Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification and Functional Characterization of Phosphorylation Sites of the Human Papillomavirus 31 E8^E2 Protein

ABSTRACT The papillomavirus E2 protein regulates transcription, replication, and nuclear retention of viral genomes. Phosphorylation of E2 in the hinge region has been suggested to modulate protein stability, DNA-binding activity, and chromosomal attachment. The papillomavirus E8^E2 protein shares the hinge domain with E2 and acts as a repressor of viral replication. Mass spectrometry analyses of human papillomavirus 31 (HPV31) E8^E2 and E2 proteins identify phosphorylated S78, S81, and S100 in E8^E2 and S266 and S269 in E2 in their hinge regions. Phos-tag analyses of wild-type and mutant proteins indicate that S78 is a major phosphorylation site in E8^E2, but the corresponding S266 in E2 is not. Phosphorylation at S78 regulates E8^E2's repression activity of reporter constructs, whereas the corresponding E2 mutants do not display a phenotype. Phosphorylation at S78 does not alter E8^E2's protein stability, nuclear localization, or binding to DNA or to cellular NCoR/SMRT complexes. Surprisingly, in the context of HPV31 genomes, mutation of E8^E2 S78 does not modulate viral replication or transcription in undifferentiated or differentiated cells. However, comparative transcriptome analyses of differentiated HPV31 E8^E2 S78A and S78E cell lines reveal that the expression of a small number of cellular genes is changed. Validation experiments suggest that the transcription of the cellular LYPD2 gene is altered in a phospho-S78 E8^E2-dependent manner. In summary, our data suggest that phosphorylation of S78 in E8^E2 regulates its repression activity by a novel mechanism, and this seems to be important for the modulation of host cell gene expression but not viral replication. IMPORTANCE Posttranslational modification of viral proteins is a common feature to modulate their activities. Phosphorylation of serine residues S298 and S301 in the hinge region of the bovine papillomavirus type 1 E2 protein has been shown to restrict viral replication. The papillomavirus E8^E2 protein shares the hinge domain with E2 and acts as a repressor of viral replication. A large fraction of HPV31 E8^E2 is phosphorylated at S78 in the hinge region, and this is important for E8^E2's repression activity. Surprisingly, phosphorylation at S78 in E8^E2 has no impact on viral replication in tissue culture but rather seems to modulate the expression of a small number of cellular genes. This may indicate that phosphorylation of viral transcription factors serves to broaden their target gene specificity.
Prehospital triage for endovascular clot removal in acute stroke patients

To establish prehospital triage in accordance with the new guidelines for endovascular therapy, we retrospectively analyzed the monitoring data of the city‐wide transportation system using the Maria Prehospital Stroke Scale (MPSS), a novel prehospital stroke scale for emergency medical technicians (EMTs) to predict the likelihood of thrombolytic therapy after transportation.
Object segmentation and recognition in 3D point cloud with language model

We proposed a recognition algorithm based on feature extraction and Bag-of-words with language model. Object recognition in 3D rang data of big scene has become an increasingly popular research topic in intelligent vehicle area. Firstly we introduce a fast ground filtering and clustering method and a convenient method to generation training samples. Then we proposed a feature extraction method based on 3D SIFT and FPFH to get descriptors with scale-invariant and rotation-invariant in 3D range data. Furthermore, we proposed a recognition algorithm based on bag-of-words and language model by add spatial semantic information to bag-of-words model to make up the shortcoming of ignoring the relationships between the visual words. At last, experimental results on real laser data depicting rural scenes are presented.
Animal models of Kennedy disease

SummarySince the identification of the polyglutamine repeat expansion responsible for Kennedy disease (KD) more than a decade ago, several laboratories have created animal models for KD. The slowly progressive nature of KD, its X-linked dominant mode of inheritance, and its recently elucidated hormone dependence have made the modeling of this lower motor neuron disease uniquely challenging. Several models have been generated in which variations in specificity, age of onset, and rate of progression have been achieved. Animal models that precisely reproduce the motor neuron specificity, delayed onset, and slow progression of disease may not support preclinical therapeutics testing, whereas models with rapidly progressing symptoms may preclude the ability to fully elucidate pathogenic pathways. Drosophila models of KD provide unique opportunities to use the power of genetics to identify pathogenic pathways at work in KD. This paper reviews the new wealth of transgenic mouse and Drosophila models for KD. Whereas differences, primarily in neuropathological findings, exist in these models, these differences may be exploited to begin to elucidate the most relevant pathological features of KD.
Oolong tea and LR‐White resin: a new method of plant sample preparation for transmission electron microscopy

Simplifying sample processing, shortening the sample preparation time, and adjusting procedures to suitable for new health and safety regulations, these issues are the current challenges which electron microscopic examinations need to face. In order to resolve these problems, new plant tissue sample processing protocols for transmission electron microscopy should be developed. In the present study, we chose the LR‐White resin‐assisted processing protocol for the ultrastructural observation of different types of plant tissues. Moreover, we explored Oolong tea extract (OTE) as a substitute for UA in staining ultrathin sections of plant samples. The results revealed that there was no significant difference between the OTE double staining method and the traditional double staining method. Furthermore, in some organelles, such as mitochondria in root cells of tomatoes and chloroplast in leaf cells of watermelons, the OTE double staining method achieved little better results than the traditional double staining method. Therefore, OTE demonstrated good potentials in replacing UA as a counterstain on ultrathin sections. In addition, sample preparation time was significantly shortened and simplified using LR‐White resin. This novel protocol reduced the time for preparing plant samples, and hazardous reagents in traditional method (acetone and UA) were also replaced by less toxic ones (ethanol and OTE).
Programmable RNA-binding protein composed of repeats of a single modular unit

Significance The ability to monitor and perturb RNAs in living cells would benefit greatly from a protein architecture that targets RNA sequences in a programmable way. We report four protein building blocks, which we call Pumby modules, each of which targets one RNA base and can be concatenated in chains of varying composition and length. The Pumby building blocks will open up many frontiers in the measurement, manipulation, and biotechnological utilization of unmodified RNAs in intact cells and systems. The ability to monitor and perturb RNAs in living cells would benefit greatly from a modular protein architecture that targets unmodified RNA sequences in a programmable way. We report that the RNA-binding protein PumHD (Pumilio homology domain), which has been widely used in native and modified form for targeting RNA, can be engineered to yield a set of four canonical protein modules, each of which targets one RNA base. These modules (which we call Pumby, for Pumilio-based assembly) can be concatenated in chains of varying composition and length, to bind desired target RNAs. The specificity of such Pumby–RNA interactions was high, with undetectable binding of a Pumby chain to RNA sequences that bear three or more mismatches from the target sequence. We validate that the Pumby architecture can perform RNA-directed protein assembly and enhancement of translation of RNAs. We further demonstrate a new use of such RNA-binding proteins, measurement of RNA translation in living cells. Pumby may prove useful for many applications in the measurement, manipulation, and biotechnological utilization of unmodified RNAs in intact cells and systems.
Comparison of the efficacy of continuous i.v. infusion versus continuous regional arterial infusion of nafamostat mesylate for severe acute pancreatitis

Continuous regional arterial infusion (CRAI) of protease inhibitors may be effective in the treatment of severe acute pancreatitis (SAP), but it is more invasive than i.v. infusion. The purpose of this study was to examine the effectiveness of continuous i.v. infusion (CIVI) for SAP compared with CRAI by unifying the dose and the administration period of nafamostat mesylate.
Reducing the stigma associated with anorexia nervosa: An evaluation of a social consensus intervention among Australian and Chinese young women

OBJECTIVE This study examined the effectiveness of a social consensus intervention in reducing stigma toward individuals with anorexia nervosa (AN) among women from Australia and mainland China. Moreover, the different predictions of informational/normative social influence theory and the social identity approach in terms of the effectiveness of the social consensus intervention were investigated. METHOD Participants were female students from the Australian National University (n = 97) and Central China Normal University (n = 76) who reported their levels of stigma toward a fictional character with AN before and after receiving normative information regarding the attitudes of others toward people with AN. Three experimental conditions of normative information were utilized: in-group, out-group, and neutral. RESULTS Chinese participants reported higher levels of baseline stigma across all measures than Australian participants. Social consensus was effective in reducing most types of AN stigma, and supported the social identity approach in that improvements in attitudinal, affective, and behavioral aspects of stigma were significantly greater for participants in the in-group (but not the out-group) versus the neutral condition. The effectiveness of the social consensus approach was not moderated by nationality. DISCUSSION A social consensus approach holds potential as an additional strategy for reducing AN stigma, with its benefits extending across diverse cultural settings. Such an approach would entail ensuring that positive messages regarding people with AN are delivered by members of a valued in-group.
Should We Stop Thinking About Inhibition? Searching for Individual and Age Differences in Inhibition Ability

Inhibition is often conceptualized as a unitary construct reflecting the ability to ignore and suppress irrelevant information. At the same time, it has been subdivided into inhibition of prepotent responses (i.e., the ability to stop dominant responses) and resistance to distracter interference (i.e., the ability to ignore distracting information). The present study investigated the unity and diversity of inhibition as a psychometric construct, and tested the hypothesis of an inhibition deficit in older age. We measured inhibition in young and old adults with 11 established laboratory tasks: antisaccade, stop-signal, color Stroop, number Stroop, arrow flanker, letter flanker, Simon, global-local, positive and negative compatibility tasks, and n-2 repetition costs in task switching. In both age groups, the inhibition measures from individual tasks had good reliabilities, but correlated only weakly among each other. Structural equation modeling identified a 2-factor model with factors for inhibition of prepotent responses and resistance to distracter interference. Older adults scored worse in the inhibition of prepotent response, but better in the resistance to distracter interference. However, the model had low explanatory power. Together, these findings call into question inhibition as a psychometric construct and the hypothesis of an inhibition deficit in older age.
Postprandial Lipid Response to High-Saturated and High-Monounsaturated Fat Meals in Normal-Weight or Overweight Women

ABSTRACT Purpose: We evaluated postprandial response of the lipid metabolism markers after the intake of a high-saturated fat (HSM) or high-monounsaturated fat meal (HMM). Methods: A randomized, controlled and acute intervention study included 63 women (age 26.9 ± 6.1 years): 35 normal weight (NW) and 28 overweight (OW) (total body fat [TBF] 24.7 ± 3.9% and 36.6 ± 3.9%, respectively). After 12 hours of fasting, each subject was given one of the two test meals standardized, including 2 muffins and water (HSM, 42.1% of saturated fat acid, or HMM, 34.5% of monounsaturated fat acid). Plasma fatty acid profile and concentrations of apolipoproteins A1 and B100, complement C3, and triacylglycerols were analyzed during fasting and at 2, 3, and 5 postprandial hours. Results: Among the markers studied, the triacylglycerol (TAG) and complement C3 were significantly higher in the OW group, compared to NW. The increment in the C3 concentration was higher after HSM intake, compared with HMM (iAUC = 4365.5 ± 5477.4 vs. 1215.2 ± 882.4; p = 0.006), with no differences between groups. After 5 hours postprandial, plasma oleic acid values remained high compared with the fasting value in the NW group, but not in the OW group (26.0 ± 4.2 vs 23.7 ± 3.9%; p < 0.001). Women with high percentage of total plasma saturated fatty acids (SFA) at the beginning of the intervention had higher incremental area under the curve (iAUC) for the palmitic, stearic, and total fatty acids (p < 0.005). Those women with a high percentage of monounsaturated fatty acids (MUFA) showed lower iAUC values for the same fatty acid profile (p < 0.005). Conclusion: This study demonstrated the effect of the HSM on postprandial increment of C3 concentration, suggesting another mechanism for saturated fat metabolism. The postprandial response to HSM appears to be the mediated by baseline lipid profile of the individuals, while the response to HMM was correlated to the weight status.
Efficacy of topical insulin in wound healing: A preliminary systematic review and meta‐analysis of randomized controlled trials

Topical insulin has been shown to promote wound healing in various studies. Considering the absence of a systematic review and quantitative synthesis on the same, the present study was carried out. Using an appropriate search strategy, electronic databases were searched for randomized controlled trials that have compared topical application of insulin in wounds with normal saline. Standardize mean differences were calculated for the following outcome measures: healing rate of ulcers/wound, percent granulation tissue growth, microvessel density, time to heal, wound area and ulcer severity score. Cochrane's risk of bias tool was used for each of the studies and RevMan 5.3 software was used to generate the pooled estimates and Forest plots. The quality of evidence was assessed by the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) working group approach. A total of 8 studies were found eligible to be included in this review and 7 for the meta‐analysis. The pooled estimates were as follows: healing rate—0.04 [−1.38, 1.46]; percent granulation tissue—10.99 [−10.07, 32.06], microvessel density—3.01 [−1.67, 7.69] and wound area—−6.59 [−9.7, −3.48]. There was only one study for each of the following outcome measures: time to heal and ulcer severity score. Hence, pooling of the results was not attempted for these outcome measures. The studies conducted in this field were preliminary and it was difficult to draw any conclusion regarding the use of insulin topically for wound healing.
Attenuated PfSPZ Vaccine induces strain-transcending T cells and durable protection against heterologous controlled human malaria infection

Significance A highly effective malaria vaccine capable of long-term protection against genetically diverse strains is urgently needed. Here, we demonstrate that a three-dose regimen of a live attenuated whole-parasite malaria vaccine conferred durable sterile protection through 33 weeks in ∼50% of subjects against a controlled human malaria infection strain that is heterologous to the vaccine strain. Prior studies by others and us have shown that T cells are critical to mediating sterile protection after live-attenuated malaria vaccination. Here, we provide evidence that this Plasmodium falciparum sporozoite vaccine (PfSPZ Vaccine) induces antigen-specific IFN-γ-producing CD8 and CD4 T cells that recognize both the homologous and the heterologous Pf strain. A live-attenuated malaria vaccine, Plasmodium falciparum sporozoite vaccine (PfSPZ Vaccine), confers sterile protection against controlled human malaria infection (CHMI) with Plasmodium falciparum (Pf) parasites homologous to the vaccine strain up to 14 mo after final vaccination. No injectable malaria vaccine has demonstrated long-term protection against CHMI using Pf parasites heterologous to the vaccine strain. Here, we conducted an open-label trial with PfSPZ Vaccine at a dose of 9.0 × 105 PfSPZ administered i.v. three times at 8-wk intervals to 15 malaria-naive adults. After CHMI with homologous Pf parasites 19 wk after final immunization, nine (64%) of 14 (95% CI, 35–87%) vaccinated volunteers remained without parasitemia compared with none of six nonvaccinated controls (P = 0.012). Of the nine nonparasitemic subjects, six underwent repeat CHMI with heterologous Pf7G8 parasites 33 wk after final immunization. Five (83%) of six (95% CI, 36–99%) remained without parasitemia compared with none of six nonvaccinated controls. PfSPZ-specific T-cell and antibody responses were detected in all vaccine recipients. Cytokine production by T cells from vaccinated subjects after in vitro stimulation with homologous (NF54) or heterologous (7G8) PfSPZ were highly correlated. Interestingly, PfSPZ-specific T-cell responses in the blood peaked after the first immunization and were not enhanced by subsequent immunizations. Collectively, these data suggest durable protection against homologous and heterologous Pf parasites can be achieved with PfSPZ Vaccine. Ongoing studies will determine whether protective efficacy can be enhanced by additional alterations in the vaccine dose and number of immunizations.
Oxidative stress and heart rate variability in patients with vertigo

Peripheral vertigo has been reported to result from oxidative stress or autonomic nervous dysfunction. Recently, heart rate variability has been used to evaluate autonomic nervous activity. Parasympathetic nervous dysfunction is associated with peripheral vertigo; however, the relationships between vertigo, oxidative stress, and autonomic nervous activity have not been investigated. The aim of this study was to elucidate the changes in oxidative stress and autonomic nervous activity in vertigo patients compared with healthy volunteers.
Computer‐aided analyses of mouse retinal OCT images – an actual application report

There is a need for automated retinal optical coherence tomography (OCT) image analysis tools for quantitative measurements in small animals. Some image processing techniques for retinal layer analysis have been developed, but reports about how useful those techniques are in actual animal studies are rare. This paper presents the use of a retinal layer detection method we developed in an actual mouse study that involves wild type and mutated mice carrying photoreceptor degeneration.
Nutrition and Physical Activity Cancer Prevention Guidelines, Cancer Risk, and Mortality in the Women's Health Initiative

Healthy lifestyle behaviors are recommended to reduce cancer risk and overall mortality. Adherence to cancer-preventive health behaviors and subsequent cancer risk has not been evaluated in a diverse sample of postmenopausal women. We examined the association between the American Cancer Society (ACS) Nutrition and Physical Activity Cancer Prevention Guidelines score and risk of incident cancer, cancer-specific mortality, and all-cause mortality in 65,838 postmenopausal women enrolled in the Women's Health Initiative Observational Study. ACS guidelines scores (0–8 points) were determined from a combined measure of diet, physical activity, body mass index (current and at age 18 years), and alcohol consumption. After a mean follow-up of 12.6 years, 8,632 incident cancers and 2,356 cancer deaths were identified. The highest ACS guidelines scores compared with the lowest were associated with a 17% lower risk of any cancer [HR, 0.83; 95% confidence interval (CI), 0.75–0.92], 22% lower risk of breast cancer (HR, 0.78; 95% CI, 0.67–0.92), 52% lower risk of colorectal cancer (HR, 0.48; 95% CI, 0.32–0.73), 27% lower risk of all-cause mortality, and 20% lower risk of cancer-specific mortality (HR, 0.80; 95% CI, 0.71–0.90). Associations with lower cancer incidence and mortality were generally strongest among Asian, black, and Hispanic women and weakest among non-Hispanic whites. Behaviors concordant with Nutrition and Physical Activity Cancer Prevention Guidelines were associated with lower risk of total, breast, and colorectal cancers and lower cancer-specific mortality in postmenopausal women. Cancer Prev Res; 7(1); 42–53. ©2014 AACR.
Mutually exclusive alternative splicing of pre‐mRNAs

Pre‐mRNA alternative splicing is an important mechanism used to expand protein diversity in higher eukaryotes, and mutually exclusive splicing is a specific type of alternative splicing in which only one of the exons in a cluster is included in functional transcripts. The most extraordinary example of this is the Drosophila melanogaster Down’s syndrome cell adhesion molecule gene (Dscam), which potentially encodes 38,016 different isoforms through mutually exclusive splicing. Mutually exclusive splicing is a unique and challenging model that can be used to elucidate the evolution, regulatory mechanism, and function of alternative splicing. The use of new approaches has not only greatly expanded the mutually exclusive exome, but has also enabled the systematic analyses of single‐cell alternative splicing during development. Furthermore, the identification of long‐range RNA secondary structures provides a mechanistic framework for the regulation of mutually exclusive splicing (i.e., Dscam splicing). This article reviews recent insights into the identification, underlying mechanism, and roles of mutually exclusive splicing.