Miracle-dz/UniFAR-FTUs huggingface dataset:
The augmin complex plays a critical role in spindle microtubule generation for mitotic progression and cytokinesis in human cells

The mitotic spindle is constructed from microtubules (MTs) nucleated from centrosomes, chromosome proximal regions, and preexisting spindle MTs. Augmin, a recently identified protein complex, is a critical factor in spindle MT-based MT generation in Drosophila S2 cells. Previously, we identified one subunit of human augmin. Here, by using mass spectrometry, we identified the full human augmin complex of 8 subunits and show that it interacts with the γ-tubulin ring complex (γ-TuRC). Unlike augmin-depleted S2 cells, in which the defect in spindle-mediated MT generation is mostly compensated by centrosomal MTs, augmin knockdown alone in HeLa cells triggers the spindle checkpoint, reduces tension on sister kinetochores, and severely impairs metaphase progression. Human augmin knockdown also reduces the number of central spindle MTs during anaphase and causes late-stage cytokinesis failure. A link between augmin and γ-TuRC is likely critical for these functions, because a γ-TuRC mutant that attenuates interaction with augmin does not restore function in vivo. These results demonstrate that MT generation mediated by augmin and γ-TuRC is critical for chromosome segregation and cytokinesis in human cells.
NHE1 Is the Sodium-Hydrogen Exchanger Active in Acute Intracellular pH Regulation in Preimplantation Mouse Embryos1

ABSTRACT Sodium-hydrogen exchangers (NHE) of the Slc9 gene family are the major regulators of intracellular pH against acidosis in mammalian cells. Of five plasma membrane NHE isoforms, mouse oocytes and preimplantation embryos express mRNAs encoding NHE1 (SLC9A1), NHE3 (SLC9A3), and NHE4 (SLC9A4), with higher mRNA levels for each in oocytes through one-cell stage embryos and lower levels after the two-cell stage. NHE2 (SLC9A2) and NHE5 (SLC9A5) are not expressed. Measurements of intracellular pH during recovery from induced acidosis indicated that recovery occurred via NHE activity at all preimplantation stages assessed (one-cell, two-cell, eight-cell and morula). Recovery from acidosis at each stage was entirely inhibited by cariporide, which is very highly selective for NHE1. In contrast, the moderately NHE3-selective inhibitor S3226 did not preferentially block recovery, nor did adding S3226 increase inhibition over cariporide alone, indicating that NHE3 did not play a role. There was no indication of NHE4 activity. Another regulator of intracellular pH against acidosis, the sodium-dependent bicarbonate/chloride exchanger (NDBCE; SLC4A8), had low or absent activity in two-cell embryos. Thus, NHE1 appears to be the only significant regulator of intracellular pH in preimplantation mouse embryos. Culturing embryos from the one-cell or two-cell stages in acidotic medium inhibited their development. Unexpectedly, inhibition of NHE1 with cariporide, NDBCE with DIDS, or both together did not affect embryo development to the blastocyst stage more substantially under conditions of chronic acidosis than at normal pH. Preimplantation mouse embryos thus appear to have limited capacity to resist chronic acidosis using intracellular pH regulatory mechanisms.
The Effects of HPA Axis Function on Cognition and Its Implications for the Pathophysiology of Bipolar Disorder

AbstractBipolar disorders (BDs) are common and complex diseases. Recent findings have provided the basis for an integrated approach linking seemingly disparate findings, based on a greater understanding of the effects of stress on those vulnerable to these illnesses and the brain’s consequent responses. Genes are associated with this disorder, although their integration into current pathophysiological models is unclear. Manic states are associated with enhanced dopaminergic transmission, and experimental stress enhances dopamine neurotransmission and impairs cognition. Stress activates the hypothalamic-pituitary-adrenal axis, and dysfunction of this axis and impairments in neurocognitive function have both been demonstrated in BD. Glucocorticoid receptors are abnormal in postmortem brain studies in BD and play an important role in the HPA axis. The glucocorticoid receptor antagonist RU-486 has been shown to improve aspects of cognitive function in BD. The implications of these findings for models of pathophysiology are discussed. Future efforts should focus on further integrating the current and emerging research findings into a coherent pathophysiological model that generates testable hypotheses.
A Two Sweeping VCO Source for Heterodyne FMCW Radar

We propose and develop a heterodyne frequency modulated continuous wave (FMCW) radar system. The system operates at 14 GHz with a 500-MHz bandwidth in a 100-μs sweeping period, based on two wideband linear RF voltage-controlled oscillator (VCO) sweeping sources, which are controlled by a direct digital synthesizer (DDS) through a phase-locked scheme, leading to a high linearity of the frequency chirping signal. To achieve low phase noise, the RF signals are synthesized from low-noise baseband signals which are generated through a generation scheme of using phase-locked oscillators operating in the 800-MHz frequency range. Additionally, the proposed architecture can eliminate the phase noise contributions and/or frequency deviation due to the uncorrelation of different VCOs. The results are verified through measurements and derivation.
Multiple Input Multiple Output current-mode universal biquad filters

Multiple-Input Multiple Output (MIMO) universal biquad filters are introduced in this paper. They are constructed from appropriately configured current mirrors in order to realize the required integration and summation/subtraction operations. Attractive characteristics of the proposed topologies are the capability for low-voltage operation and electronic adjustment of the resonant frequency. The last one is achieved by utilizing the input resistance of the current mirrors in the employed integrators topology. The performance of the filters has been studied through simulation results.
L1 expressed by glioma cells promotes adhesion but not migration

L1 is an adhesion molecule of the immunoglobulin superfamily expressed by several types of cancer, including gliomas. It has been shown that L1 can act as chemoattractant to glioma cells, while the effects of L1 expressed by glioma cells themselves are unknown to date. We established a C6 rat glioma clone, conditionally expressing murine L1 under control of a tetracycline responsive promoter. In vitro experiments revealed increased adhesion on matrigel as well as increased intercellular adhesion in the presence of L1, whereas no L1‐dependent effects on proliferation or migration on either matrigel or myelin were observed. In vivo experiments using transplantation into nude mouse striatum, where L1 expression by glioma cells was regulated by tetracycline via drinking water, did not show effects of L1 on tumor size or brain invasion. Our data suggest that L1 expressed on the surface of glioma cells increases cell‐matrix and intercellular adhesion, but has no apparent effects on proliferation and invasion. GLIA 38:146–154, 2002. © 2002 Wiley‐Liss, Inc.
The Prevalence and Sociodemographic Risk Factors of Enuresis Nocturna among Elementary School-age Children

Introduction and Aim: Many etiological reasons are blamed for enuresis nocturna (EN). The aim of this study was to research prevalence and severity of EN among elementary school-age children and sociodemographic risk factors related to it. Materials and Methods: The study was performed in three elementary schools in Ankara, Turkey between January and May 2011. It was planned to have 2500 students of 6–14 ages in the study. The questionnaire, which consisted of questions, aiming to evaluate the EN condition of participants and their characteristics, were distributed to the parents. It was observed that 2314 participants’ questionnaires (92.56%) were in accordance with evaluation criteria. Statistical Analysis: The relation between EN and the sociodemographic factors was evaluated through Chi-square test and logistic regression analysis. Results: The mean age of 2314 participants was 9.21 ± 2.08. 48.5% (n = 1123) of the students were male and 51.5% (n = 1191) were female. While the general EN prevalence was 9.9% (n = 230); 10.7% (n = 120) for males, as 9.2% (n = 110) for females. Statistical significant difference was determined between the two groups, with EN and without EN, regarding age groups (P < 0.001), education level of parents (P < 0.001, P < 0.001), and the number of sibling (P = 0.002), income level (P < 0.001), and positive family history (P < 0.001). However, logistic regression analysis revealed that there was a significant difference only between EN and age groups (odds ratio [OR] =4.42, P < 0.001), education level of mother (OR = 2.13, P = 0.017) and family history (OR = 0.12, P < 0.001). Conclusions: As a consequence, such factors as age groups, education level of parents, positive family history could be accepted as a risk of concerning EN. It is important to perform a detailed evaluation on population, carrying risk of having EN.
Evaluation of argyrophilic nucleolar organizer region staining in predicting the behavior of meningiomas

BACKGROUND The number of argyrophilic nucleolar organizer regions (AgNOR) correlates with cellular proliferative activity. Comparing non-recurrent, recurrent, atypical and malignant meningiomas we studied the value of the routine applicability of the AgNOR count in the prognostication of this tumor. PATIENTS AND METHODS Two hundred and thirty-eight meningiomas were reviewed blindly and graded using WHO grading schema. Eighty-one cases were selected and arranged in six groups according to clinical data and grading: 14 benign non-recurrent meningiomas; 14 primary benign recurrent meningiomas and their subsequent benign recurrences; 14 atypical; 11 malignant and 14 spinal meningiomas. Silver-stained slides were prepared and mean, median and standard deviation of AgNOR dots determined. RESULTS There was a proportionate increase of AgNOR dots with increasing tumor grade. There was a significant difference between benign non-recurrent tumors versus benign recurrent (P<0.0001) and atypical or malignant (P<0.0001) tumors. A difference was also noted between the recurring tumors versus malignant ones (P= 0.002) but no significant difference was seen between recurrent and atypical; atypical and malignant; intracranial and intraspinal; and primary of recurring meningiomas with their subsequent recurrences. A mean AgNOR count of <2.3 could separate benign tumors from atypical or malignant meningiomas with 93% specificity; and 93% of tumors with benign histology had no recurrence potential if their mean AgNOR count was less than 1.8. CONCLUSION This study indicates that in meningioma, the AgNOR count has a good correlation with tumor grading and recurrence, which may aid pathologists and clinicians in predicting tumor behavior.
The effect of ginger consumption on glycemic status, lipid profile and some inflammatory markers in patients with type 2 diabetes mellitus

Abstract Objective: To assess the effect of ginger consumption on glycemic status, lipid profile and some inflammatory markers in patients with type 2 diabetes mellitus. Methods: In a double-blinded, placebo-controlled clinical trial, 70 type 2 diabetic patients were enrolled. They allocated randomly into ginger group and control group. They consumed 1600 mg ginger versus 1600 mg wheat flour placebo daily for 12 weeks. Serum sugar, lipids, CRP, PGE2 and TNFα were measured before and after intervention. Results: Ginger reduced fasting plasma glucose, HbA1C, insulin, HOMA, triglyceride, total cholesterol, CRP and PGE2 significantly compared with placebo group (p < 0.05). There were no significant differences in HDL, LDL and TNFα between two groups (p > 0.05). Conclusion: Ginger improved insulin sensitivity and some fractions of lipid profile, and reduced CRP and PGE2 in type 2 diabetic patients. Therefore ginger can be considered as an effective treatment for prevention of diabetes complications.
Can Supervised Group Exercises Including Ergonomic Advice Reduce the Prevalence and Severity of Low Back Pain and Pelvic Girdle Pain in Pregnancy? A Randomized Controlled Trial

Background Many women have low back pain (LBP) or pelvic girdle pain (PGP) during pregnancy, but there is limited evidence of effective primary and secondary preventive strategies. Objective The purpose of this study was to investigate whether a group-based exercise program can reduce the prevalence and severity of LBP and PGP in pregnant women. Design An observer-blinded randomized controlled trial with equal assignments to a training group and a control group was conducted. Setting The study was conducted in primary care maternity units in 2 suburban municipalities in the southeastern part of Norway. Patients The participants were 257 pregnant women who were healthy and between 18 and 40 years of age before gestation week 20. Intervention The training group received supervised exercises in groups once a week, and the control group received standard care. Measurements The main outcome measures were self-reported LBP and self-reported PGP. Secondary outcome measures were pain intensity in the morning and evening, disability, and 8-Item Short-Form Health Survey (SF-8) Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. Follow-up measurements were performed at gestation weeks 24, 28, 32, and 36. Results Overall, there was no effect of the program on the prevalence of PGP (odds ratio=1.03, 95% confidence interval [CI]=0.66 to 1.59) or LBP (odds ratio=0.77, 95% CI=0.50 to 1.19). For the secondary outcomes, the estimated mean differences between the groups were −0.4 (95% CI=−0.8 to 0.1) for pain intensity in the morning, −0.4 (95% CI=−1.0 to 0.2) for pain intensity in the evening, −1.0 (95% CI=−2.2 to 0.0) for disability, 1.8 (95% CI=0.0 to 3.7) for the SF-8 PCS, and −0.6 (95% CI=−2.2 to 1.4) for the SF-8 MCS. Limitations Due to low statistical power, the estimates for the primary outcomes are imprecise. Conclusions Supervised group exercise did not reduce the prevalence of LBP or PGP in pregnancy.
Venous thromboembolism: disease burden, outcomes and risk factors

Summary. The epidemiology of venous thromboembolism (VTE) in the community has important implications for VTE prevention and management. This review describes the disease burden (incidence), outcomes (survival, recurrence and complications) and risk factors for deep vein thrombosis and pulmonary embolism occurring in the community. Recent comprehensive studies of the epidemiology of VTE that reported the racial demography and included the full spectrum of disease occurring within a well‐defined geographic area over time, separated by event type, incident vs. recurrent event and level of diagnostic certainty, were reviewed. Studies of VTE outcomes had to include a relevant duration of follow‐up. VTE incidence among whites of European origin exceeded 1 per 1000; the incidence among persons of African and Asian origin may be higher and lower, respectively. VTE incidence over recent time remains unchanged. Survival after VTE is worse than expected, especially for pulmonary embolism. Thirty percent of patients develop VTE recurrence and venous stasis syndrome. Exposures can identify populations at risk but have a low predictive value for the individual. An acquired or familial thrombophilia may predict the subset of exposed persons who actually develop symptomatic VTE. In conclusion, VTE is a common, lethal disease that recurs frequently and causes serious long‐term complications. To improve survival and prevent complications, VTE occurrence must be reduced. Better individual risk stratification is needed in order to modify exposures and target primary and secondary prophylaxis to the person who would benefit most.
EFFECT OF GROWTH FACTORS ON DNA LABELING AND CYTOSKELETAL PROTEIN EXPRESSION IN 17-β-ESTRADIOL AND BASIC FIBROBLAST GROWTH FACTOR PRE-TREATED ASTROCYTE CULTURES

Astrocytes react to all noxae which damage neurons. Their reactions include degeneration, hypertrophy, hyperplasia and fibre formation. Growth factors inducing proliferation and differentiation of both neurons and astrocytes in culture play a pivotal role in the dynamic flow of signaling molecules between neurons and astroglia. Estrogens as well influence astroglia and are neuroprotectants. This study has investigated the interactions between growth factors and estrogens on DNA labeling and cytoskeletal protein [glial fibrillary acidic protein (GFAP) and vimentin] expression in 22 DIV astrocyte cultures treated for 24 or 36 h under different experimental conditions. Contemporary addition of 17-β-estradiol (E2) with two or three growth factors for 24 h, significantly stimulated methyl-[3H]thymidine incorporation into DNA from 22 days in vitro (DIV) astrocyte cultures. This effect reached a peak when E2 was co-added with epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) and insulin. In astrocyte cultures treated for 36 h with E2 and EGF+insulin or bFGF+insulin added in the last 12 h, DNA labeling was remarkably increased. The parallel cyclin D1 expression positively correlated with ERK2 activation. Western blot analysis for cytoskeletal proteins showed also changes of both GFAP and vimentin expression. The above data suggest the occurrence of a scheduled interaction between “competence” or “progression” growth factors and estrogens on DNA labeling and cytoskeletal protein expression during astroglial cell proliferation and differentiation in culture. A better understanding of the mechanisms of these interactions may contribute to develop strategies for controlling astroglial reaction in cerebrovascular disease including stroke and hypertensive brain damage.
Extended lung preservation with platelet-activating factor-antagonist TCV-309 in combination with prostaglandin E1.

BACKGROUND Ischemia-reperfusion injury is one of the major problems in organ transplantation. The role of platelet-activating factor (PAF) in the pathophysiology of ischemia-reperfusion injury and the protective effect of a novel phospholipid PAF analog (TCV-309) alone and combined with prostaglandin E1 (PGE1) is investigated in an extended (20 hours) ex vivo lung preservation. METHODS Forty-two swine were divided into three groups. Group A was the control. In groups B and C, the effect of PAF was blocked with TCV-309 administered 1 hour before cross-clamping for donor and recipient. Group C received PGE1 50 micrograms bolus in the donor pulmonary plegia, and the recipients received a 50 micrograms bolus plus 0.003 microgram/kg/min infusion at the time of implantation. Donor lungs were perfused with cold modified Collins solution and maintained in hypothermic storage (4 degrees C) for 20 hours. Hemodynamics, lung mechanics, gas exchange, and biochemistry were assessed before transplantation (donor) and at 30 minutes and 24 hours after reperfusion (recipient). At 24 hours after reperfusion, the histopathologic condition of transplanted lungs was evaluated. RESULTS Radioimmunoassay demonstrated a significant (p < 0.001) increase in the production of PAF and TXB2 in transplanted lungs at 24 hours after transplantation for group A only. Hemodynamics, gas-exchange parameters, and lung compliance were significantly (p < 0.05) better after transplantation for groups B and C. Wet lung weight was significantly less (p < 0.05) for group C. Semiquantitative morphometric analysis demonstrated the highest degree of damage for group A compared with groups B and C. A strong correlation (r2 = 70) between lung weight and histologic injury scores was observed among groups. CONCLUSIONS This study suggests that PAF is responsible in part for the deleterious effects of ischemia and reperfusion, that PAF-antagonist TCV-309 protects lungs from extended (20 hours) ischemic injury, and that PGE1 seems to have an additional beneficial effect.
Effect of intracellular and extracellular pH on contraction in isolated, mammalian cardiac muscle.

1. Intracellular pH (pHi) and Na+ activity were recorded (ion‐selective microelectrodes) in guinea‐pig papillary muscle and the sheep cardiac Purkinje fibre while simultaneously recording twitch tension. The effects of intracellular acidosis and alkalosis upon contraction were investigated. 2. A fall of pHi produced by reducing pHo was associated with a fall of twitch tension. Similarly, a rise of pHi produced by raising pHo produced a rise of twitch tension. The time course of the changes in tension correlated with the time course of changes of pHi rather than pHo. These results are consistent with previous work showing that acidosis inhibits contraction and that the inhibition depends upon a fall of pHi. 3. Changes of pHi were produced while maintaining pHo constant at 7.4. Removal of NH4Cl or addition of sodium acetate (pHo 7.4) reduced pHi but this gave either an increase of tension (papillary muscle) or an initial fall followed by a subsequent recovery of tension (Purkinje fibre). The increase or recovery of tension occurred despite the fact that there was an intracellular acid load. Thus, reducing pHi at constant pHo can increase tension whereas reducing pHi at low pHo (6.4, see paragraph 2) inhibits tension. 4. The increase of recovery of tension during intracellular acidosis produced at a constant pHo (7.4) was associated with a rise of intracellular sodium activity (aiNa). Amiloride (1.5 mmol/l), an inhibitor of Na(+)‐H+ exchange, prevented the rise of aiNa during intracellular acidosis and also prevented the recovery of tension. It is concluded that the increase or recovery of tension at low pHi is secondary to a rise of aiNa caused by stimulation of Na(+)‐H+ exchange. A rise of aiNa will elevate Ca2+ via sarcolemmal Na(+)‐Ca2+ exchange and thus will elevate tension. 5. An intracellular acidosis produced by reducing pHo (6.4) does not elevate aiNa in the Purkinje fibre. In papillary muscle, aiNa rises but this occurs slowly and the rise is 50% smaller than that seen when the same intracellular acidosis is induced at normal pHo (7.4). The net depression of tension under these conditions thus correlates with the lack of a large rise of aiNa. 6. Knowing the quantitative dependence of tension upon both aiNa and pHi in the two tissues it is possible to predict the recovery of twitch tension during intracellular acidosis at constant pHo (7.4), using the changes of pHi and aiNa measured under these conditions. (ABSTRACT TRUNCATED AT 400 WORDS)
Misexpression screen for genes altering the olfactory map in Drosophila

Despite the identification of a number of guidance molecules, a comprehensive picture has yet to emerge to explain the precise anatomy of the olfactory map. From a misexpression screen of 1,515 P{GS} lines, we identified 23 genes that, when forcibly expressed in the olfactory receptor neurons, disrupted the stereotyped anatomy of the Drosophila antennal lobes. These genes, which have not been shown previously to control olfactory map development, encode novel proteins as well as proteins with known roles in axonal outgrowth and cytoskeletal remodeling. We analyzed Akap200, which encodes a Protein Kinase A‐binding protein. Overexpression of Akap200 resulted in fusion of the glomeruli, while its loss resulted in misshapen and ectopic glomeruli. The requirement of Akap200 validates our screen as an effective approach for recovering genes controlling glomerular map patterning. Our finding of diverse classes of genes reveals the complexity of the mechanisms that underlie olfactory map development. genesis 44:189–201, 2006. Published 2006 Wiley‐Liss, Inc.