Miracle-dz/UniFAR-FTUs huggingface dataset:
The N-Terminal Region of Severe Acute Respiratory Syndrome Coronavirus Protein 6 Induces Membrane Rearrangement and Enhances Virus Replication

ABSTRACT The severe acute respiratory syndrome coronavirus (SARS-CoV) accessory protein 6 (p6) is a 63-amino-acid multifunctional Golgi-endoplasmic reticulum (ER) membrane-associated protein, with roles in enhancing virus replication and in evading the innate immune response to infection by inhibiting STAT1 (signal transducer and activator of transcription factor 1) translocation to the nucleus. Here, we demonstrate that p6 has an N-terminal region-cytoplasm-C-terminal region-cytoplasm configuration with residues 2 to 37 likely membrane embedded. Expression of p6, or of its N-terminal 41-amino-acid region, in the absence of other viral proteins, induced the formation of membranous structures, some of which were similar to double membrane vesicles involved in virus replication. Consistent with a role in virus replication, p6 partially colocalized with nonstructural protein 3 (nsp3), a marker for virus replication complexes. Further, while the C-terminal region is required for preventing STAT1 translocation to the nucleus, our results also indicated that the N-terminal 18 amino acids were necessary for maximal inhibition. Collectively, these results support the notion that p6 is a two-domain protein, although the function of each is not completely independent of the other.
Interaction of 4-hydroxylated estradiol and potential-sensitive Ca2+ channels in altering uterine blood flow during the estrous cycle and early pregnancy in gilts.

This study was conducted to define further the role of catechol estrogens (CE) as intermediates in estrogen-stimulated uterine hyperemia. Previous studies from our laboratory strongly suggest that changes in uterine blood flow (UBF) result from alterations in uterine arterial tone (distensibility) and/or contractility (reactivity to alpha 1-adrenergic agonists). Tone changes appear to set the baseline rate of flow, whereas contractility changes result in short-term reductions in luminal diameter. Changes in uterine arterial tone and contractility result from alterations in Ca2+ uptake through potential-sensitive channels (PSCs) and receptor-operated channels (ROCs), respectively. Uterine and mesenteric arteries were removed from 6 gilts at estrus (Day 0), 9 gilts on Day 13 of gestation (high estrogen, high UBF), and 8 gilts on Day 13 of the estrous cycle (low estrogen, low UBF). Arterial measurements included initial tone (baseline perfusion pressure [BPP] to a constant intraluminal flow) and increased tone after exposure to KCl, the contractility in response to the alpha 1-agonist phenylephrine, and specific uptake of 45Ca before and after exposure to the CE 4-hydroxylated estradiol (4OH-E2). Contractility of uterine arteries from Day 13 nonpregnant (NP) and Day 13 pregnant (P) gilts to phenylephrine were similar and significantly greater (p less than 0.01) than contractility of vessels from estrous gilts. The BPP and responses of uterine arteries from Day 13 NP gilts to KCl were greater (p less than 0.05) than the BPP and responses of arteries from Day 13 P and estrous gilts, which were similar to each other. (ABSTRACT TRUNCATED AT 250 WORDS)
Trade Secrets Law and Mobility: Evidence from 'Inevitable Disclosure'

Professional mobility has profound importance for firm strategy, innovation, and productivity. Prior work on legal constraints on mobility has focused on non-compete covenants and patents. Here, we investigate the impact of the doctrine of inevitable disclosure in U.S. state-level trade secrets law on mobility. We find that state court rulings against inevitable disclosure are associated with mobility of university-educated workers being 9.7 percent higher and mobility of less educated workers being 3.6 percent lower. On the other hand, rulings in favor of inevitable disclosure are associated with 6.9 percent less mobility for university-educated workers and 8.8 percent less mobility for other workers. The disparity in the effects on mobility is consistent with degree-qualified workers having relatively more bargaining power vis-a-vis employers than less-educated workers. We further find that the results are stronger in states that enforce non-compete covenants weakly and among employees in managerial and sales positions. Our results have implications for the degree of knowledge spillovers between firms, and thus firm strategy and ultimately, the overall economy-wide rate of innovation and economic growth.
Do We Care about Going Green? Measuring the Effect of Green Environmental Awareness, Green Product Value and Environmental Attitude on Green Culture. An Insight from Nigeria

Abstract As the environment continues to aggravate, it has become a purposeful public concern in developed countries and has recently stirred developing countries to join the green movement. Hence, this study examines green environmental awareness, green product value and environmental attitude by applying the measurement of effects on green culture. The study applied a quantitative research approach where a cross-sectional survey designed with 267 respondents’ green consumer who lived in the urban area of Abuja and employed partial least squares structural equation modelling (PLS-SEM) using SmartPLS3 to examine the developed path model. The results indicated that all constructs were empirically supported showing significant impact on green culture while examining direct relationships. The resulting (Q2) value is larger than zero (0) in the path model, this specifies that exogenous constructs have a good index for predictive relevance on the endogenous construct being investigated. Among the construct, awareness is the most important predictor and green product value tends to show a modest impact on environmental attitude. The study suggests that policymakers should place emphasis on environmental values to boost environmental awareness among young consumers in the process of making purchases. Specifically, environmental attitude was found to have full mediation on the relationship between green product value and green culture. However, no mediation occurs in the relationship between environmental awareness and green culture. The study concluded that awareness regarding going green activism in Nigeria among young consumers is still a matter of concern despite its impact and therefore, practitioners and collaborators in the green industry need to apply aggressive efforts to achieve this pathway, to ensure the design and implementation of effective policies that will promote going green and enhance the green circular economy.
31P NMR spectroscopy of developing cartilage produced from chick chondrocytes in a hollow‐fiber bioreactor

31P NMR was used to measure the concentrations and spin‐lattice relaxation times of phosphorus‐containing metabolites in neocartilage developing in an NMR‐compatible hollow‐fiber bioreactor over four weeks. Separate studies were performed for tissue developing from chondrocytes taken from the proximal and the distal sternum of the chick embryo. The metabolite ratio β‐ATP/Pi did not change significantly with development (proximal: β‐ATP/Pi = 0.38 ± 0.12 at one week, β‐ATP/Pi = 0.44 ± 0.07 at four weeks, P < 0.63; distal: β‐ATP/Pi = 0.39 ± 0.05 at one week, β‐ATP/Pi = 0.66 ± 0.26 at four weeks, P < 0.28). ATP spin‐lattice relaxation times were found to be comparable to those in muscle and brain tissue (proximal: T1(β–ATP) = 0.5 ± 0.06 sec at one week, T1(β–ATP) = 0.4 ± 0.01 sec at four weeks; distal: T1(β–ATP) = 0.3 ± 0.12 sec at one week, T1(β–ATP) = 0.4 ± 0.04 sec at four weeks). A large increase in the spin‐lattice relaxation time of inorganic phosphate, from 1.2 ± 0.13 sec to 3.8 ± 0.04 sec (P < 0.0001) over four weeks of growth, was observed in tissue developing from chondrocytes harvested from the proximal sternum. No comparable increase in T1(Pi) was found in tissue developing from chondrocytes harvested from the distal portion of the sternum, which ossifies later in vivo. Magn Reson Med 44:367–372, 2000. Published 2000 Wiley‐Liss, Inc.
A Longitudinal Analysis of Patient Satisfaction and Subsequent Quality of Life in Hong Kong Chinese Breast and Nasopharyngeal Cancer Patients

Background:We evaluated the longitudinal course of the relationship between patient satisfaction and quality of life (QoL) in Chinese breast and nasopharyngeal cancer patients. Methods:A sample of Chinese breast (n = 250) and nasopharyngeal (n = 242) cancer patients were assessed during their first outpatient visit (baseline) and at 2 follow-up interviews (FU1 and FU2). The Chinese version of the Functional Assessment of Cancer Therapy-General Scale (FACT-G (Ch)) was adopted to assess QoL. Patient satisfaction was assessed by the 9-item Chinese Patient Satisfaction Questionnaire (ChPSQ-9) and the cognitive subscale of the Medical Interview Satisfaction Scale (MISS-Cog). Linear mixed effects models were fitted to identify predictors of patient satisfaction and QoL. Results:Recurrence after baseline (std &bgr; = 0.58; 95% CI: 0.17, 0.98; P < 0.05) was the only predictor of MISS-Cog, age (std &bgr; = 0.01; 95% CI: 0.00, 0.02; P < 0.05) and depressed mood (std &bgr; = 0.20; 95% CI: 0.10, 0.30; P < 0.001) of ChPSQ-9. After adjusting for sociodemographic and psychosocial variables, both ChPSQ-9 (std &bgr; = 0.13; 95% CI: 0.07, 0.19; P < 0.001) and MISS-Cog (std &bgr; = 0.07; 95% CI: 0.02, 0.12; P < 0.05) independently predicted FACT-G (Ch) scores. Conclusions:These findings suggest both general emotional support and informational support are important in predicting QoL among Chinese breast and nasopharyngeal cancer patients.
A voltage-sensing phosphatase, Ci-VSP, which shares sequence identity with PTEN, dephosphorylates phosphatidylinositol 4,5-bisphosphate

Phosphatidylinositol lipids play diverse physiological roles, and their concentrations are tightly regulated by various kinases and phosphatases. The enzymatic activity of Ciona intestinalis voltage sensor-containing phosphatase (Ci-VSP), recently identified as a member of the PTEN (phosphatase and tensin homolog deleted on chromosome 10) family of phosphatidylinositol phosphatases, is regulated by its own voltage-sensor domain in a voltage-dependent manner. However, a detailed mechanism of Ci-VSP regulation and its substrate specificity remain unknown. Here we determined the in vitro substrate specificity of Ci-VSP by measuring the phosphoinositide phosphatase activity of the Ci-VSP cytoplasmic phosphatase domain. Despite the high degree of identity shared between the active sites of PTEN and Ci-VSP, Ci-VSP dephosphorylates not only the PTEN substrate, phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3], but also, unlike PTEN, phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. Enzymatic action on PI(4,5)P2 removes the phosphate at position 5 of the inositol ring, resulting in the production of phosphatidylinositol 4-phosphate [PI(4)P]. The active site Cys-X5-Arg (CX5R) sequence of Ci-VSP differs with that of PTEN only at amino acid 365 where a glycine residue in Ci-VSP is replaced by an alanine in PTEN. Ci-VSP with a G365A mutation no longer dephosphorylates PI(4,5)P2 and is not capable of inducing depolarization-dependent rundown of a PI(4,5)P2-dependent potassium channel. These results indicate that Ci-VSP is a PI(3,4,5)P3/PI(4,5)P2 phosphatase that uniquely functions in the voltage-dependent regulation of ion channels through regulation of PI(4,5)P2 levels.
Study on Ticks and Tick‐Borne Zoonoses in Public Parks in Italy

A survey on tick density and on tick‐borne zoonoses was carried out in four public parks in the outskirts of Imola (northern Italy) from June to October 2006. All stages of Ixodes ricinus and only larvae of Riphicephalus sanguineus were recovered by dragging, performed on 100‐m transects. Almost all ticks (99%) were harvested in one park. I. ricinus density (nymphs/100 m2) ranged from 0 in park L to 6.3 in park F. Nymphs and adults of I. ricinus were subjected to PCR for Anaplasma phagocytophilum, Bartonella spp. , Borrelia burgdorferi s. l. and Rickettsia spp. The observed prevalences were 38.3% for Bartonella henselae, 5.2% for Bartonella clarridgeiae, 10.4% for B. burgdorferi s. l. , 2.6% for Rickettsia helvetica and 13% for Rickettsia monacensis, respectively. No DNA of A. phagocytophilum was found. Acarological risks (AR) were calculated as probabilities of collecting at least one infected nymph per transect. The AR values calculated for the various zoonotic agents were 11.4% for R. helvetica, 27.7% for B. clarridgeiae, 49.7% for B. burgdorferi s. l. , 57.2% for R. monacensis and 90.4% for B. henselae, respectively. In this study, B. clarridgeiae was for the first time identified in I. ricinus ticks.
Structure of an anti‐cholera toxin antibody Fab in complex with an epitope‐derived D‐peptide: a case of polyspecific recognition

The structure of a complex of the anti‐cholera toxin antibody TE33 Fab (fragment antibody) with the D‐peptide vpGsqhyds was solved to 1.78 Å resolution. The D‐peptide was derived from the linear L‐peptide epitope VPGSQHIDS by a stepwise transformation. Despite the very similar amino acid sequence—the only difference is a tyrosine residue in position 7—there are marked differences in the individual positions with respect to their contribution to the peptide overall affinity as ascertained by a complete substitutional analysis. This is reflected by the X‐ray structure of the TE33 Fab/D‐peptide complex where there is an inverted orientation of the D‐peptide as compared with the known structure of a corresponding complex containing the epitope L‐peptide, with the side chains establishing different contacts within the binding site of TE33. The D‐ and L‐peptide affinities are comparable and the surface areas buried by complex formation are almost the same. Thus the antibody TE33 provides a typical example for polyspecific binding behavior of IgG family antibodies. Copyright © 2007 John Wiley & Sons, Ltd.
Parylene flexible neural probe with micro fluidic channel

A flexible neural probe with an integrated fluidic channel is proposed. Since parylene thin film is used as the main structure, the probe is sufficiently flexible to perform a less invasive implant for neural recording. The micro fluidic channel of this probe can be used not only to inject certain chemicals into biological tissues but also to improve mechanical stiffness prior to the insertion when the channel is filled with rigid polymer, such as polyethylene glycol (PEG), which is dissolved into the tissues. We have succeeded in inserting the probe into a rat's brain and measuring the neural signals from it.
Immunological determinants of nerve growth factor involved in p140trk (Trk) receptor binding

Monoclonal anti‐NGF antibodies that specifically inhibit the biological activity of mouse β‐NGF were used to study the structural determinants involved in the interaction of NGF with its receptors gp75LNGFR and Trk. None of the three antibodies–N60, M15, and 27/21–showed any reactivity toward denatured NGF. Three experimental methods–radioim‐munoassay (RIA), enzyme‐linked immunoassay (ELISA), and slot blots–detected no significant cross reactivity between the antibodies and BDNF or NT‐3. RIA showed that M15 and N60 recognize the same or an overlapping antigenic site, but 27/21 recognizes a different epitope. Only 27/21, and not N60 or M15, immunoprecipitated β‐NGF crosslinked to LNGFR receptor. Thus, the epitope recognized by 27/12 does not overlap the LNGFR receptor binding site. N60, M15, and 27/21 all block binding of NGF to Trk in a manner consistent with competitive inhibition. Purified Fab fragments of N60 and M15 gave similar results to the intact antibodies. The other subunits present in the 7S complex of NGF, i.e. the α and γ subunits, competitively inhibited binding of antibodies to β‐NGF. Only the γ subunit inhibited phosphorylation of Trk and biological activity of β‐NGF. These findings suggest that the M15, N60, and 27/21 antibodies bind to a specific site on the surface of NGF where they competitively inhibit binding to the Trk NGF receptor. The region encompassing the N‐terminus, the C‐terminus, and the loop on the surface of β‐NGF containing residues 60–80 is proposed as important for binding to the Trk receptoe. © 1994 Wiley‐Liss, Inc.
Evaluating the Ability of Tree‐Based Methods and Logistic Regression for the Detection of SNP‐SNP Interaction

Most common human diseases are likely to have complex etiologies. Methods of analysis that allow for the phenomenon of epistasis are of growing interest in the genetic dissection of complex diseases. By allowing for epistatic interactions between potential disease loci, we may succeed in identifying genetic variants that might otherwise have remained undetected. Here we aimed to analyze the ability of logistic regression (LR) and two tree‐based supervised learning methods, classification and regression trees (CART) and random forest (RF), to detect epistasis. Multifactor‐dimensionality reduction (MDR) was also used for comparison. Our approach involves first the simulation of datasets of autosomal biallelic unphased and unlinked single nucleotide polymorphisms (SNPs), each containing a two‐loci interaction (causal SNPs) and 98 ‘noise’ SNPs. We modelled interactions under different scenarios of sample size, missing data, minor allele frequencies (MAF) and several penetrance models: three involving both (indistinguishable) marginal effects and interaction, and two simulating pure interaction effects. In total, we have simulated 99 different scenarios. Although CART, RF, and LR yield similar results in terms of detection of true association, CART and RF perform better than LR with respect to classification error. MAF, penetrance model, and sample size are greater determining factors than percentage of missing data in the ability of the different techniques to detect true association. In pure interaction models, only RF detects association. In conclusion, tree‐based methods and LR are important statistical tools for the detection of unknown interactions among true risk‐associated SNPs with marginal effects and in the presence of a significant number of noise SNPs. In pure interaction models, RF performs reasonably well in the presence of large sample sizes and low percentages of missing data. However, when the study design is suboptimal (unfavourable to detect interaction in terms of e.g. sample size and MAF) there is a high chance of detecting false, spurious associations.
Long-term neuropsychological development in single-suture craniosynostosis treated early.

OBJECT The authors evaluated the results of complete cognitive function examinations in a series of 65 adolescents who had undergone surgery for sagittal or unicoronal craniosynostosis when they were younger than 1 year old. METHODS Each of the 65 study participants was evaluated individually. The neuropsychological assessment, consisting of a battery of tests tailored to the patient's age, cognitive level, and level of cooperation, was conducted in 2 separate sessions on the same day. The main outcome measures included fine motor skills, language, visual motor spatial and visual perceptual skills, working and visual memory, attention, executive function, and verbal fluency. RESULTS Thirty-five children (mean age 13.4 years) were affected by sagittal synostosis and 30 (mean age 14.9 years) by unicoronal synostosis (16 right-sided, 14 left-sided). The mean age at surgery was 7.2 months. All of the children had begun school at a normal age and attended regular classes. Seven percent of those with sagittal craniosynostosis demonstrated visuospatial and constructional ability defects with associated visual memory recall deficits; 17% also exhibited selective and sustained attention deficits. Approximately one-third (30%) of the children with anterior plagiocephaly had processing and planning speech deficits. CONCLUSIONS Data in this study support the hypothesis that children with sagittal or unicoronal craniosynostosis, although they undergo early surgical treatment, may still manifest lower than average results at long-term selective neuropsychological evaluations.
Characterization of an amacrine cell type of the mammalian retina immunoreactive for vesicular glutamate transporter 3

Immunocytochemical staining of vertical sections through rat, mouse, and macaque monkey retinae with antibodies against the vesicular glutamate transporter vesicular glutamate transporter 3 (vGluT3) showed a sparse population of amacrine cells. The labeled cells had similar appearances in the three species and probably represent homologous types. They were studied in detail in the rat retina. The thin varicose dendrites of vGluT3 amacrine cells formed a convoluted dendritic tree of approximately 100 μm in diameter that was bistratified in the center of the inner plexiform layer. The dendrites of vGluT3 cells were squeezed between the two strata of cholinergic dendrites. The density of vGluT3 cells was measured in retinal wholemounts and increased from 200/mm2 in peripheral retina to 400/mm2 in central retina, accounting for about 1% of all amacrine cells in the rat retina. The vGluT3 cells had a two‐ to threefold dendritic overlap, and their cell bodies formed a regular mosaic, suggesting they represent a single type of amacrine cell. The vGluT3 amacrine cells expressed glycine and glycine transporter 1 (GlyT1) but not the vesicular glycine transporter (vesicular inhibitory amino acid transporter). They also expressed glutamate; hence, there is the possibility that, comparable to cholinergic amacrine cells, they are “dual transmitter” amacrine cells. The synaptic input of vGluT3 cells was studied by electron microscopy. They received input from bipolar cells at ribbon synapses and from other amacrine cells at conventional synapses. The types of bipolar cells possibly involved with vGluT3 cells were demonstrated by double labeling sections for vGluT3 and the calcium‐binding protein CaB5. The axon terminals of type 3 and 5 bipolar cells costratified with vGluT3 dendrites, and it is possible that vGluT3 cells have ON and OFF light responses. J. Comp. Neurol. 468:251–263, 2004. © 2003 Wiley‐Liss, Inc.
The proprioceptive and agonist roles of gastrocnemius, soleus and tibialis anterior muscles in maintaining human upright posture

Humans can stand using sensory information solely from the ankle muscles. Muscle length and tension in the calf muscles (gastrocnemius and soleus) are unlikely to signal postural sways on account of balance‐related modulation in agonist activity. These facts pose two questions: (1) Which ankle muscles provide the proprioceptive information? (2) Which peripheral mechanism could modulate agonist activity? To address these issues, subjects were asked to stand normally on two force plates. Ultrasound and surface EMG were recorded from the calf and tibialis anterior (TA) muscles. For all nine subjects, changes in muscle length of TA were mainly (84 ± 9% whole trial duration) orthodoxly correlated with bodily sway (centre of gravity, CoG), i.e. in accordance with passive ankle rotation. When orthodox, TA had the highest correlation with CoG (−0.66 ± 0.07, deep compartment, P < 0.001). For five subjects, the superficial TA compartment showed counter‐intuitive changes in muscle length with CoG, probably due to the flattening of the foot and proximal attachment geometry. Gastrocnemius and soleus were usually (duration 71 ± 23 and 81 ± 16%, respectively) active agonists (paradoxically correlated with CoG) but, for short periods of time, they could be orthodox and then presented a moderate correlation (0.38 ± 0.16 and 0.28 ± 0.09, respectively) with CoG. Considering the duration and extent to which muscle length is orthodox and correlated with CoG, TA may be a better source of proprioceptive information than the active agonists (soleus and gastrocnemius). Therefore, if a peripheral feedback mechanism modulates agonist activity then reciprocal inhibition acted by TA on the calf muscles is more likely to be effective than the autogenic pathway.