Miracle-dz/UniFAR-FTUs huggingface dataset:
Time‐lapse imaging of granule cells in mouse entorhino‐hippocampal slice cultures reveals changes in spine stability after entorhinal denervation

Principal neurons that are partially denervated after brain injury remodel their synaptic connections and show biphasic changes in their dendritic spine density: during an early phase after denervation spine density decreases and during a late phase spine density recovers again. It has been hypothesized that these changes in spine density are caused by a period of increased spine loss followed by a period of increased spine formation. We have tested this hypothesis, which is based on data from fixed tissues, by using time‐lapse imaging of denervated dentate granule cells in organotypic entorhino‐hippocampal slice cultures of Thy1‐GFP mice. Our data show that nondenervated granule cells turn over spines spontaneously while keeping their spine density constant. Denervation influenced this equilibrium and induced biphasic changes in the spine loss rate but not in the rate of spine formation: during the early phase after denervation the spine loss rate was increased and during the late phase after denervation the spine loss rate was decreased compared with nondenervated control cultures. In line with these observations, time‐lapse imaging of identified spines formed after the lesion revealed that the stability of these spines was decreased during the early phase and increased during the late phase after the lesion. We conclude that biphasic changes in spine loss rate and spine stability but not in the rate of spine formation play a central role in the reorganization of dentate granule cells after entorhinal denervation in vitro. J. Comp. Neurol. 520:1891–1902, 2012. © 2011 Wiley Periodicals, Inc.
Cell‐specific expression of neuropeptide Y Y1 receptor immunoreactivity in the rat basolateral amygdala

Activation of neuropeptide Y (NPY) Y1 receptors (Y1r) in the rat basolateral nuclear complex of the amygdala (BLA) produces anxiolysis and interferes with the generation of conditioned fear. NPY is important in regulating the output of the BLA, yet the cell types involved in mediating this response are currently unknown. The current studies employed multiple label immunocytochemistry to determine the distribution of Y1r‐immunoreactivity (‐ir) in glutamatergic pyramidal and GABAergic cell populations in the BLA using scanning laser confocal stereology. Pyramidal neurons were identified by expression of calcium‐calmodulin dependent kinase II (CaMKII‐ir) and functionally distinct interneuron subpopulations were distinguished by peptide (cholecystokinin, somatostatin) or calcium‐binding protein (parvalbumin, calretinin) content. Throughout the BLA, Y1r‐ir was predominately on soma with negligible fiber staining. The high degree of coexpression of Y1r‐ir (99.9%) in CaMKII‐ir cells suggests that these receptors colocalize on pyramidal cells and that NPY could influence BLA output by directly regulating the activity of these projection neurons. Additionally, Y1r‐ir was also colocalized with the interneuronal markers studied. Parvalbumin‐ir interneurons, which participate in feedforward inhibition of BLA pyramidal cells, represented the largest number of Y1r expressing interneurons in the BLA (≈4% of the total neuronal population). The anatomical localization of NPY receptors on different cell populations within the BLA provides a testable circuit whereby NPY could modulate the activity of the BLA via actions on both projection cells and interneuronal cell populations. J. Comp. Neurol. 517:166–176, 2009. © 2009 Wiley‐Liss, Inc.
Cleavage of Human Transferrin by Porphyromonas gingivalis Gingipains Promotes Growth and Formation of Hydroxyl Radicals

ABSTRACT Porphyromonas gingivalis, a gram-negative anaerobic bacterium associated with active lesions of chronic periodontitis, produces several proteinases which are presumably involved in host colonization, perturbation of the immune system, and tissue destruction. The aims of this study were to investigate the degradation of human transferrin by gingipain cysteine proteinases of P. gingivalis and to demonstrate the production of toxic hydroxyl radicals (HO·) catalyzed by the iron-containing transferrin fragments generated or by release of iron itself. Analysis by polyacrylamide gel electrophoresis and Western immunoblotting showed that preparations of Arg- and Lys-gingipains of P. gingivalis cleave transferrin (iron-free and iron-saturated forms) into fragments of various sizes. Interestingly, gingival crevicular fluid samples from diseased periodontal sites but not samples from healthy periodontal sites contained fragments of transferrin. By using 55Fe-transferrin, it was found that degradation by P. gingivalis gingipains resulted in the production of free iron, as well as iron bound to lower-molecular-mass fragments. Subsequent to the degradation of transferrin, bacterial cells assimilated intracellularly the radiolabeled iron. Growth of P. gingivalis ATCC 33277, but not growth of an Arg-gingipain- and Lys-gingipain-deficient mutant, was possible in a chemically defined medium containing 30% iron-saturated transferrin as the only source of iron and peptides, suggesting that gingipains play a critical role in the acquisition of essential growth nutrients. Finally, the transferrin degradation products generated by Arg-gingipains A and B were capable of catalyzing the formation of HO·, as determined by a hypoxanthine/xanthine oxidase system and spin trapping-electron paramagnetic resonance spectrometry. Our study indicates that P. gingivalis gingipains degrade human transferrin, providing sources of iron and peptides. The iron-containing transferrin fragments or the release of iron itself may contribute to tissue destruction by catalyzing the formation of toxic HO·.
Membrane Topology of γ-Secretase Component PEN-2*

PEN-2 is an integral membrane protein that is a necessary component of the γ-secretase complex, which is central in the pathogenesis of Alzheimer's disease and is also required for Notch signaling. In the absence of PEN-2, Notch signaling fails to guide normal development in Caenorhabditis elegans, and amyloid β peptide is not generated from the amyloid precursor protein. Human PEN-2 is a 101-amino acid protein containing two putative transmembrane domains. To understand its interaction with other γ-secretase components, it is important to know the membrane topology of each member of the complex. To characterize the membrane topology of PEN-2, we introduced single amino acid changes in each of the three hydrophilic regions of PEN-2 to generate N-linked glycosylation sites. We found that the N-linked glycosylation sites present in the N- and C-terminal domains of PEN-2 were utilized, whereas a site in the hydrophilic “loop” region connecting the two transmembrane domains was not. The addition of a carbohydrate structure in the N-terminal domain of PEN-2 prevented association with presenilin 1, whereas glycosylation in the C-terminal region of PEN-2 did not, suggesting that the N-terminal domain is important for interactions with presenilin 1. Immunofluorescence microscopy with selective permeabilization of the plasma membrane of cells expressing epitope-tagged forms of PEN-2 confirmed the lumenal location of both the N and C termini. A protease protection assay also demonstrated that the loop domain of PEN-2 is cytosolic. Thus, PEN-2 spans the membrane twice, with the N and C termini facing the lumen of the endoplasmic reticulum.
Nonlinear stratospheric variability: multifractal de-trended fluctuation analysis and singularity spectra

Characterizing the stratosphere as a turbulent system, temporal fluctuations often show different correlations for different time scales as well as intermittent behaviour that cannot be captured by a single scaling exponent. In this study, the different scaling laws in the long-term stratospheric variability are studied using multifractal de-trended fluctuation analysis (MF-DFA). The analysis is performed comparing four re-analysis products and different realizations of an idealized numerical model, isolating the role of topographic forcing and seasonal variability, as well as the absence of climate teleconnections and small-scale forcing. The Northern Hemisphere (NH) shows a transition of scaling exponents for time scales shorter than about 1 year, for which the variability is multifractal and scales in time with a power law corresponding to a red spectrum, to longer time scales, for which the variability is monofractal and scales in time with a power law corresponding to white noise. Southern Hemisphere (SH) variability also shows a transition at annual scales. The SH also shows a narrower dynamical range in multifractality than the NH, as seen in the generalized Hurst exponent and in the singularity spectra. The numerical integrations show that the models are able to reproduce the low-frequency variability but are not able to fully capture the shorter term variability of the stratosphere.
Determinants of survival in patients with unresectable colorectal liver metastases

Prognostic indicators in 67 patients with unresectable colorectal liver metastases were analyzed. These patients were identified to have isolated hepatic metastases after extensive radiological evaluation and demonstrated good performance status without evidence of liver failure. Univariate analysis revealed 6 of 22 factors that were associated with survival: alkaline phosphatase (AP), lactic dehydrogenase (LDH), occult intra‐ab‐dominal extrahepatic disease, percent hepatic replacement by tumor (PHR), sex, and carcinoembryonic antigen (CEA). A multivariate analysis identified two independent factors that jointly influenced survival: AP and PHR. Patients with an AP >175 U/liter had a greater than threefold relative risk of dying compared with patients with AP ⩾ 175 U/liter (P = 0.0001). Patients with PHR II or III (25–75%, >75%) also had a greater than threefold relative risk of dying compared with patients with PHR 1 (<25%; P = 0.0074). Our patient population is typical of that being entered into trials examining experimental therapies. Alkaline phosphatase and extent of liver involvement by tumor are significant prognostic indicators that should be accounted for in such studies.
Herbal Modulation of P‐Glycoprotein

P‐glycoprotein (Pgp) is a 170 kDa phosphorylated glycoprotein encoded by human MDR1 gene. It is responsible for the systemic disposition of numerous structurally and pharmacologically unrelated lipophilic and amphipathic drugs, carcinogens, toxins, and other xenobiotics in many organs, such as the intestine, liver, kidney, and brain. Like cytochrome P450s (CYP3A4), Pgp is vulnerable to inhibition, activation, or induction by herbal constituents. This was demonstrated by using an ATPase assay, purified Pgp protein or intact Pgp‐expressing cells, and proper probe substrates and inhibitors. Curcumin, ginsenosides, piperine, some catechins from green tea, and silymarin from milk thistle were found to be inhibitors of Pgp, while some catechins from green tea increased Pgp‐mediated drug transport by heterotropic allosteric mechanism, and St. John's wort induced the intestinal expression of Pgp in vitro and in vivo. Some components (e.g., bergamottin and quercetin) from grapefruit juice were reported to modulate Pgp activity. Many of these herbal constituents, in particular flavonoids, were reported to modulate Pgp by directly interacting with the vicinal ATP‐binding site, the steroid‐binding site, or the substrate‐binding site. Some herbal constituents (e.g., hyperforin and kava) were shown to activate pregnane X receptor, an orphan nuclear receptor acting as a key regulator of MDR1 and many other genes. The inhibition of Pgp by herbal constituents may provide a novel approach for reversing multidrug resistance in tumor cells, whereas the stimulation of Pgp expression or activity has implication for chemoprotective enhancement by herbal medicines. Certain natural flavonols (e.g., kaempferol, quercetin, and galangin) are potent stimulators of the Pgp‐mediated efflux of 7,12‐dimethylbenz(a)‐anthracene (a carcinogen). The modulation of Pgp activity and expression by these herb constituents may result in altered absorption and bioavailability of drugs that are Pgp substrates. This is exemplified by increased oral bioavailability of phenytoin and rifampin by piperine and decreased bioavailability of indinavir, tacrolimus, cyclosporine, digoxin, and fexofenadine by coadministered St. John's wort. However, many of these drugs are also substrates of CYP3A4. Thus, the modulation of intestinal Pgp and CYP3A4 represents an important mechanism for many clinically important herb–drug interactions. Further studies are needed to explore the relative role of Pgp and CYP3A4 modulation by herbs and the mechanism for the interplay of these two important proteins in herb–drug interactions.
Laboratory testing of femoral venous cannulae: effect of size, position and negative pressure on flow

Femoral venous cannulae (17-28 French) were tested to compare flows obtained by their placement in a simulated inferior vena cava (IVC) or right atrium (RA) and by varying drainage pressures using gravity siphon drainage or a centrifugal pump in the venous line. The circuit consisted of conventional tubing and equipment including a segment of thin-walled latex tubing to simulate the IVC connected to a flexible reservoir to simulate the RA. The test fluid was a 40% glycerin solution. Flow was measured at height differentials of 30-60 cm (cannula-to-inlet of hard-shell venous reservoir) and with a -10 to -80 mmHg negative pressure created by the centrifugal pump. A roller pump returned the test fluid to a flexible bag to maintain a filling pressure of 0-1 mmHg. Flow increased modestly with an increasing height differential. When negative pressure was applied with the centrifugal pump, flow increased 10% and 18% (IVC and RA positions, respectively) compared to gravity siphon drainage conditions. There also was a tendency for flow to plateau or cease when the centrifugal pump was used at higher levels of negative pressure or when larger cannulae were used. We conclude: (1) position of smaller cannulae in the RA yield better flows than when the cannulae are larger and placed in the IVC; (2) smaller-sized cannulae are capable of achieving higher flows when the centrifugal pump is used; (3) cannulae must be properly positioned to achieve maximum flow; (4) the centrifugal pump will augment flow, but should be regulated to avoid extreme negative pressures; and (5) cannula design has no demonstrable effect on flow.
Antigenic Specificity of the Mucosal Antibody Response to Moraxella catarrhalis in Chronic Obstructive Pulmonary Disease

ABSTRACT Moraxella catarrhalis is an important human mucosal pathogen causing otitis media in children and lower respiratory tract infection in adults with chronic obstructive pulmonary disease (COPD). Little is known about the mucosal antibody response to M. catarrhalis in adults with COPD. In this study, 10 pairs of well-characterized sputum supernatant samples from adults with COPD who had acquired and subsequently cleared M. catarrhalis from their respiratory tracts were studied in detail in an effort to begin to elucidate potentially protective immune responses. Flow cytometry analysis was used to study the distribution of immunoglobulin isotypes in paired preacquisition and postclearance sputum samples. The results showed that immunoglobulin A (IgA) is the predominant M. catarrhalis-specific immunoglobulin isotype and that the sputum IgA contains a secretory component, indicating that it is locally produced at the mucosal site. Most patients made new sputum IgA responses to the adhesins UspA1 and Hag, along with the surface protein UspA2. A smaller proportion of patients made new sputum IgA responses to the iron-regulated proteins TbpB and CopB and to lipooligosaccharide. These results have important implications in understanding the mucosal immune response to M. catarrhalis in the setting of COPD and in elucidating the elements of a protective immune response.
An analysis of two styles of arm action in the vertical countermovement jump

The aim of this study was to determine the effect of two arm swing techniques, the simultaneous arm swing and the early arm swing, on vertical countermovement jump performance and on the contribution of the arms to vertical movement at the centre of mass (CM) during the propulsion phase. Participants were 28 athletes practicing sports in which the vertical jump constitutes a basic ability. Ground reaction forces were recorded by a force platform and the sagittal plane motion was recorded by a video camera. Although at take-off the vertical velocity (2.7 ± 0.2 m/s for simultaneous technique vs. 2.8 ± 0.2 m/s for early technique; p = 0.040) and position (1.18 ± 0.06 m for simultaneous vs. 1.17 ± 0.05 m for early; p = 0.033) of the CM were significantly different, no difference was observed in jump height (1.56 ± 0.01 m in both techniques). The arm action differed during the initial and final propulsion phases in both styles but the accumulated vertical contribution was similar. The practical implication in sports is that the use of the arm-swing technique to reach the maximum jump height should be determined by tactical demands instead of the technical execution of the arms.
Approaches to screening for intimate partner violence in health care settings: a randomized trial.

CONTEXT Screening for intimate partner violence (IPV) in health care settings has been recommended by some professional organizations, although there is limited information regarding the accuracy, acceptability, and completeness of different screening methods and instruments. OBJECTIVE To determine the optimal method for IPV screening in health care settings. DESIGN AND SETTING Cluster randomized trial conducted from May 2004 to January 2005 at 2 each of emergency departments, family practices, and women's health clinics in Ontario, Canada. PARTICIPANTS English-speaking women aged 18 to 64 years who were well enough to participate and could be seen individually were eligible. Of 2602 eligible women, 141 (5%) refused participation. INTERVENTION Participants were randomized by clinic day or shift to 1 of 3 screening approaches: a face-to-face interview with a health care provider (physician or nurse), written self-completed questionnaire, and computer-based self-completed questionnaire. Two screening instruments-the Partner Violence Screen (PVS) and the Woman Abuse Screening Tool (WAST)-were administered and compared with the Composite Abuse Scale (CAS) as the criterion standard. MAIN OUTCOME MEASURES The approaches were evaluated on prevalence, extent of missing data, and participant preference. Agreement between the screening instruments and the CAS was examined. RESULTS The 12-month prevalence of IPV ranged from 4.1% to 17.7%, depending on screening method, instrument, and health care setting. Although no statistically significant main effects on prevalence were found for method or screening instrument, a significant interaction between method and instrument was found: prevalence was lower on the written WAST vs other combinations. The face-to-face approach was least preferred by participants. The WAST and the written format yielded significantly less missing data than the PVS and other methods. The PVS and WAST had similar sensitivities (49.2% and 47.0%, respectively) and specificities (93.7% and 95.6%, respectively). CONCLUSIONS In screening for IPV, women preferred self-completed approaches over face-to-face questioning; computer-based screening did not increase prevalence; and written screens had fewest missing data. These are important considerations for both clinical and research efforts in IPV screening. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00336297.
Interleukin 10- and Fcγ Receptor-Deficient Mice Resolve Leishmania mexicana Lesions

ABSTRACT Infection of C57BL/6 (B6) mice with Leishmania mexicana is associated with a minimal immune response and chronic disease. Here we show that B6 interleukin 10−/− (IL-10−/−) mice resolve their lesions and exhibit increased gamma interferon (IFN-γ), nitric oxide production, and delayed-type hypersensitivity. This enhanced resistance was dependent upon IL-12p40, since treatment of L. mexicana-infected IL-10−/− mice with anti-IL-12p40 monoclonal antibody abrogated healing. Antibody-opsonized L. mexicana induced IL-10 production by B6 macrophages in vitro, implicating antibody binding to Fc receptors as a mechanism involved in IL-10 production in this infection. Furthermore, B6 FcRγ−/− mice resolve L. mexicana lesions, and lymph node cells from these mice produced less IL-10 and more IFN-γ than cells from infected wild-type mice. These data demonstrate that removal of IL-10 or FcγR leads to resolution of L. mexicana disease and support a model in which ligation of FcγR by L. mexicana-bound immunoglobulin G promotes IL-10 production, leading to chronic disease.
County-Level Sexually Transmitted Disease Detection and Control in Texas: Do Sexually Transmitted Diseases and Family Planning Clinics Matter?

Background: Sexually transmitted disease (STD) detection and control have traditionally been performed by STD and family planning (FP) clinics. However, the magnitude of their impact (or the lack thereof) has not been examined. We examine the association between having STD and/or FP clinics and county-level STD detection and control in the state of Texas. Methods: We used county-level STD (chlamydia, gonorrhea, and primary and secondary syphilis) morbidity data from the National Electronic Telecommunications System for Surveillance for 2000 and 2007. We applied spatial regression techniques to examine the impact of the presence of STD/FP clinic(s) (included as dichotomous variables) on STD detection (i.e., morbidity) and control. We included county-level demographic characteristics as control variables. Results: Our results indicated that counties with STD or FP clinics were associated with at least 8% (P < 0.05) increase in the transformed chlamydia and gonorrhea rates, 20% (P < 0.01) increase in transformed syphilis rates in 2000, and at least 6% (P < 0.05) increase in transformed gonorrhea and Chlamydia rates in 2007. From 2000 to 2007, the transformed incidence rates of chlamydia declined by 4% (P < 0.10), 8% (P < 0.01) for gonorrhea, and 8% (P < 0.05) for primary and secondary syphilis for the counties that had at least 1 STD or FP clinic. Conclusions: The results from this ecological study are associations and do not establish a causal relationship between having an STD/FP clinic and improved STD detection and control. Finer level analyses (such as census block or cities) may be able to provide more detail information.