978 resultados para HC-SCR
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We studied the influence of surveyed area size on density estimates by means of camera-trapping in a low-density felid population (1-2 individuals/100 km(2) ). We applied non-spatial capture-recapture (CR) and spatial CR (SCR) models for Eurasian lynx during winter 2005/2006 in the northwestern Swiss Alps by sampling an area divided into 5 nested plots ranging from 65 to 760 km(2) . CR model density estimates (95% CI) for models M0 and Mh decreased from 2.61 (1.55-3.68) and 3.6 (1.62-5.57) independent lynx/100 km(2) , respectively, in the smallest to 1.20 (1.04-1.35) and 1.26 (0.89-1.63) independent lynx/100 km(2) , respectively, in the largest area surveyed. SCR model density estimates also decreased with increasing sampling area but not significantly. High individual range overlaps in relatively small areas (the edge effect) is the most plausible reason for this positive bias in the CR models. Our results confirm that SCR models are much more robust to changes in trap array size than CR models, thus avoiding overestimation of density in smaller areas. However, when a study is concerned with monitoring population changes, large spatial efforts (area surveyed ≥760 km(2) ) are required to obtain reliable and precise density estimates with these population densities and recapture rates.
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Background: Cerebral dysfunction occurring in mental disorders can show metabolic disturbances which are limited to circumscribed brain areas. Auditory hallucinations have been shown to be related to defined cortical areas linked to specific language functions. Here, we investigated if the study of metabolic changes in auditory hallucinations requires a functional rather than an anatomical definition of their location and size to allow a reliable investigation by magnetic resonance spectroscopy (MRS). Methods: Schizophrenia patients with (AH; n = 12) and without hallucinations (NH; n = 8) and healthy controls (HC; n = 11) underwent a verbal fluency task in functional MRI (fMRI) to functionally define Broca's and Wernicke's areas. Left and right Heschl's gyri were defined anatomically. Results: The mean distances in native space between the fMRI-defined regions and a corresponding anatomically defined area were 12.4 ± 6.1 mm (range: 2.7–36.1 mm) for Broca's area and 16.8 ± 6.2 mm (range: 4.5–26.4 mm) for Wernicke's area, respectively. Hence, the spatial variance was of similar extent as the size of the investigated regions. Splitting the investigations into a single voxel examination in the frontal brain and a spectroscopic imaging part for the more homogeneous field areas led to good spectral quality for almost all spectra. In Broca's area, there was a significant group effect (p = 0.03) with lower levels of N-acetyl-aspartate (NAA) in NH compared to HC (p = 0.02). There were positive associations of NAA levels in the left Heschl's gyrus with total (p = 0.03) and negative (p = 0.006) PANSS scores. In Broca's area, there was a negative association of myo-inositol levels with total PANSS scores (p = 0.008). Conclusion: This study supports the neurodegenerative hypothesis of schizophrenia only in a frontal region whereas the results obtained from temporal regions are in contrast to the majority of previous studies. Future research should test the hypothesis raised by this study that a functional definition of language regions is needed if neurochemical imbalances are expected to be restricted to functional foci.
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We present a purely physical model to determine cosmogenic production rates for noble gases and radionuclides in micrometeorites (MMs) and interplanetary dust particles (IDPs) by solar cosmic-rays (SCR) and galactic cosmic-rays (GCR) fully considering recoil loss effects. Our model is based on various nuclear model codes to calculate recoil cross sections, recoil ranges, and finally the percentages of the cosmogenic nuclides that are lost as a function of grain size, chemical composition of the grain, and the spectral distribution of the projectiles. The main advantage of our new model compared with earlier approaches is that we consider the entire SCR particle spectrum up to 240 MeV and not only single energy points. Recoil losses for GCR-produced nuclides are assumed to be equal to recoil losses for SCR-produced nuclides. Combining the model predictions with Poynting-Robertson orbital lifetimes, we calculate cosmic-ray exposure ages for recently studied MMs, cosmic spherules, and IDPs. The ages for MMs and the cosmic-spherule are in the range <2.2–233 Ma, which corresponds, according to the Poynting-Robertson drag, to orbital distances in the range 4.0–34 AU. For two IDPs, we determine exposure ages of longer than 900 Ma, which corresponds to orbital distances larger than 150 AU. The orbital distance in the range 4–6 AU for one MM and the cosmic spherule indicate an origin either in the asteroid belt or release from comets coming either from the Kuiper Belt or the Oort Cloud. Three of the studied MMs have orbital distances in the range 23–34 AU, clearly indicating a cometary origin, either from short-period comets from the Kuiper Belt or from the Oort Cloud. The two IDPs have orbital distances of more than 150 AU, indicating an origin from Oort Cloud comets.
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Endometriosis is an estrogen-dependent disease that can lead to chronic pain and subfertility. Endometriotic lesions found in different locations are heterogeneous and may represent a collection of related but distinct conditions. Whether there is a relationship between hormonal contraceptive (HC) use and endometriosis is still controversial. The purpose of this study was to determine whether HC use affected the prevalence of endometriotic lesions differently based on lesion location. Data was retrospectively collected from 161 patients presenting to the Berne University Women's Hospital between 2008 and 2012 for laparoscopic investigation. Women with histologically proven endometriosis were included in the study and patients were grouped according to lesion location and HC use. The results of the study indicate that HC users are significantly less likely to have endometriotic lesions on the ovaries, although in contrast, no difference was observed in the incidence of lesions in the rectovaginal septum (RVS) or peritoneal region. In addition, women using HC who were diagnosed with endometriotic lesions on the peritoneum were significantly younger than women with lesions in other locations. In conclusion, women with endometriosis who are currently using HC are less likely to have ovarian endometriotic lesions than in alternate locations.
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Microtubule-based transport mediates the sorting and dispersal of many cellular components and pathogens. However, the mechanisms by which motor complexes are recruited to and regulated on different cargos remain poorly understood. Here we describe a large-scale biochemical screen for novel factors associated with RNA localization signals mediating minus end-directed mRNA transport during Drosophila development. We identified the protein Lissencephaly-1 (Lis1) and found that minus-end travel distances of localizing transcripts are dramatically reduced in lis1 mutant embryos. Surprisingly, given its well-documented role in regulating dynein mechanochemistry, we uncovered an important requirement for Lis1 in promoting the recruitment of dynein and its accessory complex dynactin to RNA localization complexes. Furthermore, we provide evidence that Lis1 levels regulate the overall association of dynein with dynactin. Our data therefore reveal a critical role for Lis1 within the mRNA localization machinery and suggest a model in which Lis1 facilitates motor complex association with cargos by promoting the interaction of dynein with dynactin.
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Most previous neurophysiological studies evoked emotions by presenting visual stimuli. Models of the emotion circuits in the brain have for the most part ignored emotions arising from musical stimuli. To our knowledge, this is the first emotion brain study which examined the influence of visual and musical stimuli on brain processing. Highly arousing pictures of the International Affective Picture System and classical musical excerpts were chosen to evoke the three basic emotions of happiness, sadness and fear. The emotional stimuli modalities were presented for 70 s either alone or combined (congruent) in a counterbalanced and random order. Electroencephalogram (EEG) Alpha-Power-Density, which is inversely related to neural electrical activity, in 30 scalp electrodes from 24 right-handed healthy female subjects, was recorded. In addition, heart rate (HR), skin conductance responses (SCR), respiration, temperature and psychometrical ratings were collected. Results showed that the experienced quality of the presented emotions was most accurate in the combined conditions, intermediate in the picture conditions and lowest in the sound conditions. Furthermore, both the psychometrical ratings and the physiological involvement measurements (SCR, HR, Respiration) were significantly increased in the combined and sound conditions compared to the picture conditions. Finally, repeated measures ANOVA revealed the largest Alpha-Power-Density for the sound conditions, intermediate for the picture conditions, and lowest for the combined conditions, indicating the strongest activation in the combined conditions in a distributed emotion and arousal network comprising frontal, temporal, parietal and occipital neural structures. Summing up, these findings demonstrate that music can markedly enhance the emotional experience evoked by affective pictures.
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Choline is an essential nutrient for eukaryotic cells, where it is used as precursor for the synthesis of choline-containing phospholipids, such as phosphatidylcholine (PC). Our experiments showed – for the first time – that Trypanosoma brucei, the causative agent of human African sleeping sickness, is able to take up choline from the culture medium to use for PC synthesis, indicating that trypanosomes express a transporter for choline at the plasma membrane. Further characterization in procyclic and bloodstream forms revealed that choline uptake is saturable and can be inhibited by HC-3, a known inhibitor of choline uptake in mammalian cells. To obtain additional insights on choline uptake and metabolism, we investigated the effects of choline-analogs that were previously shown to be toxic for T. brucei parasites in culture. Interestingly, we found that all analogs tested effectively inhibited choline uptake into both bloodstream and procyclic form parasites. Subsequently, selected compounds were used to search for possible candidate genes encoding choline transporters in T. brucei, using an RNAi library in bloodstream forms. We identified a protein belonging to the mitochondrial carrier family, previously annotated as TbMCP14, as prime candidate. Down‐regulation of TbMCP14 by RNAi prevented drug-induced loss of mitochondrial membrane potential and conferred 8‐fold resistance of T. brucei bloodstream forms to choline analogs. Conversely, over‐expression of the carrier increased parasite susceptibility more than 13-fold. However, subsequent experiments demonstrated that TbMCP14 was not involved in metabolism of choline. Instead, growth curves in glucose‐depleted medium using RNAi or knock‐out parasites suggested that TbMCP14 is involved in metabolism of amino acids for energy production. Together, our data demonstrate that the identified member of the mitochondrial carrier family is involved in drug uptake into the mitochondrion and has a vital function in energy production in T. brucei.
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BACKGROUND Observational studies of a putative association between hormonal contraception (HC) and HIV acquisition have produced conflicting results. We conducted an individual participant data (IPD) meta-analysis of studies from sub-Saharan Africa to compare the incidence of HIV infection in women using combined oral contraceptives (COCs) or the injectable progestins depot-medroxyprogesterone acetate (DMPA) or norethisterone enanthate (NET-EN) with women not using HC. METHODS AND FINDINGS Eligible studies measured HC exposure and incident HIV infection prospectively using standardized measures, enrolled women aged 15-49 y, recorded ≥15 incident HIV infections, and measured prespecified covariates. Our primary analysis estimated the adjusted hazard ratio (aHR) using two-stage random effects meta-analysis, controlling for region, marital status, age, number of sex partners, and condom use. We included 18 studies, including 37,124 women (43,613 woman-years) and 1,830 incident HIV infections. Relative to no HC use, the aHR for HIV acquisition was 1.50 (95% CI 1.24-1.83) for DMPA use, 1.24 (95% CI 0.84-1.82) for NET-EN use, and 1.03 (95% CI 0.88-1.20) for COC use. Between-study heterogeneity was mild (I2 < 50%). DMPA use was associated with increased HIV acquisition compared with COC use (aHR 1.43, 95% CI 1.23-1.67) and NET-EN use (aHR 1.32, 95% CI 1.08-1.61). Effect estimates were attenuated for studies at lower risk of methodological bias (compared with no HC use, aHR for DMPA use 1.22, 95% CI 0.99-1.50; for NET-EN use 0.67, 95% CI 0.47-0.96; and for COC use 0.91, 95% CI 0.73-1.41) compared to those at higher risk of bias (pinteraction = 0.003). Neither age nor herpes simplex virus type 2 infection status modified the HC-HIV relationship. CONCLUSIONS This IPD meta-analysis found no evidence that COC or NET-EN use increases women's risk of HIV but adds to the evidence that DMPA may increase HIV risk, underscoring the need for additional safe and effective contraceptive options for women at high HIV risk. A randomized controlled trial would provide more definitive evidence about the effects of hormonal contraception, particularly DMPA, on HIV risk.
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BACKGROUND: The understanding of molecular mechanisms leading to poor prognosis in pancreatic cancer may help develop treatment options. N-myc downstream-regulated gene-1 (NDRG1) has been correlated to better prognosis in pancreatic cancer. Therefore, we thought to analyze how the loss of NDRG1 affects progression in an orthotopic xenograft animal model of recurrence. METHODS: Capan-1 cells were silenced for NDRG1 (C(sil)) or transfected with scrambled shRNA (C(scr)) and compared for anchorage-dependent and anchorage-independent growth, invasion and tube formation in vitro. In an orthotopic xenograft model of recurrence tumors were grown in the pancreatic tail. The effect of NDRG1 silencing was evaluated on tumor size and metastasis. RESULTS: The silencing of NDRG1 in Capan-1 cells leads to more aggressive tumor growth and metastasis. We found faster cell growth, double count of invaded cells and 1.8-fold increase in tube formation in vitro. In vivo local tumors were 5.9-fold larger (p = 0.006) and the number of metastases was higher in animals with tumors silenced for NDRG1 primarily (3 vs. 1.1; p = 0.005) and at recurrence (3.3 vs. 0.9; p = 0.015). CONCLUSION: NDRG1 may be an interesting therapeutic target as its silencing in human pancreatic cancer cells leads to a phenotype with more aggressive tumor growth and metastasis.
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Four Staphylococcus aureus-Escherichia coli shuttle vectors were constructed for gene expression and production of tagged fusion proteins. Vectors pBUS1-HC and pTSSCm have no promoter upstream of the multiple cloning site (MCS), and this allows study of genes under the control of their native promoters, and pBUS1-Pcap-HC and pTSSCm-Pcap contain the strong constitutive promoter of S. aureus type 1 capsule gene 1A (Pcap) upstream of a novel MCS harboring codons for the peptide tag Arg-Gly-Ser-hexa-His (rgs-his6). All plasmids contained the backbone derived from pBUS1, including the E. coli origin ColE1, five copies of terminator rrnB T1, and tetracycline resistance marker tet(L) for S. aureus and E. coli. The minimum pAMα1 replicon from pBUS1 was improved through either complementation with the single-strand origin oriL from pUB110 (pBUS1-HC and pBUS1-Pcap-HC) or substitution with a pT181-family replicon (pTSSCm and pTSSCm-Pcap). The new constructs displayed increased plasmid yield and segregational stability in S. aureus. Furthermore, pBUS1-Pcap-HC and pTSSCm-Pcap offer the potential to generate C-terminal RGS-His6 translational fusions of cloned genes using simple molecular manipulation. BcgI-induced DNA excision followed by religation converts the TGA stop codon of the MCS into a TGC codon and links the rgs-his6 codons to the 3' end of the target gene. The generation of the rgs-his6 codon-fusion, gene expression, and protein purification were demonstrated in both S. aureus and E. coli using the macrolide-lincosamide-streptogramin B resistance gene erm(44) inserted downstream of Pcap. The new His tag expression system represents a helpful tool for the direct analysis of target gene function in staphylococcal cells.
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Post-traumatic stress disorder (PTSD) is a disorder that involves impaired regulation of the fear response to traumatic reminders. This study tested how women with male-perpetrated interpersonal violence-related PTSD (IPV-PTSD) differed in their brain activation from healthy controls (HC) when exposed to scenes of male-female interaction of differing emotional content. Sixteen women with symptoms of IPV-PTSD and 19 HC participated in this study. During magnetic resonance imaging, participants watched a stimulus protocol of 23 different 20 s silent epochs of male-female interactions taken from feature films, which were neutral, menacing or prosocial. IPV-PTSD participants compared with HC showed (i) greater dorsomedial prefrontal cortex (dmPFC) and dorsolateral prefrontal cortex (dlPFC) activation in response to menacing vs prosocial scenes and (ii) greater anterior cingulate cortex (ACC), right hippocampus activation and lower ventromedial prefrontal cortex (vmPFC) activty in response to emotional vs neutral scenes. The fact that IPV-PTSD participants compared with HC showed lower activity of the ventral ACC during emotionally charged scenes regardless of the valence of the scenes suggests that impaired social perception among IPV-PTSD patients transcends menacing contexts and generalizes to a wider variety of emotionally charged male-female interactions.
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von E.W. Tschlenoff
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von Hans Fischer
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In the rabbit retina, there are two kinds of horizontal cells (HCs). The A-type HC is a large axonless cell which contacts cones exclusively. The B-type HC is an axon bearing cell. While the somatic dendrites of B-type HCs also contact cones, the axon expands into an elaborately branched structure, the axon terminal (AT), which contacts a large number of rods. It is difficult to label the different HCs selectively by immunochemical methods. Therefore, we developed dye injection methods to label each type of HC. Then it was possible, (1) to describe the detailed structure of the AT (2) to identify the glutamate receptors mediating cone input to A and B-type HCs and rod input to ATs and (3) to test the hypothesis that the B-type HCs are coupled via Cx57 gap junctions. ^ To obtain well filled examples of single HCs, it was necessary to block gap junction coupling to stop the spread of Neurobiotin through the network. We used dye coupling in A-type HCs to screen a series of potential gap junction antagonists. One of these compounds, meclofenamic acid (MFA), was potent, water soluble and easily reversible. This compound may be a useful tool to manipulate gap junction coupling. ^ In the presence of MFA, Neurobiotin passed down the axon of B-type HCs to reveal the detailed structure of the AT. We observed that only one AT ending entered each rod spherule invagination. This observation was confirmed by calculation and two dye injections. ^ Glutamate is the neurotransmitter used by both rods and cones. AMPA receptors were colocalized with the dendrites of A and B-type HCs at each cone pedicle. In addition, AMPA receptors were located on the AT ending at each rod spherule. Thus rod and cone input to HCs is mediated by AMPA receptors. ^ A-type and B-type HCs may express different connexins because they have different dye-coupling properties. Recently, we found that connexin50 (Cx50) is expressed by A-type HCs. B-type HCs and B-type ATs are also independently coupled. Cx57 was expressed in the OPL and double label studies showed that Cx 57 was colocalized with the AT matrix but not with the somatic dendrites of B-type HCs. ^ In summary, we have identified a useful gap junction antagonist, MFA. There is one AT ending at each rod spherule, rods inputs to ATs is mediated by AMPA receptors and coupling in the AT matrix is mediated by Cx57. This confirms that HCs with different properties use distinct connexins. The properties of ATs described in this research are consistent. The connections and properties reported here suggest that ATs functions as rod HCs and provide a negative feedback signal to rods. ^
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Background. The parents of a sick child likely experience situational anxiety due to their young child being unexpectedly hospitalized. The emotional upheaval may be great enough that their anxiety inhibits them in providing positive support to their hospitalized child. Because anxiety affects psychological distress as well as behavioral distress, identifying parental distress helps parents improving their coping mechanisms. ^ Purpose. The study compared situational anxiety levels between Taiwanese fathers and mothers and focused on differences between parental anxiety levels at the beginning of the child's unplanned hospitalization and at time of discharge. The study also identified factors related to the parents' distress and use of coping mechanisms. ^ Methods. A descriptive, comparative research design was used to determine the difference between the anxiety levels of 62 Taiwanese father-mother dyads during the situational crisis of their child's unexpected hospitalization. The Mandarin version (M) of Visual Analog Scale (VAS-M), State-Trait Anxiety Inventory (STAI-M), and the Index of Parent Participation/Hospitalized Child (IPP/HC-M) were used to differentiate maternal and paternal anxiety levels and identify factors related to the parents' distress. Questionnaires were completed by parents within 24-36 hours of the child's hospital admission and within 24 hours prior to discharge. A paired t-test, two sample t-test, and linear mixed regression model were used to test and support the study hypothesis. ^ Results. The findings reveal that the mothers' anxiety levels did not significantly differ from the fathers' anxiety level when their child had a sudden admission to the hospital. In particular, parental state anxiety levels did not decrease during the child's hospital stay and subsequent discharge. Moreover, anxiety levels did not differ between parents regardless of whether the child's disease was acute or chronic. The most effective factor related to parental situational anxiety was parental perception of the severity of the child's illness. ^ Conclusions. Parental anxiety was found to be significantly related to changes in their perception of the severity of their child's illness. However, the study was not able to illustrate how parental involvement in the child's hospital care was related to parental perception of the severity of their child's illness. Future studies, using a qualitative approach to gamer more information as to what variables influence parental anxiety during a situational crisis, may provide a richer database from which to modify key variables as well as the instruments used to improve the quality of the data obtained. ^