Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcytosis of HIV-1 through Vaginal Epithelial Cells Is Dependent on Trafficking to the Endocytic Recycling Pathway

Background While it is accepted that viruses can enter epithelial cells by endocytosis, the lack of an established biological mechanism for the trafficking of infectious virions through vaginal epithelial cells and their release from the plasma membrane has contributed to ongoing controversy about whether endocytosis is a mere artifact of some cell culture systems and whether squamous vaginal epithelial cells are even relevant as it pertains to HIV-1 transmission. Methodology/Principal Findings In this study, we investigated the intracellular trafficking pathway that HIV-1 exploits to transcytose vaginal epithelial cells. The reduction of endosome tubulation by recycling endosome inhibitors blocked transcytosis of HIV-1 in a cell culture and transwell system. In addition, we demonstrate that although heat-inactivated virus was endocytosed as efficiently as native virus, heat-inactivated virus was trafficked exclusively to the lysosomal pathway for degradation following endocytosis. Lysosomal protease-specific inhibitors blocked the degradation of inactivated virions. Immunofluorescence analysis not only demonstrated that HIV-1 was inside the cells but the different colocalization pattern of native vs. heat inactivated virus with transferrin provided conclusive evidence that HIV-1 uses the recycling pathway to get across vaginal epithelial cells. Conclusions/Significance Altogether, our findings demonstrate the precise intracellular trafficking pathway utilized by HIV-1 in epithelial cells, confirms that HIV-1 transcytosis through vaginal epithelial cells is a biological phenomenon and brings to light the differential intracellular trafficking of native vs heat-inactivated HIV-1 which with further exploration could prove to provide valuable insights that could be used in the prevention of transcytosis/transmission of HIV-1 across the mucosal epithelia.
CD99 Is Strongly Expressed in Basal Cells of the Normal Adult Epidermis and Some Subpopulations of Appendages: Comparison with Developing Fetal Skin

Background CD99 is a cell surface transmembrane glycoprotein expressed in various tissues. CD99 is differentially expressed between subpopulations of each tissue and is highly expressed in certain hematopoietic and precursor cells. However, there has been no comprehensive study of CD99 expression in normal skin. We evaluated CD99 expression in normal human skin and developing fetal skin. Methods Seventy-five adult skin samples containing normal skin and eight fetal skin samples of different gestational ages were collected. CD99 immunohistochemical staining was performed to evaluate expression pattern in adult and fetal skin samples. CD99 and CD34 expression were compared by double immunofluorescence. Results In normal adult skin, CD99 was strongly expressed in the membrane of epidermal basal keratinocytes, hair follicle bulges and outer root sheaths, and inner secretory cells of eccrine sweat glands. In fetal skin, CD99 was not expressed on the periderm at 16 weeks of gestation but was expressed in basal cells of fetal skin at around 19 weeks of gestation. CD99 expression became comparable to that of the adult skin after 20 weeks of gestation. CD99 and CD34 were co-expressed in hair follicle outer root sheaths, as seen by double immunofluorescence study. Conclusions This is the first study examining CD99 expression pattern in normal adult and fetal skin. CD99 tends to be expressed in the basal/precursor cells of epidermis and in hair follicles. These results provide a basis for future investigation on functions of CD99 in the skin and provide a novel potential target for the treatment of dermatologic lesions.
P2X7 Receptor Antagonism Attenuates the Intermittent Hypoxia-induced Spatial Deficits in a Murine Model of Sleep Apnea Via Inhibiting Neuroinflammation and Oxidative Stress

Background:The mechanism of the neural injury caused by chronic intermittent hypoxia (CIH) that characterizes obstructive sleep apnea syndrome (OSAS) is not clearly known. The purpose of this study was to investigate whether P2X7 receptor (P2X7R) is responsible for the CIH-induced neural injury and the possible pathway it involves. Methods:Eight-week-old male C57BL/6 mice were used. For each exposure time point, eight mice divided in room air (RA) and IH group were assigned to the study of P2X7R expression. Whereas in the 21 days-Brilliant Blue G (BBG, a selective P2X7R antagonist) study, 48 mice were randomly divided into CIH group, BBG-treated CIH group, RA group and BBG-treated RA group. The hippocampus P2X7R expression was determined by Western blotting and real-time polymerase chain reaction (PCR). The spatial learning was analyzed by Morris water maze. The nuclear factor kappa B (NF&kgr;B) and NADPH oxidase 2 (NOX2) expressions were analyzed by Western blotting. The expressions of tumor necrosis factor &agr;, interleukin 1&bgr; (IL-&bgr;), IL-18, and IL-6 were measured by real-time PCR. The malondialdehyde and superoxide dismutase levels were detected by colorimetric method. Cell damage was evaluated by Hematoxylin and Eosin staining and Terminal Transferase dUTP Nick-end Labeling method. Results:The P2X7R mRNA was elevated and sustained after 3-day IH exposure and the P2X7R protein was elevated and sustained after 7-day IH exposure. In the BBG study, the CIH mice showed severer neuronal cell damage and poorer performance in the behavior test. The increased NF&kgr;B and NOX2 expressions along with the inflammation injury and oxidative stress were also observed in the CIH group. BBG alleviated CIH-induced neural injury and consequent functional deficits. Conclusions:The P2X7R antagonism attenuates the CIH-induced neuroinflammation, oxidative stress, and spatial deficits, demonstrating that the P2X7R is an important therapeutic target in the cognition deficits accompanied OSAS.
Association between plasma paroxetine concentration and changes in plasma brain‐derived neurotrophic factor levels in patients with major depressive disorder

Recent studies have implicated brain‐derived neurotrophic factor (BDNF) in the pathophysiology of depression and in the activities of antidepressant drugs. Serum BDNF levels are lower in depressed patients and increase in response to antidepressant medications; however, no studies have examined the association between plasma concentrations of antidepressant drugs and plasma BDNF levels. We assessed plasma BDNF levels and paroxetine concentrations in 45 patients with major depression who were being treated with paroxetine. Plasma samples were collected between 10:00 h and 12:00 h at baseline and after 1, 2 and 6 weeks of treatment. The BDNF level and paroxetine concentration of each sample were measured via enzyme immunoassay and high‐performance liquid chromatography, respectively. Plasma BDNF levels increased after 2 and 6 weeks of paroxetine treatment. Plasma BDNF levels were significantly lower in men than in women. Changes in plasma BDNF level were correlated with plasma drug concentration after 2 (r = 0.309, p < 0.05) and 6 weeks (r = 0.329, p < 0.05) but not correlated with plasma drug concentration after 1 week (r = 0.284, ns). Multiple regression analysis confirmed that this change was only significantly correlated with plasma paroxetine concentration after 2 (standardised beta = 0.343, p < 0.05) and 6 weeks (standardised beta = 0.375, p < 0.05). These results suggest that paroxetine treatment increases plasma BDNF levels and that plasma paroxetine levels play an important role in changes in plasma BDNF levels. Copyright © 2011 John Wiley & Sons, Ltd.
A BACKWARD EVOLUTION MODEL FOR INFRARED SURVEYS: THE ROLE OF AGN– AND COLOR–LTIR DISTRIBUTIONS

Empirical “backward” galaxy evolution models for infrared (IR) bright galaxies are constrained using multiband IR surveys. We developed a new Monte Carlo algorithm for this task, implementing luminosity-dependent distribution functions for the galaxies' IR spectral energy distributions (SEDs) and for the active galactic nucleus (AGN) contribution, allowing for evolution of these quantities. The adopted SEDs take into account the contributions of both starbursts and AGN to the IR emission, for the first time in a coherent treatment rather than invoking separate AGN and star-forming populations. In the first part of the paper we consider the quantification of the AGN contribution for local universe galaxies, as a function of the total IR luminosity. It is made using a large sample of luminous infrared galaxies and ultraluminous infrared galaxies for which mid-IR spectra are available in the Spitzer archive. We find the ratio of AGN 6 μm luminosity and the total IR luminosity to rise with L1.4TIR over the IR luminosity range 1011–1013 L☉ and estimate its spread. Judging from the modest number of distant sources with Spitzer spectroscopy, the relation changes at high-z. In the second part we present the model. Our best-fit model adopts very strong luminosity evolution, L = L0(1 + z)3.4, up to z = 2.3, and density evolution, ρ = ρ0(1 + z)2, up to z = 1, for the population of IR galaxies. At higher z, the evolution rates drop as (1 + z)−1 and (1 + z)−1.5, respectively. To reproduce mid-IR to submillimeter number counts and redshift distributions, it is necessary to introduce both an evolution in the AGN contribution and an evolution in the luminosity–temperature relation. At a given total IR luminosity, high-redshift IR galaxies have typically smaller AGN contributions to the rest-frame mid-IR, and colder far-IR dust temperatures than locally. We also suggest an extension of the local IR galaxy population toward lower dust temperatures. Our models are in plausible agreement with current photometry-based estimates of the typical AGN contribution as a function of mid-IR flux, and well placed to be compared to upcoming Spitzer spectroscopic results. As an example of future applications, we use our best-fitting model to make predictions for surveys with Herschel.
Prostatic intraepithelial neoplasia in dogs with spontaneous prostate cancer

Prostatic intraepithelial neoplasia (PIN) is the most likely precursor of human prostate cancer. The prevalence and immunophenotype of PIN in dogs with spontaneous prostate cancer has not been previously described. To investigate the association between PIN and prostate cancer, we evaluated the prostates of dogs with spontaneous prostate carcinoma. The prevalence of PIN was determined in formalin‐fixed prostates from 29 dogs with spontaneous prostate cancer. Using immunoperoxidase techniques, we compared basal cell layer integrity (high molecular weight keratin 34 beta‐E12), proliferative index (MIB‐1), and microvessel density (Factor VIII‐related antigen) in 14 prostates which contained benign epithelium, PIN, and carcinoma. PIN was present in 19 of 29 (66%) prostates from dogs with spontaneous prostate cancer. The basal cell layer was intact in benign epithelium, disrupted in 72% of acini with PIN, and absent in carcinoma. The mean proliferative index was 17%, 25%, and 40% for benign epithelium, PIN, and carcinoma, respectively, and these differences were significant. The mean microvessel density in foci of PIN and carcinoma (32 and 39 vessels per mm2, respectively) was greater than in benign epithelium (23 vessels per mm2). High‐grade PIN is common in the prostates of dogs with spontaneous carcinoma. The basal cell layer is partially disrupted in PIN, whereas it is absent in prostate cancer. The proliferative index and microvessel density of PIN are intermediate between benign epithelium and cancer. These results are similar to those reported for human PIN and prostate cancer, and indicate that PIN is part of a morphologic continuum in the progression of prostate cancer. To our knowledge, this is the first description of high‐grade PIN spontaneously occurring in animals. The canine prostate may serve as a useful model for examining factors that modulate PIN and prostate cancer progression. Prostate 30:92–97, 1997. © 1997 Wiley‐Liss, Inc.
Healthy Connections: Online Social Networks and their Potential for Peer Support

Social and professional support for mental health is lacking in many rural areas - highlighting the need for innovative ways to improve access to services. This study explores the potential of online social networking as an avenue for peer support. Using a cross sectional survey, 74 secondary students answered questions relating to internet use, online social network use and perceptions of mental health support. Over half of the sample had experienced a need for mental health support with 53% of participants turning to the internet. Results indicate that online social networking sites were used regularly by 82% of the sample and 47% believed these sites could help with mental health problems. The study concluded that online social networking sites may be able to link young people together with others in similar situations. The popularity and frequency of use may allow these sites to provide information, advice and direction for those seeking help.
18 F-Fluorodeoxyglucose PET / CT and Dynamic Contrast-Enhanced MRI as Imaging Biomarkers in Malignant Pleural Mesothelioma

Purpose To compare the use of F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG PET/CT) and Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) to predict prognosis and monitor treatment in Malignant Pleural Mesothelioma. Methods FDG PET/CT and DCE-MRI studies carried out as part of the South West Area Mesothelioma Pemetrexed (SWAMP) trial were used. FDG PET/CT and DCE-MRI studies were carried out before treatment, and after two cycles of chemotherapy, on patients treated with Pemetrexed and Cisplatin. 73 patients were recruited, of whom 65 had PET/CT and DCE-MRI scans. Baseline measurements from FDG PET/CT (SUVmax, Metabolic Tumour Volume (MTV) and Total Lesion Glycolysis (TLG)) and DCE-MRI (Integrated Area Under the first 90s of the curve (IAUC90) and washout slope) were compared with overall survival (OS) using Kaplan Meier and Cox regression analysis, and change in imaging measurements were compared with disease progression. Results PET/CT and DCE-MRI measurements were not correlated with each other. SUVmax, MTV and TLG were significantly related to OS with Cox Regression and analysis and Kaplan-Meir analysis, and DCE-MRI washout curve shape was significantly related to overall survival. DCE-MRI curve shape can be combined with FDG PET/CT to give additional prognostic information. Changes in measurements were not related to progression free survival. Conclusions FDG-PET/CT and DCE-MRI give prognostic information in Malignant Pleural Mesothelioma. Neither PET/CT nor DCE-MRI are useful for monitoring disease progression.
Age-related changes of the representative modular structure in the brain

Describing the changes of modularity in different clinical states can help to understand the alterations of the global processing mechanisms. In the current study we applied the modularity in a local scale. The method is based on measuring the decrease of the modularity caused by shifting a node from its own module to another module. On one hand local modularity measures the influence of a node in the formation of the modular organization. On the other hand we evaluated differences in the community membership of the nodes between the modular structures of two groups. The method was tested on resting-state fMRI data of 20 young and 20 elderly subjects. Increased local modularity of the occipital module was found in the young, which is in line with the previously reported increased segregation of the visual cortex in the young. Regions of the dorsal attention network were characterized with an increased local modularity in the elderly which suggest that these regions preserve the modular structure in advanced age. These findings indicate that applying the modularity on a local scale is a promising biomarker for detecting differences between age groups.
On Capacity of Line Networks

We consider communication through a cascade of discrete memoryless channels (DMCs). The source and destination node of this cascade are allowed to use coding schemes of arbitrary complexity, but the intermediate relay nodes are restricted to process only blocks of a fixed length. We investigate how the processing at the relays must be chosen in order to maximize the capacity of the cascade, that is, the maximum achievable end-to-end rate between the source and the destination. For infinite cascades with fixed intermediate processing length at the relays, we prove that this intermediate processing can be chosen to be identical without loss of optimality, and that the capacity of the cascade coincides with the rate of the best zero-error code of length equal to the block length of the intermediate processing. We further show that for fixed and identical intermediate processing at all relays, convergence of capacity as the length of the cascade goes to infinity is exponentially fast. Finally, we characterize how the block length of the intermediate processing must scale with the length of the cascade to guarantee a constant end-to-end rate. We prove that it is sufficient that the block length scales logarithmically with the network length in order to achieve any rate above the zero-error capacity. We show that in many cases of interest logarithmic growth is also necessary.
Enteroviral meningitis in Northern Jordan: Prevalence and association with clinical findings

During the summer‐autumn of 1999, 390 specimens of cerebrospinal fluid were taken from infants and children younger than 15 years of age. They were suspected of having meningitis and were admitted to Princess Rahma Hospital, Northern Jordan. They were investigated for the presence of enteroviruses using shell vial culture and indirect immunofluorescence assays. Most cases (46.9%) occurred in children younger than 1 year of age in which males represented 71.9%. The common symptoms were fever, vomiting, and headache. Enteroviruses were isolated from 32 (8.2%) cases, coxsackievirus B types 2, 4, and 5 from 15 (46.9%) cases, and echovirus 9 (31.3%) was the most common identified serotype. The virus isolation rate was directly proportional to the number of leukocytes in the cerebrospinal fluid. However, enteroviral isolation was demonstrated in 4 (12.5%) of 32 cerebrospinal fluid specimens without pleocytosis. Leukocyte differential count revealed a predominance of polymorphonuclear cells in 71.4% of the cases. Hospitalization ranged from 1 day to 25 days with a mean of 7 days. The majority of enterovirus‐infected patients (88.9%) were treated with at least one type of antibiotic. These results emphasize the importance of shell vial culture assay for diagnosing enteroviruses, especially in laboratories that do not have access to advanced techniques such as polymerase chain reaction. J. Med. Virol. 66:224–228, 2002. © 2002 Wiley‐Liss, Inc.
Angiotensin converting enzyme (ACE) inhibitor-induced cough and substance P.

BACKGROUND: Angiotensin converting enzyme (ACE) inhibitors cause coughing in 5-10% of patients, but the exact mechanisms of this effect are still unclear. In the airways ACE degrades substance P so the cough mechanism may be related to this peptide. METHODS: Nine patients who developed a cough and five patients who did not develop a cough when taking the ACE inhibitor enalapril (2.5 or 5.0 mg/day) for hypertension were enrolled in the study. No subjects had respiratory disease and the respiratory function of all subjects was normal. One month after stopping enalapril, inhalation of hypertonic saline (4%) was performed using an ultrasonic nebuliser for 15-30 minutes to induce sputum. The concentration of substance P in the sputum sample was measured by radioimmunoassay. In four of the nine cases with a cough enalapril was given again for 1-2 weeks and the concentration of substance P in the induced sputum was again measured. RESULTS: One month after stopping enalapril the mean (SE) concentration of substance P in the sputum of the group with a cough was 16.6 (3.0) fmol/ml, significantly higher than that in the subjects without a cough (0.9 (0.5) fmol/ml). All four subjects in the group with a cough who were given a repeat dose of enalapril developed a cough again, but the concentrations of substance P in the induced sputum while taking enalapril (17.9 (3.2) fmol/ml) were similar to the values whilst off enalapril (20.0 (2.5) fmol/ml). CONCLUSIONS: The mechanisms of ACE inhibitor-induced coughing may involve substance P mediated airway priming. However, the final triggering of the ACE inhibitor-induced coughing is unlikely to be due to this peptide.
Hydrodynamic Simulations of Jet- and Wind-driven Protostellar Outflows

We present two-dimensional hydrodynamic simulations of both jet- and wind-driven models for protostellar outflows in order to make detailed comparisons to the kinematics of observed molecular outflows. The simulations are performed with the ZEUS-2D hydrodynamic code using a simplified equation of state, simplified cooling and no external heating, and no self-gravity. In simulations of steady jets, swept-up ambient gas forms a thin shell that can be identified as a molecular outflow. We find a simple ballistic bow shock model is able to reproduce the structure and transverse velocity of the shell. Position-velocity (PV) diagrams for the shell cut along the outflow axis show a convex spur structure with the highest velocity at the bow tip and low-velocity red and blue components at any viewing angle. The power-law index of the mass-velocity (MV) relationship ranges from 1.5 to 3.5, depending strongly on the inclination. If the jet is time-variable, the PV diagrams show multiple convex spur structures, and the power-law index becomes smaller than the steady jet simulation. In simulations of isothermal steady wide-angle winds, swept-up ambient gas forms a thin shell that at early stages has a similar shape to the shell in the jet-driven model; it becomes broader at later times. We find the structure and kinematics of the shell is well described by a momentum-conserving model similar to that of Shu et al. (1991). In contrast to the results from jet simulations, the PV diagrams for the shell cut along the outflow axis show a lobe structure tilted with source inclination, with components that are primarily either red or blue unless the inclination is nearly in the plane of sky. The power-law index of the MV relationship ranges from 1.3 to 1.8. If the wind is time-variable, the PV diagrams also show multiple structures, and the power-law index becomes smaller than the steady wind simulation. Comparing the different simulations with observations, we find that some outflows, e.g., HH 212, show features consistent with the jet-driven model, while others, e.g., VLA 0548, are consistent with the wind-driven model.
Positive and Negative Affectivity in Children: A Multitrait-Multimethod Investigation

Examined the validity of the tripartite model of anxiety and depression and its internal structure in children. Measures of positive affect/surgency (PA/S) and negative affect/neuroticism (NA/N) and self-report and peer nominations of symptoms of depression and anxiety were completed by 104 children (mean age = 14.9 years, SD = 1.9). Parents completed measures of temperament and anxious and depressive symptoms. Multitrait-multimethod and confirmatory factor analyses (CFA) supported a 3-factor model that included separate Child and Parent NA/N factors and a joint PA/S factor. Child and Parent NA/N were related to symptoms of both depression and anxiety, but neither parent nor peer symptom ratings related to Child NA/N. PA/S was primarily related to symptoms of depression. These results support aspects of the tripartite model in children and suggest caution in the use of multimethod assessment of children's temperament and internalizing symptoms.