Miracle-dz/UniFAR-FTUs huggingface dataset:
An extended family of novel vertebrate photopigments is widely expressed and displays a diversity of function

Light affects animal physiology and behavior more than simply through classical visual, image-forming pathways. Nonvisual photoreception regulates numerous biological systems, including circadian entrainment, DNA repair, metabolism, and behavior. However, for the majority of these processes, the photoreceptive molecules involved are unknown. Given the diversity of photophysiological responses, the question arises whether a single photopigment or a greater diversity of proteins within the opsin superfamily detect photic stimuli. Here, a functional genomics approach identified the full complement of photopigments in a highly light-sensitive model vertebrate, the zebrafish (Danio rerio), and characterized their tissue distribution, expression levels, and biochemical properties. The results presented here reveal the presence of 42 distinct genes encoding 10 classical visual photopigments and 32 nonvisual opsins, including 10 novel opsin genes comprising four new pigment classes. Consistent with the presence of light-entrainable circadian oscillators in zebrafish, all adult tissues examined expressed two or more opsins, including several novel opsins. Spectral and electrophysiological analyses of the new opsins demonstrate that they form functional photopigments, each with unique chromophore-binding and wavelength specificities. This study has revealed a remarkable number and diversity of photopigments in zebrafish, the largest number so far discovered for any vertebrate. Found in amphibians, reptiles, birds, and all three mammalian clades, most of these genes are not restricted to teleosts. Therefore, nonvisual light detection is far more complex than initially appreciated, which has significant biological implications in understanding photoreception in vertebrates.
Suppression of melanoma cell tyrosinase activity and tumorigenicity after incorporation of bromouracil for one or two cell divisions

We have studied the kinetics of suppression of tyrosinase activity and tumorigenicity in unsynchronized B16 mouse melanoma cells (clone B559) exposed to 5‐bromodeoxyuridine (BrdU, 3 m̈g/ml) for one or two cell divisions, then cultured in BrdU‐free medium (RM) for five or six days. Bromouracil replaced about 23% of thymine residues after 24 hours (1 cell division) and almost 40% after 48 hours (2 cell divisions) in the presence of BrdU. Upon subsequent growth in RM the extent of replacement declined in a manner consistent with dilution by new DNA synthesis, reaching 5–10% substitution by day 7 of these experiments. Tyrosinase activity was significantly reduced after treatment with BrdU for 24 or 48 hours but continued to decline after the cultures were changed to RM, approaching undetectable levels on day 7. The time course of reduction was similar to that previously determined in cells grown continuously for seven days in the presence of BrdU. Therefore, suppression of tyrosinase activity can result from incorporatpon of BrdU during a single cell cycle, but requires about seven days for full manifestation of the effect. Tumorigenicity decreased to 55% after 24 hours and to 15% after 48 hours with BrdU but rapidly reversed to approach that of untreated melanoma cells when subsequently grown in RM for 5–6 days. The effects of BrdU on total RNA or protein synthesis, or on plating efficiency appeared insufficient to account for the degree of suppression observed. Our results indicate that substitution by bromouracil into either strand of DNA loci controlling tyrosinase activity or tumorigenic potential may be sufficient for suppression. In addition, they demonstrate that such brief treatment with BrdU may be used to probe the regulation of differentiated function and tumorigenicity in these melanoma cells.
Inhibitory Interneurons That Express GFP in the PrP-GFP Mouse Spinal Cord Are Morphologically Heterogeneous, Innervated by Several Classes of Primary Afferent and Include Lamina I Projection Neurons among Their Postsynaptic Targets

The superficial dorsal horn of the spinal cord contains numerous inhibitory interneurons, which regulate the transmission of information perceived as touch, pain, or itch. Despite the importance of these cells, our understanding of their roles in the neuronal circuitry is limited by the difficulty in identifying functional populations. One group that has been identified and characterized consists of cells in the mouse that express green fluorescent protein (GFP) under control of the prion protein (PrP) promoter. Previous reports suggested that PrP-GFP cells belonged to a single morphological class (central cells), received inputs exclusively from unmyelinated primary afferents, and had axons that remained in lamina II. However, we recently reported that the PrP-GFP cells expressed neuronal nitric oxide synthase (nNOS) and/or galanin, and it has been shown that nNOS-expressing cells are more diverse in their morphology and synaptic connections. We therefore used a combined electrophysiological, pharmacological, and anatomical approach to reexamine the PrP-GFP cells. We provide evidence that they are morphologically diverse (corresponding to “unclassified” cells) and receive synaptic input from a variety of primary afferents, with convergence onto individual cells. We also show that their axons project into adjacent laminae and that they target putative projection neurons in lamina I. This indicates that the neuronal circuitry involving PrP-GFP cells is more complex than previously recognized, and suggests that they are likely to have several distinct roles in regulating the flow of somatosensory information through the dorsal horn.
Combined scopolamine and ethanol treatment results in a locomotor stimulant response suggestive of synergism that is not blocked by dopamine receptor antagonists.

BACKGROUND Muscarinic acetylcholine receptors (mAChRs) are well positioned to mediate ethanol's stimulant effects. To investigate this possibility, we examined the effects of scopolamine, a receptor subtype nonselective mAChR antagonist, on ethanol-induced stimulation in genotypes highly sensitive to this effect of ethanol. We also investigated whether the dopamine D1-like receptor antagonist, SCH-23390 or the dopamine D2-like receptor antagonist, haloperidol, could block the extreme stimulant response found following co-administration of scopolamine and ethanol. METHODS Scopolamine (0, 0.0625, 0.125, 0.25, or 0.5 mg/kg) was given 10 minutes prior to saline or ethanol (0.75 to 2 g/kg) to female FAST (Experiment I) or DBA/2J (Experiment II) mice that were then tested for locomotion for 30 minutes. In Experiments III and IV, respectively, SCH-23390 (0, 0.015, or 0.03 mg/kg) was given 10 minutes prior, and haloperidol (0, 0.08, or 0.16 mg/kg) was given 2 minutes prior, to scopolamine (0 or 0.5 mg/kg), followed 10 minutes later by saline or ethanol (1.5 g/kg) and female DBA/2J mice were tested for locomotion for 30 minutes. RESULTS FAST and DBA/2J mice displayed a robust enhancement of the locomotor effects of ethanol following pretreatment with scopolamine that was suggestive of synergism. SCH-23390 had no effect on the response to the scopolamine + ethanol drug combination, nor did it attenuate ethanol- or scopolamine-induced locomotor activity. Haloperidol, while attenuating the effects of ethanol, was not able to block the effects of scopolamine or the robust response to the scopolamine-ethanol drug combination. CONCLUSIONS These results suggest that while muscarinic receptor antagonism robustly enhances acute locomotor stimulation to ethanol, dopamine receptors are not involved in the super-additive interaction of scopolamine and ethanol treatment. They also suggest that in addition to cautions regarding the use of alcohol when scopolamine is clinically prescribed due to enhanced sedative effects, enhanced stimulation may also be a concern.
Chordoid meningiomas: Incidence and clinicopathological features of a case series over 18 years

Chordoid meningioma (CM) is a rare subtype of meningioma, classified as grade II, which exhibits a high rate of recurrence following subtotal resection. We retrospectively examined nine cases of chordoid meningioma over a case series of 1743 meningiomas (0.52%) operated upon at our institution from 1995 to 2013. All the reported clinicopathological findings were analyzed. Two hundred and twenty‐one CM cases have been published to date worldwide and few single‐center large case series have been issued. Seventy‐five percent of the cases that underwent subtotal resection at our institution had recurrence within 1 year. Total resection of the tumor should be the major objective of surgery to reduce the possibility of tumor recurrence. The percentage of chordoid features within the tumor specimen could assist in predicting the pathogenesis of the lesion. The correlation of the index of proliferation to recurrence rate is still controversial. Much debate exists with regard to the role of adjuvant radiotherapy in CM cases. Immunohistochemical, cytological and ultrastructural studies should be used in combination to assure a correct diagnosis of CM. Owing to the rare occurrence of this meningioma subtype, larger case series are required to assist in providing a reference for diagnosis and to improve the therapeutic management of CM.
Early effects of burning rice farm residues on respiratory symptoms of villagers in suburbs of Isfahan, Iran

Villagers residing in areas with rice farms are exposed to smoke from burning of agricultural waste that may affect respiratory health. To assess respiratory effects of this smoke-induced air pollution, a cross-sectional study has been conducted in three randomly selected villages of Isfahan rural areas. A physician-administered health questionnaire was completed for 433 male and 561 female villagers aged 1-80 years, followed by physical examinations and spirometry in symptomatic cases, before and after a rice burning episode in October 2000. Total particulate and respirable particulate maters (PM10) was doubled during burning episode. Prevalence rates for respiratory symptoms before smoke were: recent asthma attacks (7.7%), using asthma medications (3%), sleep disturbed by dyspnea and cough (7.4%), exercise-induced cough (13.3%), which increased to 9.5, 7.1, 9.3 and 17%, respectively. Mean initial values (as percent of prediction) for; FEV1, FEV1/FVC, PEFR, and FEF25-75 were: 85.9 - 22.7, 81.7 - 8, 86.2 - 26.2 and 60 - 26.4, respectively. The mentioned values decreased to to 83.2 - 19.5, 76.5 - 10.3, 85.5 - 21.1 and 54.3 - 26.4, respectively. All of the clinical and spirometric changes were statistically significant. Study findings suggest increased respiratory morbidity associated with rice burning episodes among all people living in the area.
Serological Survey of Toxoplasma gondii Infection in Free-ranging Eurasian Lynx (Lynx lynx) from Sweden

To investigate the prevalence of Toxoplasma gondii infection in free-ranging Eurasian lynx (Lynx lynx) in Sweden, serosanguinous fluids and feces were collected from 207 carcasses of lynx killed or found dead from 1996 to 1998. Sera were tested for antibodies against T. gondii by the direct agglutination test, and 156 (75.4%) of the sera tested positive at antibody titers ≥40. Antibody prevalence was significantly lower in lynx originating from the northern parts of Sweden than in lynx from the more southern regions that are more densely populated by humans. Age-related differences also were found, with a significantly lower prevalence (55%) in juvenile (<1-yr-old) than in subadult and adult animals (82%). There was no significant difference in seroprevalence between males and females. Oocysts typical of T. gondii were not detected in any of the fecal samples.
Birth outcome, not pregnancy process: Reply to van der Veen

In a recent article (Frisbie. Forbes. and Pullum 1996) we documented racial/ethnic differences in birth outcomes according to a more fine-grained classification than has typically been employed in the demographic literature. In his commentary, van der Veen focuses on the measurement of one of the dimensions of that classification, maturity of the infant. as proxied by the fetal growth ratio. The crux of the critique is easily seen in van der Veen's statement that “all of my disagreements with Frisbie et al. 's method arise from their particular use of a postnatal standard for the assessment of intrauterine growth. ” Our critic misunderstands our objective: He fails to realize our interest in birth outcome, not pregnancy process, and does not perceive that our intent was to extend the research extant in both the demographic and public-health literatures in which patently postnatal (i.e., ex utero) measures are taken as outcomes interesting in their own right and/or as risk factors for infant mortality and infant and childhood morbidity. Specifically, he does recognize that we purposefully expanded our focus to include moderately compromised births to determine if they were at higher risk than the normal births with whom they are conventionally categorized. Our discussion draws on research cited in the original article, on studies cited by our critic, and on a few more recent investigations. Although we have never argued that ours is the only, or even the best, approach in all cases, we try to clarify the rationale for, and adduce additional empirical evidence of, the utility of the method we used.
Bcl2l10, a new Tpx2 binding partner, is a master regulator of Aurora kinase A in mouse oocytes

ABSTRACT Previously, we demonstrated that Bcl-2-like 10 (Bcl2l10) is associated with meiotic spindle assembly and that the gene that is most strongly down-regulated by Bcl2l10 RNAi is targeting protein for Xklp2 (Tpx2). Tpx2 is a well-known cofactor that controls the activity and localization of Aurora kinase A (Aurka) during mitotic spindle assembly. Therefore, this study was conducted (1) to identify the associations among Bcl2l10, Tpx2, and Aurka and (2) to understand how Bcl2l10 regulates meiotic spindle assembly in mouse oocytes. Bcl2l10, Tpx2, and Aurka co-localized on the meiotic spindles, and Bcl2l10 was present in the same complex with Tpx2. Tpx2 and Aurka expression decreased whereas phospho-Aurka increased in Bcl2l10 RNAi-treated oocytes. Counterbalancing changes in the levels of these 2 activators, Tpx2 and phospho-Aurka, resulted in decreased Aurka catalytic activity after Bcl2l10 RNAi treatment. Bcl2l10 RNAi decreased the expression of microtubule organizing center (MTOC)-related proteins, disturbed MTOC formation and disrupted meiotic spindle assembly. Our data demonstrate that Bcl2l10 is a binding partner of Tpx2 and a new regulator of the complex controlling the organization of microtubules and MTOC biogenesis in meiotic spindle assembly. The discovery of Bcl2l10 as a new effector of Aurka suggests that Bcl2l10 may have diverse functions in mitotic cells.
Risk factors for candidemia in patients with acute lymphocytic leukemia.

Between 1983 and 1987 the overall incidence of candidemia at the Institut Gustave Roussy, a tertiary care referral hospital for patients with cancer, increased from 0.1% (7 of 6,801) to 0.32% (24 of 7,515) (P = .009). Because acute lymphocytic leukemia (ALL) was the most common underlying disease in patients with candidemia, risk factors for candidemia were analyzed in this subset of patients. A case-control study comparing the eight ALL patients who had candidemia with 18 ALL control patients revealed that previous bacteremia, prolonged neutropenia, prolonged fever, prolonged administration of antimicrobial agents, treatment with multiple antimicrobial agents, and a relatively high concentration of Candida organisms in stool were significant risk factors for candidemia. In a logistic regression analysis, however, only receipt of vancomycin and/or imipenem was identified as an independent risk factor for candidemia. Further analysis showed that administration of vancomycin promoted proliferation of Candida organisms in the gastrointestinal tract and that this proliferation was associated with an increased risk of candidemia.
Strategies for reduction and cessation of alcohol use: adolescent preferences.

BACKGROUND Although the majority of youth and adults resolve alcohol problems without formal treatment, we know little about the strategies used by youth in their efforts to decrease alcohol use. Recent studies have begun to address change efforts that adolescents report being helpful in cutting down or stopping alcohol use. The current study seeks to improve our understanding of adolescent change processes in alcohol use by examining the perceptions of high school students. METHODS As part of a secondary alcohol intervention study of high school students (ages 12-18; 51% male), 1069 participants completed an anonymous supplemental questionnaire on change strategies for cutting down and stopping alcohol use. Based on content analysis of youth-generated responses, a classification system consisting of nine broad categories was developed (e.g., informal-interpersonal supports, formal aids, alternative activities). Participant responses were independently coded by two raters trained to criterion. Cases with full agreement (n = 934; 96%) were used for data analyses of methods for cutting down drinking, stopping drinking, and strategies recommended for a friend. RESULTS The five most frequently youth-generated change strategies to alter drinking were environmental exposure management (e.g., avoid drinking situations, 19%); informal interpersonal supports (e.g., talk to a friend, 18%); formal aids (e.g., peer support group, counselor, 17%); behavioral self-management (e.g., limit consumption, 14%); and alternative activities (e.g., recreation, sports, 10%). Whereas informal interpersonal supports were consistently endorsed for all change situations, behavioral self-management strategies were viewed as more useful for reduction of drinking and formal aids more critical for cessation efforts. Some differences were observed in youth-generated strategies for changing their own drinking compared with efforts to help friends, with environmental changes (e.g., reducing exposure to risk situations and people, formal aids) more often considered when changing youth's own behavior, and strategies reflecting a need for personal change (e.g., education) recommended to others. CONCLUSIONS Our findings support theoretical conceptualizations of alcohol and drug problem resolution that accommodates multiple pathways to recovery. The normative information about specific change strategies generated by youth may further aid in the design of interventions more acceptable for adolescents.
Comparison of 3D SPECT imaging with a rotating slat collimator and a parallel hole collimator

Besides parallel and converging hole collimators which are frequently used in nuclear medicine, slat collimators can be used for Single Photon Emission Computed Tomography (SPECT). The higher photon collection efficiency, inherent to the geometry of rotating slat collimators results in much lower noise in the data. However, reconstruction of the plane integral data measured by a slat collimator is much more sensitive to noise accumulation compared to traditional SPECT reconstruction from line integrals. It is not a straightforward question whether the initial gain in efficiency will compensate for the larger noise accumulation during reconstruction. Therefore, a comparison of the performance of parallel hole and rotating slat collimation is needed. This study compares SPECT with rotating slat and parallel hole collimation in combination with MLEM reconstruction with accurate system modeling and correction for scatter and attenuation. A contrast-to-noise study revealed an improvement of a factor 3 to 4 for hot lesions and more than a factor of 4 for cold lesion. Rotating slat collimators are thus a valuable alternative for parallel hole collimators.
Effect of protein binding on the activity of voriconazole alone or combined with anidulafungin against Aspergillus spp. using a time-kill methodology.

OBJECTIVES the aims of the study were to explore the activity of total and free (according to protein binding) maximal concentrations achieved in serum after multiple doses of voriconazole 400/200 mg and anidulafungin 200/100 mg against Aspergillus fumigatus and Aspergillus flavus and the human albumin or serum effects on antifungal activity. MATERIAL AND METHODS Time-kill curves were performed with two A. fumigatus and two A. flavus strains at voriconazole and anidulafungin Cmax concentrations using different media: a) RPMI broth (Cmax-RPMI); b) RPMI with human serum (Cmax-HS), and c) RPMI with human albumin (Cmax-HAlb). In parallel, free-drug (fCmax) concentrations considering theoretical protein binding were performed in RPMI broth. Aspergillus metabolic activity was measured by the XTT reduction assay. RESULTS Voriconazol or voriconazole plus anidulafungin reduced >88.4% the metabolic activity of Aspergillus sp. at Cmax-RPMI and fCmax after 48 h of exposition. Anidulafungin alone showed poor metabolic reductions (<80.1% at Cmax- RPMI and <15% at fCmax). Anidulafungin activity, but not voriconazole activity alone or combined decreased in presence of HS or HAlb (more pronounced in A. flavus strains and HAlb). However, anidulafungin Cmax-HS or Cmax-HAlb against A. fumigatus strains were significantly more active (p<0.05) than fCmax in RPMI. These species and culture medium-dependent impact of human protein binding in the activity of anidulafungin was related to macroscopic and microscopic differences among mycelial mat grown in RPMI, HS or HAlb in whose XTT retention was different. CONCLUSIONS Synergism could not be demonstrated due to the high activity showed by voriconazole. Protein binding has not impact on voriconazole activity and this impact is considerably less than predicted by free concentration extrapolated from theoretical binding rate on anidulafungin. The XTT colorimetric assay needs to be standardized for use with Aspergillus spp. since without DMSO extraction the activity of echinocandins in a free-human protein RPMI medium could be overestimated.
STAT4 is a genetic risk factor for systemic sclerosis having additive effects with IRF5 on disease susceptibility and related pulmonary fibrosis.

OBJECTIVE Systemic sclerosis (SSc) belongs to the group of connective tissue disorders (CTDs), among which are several disorders characterized by a type I interferon (IFN) signature. The recent identification of an association between IRF5 and SSc further highlights a key role for IFN. STAT4, which encodes STAT-4, contributes to IFN signaling, and its genetic variants were found to be associated with CTDs. The aim of this study was to determine whether the STAT4 rs7574865 single-nucleotide polymorphism is associated with SSc, and whether it interacts with IRF5. METHODS Both the STAT4 rs7574865 and IRF5 rs2004640 polymorphisms were genotyped in 1,855 individuals of French Caucasian origin comprising a discovery set of 440 patients with SSc and 485 control subjects and a replication set of 445 patients with SSc and an additional 485 control subjects. RESULTS STAT4 rs7574865 was shown to be associated with SSc (P=0.001, odds ratio [OR] 1.29, 95% confidence interval [95% CI] 1.11-1.51). This association was not restricted to a particular phenotype. An additive effect of the STAT4 rs7574865 T allele and the IRF5 rs2004640 T allele was observed, resulting in a multiple increased 1.28-fold risk of SSc. The OR for SSc was 2.72 (95% CI 1.86-3.99) for combinations of genotypes with >or=3 risk alleles. An additive effect was also detected for fibrosing alveolitis: carriage of at least 3 risk alleles appeared to be an independent risk factor (P=2.2x10(-4), OR 1.97, 95% CI 1.28-3.04). CONCLUSION Our results establish STAT4 rs7574865 as a new SSc genetic susceptibility factor. STAT4 and IRF5 act with additive effects in terms of susceptibility to both SSc and SSc-related fibrosing alveolitis.