Miracle-dz/UniFAR-FTUs huggingface dataset:
Turning a new page on nucleostemin and self-renewal

ABSTRACT A quintessential trait of stem cells is embedded in their ability to self-renew without incurring DNA damage as a result of genome replication. One key self-renewal factor is the nucleolar GTP-binding protein nucleostemin (also known as guanine-nucleotide-binding protein-like 3, GNL3, in invertebrate species). Several studies have recently pointed to an unexpected role of nucleostemin in safeguarding the genome integrity of stem and cancer cells. Since its discovery, the predominant presence of nucleostemin in the nucleolus has led to the notion that it might function in the card-carrying event of the nucleolus – the biogenesis of ribosomes. As tantalizing as this might be, a ribosomal role of nucleostemin is refuted by evidence from recent studies, which argues that nucleostemin depletion triggers a primary event of DNA damage in S phase cells that then leads to ribosomal perturbation. Furthermore, there have been conflicting reports regarding the p53 dependency of nucleostemin activity and the cell cycle arrest profile of nucleostemin-depleted cells. In this Commentary, I propose a model that explains how the many contradictory observations surrounding nucleostemin can be reconciled and suggest that this protein might not be as multi-tasking as has been previously perceived. The story of nucleostemin highlights the complexity of the underlying molecular events associated with the appearance of any cell biological phenotype and also signifies a new understanding of the genome maintenance program in stem cells.
Decreased expression of 20‐kD homologous restriction factor (HRF20, CD59) on T lymphocytes in Epstein–Barr virus (EBV)‐induced infectious mononucleosis

HRF20 (CD59) is one of the membrane‐associated complement regulatory proteins. The characteristic function of CD59 is to prevent membrane attack complex (MAC) formation on the cell surface and to protect the cell from complement‐mediated cell lysis. We examined the expression of CD59 antigen on T cell subpopulations in patients with acute infectious mononucleosis (IM) and analysed the relationship between the amount of CD59 expression and activation‐induced cell death of mature T cells with apoptosis. Decreased expression of CD59 on CD8+ T cells, especially on CD45RO+ and HLA‐DR+ activated T cells, was marked in acute IM patients. In contrast, activated CD4+ T cells from IM patients expressed as much CD59 antigen as CD4+ T cells from healthy volunteers. After incubation‐induced cell death, viable CD8+ T cells showed normal amounts of CD59 antigen on their surface. CD59dim CD8+ T cells were more susceptible to apoptosis than CD59bright CD8+ T cells. These findings suggest that decreased expression of CD59 on CD8+ T cells may discriminate the susceptibility of activated CD8+ T cells to activation‐induced cell death in IM.
THE INTERACTION OF BEHAVIORAL AND MORPHOLOGICAL CHANGE IN THE EVOLUTION OF A NOVEL LOCOMOTOR TYPE: “FLYING” FROGS

“Flying” frogs have evolved independently several times among anurans. In all cases flyers are distinguished from their nonflying arboreal relatives by a unique set of morphological features and behavioral postures. Using both live animal field tests and wind tunnel models, this study examines the importance of this characteristic morphology and limb position on five aerial performance variables: horizontal traveling distance, minimum glide speed, maximum time aloft, maneuverability, and stability. Comparison of relative performance between a model frog with a generalized nonflying morphology and limb position and a model frog with flying morphology and limb position reveals that the morphological and positional features associated with “flying” actually decrease horizontal traveling distance but improve maneuverability. This finding suggests that maneuverability rather than horizontal travel may be the key performance parameter in the evolution of “flying” frogs.
PrimaTB STAT-PAK Assay, a Novel, Rapid Lateral-Flow Test for Tuberculosis in Nonhuman Primates

ABSTRACT Tuberculosis (TB) is the most important zoonotic bacterial disease in nonhuman primates (NHP). The current diagnostic method, the intradermal palpebral tuberculin test, has serious shortcomings. We characterized antibody responses in NHP against Mycobacterium tuberculosis to identify immunodominant antigens and develop a rapid serodiagnostic test for TB. A total of 422 NHP were evaluated, including 243 rhesus (Macaca mulatta), 46 cynomolgus (Macaca fascicularis), and 133 African green (Cercopithecus aethiops sabaeus) monkeys at five collaborative centers. Of those, 50 monkeys of the three species were experimentally inoculated with M. tuberculosis. Antibody responses were monitored every 2 to 4 weeks for up to 8 months postinfection by MultiAntigen Print ImmunoAssay with a panel of 12 recombinant antigens. All of the infected monkeys produced antibodies at various levels and with different antigen recognition patterns. ESAT-6 and MPB83 were the most frequently recognized proteins during infection. A combination of selected antigens which detected antibodies in all of the infected monkeys was designed to develop the PrimaTB STAT-PAK assay by lateral-flow technology. Serological evaluation demonstrated high diagnostic sensitivity (90%) and specificity (99%). The highest rate of TB detection was achieved when the skin test was combined with the PrimaTB STAT-PAK kit. This novel immunoassay provides a simple, rapid, and accurate test for TB in NHP.
Remarriage of Older Canadians

The remarriage experience of Canadian men and women aged 55 and over at time of survey are described using data from the Canadian Family History Survey, carried out in 1984 by Statistics Canada. Data pertain to approximately 1,300 women and 1,100 men. Remarriage is put in the context of total life cycle experience by means of a simple decomposition of the lifetime probability of remarriage. The analysis highlights the greater exposure of women to remarriage (due to high rates of widowhood) but their lower remarriage rates compared to men. The sex differential in remarriage remains when age at dissolution is controlled. A major regional differential is found in remarriage patterns in Canada, with residents of Quebec showing appreciably lower remarriage rates following divorce than the rest of the country. An interpretation of the observed patterns suggests the need for more attention to motivation in the study of remarriage behavior.
Bound by Fate: The Role of Reactive Oxygen Species in Receptor-Like Kinase Signaling[OPEN]

Receptor-like kinases and reactive oxygen species are intricately entangled and have central roles in controlling many processes in plants, but their interaction is still insufficiently understood. In plants, receptor-like kinases (RLKs) and extracellular reactive oxygen species (ROS) contribute to the communication between the environment and the interior of the cell. Apoplastic ROS production is a frequent result of RLK signaling in a multitude of cellular processes; thus, by their nature, these two signaling components are inherently linked. However, it is as yet unclear how ROS signaling downstream of receptor activation is executed. In this review, we provide a broad view of the intricate connections between RLKs and ROS signaling and describe the regulatory events that control and coordinate extracellular ROS production. We propose that concurrent initiation of ROS-dependent and -independent signaling linked to RLKs might be a critical element in establishing cellular responses. Furthermore, we discuss the possible ROS sensing mechanisms in the context of the biochemical environment in the apoplast. We suggest that RLK-dependent modulation of apoplastic and intracellular conditions facilitates ROS perception and signaling. Based on data from plant and animal models, we argue that specific RLKs could be components of the ROS sensing machinery or ROS sensors. The importance of the crosstalk between RLK and ROS signaling is discussed in the context of stomatal immunity. Finally, we highlight challenges in the understanding of these signaling processes and provide perspectives for future research.
Reduction in renal haemodynamics by exaggerated vesicovascular reflex in rats with acute urinary retention

1 We examined the possibility that a vesicovascular reflex is exaggerated by acute urinary retention, and that the increase in renal vascular resistance caused by this reflex may lead to renal dysfunction. We evaluated the vesicovascular responses to normal micturition (NM, transcystometric condition) and acute urinary retention (isovolumetric condition mimicking complete bladder‐outlet obstruction (CBOO) and partial urethral ligation mimicking partial bladder‐outlet obstruction (PBOO)) in anaesthetized female Wistar rats. 2 Acute urinary retention due to CBOO or PBOO provoked a prolonged or increased intravesical pressure, an enhancement in both bladder pelvic afferent and bladder pelvic efferent nervous activity, and an elevation in mean arterial blood pressure. 3 Single‐unit analysis showed that these vesicovascular reflexes were triggered by activation of low‐threshold and high‐threshold bladder mechanoreceptors, but not by renal uretropelvic mechanoreceptors. 4 Bladder contraction in CBOO and PBOO conditions and graded increases in bladder volume significantly reduced renal blood flow and cortical microvascular blood flow. The acute urinary retention‐induced renal vasoconstriction was mediated by the renal nerve. Renal denervation, but not bilateral ureteral resection, abolished the renal vasoconstriction associated with the vesicovascular reflexes. 5 These findings indicate that exaggerated activation of bladder afferents exerts a positive feedback effect to increase sympathetic outflow to the kidney further, thereby contributing to significant renal vasoconstriction via a renal nerve‐dependent mechanism.
Donepezil, Rivastigmine, and Vitamin E in Alzheimer Disease: A Combined P300 Event-related Potentials/Neuropsychologic Evaluation over 6 Months

The latency of P300 “cognitive” event-related potentials changes if cholinergic activities of the central nervous system are pharmacologically manipulated. We tested the hypothesis that the new cholinesterase inhibitors donepezil (DPZ) and rivastigmine (Riv) may have an effect on the frequently abnormal P300 component in patients with Alzheimer disease (AD), thereby allowing a significant evaluation of cholinesterase inhibitors. We evaluated 60 patients with mild to moderately severe probable AD, in comparison with 60 age-matched control subjects, with P300 recordings and neuropsychologic examinations. Forty patients were randomly assigned in a double-blinded trial to 5–10 mg/d DPZ versus 2,000 IU/d vitamin E, and 20 patients were instead treated in an open trial with 1.5 to 12 mg/d Riv. In patients treated with vitamin E, we observed latency increments (7.4 ± 3.5 msec) correlated with worsening neuropsychologic test scores. In patients treated with DPZ and Riv, we found significant P300 latency reductions (15.3 ± 3.2 msec and 22.0 ± 3.3 msec). Shorter P300 latencies were associated with higher Wechsler Adult Intelligence Scale scores and with lower AD Assessment Scale–cognitive subscale (ADAS-cog) scores (R = 0.72). Correlations between ADAS-cog changes and P300 changes significantly separated patients treated with DPZ and Riv from those treated with vitamin E. Administration of DPZ and Riv reduced the latencies of P300 components proportionately to neuropsychologic test improvements. Combined P300 and neuropsychologic test evaluation significantly separated DPZ-treated patients and Riv-treated patients from vitamin E-treated patients.
The occurrence of ambient temperature-regulated adhesins, curli, and the temperature-sensitive hemagglutinin tsh among avian Escherichia coli.

Escherichia coli establishes a secondary respiratory tract infection in birds following inhalation of contaminated dust and litter particles. Escherichia coli express adhesins under conditions reflective of the ambient temperatures present in poultry houses. These microbial adhesins allow E. coli to attach to cell types that it initially encounters in the respiratory tract. Ambient temperature-regulated adhesins represent a new class of bacterial hemagglutinins that include pili and the thin, aggregative, flexible filaments known as "curli. " This study examines the occurrence of the ambient temperature-regulated adhesins, curli (crl, csgA), and an avian-specific, temperature-sensitive hemagglutinin, tsh, among avian and mammalian E. coli isolates. The avian hemagglutinin gene tsh was present in approximately 46% of clinical avian E. coli isolates. This gene was not detected among commensal E. coli isolated from healthy broiler chickens. Unlike tsh, curli genes were ubiquitous among E. coli. However, curli were observed in only half of the avian E. coli examined by electron microscopy. Curli were not present among several nonavian E. coli positive for crl and csgA. Approximately 25% of avian E. coli isolates agglutinated chicken erythrocytes when bacteria were grown at room temperature. Hemagglutination was not specific to E. coli isolated from poultry. Presence of either tsh or curli genes was not indicative of an isolate's ability to agglutinate chicken red blood cells. No discernible structures were observed mediating attachment of the bacteria to chicken red blood cells. An additional avian-specific hemagglutinin appears to be present among avian E. coli.
Tuberculous meningitis among adults with and without HIV infection. Experience in an urban public hospital.

BACKGROUND Tuberculous meningitis remains a frequently diagnosed entity in urban US hospitals, with the incidence increasing as a consequence of infection with the human immunodeficiency virus (HIV). OBJECTIVE To describe the occurrence, characteristics, and therapeutic responses of tuberculous meningitis among adult patients of an urban public hospital, with special attention to the effects of HIV infection. DESIGN Retrospective clinical review of all cases identified among adults over a 12-year interval, collecting demographic and clinical variables. SETTING A 550-bed urban teaching hospital. MAIN OUTCOME MEASURE Nine-month outcome stratified by survival. RESULTS Among 31 adult patients identified as having definite or probable tuberculous meningitis, a majority (n = 20 [65%]) were infected with HIV. Cumulative rates of occurrence per 100 000 persons over the 12 years of the study were estimated at 1.72 for those without HIV infection and 400 for those with HIV infection. The most common symptoms at presentation were fever (83% [24/ 29]) and abnormal mental status (71% [20/28]). One or more abnormalities were present in the cerebrospinal fluid of 97% (30/31) of subjects, and 74% (23/31) had cerebrospinal fluid cultures positive for Mycobacterium tuberculosis. Neuroimaging of 28 patients revealed 1 or more abnormalities in 82% (n = 23). Among 30 patients with available outcome data at 9 months, 43% (n = 13) had died, 40% (n = 12) had survived without sequelae, and 17% (n = 5) had survived with morbidity. HIV infection had no discernible effect on findings. CONCLUSIONS Tuberculous meningitis remains relatively common among indigent urban nonwhite populations. While HIV infection has contributed to the increased incidence of tuberculous meningitis, it has not significantly altered the presenting clinical, laboratory, or radiographic findings or the response to therapy of this disease. Parameters associated in a multivariate regression analysis with mortality at 9 months were black race and the absence of corticosteroid use.
Linear Regression Analysis of the Cumulative Defect Curve by Sectors and Other Criteria of Glaucomatous Visual Field Progression

Purpose To analyze the progression of visual field loss using sector analysis of the cumulative defect curve and other procedures. Methods Visual fields of 260 glaucomatous eyes were analyzed over 2.8 years (SD = 1.2) with at least five examinations (mean 6.9; SD = 2.0) using Octopus 311 perimeter and TOP strategy. The authors applied Threshold Noiseless Trend (TNT) program, which performs local filtering of threshold to reduce fluctuation, and analyzed five criteria: 1) a score based on significant progression of eight sectors of the cumulative defect curve (CD); 2) a score based on the presence of points (PO) with significant progression; 3) global progression (GL) of all local deviations; 4) progression of mean defect (MD); 5) progression of the square root of loss variance (sLV). The authors estimated false diagnoses (FD), randomly reordering examinations of each patient. An index of focality of progression (FI) was obtained. Results sLV presented low sensitivity and GL low specificity. CD and PO presented twice the sensitivity of MD, often proving earlier indicators. The authors observed significant progression of some of the three criteria in 17.5% of the cases when MD <6 dB and in 20.7% when MD >6 dB (FD=5.7%). Agreement between two criteria occurred in 6.8% of cases with MD <6 dB and in 11.6% when MD >6 dB (FD=1.9%). Result reproducibility in successive examinations was observed in 9.9% of cases (FD=1.3%). Focality of progression increased with MD. Conclusions PO and CD indicate suspected progression earlier than MD. Reproduction of results in successive examinations or agreement between criteria allows confirmation of progression.
Tissue inhibitor of metalloproteinase‐1 protects MCF‐7 breast cancer cells from paclitaxel‐induced apoptosis by decreasing the stability of cyclin B1

Paclitaxel (PTX) is a very effective drug in treating tumors. It disturbs microtubule dynamics and impairs the transition of cells from metaphase to anaphase in mitosis, leading to cell death by apoptosis. However, the effectiveness of PTX in cancer chemotherapy is hampered by drug resistance in some patients. Tissue inhibitor of metalloproteinase‐1 (TIMP‐1) is well known to be capable of inhibiting apoptosis. Elevated tumor tissue TIMP‐1 levels have been significantly associated with a poor response to chemotherapy. We hypothesized that TIMP‐1 could reduce the sensitivity of breast cancer cells to PTX by inhibiting apoptosis. To test this hypothesis, we first examined the effects of TIMP‐1 on the apoptosis induced by PTX and investigated the effects of TIMP‐1 on the expression and stability of cyclin B1 that critically regulates the metaphase to anaphase transition during mitosis in MCF‐7 breast cancer cells. Our data demonstrate that TIMP‐1 could significantly decrease the sensitivity of MCF‐7 cells to PTX‐induced apoptosis, attenuate mitotic blockage in G2/M, and enhance the degradation of cyclin B1. To further investigate whether the inhibitory effect of TIMP‐1 on PTX‐induced apoptosis is mediated by lowering levels of cyclin B1, a cyclin B1‐expression plasmid was transfected into clone overexpressing TIMP‐1. The levels of PTX‐induced apoptosis were then analyzed. The data showed that the TIMP‐1‐based decrease in PTX‐induced apoptosis was reversed by cyclin B1. Our data indicate that TIMP‐1 can protect breast cancer cells from PTX‐induced apoptosis by decreasing the stability of cyclin B1.
Modeling and control of a Cúk multiple input converter (MIC) with MPPT for the PV system

This paper presents the study of dynamic modeling and control of a converter of multiple inputs (MIC) with MPPT. There are two independent inputs, wind and photovoltaic sources (PV), connected to a DC bus, and a single converter (MIC) as a means of reducing system costs. In order to extract maximum energy from the PV system for a given solar irradiance and temperature, an approach of adjusting the converter switching cycle and track the maximum power point (MPPT), with an incremental conductance algorithm is proposed. The small signal average dynamics for the multiple inputs (MIC) Cúk converter is derived and used for the control design. Simulation is made using MATLAB / Simulink.
Interaction of the amyloid imaging tracer FDDNP with hallmark Alzheimer’s disease pathologies

The distinctive cortical uptake of the tracer 18F‐FDDNP (2‐(1‐{6‐[(2‐fluoroethyl(methyl)amino]‐2‐naphthyl}ethylidene)malononitrile) in Alzheimer’s disease (AD) is believed to be because of its binding to both neurofibrillary tangles (NFTs) and highly fibrillar senile plaques. We therefore investigated the binding of a tracer concentration of 3H‐FDDNP to brain sections containing AD hallmark pathologies. Semi‐adjacent sections were labelled with 3H‐PIB (Pittsburgh compound‐B, 2‐[4′‐(methylamino)phenyl]‐6‐hydroxybenzothiazole) and 14C‐SB13 (4‐N‐methylamino‐4′‐hydroxystilbene) for comparison. Neocortical sections containing widespread senile plaques and cerebrovascular amyloid angiopathy, produced a sparse and weak labelling following incubation with 3H‐FDDNP. Furthermore, in sections containing NFTs, there was no overt labelling of the pathology by 3H‐FDDNP. In contrast, sections labelled with 3H‐PIB displayed extensive labelling of diffuse plaques, classical plaques, cerebrovascular amyloid angiopathy and NFTs. 14C‐SB13 produced a broadly similar binding pattern to PIB. Radioligand binding assays employing in vitro generated amyloid‐β peptide fibrils demonstrated a ∼10‐fold reduced affinity for 3H‐FDDNP (85.0 ± 2.0 nM) compared with 3H‐PIB (8.5 ± 1.3 nM). These data provide an alternative mechanistic explanation for the observed low cortical uptake of 18F‐FDDNP in AD; in that the ligand is only weakly retained by the hallmark neuropathology because of its low affinity for amyloid structures.
A 38-Amino-Acid Sequence Encompassing the Arm Domain of the Cucumber Necrosis Virus Coat Protein Functions as a Chloroplast Transit Peptide in Infected Plants

ABSTRACT Experiments to determine the subcellular location of the coat protein (CP) of the tombusvirus Cucumber necrosis virus (CNV) have been conducted. By confocal microscopy, it was found that an agroinfiltrated CNV CP-green fluorescent protein (GFP) fusion targets chloroplasts in Nicotiana benthamiana leaves and that a 38-amino-acid (aa) region that includes the complete CP arm region plus the first 4 amino acids of the shell domain are sufficient for targeting. Western blot analyses of purified and fractionated chloroplasts showed that the 38-aa region directs import to the chloroplast stroma, suggesting that the CNV arm can function as a chloroplast transit peptide (TP) in plants. Several features of the 38-aa region are similar to features typical of chloroplast TPs, including (i) the presence of an alanine-rich uncharged region near the N terminus, followed by a short region rich in basic amino acids; (ii) a conserved chloroplast TP phosphorylation motif; (iii) the requirement that the CNV 38-aa sequence be present at the amino terminus of the imported protein; and (iv) specific proteolytic cleavage upon import into the chloroplast stroma. In addition, a region just downstream of the 38-aa sequence contains a 14-3-3 binding motif, suggesting that chloroplast targeting requires 14-3-3 binding, as has been suggested for cellular proteins that are targeted to chloroplasts. Chloroplasts of CNV-infected plants were found to contain CNV CP, but only the shell and protruding domain regions were present, indicating that CNV CP enters chloroplasts during infection and that proteolytic cleavage occurs as predicted from agroinfiltration studies. We also found that particles of a CNV CP mutant deficient in externalization of the arm region have a reduced ability to establish infection. The potential biological significance of these findings is discussed.