearances of AlloDerm®can be helpful to exclude residual or recurrent disease.
Prenatal Diagnosis of Arthrogryposis as a Phenotype of Pena-Shokeir Syndrome using Two- and Three-dimensional Ultrasonography
Authors: Santana Eduardo Felix Martins , Oliveira Serni Priscila Nogueira , Rolo Liliam Cristine , Júnior Edward Araujo
Published: April 2014

Pena-Shokeir syndrome is a rare autosomal recessive disease, characterized by facial anomalies, arthrogryposis, polyhydramnios, fetal growth restriction, and pulmonary hypoplasia. This report describes the findings of this anomaly with two and three-dimensional ultrasound in a female in her 28th week of pregnancy, who was referred to us because the fetus presented arthrogryposis of unknown cause. These imaging methods allowed adequate evaluation of the fetal malformations and also enabled appropriate counseling of the couple.
Thrombocytopenia in Patients with Gastric Varices and the Effect of Balloon-occluded Retrograde Transvenous Obliteration on the Platelet Count
Authors: Saad W. E. , Bleibel W. , Adenaw N. , Wagner C. E. , Anderson C. , Angle J. F. , Al-Osaimi A. M. , Davies M. G. , Caldwell S.
Published: April 2014

Objectives:

Gastric varices primarily occur in cirrhotic patients with portal hypertension and splenomegaly and thus are probably associated with thrombocytopenia. However, the prevalence and severity of thrombocytopenia are unknown in this clinical setting. Moreover, one-third of patients after balloon-occluded retrograde transvenous obliteration (BRTO) have aggravated splenomegaly, which potentially may cause worsening thrombocytopenia. The aim of the study is to determine the prevalence and degree of thrombocytopenia in patients with gastric varices associated with gastrorenal shunts undergoing BRTO, to determine the prognostic factors of survival after BRTO (platelet count included), and to assess the effect of BRTO on platelet count over a 1-year period.

Materials and Methods:

This is a retrospective review of 35 patients who underwent BRTO (March 2008–August 2011). Pre- and post-BRTO platelet counts were noted. Potential predictors of bleeding and survival (age, gender, liver disease etiology, platelet count, model for end stage liver disease [MELD]-score, presence of ascites or hepatocellular carcinoma) were analyzed (multivariate analysis). A total of 91% (n= 32/35) of patients had thrombocytopenia (<150,000 platelet/cm3) pre-BRTO. Platelet counts at within 48-h, within 2 weeks and at 30-60 days intervals (up to 6 months) after BRTO were compared with the baseline pre-BRTO values.

Results:

35 Patients with adequate platelet follow-up were found. A total of 92% and 17% of patients had a platelet count of <150,000/cm3and <50,000/cm3, respectively. There was a trend for transient worsening of thrombocytopenia immediately (<48 h) after BRTO, however, this was not statistically significant. Platelet count was not a predictor of post-BRTO rebleeding or patient survival. However, MELD-score, albumin, international normalized ratio (INR), and etiology were predictors of rebleeding.

Conclusion:

Thrombocytopenia is very common (>90% of patients) in patients undergoing BRTO. However, BRTO (with occlusion of the gastrorenal shunt) has little effect on the platelet count. Long-term outcomes of BRTO for bleeding gastric varices using sodium tetradecyl sulfate in the USA are impressive with a 4-year variceal rebleed rate and transplant-free survival rate of 9% and 76%, respectively. Platelet count is not a predictor of higher rebleeding or patient survival after BRTO.
Association between Moderate-to-Severe Diarrhea in Young Children in the Global Enteric Multicenter Study (GEMS) and Types of Handwashing Materials Used by Caretakers in Mirzapur, Bangladesh
Authors: Baker Kelly K. , Dil Farzana Fahmida , Ferdous Farzana , Ahmed Shahnawaz , Kumar Das Sumon , Faruque A. S. G. , Nasrin Dilruba , Kotloff Karen L. , Nataro James P. , Kolappaswamy Krishnan , Levine Myron M.
Published: April 2014

Handwashing practices among caretakers of case and control children < 5 years of age enrolled in the Global Enteric Multicenter Study in Mirzapur, Bangladesh were characterized and analyzed for association with moderate-to-severe diarrhea. Soap or detergent ownership was common, yet 48% of case and 47.7% of control caretakers also kept ashes for handwashing, including 36.8% of the wealthiest households. Soap, detergent, and ash were used for multiple hygiene purposes and were kept together at handwashing areas. Caretakers preferred soap for handwashing, but frequently relied on ash, or a detergent/ash mixture, as a low-cost alternative. Moderate-to-severe diarrhea was equally likely for children of caretakers who kept soap versus those who kept ash (matched OR = 0.91; 0.62–1.32). Contact with ash and water reduced concentrations of bacterial enteropathogens, without mechanical scrubbing. Thus, washing hands with ash is a prevalent behavior in Mirzapur and may help diminish transmission of diarrheal pathogens to children.
A Highly Conserved Region Between Amino Acids 221 and 266 of Dengue Virus Non-Structural Protein 1 is a Major Epitope Region in Infected Patients
Authors: Omokoko Magot Diata , Pambudi Sabar , Phanthanawiboon Supranee , Masrinoul Promsin , Setthapramote Chayanee , Sasaki Tadahiro , Kuhara Motoki , Ramasoota Pongrama , Yamashita Akifumi , Hirai Itaru , Ikuta Kazuyoshi , Kurosu Takeshi
Published: April 2014

The immune response to dengue virus (DENV) infection generates high levels of antibodies (Abs) against the DENV non-structural protein 1 (NS1), particularly in cases of secondary infection. Therefore, anti-NS1 Abs may play a role in severe dengue infections, possibly by interacting (directly or indirectly) with host factors or regulating virus production. If it does play a role, NS1 may contain epitopes that mimic those epitopes of host molecules. Previous attempts to map immunogenic regions within DENV-NS1 were undertaken using mouse monoclonal Abs (MAbs). The aim of this study was to characterize the epitope regions of nine anti-NS1 human monoclonal Abs (HuMAbs) derived from six patients secondarily infected with DENV-2. These anti-NS1 HuMAbs were cross-reactive with DENV-1, -2, and -3 but not DENV-4. All HuMAbs bound a common epitope region located between amino acids 221 and 266 of NS1. This study is the first report to map a DENV-NS1 epitope region using anti-DENV MAbs derived from patients.
Performance of the CareStart Glucose-6-Phosphate Dehydrogenase (G6PD) Rapid Diagnostic Test in Gressier, Haiti
Authors: von Fricken Michael E. , Weppelmann Thomas A. , Eaton Will T. , Masse Roseline , Beau de Rochars Madsen V. E. , Okech Bernard A.
Published: April 2014

Administering primaquine (PQ) to treat malaria patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency can pose a serious risk of drug-induced hemolysis (DIH). New easy to use point-of-care rapid diagnostic tests are being developed as an alternative to labor-intensive spectrophotometric methods, but they require field testing before they can be used at scale. This study screened 456 participants in Gressier, Haiti using the Access Bio CareStart qualitative G6PD rapid detection test compared with the laboratory-based Trinity Biotech quantitative spectrophotometric assay. Findings suggest that the CareStart test was 90% sensitive for detecting individuals with severe deficiency and 84.8% sensitive for detecting individuals with moderate and severe deficiency compared with the Trinity Biotech assay. A high negative predictive value of 98.2% indicates excellent performance in determining those patients able to take PQ safely. The CareStart G6PD test holds much value for screening malaria patients to determine eligibility for PQ therapy.
Global dataset of biogenic VOC emissions calculated by the MEGAN model over the last 30 years
Authors: Sindelarova K. , Granier C. , Bouarar I. , Guenther A. , Tilmes S. , Stavrakou T. , Müller J.-F. , Kuhn U. , Stefani P. , Knorr W.
Published: April 2014

Abstract. The Model of Emissions of Gases and Aerosols from Nature (MEGANv2.1) together with the Modern-Era Retrospective Analysis for Research and Applications (MERRA) meteorological fields were used to create a global emission dataset of biogenic volatile organic compounds (BVOC) available on a monthly basis for the time period of 1980–2010. This dataset is called MEGAN-MACC. The model estimated mean annual total BVOC emission of 760 Tg (C) yr−1 consisting of isoprene (70%), monoterpenes (11%), methanol (6%), acetone (3%), sesquiterpenes (2.5%) and other BVOC species each contributing less than 2%. Several sensitivity model runs were performed to study the impact of different model input and model settings on isoprene estimates and resulted in differences of up to ±17% of the reference isoprene total. A greater impact was observed for a sensitivity run applying parameterization of soil moisture deficit that led to a 50% reduction of isoprene emissions on a global scale, most significantly in specific regions of Africa, South America and Australia. MEGAN-MACC estimates are comparable to results of previous studies. More detailed comparison with other isoprene inventories indicated significant spatial and temporal differences between the datasets especially for Australia, Southeast Asia and South America. MEGAN-MACC estimates of isoprene, α-pinene and group of monoterpenes showed a reasonable agreement with surface flux measurements at sites located in tropical forests in the Amazon and Malaysia. The model was able to capture the seasonal variation of isoprene emissions in the Amazon forest.
Using Moran's I and GIS to study the spatial pattern of forest litter carbon density in a subtropical region of southeastern China
Authors: Fu W. J. , Jiang P. K. , Zhou G. M. , Zhao K. L.
Published: April 2014

Abstract. Spatial pattern information of carbon density in forest ecosystem including forest litter carbon (FLC) plays an important role in evaluating carbon sequestration potentials. The spatial variation of FLC density in the typical subtropical forests in southeastern China was investigated using Moran's I, geostatistics and a geographical information system (GIS). A total of 839 forest litter samples were collected based on a 12 km (south–north) × 6 km (east–west) grid system in Zhejiang province. Forest litter carbon density values were very variable, ranging from 10.2 kg ha−1 to 8841.3 kg ha−1, with an average of 1786.7 kg ha−1. The aboveground biomass had the strongest positive correlation with FLC density, followed by forest age and elevation. Global Moran's I revealed that FLC density had significant positive spatial autocorrelation. Clear spatial patterns were observed using local Moran's I. A spherical model was chosen to fit the experimental semivariogram. The moderate "nugget-to-sill" (0.536) value revealed that both natural and anthropogenic factors played a key role in spatial heterogeneity of FLC density. High FLC density values were mainly distributed in northwestern and western part of Zhejiang province, which were related to adopting long-term policy of forest conservation in these areas, while Hang-Jia-Hu (HJH) Plain, Jin-Qu (JQ) Basin and coastal areas had low FLC density due to low forest coverage and intensive management of economic forests. These spatial patterns were in line with the spatial-cluster map described by local Moran's I. Therefore, Moran's I, combined with geostatistics and GIS, could be used to study spatial patterns of environmental variables related to forest ecosystem.
Protection against lightning on the geomagnetic observatory
Authors: Čop R. , Milev G. , Deželjin D. , Kosmač J.
Published: April 2014

Abstract. The Sinji Vrh Geomagnetic Observatory was built on the brow of the mountain Gora, above Ajdovščina, and all over Europe one may hardly find an area which is more often struck by lightning than this south-western part of Slovenia. When the humid air masses of a storm front hit the edge of Gora, they rise up more than 1000 m in a very short time, and this causes the additional electrical charge of stormy clouds. The reliability of operations performed in the every building of observatory could be increased by understanding the formation of lightning in the thunderstorm cloud, the application of already proven methods of protection against a strike of lightning and against its secondary effects. To reach this goal the following groups of experts have to co-operate: the experts in the field of protection against lightening phenomenon, the constructors and manufacturers of equipment and the observatory managers.
Quantification of basal friction for glide-snow avalanche mitigation measures in forested and non-forested terrain
Authors: Feistl T. , Bebi P. , Dreier L. , Hanewinkel M. , Bartelt P.
Published: April 2014

Abstract. A long-standing problem in avalanche engineering is to design defense structures and manage forest stands such that they can withstand the forces of the natural snow cover. In this way glide-snow avalanches can be prevented. Ground friction plays a crucial role in this process. To verify existing guidelines, we collected data on the vegetation cover and terrain characteristics of 101 glide-snow release areas in Davos, Switzerland. We quantified the Coulomb friction parameter μ by applying a physical model that accounts for the dynamic forces of the moving snow on the stauchzone. We investigated the role of glide length, slope steepness and friction on avalanche release. Our calculations revealed that the slope angle and slab length for smooth slopes corresponds to the technical guidelines for defense structure distances in Switzerland. Artificial defense structures, built in accordance with guidelines, prevent glide-snow avalanche releases, even when the terrain is smooth. Slopes over 40 m length and 45° steepness require a ground friction of μ = 0.7 corresponding to stumps or tree regeneration to assure protection. Forest management guidelines which define maximum forest gap sizes to prevent glide-snow avalanche release neglect the role of surface roughness and therefore underestimate the danger on smooth slopes.
IODP Expedition 336: initiation of long-term coupled microbiological, geochemical, and hydrological experimentation within the seafloor at North Pond, western flank of the Mid-Atlantic Ridge
Authors: Edwards K. , Bach W. , Klaus A. ,   the IODP Expedition 336 Scientific Party
Published: April 2014

Abstract. Integrated Ocean Drilling Program (IODP) Expedition 336 addressed questions concerning subseafloor microbial life and its relation to seawater circulation and basalt–seawater reactions in the basaltic ocean crust. Sediment and basement samples were recovered at three drill sites located in the North Pond area, an 8 × 15 km large sediment pond on the 8 Ma western flank of the Mid-Atlantic Ridge around 22°45' N and 46°05' W in roughly 4450 m water depth. The average core recovery rate in basement was approx. 31%. The subseafloor depth of the basement holes ranges from 90 to 332 m; sediment thickness is between 36 and 90 m. Two of the holes (U1382A, and U1383C) were equipped with advanced Circulation Obviation Retrofit Kit (CORK) observatories, employing – for the first time – fiberglass casing. Another CORK string was deployed in Deep Sea Drilling Project (DSDP) Hole 395A, but the wellhead broke off upon final installment. Nonetheless, the North Pond observatory is fully operational and post-cruise observatory research is already underway. Combined geochemical and microbiological studies of the drill core samples and experimental CORK materials will help understand (1) the extent and activity of microbial life in basalt and its relation to basalt alteration by circulating seawater, and (2) the mechanism of microbial inoculation of an isolated sediment pond.
The shallow boreholes at The AltotiBerina near fault Observatory (TABOO; northern Apennines of Italy)
Authors: Chiaraluce L. , Collettini C. , Cattaneo M. , Monachesi G.
Published: April 2014

Abstract. As part of an interdisciplinary research project, funded by the European Research Council and addressing the mechanics of weak faults, we drilled three 200–250 m-deep boreholes and installed an array of seismometers. The array augments TABOO (The AltotiBerina near fault ObservatOry), a scientific infrastructure managed by the Italian National Institute of Geophysics and Volcanology. The observatory, which consists of a geophysical network equipped with multi-sensor stations, is located in the northern Apennines (Italy) and monitors a large and active low-angle normal fault. The drilling operations started at the end of 2011 and were completed by July 2012. We instrumented the boreholes with three-component short-period (2 Hz) passive instruments at different depths. The seismometers are now fully operational and collecting waveforms characterised by a very high signal to noise ratio that is ideal for studying microearthquakes. The resulting increase in the detection capability of the seismic network will allow for a broader range of transients to be identified.
Exploring new drilling prospects in the southwest Pacific
Authors: Gallagher S. J. , Exon N. , Seton M. , Ikehara M. , Hollis C. J. , Arculus R. , D'Hondt S. , Foster C. , Gurnis M. , Kennett J. P. , McKay R. , Malakoff A. , Mori J. , Takai K. , Wallace L.
Published: April 2014

Abstract. A major International Ocean Discovery Program (IODP) workshop covering scientific ocean drilling in the southwest Pacific Ocean was held in Sydney, Australia, in late 2012. The workshop covered all fields of geoscience, and drilling targets in the area from the Equator to Antarctica. High-quality contributions and a positive and cooperative atmosphere ensured its success. The four science themes of the new IODP science plan were addressed. An additional resource-oriented theme considered possible co-investment opportunities involving IODP vessels. As a result of the workshop, existing proposals were revised and new ones written for the April 2013 deadline. Many of the proposals are broad and multidisciplinary in nature, hence broadening the scientific knowledge that can be produced by using the IODP infrastructure. This report briefly outlines the workshop and the related drilling plans.
Fatty Acid Profile and CLA Content of Goat Milk: Influence of Feeding System
Authors: Tudisco Raffaella , Grossi Micaela , Addi Laura , Musco Nadia , Cutrignelli Monica Isabella , Calabro Serena , Infascelli Federico
Published: April 2014

There is great interest in producing bioethanol from biomass and there is much emphasis on exploiting The effect of pasture and of diet linseed supplementation on fatty acid profile of milk was evaluated using 45 pluriparous goats, equally divided after kidding into three homogeneous groups (H, P and L). Group H (control) and L were housed in a stall receiving alfalfa hay, while group P was led to pasture. The groups received concentrate which for group L had linseed as ingredient. Average milk yield did not statistically differ between the groups. Groups P showed significantly higher fat content than group H and L (4.62% vs 3.70%, and 3.90% respectively for groups P, H and L; P < 0.01). On the contrary, milk from goats of group H and L had significantly higher content of lactose (4.65% and 4.61% vs 4.57%, respectively for groups H, L and P; P < 0.05). The levels of C18:1 cis9, C18:1 trans11 and MUFA in milk were significantly (P < 0.05) increased by both the pasture and linseed, while linoleic acid (C18:2) and PUFA were significantly (P < 0.05) higher in group P compared either to H or to L groups. The highest values of CLAs, either as t11 CLA and t10 c12 CLA or as SCLA, have been registered in milk of group P, the lowest in group H. These parameters in milk of group L were significantly (P < 0.05) lower or higher than those of group P and H, respectively.
Closing the Major Gap in PNES Research
Authors: Smith Brien J.
Published: April 2014

Psychogenic nonepileptic seizures (PNES) are events commonly encountered by primary care physicians, neurologists, pediatricians, and emergency medicine physicians in their practices, yet there continues to be significant variability in the way they are evaluated, diagnosed, and treated. Lack of understanding this condition and limited data on long-term outcome from current treatment paradigms have resulted in an environment with iatrogenic injury, morbidity, and significant costs to the patient and healthcare system. This article will review the current state of research addressing PNES treatment both in the adult and pediatric populations.
Untangling the Dravet Syndrome Seizure Network: The Changing Face of a Rare Genetic Epilepsy
Authors: Chopra Ravi , Isom Lori L.
Published: April 2014

Dravet syndrome (also known as Severe Myoclonic Epilepsy of Infancy) is a rare genetic epilepsy syndrome commonly associated with loss-of-function mutations in SCN1A, the gene encoding the α subunit of the voltage-gated sodium channel NaV1.1, resulting in haploinsufficiency. Like other voltage-gated sodium channels, NaV1.1 function contributes to the rising phase of the neuronal action potential; thus, the observation that loss-of-function mutations in this channel gene are associated with seizures has created a paradox for the field. Major work has been done to untangle this paradox during the past decade, resulting in the development of two distinct hypotheses to explain seizures in Dravet syndrome. Here, we review the history of these two hypotheses and speculate as to what the history of Dravet syndrome research might tell us about its future.
Music, Dance, and Behaviour in a New form of Expressive Culture: The RomanianManea
Authors: Giurchescu Anca , Rădulescu Speranţa
Published: April 2014

The popular music landscape of Romania today is dominated by themanea.It appeared in the late 1960s as a form of symbolic opposition by the Romani communities from the slums of the big cities on the Danube to their exclusion from Romanian society. In timemaneabecame an expression of implicit protest by ordinary people from any ethnic background. In the 1970s and 1980s, it gradually penetrated into cities and villages. After 1990, themaneaspread throughout the entire country and is now the favourite music of many teenagers, young people, and the nouveaux riches of the transition period, comprising together about one third of the population. The power of themaneaarises from the dominant role it plays in public and private events, such as weddings, baptisms, funerals, anniversaries, and all kinds of parties organized in restaurants and clubs, as well as from the high visibility it receives on private TV channels, the Internet, commercial CDs and DVDs, concerts, and shows.
Voices from “Under-the-Garland“: Singing, Christianity, and Cultural Transformations in Chuuk, Micronesia
Authors: Diettrich Brian
Published: April 2014

One way to theorize a history of native articulations is to historicize the processes of conversions to Christianity in terms of Native agencies whose investments in Christianity tactically invert and then displace canonical narratives. (Vicente M. Diaz 2010)
‘One of the Noblest Inventions of the Age’: British Steamboat Numbers, Diffusion, Services and Public Reception, 1812 – c.1823
Authors: Williams David M. , Armstrong John
Published: April 2014

The operation of the Comet, Britain's first commercial steamboat, on the Clyde in 1812 led to a period of rapid steamboat development. Drawing on little utilised sources, this study examines the impact of the steamboat in its first decade. Diffusion was rapid and relatively nationwide embracing river, coastal and short sea services. The impact in terms of services, mostly passenger orientated (but also including towage), was considerable and contributed to a new, popular appreciation of steam technology and changes in lifestyles. How the press and government responded to this new technological advance is also considered. A brief conclusion points to the special nature of the steamboat's immediate impact in a wider context.
Urban Transportation Planning Influences and Legacies: Kurt Leibbrand, Germany's Acclaimed Postwar Traffic Planner
Authors: Diefendorf Jeffry M.
Published: April 2014

This article explores several dimensions of the work and career of Kurt Leibbrand, often considered the most influential German urban transportation planner after 1945. It examines some key ideas prevalent in his publications, such as his advocacy of the priority of transportation planning, hostility to citizen participation in planning, and rejection of pedestrian zones. In assessing his status, the paper discusses his contributions to traffic plans for the cities of Basel, Mainz and Selb. The paper also examines some shifts in his career, including his move to the Swiss Federal Institutes of Technology in 1950 and his resignation there after his arrest for having ordered the murder of Italian volunteers in his army unit during the war. Leibbrand was convicted of manslaughter but not punished because the statute of limitations had expired. He continued to work as a consultant but did not again hold an academic position in the German-speaking world.
Systems analysis of the CO2 concentrating mechanism in cyanobacteria
Authors: Mangan Niall M , Brenner Michael P
Published: April 2014

Cyanobacteria are photosynthetic bacteria with a unique CO2 concentrating mechanism (CCM), enhancing carbon fixation. Understanding the CCM requires a systems level perspective of how molecular components work together to enhance CO2 fixation. We present a mathematical model of the cyanobacterial CCM, giving the parameter regime (expression levels, catalytic rates, permeability of carboxysome shell) for efficient carbon fixation. Efficiency requires saturating the RuBisCO reaction, staying below saturation for carbonic anhydrase, and avoiding wasteful oxygenation reactions. We find selectivity at the carboxysome shell is not necessary; there is an optimal non-specific carboxysome shell permeability. We compare the efficacy of facilitated CO2 uptake, CO2 scavenging, and HCO3− transport with varying external pH. At the optimal carboxysome permeability, contributions from CO2 scavenging at the cell membrane are small. We examine the cumulative benefits of CCM spatial organization strategies: enzyme co-localization and compartmentalization.
Combining growth-promoting genes leads to positive epistasis in Arabidopsis thaliana
Authors: Vanhaeren Hannes , Gonzalez Nathalie , Coppens Frederik , De Milde Liesbeth , Van Daele Twiggy , Vermeersch Mattias , Eloy Nubia B , Storme Veronique , Inzé Dirk
Published: April 2014

Several genes positively influence final leaf size in Arabidopsis when mutated or overexpressed. The connections between these growth regulators are still poorly understood although such knowledge would further contribute to understand the processes driving leaf growth. In this study, we performed a combinatorial screen with 13 transgenic Arabidopsis lines with an increased leaf size. We found that from 61 analyzed combinations, 39% showed an additional increase in leaf size and most resulted from a positive epistasis on growth. Similar to what is found in other organisms in which such an epistasis assay was performed, only few genes were highly connected in synergistic combinations as we observed a positive epistasis in the majority of the combinations with samba, BRI1OE or SAUR19OE. Furthermore, positive epistasis was found with combinations of genes with a similar mode of action, but also with genes which affect distinct processes, such as cell proliferation and cell expansion.
Structural basis of HIV-1 Vpu-mediated BST2 antagonism via hijacking of the clathrin adaptor protein complex 1
Authors: Jia Xiaofei , Weber Erin , Tokarev Andrey , Lewinski Mary , Rizk Maryan , Suarez Marissa , Guatelli John , Xiong Yong
Published: April 2014

BST2/tetherin, an antiviral restriction factor, inhibits the release of enveloped viruses from the cell surface. Human immunodeficiency virus-1 (HIV-1) antagonizes BST2 through viral protein u (Vpu), which downregulates BST2 from the cell surface. We report the crystal structure of a protein complex containing Vpu and BST2 cytoplasmic domains and the core of the clathrin adaptor protein complex 1 (AP1). This, together with our biochemical and functional validations, reveals how Vpu hijacks the AP1-dependent membrane trafficking pathways to mistraffick BST2. Vpu mimics a canonical acidic dileucine-sorting motif to bind AP1 in the cytosol, while simultaneously interacting with BST2 in the membrane. These interactions enable Vpu to build on an intrinsic interaction between BST2 and AP1, presumably causing the observed retention of BST2 in juxtanuclear endosomes and stimulating its degradation in lysosomes. The ability of Vpu to hijack AP-dependent trafficking pathways suggests a potential common theme for Vpu-mediated downregulation of host proteins.
Temporal dynamics and developmental memory of 3D chromatin architecture at Hox gene loci
Authors: Noordermeer Daan , Leleu Marion , Schorderet Patrick , Joye Elisabeth , Chabaud Fabienne , Duboule Denis
Published: April 2014

Hox genes are essential regulators of embryonic development. Their step-wise transcriptional activation follows their genomic topology and the various states of activation are subsequently memorized into domains of progressively overlapping gene products. We have analyzed the 3D chromatin organization of Hox clusters during their early activation in vivo, using high-resolution circular chromosome conformation capture. Initially, Hox clusters are organized as single chromatin compartments containing all genes and bivalent chromatin marks. Transcriptional activation is associated with a dynamic bi-modal 3D organization, whereby the genes switch autonomously from an inactive to an active compartment. These local 3D dynamics occur within a framework of constitutive interactions within the surrounding Topological Associated Domains, indicating that this regulation process is mostly cluster intrinsic. The step-wise progression in time is fixed at various body levels and thus can account for the chromatin architectures previously described at a later stage for different anterior to posterior levels.