bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concordance of Increased B1 Cell Subset and Lupus Phenotypes in Mice and Humans Is Dependent on BLK Expression Levels
Authors: Wu Ying-Yu , Georg Ina , Díaz-Barreiro Alejandro , Varela Nieves , Lauwerys Bernard , Kumar Ramesh , Bagavant Harini , Castillo-Martín Mireia , El Salem Fadi , Marañón Concepción , Alarcón-Riquelme Marta E. 
Published: May 2015

Abstract
Polymorphisms in the B lymphoid tyrosine kinase (BLK) gene have been associated with autoimmune diseases, including systemic lupus erythematosus, with risk correlating with reduced expression of BLK. How reduced expression of BLK causes autoimmunity is unknown. Using Blk+/+, Blk+/−, and Blk−/− mice, we show that aged female Blk+/− and Blk−/− mice produced higher anti-dsDNA IgG Abs and developed immune complex–mediated glomerulonephritis, compared with Blk+/+ mice. Starting at young age, Blk+/− and Blk−/− mice accumulated increased numbers of splenic B1a cells, which differentiated into class-switched CD138+ IgG-secreting B1a cells. Increased infiltration of B1a-like cells into the kidneys was also observed in aged Blk+/− and Blk−/− mice. In humans, we found that healthy individuals had BLK genotype-dependent levels of anti-dsDNA IgG Abs as well as increased numbers of a B1-like cell population, CD19+CD3−CD20+CD43+CD27+, in peripheral blood. Furthermore, we describe the presence of B1-like cells in the tubulointerstitial space of human lupus kidney biopsies. Taken together, our study reveals a previously unappreciated role of reduced BLK expression on extraperitoneal accumulation of B1a cells in mice, as well as the presence of IgG autoantibodies and B1-like cells in humans.
CD81 Controls Immunity to Listeria Infection through Rac-Dependent Inhibition of Proinflammatory Mediator Release and Activation of Cytotoxic T Cells
Authors: Martínez del Hoyo Gloria , Ramírez-Huesca Marta , Levy Shoshana , Boucheix Claude , Rubinstein Eric , Minguito de la Escalera María , González-Cintado Leticia , Ardavín Carlos , Veiga Esteban , Yáñez-Mó María , Sánchez-Madrid Francisco 
Published: May 2015

Abstract
Despite recent evidence on the involvement of CD81 in pathogen binding and Ag presentation by dendritic cells (DCs), the molecular mechanism of how CD81 regulates immunity during infection remains to be elucidated. To investigate the role of CD81 in the regulation of defense mechanisms against microbial infections, we have used the Listeria monocytogenes infection model to explore the impact of CD81 deficiency in the innate and adaptive immune response against this pathogenic bacteria. We show that CD81−/− mice are less susceptible than wild-type mice to systemic Listeria infection, which correlates with increased numbers of inflammatory monocytes and DCs in CD81−/− spleens, the main subsets controlling early bacterial burden. Additionally, our data reveal that CD81 inhibits Rac/STAT-1 activation, leading to a negative regulation of the production of TNF-α and NO by inflammatory DCs and the activation of cytotoxic T cells by splenic CD8α+ DCs. In conclusion, this study demonstrates that CD81–Rac interaction exerts an important regulatory role on the innate and adaptive immunity against bacterial infection and suggests a role for CD81 in the development of novel therapeutic targets during infectious diseases.
The Frequency of Naive and Early-Activated Hapten-Specific B Cell Subsets Dictates the Efficacy of a Therapeutic Vaccine against Prescription Opioid Abuse
Authors: Laudenbach Megan , Baruffaldi Federico , Vervacke Jeffrey S. , Distefano Mark D. , Titcombe Philip J. , Mueller Daniel L. , Tubo Noah J. , Griffith Thomas S. , Pravetoni Marco 
Published: May 2015

Abstract
Translation of therapeutic vaccines for addiction, cancer, or other chronic noncommunicable diseases has been slow because only a small subset of immunized subjects achieved effective Ab levels. We hypothesize that individual variability in the number of naive and early-activated hapten-specific B cells determines postvaccination serum Ab levels and vaccine efficacy. Using a model vaccine against the highly abused prescription opioid oxycodone, the polyclonal B cell population specific for an oxycodone-based hapten (6OXY) was analyzed by flow cytometry paired with Ag-based magnetic enrichment. A higher frequency of 6OXY-specific B cells in either spleen biopsies or blood, before and after immunization, correlated to subsequent greater oxycodone-specific serum Ab titers and their efficacy in blocking oxycodone distribution to the brain and oxycodone-induced behavior in mice. The magnitude of 6OXY-specific B cell activation and vaccine efficacy was tightly correlated to the size of the CD4+ T cell population. The frequency of enriched 6OXY-specific B cells was consistent across various mouse tissues. These data provide novel evidence that variations in the frequency of naive or early-activated vaccine-specific B and T cells can account for individual responses to vaccines and may predict the clinical efficacy of a therapeutic vaccine.
Cutting Edge: Role of Osteopontin and Integrin αv in T Cell–Mediated Anti-Inflammatory Responses in Endotoxemia
Authors: Inoue Makoto , Shinohara Mari L. 
Published: May 2015

Abstract
The immune system is equipped with mechanisms that downregulate hyperinflammation to avoid collateral damage. We demonstrated recently that unprimed T cells downregulate macrophage TNF production through direct interaction with macrophages in the spleen during LPS endotoxemia. How T cell migration toward macrophages occurs upon LPS injection is still not clear. In this study, we demonstrate that secreted osteopontin (sOPN) plays a role in the T cell migration to initiate the suppression of hyperinflammation during endotoxemia. Osteopontin levels in splenic macrophages were upregulated 2 h after LPS treatment, whereas T cell migration toward macrophages was observed 3 h after treatment. Neutralization of sOPN and blockade of its receptor, integrin αv, significantly inhibited CD4+ T cell migration and increased susceptibility to endotoxemia. Our study demonstrates that the sOPN/integrin αv axis, which induces T cell chemotaxis toward macrophages, is critical for suppressing hyperinflammation during the first 3 h of endotoxemia.
Building laboratory capacity to support HIV care in Nigeria: Harvard/APIN PEPFAR, 2004–2012
Authors: Hamel Donald J. , Sankalé Jean-Louis , Samuels Jay O. , Sarr Abdoulaye D. , Chaplin Beth , Ofuche Eke , Meloni Seema T. , Okonkwo Prosper , Kanki Phyllis J. 
Published: May 2015

Introduction: From 2004–2012, the Harvard/AIDS Prevention Initiative in Nigeria, funded through the US President’s Emergency Plan for AIDS Relief programme, scaled up HIV care and treatment services in Nigeria. We describe the methodologies and collaborative processes developed to improve laboratory capacity significantly in a resource-limited setting. These methods were implemented at 35 clinic and laboratory locations.Methods: Systems were established and modified to optimise numerous laboratory processes. These included strategies for clinic selection and management, equipment and reagent procurement, supply chains, laboratory renovations, equipment maintenance, electronic data management, quality development programmes and trainings.Results: Over the eight-year programme, laboratories supported 160 000 patients receiving HIV care in Nigeria, delivering over 2.5 million test results, including regular viral load quantitation. External quality assurance systems were established for CD4+ cell count enumeration, blood chemistries and viral load monitoring. Laboratory equipment platforms were improved and standardised and use of point-of-care analysers was expanded. Laboratory training workshops supported laboratories toward increasing staff skills and improving overall quality. Participation in a World Health Organisation-led African laboratory quality improvement system resulted in significant gains in quality measures at five laboratories.Conclusions: Targeted implementation of laboratory development processes, during simultaneous scale-up of HIV treatment programmes in a resource-limited setting, can elicit meaningful gains in laboratory quality and capacity. Systems to improve the physical laboratory environment, develop laboratory staff, create improvements to reduce costs and increase quality are available for future health and laboratory strengthening programmes. We hope that the strategies employed may inform and encourage the development of other laboratories in resource-limited settings.
Organizational Behavior of Terrorist Groups
Authors: Jung Jeyong , Lee Julak 
Published: May 2015

Terror attacks have been typically performed by group members, which implies that perpetrators were not independent actors, but acted violently as being part of a larger group. In addition, the execution of terrorist attacks is not only facilitated by macro-level factors but also as the tools to increase payoffs, survival, and maintenance at the group level. As links between disgruntled individuals and society, organizational behavior elements are something that needs to be examined. In this paper, several organizational behavior theories to compare were applied and contrast between terrorist groups and normal organizations under the categories of mobilizations, decision-making, and leadership.
In Vitro Differentiation of Human Neural Progenitor Cells Into Striatal GABAergic Neurons
Authors: Lin Lin , Yuan Juan , Sander Bjoern , Golas Monika M. 
Published: May 2015

Abstract

Huntington's disease (HD) results from a CAG repeat expansion in the gene encoding the huntingtin protein. This inherited disorder is characterized by progressive neurodegeneration. In particular, HD progression involves the loss of striatal projection neurons. The limited availability of reliable sources of human striatal projection neurons currently hampers our understanding of HD mechanisms and hinders the development of novel HD treatments. In this paper, we described two- and three-step methods for differentiating human neural progenitor cells toward striatal projection neurons. In the two-step differentiation protocol, 90%, 54%, and 6% of MAP2-positive cells were immunopositive for GABA, calbindin (CALB1), and DARPP-32/PPP1R1B, respectively. In the three-step differentiation protocol, 96%, 84%, and 21% of MAP2-positive cells were immunopositive for GABA, calbindin, and DARPP-32/PPP1R1B, respectively. In line with a striatal projection neuron phenotype, cells differentiated with our protocols displayed significantly increased expression of MAP2, CALB1, DARPP-32/PPP1R1B, ARPP21, and CTIP2. Application of glutamate receptor agonists induced calcium influx; accordingly, the cells also expressed various ionotropic glutamate receptor subunits. Differentiated cells also released GABA on stimulation. We suggest that our three-step differentiation protocol presents a reliable and simplified method for the generation of striatal projection neurons, yielding a critical resource for neuronal physiology and neurodegenerative disorder studies.

Significance
The earliest changes in the neurodegenerative disorder Huntington's disease affect a specific type of brain neurons, the so-called medium spiny neurons of the striatum. In this study, two protocols were developed for the differentiation of neural progenitor cells into striatal medium spiny neurons, and the differentiated neurons were extensively characterized. The data indicate that the three-step differentiation protocol presents a reliable and simplified method for the generation of striatal medium spiny neurons. The generated striatal medium spiny neurons could represent a critical resource for the study of neurodegenerative disorders, a model system for drug discovery, and a step toward cell-based regeneration therapies.
Megestrol Acetate Increases the Proliferation, Migration, and Adipogenic Differentiation of Adipose-Derived Stem Cells via Glucocorticoid Receptor
Authors: Sung Jong-Hyuk , An Hyo-Sun , Jeong Jin-Hyun , Shin Soyoung , Song Seung Yong 
Published: May 2015

Abstract

Because adipose-derived stem cells (ASCs) are usually expanded to acquire large numbers of cells for therapeutic applications, it is important to increase the production yield and regenerative potential during expansion. Therefore, a tremendous need exists for alternative ASC stimuli during cultivation to increase the proliferation and adipogenic differentiation of ASCs. The present study primarily investigated the involvement of megestrol acetate (MA), a progesterone analog, in the stimulation of ASCs, and identifies the target receptors underlying stimulation. Mitogenic and adipogenic effects of MA were investigated in vitro, and pharmacological inhibition and small interfering (si) RNA techniques were used to identify the molecular mechanisms involved in the MA-induced stimulation of ASCs. MA significantly increased the proliferation, migration, and adipogenic differentiation of ASCs in a dose-dependent manner. Glucocorticoid receptor (GR) is highly expressed compared with other nuclear receptors in ASCs, and this receptor is phosphorylated after MA treatment. MA also upregulated genes downstream of GR in ASCs, including ANGPTL4, DUSP1, ERRF11, FKBP5, GLUL, and TSC22D3. RU486, a pharmacological inhibitor of GR, and transfection of siGR significantly attenuated MA-induced proliferation, migration, and adipogenic differentiation of ASCs. Although the adipogenic differentiation potential of MA was inferior to that of dexamethasone, MA had mitogenic effects in ASCs. Collectively, these results indicate that MA increases the proliferation, migration, and adipogenic differentiation of ASCs via GR phosphorylation.

Significance
Magestrol acetate (MA) increases the proliferation, migration, and adipogenic differentiation of adipose-derived stem cells (ASCs) via glucocorticoid receptor phosphorylation. Therefore, MA can be applied to increase the production yield during expansion and can be used to facilitate adipogenic differentiation of ASCs.
Seismic interferometry and stationary phase at caustics
Authors: Snieder Roel , Sens‐Schönfelder Christoph 
Published: May 2015

AbstractWaves that propagate between two receivers can be extracted by cross correlating noise recorded at these receivers if the noise is generated by sources on a closed surface surrounding the receivers. This concept is called seismic interferometry. Of all these noise sources, those for whom the travel time difference for propagation to the two receivers is in the stationary phase zone, give the dominant contribution. In this paper we analyze the stationary phase properties when one receiver is at a caustic for waves leaving the other receiver. A simple model for a waveguide and a general treatment of caustics show that, at a caustic, the curvature of the travel time difference at the stationary phase zone vanishes. As a result the stationary phase region is considerably wider at a caustic than at other points, and it is more likely that noise sources are present in the stationary phase region. This explains why it is easier to extract waves from seismic interferometry when the receivers are at caustics such as antipodal receivers on the Earth.
Potential of ambient seismic noise techniques to monitor the St. Gallen geothermal site (Switzerland)
Authors: Obermann A. , Kraft T. , Larose E. , Wiemer S. 
Published: May 2015

AbstractThe failures of two recent deep geothermal energy projects in Switzerland (Basel, 2006; St. Gallen, 2013) have again highlighted that one of the key challenges for the successful development and operation of deep underground heat exchangers is to control the risk of inducing potentially hazardous seismic events. In St. Gallen, after an injection test and two acid injections that were accompanied by a small number of micro‐earthquakes (ML<0.2), operators were surprised by an uncontrolled gas release from the formation (gas kick). The “killing” procedures that had to be initiated following standard drilling procedures led to a ML3.5 earthquake. With ambient seismic noise cross correlations from nine stations, we observe a significant loss of waveform coherence that we can horizontally and vertically constrain to the injection location of the fluid. The loss of waveform coherence starts with the onset of the fluid injections 4 days prior to the gas kick. We interpret the loss of coherence as a local perturbation of the medium. We show how ambient seismic noise analysis can be used to assess the aseismic response of the subsurface to geomechanical well operations and how this method could have helped to recognize the unexpected reservoir dynamics at an earlier stage than the microseismic response alone, allowed.
Synthesis and structural characterization of ferrous trioctahedral smectites: Implications for clay mineral genesis and detectability on Mars
Authors: Chemtob Steven M. , Nickerson Ryan D. , Morris Richard V. , Agresti David G. , Catalano Jeffrey G. 
Published: May 2015

AbstractWidespread detections of phyllosilicates in Noachian terrains on Mars imply a history of near‐surface fluid‐rock interaction. Ferrous trioctahedral smectites are thermodynamically predicted products of basalt weathering on early Mars, but to date only Fe3+‐bearing dioctahedral smectites have been identified from orbital observations. In general, the physicochemical properties of ferrous smectites are poorly studied because they are susceptible to air oxidation. In this study, eight Fe2+‐bearing smectites were synthesized from Fe2+‐Mg‐Al silicate gels at 200°C under anoxic conditions. Samples were characterized by inductively coupled plasma optical emission spectrometry, powder X‐ray diffraction, Fe K‐edge X‐ray absorption spectroscopy (XAS), Mössbauer spectroscopy, and visible/near‐infrared (VNIR) reflectance spectroscopy. The range of redox states was Fe3+/ΣFe = 0 to 0.06 ± 0.01 as determined by both XAS and, for short integration times, Mössbauer. The smectites have 060 distances (d(060)) between 1.53 and 1.56 Å, indicating a trioctahedral structure. d(060) and XAS‐derived interatomic Fe‐(Fe,Mg,Al) distance scaled with Fe content. Smectite VNIR spectra feature OH/H2O absorption bands at 1.4 and 1.9 µm, (Fe2+,Mg,Al)3‐OH stretching bands near 1.4 µm, and Fe2+Fe2+Fe2+‐OH, MgMgMg‐OH, AlAl(Mg,Fe2+)‐OH, and AlAl‐OH combination bands at 2.36 µm, 2.32 µm 2.25 µm, and 2.20 µm, respectively. The spectra for ferrous saponites are distinct from those for dioctahedral ferric smectites, permitting their differentiation from orbital observations. X‐ray diffraction patterns for synthetic high‐Mg ferrosaponite and high‐Mg ferrian saponite are both consistent with the Sheepbed saponite detected by the chemistry and mineralogy (CheMin) instrument at Gale Crater, Mars, suggesting that anoxic basalt alteration was a viable pathway for clay mineral formation on early Mars.
Separating physical and biological controls on long‐term evapotranspiration fluctuations in a tropical deciduous forest subjected to monsoonal rainfall
Authors: Igarashi Yasunori , Katul Gabriel G. , Kumagai Tomo'omi , Yoshifuji Natsuko , Sato Takanori , Tanaka Nobuaki , Tanaka Katsunori , Fujinami Hatsuki , Suzuki Masakazu , Tantasirin Chatchai 
Published: May 2015

AbstractEvapotranspiration (ET), especially in the mainland of the Indochina Peninsula, can impact and is impacted by the Asian monsoonal (AM) system, thereby prompting interest in its long‐term variability. To separate the physical and biological factors controlling ET variability in a tropical deciduous forest under the AM influence, 7 year eddy covariance and ancillary measurements were collected and analyzed. The 7 year mean rainfall (Pr) and ET along with their standard deviations were 1335 ± 256 and 977 ± 108 mm (about 73% of Pr), respectively, suggesting close coupling between these two hydrologic fluxes. However, other physical and biological drivers decouple seasonal and annual variations of ET from Pr. To explore them, a big‐leaf model complemented by perturbation analysis was employed. The big‐leaf model agreed well with the measured ET at daily to multiyear time scales, lending confidence in its ability to separate biological and physical controls on ET. Using this formulation, both first‐order and second‐order Taylor series expansions of the total ET derivatives were applied to the big‐leaf model and compared with measured changes in ET (dET). Higher‐order and joint terms in the second‐order expansion were necessary for matching measured and analyzed dET. Vapor pressure deficit (D) was the primary external physical controlling driver of ET. Leaf area index (LAI) and bulk stomatal conductance (gs) were shown to be the main significant biological drivers of the transpiration component of ET. It can be surmised that rainfall variability controls long‐term ET through physical (mainly D) and biological (mainly LAI and gs) factors in this ecosystem.
The interplay between transport and reaction rates as controls on nitrate attenuation in permeable, streambed sediments
Authors: Lansdown K. , Heppell C. M. , Trimmer M. , Binley A. , Heathwaite A. L. , Byrne P. , Zhang H. 
Published: May 2015

AbstractAnthropogenic nitrogen fixation and subsequent use of this nitrogen as fertilizer have greatly disturbed the global nitrogen cycle. Rivers are recognized hot spots of nitrogen removal in the landscape as interaction between surface water and sediments creates heterogeneous redox environments conducive for nitrogen transformations. Our understanding of riverbed nitrogen dynamics to date comes mainly from shallow sediments or hyporheic exchange flow pathways with comparatively little attention paid to groundwater‐fed, gaining reaches. We have used 15N techniques to quantify in situ rates of nitrate removal to 1 m depth within a groundwater‐fed riverbed where subsurface hydrology ranged from strong upwelling to predominantly horizontal water fluxes. We combine these rates with detailed hydrologic measurements to investigate the interplay between biogeochemical activity and water transport in controlling nitrogen attenuation along upwelling flow pathways. Nitrate attenuation occurred via denitrification rather than dissimilatory nitrate reduction to ammonium or anammox (range = 12 to >17,000 nmol 15N L−1 h−1). Overall, nitrate removal within the upwelling groundwater was controlled by water flux rather than reaction rate (i.e., Damköhler numbers <1) with the exception of two hot spots of biogeochemical activity. Deep sediments were as important a nitrate sink as shallow sediments with fast rates of denitrification and short water residence time close to the riverbed surface balanced by slower rates of denitrification and water flux at depth. Within this permeable riverbed >80% of nitrate removal occurs within sediments not exposed to hyporheic exchange flows under base flow conditions, illustrating the importance of deep sediments as nitrate sinks in upwelling systems.
Detecting soil moisture impacts on convective initiation in Europe
Authors: Taylor Christopher M. 
Published: May 2015

AbstractFeedbacks between soil moisture and precipitation are important for understanding hydroclimatic variability in many regions. However, much uncertainty remains about how land surface fluxes influence the initiation of deep convection locally. While some studies consider only atmospheric and soil profiles, in a one‐dimensional sense, others have argued that horizontal variability in fluxes plays an important role in convective triggering, via mesoscale circulations. This paper presents the first comprehensive observational analysis over Europe linking convective initiation to soil moisture, based on satellite observations of cloud top and land surface temperature, and soil moisture. The results show that convective initiations are favored on the downwind side of dry surfaces, close to wetter areas. The signal is clearest following dry periods and under light winds, consistent with forcing by a mesoscale circulation. Overall, the detected signal in Europe is weaker than in previous Sahelian analysis, but key spatial characteristics are essentially the same.