bluuebunny/crossref_metadata_2025 huggingface dataset:
Sodium and potassium regulate endothelial phospholipase C-γ and Bmx
Authors: Ying Wei-Zhong , Aaron Kristal J. , Sanders Paul W.
Published: May 2014

The amount of Na+and K+in the diet promotes significant changes in endothelial cell function. In the present study, a series of in vitro and in vivo experiments determined the role of Na+and K+in the regulation of two pleckstrin homology domain-containing intracellular signaling molecules, phospholipase C (PLC)-γ1and epithelial and endothelial tyrosine kinase/bone marrow tyrosine kinase on chromosome X (Bmx), and agonist-generated Ca2+signaling in the endothelium. Extracellular K+concentration regulated the levels of activated PLC-γ1, Bmx, and carbachol-stimulated intracellular Ca2+mobilization in human endothelial cells. Additional experiments confirmed that high-conductance Ca2+-activated K+channels and phosphatidylinositol 3-kinase mediated these effects. The content of Na+and K+in the diet also regulated Bmx levels in endothelial cells and activated PLC-γ1levels in rats in vivo. The effects of dietary K+on Bmx were more pronounced in rats fed a high-salt diet compared with rats fed a low-salt diet. These experiments elucidated an endothelial cell signaling mechanism regulated by electrolytes, further demonstrating an integral relationship between endothelial cell function and dietary Na+and K+content.
Body stability and muscle and motor cortex activity during walking with wide stance
Authors: Farrell Brad J. , Bulgakova Margarita A. , Beloozerova Irina N. , Sirota Mikhail G. , Prilutsky Boris I.
Published: May 2014

Biomechanical and neural mechanisms of balance control during walking are still poorly understood. In this study, we examined the body dynamic stability, activity of limb muscles, and activity of motor cortex neurons [primarily pyramidal tract neurons (PTNs)] in the cat during unconstrained walking and walking with a wide base of support (wide-stance walking). By recording three-dimensional full-body kinematics we found for the first time that during unconstrained walking the cat is dynamically unstable in the forward direction during stride phases when only two diagonal limbs support the body. In contrast to standing, an increased lateral between-paw distance during walking dramatically decreased the cat's body dynamic stability in double-support phases and prompted the cat to spend more time in three-legged support phases. Muscles contributing to abduction-adduction actions had higher activity during stance, while flexor muscles had higher activity during swing of wide-stance walking. The overwhelming majority of neurons in layer V of the motor cortex, 82% and 83% in the forelimb and hindlimb representation areas, respectively, were active differently during wide-stance walking compared with unconstrained condition, most often by having a different depth of stride-related frequency modulation along with a different mean discharge rate and/or preferred activity phase. Upon transition from unconstrained to wide-stance walking, proximal limb-related neuronal groups subtly but statistically significantly shifted their activity toward the swing phase, the stride phase where most of body instability occurs during this task. The data suggest that the motor cortex participates in maintenance of body dynamic stability during locomotion.
The flexible recruitment of muscle synergies depends on the required force-generating capability
Authors: Hagio Shota , Kouzaki Motoki
Published: May 2014

To simplify redundant motor control, the central nervous system (CNS) may modularly organize and recruit groups of muscles as “muscle synergies.” However, smooth and efficient movements are expected to require not only low-dimensional organization, but also flexibility in the recruitment or combination of synergies, depending on force-generating capability of individual muscles. In this study, we examined how the CNS controls activations of muscle synergies as changing joint angles. Subjects performed multidirectional isometric force generations around right ankle and extracted the muscle synergies using nonnegative matrix factorization across various knee and hip joint angles. As a result, muscle synergies were selectively recruited with merging or decomposition as changing the joint angles. Moreover, the activation profiles, including activation levels and the direction indicating the peak, of muscle synergies across force directions depended on the joint angles. Therefore, we suggested that the CNS selects appropriate muscle synergies and controls their activation patterns based on the force-generating capability of muscles with merging or decomposing descending neural inputs.
Directional selective neurons in the awake LGN: response properties and modulation by brain state
Authors: Hei (黑晓娟) Xiaojuan , Stoelzel Carl R. , Zhuang (庄骏) Jun , Bereshpolova Yulia , Huff Joseph M. , Alonso Jose-Manuel , Swadlow Harvey A.
Published: May 2014

Directionally selective (DS) neurons are found in the retina and lateral geniculate nucleus (LGN) of rabbits and rodents, and in rabbits, LGN DS cells project to primary visual cortex. Here, we compare visual response properties of LGN DS neurons with those of layer 4 simple cells, most of which show strong direction/orientation selectivity. These populations differed dramatically, suggesting that DS cells may not contribute significantly to the synthesis of simple receptive fields: 1) whereas the first harmonic component (F1)-to-mean firing rate (F0) ratios of LGN DS cells are strongly nonlinear, those of simple cells are strongly linear; 2) whereas LGN DS cells have overlapped ON/OFF subfields, simple cells have either a single ON or OFF subfield or two spatially separate subfields; and 3) whereas the preferred directions of LGN DS cells are closely tied to the four cardinal directions, the directional preferences of simple cells are more evenly distributed. We further show that directional selectivity in LGN DS neurons is strongly enhanced by alertness via two mechanisms, 1) an increase in responses to stimulation in the preferred direction, and 2) an enhanced suppression of responses to stimuli moving in the null direction. Finally, our simulations show that these two consequences of alertness could each serve, in a vector-based population code, to hasten the computation of stimulus direction when rabbits become alert.
Emergence of band-pass filtering through adaptive spiking in the owl's cochlear nucleus
Authors: Fontaine Bertrand , MacLeod Katrina M. , Lubejko Susan T. , Steinberg Louisa J. , Köppl Christine , Peña Jose L.
Published: May 2014

In the visual, auditory, and electrosensory modalities, stimuli are defined by first- and second-order attributes. The fast time-pressure signal of a sound, a first-order attribute, is important, for instance, in sound localization and pitch perception, while its slow amplitude-modulated envelope, a second-order attribute, can be used for sound recognition. Ascending the auditory pathway from ear to midbrain, neurons increasingly show a preference for the envelope and are most sensitive to particular envelope modulation frequencies, a tuning considered important for encoding sound identity. The level at which this tuning property emerges along the pathway varies across species, and the mechanism of how this occurs is a matter of debate. In this paper, we target the transition between auditory nerve fibers and the cochlear nucleus angularis (NA). While the owl's auditory nerve fibers simultaneously encode the fast and slow attributes of a sound, one synapse further, NA neurons encode the envelope more efficiently than the auditory nerve. Using in vivo and in vitro electrophysiology and computational analysis, we show that a single-cell mechanism inducing spike threshold adaptation can explain the difference in neural filtering between the two areas. We show that spike threshold adaptation can explain the increased selectivity to modulation frequency, as input level increases in NA. These results demonstrate that a spike generation nonlinearity can modulate the tuning to second-order stimulus features, without invoking network or synaptic mechanisms.
A neuromechanical strategy for mediolateral foot placement in walking humans
Authors: Rankin Bradford L. , Buffo Stephanie K. , Dean Jesse C.
Published: May 2014

Stability is an important concern during human walking and can limit mobility in clinical populations. Mediolateral stability can be efficiently controlled through appropriate foot placement, although the underlying neuromechanical strategy is unclear. We hypothesized that humans control mediolateral foot placement through swing leg muscle activity, basing this control on the mechanical state of the contralateral stance leg. Participants walked under Unperturbed and Perturbed conditions, in which foot placement was intermittently perturbed by moving the right leg medially or laterally during the swing phase (by ∼50–100 mm). We quantified mediolateral foot placement, electromyographic activity of frontal-plane hip muscles, and stance leg mechanical state. During Unperturbed walking, greater swing-phase gluteus medius (GM) activity was associated with more lateral foot placement. Increases in GM activity were most strongly predicted by increased mediolateral displacement between the center of mass (CoM) and the contralateral stance foot. The Perturbed walking results indicated a causal relationship between stance leg mechanics and swing-phase GM activity. Perturbations that reduced the mediolateral CoM displacement from the stance foot caused reductions in swing-phase GM activity and more medial foot placement. Conversely, increases in mediolateral CoM displacement caused increased swing-phase GM activity and more lateral foot placement. Under both Unperturbed and Perturbed conditions, humans controlled their mediolateral foot placement by modulating swing-phase muscle activity in response to the mechanical state of the contralateral leg. This strategy may be disrupted in clinical populations with a reduced ability to modulate muscle activity or sense their body's mechanical state.
Ion/Water Channels for Embryo Implantation Barrier
Authors: Liu Xin-Mei , Zhang Dan , Wang Ting-Ting , Sheng Jian-Zhong , Huang He-Feng
Published: May 2014

Successful implantation involves three distinct processes, namely the embryo apposition, attachment, and penetration through the luminal epithelium of the endometrium to establish a vascular link to the mother. After penetration, stromal cells underlying the epithelium differentiate and surround the embryo to form the embryo implantation barrier, which blocks the passage of harmful substances to the embryo. Many ion/water channel proteins were found to be involved in the process of embryo implantation. First, ion/water channel proteins play their classical role in establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of ions across the cell membrane. Second, most of ion/water channel proteins are regulated by steroid hormone (estrogen or progesterone), which may have important implications to the embryo implantation. Last but not least, these proteins do not limit themselves as pure channels but also function as an initiator of a series of consequences once activated by their ligand/stimulator. Herein, we discuss these new insights in recent years about the contribution of ion/water channels to the embryo implantation barrier construction during early pregnancy.
Beyond the Genome: Epigenetic Mechanisms in Lung Remodeling
Authors: Hagood James S.
Published: May 2014

The lung develops from a very simple outpouching of the foregut into a highly complex, finely structured organ with multiple specialized cell types that are required for its normal physiological function. During both the development of the lung and its remodeling in the context of disease or response to injury, gene expression must be activated and silenced in a coordinated manner to achieve the tremendous phenotypic heterogeneity of cell types required for homeostasis and pathogenesis. Epigenetic mechanisms, consisting of DNA base modifications such as methylation, alteration of histones resulting in chromatin modification, and the action of noncoding RNA, control the regulation of information “beyond the genome” required for both lung modeling and remodeling. Epigenetic regulation is subject to modification by environmental stimuli, such as oxidative stress, infection, and aging, and is thus critically important in chronic remodeling disorders such as idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), bronchopulmonary dysplasia (BPD), and pulmonary hypertension (PH). Technological advances have made it possible to evaluate genome-wide epigenetic changes (epigenomics) in diseases of lung remodeling, clarifying existing pathophysiological paradigms and uncovering novel mechanisms of disease. Many of these represent new therapeutic targets. Advances in epigenomic technology will accelerate our understanding of lung development and remodeling, and lead to novel treatments for chronic lung diseases.
Alcohol Abuse: Critical Pathophysiological Processes and Contribution to Disease Burden
Authors: Molina Patricia E. , Gardner Jason D. , Souza-Smith Flavia M. , Whitaker Annie M.
Published: May 2014

Alcohol abuse; the most common and costly form of drug abuse, is a major contributing factor to many disease categories. The alcohol-attributable disease burden is closely related to the average volume of alcohol consumption, with dose-dependent relationships between amount and duration of alcohol consumption and the incidence of diabetes mellitus, hypertension, cardiovascular disease, stroke, and pneumonia. The frequent occurrence of alcohol use disorders in the adult population and the significant and widespread detrimental organ system effects highlight the importance of recognizing and further investigating the pathophysiological mechanisms underlying alcohol-induced tissue and organ injury.
The Brain Melanocortin System, Sympathetic Control, and Obesity Hypertension
Authors: da Silva Alexandre A. , do Carmo Jussara M. , Wang Zhen , Hall John E.
Published: May 2014

Excess weight gain is the most significant, preventable cause of increased blood pressure (BP) in patients with primary (essential) hypertension and increases the risk for cardiovascular and renal diseases. In this review, we discuss the role of the brain melanocortin system in causing increased sympathetic activity in obesity and other forms of hypertension. In addition, we highlight potential mechanisms by which the brain melanocortin system modulates metabolic and cardiovascular functions.
NFE2L2 polymorphisms, mortality, and metabolism in the general population
Authors: Figarska Sylwia M. , Vonk Judith M. , Boezen H. Marike
Published: May 2014

The nuclear factor (erythroid-derived 2)-like 2 ( NFE2L2 or NRF2) gene regulates transcription of enzymes involved in cellular detoxification and lipids homeostasis. NFE2L2 is associated with pathophysiology of atherosclerosis and chronic obstructive pulmonary disease (COPD). Therefore we studied the relation between NFE2L2 and all-cause, cardiovascular, and COPD mortality and its associations with triglyceride and cholesterol levels. We genotyped five tagging single nucleotide polymorphisms (SNPs) (rs4243387, rs2364723, rs13001694, rs1806649, and rs6726395) in NFE2L2 in 1,390 subjects from the Vlagtwedde-Vlaardingen cohort. Participants were examined in 1989/1990 and followed up till the vital status evaluation on December 31st, 2008. Associations between SNPs and mortality were estimated by Cox proportional hazards regression, and associations between SNPs and triglyceride and cholesterol levels were tested with linear regression. After 18 yr, 284 (20.4%) subjects had died, 107 from cardiovascular disease and 20 from COPD. Minor allele carriers of rs13001694 had a significantly reduced risk of all-cause mortality compared with wild types: hazard ratio (HR) 0.8 [95% confidence interval (CI) 0.6 to 1.0]. Minor allele carriers of rs2364723 had significantly reduced risk of cardiovascular mortality: HR = 0.5 (95% CI: 0.3–0.7). This result was consistent in stratified analyses: females 0.4 (0.2–0.7), males 0.6 (0.3–0.9), never smokers 0.5 (0.2–1.1), ever smokers 0.5 (0.3–0.8). Minor allele carriers of rs1806649 had a markedly reduced COPD mortality: HR = 0.3 (95% CI: 0.1–0.9). Rs2364723 was associated with lower triglyceride levels. None of the SNPs was associated with cholesterol levels. This study shows for the first time that NFE2L2 is associated with reduced risk of all-cause, cardiovascular and COPD mortality in humans.
The Natural History of Cervical Cancer in Chinese Women: Results from an 11-Year Follow-Up Study in China Using a Multistate Model
Authors: Zhang Shao-Kai , Kang Le-Ni , Chang Irene J. , Zhao Fang-Hui , Hu Shang-Ying , Chen Wen , Shi Ju-Fang , Zhang Xun , Pan Qin-Jing , Li Shu-Min , Qiao You-Lin
Published: May 2014

Background: It is important to understand the natural history of cervical cancer, which has implications for cancer prevention and management. However, a dearth of studies on the long-term development of cervical cancer exists in China.

Methods: We investigated the natural history of cervical cancer in Chinese women by creating a multistate model using 11 years of follow-up data from the Shanxi Province Cervical Cancer Screening Study I conducted from 1999 to 2010. In 1999, a total of 1,997 eligible women, ages 35 to 45 years, were enrolled in Xiangyuan County, Shanxi Province. Participants were followed up in 2005 and 2010, respectively.

Results: The average time a subject spent in CIN1 before transiting into another state was 1.4693 years [95% confidence interval (CI): 1.1215–1.9251] and the average time a subject spent in CIN2 was 2.9822 years (95% CI: 1.9790–4.4938). A subject's transition probability from CIN1 to normal increased with time. However, the transition probability from CIN1 to CIN2 was relatively lower, with 3-, 5-, and 10-year transition probabilities of 0.1415, 0.1066, and 0.0437. Comparison of 5-year transition probabilities between CIN2 to normal/CIN1 and CIN2 to CIN3+ yielded a ratio of 2.74.

Conclusions: Women with CIN1 had a substantial tendency for regression. Similarly, women with CIN2 had a higher probability of regression to normal/CIN1 than progression to CIN3+. Findings in this study may have significant implications for the development and evaluation of formal cervical cancer preventive strategies in China.

Impact: This study may serve as a valuable reference to future research on other multistate cancer processes. Cancer Epidemiol Biomarkers Prev; 23(7); 1298–305. ©2014 AACR.
One-Carbon Metabolism Dietary Factors and Distal Gastric Cancer Risk in Chinese Women
Authors: Kweon Sun-Seog , Shu Xiao-Ou , Xiang Yongbing , Yang Gong , Ji Bu-Tian , Li Honglan , Gao Yu-Tang , Zheng Wei , Shrubsole Martha J.
Published: May 2014

Background: Previous studies on the association between one-carbon dietary factors and gastric cancer risk have been inconsistent.

Methods: We investigated this association using data from a prospective study, the Shanghai Women's Health Study (1997–2010), including 323 distal gastric cancer cases identified from 73,009 Chinese women. HRs and 95% confidence intervals (CI) were estimated using Cox proportional hazard regression after adjusting for confounders.

Results: Overall, no statistically significant association of gastric cancer was observed with dietary intake of folate, methionine, or B vitamins. However, when stratified by menopausal status, higher intake of riboflavin was associated with decreased gastric cancer risk in premenopausal women with HR of 0.35 (95% CI, 0.17–0.73), 0.48 (0.24–0.97), 0.28 (0.12–0.65), and 0.23 (0.07–0.91), respectively, for the quintiles 2 to 5 intake groups compared with the lowest quintile intake (P for trend = 0.02). Among premenopausal women, highest intake of folate was associated with increased gastric cancer risk (HR, 2.62; 95% CI, 1.04–6.59). There were no statistically significant associations observed among postmenopausal women.

Conclusions: These results suggest that dietary factors involved in one-carbon metabolism are associated with gastric cancer risk among premenopausal women.

Impact: Riboflavin may be a protective factor and folate may be a risk factor for premenopausal gastric cancer. Cancer Epidemiol Biomarkers Prev; 23(7); 1374–82. ©2014 AACR.
FANCD2 Is a Potential Therapeutic Target and Biomarker in Alveolar Rhabdomyosarcoma Harboring the PAX3–FOXO1 Fusion Gene
Authors: Singh Mamata , Leasure Justin M. , Chronowski Christopher , Geier Brian , Bondra Kathryn , Duan Wenrui , Hensley Lauren A. , Villalona-Calero Miguel , Li Ning , Vergis Anthony M. , Kurmasheva Raushan T. , Shen Changxian , Woods Gary , Sebastian Nikhil , Fabian Denise , Kaplon Rita , Hammond Sue , Palanichamy Kamalakannan , Chakravarti Arnab , Houghton Peter J.
Published: May 2014

Purpose: Alveolar rhabdomyosarcoma that harbors the PAX3–FOXO1 fusion gene (t-ARMS) is a common and lethal subtype of this childhood malignancy. Improvement in clinical outcomes in this disease is predicated upon the identification of novel therapeutic targets.

Experimental Design: Robust mouse models were used for in vivo analysis, and molecular studies were performed on xenografts treated in parallel. Two independent patient sets (n = 101 and 124) of clinically annotated tumor specimens were used for analysis of FANCD2 levels and its association with clinical and molecular characteristics and outcomes.

Results: Our xenograft studies reveal a selective suppression of FANCD2 by m-TOR kinase inhibition and radiosensitization of the t-ARMS line only. In the initial patient set, we show that FANCD2 transcript levels are prognostic in univariate analysis, and are significantly associated with metastatic disease and that the copresence of the translocation and high expression of FANCD2 is independently prognostic. We also demonstrate a significant and nonrandom enrichment of mTOR-associated genes that correlate with FANCD2 gene expression within the t-ARMS samples, but not within other cases. In the second patient set, we show that on a protein level, FANCD2 expression correlates with PAX3–FOXO1 fusion gene and is strongly associated with phospho-P70S6K expression in cases with the fusion gene.

Conclusions: Our data demonstrate that FANCD2 may have a significant role in the radiation resistance and virulence of t-ARMS. Indirectly targeting this DNA repair protein, through mTOR inhibition, may represent a novel and selective treatment strategy. Clin Cancer Res; 20(14); 3884–95. ©2014 AACR.
Vitamin D Deficiency Predicts Prostate Biopsy Outcomes
Authors: Murphy Adam B. , Nyame Yaw , Martin Iman K. , Catalona William J. , Hollowell Courtney M.P. , Nadler Robert B. , Kozlowski James M. , Perry Kent T. , Kajdacsy-Balla Andre , Kittles Rick
Published: May 2014

Purpose: The association between vitamin D and prostate biopsy outcomes has not been evaluated. We examine serum vitamin D levels with prostate biopsy results in men with an abnormal prostate-specific antigen and/or digital rectal examination.

Experimental Design: Serum 25-hydroxyvitamin D (25-OH D) was obtained from 667 men, ages 40 to 79 years, prospectively enrolled from Chicago urology clinics undergoing first prostate biopsy. Logistic regression was used to evaluate the associations between 25-OH D status and incident prostate cancer, Gleason score, and tumor stage.

Results: Among European American (EA) men, there was an association of 25-OH D <12 ng/mL with higher Gleason score ≥ 4+4 [OR, 3.66; 95% confidence interval (CI), 1.41–9.50; P = 0.008] and tumor stage [stage ≥ cT2b vs. ≤ cT2a, OR, 2.42 (1.14–5.10); P = 0.008]. In African American (AA) men, we find increased odds of prostate cancer diagnosis on biopsy with 25-OH D < 20 ng/mL [OR, 2.43 (1.20–4.94); P = 0.01]. AA men demonstrated an association between 25-OH D < 12 ng/mL and Gleason ≥ 4+4 [OR, 4.89 (1.59–15.07); P = 0.006]. There was an association with tumor stage ≥ cT2b vs. ≤ cT2a [OR, 4.22 (1.52–11.74); P = 0.003].

Conclusions: In AA men, vitamin D deficiency was associated with increased odds of prostate cancer diagnosis on biopsy. In both EA and AA men, severe deficiency was positively associated with higher Gleason grade and tumor stage. Clin Cancer Res; 20(9); 2289–99. ©2014 AACR.
Vitamin D Status: Ready for Guiding Prostate Cancer Diagnosis and Treatment?
Authors: Grant William B.
Published: May 2014

Vitamin D deficiency is associated with increased risk of prostate cancer for those with elevated prostate-specific antigen (PSA) level or abnormal digital rectal examination. Vitamin D deficiency is also associated with aggressive prostate cancer. Vitamin D level could be added as an additional factor to consider before ordering a biopsy. Clin Cancer Res; 20(9); 2241–3. ©2014 AACR.
Preferential Estrogen Receptor β Ligands Reduce Bcl-2 Expression in Hormone-Resistant Breast Cancer Cells to Increase Autophagy
Authors: Ruddy Samantha C. , Lau Rosanna , Cabrita Miguel A. , McGregor Chelsea , McKay Bruce C. , Murphy Leigh C. , Wright James S. , Durst Tony , Pratt M.A. Christine
Published: May 2014

Acquired resistance to selective estrogen receptor (ER) modulators (SERM) and downregulators (SERD) is a significant clinical problem in the treatment of estrogen (E2) receptor-positive (ER+) breast cancers. There are two ER subtypes, ERα and ERβ, which promote and inhibit breast cancer cell proliferation, respectively. Although ER+ breast cancers typically express a high ratio of ERα to ERβ, the acquisition of SERM resistance in vitro and in vivo is associated with increased relative expression of the ERβ. On some gene enhancers, ERβ has been shown to function in opposition to the ERα in the presence of E2. Here, we demonstrate that two different ERβ agonists, WAY-20070 and a novel “A-CD” estrogen called L17, produce a marked reduction in G2–M phase correlated with effects on cyclin D1 and cyclin E expression in a SERM/SERD-resistant breast cancer cell line. ERβ agonists recruited both the ERα and ERβ to the Bcl-2 E2-response element strongly reducing Bcl-2 mRNA and protein in an ERβ-dependent manner. L17 recruited RIP140 to the Bcl-2 promoter in cells overexpressing ERβ. Exposure to the ERβ ligands also resulted in increased processing of LC3-I to LC3-II, indicative of enhanced autophagic flux. The coaddition of ERβ agonist and the autophagy inhibitor chloroquine resulted in a significant accumulation of sub-G1 DNA which was completely prevented by the addition of the caspase inhibitor Z-VAD-FMK. We propose that combined therapies with an ERβ agonist and an inhibitor of autophagy may provide the basis for a novel approach to the treatment of SERM/SERD-resistant breast cancers. Mol Cancer Ther; 13(7); 1882–93. ©2014 AACR.
SPSB1 Promotes Breast Cancer Recurrence by Potentiating c-MET Signaling
Authors: Feng Yi , Pan Tien-Chi , Pant Dhruv K. , Chakrabarti Kristi R. , Alvarez James V. , Ruth Jason R. , Chodosh Lewis A.
Published: May 2014

Breast cancer mortality is principally due to tumor recurrence; however, the molecular mechanisms underlying this process are poorly understood. We now demonstrate that the suppressor of cytokine signaling protein SPSB1 is spontaneously upregulated during mammary tumor recurrence and is both necessary and sufficient to promote tumor recurrence in genetically engineered mouse models. The recurrence-promoting effects of SPSB1 result from its ability to protect cells from apoptosis induced by HER2/neu pathway inhibition or chemotherapy. This, in turn, is attributable to SPSB1 potentiation of c-MET signaling, such that preexisting SPSB1-overexpressing tumor cells are selected for following HER2/neu downregulation. Consistent with this, SPSB1 expression is positively correlated with c-MET activity in human breast cancers and with an increased risk of relapse in patients with breast cancer in a manner that is dependent upon c-MET activity. Our findings define a novel pathway that contributes to breast cancer recurrence and provide the first evidence implicating SPSB proteins in cancer.

Significance: The principal cause of death from breast cancer is recurrence. This study identifies SPSB1 as a critical mediator of breast cancer recurrence, suggests activation of the SPSB1–c-MET pathway as an important mechanism of therapeutic resistance in breast cancers, and emphasizes that pharmacologic targets for recurrence may be unique to this stage of tumor progression. Cancer Discov; 4(7); 790–803. ©2014 AACR.

See related commentary by Qin and McAllister, p. 760

This article is highlighted in the In This Issue feature, p. 745
Predictors of Spontaneous Reverse Remodeling in Mild Heart Failure Patients With Left Ventricular Dysfunction
Authors: Brenyo Andrew , Barsheshet Alon , Kutyifa Valentina , Ruwald Anne-Christine , Rao Mohan , Zareba Wojciech , Pouleur Anne-Catherine , Knappe Dorit , Solomon Scott D. , McNitt Scott , Huang David T. , Moss Arthur J. , Goldenberg Ilan
Published: May 2014

Background—

There are limited data regarding factors associated with spontaneous left ventricular reverse remodeling (S-LVRR) among mildly symptomatic heart failure (HF) patients and its prognostic implications on clinical outcomes.

Methods and Results—

Best subsets logistic regression analysis was used to identify factors associated with S-LVRR (defined as ≥15% reduction in left ventricular end-systolic volume at 1-year of follow-up) among 612 patients treated with internal cardioverter defibrillator–only therapy in Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT) and to create a score for the prediction of S-LVRR. Cox proportional hazards regression modeling was used to assess the clinical outcome of all internal cardioverter defibrillator–only patients (n=714) with a high S-LVRR score. S-LVRR occurred in 25% of internal cardioverter defibrillator–only patients. Predictors of S-LVRR included systolic blood pressure≥140 mm Hg, serum creatinine<1.0 mg/dL, QRS 130 to 160 ms, and nonischemic cardiomyopathy. Multivariate analysis showed that each 1-point increment in S-LVRR score (range, 0–7) was associated with an 11% (
P
=0.019) reduction in the risk of HF or death. Treatment with cardiac resynchronization therapy was associated with a significant reduction in the risk of HF or death only among internal cardioverter defibrillator–treated patients with a low (Q1–3) S-LVRR score (hazard ratio=0.55;
P
<0.001), but not among those with a higher (Q4) score (hazard ratio=1.06;
P
=0.72).

Conclusions—

Our data suggest that approximately one quarter of mild HF patients eligible for biventricular pacing experience S-LVRR. Combined assessment of clinical factors associated with S-LVRR can be used to identify mild HF patients with a low risk for clinical events without cardiac resynchronization therapy intervention.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00180271.
Extravirgin Olive Oil Consumption Reduces Risk of Atrial Fibrillation
Authors: Martínez-González Miguel Á. , Toledo Estefanía , Arós Fernando , Fiol Miquel , Corella Dolores , Salas-Salvadó Jordi , Ros Emilio , Covas Maria I. , Fernández-Crehuet Joaquín , Lapetra José , Muñoz Miguel A. , Fitó Monserrat , Serra-Majem Luis , Pintó Xavier , Lamuela-Raventós Rosa M. , Sorlí Jose V. , Babio Nancy , Buil-Cosiales Pilar , Ruiz-Gutierrez Valentina , Estruch Ramón , Alonso Alvaro ,   for the PREDIMED Investigators*
Published: May 2014

Background—

The PREDIMED (Prevención con Dieta Mediterránea) primary prevention trial showed that a Mediterranean diet enriched with either extravirgin olive oil or mixed nuts reduces the incidence of stroke, myocardial infarction, and cardiovascular mortality. We assessed the effect of these diets on the incidence of atrial fibrillation in the PREDIMED trial.

Methods and Results—

Participants were randomly assigned to 1 of 3 diets: Mediterranean diet supplemented with extravirgin olive oil, Mediterranean diet supplemented with mixed nuts, or advice to follow a low-fat diet (control group). Some departures from individual randomization occurred in a subset of the trial because members of the same household and small clinics in one of the 11 recruiting centers were allocated by clusters instead of individually. Incident atrial fibrillation was adjudicated during follow-up by an events committee blinded to dietary group allocation. Among 6705 participants without prevalent atrial fibrillation at randomization, we observed 72 new cases of atrial fibrillation in the Mediterranean diet with extravirgin olive oil group, 92 in the Mediterranean diet with mixed nuts group, and 89 in the control group after median follow-up of 4.7 years. The Mediterranean diet with extravirgin olive oil significantly reduced the risk of atrial fibrillation (hazard ratio, 0.62; 95% confidence interval, 0.45–0.86 compared with the control group) after adjusting for propensity scores and using robust variance estimators to account for the intra-cluster correlations. No effect was found for the Mediterranean diet with nuts (hazard ratio, 0.86; 95% confidence interval, 0.63–1.16). In secondary analyses done after excluding all participants randomized in clusters, the results did not materially change.

Conclusions—

In the absence of proven interventions for the primary prevention of atrial fibrillation, this post hoc analysis of the PREDIMED trial suggests that a lower incidence of atrial fibrillation was found after an intervention with extravirgin olive oil in the context of a Mediterranean dietary pattern.

Clinical Trial Registration—

URL:
http://www.controlled-trials.com
. Unique identifier: ISRCTN35739639.
The syrphids of Serra do Courel, Northern Spain and description of a new Cheilosia Meigen species (Diptera: Syrphidae)
Authors: RICARTE ANTONIO , ROTHERAY GRAHAM E. , LYSZKOWSKI RICHARD M. , HANCOCK E. GEOFFREY , HEWITT STEPHEN M. , WATT KENNETH R. , HORSFIELD DAVID , MACGOWAN IAIN
Published: May 2014

The syrphids (Syrphidae) of Serra do Courel, a mountainous locality of just over 20,000ha at the west end of the Cantabrian Mountains, northern Spain are poorly known. The Scottish based, Malloch Society visited the locality in May 2012 and collected a total of 462 specimens of 98 syrphid species and 36 genera. These represent the first syrphid records from Serra do Courel. The area has many meadows and small woodlands or ‘soutos’ and these habitats combined were the most productive, 69 spp. recorded. Cheilosia lucense Ricarte sp. nov. is described from Courel and compared with other species of the alpina group. Six other syrphid species were new to the Iberian Peninsula, three of which belong to the saproxylic genus, Brachyopa. In common with studies elsewhere in the Cantabrian Mountains, Cheilosia was the most diverse genus and 21 species were recorded. The syrphid fauna of the Cantabrian Mountains includes 203 species of which 24 are here added and a species checklist provided.
Revision of the Embolemidae of Japan (Hymenoptera: Chrysidoidea), with description of a new genus and two new species
Authors: OLMI MASSIMO , MITA TOSHIHARU , GUGLIELMINO ADALGISA
Published: May 2014

Seven species of Embolemidae are recognized in Japan. They belong to two genera: Embolemus Westwood 1833 and Trogloembolemus Olmi, Mita et Guglielmino, gen. nov. (type species T. fujiei Olmi, Mita et Guglielmino, sp. nov.) Embolemus honshuensis Olmi, Mita et Guglielmino, sp. nov. (Japan, Honshu) and Trogloembolemus fujiei Olmi, Mita & Guglielmino, sp. nov. (Japan, Honshu) are described and figured. A key to the genera and species of Japan is presented. Trogloembolemus fujiei sp. nov., collected in the soil at a depth of two metres and almost blind, is the first species of Embolemidae with troglobitic habitus.
A new species of Didogobius (Teleostei: Gobiidae) from the Canary Islands
Authors: VAN TASSELL JAMES L. , KRAMER ANNEMARIE
Published: May 2014

Didogobius helenae is described from the Canary Islands. It has a sensory papillae pattern that is consistent with the current diagnosis for Didogobius, but lacks all head canals and pores that are present in other members of the genus. Pores, in general, are replaced by large papillae.  The species is defined by first dorsal fin VI; second dorsal fin I,10; anal fin I,9; pectoral fin 16–17; pelvic fin I,5 and disk shaped; lateral scales 28–30, cycloid at anterior, becoming ctenoid posteriorly; cycloid scales present on belly and posterior breast; predorsal region, cheek, operculum and base of pectoral fin without scales; lower most scale on the caudal fin-base with elongate, thickened ctenii along the upper and lower posterior edges. Color in life consists of four mottled, wide brown-orange bars separated by narrower white bars on the trunk, the cheek whitish with 5 more or less circular blotches of orange, outlined in dark brown and a black spot on ventral operculum. A key to the species is provided.
Studies in Mexican Grasshoppers: Liladownsia fraile, a new genus and species of Dactylotini (Acrididae: Melanoplinae) and an updated molecular phylogeny of Melanoplinae
Authors: WOLLER DEREK A. , FONTANA PAOLO , MARIÑO-PÉREZ RICARDO , SONG HOJUN
Published: May 2014

Liladownsia fraile gen. nov. sp. nov. Fontana, Mariño-Pérez, Woller & Song (Lila Downs’ friar grasshopper) of the tribe Dactylotini (Orthoptera: Acrididae: Melanoplinae) is described from the pine-oak forest of the Sierra Madre del Sur Mountain Range in Oaxaca, Mexico. Taxonomic placement of this new genus is justified based on morphological characters as well as a molecular phylogeny. Information about the probable host plant, phenology, and known localities is also presented. We also present an updated molecular phylogeny of Melanoplinae, which includes representatives of five of the seven recognized tribes. The monophyly of the subfamily and the included tribes is tested and we find Dactylotini to be paraphyletic because of the placement of Hesperotettix Scudder, 1876. We also recover strong close relationships between the new genus and Perixerus Gerstaecker, 1873 and Dactylotum Charpentier, 1845.
Asprothrips bimaculatus sp.n. (Thripidae, Dendrothripinae) from Martinique
Authors: MICHEL BRUNO , RYCKEWAERT PHILIPPE
Published: May 2014

Asprothrips bimaculatus sp. n. is described from Martinique. It is unique among the five species now recognised in this genus in having the body sharply bicoloured, with the head and thorax dark but the abdomen white.
Dissociative identity disorder: An empirical overview
Authors: Dorahy Martin J , Brand Bethany L , Şar Vedat , Krüger Christa , Stavropoulos Pam , Martínez-Taboas Alfonso , Lewis-Fernández Roberto , Middleton Warwick
Published: May 2014

Objective:

Despite its long and auspicious place in the history of psychiatry, dissociative identity disorder (DID) has been associated with controversy. This paper aims to examine the empirical data related to DID and outline the contextual challenges to its scientific investigation.

Methods:

The overview is limited to DID-specific research in which one or more of the following conditions are met: (i) a sample of participants with DID was systematically investigated, (ii) psychometrically-sound measures were utilised, (iii) comparisons were made with other samples, (iv) DID was differentiated from other disorders, including other dissociative disorders, (v) extraneous variables were controlled or (vi) DID diagnosis was confirmed. Following an examination of challenges to research, data are organised around the validity and phenomenology of DID, its aetiology and epidemiology, the neurobiological and cognitive correlates of the disorder, and finally its treatment.

Results:

DID was found to be a complex yet valid disorder across a range of markers. It can be accurately discriminated from other disorders, especially when structured diagnostic interviews assess identity alterations and amnesia. DID is aetiologically associated with a complex combination of developmental and cultural factors, including severe childhood relational trauma. The prevalence of DID appears highest in emergency psychiatric settings and affects approximately 1% of the general population. Psychobiological studies are beginning to identify clear correlates of DID associated with diverse brain areas and cognitive functions. They are also providing an understanding of the potential metacognitive origins of amnesia. Phase-oriented empirically-guided treatments are emerging for DID.

Conclusions:

The empirical literature on DID is accumulating, although some areas remain under-investigated. Existing data show DID as a complex, valid and not uncommon disorder, associated with developmental and cultural variables, that is amenable to psychotherapeutic intervention.
The Family Liaison Position in High-Poverty, Urban Schools
Authors: Dretzke Beverly J. , Rickers Susan R.
Published: May 2014

This study examined the roles and responsibilities of family liaisons working in urban schools with enrollments characterized by high poverty, high mobility, and ethnic diversity. Results indicated that the major responsibilities of the liaisons were creating a trusting and welcoming environment, facilitating parent involvement in the school, keeping parents informed on school-related topics, and connecting parents with resources. During job shadows, family liaisons were primarily observed coordinating parent involvement activities, interacting with students, performing routine office tasks, and carrying out other duties as assigned (e.g., cafeteria supervision). To increase their effectiveness, the liaisons requested greater job clarity, more flexibility in their formal work hours, and less time spent on other duties as assigned. In general, it appeared that the family liaisons investigated in this study placed a stronger emphasis on creating a welcoming environment and establishing trust than has been found in research on family liaisons in more affluent communities.
PSAT Component Scores as a Predictor of Success on AP Exam Performance for Diverse Students
Authors: Richardson Cristianne C. , Gonzalez Alejandro , Leal Lonnie , Castillo Mary Z. , Carman Carol A.
Published: May 2014

While studies have shown the positive effect of the Advanced Placement (AP) program on college readiness, there are still barriers preventing minority and low socioeconomic status (SES) students who possess high academic potential from participating in the opportunity that AP courses offer. One tool that could help identify students for participation in AP courses is their Preliminary Scholastic Aptitude Test (PSAT) results. Results from multiple regression analyses suggest that portions of the PSAT are significant predictors of AP test performance above and beyond student ethnicity and/or SES.
Educating for the Global Agenda: Internationally relevant conceptual frameworks and knowledge for social work education
Authors: Healy Lynne M , Wairire Gidraph G
Published: May 2014

In this article, we discuss the capacity of social work educational programs to prepare graduates to contribute to the human, social and environmental challenges outlined in the Global Agenda for Social Work and Social Development. The educational sector must play a lead role through training and research. Using examples from Kenya and the United States, we argue more curriculum emphasis on such areas as social and economic development, human rights, and social integration is required. The article concludes with recommendations for strengthening curriculum and dialogue on the globally relevant concepts identified in the Global Agenda.
Using citizenship theory to challenge nationalist assumptions in the construction of international social work education
Authors: Moosa-Mitha Mehmoona
Published: May 2014

I argue that international social work education is constructed using nationalist assumptions that define and limit practices of social care to nation-state boundaries. This is particularly true of the profession as it is practiced in (neo)liberal welfare states of the global north. Using citizenship theory I interrogate interpretations of liberal citizenship to illuminate and analyze its relationship to nationalist definitions of social work practice. I posit an alternative notion of citizenship that defines citizenship more broadly in terms of participation and belonging irrespective of nation-state boundaries and acknowledges the transnational realities of people, social issues and socio-economic hierarchies.
Using Power Laws to Estimate Conflict Size
Authors: Friedman Jeffrey A.
Published: May 2014

Casualty counts are often controversial, and thorough research can only go so far in resolving such debates—there will almost always be missing data, and thus, a need to draw inferences about how comprehensively violence has been recorded. This article addresses that challenge by developing an estimation strategy based on the observation that violent events are generally distributed according to power laws, a pattern that structures expectations about what event data on armed conflict would look like if those data were complete. This technique is applied to estimate the number of Native American and US casualties in the American Indian Wars between 1776 and 1890, demonstrating how scholars can use power laws to estimate conflict size, even (and perhaps especially) where previous literature has been unable to do so.
Measurement Invariance, Response Styles, and Rural–Urban Measurement Comparability
Authors: Thomas Troy Devon , Abts Koen , Vander Weyden Patrick
Published: May 2014

This article investigates the effect of response styles (RSs) on rural–urban measurement comparability in Guyana. It uses the representative indicators response styles means and covariance structure (RIRSMACS) model and finds that traditional measurement invariance (MI) tests provide inadequate assurance of the absence of rural–urban measurement bias when RSs are not controlled. Even when MI is achieved, RSs can still differentially affect measurements and substantive results between rural and urban regions. In addition, a lack of MI may be at least partially due to RSs bias, but MI may also be due to RSs. Therefore, adjustments for RSs are necessary and researchers should be cautious about pooling data across rural and urban areas without controlling RSs.
Difficult Texts: Colossians 3.22 – Slaves, obey your earthly masters in everything
Authors: Carson Marion L. S.
Published: May 2014

According to the US State Department's Trafficking in Persons report there are 27 million people in slavery today. In the face of such suffering, the conventional interpretation of Colossians 3.22 as a rule for Christian behaviour in the workplace seems blinkered. This article suggests that the eighteenth-century Abolitionists' focus on the redeeming love of God, rather than rules for the individual, might help us to look beyond our own lives and towards serving others.
The Church of England and the love of learning
Authors: Bergquist Anders
Published: May 2014

This article draws attention to the Church of England's relative indifference to a strategy for the encouragement of research and scholarship within its ranks, especially among its clergy. Reasons are suggested for the continuing necessity of learning for the Church's flourishing, and suggestions are made for the promotion of scholarship outside avowedly academic institutions as well as within them.
St Gregory and managerialism
Authors: Lewis-Anthony Justin
Published: May 2014

The Church of England has always congratulated itself on its ecclesiological pragmatism, a pragmatism rooted in Augustine’s mission to Kent. Does this pragmatism encompass every secular innovation or should St Gregory’s directions to the Roman missionaries provide us with a proper scepticism when faced with some of the business world’s more ideological assumptions?