Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of class I histone deacetylases blunts cardiac hypertrophy through TSC2-dependent mTOR repression

HDAC inhibitors prevent pathological cardiac hypertrophy by suppressing a growth-promoting kinase. Keeping mTORC1 in check in the heart In response to the increased workload caused by high blood pressure, the cells in the heart expand in size, causing the walls of the heart to thicken. Although this process of cardiac hypertrophy may be initially beneficial, it can lead to heart failure if not restrained. Using cardiomyocytes and mice with surgically induced heart failure, Morales et al. investigated how pathological cardiac hypertrophy is suppressed by inhibitors of histone deacetylases (HDACs), enzymes that remodel chromatin and alter gene expression. They found that these drugs increased the expression of a gene encoding an inhibitor of mTORC1, a multiprotein complex that stimulates cell growth. HDAC inhibitors have been approved to treat various cancers, and these results explain how these drugs could work when repurposed to prevent heart failure. Altering chromatin structure through histone posttranslational modifications has emerged as a key driver of transcriptional responses in cells. Modulation of these transcriptional responses by pharmacological inhibition of class I histone deacetylases (HDACs), a group of chromatin remodeling enzymes, has been successful in blocking the growth of some cancer cell types. These inhibitors also attenuate the pathogenesis of pathological cardiac remodeling by blunting and even reversing pathological hypertrophy. The mechanistic target of rapamycin (mTOR) is a critical sensor and regulator of cell growth that, as part of mTOR complex 1 (mTORC1), drives changes in protein synthesis and metabolism in both pathological and physiological hypertrophy. We demonstrated through pharmacological and genetic methods that inhibition of class I HDACs suppressed pathological cardiac hypertrophy through inhibition of mTOR activity. Mice genetically silenced for HDAC1 and HDAC2 had a reduced hypertrophic response to thoracic aortic constriction (TAC) and showed reduced mTOR activity. We determined that the abundance of tuberous sclerosis complex 2 (TSC2), an mTOR inhibitor, was increased through a transcriptional mechanism in cardiomyocytes when class I HDACs were inhibited. In neonatal rat cardiomyocytes, loss of TSC2 abolished HDAC-dependent inhibition of mTOR activity, and increased expression of TSC2 was sufficient to reduce hypertrophy in response to phenylephrine. These findings point to mTOR and TSC2-dependent control of mTOR as critical components of the mechanism by which HDAC inhibitors blunt pathological cardiac growth. These results also suggest a strategy to modulate mTOR activity and facilitate the translational exploitation of HDAC inhibitors in heart disease.
Spatially robust estimates of biological nitrogen (N) fixation imply substantial human alteration of the tropical N cycle

Significance Biological nitrogen fixation (BNF) is the largest natural source of new nitrogen (N) to terrestrial ecosystems. Tropical forest ecosystems are a putative global hotspot of BNF, but direct, spatially explicit measurements in the biome are virtually nonexistent. Nonetheless, robust estimates of tropical forest BNF are critical for understanding how these important ecosystems may respond to global change and assessing human perturbations to the N cycle. Here, we introduce a spatial sampling method to assess BNF and present evidence that tropical forest BNF is much lower than previously assumed. Our results imply that humans have roughly doubled N inputs to the tropical forest biome relative to N inputs through BNF. Biological nitrogen fixation (BNF) is the largest natural source of exogenous nitrogen (N) to unmanaged ecosystems and also the primary baseline against which anthropogenic changes to the N cycle are measured. Rates of BNF in tropical rainforest are thought to be among the highest on Earth, but they are notoriously difficult to quantify and are based on little empirical data. We adapted a sampling strategy from community ecology to generate spatial estimates of symbiotic and free-living BNF in secondary and primary forest sites that span a typical range of tropical forest legume abundance. Although total BNF was higher in secondary than primary forest, overall rates were roughly five times lower than previous estimates for the tropical forest biome. We found strong correlations between symbiotic BNF and legume abundance, but we also show that spatially free-living BNF often exceeds symbiotic inputs. Our results suggest that BNF in tropical forest has been overestimated, and our data are consistent with a recent top-down estimate of global BNF that implied but did not measure low tropical BNF rates. Finally, comparing tropical BNF within the historical area of tropical rainforest with current anthropogenic N inputs indicates that humans have already at least doubled reactive N inputs to the tropical forest biome, a far greater change than previously thought. Because N inputs are increasing faster in the tropics than anywhere on Earth, both the proportion and the effects of human N enrichment are likely to grow in the future.
Surgical approaches for stage I and II thymoma-associated myasthenia gravis: feasibility of complete video-assisted thoracoscopic surgery (VATS) thymectomy in comparison with trans-sternal resection

Complete resection could be achieved in virtually all myasthenic patients with Masaoka stage I and II thymoma using the trans-sternal technique. Whether this is appropriate for minimally invasive approach is not yet clear. We evaluated the feasibility of complete video-assisted thoracoscopic surgery (VATS) thymectomy for the treatment of Masaoka stage I and II thymoma-associated myasthenia gravis, compared to conventional trans-sternal thymectomy. We summarized 33 patients with Masaoka stage I and II thymoma-associated myasthenia gravis between April 2006 and September 2011. Of these, 15 patients underwent right-sided complete VATS (the VATS group) by using adjuvant pneuomomediastinum, comparing with 18 patients using the trans-sternal approach (the T3b group). No intraoperative death was found and no VATS case required conversion to median sternotomy. Significant differences between the two groups regarding duration of surgery and volume of intraoperative blood loss (P = 0.001 and P < 0.001, respectively) were observed. Postoperative morbidities were 26.7% and 33.3% for the VATS and T3b groups, respectively. All 33 patients were followed up for 12 to 61 months in the study. The cumulative probabilities of reaching complete stable remission and effective rate were 26.7% (4/15) and 93.3% (14/15) in the VATS group, which had a significantly higher complete stable remission and effective rate than those in the T3b group (P = 0.026 and P = 0.000, respectively). We conclude that VATS thymectomy utilizing adjuvant pneuomomediastinum for the treatment of stage I and II thymoma-associated myasthenia gravis is technically feasible but deserves further investigation in a large series with long-term follow-up.
Experimental Antioxidant Therapy in Ataxia Telangiectasia

Ataxia telangiectasia (AT) is a rare genetic disorder characterized by immunodeficiency, early onset neurological degeneration, hypersensitivity to ionizing radiation and a high incidence of lymphoid cancers. The disease results from bi-allelic mutations in the AT mutated (ATM) gene involved in cell cycle checkpoint control and repair of DNA double-strand breaks. Evidence has been accumulating that oxidative stress is associated with AT and may be involved in the pathogenesis of the disease. This led to a hypothesis that antioxidant therapy may mitigate the symptoms of AT, especially neurological degeneration and tumorigenesis. Consequently, several studies examined the effect of antioxidants in Atm deficient mice used as an animal model of AT. N-acetyl-L-cysteine (NAC), EUK-189, tempol and 5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl (CTMIO) have been tested for their chemopreventive properties and had some beneficial effects. In addition to antioxidants, cancer therapeutic agent dexamethasone was examined for cancer prevention in Atm deficient mice. Of the tested antioxidants, only NAC has wide clinical applications due to safety and efficacy and is available as an over-the-counter dietary supplement. In this article, we review chemoprevention studies in Atm deficient mice and, in more detail, our findings on the effect of NAC. The short-tem study showed that NAC suppressed genome rearrangements linked to cancer. The long-term study demonstrated that NAC reduced both the incidence and multiplicity of lymphoma.
Synthesis of Zinc Oxide and Titanium Dioxide Composite Nanorods and Their Photocatalytic Properties

Zinc oxide and titanium dioxide composite nanorods have been synthesized by the hydrothermal process using zinc acetate and titanium butoxide as the raw materials. X-ray diffraction (XRD) shows that the composite nanorods are composed of hexagonal ZnO and tetragonal TiO2 phases. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images show that the length and diameter of the composite nanorods are 1–5 μm and 80–350 nm, respectively. Hydrothermal temperature and duration time have important roles in the formation of the composite nanorods. Using rhodamine B (RB) degradation as the probe reaction, the photocatalytic activities of the composite nanorods under UV light irradiation have been analysed. The roles of the irradiation time, content of the composite nanorods and RB concentration in the photocatalytic activities of the composite nanorods have been investigated. 10 mL 10 mgL−1 RB solution can be totally degraded using 10 mg composite nanorods under UV light irradiation for 90 min.
Active Avoidance Requires a Serial Basal Amygdala to Nucleus Accumbens Shell Circuit

Freezing is a species-typical defensive reaction to conditioned threats. While the neural circuitry of aversive Pavlovian behavior has been extensively studied, less is known about the circuitry underlying more active responses to danger. Here we show that the flow of information between the basal amygdala (BA) and the nucleus accumbens (NAcc) is necessary for signaled active avoidance behavior. Rats trained to avoid shock by shuttling during an auditory conditioned stimulus showed increased expression of the activity-dependent protein c-Fos in the NAcc, specifically the shell subregion (NAccSh). Silencing neural activity in the NAccSh, but not in the adjacent NAcc core, disrupted avoidance behavior. Disconnection of the BA and the NAccSh was just as effective at disrupting avoidance behavior as bilateral NAccSh inactivations, suggesting learned avoidance behavior requires an intact BA-NAccSh circuit. Together, these data highlight an essential role for the amygdalar projection to the ventral striatum in aversively motivated actions.
Innovative Issues and Approaches in Social Sciences

ing and Indexing services COBISS, International Political Science Abstracts, CSA Worldwide Political Science Abstracts, CSA Sociological Abstracts, PAIS International. Publication Data: SIdip – Slovenian Association for Innovative Political Science (Slovensko društvo za inovativno politologijo) Innovative issues and approaches in social sciences, 2012, vol. 5, no. 3 ISSN 1855-0541 Additional information available on: www.iiass. com Innovative Issues and Approaches in Social Sciences, Vol. 5, No. 3
Curcumin, Silybin Phytosome® and α‐R‐Lipoic Acid Mitigate Chronic Hepatitis in Rat by Inhibiting Oxidative Stress and Inflammatory Cytokines Production

Chronic hepatitis is recognized as a worldwide health problem that gradually progresses towards cirrhosis and hepatocellular carcinoma. Despite the large number of experiments using animal models for allergic hepatitis, it is still difficult to produce a picture of chronic hepatitis. Therefore, this study was conducted to introduce an animal model approximating to the mechanism of chronicity in human hepatitis. The study also aimed to examine the hepatoprotective effects of curcumin, silybin phytosome® and α‐R‐lipoic acid against thioacetamide (TAA)‐induced chronic hepatitis in rat model. TAA was administered intraperitoneally at a dose of 200 mg/kg three times weekly for 4 weeks. At the end of this period, a group of rats was killed to assess the development of chronic hepatitis in comparison with their respective control group. TAA administration was then discontinued, and the remaining animals were subsequently allocated into four groups. Group 1 was left untreated, whereas groups 2–4 were allowed to receive daily oral doses of curcumin, silybin phytosome® or α‐R‐lipoic acid, respectively, for 7 weeks. Increases in hepatic levels of malondialdehyde associated with TAA administration were inhibited in groups receiving supplements. Furthermore, glutathione depletion, collagen deposition, macrophage activation and nuclear factor κappa‐B expression as well as tumour necrosis factor‐α and interleukin‐6 levels were significantly decreased in response to supplements administration. Serological analysis of liver function and liver histopathological examination reinforced the results. The above evidence collectively indicates that the antioxidant and anti‐inflammatory activities of curcumin, silybin phytosome® and α‐R‐lipoic acid may confer therapeutic efficacy against chronic hepatitis.
Horticultural Production Systems Influence Ground Beetle (Coleoptera: Carabidae) Distribution and Diversity in Cucurbits

Abstract Commercial cucurbit production typically involves agriculturally intensive practices, with fields prepared using conventional tillage, plasticulture, and chemically based pestmanagement. Conservation-basedmanagement options are limited. In this study, we consider two alternative strategies, strip tillage and the use of row covers. We compare their impact on the beneficial carabid beetle (Coleoptera: Carabidae) community in melons and squash, following conventional or organic systems, over two years. Multivariate analysis demonstrated that soil management system (strip tillage versus plasticulture) was the primary variable influencing carabid distribution; row cover was a less important factor. The response to soilmanagement was species dependent. Some dominant species, such as Harpalus pensylvanicus DeGeer, demonstrated no preference for a particular soil treatment. For others, including the tiger beetle, Cicindela punctulata Olivier, and a slug predator, Chlaenius tricolor Dejean, activity–density was higher in strip-tillage production systems. Our analysis suggested that strip-tillage production systems support a richer, more diverse carabid community. These results demonstrate that even within intensive annual horticultural systems, production practices can play a critical role in shaping the beneficial arthropod community, potentially encouraging or limiting ecosystem services.
The effect of dust lead control on blood lead in toddlers: a randomized trial.

BACKGROUND Contaminated household dust is believed to be a major source of exposure for most children with elevated blood lead levels. To determine if a vigorous dust clean-up effort would reduce this exposure we conducted a randomized controlled field trial. METHODS We randomized 113 urban children between the ages of 6 and 36 months: 56 children to a lead dust intervention composed of maternal education and biweekly assistance with household cleaning and 57 children to a control group. Household cleaning was done by two trained lay workers who focused their efforts on wet mopping of floors, damp-sponging of walls and horizontal surfaces, and vacuuming with a high-efficiency particle accumulating vacuum. Household dust lead levels, child blood lead levels, and maternal knowledge of lead poisoning and sources of exposure were measured before and after the intervention. RESULTS Ninety-nine children were successfully followed for 12 +/- 3 months: 46 children in the lead group and 53 children in the control group. Age and blood lead were similar in the two groups at baseline and averaged 20 months and 12.0 micrograms/dL, respectively. Blood lead fell 17% in the intervention group and did not change among controls. Household dust and dust lead measures also fell significantly in the intervention group. Children in homes cleaned 20 or more times throughout the year had an average blood lead reduction of 34%. CONCLUSIONS Regular home cleaning, accompanied by maternal education, is a safe and partially effective intervention that should be recommended for the large majority of lead-exposed children for whom, unfortunately, removal to lead-safe housing is not an option.
Voltage-gated sodium channels are present on both the neural and capsular structures of Pacinian corpuscles

It has long been accepted that action potentials arising from Pacinian corpuscles (PCs) originate at the first node of Ranvier located within the PC and that the mechanotransduction events (receptor potentials) are formed by stretch-activated channels selectively sensitive predominantly to Na +. Also, it has been shown previously that tetrodotoxin (TTX) affects the receptor potential suggesting that transduction may involve voltage-sensitive Na + channels. To determine whether voltage-sensitive Na + channels exist in the membrane thought to be responsible for transduction, immunocytochemical studies were performed using polyclonal antibodies raised in rabbit against the alpha subunit of rat type I and type II voltage-gated sodium channels. The results show the presence of label on the neurite and axolemma, as well as in the node regions. Interestingly, labeling is also found on the inner and outer lamellae that form the non-neural accessory structure surrounding the neurite. The presence of this label in the surrounding lamellae suggests that voltage-sensitive Na + channels, that are involved in both transduction and action-potential generation, may be made available to the neurite via transport from the lamellae, a mechanism perhaps operating in parallel to axoplasmic transport.
Themes of Grief

A thematic analysis of 30 narrative accounts of bereavement revealed nine themes that included five core themes in bereavement—being stopped, hurting, missing, holding, and seeking; three meta-themes about bereavement—change, expectations, and inexpressibility; and a contextual theme—personal history. The themes were compared with three theoretical perspectives on bereavement by Freud, Kübler-Ross, and one defined as existential-phenomenological. Features of bereavement that are dissimilar or unaddressed by the theoretical perspectives were: (a) the quality of grief's changing character, including “waves” and intense pain which may be triggered years after the death; (b) holding, an individual process of preserving the fact and meaning of the loved one's existence; (c) expectations, both social and personal, as to how the bereaved should be overlaying the experience; and (d) the critical importance of personal history in affecting the quality and meaning of individual bereavement.
Beneficial Effects of GH in Young Adults With Prader-Willi Syndrome: A 2-Year Crossover Trial.

CONTEXT Patients with Prader-Willi syndrome (PWS) are severely at risk to develop morbid obesity, diabetes mellitus type 2, and cardiovascular disease, leading to high mortality. They have an increased fat mass (FM) and decreased lean body mass (LBM). During childhood, GH treatment counteracts the natural course of increasing obesity. Discontinuation of GH treatment at attainment of adult height (AH) might deteriorate their improved clinical condition, whereas continuation might benefit them. OBJECTIVE To investigate the effects of GH versus placebo on body composition in young adults with PWS who were GH treated for many years during childhood and had attained AH. DESIGN Two-year, randomized, double-blind, placebo-controlled crossover study with stratification for gender and body mass index in 27 young adults with PWS. SETTING PWS Reference Center in The Netherlands. INTERVENTION Crossover intervention with GH (0.67 mg/m2 · d) and placebo, both during 1 year. MAIN OUTCOME MEASURES Body composition, measured by dual-energy x-ray absorptiometry. RESULTS During placebo, FM increased (relative change +21.5%; P < .001). Compared with placebo, GH treatment resulted in lower FM (-2.9 kg; P = .004) and higher LBM (+1.5 kg; P = .005), representing relative changes of -17.3% FM and +3.5% LBM. Both limb and trunk FM percentage were lower during GH versus placebo (relative change +17.3% and +15.6%; P < .001 and P = .007, respectively). No GH-related adverse events occurred. CONCLUSIONS GH-treated young adults with PWS who have attained AH benefit from continuation of GH treatment. FM increases during placebo, whereas GH versus placebo results in lower FM and higher LBM. Thus, GH treatment maintains the improved body composition without safety concerns.
Melanoma-initiating cells exploit M2 macrophage TGFβ and arginase pathway for survival and proliferation

M2 macrophages promote tumor growth and metastasis, but their interactions with specific tumor cell populations are poorly characterized. Using a mouse model of spontaneous melanoma, we showed that CD34− but not CD34+ tumor-initiating cells (TICs) depend on M2 macrophages for survival and proliferation. Tumor-associated macrophages (TAMs) and macrophage-conditioned media protected CD34− TICs from chemotherapy in vitro. In vivo, while inhibition of CD115 suppressed the macrophage-dependent CD34− TIC population, chemotherapy accelerated its development. The ability of TICs to respond to TAMs was acquired during melanoma progression and immediately preceded a surge in metastatic outgrowth. TAM-derived transforming growth factor-β (TGFβ) and polyamines produced via the Arginase pathway were critical for stimulation of TICs and synergized to promote their growth.
Second transplants for patients with chronic myeloid leukaemia in relapse after original transplant with T‐depleted donor marrow: feasibility of using busulphan alone for re‐conditioning

Summary. Between July 1986 and March 1991, 16 patients who had relapsed after T‐lymphocyte depleted bone marrow transplantation (BMT) for chronic myeloid leukaemia (CML) received a second transplant using unmanipulated marrow cells from the same HLA‐identical sibling donor. The median numbers of days from first BMT to haematological relapse and to second BMT were 557 (range 273–1543) and 1211 (range 476–2310) respectively. 11 patients were in uncomplicated chronic phase at time of second BMT, and five had more advanced disease. As conditioning for second BMT, eight patients received various combinations of cytotoxic drugs, and eight received high‐dose busulphan alone. Eight (50%) patients survive at a median of 424 d post‐second BMT (range 158–1789) and all are free of leukaemia by conventional criteria: five had been conditioned with high‐dose busulphan alone. Causes of death in the eight patients who died included relapse (n= 2), graft‐versus‐host disease (n= 2). interstitial pneumonias (n= 2), and infection (n= 2). We conclude that patients relapsing into chronic phase after BMT with T‐lymphocyte depleted donor marrow may be offered the option of second BMT with unmanipulated marrow from the original donor. Conditioning with high‐dose busulphan alone may be safer than use of more intensive schedules.