Miracle-dz/UniFAR-FTUs huggingface dataset:
Special structure of mitochondrial DNA control region and phylogenetic relationship among individuals of the black rockfish, Sebastes schlegelii

This study deals with the structure of mitochondrial DNA (mtDNA) control region (CR) of the black rockfish, Sebastes schlegelii. Two termination-associated sequences (TASs), two complementary termination-associated sequences (cTASs), and conserved sequence block (CSB), such as CSB-F, CSB-E, CSB-D, CSB1, CSB2, and CSB3, were detected in S. schlegelii. The results indicated that the structures of these blocks are similar to most marine fishes, but it is special that there are two TASs and two cTASs in the CR of S. schlegelii. One conserved region was found from 450 bp to the end of the CR, which is also a special feature of S. schlegelii. All sequences of CSB1, CSB2, and CSB3 blocks are the consensus among different individuals, which is quite different from most vertebrates. In addition, the complete mtDNA CR sequences and the first 449 bp of the CR are used to analyze the phylogenetic relationships of S. schlegelii. The phylogenetic trees show a lack of genetic structure among individuals. This study also indicated a signal that the genetic diversity might be similar between the wild and cultured individuals, which may be helpful to the fisheries management.
On the Relationship between Handedness and Season of Birth for Men

A sample of 8,929 male baseball players and a sample of 2,234 males from the U.S. National Health and Nutrition Examination Survey are used to assess the relation between handedness and season of birth. The results, when coupled with a further examination of the 1991 data of Dellatolas, Curt, and Lellouch, lead to the conclusion that those born during the spring and early summer are more likely to be left-handed than are those born during the fall and winter.
THE ELECTROCARDIOGRAM IN SINGLE VENTRICLE

Few electrocardiograms in cases of single ventricle have been published. Brown (1950) found that right axis deviation was usual, although left axis deviation occurred in one of his cases and he found others with no axis deviation. In cases where pulmonary stenosis is an associated defect, Campbell, Reynolds, and Trounce (1953) concluded that analysis of the cardiogram failed to reveal any basic common pattern in addition to that of right ventricular hypertrophy: five of their cases showed right axis deviation and evidence of hypertrophy of the right side of the ventricle. Taussig (1960) found it subject to wide variation: the standard leads may show either right or left axis deviation, and there may be gross disparity between the findings in the standard and in the pracordial leads. Wood (1956) said that normal Q waves were usually seen in the antero-lateral chest leads or in one of the left-sided unipolar limb leads, despite the absence of the interventricular septum; otherwise the graph is apt to show changes that might ordinarily be more easily attributed to clockwise or anticlockwise rotation. Neill and Brink (1955) reported 8 cases of single ventricle with left axis deviation, 7 of which had prvcordial leads; a pattern of left ventricular preponderance was present in 3, of right ventricular preponderance in 1, and of equiphasic QRS in V 1-5 in 3: the P waves were increased in amplitude in 4 of these cases. Keith, Rowe, and Vlad (1958) suggested three patterns that may give one a lead in single ventricle: (1) right ventricular hypertrophy with a QR or rsR in the right prwcordial leads, (2) the pattern of negative complexes across the precordium, and (3) the presence of equiphasic complexes across the precordium. Honey, Rushton, and Taylor (1960) described a case of single ventricle, with a rudimentary chamber associated with inverted transposition of the great vessels, that showed a prolonged P-R interval and P mitrale. The object of this paper is to review and discuss the electrocardiograms of cases of single ventricle seen at Guy's Hospital and at Southampton Chest Hospital. Our criteria for acceptance into the study were that they should not have mitral atresia, tricuspid atresia, or a bilocular heart.
Plan to be Flexible: A Commentary on Adaptive Designs

This is a discussion of the following three papers appearing in this special issue on adaptive designs: ‘Nested repeated confidence intervals and switching between noninferiority and superiority’ by Joachim Hartung and Guido Knapp; ‘Confirmatory Seamless Phase II/III Clinical trials with Hypotheses Selection at Interim: General Concepts’ by Frank Bretz, Heinz Schmidli, Franz König, Amy Racine and Willi Maurer; and ‘Confirmatory Seamless Phase II/III Clinical Trials with Hypotheses Selection at Interim: Applications and Practical Considerations’ by Heinz Schmidli, Frank Bretz, Amy Racine and Willi Maurer. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Induction of Hairy Roots in Gmelina arborea Roxb . Using Agrobacterium rhizogenes

Seedling tissues of Gmelina arborea, a medicinally important tree species, were infected with wild type Agrobacterium rhizogenes strain ATTCC 15834, which led to the induction of hairy roots in 32% of the explants. Transgenic nature of the hairy roots was confirmed by PCR using rolB specific primers, and subsequently by Southern analysis of the PCR products. Eight transformed clones of hairy roots were established and grown in liquid medium for the analysis of secondary metabolites.
Functional interaction of VEGF‐C and VEGF‐D with neuropilin receptors

Lymphatic vascular development is regulated by vascular endothelial growth factor receptor‐3 (VEGFR‐3), which is activated by its ligands VEGF‐C and VEGF‐D. Neuropilin‐2 (NP2), known to be involved in neuronal development, has also been implicated to play a role in lymphangiogenesis. We aimed to elucidate the mechanism by which NP2 is involved in lymphatic endothelial cell signaling. By in vitro binding studies we found that both VEGF‐C and VEGF‐D interact with NP2, VEGF‐C in a heparin‐independent and VEGF‐D in a heparin‐dependent manner. We also mapped the domains of VEGF‐C and NP2 required for their binding. The functional importance of the interaction of NP2 with the lymphangiogenic growth factors was demonstrated by cointernalization of NP2 along with VEGFR‐3 in endocytic vesicles of lymphatic endothelial cells upon stimulation with VEGF‐C or VEGF‐D. NP2 also interacted with VEGFR‐3 in coprecipitation studies. Our results show that NP2 is directly involved in an active signaling complex with the key regulators of lymphangiogenesis and thus suggest a mechanism by which NP2 functions in the development of the lymphatic vasculature. —Kärpänen, T. , Heckman, C. A. , Keskitalo, S. , Jeltsch, M. , Ollila, H. , Neufeld, G. , Tamagnone, L. , Alitalo, K. Functional interaction of VEGF‐C and VEGF‐D with neuropilin receptors. FASEB J. 20, 1462–1472 (2006)
Digoxin Derivatives with Enhanced Selectivity for the α2 Isoform of Na,K-ATPase

Background: The α2 isoform of Na,K-ATPase may play a major role in aqueous humor production. Results: We have chemically modified digoxin and obtained derivatives with enhanced selectivity for α2. When applied topically, they effectively reduce intraocular pressure in rabbits. Conclusion: α2 is crucial for aqueous humor production. Significance: Potentially, the derivatives may be useful for control of intraocular pressure. In the ciliary epithelium of the eye, the pigmented cells express the α1β1 isoform of Na,K-ATPase, whereas the non-pigmented cells express mainly the α2β3 isoform of Na,K-ATPase. In principle, a Na,K-ATPase inhibitor with selectivity for α2 could effectively reduce intraocular pressure with only minimal local and systemic toxicity. Such an inhibitor could be applied topically provided it was sufficiently permeable via the cornea. Previous experiments with recombinant human α1β1, α2β1, and α3β1 isoforms showed that the classical cardiac glycoside, digoxin, is partially α2-selective and also that the trisdigitoxose moiety is responsible for isoform selectivity. This led to a prediction that modification of the third digitoxose might increase α2 selectivity. A series of perhydro-1,4-oxazepine derivatives of digoxin have been synthesized by periodate oxidation and reductive amination using a variety of R-NH2 substituents. Several derivatives show enhanced selectivity for α2 over α1, close to 8-fold in the best case. Effects of topically applied cardiac glycosides on intraocular pressure in rabbits have been assessed by their ability to either prevent or reverse acute intraocular pressure increases induced by 4-aminopyridine or a selective agonist of the A3 adenosine receptor. Two relatively α2-selective digoxin derivatives efficiently normalize the ocular hypertension, by comparison with digoxin, digoxigenin, or ouabain. This observation is consistent with a major role of α2 in aqueous humor production and suggests that, potentially, α2-selective digoxin derivatives could be of interest as novel drugs for control of intraocular pressure.
Cerebral microhemorrhage and brain β-amyloid in aging and Alzheimer disease

Objectives: Incidental cerebral microhemorrhage (MH) is frequently found in older individuals scanned with susceptibility-weighted MRI (SWI) or gradient-recalled echo MRI. MH have been linked with β-amyloid (Aβ) deposition using 11C-Pittsburgh compound B (PiB) PET in Alzheimer disease (AD) and cerebral amyloid angiopathy (CAA). We hypothesized that Aβ deposition in asymptomatic elderly individuals is associated with lobar MH (LMH). Methods: This was a cross-sectional study of 84 elderly healthy controls (HC), 28 subjects with mild cognitive impairment (MCI), and 26 subjects with probable AD who underwent 3-T SWI and 11C-PiB PET. 11C-PiB cortical binding was quantified normalized to cerebellar cortex (standardized uptake value ratio [SUVR]) and scans classified as positive (PiB+) or negative (PiB−) by visual inspection. MH were manually counted and categorized by region and as lobar or nonlobar. Results: LMH were present in 30.8% of AD, 35.7% of MCI, and 19.1% of HC. The prevalence of LMH among PiB+ subjects was similar, regardless of clinical classification (AD 30.8%, MCI 38.9%, HC 41.4%, p > 0.7). HC with LMH had significantly higher mean neocortical SUVR (1.7 ± 0.5) than HC without LMH (1.3 ± 0.3, p ± 0.01). In HC, there was a positive correlation between number of LMH and SUVR, and between LMH and age. In HC, PiB+ (odds ratio [OR] 7.3, 95% confidence interval [CI] 1.6–33.7, p = 0.01) and age (OR 1.2, 95% CI 1.03–1.3, p = 0.02) both independently predicted the occurrence of LMH using logistic regression. Conclusion: Asymptomatic Aβ deposition in older adults is strongly associated with LMH.
Efavirenz Versus Nevirapine in Current Clinical Practice: A Prospective, Open-Label Observational Study

Abstract:An open-label, observational, prospective 18-month survey was conducted to compare the efficacy and tolerability of the 2 available nonnucleoside reverse transcriptase inhibitors (NNRTIs) in all possible indications of current clinical practice. A broad range of clinical and laboratory variables accounting for drug efficacy and tolerability (with special emphasis on metabolic and hepatic toxicity) were measured in 287 evaluable patients treated with efavirenz, compared with 258 subjects taking nevirapine for 18 months. A separate efficacy analysis was performed in 154 antiretroviral-naive subjects, 298 patients experienced with 2–7 prior anti-HIV lines who abandoned protease inhibitors (PIs), and 103 subjects entering a salvage regimen containing at least 4 drugs, including PIs. Antiretroviral-naive patients experienced greater efavirenz activity at 3–12 months (maximum HIV RNA drop = −2.4 log10 copies/mL), associated with a significantly higher rate of complete viral suppression, while immunologic results proved significant only after 6–9 months. When assessing experienced patients and those on rescue regimens, a similar and progressively blunted laboratory response was achieved, on the ground of a worse baseline virologic and immunologic profile, and duration of prior anti-HIV therapy. Both first-month (4.2 and 4.3% for efavirenz and nevirapine, respectively) and overall discontinuation rates (11.5 and 12%, respectively) proved similar, but a profound difference emerged as to the different spectrum of untoward events: central nervous system (CNS) disturbances, persisting metabolic abnormalities, and possibly gynecomastia and laboratory pancreatic abnormalities for efavirenz vs. immediate allergy and increased hepatotoxicity (regardless of chronic infection with hepatitis B or C virus and methadone use) for nevirapine. A limited virologic and immunologic advantage of efavirenz was observed in the first 12-month assessment of antiretroviral-naive patients, whereas all other examined situations did not disclose relevant efficacy differences between efavirenz and nevirapine throughout the 18-month comparison. Although the short- and long-term toxicity and withdrawal rates of the 2 drugs were comparable, the different pathways prompting allergic, metabolic, liver, and CNS disturbances observed with NNRTIs deserve careful investigation, to prevent toxicity of these relevant antiretroviral compounds.
Cardiac Function and Organ Blood Flow at Early Stage Following Severe Burn

Multiple organ dysfunction syndrome (MODS) has been the difficulty in clinical treatment of severe burns. In the 1990s, the incidence rate of MODS was 28.1% in severe burn patients, while the mortality rate was as high as 78%-98% (Huang et al., 1998). MODS was caused by two “attacks": the first attack was the early plasma leakage and the effective circulating blood volume reduction, as resulted in the systemic hypoxic-ischemic damage; the second attack was the invasion of consequent systemic inflammatory response and sepsis on the organs (Sheng, 2002). With enhancement of the clinical treatment of burns, the present point of view argues that the key to prevention of MODS is against the first "attack", ie, to control the burn shock, which can effectively prevent or mitigate the second "attack" to reduce the incidence of MODS (Sheng, 2002).
Context-Dependent Functions of the PII and GlnK Signal Transduction Proteins in Escherichia coli

ABSTRACT Two closely related signal transduction proteins, PII and GlnK, have distinct physiological roles in the regulation of nitrogen assimilation. Here, we examined the physiological roles of PII and GlnK when these proteins were expressed from various regulated or constitutive promoters. The results indicate that the distinct functions of PII and GlnK were correlated with the timing of expression and levels of accumulation of the two proteins. GlnK was functionally converted into PII when its expression was rendered constitutive and at the appropriate level, while PII was functionally converted into GlnK by engineering its expression from the nitrogen-regulated glnK promoter. Also, the physiological roles of both proteins were altered by engineering their expression from the nitrogen-regulated glnA promoter. We hypothesize that the use of two functionally identical PII-like proteins, which have distinct patterns of expression, may allow fine control of Ntr genes over a wide range of environmental conditions. In addition, we describe results suggesting that an additional, unknown mechanism may control the cellular level of GlnK.
Mutation and Mutagenesis of thiol peroxidase of Escherichia coli and a new type of thiol peroxidase family

A novel thioredoxin-linked thiol peroxidase (Px) from Escherichia coli has been reported previously (M. K. Cha, H. K. Kim, and I. H. Kim, J. Biol. Chem. 270:28635-28641, 1995). In an attempt to perform physiological and biochemical characterizations of the thiol Px, a thiol Px null (tpx) mutant and a functional-residue mutant of thiol Px were produced. The tpx mutant was viable in aerobic culture but grew more slowly than the wild-type cells. The difference in growth rate became more pronounced when oxidative-stress-inducing reagents, such as peroxides and paraquat, were added to the cultures. The viability of the individual tpx mutant under oxidative stress was much lower than that of wild-type cells. tpx mutants growing aerobically respond to paraquat with a sixfold greater induction of Mn-superoxide dismutase than that of the wild-type cells. The deduced amino acid sequence of the thiol Px was found to be from 42 to 72% identical to the sequences of proteins from Haemophilus influenzae (ToxR regulon), Vibrio cholerae (ToxR regulon), and three kinds of streptococci (coaggregation-mediating adhesins), suggesting that they all belong to a new thiol Px family. Alignment of the amino acid sequences of the thiol Px family members showed that one cysteine, which corresponds to Cys-94 in E. coli thiol Px, is perfectly conserved. The substitution of serine for this cysteine residue resulted in complete loss of Px activity. These results suggest that the members of the thiol Px family, including E. coli thiol Px, have a functional cysteine residue and function in vivo as peroxidases.
Cognitive Style Predictors of Affect Change in Older Adults

Cognitive styles are the lenses through which individuals habitually process information from their environment. In this study, we evaluated whether different cognitive style individual difference variables, such as explanatory style and dispositional optimism, could predict changes in affective state over time in community-dwelling older adults. Based on previous research, we hypothesized that an optimistic explanatory style would be adaptive except when combined with life stressors, but that dispositional optimism would predict positive affective states regardless of life events. We found that older adults with a more optimistic explanatory style for health/cognitive events actually appeared to develop more depressive symptoms over six months of follow-up. However, dispositional optimism and orientation toward the future predicted a better affective profile over time.
Characterization of Two [3H]Ketanserin Recognition Sites in Rat Striatum

Two [3H]ketanserin recognition sites are present in the rat striatum. The high‐affinity site (Kd, 0.39 nM) is similar to the 5‐hydroxytryptamine2 (5‐HT2) site previously characterized by various investigators. The low‐affinity site (Kd, 21.8 nM) has a unique pharmacologic specificity and is preferentially localized to rat striatum and septum. Conventional 5‐HT2 antagonists as well as 5‐HT and 5‐HT uptake inhibitors are ineffective at inhibiting [3H]ketanserin binding to this low‐affinity site. Also, chronic treatment with p‐chlorophenylalanine, which depletes brain 5‐HT, upregulates only the high‐affinity site. Thus, in the striatum and septum, [3H]ketanserin labels a unique recognition site. This site has recently been shown to be associated with dopaminergic nerve endings and may regulate biogenic amine release.
Small-vessel vasculitis.

Vasculitis is inflammation of vessel walls. It has many causes, although they result in only a few histologic patterns of vascular inflammation. Vessels of any type in any organ can be affected, a fact that results in a wide variety of signs and symptoms. These protean clinical manifestations, combined with the etiologic nonspecificity of the histologic lesions, complicate the diagnosis of specific forms of vasculitis. This is problematic because different vasculitides with indistinguishable clinical presentations have very different prognoses and treatments. For example, a patient with purpura, nephritis, and abdominal pain caused by Henoch–Schonlein purpura usually has a good prognosis .
PREVALENCE OF VITAMIN D DEFICIENCY IN SOUTH ASIA

Vitamin D, also described as ‘the Sun Vitamin’ is a steroid with hormone-like activity. It regulates the functions of over 200 genes and is essential for growth and development of the body. Vitamin D deficiency is quite prevalent throughout the world, but it appears to be much worse in the countries of sunny South Asia, especially among children, women and elderly. Poor diet, cultural practices of the region and poverty are some of the important reasons for vitamin D deficiency. Hypovitaminosis D (vitamin D deficiency) is considered responsible for rickets, birth defects, osteoporosis, osteoarthritis, osteomalacia, chronic pain and muscle pain. Recent research has associated vitamin D deficiency as a contributing factor in diseases, such as heart disease, hypertension, neurological disorders, autoimmune disease, depression and cancer. This paper reviews the problem of vitamin D deficiency with special reference to South Asia and recommends that education regarding adequate exposure to sunlight, proper diet and fortification of selected foodstuff with vitamin D may be helpful in reducing vitamin D deficiency in this part of the world.
Pharmacokinetics and pharmacodynamics of BIBT 986, a novel small molecule dual inhibitor of thrombin and factor Xa

Summary. Background: Current anticoagulant development focuses on agents with predictable pharmacokinetic and pharmacodynamic (PD) properties. BIBT 986 is a novel potent anticoagulant with a dual mechanism of action: it competitively inhibits factor (F) Xa and FIIa. Aims: To determine the safety, tolerability, pharmacokinetics (PK) and PD of BIBT 986 following intravenous infusion in healthy male volunteers. Methods: In three randomized, double‐blind, placebo‐controlled trials, subjects were administered by intravenous infusion escalating doses of BIBT 986 for up to 32 h. BIBT 986 concentrations were determined in plasma and urine samples by high pressure liquid chromatography tandem mass spectrometry. Pharmacodynamic response was assessed by measuring the changes in blood coagulation times. Activated partial thromboplastin time, International Normalized Ratio, thrombin time and ecarin clotting time were determined and compared with baseline results. Results: In all three studies, intravenous infusion of BIBT 986 was safe and well tolerated. BIBT 986 exhibited linear PK over the dose range tested. Clearance was about 8 L h−1 and Vss about 50 L. Apparent steady state concentrations were reached within 24 h, indicating a dominant half‐life of about 6 h. The terminal half‐life of BIBT 986 was approximately 12 h. Renal excretion contributes approximately 50% to total elimination. Overall interindividual variability in pharmacokinetic and PD parameters was < 40%. There was a linear correlation between plasma concentrations and PD responses, suggesting excellent predictability. Conclusion: BIBT 986 is the first small molecule of a novel class of anticoagulants that potently and directly inhibits both coagulation FXa and thrombin. It has predictable pharmacokinetic and PD characteristics.