bluuebunny/crossref_metadata_2025 huggingface dataset:
Fe‐S Clusters Emerging as Targets of Therapeutic Drugs
Authors: Vernis Laurence , El Banna Nadine , Baïlle Dorothée , Hatem Elie , Heneman Amélie , Huang Meng-Er
Published: December 2017

Fe‐S centers exhibit strong electronic plasticity, which is of importance for insuring fine redox tuning of protein biological properties. In accordance, Fe‐S clusters are also highly sensitive to oxidation and can be very easily altered in vivo by different drugs, either directly or indirectly due to catabolic by‐products, such as nitric oxide species (NOS) or reactive oxygen species (ROS). In case of metal ions, Fe‐S cluster alteration might be the result of metal liganding to the coordinating sulfur atoms, as suggested for copper. Several drugs presented through this review are either capable of direct interaction with Fe‐S clusters or of secondary Fe‐S clusters alteration following ROS or NOS production. Reactions leading to Fe‐S cluster disruption are also reported. Due to the recent interest and progress in Fe‐S biology, it is very likely that an increasing number of drugs already used in clinics will emerge as molecules interfering with Fe‐S centers in the near future. Targeting Fe‐S centers could also become a promising strategy for drug development.
Enrichment of Phenolic Compounds from Olive Mill Wastewater and In Vitro Evaluation of Their Antimicrobial Activities
Authors: Abu-Lafi Saleh , Al-Natsheh Mahmoud Sami , Yaghmoor Reem , Al-Rimawi Fuad
Published: December 2017

The production of olive oil generates massive quantities of by‐product called olive mill wastewater (OMWW). The uncontrolled disposal of OMWW poses serious environmental problems. The OMWW effluent is rich in several polyphenolic compounds. Liquid‐liquid extraction of OMWW using ethyl acetate solvent was used to enrich phenolic compounds under investigation. Total phenolic and flavonoid content and antioxidant activity of the extract were determined. HPLC coupled to photodiode array (PDA) detector was used to analyze the main three phenolic compounds of OMWW, namely, hydroxytyrosol, tyrosol, and oleuropein. The antimicrobial activity of the extract was also investigated. Additionally, the OMWW extract was used as natural preservative and antioxidants for olive oil. Results showed that OMWW is very rich in phenolic compounds and has strong antioxidant activity. HPLC analysis showed that the extract contains mainly hydroxytyrosol and tyrosol but no oleuropein. The OMWW extract showed also positive activities as antibacterial (gram positive and gram negative) and antifungal as well as activities against yeast. The addition of OMWW extract to olive oil samples has an effect on the stability of olive oil as reflected by its acid value, peroxide value, K232 and K270, and total phenolic content.
Treatment of Recurrent or Metastatic Uterine Adenosarcoma
Authors: Nathenson Michael J. , Conley Anthony P. , Lin Heather , Fleming Nicole , Ravi Vinod
Published: December 2017

Purpose. This study retrospectively evaluated overall survival (OS) by treatment of recurrent or metastatic uterine adenosarcoma including surgery, radiation, chemotherapy, and hormonal therapy and evaluated OS and progression-free survival (PFS) after 1st line systemic chemotherapy.Methods. 78 patients with recurrent or metastatic adenosarcoma comprised the study population. The Kaplan-Meier method was used to estimate OS and PFS. The log-rank test was performed to test the difference in survival between groups.Results. Median OS from diagnosis of recurrent or metastatic disease was 1.8 yrs. OS was influenced by pathology on recurrence,p=0.035. Median OS differed by surgery for 1st recurrence 26.3 months versus 15.1 months. OS was not influenced by chemotherapy,p=0.58, palliative radiation,p=0.58, or hormonal therapy,p=0.15. The response rate (CR + PR) per RECIST 1.1 for chemotherapy was 31.2% for doxorubicin-based regimens and 14.3% for gemcitabine/docetaxel. OS since 1st line chemotherapy was not significantly different among chemotherapy regimens. However, the median PFS was superior for doxorubicin/ifosfamide (15.4 months) compared to gemcitabine/docetaxel (5.0 months), platinum-based regimens (5.7 mo), or other doxorubicin-based regimens (6.5 months).Conclusion. These results suggest that surgery is an important treatment modality for recurrent or metastatic uterine adenosarcoma, and the most effective chemotherapeutics are doxorubicin/ifosfamide and gemcitabine/docetaxel.
An IoT-Aware Architecture for Collecting and Managing Data Related to Elderly Behavior
Authors: Almeida Aitor , Fiore Alessandro , Mainetti Luca , Mulero Ruben , Patrono Luigi , Rametta Piercosimo
Published: December 2017

The world population will be made up of a growing number of elderly people in the near future. Aged people are characterized by some physical and cognitive diseases, like mild cognitive impairment (MCI) and frailty, that, if not timely diagnosed, could turn into more severe diseases, like Alzheimer disease, thus implying high costs for treatments and cares. Information and Communication Technologies (ICTs) enabling the Internet of Things (IoT) can be adopted to create frameworks for monitoring elderly behavior which, alongside normal clinical procedures, can help geriatricians to early detect behavioral changes related to such pathologies and to provide customized interventions. As part of the City4Age project, this work describes a novel approach for collecting and managing data about elderly behavior during their normal activities. The data capturing layer is an unobtrusive and low-cost sensing infrastructure abstracting the heterogeneity of physical devices, while the data management layer easily manages the huge quantity of sensed data, giving them semantic meaning and fostering data shareability. This work provides a functional validation of the proposed architecture and introduces how the data it manages can be used by the whole City4Age platform to early identify risks related to MCI/frailty and promptly intervene.
Higher Ratio of Abdominal Subcutaneous to Visceral Adipose Tissue Related with Preservation of Islet β-Cell Function in Healthy Individuals
Authors: Liu Juan , Liu Jianbin , Li Hai , Liu Liehua , Zheng Jing , Huang Zhimin , Cao Xiaopei , Xiao Haipeng , Li Yanbing
Published: December 2017

Objective. To investigate the relationship between abdominal adipose tissue distribution, β-cell function, and insulin sensitivity (IS) in a Chinese population. Methods. One hundred and eighty-eight healthy subjects (healthy group), 239 with normal glucose, and 1~4 abnormal metabolic traits (metabolic dysfunction group, MD group) and 125 with hyperglycemia (hyperglycemia group) were studied. HOMA-IR, HOMA-B, Matsuda index, early- (I0–30/G0–30) and late-phase (I30–120/G30–120) insulin responses and the corresponding disposition indexes (DI) were calculated. The area of abdominal subcutaneous adipose tissue (ASAT) and visceral adipose tissue (VAT) was measured and the ratio of ASAT to VAT (SVR) was calculated. Results. SVR was correlated positively with Matsuda index in healthy, MD, and hyperglycemia groups, and inversely with HOMA-IR. SVR positively related with both early- and late-phase DI in the healthy group only. In the healthy group, the hyperbolas of I0–30/G0–30 and I30–120/G30–120 versus Matsuda index in the highest quarter of SVR were significantly right shifted compared to those in the lowest (both P<0.05). Conclusions. In healthy adults, higher SVR was a protective factor for β-cell function and IS, while in those with glucometabolic abnormality, higher SVR contributed to a relative better IS, indicating SVR is possible to be an early predicator of type 2 diabetes development.
Aqueous Extracts of Herba Cistanche Promoted Intestinal Motility in Loperamide‐Induced Constipation Rats by Ameliorating the Interstitial Cells of Cajal
Authors: Yan Shuai , Yue Yin-zi , Wang Xiao-peng , Dong Hong-li , Zhen Shu-guang , Wu Ben-sheng , Qian Hai-hua
Published: December 2017

Traditional Chinese medicine was reported to have good effects in treating functional constipation. This work attempted to prove the effects of aqueous extracts of Herba Cistanche (AEHC) on STC treatment and to determine the possible mechanisms by a loperamide‐induced slow transit constipation (STC) model. HPLC was performed for identification and confirmation of the bioactive components in the AEHC. It was found that AEHC attenuated STC responses based on increased fecal quantity, moisture content, and intestinal transit rate, as well as serum levels of GAS, MTL, SS, and CGRP. The protein and mRNA levels of c‐kit, a labeling of interstitial cells of Cajal (ICC), also increased. Meanwhile, only the protein level of SCF, a ligand of c‐kit, increased. The analysis of our data suggested that AEHC could obviously improve the function of ICC via a signaling pathway involving PI3K, SCF, and c‐kit and enhance colonic motility indices such as GAS, MTL, SS, and CGRP. It is interesting to note that AEHC appeared to be effective on constipation, so further experiments are necessary to clarify the exact mechanisms involved.
Resilience of Core-Periphery Networks in the Case of Rich-Club
Authors: Cinelli Matteo , Ferraro Giovanna , Iovanella Antonio
Published: December 2017

Core-periphery networks are structures that present a set of central and densely connected nodes, namely, the core, and a set of noncentral and sparsely connected nodes, namely, the periphery. The rich-club refers to a set in which the highest degree nodes show a high density of connections. Thus, a network that displays a rich-club can be interpreted as a core-periphery network in which the core is made up of a number of hubs. In this paper, we test the resilience of networks showing a progressively denser rich-club and we observe how this structure is able to affect the network measures in terms of both cohesion and efficiency in information flow. Additionally, we consider the case in which, instead of making the core denser, we add links to the periphery. These two procedures of core and periphery thickening delineate a decision process in the placement of new links and allow us to conduct a scenario analysis that can be helpful in the comprehension and supervision of complex networks under the resilience perspective. The advantages of the two procedures, as well as their implications, are discussed in relation to both network efficiency and node heterogeneity.
Robust Master‐Slave Synchronization of Neuronal Systems
Authors: Puebla Hector , Hernández-Martínez Eliseo , Rodriguez-Jara Mariana , Lopez-Monsalvo Cesar S.
Published: December 2017

The desire to understand physiological mechanisms of neuronal systems has led to the introduction of engineering concepts to explain how the brain works. The synchronization of neurons is a central topic in understanding the behavior of living organisms in neurosciences and has been addressed using concepts from control engineering. We introduce a simple and reliable robust synchronization approach for neuronal systems. The proposed synchronization method is based on a master‐slave configuration in conjunction with a coupling input enhanced with compensation of model uncertainties. Our approach has two nice features for the synchronization of neuronal systems: (i) a simple structure that uses the minimum information and (ii) good robustness properties against model uncertainties and noise. Two benchmark neuronal systems, Hodgkin‐Huxley and Hindmarsh‐Rose neurons, are used to illustrate our findings. The proposed synchronization approach is aimed at gaining insight into the effect of external electrical stimulation of nerve cells.
Effect ofCurcuma xanthorrhizaSupplementation on Systemic Lupus Erythematosus Patients with Hypovitamin D Which Were Given Vitamin D3towards Disease Activity (SLEDAI), IL-6, and TGF-β1 Serum
Authors: Singgih Wahono C. , Diah Setyorini Cameleia , Kalim Handono , Nurdiana Nurdiana , Handono Kusworini
Published: December 2017

Background.Curcumin contained inCurcuma xanthorrhizais an immunomodulator that has similar biological effect as vitamin D. Combination of curcumin and vitamin D3is expected to work synergistically.Objective.To determine the effect ofCurcuma xanthorrhizasupplementation on vitamin D3administration to SLEDAI, IL-6, and TGF-β1 serum in SLE patients with hypovitamin D.Methods.This was a double-blind RCT conducted in Saiful Anwar Hospital, Malang, in January 2016–March 2017. Subjects were SLE active (SLEDAI > 3) with levels of 25(OH)D3 ≤ 30 ng/ml and divided into two groups: those receiving cholecalciferol 3 × 400 IU and placebo 3 × 1 tablets (group I) and those receiving 3 × 400 IU cholecalciferol andCurcuma xanthorrhiza3 × 20 mg for 3 months (group II). SLEDAI, levels of vitamin D, IL-6, and TGF-β1 in serum were evaluated before and after the treatment.Results.There were no significant differences in SLEDAI reduction, decreased serum levels of IL-6, and increased levels of TGF-β1 serum among groups after the treatment. Decreased levels of serum IL-6 have a positive correlation with SLEDAI reduction.Conclusion. Curcuma xanthorrhizasupplementation on vitamin D3had no effects on SLEDAI and serum levels of IL-6 and TGF-β1. This clinical trial is registered withNCT03155477.
Simvastatin Ameliorates PAK4 Inhibitor-Induced Gut and Lung Injury
Authors: Pan Shuming , Wu Zengbin , Liu Xuan , Chen Jiameng , Wang Huiqi , Liu Dan , Fei Aihua , Chen Liang , Gao Chengjin
Published: December 2017

P21 activated kinase 4 (PAK4), a key regulator of cytoskeletal rearrangement and endothelial microparticles (EMPs), is released after lipopolysaccharide (LPS) stimulation. In addition, it participates in LPS-induced lung injury. In this study, forty-eight Sprague Dawley (SD) rats were divided into two groups, including PAK4 inhibitor (P) and PAK4 inhibitor + simvastatin (P + S) treatment groups. All rats were given PAK4 inhibitor (15 mg/kg/d) orally. Immediately after PAK4 inhibitor administration, simvastatin was injected intraperitoneally to P + S group animals at 20 mg/kg/day. Then, treatment effects on the intestinal mucosal barrier and lung injury caused by PAK4 inhibitor and simvastatin were assessed. The results showed that gut Zonula Occludens- (ZO-) 1, PAK4, mitogen-activated protein kinase 4 (MPAK4), and CD11c protein levels were reduced, while plasma endotoxin levels were increased after administration of PAK4 inhibitor. Furthermore, compared with normal rats, wet-to-dry (W/D) values of lung tissues and circulating EMP levels were increased in the treatment group, while PAK4 and CD11c protein amounts were reduced. Therefore, in this lung injury process induced by PAK4 inhibitor, the protective effects of simvastatin were reflected by intestinal mucosal barrier protection, inflammatory response regulation via CD11c+ cells, and cytoskeleton stabilization. In summary, PAK4 is a key regulator in the pathophysiological process of acute lung injury (ALI) and can be a useful target for ALI treatment.
Common Fixed Points of Four Maps SatisfyingF-Contraction onb-Metric Spaces
Authors: Nazam Muhammad , Zhenhua Ma , Khan Sami Ullah , Arshad Muhammad
Published: December 2017

We manifest some common fixed point theorems for four maps satisfying Círíc typeF-contraction and Hardy-Rogers typeF-contraction defined on completeb-metric spaces. We apply these results to infer several new and old corresponding results. These results also generalize some results obtained previously. We dispense examples to validate our results.
Concept Design and Analysis of a Novel Steamer-Filling Robot
Authors: Xing Enhong , Li Bin , Zhao Xinhua
Published: December 2017

Steamer-filling operation is a crucially important process in the liquor-making process, directly related to liquor yield and liquor quality. But so far, this process is still dominated by manual operation. In view of working environment and labor shortages in this industry, a novel exclusive steamer-filling robot is proposed in this paper. Firstly, the steamer-filling operation process is described, and the structure composition and function realization of the robot are particularly introduced. Secondly, the kinematics problems in terms of position analysis and workspace of the robot are analyzed in detail. Thirdly, experimental analyses are made to prove the validity and efficiency of the robot system. Finally, some conclusions and the future developing direction are prescribed.
No Association between Organochlorine Concentrations in Adipose Tissue and Survival after Non-Hodgkin Lymphoma
Authors: Roswall Nina , Sørensen Mette , Bräuner Elvira Vaclavik , Tjønneland Anne , Raaschou-Nielsen Ole
Published: December 2017

Background: Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy in the world. Involvement of organochlorines has been proposed in disease etiology. No study has investigated organochlorine exposure in relation to survival after a NHL diagnosis.

Methods: In a survivor cohort consisting of 232 NHL cases from the Danish Diet, Cancer and Health cohort, we examined the association between adipose tissue organochlorine concentrations [polychlorinated biphenyls (PCBs) and pesticides] and subsequent survival, using Cox proportional hazards models.

Results: We found no statistically significant association between organochlorine concentrations and subsequent survival. If anything, there was a nonsignificant tendency toward an inverse association with PCBs, but not pesticides.

Conclusions: In conclusion, the current study does not support an increased risk of death among NHL patients with high tissue concentrations of organochlorines.

Impact: This is the first study to investigate adipose organochlorine concentrations and survival after a NHL diagnosis. Cancer Epidemiol Biomarkers Prev; 27(2); 224–6. ©2017 AACR.
PIK3CA C2 Domain Deletions Hyperactivate Phosphoinositide 3-kinase (PI3K), Generate Oncogene Dependence, and Are Exquisitely Sensitive to PI3Kα Inhibitors
Authors: Croessmann Sarah , Sheehan Jonathan H. , Lee Kyung-min , Sliwoski Gregory , He Jie , Nagy Rebecca , Riddle David , Mayer Ingrid A. , Balko Justin M. , Lanman Richard , Miller Vincent A. , Cantley Lewis C. , Meiler Jens , Arteaga Carlos L.
Published: December 2017

Purpose: We describe herein a novel P447_L455 deletion in the C2 domain of PIK3CA in a patient with an ER+ breast cancer with an excellent response to the PI3Kα inhibitor alpelisib. Although PIK3CA deletions are relatively rare, a significant portion of deletions cluster within amino acids 446–460 of the C2 domain, suggesting these residues are critical for p110α function.

Experimental Design: A computational structural model of PIK3CAdelP447-L455 in complex with the p85 regulatory subunit and MCF10A cells expressing PIK3CAdelP447-L455 and PIK3CAH450_P458del were used to understand the phenotype of C2 domain deletions.

Results: Computational modeling revealed specific favorable inter-residue contacts that would be lost as a result of the deletion, predicting a significant decrease in binding energy. Coimmunoprecipitation experiments showed reduced binding of the C2 deletion mutants with p85 compared with wild-type p110α. The MCF10A cells expressing PIK3CA C2 deletions exhibited growth factor–independent growth, an invasive phenotype, and higher phosphorylation of AKT, ERK, and S6 compared with parental MCF10A cells. All these changes were ablated by alpelisib treatment.

Conclusions: C2 domain deletions in PIK3CA generate PI3K dependence and should be considered biomarkers of sensitivity to PI3K inhibitors. Clin Cancer Res; 24(6); 1426–35. ©2017 AACR.
Structural Alterations of MET Trigger Response to MET Kinase Inhibition in Lung Adenocarcinoma Patients
Authors: Plenker Dennis , Bertrand Miriam , de Langen Adrianus J. , Riedel Richard , Lorenz Carina , Scheel Andreas H. , Müller Judith , Brägelmann Johannes , Daßler-Plenker Juliane , Kobe Carsten , Persigehl Thorsten , Kluge Alexander , Wurdinger Thomas , Schellen Pepijn , Hartmann Gunther , Zacherle Tobias , Menon Roopika , Thunnissen Erik , Büttner Reinhard , Griesinger Frank , Wolf Jürgen , Heukamp Lukas , Sos Martin L. , Heuckmann Johannes M.
Published: December 2017

Purpose: We sought to investigate the clinical response to MET inhibition in patients diagnosed with structural MET alterations and to characterize their functional relevance in cellular models.

Experimental Design: Patients were selected for treatment with crizotinib upon results of hybrid capture–based next-generation sequencing. To confirm the clinical observations, we analyzed cellular models that express these MET kinase alterations.

Results: Three individual patients were identified to harbor alterations within the MET receptor. Two patients showed genomic rearrangements, leading to a gene fusion of KIF5B or STARD3NL and MET. One patient diagnosed with an EML4-ALK rearrangement developed a MET kinase domain duplication as a resistance mechanism to ceritinib. All 3 patients showed a partial response to crizotinib that effectively inhibits MET and ALK among other kinases. The results were further confirmed using orthogonal cellular models.

Conclusions: Crizotinib leads to a clinical response in patients with MET rearrangements. Our functional analyses together with the clinical data suggest that these structural alterations may represent actionable targets in lung cancer patients. Clin Cancer Res; 24(6); 1337–43. ©2017 AACR.
β-Catenin mRNA Silencing and MEK Inhibition Display Synergistic Efficacy in Preclinical Tumor Models
Authors: Ganesh Shanthi , Shui Xue , Craig Kevin P. , Koser Martin L. , Chopda Girish R. , Cyr Wendy A. , Lai Chengjung , Dudek Henryk , Wang Weimin , Brown Bob D. , Abrams Marc T.
Published: December 2017

Colorectal carcinomas harbor well-defined genetic abnormalities, including aberrant activation of Wnt/β-catenin and MAPK pathways, often simultaneously. Although the MAPK pathway can be targeted using potent small-molecule drugs, including BRAF and MEK inhibitors, β-catenin inhibition has been historically challenging. RNAi approaches have advanced to the stage of clinical viability and are especially well suited for transcriptional modulators, such as β-catenin. In this study, we report therapeutic effects of combined targeting of these pathways with pharmacologic agents. Using a recently described tumor-selective nanoparticle containing a β-catenin–targeting RNAi trigger, in combination with the FDA-approved MEK inhibitor (MEKi) trametinib, we demonstrate synergistic tumor growth inhibition in in vivo models of colorectal cancer, melanoma, and hepatocellular carcinoma. At dose levels that were insufficient to significantly impact tumor growth as monotherapies, combination regimens resulted in synergistic efficacy and complete tumor growth inhibition. Importantly, dual MEKi/RNAi therapy dramatically improved survival of mice bearing colorectal cancer liver metastases. In addition, pharmacologic silencing of β-catenin mRNA was effective against tumors that are inherently resistant or that acquire drug-induced resistance to trametinib. These results provide a strong rationale for clinical evaluation of this dual-targeting approach for cancers harboring Wnt/β-catenin and MAPK pathway mutations. Mol Cancer Ther; 17(2); 544–53. ©2017 AACR.
DKK3 (Dickkopf 3) Alters Atherosclerotic Plaque Phenotype Involving Vascular Progenitor and Fibroblast Differentiation Into Smooth Muscle Cells
Authors: Karamariti Eirini , Zhai Chungang , Yu Baoqi , Qiao Lei , Wang Zhihong , Potter Claire M.F. , Wong Mei Mei , Simpson Russell M.L. , Zhang Zhongyi , Wang Xiaocong , del Barco Barrantes Ivan , Niehrs Christof , Kong Deling , Zhao Qiang , Zhang Yun , Hu Yanhua , Zhang Cheng , Xu Qingbo
Published: December 2017

Objective—

DKK3 (dickkopf 3), a 36-kD secreted glycoprotein, has been shown to be involved in the differentiation of partially reprogrammed cells and embryonic stem cells to smooth muscle cells (SMCs), but little is known about its involvement in vascular disease. This study aims to assess the effects of DKK3 on atherosclerotic plaque composition.

Approach and Results—

In the present study, we used a murine model of atherosclerosis (
ApoE
−/−
) in conjunction with
DKK3
−/−
and performed tandem stenosis of the carotid artery to evaluate atherosclerotic plaque development. We found that the absence of DKK3 leads to vulnerable atherosclerotic plaques, because of a reduced number of SMCs and reduced matrix protein deposition, as well as increased hemorrhage and macrophage infiltration. Further in vitro studies revealed that DKK3 can induce differentiation of Sca1
+
(stem cells antigen 1) vascular progenitors and fibroblasts into SMCs via activation of the TGF-β (transforming growth factor-β)/ATF6 (activating transcription factor 6) and Wnt signaling pathways. Finally, we assessed the therapeutic potential of DKK3 in mouse and rabbit models and found that DKK3 altered the atherosclerotic plaque content via increasing SMC numbers and reducing vascular inflammation.

Conclusions—

Cumulatively, we provide the first evidence that DKK3 is a potent SMC differentiation factor, which might have a therapeutic effect in reducing intraplaque hemorrhage related to atherosclerotic plaque phenotype.
Filamin A Modulates Store-Operated Ca
2+
Entry by Regulating STIM1 (Stromal Interaction Molecule 1)–Orai1 Association in Human Platelets
Authors: Lopez Jose J. , Albarrán Letizia , Jardín Isaac , Sanchez-Collado Jose , Redondo Pedro C. , Bermejo Nuria , Bobe Regis , Smani Tarik , Rosado Juan A.
Published: December 2017

Objective—

Here, we provide evidence for the role of FLNA (filamin A) in the modulation of store-operated calcium entry (SOCE).

Approach and Results—

SOCE is a major mechanism for calcium influx controlled by the intracellular Ca
2+
stores. On store depletion, the endoplasmic reticulum calcium sensor STIM1 (stromal interaction molecule 1) redistributes into puncta at endoplasmic reticulum/plasma membrane junctions, a process supported by the cytoskeleton, where it interacts with the calcium channels; however, the mechanism for fine-tuning SOCE is not completely understood. Our results demonstrate that STIM1 interacts with FLNA on calcium store depletion in human platelets. The interaction is dependent on the phosphorylation of FLNA at Ser
2152
by the cAMP-dependent protein kinase. Impairment of FLNA phosphorylation and knockdown of FLNA expression using siRNA increased SOCE in platelets. Similarly, SOCE was significantly greater in FLNA-deficient melanoma M2 cells than in the FLNA-expressing M2 subclone A7. Expression of FLNA in M2 cells attenuated SOCE, an effect prevented when the cells were transfected with the nonphosphorylatable FLNA S2152A mutant. Transfection of M2 cells with the STIM1(K684,685E) mutant reduced the STIM1–FLNA interaction. In platelets, attenuation of FLNA expression using siRNA resulted in enhanced association of STIM1 with the cytoskeleton, greater STIM1–Orai1 interaction, and SOCE. Introduction of an anti-FLNA (2597–2647) antibody attenuated the STIM1–FLNA interaction and enhanced thrombin-induced platelet aggregation.

Conclusions—

Our results indicate that FLNA modulates SOCE and then the correct platelet function, by fine-tuning the distribution of STIM1 in the cytoskeleton and the interaction with Orai1 channels.
Melanocortin 1 Receptor Deficiency Promotes Atherosclerosis in Apolipoprotein E
−/−
Mice
Authors: Rinne Petteri , Kadiri James J. , Velasco-Delgado Mauricio , Nuutinen Salla , Viitala Miro , Hollmén Maija , Rami Martina , Savontaus Eriika , Steffens Sabine
Published: December 2017

Objective—

The MC1-R (melanocortin 1 receptor) is expressed by monocytes and macrophages where it mediates anti-inflammatory actions. MC1-R also protects against macrophage foam cell formation primarily by promoting cholesterol efflux through the ABCA1 (ATP-binding cassette transporter subfamily A member 1) and ABCG1 (ATP-binding cassette transporter subfamily G member 1). In this study, we aimed to investigate whether global deficiency in MC1-R signaling affects the development of atherosclerosis.

Approach and Results—

Apoe
−/−
(apolipoprotein E deficient) mice were crossed with recessive yellow (Mc1r
e/e
) mice carrying dysfunctional MC1-R and fed a high-fat diet to induce atherosclerosis. Apoe
−/−
Mc1r
e/e
mice developed significantly larger atherosclerotic lesions in the aortic sinus and in the whole aorta compared with Apoe
−/−
controls. In terms of plaque composition, MC1-R deficiency was associated with less collagen and smooth muscle cells and increased necrotic core, indicative of more vulnerable lesions. These changes were accompanied by reduced
Abca1
and
Abcg1
expression in the aorta. Furthermore, Apoe
−/−
Mc1r
e/e
mice showed a defect in bile acid metabolism that aggravated high-fat diet–induced hypercholesterolemia and hepatic lipid accumulation. Flow cytometric analysis of leukocyte profile revealed that dysfunctional MC1-R enhanced arterial accumulation of classical Ly6C
high
monocytes and macrophages, effects that were evident in mice fed a normal chow diet but not under high-fat diet conditions. In support of enhanced arterial recruitment of Ly6C
high
monocytes, these cells had increased expression of L-selectin and P-selectin glycoprotein ligand 1.

Conclusions—

The present study highlights the importance of MC1-R in the development of atherosclerosis. Deficiency in MC1-R signaling exacerbates atherosclerosis by disturbing cholesterol handling and by increasing arterial monocyte accumulation.
Comparison of Risk Factor Control in the Year After Discharge for Ischemic Stroke Versus Acute Myocardial Infarction
Authors: Bravata Dawn M. , Daggy Joanne , Brosch Jared , Sico Jason J. , Baye Fitsum , Myers Laura J. , Roumie Christianne L. , Cheng Eric , Coffing Jessica , Arling Greg
Published: December 2017

Background and Purpose—

The Veterans Health Administration has engaged in quality improvement to improve vascular risk factor control. We sought to examine blood pressure (<140/90 mm Hg), lipid (LDL [low-density lipoprotein] cholesterol <100 mg/dL), and glycemic control (hemoglobin A1c <9%), in the year post-hospitalization for acute ischemic stroke or acute myocardial infarction (AMI).

Methods—

We identified patients who were hospitalized (fiscal year 2011) with ischemic stroke, AMI, congestive heart failure, transient ischemic attack, or pneumonia/chronic obstructive pulmonary disease. The primary analysis compared risk factor control after incident ischemic stroke versus AMI. Facilities were included if they cared for ≥25 ischemic stroke and ≥25 AMI patients. A generalized linear mixed model including patient- and facility-level covariates compared risk factor control across diagnoses.

Results—

Forty thousand two hundred thirty patients were hospitalized (n=75 facilities): 2127 with incident ischemic stroke and 4169 with incident AMI. Fewer stroke patients achieved blood pressure control than AMI patients (64%; 95% confidence interval, 0.62–0.67 versus 77%; 95% confidence interval, 0.75–0.78;
P
<0.0001). After adjusting for patient and facility covariates, the odds of blood pressure control were still higher for AMI than ischemic stroke patients (odds ratio, 1.39; 95% confidence interval, 1.21–1.51). There were no statistical differences for AMI versus stroke patients in hyperlipidemia (
P
=0.534). Among patients with diabetes mellitus, the odds of glycemic control were lower for AMI than ischemic stroke patients (odds ratio, 0.72; 95% confidence interval, 0.54–0.96).

Conclusions—

Given that hypertension control is a cornerstone of stroke prevention, interventions to improve poststroke hypertension management are needed.
Carotid Intima-Media Thickness Is Associated With White Matter Hyperintensities
Authors: Della-Morte David , Dong Chuanhui , Markert Matthew S. , Elkind Mitchell S.V. , Sacco Ralph L. , Wright Clinton B. , Rundek Tatjana
Published: December 2017

Background and Purpose—

Brain white matter hyperintensities (WMH) have been associated with increased risk of stroke, cognitive decline, and dementia. WMH can be a manifestation of small vessel disease, although the total microvascular contribution to multifactorial WMH pathophysiology remains unknown. We hypothesized a possible relationship between carotid intima-media thickness (cIMT), an ultrasound imaging marker of subclinical vascular disease, and brain WMH in a multiethnic, elderly stroke-free community-based cohort.

Methods—

We evaluated the relationship between cIMT and WMH in the population-based Northern Manhattan Study, among individuals free of stroke. We used linear regression to examine the association of continuous measures of cIMT with quantitatively derived WMH volume, as a proportion of cranial volume, measured from fluid-attenuaded inversion recovery magnetic resonance imaging while adjusting for sociodemographics, lifestyle, and vascular risk factors.

Results—

In a cohort of 1229 participants (mean age, 71±9 years; 60% women, 15% White; 18% Black; 65% Hispanics), the mean cIMT was 0.71±0.08 mm and the median log-transformed WMH volume was 0.36 (interquartile range, 0.21–0.76). In a multivariable model, larger cIMT was significantly associated with greater WMH volume (β=0.046 per SD cIMT;
P
=0.04). Age and race/ethnicity were significant modifiers (
P
for age, 0.02; and
P
for race/ethnicity, 0.04). cIMT was associated with WMH volume in participants 70 years or older (β=0.088 per SD cIMT;
P
=0.01) and among Hispanics (β=0.084 per SD cIMT;
P
=0.003).

Conclusions—

Larger cIMT was associated with greater burden of cerebral WM lesions independently of demographics and traditional vascular risk factors, particularly among elderly and Hispanic participants, who are at high risk for stroke and cognitive decline.
Association Between Heart Rate and Subclinical Cerebrovascular Disease in the Elderly
Authors: Nakanishi Koki , Jin Zhezhen , Homma Shunichi , Elkind Mitchell S.V. , Rundek Tatjana , Lee Seitetz C. , Tugcu Aylin , Yoshita Mitsuhiro , DeCarli Charles , Wright Clinton B. , Sacco Ralph L. , Di Tullio Marco R.
Published: December 2017

Background and Purpose—

Although increased heart rate (HR) is a predictor of cardiovascular events and mortality, its possible association with subclinical cerebrovascular disease, which is prevalent in the elderly, has not been evaluated. This study aimed to investigate the association of daytime, nighttime, 24-hour HR, and HR variability with subclinical cerebrovascular disease in an elderly cohort without history of stroke.

Methods—

The study cohort consisted of 680 participants (mean age, 73±7 years; 42% men) in sinus rhythm who underwent 24-hour ambulatory blood pressure and HR monitoring, 2-dimensional echocardiography, and brain magnetic resonance imaging as part of the CABL study (Cardiac Abnormalities and Brain Lesion). Subclinical cerebrovascular disease was defined as silent brain infarcts and white matter hyperintensity volume (WMHV). The relationship of HR measures with the presence of silent brain infarct and upper quartile of log WMHV (log WMHV4) was analyzed.

Results—

Presence of silent brain infarct was detected in 93 participants (13.7%); mean log WMHV was −0.92±0.93 (median, −1.05; min, −5.88; max, 1.74). Multivariate analysis showed that only nighttime HR (adjusted odds ratio, 1.29 per 10 bpm; 95% confidence interval, 1.03–1.61;
P
=0.026) was significantly associated with log WMHV4, independent of traditional cardiovascular risk factors, ambulatory systolic blood pressure, and echocardiographic parameters. No similar association was observed for daytime HR and HR variability. There was no significant association between all HR measures and silent brain infarct.

Conclusions—

In a predominantly elderly cohort, elevated nighttime HR was associated with WMHV, suggesting an independent role of HR in subclinical cerebrovascular disease.
A Multivariate Estimate of the Cold Season Atmospheric Response to North Pacific SST Variability
Authors: Révelard Adèle , Frankignoul Claude , Kwon Young-Oh
Published: December 2017

The Generalized Equilibrium Feedback Analysis (GEFA) is used to distinguish the influence of the Oyashio Extension (OE) and the Kuroshio Extension (KE) variability on the atmosphere from 1979 to 2014 from that of the main SST variability modes, using seasonal mean anomalies. Remote SST anomalies are associated with each single oceanic regressor, but the multivariate approach efficiently confines their SST footprints. In autumn [October–December (OND)], the OE meridional shifts are followed by a North Pacific Oscillation (NPO)-like signal. The OE influence is not investigated in winter [December–February (DJF)] because of multicollinearity, but a robust response with a strong signal over the Bering Sea is found in late winter/early spring [February–April (FMA)], a northeastward strengthening of the Aleutian low following a northward OE shift. A robust response to the KE variability is found in autumn, but not in winter and late winter when the KE SST footprint becomes increasingly small and noisy as regressors are added in GEFA. In autumn, a positive PDO is followed by a northward strengthening of the Aleutian low and a southward shift of the storm track in the central Pacific, reflecting the surface heat flux footprint in the central Pacific. In winter, the PDO shifts the maximum baroclinicity and storm track southward, the response strongly tilts westward with height in the North Pacific, and there is a negative NAO-like teleconnection. In late winter, the North Pacific NPO-like response to the PDO interferes negatively with the response to the OE and is only detected when the OE is represented in GEFA. A different PDO influence on the atmospheric circulation is found from 1958 to 1977.
Evolution of Turbulence in the Diurnal Warm Layer
Authors: Moulin Aurélie J. , Moum James N. , Shroyer Emily L.
Published: December 2017

The daily evolution of temperature, stratification, and turbulence in the diurnal warm layer is described from time series measurements at low to moderate winds and strong insolation in the equatorial Indian Ocean. At 2.0-m depth, turbulence dissipation rates (ε) decreased by two orders of magnitude over 1–2 h immediately after sunrise, initiated by stratification caused by penetrating solar radiation prior to the change in sign of net surface heat flux from cooling to warming. Decaying turbulence preceded a period of rapid growth, in which ε increased by two orders of magnitude over a few hours, and following which ε approached a daytime period of near-steady state. Decay and growth rates predicted by a simplified turbulence model are consistent with those observed. During the daytime period of near-steady state, asymmetric temperature ramps were associated with enhanced ε, supporting the interpretation that this period represents a balance between buoyancy and shear production associated with a shear-driven response to trapping of momentum within the diurnal warm layer.
A Newly Identified Stela from Wadi El-Hudi (Cairo Je 86119)
Authors: Espinel Andrés D.
Published: December 2017

Publication of a late Middle Kingdom stela Cairo JE 86119, probably from Wadi el-Hudi. This small monument consists of a curious statue representation accompanied by a brief autobiography. The inscription describes new aspects of Egyptian activities in the wadi, mentioning the presence of ‘ntyw to praise Hathor in a temple in the area and there is a reference to thirst. This study analyses the iconography, the text and the title (‘iry-'t n pr-ḥd) of its owner, and the stela and its dedicant are placed within the context of cult, pious actions, ethics and social effectiveness.
An Eighteenth Dynasty ḥs.ty-‘.w of Heliopolis in Adelaide, South Australia
Authors: Ockinga Boyo G.
Published: December 2017

Publication of a fragmentary stela and associated offering table now in the Classics Museum of Adelaide University, South Australia. The monuments are inscribed for an Eighteenth Dynasty Mayor of Heliopolis called Menkheper and his extended family. The recent history of the objects is also discussed.
‘All that has been done to the Shabtis’: Some Considerations on the Decree for the Shabtis of Neskhons and P. Bm Ea 10800
Authors: Poole Federico
Published: December 2017

The article discusses two texts concerning the purchase of shabtis: the Decree for the Shabtis of Neskhons, and a quittance for the sale of a set of shabtis (P. BM EA 10800). The author reconsiders the view held by D. Warburton and several other scholars that, in both documents, it is the shabtis themselves who are the recipients of the payment, and proposes a new reading of a perplexing passage in the Decree for the Shabtis of Neskhons.
Prehistoric Settlement in the Western Delta: A Regional and Local view from SAIS (SA EL-HAGAR)
Authors: Wilson Penelope
Published: December 2017

This paper publishes Prehistoric archaeological material from the EES work at Sais. Excavation 3 was carried out in 2001 in the ‘Great Pit’ and produced pottery, lithics, and faunal and floral material from three main phases: the Early Neolithic (c. 4,500–4,200 BC), Middle to Late Neolithic (c. 4,000–3,800 BC) and the Buto-Maadi Period (c. 3,500 BC). The pottery and object catalogue discusses the typology and wares of the pottery from each phase as well as individual objects, diagnostic lithics and bones, and compares them with datasets from other Lower Egyptian sites including Merimde and Buto. Sais is put into its wider regional context by combining geomorphological data from the drill core programme of the EES Survey and Vertical Electrical Sounding data from the University of Mansoura work in order to reconstruct the ancient environment at Sais. The palaeoenvironmental work shows that Sais was situated upon a river levee on the inside of a significant river channel, with marshes and other sand hills further west. The site seems to have been a fishing camp in the Early Neolithic which was settled in the Middle to Later Neolithic Period for the cultivation of the floodplain. There is a gap in the settlement record of at least 300 years in the early fourth millennium until the Buto-Maadi culture settlement was established at Sais around 3,500 BC. The possible reasons for and implications of the hiatus in continuous settlement at Sais are explored in the context of the development of Lower Egyptian centres of power.
Expeditions to the Wadi Hammamat during the New Kingdom
Authors: Hikade Thomas
Published: December 2017

From the Old Kingdom on Egyptians were procuring raw materials from sites in the Eastern Desert or the Sinai peninsula at an organised and sophisticated level. The Wadi Hammamat has yielded abundant textual and archaeological material for the New Kingdom. This article focuses on the textual evidence of that period and examines the organisation and supply efforts which the Egyptians undertook on a grand scale, sometimes equipping more than 8,000 men. The economic effects of these large enterprises had profound repercussions for the Egyptian economy, stretching its capabilities and potential to the limits. Within the overall political situation, this certainly contributed to the fading power of the late Ramesside rulers domestically and internationally.
Two Coptic Epitaphs from Qasr Ibrim
Authors: Van Der Vliet Jacques
Published: December 2017

A first edition and brief discussion of two Coptic funerary stelae from the medieval cemeteries of Qasr Ibrim in Northern Nubia (ancient Nobadia).
Noun/Personal Pronoun + Personal Pronoun as a Grammatical Construction in Earlier Egyptian
Authors: Uljas Sami
Published: December 2017

The construction noun/personal pronoun + personal (dependent) pronoun is defined as a valid Earlier Egyptian nominal sentence pattern and shown to represent a syntactic and semantic-pragmatic intermediary between nominal and adjectival sentences.
A Ramessid Statue from Abydos Bearing a Sacred Emblem
Authors: Frood Elizabeth
Published: December 2017

Re-publication of a statue fragment from Abydos, now in The Manchester Museum, including the first photographs of the object and new translations of its biographical inscriptions. The statue displays an otherwise unattested combination of iconographic features, including a possible representation of an jmjwt against one shoulder.
The Golden Horus name of Amenmesse
Authors: Hardwick Tom
Published: December 2017

Publication of a fragment of a kilt from a standing royal statue of the later New Kingdom, now in Cairo. It is inscribed with a Golden Horus name which is not published elsewhere but which matches the traces preserved of the Golden Horus name of the Nineteenth Dynasty ruler Amenmesse.
De L'Origine Chtonienne des Musaraignes
Authors: Agut-Labordère Damien
Published: December 2017

Explanation of an anecdote related by Diodorus about the birth of the Egyptian shrew-mouse from the mud. A forerunner of the same story is found in the Brooklyn Magical Papyrus. This legend seems to be linked with a pun on one of the Egyptian designations of ‘shrew-mouse’.
A New Case of Ancient Restoration on an Egyptian Mummy
Authors: Giuffra Valentina , Fornaciari Gino , Ciranni Rosalba
Published: December 2017

A new example of restoration performed by the ancient Egyptian embalmers on a mummified body is reported. An imaging study of the mummy labelled 2343 in the Archaeological Museum of Naples has revealed the substitution of an artificial wooden ‘prosthesis’ for missing feet. The mummy probably dates to the Ptolemaic-early Roman Period, when other examples of prosthetics occur.
The Vitaliano Donati collection at the Turin Egyptian Museum
Authors: Morecroft Angela Scattolin
Published: December 2017

Preliminary announcement of the discovery of a manuscript found in Turin which lists the collection of ancient artefacts and scientific specimens sent by Vitaliano Donati from Alexandria to Turin on 20 February 1761. Donati's collection was one of the founding elements of the original Egyptian collection in the Regio Museo di Antichità, University of Turin. Today, the bulk of the collection is unidentified and only three statues attributed to Donati are on display at the Egyptian Museum in Turin. In addition, there is no published evidence that confirms the size of the collection or describes the objects.
Gut Bacterial Metabolism of the Soy Isoflavone Daidzein: Exploring the Relevance to Human Health
Authors: Atkinson Charlotte , Frankenfeld Cara L. , Lampe Johanna W.
Published: December 2017

The indigenous intestinal microflora are involved in a variety of processes within the human body, and are important for maintaining host health. As such, interindividual differences in the ability to harbor certain intestinal bacteria might be associated with interindividual differences in health and/or disease susceptibility. In the last decade there has been considerable interest in phytoestrogen intakes in relation to human health. Daidzein, an isoflavone phytoestrogen found in soy, is metabolized to equol and O-desmethylangolensin (O-DMA) by intestinal bacteria. The specific bacterium/bacteria responsible for equol and O-DMA production in humans have yet to be identified definitively, but in vitro and animal studies have suggested that equol and O-DMA are more biologically active than their precursor daidzein. Interestingly, substantial interindividual differences in daidzein metabolism exist; following soy or daidzein consumption, approximately 30%–0% of the human population produce equol, and approximately 80%–90% produce O-DMA. Observational and intervention studies in humans have suggested that the ability to produce equol and O-DMA may be associated with reduced risk of certain diseases including breast and prostate cancers. However, relatively few studies have been conducted to date. In this review, we discuss the available evidence for a relationship between daidzein-metabolizing phenotypes and human health, and suggest potential mechanisms for some of the reported relationships.