bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasmid DNA nicking- a Novel Activity of Soybean Trypsin Inhibitor and Bovine Aprotinin
Authors: Islam M. Rafiq , Ihenacho Kelvin , Park Jae Whan , Islam I. Sakif 
Published: August 2019

AbstractProtease inhibitors, such as trypsin inhibitor, serum alpha-1 antitrypsin, or liver aprotinin, are a class of proteins that competitively bind and block the catalytic activity of proteolytic enzymes with wide ranging biological functions. A significant number of protease inhibitors have also been shown to possess antimicrobial activity, presumed to contribute in defense against pathogenic microorganisms as plants with higher levels of protease inhibitors tend to exhibit increased resistance towards pathogens. Two proposed mechanisms for the antimicrobial activity are combating microbial proteases that play roles in disease development and disruption of microbial cell wall & membrane necessary for survival. Here we show for the first time a novel activity of soybean trypsin inhibitor and bovine aprotinin that they nick supercoiled, circular plasmid DNA. A number of experiments conducted to demonstrate the observed DNA nicking activity is inherent, rather than a co-purified, contaminating nuclease. The nicking of the plasmid results in markedly reduced efficiencies in transformation of E. coli and transfection of HEK293T cells. Thus, this work reveals yet a new mechanism for the antimicrobial activity by protease inhibitors.
Outcome and Prognosis of Patients With Lupus Nephritis Submitted to Renal Transplantation
Authors: Albuquerque Bruna Coelho , Salles Vivian Brito , Tajra Rodrigo Dib de Paulo , Rodrigues Carlos Ewerton Maia 
Published: August 2019

AbstractThis stydy aimed to evaluate the epidemiological and clinical profile and outcome of patients with lupus nephritis (LN) submitted to renal transplantation. Retrospective cohort study based on the records of 35 LN patients submitted to renal transplantation at a single center in Brazil between July 1996 and May 2016. The Kaplan-Meier method was used to estimate 6-month, 1-year and 5-year graft survival. The sample included 38 transplantations (3 of which retransplantations). The mean age at the time of SLE diagnosis was 23.7 ± 9.0 years. Most patients were female (94.7%) and 68.4% were non-Caucasian. Twenty-two (57.9%) underwent renal biopsy prior to transplantation. The mean time from SLE diagnosis to transplantation was 10.3 ± 6.4 years. The mean pre-transplantation dialysis time was 3.8 ± 3.7 years. The grafts came from living related (n = 11) or deceased (n = 27) donors. Three (7.9%) patients experienced acute rejection in the first year. Graft and patient survival rates were, respectively, 97.1% and 100% at 6 months, 84.9% and 96.9% at 1 year, and 76.3% and 92.5% at 5 years. One (2.6%) patient had SLE recurrence. Venous thrombosis (p = 0.017) and antiphospholipid syndrome (APS) (p = 0.036) were more prevalent in patients with graft loss. In our cohort of LN patients submitted to renal transplantation, the 5-year survival rate was high, and APS was an important predictor of poor renal outcome (graft loss).
Peripheral sounds elicit stronger activity in contralateral occipital cortex in blind than sighted individuals
Authors: Amadeo Maria Bianca , Störmer Viola S. , Campus Claudio , Gori Monica 
Published: August 2019

AbstractPrevious research has shown that peripheral, task-irrelevant sounds elicit activity in contralateral visual cortex of sighted people, as revealed by a sustained positive deflection in the event-related potential (ERP) over the occipital scalp contralateral to the sound’s location. This Auditory-evoked Contralateral Occipital Positivity (ACOP) appears between 200–450 ms after sound onset, and is present even when the task is entirely auditory and no visual stimuli are presented at all. Here, we investigate whether this cross-modal activation of contralateral visual cortex is influenced by visual experience. To this end, ERPs were recorded in 12 sighted and 12 blind subjects during a unimodal auditory task. Participants listened to a stream of sounds and pressed a button every time they heard a central target tone, while ignoring the peripheral noise bursts. It was found that task-irrelevant noise bursts elicited a larger ACOP in blind compared to sighted participants, indicating for the first time that peripheral sounds can enhance neural activity in visual cortex in a spatially lateralized manner even in visually deprived individuals. Overall, these results suggest that the cross-modal activation of contralateral visual cortex triggered by peripheral sounds does not require any visual input to develop, and is rather enhanced by visual deprivation.
Genomic Polymorphism Associated with the Emergence of Virulent Isolates of Mycobacterium bovis in the Nile Delta
Authors: Abdelaal Hazem F. M. , Spalink Daniel , Amer Ali , Steinberg Howard , Hashish Emad A. , Nasr Essam A. , Talaat Adel M. 
Published: August 2019

AbstractMycobacterium bovis is responsible for bovine tuberculosis in both animals and humans. Despite being one of the most important global zoonotic disease, data related to the ecology and pathogenicity of bovine tuberculosis is scarce, especially in developing countries. In this report, we examined the dynamics of M. bovis transmission among dairy cattle in the Nile Delta of Egypt. Animals belonging to 27 herds from 7 governorates were tested by the Single Intradermal Comparative Skin Tuberculin (SICST), as a preliminary screen for the presence of bovine tuberculosis. Positive SICST reactors were identified in 3% of the animals spread among 40% of the examined herds. Post-mortem examination of slaughtered reactors confirmed the presence of both pulmonary and/or digestive forms of tuberculosis in > 50% of the examined animals. Targeted and whole-genome analysis of M. bovis isolates indicated the emergences of a predominant spoligotype (SB0268) between 2013–2015, suggesting a recent clonal spread of this isolate within the Nile Delta. Surprisingly, 2 isolates belonged to M. bovis BCG group, which are not allowed for animal vaccination in Egypt, while the rest of isolates belonged to the virulent M. bovis clonal complex European 2 present in Latin America and several European countries. Analysis of strain virulence in the murine model of tuberculosis indicated the emergence of a more virulent strain (MBE4) with a specific genotype. More analysis is needed to understand the molecular basis for successful spread of virulent isolates of bovine tuberculosis among animals and to establish genotype/phenotype association.
Brief oxygenation events in locally anoxic oceans during the Cambrian solves the animal breathing paradox
Authors: Dahl Tais W. , Siggaard-Andersen Marie-Louise , Schovsbo Niels H. , Persson Daniel O. , Husted Søren , Hougård Iben W. , Dickson Alexander J. , Kjær Kurt , Nielsen Arne T. 
Published: August 2019

AbstractOxygen is a prerequisite for all large and motile animals. It is a puzzling paradox that fossils of benthic animals are often found in black shales with geochemical evidence for deposition in marine environments with anoxic and sulfidic bottom waters. It is debated whether the geochemical proxies are unreliable, affected by diagenesis, or whether the fossils are transported from afar or perhaps were not benthic. Here, we improved the stratigraphic resolution of marine anoxia records 100–1000 fold using core-scanning X-Ray Fluorescence and established a centennial resolution record of oxygen availability at the seafloor in an epicontinental sea that existed ~501–494 million years ago. The study reveals that anoxic bottom-water conditions, often with toxic hydrogen sulfide present, were interrupted by brief oxygenation events of 600–3000 years duration, corresponding to 1–5 mm stratigraphic thickness. Fossil shells occur in some of these oxygenated intervals suggesting that animals invaded when conditions permitted an aerobic life style at the seafloor. Although the fauna evidently comprised opportunistic species adapted to low oxygen environments, these findings reconcile a long-standing debate between paleontologists and geochemists, and shows the potential of ultra-high resolution analyses for reconstructing redox conditions in past oceans.
Curcumin diethyl disuccinate, a prodrug of curcumin, enhances anti-proliferative effect of curcumin against HepG2 cells via apoptosis induction
Authors: Muangnoi Chawanphat , Ratnatilaka Na Bhuket Pahweenvaj , Jithavech Ponsiree , Supasena Wiwat , Paraoan Luminita , Patumraj Suthiluk , Rojsitthisak Pornchai 
Published: August 2019

AbstractCurcumin (Cur) has been reported to have anti-hepatocellular carcinoma activity but its poor oral bioavailability limits its further development as a chemotherapeutic agent. We synthesized previously a succinate ester prodrug of Cur, curcumin diethyl disuccinate (CurDD) with better chemical stability in a buffer solution pH 7.4. Here, we further investigated and compared the cellular transport and anti-proliferative activity against HepG2 cells of CurDD and Cur. Transport of CurDD across the Caco-2 monolayers provided a significantly higher amount of the bioavailable fraction (BF) of Cur with better cytotoxicity against HepG2 cells compared to that of Cur (p < 0.05). Flow cytometric analysis showed that the BF of CurDD shifted the cell fate to early and late apoptosis to a higher extent than that of Cur. The Western blot analysis revealed that CurDD increased Bax protein expression, downregulated Bcl-2 protein, activated caspase-3 and -9 and increased LC3-II protein level in HepG2 cells. Flow cytometric and immunoblotting results suggest that CurDD can induce HepG2 cell death via an apoptotic pathway. We suggest that CurDD can overcome the limitations of Cur in terms of cellular transport with a potential for further extensive in vitro and in vivo studies of anti-hepatocellular carcinoma effects.
Tiotropium inhibits proinflammatory microparticle generation by human bronchial and endothelial cells
Authors: Neri Tommaso , Scalise Valentina , Passalacqua Ilaria , Sanguinetti Chiara , Lombardi Stefania , Pergoli Laura , Bollati Valentina , Pedrinelli Roberto , Paggiaro Pierluigi , Celi Alessandro 
Published: August 2019

AbstractTiotropium is a muscarinic antagonist that reduces the risk of acute exacerbations of chronic obstructive pulmonary disease, possibly through an as yet incompletely characterized anti-inflammatory activity. We hypothesized that muscarinic activation of bronchial epithelial cells and endothelial cells causes the release of proinflammatory microparticles and that tiotropium inhibits the phenomenon. Microparticle generation was assessed by a functional assay, by flow cytometry and by NanoSight technology. Immortalized bronchial epithelial cells (16HBE) and umbilical vein endothelial cells were treated with acetylcholine in the presence of varying concentrations of tiotropium. Intracellular calcium concentration, extracellular regulated kinase phosphorylation and chemokine content in the conditioned media were assessed by commercial kits. Acetylcholine causes microparticle generation that is completely inhibited by tiotropium (50 pM). Microparticles generated by acetylcholine-stimulated cells increase the synthesis of proinflammatory mediators in an autocrine fashion. Acetylcholine-induced upregulation of microparticle generation is inhibited by an inhibitor of extracellular regulated kinase phosphorylation and by a phospholipase C inhibitor. Tiotropium blocks both extracellular regulated kinase phosphorylation and calcium mobilization, consistent with the hypothesis that the drug prevents microparticle generation through inhibition of these critical pathways. These results might contribute to explain the effect of tiotropium in reducing acute exacerbations of chronic obstructive pulmonary disease.
Identification of a factor controlling lysosomal homeostasis using a novel lysosomal trafficking probe
Authors: Ishii Shunsuke , Matsuura Akira , Itakura Eisuke 
Published: August 2019

AbstractLysosomes are largely responsible for significant degradation of intracellular and extracellular proteins via the secretory pathway, autophagy, and endocytosis. Therefore, dysregulation of lysosomal homeostasis influences diverse cellular functions. However, a straightforward and quantitative method to measure the integrity of the lysosomal pathway has not been developed. Here, we report the plasmid-based lysosomal-METRIQ (MEasurement of protein Transporting integrity by RatIo Quantification) probe that enables simple quantification of lysosomal integrity by lysosomal green and cytosolic red fluorescent proteins using a flow cytometer. In cultured cells, the lysosomal-METRIQ probe detected not only suppression of the lysosomal pathway but also upregulation of lysosomal activity such as lysosomal biogenesis. To identify factors involved in lysosomal homeostasis, we carried out compound screening and found that the cyclin-dependent kinase (CDK) inhibitors kenpaullone and purvalanol A induce synthesis of cathepsin D and an increase in the number of lysosomes. Subsequent studies revealed that CDK5 maintains lysosomal homeostasis independently of cell cycle arrest. Our results suggest that the lysosomal-METRIQ probe is an effective and efficient tool for measuring lysosomal activity in mammalian cells.
Exosomal miR-16-5p as a target for malignant mesothelioma
Authors: Munson Phillip B. , Hall Elizabeth M. , Farina Nicholas H. , Pass Harvey I. , Shukla Arti 
Published: August 2019

AbstractMalignant mesothelioma (MM) is an asbestos-induced cancer arising on the mesothelial surface of organ cavities. MM is essentially incurable without a means of early diagnosis and no successful standard of care. These facts indicate a deep chasm of knowledge that needs to be filled. Our group recently delved into MM tumor biology from the perspective of exosome-contained microRNAs (miRNAs). We discovered that the most abundant miRNAs in MM cancer exosomes were tumor suppressors, particularly miR-16-5p. This observation lead us to hypothesize that MM cells preferentially secreted tumor-suppressor miRNAs via exosomes. Through separate avenues of potential therapeutic advance, we embarked on an innovative strategy to kill MM tumor cells. We employed small molecule inhibitors to block exosome secretion, thereby reducing miR-16-5p exosome loss and replenishing cellular miR-16-5p leading to reduced tumorigenic capacity and miR-16-5p target oncoproteins CCND1 and BCL2. Additionally, we force-fed MM tumor exosomes back to MM tumor cells, which led to cell death, and a reduction in the same oncoproteins. We recapitulated these results with direct transfection of miR-16-5p, confirmed that this is a cancer-cell specific effect, and elucidated a part of the miR-16-5p mechanism of exosome loading.
Enrichment of intracellular sulphur cycle –associated bacteria in intertidal benthic foraminifera revealed by 16S and aprA gene analysis
Authors: Salonen I. S. , Chronopoulou P. -M. , Bird C. , Reichart G. -J. , Koho K. A. 
Published: August 2019

AbstractBenthic foraminifera are known to play an important role in marine carbon and nitrogen cycles. Here, we report an enrichment of sulphur cycle -associated bacteria inside intertidal benthic foraminifera (Ammoniasp. (T6),Haynesinasp. (S16) andElphidiumsp. (S5)), using a metabarcoding approach targeting the 16S rRNA andaprA-genes. The most abundant intracellular bacterial groups included the genusSulfurovumand the order Desulfobacterales. The bacterial 16S OTUs are likely to originate from the sediment bacterial communities, as the taxa found inside the foraminifera were also present in the sediment. The fact that 16S rRNA andaprA–gene derived intracellular bacterial OTUs were species-specific and significantly different from the ambient sediment community implies that bacterivory is an unlikely scenario, as benthic foraminifera are known to digest bacteria only randomly. Furthermore, these foraminiferal species are known to prefer other food sources than bacteria. The detection of sulphur-cycle related bacterial genes in this study suggests a putative role for these bacteria in the metabolism of the foraminiferal host. Future investigation into environmental conditions under which transcription of S-cycle genes are activated would enable assessment of their role and the potential foraminiferal/endobiont contribution to the sulphur-cycle.
A New Method for Intense Cavitation Bubble Generation on Layer-by-Layer Assembled SLIPS
Authors: Aghdam Araz Sheibani , Ghorbani Morteza , Deprem Gokberk , Cebeci Fevzi Çakmak , Koşar Ali 
Published: August 2019

AbstractThe importance of surface topology for the generation of cavitating flows in micro scale has been emphasized during the last decade. In this regard, the utilization of surface roughness elements is not only beneficial in promoting mass transportation mechanisms, but also in improving the surface characteristics by offering new interacting surface areas. Therefore, it is possible to increase the performance of microfluidic systems involving multiphase flows via modifying the surface. In this study, we aim to enhance generation and intensification of cavitating flows inside microfluidic devices by developing artificial roughness elements and trapping hydrophobic fluorinated lubricants. For this, we employed different microfluidic devices with various hydraulic diameters, while roughness structures with different lengths were formed on the side walls of microchannel configurations. The surface roughness of these devices was developed by assembling various sizes of silica nanoparticles using the layer-by-layer technique (D2). In addition, to compare the cavitating flow intensity with regular devices having plain surfaces (D1), highly fluorinated oil was trapped within the pores of the existing thin films in the configuration D2 via providing the Slippery Liquid-Infused Porous Surface (D3). The microfluidic devices housing the short microchannel and the extended channel were exposed to upstream pressures varying from 1 to 7.23 MPa. Cavitation inception and supercavitation condition occured at much lower upstream pressures for the configurations of D2 and D3. Interestingly, hydraulic flip, which rarely appears in the conventional conical nozzles at high pressures, was observed at moderate upstream pressures for the configuration D2 proving the air passage existence along one side of the channel wall.
Evidence for a link between the Atlantic Multidecadal Oscillation and annual asthma mortality rates in the US
Authors: Bonomo Sergio , Ferrante Giuliana , Palazzi Elisa , Pelosi Nicola , Lirer Fabrizio , Viegi Giovanni , La Grutta Stefania 
Published: August 2019

AbstractAn association between climatic conditions and asthma mortality has been widely assumed. However, it is unclear whether climatic variations have a fingerprint on asthma dynamics over long time intervals. The aim of this study is to detect a possible correlation between climatic indices, namely the Atlantic Multidecadal Oscillation and Pacific Decadal Oscillation, and asthma mortality rates over the period from 1950 to 2015 in the contiguous US. To this aim, an analysis of non-stationary and non-linear signals was performed on time series of US annual asthma mortality rates, AMO and PDO indices to search for characteristic periodicities. Results revealed that asthma death rates evaluated for four different age groups (5–14 yr; 15–24 yr; 25–34 yr; 35–44 yr) share the same pattern of fluctuation throughout the 1950–2015 time interval, but different trends, i.e. a positive (negative) trend for the two youngest (oldest) categories. Annual asthma death rates turned out to be correlated with the dynamics of the AMO, and also modulated by the PDO, sharing the same averaged ∼44 year-periodicity. The results of the current study suggest that, since climate patterns have proved to influence asthma mortality rates, they could be advisable in future studies aimed at elucidating the complex relationships between climate and asthma mortality.
Antiretroviral therapy partially improves the abnormalities of dendritic cells and lymphoid and myeloid regulatory populations in recently infected HIV patients
Authors: Márquez-Coello Mercedes , Montes de Oca Arjona Montserrat , Martín-Aspas Andrés , Guerrero Sánchez Francisca , Fernández-Gutiérrez del Álamo Clotilde , Girón-González José A. 
Published: August 2019

AbstractThis study aimed to evaluate the effects of antiretroviral therapy on plasmacytoid (pDC) and myeloid (mDC) dendritic cells as well as regulatory T (Treg) and myeloid-derived suppressor (MDSC) cells in HIV-infected patients. Forty-five HIV-infected patients (20 of them with detectable HIV load −10 recently infected and 10 chronically infected patients-, at baseline and after antiretroviral therapy, and 25 with undetectable viral loads) and 20 healthy controls were studied. The influence of HIV load, bacterial translocation (measured by 16S rDNA and lipopolysaccharide-binding protein) and immune activation markers (interleukin –IL- 6, soluble CD14, activated T cells) was analyzed. The absolute numbers and percentages of pDC and mDC were significantly increased in patients. Patients with detectable viral load exhibited increased intracellular expression of IL-12 by mDCs and interferon -IFN- α by pDCs. Activated population markers were elevated, and the proportion of Tregs was significantly higher in HIV-infected patients. The MDSC percentage was similar in patients and controls, but the intracellular expression of IL-10 was significantly higher in patients. The achievement of undetectable HIV load after therapy did not modify bacterial translocation parameters, but induce an increase in pDCs, mDCs and MDSCs only in recently infected patients. Our data support the importance of early antiretroviral therapy to preserve dendritic and regulatory cell function in HIV-infected individuals.
Targeted sequencing of linkage region in Dominican families implicates PRIMA1 and the SPATA7-PTPN21-ZC3H14-EML5-TTC8 locus in carotid-intima media thickness and atherosclerotic events
Authors: Wang Liyong , Dueker Nicole , Beecham Ashley , Blanton Susan H. , Sacco Ralph L. , Rundek Tatjana 
Published: August 2019

AbstractCarotid intima-media thickness (cIMT) is a subclinical marker for atherosclerosis. Previously, we reported a quantitative trait locus (QTL) for total cIMT on chromosome 14q and identified PRiMA1, FOXN3 and CCDC88C as candidate genes using a common variants (CVs)-based approach. Herein, we further evaluated the genetic contribution of the QTL to cIMT by resequencing. We sequenced all exons within the QTL and genomic regions of PRiMA1, FOXN3 and CCDC88C in Dominican families with evidence for linkage to the QTL. Unrelated Dominicans from the Northern Manhattan Study (NOMAS) were used for validation. Single-variant-based and gene-based analyses were performed for CVs and rare variants (RVs). The strongest evidence for association with CVs was found in PRiMA1 (p = 8.2 × 10−5 in families, p = 0.01 in NOMAS at rs12587586), and in the five-gene cluster SPATA7-PTPN21-ZC3H14-EML5-TTC8 locus (p = 1.3 × 10−4 in families, p = 0.01 in NOMAS at rs2274736). No evidence for association with RVs was found in PRiMA1. The top marker from previous study in PRiMA1 (rs7152362) was associated with fewer atherosclerotic events (OR = 0.67; p = 0.02 in NOMAS) and smaller cIMT (β = −0.58, p = 2.8 × 10−4 in Family). Within the five-gene cluster, evidence for association was found for exonic RVs (p = 0.02 in families, p = 0.28 in NOMAS), which was enriched among RVs with higher functional potentials (p = 0.05 in NOMAS for RVs in the top functional tertile). In summary, targeted resequencing provided validation and novel insights into the genetic architecture of cIMT, suggesting stronger effects for RVs with higher functional potentials. Furthermore, our data support the clinical relevance of CVs associated with subclinical atherosclerosis.