Miracle-dz/UniFAR-FTUs huggingface dataset:
The Norovirus NS3 Protein Is a Dynamic Lipid- and Microtubule-Associated Protein Involved in Viral RNA Replication

ABSTRACT Norovirus (NoV) infections are a significant health burden to society, yet the lack of reliable tissue culture systems has hampered the development of appropriate antiviral therapies. Here we show that the NoV NS3 protein, derived from murine NoV (MNV), is intimately associated with the MNV replication complex and the viral replication intermediate double-stranded RNA (dsRNA). We observed that when expressed individually, MNV NS3 and NS3 encoded by human Norwalk virus (NV) induced the formation of distinct vesicle-like structures that did not colocalize with any particular protein markers to cellular organelles but localized to cellular membranes, in particular those with a high cholesterol content. Both proteins also showed some degree of colocalization with the cytoskeleton marker β-tubulin. Although the distribution of MNV and NV NS3s were similar, NV NS3 displayed a higher level of colocalization with the Golgi apparatus and the endoplasmic reticulum (ER). However, we observed that although both proteins colocalized in membranes counterstained with filipin, an indicator of cholesterol content, MNV NS3 displayed a greater association with flotillin and stomatin, proteins known to associate with sphingolipid- and cholesterol-rich microdomains. Utilizing time-lapse epifluorescence microscopy, we observed that the membrane-derived vesicular structures induced by MNV NS3 were highly motile and dynamic in nature, and their movement was dependent on intact microtubules. These results begin to interrogate the functions of NoV proteins during virus replication and highlight the conserved properties of the NoV NS3 proteins among the seven Norovirus genogroups. IMPORTANCE Many mechanisms involved in the replication of norovirus still remain unclear, including the role for the NS3 protein, one of seven nonstructural viral proteins, which remains to be elucidated. This study reveals that murine norovirus (MNV) NS3 is intimately associated with the viral replication complex and dsRNA. We observed that the NS3 proteins of both MNV and Norwalk virus (NV) induce prominent vesicular structures and that this formation is dependent on microtubules and cellular cholesterol. Thus, this study contributes to our understanding of protein function within different Norovirus genogroups and expands a growing knowledge base on the interaction between positive-strand RNA [(+)RNA] viruses and cellular membranes that contribute to the biogenesis of virus-induced membrane organelles. This study contributes to our understanding of viral protein function and the ability of a viral protein to recruit specific cellular organelles and lipids that enable replication.
The Fibroblast Growth Factor signaling pathway

The signaling component of the mammalian Fibroblast Growth Factor (FGF) family is comprised of eighteen secreted proteins that interact with four signaling tyrosine kinase FGF receptors (FGFRs). Interaction of FGF ligands with their signaling receptors is regulated by protein or proteoglycan cofactors and by extracellular binding proteins. Activated FGFRs phosphorylate specific tyrosine residues that mediate interaction with cytosolic adaptor proteins and the RAS‐MAPK, PI3K‐AKT, PLCγ, and STAT intracellular signaling pathways. Four structurally related intracellular non‐signaling FGFs interact with and regulate the family of voltage gated sodium channels. Members of the FGF family function in the earliest stages of embryonic development and during organogenesis to maintain progenitor cells and mediate their growth, differentiation, survival, and patterning. FGFs also have roles in adult tissues where they mediate metabolic functions, tissue repair, and regeneration, often by reactivating developmental signaling pathways. Consistent with the presence of FGFs in almost all tissues and organs, aberrant activity of the pathway is associated with developmental defects that disrupt organogenesis, impair the response to injury, and result in metabolic disorders, and cancer. WIREs Dev Biol 2015, 4:215–266. doi: 10.1002/wdev.176
A cultural algorithm for spatial forest harvest scheduling

This paper proposes a cultural algorithm for the spatial forest harvest scheduling for maximizing the total harvested timber volume, under the constraints of minimum harvest age, minimum adjacency green-up age, and approximately even volume flow for each period of the schedule. In order to increase the solution-search ability, the cultural algorithm extracts problem-specific information during the evolutionary solution search to update the belief space of a generation, which has cultural influences and guidance on the next generation. The key design of our cultural algorithm is to propose the cultural and evolutionary operators specifically for the problem. Experimental analysis shows that our cultural algorithm performs better than the previous approaches.
Chapter 5: The Effects of Welfare Reform on the Educational Outcomes of Parents and Their Children

Economic well-being and educational attainment go hand in hand. Linked to future employability and financial well-being, education is often considered the primary way to “get ahead” in society. It is ironic, then, that even as the Bush administration touts the importance of education, particularly for disadvantaged children, education for low-income adults has taken a back seat in recent years to the “work-first” approach of welfare reform. The Personal Responsibility and Work Opportunity Reconciliation Act (PRWORA) of 1996 effectively ended 61 years of federally guaranteed cash assistance to poor families and, in its place, created a time-limited program focused primarily on reducing welfare caseloads and increasing employment. Many consider the law to be the single most important welfare legislation since the inception of the system in 1935. The 1996 legislation differs from previous legislation primarily because it emphasizes the rapid movement from welfare to work and thereby greatly reduces opportunities for welfare recipients to engage in such human capital development activities as education and job training. Proponents of the “work-first” philosophy of welfare reform argued that getting parents into the workforce quickly would benefit families by providing important work experience for adults, positive role models for children, and possibly increased family income. Opponents, on the other hand, worried that strong employment requirements coupled with few supports would greatly exacerbate hardship for families already at risk. Now, years after the passage of PRWORA, the impact of welfare reform on poor families continues to be widely discussed, and it appears that policymakers on each side of the debate have had some of their objectives, as well as some of their fears, realized.
SIRT 2 regulates nuclear envelope reassembly via ANKLE 2 deacetylation

Sirtuin 2 (SIRT2) is an NAD-dependent deacetylase known to regulate microtubule dynamics and cell cycle progression. SIRT2 has also been implicated in the pathology of cancer, neurodegenerative diseases and progeria. Here we show that SIRT2 depletion or overexpression causes nuclear envelope reassembly defects. We link this phenotype to the recently identified regulator of nuclear envelope reassembly ANKLE2. ANKLE2 acetylation at K302 and phosphorylation at S662 are dynamically regulated throughout the cell cycle by SIRT2 and are essential for normal nuclear envelope reassembly. The function of SIRT2 therefore extends beyond the regulation of microtubules to include the regulation of nuclear envelope dynamics. Jo ur na l o f C el l S ci en ce • A dv an ce a rt ic le
Genetic Variants in XRCC2: New Insights Into Colorectal Cancer Tumorigenesis

Polymorphisms in DNA double-strand break repair gene XRCC2 may play an important role in colorectal cancer etiology, specifically in disease subtypes. Associations of XRCC2 variants and colorectal cancer were investigated by tumor site and tumor instability status in a four-center collaboration including three U.K. case-control studies (Sheffield, Leeds, and Dundee) and a U.S. case-control study of cases from high-risk Utah pedigrees (total: 1,252 cases and 1,422 controls). The 14 variants studied were tagging single nucleotide polymorphisms (SNP) selected from National Institute of Environmental Health Sciences/HapMap data supplemented with SNPs identified from sequencing of 125 cases chosen to represent multiple colorectal cancer groups (familial, metastatic disease, and tumor subsite). Monte Carlo significance testing using Genie software provided valid meta-analyses of the total resource that includes family-based data. Similar to reports of colorectal cancer and other cancer sites, the rs3218536 R188H allele was not associated with increased risk. However, we observed a novel, highly significant association of a common SNP, rs3218499G>C, with increased risk of rectal tumors (odds ratio, 2.1; 95% confidence interval, 1.3-3.3; Pχ2 = 0.0006) versus controls, with the largest risk found for female rectal cases (odds ratio, 3.1; 95% confidence interval, 1.6-6.1; Pχ2 = 0.0006). This difference was significantly different to that for proximal and distal colon cancers (Pχ2 = 0.02). Our investigation supports a role for XRCC2 in colorectal cancer tumorigenesis, conferring susceptibility to rectal tumors. (Cancer Epidemiol Biomarkers Prev 2009;18(9):2476–84)
Novel Relay Selection Rules for Average Interference-Constrained Cognitive AF Relay Networks

Cooperative relaying combined with selection exploits spatial diversity to significantly improve the performance of interference-constrained secondary users in an underlay cognitive radio (CR) network. However, unlike conventional relaying, the state of the links between the relay and the primary receiver affects the choice of the relay. Further, while the optimal amplify-and-forward (AF) relay selection rule for underlay CR is well understood for the peak interference-constraint, this is not so for the less conservative average interference constraint. For the latter, we present three novel AF relay selection (RS) rules, namely, symbol error probability (SEP)-optimal, inverse-of-affine (IOA), and linear rules. We analyze the SEPs of the IOA and linear rules and also develop a novel, accurate approximation technique for analyzing the performance of AF relays. Extensive numerical results show that all the three rules outperform several RS rules proposed in the literature and generalize the conventional AF RS rule.
Adenosine A2A receptor in the monkey basal ganglia: Ultrastructural localization and colocalization with the metabotropic glutamate receptor 5 in the striatum

The adenosine A2A receptor (A2AR) is a potential drug target for the treatment of Parkinson's disease and other neurological disorders. In rodents, the therapeutic efficacy of A2AR modulation is improved by concomitant modulation of the metabotropic glutamate receptor 5 (mGluR5). To elucidate the anatomical substrate(s) through which these therapeutic benefits could be mediated, pre‐embedding electron microscopy immunohistochemistry was used to conduct a detailed, quantitative ultrastructural analysis of A2AR localization in the primate basal ganglia and to assess the degree of A2AR/mGluR5 colocalization in the striatum. A2AR immunoreactivity was found at the highest levels in the striatum and external globus pallidus (GPe). However, the monkey, but not the rat, substantia nigra pars reticulata (SNr) also harbored a significant level of neuropil A2AR immunoreactivity. At the electron microscopic level, striatal A2AR labeling was most commonly localized in postsynaptic elements (58% ± 3% of labeled elements), whereas, in the GPe and SNr, the labeling was mainly presynaptic (71% ± 5%) or glial (27% ± 6%). In both striatal and pallidal structures, putative inhibitory and excitatory terminals displayed A2AR immunoreactivity. Striatal A2AR/mGluR5 colocalization was commonly found; 60–70% of A2AR‐immunoreactive dendrites or spines in the monkey striatum coexpress mGluR5. These findings provide the first detailed account of the ultrastructural localization of A2AR in the primate basal ganglia and demonstrate that A2AR and mGluR5 are located to interact functionally in dendrites and spines of striatal neurons. Together, these data foster a deeper understanding of the substrates through which A2AR could regulate primate basal ganglia function and potentially mediate its therapeutic effects in parkinsonism. J. Comp. Neurol. , 2012;520:570–589. © 2011 Wiley Periodicals, Inc.
Distributed leadership: three questions, two answers A review of the Hay Group Education research, July 2004

On 29 November, 2004, NCSL held its first distributed leadership conference. A website, and pack of materials (£30, published by NCSL) complemented this event. The pack comprises a variety of research findings on distributed leadership in schools and materials to support schools in their development of this management concept. This article summarises and reviews the research by the Hay Group Education into distributed leadership, commissioned by NCSL in July 2004. (Forthcoming articles by Arrowsmith critique the other research elements and the pack in its entirety) There are two versions of the Hay study included in the NCSL Distributed Leadership pack: a comprehensive Word file included on the CD ROM, and a 35-page A5 booklet: The Five Pillars of Distributed Leadership in Schools (Hay). As most school leaders, through pressure of time will naturally turn to the A5 booklet, this review draws predominantly on this source. The full title of the Hay research is: An investigation into the advantages and disadvantages, causes and constraints of a more distributed form of leadership in schools. There are essentially three key questions to which Hay offers both comprehensive and partial answers: they are the questions that Gronn, Spillane, Harris, Bennett and other current researchers into distributed leadership have been addressing, and continue to address: 1. What is distributed leadership? 2. How can it be achieved? 3. What are the consequences of establishing distributed leadership? Following responses to an advertisement, Russell Hobby of Hay selected schools with established distributed leadership and the following characteristics for the study:
Suburban Secondary School Principals' Perceptions of Administrative Control in Schools.

Examines the control mechanisms which superintendents used to shape and direct the work of suburban high school principals. Includes four hierarchical controls (supervision, input, behaviour and output) and two non‐hierarchical controls (section/socialization and environmental). Examines two additional areas, the social status of the school and the size of the district, for their effects on the application of the six control mechanisms. Finds the control mechanisms were used in all of the schools in varying degrees, but the extent of use across areas conveys how controls were “zoned” with tight controls (constraints) over some areas or loose controls (autonomy) over other areas. Concludes that district size does affect the variability of control and autonomy.
Rates of diagnostic transition and cognitive change at 18-month follow-up among 1,112 participants in the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing (AIBL)

ABSTRACT Background: The Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing is a prospective study of 1,112 individuals (211 with Alzheimer's disease (AD), 133 with mild cognitive impairment (MCI), and 768 healthy controls (HCs)). Here we report diagnostic and cognitive findings at the first (18-month) follow-up of the cohort. The first aim was to compute rates of transition from HC to MCI, and MCI to AD. The second aim was to characterize the cognitive profiles of individuals who transitioned to a more severe disease stage compared with those who did not. Methods: Eighteen months after baseline, participants underwent comprehensive cognitive testing and diagnostic review, provided an 80 ml blood sample, and completed health and lifestyle questionnaires. A subgroup also underwent amyloid PET and MRI neuroimaging. Results: The diagnostic status of 89.9% of the cohorts was determined (972 were reassessed, 28 had died, and 112 did not return for reassessment). The 18-month cohort comprised 692 HCs, 82 MCI cases, 197 AD patients, and one Parkinson's disease dementia case. The transition rate from HC to MCI was 2.5%, and cognitive decline in HCs who transitioned to MCI was greatest in memory and naming domains compared to HCs who remained stable. The transition rate from MCI to AD was 30.5%. Conclusion: There was a high retention rate after 18 months. Rates of transition from healthy aging to MCI, and MCI to AD, were consistent with established estimates. Follow-up of this cohort over longer periods will elucidate robust predictors of future cognitive decline.
Verb Argument Structure Processing: The Role of Verb-Specific and Argument-Specific Information☆☆☆

Abstract The processing of semantic and structural information concerning the relation between a verb and its arguments is investigated in German in two experiments: In Experiment 1 the verb precedes all its arguments, whereas in Experiment 2 all arguments precede the verb. In both experiments, participants read sentences containing a semantic violation concerning the thematic role, a violation of the number of arguments, or a violation of the grammatical type of the argument (direct versus indirect object) indicated by case marking. Event-related brain potentials (ERPs) were recorded during sentence reading. ERPs displayed different patterns for each of the violation types in the two experiments. The specific ERP patterns found for the different violation types indicate that the processes concerning the thematic role violation are primarily semantic in nature and that those concerning the grammatical type of argument are purely syntactic. Interestingly, processes concerning the number of arguments seem to trigger semantic processes followed by syntactic processes. The combined findings from the two experiments suggest that the parser uses verb-specific information to build up syntactic and thematic structures against which incoming arguments are checked and that argument-specific information can be used to build up syntactic and thematic structures against which the incoming verb has to be checked to allow lexical integration.
T Cell–Based Immunotherapy of Metastatic Renal Cell Carcinoma: Modest Success and Future Perspective

Metastatic renal cell carcinoma (MRCC) remains a challenging malignancy to treat. Cancer immunotherapies have been extensively explored in melanoma and RCC as they poorly respond to conventional cytotoxic agents but show responses to a variety of immunologic agents. The recent considerable success of T cell–based immunotherapy in melanoma warrants further efforts to apply this treatment to other cancers including MRCC. Although RCC is an immunosensitive cancer, similar attempts in MRCC have shown a very limited success. In this review, we summarize the clinical data on T cell–based immunotherapies for MRCC showing the modest success that has been achieved to date. More importantly, we discuss potential strategies for improving its efficacy for the treatment of MRCC in light of the important achievements for treating metastatic melanoma. In particular, the growing evidence of success by combining expanded tumor-infiltrating lymphocytes with lymphodepletion merits investigation in MRCC. Identifying new RCC-associated antigens, optimized methods, and conditions for detection, isolation, and/or modification and expansion of tumor-specific T cells are all important strategies to be pursued for improving T cell–based immunotherapy of MRCC. (Clin Cancer Res 2009;15(21):6503–10)
PRIMARY STUDENT TEACHERS’ UNDERSTANDING OF THE PROCESS AND EFFECTS OF DISTILLATION

One-to-one interviews were administered to a sample of thirty female, primary student teachers of different backgrounds in science. A distillation apparatus accompanied by a diagram was presented to each student and its use for distilling liquids was fully discussed. Students were then asked to describe the macroscopic and microscopic changes which would occur when different water solutions were to be distilled. The majority of the students exhibited limited understanding of the particulate nature of matter and the connection between the observable macroscopic changes (i.e., evaporation or liquefaction) and the way molecules move in relation to one another, and how they are held together. They did not also develop appropriate concepts related to boiling point, latent heat of evaporation, and fractional distillation. They had difficulties in realizing the effects of distillation on water solutions and proposed that the product of distillation would not change taste and color, or that its taste and color would be lighter. These difficulties were progressively greater for salt solution, sugar solution, tap water, aqueous alcoholic solution, tea, and coke or wine. Implications of students' conceptions on curriculum planning and teaching practices conducive to conceptual growth are discussed. [Chem. Educ. Res. Pract. Eur. : 2000, 1, 355-364]
Molecular Mechanisms of Glucose-Stimulated GLP-1 Secretion From Perfused Rat Small Intestine

Glucose is an important stimulus for glucagon-like peptide 1 (GLP-1) secretion, but the mechanisms of secretion have not been investigated in integrated physiological models. We studied glucose-stimulated GLP-1 secretion from isolated perfused rat small intestine. Luminal glucose (5% and 20% w/v) stimulated the secretion dose dependently, but vascular glucose was without significant effect at 5, 10, 15, and 25 mmol/L. GLP-1 stimulation by luminal glucose (20%) secretion was blocked by the voltage-gated Ca channel inhibitor, nifedipine, or by hyperpolarization with diazoxide. Luminal administration (20%) of the nonmetabolizable sodium-glucose transporter 1 (SGLT1) substrate, methyl-α-d-glucopyranoside (α-MGP), stimulated release, whereas the SGLT1 inhibitor phloridzin (luminally) abolished responses to α-MGP and glucose. Furthermore, in the absence of luminal NaCl, luminal glucose (20%) did not stimulate a response. Luminal glucose-stimulated GLP-1 secretion was also sensitive to luminal GLUT2 inhibition (phloretin), but in contrast to SGLT1 inhibition, phloretin did not eliminate the response, and luminal glucose (20%) stimulated larger GLP-1 responses than luminal α-MGP in matched concentrations. Glucose transported by GLUT2 may act after metabolization, closing KATP channels similar to sulfonylureas, which also stimulated secretion. Our data indicate that SGLT1 activity is the driving force for glucose-stimulated GLP-1 secretion and that KATP-channel closure is required to stimulate a full-blown glucose-induced response.
Remembering intentions: A critical review of existing experimental paradigms

Remembering that one intends to do something is distinguished from remembering what one intends to do, and crucial design requirements for research on the former are elucidated. All of the few published studies on remembering intentions are classified into four possible research paradigms and are reviewed for design adequacy in the light of these crucial requirements. It is concluded that the best, but perhaps most difficult to implement, studies in the domain are those conducted under laboratory control in which one must remember to perform a single, repeated or multiple instances of natural-seeming behaviour that one perceives to be entirely irrelevant to the purposes of the study in which one is engaged.