Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantitative Disassembly and Reassembly of Human Papillomavirus Type 11 Viruslike Particles In Vitro

ABSTRACT The human papillomavirus (HPV) capsid is primarily composed of a structural protein denoted L1, which forms both pentameric capsomeres and capsids composed of 72 capsomeres. The L1 protein alone is capable of self-assembly in vivo into capsidlike structures referred to as viruslike particles (VLPs). We have determined conditions for the quantitative disassembly of purified HPV-11 L1 VLPs to the level of capsomeres, demonstrating that disulfide bonds alone are essential to maintaining long-term HPV-11 L1 VLP structure at physiological ionic strength. The ionic strength of the disassembly reaction was also important, as increased NaCl concentrations inhibited disassembly. Conversely, chelation of cations had no effect on disassembly. Quantitative reassembly to a homogeneous population of 55-nm, 150S VLPs was reliably achieved by the re-formation of disulfide linkages following removal of reducing agent at near-neutral pH and moderate NaCl concentration. HPV-11 L1 VLPs could also be dissociated by treatment with carbonate buffer at pH 9.6, but VLPs could not be regenerated following carbonate treatment. When probed with conformationally sensitive and/or neutralizing monoclonal antibodies, both capsomeres generated by disulfide reduction of purified VLPs and reassembled VLPs formed from capsomeres upon removal of reducing agents exhibited epitopes found on the surface of authentic HPV-11 virions. Antisera raised against either purified VLP starting material or reassembled VLPs similarly neutralized infectious HPV-11 virions. The ability to disassemble and reassemble VLPs in vitro and in bulk allows basic features of capsid assembly to be studied and also opens the possibility of packaging selected exogenous compounds within the reassembled VLPs.
Pyridine nucleotides induce changes in cytosolic pools of calcium in Arabidopsis

ABSTRACT NAD is a pyridine nucleotide that is involved in cell metabolism and signaling of plant growth and stress. Recently, we reported on the multifaceted nature of NAD-inducible immunity in Arabidopsis. We identified NAD as an integral regulator of multiple defense layers such as production of ROS, deposition of callose, stimulation of cell death and modulation of defense metabolism including the defense hormones SA, JA and ABA, and other defense-associated metabolites. Altogether, NAD-induced immune effects confer resistance to diverse pathogenic microbes. Our addendum to this work further demonstrates an impact of NAD on the cytosolic calcium pool, a well-known component of early plant defense response.
Lack of association of body composition and functionality variables with metabolic syndrome in the elderly.

BACKGROUND The aging process causes alterations in body composition (decrease in lean mass and increase in fat mass), diminution of functionality (strength, mobility, and physical performance), and an increased prevalence of chronic diseases such as metabolic syndrome and obesity. The aim of this study was to investigate the association of body composition and functionality with metabolic syndrome in the elderly. METHODS A cross-sectional study was conducted in the Outpatient Clinic of the Geriatric Service of Hospital São Lucas of Pontifical Catholic University of Rio Grande do Sul (PUCRS) involving 74 patients (14 males and 60 females). The patients were separated into two groups: Group 1=elderly with metabolic syndrome [through the National Cholesterol Education Program Adult Treatment Panel III (NECP ATP III) criteria; n=34], group 2=elderly without metabolic syndrome (n=40). The variables evaluated included age, gender, body composition (circumferences, skinfold thickness, BMI, muscle and fat thickness and muscle mass), functional variables [hand grip strength, Timed Up and Go Test (TUGT), and Sit-to-Stand Test]. RESULTS The results showed that elderly individuals with metabolic syndrome had a higher mean of the anthropometric measures (except abdominal skinfold thickness) compared to subjects without metabolic syndrome (P<0.005). We observed significant differences for muscle mass index (higher, P=0.029), TUGT (longer time, P=0.008), and hand grip strength (lower, P=0.015) in elderly with metabolic syndrome compared with subjects without metabolic syndrome. However, when these variables were adjusted for gender, age, and body mass index (BMI), none showed a significant association with metabolic syndrome. CONCLUSION We did not observe associations among metabolic syndrome, body composition, and functionality variables.
In Vivo measurement of cerebral oxygen consumption and blood flow using 17O magnetic resonance imaging

We used 17O NMR imaging techniques to measure the H217O concentration in a 0.8‐ml voxel in the cat brain following injection of an arterial bolus of enriched H217O and during inhalation of enriched 17O2. We also measured the H217O concentration in arterial blood during 17O2 inhalation. The data from the first measurement were used to calculate the blood flow in the voxel. The data from all three measurements were combined to calculate the oxygen consumption in the voxel. The values of cerebral blood flow and oxygen consumption calculated with 17O NMR techniques agree reasonably well with values calculated for a similar region of the cat brain using autoradiographic techniques. © 1991 Academic Press, Inc.
The messages presented in online electronic cigarette promotions and discussions: a scoping review protocol

Introduction Electronic cigarettes have become increasingly popular over the last 10 years. These devices represent a new paradigm for tobacco control offering smokers an opportunity to inhale nicotine without inhaling tobacco smoke. To date there are no definite conclusions regarding the safety and long-term health effects of electronic cigarettes; however, there is evidence that they are being marketed online as a healthier alternative to traditional cigarettes. This scoping review aims to identify and describe the breadth of messages (eg, health, smoking-cessation and price related claims) presented in online electronic cigarette promotions and discussions. Methods and analysis A scoping review will be undertaken adhering to the methodology outlined in The Joanna Briggs Institute Manual for Scoping Reviews. Six key electronic databases will be searched to identify eligible studies. Studies must be published in English between 2007 and 2017, examine and/or analyse content captured from online electronic cigarette promotions or discussions and report results for electronic cigarettes separately to other forms of tobacco delivery. Studies will be screened initially by title and abstract, followed by full-text review. Results of the search strategy will be reported in a PRISMA flow diagram and presented in tabular form with accompanying narrative summary. Ethics and dissemination The methodology consists of reviewing and collecting data from publicly available studies, and therefore does not require ethics approval. Results will be published in a peer reviewed journal and be presented at national/international conferences. Additionally, findings will be disseminated via social media and online platforms. Advocacy will be key to informing policy makers of regulatory and health issues that need to be addressed. Registration details The review was registered prospectively with The Joanna Briggs Institute Systematic Reviews database.
DNA mismatch binding and incision at modified guanine bases by extracts of mammalian cells: implications for tolerance to DNA methylation damage.

Two activities involved in separate pathways for correcting G.T mispairs in DNA have been assayed on duplex substrates containing modified guanine bases. The first, the G.T mismatch incision activity, is specifically involved in short-patch repair of mispairs arising via deamination of 5-methylcytosine. The second activity can be detected by its ability to bind to G.T mispairs and may initiate correction by a long-patch mechanism. 6-Thioguanine and O6-methylguanine paired with thymine were efficiently incised by cell extracts if the modified guanine was in a CpG dinucleotide. Incision was not observed when either purine was paired with cytosine. Extracts of cells that are tolerant both to methylation damage and to 6-thioguanine in DNA also incised 6-thioguanine.T and O6-methylguanine.T base pairs. The data suggest that this activity is unlikely to contribute significantly to the biological effects of O6-methylguanine in DNA. A defect in this pathway is therefore unlikely to explain the cross-resistance of tolerant cells to the two base analogs in DNA. In binding assays, 6-thioguanine.T base pairs were recognized efficiently and to an equivalent extent by the same protein complex as G.T mispairs. O6-Methylguanine.T base pairs were also recognized but with reduced efficiency. No binding was observed to 6-thioguanine.C or O6-methylguanine.C base pairs. Recognition by the binding complex was essentially independent of the base immediately 5' to the mismatched guanine but was somewhat more efficient if O6-methylguanine was preceded by a purine. Extracts of two tolerant lines with a known defect in G.T mismatch binding failed to form complexes with substrates containing the modified bases. (ABSTRACT TRUNCATED AT 250 WORDS)
Childhood development patterns of hospitalized adult schizophrenic and nonschizophrenic patients and their siblings.

Childhood characteristics, rated “blind” from maternal retrospective reports, were compared for 44 young adult psychiatric inpatients and their “normal” siblings. Patients differed significantly from siblings on several childhood variables and had poorer overall childhood adjustments. Those with the most deviant childhood histories had significantly earlier onsets of psychiatric illness.
The protein tyrosine kinase inhibitor AG126 prevents the massive microglial cytokine induction by pneumococcal cell walls

Central nervous system (CNS) infections caused by Streptococcus pneumoniae still have a disastrous outcome. Underlying immunological and CNS cellular events are largely enigmatic. We used pneumococcal cells walls (PCW) to investigate microglial responses as these cells are prominent sensors and effectors during neuropathological changes. PCW stimulation of mouse microglia invitro evoked the release of the cyto‐ and chemokines, TNF‐α, IL‐6, IL‐12, KC, MCP‐1, MIP‐1α, MIP‐2 and RANTES as well as soluble TNF receptor II, a potential TNF‐α antagonist. The release induction followed extremely steep dose‐response relations, and short exposure periods (15 min) were already sufficient to trigger substantial responses. PCW signaling controlling the release depended on both p38 and p42 / p44 (ERK2 / ERK1) MAP kinase activities. The kinase inhibitor, tyrphostin AG126 prevented the PCW‐inducible phosphorylation of p42 / p44MAPK, potently blocked cytokine release and drastically reduced the bioavailable TNF‐α, since it only marginally affected the release of soluble TNF receptors. Moreover, in an in vivo model of pneumococcal meningitis, AG126 significantly attenuated the PCW‐induced leukocyte influx to the cerebrospinal fluid. The findings imply that pneumococcal CNS infection can cause a rapid and massive microglial activation and that ERK / MAPK pathway(s) are potential targets for pharmacological interventions.
The differential effects of Autism and Down's syndrome on sexual behavior

Although sexuality plays a major role in the socialization of people, few studies have examined the sexual behaviors of individuals with developmental disabilities. Because of this, we decided to investigate sexuality in adolescents with autism spectrum disorder (ASD) and Down's syndrome (Ds) and to compare them with typically developing adolescents, by surveying their parents. Specifically, it was hypothesized that young people with ASD would display lower levels over five domains: social behavior, privacy, sex education, sexual behavior, and parental concerns, than peers with Ds and typically developing young people. In addition, we sought to verify developmental trends in five domains with age for each group. Overall, 269 parents participated; 94 parents of typically developing adolescents, 93 parents of adolescents diagnosed with Ds, and 82 parents of adolescents diagnosed with ASD. Participants were surveyed with a Sexual Behavior Scale developed by Stokes and Kaur [ ] that assesses parents' reports of their child's: social behavior, privacy awareness, sex education, sexual behavior and parental concerns about the child's behaviors. It was found that three groups were significantly different on all five domains, adolescents with ASD reportedly displaying lower levels than other groups. Moreover, there was a significant improvement in knowledge of privacy and parental concerns with age for adolescents with ASD and a decline in sex education for adolescents with Ds. The results obtained emphasize the need to train adolescents with developmental disability, and especially for adolescents with ASD through sex education programs. Autism Res 2015. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
Mice overexpressing rat heat shock protein 70 are protected against cerebral infarction

Increased expression of heat shock protein 70 (HSP70) in the brain has been extensively documented in association with a variety of insults, including ischemia, and is suggested to play a role in cell survival and recovery after ischemic injury. To more directly assess the protective role of HSP70 during ischemic brain damage, we used transgenic mice overexpressing the rat HSP70 (HSP70tg mice). In contrast to wild‐type (wt) littermates, high levels of HSP70 messenger RNA and protein were detected in brains of HSP70tg mice under normal conditions, and immunohistochemical analysis revealed primarily neuronal expression of HSP70. Heterozygous HSP70tg mice and their wt littermates were subjected to permanent focal cerebral ischemia by intraluminal blockade of the middle cerebral artery. Cerebral infarction after 6 hours of ischemia, as evaluated by Nissl staining, was significantly less in HSP70tg mice compared with wt mice. This reduction in infarction volume in HSP70tg mice was not attributable to an altered cardiovascular anatomy or to initial differences in body temperature or hemodynamic parameters. The HSP70tg mice were still protected against cerebral infarction 24 hours after permanent focal ischemia. The data suggest that HSP70 can markedly protect the brain against ischemic damage and that approaches aimed at inducing HSP70 may lead to new therapeutic interventions in cerebrovascular injuries. Ann Neurol 2000;47:782–791
Thrombospondin-1 expression correlates with angiogenesis in experimental cirrhosis.

AIM To investigate the significance of Thrombospondin-1 (TSP-1) expression and its relationship with angiogenesis during experimental fibrosis. METHODS Cirrhosis was induced in male Wistar rats by intraperitoneal administration of diethyl nitrosamine (DEN). The serial sections from liver tissues were stained with anti-CD34 and anti-TSP-1 antibodies before being quantitated by light microscopy. RESULTS Our results showed that of TSP-1 expression gradually increases according to the severity of fibrosis (P < 0.05). Moreover, TSP-1 expression was found to be correlated with angiogenesis (P < 0.05). CONCLUSION The correlative evidence of the link between TSP-1 and fibrosis or angiogenesis provided by this study suggests that besides its role as a strong promoter of transforming growth factor-beta 1 (TGF-beta 1), TSP-1 might have an additional role in liver fibrogenesis by stimulating angiogenesis and this protein could be a potential target to prevent fibrogenesis in chronic inflammatory diseases of the liver.
Phototoxic effect of photodynamic therapy on lung cancer cells grown as a monolayer and three dimensional multicellular spheroids

Photodynamic therapy (PDT) is a minimally invasive therapeutic modality for the treatment of neoplastic and non‐neoplastic diseases. The photochemical interaction of light, photosensitizer (PS) and molecular oxygen produces singlet oxygen which induces cell death. The effectiveness of zinc sulfophthalocyanine (ZnPcSmix) has been shown on A549 monolayers and not on MCTS. The objective of this study was to investigate whether the same pattern of cell death would be induced in lung cancer cells (A549) grown as monolayer cells compared to three dimensional multicellular tumor spheroids (MCTS) using the same laser parameters.
Comparison of four DNA extraction methods for detecting Mycobacterium tuberculosis by real-time PCR and its clinical application in pulmonary tuberculosis.

OBJECTIVES China is one of the countries with a high burden of Mycobacterium tuberculosis (MTB) infection. One challenge for the earlier diagnosis of tuberculosis is the DNA extraction of MTB. This study was to compare four MTB DNA extraction methods, and use the best one in the diagnosis of pulmonary tuberculosis. METHODS A total of 43 serum and 94 plasma samples were collected from 124 clinical diagnosed pulmonary tuberculosis patients. Four different MTB DNA extraction methods, including phenol-chloroform method, Qiagen kit, Omega kit and magnetic bead method, were compared to determine which method displayed the highest sensitivity. A quantitative fluorescent PCR assay was also designed for the detection of MTB DNA. RESULTS The highest DNA extraction efficiency (52.8%) and the best reproducibility (coefficient of variance =26.7%) were observed using the magnetic bead method. For 39 of the 124 (31.5%) pulmonary tuberculosis patients, MTB DNA was detected in their plasma or serum samples. Interestingly, 35.3% (12/34) of smear-negative cases were MTB DNA positive. CONCLUSIONS In conclusion, magnetic bead method is the best one for the DNA extraction of MTB. The detection of MTB DNA may provide valuable information for the diagnosis of acid-fast bacilli (AFB) negative pulmonary tuberculosis patients.
Vasomotor reactivity as a predictor for syncope in patients with orthostatism

Gur AY, Auriel E, Korczyn AD, Gadoth A, Shopin L, Giladi N, Bornstein NM, Gurevich T. Vasomotor reactivity as a predictor for syncope in patients with orthostatism. Acta Neurol Scand: 2012: 126: 32–36. © 2011 John Wiley & Sons A/S.
Macrolides and Mortality in Critically Ill Patients With Community-Acquired Pneumonia: A Systematic Review and Meta-Analysis*

Objective:Some studies suggest better outcomes with macrolide therapy for critically ill patients with community-acquired pneumonia. To further explore this, we performed a systematic review of studies with mortality endpoints that compared macrolide therapy with other regimens in critically ill patients with community-acquired pneumonia. Data Sources:Studies were identified via electronic databases, grey literature, and conference proceedings through May 2013. Study Selection:Using prespecified criteria, two reviewers selected studies; studies of outpatients and hospitalized noncritically ill patients were excluded. Data Extraction:Two reviewers extracted data and evaluated bias using the Newcastle-Ottawa Scale. Random effects models were used to generate pooled risk ratios and evaluate heterogeneity (I2). Data Synthesis:Twenty-eight observational studies (no randomized control trials) were included. Average age ranged from 58 to 78 years and 14–49% were women. In our primary analysis of 9,850 patients, macrolide use was associated with statistically significant lower mortality compared with nonmacrolides (21% [846 of 4,036 patients] vs 24% [1,369 of 5,814]; risk ratio, 0.82; 95% CI, 0.70–0.97; p = 0.02; I2 = 63%). When macrolide monotherapy was excluded, the macrolide mortality benefit was maintained (21% [737 of 3,447 patients] vs 23% [1,245 of 5,425]; risk ratio, 0.84; 95% CI, 0.71–1.00; p = 0.05; I2 = 60%). When broadly guideline-concordant regimens were compared, there was a trend to improved mortality and heterogeneity was reduced (20% [511 of 2,561 patients] mortality with beta-lactam/macrolide therapy vs 23% [386 of 1,680] with beta-lactam/fluoroquinolone; risk ratio, 0.83; 95% CI, 0.67–1.03; p = 0.09; I2 = 25%). When adjusted risk estimates were pooled from eight studies, macrolide therapy was still associated with a significant reduction in mortality (risk ratio, 0.75; 95% CI, 0.58–0.96; p = 0.02; I2 = 57%). Conclusions:In observational studies of almost 10,000 critically ill patients with community-acquired pneumonia, macrolide use was associated with a significant 18% relative (3% absolute) reduction in mortality compared with nonmacrolide therapies. After pooling data from studies that provided adjusted risk estimates, an even larger mortality reduction was observed. These results suggest that macrolides be considered first-line combination treatment in critically ill patients with community-acquired pneumonia and support current guidelines.
Tracking Progress Toward the 2010 Biodiversity Target and Beyond

Biodiversity indicators used by policy-makers are underdeveloped and underinvested. In response to global declines in biodiversity, some 190 countries have pledged, under the Convention on Biological Diversity (CBD), to reduce the rate of biodiversity loss by 2010 (1, 2). Moreover, this target has recently been incorporated into the Millennium Development Goals in recognition of the impact of biodiversity loss on human well-being (3). Timely information on where and in what ways the target has or has not been met, as well as the likely direction of future trends, depends on a rigorous, relevant, and comprehensive suite of biodiversity indicators with which to track changes over time, to assess the impacts of policy and management responses, and to identify priorities for action. How far have we come in meeting these needs, and is it sufficient?
A comparison of four stent designs on arterial injury, cellular proliferation, neointima formation, and arterial dimensions in an experimental porcine model

The stent‐artery interactions of different stent designs have implications for their clinical effects. We studied four different stent designs to compare their effects on arterial injury, cellular proliferation, neointima formation, and arterial dimensions. Eighteen nonatherosclerotic miniswine underwent random placement of 52 coronary stents (3.0 mm), including self‐expanding nitinol stents (no postdilation; Radius, n = 13) and balloon‐expandable stents (8 atm × 45 sec; Palmaz‐Schatz, n = 13; BX, n = 12; and Multilink, n = 14). Cellular proliferation was determined by S‐phase labeling with BrdU at 7, 14, and 28 days. Proliferation, injury scores, and arterial morphometry were blindly evaluated. All four stent designs had similar injury scores, cellular proliferation indexes (neointimal and medial), and adventitial areas. Nitinol stents resulted in a twofold increase in neointimal area and thickness in 28‐day vessels (P = 0.002). However, lumen area was similar for all stent designs because of an offsetting expansion in vessel area in nitinol stents (20% greater than balloon‐expandable stents) occurring between 7 and 14 days after stent deployment (P = 0.03). Reduced neointimal cell density in nitinol stents (20% less than balloon‐expandable stents, P = 0.012) suggests that extracellular matrix expansion accounts for the larger neointima in nitinol stents. Self‐expansion of nitinol stents within normal porcine arteries results in a similar degree of arterial injury compared to balloon‐expandable stent designs. Progressive enlargement of nitinol stents between 7 and 14 days after deployment is associated with the development of a larger, matrix‐rich neointima, with a preserved lumen area. Cathet Cardiovasc Intervent 2001;53:420–425. Published 2001 Wiley‐Liss, Inc.