Miracle-dz/UniFAR-FTUs huggingface dataset:
Malformation of the radial glial scaffold in the dentate gyrus of reeler mice, scrambler mice, and ApoER2/VLDLR‐deficient mice

We studied the postnatal development of the radial glial scaffold in the dentate gyrus of reeler mice, lacking the extracellular matrix protein Reelin, in scrambler mice, deficient in the intracellular adaptor protein disabled1 (Dab1), which is required for the transmission of the Reelin signal into the cell, and in mutant mice lacking the Reelin receptors apolipoprotein receptor 2 (ApoER2) and/or the very low density lipoprotein receptor (VLDLR), known to transmit the Reelin signal via Dab1. By immunolabeling for the glial fibrillary acidic protein (GFAP), we show that a regular dentate radial glial scaffold fails to form in mutants deficient of Reelin, Dab1, and VLDLR and ApoER2. Mutant mice lacking only one of the Reelin receptors, VLDLR or ApoER2, display a gradual expression of the radial glial defects seen in mutants that lack both receptors. Our results suggest that Reelin signaling via ApoER2, VLDLR, and Dab1 is required for the formation of a regular radial glial scaffold in the dentate gyrus. J. Comp. Neurol. 460:56–65, 2003. © 2003 Wiley‐Liss, Inc.
Optimal Thresholds and Discriminatory Power of 48-h Wireless Esophageal pH Monitoring in the Diagnosis of GERD

BACKGROUND: The discriminative power of 48-h wireless esophageal pH monitoring in the diagnosis of gastroesophageal reflux disease has not been clearly demonstrated, and the cutoff level for esophageal acid exposure generating the optimal sensitivity and specificity is unknown.SUBJECTS AND Patients with typical reflux symptoms and a distinct response to acid suppressive medicationMETHODS: underwent upper GI endoscopy followed by 48-h wireless esophageal pH studies with the pH electrode placed 6 cm above the squamocolumnar junction. The results were compared to those obtained in 55 healthy controls. Sensitivity, specificity, and thresholds for esophageal acid exposure were analyzed using receiver operating characteristic (ROC) curves.RESULTS: The patient population consisted of 64 patients, 25 women and 39 men, with a median age of 48 yr.Analysis of the area under the ROC curve showed that, for all patients as well as for subgroups of patients with (N = 33) and without (N = 31) esophagitis, the total percent time with pH <4 for the 48-h study period was the best parameter to discriminate patients from controls. Analysis of acid exposure for day 1, day 2, or using the day with the highest acid exposure did not improve the diagnostic accuracy. A test specificity in the range of 90–95% resulted in a cutoff level of 3.6–4.4% of the total time with pH <4 for the 48-h period. This threshold generated a test sensitivity of 59–64% in all patients, 76–79% for patients with esophagitis and 42–48% in patients with no esophagitis.CONCLUSIONS: The total percentage of time that esophageal pH was less than 4 for the entire 48-h study period was the parameter that best discriminated patients with typical reflux symptoms from healthy controls, and to achieve a specificity of 90–95% a cutoff level of 4% is recommended. The low sensitivity of wireless pH recording in patients without erosive esophagitis substantially reduces the clinical value of the test.
Compatibility and stability of fentanyl admixtures in polypropylene syringes

Objective: To determine the physicochemical stability of fentanyl in combination with midazolam and either hyoscine butylbromide or metoclo‐ pramide, and stored in 30 ml polypropylene syringes. Methods: Solutions containing approximately 40 μg/ml of fentanyl in combination with midazolam (approximately 600 μg/ml) and either metoclopramide (approximately 700 μg/l) or hyoscine (approximately 850 μg/ml) were prepared from commercial ampoules of the drugs. The solutions were stored, in triplicate, in the dark at 32 °C (to simulate usage conditions) for 10 days, and the concentration of each constituent drug was periodically determined using a stability‐indicating high‐performance liquid chromatography assay. Results: The combinations were relatively stable, with all drugs maintaining over 90% of their initial chemical potency for at least 1 week. There were no evident changes in either the physical appearance or pH values of the solutions over the course of the study. Conclusions: On the basis of physicochemical stability, polypropylene syringes containing fentanyl with midazolam and either hyoscine butylbromide or metoclopramide can be safely prepared and stored at or below 32 °C for periods of up to 1 week prior to use by palliative care patients receiving the drugs via a portable subcutaneous infusion device.
Oleocanthal: A Naturally Occurring Anti-Inflammatory Agent in Virgin Olive Oil

Research on the non-steroidal anti-inflammatory olive oil phenolic, (-)decarboxymethyl ligstroside aglycone (more commonly known as oleocanthal) has supported speculation that this compound may confer some of the health benefits associated with the traditional Mediterranean diet. Oleocanthal elicits a peppery, stinging sensation at the back of the throat similar to that of the non-steroidal anti-inflammatory drug (NSAID), ibuprofen (Beauchamp et al., 2005) and this localized irritation is due to stimulation of the transient receptor potential cation channel A1 (TRPA1) (Peyrot des Gachons et al., 2011). The perceptual similarity between oleocanthal and ibuprofen spurred the hypothesis that these two compounds may possess similar pharmacological properties. Further investigation demonstrated that oleocanthal inhibits inflammation in the same way as ibuprofen, and moreover, is substantially more potent on a equimolar basis (Beauchamp et al., 2005). Subsequent studies have shown that oleocanthal exhibits various modes of action in reducing inflammatoryrelated disease, including neuro-degenerative disease (Pitt et al., 2009, Li et al., 2009), jointdegenerative disease (Iacono et al., 2010) and specific cancers (Elnagar et al., 2011). Therefore, long term consumption of extra virgin olive oil (EVOO) containing oleocanthal may contribute to the health benefits associated with the Mediterranean dietary pattern. This chapter summarizes the current knowledge on oleocanthal, in terms of its sensory and physiological properties, its extraction from the oil matrix and subsequent identification and quantification, and finally the factors that may influence the concentration of oleocanthal in EVOO.
Expression of constitutively active alpha-PAK reveals effects of the kinase on actin and focal complexes

The family of p21-activated protein kinases (PAKs) appear to be present in all organisms that have Cdc42-like GTPases. In mammalian cells, PAKs have been implicated in the activation of mitogen-activated protein kinase cascades, but there are no reported effects of these kinases on the cytoskeleton. Recently we have shown that a Drosophila PAK is enriched in the leading edge of embryonic epithelial cells undergoing dorsal closure (N. Harden, J. Lee, H.-Y. Loh, Y.-M. Ong, I. Tan, T. Leung, E. Manser, and L. Lim, Mol. Cell. Biol. 16:1896-1908, 1996), where it colocalizes with structures resembling focal complexes. We show here by transfection that in epithelial HeLa cells alpha-PAK is recruited from the cytoplasm to distinct focal complexes by both Cdc42(G12V) and Rac1(G12V), which themselves colocalize to these sites. By deletion analysis, the N terminus of PAK is shown to contain targeting sequences for focal adhesions which indicate that these complexes are the site of kinase function in vivo. Cdc42 and Rac1 cause alpha-PAK autophosphorylation and kinase activation. Mapping alpha-PAK autophosphorylation sites has allowed generation of a constitutively active kinase mutant. By fusing regions of Cdc42 to the C terminus of PAK, activated chimeras were also obtained. Plasmids encoding these different constitutively active alpha-PAKs caused loss of stress fibers when introduced into both HeLa cells and fibroblasts, which was similar to the effect of introducing Cdc42(G12V) or Rac1(G12V). Significantly dramatic losses of focal adhesions were also observed. These combined effects resulted in retraction of the cell periphery after plasmid microinjection. These data support our previous suggestions of a role for PAK downstream of both Cdc42 and Rac1 and indicate that PAK functions include the dissolution of stress fibers and reorganization of focal complexes.
Vision based static hand gesture recognition techniques

Human-Computer Interaction (HCI), the study of how people interact with machines or specifically computers in an efficient manner, is of great interest from last few years because of several concrete applications anticipated in the near future, one such approach for computer interaction is static hand gesture recognition. The main aim of gesture recognition system is to detect the specific gesture of hand and use the information for a variety of applications. Current work deals with explaining the steps involved in vision-based automatic hand gesture recognition, along with elaborating some of the preprocessing, feature extraction and classification techniques.
Balancing of B6 Vitamers Is Essential for Plant Development and Metabolism in Arabidopsis

Manipulating the levels of the vitamin B6 salvage enzyme PDX3 reveals that alterations in vitamin B6 homeostasis and nitrogen metabolism are linked. Vitamin B6 comprises a family of compounds that is essential for all organisms, most notable among which is the cofactor pyridoxal 5′-phosphate (PLP). Other forms of vitamin B6 include pyridoxamine 5′-phosphate (PMP), pyridoxine 5′-phosphate (PNP), and the corresponding nonphosphorylated derivatives. While plants can biosynthesize PLP de novo, they also have salvage pathways that serve to interconvert the different vitamers. The selective contribution of these various pathways to cellular vitamin B6 homeostasis in plants is not fully understood. Although biosynthesis de novo has been extensively characterized, the salvage pathways have received comparatively little attention in plants. Here, we show that the PMP/PNP oxidase PDX3 is essential for balancing B6 vitamer levels in Arabidopsis thaliana. In the absence of PDX3, growth and development are impaired and the metabolite profile is altered. Surprisingly, RNA sequencing reveals strong induction of stress-related genes in pdx3, particularly those associated with biotic stress that coincides with an increase in salicylic acid levels. Intriguingly, exogenous ammonium rescues the growth and developmental phenotype in line with a severe reduction in nitrate reductase activity that may be due to the overaccumulation of PMP in pdx3. Our analyses demonstrate an important link between vitamin B6 homeostasis and nitrogen metabolism.
Fractional Photothermolysis Laser Treatment of Male Pattern Hair Loss

BACKGROUND Various trials have been conducted on the management of male pattern hair loss (MPHL). A variety of laser and light sources have been used for the treatment of MPHL. OBJECTIVE To understand the effects of a 1,550‐nm fractional erbium‐glass laser on the hair cycle in an alopecia mouse model and to study the clinical effects of the same laser used as treatment for MPHL. MATERIALS AND METHODS Irradiation was applied to the shaved skin of C3H/HeN mice using various energy and density settings and varied irradiation intervals. In a clinical pilot study involving human subjects, 20 participants were treated over five sessions at 2‐week intervals. A fractional photothermolysis laser was used at the energy of 5 mJ and a total density of 300 spots/cm2. RESULTS In the animal study, the hair stimulation effects were dependent upon the energy level, density, and irradiation interval. The anagen conversion of hair and the increase in Wnt 5a, &bgr;‐catenin signals were observed. In the human pilot study, incremental improvements in hair density and growth rate were observed. CONCLUSIONS This pilot study showed that a 1,550‐nm fractional erbium‐glass laser might induce hair growth, but more intensive studies are required to clarify the clinical applications of this treatment. The authors have indicated no significant interest with commercial supporters.
Rates of self-directed behaviour and faecal glucocorticoid levels are not correlated in female wild olive baboons (Papio hamadryas anubis)

Non-invasive methods to quantify components of stress in non-human animals rely typically on the use of physiological or behavioural measures. At the physiological level, stress is usually measured non-invasively in terms of faecal or urinary glucocorticoid output. A common group of behavioural measures used are self-directed behaviours (SDBs), which have been shown to be linked to anxiety, a subset of stress, although a number of authors have explicitly linked SDBs to stress more generally. Whether increased rates of SDBs are likely to be associated with increased faecal glucocorticoid ouput in wild mammals remains unclear. Here, for wild female olive baboons, we show no association between day-to-day changes in levels of SDB and cortisol metabolite excretion. We also show no relationship between long-term mean levels of these variables. We discuss several possible interpretations of our results, including the possibility that SDBs represent a behavioural coping mechanism, helping to ameliorate the physiological stress response.
Unconditionally Stable CN-PML Algorithm for Frequency-Dispersive Left-Handed Materials

An efficient and unconditionally stable stretched coordinate perfectly matched layer (PML) is proposed to truncate the computational domain of the finite-difference time-domain (FDTD) method, which is suitable to solve problems containing frequency-dispersive left-handed materials (LHMs). Here, the complex frequency-shifted scheme is used to combine the Crank–Nicolson Douglas–Gunn and auxiliary differential equation methods. A numerical example is carried out in the two-dimensional frequency-dispersive LHM domain, showing that the proposed PML is unconditionally stable for the time-step over the Courant–Friedrich–Lewy limit of the conventional FDTD.
Histochemical composition, distribution of fibres and fatiguability of single motor units. Anterior tibial muscle of the rat.

Histochemically, the anterior tibial muscle of the albino rat presents a mosaic pattern of fibres with different enzymatic activity. From the standpoint of esterase and oxidative enzymes, such as succinic dehydrogenase, three different types of fibres have been distinguished: type A fibres, which are the classical white muscle fibres, and B and C fibres, which aretwokinds of red fibres (Stein and Padykula, 1962). The A fibres are large with low enzymatic activity and the C fibres small with high enzymatic activity. The B fibres form a more heterogeneous group with various intermediate sizes and intensities of activity. It has been shown that muscle contractions in-duced by shock stimulation to the sciatic nerve produce striking changes in the phosphorylase activity and glycogen content, which vary in the different types of fibres (Kugelberg and Edstr6m, 1968a, b). The changes were sufficiently distinct and constant to serve as a histochemical index of previous muscle activity. In a few experiments the effect of stimulation of single motor nerve fibres and contractions of single motor units were studied instead of the synchronized contractions of the whole muscle. This seemed to provide a picture of the histochemical composition and distribution of the fibres within a single motor unit and permitted correlation between its histochemical and physiological properties. From the clinical point of view this is of interest for the interpretation of the electromyogram and the findings in muscle biop- sies. Some of these aspects of the motor unit have been investigated earlier by less direct methods (see Discussion) and therefore require further study in a heterogeneous muscle. In the present study the effects of stimulation of single motor nerve fibres and contractions of single motor units have been studied in greater detail. A brief account of our findings
Defective Leukocyte Interferon Response in Children with Recurrent Infections Accompanied by Arthralgia

ABSTRACT. Children with recurrent and/or unusually severe infections were investigated for possible defects in the interferon (IFN)‐natural killer (NK) cell system. Two series, each of 13 children, were examined, one in 1982 and one in 1983. Healthy children, seven in 1982 and eight in 1983, served as controls. Peripheral blood mononuclear leukocytes were examined for IFN production induced by the IFN‐α inducers Sendai virus and Escherichia coli and by the IFN‐γ inducers Concanavalin A and Lens culinaris lectin. None of these inducers discriminated patients from controls. However, the bacteria Staphylococcus aureus Cowan I (SACol), inducers of atypical IFN in null lymphocytes, yielded significantly lower IFN production in infection‐prone children than in controls, particularly in children with recurrent infections accompanied by arthralgia. No differences in basal NK activity or in the in vitro enhancement of such activity by IFN‐α were found between patients and controls.
Fish-oil-derived eicosapentaenoic acid decreases survivin expression and induces wt-p53 accumulation with caspase-3 activation in acute lymphoblastic leukemia cells

Background: Defects in modulating wild-type (wt) p53 and survivin are associated with a resistant disease in acute lymphoblastic leukemia (ALL). Yet, no wt-p53 and survivin modulating drugs have been approved for clinical application in ALL. Here, we investigated if in vitro eicosapentaenoic acid (EPA) concentrations equal to human plasma levels are able to target wt-p53 and survivin. Methods: Wt-p53 Molt-4 cells (ALL cell line) were treated with 50, 100, 150, and 200 µM of EPA after which cell number, viability, proliferation rate, survivin expression, wt-p53 accumulation, caspase-3 activation, and apoptosis were evaluated. Results: After 48- and 72-h treatments with EPA at concentrations ranging from 50 to 200 µM, cell proliferation rates were measured to be 71.5–32.6% and 68.2–13.7% and metabolic activities were measured to be 77–44% and 71–26%, respectively. Treatment with 50–200 µM of EPA for 48 h resulted in 14.1–74.6% and 69.5–45.5% decreases in survivin mRNA and protein levels, respectively. EPA induced 1.3–6 and 1.9–20-fold increases in caspase-3 activation and wt-p53 accumulation, respectively. Increase in wt-p53/survivin and caspase-3/survivin ratios from 1 in untreated cells to 20.3 and 5.8 was measured for 150 µM of EPA. Low necrotic rates ranging from 0.3% to 2.8% and an increase in the number of total apoptotic cells (early + late) ranging from 9.8% to 81% were also observed with increasing EPA concentrations. Conclusion: EPA induces strongly wt-p53 with a remarkable decrease in survivin expression, representing an attractive compound to modulate wt-p53 and survivin in ALL cells.
Scaleable chromatographic purification process for recombinant adeno‐associated virus (rAAV)

Adeno‐associated virus (AAV) is a human parvovirus currently being developed as a vector for gene therapy applications. Traditionally AAV has been purified from cell lysates using CsCl gradients; this approach however is not likely to be useful in large‐scale manufacturing. Moreover gradient‐purified AAV vectors tend to be contaminated with significant levels of cellular and adenoviral proteins and nucleic acid. To address the issue of purification we have developed a process scale method for the rapid and efficient purification of recombinant AAV (rAAV) from crude cellular lysates.
Targeted deletion of ROCK1 protects the heart against pressure overload by inhibiting reactive fibrosis

Ventricular myocyte hypertrophy is an important compensatory growth response to pressure overload. However, pathophysiological cardiac hypertrophy is accompanied by reactive fibrosis and remodeling. The Rho kinase family, consisting of ROCK1 and ROCK2, has been implicated in cardiac hypertrophy and ventricular remodeling. However, these previous studies relied heavily on pharmacological inhibitors, and not on gene deletion. Here we used ROCK1 knockout (ROCK1−/−) mice to investigate role of ROCK1 in the development of ventricular remodeling induced by transverse aortic banding. We observed that ROCK1 deletion did not impair compensatory hypertrophic response induced by pressure overload. However, ROCK1−/− mice exhibited reduced perivascular and interstitial fibrosis, which was observed at 3 wk but not at 1 wk after the banding. The reduced fibrosis in the myocardium of ROCK1−/− mice was closely associated with reduced expression of a variety of extracellular matrix (ECM) proteins and fibrogenic cytokines such as TGFβ2 and connective tissue growth factor. This inhibitory effect of ROCK1 deletion on pathophysiological induction of fibrogenic cytokines was further confirmed in the myocardium of transgenic mice with cardiomyocyte‐specific overexpression of Gαq. Thus, these results indicate that ROCK1 contributes to the development of cardiac fibrosis and induction of fibrogenic cytokines in cardiomyocytes in response to pathological stimuli. Zhang, Y. ‐M. , Bo, J., Taffet, G. E. , Chang, J., Shi, J., Reddy, A. K. , Michael, L. H. , Schneider, M. D. , Entman, M. L. , Schwartz, R. J., Wei, L. Targeted deletion of ROCK1 protects the heart against pressure overload by inhibiting reactive fibrosis. FASEB J. 20, 916–925 (2006)
Venous Smooth Muscle in Hypertension: ENHANCED CONTRACTILITY OF PORTAL VEINS FROM SPONTANEOUSLY HYPERTENSIVE RATS

In isolated bath studies smooth muscle from the rat portal vein was evaluated for its reactivity and contractility, and the whole vessel wall was evaluated for its extensibility. Smooth muscle from the spontaneously hypertensive rat (SHR) had the following characteristics when compared with that from normotensive controls: (1) Spontaneous phasic contractions were more frequent and developed more tension; (2) threshold concentrations for responses to prostaglandins A2 and B2 were lower, but those for responses to epinephrine, norepinephrine, KC1, BaCl2, and SrCl2 were similar; (3) high concentrations of calcium had a less depressant action on the responses to the prostaglandins but not on the responses to the other agonists; (4) maximal contractile tensions to all agonists were greater; and (5) passive extensibility was less. These differences, because they are in the venous system, cannot be secondary to the increase in wall stress of arterial hypertension. The decreased passive extensibility in this vein in SHR creates a stiffer framework on which the active contractile process is able to develop greater tension. If this increase in active tension is generalized to all veins, it could be responsible for a decrease in venous capacity which increases the rate of venous return and, hence, increases cardiac output.