Miracle-dz/UniFAR-FTUs huggingface dataset:
Endothelial Mechanosignaling: Does One Sensor Fit All?

Abstract Significance: Forces are important in the cardiovascular system, acting as regulators of vascular physiology and pathology. Residing at the blood vessel interface, cells (endothelial cell, EC) are constantly exposed to vascular forces, including shear stress. Shear stress is the frictional force exerted by blood flow, and its patterns differ based on vessel geometry and type. These patterns range from uniform laminar flow to nonuniform disturbed flow. Although ECs sense and differentially respond to flow patterns unique to their microenvironment, the mechanisms underlying endothelial mechanosensing remain incompletely understood. Recent Advances: A large body of work suggests that ECs possess many mechanosensors that decorate their apical, junctional, and basal surfaces. These potential mechanosensors sense blood flow, translating physical force into biochemical signaling events. Critical Issues: Understanding the mechanisms by which proposed mechanosensors sense and respond to shear stress requires an integrative approach. It is also critical to understand the role of these mechanosensors not only during embryonic development but also in the different vascular beds in the adult. Possible cross talk and integration of mechanosensing via the various mechanosensors remain a challenge. Future Directions: Determination of the hierarchy of endothelial mechanosensors is critical for future work, as is determination of the extent to which mechanosensors work together to achieve force-dependent signaling. The role and primary sensors of shear stress during development also remain an open question. Finally, integrative approaches must be used to determine absolute mechanosensory function of potential mechanosensors. Antioxid. Redox Signal. 25, 373–388.
Ginsenoside Rg1 Protects Cardiomyocytes Against Hypoxia/Reoxygenation Injury via Activation of Nrf2/HO-1 Signaling and Inhibition of JNK

Background/Aims: Excessive reactive oxygen species (ROS) disturb the physiology of H9c2 cells, which is regarded as a major cause of H9c2 cardiomyocyte apoptosis. Ginsenoside Rg1 is the main active extract of ginseng, which has important antioxidant properties in various cell models. This project investigated the role of ginsenoside Rg1 in hypoxia/reoxygenation (H/R)-induced oxidative stress injury in cultured H9c2 cells to reveal the underlying signaling pathways. Methods: H9c2 cells were pretreated with ginsenoside Rg1 for 12 h before exposure to H/R. In the absence or presence of Nrf2siRNA, HO-1 inhibitor (ZnPP-IX), and inhibitors of the MAPK pathway (SB203580, PD98059, SP600125), H9c2 cells were subjected to H/R with Rg1 treatment. The effects and mechanisms of H/R-induced cardiomyocyte injury were measured. Results: Ginsenoside Rg1 treatment suppressed H/R-induced apoptosis and caspase-3 activation. Ginsenoside Rg1 treatment decreased ROS production and mitochondrial membrane depolarization by elevating the intracellular antioxidant capacity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and reduced glutathione (GSH). Furthermore, ginsenoside Rg1 stimulation appeared to result in nuclear translocation of NF-E2-related factor 2 (Nrf2), along with enhanced expression of the downstream target gene heme oxygenase-1 (HO-1) in a dose-dependent manner. However, ginsenoside Rg1-mediated cardioprotection was abolished by Nrf2-siRNA and HO-1 inhibitor. H/R treatment increased the levels of phosphorylated c-Jun N-terminal kinases (p-JNK), which was dramatically attenuated by ginsenoside Rg1 and SP600125 (a specific JNK inhibitor). Conclusion: These observations indicate that ginsenoside Rg1 activates the Nrf2/HO-1 axis and inhibits the JNK pathway in H9c2 cells to protect against oxidative stress.
Increased bladder permeability in interstitial cystitis/painful bladder syndrome

The definition of interstitial cystitis (IC) has evolved over the years from being a well-defined entity characterized by diagnostic lesion (Hunner’s ulcer) in the urothelium to a clinical diagnosis by exclusion [painful bladder syndrome (PBS)]. Although the etiology is unknown, a central theme has been an association with increased permeability of the bladder. This article reviews the evidence for increased permeability being important to the symptoms of interstitial cystitis/painful bladder syndrome (IC/PBS) and in treating the disorder. Recent work showing cross-communication among visceral organs is also reviewed to provide a basis for understanding IC/PBS as a systemic disorder of a complex, interconnected system consisting of the bladder, bowel and other organs, nerves, cytokine-responding cells and the nervous system.
Phosphorous and Phosphate Solubilising Bacteria and their Role in Plant Nutrition

Plant-bacteria-soil interactions are the determinants of soil fertility and plant health. The success in the use of the beneficial microorganisms requires an excellent understanding of the complex interactions taking place between the different components of the complex plant-soilmicroorganisms (Hani Antoun, 2012). The soil surrounding the germinating seed is known as spermosphere. This ecological niche is the first habitat used by any developed microorganisms by seed inoculation and supports microbial activity. This in turn influences plant growth. As the plant grows older the growing roots are surrounded by strongly adhering soil particles and this soil-root interaction zone is known as rhizosphere (Hani Antoun, 2012). Plant root, exudates the organic content into the rhizosphere and supports the microbial activities, termed by Hiltner as Rhizospheric effect (Flaishman et al., 1996). Soil bacterial genera are involved in various biotic activities of the soil ecosystem to make it dynamic for nutrient turn over and sustainable for crop production (Munees et al., 2014). Sufficient and balanced quantities of nutrients require for optimum plant growth (Almas Zaidi et al., 2010). International Journal of Current Microbiology and Applied Sciences ISSN: 2319-7706 Volume 6 Number 4 (2017) pp. 2133-2144 Journal homepage: http://www.ijcmas. com
Hippocampal contributions to the episodic simulation of specific and general future events

Recent studies have demonstrated that remembering past experiences and imagining future scenarios recruits a core network including the hippocampus. Even so, constructing future events engages the hippocampus more than remembering past events. This fMRI study examined whether increased hippocampal activity for future events includes both specific and general events. Participants constructed specific and general past and future events during fMRI scanning. We replicated previous findings of increased activity in the right anterior hippocampus when constructing future relative to past events, and when constructing specific relative to general events. Importantly, both effects were driven by a significant interaction between temporal direction and specificity, with specific future events resulting in more activity than other conditions, including general future events. No regions exhibited greater activity during the construction of past relative to future events, or general relative to specific events. These results suggest that the process of constructing a detailed representation of a novel and specific future event differentially engages the right anterior hippocampus compared with other forms of event simulation and recall. Future work is needed to disambiguate the role of encoding, novelty and detail recombination in engaging the right anterior hippocampus during simulation. © 2010 Wiley‐Liss, Inc.
Family Caregivers of Older Adults, 1999–2015: Trends in Characteristics, Circumstances, and Role-Related Appraisal

Purpose of Study To assess trends in family caregiving between 1999 and 2015. Design and Methods We construct nationally representative profiles of community-dwelling older adults receiving help with self-care or indoor mobility and their "primary" family or unpaid caregiver using the 1999 and 2004 National Long Term Care Survey, 2011 and 2015 National Health and Aging Trends Study, and linked caregiver surveys. Trends are examined. Results Older adults receiving help were incrementally younger, more racially diverse, and better educated in 2015. Primary caregivers overwhelmingly continued to be spouses and adult children. Arrangements were increasingly 4 years or longer in duration (shifting from 44.8% in 1999 to 60.5% by 2015). On average, primary caregivers provided about or in excess of 30 hr per week at all four time points. Spouses provided fewer hours of care, were twice as likely to work, and half as likely to report substantial emotional, physical, and financial difficulty due to caregiving in 2015 than 1999. Adult children provided comparable hours of care to a more impaired population; a similar proportion reported substantial caregiving-related difficulty at each time. Use of respite care nearly doubled from 8.5% in 1999 to 15.7% in 2015. Dementia caregivers were less likely to report substantial physical and financial difficulty and more likely to use respite care in 2015 than 1999. Implications Family caregivers' circumstances generally improved during the 16-year period. Results diverge from prevailing concerns regarding the state of family caregiving and demonstrate the importance of longitudinally monitoring trends in late-life family caregiving.
Native Human Monoclonal Antibodies with Potent Cross-Lineage Neutralization of Influenza B Viruses

ABSTRACT Although antibodies that effectively neutralize a broad set of influenza viruses exist in the human antibody repertoire, they are rare. We used a single-cell screening technology to identify rare monoclonal antibodies (MAbs) that recognized a broad set of influenza B viruses (IBV). The screen yielded 23 MAbs with diverse germ line origins that recognized hemagglutinins (HAs) derived from influenza strains of both the Yamagata and Victoria lineages of IBV. Of the 23 MAbs, 3 exhibited low expression in a transient-transfection system, 4 were neutralizers that bound to the HA head region, 11 were stalk-binding nonneutralizers, and 5 were stalk-binding neutralizers, with 4 of these 5 having unique antibody sequences. Of these four unique stalk-binding neutralizing MAbs, all were broadly reactive and neutralizing against a panel of multiple strains spanning both IBV lineages as well as highly effective in treating lethal IBV infections in mice at both 24 and 72 h postinfection. The MAbs in this group were thermostable and bound different epitopes in the highly conserved HA stalk region. These characteristics suggest that these MAbs are suitable for consideration as candidates for clinical studies to address their effectiveness in the treatment of IBV-infected patients.
Dynamics of forest cover conversion in and around Bwindi impenetrable forest, Southwestern Uganda

Forest cover has been converted to agricultural land use in and around the protected areas of Uganda. The objectives of this study were; to examine the dynamics of forest cover change in and around Bwindi impenetrable forest between 1973 and 2010 and to identify the drivers of forest cover change. The trend in forest cover change was assessed by analyzing a series of orthorectified landsat imageries of 1973, 1987 and 2001 using unsupervised and supervised classification. Land use/cover map for 2010 was reconstructed by analyzing 2001 image, validated and/or reconstructed by ground truthing, use of secondary data and key informant interviews. A series of focused group discussions and key informant interviews were also used to identify drivers of land use/cover change. Policies and institutional arrangements that could have affected forest cover change for the studied time period were also identified. Results showed that protected forest and woodlot in unprotected area had declined by 7.8% and 70.7% respectively as small scale farming and tea plantations had increased by 13.9% and 78.3% respectively between 1973 and 2010. The conversions were attributed to land use pressure due to population growth, change in socio-economic conditions and institutional arrangements. The severe loss of woodlot outside the protected area not only poses a potential threat to the protected forest but also calls for intervention measures if efforts to mitigate climate change impacts are to be realized.
Enzyme-Assisted Extraction Optimization, Characterization and Antioxidant Activity of Polysaccharides from Sea Cucumber Phyllophorus proteus

Enzyme-assisted extraction optimization, characterization and in vitro antioxidant activity of polysaccharides from sea cucumber Phyllophorus proteus (PPP) were investigated in the present study. The optimal extraction conditions with a yield of 6.44 ± 0.06% for PPP were determined as follows: Extraction time of 2.89 h, ratio of extraction solvent to raw material of 16.26 mL/g, extraction pH of 6.83, exraction temperature of 50 °C and papain concentration of 0.15%. Three purified fractions, PPP-1a, PPP-1b and PPP-2 with molecular weights of 369.60, 41.73 and 57.76 kDa, respectively, were obtained from PPP by chromatography of FPA98Cl and Sepharose CL-6B columns. Analysis of monosaccharide compositions showed that PPP-1a consisted of N-acetyl-galactosamine (GalNAc), galactose (Gal) and fucose (Fuc), PPP-1b of Fuc as the only monosaccharide and PPP-2 of glucuronic acid, GalNAc and Fuc. Sulfate contents of PPP, PPP-1a, PPP-1b and PPP-2 were determined to be 21.9%, 20.6%, 25.2% and 28.0% (w/w), respectively. PPP and PPP-1a had higher molecular weight and intrinsic viscosity than those of the PPP-1b and PPP-2. PPP, PPP-1a, PPP-1b and PPP-2 exhibited obvious activities of scavenging 1,1-diphenyl-2-picrylhydrazyl radical, hydroxyl radical, superoxide radical and ABTS radical in different extent, which suggested that the polysaccharides from Phyllophorus proteus may be novel agents having potential value for antioxidation.
of the clinical evidence for interferon β 1 a ( Rebif ® ) in the treatment of multiple sclerosis

Correspondence: Fabio Monzani Department of Internal Medicine, University of Pisa, Via Roma 67, 56126 Pisa, Italy Tel +39 050 993 490 Fax +39 050 553 235 Email fmonzani@med.unipi. it Abstract: Interferon (INF) β 1a 22 or 44 μg (Rebif ) administered s.c. 3 times a week (t.i.w) is a well established immunomodulating treatment for relapsing remitting multiple sclerosis (RRMS). This review focuses on its mechanisms of action, evidence of effi cacy, safety, and tolerability. Several pharmacodynamic properties explain the immunomodulatory actions of INF β 1a 22 or 44 μg s.c. t.i. w. Pivotal trials and post-marketing studies proved that the drug is effective in reducing disease activity and likely in slowing disease progression. Head-to-head comparative studies with other marketed INFs β in RRMS suggested a better therapeutic response associated with higher doses and frequency of administration of Rebif . Additional evidence indicated a benefi cial effect of INF β 1a in patients with clinically isolated syndromes (CIS) suggestive of MS, as treatment reduced time to conversion to clinically defi nite (CD) disease. Further, although the drug did not prove to slow time to progression there were benefi ts on relapseand MRI-related secondary outcome measures in secondary progressive (SP) MS. Pivotal trials, their cross-over extensions, and post-marketing studies consistently showed that INF β 1a 22 or 44 μg s.c. t.i. w. is safe and well tolerated, as adverse drug reactions are usually mild and manageable.
The intrinsic microglial clock system regulates interleukin‐6 expression

Similar to neurons, microglia have an intrinsic molecular clock. The master clock oscillator Bmal1 modulates interleukin‐6 upregulation in microglial cells exposed to lipopolysaccharide. Bmal1 can play a role in microglial inflammatory responses. We previously demonstrated that gliotransmitter ATP induces transient expression of the clock gene Period1 via P2X7 purinergic receptors in cultured microglia. In this study, we further investigated mechanisms underlying the regulation of pro‐inflammatory cytokine production by clock molecules in microglial cells. Several clock gene transcripts exhibited oscillatory diurnal rhythmicity in microglial BV‐2 cells. Real‐time luciferase monitoring also showed diurnal oscillatory luciferase activity in cultured microglia from Per1::Luciferase transgenic mice. Lipopolysaccharide (LPS) strongly induced the expression of pro‐inflammatory cytokines in BV‐2 cells, whereas an siRNA targeting Brain and muscle aryl hydrocarbon receptor nuclear translocator‐like protein 1 (Bmal1), a core positive component of the microglial molecular clock, selectively inhibited LPS‐induced interleukin‐6 (IL‐6) expression. In addition, LPS‐induced IL‐6 expression was attenuated in microglia from Bmal1‐deficient mice. This phenotype was recapitulated by pharmacological disruption of oscillatory diurnal rhythmicity using the synthetic Rev‐Erb agonist SR9011. Promoter analysis of the Il6 gene revealed that Bmal1 is required for LPS‐induced IL‐6 expression in microglia. Mice conditionally Bmal1 deficient in cells expressing CD11b, including microglia, exhibited less potent upregulation of Il6 expression following middle cerebral artery occlusion compared with that in control mice, with a significant attenuation of neuronal damage. These results suggest that the intrinsic microglial clock modulates the inflammatory response, including the positive regulation of IL‐6 expression in a particular pathological situation in the brain, GLIA 2016. GLIA 2017;65:198–208
Buffering and Amplifying Interactions among OAW (Ocean Acidification & Warming) and Nutrient Enrichment on Early Life-Stage Fucus vesiculosus L. (Phaeophyceae) and Their Carry Over Effects to Hypoxia Impact

Ocean acidification and warming (OAW) are occurring globally. Additionally, at a more local scale the spreading of hypoxic conditions is promoted by eutrophication and warming. In the semi-enclosed brackish Baltic Sea, occasional upwelling in late summer and autumn may expose even shallow-water communities including the macroalga Fucus vesiculosus to particularly acidified, nutrient-rich and oxygen-poor water bodies. During summer 2014 (July–September) sibling groups of early life-stage F. vesiculosus were exposed to OAW in the presence and absence of enhanced nutrient levels and, subsequently to a single upwelling event in a near-natural scenario which included all environmental fluctuations in the Kiel Fjord, southwestern Baltic Sea, Germany (54°27 ´N, 10°11 ´W). We strove to elucidate the single and combined impacts of these potential stressors, and how stress sensitivity varies among genetically different sibling groups. Enhanced by a circumstantial natural heat wave, warming and acidification increased mortalities and reduced growth in F. vesiculosus germlings. This impact, however, was mitigated by enhanced nutrient conditions. Survival under OAW conditions strongly varied among sibling groups hinting at a substantial adaptive potential of the natural Fucus populations in the Western Baltic. A three-day experimental upwelling caused severe mortality of Fucus germlings, which was substantially more severe in those sibling groups which previously had been exposed to OAW. Our results show that global (OAW), regional (nutrient enrichment) and local pressures (upwelling), both alone and co-occurring may have synergistic and antagonistic effects on survival and/or growth of Fucus germlings. This result emphasizes the need to consider combined stress effects.
Cone beam computed tomography evaluation of ponticulus posticus in patients with cleft lip and palate: a retrospective radio-anatomic study.

BACKGROUND Ponticulus posticus (PP) is an abnormal bony bridge on the atlas. It plays a significant role in patients undergoing C1 lateral mass screw procedure. Patients with cleft lip and palate (CLP) have higher risk than patients in general population for the appearance of cervical vertebral anomalies. The purpose of the this study was twofold: to determine the prevalence and characteristics of PP in patients with CLP, and to compare the findings with patients in general population using cone beam computed tomography. MATERIALS AND METHODS Cone beam computed tomography images from 54 individuals who had undergone surgical repair of cleft lip and/or palate were analysed as the study group. For comparison purposes a control group was randomly selected from 108 patients and matched with the CLP subjects. RESULTS Although 12 of the 54 (22.3%) patients with surgically repaired cleft lip and/or palate in the study group were identified to have PP, only 10 of the 108 (9.2%) patients in the control group had PP. The distribution of the presence of PP between the groups was statistically significant. CONCLUSIONS Ponticulus posticus is an important anomaly and the presence of PP is important for patients. PP can have clinical significance in cervical spine surgery as this study has indicated that the likelihood of encountering PP is higher in patients with CLP. We suggest that PP should be taken into account prior to cervical vertebral surgery in patients with CLP. (Folia Morphol 2018; 77, 1: 72-78).
Deregulation of miR-183 promotes melanoma development via lncRNA MALAT1 regulation and ITGB1 signal activation

Dysregulation of miR-183 has been recently elucidated in several carcinomas. However, the expression patterns and mechanisms of miR-183 involved in malignant melanoma remain unidentified. Here, we found down-regulation of miR-183 in melanoma tissues and cells. Decreased level of miR-183 was relevant to poor overall survival, while miR-183 up-regulation resulted in a marked suppression of cell growth in vitro and in vivo. We further found that the expression and function of miR-183 were suppressed by MALAT1. Integrin β1 (ITGB1) was then speculated and confirmed as a direct target of miR-183. We also illustrated that MALAT1 may function as a sponge competitive endogenous RNA (ceRNA) for miR-183, and thus regulate the molecular expression of ITGB1. Collectively, we found a new signaling pathway promoting melanoma development by MALAT1-miR-183-ITGB1 axis, which may be clinically valuable as new targets for malignant melanoma therapy.