bluuebunny/crossref_metadata_2025 huggingface dataset:
Repeated large-scale mass-transport deposits and consequent rapid sedimentation in the western part of the Bay of Bengal, India
Authors: Yamamoto Yuzuru , Chiyonobu Shun , Kanamatsu Toshiya , Ahagon Naokazu , Aoike Kan , Kamiya Nana , Ojima Takanori , Hirose Takehiro , Sugihara Takamitsu , Saito Saneatsu , Kinoshita Masataka , Kubo Yusuke , Yamada Yasuhiro ,   NGHP-02 Scientists
Published: March 2018

The National Gas Hydrate Program Expedition 02 was conducted in early 2015 using the Drilling Vessel
Chikyu
in the western part of the Bay of Bengal, India. During drilling off Vishakhapatnam, NE India, some bottom-simulating reflectors were penetrated, and numerous mass-transport deposits (MTDs) were identified. The recovered cores were composed of post-late Miocene muddy slope deposits containing the late Miocene–Pliocene hiatus that is widespread in that region. Based on detailed visual core descriptions and calcareous nannofossil biostratigraphy, two major MTD-rich intervals were identified: the Pleistocene interval above the hiatus, and the middle–late Miocene interval below it. Although the MTDs in both intervals are composed of variously coloured clay–silt blocks in an olive-black or olive-grey silty clay matrix (muddy MTDs), the Pleistocene MTDs consist of larger-sized blocks (mostly less than a few metres but with some >10 m) without clear shear fabrics, whereas the Miocene MTDs contain smaller blocks (<0.1 m) with asymmetrical shear fabrics. The muddy blocks are composed of older components (Pliocene–Cretaceous) compared with the depositional ages of the MTDs. The high abundance of MTDs above the hiatus and the depositional ages of the interbedded coherent layers indicate that large-scale MTDs occurred repeatedly during the Pleistocene. Such repeated MTDs contributed to maintaining the high sedimentation rate in this area and potentially provided stable pressure and temperature conditions for the formation of gas hydrates.
New evidence for a major late Quaternary submarine landslide on the external western levee of Laurentian Fan
Authors: Normandeau Alexandre , Campbell D. Calvin , Piper David J. W. , Jenner Kimberley A.
Published: March 2018

The Laurentian Fan is one of the largest submarine fans on the western margin of the North Atlantic. Recently acquired high-resolution multibeam bathymetric data (60 m horizontal resolution) reveal a major mass-transport deposit (MTD) on the Western Levee of Western Valley (WLWV), covering >14 000 km
2
in water depths from 3900 to >5000 m. Typical submarine landslide features are observed such as headscarps that in places reach the crest of the levee, crown cracks, extensional ridges, blocky debris and flow lineations. Multiple headwalls are observed on 3.5 kHz sub-bottom profiles, indicating that the landslide retrogressed upslope. While the upper parts of the MTD consist of intact blocks that were displaced downslope as ridges and troughs, the lower parts exhibit a
c.
30 m thick incoherent to transparent acoustic facies, typical of debris flows. Landslide geomorphology therefore suggests that it was generated as a retrogressive spread and that slide blocks disintegrated downslope to become a blocky landslide with a surficial debris flow. The blocky landslide/debris flow extends downslope
c.
90 km and partially fills a submarine channel. The superposition of the MTD filling the channel and its location at the top of the stratigraphic succession in the levee suggests that it is late Quaternary in age, possibly Holocene. Deeper seismic reflection data also show that this is a rare event during the Quaternary; it is the largest MTD observed in the upper
c.
375 m of the levee succession and among the largest and deepest in the western North Atlantic.
A consistent global approach for the morphometric characterization of subaqueous landslides
Authors: Clare Michael , Chaytor Jason , Dabson Oliver , Gamboa Davide , Georgiopoulou Aggeliki , Eady Harry , Hunt James , Jackson Christopher , Katz Oded , Krastel Sebastian , León Ricardo , Micallef Aaron , Moernaut Jasper , Moriconi Roberto , Moscardelli Lorena , Mueller Christof , Normandeau Alexandre , Patacci Marco , Steventon Michael , Urlaub Morelia , Völker David , Wood Lesli , Jobe Zane
Published: March 2018

Landslides are common in aquatic settings worldwide, from lakes and coastal environments to the deep sea. Fast-moving, large-volume landslides can potentially trigger destructive tsunamis. Landslides damage and disrupt global communication links and other critical marine infrastructure. Landslide deposits act as foci for localized, but important, deep-seafloor biological communities. Under burial, landslide deposits play an important role in a successful petroleum system. While the broad importance of understanding subaqueous landslide processes is evident, a number of important scientific questions have yet to receive the needed attention. Collecting quantitative data is a critical step to addressing questions surrounding subaqueous landslides.

Quantitative metrics of subaqueous landslides are routinely recorded, but which ones, and how they are defined, depends on the end-user focus. Differences in focus can inhibit communication of knowledge between communities, and complicate comparative analysis. This study outlines an approach specifically for consistent measurement of subaqueous landslide morphometrics to be used in the design of a broader, global open-source, peer-curated database. Examples from different settings illustrate how the approach can be applied, as well as the difficulties encountered when analysing different landslides and data types. Standardizing data collection for subaqueous landslides should result in more accurate geohazard predictions and resource estimation.
Subsurface controls on the development of the Cape Fear Slide Complex, central US Atlantic Margin
Authors: Hill Jenna C. , Brothers Daniel S. , Hornbach Matthew J. , Sawyer Derek E. , Shillington Donna J. , Bécel Anne
Published: March 2018

The Cape Fear Slide is one of the largest (>25 000 km
3
) submarine slope failure complexes on the US Atlantic margin. Here we use a combination of new high-resolution multichannel seismic data (MCS) from the National Science Foundation Geodynamic Processes at Rifting and Subducting Margins (NSF GeoPRISMS) Community Seismic Experiment and legacy industry MCS to derive detailed stratigraphy of this slide and constrain the conditions that lead to slope instability. Limited outer-shelf and upper-slope accommodation space during the Neogene, combined with lowstand fluvial inputs and northwards Gulf Stream sediment transport, appears to have contributed to thick Miocene and Pliocene deposits that onlapped the lower slope. This resulted in burial of an upper-slope bypass zone developed from earlier erosional truncation of Paleogene strata. These deposits created a broad ramp that allowed accumulation of thick Quaternary strata across a low-gradient (<3.5°) upper slope. Upslope of one of the larger headwalls, undulating Quaternary strata appear to downlap onto a buried failure plane. Many of the nested headwalls of the upper-slope portion of slide complex are underlain by deformed strata, which may be the result of fluid migration associated with localized subsidence from salt migration. These new data and observations suggest that antecedent margin physiography, sediment loading and substrate fluid flow were key factors in preconditioning the Cape Fear slope for failure.
Shear margin moraine, mass transport deposits and soft beds revealed by high-resolution P-Cable three-dimensional seismic data in the Hoop area, Barents Sea
Authors: Bellwald Benjamin , Planke Sverre
Published: March 2018

High-resolution seismic data are powerful tools that can help the offshore industries to better understand the nature of the shallow subsurface and plan the development of vulnerable infrastructure. Submarine mass movements and shallow gas are among the most significant geohazards in petroleum prospecting areas. A variety of high-resolution geophysical datasets collected in the Barents Sea have significantly improved our knowledge of the shallow subsurface in recent decades. Here we use a
c.
200 km
2
high-resolution P-Cable 3D seismic cube from the Hoop area, SW Barents Sea, to study a 20–65 m thick glacial package between the seabed and the Upper Regional Unconformity (URU) horizons. Intra-glacial reflections, not visible in conventional seismic reflection data, are well imaged. These reflections have been mapped in detail to better understand the glacial deposits and to assess their impact on seabed installations. A shear margin moraine, mass transport deposits and thin soft beds are examples of distinct units only resolvable in the P-Cable 3D seismic data. The top of the shear margin moraine is characterized by a positive amplitude reflection incised by glacial ploughmarks. Sedimentary slide wedges and shear bands are characteristic sedimentary features of the moraine. A soft reflection locally draping the URU is interpreted as a coarser grained turbidite bed related to slope failure along the moraine. The bed is possibly filled with gas. Alternatively, this negative amplitude reflection represents a thin, soft bed above the URU. This study shows that P-Cable 3D data can be used successfully to identify and map the external and internal structures of ice stream shear margin moraines and that this knowledge is useful for site-survey investigations.
Hard-rock aquifer response to pumping and sustainable yield of wells in some areas of Mediterranean Region
Authors: Baiocchi Antonella , Lotti Francesca , Piscopo Vincenzo , Sammassimo Valentina
Published: March 2018

Pumping tests carried out in three highly tectonized Mediterranean areas, which share similar climate conditions, were used to characterize hard-rock aquifers and examine the issue of the sustainable yield of wells. On the basis of the identified drawdown trends and hydraulic parameters, pumping scenarios were simulated through different methods. The results show that the long-term trend in the drawdown and the initial thickness of the aquifer constrain the sustainable yield of a well. In the worst cases examined, namely those related to an aquifer with a barrier boundary and a delayed response of the aquifer, the sustainable well yield is 1–2 L s
−1
. These well discharge values are significant when compared with those found in other regions of the world, and may be related to the dense network of the discontinuities which characterizes the sites.
Understanding and Improving the Activity of Flavin-Dependent Halogenases via Random and Targeted Mutagenesis
Authors: Andorfer Mary C. , Lewis Jared C.
Published: March 2018

Flavin-dependent halogenases (FDHs) catalyze the halogenation of organic substrates by coordinating reactions of reduced flavin, molecular oxygen, and chloride. Targeted and random mutagenesis of these enzymes have been used to both understand and alter their reactivity. These studies have led to insights into residues essential for catalysis and FDH variants with improved stability, expanded substrate scope, and altered site selectivity. Mutations throughout FDH structures have contributed to all of these advances. More recent studies have sought to rationalize the impact of these mutations on FDH function and to identify new FDHs to deepen our understanding of this enzyme class and to expand their utility for biocatalytic applications.
Regulation of RNA Polymerase I Transcription in Development, Disease, and Aging
Authors: Sharifi Samim , Bierhoff Holger
Published: March 2018

Ribosome biogenesis is a complex and highly energy-demanding process that requires the concerted action of all three nuclear RNA polymerases (Pol I–III) in eukaryotes. The three largest ribosomal RNAs (rRNAs) originate from a precursor transcript (pre-rRNA) that is encoded by multicopy genes located in the nucleolus. Transcription of these rRNA genes (rDNA) by Pol I is the key regulation step in ribosome production and is tightly controlled by an intricate network of signaling pathways and epigenetic mechanisms. In this article, we give an overview of the composition of the basal Pol I machinery and rDNA chromatin. We discuss rRNA gene regulation in response to environmental signals and developmental cues and focus on perturbations occurring in diseases linked to either excessive or limited rRNA levels. Finally, we discuss the emerging view that rDNA integrity and activity may be involved in the aging process.
Muscle coactivation: definitions, mechanisms, and functions
Authors: Latash Mark L.
Published: March 2018

The phenomenon of agonist-antagonist muscle coactivation is discussed with respect to its consequences for movement mechanics (such as increasing joint apparent stiffness, facilitating faster movements, and effects on action stability), implication for movement optimization, and involvement of different neurophysiological structures. Effects of coactivation on movement stability are ambiguous and depend on the effector representing a kinematic chain with a fixed origin or free origin. Furthermore, coactivation is discussed within the framework of the equilibrium-point hypothesis and the idea of hierarchical control with spatial referent coordinates. Relations of muscle coactivation to changes in one of the basic commands, the c-command, are discussed and illustrated. A hypothesis is suggested that agonist-antagonist coactivation reflects a deliberate neural control strategy to preserve effector-level control and avoid making it degenerate and facing the necessity to control at the level of signals to individual muscles. This strategy, in particular, allows stabilizing motor actions by covaried adjustments in spaces of control variables. This hypothesis is able to account for higher levels of coactivation in young healthy persons performing challenging tasks and across various populations with movement impairments.
Identification of Binding Partners of Deafness-Related Protein PDZD7
Authors: Du Haibo , Ren Rui , Chen Panpan , Xu Zhigang , Wang Yanfei
Published: March 2018

PDZD7 is an important deafness gene, whose mutations are associated with syndromic and nonsyndromic hearing loss. PDZD7 contains multiple PDZ domains that are essential for organizing various proteins into protein complex. Several PDZD7-binding proteins have been identified, including usherin, ADGRV1, whirlin, harmonin, SANS, and MYO7A, all belonging to USH proteins. Here, we report the identification of novel PDZD7-binding partners through yeast two-hybrid screening using the first two PDZ domains of PDZD7 as bait. Eleven proteins were identified, most of which have not been reported as PDZD7-binding partners before. Among the identified proteins, ADGRV1, gelsolin, and β-catenin have been shown to play important roles in hearing, whereas the functions of other proteins in the inner ear remain elusive. We confirmed the expression of one candidate PDZD7-binding protein, CADM1, in the mouse inner ear and evaluated the auditory function of Cadm1 knockout mice by performing auditory brainstem response (ABR) measurement. Unexpectedly, Cadm1 knockout mice show normal hearing threshold, which might be explained by the possible compensation by its homologs that are also expressed in the inner ear. Taken together, our work identified several novel PDZD7-binding proteins, which will help us to further understand the role of PDZD7 in hearing transduction.
Fatigue Delamination Crack Growth in GFRP Composite Laminates: Mathematical Modelling and FE Simulation
Authors: Ijaz Hassan , Saleem Waqas , Zain-ul-abdein Muhammad , Taimoor Aqeel Ahmad , Mahfouz Abdullah Salmeen Bin
Published: March 2018

Glass fibre-reinforced plastic (GFRP) composite laminates are used in many industries due to their excellent mechanical and thermal properties. However, these materials are prone to the initiation and propagation of delamination crack growth between different plies forming the laminate. The crack propagation may ultimately result in the failure of GFRP laminates as structural parts. In this research, a comprehensive mathematical model is presented to study the delamination crack growth in GFRP composite laminates under fatigue loading. A classical static damage model proposed by Allix and Ladevèze is modified as a fatigue damage model. Subsequently, the model is implemented in commercial finite element software via UMAT subroutine. The results obtained by the finite element simulations verify the experimental findings of Kenane and Benzeggagh for the fatigue crack growth in GFRP composite laminates.
Analysis and Synthesis of Double Negative Dielectric Media Rectenna Systems for Ambient Microwave Energy Harvesting
Authors: Karampatea Apostolia , Siakavara Katherine
Published: March 2018

The concept of harvesting the ambient electromagnetic radiation energy, coming from public telecommunication wireless networks, has been recently subject of extensive research. Techniques proposed for this target use mainly antennas, as the grade gathering the radiation power. In this work, a method introducing the usage of specific dielectric structures with artificially negative electric permittivity and magnetic permeability (double negative media or DNG) in combination with wire dipole antenna sensors is proposed as an RF harvesting system. Theoretical study of the synthesized DNG medium’s performance and the distribution of the electromagnetic field in its interior is made, with the intention of finding the areas of maximum electric field intensity at which the antenna sensors would be positioned for maximum power scavenging. The received numerical results show that the synthesized schemes are capable of enhancing the energy gathering ability. Compared to the same antenna sensors positioned in free space, they ensure higher input voltage to the rectifier and also an increase of the available power about 10 dB. Moreover, they exhibit this performance for every direction of arrival of the incoming waves. The hybrid schemes DNG dipole antenna were designed for the Universal Mobile Telecommunication System (UMTS) frequency band, but the method is general and would be applied to any other frequency band and also with other antenna types.
5-Fluorouracil Enhances Protoporphyrin IX Accumulation and Lesion Clearance during Photodynamic Therapy of Actinic Keratoses: A Mechanism-Based Clinical Trial
Authors: Maytin Edward V. , Anand Sanjay , Riha Margo , Lohser Sara , Tellez Alejandra , Ishak Rim , Karpinski Lauren , Sot Janine , Hu Bo , Denisyuk Anton , Davis Scott C. , Kyei Angela , Vidimos Allison
Published: March 2018

Purpose: Actinic keratoses (AK) are precancerous lesions that can progress to squamous cell carcinoma. Photodynamic therapy (PDT) and topical 5-fluorouracil (5FU) are commonly used agents for AK. Empirical reports suggest that combining them can improve the therapeutic response. However, the optimal combined regimen was not clear in terms of proper sequence, timing, and mechanism. This clinical study explored mechanisms of action for neoadjuvantal 5FU and PDT for treatment of AK.

Patients and Methods: A bilaterally controlled trial (17 patients) was performed. One side of the body (face, scalp, forearms) received 5FU pretreatment for 6 days, whereas the other side served as no-pretreatment control. Methylaminolevulinate cream was applied to both sides for 3 hours, and protoporphyrin IX (PpIX) levels were measured by noninvasive fluorimetry and skin biopsy. After red light illumination, lesion clearance was assessed at 3, 6, 9, and 12 months after PDT.

Results: PpIX levels were increased 2- to 3-fold in 5FU-pretreated lesions versus controls. Altered expression of heme-synthetic enzymes (coproporphyrinogen oxidase and ferrochelatase) and induction of p53 were observed, probably accounting for increased PpIX and subsequent cancer cell death. Relative clearance rates after PDT with or without 5FU pretreatment were 75% versus 45% at 3 months, and 67% versus 39% at 6 months, respectively; these differences were statistically significant.

Conclusions: Serial 5FU and PDT improve AK clearance by at least two mechanisms, enhanced photosensitizer accumulation and p53 induction. Because 5FU and PDT are FDA-approved modalities, the combined regimen can be readily employed in clinical practice to reduce AK burden and reduce SCC risk. Clin Cancer Res; 24(13); 3026–35. ©2018 AACR.
T-cell Dysfunction in Glioblastoma: Applying a New Framework
Authors: Woroniecka Karolina I. , Rhodin Kristen E. , Chongsathidkiet Pakawat , Keith Kristin A. , Fecci Peter E.
Published: March 2018

A functional, replete T-cell repertoire is an integral component to adequate immune surveillance and to the initiation and maintenance of productive antitumor immune responses. Glioblastoma (GBM), however, is particularly adept at sabotaging antitumor immunity, eliciting severe T-cell dysfunction that is both qualitative and quantitative. Understanding and countering such dysfunction are among the keys to harnessing the otherwise stark potential of anticancer immune-based therapies. Although T-cell dysfunction in GBM has been long described, newer immunologic frameworks now exist for reclassifying T-cell deficits in a manner that better permits their study and reversal. Herein, we divide and discuss the various T-cell deficits elicited by GBM within the context of the five relevant categories: senescence, tolerance, anergy, exhaustion, and ignorance. Categorization is appropriately made according to the molecular bases of dysfunction. Likewise, we review the mechanisms by which GBM elicits each mode of T-cell dysfunction and discuss the emerging immunotherapeutic strategies designed to overcome them. Clin Cancer Res; 24(16); 3792–802. ©2018 AACR.
Nano-Engineered Mesenchymal Stem Cells Increase Therapeutic Efficacy of Anticancer Drug Through True Active Tumor Targeting
Authors: Layek Buddhadev , Sadhukha Tanmoy , Panyam Jayanth , Prabha Swayam
Published: March 2018

Tumor-targeted drug delivery has the potential to improve therapeutic efficacy and mitigate non-specific toxicity of anticancer drugs. However, current drug delivery approaches rely on inefficient passive accumulation of the drug carrier in the tumor. We have developed a unique, truly active tumor-targeting strategy that relies on engineering mesenchymal stem cells (MSC) with drug-loaded nanoparticles. Our studies using the A549 orthotopic lung tumor model show that nano-engineered MSCs carrying the anticancer drug paclitaxel (PTX) home to tumors and create cellular drug depots that release the drug payload over several days. Despite significantly lower doses of PTX, nano-engineered MSCs resulted in significant inhibition of tumor growth and superior survival. Anticancer efficacy of nano-engineered MSCs was confirmed in immunocompetent C57BL/6 albino female mice bearing orthotopic Lewis Lung Carcinoma (LL/2-luc) tumors. Furthermore, at doses that resulted in equivalent therapeutic efficacy, nano-engineered MSCs had no effect on white blood cell count, whereas PTX solution and PTX nanoparticle treatments caused leukopenia. Biodistribution studies showed that nano-engineered MSCs resulted in greater than 9-fold higher AUClung of PTX (1.5 μg.day/g) than PTX solution and nanoparticles (0.2 and 0.1 μg.day/g tissue, respectively) in the target lung tumors. Furthermore, the lung-to-liver and the lung-to-spleen ratios of PTX were several folds higher for nano-engineered MSCs relative to those for PTX solution and nanoparticle groups, suggesting that nano-engineered MSCs demonstrate significantly less off-target deposition. In summary, our results demonstrate that nano-engineered MSCs can serve as an efficient carrier for tumor-specific drug delivery and significantly improved anti-cancer efficacy of conventional chemotherapeutic drugs. Mol Cancer Ther; 17(6); 1196–206. ©2018 AACR.
ABT-165, a Dual Variable Domain Immunoglobulin (DVD-Ig) Targeting DLL4 and VEGF, Demonstrates Superior Efficacy and Favorable Safety Profiles in Preclinical Models
Authors: Li Yingchun , Hickson Jonathan A. , Ambrosi Dominic J. , Haasch Deanna L. , Foster-Duke Kelly D. , Eaton Lucia J. , DiGiammarino Enrico L. , Panchal Sanjay C. , Jiang Fang , Mudd Sarah R. , Zhang Catherine , Akella Surekha S. , Gao Wenqing , Ralston Sherry L. , Naumovski Louie , Gu Jijie , Morgan-Lappe Susan E.
Published: March 2018

Antiangiogenic therapy is a clinically validated modality in cancer treatment. To date, all approved antiangiogenic drugs primarily inhibit the VEGF pathway. Delta-like ligand 4 (DLL4) has been identified as a potential drug target in VEGF-independent angiogenesis and tumor-initiating cell (TIC) survival. A dual-specific biologic targeting both VEGF and DLL4 could be an attractive strategy to improve the effectiveness of anti-VEGF therapy. ABT-165 was uniquely engineered using a proprietary dual-variable domain immunoglobulin (DVD-Ig) technology based on its ability to bind and inhibit both DLL4 and VEGF. In vivo, ABT-165 induced significant tumor growth inhibition compared with either parental antibody treatment alone, due, in part, to the disruption of functional tumor vasculature. In combination with chemotherapy agents, ABT-165 also induced greater antitumor response and outperformed anti-VEGF treatment. ABT-165 displayed nonlinear pharmacokinetic profiles in cynomolgus monkeys, with an apparent terminal half-life > 5 days at a target saturation dose. In a GLP monkey toxicity study, ABT-165 was well-tolerated at doses up to 200 mg/kg with non-adverse treatment–related histopathology findings limited to the liver and thymus. In summary, ABT-165 represents a novel antiangiogenic strategy that potently inhibits both DLL4 and VEGF, demonstrating favorable in vivo efficacy, pharmacokinetic, and safety profiles in preclinical models. Given these preclinical attributes, ABT-165 has progressed to a phase I study. Mol Cancer Ther; 17(5); 1039–50. ©2018 AACR.
Ferroptosis-Induced Endoplasmic Reticulum Stress: Cross-talk between Ferroptosis and Apoptosis
Authors: Lee Young-Sun , Lee Dae-Hee , Choudry Haroon A. , Bartlett David L. , Lee Yong J.
Published: March 2018

Since its discovery in 2012, ferroptosis has been well characterized by the accumulation of lipid peroxides due to the failure of glutathione-dependent antioxidant defenses. It is known as an iron-dependent form of programmed cell death, which is distinct from other forms of cell death such as apoptosis and necrosis. Nonetheless, little is known about the ferroptotic agent-induced endoplasmic reticulum (ER) stress response and its role in cell death. Recent studies reveal that the ferroptotic agent-induced ER stress response plays an important role in the cross-talk between ferroptosis and other types of cell death. Ferroptotic agents induce the unfolded protein response and subsequently ER stress–mediated activation of the PERK–eIF2α–ATF4–CHOP pathway. CHOP (C/EBP homologous protein) signaling pathway–mediated p53-independent PUMA (p53 upregulated modulator of apoptosis) expression is involved in the synergistic interaction between ferroptosis and apoptosis. This review highlights the recent literature on ferroptotic and apoptotic agent interactions through the ER stress–mediated PERK–eIF2α–ATF4–CHOP–PUMA pathway and implicates combined treatment to effectively enhance tumoricidal efficacy as a novel therapeutic strategy for cancer. Mol Cancer Res; 16(7); 1073–6. ©2018 AACR.
Misleading Allergens in the Diagnosis of Latex Allergy: Profilin and Cross-Reactive Carbohydrate Determinants
Authors: Gürlek Feridun , Ünsel Mehmet , Ardeniz Ömür , Peker Koc Zeynep , Gülbahar Okan , Sin Aytül Zerrin , Kokuludag Ali , Mete Gokmen Nihal
Published: March 2018

Background: It has been suggested that latex-specific IgE analysis may lead to false-positive results, especially in patients with pollen allergy. In the present study, the reasons underlying clinically irrelevant latex-specific IgE positivity were investigated. Methods: Thirty patients with latex allergy (group 1), 89 patients sensitised to aeroallergens (group 2a), and 98 healthy individuals without allergy (group 2b) were enrolled. Participants from all 3 groups were subjected to skin prick tests with aeroallergens including latex, latex-specific IgE analysis (ImmunoCAP), and nasal provocation test with latex. All cases demonstrating positive latex-specific IgE also underwent specific IgE tests (ImmunoCAP) with latex profilin, birch pollen profilin, peach lipid transfer protein, and pineapple bromelain as cross-reactive carbohydrate determinants. Results: Comparison of the atopic and healthy control groups showed that the rate of positive latex-specific IgE was significantly higher in group 2a. Latex profilin-, birch pollen profilin-, and bromelain-specific IgE were remarkably higher in group 2a. Conclusion: False positivity to latex-specific IgE in ImmunoCAP analysis may be observed in approximately 19% of patients with pollen allergy. Profilins and bromelain are the main contributors to clinically irrelevant positive latex-specific IgE.
Beneficial Effect of Bendamustine in a Patient with Anti-MAG/SGPG Neuropathy and Bing-Neel Syndrome Associated with Waldenström Macroglobulinemia: A Case Report
Authors: Ueki Syugo , Nakamura Masataka , Sasaki Risa , Okada Yoichiro , Yoshikawa Keisuke , Kusunoki Susumu , Ishii Kazuyoshi , Kusaka Hirofumi , Kondo Takayuki
Published: March 2018

A 71-year-old man with Waldenström macroglobulinemia (WM) presented with a slowly progressive sensory disturbance and mild weakness predominantly affecting the distal portion of the limbs over the course of 6 months. Cervical magnetic resonance imaging (MRI) showed a long hyperintense lesion at the C1–C4 level. Nerve conduction studies (NCS) revealed prolongation of distal latency, slowed conduction velocity, and conduction block. His serum IgM level was increased, and he was positive for anti-myelin-associated glycoprotein (MAG) and anti-sulfoglucuronyl paragloboside (SGPG) IgM antibodies. Based on the presence of anti-MAG/SGPG antibodies and a single atypical cell with lymphoplasmacytic character in the cerebral spinal fluid, he was diagnosed as having anti-MAG/SGPG neuropathy and Bing-Neel syndrome (BNS) associated with WM. Following 6 cycles of bendamustine monotherapy, the patient’s neurological impairment improved; and the serum IgM level became normalized. Furthermore, NCS findings indicated improvement; and the hyperintense lesion on MRI had almost completely disappeared. The present findings suggest that bendamustine monotherapy is effective not only for WM but also for its associated MAG/SGPG neuropathy and BNS.
Dysphagia Causes Symptom Fluctuations after Oral L-DOPA Treatment in a Patient with Parkinson Disease
Authors: Sato Hiromasa , Yamamoto Toshiyuki , Sato Masako , Furusawa Yoshihiko , Murata Miho
Published: March 2018

Objective: The causes of “delayed-on” and “no-on” phenomena in Parkinson disease (PD) are thought to have some impact on the progress of L-DOPA from the time of ingestion until it reaches the brain and is converted to dopamine. Dysphagia can cause fluctuating symptom expression in L-DOPA therapy for PD. Case Description: A 69-year-old man with PD presented with “delayed-on” and “no-on” phenomena. The patient developed a gait disorder at age 60 years, and he began coughing on his food during breakfast at age 64 years. Even though he was independent in daily life, he could not eat because of dysphagia in an “off” state. Videofluoroscopic examination of swallowing in an “off” state revealed bradykinesia of the tongue and the retention of tablets in the epiglottic vallecula. We trained him to keep his tongue in strong contact with the upper incisors before swallowing. After rehabilitation of dysphagia, the frequency of “delayed-on” and “no-on” phenomena decreased, and his peak L-DOPA plasma concentration was elevated. Additionally, transdermal rotigotine (RTG) was initiated at a maintenance dose of 9.0 mg. The patient reported improvement in swallowing, and the frequency of “no-on” phenomena decreased. Conclusion: In PD patients, the “no-on” phenomenon can be caused by posterior contractile dysfunction of the tongue, and it can be improved with training of the tongue and transdermal RTG administration.
Acetylation of GATA4 on Lysine Residue K313 Promotes Osteoblastic Cells Growth
Authors: You Wenjun , Song Lijuan , Wang Kun
Published: March 2018

Background/Aims: GATA4, a protein related to osteoblast differentiation and mineralization, whose acetylation is essential for cardiac defects. Here, we aimed to explore the functional impacts of GATA4 acetylation on osteoporosis (OS). Methods: GATA4 acetylation in hFOB1.19 and 293T cells was detected after exposure of HDAC inhibitors (TSA and SAHA). Co-immunoprecipitation was conducted to determine which HATs and HDACs was involved in the modulation of GATA4 acetylation/deacetylation, and to identify the acetylation site. The transcriptional activity of GATA4 was measured in the presence or absence of cycloheximide. Furthermore, hFOB1.19 cells viability and apoptosis were evaluated after transfection with acetylation-defective mutant of GATA4. Results: As a result, GATA4 acetylation was identified as a pivotal event in hFOB1.19 cells. GATA4 can be acetylated by P300/CBP, and the acetylation site was on lysine residue K313. Besides, the acetylation of GATA4 can be impaired by HDAC1, rather than by HDAC2-5. GATA4 acetylation contributed to the stability and transcription of GATA4. Moreover, GATA4 acetylation activated CCND2 transcription, and mutation of GATA4 on K-313 reduced cell viability and increased a mitochondria-dependent apoptosis in hFOB1.19 cells. Conclusion: Our data suggest that GATA4 exists as an acetylated protein in hFOB1.19 cells. Acetylation regulates the stability and transcription of GATA4, and activates CCND2 transcription, which may explain the growth-promoting functions of GATA4 in hFOB1.19 cells.
Angiotensin II Suppresses Rev-erbα Expression in THP-1 Macrophages via the Ang II Type 1 Receptor/Liver X Receptor α Pathway
Authors: Wang Shipeng , Gu Xia , Zhang Qi , Zhang Xiling , Li Yilan , Yao Yuan , Yu Bo , Zhang Yao
Published: March 2018

Background/Aims: Angiotensin II (Ang II) regulates the expression of some core clock genes; excess Ang II leads to atherosclerosis advancement. Macrophage Rev-erbα mediates clockwork and inflammation, and plays a role in atherosclerotic lesion progression. However, the role of Ang II in regulating Rev-erbα expression in macrophages remains unclarified. Methods: We induced THP-1 macrophages by phorbol 12-myristate 13-acetate and investigated the effect of Ang II on Rev-erbα expression via real-time polymerase chain reaction, western blotting and small interfering RNA (siRNA) techniques. The cytotoxicity of the Rev-erbα agonist SR9009 was analyzed using a (3-[4,5-dimethylthiazol-2-yl])-2,5- diphenyltetrazolium bromide assay. Results: Ang II suppressed Rev-erbα mRNA and protein expression in THP-1 macrophages in a dose and time dependent manner. This effect was mediated via Ang II type 1 receptor (AT1R), and not Ang II type 2 receptor or peroxisome proliferator-activated receptor γ (PPARγ). Consistent with Rev-erbα expression regulated by Ang II, the liver X receptor α (LXRα) protein expression was downregulated in a time-dependent manner after Ang II treatment. The activation or silence of LXRα significantly increased or decreased Rev-erbα expression regulated by Ang II, respectively. This suggests that LXRα is involved in the effect of Ang II on Rev-erbα expression. MMP-9 mRNA expressions were significantly suppressed by SR9009 in THP-1 and RAW264.7 macrophages; moreover, SR9009-treatment significantly reduced Ang II–induced MMP-9 protein expressions in two types of macrophages. Conclusion: Ang II downregulates Rev-erbα expression in THP-1 macrophages via the AT1R/LXRα pathway.
MiR-27a Promotes Hemin-Induced Erythroid Differentiation of K562 Cells by Targeting CDC25B
Authors: Wang Dongsheng , Si Si , Wang Qiang , Luo Guangcheng , Du Qin , Liang Qi , Guo Xiaolan , Zhang Guoyuan , Feng Jiafu , Leng Zhengwei
Published: March 2018

Background/Aims: MicroRNAs (miRNAs) play a crucial role in erythropoiesis. MiR-23a∼27a∼24-2 clusters have been proven to take part in erythropoiesis via some proteins. CDC25B (cell division control Cdc2 phosphostase B) is also the target of mir-27a; whether it regulates erythropoiesis and its mechanism are unknown. Methods: To evaluate the potential role of miR-27a during erythroid differentiation, we performed miR-27a gain- and loss-of-function experiments on hemin-induced K562 cells. We detected miR-27a expression after hemin stimulation at different time points. At the same time, the γ-globin gene also was measured via real-time PCR. According to the results of the chips, we screened the target protein of miR-27a through a dual-luciferase reporter assay and identified it via Western blot analyses. To evaluate the function of CDC25B, benzidine staining and flow cytometry were employed to detect the cell differentiation and cell cycle. Results: We found that miR-27a promotes hemin-induced erythroid differentiation of human K562 cells by targeting cell division cycle 25 B (CDC25B). Overexpression of miR-27a promotes the differentiation of hemin-induced K562 cells, as demonstrated by γ-globin overexpression. The inhibition of miR-27a expression suppresses erythroid differentiation, thus leading to a reduction in the γ-globin gene. CDC25B was identified as a new target of miR-27a during erythroid differentiation. Overexpression of miR-27a led to decreased CDC25B expression after hemin treatment, and CDC25B was up-regulated when miR-27a expression was inhibited. Moreover, the inhibition of CDC25B affected erythroid differentiation, as assessed by γ-globin expression. Conclusion: This study is the first report of the interaction between miR-27a and CDC25B, and it improves the understanding of miRNA functions during erythroid differentiation.
Intra-Cardiac Release of Extracellular Vesicles Shapes Inflammation Following Myocardial Infarction
Authors: Loyer Xavier , Zlatanova Ivana , Devue Cecile , Yin Min , Howangyin Kiave-Yune , Klaihmon Phatchanat , Guerin Coralie L. , Kheloufi Marouane , Vilar Jose , Zannis Konstantinos , Fleischmann Bernd K. , Hwang Do Won , Park Jongmin , Lee Hakho , Menasché Philippe , Silvestre Jean-Sébastien , Boulanger Chantal M.
Published: March 2018

Rationale:

A rapid and massive influx of inflammatory cells occurs into ischemic area after myocardial infarction (MI), resulting in local release of cytokines and growth factors. Yet, the mechanisms regulating their production are not fully explored. The release of extracellular vesicles (EVs) in the interstitial space curbs important biological functions, including inflammation, and influences the development of cardiovascular diseases. To date, there is no evidence for in situ release of cardiac EVs after MI.

Objective:

The present study tested the hypothesis that local EV generation in the infarcted heart coordinates cardiac inflammation after MI.

Methods and Results:

Coronary artery ligation in mice transiently increases EV levels in the left ventricle when compared with sham animals. EVs from infarcted hearts were characterized as large vesicles (252±18 nm) expressing cardiomyocyte and endothelial markers and small EVs (118±4 nm) harboring exosomal markers, such as CD (cluster of differentiation) 63 and CD9. Cardiac large EVs generated after MI, but not small EVs or sham EVs, increased the release of IL (interleukin)-6, CCL (chemokine ligand) 2, and CCL7 from fluorescence-activated cell–sorted Ly6C
+
cardiac monocytes. EVs of similar diameter were also isolated from fragments of interventricular septum obtained from patients undergoing aortic valve replacement, thus supporting the clinical relevance of our findings in mice.

Conclusions:

The present study demonstrates that acute MI transiently increases the generation of cardiac EVs characterized as both exosomes and microvesicles, originating mainly from cardiomyocytes and endothelial cells. EVs accumulating in the ischemic myocardium are rapidly taken up by infiltrating monocytes and regulate local inflammatory responses.
Taxonomic revision of the sub-Saharan Anthidiellum Cockerell (Apoidea: Megachilidae: Anthidiini)
Authors: EARDLEY CONNAL
Published: March 2018

The Afrotropical species of the genus Anthidiellum Cockerell are revised. There are twelve species in two distinct subgenera; Pycnanthidium and Chloranthidiellum. An early record of Anthidiellum sensu stricto from Africa resulted from a misidentification. Two new species are described, Anthidiellum (Chloranthidiellum) pamae and Anthidiellum (Pycnanthidium) somaliense. Anthidiellum eritrinum is moved from the nominative subgenus to Chloranthidiellum, and a key for the identification of both sexes of the species is given. The species are redescribed with illustrations of male terminalia for most species, which have not been published before, and colour photographs. Four names are held in abeyance because their identity, and therefore status as valid species, is uncertain. They are Anthidiellum tegwaniense (Cockerell); Anthidiellum bulawayense Mavromoustakis; Anthidiellum nigripes (Friese) and Anthidiellum orichalciscopatum (Strand). They are here tentatively presumed to be junior synonyms of Anthidiellum zebra Friese.
Autapomorphies in the generic classification of Plectrothripini (Thysanoptera, Phlaeothripinae), with a new genus and a new record from Malaysia
Authors: MOUND L.A. , NG Y. F.
Published: March 2018

Bangithrips mei gen. et sp. n. is described from Peninsular Malaysia. The significance is discussed of outstanding structural autapomorphies that are commonly used in classifications of Thysanoptera. Argyrothrips ommatos described recently from northern Australia is recorded from Malaysia.
Two new species of penicillate millipedes (Diplopoda, Polyxenidae) from Phu Quoc Island in southern Vietnam
Authors: HUYNH CUONG , VEENSTRA ANNEKE A
Published: March 2018

Two new penicillate millipede species from the genera Unixenus and Monographis (Diplopoda, Polyxenidae) were collected from Phu Quoc Island, Vietnam’s largest island. Unixenus intragramineus sp. n. was found within the stem of a creeping grass growing on an unstable, sandy substrate in the intertidal zone. The defining taxonomic characteristics of the genus Unixenus were apparent in U. intragramineus sp. n., but it is distinctively different from all described species. Monographis phuquocensis sp. n. belongs to a group of Monographis species which have their antennal sensilla arranged in a crescent-shape; but the structure of the labrum and telotarsus observed in this new species differs from other described Monographis.
Twentieth-Century Climate Change over Africa: Seasonal Hydroclimate Trends and Sahara Desert Expansion
Authors: Thomas Natalie , Nigam Sumant
Published: March 2018

Twentieth-century trends in seasonal temperature and precipitation over the African continent are analyzed from observational datasets and historical climate simulations. Given the agricultural economy of the continent, a seasonal perspective is adopted as it is more pertinent than an annual-average one, which can mask offsetting but agriculturally sensitive seasonal hydroclimate variations. Examination of linear trends in seasonal surface air temperature (SAT) shows that heat stress has increased in several regions, including Sudan and northern Africa where the largest SAT trends occur in the warm season. Broadly speaking, the northern continent has warmed more than the southern one in all seasons. Precipitation trends are varied but notable declining trends are found in the countries along the Gulf of Guinea, especially in the source region of the Niger River in West Africa, and in the Congo River basin. Rainfall over the African Great Lakes—one of the largest freshwater repositories—has, however, increased. It is shown that the Sahara Desert has expanded significantly over the twentieth century, by 11%–18% depending on the season, and by 10% when defined using annual rainfall. The expansion rate is sensitively dependent on the analysis period in view of the multidecadal periods of desert expansion (including from the drying of the Sahel in the 1950s–80s) and contraction in the 1902–2013 record, and the stability of the rain gauge network. The desert expanded southward in summer, reflecting retreat of the northern edge of the Sahel rainfall belt, and to the north in winter, indicating potential impact of the widening of the tropics. Specific mechanisms for the expansion are investigated. Finally, this observational analysis is used to evaluate the state-of-the-art climate simulations from a comparison of the twentieth-century hydroclimate trends. The evaluation shows that modeling regional hydroclimate change over the African continent remains challenging, warranting caution in the development of adaptation and mitigation strategies.
A New Monthly Pressure Dataset Poleward of 60°S since 1957
Authors: Fogt Ryan L. , Clark Logan N. , Nicolas Julien P.
Published: March 2018

This study presents a new monthly pressure dataset poleward of 60°S, from 1957 to 2016, based on a kriging interpolation from observed pressure anomalies across the Antarctic continent. Overall, the reconstruction performs well when evaluated against ERA-Interim. In comparison to other reanalyses, the reconstruction has interannual variability after 1970 similar to products that span the entire twentieth century and is a marked improvement on the first-generation reanalysis products. The reconstruction also produces weaker pressure trends than the reanalysis products evaluated here, which are consistent with observations. However, the skill of the reconstruction is weaker in the South Pacific and therefore does not improve the understanding of long-term pressure variability and trends in this region, where circulation changes have been key drivers of climate variability in West Antarctica and the Antarctic Peninsula.
Potential Vorticity Dynamics of Forecast Errors: A Quantitative Case Study
Authors: Baumgart Marlene , Riemer Michael , Wirth Volkmar , Teubler Franziska , Lang Simon T. K.
Published: March 2018

Synoptic-scale error growth near the tropopause is investigated from a process-based perspective. Following previous work, a potential vorticity (PV) error tendency equation is derived and partitioned into individual contributions to yield insight into the processes governing error growth near the tropopause. Importantly, we focus here on the further amplification of preexisting errors and not on the origin of errors. The individual contributions to error growth are quantified in a case study of a 6-day forecast. In this case, localized mesoscale error maxima have formed by forecast day 2. These maxima organize into a wavelike pattern and reach the Rossby wave scale around forecast day 6. Error growth occurs most prominently within the Atlantic and Pacific Rossby wave patterns. In our PV framework, the error growth is dominated by the contribution of upper-level, near-tropopause PV anomalies (near-tropopause dynamics). Significant contributions from upper-tropospheric divergent flow (prominently associated with latent heat release below) and lower-tropospheric anomalies [tropospheric-deep (i.e., baroclinic) interaction] are associated with a misrepresentation of the surface cyclone development in the forecast. These contributions are, in general, of smaller importance to error growth than near-tropopause dynamics. This result indicates that the mesoscale errors generated near the tropopause do not primarily project on differences in the subsequent baroclinic growth, but instead directly project on the tropopause evolution and amplify because of differences in the nonlinear Rossby wave dynamics.