Miracle-dz/UniFAR-FTUs huggingface dataset:
MAMLD1 (CXorf6): A New Gene for Hypospadias

MAMLD1 (mastermind-like domain containing 1), also known as CXorf6 (chromosome X open reading frame 6) has been shown to be a causative gene for hypospadias. This is primarily based on the identification of nonsense mutations (E124X, Q197X, and R653X) which undergo nonsense mediated mRNA decay in patients with penoscrotal hypospadias. Subsequent molecular studies have shown that (1) the mouse homolog is transiently expressed in fetal Sertoli and Leydig cells around the critical period for sex development; (2) CXorf6 protein shares homology to mastermind-like 2 (MAML2) protein that functions as a co-activator in canonical Notch signaling; (3) CXorf6 localizes to the nuclear bodies and transactivates the promoter activity of a non-canonical Notch target gene hairy/enhancer of split 3(Hes3) without demonstrable DNA binding capacity; (4) transient knockdown of CXorf6 results in significantly reduced testosterone production in murine Leydig tumor cells; and (5) CXorf6 can be regulated by steroidogenic factor 1 (SF-1). These findings suggest that the CXorf6 mutations cause hypospadias primarily because of testicular dysfunction and resultant compromised testosterone production around that period, and provide useful information for the molecular network involved in fetal testosterone production.
Barra Risk Model Based Idiosyncratic Momentum for Chinese Equity Market

We propose a different way of constructing an idiosyncratic momentum factor using the Barra Global Multi-factor Risk Model. Also, we examine the properties as well as the performance of this new factor by applying it to the China's stock market. Out analysis shows that the idiosyncratic momentum factor constructed here carries the resemblance of the conventional price momentum factor, but with much lower variance and exposure to the common market factors, such as value, size, and volatility. In the long-short portfolio test for both China's A-Share IMI and CSI 500 Indies, we observe the significant improvement of this factor's return over the conventional momentum. In particular, this factor delivers consistent high returns with a moderate IC increase but a significant IR improvement. The performance results strongly suggest that, compared with the traditional momentum factor, the idiosyncratic momentum factor is more reliable and possesses high predictive power for future stock returns. This factor is a good candidate to replace the traditional momentum factor when constructing an effective momentum strategy for investing in China's stock market.
Resveratrol engages selective apoptotic signals in gastric adenocarcinoma cells.

AIM To investigate the intracellular apoptotic signals engaged by resveratrol in three gastric adenocarcinoma cancer cell lines, two of which (AGS and SNU-1) express p53 and one (KATO-III) with deleted p53. METHODS Nuclear fragmentation was used to quanti-tate apoptotic cells; caspase activity was determined by photometric detection of cleaved substrates; formation of oxidized cytochrome C was used to measure cytochrome C activity, and Western blot analysis was used to determine protein expression. RESULTS Gastric cancer cells, irrespective of their p53 status, responded to resveratrol with fragmentation of DNA and cleavage of nuclear lamins A and B and PARP. Resveratrol, however, has no effect on mitochondria-associated apoptotic proteins Bcl-2, Bcl-xl, Bax, Bid or Smac/Diablo, and did not promote sub-cellular redistribution of cytochrome C, indicating that resveratrol-induced apoptosis of gastric carcinoma cells does not require breakdown of mitochondrial membrane integrity. Resveratrol up-regulated p53 protein in SNU-1 and AGS cells but there was a difference in response of intracellular apoptotic signals between these cell lines. SNU-1 cells responded to resveratrol treatment with down-regulation of survivin, whereas in AGS and KATO-III cells resveratrol stimulated caspase 3 and cytochrome C oxidase activities. CONCLUSION These findings indicate that even within a specific cancer the intracellular apoptotic signals engaged by resveratrol are cell type dependent and suggest that such differences may be related to differentiation or lack of differentiation of these cells.
Inspiratory neural drive response to hypoxia adequately estimates peripheral chemosensitivity in OSAHS patients

The aim of the present study was to examine the relationships between the responses to progressive isocapnic hypoxia and hypoxic withdrawal test in patients with obstructive sleep apnoea-hypopnoea syndrome (OSAHS) and to analyse the determinants of carotid body sensitivity in OSAHS. Nineteen consecutive OSAHS patients and 13 healthy subjects were selected. Ventilatory (ΔV′I/Sa,O2/BSA) and inspiratory neural drive (ΔP0.1/Sa,O2) responses to progressive isocapnic hypoxia were determined. Peripheral chemosensitivity was evaluated by the hypoxic withdrawal test, which measures the decrease in ventilation caused by two breaths of 100% oxygen (%ΔV′I). Withdrawal response and ventilatory and inspiratory neural drive responses to hypoxia were lower in OSAHS patients than in control subjects. In patients with OSAHS, %ΔV′I correlated significantly with ΔV′I/Sa,O2/BSA and with ΔP0. 1/Sa,O2. On stepwise multiple linear regression analysis, a strong correlation between %ΔV′I and ΔP0. 1/Sa,O2 was found. Moreover, %ΔV′I, ΔV′I/Sa,O2/BSA and ΔP0. 1/Sa,O2 were significantly correlated with minimum arterial oxygen saturation and with arousal index. Obstructive sleep apnoea-hypopnoea syndrome patients have a strong relationship between peripheral chemosensitivity and respiratory response to hypoxia, suggesting that hypoxic stimulation of central chemoreceptors is minimally relevant in obstructive sleep apnoea-hypopnoea syndrome. Moreover, sensitivity of the carotid body in patients with obstructive sleep apnoea-hypopnoea syndrome is related to sleep disruption and to nocturnal hypoxia.
Contribution of Direct and Cross-Presentation to CTL Immunity against Herpes Simplex Virus 11

Dendritic cells (DC), which can be subdivided into different phenotypic and functional subsets, play a pivotal role in the generation of cytotoxic T cell immunity against viral infections. Understanding the modes of Ag acquisition, processing and presentation by DC is essential for the design of effective antiviral vaccines. We aimed to assess the contribution of direct vs cross-presentation for the induction of HSV1-specific CD8+ T lymphocyte responses in mice. Using HSV1 strains expressing fluorescence proteins, we provide evidence for the ability of HSV1 to induce viral transcription. Using HSV1-wild-type as well as gB- or gH-deficient mutants to either directly inoculate DC or to infect target cells, which then were given to DC, we show that DC acquired viral Ag via phagocytosis of target cells and via direct inoculation of virus being released from target cells. Our study corroborates the function of the CD8+ DC specialized in Ag cross-presentation and confirms this specific feature for Ags that these DC acquire directly from HSV1. However, although infection of cross-presenting DC amplified T cell responses, it was not a requirement for presentation of viral Ags, both in vitro and in vivo. Finally, we provide evidence that direct presentation did not contribute to the Ag presentation capacity of CD8+ DC after phagocytosis of infected target cells. We conclude that cross-presentation is of major importance for the induction of CTL immunity in mice.
Mitochondrial DNA phylogeography of the Mesoamerican spiny‐tailed lizards (Ctenosaura quinquecarinata complex): historical biogeography, species status and conservation

Through the examination of past and present distributions of plants and animals, historical biogeographers have provided many insights on the dynamics of the massive organismal exchange between North and South America. However, relatively few phylogeographic studies have been attempted in the land bridge of Mesoamerica despite its importance to better understand the evolutionary forces influencing this biodiversity ‘hotspot’. Here we use mitochondrial DNA sequence data from fresh samples and formalin‐fixed museum specimens to investigate the genetic and biogeographic diversity of the threatened Mesoamerican spiny‐tailed lizards of the Ctenosaura quinquecarinata complex. Species boundaries and their phylogeographic patterns are examined to better understand their disjunct distribution. Three monophyletic, allopatric lineages are established using mtDNA phylogenetic and nested clade analyses in (i) northern: México, (ii) central: Guatemala, El Salvador and Honduras, and (iii) southern: Nicaragua and Costa Rica. The average sequence divergence observed between lineages varied between 2.0% and 3.7% indicating that they do not represent a very recent split and the patterns of divergence support the recently established nomenclature of C. quinquecarinata, Ctenosaura flavidorsalis and Ctenosaura oaxacana. Considering the geological history of Mesoamerica and the observed phylogeographic patterns of these lizards, major evolutionary episodes of their radiation in Mesoamerica are postulated and are indicative of the regions’ geological complexity. The implications of these findings for the historical biogeography, taxonomy and conservation of these lizards are discussed.
Correlation between the bronchial subepithelial layer and whole airway wall thickness in patients with asthma

Background: The epithelial reticular basement membrane (Rbm) of the airway wall thickens in patients with asthma. However, whether the thickening parallels whole airway wall thickening, which limits airflow, is unknown. The aim of this study was to examine the correlation between the bronchial Rbm thickening and whole airway wall thickening in asthma. In addition, the association of Rbm and whole wall thickening with airflow obstruction was examined. Methods: Forty nine patients with asthma and 18 healthy control subjects took part in the study. The Rbm thickness was measured in bronchial biopsy specimens and whole airway wall thickness was assessed with high resolution computed tomographic (HRCT) scanning after pretreatment with oral steroids for 2 weeks and inhaled β2 agonist to minimise reversible changes of the airway walls. The percentage airway wall area (WA%; defined as (wall area/total airway area) × 100) and percentage airway wall thickness (WT%; defined as [(ideal outer diameter – ideal luminal diameter)/ideal outer diameter] × 100) were determined from HRCT scans to assess whole airway wall thickness. Spirometric tests were also performed. Results: WA% and WT% were higher in patients with asthma than in healthy subjects. Both WA% and WT% were strongly correlated with Rbm thickness. Moreover, these three indices of airway wall thickness were inversely correlated with the percentage of predicted forced expiratory volume in 1 second in patients with asthma. Conclusions: These findings indicate that Rbm thickening parallels whole airway wall thickening which can cause irreversible airflow obstruction in patients with asthma.
Fractures on the chest radiograph in detection of alcoholic liver disease.

The presence of fractures seen on routine chest radiography was assessed in patients with liver disease to see whether it might provide a useful marker of alcoholism. Chest radiographs taken at the time of liver biopsy were examined in 149 patients--72 with alcoholic liver disease (32 (44%) cirrhotic) and 77 with various forms of non-alcoholic liver disease (15 (19 . 5%) cirrhotic)--and in 149 controls. Fractures (85 rib, two clavicular) were much more common in patients with alcoholic liver disease (20 subjects; 28%) than in patients with non-alcoholic liver disease (1; 1 . 3%) or controls 10; 6 . 7%). In alcoholic liver disease rib fractures were significantly more likely to be bilateral or multiple (more than two) or both (p less than 0 . 01). Of patients with alcoholic liver disease, those with fractures were significantly older than those without, but there was no difference in sex, social class, the proportion with cirrhosis, or the proportion known to be alcoholic at the time of the radiograph. In liver disease fractures on the chest radiograph diagnosed alcoholism with 95% specificity and 28% sensitivity. These often overlooked or ignored findings in the chest radiograph may have a wider role in the detection of alcoholism.
How people perceive different robot types: A direct comparison of an android, humanoid, and non-biomimetic robot

During first encounters and short-term interaction with robots, the robot's appearance and initial behavior plays a major role. In this paper we compare the outcome of three human-robot interaction studies using three different robot types in two different countries, Japan and Australia. The participants' perception of an android robot, a humanoid robot and a non-biomimetic robot are compared before and after interacting with the robots. The experimental results show significant differences in the way people perceive the robots based on appearance alone, and based on appearance and behavior after a short interaction.
Enhanced Infectivity of an R5-Tropic Simian/Human Immunodeficiency Virus Carrying Human Immunodeficiency Virus Type 1 Subtype C Envelope after Serial Passages in Pig-Tailed Macaques (Macaca nemestrina)

ABSTRACT The increasing prevalence of human immunodeficiency virus type 1 (HIV-1) subtype C infection worldwide calls for efforts to develop a relevant animal model for evaluating strategies against the transmission of the virus. A chimeric simian/human immunodeficiency virus (SHIV), SHIVCHN19, was generated with a primary, non-syncytium-inducing HIV-1 subtype C envelope from a Chinese strain in the background of SHIV33. Unlike R5-tropic SHIV162, SHIVCHN19 was not found to replicate in rhesus CD4+ T lymphocytes. SHIVCHN19 does, however, replicate in CD4+ T lymphocytes of pig-tailed macaques (Macaca nemestrina). The observed replication competence of SHIVCHN19 requires the fulltat/rev genes and partial gp41 region derived from SHIV33. To evaluate in vivo infectivity, SHIVCHN19 was intravenously inoculated, at first, into two pig-tailed and two rhesus macaques. Although all four animals became infected, the virus replicated preferentially in pig-tailed macaques with an earlier plasma viral peak and a faster seroconversion. To determine whether in vivo adaptation would enhance the infectivity of SHIVCHN19, passages were carried out serially in three groups of two pig-tailed macaques each, via intravenous blood-bone marrow transfusion. The passages greatly enhanced the infectivity of the virus as shown by the increasingly elevated viral loads during acute infection in animals with each passage. Moreover, the doubling time of plasma virus during acute infection became much shorter in passage 4 (P4) animals (0.2 day) in comparison to P1 animals (1 to 2 days). P2 to P4 animals all became seropositive around 2 to 3 weeks postinoculation and had a decline in CD4/CD8 T-cell ratio during the early phase of infection. In P4 animals, a profound depletion of CD4 T cells in the lamina propria of the jejunum was observed. Persistent plasma viremia has been found in most of the infected animals with sustained viral loads ranging from 103 to 105per ml up to 6 months postinfection. Serial passages did not change the viral phenotype as confirmed by the persistence of the R5 tropism of SHIVCHN19 isolated from P4 animals. In addition, the infectivity of SHIVCHN19 in rhesus peripheral blood mononuclear cells was also increased after in vivo passages. Our data indicate that SHIVCHN19 has adapted well to grow in macaque cells. This established R5-tropic SHIVCHN19/macaque model would be very useful for HIV-1 subtype C vaccine and pathogenesis studies.
Childhood brucellosis in Israel.

BACKGROUND Brucellosis has become a major medical problem in Israel particularly in the Muslim Arab population. METHODS Eighty-eight children with acute brucellosis are described. Sixty-seven were studied retrospectively during 1987 through 1988, and 21 children were studied prospectively during 1989 through 1992. Epidemiologic, clinical and laboratory features were evaluated, and the outcome of 4 antimicrobial regimens are compared. RESULTS Although the clinical manifestation varied, the classical triad of fever (91%), arthralgia or arthritis (83%) and hepato- and/or splenomegaly (63%) characterized most patients. Sixty-one percent of the children had elevated liver enzymes. Brucella melitensis was isolated from 61% of blood cultures. The relapse rate in patients who were treated with monotherapy (doxycycline) was 43% compared with 14% with regimens of combined therapy with rifampin and doxycycline, streptomycin and doxycycline or rifampin and trimethoprim-sulfamethoxazole (P < 0.049). Eleven children (33%) who were treated for 3 weeks had relapse compared with 1 patient (3.5%) treated for 4 weeks or longer. The total relapse or reinfection rate was 20%. All patients with relapse recovered after a second course of antibiotic therapy. During the 2 years of follow-up one child progressed to chronic osteomyelitis. CONCLUSIONS Combination therapy and extending treatment for 4 weeks or longer gave significantly better results than monotherapy or shorter courses of therapy and resulted in fewer relapses.
Vitamin A and retinoids in antiviral responses

Vitamin A deficiency results in multiple derangements that impair the response to infection. This review focuses on experimental models of specific virus infections and on cytokines and cells with cytolytic activity important to antiviral defenses. Altered specific antibody responses and greater epi‐thelial damage in vitamin A‐deficient hosts are consistent findings. The cytolytic activity of natural killer cells and various cytokine responses are altered. The inflammatory response to infection may also result in derangements in the transport and metabolism of retinol. We speculate that interaction of several factors may combine to explain the greater severity of infection seen in vitamin A‐deficient animals and children. In addition to a preexisting lack of tissue vitamin A, these factors may include reduced mobilization and increased excretion of retinol during the acute phase response to infection, poor innate and specific immune response to virus, and delayed repair of damaged epithelia. Foci of vitamin A‐deficient epithelia may be sites of penetration of bacteria and other agents, leading to secondary infections and contributing to an increased severity of infections and poor outcome in vitamin A‐deficient animals and humans. —Ross, A. C. , Stephensen, C. B. Vitamin A and retinoids in antiviral responses. FASEB J. 10, 979‐985 (1996)
One market fits all? Market access and the origins of the Italian north–south divide

ABSTRACT Italy’s economic development since its unification in 1861 has been characterized by extensive regional inequality. Northern regions were the frontrunners of modern industrialization in the late 19th century, while southern regions never closed the gap. New Economic Geography (NEG) proposes market access as the main driver of regional income differentials. But is its effect homogeneous across regions? The NEG hypothesis is here for the first time considered for the north and the south of Italy separately in the period 1871–1911. Following previous work by the author, both domestic and total market potentials are taken into account as possible drivers of regional gross domestic product (GDP) per capita. The results differ for the two macro-areas: in the south, both market potentials have a strong role in determining the levels of GDP per capita, but they do not affect the growth rates from period to period; and in the north, only domestic market potential is significant in both levels and growth rates. These results point to different dynamics at the sub-national level that should be further qualified by extending the analysis from the NUTS-2 to the NUTS-3 level. The policy implication is that market-oriented measures might not be effective for the most disadvantaged regions before other prerequisites for growth are achieved.
Endogenously Expressed Epithelial Sodium Channel Is Present in Lipid Rafts in A6 Cells*

The epithelial sodium channel (ENaC) present in the kidney collecting duct, distal colon, and the lung is responsible for salt reabsorption and whole body volume regulation. It is composed of three homologous subunits, α, β, and γ, and mutations to these subunits can lead to the salt wasting disease pseudohypoaldosteronism type I, associated with decreased channel density at the plasma membrane or to the hypertensive disorder, Liddle's syndrome, in which channel residency time at the plasma membrane is enhanced. Regulation of ENaC trafficking and turnover is therefore critical to sodium homeostasis. In this study we examined whether ENaC is present in the cholesterol-enriched microdomains commonly called lipid rafts, in the endogenously expressing A6 cell line. We demonstrate that a fraction of α, β, and γ ENaC is present in detergent-insoluble membranes, that subunits exist in membranes that float on discontinuous sucrose density gradients, and that methyl-β-cyclodextrin treatment causes a redistribution of ENaC subunits to higher density membranes. Furthermore, chronic aldosterone stimulation results in a shift in the membrane density of all three subunits. Biotinylation of apical membrane proteins revealed that ENaC is present in lipid rafts on the plasma membrane. In conclusion, these results show that ENaC is present in lipid rafts both intracellularly and on the cell surface. Raft association may be important for trafficking and/or function of the channel.
Preservation of Cells of the Organ of Corti and Innervating Dendritic Processes Following Cochlear Implantation in the Human: An Immunohistochemical Study.

HYPOTHESIS This study evaluates the degree of preservation of hair cells, supporting cells, and innervating dendritic processes after cochlear implantation in the human using immunohistochemical methods. BACKGROUND Surgical insertion of a cochlear implant electrode induces various pathologic changes within the cochlea including insertional trauma, foreign body response, inflammation, fibrosis, and neo-osteogenesis. These changes may result in loss of residual acoustic hearing, adversely affecting the use of hybrid implants, and may result in loss of putative precursor cells, limiting the success of future regenerative protocols. METHODS Twenty-eight celloidin-embedded temporal bones from 14 patients with bilateral severe to profound sensorineural hearing loss and unilateral cochlear implants were studied. Two sections including the modiolus or basal turn from each temporal bone were stained using antineurofilament, antimyosin-VIIa, and antitubulin antibodies in both the implanted and unimplanted ears. RESULTS Inner and outer hair cells: Immunoreactivity was reduced throughout the implanted cochlea and in the unimplanted cochlea with the exception of the apical turn.Dendritic processes in the osseous spiral lamina: Immunoreactivity was significantly less along the electrode of the implanted cochlea than in the other segments.Inner and outer pillars, inner and outer spiral bundles, and Deiters' cells: Immunoreactivity was similar in the implanted and unimplanted cochleae. CONCLUSION Insertion of a cochlear implant electrode may significantly affect the inner and outer hair cells both along and apical to the electrode, and dendritic processes in the osseous spiral lamina along the electrode. There was less effect on pillar cells, Deiters' cells, and spiral bundles.