Miracle-dz/UniFAR-FTUs huggingface dataset:
Clozapine Induced Disturbances in Hepatic Glucose Metabolism: The Potential Role of PGRMC1 Signaling

Newly emerging evidence has implicated that progesterone receptor component 1 (PGRMC1) plays a novel role not only in the lipid disturbance induced by atypical antipsychotic drugs (AAPD) but also in the deterioration of glucose homoeostasis induced by clozapine (CLZ) treatment. The present study aimed to investigate the role of PGRMC1 signaling on hepatic gluconeogenesis and glycogenesis in male rats following CLZ treatment (20 mg/kg daily for 4 weeks). Recombinant adeno-associated viruses (AAV) were constructed for the knockdown or overexpression of hepatic PGRMC1. Meanwhile, AG205, the specific inhibitor of PGRMC1 was also used for functional validation of PGRMC1. Hepatic protein expressions were measured by western blotting. Meanwhile, plasma glucose, insulin and glucagon, HbA1c and hepatic glycogen were also determined by assay kits. Additionally, concentrations of progesterone (PROG) in plasma, liver and adrenal gland were measured by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Our study demonstrated that CLZ promoted the process of gluconeogenesis and repressed glycogenesis, respectively mediated by PI3K-Akt-FOXO1 and GSK3β signaling via inhibition of PGRMC1-EGFR/GLP1R in rat liver, along with an increase in fasting blood glucose, HbA1c levels and a decrease in insulin and hepatic glycogen levels. Furthermore, through PGRMC1-EGFR/GLP1R-PI3K-Akt pathway, knockdown or inhibition (by AG205) of PGRMC1 mimics, whereas its overexpression moderately alleviates CLZ-induced glucose disturbances. Potentially, the PGRMC1 target may be regarded as a novel therapeutic strategy for AAPD-induced hepatic glucose metabolism disorder.
Role of trehalose and heat in the structure of the C‐terminal activation domain of the heat shock transcription factor

The heat shock transcription factor (HSF) is the primary transcriptional regulator of the heat shock response in eukaryotes. Saccharomyces cerevisiae HSF1 has two functional transcriptional activation domains, located N‐ and C‐terminal to the central core of the protein. These activation domains have a low level of transcriptional activity prior to stress, but they acquire a high level of transcriptional activity in response to stresses such as heat. Previous studies on the N‐terminal activation domain have shown that it can be completely disordered. 1 In contrast, we show that the C‐terminal activation domain of S. cerevisiae HSF1 does contain a certain amount of secondary structure as measured by circular dichroism (CD) and protease resistance. The α‐helical content of the domain can be increased by the addition of the disaccharide trehalose but not by sucrose. Trehalose, but not sucrose, causes a blue shift in the fluorescence emission spectra, which is suggestive of an increase in tertiary structure. Trehalose, which is known to be a chemical chaperone, also increases proteases' resistance and promotes heat‐induced increases in α‐helicity. The latter is particularly intriguing because of the physiological role of trehalose in yeast. Trehalose levels are increased dramatically after heat shock, and this is thought to protect protein structure prior to the increase of heat shock protein levels. Our results suggest that the dramatic changes in S. cerevisiae HSF1 transcriptional activity in response to stress might be linked to the combined effects of trehalose and elevated temperatures in modifying the overall structure of HSF1's C‐terminal activation domain. Proteins 2005. © 2005 Wiley‐Liss, Inc.
Social Isolation, Loneliness and Health Among Older Adults

Objective: To examine the relationship of social isolation, loneliness and health outcomes among older adults. Methods: Using data from the Leave Behind Questionnaire of the Health and Retirement Study (2006 and 2008), (n = 11,825) several indicators of social isolation were scaled and the Hughes 3-Item Loneliness Scale was used. Two measures of health (self-rated health and mental health conditions) were examined using logistic regression. Results: Loneliness and social isolation were not highly correlated with one another (r = 0.201, p = 0.000). Loneliness was associated with higher odds of having a mental health problem (OR: 1.17; CI: [1.13, 1.21], p = 0.000); and isolation was associated with higher odds of reporting one’s health as being fair/poor (OR:1.39; CI: [1.21, 1.59], p = 0.000). Discussion: The results suggest that global measures of isolation, that fail to distinguish between social isolation and feelings of loneliness, may not detect the impact on physical and mental health in older adults.
Lateral Transmission of Yeast Symbionts Among Lucanid Beetle Taxa

To deepen understanding the evolutionary process of lucanid–yeast association, the lateral transmission process of yeast symbionts among stag beetle genera Platycerus and Prismognathus around the border between Japan and South Korea was estimated based on molecular analyses and species distribution modelings. Phylogenetic analyses were based on yeast ITS and IGS sequences and beetle COI sequences using Prismognathus dauricus from the Tsushima Islands and Pr. angularis from Kyushu, Japan, as well as other sequence data from our previous studies. The range overlap based on the species distribution model (SDM) and differentiation in ecological space were analyzed. Based on the IGS sequences, Clade II yeast symbionts were shared by Platycerus hongwonpyoi and Pr. dauricus in South Korea and the Tsushima Islands, and Platycerus viridicuprus in Japan. Clade III yeasts were shared by Pr. dauricus from the Tsushima Islands and Pr. angularis in Japan. During the Last Interglacial period when the land bridge between Japan and the Korean Peninsula existed, range overlap was predicted to occur between Pl. viridicuprus and Pr. dauricus in Kyushu and between Pr. dauricus and Pr. angularis in Kyushu and the Tsushima Islands. The ecological space of Pl. hongwonpyoi was differentiated from that of Pl. viridicuprus and Pr. angularis. We demonstrated the paleogeographical lateral transmission process of Scheffersomyces yeast symbionts among lucanid genera and species: putative transmission of yeasts from Pr. dauricus to Pl. viridicuprus in Kyushu and from Pr. angularis to Pr. dauricus in Kyushu or the Tsushima Islands. We also found that the yeast symbionts are likely being replaced in Pr. dauricus on the Tsushima Islands. We present novel estimates of the lateral transmission process of microbial symbionts based on phylogenetic, SDM and environmental analyses among lucanid beetles.
Interoperability Optimizations For Administrative Services

Romania is facing major challenges in the public administration field as a new member of the European Union. It has become a mandatory requirement to adhere to the European dimension of the public administration reform process. In this paper, we are going to discuss how the European Union Services Directive has influenced the reform process, as effectively implementations of a Single Point of Contact (PSC) in Romania is coming to reality. The discussion is based on the experience gained as contributors to the implementation of a PSC prototype in Romania. Therefore we intend to identify several future challenges and possible solutions considering that the service directive implementation is just a first step for aligning the EU countries to the same technical and operational perspective.
Cognitive deficits of mild dementia:A comparison between dementia of the Alzheimer's type and vascular dementia

Abstract This study was designed to examine the profiles of cognitive deficits in 11 mildly demented patients with dementia of Alzheimer's type (DAT), five with vascular dementia with multiple subcortical lacunar infarcts (VDS), and seven with vascular dementia with extensive white matter lesions (VDW) in comparison with 23 aged individuals without dementia. Memory, attention, abstract thinking, and visuospatial function were assessed using the Japanese translation of the Wechsler Memory Scale‐Revised (WMS‐R) and the Japanese version of the Wechsler Adult Intelligence Scale‐Revised (WAIS‐R). Compared with normal aged individuals, three dementia groups were significantly impaired in the memory and abstract thinking. However, the performances on several tests on attention (i.e. Mental Control and Visual Memory Span Backward from WMS‐R) and visuospatial function (i.e. Object Assembly from WAIS‐R) differed significantly between the DAT and VDS groups, with VDS being the worst in terms of performance than was DAT. This study suggests that, in the mildly demented stage, the patients with DAT have few problems in the attention and visuospatial function, but those with VDS have impairments in these cognitive abilities.
Distribution of Neuropeptide FF-Like Immunoreactivity in the Brain of Dermophis mexicanus (Amphibia; Gymnophiona): Comparison with FMRFamide Immunoreactivity

Neuropeptide FF (NPFF) is an FMRFamide-related peptide widely distributed in the mammalian brain. NPFF immunohistochemistry labeled cell bodies in a few locations and dense fiber networks throughout the brain. Recently, the distribution of NPFF immunoreactive (NPFF-ir) cells and fibers in the brain of anuran and urodele amphibians was studied and, as in mammals, significant species differences were noted. To further assess general and derived features of the NPFF-containing neuron system in amphibians, we have investigated the distribution of NPFF-ir cell bodies and fibers in the brain of the gymnophionan Dermophis mexicanus by means of an antiserum against bovine NPFF. This distribution was compared to that of FMRFamide immunoreactivity. Major traits shared with anurans and urodeles were the abundant fiber labeling in the ventral telencephalon, hypothalamus, isthmus, ventrolateral medulla and dorsal spinal cord. In addition, in the three amphibian orders the majority of the NPFF-ir cells were located in the preoptic-hypothalamic region. However, distinct particular features were present in the gymnophionan such as the lack of NPFF-ir cells in the telencephalon, brainstem and spinal cord and the absence of NPFF-ir fibers in the hypophysis and the olfactory bulbs. This pattern was distinct from that observed for FMRFamide distribution. Striking differences were noted in the pallium, caudal hypothalamus and midbrain tegmentum where FMRFamide – containing cells were localized. The present results in Dermophis support the idea that data from gymnophionans must be included when stating the amphibian condition of a given system because important variations are obvious when gymnophionans are compared with anurans and urodeles.
Identification of Candidate Cotton Genes Associated With Fiber Length Through Quantitative Trait Loci Mapping and RNA-Sequencing Using a Chromosome Segment Substitution Line

Fiber length is an important determinant of fiber quality, and it is a quantitative multi-genic trait. Identifying genes associated with fiber length is of great importance for efforts to improve fiber quality in the context of cotton breeding. Integrating transcriptomic information and details regarding candidate gene regions can aid in candidate gene identification. In the present study, the CCRI45 line and a chromosome segment substitution line (CSSL) with a significantly higher fiber length (MBI7747) were utilized to establish F2 and F2:3 populations. Using a high-density genetic map published previously, six quantitative trait loci (QTLs) associated with fiber length and two QTLs associated with fiber strength were identified on four chromosomes. Within these QTLs, qFL-A07-1, qFL-A12-2, qFL-A12-5, and qFL-D02-1 were identified in two or three environments and confirmed by a meta-analysis. By integrating transcriptomic data from the two parental lines and through qPCR analyses, four genes associated with these QTLs including Cellulose synthase-like protein D3 (CSLD3, GH_A12G2259 for qFL-A12-2), expansin-A1 (EXPA1, GH_A12G1972 for qFL-A12-5), plasmodesmata callose-binding protein 3 (PDCB3, GH_A12G2014 for qFL-A12-5), and Polygalacturonase (At1g48100, GH_D02G0616 for qFL-D02-1) were identified as promising candidate genes associated with fiber length. Overall, these results offer a robust foundation for further studies regarding the molecular basis for fiber length and for efforts to improve cotton fiber quality.
Survival-Span Method: How to Qualitatively Estimate Lifespan to Improve the Study of Aging, and not Disease, in Aging Studies

Lifespan analyses are important for advancing our understanding of the aging process. There are two major issues in performing lifespan studies: 1) late-stage animal lifespan analysis may include animals with non-terminal, yet advanced illnesses, which can pronounce indirect processes of aging rather than the aging process per se and 2) they often involves challenging welfare considerations. Herein, we present an option to the traditional way of performing lifespan studies by using a novel method that generates high-quality data and allows for the inclusion of excluded animals, even animals removed at early signs of disease. This Survival-span method is designed to be feasibly done with simple means by any researcher and strives to improve the quality of aging studies and increase animal welfare.
Effects of the immunosuppressant FK506 on intracellular Ca2+ release and Ca2+ accumulation mechanisms

1 The immunophilin FKBP12 associates with intracellular Ca2+ channels and this interaction can be disrupted by the immunosuppressant FK506. We have investigated the effect of FK506 on Ca2+ release and Ca2+ uptake in permeabilized cell types. 2 Changes in medium free [Ca2+] were detected by the fluorescent Ca2+ indicator fluo‐3 in digitonin‐permeabilized SH‐SY5Y human neuroblastoma cells, DT40 and R23‐11 (i.e. triple inositol 1,4,5‐trisphosphate (IP3) receptor knockout cells) chicken B lymphocytes and differentiated and undifferentiated BC3H1 skeletal muscle cells. 45Ca2+ fluxes were studied in saponin‐permeabilized A7r5 rat smooth muscle cells. 3 Addition of FK506 to permeabilized SH‐SY5Y cells led to a sustained elevation of the medium [Ca2+] corresponding to ∼30% of the Ca2+ ionophore A23187‐induced [Ca2+] rise. This rise in [Ca2+] was not dependent on mitochondrial activity. 4 This FK506‐induced [Ca2+] rise was related to the inhibition of the sarcoplasmic/endoplasmic reticulum Ca2+‐Mg2+‐ATPase (SERCA) Ca2+ pump. Oxalate‐facilitated 45Ca2+ uptake in SH‐SY5Y microsomes was inhibited by FK506 with an IC50 of 19 μm. 5 The inhibition of the SERCA Ca2+ pump was not specific since several macrocyclic lactone compounds (ivermectin > FK506, ascomycin and rapamycin) were able to inhibit Ca2+ uptake activity. 6 FK506 (10 μm) did not affect IP3‐induced Ca2+ release in permeabilized SH‐SY5Y and A7r5 cells, but enhanced caffeine‐induced Ca2+ release via the ryanodine receptor (RyR) in differentiated BC3H1 cells. 7 In conclusion, FK506 inhibited active Ca2+ uptake by the SERCA Ca2+ pump; in addition, FK506 enhanced intracellular Ca2+ release through the RyR, but it had no direct effect on IP3‐induced Ca2+ release.
Optimal allocation of reactive power sources using network partitioning

Reactive power cannot be transmitted over long distances and voltage stability is considered as more of local problem rather than a global problem. So this paper presents a new method of combining network partitioning and voltage stability sensitivity index for optimal allocation of reactive sources to enhance voltage stability. The concept of electrical distance is introduced for network partitioning, partitioning a power network into strongly connected sub-networks. By applying this approach, the reactive sources can be allocated most reasonable, reactive compensation balance in every zone. The simulation results indicated that the method is practicable and effective to improve the voltage stability of power systems.
The “work” of women when considering and using interventions to reduce mother-to-child transmission (MTCT) of HIV

Abstract This paper explores HIV-infected women's experiences of considering and using recommended interventions during pregnancy and postpartum to reduce mother-to-child transmission of HIV. Data were collected from 45 HIV-infected women aged 18–44 years living in Melbourne, Australia. A semi-structured interview was used to collect qualitative information on women's reproductive experience and intentions. The 15 women who had their children after their HIV diagnosis engaged in significant work including surveillance and safety work to minimise stigma and infection, information work to inform decisions and actions, accounting work to calculate risk and benefit, hope and worry work concerning a child's infection status and impact of interventions, work to redefine an acceptable maternal identity, work to prepare an alternative story to counter the disclosure effect of the intervention and emotional work to reconcile guilt when considering these interventions. This study provides a framework to help clinicians understand the real and on-going “work” that women engage in when they are considering interventions recommended by their physicians to reduce transmission of HIV. Even in circumstances where access to and acceptance of interventions are high, women continue to engage in this work even after they have a made a decision about a particular intervention.
Parenteral Nutrition Safe Practices: Results of the 2003 American Society for Parenteral and Enteral Nutrition Survey.

BACKGROUND The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) recently published a revision of its "Safe Practices for Parenteral Nutrition" guidelines. Because there is a paucity of published scientific evidence to support good practices related to ordering, compounding, and administering parenteral nutrition (PN), a survey was performed in the process of the revision to gain insight into the discrepancies between reported practices and previous guidelines. METHODS A web-based survey consisting of 45 questions was conducted (n = 651) June 1-30, 2003. Respondents were queried about primary practice setting, professional background, processes for writing PN orders, computer order entry of PN orders, problems with PN orders, and adverse events related to PN. RESULTS There were 651 survey responses, 90% of which were from hospital-based practitioners. Almost 75% of responders processed between 0 and 20 PN orders per day. Overall, physicians (78%) were responsible for writing PN orders, but dietitians and pharmacists had significant involvement. PN base components were most often ordered as percentage final concentration after admixture (eg, 20% dextrose), which is inconsistent with safe practice guidelines of ordering by total amount per day (eg, 200 g/day). There was no consistent method for ordering PN electrolytes. Approximately 45% of responders reported adverse events directly related to PN that required intervention. Of these events, 25% caused temporary or permanent harm, and 4.8% resulted in a near-death event or death. CONCLUSIONS Although the survey found consistency in PN practices for many areas queried, significant variation exists in the manner by which PN is ordered and labeled.
StructRank: A New Approach for Ligand-Based Virtual Screening

Screening large libraries of chemical compounds against a biological target, typically a receptor or an enzyme, is a crucial step in the process of drug discovery. Virtual screening (VS) can be seen as a ranking problem which prefers as many actives as possible at the top of the ranking. As a standard, current Quantitative Structure-Activity Relationship (QSAR) models apply regression methods to predict the level of activity for each molecule and then sort them to establish the ranking. In this paper, we propose a top-k ranking algorithm (StructRank) based on Support Vector Machines to solve the early recognition problem directly. Empirically, we show that our ranking approach outperforms not only regression methods but another ranking approach recently proposed for QSAR ranking, RankSVM, in terms of actives found.
Towards Effective Content-Based Music Retrieval With Multiple Acoustic Feature Combination

In this paper, we present a new approach to constructing music descriptors to support efficient content-based music retrieval and classification. The system applies multiple musical properties combined with a hybrid architecture based on principal component analysis (PCA) and a multilayer perceptron neural network. This architecture enables straightforward incorporation of multiple musical feature vectors, based on properties such as timbral texture, pitch, and rhythm structure, into a single low-dimensioned vector that is more effective for classification than the larger individual feature vectors. The use of supervised training enables incorporation of human musical perception that further enhances the classification process. We compare our approach with state of the art techniques and demonstrate its effectiveness on content-based music retrieval. In addition, extensive experimental study illustrates its effectiveness and robustness against various kinds of audio alteration
Distribution of apolipoprotein E phenotypes in Friedreich's ataxia

Abstract Allelic polymorphism at the apolipoprotein E (apo E) gene locus (alleles ɛ2, ɛ3 and ɛ4) is responsible for the existence of 6 discrete electrophoretic phenotypes of plasma apo E. Since the presence of the ɛ2 allele in the genotype tends to be associated with higher triglyceride levels, a study was undertaken to determine if a higher frequency of this allele could account for the presence of higher plasma triglycerides in subsets of patients with Friedreich's Ataxia. The frequency of the apo E phenotypes was determined in 37 subjects with Friedreich's Ataxia and compared with that of 102 normolipidemic and 102 hyperlipidemic individuals. There was no increased prevalence of the E3/2 phenotype and the ɛ2 allele in the Friedreich's sample as is found in a hyperlipidemic sample. Furthermore, the ɛ2 subset did not have significantly higher plasma triglycerides than the non-ɛ2 subset and the hypothesis was rejected. On the other hand, there was a trend for a decreased frequency of the E4/3 phenotype in the Friedreich's sample relative to the hyperlipidemic group but the difference did not reach statistical significance. The apo E phenotype distribution was also measured in a smaller sample of Charlevoix-Saguenay disease; this led to the discovery of two siblings with the relatively rare E2/2 phenotype and unexpectedly low levels of plasma lipid and lipoprotein concentrations. Plasma apolipoprotein E concentrations in both diseases were within the normal range except for subjects bearing the E2/2 phenotype.