Miracle-dz/UniFAR-FTUs huggingface dataset:
Altered gene expression in neurons during programmed cell death: identification of c-jun as necessary for neuronal apoptosis

We have examined the hypothesis that neuronal programmed cell death requires a genetic program; we used a model wherein rat sympathetic neurons maintained in vitro are deprived of NGF and subsequently undergo apoptosis. To evaluate gene expression potentially necessary for this process, we used a PCR-based technique and in situ hybridization; patterns of general gene repression and selective gene induction were identified in NGF-deprived neurons. A temporal cascade of induced genes included "immediate early genes," which were remarkable in that their induction occurred hours after the initial stimulus of NGF removal and the synthesis of some required ongoing protein synthesis. The cascade also included the cell cycle gene c-myb and the genes encoding the extracellular matrix proteases transin and collagenase. Concurrent in situ hybridization and nuclear staining revealed that while c-jun was induced in most neurons, c-fos induction was restricted to neurons undergoing chromatin condensation, a hallmark of apoptosis. To evaluate the functional role of the proteins encoded by these genes, neutralizing antibodies were injected into neurons. Antibodies specific for either c-Jun or the Fos family (c-Fos, Fos B, Fra-1, and Fra-2) protected NGF-deprived neurons from apoptosis, whereas antibodies specific for Jun B, Jun D, or three nonimmune antibody preparations had no protective effect. Because these induced genes encode proteins ranging from a transcription factor necessary for death to proteases likely involved in tissue remodeling concurrent with death, these data may outline a genetic program responsible for neuronal programmed cell death.
Pioglitazone and mechanisms of CV protection.

BACKGROUND AND AIM Pioglitazone has diverse multiple effects on metabolic and inflammatory processes that have the potential to influence cardiovascular disease pathophysiology at various points in the disease process, including atherogenesis, plaque inflammation, plaque rupture, haemostatic disturbances and microangiopathy. RESULTS Linking the many direct and indirect effects on the vasculature to the reduction in key macrovascular outcomes reported with pioglitazone in patients with type 2 diabetes presents a considerable challenge. However, recent large-scale clinical cardiovascular imaging studies are beginning to provide some mechanistic insights, including a potentially important role for improvements in high-density lipoprotein cholesterol with pioglitazone. In addition to a role in prevention, animal studies also suggest that pioglitazone may minimize damage and improve recovery during and after ischaemic cardio- and cerebrovascular events. DESIGN AND METHODS In this review, we consider potential cardiovascular protective mechanisms of pioglitazone by linking preclinical data and clinical cardiovascular outcomes guided by insights from recent imaging studies. CONCLUSION Pioglitazone may influence CVD pathophysiology at multiple points in the disease process, including atherogenesis, plaque inflammation, plaque rupture and haemostatic disturbances (i.e. thrombus/embolism formation), as well as microangiopathy.
Investigating biomass saccharification for the production of cellulosic ethanol

The production of second generation biofuels -cellulosic ethanol from renewable lignocellulosic biomass has the potential to lead the bioindustrial revolution necessary to the transition from a fossil fuel-based economy to a sustainable carbohydrate economy. Effective release of fermentable sugars through biomass pretreatment followed by enzymatic hydrolysis is among the most costly steps for emerging cellulosic ethanol biorefineries. In this project, two pretreatment methods (dilute acid, DA, and cellulose solventand organic solvent-lignocellulose fractionation, COSLIF) for corn stover were compared. It was found that glucan digestibility of the corn stover pretreated by COSLIF was much higher, along with faster hydrolysis rate, than that by DApretreated. This difference was more significant at a low enzyme loading. Quantitative measurements of total substrate accessibility to cellulase (TSAC), cellulose accessibility to cellulase (CAC), and noncellulose accessibility to cellulase (NCAC) based on adsorption of a non-hydrolytic recombinant protein TGC were established to find out the cause. The COSLIF-pretreated corn stover had a CAC nearly twice that of the DA-pretreated biomass. Further supported by qualitative scanning electron microscopy images, these results suggested that COSLIF treatment disrupted microfibrillar structures within biomass while DA treatment mainly removed hemicelluloses, resulting in a much less substrate accessibility of the latter than of the former. It also concluded that enhancing substrate accessibility was the key to an efficient bioconversion of lignocellulose. A simple method for determining the adsorbed cellulase on cellulosic materials or pretreated lignocellulose was established for better understanding of cellulase adsorption and desorption. This method involved hydrolysis of adsorbed cellulase in the presence of
Like cures like: A neuroimmunological model based on electromagnetic resonance

Objectives: Recent investigations have pointed to the production of characteristic electromagnetic (EM) waves in highly diluted sterile filtrates of different microorganisms and their associated DNA molecules. Analysis of these diluted solutions that are prepared using methods almost identical to the way that homeopathic medicines are prepared has pointed to the existence of nanostructures capable of emitting EM waves. Combining these results with findings that point to the interaction of EM waves with sensory nerves with subsequent activation of homeostatic efferent pathways, we propose a model to describe mechanisms underlying the effects of homeopathic remedies. The Model: Living cells and tissues are capable of generating EM waves in their physiological conditions. When a cell deviates from its physiological state, in addition to normal EM emissions, it starts to produce EM waves with altered characteristics. According to our model, the main cause of the therapeutic effects of homeopathic remedies is the occurrence of resonance between the non-physiological EM waves of the patient and extremely low-frequency EM waves produced by nanostructures present in the homeopathic remedy. Resonance occurs if the frequency and amplitude characteristics of the patient's non-physiological EM waves and those produced by nanostructures of the applied homeopathic remedy are similar. Once resonance occurs, stimulation of the patient's sensory neurons, which are sensitized due to inflammation of any origin, leads to triggering of different regulatory mechanisms, including the activation of descending antinociceptive and/or cholinergic anti-inflammatory pathways, which leads to the restoration of homeostasis.
Lung metastases from differentiated thyroid carcinoma. A 40 years' experience.

AIM Retrospective studies have been carried out to estimate the survival of 96 patients with lung metastases from differentiated thyroid carcinoma, observed from 1958 to 2000. METHODS All patients had undergone total thyroidectomy. Case histories were analysed with respect to age at diagnosis, sex, histology, local lymph node involvement, size of lung metastases and 131I uptake by metastases. Survival functions were calculated. Cox regression was performed. RESULTS There was no statistically significant difference in histological type and lymph node involvement, whereas a significantly longer survival time was observed in patients under 45 years of age at diagnosis (p= or <0.0001), in those with metastases concentrating 131I (p= or <0.0001) and in those with fine miliaric metastases (p=0.0037). Multi-variate analysis revealed that the risk of death increases about 5.4-fold in patients over 45 years old, whereas 131I treatment is likely to reduce this risk to nearly 1/6. Conclusion. In conclusion, in patients with lung metastases from differentiated thyroid carcinoma, young age at diagnosis and 131I uptake by metastases are the most important factors positively affecting survival time. Radioiodine therapy, also with high cumulative 131I activity, can lead to longer survival time or complete recovery.
POSITIVE MENTAL HEALTH: A TURN OF THE CENTURY PERSPECTIVE

Within the last decade, a national prevention research, training, and practice agenda on mental health has been established to address the epidemiological increases in mental disorders and associated emotional and financial costs to individuals, families, and communities. In this article, the author reviews theoretical, empirical, and public policy support in favor of prevention science that inherently includes a broad positive mental health orientation with an emphasis on mental health promotion processes. Prevention within the mental health field needs to include not only minimizing mental disorders, but also enhancing positive qualities of daily functioning. The socioeconomic and cultural context of positive mental health is emphasized with particular attention given to the interrelatedness of individual, family, and community "collective sense of well being. " Nursing and interdisciplinary contributions are reviewed, noting implications for future public policy and service system changes. Innovative ways to enhance mental health will require study of system integration across primary and mental health services as well as incorporating services within societal institutions such as schools and the workplace.
MLV integration site selection is driven by strong enhancers and active promoters

Retroviruses integrate into the host genome in patterns specific to each virus. Understanding the causes of these patterns can provide insight into viral integration mechanisms, pathology and genome evolution, and is critical to the development of safe gene therapy vectors. We generated murine leukemia virus integrations in human HepG2 and K562 cells and subjected them to second-generation sequencing, using a DNA barcoding technique that allowed us to quantify independent integration events. We characterized >3 700 000 unique integration events in two ENCODE-characterized cell lines. We find that integrations were most highly enriched in a subset of strong enhancers and active promoters. In both cell types, approximately half the integrations were found in <2% of the genome, demonstrating genomic influences even narrower than previously believed. The integration pattern of murine leukemia virus appears to be largely driven by regions that have high enrichment for multiple marks of active chromatin; the combination of histone marks present was sufficient to explain why some strong enhancers were more prone to integration than others. The approach we used is applicable to analyzing the integration pattern of any exogenous element and could be a valuable preclinical screen to evaluate the safety of gene therapy vectors.
MicroRNA-125b expands hematopoietic stem cells and enriches for the lymphoid-balanced and lymphoid-biased subsets

MicroRNAs profoundly impact hematopoietic cells by regulating progenitor cell-fate decisions, as well as mature immune effector function. However to date, microRNAs that regulate hematopoietic stem cell (HSC) function have been less well characterized. Here we show that microRNA-125b (miR-125b) is highly expressed in HSCs and its expression decreases in committed progenitors. Overexpression of miR-125b in mouse HSC enhances their function, demonstrated through serial transplantation of highly purified HSC, and enriches for the previously described Slamf1loCD34− lymphoid-balanced and the Slamf1negCD34− lymphoid-biased cell subsets within the multipotent HSC (CD34-KLS) fraction. Mature peripheral blood cells derived from the miR-125b–overexpressing HSC are skewed toward the lymphoid lineage. Consistent with this observation, miR-125b overexpression significantly increases the number of early B-progenitor cells within the spleen and induces the expansion and enrichment of the lymphoid-balanced and lymphoid-biased HSC subset via an antiapoptotic mechanism, reducing the mRNA expression levels of two proapoptotic targets, Bmf and KLF13. The antiapoptotic effect of miR-125b is more pronounced in the lymphoid-biased HSC subset because of their intrinsic higher baseline levels of apoptosis. These effects of miR-125b are associated with the development of lymphoproliferative disease, marked by expansion of CD8+ T lymphocytes. Taken together, these data reveal that miR-125b regulates HSC survival and can promote lymphoid-fate decisions at the level of the HSC by preferentially expanding lymphoid-balanced and lymphoid-biased HSC.
Trauma type, age, and gender as determinants of hip fracture

We determined the trauma type of femoral neck and trochanteric fractures in men and women aged >20 years in 19, 128 fractures reported to a computerized medical information register during 1972–1981. We found that the earlier known exponential increase of fracture incidence by age started in early adulthood rather than during middle age. An age‐related increase was found for each type of injury as well, although the incidence of fractures resulting from severe trauma increased less than that of fractures associated with moderate trauma. The incidence of low‐energy fractures in men as well as in women displayed a constant increase rate with age from young adulthood on, impugning the widely held belief that the menopause is a significant risk factor for fractures. The dominating risk factor for proximal femoral fracture in adults appears to be age, irrespective of the cause of injury, with a chronological decline in bone strength as the most likely cause of the exponential increase in the fracture incidence during adult life.
Prolonged‐release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects

Melatonin, secreted nocturnally by the pineal gland, is an endogenous sleep regulator. Impaired melatonin production and complaints on poor quality of sleep are common among the elderly. Non‐restorative sleep (perceived poor quality of sleep) and subsequently poor daytime functioning are increasingly recognized as a leading syndrome in the diagnostic and therapeutic process of insomnia complaints. The effects of 3‐weeks prolonged‐release melatonin 2 mg (PR‐melatonin) versus placebo treatment were assessed in a multi‐center randomized placebo‐controlled study in 170 primary insomnia outpatients aged ≥55 years. Improvements in quality of sleep (QOS) the night before and morning alertness (BFW) were assessed using the Leeds Sleep Evaluation Questionnaire and changes in sleep quality (QON) reported on five categorical unit scales. Rebound insomnia and withdrawal effects following discontinuation were also evaluated. PR‐melatonin significantly improved QOS (−22.5 versus −16.5 mm, P = 0.047), QON (0.89 versus 0.46 units; P = 0.003) and BFW (−15.7 versus −6.8 mm; P = 0.002) compared with placebo. The improvements in QOS and BFW were strongly correlated (Rval = 0.77, P < 0.001) suggesting a beneficial treatment effect on the restorative value of sleep. These results were confirmed in a subgroup of patients with a greater symptom severity. There was no evidence of rebound insomnia or withdrawal effects following treatment discontinuation. The incidence of adverse events was low and most side‐effects were judged to be of minor severity. PR‐melatonin is the first drug shown to significantly improve quality of sleep and morning alertness in primary insomnia patients aged 55 years and older‐suggesting more restorative sleep, and without withdrawal symptoms upon discontinuation.
Video Self-Modeling and Cooperative Classroom Behavior in Children with Learning and Behavior Problems: Training and Generalization Effects

This study investigated the effects of an instructional package incorporating videotaped self-assessment, self-modeling, discrimination training, and behavioral rehearsal on the cooperative classroom behavior of two second-grade children with learning and behavior problems. Observations were made of selected classroom behaviors in three different classes each day. Results indicate that the intervention was effective in helping young children acquire cooperative classroom behaviors, generalize these behaviors to settings not a part of the training environment, and maintain these behaviors in both the training and generalization settings. The video intervention package also was effective in reducing inappropriate behaviors in the training and generalization settings. Further, there was a marked reduction in variability of behavior for both children. The results suggest that video-based modeling, coupled with discrimination training and rehearsal, is an effective and efficient intervention for early elementary school children with learning and behavior problems.
Adaptive response of the enterohepatic circulation of bile acids to extrahepatic cholestasis

Experimental cholestasis induced by ligation of the common bile duct results in morphological and functional changes in the rat hepatocyte. The aim of this study was to evaluate the adaptive response of the transport process involved in the enterohepatic circulation of bile salts to obstructive cholestasis. Male Sprague‐dawley rats with common bile duct ligation were killed after 48 and 72 hours. Portal and systemic blood and duodenal aspirates were collected. Taurocholate transport was measured in isolated ileal brush border (BBM) and liver basolateral membranes (BLM). Drastic reduction in intraluminal bile salt concentrations in ligated rats accompanied decreases in saturable taurocholate uptake by ileal BBMs. Kinetic analysis indicated that the decrease was attributable to reduction in transporter density and alteration in affinity for the substrate, both of which accentuated with increase in postligation time. In contrast, despite 20‐fold higher portal venous bile salt concentrations, taurocholate uptake by hepatic sinusoidal membrane was lower in rats. Kinetic analysis and immunoblots developed using polyclonal antisera to the liver BLM bile acid transporter demonstrated a gradual decrease in transporter density with increase in postligation time accompanied by reduced taurocholate uptake by basolateral membrane. These results further support the concept that the ileal brush border membrane transporter is regulated by the availability of the substrate, whereas regulation of the bile salt transport across the liver BLM is independent of portal venous bile acid concentration.
Leptin Regulates Proliferation and Apoptosis in Human Prostate

This paper aimed to evaluate the leptin role on the cellular proliferation and the expression of fibroblast growth factor 2, aromatase enzyme, and apoptotic genes in the human prostate tissue. Methods. Fifteen samples of hyperplasic prostate tissue were divided in four symmetric parts maintained in RPMI medium supplemented with 10% fetal bovine serum, 1 ng/mL of gentamicin, and added with 50 ng/mL leptin (L) or not (C). After 3 hours of incubation, gene expression was evaluated by real time RT-PCR. Cellular proliferation was evaluated by immunohistochemistry for PCNA. Results. The leptin treatment led to an increase cellular proliferation (C = 21.8 ± 0.5; L = 64.8 ± 0.9; P < 0.0001) and in the expression of Bax (C = 0.4 ± 0.1; L = 0.9 ± 0.2; P < 0.05) while Bcl-2 (C = 19.9 ± 5.6; L = 5.6 ± 1.8; P < 0.05), Bcl-x (C = 0.2 ± 0.06; L = 0.07 ± 0.02; P < 0.05), and aromatase expressions (C = 1.9 ± 0.6; L = 0.4 ± 0.1; P < 0.04) were significantly reduced. Conclusion. Leptin has an important role in maintaining the physiological growth of the prostate since it stimulates both cellular proliferation and apoptosis, with the decrement in the aromatase gene expression.
Energy trade-offs between intensive biomass utilization , site productivity loss , and ameliorative treatments in loblolly pine plantations

Loblolly pine plantations are the most important source of forest products in the US and the slash remaining after conventional harvest represents a significant potential source of bioenergy. However, slash removal in intensive harvests might, under some circumstances, reduce site productivity by reducing soil organic matter and associated nutrients. Two complimentary studies in the Gulf Coastal Plain of the southeastern US were designed to test whether harvest intensity (level of biomass removal) could have a negative long-term impact on site productivity. Harvesting tree crowns in addition to the merchantable bole had a negative impact (18%) on pine biomass accumulation by age 7-10 years on 15 of 19 research blocks. Sites at risk of harvest-induced reductions in productivity were relatively unproductive prior to harvest and had low soil phosphorus (P) concentrations. Intensive harvesting, fertilization, and chemical control of non-crop vegetation were all energy efficient; the additional biomass energy gained through these practices was two-orders of magnitude greater than the energy needed to conduct the activities. Harvest of slash for bioenergy in the Gulf Coastal Plain of the southeastern US has the potential to reduce productivity on infertile soils, but fertilization has the potential to restore and even improve productivity on those sites in an energy-efficient way. Published by Elsevier Ltd.
The HIRA complex that deposits the histone H3.3 is conserved in Arabidopsis and facilitates transcriptional dynamics

ABSTRACT In animals, replication-independent incorporation of nucleosomes containing the histone variant H3.3 enables global reprogramming of histone modifications and transcriptional profiles. H3.3 enrichment over gene bodies correlates with gene transcription in animals and plants. In animals, H3.3 is deposited into chromatin by specific protein complexes, including the HIRA complex. H3.3 variants evolved independently and acquired similar properties in animals and plants, questioning how the H3.3 deposition machinery evolved in plants and what are its biological functions. We performed phylogenetic analyses in the plant kingdom and identified in Arabidopsis all orthologs of human genes encoding members of the HIRA complex. Genetic analyses, biochemical data and protein localisation suggest that these proteins form a complex able to interact with H3.3 in Arabidopsis in a manner similar to that described in mammals. In contrast to animals, where HIRA is required for fertilization and early development, loss of function of HIRA in Arabidopsis causes mild phenotypes in the adult plant and does not perturb sexual reproduction and embryogenesis. Rather, HIRA function is required for transcriptional reprogramming during dedifferentiation of plant cells that precedes vegetative propagation and for the appropriate transcription of genes responsive to biotic and abiotic factors. We conclude that the molecular function of the HIRA complex is conserved between plants and animals. Yet plants diversified HIRA functions to enable asexual reproduction and responsiveness to the environment in response to the plant sessile lifestyle.