bluuebunny/crossref_metadata_2025 huggingface dataset:
A systems genetics approach identifiesTrp53inp2as a link between cardiomyocyte glucose utilization and hypertrophic response
Authors: Seldin Marcus M. , Kim Eric D. , Romay Milagros C. , Li Shen , Rau Christoph D. , Wang Jessica J. , Krishnan Karthickeyan Chella , Wang Yibin , Deb Arjun , Lusis Aldons J.
Published: February 2017

Cardiac failure has been widely associated with an increase in glucose utilization. The aim of our study was to identify factors that mechanistically bridge this link between hyperglycemia and heart failure. Here, we screened the Hybrid Mouse Diversity Panel (HMDP) for substrate-specific cardiomyocyte candidates based on heart transcriptional profile and circulating nutrients. Next, we utilized an in vitro model of rat cardiomyocytes to demonstrate that the gene expression changes were in direct response to substrate abundance. After overlaying candidates of interest with a separate HMDP study evaluating isoproterenol-induced heart failure, we chose to focus on the gene Trp53inp2 as a cardiomyocyte glucose utilization-specific factor. Trp53inp2 gene knockdown in rat cardiomyocytes reduced expression and protein abundance of key glycolytic enzymes. This resulted in reduction of both glucose uptake and glycogen content in cardiomyocytes stimulated with isoproterenol. Furthermore, this reduction effectively blunted the capacity of glucose and isoprotereonol to synergistically induce hypertrophic gene expression and cell size expansion. We conclude that Trp53inp2 serves as regulator of cardiomyocyte glycolytic activity and can consequently regulate hypertrophic response in the context of elevated glucose content.

NEW & NOTEWORTHY Here, we apply a novel method for screening transcripts based on a substrate-specific expression pattern to identify Trp53inp2 as an induced cardiomyocyte glucose utilization factor. We further show that reducing expression of the gene could effectively blunt hypertrophic response in the context of elevated glucose content.
Cardiovascular consequences of the inspiratory muscle metaboreflex: effects of age and sex
Authors: Smith Joshua R. , Alexander Andrew M. , Hammer Shane M. , Didier Kaylin D. , Kurti Stephanie P. , Broxterman Ryan M. , Barstow Thomas J. , Harms Craig A.
Published: February 2017

With inspiratory muscle metaboreflex activation, we hypothesized that, compared with their younger counterparts, older men and women would exhibit greater 1) increases in mean arterial pressure (MAP) and limb vascular resistance (LVR) and 2) decreases in limb blood flow (Q̇L) but 3) no sex differences would be present in older adults. Sixteen young adults [8 young men (YM) and 8 young women (YW), 18–24 yr] and 16 older adults [8 older men (OM) and 8 older women (OW), 60–73 yr] performed inspiratory resistive breathing tasks (IRBTs) at 2% and 65% of their maximal inspiratory pressure. During the IRBTs, breathing frequency was 20 breaths/min with a 50% duty cycle. At baseline and during the IRBTs, MAP was measured via automated oscillometry, Q̇Lwas determined via Doppler ultrasound, and LVR was calculated. The 65% IRBT led to significantly greater increases in MAP in OW (15.9 ± 8.1 mmHg) compared with YW (6.9 ± 1.4 mmHg) but not ( P > 0.05) between OM (12.3 ± 5.7 mmHg) and YM (10.8 ± 5.7 mmHg). OW (−20.2 ± 7.2%) had greater ( P < 0.05) decreases in Q̇Lcompared with YW (−9.4 ± 10.2%), but no significant differences were present between OM (−22.8 ± 9.7%) and YM (−22.7 ± 11.3%) during the 65% IRBT. The 65% IRBT led to greater ( P < 0.05) increases in LVR in OW (48.2 ± 25.5%) compared with YW (19.7 ± 15.0%), but no differences ( P > 0.05) existed among OM (54.4 ± 17.8%) and YM (47.1 ± 23.3%). No significant differences were present in MAP, Q̇L, or LVR between OM and OW. These data suggest that OW exhibit a greater inspiratory muscle metaboreflex compared with YW, whereas no differences between OM and YM existed. Finally, sex differences in the inspiratory muscle metaboreflex are not present in older adults.

NEW & NOTEWORTHY Premenopausal women exhibit an attenuated inspiratory muscle metaboreflex compared with young men; however, it is unknown whether these sex differences are present in older adults. Older women exhibited a greater inspiratory muscle metaboreflex compared with premenopausal women, whereas no differences were present between older and younger men.
The mast cell–B cell axis in lung vascular remodeling and pulmonary hypertension
Authors: Breitling Siegfried , Hui Zhang , Zabini Diana , Hu Yijie , Hoffmann Julia , Goldenberg Neil M. , Tabuchi Arata , Buelow Roland , Dos Santos Claudia , Kuebler Wolfgang M.
Published: February 2017

Over past years, a critical role for the immune system and, in particular, for mast cells in the pathogenesis of pulmonary hypertension (PH) has emerged. However, the way in which mast cells promote PH is still poorly understood. Here, we investigated the mechanisms by which mast cells may contribute to PH, specifically focusing on the interaction between the innate and adaptive immune response and the role of B cells and autoimmunity. Experiments were performed in Sprague-Dawley rats and B cell-deficient JH-KO rats in the monocrotaline, Sugen/hypoxia, and the aortic banding model of PH. Hemodynamics, cell infiltration, IL-6 expression, and vascular remodeling were analyzed. Gene array analyses revealed constituents of immunoglobulins as most prominently regulated mast cell-dependent genes in the lung in experimental PH. IL-6 was shown to link mast cells to B cells, as 1) IL-6 was upregulated and colocalized with mast cells and was reduced by mast-cell stabilizers and 2) IL-6 or mast cell blockade reduced B cells in lungs of monocrotaline-treated rats. A functional role for B cells in PH was demonstrated in that either blocking B cells by an anti-CD20 antibody or B-cell deficiency in JH-KO rats attenuated right ventricular systolic pressure and vascular remodeling in experimental PH. We here identify a mast cell–B cell axis driven by IL-6 as a critical immune pathway in the pathophysiology of PH. Our results provide novel insights into the role of the immune system in PH, which may be therapeutically exploited by targeted immunotherapy.
Human airway trypsin-like protease, a serine protease involved in respiratory diseases
Authors: Menou Awen , Duitman JanWillem , Flajolet Pauline , Sallenave Jean-Michel , Mailleux Arnaud André , Crestani Bruno
Published: February 2017

More than 2% of all human genes are coding for a complex system of more than 700 proteases and protease inhibitors. Among them, serine proteases play extraordinary, diverse functions in different physiological and pathological processes. The human airway trypsin-like protease (HAT), also referred to as TMPRSS11D and serine 11D, belongs to the emerging family of cell surface proteolytic enzymes, the type II transmembrane serine proteases (TTSPs). Through the cleavage of its four major identified substrates, HAT triggers specific responses, notably in epithelial cells, within the pericellular and extracellular environment, including notably inflammatory cytokine production, inflammatory cell recruitment, or anticoagulant processes. This review summarizes the potential role of this recently described protease in mediating cell surface proteolytic events, to highlight the structural features, proteolytic activity, and regulation, including the expression profile of HAT, and discuss its possible roles in respiratory physiology and disease.
Combined long-term caffeine intake and exercise inhibits the development of diabetic nephropathy in OLETF rats
Authors: Suzuki Masato , Shindo Daisuke , Suzuki Ryuichiro , Shirataki Yoshiaki , Waki Hidefumi
Published: February 2017

This study was performed to examine the effects of long-term caffeine-intake, with and without exercise, on the progression of diabetic nephropathy (DN) in an obese diabetic rat model. Thirty-two male Otsuka Long-Evans Tokushima fatty (OLETF) rats were assigned to sedentary (OLETF-Sed), exercise (OLETF-Ex), caffeine-intake (OLETF-Caf), and combined (OLETF-Caf + Ex) groups. Caffeine-intake groups were fed rat chow containing caffeine (90.7 ± 4.7 mg/kg/day). The OLETF-Ex and OLETF-Caf + Ex groups were able to run voluntarily at any time using a rotatory wheel. Body weight (BW) and blood pressure (BP) were measured weekly from 24 to 29 wk of age. Pre- and posttreatment serum glucose, insulin, and creatinine concentrations were measured, and a 24 h urine sample was collected for measurement of creatinine clearance (Ccr) and albumin excretion (UEAlb). After treatment, the kidneys were removed for morphological analysis. The OLETF-Caf and OLETF-Caf + Ex groups exhibited no BP increase during the study. Both the caffeine-intake groups exhibited a significant increase in urine volume (UV), electrolyte excretion, and Ccr, and decreased UEAlb, following treatment. Furthermore, no structural damage was observed in the kidneys of rats from either caffeine-intake group, whereas the OLETF-Sed and OLETF-Ex groups exhibited DN progression. This study demonstrates that caffeine-intake alone and/or combined with exercise significantly decreases BW and improves glucose intolerance, without the progression of DN. Further research should be performed to examine whether the quantities of caffeine contained in a normal human daily intake also have a protective effect against kidney damage.

NEW & NOTEWORTHY The present study showed that caffeine administration alone and/or combined with exercise results in an improvement of diabetic nephropathy (DN), including an increase in creatinine clearance and urinary Na excretion, a decrease in urinary protein excretion, and in renal morphological findings. To our knowledge, there are no other studies showing that caffeine administration inhibits DN progression.
In vivo assessment of regional mechanics post-myocardial infarction: A focus on the road ahead
Authors: Romito Eva , Shazly Tarek , Spinale Francis G.
Published: February 2017

Cardiovascular disease, particularly the occurrence of myocardial infarction (MI), remains a leading cause of morbidity and mortality (Go et al., Circulation 127: e6–e245, 2013; Go et al. Circulation 129: e28–e292, 2014). There is growing recognition that a key factor for post-MI outcomes is adverse remodeling and changes in the regional structure, composition, and mechanical properties of the MI region itself. However, in vivo assessment of regional mechanics post-MI can be confounded by the species, temporal aspects of MI healing, as well as size, location, and extent of infarction across myocardial wall. Moreover, MI regional mechanics have been assessed over varying phases of the cardiac cycle, and thus, uniform conclusions regarding the material properties of the MI region can be difficult. This review assesses past studies that have performed in vivo measures of MI mechanics and attempts to provide coalescence on key points from these studies, as well as offer potential recommendations for unifying approaches in terms of regional post-MI mechanics. A uniform approach to biophysical measures of import will allow comparisons across studies, as well as provide a basis for potential therapeutic markers.
Sigma1 Targeting to Suppress Aberrant Androgen Receptor Signaling in Prostate Cancer
Authors: Thomas Jeffrey D. , Longen Charles G. , Oyer Halley M. , Chen Nan , Maher Christina M. , Salvino Joseph M. , Kania Blase , Anderson Kelsey N. , Ostrander William F. , Knudsen Karen E. , Kim Felix J.
Published: February 2017

Suppression of androgen receptor (AR) activity in prostate cancer by androgen depletion or direct AR antagonist treatment, although initially effective, leads to incurable castration-resistant prostate cancer (CRPC) via compensatory mechanisms including resurgence of AR and AR splice variant (ARV) signaling. Emerging evidence suggests that Sigma1 (also known as sigma-1 receptor) is a unique chaperone or scaffolding protein that contributes to cellular protein homeostasis. We reported previously that some Sigma1-selective small molecules can be used to pharmacologically modulate protein homeostasis pathways. We hypothesized that these Sigma1-mediated responses could be exploited to suppress AR protein levels and activity. Here we demonstrate that treatment with a small-molecule Sigma1 inhibitor prevented 5α- dihydrotestosterone-mediated nuclear translocation of AR and induced proteasomal degradation of AR and ARV, suppressing the transcriptional activity and protein levels of both full-length and splice-variant AR. Consistent with these data, RNAi knockdown of Sigma1 resulted in decreased AR levels and transcriptional activity. Furthermore, Sigma1 physically associated with ARV7 and ARv567es as well as full-length AR. Treatment of mice xenografted with ARV-driven CRPC tumors with a drug-like small-molecule Sigma1 inhibitor significantly inhibited tumor growth associated with elimination of AR and ARV7 in responsive tumors. Together, our data show that Sigma1 modulators can be used to suppress AR/ARV–driven prostate cancer cells via regulation of pharmacologically responsive Sigma1-AR/ARV interactions, both in vitro and in vivo. Cancer Res; 77(9); 2439–52. ©2017 AACR.
Armed Oncolytic Adenovirus–Expressing PD-L1 Mini-Body Enhances Antitumor Effects of Chimeric Antigen Receptor T Cells in Solid Tumors
Authors: Tanoue Kiyonori , Rosewell Shaw Amanda , Watanabe Norihiro , Porter Caroline , Rana Bhakti , Gottschalk Stephen , Brenner Malcolm , Suzuki Masataka
Published: February 2017

Chimeric antigen receptor–modified T cells (CAR T cells) produce proinflammatory cytokines that increase expression of T-cell checkpoint signals such as PD-L1, which may inhibit their functionality against solid tumors. In this study, we evaluated in human tumor xenograft models the proinflammatory properties of an oncolytic adenovirus (Onc.Ad) with a helper-dependent Ad (HDAd) that expresses a PD-L1 blocking mini-antibody (mini-body; HDPDL1) as a strategy to enhance CAR T-cell killing. Coadministration of these agents (CAd-VECPDL1) exhibited oncolytic effects with production of PD-L1 mini-body locally at the tumor site. On their own, HDPDL1 exhibited no antitumor effect and CAd-VECPDL1 alone reduced tumors only to volumes comparable to Onc.Ad treatment. However, combining CAd-VECPDL1 with HER2.CAR T cells enhanced antitumor activity compared with treatment with either HER2.CAR T cells alone or HER2.CAR T cells plus Onc.Ad. The benefits of locally produced PD-L1 mini-body by CAd-VECPDL1 could not be replicated by infusion of anti-PD-L1 IgG plus HER2.CAR T cells and coadministration of Onc.Ad in an HER2+ prostate cancer xenograft model. Overall, our data document the superiority of local production of PD-L1 mini-body by CAd-VECPDL1 combined with administration of tumor-directed CAR T cells to control the growth of solid tumors. Cancer Res; 77(8); 2040–51. ©2017 AACR.
Cellular and Molecular Identity of Tumor-Associated Macrophages in Glioblastoma
Authors: Chen Zhihong , Feng Xi , Herting Cameron J. , Garcia Virginia Alvarez , Nie Kai , Pong Winnie W. , Rasmussen Rikke , Dwivedi Bhakti , Seby Sandra , Wolf Susanne A. , Gutmann David H. , Hambardzumyan Dolores
Published: February 2017

In glioblastoma (GBM), tumor-associated macrophages (TAM) represent up to one half of the cells of the tumor mass, including both infiltrating macrophages and resident brain microglia. In an effort to delineate the temporal and spatial dynamics of TAM composition during gliomagenesis, we used genetically engineered and GL261-induced mouse models in combination with CX3CR1GFP/WT;CCR2RFP/WT double knock-in mice. Using this approach, we demonstrated that CX3CR1LoCCR2Hi monocytes were recruited to the GBM, where they transitioned to CX3CR1HiCCR2Lo macrophages and CX3CR1HiCCR2− microglia-like cells. Infiltrating macrophages/monocytes constituted approximately 85% of the total TAM population, with resident microglia accounting for the approximately 15% remaining. Bone marrow–derived infiltrating macrophages/monocytes were recruited to the tumor early during GBM initiation, where they localized preferentially to perivascular areas. In contrast, resident microglia were localized mainly to peritumoral regions. RNA-sequencing analyses revealed differential gene expression patterns unique to infiltrating and resident cells, suggesting unique functions for each TAM population. Notably, limiting monocyte infiltration via genetic Ccl2 reduction prolonged the survival of tumor-bearing mice. Our findings illuminate the unique composition and functions of infiltrating and resident myeloid cells in GBM, establishing a rationale to target infiltrating cells in this neoplasm. Cancer Res; 77(9); 2266–78. ©2017 AACR.
Cellular Hierarchy as a Determinant of Tumor Sensitivity to Chemotherapy
Authors: Rodriguez-Brenes Ignacio A. , Kurtova Antonina V. , Lin Christopher , Lee Yu-Cheng , Xiao Jing , Mims Martha , Chan Keith Syson , Wodarz Dominik
Published: February 2017

Chemotherapy has been shown to enrich cancer stem cells in tumors. Recently, we demonstrated that administration of chemotherapy to human bladder cancer xenografts could trigger a wound-healing response that mobilizes quiescent tumor stem cells into active proliferation. This phenomenon leads to a loss of sensitivity to chemotherapy partly due to an increase in the number of tumor stem cells, which typically respond to chemotherapy-induced cell death less than more differentiated cells. Different bladder cancer xenografts, however, demonstrate differential sensitivities to chemotherapy, the basis of which is not understood. Using mathematical models, we show that characteristics of the tumor cell hierarchy can be crucial for determining the sensitivity of tumors to drug therapy, under the assumption that stem cell enrichment is the primary basis for drug resistance. Intriguingly, our model predicts a weaker response to therapy if there is negative feedback from differentiated tumor cells that inhibits the rate of tumor stem cell division. If this negative feedback is less pronounced, the treatment response is predicted to be enhanced. The reason is that negative feedback on the rate of tumor cell division promotes a permanent rise of the tumor stem cell population over time, both in the absence of treatment and even more so during drug therapy. Model application to data from chemotherapy-treated patient-derived xenografts indicates support for model predictions. These findings call for further research into feedback mechanisms that might remain active in cancers and potentially highlight the presence of feedback as an indication to combine chemotherapy with approaches that limit the process of tumor stem cell enrichment. Cancer Res; 77(9); 2231–41. ©2017 AACR.
High-Throughput Genomic Profiling of Adult Solid Tumors Reveals Novel Insights into Cancer Pathogenesis
Authors: Hartmaier Ryan J. , Albacker Lee A. , Chmielecki Juliann , Bailey Mark , He Jie , Goldberg Michael E. , Ramkissoon Shakti , Suh James , Elvin Julia A. , Chiacchia Samuel , Frampton Garrett M. , Ross Jeffrey S. , Miller Vincent , Stephens Philip J. , Lipson Doron
Published: February 2017

Genomic profiling is widely predicted to become a standard of care in clinical oncology, but more effective data sharing to accelerate progress in precision medicine will be required. Here, we describe cancer-associated genomic profiles from 18,004 unique adult cancers. The dataset was composed of 162 tumor subtypes including multiple rare and uncommon tumors. Comparison of alteration frequencies to The Cancer Genome Atlas identified some differences and suggested an enrichment of treatment-refractory samples in breast and lung cancer cohorts. To illustrate novelty within the dataset, we surveyed the genomic landscape of rare diseases and identified an increased frequency of NOTCH1 alterations in adenoid cystic carcinomas compared with previous studies. Analysis of tumor suppressor gene patterns revealed disease specificity for certain genes but broad inactivation of others. We identified multiple potentially druggable, novel and known kinase fusions in diseases beyond those in which they are currently recognized. Analysis of variants of unknown significance identified an enrichment of SMAD4 alterations in colon cancer and other rare alterations predicted to have functional impact. Analysis of established, clinically relevant alterations highlighted the spectrum of molecular changes for which testing is currently recommended, as well as opportunities for expansion of indications for use of approved targeted therapies. Overall, this dataset presents a new resource with which to investigate rare alterations and diseases, validate clinical relevance, and identify novel therapeutic targets. Cancer Res; 77(9); 2464–75. ©2017 AACR.
Telomere Length Is Predictive of Breast Cancer Risk inBRCA2Mutation Carriers
Authors: Thorvaldsdottir Birna , Aradottir Margret , Stefansson Olafur A. , Bodvarsdottir Sigridur K. , Eyfjörd Jorunn E.
Published: February 2017

Background: Germline BRCA2 mutations increase risk of breast cancer and other malignancies. BRCA2 has been shown to play a role in telomere protection and maintenance. Telomere length (TL) has been studied as a modifying factor for various diseases, including breast cancer. Previous research on TL in BRCA mutation carriers has produced contradicting results.

Methods: We measured blood TL, using a high-throughput monochrome multiplex qPCR method, in a well-defined Icelandic cohort of female BRCA2 mutation carriers (n = 169), sporadic breast cancer patients (n = 561), and healthy controls (n = 537).

Results: Breast cancer cases had significantly shorter TL than unaffected women (P < 0.0001), both BRCA2 mutation carriers (P = 0.0097) and noncarriers (P = 0.00006). Using exclusively samples acquired before breast cancer diagnosis, we found that shorter telomeres were significantly associated with increased breast cancer risk in BRCA2 mutation carriers [HR, 3.60; 95% confidence interval (CI), 1.17–11.28; P, 0.025] but not in non-carriers (HR,1.40; 95% CI, 0.89–2.22; P, 0.15). We found no association between TL and breast cancer–specific survival.

Conclusions: Blood TL is predictive of breast cancer risk in BRCA2 mutation carriers. Breast cancer cases have significantly shorter TL than unaffected women, regardless of BRCA2 status, indicating that samples taken after breast cancer diagnosis should not be included in evaluations of TL and breast cancer risk.

Impact: Our study is built on a well-defined cohort, highly accurate methods, and long follow-up and can therefore help to clarify some previously published, contradictory results. Our findings also suggest that BRCA2 has an important role in telomere maintenance, even in normal blood cells. Cancer Epidemiol Biomarkers Prev; 26(8); 1248–54. ©2017 AACR.
FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma
Authors: Chuk Meredith K. , Chang Jennie T. , Theoret Marc R. , Sampene Emmanuel , He Kun , Weis Shawna L. , Helms Whitney S. , Jin Runyan , Li Hongshan , Yu Jingyu , Zhao Hong , Zhao Liang , Paciga Mark , Schmiel Deborah , Rawat Rashmi , Keegan Patricia , Pazdur Richard
Published: February 2017

On September 4, 2014, the FDA approved pembrolizumab (KEYTRUDA; Merck Sharp & Dohme Corp.) with a recommended dose of 2 mg/kg every 3 weeks by intravenous infusion for the treatment of patients with unresectable or metastatic melanoma who have progressed following treatment with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on demonstration of objective tumor responses with prolonged response durations in 89 patients enrolled in a randomized, multicenter, open-label, dose-finding, and activity-estimating phase 1 trial. The overall response rate (ORR) by blinded independent central review per RECIST v1.1 was 24% (95% confidence interval, 15–34); with 6 months of follow-up, 86% of responses were ongoing. The most common (≥20%) adverse reactions were fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. Immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, hypophysitis, and thyroid disorders. The benefits of the observed ORR with prolonged duration of responses outweighed the risks of immune-mediated adverse reactions in this life-threatening disease and represented an improvement over available therapy. Important regulatory issues in this application were role of durability of response in the evaluation of ORR for accelerated approval, reliance on data from a first-in-human trial, and strategies for dose selection. Clin Cancer Res; 23(19); 5666–70. ©2017 AACR.
Abstract P6-12-12: Phase I study of the JAK 1/2 inhibitor ruxolitinib with weekly paclitaxel for the treatment of HER2 negative metastatic breast cancer (MBC)
Authors: Overmoyer B , Regan M , Schlosnagle E , Bunnell C , Freedman R , Tolaney S , Chen W , Mayer E , Partridge A , Silver D , Winer E
Published: March 2017

This abstract was not presented at the symposium.
Dual Targeting of Mesenchymal and Amoeboid Motility Hinders Metastatic Behavior
Authors: Jones Brandon C. , Kelley Laura C. , Loskutov Yuriy V. , Marinak Kristina M. , Kozyreva Varvara K. , Smolkin Matthew B. , Pugacheva Elena N.
Published: February 2017

Commonly upregulated in human cancers, the scaffolding protein NEDD9/HEF1 is a known regulator of mesenchymal migration and cancer cell plasticity. However, the functional role of NEDD9 as a regulator of different migration/invasion modes in the context of breast cancer metastasis is currently unknown. Here, it is reported that NEDD9 is necessary for both mesenchymal and amoeboid individual cell migration/invasion in triple-negative breast cancer (TNBC). NEDD9 deficiency results in acquisition of the amoeboid morphology, but severely limits all types of cell motility. Mechanistically, NEDD9 promotes mesenchymal migration via VAV2-dependent Rac1 activation, and depletion of VAV2 impairs the ability of NEDD9 to activate Rac1. In addition, NEDD9 supports a mesenchymal phenotype through stimulating polymerization of actin via promoting CTTN phosphorylation in an AURKA-dependent manner. Interestingly, an increase in RhoA activity in NEDD9-depleted cells does not facilitate a switch to functional amoeboid motility, indicating a role of NEDD9 in the regulation of downstream RhoA signaling effectors. Simultaneous depletion of NEDD9 or inhibition of AURKA in combination with inhibition of the amoeboid driver ROCK results in an additional decrease in cancer cell migration/invasion. Finally, we confirmed that a dual targeting strategy is a viable and efficient therapeutic approach to hinder the metastasis of breast cancer in xenograft models, showcasing the important need for further clinical evaluation of this regimen to impede the spread of disease and improve patient survival.

Implications: This study provides new insight into the therapeutic benefit of combining NEDD9 depletion with ROCK inhibition to reduce tumor cell dissemination and discovers a new regulatory role of NEDD9 in the modulation of VAV2-dependent activation of Rac1 and actin polymerization. Mol Cancer Res; 15(6); 670–82. ©2017 AACR.
New records of Aplousobranch ascidians to Indian waters from Andaman Islands
Authors: Mondal Jhimli , Raghunathan C. , Venkataraman K.
Published: February 2017

Aplousobranchia represents the largest order under the class Ascidiacea.  Two reef associated aplousobranch ascidians, Rhopalaea macrothorax Tokioka, 1953 under the family Diazonidae and Clavelina robusta Kott, 1990 under the family Clavelinidae, found from the Andaman group of islands are reported as new records to the Indian waters.  The present paper describes the taxonomic characters and distribution of these two newly recorded species.
Twenty-three new records of mantodea (Insecta) from some states of India
Authors: Mukherjee Tushar Kanti , Iyer Geetha , Chatterjee Parbati
Published: February 2017

Photography of mantises in their natural habitat clearly indicates the presence of a good number of species in our country. The study disclosed new records of 23 species of mantises from different forests and rural greens of India. Photographs are also provided. All photographs, unless specified otherwise, are by Geetha Iyer. None of the mantises were collected.
Additions to the scorpion fauna (Arachnida: Scorpiones) of Kerala, India, with an illustrated key to the genera
Authors: Aswathi K. , Sureshan P. M.
Published: February 2017

Twospecies of scorpions ( Arachnida : Scorpiones) viz., LychaslaevifronsPocock and Heterometrus flavimanus (Pocock) are reported for the first time form Kerala and an illustrated key to the  genera and checklist of scorpion species of Kerala are  provided. Currently    21species under 09genera of scorpions are known from the state.
A report on occurrence of aphidophagous predators of Aphis odinae (van der Goot) (Hemiptera: Aphididae) in cashew ecosystem from Goa, India
Authors: Maruthadurai Ramasamy , Singh Narendra Pratap
Published: February 2017

The aphid, Aphis odinae (Van der Goot) (Hemiptera: Aphididae) is a polyphagous, occasional insect pest of cashew.  A field survey was conducted from 2014 to 2015 in cashew plantations to record the incidence of aphid and its predators.  Periodical sampling revealed, the occurrence of six species of aphidophagous predators comprising three species of coccinellids, viz., Scymnus castaneus Sicard, Cheilomenes sexmaculata (Fabricius) and Pseudaspidimerus flaviceps (Walker) and three species of syrphids, viz., Paragus serratus (Fabricius), Dideopsis aegrota (Fabricius) and Ischidon scutellaris (Fabricius) were found predating on A. odinae.  All the immature stages of predators were found predating on first, second, third and fourth instars of the aphid.  Among the coccinellids, the dominant species were S. castaneus (4.26 grubs/nut) followed by C. sexmaculata (0.42 grubs/leaf) and P. flaviceps (0.14 grubs/nut).  Of the syrphids, P. serratus 2.39 larvae/nut was the major predator. The species D. aegrota (1.2 larvae/leaf) and I. scutellaris (0.5 larvae/nut) were recorded as minor predators.  Seasonal abundance of predators was synchronized with the aphid with a maximum occurrence during February 2015.  The aphid population gradually reduced from April onwards due to the voracious feeding activity of the predators.  The study concluded that the aphidophagous predators, viz., coccinellids and syrphids play a  major role in managing the aphid A. odinae in cashew and could be encouraged for augmentation and conservation of these predators in a cashew based ecosystem.
Moths of the family Limacodidae Duponchel, 1845 (Lepidoptera: Zygaenoidea) from Bhutan with six new generic and 12 new species records
Authors: Irungbam Jatishwor Singh , Chib Meenakshi Singh , Solovyev Alexey V.
Published: February 2017

The present paper provides a checklist of 51 species in 37 genera of moths belonging to the family Limacodidae from Bhutan, of which, six genera, Setora Walker, 1855, Tennya Solovyev & Witt, 2009, Iraga Matsumura, 1927, Vanlangia Solovyev & Witt 2009, Sansarea Solovyev & Witt, 2009, and Belippa Walker, 1865 are reported for the first time from Bhutan, and 12 species, Setora postornata (Hampson, 1900), Setora fletcheri Holloway, 1987, Scopelodes testacea Butler, 1886, Thosea magna Hering, 1931, Miresa fulgida Wileman, 1910, Susica himalayana Holloway, 1982, Tennya propolia (Hampson, 1900), Iraga rugosa (Wileman, 1911), Cheromettia ferruginea (Moore, 1877), Vanlangia uniformis (Hering, 1931), Sansarea circulifera (Hering, 1933) and Belippa horrida Walker, 1865 are new records for Bhutan.  The study was conducted at Tsirang, Dagana and Sarpang districts of Bhutan from 2013 to 2015.
Diversity of two families Libellulidae and Coenagrionidae (Odonata) in Regional Institute of Education Campus, Bhubaneswar, Odisha, India
Authors: Pandey Priyamvada , Mohapatra Animesh Kumar
Published: February 2017

Libellulidae and Coenagrionidae are the most dominant families among dragonflies and damselflies.  The present study deals with the diversity, occurrence and present status of libellulids and coenagrionids within the Regional Institute of Education Campus in Bhubaneswar, Odisha, India (RIEC). The major objectives of this study are to prepare a preliminary checklist of libellulids and coenagrionids species in the RIEC and to find out the status and distribution of genera and species in their respective families.  This study is also aimed at systematic planning for developing different strategies for conservation of odonates in the campus.  During this study a total of 24 species have been recorded out of which 20 species belong to the family Libellulidae representing 15 genera and four species belong to the family Coenagrionidae representing four genera.  The findings of this study are based on the survey which was carried out for a period of four months in 2015.
On the feeding habit of the Guiana Dolphin Sotalia guianensis (van Bénedèn, 1864) (Mammalia: Cetartiodactyla: Delphinidae) in southeastern Brazil (~220S): has there been any change in more than two decades?
Authors: Di Beneditto Ana Paula Madeira , Badia Clara Da Cruz Vidart , Siciliano Salvatore
Published: February 2017

Along the north and central coast of Rio de Janeiro State (22025’S–23000’S), southeastern Brazil, the Guiana Dolphin Sotalia guianensis forages on neritic prey, mainly fish.  From the analysis of the dolphin’s stomach contents and the identification of partially digested prey, it was verified that the most frequent prey species were young specimens of Trichiurus lepturus.  Comparing our results with previous studies on the feeding habits of Guiana Dolphin in the same region, we noticed the maintenance of its feeding preferences during more than two decades, indicating little or no change in the use of prey by this top predator.
First report of the parasitoid wasp Piestopleura Förster (Hymenoptera: Platygastroidea: Platygastridae) from India
Authors: Veenakumari Kamalanathan , Buhl Peter Neerup , Rameshkumar Anandhan , Mohanraj Prashanth
Published: February 2017

The genus Piestopleura is reported for the first time from India.
A new critical habitat for conservation of the White-bellied Heron Ardea insignis Hume, 1878 (Aves: Ardeidae) from Bhutan
Authors: Wangdi Karma , Dhendup Tashi , Tshering Tsethup
Published: February 2017

The White-bellied Heron Ardea insignis is listed as Critically Endangered on the IUCN Red List of Threatened Species due to its extremely small and rapidly dwindling population. Bhutan is home to the highest number of White-bellied Heron and the species is distributed patchily across 11 different sites in central and south-west Bhutan. In this note, we present the first evidence of the species in eastern Bhutan, on the Drangmechhu River in Trashi Yangtse district. The finding extends the distribution of the species in Bhutan and recognizes one more potentially critical habitat for immediate conservation attention. As elsewhere, the new site is found to be primarily threatened by hydropower development. The need for conservation initiatives for the species is immediate and highly recommended.
A century later the Manipur Argus Callerebia suroia Tytler, 1914 (Lepidoptera: Nymphalidae: Satyrinae) recorded in its type locality in Manipur, India
Authors: Irungbam Jatishwor Singh , Huidrom Harmenn , Soibam Baleshwor Singh
Published: February 2017

The present paper reports the sighting of Callerebia suroia Tytler, 1914 at Shirui Kashong Peak, Ukhrul District which confirms the continued presence of the species in Manipur State, India.  The butterfly was sighted on 13 July 2016 near the footpath leading to the summit at an altitude of 2,330m.  Callerebia suroia Tytler, 1914 is protected under Schedule II of the Indian Wildlife (Protection) Act 1972.  The sighting of such very rare species in Manipur after a decade shows that more surveys are needed in the hills and valleys of Manipur to determine the butterfly fauna of the region.
Odonates of Coimbatore District, Tamil Nadu, India
Authors: Muhil M. Suhirtha , Pramod P.
Published: February 2017

Odonates were surveyed in Coimbatore District from September 2012 to January 2016.  The survey sites covered three major rivers—the Noyyal, Bhavani and Aliyar.  Aquatic habitats such as forest streams, riverine sites, irrigational tanks and paddy fields were surveyed in the study.  A total of 70 species of odonates were recorded in the survey, which brings the list of odonates in Coimbatore to 87 species.  Eighteen species are first time records to the district.  In this paper, we catalogue odonates and their distribution from the present survey and pre-existing records.
Additions to the flora of Coimbatore hills, Tamil Nadu, India
Authors: Kiruthika K. , Sulaiman M. , Gopalan R.
Published: February 2017

The occurrence of Cosmostigma racemosum, Blachia umbellata and Vanilla walkeriae are being reported for the first time from Coimbatore hills.
Distribution of Cryptopotamon anacoluthon (Kemp, 1918) (Crustacea: Brachyura: Potamidae), a freshwater crab endemic to Hong Kong
Authors: Stanton David John , Leven Micheal Robertson , Hui Tommy Chung Hong
Published: February 2017

Cryptopotamon anacoluthon Kemp, 1918 is a tropical freshwater crab currently considered endemic to Hong Kong. The species is more widely distributed than previously known and potentially occurs outside Hong Kong. However, its habitat is under threat from development and channelisation of watercourses. It is hoped that understanding of the species’ distribution will aid in its conservation.
First record of the predatory stinkbug Eocanthecona concinna (Walker, 1867) (Pentatomidae: Asopinae) from India
Authors: Waghmare Sadashiv Hanumant , Gaikwad Sunil Madhukar
Published: February 2017

The genus Eocanthecona is distributed in oriental, Ethiopian and Australasian regions.  This genus is represented by 24 species from the world of which only five species are reported from India.  The bug Eocanthecona concinna was first reported from Hong Kong, China in 1867.  Later again reported from different regions of China and Taiwan in 1910, 1934, 1961 and 2013.  The review of literature indicates no record of E. concinna in India.  Hence, the report of this stinkbug from Kolhapur becomes first report for India and the geographic range of the species in China and Taiwan is extended towards India.
Flora richness as an indicator of desert habitat quality in Kuwait
Authors: Al-Shehabi Yahya , Murphy Kevin
Published: February 2017

An assessment of the vegetation in the arid desert habitats of Kuwait was carried out in 2008 and 2009.  The richness of vegetation was examined in relation to human activity (e.g., grazing, recreational camping) and impact factors in two open areas (north of SAANR, NS; south of Kabd, SK) were compared with two protected areas (SAANR, Kabd).  In total, 420 quadrats were sampled along 84 transects at random locations along off-road vehicle tracks in the study area.  The data were classified using two-way indicator species analysis (TWINSPAN) to divide samples into three groups of high internal similarity in terms of plant species presence.  Total plant species richness was 20, 35, 2 and 17 species per area in SAANR, Kabd, NS and SK, respectively.  Compared to protected areas, open grazed land had markedly fewer species and reduced vegetation cover in the form of grasses, forbs and shrubs.  Habitat conditions were especially impoverished in NS, with 99% of samples supporting only one plant species.  The low plant diversity in the unprotected open rangelands demonstrates the need for a new strategy to rehabilitate ecological habitats.
Management and Outcome of Patients With Acute Coronary Syndrome Caused by Plaque Rupture Versus Plaque Erosion: An Intravascular Optical Coherence Tomography Study
Authors: Hu Sining , Zhu Yinchun , Zhang Yingying , Dai Jiannan , Li Lulu , Dauerman Harold , Soeda Tsunenari , Wang Zhao , Lee Hang , Wang Chao , Zhe Chunyang , Wang Yan , Zheng Gonghui , Zhang Shaosong , Jia Haibo , Yu Bo , Jang Ik‐Kyung
Published: February 2017

Background

Plaque rupture and erosion are the 2 most common mechanisms for acute coronary syndromes. However, the outcome of these 2 distinct pathologies in patients with acute coronary syndromes has never been studied.

Methods and Results

We retrospectively studied 141 patients with acute coronary syndromes who underwent optical coherence tomography (
OCT
) imaging of the culprit lesion prior to stenting from the Massachusetts General Hospital
OCT
Registry. Management (stent versus no stent), poststent
OCT
findings, and outcomes were compared. Among the 141 culprit lesions, rupture was found in 79 (56%) patients and erosion in 62 (44%). Stent implantation was performed in 77 (97.5%) patients with rupture versus 49 (79.0%) in those with erosion (
P
<0.001). Immediately after percutaneous coronary intervention,
OCT
showed a higher incidence of malapposition (37.5% versus 7.3%,
P
<0.001), thrombus (59.4% versus 14.6%,
P
<0.001), and protrusion (93.8% versus 73.2%,
P
=0.008) in the rupture group compared with the erosion group. Plaque rupture was associated with a higher incidence of no reflow or slow flow and distal embolization. Although cardiac event rates were comparable between the two groups at the 1‐year follow‐up, none of the erosion patients who were treated conservatively without stenting had adverse cardiac events.

Conclusions

Unfavorable poststent
OCT
findings were more frequent in rupture patients compared with erosion patients. A subset of erosion patients who were treated conservatively without stenting remained free of adverse cardiac events for up to 1 year.
Prehospital Emergency Care in Childhood Arterial Ischemic Stroke
Authors: Stojanovski Belinda , Monagle Paul T. , Mosley Ian , Churilov Leonid , Newall Fiona , Hocking Grant , Mackay Mark T.
Published: February 2017

Background and Purpose—

Immediately calling an ambulance is the key factor in reducing time to hospital presentation for adult stroke. Little is known about prehospital care in childhood arterial ischemic stroke (AIS). We aimed to determine emergency medical services call-taker and paramedic diagnostic sensitivity and to describe timelines of care in childhood AIS.

Methods—

This is a retrospective study of ambulance-transported children aged <18 years with first radiologically confirmed AIS, from 2008 to 2015. Interhospital transfers of children with preexisting AIS diagnosis were excluded.

Results—

Twenty-three children were identified; 4 with unavailable ambulance records were excluded. Nineteen children were included in the study. Median age was 8 years (interquartile range, 3–14); median Pediatric National Institutes of Stroke Severity Scale score was 8 (interquartile range, 3–16). Emergency medical services call-taker diagnosis was stroke in 4 children (21%). Priority code 1 (lights and sirens) ambulances were dispatched for 13 children (68%). Paramedic diagnosis was stroke in 5 children (26%), hospital prenotification occurred in 8 children (42%), and 13 children (68%) were transported to primary stroke centers. Median prehospital timelines were onset to emergency medical services contact 13 minutes, call to scene 12 minutes, time at scene 14 minutes, transport time 43 minutes, and total prehospital time 71 minutes (interquartile range, 60–85).

Conclusions—

Emergency medical services call-taker and paramedic diagnostic sensitivity and prenotification rates are low in childhood AIS.
Successful Reperfusion With Mechanical Thrombectomy Is Associated With Reduced Disability and Mortality in Patients With Pretreatment Diffusion-Weighted Imaging–Alberta Stroke Program Early Computed Tomography Score ≤6
Authors: Desilles Jean-Philippe , Consoli Arturo , Redjem Hocine , Coskun Oguzhan , Ciccio Gabriele , Smajda Stanislas , Labreuche Julien , Preda Cristian , Ruiz Guerrero Clara , Decroix Jean-Pierre , Rodesch Georges , Mazighi Mikael , Blanc Raphaël , Piotin Michel , Lapergue Bertrand , Wang Adrien , Evrard Serge , Tchikviladzé Maya , Bourdain Frederic , Gonzalez-Valcarcel Jaime , Di Maria Federico , Pico Fernando , Rakotoharinandrasana Haja , Tassan Philippe , Poll Roxanna , Corabianu Ovide , de Broucker Thomas , Smadja Didier , Alamowitch Sonia , Obadia Michael , Ille Olivier , Manchon Eric , Garcia Pierre-Yves
Published: February 2017

Background and Purpose—

In acute ischemic stroke patients, diffusion-weighted imaging (DWI)–Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is correlated with infarct volume and is an independent factor of functional outcome. Patients with pretreatment DWI-ASPECTS ≤6 were excluded or under-represented in the recent randomized mechanical thrombectomy trials. Our aim was to assess the impact of reperfusion in pretreatment DWI-ASPECTS ≤6 patients treated with mechanical thrombectomy.

Methods—

We analyzed data collected between January 2012 and August 2015 in a bicentric prospective clinical registry of consecutive acute ischemic stroke patients treated with mechanical thrombectomy. Every patient with a documented internal carotid artery or middle cerebral artery occlusion with pretreatment DWI-ASPECTS ≤6 was eligible for this study. The primary end point was a favorable outcome defined by a modified Rankin Scale score ≤2 at 90 days.

Results—

Two hundred and eighteen patients with a DWI-ASPECTS ≤6 were included. Among them, 145 (66%) patients had successful reperfusion at the end of mechanical thrombectomy. Reperfused patients had an increased rate of favorable outcome (38.7% versus 17.4%;
P
=0.002) and a decreased rate of mortality at 3 months (22.5% versus 39.1%;
P
=0.013) compared with nonreperfused patients. The symptomatic intracranial hemorrhage rate was not different between the 2 groups (13.0% versus 14.1%;
P
=0.83). However, in patients with DWI-ASPECTS <5, favorable outcome was low (13.0% versus 9.5%;
P
=0.68) with a high mortality rate (45.7% versus 57.1%;
P
=0.38) with or without successful reperfusion.

Conclusions—

Successful reperfusion is associated with reduced mortality and disability in patients with a pretreatment DWI-ASPECTS ≤6. Further data from randomized studies are needed, particularly in patients with DWI-ASPECTS <5.
Distributions of Subclinical Cardiovascular Disease in a Socioeconomically and Racially Diverse Sample
Authors: Wendell Carrington R. , Waldstein Shari R. , Evans Michele K. , Zonderman Alan B.
Published: February 2017

Background and Purpose—

Differential subgroup vulnerability to subclinical cardiovascular disease is likely, and yet few, if any, studies have addressed interactive relations of age, sex, race, and socioeconomic status (SES) to these conditions to examine nuances of known health disparities. We examined distributions of carotid atherosclerosis and arterial stiffness in a socioeconomically diverse, biracial, urban sample.

Methods—

Participants (n=2270) in the population-based HANDLS study (Healthy Aging in Neighborhoods of Diversity Across the Life Span; 30–64 years old, 44% men, 57% African American, 39% with household income <125% federal poverty threshold) underwent carotid intimal medial thickness (IMT) and pulse wave velocity assessment.

Results—

In cross-sectional hierarchical regression analyses, interactive race×SES effects were identified for IMT and pulse wave velocity, such that high SES African Americans had significantly thicker IMTs and faster pulse wave velocities than all other subgroups (ie, low SES African Americans, low SES whites, and high SES whites). A race×sex effect was also identified for IMT, such that the IMT discrepancy between white men and women was more pronounced than the discrepancy between African American men and women. Finally, an SES×sex effect indicated that while IMTs of high SES and low SES men did not significantly differ, high SES women had marginally thicker IMTs than low SES women.

Conclusions—

High SES African Americans may be particularly vulnerable to subclinical cardiovascular diseases, placing them at enhanced risk for clinical cardiovascular diseases, including stroke. These findings suggest that male sex, low SES, and African American ancestry may represent imprecise generalizations as risk factors for subclinical cardiovascular disease.