Miracle-dz/UniFAR-FTUs huggingface dataset:
A TrkB antibody agonist promotes plasticity following cervical spinal cord injury in adult rats.

Following spinal cord injury (SCI) in mammals, there is only limited repair and consequently only moderate recovery. One mechanism frequently discussed to be involved in this recovery is plasticity, i.e., adaptations in spared neuronal circuitries. In the current study we tested the effect of an intrathecal application of the TrkB agonist antibody 29D7 on plasticity following cervical SCI in adult rats. Treatment with 29D7 for 4 weeks resulted in ~50 % increase in collateral sprouting of severed corticospinal tract fibers above the lesion compared to the control group, and enhanced branching in the grey matter rostral to the injury. GAP-43 immunoreactivity in the spinal cord rostral to the level of the injury as well as contralateral to the lesion was also increased. These indications of enhanced plasticity by 29D7 were paralleled by improved performances of the mildly affected paw, as assessed by Montoya and tray reaching tasks. The reaching behaviors of the paw ipsilateral to the side of severe injury to the cortico- and rubro-spinal tract were not altered by the treatment. The present study suggest that 29D7 may be a potential candidate to promote plasticity and functional recovery, especially following moderate SCI. Future studies confirming these results, along with a potential combinatory therapy including rehabilitative training, will be needed to evaluate the clinical value of such a treatment.
Amyloid Angiopathy–Related Vascular Cognitive Impairment

We review accumulating evidence that cerebrovascular amyloid deposition (cerebral amyloid angiopathy [CAA]) is an independent risk factor for cognitive dysfunction. The two population-based autopsy studies that have analyzed cognitive status during life as a function of CAA have each suggested deleterious effects of CAA on cognition even after controlling for age and Alzheimer disease pathology. We also review data from patients with CAA-related intracerebral hemorrhage (the one form of CAA that can be noninvasively recognized) suggesting associations of CAA with radiographic white matter abnormalities and cognitive impairment. These data highlight the importance of elucidating the effects of vascular amyloid on cerebrovascular function and of developing therapeutic strategies for this potentially widespread form of microvascular cognitive impairment.
Host specificity, evolutionary relationships and macrogeographic differentiation among Ascaris populations from humans and pigs

We describe a variety of restriction site polymorphisms in the introns of Ascaris nuclear genes and in the ribosomal DNA spacers. We use these markers, in addition to previously described mitochondrial variation, to clarify our understanding of the epidemiology of Ascaris in Guatemalan villages where humans and pigs occur in sympatry and to describe the genetic structure of host-associated Ascaris populations from world-wide locations. Intron sequences were amplified from individual worms and alleles defined by endonuclease digestion. Two loci were monomorphic, while 4 length variants and 22 point mutations were detected in the other 7 loci. Within sympatric Guatemalan populations no single locus from either the nuclear or mitochondrial genome was fixed for alternative alleles, although allele frequencies were significantly different at many loci. Phenograms constructed from multilocus nuclear genotypes of individual worms failed to reveal a single case of cross-infection, and demonstrate that divergent mtDNA genotypes are segregating within host-associated populations. On a world-wide scale, the data suggest that extant worm populations result from a single host shift, although characterization of genetic variation in additional loci will be necessary to confirm this. The direction and the geographical origin of the host shift were unresolved. Overall 65% of nuclear genetic variation was found within populations, host (human or pig) explained 18%, while geographical variation within host-associated populations explained 17%. The results (a) demonstrate the utility of introns for studying the epidemiology of parasites showing limited allozyme variation (b) suggest that programmes aiming to control Ascaris infection in the human population can safely ignore zoonotic infection from pigs and (c) illustrate the problems inherent in using single genetic markers to make inferences about the epidemiology of closely related parasite taxa.
Evaluation of chlamydiazyme for the detection of genital infections caused by Chlamydia trachomatis

Chlamydiazyme is a 4-h enzyme-linked immunoassay that detects an antigen of Chlamydia trachomatis directly in clinical specimens. This immunoassay was compared with cell culture for the diagnosis of chlamydial infections of the genital tract. The assay was evaluated at five clinics with a total of 1,277 cervical specimens of which 239 were culture positive. At three of these clinics where urethral samples were taken from males, 99 of 363 samples were culture positive. The sensitivity of the assay averaged 89.5% for detecting cervical infections and 78.8% for detecting male urethral infections. Specificity was 97.0% when samples from either males or females were tested. Some patients who were culture negative were infected with chlamydiae according to both Chlamydiazyme and a monoclonal antibody test that detected a chlamydial antigen distinct from the antigen detected by Chlamydiazyme. If the 15 females and 2 males who were positive by both immunoassays but culture negative were considered positive for chlamydial infection, the specificity of the assay was 98.4% in females and 97.7% in males. Chlamydiazyme is a simple and relatively rapid immunoassay that has sufficient sensitivity and specificity to supplant culture in the detection of genital chlamydial infections.
A Novel Mechanism of CD4 Down-modulation Induced by Monosialoganglioside GM3

In this report the molecular mechanism(s) involved in the rapid and selective endocytosis of cell surface glycoprotein CD4 induced by exogenous monosialoganglioside GM3 in human peripheral blood lymphocytes have been investigated. Inhibition of the GM3-induced CD4 down-modulation was observed in the presence of specific protein kinase C (PKC) inhibitors. Scanning confocal microscopy revealed the translocation and clustering on the cell surface of PKC isozymes δ and θ (more evidently than α and β) after GM3 treatment, suggesting the involvement of these isozymes in the ganglioside-induced CD4 down-modulation. Exogenous GM3 induced phosphorylation of CD4 molecule, which then dissociated from p56 lck , as early as after 5 min. Moreover, addition of GM3 resulted in a rapid (1 min) cytosolic phospholipase A2 activation with consequent arachidonic acid release, whereas no phosphatidylinositol-phospholipase C activity was observed. Both PKC translocation and CD4 down-modulation were blocked by the trifluoromethylketone analog of arachidonic acid, a selective inhibitor of cytosolic phospholipase A2 and by mitogen-activated protein kinase inhibitor PD98059. Taken together, these findings strongly suggest that GM3 may trigger a novel mechanism of modulation of the CD4 surface expression through the activation of enzyme(s) involved in the regulation of cellular functions.
Insights and challenges in using C. elegans for investigation of fat metabolism

Abstract C. elegans provides a genetically tractable system for deciphering the homeostatic mechanisms that underlie fat regulation in intact organisms. Here, we provide an overview of the recent advances in the C. elegans fat field with particular attention to studies of C. elegans lipid droplets, the complex links between lipases, autophagy, and lifespan, and analyses of key transcriptional regulatory mechanisms that coordinate lipid homeostasis. These studies demonstrate the ancient origins of mammalian and C. elegans fat regulatory pathways and highlight how C. elegans is being used to identify and analyze novel lipid pathways that are then shown to function similarly in mammals. Despite its many advantages, study of fat regulation in C. elegans is currently faced with a number of conceptual and methodological challenges. We critically evaluate some of the assumptions in the field and highlight issues that we believe should be taken into consideration when interpreting lipid content data in C. elegans.
Electron Microscopy and Image Processing: Essential Tools for Structural Analysis of Macromolecules

Macromolecular electron microscopy typically depicts the structures of macromolecular complexes ranging from ∼200 kDa to hundreds of MDa. The amount of specimen required, a few micrograms, is typically 100 to 1000 times less than needed for X‐ray crystallography or nuclear magnetic resonance spectroscopy. Micrographs of frozen‐hydrated (cryogenic) specimens portray native structures, but the original images are noisy. Computational averaging reduces noise, and three‐dimensional reconstructions are calculated by combining different views of free‐standing particles (“single‐particle analysis”). Electron crystallography is used to characterize two‐dimensional arrays of membrane proteins and very small three‐dimensional crystals. Under favorable circumstances, near‐atomic resolutions are achieved. For structures at somewhat lower resolution, pseudo‐atomic models are obtained by fitting high‐resolution components into the density. Time‐resolved experiments describe dynamic processes. Electron tomography allows reconstruction of pleiomorphic complexes and subcellular structures and modeling of macromolecules in their cellular context. Significant information is also obtained from metal‐coated and dehydrated specimens. © 2015 by John Wiley & Sons, Inc.
Increased fatty acid synthase expression and activity during progression of prostate cancer in the TRAMP model

Fatty acid synthase (FAS) is the major enzyme required to convert carbohydrates to fatty acids. Recent evidence suggests that FAS activity is essential for prostate cancer growth and survival, since blocking the enzyme activity results in cell death. In this study, the role of FAS up‐regulation during prostate tumor progression in the transgenic adenocarcinoma of mouse prostate (TRAMP) model was investigated. Sensitivity to FAS anti‐metabolites was also analyzed in TRAMP prostate tumor cells and tissue to determine therapeutic potential of FAS inhibition in the treatment of prostate cancer.
Joint diagonalization in ACMA and its application to multiple-tag RFID systems

This paper discusses the separation of signals in multiple-tag radio frequency identification (RFID) systems. First, a model for the RFID system in both single and multiple tag environments is presented. Then, an analytical constant modulus algorithm (ACMA) for the blind source separation problem is reviewed. An alternative approach to the traditional ACMA using joint diagonalization is considered. Finally, both the ACMAs are applied to the multiple-tag RFID environment and performance of the system is studied. Simulations are carried out for 4-QAM and 16-QAM modulations at tag and analyses of the simulation results reveal that the ACMA with joint diagonalization takes lesser CPU time to execute compared to the traditional ACMA, but with higher average modulus error (AME). The variation of system performance with the number of measurements, SNR (signal to noise ratio), number of tags and number of antennas at the reader is also studied. Based on these, some design guidelines are presented. Interestingly both the ACMA algorithms work for the 16-QAM case and yield trends similar to those of 8-PSK and 4-QAM.
An adaptive haptic guidance software module for I-TOUCH: example through a handwriting teaching simulation and a 3D maze

This paper introduces a new method for virtual reality teaching and its implementation into the I-TOUCH framework. From a thorough analysis of previous works dealing with virtual training, we developed a four steps method to be used for teaching and training. The I-TOUCH framework has been designed in order to quickly prototype computer haptic research and subsequently generate actual industry interactive simulations. Adding a progressively adapting guidance software module, the software can also be used to teach and train people on skill manipulation, where the use of haptic feedback increases learning. Thus, we decided to conceive a replay mode where four different haptic displays were possible: from total guidance, through more or less haptic correction of the user gesture, to a simple visual mode, where the ideal motion is visually displayed.
Effect of chitosan incorporation and scaffold geometry on chondrocyte function in dense collagen type I hydrogels.

Tissue engineering approaches for articular cartilage (AC) repair using collagen type I (Coll)-based hydrogels are limited by their low collagen fibril density (CFD; <0.5 wt%) and their poor capacity to support chondrocyte differentiation. Chitosan (CTS) is a well-characterized polysaccharide that mimics the glycosaminoglycans (GAGs) present in native AC extracellular matrix and exhibits chondroprotective properties. Here dense Coll/CTS hydrogel discs (16 mm diameter, 140-250 μm thickness) with CFD (∼6 wt%) approaching that of AC were developed to investigate the effect of CTS content on the growth and differentiation of three-dimensionally seeded RCJ3.1C5. 18 chondroprogenitor cells. Compared to dense Coll alone, cells seeded within Coll/CTS showed increased viability and metabolic activity, as well as a decrease in cell-mediated gel contraction. Immunohistochemistry for collagen type II, in combination with Safranin O staining and GAG quantification, indicated greater chondroprogenitor differentiation within Coll/CTS, compared to cells seeded within Coll alone. The complex interplay between scaffold geometry, microstructure, composition, mechanical properties and cell function was further evaluated by rolling dense planar sheets to prepare cylindrically shaped constructs having clinically relevant diameters (3-5 mm diameter, 9 mm height). The compressive modulus of the cylindrically shaped constructs decreased significantly after 7 days in culture, and remained unchanged up to 21 days for each scaffold composition. Unlike Coll, cells seeded within Coll/CTS showed greater viability along the entire radial extent of the cylindrical rolls and increased GAG production at each time point. While GAG content decreased over time and reduced cell viability was observed within the core region of all cylindrical rolls, the incorporation of CTS diminished both these effects. In summary, these findings provide insight into the challenges involved when scaling up scaffolds designed and optimised in vitro for tissue repair.
Statistical aspects of van't Hoff analysis: a simulation study

The thermodynamics of biological interactions is frequently studied by the van't Hoff analysis whereby data on variation of the binding constant KD with temperature are used to obtain estimates of standard enthalpy (ΔH°), entropy (ΔS°), and heat capacity (ΔCP°) of complex formation. A Monte Carlo simulation demonstrates that the absolute error of the above parameters is proportional to the relative error of KD and independent of the actual values of KD and of the way they vary with temperature. The error of ΔH° is approximately the same as that of TΔS° (within 14% in the temperature range 5–45°C). The error depends both on the number of temperature points within the experimental temperature range and on the size of the range, but it is more sensitive to the latter. Using the linear form of the van't Hoff equation to fit data with non‐zero ΔCP° gives erroneous ΔH° and ΔS° estimates at standard temperature except for the case when the T points are placed symmetrically with respect to the standard temperature. With the range of ΔCP° values usual for protein–protein interactions, the KD error must be very low to confidently infer that ΔCP° is non‐zero or to claim that two interactions have different ΔCP°. Copyright © 2007 John Wiley & Sons, Ltd.
Ultrahigh Sensitivity Refractive Index Sensor Based on Optical Microfiber

We demonstrate a nonadiabatic microfiber sensor with a taper diameter of few micrometers. The modal interference caused by the abrupt taper results in a sinusoidal spectral response. The wavelength shift arising because of the changes in the external refractive index is found to be significant, achieving a maximum sensitivity of 18681.82 nm/RIU. The measured results show good agreement with the theoretical predictions. The high sensitivity and the simplicity offer the sensor the potential for many real applications.
Language difficulties and criminal justice: the need for earlier identification.

BACKGROUND At least 60% of young people in the UK who are accessing youth justice services present with speech, language and communication difficulties which are largely unrecognized. The contributing reasons for this are discussed, suggesting that early language difficulty is a risk factor for other problems such as literacy difficulties and educational failure that may increasingly put the young person at risk of offending. Opportunities for identification and remediation of language difficulties before young people reach youth justice services are also outlined. AIMS To examine language skills in a sample of children in a secure children's home aged 11-17 years. METHODS & PROCEDURES A sample of 118 males were routinely assessed on four Comprehensive Evaluation of Language Fundamentals (CELF) subtests and the British Picture Vocabulary Scale (BPVS). OUTCOMES & RESULTS Around 30% of the participants presented with language difficulties scoring 1.5 SD (standard deviation) below the mean on the assessments. Despite them entering the home because their vulnerability was recognized, only two participants had a previous record of language difficulties. A total of 20% of the participants had a diagnosis of mental illness, 50% had a history of drug abuse and 31% had looked-after status prior to entry to the home. CONCLUSIONS & IMPLICATIONS Children experiencing educational or emotional difficulties need to be routinely assessed for speech, language and communication difficulties. More population-based approaches to supporting the development of oral language skills in children and young people are also supported.
Corporate e-learning: Justification for implementation and evaluation of benefits. A study examining the views of training managers and training providers

This study examines the experience and perceptions of training managers and training suppliers with respect to provision of e-training to corporate clients – a rapidly growing area of commercial activity. In particular the study explores the justification for implementing e-training and the consequent benefits which are anticipated by training managers. The literature review broadly examines how the business case for using e-training is supported and is subdivided into 3 sections which respectively examine the technological basis for e-training, the rationale provided to support e-training, and the manner in which anticipated benefits of training are measured. Two questionnaire surveys were used to gather opinions of both users and providers of e-training services and these were supplemented by interviews with both training managers and training providers. The results demonstrate that the market for e-training services is growing rapidly but that the business case to justify its implementation is often not clearly articulated. In addition the results of the questionnaire survey and interviews demonstrate a significant difference between training managers and training providers with respect to the relative importance of a range of potential benefits of e-training. The measurement and evaluation of benefits by training managers is often not well considered and robust evaluation methods require more critical investigation.
Brain and cerebrospinal fluid motion: real-time quantification with M-mode MR imaging.

PURPOSE To assess motion of brain parenchyma and cerebrospinal fluid (CSF) with magnetic resonance (MR) phase imaging in real time. MATERIALS AND METHODS Repetitive excitation of a cylinder with two-dimensional selective excitation followed by one-dimensional imaging along the cylinder axis yielded profiles analogous to those of M-mode echography. Bipolar gradients provided velocity sensitivity in an arbitrary spatial direction. RESULTS Brain and CSF of healthy volunteers exhibited periodic motion in the frequency range of normal heart rate. Both brain hemispheres showed periodic squeezing of the ventricles, with peak velocities up to 1 mm/sec followed by a slower recoil. Superimposed on the regular displacement of the brain stem was a slow, respiratory-related periodic shift of the neutral position. During the Valsalva maneuver, the brain stem showed initial caudal and subsequent cranial displacement of 2-3 mm. Coughing produced a short swing of CSF in the cephalic direction. CONCLUSION Real-time MR phase imaging allows observation of non-periodic events in brain and CSF motion.
HPIP is upregulated in liver cancer and promotes hepatoma cell proliferation via activation of G2/M transition

Hematopoietic pre‐B‐cell leukemia transcription factor (PBX)‐interacting protein (HPIP) has been shown to play a role in cancer development and progression. However, the detailed role of HPIP in cancer cell growth and the exact mechanism by which HPIP regulates cancer cell proliferation remains unclear. Here, we report that HPIP is overexpressed in most of 328 liver cancer patients and regulates hepatoma cell proliferation through G2/M checkpoint activation. HPIP increased anchorage‐dependent and ‐independent growth of human liver cancer cell lines. The amino acid region 531–631 of HPIP was important for its modulation of liver cancer cell growth. The increased effects of HPIP on liver cancer cell proliferation were associated with activation of the G2/M cell‐cycle concomitant with a marked increase of cyclin B1 and the inhibition of the negative G2/M phase regulator GADD45α. HPIP knockdown dramatically suppressed the growth of HepG2 liver cancer cells in nude mice. These data highlight the important role of HPIP in liver cancer cell growth and suggest that HPIP may be a good target for liver cancer therapy. © 2013 IUBMB Life, 65(10):873‐882, 2013
Three-dimensional structural analysis reveals a Cdk5-mediated kinase cascade regulating hepatic biliary network branching in zebrafish

The intrahepatic biliary network is a highly branched three-dimensional network lined by biliary epithelial cells, but how its branching patterns are precisely established is not clear. We designed a new computer-based algorithm that quantitatively computes the structural differences of the three-dimensional networks. Utilizing the algorithm, we showed that inhibition of Cyclin-dependent kinase 5 (Cdk5) led to reduced branching in the intrahepatic biliary network in zebrafish. Further, we identified a previously unappreciated downstream kinase cascade regulated by Cdk5. Pharmacological manipulations of this downstream kinase cascade produced a crowded branching defect in the intrahepatic biliary network and influenced actin dynamics in biliary epithelial cells. We generated larvae carrying a mutation in cdk5 regulatory subunit 1a (cdk5r1a), an essential activator of Cdk5. cdk5r1a mutant larvae show similar branching defects as those observed in Cdk5 inhibitor-treated larvae. A small-molecule compound that interferes with the downstream kinase cascade rescued the mutant phenotype. These results provide new insights into branching morphogenesis of the intrahepatic biliary network. Highlighted article: Inactivation of Cdk5, or its regulator Cdk5r1a, leads to reduced network branching and disrupts actin organization in the zebrafish adult intrahepatic biliary network.