Miracle-dz/UniFAR-FTUs huggingface dataset:
Mouse Models of Tuberous Sclerosis Complex

The most devastating complications of tuberous sclerosis complex affect the central nervous system and include epilepsy, mental retardation, autism, and glial tumors. Mutations in one of two genes, TSC1 and TSC2, result in a similar disease phenotype by disrupting the normal interaction of their protein products, hamartin and tuberin, which form a functional signaling complex. Disruption of these genes in the brain results in abnormal cellular differentiation, migration, and proliferation, giving rise to characteristic brain lesions called cortical tubers. Relevant animal models, including conventional and conditional knockout mice, are valuable tools for studying the normal functions of tuberin and hamartin and how disruption of their expression gives rise to the variety of clinical features that characterize tuberous sclerosis complex. In the future, these animals will be invaluable preclinical models for the development of highly specific and efficacious treatments for children affected with tuberous sclerosis complex. (J Child Neurol 2004;19:726—733).
Complete mitochondrial genome of the Swan Goose (Anser cygnoides L.) and its phylogenetic analysis

Abstract In this study, we undertook the first complete the Swan Goose (Anser cygnoides L.) mitochondrial genome. The total length of the mitogenome is 16,739 bp. It contains the typical structure, including 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes, and one D-loop region. The overall composition of the mitogenome is A (29.2%), G (15.8%), C (32.8%), and T (22.2%). Besides, the base preference of AT was not determined. Twenty-two kinds of tRNA were all typically cloverleaf structures. According to the phylogenetic analysis, A. cygnoides L. has a closer relationship with Anser anser.
Ovulatory follicular fluid induces sperm phagocytosis by neutrophils, but oviductal fluid around oestrus suppresses its inflammatory effect in the buffalo oviduct in vitro

We have recently shown that the conditioned media from bovine oviductal epithelial cell culture suppress sperm phagocytosis by neutrophils, suggesting that the oviduct around oestrus supplies the anti‐inflammatory microenvironment. To investigate the immune response of neutrophils toward the sperm at ovulation in the buffalo oviduct, we examined (a) a detailed distribution of neutrophils in the oviduct in buffaloes, (b) the effect of ovulatory follicular fluid (FF) and oviductal fluid (OF) on sperm phagocytosis by neutrophils, and (c) the interaction of the ovulatory FF with OF on sperm phagocytosis by neutrophils in vitro. Buffalo oviducts were collected from healthy reproductive tracts at a local slaughterhouse. A detailed observation by histological examination and transmission electron microscopy revealed that neutrophils exist in the oviduct epithelium and lumen throughout the oestrous cycle in buffaloes. The number of neutrophils at the oestrus stage was higher in ampulla compared with those in isthmus, whereas they remained relatively constant at the dioestrus stage. Two hours of preincubation of neutrophils with FF enhanced sperm phagocytosis through the formation of neutrophil extracellular traps (NETs) together with H2O2 production, whereas OF around oestrus (eOF) suppressed sperm phagocytosis, NETs formation, and H2O2 production and relieved the above FF‐induced inflammatory response. Our findings show that neutrophils exist in the healthy cyclic oviduct across bovine species, and the OF supplies a strong anti‐inflammatory environment that could minimize the inflammatory effect of the FF that flows into the oviduct lumen after ovulation and supports the occurrence of fertilization.
A multicenter, double-blind, placebo-controlled trial comparing piperacillin-tazobactam with and without amikacin as empiric therapy for febrile neutropenia.

In a prospective, multicenter, double-blind, randomized clinical trial, we compared the efficacy of piperacillin-tazobactam (4.5 g 3 times daily intravenously) plus placebo versus piperacillin-tazobactam plus amikacin (7.5 mg/kg twice daily intravenously) for the treatment of 760 febrile, adult patients with cancer with chemotherapy-induced profound (<500 neutrophils/mm3) and prolonged (>10 days) neutropenia. A total of 733 patients were assessable for efficacy of the drug regimens, and an overall successful outcome was reported in 49% (179 of 364) of the patients who received monotherapy, compared with 53% (196 of 369) of patients who received combination therapy (P=.2). Response rates were similar with both regimens, as were incidences of bacteremia and clinically documented and possible infections. In our epidemiological setting, the initial empiric combination therapy was not associated with improved outcomes when compared with initial monotherapy.
Temperature as a Circadian Marker in Older Human Subjects: Relationship to Metabolic Syndrome and Diabetes

Background: Circadian rhythms are characterized by approximate 24-hour oscillations in physiological and behavioral processes. Disruptions in these endogenous rhythms, most commonly associated with shift work and/or lifestyle, are recognized to be detrimental to health. Several studies have demonstrated a high correlation between disrupted circadian rhythms and metabolic disease. The aim of this study was to determine which metabolic parameters correlate with physiological measures of circadian temperature amplitude (TempAmp) and stability (TempStab). Methods: Wrist skin temperature was measured in 34 subjects (ages 50 to 70, including lean, obese, and diabetic subjects) every 10 minutes for 7 consecutive days. Anthropometric measures and fasting blood draws were conducted to obtain data on metabolic parameters: body mass index, hemoglobin A1C, triglycerides, cholesterol, high-density lipoprotein, and low-density lipoprotein. A history of hypertension and current blood pressure was noted. Results: Analysis of the data indicated a substantial reduction in TempAmp and TempStab in subjects with metabolic syndrome (three or more risk factors). To determine the impact of individual interdependent metabolic factors on temperature rhythms, stepwise multilinear regression analysis was conducted using metabolic syndrome measurements. Interestingly, only triglyceride level was consistently correlated by the analysis. Triglyceride level was shown to contribute to 33% of the variability in TempAmp and 23% of the variability in TempStab. Conclusion: Our results demonstrate that elevated triglycerides are associated with diminished TempAmp and TempStab in human subjects, and triglycerides may serve as a primary metabolic predictor of circadian parameters.
Identification of RNA-binding proteins in exosomes capable of interacting with different types of RNA: RBP-facilitated transport of RNAs into exosomes

The RNA that is packaged into exosomes is termed as exosomal-shuttle RNA (esRNA); however, the players, which take this subset of RNA (esRNA) into exosomes, remain largely unknown. We hypothesized that RNA binding proteins (RBPs) could serve as key players in this mechanism, by making complexes with RNAs and transporting them into exosomes during the biosynthesis of exosomes. Here, we demonstrate the presence of 30 RBPs in exosomes that were shown to form RNA–RBP complexes with both cellular RNA and exosomal-RNA species. To assess the involvement of these RBPs in RNA-transfer into exosomes, the gene transcripts encoding six of the proteins identified in exosomes (HSP90AB1, XPO5, hnRNPH1, hnRNPM, hnRNPA2B1, and MVP) were silenced by siRNA and subsequent effect on esRNA was assessed. A significant reduction of total esRNA was observed by post-transcriptional silencing of MVP, compared to other RBPs. Furthermore, to confirm the binding of MVP with esRNA, a biotinylated-MVP was transiently expressed in HEK293F cells. Higher levels of esRNA were recovered from MVP that was eluted from exosomes of transfected cells, as compared to those of non-transfected cells. Our data indicate that these RBPs could end up in exosomes together with RNA molecules in the form of RNA–ribonucleoprotein complexes, which could be important for the transport of RNAs into exosomes and the maintenance of RNAs inside exosomes. This type of maintenance may favor the shuttling of RNAs from exosomes to recipient cells in the form of stable complexes.
Point/Counterpoint: Routine Use of Autologous Stem Cell Transplantation in Multiple Myeloma. ASCT is imperative in the treatment of younger patients.

Multiagent induction chemotherapy leads to high response rates in multiple myeloma. The phase III Southwest Oncology Group trial involving 525 patients established lenalidomide, bortezomib, and dexamethasone (RVD) as a preferred induction regimen; in this trial, RVD demonstrated an overall response rate of 81.5%, with 15.7% of responses complete responses (CR), and 27.8% very good partial responses (VGPR). [1] Nonetheless, autologous stem cell transplantation (ASCT) still is and will remain a mainstay of therapy, with 6,300 transplants done in the United States for myeloma in 2013. [2] Phase III trials continue to support the use of high-dose chemotherapy over conventional therapy, even with novel agents.
Protein kinase C modulation of recombinant ATP‐sensitive K+ channels composed of Kir6.1 and/or Kir6.2 expressed with SUR2B

The molecular identity of smooth muscle ATP‐sensitive K+ channels (KATP) is not established with certainty. Patch clamp methods were employed to determine if recombinant KATP channels composed of Kir6.1 and SUR2B subunits expressed by human embryonic kidney (HEK293) cells share an identical modulation by protein kinase C (PKC) with the vascular KNDP subtype of KATP channel. The open probability of Kir6.1/SUR2B channels was determined before and after sequential exposure to pinacidil (50 μM) and the combination of pinacidil and phorbol 12,13‐dibutyrate (PdBu; 50 nm). Treatment with PdBu caused a decline in channel activity, but this was not seen with an inactive phorbol ester, 4α‐phorbol 12,13‐didecanoate (PdDe; 50 nm). Angiotensin II (0.1 μM) induced a similar inhibition of Kir6.1/SUR2B channels in cells expressing angiotensin AT1 receptors. The effects of PdBu and angiotensin II were blocked by the PKC inhibitor, chelerythrine (3 μM). Purified PKC inhibited Kir6.1/SUR2B activity (in 0.5 mm ATP/ 0.5 mm ADP), and the inhibition was blocked by a specific peptide inhibitor of PKC, PKC(19‐31). In contrast, PdBu increased the activity of recombinant KATP channels composed of Kir6.2 and SUR2B, or the combination of Kir6.1, Kir6.2 and SUR2B subunits. The results indicate that the modulation by PKC of Kir6.1/SUR2B, but not Kir6.2/SUR2B or Kir6.1‐Kir6.2/SUR2B channel gating mimics that of native vascular KNDP channels. Physiological inhibition of vascular KATP current by vasoconstrictors which utilize intracellular signalling cascades involving PKC is concluded to involve the modulation of KNDP channel complexes composed of four Kir6.1 and their associated SUR2B subunits.
Trust, trustworthiness and cooperation: Social capital and community resource management

Social capital is considered one of the main determinants of community resource management success. Trust and trustworthiness are important measures of social capital. We combine experimental and household survey data from five rural villages in India to analyze (i) how these measures are correlated with socio–cultural community characteristics, and (ii) how social capital affects community resource management.
Endotoxin-induced macrophage gene expression depends on platelet-activating factor.

BACKGROUND The development of multiple organ failure in septic patients is due to a systemic inflammation orchestrated by macrophages (Mphi). Elucidation and control of the mechanism involved in Mphi activation in sepsis is crucial to improving survival. An early event of Mphi activation involves the hydrolysis of membrane phospholipid by phospholipase A2 (PLA2) and subsequent generation of platelet-activating factor (PAF). OBJECTIVE We designed this study to test the hypothesis that Mphi gene expression depends on PAF. DESIGN Rabbit alveolar Mphi were obtained by bronchoalveolar lavage and were stimulated with 10 ng/mL of Escherichia coli endotoxin lipopolysaccharide (LPS), PAF (1 micromol/L), LPS+/-CV3988 (10 micromol/L), a PAF receptor antagonist, or LPS+/-PLA2 inhibitors: AACOCF3 (50 micromol/L) or manoalide (10 micromol/L). After 4 hours of incubation, Mphi tumor necrosis factor (TNF) messenger RNA (mRNA) expression was assessed by Northern blot analyses. The TNF production in the Mphi supernatant was measured by L929 bioassays. RESULTS The LPS-stimulated Mphi expressed increased levels of TNF mRNA and produced an enormous amount of TNF. CV3988, a PAF antagonist, inhibited LPS-induced TNF mRNA. Furthermore, inhibiting PAF production with AACOCF3, or manoalide, also inhibited LPS-induced Mphi TNF mRNA expression. The effect of PAF depends on changes in intracellular calcium concentration. Inhibitors of calcium flux attenuated the PAF effects on LPS-stimulated Mphi. CONCLUSIONS Our data suggest that LPS-induced Mphi gene expression is mediated by PAF. It is likely that modulation of PAF production or activity may be beneficial in down-regulating the overactivity of Mphi in sepsis.
Consumers' valuation of food quality labels: The case of the European geographic indication and organic farming labels

This paper assesses consumers' preferences and willingness to pay for European Union geographical indication quality labels [Protected Designation of Origin (PDO) and Protected Geographical Indications (PGI)], organic farming label and other product quality cues. Using a choice experiment, random parameter logit model and olive oil as product of interest, results suggest that respondents are willing to pay the highest premium price for a product with a PDO label, followed by organic farming label, a quality cue describing the product as extra-virgin olive oil and then a PGI label.
Impact of infectious diseases on population health using incidence-based disability-adjusted life years (DALYs): results from the Burden of Communicable Diseases in Europe study, European Union and European Economic Area countries, 2009 to 2013

Background and aims The Burden of Communicable Diseases in Europe (BCoDE) study aimed to calculate disability-adjusted life years (DALYs) for 31 selected diseases in the European Union (EU) and European Economic Area (EEA). Methods: DALYs were estimated using an incidence-based and pathogen-based approach. Incidence was estimated through assessment of data availability and quality, and a correction was applied for under-estimation. Calculation of DALYs was performed with the BCoDE software toolkit without applying time discounting and age-weighting. Results: We estimated that one in 14 inhabitants experienced an infectious disease episode for a total burden of 1.38 million DALYs (95% uncertainty interval (UI): 1.25–1.5) between 2009 and 2013; 76% of which was related to the acute phase of the infection and its short-term complications. Influenza had the highest burden (30% of the total burden), followed by tuberculosis, human immunodeficiency virus (HIV) infection/AIDS and invasive pneumococcal disease (IPD). Men had the highest burden measured in DALYs (60% of the total), adults 65 years of age and over had 24% and children less than 5 years of age had 11%. Age group-specific burden showed that infants (less than 1 year of age) and elderly people (80 years of age and over) experienced the highest burden. Conclusions: These results provide baseline estimates for evaluating infectious disease prevention and control strategies. The study promotes an evidence-based approach to describing population health and assessing surveillance data availability and quality, and provides information for the planning and prioritisation of limited resources in infectious disease prevention and control.
Union revitalisation in advanced economies : assessing the contribution of union organising

What is to be Done with 'Union Organising'? G.Gall Organising and Union Modernization: Narratives of Renewal in Britain M.M. Lucio & M.Stuart Goodbye to all That? Assessing 'the' Organizing Model S.de Turberville Union Organizing and Partnership in Manufacturing, Finance and Public Services in Britain A.Danford, M.Richardson, S.Tailby & M.Upchurch Organizing, Militancy and Revitalization: The Case of the RMT Union R.Darlington Union Organizing in a Recognized Environment: A Case Study of Mobilization N.McCarthy Building Stronger Unions: A Review of Organizing in Britain P.Nowak Can Unions Rebound? Decline and Renewal in the US Labour Movement M.Dixon & J.Fiorito Union Organizing and Union Revitalization in Canada J.B. Rose Union Organising in New Zealand: The Near Death Experience R.May & P.Goulter Conclusion G.Gall
Race influences parent report of concerns about symptoms of autism spectrum disorder

Racial differences in parent report of concerns about their child’s development to healthcare providers may contribute to delayed autism spectrum disorder diagnoses in Black children. We tested the hypotheses that compared to White parents, Black parents of children with autism spectrum disorder would report fewer concerns about autism symptoms and would be more likely to report concerns about disruptive behaviors. A sample of 18- to 40-month-old toddlers (N = 174) with autism spectrum disorder and their parent participated. After screening positive for autism spectrum disorder risk, but prior to a diagnostic evaluation, parents completed free-response questions soliciting concerns about their child’s development. Parent responses were coded for the presence or the absence of 10 possible concerns, which were grouped into autism concerns (e.g. social and restricted and repetitive behavior concerns) or non-autism concerns (e.g. general developmental and disruptive behavior concerns). Compared to White parents, Black parents reported significantly fewer autism concerns and fewer social and restricted and repetitive behavior concerns. However, Black parents did not report significantly fewer non-autism concerns. Race did not influence parent report of disruptive behavior concerns. Lower reporting of autism concerns by Black parents may impact providers’ abilities to identify children who need further screening or evaluation.
The Knowledge of Teaching--Pedagogical Content Knowledge (PCK).

Pedagogical content knowledge (PCK) was first introduced by Shulman in the 80’s. It is defined as the integration or amalgamation of pedagogy and content which basically covers the ‘what’ and ‘how’ of teaching. PCK was considered as the missing paradigm in the study of teaching. This integration of knowledge was long searched by the scholars in the United States in their effort to elevate teaching to the professional status similar to that of doctor, lawyer and engineer. As PCK is the knowledge of teaching, this concept paper presents an overview on definitions of teaching, indicators and knowledge bases required in good teaching. This paper also presents the conceptions and models of PCK, the processes (PRA Model) involved in the growth and development of PCK of teachers and the importance of PCK.
Sequencing and analysis of the complete mitochondrial genome of tundra shrew (Sorex tundrensis) from China

Abstract The complete mitogenome sequence of tundra shrew (Sorex tundrensis) was determined using long PCR. The genome was 17,444 bp in length and contained 13 protein-coding genes, 2 ribosomal RNA genes, 23 transfer RNA genes, 1 origin of L strand replication and 1 control region. The overall base composition of the heavy strand is A (32.9%), C (24.8%), T (29.0%), and G (13.3%). The base compositions present clearly the A–T skew, which is most obviously in the control region and protein-coding genes. The extended termination-associated sequence domain, the central conserved domain and the conserved sequence block domain are defined in the mitochondrial genome control region of tundra shrew. Mitochondrial genome analyses based on MP, ML, NJ and Bayesian analyses yielded identical phylogenetic trees. The three Sorex species formed a monophyletic group with the high bootstrap value (100 %) in all examinations.
Distinct Transcriptional Profiles of Adipogenesisin Vivo and in Vitro *

Obesity, defined as an increase in adipose tissue mass, is the most prevalent nutritional disorder in industrialized countries and is a growing problem in developing countries. An increase in adipose tissue mass can be the result of the production of new fat cells through the process of adipogenesis and/or the deposition of increased amounts of cytoplasmic triglyceride per cell. Although much has been learned about the differentiation of adipocytes in vitro, less is known about the molecular basis for the mechanisms regulating adipogenesis in vivo. Here oligonucleotide microarrays have been used to compare the patterns of gene expression in preadipocytes and adipocytes in vitro and in vivo. These data indicate that the cellular programs associated with adipocyte differentiation are considerably more complex than previously appreciated and that a greater number of heretofore uncharacterized gene regulatory events are activated during this process in vitro. In addition, the gene expression changes associated with adipocyte development in vivo and in vitro, while overlapping, are in some respects quite different. These data further suggest that one or more transcriptional programs are activated exclusively in vivoto generate the full adipocyte phenotype. This gene expression survey now sets the stage for further studies to dissect the molecular differences between in vivo and in vitroadipocytes.
A Source-Differentiated Analysis of U.S. Meat Demand

The Rotterdam model is used to estimate U.S. source-differentiated meat demand. Price and expenditure elasticities indicate that U.S. grain-fed beef and U.S. pork have a competitive advantage in the U.S. beef and pork markets, respectively. Expenditure elasticities reveal that beef from Canada has the most to gain from an expansion in U.S. meat expenditures, followed by ROW pork, U.S. grain-fed beef, and U.S. poultry. BSE outbreaks in Canada and the United States are shown to have small impacts on meat demand, while seasonality is found to have a significant effect in determining U.S. meat consumption patterns.
Akt inhibitor MK‐2206 in combination with bendamustine and rituximab in relapsed or refractory chronic lymphocytic leukemia: Results from the N1087 alliance study

Akt is a downstream target of B cell receptor signaling and is a central regulator of CLL cell survival. We aim to investigate the safety and efficacy of the Akt inhibitor MK‐2206 in combination with bendamustine and rituximab (BR) in relapsed and/or refractory CLL in a phase I/II study. A standard phase I design was used with cohorts of three plus three patients to determine the maximum tolerated dose (MTD) of MK‐2206 in combination with BR in relapsed CLL. Single‐agent MK‐2206 (weekly dosed) was administered one‐week in advance before BR on cycle 1 and subsequently was given with BR at the same time for cycle 2‐6. Phase II employed the MTD of MK‐2206 with BR to evaluate safety and efficacy of this study combination. Thirteen relapsed/refractory CLL were treated for maximal 6‐cycle of therapy. The maximum tolerated dose of MK‐2206 was 90 mg by mouth once weekly. The most common grade 3/4 adverse events were neutropenia (46%), febrile neutropenia (23%), rash (15%), diarrhea (15%), and thrombocytopenia (15%). Overall response rate was 92% with a median progression free survival and treatment free survival of 16 and 24 months, respectively. Five patients (38%) achieved complete remission or complete remission with incomplete count recovery, two of whom were MRD negative. The efficacy and tolerability of this combination indicates that Akt inhibition combined with chemoimmunotherapy is a promising novel treatment combination in CLL and deserves further prospective clinical trial.