Miracle-dz/UniFAR-FTUs huggingface dataset:
Processing of Human Cytomegalovirus UL37 Mutant Glycoproteins in the Endoplasmic Reticulum Lumen prior to Mitochondrial Importation

ABSTRACT The human cytomegalovirus (HCMV) UL37 glycoprotein (gpUL37) is internally cleaved and its products divergently traffic to mitochondria or are retained in the secretory pathway. To define the requirements for gpUL37 cleavage, residues −1 and −3 of the consensus endoplasmic reticulum (ER) signal peptidase I site within exon 3 (UL37x3) were replaced by bulky tyrosines (gpUL37 cleavage site mutant I). Internal cleavage of this UL37x3 mutant was inhibited, verifying usage of the consensus site at amino acids (aa) 193/194. The full-length mitochondrial species of gpUL37 cleavage site mutant I was N glycosylated and endoglycosidase H sensitive, indicating that ER translocation and processing took place prior to its mitochondrial importation. Moreover, these results suggest that internal cleavage of gpUL37 is not necessary for its N glycosylation. Partial deletion or disruption of the UL37 hydrophobic core immediately upstream of the cleavage site resulted in decreased protein abundance, suggesting that the UL37x3 hydrophobic α-helix contributes to either correct folding or stability of gpUL37. Insertion of the UL37x3 hydrophobic core and cleavage site into pUL37M, a splice variant of gpUL37 which lacks these sequences and is neither proteolytically cleaved nor N glycosylated, resulted in its internal cleavage and N glycosylation. Its NH2-terminal fragment, pUL37M-NH2, was detected more abundantly in mitochondria, while its N-glycosylated C-terminal fragment, gpUL37M-COOH, was detected predominantly in the ER in a manner analogous to that of gpUL37 cleavage products. These results indicate that UL37x3 aa 178 to 205 are prerequisite for gpUL37 internal cleavage and alter UL37 protein topology allowing N glycosylation of its C-terminal sequences. In contrast, the NH2-terminal UL37x1 hydrophobic leader, present in pUL37x1, pUL37M, and gpUL37, is not cleaved from mature UL37 protein, retaining a membrane anchor for UL37 isoforms during trafficking. Taken together, these results suggest that HCMV gpUL37 undergoes sequential trafficking, during which it is ER translocated, processed, and then mitochondrially imported.
Education’s not black and white, it’s vibrant grey

This paper offers a learner’s eye-view of a journey through education, written in an auto-narrative style. Sarah’s story spans from Secondary School to College and through University finishing at the point of Graduation. Revealed in this open and honest account is an insight to coping with home life whilst navigating the trials of the Education system. Sarah makes criticisms of her peers at every level reminding us how competitive some students have to be to get on and achieve success in their education. Critical judgements are also made about Sarah’s School teachers and University lecturers, which are at times as rewarding as they are uncomfortable, but always truthful. Consequently, there is much to learn by both academics and students from this sensitive and vulnerable personal revelation. Sarah’s evidence in turn points to some fundamental questions about the genuine outcomes of the Educational system, e.g. what are we actually teaching young people to be like? And do we like the product in terms of their values, beliefs and motives? A concluding message from Sarah’s perspective is that greater independence in learning, freedom in thinking and equipping people to reason, judge and make decisions in whatever realm, may be defining steps towards becoming educated.
The explained effects of computer mediated conferencing on student learning outcomes and engagement

There has been an increasing growth in the use of technology resources in traditional classroom styled higher education courses. This growth has received with both optimism and criticism. One of the issues critics have posed is that the use of technology resources does little, if anything, to improve student learning. As a result, this research examined if the use of technology contributes to student learning outcomes and student engagement activities, above and beyond student demographic variables. Specifically, this study investigated if the use of computer mediated conferencing (CMC) tools (i.e., email and electronic discussion boards) and computer aided instructional (CAI) resources (i.e., use of the computer and the Internet) contribute to student learning. Included in the sample were 2000 college students, which were randomly drawn from the 2003 College Student Experience Questionnaire database. The survey included 53 Likert scale items with reliability ranges from . 78 to . 88 on each of the composite scales. For the data analysis, eight multiple regressions were conducted on student learning outcomes and student learning engagement. Student learning outcomes included four composite scales, measuring students' personal and social development, general education gains, intellectual development, science and technology gains, and vocational preparation. The student engagement scale was comprised of three composite scales, which included faculty interactions, social, political and scientific discussions, and diversity and social interactions. The findings revealed that the use of technology resources does contribute to student learning, above and beyond student's background variables. The model inclusive of technology variables explained 4% to 7% of the gains in student learning, while student background variables contributed . 03% to 2% of the gains. The findings suggest incorporating the use of technology can aid students in the learning process, though the effect size was fairly modest in most cases. The use of computer mediated conferencing and computer assisted learning tools should be used in combination with traditional classroom instructions to have the best effects.
Identification of the Nuclear Export Signal and STAT-Binding Domains of the Nipah Virus V Protein Reveals Mechanisms Underlying Interferon Evasion

ABSTRACT The V proteins of Nipah virus and Hendra virus have been demonstrated to bind to cellular STAT1 and STAT2 proteins to form high-molecular-weight complexes that inhibit interferon (IFN)-induced antiviral transcription by preventing STAT nuclear accumulation. Analysis of the Nipah virus V protein has revealed a region between amino acids 174 and 192 that functions as a CRM1-dependent nuclear export signal (NES). This peptide is sufficient to complement an export-defective human immunodeficiency virus Rev protein, and deletion and substitution mutagenesis revealed that this peptide is necessary for both V protein shuttling and cytoplasmic retention of STAT1 and STAT2 proteins. However, the NES is not required for V-dependent IFN signaling inhibition. IFN signaling is blocked primarily by interaction between Nipah virus V residues 100 to 160 and STAT1 residues 509 to 712. Interaction with STAT2 requires a larger Nipah virus V segment between amino acids 100 and 300, but deletion of residues 230 to 237 greatly reduced STAT2 coprecipitation. Further, V protein interactions with cellular STAT1 is a prerequisite for STAT2 binding, and sequential immunoprecipitations demonstrate that V, STAT1, and STAT2 can form a tripartite complex. These findings characterize essential regions for Henipavirus V proteins that represent potential targets for therapeutic intervention.
Real-time Analysis of G Protein-coupled Receptor Reconstitution in a Solubilized System*

Receptor based signaling mechanisms are the primary source of cellular regulation. The superfamily of G protein-coupled receptors is the largest and most ubiquitous of the receptor mediated processes. We describe here the analysis in real-time of the assembly and disassembly of soluble G protein-coupled receptor-G protein complexes. A fluorometric method was utilized to determine the dissociation of a fluorescent ligand from the receptor solubilized in detergent. The ligand dissociation rate differs between a receptor coupled to a G protein and the receptor alone. By observing the sensitivity of the dissociation of a fluorescent ligand to the presence of guanine nucleotide, we have shown a time- and concentration-dependent reconstitution of theN-formyl peptide receptor with endogenous G proteins. Furthermore, after the clearing of endogenous G proteins, purified Gα subunits premixed with bovine brain Gβγ subunits were also able to reconstitute with the solubilized receptors. The solubilizedN-formyl peptide receptor and Gαi3 protein interacted with an affinity of ∼10−6 m with other α subunits exhibiting lower affinities (Gαi3 > Gαi2 > Gαi1 ≫ Gαo). TheN-formyl peptide receptor-G protein interactions were inhibited by peptides corresponding to the Gαi C-terminal regions, by Gαi mAbs, and by a truncated form of arrestin-3. This system should prove useful for the analysis of the specificity of receptor-G protein interactions, as well as for the elucidation and characterization of receptor molecular assemblies and signal transduction complexes.
Regulation of RARβ expression by RAR‐ and RXR‐selective retinoids in human lung cancer cell lines: Effect on growth inhibition and apoptosis induction

Retinoids regulate the growth and differentiation of human tracheobronchial epithelial cells. In this study, we investigated the effects of all‐trans‐retinoic acid (trans‐RA) and receptor class‐selective retinoids on the growth and apoptosis of human lung cancer cell lines. Trans‐RA significantly inhibited the growth of Calu‐6 and H460 cells, accompanied by induction of RA receptor (RAR)β expression. In contrast, it had little effect on the growth of H292, SK‐MES‐1 and H661 lung cancer cell lines, in which RARβ expression was not induced. Stable expression of RARβ in RARβ‐negative, trans‐RA‐resistant SK‐MES‐1 and H661 lung cancer cells led to recovery of trans‐RA‐induced growth inhibition, which occurred, however, only at low serum concentration. Using fluorescent microscopy and the terminal deoxyribonucleotidyl transferase (TdT) assay, we demonstrated that induction of apoptosis by trans‐RA contributed to its growth‐inhibitory effect in trans‐RA‐sensitive lung cancer cell lines. Analysis of RAR‐selective and retinoid X receptor (RXR)‐selective retinoids showed that activation of both RARs and RXRs could induce growth inhibition in trans‐RA‐sensitive lung cancer cells. Also, an additive synergistic effect on growth inhibition and RARβ induction was observed when cells were treated with combinations of RAR‐selective and RXR‐selective retinoids. Together, our results show that expression of RARβ plays a role in mediating retinoid response in lung cancer cells and that activation of RARs or RXRs contributes to induction of RARβ, growth inhibition and apoptosis by retinoids. Int. J. Cancer 75:88–95, 1998. © 1998 Wiley‐Liss, Inc.
Follicle Structure Influences the Availability of Oxygen to the Oocyte in Antral Follicles

The ability of an oocyte to successfully mature is highly dependent on intrafollicular conditions, including the size and structure of the follicle. Here we present a mathematical model of oxygen transport in the antral follicle. We relate mean oxygen concentration in follicular fluid of bovine follicles to the concentration in the immediate vicinity of the cumulus-oocyte complex (COC). The model predicts that the oxygen levels within the antral follicle are dependent on the size and structure of the follicle and that the mean level of dissolved oxygen in follicular fluid does not necessarily correspond to that reaching the COC.
Hybridization at an ecotone: ecological and genetic barriers between three Iberian vipers

The formation of stable genetic boundaries between emerging species is often diagnosed by reduced hybrid fitness relative to parental taxa. This reduced fitness can arise from endogenous and/or exogenous barriers to gene flow. Although detecting exogenous barriers in nature is difficult, we can estimate the role of ecological divergence in driving species boundaries by integrating molecular and ecological niche modelling tools. Here, we focus on a three‐way secondary contact zone between three viper species (Vipera aspis, V. latastei and V. seoanei) to test for the contribution of ecological divergence to the development of reproductive barriers at several species traits (morphology, nuclear DNA and mitochondrial DNA). Both the nuclear and mitochondrial data show that all taxa are genetically distinct and that the sister species V. aspis and V. latastei hybridize frequently and backcross over several generations. We find that the three taxa have diverged ecologically and meet at a hybrid zone coincident with a steep ecotone between the Atlantic and Mediterranean biogeographical provinces. Integrating landscape and genetic approaches, we show that hybridization is spatially restricted to habitats that are suboptimal for parental taxa. Together, these results suggest that niche separation and adaptation to an ecological gradient confer an important barrier to gene flow among taxa that have not achieved complete reproductive isolation.
Attending to the role of identity exploration in self-esteem

Although research suggests an interplay between identity development and self-esteem, most studies focused on the role of identity commitment and measured only level of self-esteem. This study examined longitudinal associations between Berzonsky’s (2011) styles of identity exploration and two distinct features of self-esteem: level of self-esteem and contingent self-esteem. Participants were 167 college students (mean age = 19 years; 66% female) who completed questionnaires tapping into identity styles and features of self-esteem at two measurement waves separated by a 4-month interval. Both information-oriented and normative styles were found to be predicted by contingent self-esteem. Follow-up analyses demonstrated that the content of contingent self-esteem predicting both identity styles was different. A diffuse-avoidant identity style was predicted mainly by low levels of self-esteem. Although we also observed some effects of identity styles on the self-esteem variables, the self-esteem variables had overall a more consistent influence on the identity styles than the other way around.
Goal-directed, dynamic animation of human walking

This paper presents a hybrid approach to the animation of human locomotion which combines goal-directed and dynamic motion control. Knowledge about a locomotion cycle is incorporated into a hierarchical control process. The desired locomotion is conveniently specified at the top level as a task (e.g. walk at speed v), which is then decomposed by application of the concepts of step symmetry and state-phase-timings. As a result of this decomposition, the forces and torques that drive the dynamic model of the legs are determined by numerical approximation techniques. Rather than relying on a general dynamic model, the equations of motion of the legs are tailored to locomotion and analytically constrained to allow for only a specific range of movements. The dynamics of the legs produce a generic, natural locomotion pattern which is visually upgraded by some kinematic "cosmetics" derived from such principles as virtual leg and determinants of gait. A system has been implemented based on these principles and has shown that when a few parameters, such as velocity, step length and step frequency are specified, a wide variety of human walks can be generated in almost real-time.
Deficiency of ovarian ornithine decarboxylase contributes to aging‐related egg aneuploidy in mice

It has been known for more than four decades that during mammalian estrous cycles, luteinizing hormone stimulates a transitory rise in the ovaries of ornithine decarboxylase (ODC) activity and its enzymatic product putrescine, concurrent with oocyte maturation in vivo. Inhibition of this transitory ODC/putrescine rise, however, does not appear to affect oocyte maturation or ovulation. Using several mouse models and combining in vitro and in vivo approaches, we demonstrated that deficiency of ODC during oocyte maturation is correlated with increased levels of egg aneuploidies. These results suggest that the transitory ovarian ODC rise in late proestrus is important for ensuring proper chromosome segregation during oocyte maturation. Older mice (8 months of age) exhibited about 1/3 that of young mice in LH‐stimulated ovarian ODC activity and a corresponding increase in egg aneuploidies. Moreover, a combination of putrescine supplementation in mouse drinking water leading up to oocyte retrieval and in oocyte maturation medium reduced egg aneuploidies of the older mice from 12.7% to 5.3%. Therefore, ovarian ODC deficiency might be an important etiology of maternal aging‐related aneuploidies, and peri‐ovulatory putrescine supplementation might reduce the risk of aneuploid conceptions in older women.
Perceptions of Male and Female STEM Aptitude

This study investigated evaluations and advice communicated to male and female technology interns experiencing work difficulties, using a 2 (workplace issue: ability or interpersonal) ×2 (intern gender: male vs. female) between-subjects experimental design. Technology professionals rated hypothetical interns on competence, qualifications, intelligence, and potential field issues. Results suggest that female interns with ability issues are viewed as having lower field aptitude than male interns with ability issues, when judged by individuals holding both hostile and benevolent sexist beliefs. Rater gender was not a significant predictor of aptitude rating. Aptitude assessments of male and female interns with interpersonal issues did not differ; however, open-ended analyses revealed that male interns were expected to be agentic and dissuaded from help seeking when facing interpersonal issues, while female interns were expected to find mentors and control their emotions. Findings show how sexist beliefs, workplace issues, and intern gender can affect responses and assessments by potential mentors.
Effects of listener factors and stimulus properties on the intelligibility, comprehensibility and accentedness of L2 speech

The intelligibility, comprehensibility and foreign accentedness of native and Polish-accented English sentences were evaluated by six Polish, six Spanish and six English speakers. The nonnative data were also analyzed for segmental and word stress errors. Results indicated that the three measures were partially independent of one another, supporting earlier findings that accented speech can be intelligible and comprehensible. An interlanguage speech intelligibility detriment was observed for Spanish listeners, but no clear evidence of an interlanguage speech intelligibility benefit was found, as nonnative listeners never outperformed native listeners. The number of segmental errors, rather than lexical stress errors, was found to correlate with comprehensibility and accentedness ratings of nonnative speech, but not with intelligibility scores. In general, the results point to a greater effect of stimulus properties than of listeners’ L1s in the perception of nonnative speech.
Active and passive smoking and development of glucose intolerance among young adults in a prospective cohort: CARDIA study

Abstract Objective To assess whether active and passive smokers are more likely than non-smokers to develop clinically relevant glucose intolerance or diabetes. Design Coronary artery risk development in young adults (CARDIA) is a prospective cohort study begun in 1985-6 with 15 years of follow-up. Setting Participants recruited from Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota; and Oakland, California, USA. Participants Black and white men and women aged 18-30 years with no glucose intolerance at baseline, including 1386 current smokers, 621 previous smokers, 1452 never smokers with reported exposure to secondhand smoke (validated by serum cotinine concentrations 1-15 ng/ml), and 1113 never smokers with no exposure to secondhand smoke. Main outcome measure Time to development of glucose intolerance (glucose ≥ 100 mg/dl or taking antidiabetic drugs) during 15 years of follow-up. Results Median age at baseline was 25, 55% of participants were women, and 50% were African-American. During follow-up, 16.7% of participants developed glucose intolerance. A graded association existed between smoking exposure and the development of glucose intolerance. The 15 year incidence of glucose intolerance was highest among smokers (21.8%), followed by never smokers with passive smoke exposure (17.2%), and then previous smokers (14.4%); it was lowest for never smokers with no passive smoke exposure (11.5%). Current smokers (hazard ratio 1.65, 95% confidence interval 1.27 to 2.13) and never smokers with passive smoke exposure (1.35, 1.06 to 1.71) remained at higher risk than never smokers without passive smoke exposure after adjustment for multiple baseline sociodemographic, biological, and behavioural factors, but risk in previous smokers was similar to that in never smokers without passive smoke exposure. Conclusion These findings support a role of both active and passive smoking in the development of glucose intolerance in young adulthood.
[Mobbing--special reference to the nursing profession].

INTRODUCTION Heinz Leymann defined this phenomenon as a hostile and unethical communication. In his definition Leymann points out that the distinction between "conflict" and "mobbing" does not focus on what is done or how it is done, but rather on the frequency and duration of whatever is done. The exposure to the strain of mobbing begins to result in psychiatrically or psychosomatically pathological conditions due to the accumulation of negative emotions. Leyman emphasizes four main factors which cause harrasment in the workplace: lack of clarity of goals in work, inadequate management, victim's social status and low moral standards in the work environment. EPIDEMIOLOGICAL FINDINGS The epidemiological data in the European Union, indicate great national differences relative to the percentage of those subjected to mobbing, with increasing exposure rates in all professions, the highest being found in education (14%) and health services. MOBBING IN NURSING PROFESSION Nurses are considered a professional group at a rather high risk for trauma caused by harrasment in the workplace. "Horizontal violence" is a widely used term regarding mobbing aclions in nursing profession even though vertical violence is present both in this profession and all other health services. Horizontal violence is implied due to the traditional assumption that nurses have a subordinate role compared to doctors, which often brings them into conflict with their peers. CONCLUSION Mobbing may be prevented by systematic primary prevention, information, education, and training in communication skills. As a result, we could expect to get a higher quality of nursing care and healthier nurses.
Perpetuating the Myth of the Culture War Court? Issue Attention in Newspaper Coverage of U.S. Supreme Court Nominations

Using digital text analysis methods, we analyze over 3800 newspaper articles covering U.S. Supreme Court judicial appointments between 1981 and 2009 to measure the level of (in)congruence between the Court’s agenda and the issues emphasized by the media. We find that newspapers highlight “culture war” issues at the expense of other important issues addressed much more frequently by the Court. Moreover, abortion in particular receives attention in more articles and in much greater depth than any other issue. With a few minor deviations, these patterns are consistent across nominations. These findings raise normative concerns regarding the didactic function of the print media in American democracy and shed empirical light on positive theories of media behavior.