Miracle-dz/UniFAR-FTUs huggingface dataset:
Correction of stromal cell defect after bone marrow transplantation in aplastic anaemia

Defects in stromal cell function have been demonstrated in a number of aplastic anaemia (AA) patients. Here we have studied a patient with severe AA and abnormal stromal cell function who underwent bone marrow transplantation (BMT). The objective of this study was to investigate the timing and the mechanism of correction of the stromal defect after transplantation. The patient, a 25‐year‐old woman with severe AA, underwent BMT from her brother. BM was obtained from the patient on five occasions: 2 weeks pre BMT, and 3, 8, 16 and 21 months post BMT. Stromal cells were grown to confluence and recharged with purified CD34+ cells from normal donors. The support of such cells, as assessed by weekly colony‐forming assay (CFU) of non‐adherent cells, was compared with that of stromal layers grown from normal BM. A novel technique of combined fluorescence in situ hybridization (FISH) and immunocytochemistry was used to determine the origin of specific stromal cell types on cytospins of stroma post BMT. Stromal function was defective at 2 weeks pre BMT and at 3 months post BMT, but returned to normal at 8 and 16 months post BMT. At 21 months post BMT, stromal fibroblasts and endothelial cells were shown to be of recipient origin, and macrophages and T cells were of donor origin. We present here evidence in a case of severe AA for defective stromal function before BMT and delayed normalization of function after BMT. This correlated with engraftment of donor macrophages and T cells, but not fibroblasts and endothelial cells.
Effects of calcium channel agonist and antagonists on calcium‐dependent events in CA1 hippocampal neurons

Summary— The effects of a variety of calcium channel modulators on different calcium‐dependent events in CA1 pyramidal hippocampal neurons were analysed using intracellular recordings in an in vitro slice preparation. The following substances were tested: the dihydropyridine calcium agonist BAY K 8644, the dihydropyridine calcium antagonist nimodipine, the phenylalkylamine verapamil and the snail toxin ω‐conotoxin GVIA (ω‐CgTx). BAY K 8644 increased the repolarization time of the after hyperpolarization (AHP) following a spike burst. This effect was antagonized by nimodipine. BAY K 8644 also prolonged the calcium spike and, in some cases, increased the size of the synaptic events resulting from activation of the Schaffer collateral/commissural system. Nimodipine decreased the size of the AHP in some neurons but had no consistent effect on synaptic events. Verapamil at low concentrations (1–10 μM) had no significant effects on the calcium‐dependent events in the hippocampus. Increasing the concentration (up to 100 μM) led to a progressive suppression of the AHP and of the slow inhibitory postsynaptic potential (IPSP), probably via an action on potassium conductances. In addition, the baclofen‐induced hyperpolarization was blocked by verapamil. Interestingly, at this higher concentration, verapamil could suppress the AHP without depressing the calcium spike. ω‐CgTx selectively blocked the synaptic events (especially the IPSPs) but had no effect on non‐synaptic events. This last compound exhibits a high degree of selectivity, acting on N‐type calcium channels which are involved in neurotransmitter release. Our results provide evidence that different classes of agents which act on calcium channels can be used to discriminate between different calcium‐dependent responses in CA1 hippocampal neurons.
Beliefs and practices regarding Alzheimer's disease and related dementias among Filipino home care workers in Israel

Background: In the past few decades, foreign home care to frail older adults has become a common alternative to family care in many developed countries. Whereas Alzheimer's disease and related dementias (ADRD) are common conditions in this population of frail older adults, little is known about the beliefs of foreign home care workers about ADRD or about their practices. Methods: A mixed-methods design was conducted in 2006–2007 in Israel. The study included a survey of beliefs about ADRD completed by 184 Filipino home care workers and qualitative interviews with 29 Filipino home care workers. Results: On seven of the 14 belief items, more than 30% of the workers were in discordance with scientific view about ADRD. Those workers who were not informed about the care recipient's medical conditions were more likely to report beliefs that were inconsistent with current scientific knowledge. In qualitative interviews, Filipino home care workers reported using intuitively behavioral techniques when caring for older adults with ADRD. Conclusions: Despite the fact that some of the workers’ beliefs are inconsistent with current scientific view, their actual intuitive practices are consistent with the scientific paradigm. Specific emphasis has to be placed on encouraging workers’ intuitive approach to ADRD and providing workers with ample information about the medical conditions and needs of the care recipient.
Asymmetries in Mobbing Behavior Among Nuclear Flockmates

Abstract Tufted Titmice (Baeolophus bicolor) and Carolina Chickadees (Poecile carolinensis) often occur together in mixed species flocks during the non-breeding season and, as nuclear species, often initiate mobbing bouts. We compared the mobbing behavior of Tufted Titmice and Carolina Chickadees and, specifically, their tendency to approach five potential predators. We exposed flocks of chickadees and titmice to study skins of five species of raptors in 2008; raptors were categorized as either low-threat (rarely preying on chickadees or titmice) or high-threat (more likely to prey on chickadees or titmice). We noted the distance of closest approach by titmice and chickadees during trials, and whether a chickadee or titmouse spent more time within 5 m of the raptor. Titmice were more likely to remain within 5 m of both low (p = 0.0008) and high-threat (p = 0.0015) raptors. Titmice approached low-threat raptors closer than chickadees (p = 0.014). There was no difference in the mean distance of closest approach by chickadees and titmice during high-threat trials (p = 0.34). Titmice generally approached and remained closer to raptors during mobbing bouts than chickadees, possibly because larger titmice (∼ 21 g) are more likely targets of aerial predators than smaller chickadees (∼ 11 g). Titmice may be willing to take greater risks because the potential benefits (reduced risk of predation) are greater if mobbing causes potential predators to leave an area.
Breast cancer immunohistochemical features in young women with BRCA 1/2 mutations.

UNLABELLED Breast cancer among young women is a rare pathology. In most studies published so far, this patients group is not being analyzed separately. Particularities of this pathology require an additional examination of the immunohistochemical and molecular-genetic markers of the disease for development of the effective treatment protocols. The mutations of BRCA1/2 are the important factor impacting to the disease prognosis along the age of the patient. AIM To compare the expression of prognostically meaningful immunohistochemical markers such as estrogen receptor (ER), progesterone receptor (PR), HER-2, p53, Ki-67, in tumor cells of the female patients with breast cancer aged less than 36 depending on the presence of absence of mutations in CRCA1/2 genes. METHODS Two hundred forty-eight patients aged less than 36 at the time of diagnosis of breast cancer were examined clinically. Expression of ER, PR HER-2, p53, Ki-67 was determined by indirect immunohistochemical method. mutations of BRCA1 (185delAG, o5382insC) and BRCA2(6174delT) genes were screened using multiplex PCR in 99 patients. RESULTS Mutations of BRCA1/2 genes were found in 9.1% of patients. More aggressive clinical course of the disease was seen in mutations carriers, who had 3-years survival of only 55.6%. They did not demonstrated of ER, PR, and HER-2 in 88.0% of the cases. Whereas, patients without BRCA1/2 mutations did no express ER, PR, and HER-2 in only 42.0% of cases. There were no differences between patients with and without mutations in terms of tumor size, presence of metastases in lymph nodes, p53 and Ki-67 expression. CONCLUSION Presence of BRCA1/2 genes mutations in young women is associated with more aggressiveness of the breast cancer (their 3-years survival is 25,5% less) and absence of the ER, PR, HER-2 receptors, which is unfavorable prognostic factor in terms of hormone therapy. These data should be taken into account at chemotherapy planning, especially in patients with early stages of the disease. There were no differences between patients with and without BRCA1/2 mutations in terms of tumor size, lymph nodes involvement, tumor histology, and p53 and Ki-67 proteins expression.
N-Glycosylation of TRPM8 Ion Channels Modulates Temperature Sensitivity of Cold Thermoreceptor Neurons*

Background: TRPM8 channel is N-glycosylated, a post-translational modification affecting trafficking and gating properties of other TRP channels. Results: Preventing N-glycosylation reduces responses of TRPM8 to agonists (cold and menthol) due to a change in its biophysical properties. Conclusion: N-Glycosylation is an important determinant of TRPM8 sensitivity to chemical and thermal stimuli. Significance: N-Glycosylation of TRPM8 could play a modulatory role in cold thermoreceptor activity. TRPM8 is a member of the transient receptor potential ion channel superfamily, which is expressed in sensory neurons and is activated by cold and cooling compounds, such as menthol. Activation of TRPM8 by agonists takes place through shifts in its voltage activation curve, allowing channel opening at physiological membrane potentials. Here, we studied the role of the N-glycosylation occurring at the pore loop of TRPM8 on the function of the channel. Using heterologous expression of recombinant channels in HEK293 cells we found that the unglycosylated TRPM8 mutant (N934Q) displays marked functional differences compared with the wild type channel. These differences include a shift in the threshold of temperature activation and a reduced response to menthol and cold stimuli. Biophysical analysis indicated that these modifications are due to a shift in the voltage dependence of TRPM8 activation toward more positive potentials. By using tunicamycin, a drug that prevents N-glycosylation of proteins, we also evaluated the effect of the N-glycosylation on the responses of trigeminal sensory neurons expressing TRPM8. These experiments showed that the lack of N-glycosylation affects the function of native TRPM8 ion channels in a similar way to heterologously expressed ones, causing an important shift of the temperature threshold of cold-sensitive thermoreceptor neurons. Altogether, these results indicate that post-translational modification of TRPM8 is an important mechanism modulating cold thermoreceptor function, explaining the marked differences in temperature sensitivity observed between recombinant and native TRPM8 ion channels.
Regulation of Constitutive Protein Transit by Phospholipase D in HT29-cl19A Cells*

Phospholipase D (PLD) plays a central role in the control of vesicle budding and protein transit. We previously showed that in resting epithelial HT29-cl19A cells, PLD is implicated in the control of constitutive protein transit, from the trans-Golgi network to the plasma membrane, and that phorbol ester stimulation of protein transit is correlated with PLD activation (Auger, R., Robin, P., Camier, B., Vial, G., Rossignol, B., Tenu, J.-P., and Raymond, M.-N. (1999) J. Biol. Chem. 274, 28652–28659). In this paper we demonstrate that: 1) PLD is not implicated in the earliest phases of protein transit; 2) PLD controls apical but not basolateral protein transit; 3) HT29-cl19A cells express PLD1b and PLD2a mRNAs and proteins; 4) the expression of a catalytically inactive mutant of PLD2 (mPLD2-K758R) significantly inhibited apical constitutive protein transit whereas expression of a catalytically inactive mutant of PLD1 (hPLD1b-K898R) prevented increases in the rate of apical transit as triggered by phorbol esters; 5) PLD2 appears to be located in a perinuclear region containing the Golgi whereas PLD1, which is scattered in the cytoplasm in resting cells, is translocated to the plasma membrane after phorbol ester stimulation. Taken together, these data lead to the conclusion that in HT29-cl19A cells, both PLDs regulate protein transit between the trans-Golgi network and the apical plasma membrane, but that they do so at different steps in the pathway.
Changes in three types of ubiquitin mRNA and ubiquitin-protein conjugate levels during lens development.

Ubiquitin is a small, highly conserved protein that covalently attaches to other proteins to form a unique branched protein structure. The best characterized function of this post-translational modification is to mark the modified protein for degradation by the proteasome. To investigate whether ubiquitin genes are regulated in lens development, the authors analyzed the levels of three ubiquitin mRNAs (UbA(52), UbB and UbC) in freshly dissected fiber and epithelial cells, and in epithelial explants induced to differentiate ex vivo. Explants, comprising the capsule and adherent epithelial cells, were dissected from lenses of 3 day old Sprague Dawley rats and cultured +/-bFGF to induce differentiation. Quantitative competitive RT-PCR was used to determine the mRNA levels in fresh and cultured cells. UbA(52), UbB and UbC mRNAs were 3.2 (P < 0.0001), 5.0 (P < 0.0001) and 6.8 (P < 0.0001) fold higher, respectively, in freshly dissected epithelial cells than in differentiated fiber cells. Immunological spot assays showed that ubiquitin protein is over two fold as high in rat pup lens epithelial cells as in fiber cells. The ubiquitin protein in fiber cells of adult rat is lower than that in adult epithelium and in pup fiber cells, indicating that ubiquitin content further decreased during lens fiber maturation. Western blots showed a greater amount of protein-conjugated ubiquitin (MW > 81 kD) in epithelial cells than in fiber cells, demonstrating a parallel pattern between the expression of ubiquitin mRNA, the level of ubiquitin protein and the level of conjugates in the cells. Epithelial cell explant cultures permit study of cells initiating differentiation. In contrast to fully differentiated fiber cells, explant cultures induced to initiate differentiation underwent differential up-regulation of ubiquitin gene expression. UbA(52) and UbB mRNA levels in +bFGF (differentiating) explant cultures were 2.6 (P < 0.001) and 1.4 (P < 0.001) fold higher, respectively, than those of -bFGF cultures. UbC mRNA content was similar in explants cultured with or without bFGF. Dissection of the isolated epithelial cells into regions representing distinct populations gave results consistent with this observation of the explant results. UbA(52), UbB and UbC mRNAs are 2.0, 2.2 and 1.76 fold higher, respectively, in the peripheral (initiating differentiation) than in the central (undifferentiated) region of epithelial cells. These results together indicate that UbA(52) and UbB mRNAs are transiently increased during the initiation and early stages of differentiation. However, UbC mRNA appears to be relatively unaffected at the earliest stage in this differentiation model and may have a different distribution than UbA(52) and UbB in the anterior lens cells. These data are consistent with an important role for ubiquitin during the early stages of lens differentiation. The selective expression indicates that the three genes have specific differentiation related functions.
SEX-LINKED OCULAR DISORDERS: TRAIT EXPRESSIVITY IN MALES AND CARRIER FEMALES.

A heritable trait is said to have a sex-linked mode of transmission when the gene responsible for the trait is located on one or both of the X chromosomes. * The female with her complement of two matched X chromosomes would not be expected to show the influence of a single sex-linked recessive gene when a normal gene is present on the fellow X chromosome. On the other hand, no such impunity exists for the male. Because the X and Y chromosomes in the male are not a matched pair, he expresses fully the effects of a single recessive gene. Thus sex-linked inheritance has as its hallmark the relatively normal carrier female and her affected male offspring. It has become increasingly apparent, however, that the heterozygous female, carrying one normal and one recessive gene on her sex chromosomes, may exhibit pathology similar to, but usually less severe than, that of the
Correlates versus predictors of courtship success: courtship song in
 Drosophila silvestris
 and
 D. heteroneura
 


Males of the picture-winged flies Drosophila silvestris and D. heteroneura produce a sound during courtship wing vibration; successful courtships include more time spent in wing vibration. We clipped male wings to test whether this sound is a necessary signal for the success of male courtship. We tested females in no-choice tests and also in choice tests in which each female was provided with a clipped and normal male simultaneously. We found no differences in the probability of copulation for either species in no-choice tests, and no difference for the choice tests with D. heteroneuraSurprisingly, clipped males were significantly more successful than control males in the choice tests with D. silvestrisThe latencies to copulate did not differ by treatment in any tests. Consequently, the sound produced by courtship wing vibration does not influence male mating success and thus does not meet the most important criterion for being a sexual signal. We propose that the vibration of thoracic muscles, transmitted through the substrate or through the male's forelegs, could provide a sexual signal in these species.1997The Association for the Study of Animal Behaviour
The specific degree-of-polymerization of A-type proanthocyanidin oligomers impacts Streptococcus mutans glucan-mediated adhesion and transcriptome responses within biofilms

Cranberry A-type proanthocyanidins (PACs) have been recognized for their inhibitory activity against bacterial adhesion and biofilm-derived infections. However, the precise identification of the specific classes of degree-of-polymerization (DP) conferring PACs bioactivity remains a major challenge owing to the complex chemistry of these flavonoids. In this study, chemically characterized cranberries were used in a multistep separation and structure-determination technique to isolate A-type PAC oligomers of defined DP. The influences of PACs on the 3D architecture of biofilms and Streptococcus mutans-transcriptome responses within biofilms were investigated. Treatment regimens that simulated topical exposures experienced clinically (twice-daily, 60 s each) were used over a saliva-coated hydroxyapatite biofilm model. Biofilm accumulation was impaired, while specific genes involved in the adhesion of bacteria, acid stress tolerance, and glycolysis were affected by the topical treatments (vs the vehicle-control). Genes (rmpC, mepA, sdcBB, and gbpC) associated with sucrose-dependent binding of bacteria were repressed by PACs. PACs of DP 4 and particularly DP 8 to 13 were the most effective in disrupting bacterial adhesion to glucan-coated apatitic surface (>85% inhibition vs vehicle control), and gene expression (eg rmpC). This study identified putative molecular targets of A-type cranberry PACs in S. mutans while demonstrating that PAC oligomers with a specific DP may be effective in disrupting the assembly of cariogenic biofilms.
Model-based global and local motion estimation for videoconference sequences

In this work, we present an algorithm for face 3-D motion estimation in videoconference sequences. The algorithm is able to estimate both the position of the face as an object in 3-D space (global motion) and the movements of portions of the face, like the mouth or the eyebrows ( local motion). The algorithm uses a modified version of the standard 3-D face model CANDIDE. We present various techniques to increase robustness of the global motion estimation which is based on feature tracking and an extended Kalman filter. Global motion estimation is used as a starting point for local motion detection in the mouth and eyebrow areas. To this purpose, synthetic images of these areas (templates) are generated with texture mapping techniques, and then compared to the corresponding regions in the current frame. A set of parameters, called action unit vectors (AUVs) influences the shape of the synthetic mouth and eyebrows. The optimal AUV values are determined via a gradient-based minimization procedure of the error energy between the templates and the actual face areas. The proposed scheme is robust and was tested with success on sequences of many hundreds of frames.
THE PHENOMENOLOGY OF SMALL-SCALE TURBULENCE

Small-scale turbulence has been an area of especially active research in the recent past, and several useful research directions have been pursued. Here, we selectively review this work. The emphasis is on scaling phenomenology and kinematics of small-scale structure. After providing a brief introduction to the classical notions of universality due to Kolmogorov and others, we survey the existing work on intermittency, refined similarity hypotheses, anomalous scaling exponents, derivative statistics, intermittency models, and the structure and kinematics of small-scale structure—the latter aspect coming largely from the direct numerical simulation of homogeneous turbulence in a periodic box.
Short-long-short sequence-induced torsade de pointes after transcatheter aortic-valve implantation

The gold-standard treatment of symptomatic aortic stenosis (AS) is surgical aortic-valve replacement (SAVR); however, many patients owing to high operative risks are not candidates for this treatment (1). Hence, transcatheter aortic-valve implantation (TAVI) was introduced to be an alternative modality to SAVR. Because of older patient population and structural heart disease, TAVI patients may have proarrhythmic tendencies related to electrolyte imbalances and drug-drug interactions. Among patients with pacemakers, implantable cardioverter-defibrillators (ICD), and cardiac resynchronization therapy (CRT) receivers, the proarrhythmic effect of pacing was described earlier (2-4). Torsades de pointes (TdP) is a polymorphic ventricular tachycardia in the setting of a prolonged QTc interval (5); however, pacing related episodes and triggered activity related TdP in AS patients were cited in several reports (2-4, 6, 7). This report describes a 78-year-old patient being VVI paced, who experienced a short-long-short sequence-induced TdP without QT prolongation in intensive care unit after TAVI.