Miracle-dz/UniFAR-FTUs huggingface dataset:
Core Protein Phosphorylation Modulates Pregenomic RNA Encapsidation to Different Extents in Human and Duck Hepatitis B Viruses

To clarify the role of core protein phosphorylation in pregenomic-RNA encapsidation of human and duck hepatitis B viruses (HBV and DHBV, respectively), we have examined the phosphorylation states of different forms of intracellular HBV core protein and the phenotypic effects of mutations in the phosphorylation sites of HBV and DHBV core proteins. We show that HBV core protein is phosphorylated to similar extents in the form of protein dimers and after further assembly in pregenomic RNA-containing capsids. Individual and multiple substitutions of alanine and aspartic acid for serine in the phosphorylation sites of HBV core protein resulted in site-specific and synergistic effects on RNA encapsidation, ranging from 2-fold enhancement to more than 10-fold inhibition. Core protein variants with mutations in all phosphorylation sites exhibited dominant-negative effects on RNA encapsidation by wild-type protein. The results suggest that the presence of phosphoserine at position 162 of HBV core protein is required for pregenomic-RNA encapsidation, whereas phosphoserine at position 170 optimizes the process and serine might be preferable in position 155. Examination of the pregenomic-RNA-encapsidating capacities of DHBV core protein variants, in which four phosphorylation sites were jointly mutated to alanine or aspartic acid, suggests that phosphorylation of DHBV core protein at these sites may optimize pregenomic-RNA encapsidation but that its impact is much less profound than in the case of HBV. The possible mechanisms by which RNA encapsidation may be modulated by core protein phosphorylation are discussed in the context of the observed differences between the two viruses.
Effect of Yeast CTA1 Gene Expression on Response of Tobacco Plants to Tobacco Mosaic Virus Infection1

The response of tobacco (Nicotiana tabacum L. cv Xanthi-nc) plants with elevated catalase activity was studied after infection by tobacco mosaic virus (TMV). These plants contain the yeast (Saccharomyces cerevisiae) peroxisomal catalase geneCTA1 under the control of the cauliflower mosaic virus 35S promoter. The transgenic lines exhibited 2- to 4-fold higher total in vitro catalase activity than untransformed control plants under normal growth conditions. Cellular localization of the CTA1 protein was established using immunocytochemical analysis. Gold particles were detected mainly inside peroxisomes, whereas no significant labeling was detected in other cellular compartments or in the intercellular space. The physiological state of the transgenic plants was evaluated in respect to growth rate, general appearance, carbohydrate content, and dry weight. No significant differences were recorded in comparison with non-transgenic tobacco plants. The 3,3′-diaminobenzidine-stain method was applied to visualize hydrogen peroxide (H2O2) in the TMV infected tissue. Presence of H2O2 could be detected around necrotic lesions caused by TMV infection in non-transgenic plants but to a much lesser extent in the CTA1 transgenic plants. In addition, the size of necrotic lesions was significantly bigger in the infected leaves of the transgenic plants. Changes in the distribution of H2O2 and in lesion formation were not reflected by changes in salicylic acid production. In contrast to the local response, the systemic response in upper noninoculated leaves of both CTA1 transgenic and control plants was similar. This suggests that increased cellular catalase activity influences local but not systemic response to TMV infection.
Shrub tundra ecohydrology: rainfall interception is a major component of the water balance

As shrubs expand across the Arctic, they alter all cycles in the Earth system, including the water cycle. However, the coupling of shrubs with the water cycle during summer remains poorly understood. Rainfall interception, a major cause of divergent hydrological responses between vegetated and non-vegetated environments, is particularly poorly constrained. We quantified shrub rainfall interception and redistribution in birch and alder in the Western Canadian Arctic using networks of throughfall and stemflow gauges. We find that rainfall interception losses are a major component of the water budget, as effective rainfall was reduced by 15%–30% in the birches. Underneath alders, effective rainfall was almost as large or larger than gross rainfall, but they also left a rain shadow. The spatial variability in throughfall was substantial underneath both shrub species. Stemflow was a small but non-negligible component, as the alders concentrated ∼15% of rainfall to their few vertical stems, compared to the ∼8% the birches funnelled along their numerous, predominantly skewed stems. The substantial small-scale variability in effective rainfall may create islands in which conditions for certain biogeochemical processes are particularly favourable. On larger scales, rainfall interception reduces the water yield and thus the runoff received by downstream ecosystems such as lakes. The interception losses are predicted to increase with shrub density in a way that also depends on climatic conditions, with large losses in many coastal environments. The extent to which shrub expansion leads to drier Arctic ecosystems is, however, unclear because of the complex interplay between many ecohydrological processes. Shrub rainfall interception is one major, previously overlooked piece of this puzzle.
Postpubertal Architectural Developmental Patterns Differ Between the L3 Vertebra and Proximal Tibia in Three Inbred Strains of Mice

An understanding of normal microarchitectural bone development patterns of common murine models is needed. Longitudinal, structural, and mineralization trends were evaluated by in vivo μCT over 12 time points from 6–48 wk of age at the vertebra and tibia of C3H/HeN, C57BL/6, and BALB/C mice. Longitudinal growth occurred rapidly until 8–10 wk, slowed as the growth plate bridged, and fused at 8–10 mo. Structural augmentation occurred through formation of trabeculae at the growth plate and thickening of existing ones. In the vertebrae, BV/TV increased rapidly until 12 wk in all strains. Between 12 and 32 wk, the architecture was stable with BV/TV deviating <1.1%, 1.6%, and 3.4% for the C57BL/6, BALB/C, and C3H/HeN mice. In contrast, the tibial architecture changed continuously but more moderately for BV/TV and TbTh compared with the vertebra and with comparable or larger changes for TbN and TbSp. Age‐related trabecular deterioration (decreased BV/TV and TbN; increased TbSp and structure model index) was evident at both sites at 32 wk. In all strains, the cortex continued to develop after trabecular values peaked. The temporal plateau of BMD was variable across mouse strains and site, whereas tissue mineral density was attained at ∼6 mo for all sites and strains. Geometric changes at the tibial diaphysis occurred rapidly until 8–10 wk, providing the C57BL/6 mice and C3H/HeN mice with the highest torsional and compressive rigidity, respectively. In summary, key skeletal development milestones were identified, and architectural topology at the vertebra was found to be more stable than at the tibia.
Ethical dilemmas in palliative care in traditional developing societies, with special reference to the Indian setting

Background: There are intriguing and challenging ethical dilemmas in the practice of palliative care in a traditional developing society. Objective: To review the different ethical issues involved in cancer and palliative care in developing countries, with special reference to India. Methods: Published literature on pain relief and palliative care in the developing countries was reviewed to identify ethical issues and dilemmas related to these, and ways in which ethical principles could be observed in delivery of palliative care in such countries are discussed. Results: The literature review revealed a number of ethical dilemmas and challenges that professionals, cancer patients and their families encountered during palliative care. It was noted that patients’ preferences and decisions are influenced by family members. Dilemmas leave the professionals and families confused about how ethical their actions have been. Specific ethical issues were noted in relation to the availability and use of oral morphine for pain relief, spiritual care, lack of adequate palliative care services, and palliative care education. Conclusions: The four principles of ethics posed difficulties in understanding the complex ethical issues in a developing country with a traditional background. Ethical issues need to be handled delicately and sensitively in palliative care settings, within the framework of the traditions and culture of the society and financial constraints. The possible role of ethics committees in palliative care settings to help decision-making needs to be studied and discussed.
Detraining of exercise-trained rats: effects on energetic efficiency and brown adipose tissue thermogenesis

1. Complete energy balance measurements were made in exercise-trained (treadmill running) rats subjected to 27 d of exercise detraining. 2. The 20% difference in body-weight that existed at the end of the training period between sedentary and trained rats was negated by detraining. Detrained rats had twice the body-weight gain of their untrained controls. 3. An elevation (12%) in metabolizable energy (ME) intake (relative to body-weight) was observed in detrained rats while their gross energetic efficiency was augmented by 60%. 4. Energy expenditure, excluding the estimated costs of fat and protein storage, was similar for detrained and untrained rats. Complementing the latter was the finding that thermogenesis in brown adipose tissue, a known energy buffering process, was also similar. 5. Elevated ME intake (relative to body-weight) largely contributed to the increased energetic efficiency of detrained rats.
Background to crack cocaine addiction and HIV high-risk behavior: the next epidemic.

BACKGROUND Increasing rates of sexually transmitted diseases among users of noninjection drugs prompt speculation that crack cocaine users who do not inject are at particularly high risk of HIV (human immunodeficiency virus) infection. METHODS A street recruitment technique was employed to enroll 331 primarily African-American men aged 18-29 in an area of San Francisco where crack cocaine is sold openly. One-half were regular crack users and the other half had never used the drug. Few reported injection drug use or male-to-male sex. In a face-to-face interview, participants reported on their drug use, knowledge of HIV, sexual practice, condom use, and demographic characteristics. Following counseling, each was tested for HIV and syphilis. RESULTS Comparisons showed that demographically similar, crack users reported more sexual partners in the last 12 months, more sexually transmitted diseases (STDs) in their lifetime, and greater frequencies of paying for sex, exchanging sex for drugs, and having sex with injection drug users. Users reported greater current depression, anxiety, and social isolation. They reported earlier initiation into alcohol use and less positive parenting experiences during their adolescence. CONCLUSION These results are consistent with findings that report the comorbidity of drug abuse and mental illness. Implications are drawn for reducing HIV infection among this high-risk population for early adolescent, community mental health, and substance abuse treatment programs.
Role for Hes1-Induced Phosphorylation in Groucho-Mediated Transcriptional Repression

ABSTRACT Transcriptional corepressors of the Groucho/transducin-like Enhancer of split (Gro/TLE) family regulate a number of developmental pathways in both invertebrates and vertebrates. They form transcription repression complexes with members of several DNA-binding protein families and participate in the regulation of the expression of numerous genes. Despite their pleiotropic roles, little is known about the mechanisms that regulate the functions of Gro/TLE proteins. It is shown here that Gro/TLEs become hyperphosphorylated in response to neural cell differentiation and interaction with the DNA-binding cofactor Hairy/Enhancer of split 1 (Hes1). Hyperphosphorylation of Gro/TLEs is correlated with a tight association with the nuclear compartment through interaction with chromatin, suggesting that hyperphosphorylated Gro/TLEs may mediate transcriptional repression via chromatin remodeling mechanisms. Pharmacological inhibition of protein kinase CK2 reduces the Hes1-induced hyperphosphorylation of Gro/TLEs and causes a decrease in the chromatin association of the latter. Moreover, the transcription repression activity of Gro/TLEs is reduced by protein kinase CK2 inhibition. Consistent with these observations, Gro/TLEs are phosphorylated in vitro by purified protein kinase CK2. Taken together, these results implicate protein kinase CK2 in Gro/TLE functions. They suggest further that this kinase is involved in a hyperphosphorylation mechanism activated by Hes1 that promotes the transcription repression functions of Hes1-Gro/TLE protein complexes.
Maternal cannabis use and birth weight: a meta-analysis.

AIMS To estimate the effect of maternal cannabis use on birth weight. DESIGN Meta-analysis of published observational studies adjusted for cigarette smoking. Separate analyses were performed for studies of low birth weight and mean birth weight. We used fixed and random effects models, but in all cases the results were identical. SETTING From the Medline database, we identified 10 studies in which the results were adjusted for cigarette smoking. In seven studies, information on cannabis use was collected prenatally. Five studies reported results for differences in mean birth weight associated with maternal cannabis use. PARTICIPANTS 32,483 women giving birth to live-born infants. MEASUREMENTS Mean birth weight and odds ratio for low birth weight. FINDINGS Three analyses of the studies on mean birth weight were conducted to avoid double-counting women from one study. The largest reduction in mean birth weight for any cannabis use during pregnancy was 48 g (95% confidence interval (CI) 83-14 g), with considerable heterogeneity among the five studies. Mean birth weight was increased by 62 g (95% CI 8 g reduction-132 g increase; p heterogeneity 0.59) among infrequent users (< or = weekly) whereas cannabis use at least four times per week had a 131 g reduction in mean birth weight (95% CI 52-209 g reduction; p heterogeneity 0.25). From the five studies of low birth weight, the pooled odds ratio for any use was 1.09 (95% CI 0.94-1.27, p heterogeneity 0.19). CONCLUSIONS There is inadequate evidence that cannabis, at the amount typically consumed by pregnant women, causes low birth weight.
Antimyocarditic activity of the guanine derivative BIOLF-70 in a coxsackievirus B3 murine model

Prophylactic administration of a nontoxic dose of 9-[[2-benzyloxyl-1-(benzyloxymethyl)ethoxy]methyl]-6-chlo roguanine (BIOLF-70) to mice reduced the number of myocarditic lesions induced by coxsackievirus B3 (CVB3). BIOLF-70 exhibited minimal antiviral activity against CVB3 in HeLa cells and murine neonatal skin fibroblasts and minimally reduced CVB3 yields in heart tissues. The drug had no effect on serum anti-CVB3 neutralizing antibody titers and did not induce the production of interferon. Flow microfluorometric analyses of splenic lymphocytes taken from BIOLF-70-treated, CVB3-inoculated mice at 7 days postinoculation showed that the proportion of T lymphocytes was increased, as measured by fluorescent staining of Thy-1 and Lyt-2 surface markers, compared with the proportion of T lymphocytes in splenic cells from virus-inoculated or BIOLF-70-treated or normal groups of mice. Splenic lymphocytes from BIOLF-70-treated, CVB3-inoculated mice showed reduced cytotoxic activity against CVB3-infected target fibroblasts. Splenic cells from BIOLF-70-treated, CVB3-inoculated mice had slightly higher natural killer cell activity than did those from the other three groups of mice, which had comparatively similar levels of natural killer cell activity. The data suggest that BIOLF-70 exerts antimyocarditic activity perhaps by some antiviral activity in heart tissues and by immunomodulatory mechanisms which appear to involve T suppressor or T cytotoxic lymphocyte subpopulations and natural killer cells.
Analysis of the T-cell receptor repertoire of human T-cell leukemia virus type 1 (HTLV-1) Tax-specific CD8+ cytotoxic T lymphocytes from patients with HTLV-1-associated disease: evidence for oligoclonal expansion

Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic, progressive neurological disease characterized by marked degeneration of the spinal cord and the presence of antibodies against HTLV-1. Patients with HAM/TSP, but not asymptomatic carriers, show very high precursor frequencies of HTLV-1-specific CD8+ T cells in peripheral blood and cerebrospinal fluid, suggestive of a role of these T cells in the pathogenesis of the disease. In HLA-A2+ HAM/TSP patients, HTLV-1-specific T cells were demonstrated to be directed predominantly against one HTLV-1 epitope, namely, Tax11-19. In the present study, we analyzed HLA-A2-restricted HTLV-1 Tax11-19-specific cytotoxic T cells from three patients with HAM/TSP. An analysis of the T-cell receptor (TCR) repertoire of these cells revealed an absence of restricted variable (V) region usage. Different combinations of TCR V alpha and V beta genes were utilized between, but also within, the individual patients for the recognition of Tax11-19. Sequence analysis of the TCR showed evidence for an oligoclonal expansion of few founder T cells in each patient. Apparent structural motifs were identified for the CDR3 regions of the TCR beta chains. One T-cell clone could be detected within the same patient over a period of 3 years. We suggest that these in vivo clonally expanded T cells might play a role in the pathogenesis of HAM/TSP and provide information on HTLV-1-specific TCR which may elucidate the nature of the T cells that infiltrate the central nervous system in HAM/TSP patients.
Asian sand dust aggravates allergic rhinitis in guinea pigs induced by Japanese cedar pollen

Asian sand dust (ASD) contains microbial materials, sulfate (SO42−), and nitrate (NO3−), and is derived from air pollutants in East China. ASD reportedly causes adverse respiratory health effects; a case in point is aggravated allergen-associated experimental lung eosinophilia. Guinea pigs were administered normal saline (control), ASD (0.3 mg/animal), ASD (0.6 mg/animal), Japanese cedar pollen (JCP) (0.2 mg/kg body weight), JCP + ASD (0.3 mg/animal), or JCP + ASD (0.6 mg/animal), into their nasal cavities at seven weekly intervals. The number of sneezes, amount of nasal secretions, and nasal obstructing response were measured as indices of nasal responses. Total immunoglobulin E (IgE) antibodies in serum and the number of eosinophils, histamine, and arachidonic acid metabolites in nasal cavity lavage fluids (NCLF) were also measured. ASD enhanced the JCP-associated nasal obstructing response, but not the number of sneezes or amount of nasal secretions. ASD enhanced JCP-associated cysteinyl leukotrienes (C4, D4, E4) and histamine production in NCLF. ASD augmented the number of eosinophils in NCLF and total IgE in serum induced by JCP. ASD enhanced eosinophil recruitment in the nasal mucosa, and goblet cell proliferation in the nasal epithelium induced by JCP. These results suggest that ASD enhances the nasal allergic reaction induced by repeated JCP administration in guinea pigs.
Multisecond oscillations in the subthalamic nucleus: Effects of apomorphine and dopamine cell lesion

Clinical and preclinical data indicate that the subthalamic nucleus (STN) plays a critical role in mediating the hyper‐ and hypoactive behavioral states associated with increases and decreases in dopamine receptor stimulation in the basal ganglia. The present study investigates effects of dopamine receptor stimulation on slow multisecond oscillations in firing rates in STN neurons. Extracellular, single‐unit recordings were performed in locally anesthetized and immobilized rats which were either intact or had received unilateral 6‐OHDA lesions of the medial forebrain bundle. The majority (64%) of spike trains recorded from STN neurons exhibited periodic oscillations in firing rate within the range of 2–60 sec, with an average period of 24 sec. The distribution of these baseline periodicities was not altered by unilateral 6‐OHDA lesion, but periods were significantly shortened by systemic administration of the D1/D2 agonist apomorphine. This effect was observed in a greater proportion of neurons recorded from 6‐OHDA‐lesioned rats as compared to intact rats, was notably diminished in rats systemically anesthetized with chloral hydrate, and did not correlate with drug‐induced changes in firing rate. These oscillations are similar to slow periodicities in firing rate recently reported in other basal ganglia nuclei. The possibility that these periodic oscillations in firing rate play a significant role in basal ganglia function was supported by the observation that the time of onset of apomorphine induced alterations in amplitude and periodicity of slow oscillations in STN spike trains is coincident with the onset of behavioral effects of this drug in 6‐OHDA‐lesioned animals. Synapse 38:38–50, 2000. Published 2000 Wiley‐Liss, Inc.
Enhancing Brand Awareness, Reputation and Loyalty: The Role of Social Media

The paper analyzes three models in order to identify the causal combinations of social media usage and management that lead to an improvement of, respectively, brand awareness, brand reputation, and brand loyalty. Data collected from 268 managers operating in organizational units closely involved in marketing and communication activities have been analyzed using fuzzy-set qualitative comparative analysis (fsQCA). Different equifinal pathways emerge, highlighting some commonalities, as well as some specificities. Social media integration with other communication channels and dissemination of information collected through social media within the organization turn out to be two managerial practices with a relevant role in achieving higher brand awareness, brand reputation, and brand loyalty. Moreover, social media responsiveness appears to be crucial for enhancing brand loyalty. These results contribute to the branding and social media literature, providing also interesting insights for practitioners to understand how to strength brands in the social media era.