bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preservation of Peripheral T Follicular Helper Cell Function in HIV Controllers
Authors: Buranapraditkun Supranee , Pissani Franco , Teigler Jeffrey E. , Schultz Bruce T. , Alter Galit , Marovich Mary , Robb Merlin L. , Eller Michael A. , Martin Jeff , Deeks Steven , Michael Nelson L. , Streeck Hendrik 
Published: May 2017

ABSTRACT

The maturation process of high-affinity antibodies is a result of intricate interactions between B cells and follicular helper T (Tfh) cells occurring in lymphoid germinal centers. HIV infection induces significant chronic immune activation, phenotypic skewing, and inflammation driven by years of continuous viral replication. High levels of viremia as well as immune activation and dysfunction have been demonstrated to have a perturbing impact on the B cell memory compartment and contribute to B cell exhaustion. Counterintuitively, the factors associated with perturbation of the B cell compartment seem to be favorable for the generation of highly affinity-matured Env-specific antibodies in a minority of HIV-infected individuals. Thus, the impact of HIV antigenemia on B cells and Tfh cell interactions warrants further exploration. We therefore studied immunophenotypes of HIV-specific B cells in individuals with differing levels of viral control using HIV Env gp120 probes and characterized the functionality of matched T cells in peripheral blood. While CXCR5
+
CD4
+
T cells were significantly diminished in HIV progressors, we found that a small subset of gp120-specific interleukin-21 (IL-21)-secreting CXCR5
+
CD4
+
T cells were significantly associated with gp120-specific B cell frequencies. In contrast, neither bulk CXCR5
+
CD4
+
T cells nor other HIV antigen specificities were associated with gp120-specific B cell levels. HIV-specific B cells derived from elite controllers displayed greater amounts of gp120-specific B cells in the resting memory subset, whereas HIV-specific B cells in progressors accumulated in tissue-like and activated memory subsets. Furthermore, CXCR5
+
CD4
+
T cells from elite controllers showed a stronger
ex vivo
capacity to induce B cell maturation and immunoglobulin class switching than cells from HIV progressors.

IMPORTANCE
Dissecting the factors that are involved in B cell maturation and antibody development is important for HIV vaccine design. In this study, we found that HIV Env-specific CXCR5
+
CD4
+
T cells that secrete interleukin-21 are strongly associated with B cell memory phenotypes and function. Moreover, we found that the immune responses of HIV controllers showed intrinsically better helper activity than those of HIV progressors.
CD177+neutrophils as functionally activated neutrophils negatively regulate IBD
Authors: Zhou Guangxi , Yu Lin , Fang Leilei , Yang Wenjing , Yu Tianming , Miao Yinglei , Chen Minhu , Wu Kaichun , Chen Feidi , Cong Yingzi , Liu Zhanju 
Published: May 2017

BackgroundNeutrophils are accumulated in inflamed mucosa of IBD and play an important role in the pathogenesis. CD177 is expressed in neutrophils specifically and upregulated during inflammation. However, the role of CD177+neutrophils in pathogenesis of IBD remains elusive.Materials and methodsExpression of CD177 was analysed in peripheral blood and intestinal mucosa from patients with IBD using quantitative RT-PCR, flow cytometry and immunohistochemistry. CD177+and CD177−neutrophils were isolated to determine gene differences by RNA sequencing. Colitis was established in CD177−/−and wild-type mice in response to dextran sulfate sodium (DSS) insults to determine the role of CD177+neutrophils in IBD.ResultsCD177+neutrophils were markedly increased in peripheral blood and inflamed mucosa from patients with active IBD compared with healthy controls. RNA sequencing revealed that differential gene expression between CD177+and CD177−neutrophils from patients with IBD was associated with response to bacterial defence, hydrogen peroxide and reactive oxygen species (ROS). CD177+neutrophils produced lower levels of proinflammatory cytokines (ie, interferon-γ, interleukin (IL)-6, IL-17A), but higher levels of IL-22 and transforming growth factor-β, and exhibited increased bactericidal activities (ie, ROS, antimicrobial peptides, neutrophil extracellular trap) compared with CD177−subset. CD177−/−mice developed more severe colitis on DSS insults compared with wild-type mice. Moreover, CD177 deficiency led to compromised intestinal barrier and impaired antibacterial immunity through decreased production of IL-22 by CD177−neutrophils.ConclusionsCD177+neutrophils represent functionally activated population and play a protective role in IBD through increased bactericidal activity and IL-22 production. Targeting CD177+neutrophils may be beneficial for treatment of IBD.
Throughput optimization for dual collaborative spectrum sensing with dynamic scheduling
Authors: Cui Cuimei , Yang Dezhi 
Published: May 2017

Cognitive radio technology is envisaged to alleviate both spectrum inefficiency and spectrum scarcity problems by exploiting the existing licensed spectrum opportunistically. However, cognitive radio ad hoc networks (CRAHNs) impose unique challenges due to the high dynamic scheduling in the available spectrum, diverse quality of service (QOS) requirements, as well as hidden terminals and shadow fading issues in a harsh radio environment. To solve these problems, this paper proposes a dynamic and variable time-division multiple-access scheduling mechanism (DV-TDMA) incorporated with dual collaborative spectrum sensing scheme for CRAHNs. This study involves the cross-layered cooperation between the Physical (PHY) layer and Medium Access Control (MAC) layer under the consideration of average sensing time, sensing accuracy and the average throughput of cognitive radio users (CRs). Moreover, multiple-objective optimization algorithm is proposed to maximize the average throughput of CRs while still meeting QOS requirements on sensing time and detection error. Finally, performance evaluation is conducted through simulations, and the simulation results reveal that this optimization algorithm can significantly improve throughput and sensing accuracy and reduce average sensing time.
Improvement of Stress Intensity Factor Analysis Using Overall Defined Basic Density Function on Crack Face
Authors: Hasib Md. Abdul , Sonobe Yohei , Saimoto Akihide 
Published: May 2017

In this study, an improved technique for the evaluation of stress intensity factor (SIF) along the 3D planar crack front is proposed. In the present analysis, a planar triangular element is used to cover the total crack face. The stress field induced by a body force doublet in an infinite body is used for a fundamental solution. In the present analysis, overall defined basic density function of body force doublet is introduced. The crack problem is formulated as hypersingular boundary integral equations and the magnitudes of distributed point force doublets are determined through boundary conditions. The numerical SIF solution obtained using the present approach was compared with the solution obtained using the conventional basic density function. The results indicate that the proposed technique improves the accuracy of SIF. In addition, some numerical examples were examined to verify the effectiveness and the robustness of the proposed technique.
Activation of stylolites as conduits for overpressured fluid flow in dolomitized platform carbonates
Authors: Martín-Martín J. D. , Gomez-Rivas E. , Gómez-Gras D. , Travé A. , Ameneiro R. , Koehn D. , Bons P. D. 
Published: May 2017

Abstract
This study investigates the Late Aptian–earliest Albian platform carbonates of the Benicàssim area (Maestrat Basin, Spain) in order to assess the relationship between bed-parallel stylolites and the flow of diagenetic fluids during dolomitization and subsequent hydrothermal alteration. Dolostones and burial dolomite and calcite cements were studied by a combination of field geology and standard petrographic and isotope analysis. Field data indicate that dolostones are closely associated with seismic-scale synsedimentary faults, preferentially replace grain-dominated facies and typically show wavy dolomitizing fronts that mostly correspond to bed-parallel stylolites. The dolostones are corroded and contain bed-parallel pores that are filled with hydrothermal saddle dolomite and blocky calcite cements. This late calcite cement frequently engulfs clasts of the host dolostones, suggesting that hydraulic brecciation likely associated with overpressured fluid occurred. Results indicate that stylolites play a key role in the distribution of dolostones and subsequent hydrothermal mineralization. During the replacement stage, stylolites acted as baffles for the dolomitzing fluids controlling lateral fluid flow and resulting in the stratabound dolostone distribution. During the post-dolomitization stage, stylolites became preferred pathways for overpressured hydrothermal corrosive and mineralizing fluids that likely came from the underlying basement, and increased bed-parallel stylolitic porosity and probably also permeability.
Experimental dyspnea as a stressor: differential cardiovegetative responses to inspiratory threshold loading in healthy men and women
Authors: Niérat Marie-Cécile , Laviolette Louis , Hudson Anna , Similowski Thomas , Sévoz-Couche Caroline 
Published: May 2017

Dyspnea is associated with an emotional reaction that involves limbic activation. The inspiratory threshold load (ITL) is known to elicit a dyspneic response in healthy subjects. Laboratory-induced stress conditions have been shown to elicit sex-related differences in cardiovascular responses. The aim of this study was to evaluate how healthy men ( n = 8) and women ( n = 9) react and adapt to 5-min periods of ITL at three levels (low, medium, and high) in terms of heart rate (HR), temporal (RMSSD) and spectral (LF, HF, LF/HF ratio) HRV indexes, and rating of breathing discomfort. HR increased with low, medium, and high ITL in men, whereas it increased only with high ITL in women. LF/HF ratio increased at low ITL in both men and women. Modifications appear to depend essentially on increased LF in men and on reduced HF in women. In addition, HRV modifications differ between men and women, following the order of presentation of ITLs. Our results show a continuous and sustained stress in men (increased HR, LF, and LF/HF ratio across ITL presentation) and a stress adaptation in women. Subjective responses of breathing discomfort were not correlated with sympatho-vagal balance modifications for a subgroup of subjects ( n = 10). Breathing against the ITL induced autonomic modifications that are different between men and women, i.e., driven by sympathetic mediated responses in men, whereas women showed a greater parasympathetic modulation of cardiovascular activity. These results highlight the role of the mechanical inspiratory load in the heart rate variability seen in chronic obstructive pulmonary disease. NEW & NOTEWORTHY Breathing against the ITL induced autonomic modifications driven by sympathetic mediated responses in men, whereas women showed a greater parasympathetic modulation of cardiovascular activity, even for low load. A stress circuit could be at the origin of autonomic modifications induced by ITL. Our results would underline the role of the mechanic inspiratory load in the abnormalities in heart rate variability seen in COPD patients.
Progression and variability of physiologic deterioration in an ovine model of lung infection sepsis
Authors: Yaghouby Farid , Daluwatte Chathuri , Fukuda Satoshi , Nelson Christina , Salsbury John , Kinsky Michael , Kramer George C. , Strauss David G. , Enkhbaatar Perenlei , Scully Christopher G. 
Published: May 2017

In this study, a lung infection model of pneumonia in sheep ( n = 12) that included smoke inhalation injury followed by methicillin-resistant Staphylococcus aureus placement into the lungs was used to investigate hemodynamic and pulmonary dysfunctions during the course of sepsis progression. To assess the variability in disease progression, animals were retrospectively divided into survivor ( n = 6) and nonsurvivor ( n = 6) groups, and a range of physiological indexes reflecting hemodynamic and pulmonary function were estimated and compared to evaluate variability in dynamics underlying sepsis development. Blood pressure and heart rate variability analyses were performed to assess whether they discriminated between the survivor and nonsurvivor groups early on and after intervention. Results showed hemodynamic deterioration in both survivor and nonsurvivor animals during sepsis along with a severe oxygenation disruption (decreased peripheral oxygen saturation) in nonsurvivors separating them from survivor animals of this model. Variability analysis of beat-to-beat heart rate and blood pressure reflected physiologic deterioration during infection for all animals, but these analyses did not discriminate the nonsurvivor animals from survivor animals. NEW & NOTEWORTHY Variable pulmonary response to injury results in varying outcomes in a previously reported animal model of lung injury and methicillin-resistant Staphylococcus aureus-induced sepsis. Heart rate and blood pressure variability analyses were investigated to track the varying levels of physiologic deterioration but did not discriminate early nonsurvivors from survivors.
Sex differences in sympathetic vasoconstrictor responsiveness and sympatholysis
Authors: Just Timothy P. , DeLorey Darren S. 
Published: May 2017

Sex differences in the neurovascular control of blood pressure and vascular resistance have been reported. However, the mechanisms underlying the modulatory influence of sex have not been fully elucidated. Nitric oxide (NO) has been shown to inhibit sympathetic vasoconstriction in resting and contracting skeletal muscle, and estrogen modulates NO synthase (NOS) expression and NO bioavailability. Therefore NO-mediated inhibition of sympathetic vasoconstriction may be enhanced in females. Thus the purpose of the present study was to investigate the hypothesis that sympathetic vasoconstrictor responsiveness would be blunted and NO-mediated inhibition of sympathetic vasoconstriction would be enhanced in females compared with males. Male (M; n = 8) and female (F; n = 10) Sprague-Dawley rats were anesthetized and surgically instrumented for measurement of arterial blood pressure and femoral artery blood flow and stimulation of the lumbar sympathetic chain. The percentage change of femoral vascular conductance in response to sympathetic chain stimulation delivered at 2 and 5 Hz was determined at rest and during triceps surae muscle contraction before (control) and after NOS blockade [ Nω-nitro-l-arginine methyl ester (l-NAME), 10 mg/kg iv]. At rest, sympathetic vasoconstrictor responsiveness was augmented ( P < 0.05) in female compared with male rats at 2 Hz [F: −33 ± 8% (SD); M: −26 ± 6%] but was not different at 5 Hz (F: −55 ± 7%; M: −47 ± 7%). During muscle contraction, evoked vasoconstriction was similar ( P > 0.05) in females and males at 2 Hz (F: −12 ± 5%; M: −13 ± 5%) but was blunted ( P < 0.05) in females compared with males at 5 Hz (F: −24 ± 5%; M: −34 ± 8%). l-NAME increased ( P < 0.05) sympathetic vasoconstrictor responsiveness in both groups at rest and during contraction. Contraction-mediated inhibition of vasoconstriction (sympatholysis) was enhanced ( P < 0.05) in females compared with males; however, sympatholysis was not different ( P > 0.05) between males and females in the presence of NOS blockade, indicating that NO-mediated sympatholysis was augmented in female rats. These data suggest that sex modulates sympathetic vascular control in resting and contracting skeletal muscle and that a portion of the enhanced sympatholysis in female rats was NO dependent. NEW & NOTEWORTHY Sex differences in the neurovascular regulation of blood pressure and vascular resistance have been documented. However, our understanding of the underlying mechanisms that mediate these differences is incomplete. The present study demonstrates that female rats have an enhanced capacity to inhibit sympathetic vasoconstriction during exercise (sympatholysis) and that NO mediates a portion of the enhanced sympatholysis.
Evidence for β-adrenergic modulation of sweating during incremental exercise in habitually trained males
Authors: Amano Tatsuro , Shitara Yosuke , Fujii Naoto , Inoue Yoshimitsu , Kondo Narihiko 
Published: May 2017

The aim of the present study was to determine the β-adrenergic contribution to sweating during incremental exercise in habitually trained males. Nine habitually trained and 11 untrained males performed incremental cycling until exhaustion (20 W/min). Bilateral forearm sweat rates (ventilated capsule) were measured at two skin sites that were transdermally administered via iontophoresis with either 1% propranolol (Propranolol, a nonselective β-adrenergic receptor antagonist) or saline (Control). The sweat rate was evaluated as a function of both relative (percentage of maximum workload) and absolute exercise intensities. The sweat rate at the Propranolol site was lower than the control during exercise at 80 (0.57 ± 0.21 and 0.45 ± 0.19 mg·cm−2·min−1 for Control and Propranolol, respectively) and 90% (0.74 ± 0.22 and 0.65 ± 0.17 mg·cm−2·min−1, respectively) of maximum workload in trained males (all P < 0.05). By contrast, no between-site differences in sweat rates were observed in untrained counterparts (all P > 0.05). At the same absolute intensity, higher sweat rates on the control site were observed in trained males relative to the untrained during exercise at 160 (0.23 ± 0.20 and 0.04 ± 0.05 mg·cm−2·min−1 for trained and untrained, respectively) and 180 W (0.40 ± 0.20 and 0.13 ± 0.13 mg·cm−2·min−1, respectively) (all P < 0.05), whereas this between-group difference was not observed at the Propranolol site (all P > 0.05). We show that the β-adrenergic mechanism does modulate sweating during exercise at a submaximal high relative intensity in habitually trained males. The β-adrenergic mechanism may in part contribute to the greater sweat production in habitually trained males than in untrained counterparts during exercise. NEW & NOTEWORTHY We demonstrated for the first time that the β-adrenergic mechanism does modulate sweating (i.e., β-adrenergic sweating) during exercise using a localized β-adrenoceptor blockade in humans in vivo. β-Adrenergic sweating was evident in habitually trained individuals during exercise at a submaximal high relative intensity (80–90% maximal work). This observation advances our understanding of human thermoregulation during exercise and of the mechanism that underlies sweat gland adaptation to habitual exercise training.
Lower limb explosive strength capacity in elderly women: effects of resistance training and healthy diet
Authors: Edholm Peter , Strandberg Emelie , Kadi Fawzi 
Published: May 2017

The effects of 24 wk of resistance training combined with a healthy diet on lower limb explosive strength capacity were investigated in a population of healthy elderly women. Participants ( n = 63; 67.5 ± 0.4 yr) were randomized into three groups; resistance training (RT), resistance training and healthy diet (RT-HD), and control (CON). Progressive resistance training was performed at a load of 75–85% one-repetition maximum. A major adjustment in the healthy dietary approach was an n-6/n-3 polyunsaturated fatty acid (PUFA) ratio below 2. Lower limb maximal strength, explosive force capacity during dynamic and isometric movements, whole body lean mass, and physical function were assessed. Whole body lean mass significantly increased by 1.5 ± 0.5% in RT-HD only. Isometric strength performance during knee extension as well as the performance in the five sit-to-stand and single-leg-stance tests increased similarly in RT and RT-HD. Improvements in dynamic peak power and time to reach peak power (i.e shorter time) during knee extension occurred in both RT (+15.7 ± 2.6 and −11.0 ± 3.8%, respectively) and RT-HD (+24.6 ± 2.6 and −20.3 ± 2.7%, respectively); however, changes were significantly larger in RT-HD. Similarly, changes in peak force and rate of force development during squat jump were higher in RT-HD (+58.5 ± 8.4 and +185.4 ± 32.9%, respectively) compared with RT (+35.7 ± 6.9 and +105.4 ± 22.4%, respectively). In conclusion, a healthy diet rich in n-3 PUFA can optimize the effects of resistance training on dynamic explosive strength capacity during isolated lower limb movements and multijoint exercises in healthy elderly women. NEW & NOTEWORTHY Age-related decline in lower limb explosive strength leads to impaired ability to perform daily living tasks. The present randomized controlled trial demonstrates that a healthy diet rich in n-3 polyunsaturated fatty acid (n-3 PUFA) enhances resistance training-induced gains in dynamic explosive strength capacity during isolated lower limb movements and multijoint exercises in healthy elderly women. This supports the use of strategies combining resistance training and dietary changes to mitigate the decline in explosive strength capacity in older adults.
Discovery and Characterization of Novel Nonsubstrate and Substrate NAMPT Inhibitors
Authors: Wilsbacher Julie L. , Cheng Min , Cheng Dong , Trammell Samuel A.J. , Shi Yan , Guo Jun , Koeniger Stormy L. , Kovar Peter J. , He Yupeng , Selvaraju Sujatha , Heyman H. Robin , Sorensen Bryan K. , Clark Richard F. , Hansen T. Matthew , Longenecker Kenton L. , Raich Diana , Korepanova Alla V. , Cepa Steven , Towne Danli L. , Abraham Vivek C. , Tang Hua , Richardson Paul L. , McLoughlin Shaun M. , Badagnani Ilaria , Curtin Michael L. , Michaelides Michael R. , Maag David , Buchanan F. Gregory , Chiang Gary G. , Gao Wenqing , Rosenberg Saul H. , Brenner Charles , Tse Chris 
Published: May 2017

Abstract
Cancer cells are highly reliant on NAD+-dependent processes, including glucose metabolism, calcium signaling, DNA repair, and regulation of gene expression. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme for NAD+ salvage from nicotinamide, has been investigated as a target for anticancer therapy. Known NAMPT inhibitors with potent cell activity are composed of a nitrogen-containing aromatic group, which is phosphoribosylated by the enzyme. Here, we identified two novel types of NAM-competitive NAMPT inhibitors, only one of which contains a modifiable, aromatic nitrogen that could be a phosphoribosyl acceptor. Both types of compound effectively deplete cellular NAD+, and subsequently ATP, and produce cell death when NAMPT is inhibited in cultured cells for more than 48 hours. Careful characterization of the kinetics of NAMPT inhibition in vivo allowed us to optimize dosing to produce sufficient NAD+ depletion over time that resulted in efficacy in an HCT116 xenograft model. Our data demonstrate that direct phosphoribosylation of competitive inhibitors by the NAMPT enzyme is not required for potent in vitro cellular activity or in vivo antitumor efficacy. Mol Cancer Ther; 16(7); 1236–45. ©2017 AACR.