Miracle-dz/UniFAR-FTUs huggingface dataset:
Cartilage Shear Kinematics During Tibio-Femoral Articulation: Effect of Acute Joint Injury & Tribosupplementation on Synovial Fluid Lubrication

Objective— To determine the effects of acute injury and tribosupplementation by hyaluronan (HA) on synovial fluid (SF) modulation of cartilage shear during tibio-femoral articulation. Methods— Human osteochondral blocks from the lateral femoral condyle (LFC) and tibial plateau (LTP) were apposed, compressed 13%, and subjected to sliding under video microscopy. Tests were conducted with equine SF from normal joints (NL-SF), SF from acutely injured joints (AI-SF), and AI-SF to which HA was added (AI-SF+HA). Local and overall shear strain (E xz ) and the lateral displacement ( Δ x) at which E xz reached 50% of peak values ( Δ x 1/2 ) were determined. Results— During articulation, LFC and LTP cartilage E xz increased with Δ x and peaked when surfaces slid, with peak E xz being maintained during sliding. With AI-SF as lubricant, surface and overall Δ x 1/2 were ~40% and ~20% higher, respectively than values with NL-SF and AI-SF+HA as lubricant. Also, peak E xz was markedly higher with AI-SF as lubricant than with NL-SF as lubricant, both near the surface (~80%) and overall (50–200%). Following HA supplementation to AI-SF, E xz was reduced from values with AI-SF alone by 30–50% near the surface and 20–30% overall. Magnitudes of surface and overall E xz were markedly (~50–80%) higher in LTP cartilage than LFC cartilage for all lubricants. Conclusion— Acute injury impairs SF function, elevating cartilage E xz markedly during tibiofemoral articulation; such elevated E xz may contribute to post-injury associated cartilage degeneration. Since HA partially restores the function of AI-SF, as indicated by E xz , tribosupplements may be beneficial in restoring cartilage mechanobiology.
In Situ Characterization of the Ca 2 1 Sensitivity of Large Conductance Ca 2 1 -Activated K 1 Channels: Implications for Their Use as Near-Membrane Ca 2 1 Indicators in Smooth Muscle Cells

The Ca 2 1 sensitivity of large conductance Ca 2 1 - and voltage-activated K 1 channels (BK V,Ca ) has been determined in situ in freshly isolated myocytes from the guinea pig urinary bladder. In this study, in situ denotes that BK V,Ca channel activity was recorded without removing the channels from the cell. By combining patch clamp recording in the cell-attached configuration and microfluorometry of fura-2, we were able to correlate BK V,Ca channel activity with changes in cytoplasmic intracellular [Ca 2 1 ] ([Ca 2 1 ] i ). The latter were induced by ionomycin, an electroneutral Ca 2 1 ionophore. At 0 mV, the Hill coefficient ( n H ) and the [Ca 2 1 ] i to attain half of the maximal BK V,Ca channel activity (Ca 50 ) were 8 and 1 m M, respectively. The data suggest that this large Hill number was not a consequence of the difference between the near-membrane [Ca 2 1 ] ([Ca 2 1 ] s ) and the bulk [Ca 2 1 ] i , indicated by fura-2. High Hill numbers in the activation by Ca 2 1 of BK V,Ca channels have been seen by different groups (e.g., filled squares in Fig. 4 of Silberberg, S. D., A. Lagrutta, J. P. Adelman, and K. L. Magleby. 1996. Biophys. J. 70:2640–2651). However, such high n H has always been considered a peculiarity rather than the rule. This work shows that a high Ca 2 1 cooperativity is the normal situation for BK V,Ca channels in myocytes from guinea pig urinary bladder. Furthermore, the Ca 50 did not display any significant variation among different channels or cells. It was also evident that BK V,Ca channel activity could decrease in elevated [Ca 2 1 ] i , either partially or completely. This work implies that the complete activation of BK V,Ca channels occurs with a smaller increment in [Ca 2 1 ] s than previously expected from in vitro characterization of the Ca 2 1 sensitivity of these channels. Additionally, it appears that the activity of BK V,Ca channels in situ does not strictly follow changes in near-membrane [Ca 2 1 ].
Detailed Genomic Analysis of the W (cid:2) and (cid:3) Phages Infecting Bacillus anthracis : Implications for Evolution of Environmental Fitness and Antibiotic Resistance† adaptations to low-nutrient oce-*

Phage-mediated lysis has been an essential laboratory tool for rapidly identifying Bacillus anthracis for more than 40 years, relying on the (cid:1) phage derivative of a Bacillus cereus prophage called W. The complete genomic sequences of the temperate W phage, referred to as W (cid:2) , and its lytic variant (cid:1) were determined and found to encode 53 open reading frames each, spanning 40,864 bp and 37,373 bp, respectively. Direct comparison of the genomes showed that (cid:1) evolved through mutations at key loci controlling host recognition, lysogenic growth, and possibly host phenotypic modiﬁcation. Included are a cluster of point mutations at the gp14 tail ﬁber locus of (cid:1) , encoding a protein that, when fused to green ﬂuorescent protein, binds speciﬁcally to B . anthracis . A large 2,003-bp deletion was also identiﬁed at the (cid:1) lysogeny module, explaining its shift from a temperate to a lytic lifestyle. Finally, evidence of recombination was observed at a dicistronic W (cid:2) locus, encoding putative bacterial cell surface-modifying proteins, replaced in (cid:1) with a locus, likely obtained from a B . anthracis prophage, encoding demonstrable fosfomycin resistance. Reverse transcriptase PCR analysis conﬁrmed strong induction at the dicistronic W (cid:2) locus and at four other phage loci in B . anthracis and/or B . cereus lysogens. In all, this study represents the ﬁrst genomic and functional description of two historically important phages and is part of a broader investigation into contributions of phage to the B . anthracis life cycle. Initial ﬁndings suggest that lysogeny of B . anthracis promotes ecological adaptation, rather than virulence, as with other gram-positive pathogens.
C1q Inhibits Antibody-Dependent Enhancement of Flavivirus Infection In Vitro and In Vivo in an IgG Subclass Specific Manner

SUMMARY Severe dengue virus (DENV) infection occurs in humans with pre-existing antibodies. To explain this, a hypothesis emerged that antibody-dependent enhancement of infection (ADE) increases viral burden and causes more severe disease. In vitro , ADE has been described for multiple viruses, including DENV and West Nile virus (WNV). However, the demonstration of ADE in vivo and its linkage to disease remains controversial. Herein, we demonstrate that the complement component C1q restricts ADE by anti-flavivirus antibodies in an IgG subclass-specific manner in cell culture and mice. IgG subclasses that bind C1q avidly induce minimal ADE in the presence of C1q, whereas subclasses that bind C1q weakly strongly enhance infection. These studies describe a new small animal model of ADE in vivo and identify an unappreciated layer of complexity for the analysis of humoral immunity and flavivirus infection. common nucleic acid genome structure (positive-polarity, ~11 kilobase single-stranded RNA), organization (three structural and seven non-structural
LOSS OF DENTIN SIALOPHOSPHOPROTEIN (DSPP) LEADS TO PERIODONTAL DISEASES IN MICE

Background and Objective— Dentin sialophosphoprotein (DSPP) and its cleaved products, dentin phosphoprotein (DPP) and dentin sialoprotein (DSP), play important roles in biomineralization. Recently, we observed that DSPP is highly expressed in the alveolar bone and cementum, indicating that this molecule may play an important role in the formation and maintenance of a healthy periodontium, and its deletion may cause increased susceptibility to periodontal diseases. The objective of this investigation was to study the effects of Dspp ablation on periodontal tissues by analyzing Dspp null mice. Methods— Newborn to 6-month-old Dspp null mice were examined, and the 3-month and 6-month-old Dspp null mice were characterized in detail using X-ray radiography, histology and scanning electron microscopy (backscattered as well as resin-infiltrating). Wild-type mice of the same age groups served as the normal controls. Results— The Dspp null mice showed a significant loss of alveolar bone and cementum, particularly in the furcation and the interproximal regions of the molars. The alveolar bone appeared more porous while the quantity of cementum was reduced in the apical region. The canalicular systems and osteocytes in the alveolar bone were abnormal, with reduced numbers of canaliculi and an altered osteocyte morphology. The loss of alveolar bone and cementum along with the detachment of the periodontal ligaments (PDL) led to the apical migration of the epithelial attachment and the formation of periodontal pockets. Inactivation of DSPP leads to the loss of the alveolar bone and cementum and increased susceptibility to bacterial infections in the PDL of Dspp null mice. The fact that the loss of DSPP results in periodontal diseases indicates that this molecule plays a vital role in maintaining the health of the periodontium.
A luminometric assay for peroxisomal f-oxidation Effects of fasting and streptozotocin-diabetes on peroxisomal fl-oxidation

1. A luminometric assay for acyl-CoA oxidase activity is described. The assay uses the luminol/micro-peroxidase system to monitor continuously acyl-CoA-dependent generation of H202. The assay is rapid, convenient, and lends itself to automation with an LKB 1251 luminometer. The assay is extremely sensitive, requiring at the most 10,g of liver-homogenate protein per assay. 2. The assay can also be used to measure other oxidases, e.g. glycollate oxidase (EC 1.1.3.15), D-aspartate oxidase (EC 1.4.3.1) and urate oxidase (EC 1.7.3.3), the only modification being substitution of substrates to appropriate concentration. 3. With rat liver homogenates, spectrophotometrically measured rates of palmitoyl-CoA-dependent NAD+ reduction and acyl-CoA oxidase activity [Hryb & Hogg (1979) Biochem. Biophys. Res. Commun. 87, 1200-1206] was generally found in good agreement with luminometrically measured acyl-CoA oxidase activity. 4. With liver homogenates from streptozotocin-diabetic rats, however, rates of palmitoyl-CoA-dependent NAD+ reduction were consistently lower than the corresponding acyl-CoA oxidase activity. This difference was most marked with respect to luminometrically assayed acyl-CoA oxidase activity.
Current Use of Underage Alcohol Compliance Checks by Enforcement Agencies in the U.S.

, Abstract Background— Compliance checks conducted by law enforcement agents can significantly reduce the likelihood of illegal alcohol sales to underage individuals, but these checks need to be conducted using optimal methods to maintain effectiveness. Materials and Methods— We conducted a national survey of local and state enforcement agencies in 2010–2011 to assess: (1) how many agencies are currently conducting underage alcohol compliance checks, (2) how many agencies that conduct compliance checks use optimal methods—including checking all establishments in the jurisdiction, conducting checks at least 3–4 times per year, conducting follow-up checks within 3 months, and penalizing the licensee (not only the server/clerk) for failing a compliance check, and (3) characteristics of the agencies that conduct compliance checks. Results— Just over one third of local law enforcement agencies and over two thirds of state agencies reported conducting compliance checks. However, only a small percentage of the agencies (4–6%) reported using all of the optimal methods to maximize effectiveness of these compliance checks. Local law enforcement agencies with an alcohol-related division, those with at least one full-time officer assigned to work on alcohol, and those in larger communities were significantly more likely to conduct compliance checks. State agencies with more full-time agents and those located in states where the state agency or both state and local enforcement agencies have primary responsibility (vs. only the local law agency) for enforcing alcohol retail laws were also more likely to conduct compliance checks; however, these agency characteristics did not remain statistically significant in the multivariate analyses. Conclusions— Continued effort is needed to increase the number of local and state agencies conducting compliance checks using optimal methods to reduce youth access to alcohol.
Comparing the 7-Day PAR with a Triaxial Accelerometer for Measuring Time in Exercise

Purpose— The primary study aim was to evaluate associations of estimated weekly minutes of moderate-to-vigorous intensity exercise from self-reports of the telephone-administered 7-Day Physical Activity Recall (PAR) with data captured by the RT3 triaxial accelerometer. Methods— This investigation was undertaken as part of the FRESH START study, a randomized clinical trial that tested an iteratively-tailored diet and exercise mailed print intervention among newly diagnosed breast and prostate cancer survivors. A convenience sample of 139 medically-eligible subjects living within a 60-mile radius of the study center provided both 7-Day PAR and accelerometer data at enrollment. Ultimately n=115 substudy subjects were found eligible for the FRESH START study and randomized to one of two study treatment arms. Follow-up assessments at Year 1 (n=103) and Year 2 (n=99) provided both the 7-Day PAR and accelerometer data. Results— There was moderate agreement between the 7-Day PAR and the accelerometer with longitudinal serial correlation coefficients of . 54 (baseline), . 24 (Year 1) and . 53 (Year 2), all P-values < . 01, though the accelerometer estimates for weekly time in moderate-to-vigorous physical activity were much higher than those of the 7-Day PAR at all time points. The two methods were poorly correlated in assessing sensitivity to change from baseline to Year 1 (rho=.11, P=.30). Using mixed models repeated measures analysis, both methods exhibited similar non-significant treatment arm X time interaction P-values (7-Day PAR=.22, accelerometer=.23). Conclusions— The correlations for three serial time points were in agreement with findings of other studies that compared self-reported time in exercise with physical activity captured by accelerometry. However, these methods capture somewhat different dimensions of physical activity and provide differing estimates of change over time.
Fine-tuning Serotonin 2C Receptor Function in the Brain: Molecular and Functional Implications

The serotonin 2C receptor (5-HT 2C R) is a member of the serotonin 2 family of 7-transmembrane-spanning (7-TMS) receptors, which possesses unique molecular and pharmacological properties such as constitutive activity and RNA-editing. The 5-HT 2C R is widely expressed within the central nervous system, where is thought to play a major role in the regulation of neuronal network excitability. In keeping with its ability to modulate dopamine (DA) neuron function in the brain, the 5-HT 2C R is currently considered as a major target for improved treatments of neuropsychiatric disorders related to DA neuron dysfunction, such as depression, schizophrenia, Parkinson’s disease or drug addiction. The aim of this review is to provide an update of the functional status of the central 5-HT 2C R, covering molecular, cellular, anatomical, biochemical and behavioral aspects to highlight its distinctive regulatory properties, the emerging functional significance of constitutive activity and RNA-editing in vivo , and the therapeutic potential of inverse agonism.
VASOACTIVE INTESTINAL PEPTIDE (VIP) ACTS VIA MULTIPLE SIGNAL PATHWAYS TO REGULATE HIPPOCAMPAL NMDA RECEPTORS AND SYNAPTIC TRANSMISSION

Vasoactive intestinal peptide (VIP) is a 28 amino acid peptide which belongs to a superfamily of structurally related peptide hormones including pituitary adenylate cyclase-activating polypeptide (PACAP). Although several studies have identified the involvement of PACAP in learning and memory, little work has been done to investigate such a role for VIP. At least three receptors for VIP have been identified including the PACAP receptor (PAC1-R) and the two VIP receptors (VPAC receptors). VIP can activate the PAC1-R only if it is used at relatively high concentrations (e.g. 100 nM); however, at lower concentrations (e.g. 1 nM) it is selective for the VPAC receptors. Our lab has showed that PAC1-R activation signals through PKC/CAK β /Src pathway to regulate NMDA receptors, however there is little known about the potential regulation of NMDA receptors by VPAC receptors. Our studies demonstrated that application of 1nM VIP enhanced NMDA currents by stimulating VPAC receptors as the effect was blocked by VPAC receptor antagonist [Ac-Tyr 1 , D-Phe 2 (1–29). This enhancement of NMDA currents was blocked by both Rp-cAMPS and PKI 14–22 (they are highly specific PKA inhibitors), but not by the specific PKC inhibitor, bisindolylmaleimide I. In addition, the VIP-induced enhancement of NMDA currents was accentuated by inhibition of phosphodiesterase 4, which inhibits the degradation of cAMP. This regulation of NMDA receptors also required the scaffolding protein AKAP. In contrast, the potentiation induced by high concentration of VIP (e.g. 100 nM) was mediated by PAC1-R as well as by Src kinase. Overall, these results show that VIP can regulate NMDA receptors through different receptors and signaling pathways.
Revisiting the Role of Ca 2 1 in Shaker K 1 Channel Gating

Shaker K 1 channels were expressed in outside-out macropatches excised from Xenopus oocytes, and the effects on gating of removal of extracellular Ca 2 1 were examined in the complete absence of intracellular divalent cations. Removal of extracellular Ca 2 1 by perfusion with EDTA-containing solution caused a small negative shift in the channel’s voltage-activation curve and led to an increased nonselective leak, but did not otherwise alter or disrupt the channels. The results contradict the proposal that Ca 2 1 is an essential component required for maintenance of ion selectivity and proper gating of K v -type K 1 channels. The large nonselective leak in Ca 2 1 -free conditions was found to be a patch-seal phenomenon related to F 2 ion in the recording pipette. was filtered at 5 kHz and sampled at 20 kHz using an analog-to-digital converter (DigiData 1200) interfaced with a personal computer, and pClamp 8 software (Axon Instruments) was used for acqui- sition and analysis. The standard pulse protocol employed a holding potential of 2 90 mV followed by repeated test pulses to 1 30 mV for 25 ms at 3-s intervals. Voltage-activation curves were examined with inacti- vation-removed Shaker B, with 30-ms command pulses from 2 80 to 1 10 mV in 5-mV increments followed by a 15-ms tail pulse to 2 80 mV at 1-s interpulse intervals. Activation curves were calculated using standard tail-current analysis (Liman et al., 1991), by fitting data to a Boltzmann function, I / I max 5 1/{1 1 exp[ 2 zF ( V 2 V o )/ RT ]}, to determine V o (half- maximal activation voltage) and z (slope factor). The data were obtained from 3–10 patches for each condition of experiments.
On the nucleation and growth of amyloid ,8-protein fibrils: Detection of nuclei and quantitation of rate constants

We have studied the fibrillogenesis of synthetic amyloid 13-protein-(1-40) fragment (Aj3) in 0.1 M HCI. At low pH, Af3 formed fibrils at a rate amenable to detailed monitoring by quasi-elastic light-scattering spectroscopy. Examination of the fibrils with circular dichroism spectroscopy and electron microscopy showed them to be highly similar to those found in amyloid plaques. We determined the hydrodynamic radii ofA,8 aggregates during the entire process of fibril nucleation and growth. Above an Aj3 concentration of :0.1 mM, the initial rate of elongation and the final size of fibrils were independent of Aj3 concentration. Below an A,j concentration of0.1 mM, the initial elongation rate was proportional to the peptide concentration, and the resulting fibrils were significantly longer than those formed at higher concentration. We also found that the surfactant n-dodecylhexaoxyeth-ylene glycol monoether (C12E6) slowed nucleation and elongation of fibrils in a concentration-dependent manner.
Increased PD-1 expression in CMV disease and acute GVHD after allogeneic HCT

To study the role of PD-1 in CMV infection and disease after allogeneic HCT, 206 subjects were followed prospectively for immune response to CMV and assigned to three groups based on CMV outcome. They were analyzed retrospectively for PD-1 expression in cryopreserved CD4 and CD8 + T-cells collected at days 40, 90, 120, 150, 180, and 360 post-transplant. HCT recipients with CMV disease (n=14), were compared to recipients with prolonged CMV infection but no CMV disease (median duration of infection: 3 months; n=14) and to similarly transplanted controls with no CMV infection (n=22). The CMV Disease Group had a mean fluorescence intensity (MFI) of PD-1 which was significantly higher in CD4+ (p< 0.05) and CD8+ (p<0.05) lymphocytes at all time points studied. In addition, PD-1 was significantly increased in those with severe acute graft vs host disease (aGVHD), including the No-Viremia group. The data suggest that PD-1 is induced by aGVHD even in absence of CMV infection. This enhancement of PD-1 aGVHD and
FULL Radiomic signatures derived from multiparametric MRI for the pretreatment prediction of response to neoadjuvant chemotherapy in breast cancer

Objectives: To investigate the ability of radiomic signatures based on MRI to evaluate the response and effi-ciency of neoadjuvant chemotherapy (NAC) for treating breast cancers. Methods: All patients with breast cancer underwent a preoperative breast MRI and the Miller–Payne grading system was applied to evaluate response to NAC. Quantitative parameters were compared between patients with sensitive and insensitive responses to NAC and between those with pathological complete responses (pCR) and non-pCR. Four radiomic signatures were built based on T2W imaging, diffusion- weighted imaging, dynamic contrast-enhanced imaging and their combination, and radiomics scores (Rad- score) were calculated. The combination of the clinical factors and Rad- scores created a nomogram model. Multivariate logistic regression was performed to assess the association between MRI features and independent clinical risk factors. Results: 20 features and 18 features were selected to build the radiomic signature for evaluating sensitivity and the possibility of pCR, respectively. The combined radiomic signature and nomogram model showed a similar discrimination in the training (AUC 0.91, 0.92, 95% confidence interval [CI], 0.85–0.96, 0.86–0.98) and validation (AUC 0.93, 0.91, 95% CI, 0.86–1.00, 0.82–1.00) sets. The clinical factor model exhibited reduced performance (AUC 0.74, 0.64, 95% CI, 0.64–0.84, 0.46–0.82) in NAC and pCR. combined radiomic