Miracle-dz/UniFAR-FTUs huggingface dataset:
Phospholipase A2 Activity Triggers the Wound-Activated Chemical Defense in the Diatom Thalassiosira rotula

The activation of oxylipin-based chemical defense in the diatom Thalassiosira rotula is initiated by phospholipases that act immediately after cell damage. This lipase activity is responsible for the preferential release of free mono- and polyunsaturated fatty acids. Among these, eicosatetraenoic- and eicosapentaenoic acid are further converted by lipoxygenases to reactive defensive metabolites such as the antiproliferative α,β,γ,δ-unsaturated aldehydes 2,4-decadienal and 2,4,7-decatrienal. We show that mainly saturated free fatty acids are present in the intact diatom T. rotula, whereas the amount of free polyunsaturated eicosanoids is drastically increased in the first minutes after wounding. Using fluorescent probes, the main enzyme activity responsible for initiation of the aldehyde-generating lipase/lipoxygenase/hydroperoxide lyase cascade was characterized as a phospholipase A2. All enzymes involved in this specific defensive reaction are active in seawater over several minutes. Thus, the mechanism allows the unicellular algae to overcome restrictions arising out of potential dilution of defensive metabolites. Only upon predation are high local concentrations of aldehydes formed in the vicinity of the herbivores, whereas in times of low stress, cellular resources can be invested in the formation of eicosanoid-rich phospholipids. In contrast to higher plants, which use lipases acting on galactolipids to release C18 fatty acids for production of leaf-volatile aldehydes, diatoms rely on phospholipids and the transformation of C20 fatty acids to form 2,4-decadienal and 2,4,7-decatrienal as an activated defense.
Daily Behavioral Rhythmicity and Organization of the Suprachiasmatic Nuclei in the Diurnal Rodent, Lemniscomys barbarus

Wheel‐running activity was recorded in Lemniscomys barbarus exposed to different lighting conditions. This rodent shows rhythmic locomotor activity under natural twilight‐light/dark (LD) as well as squared‐LD cycles. A mean of 77% of the activity occurred during the light phase. Under different controlled photoperiods, the quantity of daily locomotor activity was relatively stable except for a lower level in the shortest photoperiod tested (LD 06∶18). The duration of the active phase tended to increase with the duration of the light phase, especially in the longer photoperiods. Whatever the lighting conditions, Lemniscomys barbarus started running before lights‐on and stopped after lights‐off. The phase angle of activity offset relative to lights‐off was stable in each squared‐photoperiod, whereas the phase angle of activity onset relative to lights‐on was significantly the highest under the shortest photoperiods. Recording of activity under constant lighting conditions showed that the daily rhythm of locomotor activity is fundamentally circadian. The endogenous period was slightly<24 h (mean=23.8 h) in permanent darkness and>24 h (mean=24.5 h) in continuous light. Re‐entrainment of the locomotor activity rhythm after a 6 h phase advance or delay requires only four days on average. Moreover, the phase‐responses curve to a 30 min light pulse (200 lux) in Lemniscomys barbarus kept in constant dark reveals large phase shifts according to circadian times (CT). With CT0 being defined as the onset of daily activity, maximum phase delay and advance shifts were observed at CT11 (Δ Ψ=‐5.7 h±2.3 h) and CT21 (Δ Ψ =4.9±1.2 h), respectively. Interestingly, the phase‐response curve to light did not show any dead zone. Immunohistochemical staining of the suprachiasmatic nuclei indicates that arginine vasopressin‐immunoreactive cell bodies and fibers delimited a dorsal subregion that extends laterally and medially. The ventral subregion is rich in vasoactive intestinal peptide‐immunoreactive neurones overlapping a smaller area containing gastrin‐releasing peptide‐expressing cells and receives numerous fibers labeled with neuropeptide Y antibody. The results of this study clearly demonstrate that Lemniscomys barbarus is a diurnal species highly sensitive to the shifting effects of light. Overall, this rodent can be considered a new and interesting model for circadian rhythm neurobiology.
Symptoms of Sensory Neuropathy in Adults with NIDDM in the U.S. Population

OBJECTIVE To ascertain the prevalence and determinants of sensory neuropathy symptoms through structured interview of a representative sample of people with diabetes in the U.S. population. RESEARCH DESIGN AND METHODS The 1989 National Health Interview Survey consisted of a representative sample of 84,572 persons in the U.S. ≥ 18 yr of age. A household respondent identified all people in the household believed to have diabetes (n = 2829). Subjects who could not be personally interviewed (n = 129) and individuals who stated they did not have diabetes (n = 295) were excluded. A detailed questionnaire was administered to 99.3% of the remaining 2405 subjects. Questions on symptoms of sensory neuropathy included whether during the past 3 mo the subjects had experienced numbness or loss of feeling, pain or tingling, or decreased ability to feel hot or cold. The neuropathy questions were also administered to a representative sample of 20,037 subjects who were not known to have diabetes. RESULTS Prevalence of symptoms of sensory neuropathy was 30.2% among people with IDDM. This prevalence was 36.0% for men with NIDDM and 39.8% for women with NIDDM, compared with 9.8 and 11.8% for nondiabetic men and women, respectively. In logistic regression, factors independently related to symptoms of sensory neuropathy in people with NIDDM included duration of diabetes, hypertension, hyperglycemia, and glycosuria. Long duration of NIDDM (>20 yr) was associated with a twofold increased risk of symptoms of sensory neuropathy compared with those with 0-4 yr of diabetes. Hypertension was associated with a 60% higher likelihood of symptoms. Diabetic individuals whose blood glucose was high all or most of the time or whose urine tests showed glucose all of the time were > 2 times as likely to have symptoms of sensory neuropathy than those who did not report hyperglycemia or glycosuria. Age, sex, ethnicity, cigarette smoking, and height were not determinants of sensory neuropathy. CONCLUSIONS Symptoms of sensory neuropathy affect 30–40% of diabetic patients in the U.S. Men and women are affected equally. Prevalence of these symptoms increases with longer duration of diabetes; hypertension and hyperglycemia predispose to symptoms of sensory neuropathy.
Why can patients with erectile dysfunction be considered lucky? The association with testosterone deficiency and metabolic syndrome

Metabolic syndrome (MetS) is a diagnostic category, based on a cluster of risk factors (hyperglycemia/diabetes, abdominal obesity, hypertriglyceridaemia, low HDL cholesterol and hypertension), which identifies subjects at high risk for forthcoming type 2 diabetes mellitus and cardiovascular (CV) diseases. Recently, a close association between MetS, erectile dysfunction (ED) and male hypogonadism has been reported. In patients with MetS, hypogonadism can exacerbate sexual dysfunction and arteriogenic ED because of its typical symptoms, such as decreased sexual desire and mood disturbances. On the other hand, hypogonadism per se has been associated with an increased risk of CV and overall mortality. Obesity and in particular central obesity is nowadays considered the most important determinant of MetS-induced hypogonadism whereas hypertension and diabetes play a major role in ED associated with MetS. This review analyses the current literature regarding the relationship between ED, MetS and hypogonadism emphasising the epidemiological and psychopathological aspects and stressing the concept that ED subjects are ‘lucky’, because ED offers a unique chance to undergo medical examination and therefore to improve not only their sexual but, most importantly, their overall health.
Patient-evaluated dentistry: development and validation of a patient satisfaction questionnaire for fixed prosthodontic treatment.

PURPOSE The aim of this study was to develop and verify the reliability and validity of a questionnaire to assess patient satisfaction with fixed dental prostheses (FDPs). MATERIALS AND METHODS A questionnaire was developed, pilot-tested, and modified. It assessed esthetics, masticatory function, phonetics, cleansibility, and cost satisfaction using a visual analog scale and whether patients would elect to undergo the same treatment again (yes/no). It was sent to patients with a known evidence-based outcome (survival) who received FDPs from 1984 to 2005 (n = 986) in one private prosthodontic practice. Reliability and validity were analyzed using the Student t, Mann-Whitney U, Kruskal Wallis, Cronbach alpha, Spearman-Brown, Correlation matrix, Bartlett sphericity, Kaiser-Meyer-Olkin (KMO), and factor analysis tests. Significance was set at P = . 05. RESULTS Five hundred patients responded (50.7%). A Cronbach alpha value of 0.8 and split-sample Spearman-Brown value of 0.7 indicated good reliability. Step-wise removal of items did not improve internal consistency. Discriminant construct validity assessment showed no item redundancy. Satisfaction of patients who had experienced prosthesis failure (n = 52) was significantly less than their counterparts (73% ± 3% vs 83% ± 0.6%, P = .004), ascertaining convergent construct validity. Factor analysis (Bartlett sphericity, P < .001; KMO = 0.84) identified two components (Eigenvalues ⋝ 1.0) that explained 93.18% (varimax rotation) of variations. Component 1 included satisfaction with function (esthetics, mastication, phonetics, and cleansibility); component 2 included satisfaction with costs and whether patients would undergo the same treatment again. CONCLUSIONS The Patient Satisfaction Questionnaire developed proved reliable and valid for assessing patient-evaluated outcomes of FDPs. Use of this questionnaire in further research is justified. Int J Prosthodont 2011;24:332-341.
Cardiovascular Reactivity and Development of Preclinical and Clinical Disease States

Objective The objective of this review is to evaluate the evidence for the hypothesis that cardiovascular reactivity can predict the development of preclinical (elevated blood pressure, ventricular remodeling, carotid atherosclerosis) and/or clinical cardiovascular disease states. Methods A review of the literature was conducted examining prospective studies. Results Three large epidemiological studies with long-term follow-up periods (20 years or more) have found blood pressure responses to the cold pressor task to be predictive of subsequent essential hypertension in initially normotensive samples. Studies showing less consistent results have tended to use shorter-term follow-up periods. A larger body of literature demonstrates consistent associations between stress-related cardiovascular reactivity and blood pressure elevations in youth over the course of 1 to 6 years; such relationships have not been consistently shown among adult samples. Moderately consistent evidence points to a positive relationship between reactivity and other measures of subclinical disease (increased left ventricular mass and carotid atherosclerosis) among the few prospective studies that have examined these issues to date. A number of additional factors, however, such as baseline levels of disease risk and exposure to psychosocial stress, seem to moderate these relationships. Health status at baseline also seems to moderate the association between reactivity and clinical coronary heart disease in recent reports: two of three existing studies in initially healthy samples show no evidence of a relationship between reactivity and clinical outcomes, whereas three of four studies in samples with preexisting coronary heart disease or essential hypertension show a positive relationship between reactivity and subsequent disease states. Conclusions There is reasonable evidence to suggest that cardiovascular reactivity can predict the development of some preclinical states (eg, increased left ventricular mass and blood pressure) states and perhaps even new clinical events in some patients with essential hypertension or coronary heart disease. However, much more information is needed concerning moderating and potentially confounding variables before the robustness of the positive relationships can become clinically useful.
VSTM2L is a novel secreted antagonist of the neuroprotective peptide Humanin

Humanin (HN) is a 24‐residue peptide displaying a protective activity in vitro against a range of cytotoxic and neurotoxic insults, as well as mediating in vivo amelioration of Alzheimer disease (AD)‐related memory impairment in experimental models. Published evidence suggests that the mechanisms through which HN exerts its cyto‐ and neuroprotective activity may include its secretion and binding to membrane‐associated receptors. Here, we describe the identification of a new modulator of HN neuroprotective activity, V‐set and transmembrane domain containing 2 like (VSTM2L), previously known as C20orf102. VSTM2L interacts with HN in both yeast and mammalian cells, is secreted in cultured cells, is present in serum, and is selectively expressed in the central nervous system. VSTM2L colocalizes with HN in distinct brain areas as well as in primary cultured neurons, where it plays a role in the modulation of neuronal viability. When tested in HN neuroprotection bioassays, VSTM2L acts as a strong antagonist of HN neuroprotective activity. In summary, VSTM2L is the first example of a secreted antagonist of HN and may play a role in the modulation of HN biological functions. —Rossini, L. , Hashimoto, Y. , Suzuki, H. , Kurita, M. , Gianfriddo, M. , Scali, C. , Roncarati, R. , Scali, C. , Franceschini, D. Scali, C. , Pollio, G. , Trabalzini, L. , Roncarati, R. , Scali, C. , Terstappen, G. C. , Scali, C. , Matsuoka, M. , Scali, C. , Caricasole, A. VSTM2L is a novel secreted antagonist of the neuroprotective peptide Humanin. FASEB J. 25, 1983–2000 (2011). www.fasebj. org
A Single Bifunctional UDP-GlcNAc/Glc 4-Epimerase Supports the Synthesis of Three Cell Surface Glycoconjugates in Campylobacter jejuni*

The major cell-surface carbohydrates (lipooligosaccharide, capsule, and glycoprotein N-linked heptasaccharide) of Campylobacter jejuni NCTC 11168 contain Gal and/or GalNAc residues. GalE is the sole annotated UDP-glucose 4-epimerase in this bacterium. The presence of GalNAc residues in these carbohydrates suggested that GalE might be a UDP-GlcNAc 4-epimerase. GalE was shown to epimerize UDP-Glc and UDP-GlcNAc in coupled assays with C. jejuni glycosyltransferases and in sugar nucleotide epimerization equilibria studies. Thus, GalE possesses UDP-GlcNAc 4-epimerase activity and was renamed Gne. The K m(app) values of a purified MalE-Gne fusion protein for UDP-GlcNAc and UDP-GalNAc are 1087 and 1070 μm, whereas those for UDP-Glc and UDP-Gal are 780 and 784 μm. The kcat and kcat/K m(app) values were three to four times higher for UDP-GalNAc and UDP-Gal than for UDP-GlcNAc and UDP-Glc. The comparison of the kinetic parameters of MalE-Gne to those of other characterized bacterial UDP-GlcNAc 4-epimerases indicated that Gne is a bifunctional UDP-GlcNAc/Glc 4-epimerase. The UDP sugar-binding site of Gne was modeled by using the structure of the UDP-GlcNAc 4-epimerase WbpP from Pseudomonas aeruginosa. Small differences were noted, and these may explain the bifunctional character of the C. jejuni Gne. In a gne mutant of C. jejuni, the lipooligosaccharide was shown by capillary electrophoresis-mass spectrometry to be truncated by at least five sugars. Furthermore, both the glycoprotein N-linked heptasaccharide and capsule were no longer detectable by high resolution magic angle spinning NMR. These data indicate that Gne is the enzyme providing Gal and GalNAc residues with the synthesis of all three cell-surface carbohydrates in C. jejuni NCTC 11168.
Women's knowledge, practises, and intentions regarding correct pelvic floor exercises

Although research has demonstrated the efficacy of pelvic floor exercises (PFXs) for the prevention and treatment of female urinary incontinence (FUI), adherence to PFX regimens is commonly poor. There is some evidence that this finding is in part due to a lack of knowledge about how to perform PFXs correctly and misconceptions about the required frequency and duration of PFX regimens.
Functional receptor‐channel coupling compared in contractile and proliferative human vascular smooth muscle

We have previously identified a human vascular smooth muscle clone that can reversibly convert between proliferative and contractile phenotypes. Here we compared receptor‐channel coupling in these cells using fura‐2 to monitor [Ca2+]i and patch‐clamp to record currents. Histamine elevated [Ca2+]i in all cells and caused contraction of cells exhibiting the contractile phenotype. The rise of [Ca2+]i persisted in Ca2+‐free solution and was abolished by thapsigargin, indicating involvement of stores. Whole cell electrophysiological recording revealed that histamine evoked transient outward K+ current, indicating functional receptor‐channel coupling. The time‐course and amplitude of the histamine‐activated current were similar in cells of the proliferative and contractile phenotypes. Moreover, a large conductance K+ channel was recorded in cell‐attached patches and was activated by histamine as well as the Ca2+ ionophore A‐23187, identifying it as the large conductance Ca2+‐dependent K+ channel. This K+ channel showed similar characteristics and activation in both proliferative and contractile phenotypes, indicating that expression was independent of phenotype. In contrast, histamine also elicited an inward Cl− current in some contractile cells, suggesting differential regulation of this current depending on phenotype. These studies demonstrate the usefulness of this human vascular cell clone for studying functional plasticity of smooth muscle, while avoiding complications arising from extended times in culture. © 2001 Wiley‐Liss, Inc.
Stable high level expression of a transfected human HSP70 gene protects a heart-derived muscle cell line against thermal stress.

Heat shock protein 70 (HSP70) has been shown to play a fundamental role in the induction of thermotolerance in many biological systems. Elevated synthesis of HSP70 in response to diverse stresses such as heat, anoxia, ischaemia, ethanol and heavy metals has been correlated with protection against subsequent more severe stress and cross-tolerance to differing stresses. In this respect, exposure of the mammalian heart to sublethal heat treatment or ischaemia has been shown to protect against subsequent myocardial ischaemia with concomitant elevation of HSP70. However, direct demonstration that HSP70 can alone confer thermotolerance has until recently been restricted to transfection of fibroblasts with an HSP70 gene, although preliminary data from others suggests that transfection of H9c2 myocytes with an HSP70 gene can confer tolerance to substrate-free hypoxia. The purpose of this study was, therefore, to test directly whether a myocyte cell line which retains certain features of cardiac cells (as opposed to non-myocyte cells) can be protected against lethal thermal stress by transfection with a single HSP70 gene. Rat heart-derived H9c2 cells were transfected either with a plasmid from which high level expression of a human HSP70 gene is driven by a strong, heterologous (human) beta-actin promoter (APr-HS70), or with an analogous control plasmid containing no HSP70 gene (pAPr-1 neo). Following selection with the neomycin analogue G418, several clones were isolated which either expressed no HSP70 (control: pAPr-1 neo-derived) or stably expressed high constitutive levels of an inducible isoform of HSP70 (HSP70i) (APr-HS70-derived) as determined by Western blotting with a specific monoclonal antibody to HSP70i. (ABSTRACT TRUNCATED AT 250 WORDS)
Cerebral intraarterial fibrinolysis at the crossroads: is a phase III trial advisable at this time?

PURPOSE To describe the rationale for fibrinolysis, review the state of the art in cerebral fibrinolysis, and discuss whether it is time for phase III studies of cerebral intraarterial fibrinolysis. METHODS Critical review of the literature with statistical reevaluation of significant clinical data. RESULTS There are abundant phase III data supporting the use of thrombolysis in the cardiovascular system. However, there are no published phase III trials of intraarterial fibrinolysis in stroke. All reports of cerebral intraarterial fibrinolysis are case series. The studies are typically small with variable treatment protocols and designs that are susceptible to bias. The only analysis comparing cerebral intraarterial fibrinolysis with conventional therapy is based on nonconcurrent controls. CONCLUSIONS Stroke is common and costly. Acute stroke intervention with fibrinolytic drugs is theoretically justified. Studies done to date have significant, inferential limitations. The data suggest an association between thrombolysis, recanalization, and prognosis. However, imprecision and inadequate control of systematic error preclude conclusions regarding clinical outcomes. Randomized, controlled trials are needed to establish the clinical value of cerebral local intraarterial fibrinolysis. However, cerebral local intraarterial fibrinolysis availability, the cerebral local intraarterial arterial fibrinolysis learning curve, anticipated technological advances, unresolved procedural controversies, and ethical and fiscal considerations make a large phase III trial impractical and ill-advised at the present time. Additional basic research is needed to set the stage for a successful clinical trial.
Protein Kinase B Is Regulated in Platelets by the Collagen Receptor Glycoprotein VI*

Phosphoinositide 3-kinase (PI3K) is a critical component of the signaling pathways that control the activation of platelets. Here we have examined the regulation of protein kinase B (PKB), a downstream effector of PI3K, by the platelet collagen receptor glycoprotein (GP) VI and thrombin receptors. Stimulation of platelets with collagen or convulxin (a selective GPVI agonist) resulted in PI3K-dependent, and aggregation independent, Ser473 and Thr308 phosphorylation of PKBα, which results in PKB activation. This was accompanied by translocation of PKB to cell membranes. The phosphoinositide-dependent kinase PDK1 is known to phosphorylate PKBα on Thr308, although the identity of the kinase responsible for Ser473phosphorylation is less clear. One candidate that has been implicated as being responsible for Ser473 phosphorylation, either directly or indirectly, is the integrin-linked kinase (ILK). In this study we have examined the interactions of PKB, PDK1, and ILK in resting and stimulated platelets. We demonstrate that in platelets PKB is physically associated with PDK1 and ILK. Furthermore, the association of PDK1 and ILK increases upon platelet stimulation. It would therefore appear that formation of a tertiary complex between PDK1, ILK, and PKB may be necessary for phosphorylation of PKB. These observations indicate that PKB participates in cell signaling downstream of the platelet collagen receptor GPVI. The role of PKB in collagen- and thrombin-stimulated platelets remains to be determined.