bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract LB-267: Role of VEGFR-1 signaling in obesity-induced tumor progression
Authors: Incio Joao , Tam Joshua , Rahbari Nuh , Suboj Priya , McManus Daniel , Chin Shan , Vardan-Kaur Trupti , Batista Ana , Babycutty Suboj , Jung Keehoon , Khachatryan Anna , Shibuya Masabumi , Soares Raquel , Duda Dan , Jain Rakesh K. , Fukumura Dai
Published: August 2015

Background: Obesity associates with angiogenesis and increased macrophage infiltration in adipose tissues during weight gain. Whether these effects also occur in cancer to promote tumor progression in obese condition remains unclear. We have shown that the vascular endothelial growth factor receptor-1 (VEGFR-1) pathway can modulate tumor angiogenesis and recruitment of tumor-associated macrophages (TAMs). Here, we tested the emerging hypothesis that obesity enhances tumor progression and metastasis by augmenting angiogenesis and TAM recruitment via activation of the VEGFR-1 pathway.

Methods: We used a high-fat diet-induced obesity model in either wild type (WT) or VEGFR-1 tyrosine kinase null (Flt1TK-/-) C57BL/6 mice. Then, we implanted orthotopically syngeneic pancreatic (PAN02) or breast (E0771) carcinomas. We evaluated the role of VEGFR-1 activity on systemic metabolism, tumor angiogenesis and immune environment, and tumor growth and metastasis.

Results: Obesity increased p38-MAPK activation and TAM infiltration, tumor growth (p = 0.001) and metastasis (p = 0.035) in PAN02 tumors. VEGFR-1 inhibition reduced tumor growth (p = 0.007) and metastasis (p = 0.017) in obese but not lean mice. This was associated with a decreased p38-MAPK activity and a shift in TAM polarization towards the M1 phenotype with reduced secretion of pro-tumor cytokines, but no change in vascular density or number of TAMs. In the E0771 model, VEGFR-1 inhibition reduced MMP-9 expression and decreased lung metastatic burden (p = 0.026) in obese mice. In addition to these tumor effects, VEGFR-1 inhibition reduced weight gain, but caused metabolic disorder-hyperinsulinemia-during obesity. Combining metformin with VEGFR-1 inhibition not only prevented this metabolic alteration, but also by recruiting cytotoxic cells further decreased tumor growth in the PAN02 model (p = 0.047).

Conclusion: Inactivation of VEGFR-1 signaling prevents weight gain and obesity-induced acceleration of tumor progression in pancreatic and breast cancer models. Targeting VEGFR-1 signaling axis in combination with an anti-diabetic drug such as metformin might be a considerable cancer therapeutic option in the obese setting.

Note: This abstract was not presented at the meeting.

Citation Format: Joao Incio, Joshua Tam, Nuh Rahbari, Priya Suboj, Daniel McManus, Shan Chin, Trupti Vardan-Kaur, Ana Batista, Suboj Babycutty, Keehoon Jung, Anna Khachatryan, Masabumi Shibuya, Raquel Soares, Dan Duda, Rakesh K. Jain, Dai Fukumura. Role of VEGFR-1 signaling in obesity-induced tumor progression. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-267. doi:10.1158/1538-7445.AM2015-LB-267
Abstract LB-298: The multiple-myeloma associated snoRNA, ACA11 increases oxidative stress and cell proliferation
Authors: Mahajan Nitin , Maggi Leonard B. , Tomasson Michael H. , Weber Jason D.
Published: August 2015

Multiple myeloma (MM) is an incurable malignancy of antibody secreting plasma B cells. The t(4;14) translocation is detected in 20% of MM and is associated with shortened patient survival. Although the t(4;14) is known to up regulate the MMSET proteins, its role in MM remains unclear. Previously, we identified a novel orphan box H/ACA class small nucleolar RNA (snoRNA), that is located within intron 19 of MMSET, and is expressed in MM cells harboring the t(4;14) translocation. H/ACA small RNAs are an evolutionarily conserved class of abundant noncoding RNAs (ncRNA) involved in a diverse range of processes including posttranslational modifications of functional RNAs, preribosomal RNA processing, and telomere maintenance, yet their contribution to human disease remains largely unexplored. In this study, t(4:14) positive and negative MM patient tumor cells were analyzed by RNA sequencing. This revealed a unique signature of up regulated genes involved in mitochondrial respiration and oxidative stress. Our hypothesis is ACA11 plays critical role in MM cell proliferation and cell transformation by increasing oxidative stress. We found that acute ACA11 overexpression leads to the increased oxidative stress in primary splenic B-cells, established myeloma cell lines, as well as embryonic fibroblasts. In particular, cells overexpressing ACA11 showed enhanced proliferation, significantly larger colony sizes in soft agar assays, and elevated ERK1/2 phosphorylation, a downstream consequence of oxidative stress. In addition, we found that the transcription factor nuclear factor erythroid-derived 2-related factor 2 (Nrf2), which regulates anti-oxidant signaling, dissociated from Keap1 and translocated to the nucleus, but failed to activate anti-oxidant downstream targets in ACA11 overexpressing cells. Furthermore, ACA11 up regulated TXNIP, which encodes an inhibitor of ROS scavenger thioredoxin. In conclusion, we propose that acute overexpression of ACA11 up regulates TXNIP and suppresses the ability of Nrf2 to induce target anti-oxidants genes, resulting in increased oxidative stress and cell proliferation. These changes may be critical events in the development and/or progression of multiple myeloma.

Citation Format: Nitin Mahajan, Leonard B. Maggi, Michael H. Tomasson, Jason D. Weber. The multiple-myeloma associated snoRNA, ACA11 increases oxidative stress and cell proliferation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-298. doi:10.1158/1538-7445.AM2015-LB-298
Abstract LB-299: Gene knockdown by EpCAM aptamer-siRNA chimeras suppresses epithelial breast cancers and their tumor-initiating cells
Authors: Gilboa-Geffen Adi , Hamar Peter , Wheeler Lee Adam , Trifonova Radiana , Petrocca Fabio , Wittrup Anders , Lieberman Judy
Published: August 2015

Effective therapeutic strategies for in vivo siRNA delivery to knockdown genes in cells outside the liver are needed to harness RNA interference for treating cancer. EpCAM is a tumor-associated antigen highly expressed on common epithelial cancers and their tumor-initiating cells (T-IC, also known as cancer stem cells). Here we show that aptamer-siRNA chimeras (AsiC, an EpCAM aptamer linked to an siRNA sense strand and annealed to the siRNA antisense strand) are selectively taken up and knockdown gene expression in EpCAM+ cancer cells in vitro and in human cancer biopsy tissues. PLK1 EpCAM-AsiCs inhibit colony and mammosphere formation (in vitro T-IC assays) and tumor initiation by EpCAM+ luminal and basal-A triple negative breast cancer (TNBC) cell lines, but not EpCAM- mesenchymal basal-B TNBCs, in nude mice. Subcutaneously administered EpCAM-AsiCs concentrate in EpCAM+ Her2+ and TNBC tumors and suppress their growth. Thus EpCAM-AsiCs provide an attractive approach for treating epithelial cancer.

Note: This abstract was not presented at the meeting.

Citation Format: Adi Gilboa-Geffen, Peter Hamar, Lee Adam Wheeler, Radiana Trifonova, Fabio Petrocca, Anders Wittrup, Judy Lieberman. Gene knockdown by EpCAM aptamer-siRNA chimeras suppresses epithelial breast cancers and their tumor-initiating cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-299. doi:10.1158/1538-7445.AM2015-LB-299
Abstract LB-300: Reintroduction of tumor-suppressor miR-34a shows therapeutic efficacy in triple-negative breast cancer
Authors: Adams Brian D. , Wali Vikram , Cheng Chris , Inukai Sachi , Rimm David , Pusztai Lajos , Saltzman Mark , Slack Frank
Published: August 2015

Triple-negative breast cancer (TNBC) accounts for a disproportionate share of the total breast cancer morbidity because of its aggressive behavior and lack of effective targeted therapies to treat the disease. MicroRNAs, global regulators of survival and proliferation pathways important in tumor development and maintenance, are highly dysregulated in cancer. We identified miR-34a to be aberrantly lost in TNBC lines when compared to both a luminal cancer subtype as well as normal breast cells. Re-introduction of miR-34a in TNBC lines results in inhibition of cell proliferation and invasion, reactivation of senescence, and enhanced sensitivity to apoptosis inducing agents. Furthermore, intratumoral delivery of miR-34a into subcutaneous tumors in nude mice, as well as systemic delivery of poly(amine-co-ester) PACE-loaded miR-34a in an orthotopic setting, delayed tumor growth. In conclusion, re-introduction of miR-34a in TNBC promotes potent anti-tumorigenic phenotypes in vitro and in vivo, and could be a promising targeted therapeutic agent to treat the disease.

Citation Format: Brian D. Adams, Vikram Wali, Chris Cheng, Sachi Inukai, David Rimm, Lajos Pusztai, Mark Saltzman, Frank Slack. Reintroduction of tumor-suppressor miR-34a shows therapeutic efficacy in triple-negative breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-300. doi:10.1158/1538-7445.AM2015-LB-300
Abstract SY07-01: New targets in combination cancer immunotherapies
Authors: Smyth Mark J.
Published: August 2015

Cancer immunotherapy may become the treatment backbone in many cancers over the next decade. The demonstration that an intratumor TH1 immune polarity is prognostic of good clinical outcome and the recent success with co-immune checkpoint blockade in humans now sets the stage for rational tailoring of immunotherapies to treat specific cancer types. The recently approved anti-PD-1 monoclonal antibody (mAb)(pembrolizumab) and other mAbs targeting PD-L1 have revolutionized the field. Pre-clinical data and combinations between anti-CTLA-4 (ipilimumab) and anti-PD-1 (Nivolumab) in advanced malignant melanoma demonstrate the anti-tumor potential and dangers of targeting more than one immune evasion pathway. There are four different types of tumor microenvironment based on the presence or absence of tumor infiltrating lymphocytes and programmed death-ligand 1 (PD-L1) expression. This stratification may be an approach for rationally designing ideal combinations between various new immunotherapies and conventional cancer treatments. This seminar will discuss our recent work to determine which tumors are responsive to anti-PD-1 and what pathways are necessary for, or an impediment to, anti-PD-1 anti-tumor activity. Our efforts to pre-clinically examine two new target pathways including immune checkpoints CD96/TIGIT and the immune suppressive metabolite adenosine will be described. Their combination with anti-PD-1 therapies will be detailed. Further, the ability of some targeted therapies to act in part via host immunity has created opportunities to rationally combine these approaches with immunotherapy in humans. These and other pre-clinical studies of combinations that concurrently relieve Treg- and M2 macrophage-mediated immune suppression will be discussed. Mouse models for combination treatment sequencing in the context of adjuvant therapy and safety in relation to immune related adverse events will be presented.

Citation Format: Mark J. Smyth. New targets in combination cancer immunotherapies. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr SY07-01. doi:10.1158/1538-7445.AM2015-SY07-01
Abstract SY27-04: Induction of cancer stemness and drug resistance by EGFR blockade
Authors: Cheresh David A.
Published: August 2015

Tumor drug resistance is often accompanied by genetic and biological changes in the tumor cell population reflecting the acquisition of a stem-like state. However, it is not clear whether cancer therapies select for the growth of drug resistance cancer stem cells and/or directly induce the reprograming of tumor cells to a cancer stem-like, drug resistance state. We provide evidence that breast, pancreas and lung carcinomas in the presence of prolonged exposure to EGFR inhibitors undergo an epigenetic reprogramming resulting in a drug resistant stem-like tumor population expressing the cell surface marker CD61 (b3 integrin). In fact, CD61 in the context of KRAS, is necessary and sufficient to account for drug resistance, tumor initiation, self-renewal and expression of the pluripotent genes Oct 4 and Nanog. Once expressed, CD61 in the unligated state recruits KRAS to the plasma membrane leading to the activation of RalB, TBK1 and c-Rel driving both stemness and EGFR inhibitor resistance. Pharmacological targeting this pathway with drugs such as bortezomib or revlimid not only reverses stemness but resensitizes these epithelial tumors to EGFR inhibition. This epigenetic pathway can also be initiated by range of cellular stresses found within the tumor microenvironment such as hypoxia, nutrient deprivation, low pH, and oxidative stress. In normal tissues CD61 is induced during tissue remodeling and repair. For example, CD61 was found to be critical for mammary gland remodeling during pregnancy and as a mediator of pathological neovascularization. Together these findings reveal a stress-induced epigenetic pathway characterized by the upregulation of CD61 that promotes the remodeling of normal tissues but in tumors contributes to EGFR inhibitor resistance and tumor progression.

Citation Format: David A. Cheresh. Induction of cancer stemness and drug resistance by EGFR blockade. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr SY27-04. doi:10.1158/1538-7445.AM2015-SY27-04
Abstract SY30-02: Understanding the proteome through the chaperome: From mechanisms to diagnostics and drugs
Authors: Chiosis Gabriela
Published: August 2015

Malignant cellular function is maintained by a functionally altered proteome. Helping the proteome in this context is the chaperome, a network of molecular chaperones and folding enzymes. This talk will discuss how, by using chemical tools that selectively target the stress chaperome, one may perform mechanistic and therapeutic investigations into the tumor proteome. Specifically, using chemical tools as affinity-purification baits or as global perturbers of the altered proteome one may inquire into its nature (i.e., identify and investigate). By attacking specifically the stress chaperome, one may inactivate the altered proteome, and thus revert or slow the disease phenotype (i.e., treat).

In summary, I will discuss how by chemically sensing the stress chaperome one may investigate, understand and destabilize the tumor proteome.

Citation Format: Gabriela Chiosis. Understanding the proteome through the chaperome: From mechanisms to diagnostics and drugs. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr SY30-02. doi:10.1158/1538-7445.AM2015-SY30-02
Abstract SY33-04: Integrated omic analysis of lung cancer reveals metabolism-proteome signatures with prognostic impact
Authors: Moran Michael F. , Li Lei , Wei Yuhong , Taylor Paul , To Christine , Tong Jiefei , Ignatchenko Vladimir , Pintilie Melania , Pham Nhu-An , Zhang Wen , Muthuswamy Lakshmi , Shepherd Frances A. , Kislinger Thomas , Tsao Ming S.
Published: August 2015

Cancer results from processes prone to selective pressure and dysregulation acting along the sequence-to- phenotype continuum DNA→RNA→Protein→Disease. An Omics Array integrating DNA gene copy number, mRNA transcriptome, and quantified proteome was assembled into a genetic map representing non-small cell lung carcinoma (NSCLC). Data were collected from patient-matched normal lung, primary tumors, and patient tumor-derived xenograft (PDX) tumors. Dysregulated proteins not previously implicated as cancer drivers were found encoded throughout the genome including but not limited to regions of recurrent DNA amplification/deletion in NSCLC. Unsupervised clustering revealed signatures comprising metabolism proteins particularly highly recapitulated between matched primary and PDX tumors, and which distinguished between the major NSCLC histological subtypes adenocarcinoma (ADC) and squamous cell carcinoma (SCC). Interrogation of The Cancer Genome Atlas (TCGA) revealed sizeable cohorts of NSCLC patients with DNA alterations in genes encoding the metabolism proteome signatures, and accompanied by differences in survival. Similar to the proteome signatures from which they were extrapolated, the gene mutation signatures with prognostic impact discriminated between the lung ADC and SCC subtypes. Serine hydroxymethyltransferase 2 (SHMT2), a key enzyme in serine/glycine and folate- dependent one-carbon metabolism, is upregulated in the proteomes of NSCLC primary and PDX tumours, and is implicated as a driver of recurrent chromosome 12q14.1 amplification in NSCLC. SHMT2, along with other enzymes implicated as anti-folate targets, is also part of a metabolism proteome signature associated with poor outcome in lung ADC. The interrogation of cancer genomes and proteomes for alterations that are related products of selective pressures driving the cancer phenotype may be a general approach to uncover and group together cryptic, polygenic cancer drivers, which might represent new anti-cancer therapeutic targets.

Citation Format: Michael F. Moran, Lei Li, Yuhong Wei, Paul Taylor, Christine To, Jiefei Tong, Vladimir Ignatchenko, Melania Pintilie, Nhu-An Pham, Wen Zhang, Lakshmi Muthuswamy, Frances A. Shepherd, Thomas Kislinger, Ming S. Tsao. Integrated omic analysis of lung cancer reveals metabolism-proteome signatures with prognostic impact. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr SY33-04. doi:10.1158/1538-7445.AM2015-SY33-04
The Effect of Telephone-Based Cognitive-Behavioral Therapy on Postnatal Depression: A Randomized Controlled Trial
Authors: Ngai Fei-Wan , Wong Paul Wai-Ching , Leung Kwok-Yin , Chau Pui-Hing , Chung Ka-Fai
Published: August 2015

Background: Cognitive-behavioral therapy (CBT) is one of the most effective interventions for postnatal depression. However, few studies have evaluated the effect of CBT delivered via telephone for newborn mothers. The purpose of this study was to evaluate the efficacy of telephone-based CBT for postnatal depression at 6 weeks and 6 months postpartum. Methods: A multisite randomized controlled trial was conducted in the postnatal units at 3 regional hospitals in Hong Kong. A total of 397 women with an Edinburgh Postnatal Depression Scale (EPDS) score ≥10 on the second or third day postpartum were randomized to receive telephone-based CBT (n = 197) or standard care (n = 200). Primary outcome was the total EPDS score. A cutoff score of 9/10 on the EPDS was used to define women at risk of postnatal depression. Results: Telephone-based CBT was associated with significantly lower depressive symptoms compared with standard care, when assessed at 6 weeks postpartum in the subgroups of mothers with minor depression (EPDS 10-12; difference = 1.90, 95% CI: 0.72-3.08; p = 0.002) and major depression (EPDS ≥13; difference = 5.00, 95% CI: 3.12-6.88; p < 0.001). The effect was sustained at 6 months postpartum in the subgroup with minor depression (difference = 1.20, 95% CI: 0.09-2.32; p = 0.034) but not significant in the subgroup with major depression (difference = 1.69, 95% CI: -0.10-3.47; p = 0.064). The proportion of women who satisfied our definition of postnatal depression was significantly lower in the intervention group at 6 weeks (difference = 23.3%, 95% CI: 13.7-33.0%; p < 0.001) and 6 months postpartum (difference = 11.4%, 95% CI: 1.9-20.8%; p = 0.019). Conclusions: Telephone-based CBT produced a significantly greater reduction in depressive symptoms than standard care during the postpartum period.
The Effectiveness of a Patient-Centred Assessment with a Solution-Focused Approach (DIALOG+) for Patients with Psychosis: A Pragmatic Cluster-Randomised Controlled Trial in Community Care
Authors: Priebe Stefan , Kelley Lauren , Omer Serif , Golden Eoin , Walsh Sophie , Khanom Husnara , Kingdon David , Rutterford Clare , McCrone Paul , McCabe Rosemarie
Published: August 2015

Background: DIALOG+ was developed as a computer-mediated intervention, consisting of a structured assessment of patients' concerns combined with a solution-focused approach to initiate change. This study tested the effectiveness of DIALOG+ in the community treatment of patients with psychosis. Method: This was a pragmatic, exploratory, parallel-group, cluster-randomised controlled trial. Clinicians within community teams - along with patients with psychosis under their care - were randomised to use DIALOG+ once per month for 6 months or an active control. The primary outcome (subjective quality of life, SQOL) and secondary outcomes were assessed after 3, 6 and 12 months by blinded assessors and analysed using mixed-effect models. Results: A total of 49 clinicians and 179 patients were randomised. Implementation of DIALOG+ was variable, with an average of 1.8 sessions (SD = 1.6) in the first 3 months and 1.1 (SD = 1.2) in the following 3 months. Patients in the DIALOG+ arm had better SQOL at 3, 6 and 12 months (p = 0.035, 0.058 and 0.014, respectively; Cohen's d = 0.29-0.34). They also had significantly fewer unmet needs at 3 and 6 months, fewer general psychopathological symptoms at all time points and better objective social outcomes at 12 months, with no significant differences in other outcomes. Overall care costs were lower in the intervention group. Conclusion: Despite variable implementation, DIALOG+ is a beneficial intervention for community patients with psychosis. As a non-expensive and potentially cost-saving, generic intervention, DIALOG+ may be widely used and may improve the effectiveness of community treatment. Further trials should test DIALOG+ in different patient groups and contexts.
Interhemispheric Vertical Hemispherotomy: A Single Center Experience
Authors: Iwasaki Masaki , Uematsu Mitsugu , Osawa Shin-ichiro , Shimoda Yoshiteru , Jin Kazutaka , Nakasato Nobukazu , Tominaga Teiji
Published: August 2015

Purpose: Hemispheric epileptogenic lesions such as hemimegalencephaly often manifest as intractable epilepsy in early infancy. Hemispherotomy is the treatment of choice for controlling intractable hemispheric epilepsy. Less invasive procedures are desirable for surgery on infants with low body weight. This study compared our experience with interhemispheric vertical hemispherotomy (IVH) and peri-insular lateral hemispherotomy (PIH). Methods: Thirteen consecutive patients underwent hemispherotomy for treatment of intractable epilepsy in our institution between 2001 and 2012. The etiology of epilepsy included hemimegalencephaly in 7 patients and cortical dysplasia in 3. PIH was performed on the first 5 patients and IVH on the last 8 patients. In the latter procedure, complete section of the corpus callosum was first performed via the interhemispheric approach. After removing part of the cingulate gyrus, section of the descending fibers was performed anterolaterally to the thalamus. Clinical characteristics, duration of operation and amount of blood transfusion were compared between the PIH and IVH groups. Results: There was no difference in age at surgery, body weight and age of epilepsy onset between the two groups. No surgery-related death was observed. No patients required shunt operation. One patient who underwent IVH required reoperation for incomplete disconnection. The amount of intraoperative blood transfusion was smaller and the total duration of operation was shorter in the IVH group than in the PIH group. Conclusion: The interhemispheric approach minimizes cortical resection and may be less invasive than PIH. IVH is advantageous for treating infants with low body weight.
Partial Sequence of a Novel Virus Isolated from Pelodiscus sinensis Hemorrhagic Disease
Authors: Liu Li , Cao Zheng , Lin Feng , Ye Xue-ping , Xu Yi
Published: August 2015

Outbreaks of hemorrhagic syndrome-like disease with high mortality rates have frequently occurred in Pelodiscus sinensis farms. The purpose of this study was to investigate the pathogen through challenge infection assays and partial sequencing of the genome of the pathogen. A 453-bp amplicon was obtained by random PCR using the nucleic acid extracted from the tissue homogenate filtrate and showed 32% identity at the amino acid level with the replicase polyprotein of the porcine reproductive and respiratory syndrome virus by Blastx. Multiple alignments indicated the putative protein sequence has some similarities to the replicase polyprotein of Arteriviridae, and the phylogenetic tree showed it was closely related to equine arteritis virus. This sequence was found in the lung of the diseased P. sinensis by in situ hybridization. Dot blot hybridization and quantitative RT-PCR showed that the lung had the highest content of virus. The peak replication of P. sinensis hemorrhagic syndrome virus (TSHSV) in the lung occurred 4 days after infection. The ribonucleic nature of the viral genome was confirmed by RNase A or DNase I treatments. We named the virus TSHSV in this study as P. sinensis is also known as Trionyx sinensis. These results provide a fundamental basis for further understanding the biology and the molecular mechanisms of TSHSV.
Cardiac Hypertrophy Is Inhibited by a Local Pool of cAMP Regulated by Phosphodiesterase 2
Authors: Zoccarato Anna , Surdo Nicoletta C. , Aronsen Jan M. , Fields Laura A. , Mancuso Luisa , Dodoni Giuliano , Stangherlin Alessandra , Livie Craig , Jiang He , Sin Yuan Yan , Gesellchen Frank , Terrin Anna , Baillie George S. , Nicklin Stuart A. , Graham Delyth , Szabo-Fresnais Nicolas , Krall Judith , Vandeput Fabrice , Movsesian Matthew , Furlan Leonardo , Corsetti Veronica , Hamilton Graham , Lefkimmiatis Konstantinos , Sjaastad Ivar , Zaccolo Manuela
Published: August 2015

Rationale
:

Chronic elevation of 3′-5′-cyclic adenosine monophosphate (cAMP) levels has been associated with cardiac remodeling and cardiac hypertrophy. However, enhancement of particular aspects of cAMP/protein kinase A signaling seems to be beneficial for the failing heart. cAMP is a pleiotropic second messenger with the ability to generate multiple functional outcomes in response to different extracellular stimuli with strict fidelity, a feature that relies on the spatial segregation of the cAMP pathway components in signaling microdomains.

Objective
:

How individual cAMP microdomains affect cardiac pathophysiology remains largely to be established. The cAMP-degrading enzymes phosphodiesterases (PDEs) play a key role in shaping local changes in cAMP. Here we investigated the effect of specific inhibition of selected PDEs on cardiac myocyte hypertrophic growth.

Methods and Results
:

Using pharmacological and genetic manipulation of PDE activity, we found that the rise in cAMP resulting from inhibition of PDE3 and PDE4 induces hypertrophy, whereas increasing cAMP levels via PDE2 inhibition is antihypertrophic. By real-time imaging of cAMP levels in intact myocytes and selective displacement of protein kinase A isoforms, we demonstrate that the antihypertrophic effect of PDE2 inhibition involves the generation of a local pool of cAMP and activation of a protein kinase A type II subset, leading to phosphorylation of the nuclear factor of activated T cells.

Conclusions
:

Different cAMP pools have opposing effects on cardiac myocyte cell size. PDE2 emerges as a novel key regulator of cardiac hypertrophy in vitro and in vivo, and its inhibition may have therapeutic applications.
Rate of Contrast Extravasation on Computed Tomographic Angiography Predicts Hematoma Expansion and Mortality in Primary Intracerebral Hemorrhage
Authors: Brouwers H. Bart , Battey Thomas W.K. , Musial Hayley H. , Ciura Viesha A. , Falcone Guido J. , Ayres Alison M. , Vashkevich Anastasia , Schwab Kristin , Viswanathan Anand , Anderson Christopher D. , Greenberg Steven M. , Pomerantz Stuart R. , Ortiz Claudia J. , Goldstein Joshua N. , Gonzalez R. Gilberto , Rosand Jonathan , Romero Javier M.
Published: August 2015

Background and Purpose—

In primary intracerebral hemorrhage, the presence of contrast extravasation after computed tomographic angiography (CTA), termed the spot sign, predicts hematoma expansion and mortality. Because the biological underpinnings of the spot sign are not fully understood, we investigated whether the rate of contrast extravasation, which may reflect the rate of bleeding, predicts expansion and mortality beyond the simple presence of the spot sign.

Methods—

Consecutive intracerebral hemorrhage patients with first-pass CTA followed by a 90-second delayed postcontrast CT (delayed CTA) were included. CTAs were reviewed for spot sign presence by 2 blinded readers. Spot sign volumes on first-pass and delayed CTA and intracerebral hemorrhage volumes were measured using semiautomated software. Extravasation rates were calculated and tested for association with hematoma expansion and mortality using uni- and multivariable logistic regressions.

Results—

One hundred and sixty-two patients were included, 48 (30%) of whom had ≥1 spot sign. Median spot sign volume was 0.04 mL on first-pass CTA and 0.4 mL on delayed CTA. Median extravasation rate was 0.23 mL/min overall and 0.30 mL/min among expanders versus 0.07 mL/min in nonexpanders. Extravasation rates were also significantly higher in patients who died in hospital: 0.27 mL/min versus 0.04 mL/min. In multivariable analysis, the extravasation rate was independently associated with in-hospital mortality (odds ratio, 1.09 [95% confidence interval, 1.04–1.18],
P
=0.004), 90-day mortality (odds ratio, 1.15 [95% confidence interval, 1.08–1.27];
P
=0.0004), and hematoma expansion (odds ratio, 1.03 [95% confidence interval, 1.01–1.08];
P
=0.047).

Conclusions—

Contrast extravasation rate, or spot sign growth, further refines the ability to predict hematoma expansion and mortality. Our results support the hypothesis that the spot sign directly measures active bleeding in acute intracerebral hemorrhage.
Neurorestorative Therapy of Stroke in Type 2 Diabetes Mellitus Rats Treated With Human Umbilical Cord Blood Cells
Authors: Yan Tao , Venkat Poornima , Chopp Michael , Zacharek Alex , Ning Ruizhuo , Cui Yisheng , Roberts Cynthia , Kuzmin-Nichols Nicole , Sanberg Cyndy Davis , Chen Jieli
Published: August 2015

Background and Purpose—

Diabetes mellitus is a high-risk factor for ischemic stroke. Diabetic stroke patients suffer worse outcomes, poor long-term recovery, risk of recurrent strokes, and extensive vascular damage. We investigated the neurorestorative effects and the underlying mechanisms of stroke treatment with human umbilical cord blood cells (HUCBCs) in type 2 diabetes mellitus (T2DM) rats.

Methods—

Adult male T2DM rats were subjected to 2 hours of middle cerebral artery occlusion (MCAo). Three days after MCAo, rats were treated via tail-vein injection with (1) PBS and (2) HUCBCs (5×10
6
), n=10 per group.

Results—

HUCBC stroke treatment initiated 3 days after MCAo in T2DM rats did not significantly decrease blood–brain barrier leakage (
P
=0.1) and lesion volume (
P
=0.078), but significantly improved long-term functional outcome and decreased brain hemorrhage (
P
<0.05) when compared with the PBS-treated T2DM MCAo control group. HUCBC treatment significantly promoted white matter remodeling as indicated by increased expression of Bielschowsky silver (axons marker), Luxol fast blue (myelin marker), SMI-31 (neurofilament), and Synaptophysin in the ischemic border zone. HUCBC promoted vascular remodeling and significantly increased arterial and vascular density. HUCBC treatment of stroke in T2DM rats significantly increased M2 macrophage polarization (increased M2 macrophage, CD163and CD 206; decreased M1 macrophage, ED1 and inducible nitric oxide synthase expression) in the ischemic brain compared with PBS-treated T2DM MCAo controls (
P
<0.05). HUCBC also significantly decreased proinflammatory factors, that is, matrix metalloproteinase 9, receptor for advanced glycation end products and toll-like receptor 4 expression in the ischemic brain.

Conclusions—

HUCBC treatment initiated 3 days after stroke significantly increased white matter and vascular remodeling in the ischemic brain as well as decreased neuroinflammatory factor expression in the ischemic brain in T2DM rats and promoted M2 macrophage polarization. HUCBC reduction of neuroinflammation and increased vascular and white matter axonal remodeling may contribute to the HUCBC-induced beneficial effects in T2DM stroke rats.
Rosiglitazone Promotes White Matter Integrity and Long-Term Functional Recovery After Focal Cerebral Ischemia
Authors: Han Lijuan , Cai Wei , Mao Leilei , Liu Jia , Li Peiying , Leak Rehana K. , Xu Yun , Hu Xiaoming , Chen Jun
Published: August 2015

Background and Purpose—

Oligodendrogenesis is essential for white matter repair after stroke. Although agonists of peroxisome proliferator–activated receptors γ confer neuroprotection in models of cerebral ischemia, it is not known whether this effect extends to white matter protection. This study tested the hypothesis that the peroxisome proliferator–activated receptors γ agonist rosiglitazone enhances oligodendrogenesis and improves long-term white matter integrity after ischemia/reperfusion.

Methods—

Male adult C57/BL6 mice (25–30 g) were subjected to 60-minute middle cerebral artery occlusion and reperfusion. Rosiglitazone (3 mg/kg) was injected intraperitoneally once daily for 14 days beginning 2 hours after reperfusion. Sensorimotor and cognitive functions were evaluated ≤21 days after middle cerebral artery occlusion. Immunostaining was used to assess infarct volume, myelin loss, and microglial activation. Bromodeoxyuridine (BrdU) was injected for measurements of proliferating NG2
+
oligodendrocyte precursor cells (OPCs) and newly generated adenomatous polyposis coli
+
oligodendrocytes. Mixed glial cultures were used to confirm the effect of rosiglitazone on oligodendrocyte differentiation and microglial polarization.

Results—

Rosiglitazone significantly reduced brain tissue loss, ameliorated white matter injury, and improved sensorimotor and cognitive functions for at least 21 days after middle cerebral artery occlusion. Rosiglitazone enhanced OPC proliferation and increased the numbers of newly generated mature oligodendrocytes after middle cerebral artery occlusion. Rosiglitazone treatment also reduced the numbers of Iba1
+
/CD16
+
M1 microglia and increased the numbers of Iba1
+
/CD206
+
M2 microglia after stroke. Glial culture experiments confirmed that rosiglitazone promoted oligodendrocyte differentiation, perhaps by promoting microglial M2 polarization.

Conclusions—

Rosiglitazone treatment improves long-term white matter integrity after cerebral ischemia, at least, in part, by promoting oligodendrogenesis and facilitating microglial polarization toward the beneficial M2 phenotype.
Facial Action and Emotional Language: ERP Evidence that Blocking Facial Feedback Selectively Impairs Sentence Comprehension
Authors: Davis Joshua D. , Winkielman Piotr , Coulson Seana
Published: August 2015

There is a lively and theoretically important debate about whether, how, and when embodiment contributes to language comprehension. This study addressed these questions by testing how interference with facial action impacts the brain's real-time response to emotional language. Participants read sentences about positive and negative events (e.g., “She reached inside the pocket of her coat from last winter and found some (cash/bugs) inside it.”) while ERPs were recorded. Facial action was manipulated within participants by asking participants to hold chopsticks in their mouths using a position that allowed or blocked smiling, as confirmed by EMG. Blocking smiling did not influence ERPs to the valenced words (e.g., cash, bugs) but did influence ERPs to final words of sentences describing positive events. Results show that affectively positive sentences can evoke smiles and that such facial action can facilitate the semantic processing indexed by the N400 component. Overall, this study offers causal evidence that embodiment impacts some aspects of high-level comprehension, presumably involving the construction of the situation model.
Methodological Issues concerning the Astronomy of Qumran
Authors: Ratzon Eshbal
Published: August 2015

In the 21st issue of Dead Sea Discoveries, Dennis Duke and Matthew Goff offered their collaboration as physicist and Dead Sea Scrolls scholar in order to study the lunar theory of the Aramaic Astronomical Book (aab). They use the astronomical model of lunar elongation—the angular distance between the moon and the sun on the observed heavenly sphere—to compute the times of the moon’s visibility and invisibility. They conclude that the times written on the Aramaic fragments are closer to reality than the times written in the Babylonian sources of the aab. This paper concludes that lunar elongation is not the best explanation of the astronomical data of the aab, and Duke and Goff’s computations should be refined according to some astronomical, cosmological, textual, and historical considerations.
Chromosome Numbers in various Mosses from Papua New Guinea
Authors: Ramsay Helen P.
Published: August 2015

Chromosome numbers, obtained from meiotic and /or mitotic studies on various mosses from Papua New Guinea, represent new data for 18 species in 15 genera in the following 13 families:- Entodontaceae, Funariaceae, Garovagliaceae; Hookeriaceae, Hypnaceae, Hypopterygiaceae, Leucobryaceae, Mniaceae, Pottiaceae, Pterobryaceae, Racopilaceae, Rhizogoniaceae, and Spiridentaceae.
Eohypopterygiopsis dominicensis, a new genus and species, and Pyrrhobryum spiniforme from the Miocene of the Dominican Republic
Authors: Frahm Jan-Peter
Published: August 2015

A strange moss is illustrated and described from Dominican amber (Miocene). It is densely triseriate foliate with ligulate lateral leaves which are strongly auriculate at base and small costate ventral leaves. A similar combination of characters is found in the Hypopterygiaceae, however, no extant species of this family matches the fossil. It is therefore described as Eophypopterygiopsis dominicensis J.-P. ,Frahm as new species in a new (possibly extinct) genus. In addition, the pantropical Pyrrhobryum spiniforme (Hedw.) Mitt. is recorded from Dominican amber for the first time, and Calyptothecium duplicatum (Schwaegr.) Broth. as well as a species of Homalia are reported.
Revisión de Plagiomnium (Plagiomniaceae, Bryopsida) en Argentina
Authors: Fuertes Esther , Oliván Gisela
Published: August 2015

The genus Plagiomnium T.J. Kop. is revised for Argentina, based on examination of herbarium specimens and on specimens collected during three field expeditions (2005-07). The following species are recognized for the Argentinean Bryological Flora: Plagiomnium undulatum (Hedw.) T.J. Kop., P. ellipticum (Brid.) T.J. Kop., and P. rhynchophorum (Hook.) T.J. Kop. This last taxon is a new record for the bryological flora of Argentina. All the specimens revised and previously identified as Plagiomnium rostratum (Schrad.) T.J. Kop. or their synonyms have been re-identified as P. rhynchophorum. Thus, we suspect that P. rostratum does not occur in Argentina. We suggest, before excluding this taxon from the Checklist of Mosses of Argentina, that the genus should be revised. The threats to Plagiomnium populations in Argentina are analyzed. Identification keys, descriptions, iconography, and distribution maps for all the species are provided.
A new species of Waldeckia from the Austral Isles, Society Islands (Amphipoda, Lysianassoidea, Lysianassidae, Waldeckiinae)
Authors: LOWRY J.K. , KILGALLEN N.M.
Published: August 2015

A new species of the scavenging lysianassid amphipod genus Waldeckia, W. bamberi sp. nov., is described from the Austral Isles, Society Isles, the first record of Waldeckia on the Pacific Plate.
A new amphipod Nicippe rogeri sp. nov. (Crustacea, Pardaliscidae) from New Zealand’s deep sea
Authors: LÖRZ ANNE-NINA , SCHNABEL KAREEN
Published: August 2015

The amphipod family Pardaliscidae has a worldwide distribution and is considered to be especially common in the deep sea. This is the first record of the genus Nicippe in New Zealand waters and a new species, N. rogeri sp. nov is described in honour of Dr. Roger Bamber. This brings the number of species in the genus Nicippe worldwide to four. The new species is described in detail and a key to the four species of Nicippe is provided.
A new species of heterochelous tanaidacean Tanaissus (Paratanaoidea: Tanaissuidae) from the north-west Iberian Peninsula
Authors: ESQUETE PATRICIA , RUBAL MARCOS
Published: August 2015

A new species of tanaidomorph, Tanaissus bamberi, is described from the north-western region of the Iberian Peninsula. Its most remarkable character is the presence of morphologically different right and left chelae in the males. The species occurs sympatrically with T. lilljeborgi, mainly in intertidal and subtidal sediments of medium to muddy sands typical of fully marine and estuarine salinities.
Deep-water Thyasiridae (Mollusca: Bivalvia) from the Oman Margin, Arabian Sea, new species and examples of endemism and cosmopolitanism
Authors: OLIVER P. GRAHAM
Published: August 2015

Seven species of Thyasiridae are reported from the Oman Margin of the Arabian Sea at depths between 688 m and 3356 m. Hypoxic conditions exist at depths between 400 and 1200 m and three species are restricted to this zone and to the Arabian Sea. Leptaxinus indusarium has also been recorded from the Indus Fan and Channelaxinus investigatoris from off Sri Lanka. A new species Thyasira anassa sp. nov. is described from the hypoxic zone. Another four species are recorded from the abyssal zone where oxygen levels are typical for the deep ocean. Here another new species is described, Parathyasira bamberi sp. nov. but the other species could not be conclusively identified because of close affinity with populations from other oceans.  Deep water Atlantic species Axinulus croulinensis and Mendicula ferruginosa are apparently present in the abyssal Indian Ocean while another thyasirid shell is very close to Channelaxinus excavatus from the Eastern Pacific and C. perplicata from the Atlantic. Accompanying these abyssal thyasirids were other bivalve species, Deminucula atacellana, Limopsis pelagica and Bentharca asperula that cannot be distinguished by morphology from their Atlantic populations. It is concluded that using morphology alone that the abyssal species may well be cosmopolitan in distribution.
Antonbruunia sociabilis sp. nov. (Annelida: Antonbruunidae) associated with the chemosynthetic deep-sea bivalve Thyasira scotiae Oliver & Drewery, 2014, and a re-examination of the systematic affinities of Antonbruunidae
Authors: MACKIE ANDREW S.Y. , OLIVER P. GRAHAM , NYGREN ARNE
Published: August 2015

Antonbruunia sociabilis sp. nov., an abundant endosymbiont of Thyasira scotiae from a putative sulphidic ‘seep’ in the Hatton-Rockall Basin (1187–1200 m), North-East Atlantic Ocean, is described. The new species is compared with A. viridis and A. gerdesi from the West Indian Ocean and South-East Pacific Ocean respectively. The three species can be distinguished using a suite of morphological characters, and are associated with geographically separated chemosynthetic bivalve molluscs from different families (Thyasiridae, Lucinidae, Vesicomyidae) living in sediments at different depths. New morphological features are recognized for Antonbruunia and a re-assessment of its systematic affinities indicates a close relationship with the Pilargidae. Previous suggestions of an affiliation with the Nautiliniellidae, recently incorporated into the Calamyzinae (Chrysopetalidae), were not supported. The apparent morphological similarities between the two groups are indicative of convergence related to their shared relationships with chemosynthetic bivalves. The first molecular analyses of Antonbruunia (16S and 18S rDNA) clearly indicate that a close relationship to Pilargidae (represented by Ancistrosyllis sp. and Sigambra sp.) is more likely than an affinity to Calamyzinae (represented by Calamyzas amphictenicola, Natushima sp., and Vigtorniella sp.).
Cheilopallene ogasawarensis, a New Species of Shallow-Water Pycnogonid (Arthropoda: Pycnogonida) from the Ogasawara (Bonin) Islands, Japan, Northwest Pacific
Authors: NAKAMURA KOICHIRO , AKIYAMA TADASHI
Published: August 2015

A new species of pycnogonid recorded from the shallow waters of Ogasawara (Bonin) Island, Japan, Cheilopallene ogasawarensis n. sp. is described, illustrated and compared with similar species. Cheilopallene ogasawarensis is only the third pycnogonid species recorded from these islands. Morphological characters clearly distinguish the new species from its geographically closest congener C. nodulosa Hong and Kim, 1987, also recorded from Japanese waters.
Contrasting Influences of Recent Aerosol Changes on Clouds and Precipitation in Europe and East Asia
Authors: Stjern Camilla W. , Kristjánsson Jón Egill
Published: August 2015

Over the last few decades, aerosol loadings have increased greatly over Southeast Asia, while Europe and North America have experienced huge reductions. Previous studies have suggested that these changes may have influenced the temperature trends as well as precipitation patterns due to the direct and semidirect aerosol effects. Here, an Earth system model with parameterized aerosol–radiation and aerosol–cloud interactions is used to investigate changes in cloud properties and precipitation between 1975 and 2005. This is done globally as well as for the two focus areas Europe and East Asia. Despite systematic changes in cloud droplet number concentration and cloud droplet size, changes in stratiform precipitation are less clear. In both regions there is a dominance of autoconversion over liquid water accretion as the primary precipitation release mechanism, which alone should imply a strong sensitivity to changes in cloud droplet size. However, in these areas liquid water paths are relatively low and background concentrations are high, which produce low simulated precipitation susceptibilities. High susceptibilities are instead found over remote ocean regions, in agreement with expectations. For convective precipitation, both regions show statistically significant changes that are consistent with oppositely signed changes in direct aerosol forcing over Europe and East Asia, respectively.