Miracle-dz/UniFAR-FTUs huggingface dataset:
Common Transcriptional Mechanisms for Visual Photoreceptor Cell Differentiation among Pancrustaceans

A hallmark of visual rhabdomeric photoreceptors is the expression of a rhabdomeric opsin and uniquely associated phototransduction molecules, which are incorporated into a specialized expanded apical membrane, the rhabdomere. Given the extensive utilization of rhabdomeric photoreceptors in the eyes of protostomes, here we address whether a common transcriptional mechanism exists for the differentiation of rhabdomeric photoreceptors. In Drosophila, the transcription factors Pph13 and Orthodenticle (Otd) direct both aspects of differentiation: rhabdomeric opsin transcription and rhabdomere morphogenesis. We demonstrate that the orthologs of both proteins are expressed in the visual systems of the distantly related arthropod species Tribolium castaneum and Daphnia magna and that their functional roles are similar in these species. In particular, we establish that the Pph13 homologs have the ability to bind a subset of Rhodopsin core sequence I sites and that these sites are present in key phototransduction genes of both Tribolium and Daphnia. Furthermore, Pph13 and Otd orthologs are capable of executing deeply conserved functions of photoreceptor differentiation as evidenced by the ability to rescue their respective Drosophila mutant phenotypes. Pph13 homologs are equivalent in their ability to direct both rhabdomere morphogenesis and opsin expression within Drosophila, whereas Otd paralogs demonstrate differential abilities to regulate photoreceptor differentiation. Finally, loss-of-function analyses in Tribolium confirm the conserved requirement of Pph13 and Otd in regulating both rhabdomeric opsin transcription and rhabdomere morphogenesis. Taken together, our data identify components of a regulatory framework for rhabdomeric photoreceptor differentiation in Pancrustaceans, providing a foundation for defining ancestral regulatory modules of rhabdomeric photoreceptor differentiation.
Genetic Factors in Type 2 Diabetes — In Search of New Links Differential Levels of Diabetogenic Stress in Two New Mouse Models of Obesity and Type 2 Diabetes

The genetic basis for the more common forms of human obesity predisposing to insulin resistance and development of type 2 diabetes is multigenic rather than monogenic in origin. New mouse “diabesity” models have been created by combining independent diabetes risk– conferring quantitative trait loci from two unrelated parental strains: New Zealand Obese (NZO/HlLt) and Nonobese Nondiabetic (NON/Lt). F1 hybrid males, heterozygous at all polymorphic autosomal loci distinguishing the two parental strains, are driven to obesityinduced diabetes (diabesity) at high frequencies. This review focuses on two new recombinant congenic strains (RCSs) developed by introgressing multiple NZO/HlLt chromosomal segments into the nominally diabesity-resistant NON/Lt strain background. Both RCSs gain more weight than NON animals. Although exhibiting comparable weight gain and adiposity, only one of the two RCSs develops diabetes. Hence, these two RCSs will be instructive in elucidating genetic and pathophysiological differences underlying uncomplicated obesity syndromes versus diabetogenic obesity (diabesity) syndromes. Unlike mice with null mutations in a single gene producing morbid obesity, the new models develop a more moderate obesity produced by the interaction of numerous genes with relatively small effects. These RCSs are differentially sensitive to adverse side effects of thiazolidinediones and thus should be particularly useful for pharmacogenetic analyses. Diabetes 53 (Suppl. 1):S4–S11, 2004
An Impulsive Delay Inequality Involving Unbounded Time-Varying Delay and Applications

In this paper, a new impulsive delay inequality that involves unbounded and nondifferentiable time-varying delay is presented. As an application, some sufficient conditions ensuring stability and stabilization of impulsive systems with unbounded time-varying delay are derived. Some numerical examples are given to illustrate the results. Especially, a stabilizing memoryless controller for a second-order time-varying system with unbounded time-varying delay is proposed.
Vaccination with a Haemophilus influenzae type b conjugate vaccine reduces oropharyngeal carriage of H. influenzae type b among Gambian children.

The effect of a Haemophilus influenzae type b (Hib) polyribosylribitol phosphate-tetanus toxoid conjugate vaccine (Hib/PRP-T) on oropharyngeal carriage of Hib was studied during an efficacy trial in Gambian infants. Children were vaccinated with Hib/PRP-T and diphtheria-tetanus toxoids-pertussis (DTP) or DTP alone at ages 2, 3, and 4 months. Groups of 1000 children aged 1-2 years were studied each year for 4 years. Hib was detected by production of a halo on antiserum agar plates. Carriage was significantly lower among children fully vaccinated with Hib/PRP-T given with DTP (4.4%; 95% confidence interval [CI], 3.8%-5.7%) than among children fully vaccinated with DTP alone (11.0%; 95% CI, 8.9%-13.0%) (protective effect adjusted by year = 60%; 95% CI, 44%-72%; P < .001). Hib carriage varied by year among nonvaccinated children. Hib conjugate vaccines are likely to produce a herd protective effect in underdeveloped communities, as recorded in Europe and the United States.
New simulation method of ecosystem evolution based on Neural Network

In this paper, the maximum flux principle (MFP) is proposed to describe complex interactions among agents in ecosystem which usually tend to generate intricate patterns under specific environmental constraints. Accordingly, we introduce a new simulation method based on Neural Network to reveal the dynamic mechanisms of ecosystem evolution. The new simulation method may provide important implications for ecological restoration and sustainable development.
Anti-Neuroinflammatory Effects of the Calcium Channel Blocker Nicardipine on Microglial Cells: Implications for Neuroprotection

Background/Objective Nicardipine is a calcium channel blocker that has been widely used to control blood pressure in severe hypertension following events such as ischemic stroke, traumatic brain injury, and intracerebral hemorrhage. However, accumulating evidence suggests that inflammatory processes in the central nervous system that are mediated by microglial activation play important roles in neurodegeneration, and the effect of nicardipine on microglial activation remains unresolved. Methodology/Principal Findings In the present study, using murine BV-2 microglia, we demonstrated that nicardipine significantly inhibits microglia-related neuroinflammatory responses. Treatment with nicardipine inhibited microglial cell migration. Nicardipine also significantly inhibited LPS plus IFN-γ-induced release of nitric oxide (NO), and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, nicardipine also inhibited microglial activation by peptidoglycan, the major component of the Gram-positive bacterium cell wall. Notably, nicardipine also showed significant anti-neuroinflammatory effects on microglial activation in mice in vivo. Conclusion/Significance The present study is the first to report a novel inhibitory role of nicardipine on neuroinflammation and provides a new candidate agent for the development of therapies for inflammation-related neurodegenerative diseases.
The Effect of Short-Term Auditory Training on Speech in Noise Perception and Cortical Auditory Evoked Potentials in Adults with Cochlear Implants

Abstract This study investigated whether a short intensive psychophysical auditory training program is associated with speech perception benefits and changes in cortical auditory evoked potentials (CAEPs) in adult cochlear implant (CI) users. Ten adult implant recipients trained approximately 7 hours on psychophysical tasks (Gap-in-Noise Detection, Frequency Discrimination, Spectral Rippled Noise [SRN], Iterated Rippled Noise, Temporal Modulation). Speech performance was assessed before and after training using Lexical Neighborhood Test (LNT) words in quiet and in eight-speaker babble. CAEPs evoked by a natural speech stimulus /baba/ with varying syllable stress were assessed pre- and post-training, in quiet and in noise. SRN psychophysical thresholds showed a significant improvement (78% on average) over the training period, but performance on other psychophysical tasks did not change. LNT scores in noise improved significantly post-training by 11% on average compared with three pretraining baseline measures. N1P2 amplitude changed post-training for /baba/ in quiet (p = 0.005, visit 3 pretraining versus visit 4 post-training). CAEP changes did not correlate with behavioral measures. CI recipients' clinical records indicated a plateau in speech perception performance prior to participation in the study. A short period of intensive psychophysical training produced small but significant gains in speech perception in noise and spectral discrimination ability. There remain questions about the most appropriate type of training and the duration or dosage of training that provides the most robust outcomes for adults with CIs.
Implications of Advancing Paternal Age: Does It Affect Offspring School Performance?

Average paternal age is increasing in many high income countries, but the implications of this demographic shift for child health and welfare are poorly understood. There is equivocal evidence that children of older fathers are at increased risk of neurodevelopmental disorders and reduced IQ. We therefore report here on the relationship between paternal age and a composite indicator of scholastic achievement during adolescence, i.e. compulsory school leaving grades, among recent birth cohorts in Stockholm County where delayed paternity is notably common. We performed a record-linkage study comprising all individuals in Stockholm County who finished 9 years of compulsory school from 2000 through 2007 (n = 155,875). Data on school leaving grades and parental characteristics were retrieved from administrative and health service registers and analyzed using multiple linear regression. Advancing paternal age at birth was not associated with a decrease in school leaving grades in adolescent offspring. After adjustment for year of graduation, maternal age and parental education, country of birth and parental mental health service use, offspring of fathers aged 50 years or older had on average 0.3 (95% CI −3.8, 4.4) points higher grades than those of fathers aged 30–34 years. In conclusion, advancing paternal age is not associated with poorer school performance in adolescence. Adverse effects of delayed paternity on offspring cognitive function, if any, may be counterbalanced by other potential advantages for children born to older fathers.
Effect of Disinfectants on Preventing the Cross-Contamination of Pathogens in Fresh Produce Washing Water

The potential cross-contamination of pathogens between clean and contaminated produce in the washing tank is highly dependent on the water quality. Process wash water disinfectants are applied to maintain the water quality during processing. The review examines the efficacy of process wash water disinfectants during produce processing with the aim to prevent cross-contamination of pathogens. Process wash water disinfection requires short contact times so microorganisms are rapidly inactivated. Free chlorine, chlorine dioxide, ozone, and peracetic acid were considered suitable disinfectants. A disinfectant’s reactivity with the organic matter will determine the disinfectant residual, which is of paramount importance for microbial inactivation and should be monitored in situ. Furthermore, the chemical and worker safety, and the legislative framework will determine the suitability of a disinfection technique. Current research often focuses on produce decontamination and to a lesser extent on preventing cross-contamination. Further research on a sanitizer’s efficacy in the washing water is recommended at the laboratory scale, in particular with experimental designs reflecting industrial conditions. Validation on the industrial scale is warranted to better understand the overall effects of a sanitizer.
Quercetin reduces oxidative stress and inhibits activation of c-Jun N-terminal kinase/activator protein-1 signaling in an experimental mouse model of abdominal aortic aneurysm

Oxidative stress is becoming increasingly linked to the pathogenesis of abdominal aortic aneurysms (AAAs). The antioxidant activity of flavonoids has attracted attention for their possible role in the prevention of cardiovascular diseases. The purpose of this study was to determine whether an antioxidant mechanism is involved in the aneurysm formation inhibitory effect afforded by quercetin. Male C57/BL6 mice received quercetin continuously from 2 weeks prior to and 6 weeks following the AAA induction with extraluminal CaCl2. Quercetin treatment decreased AAA incidence and inhibited the reactive oxygen species generation, nitrotyrosine formation and lipid peroxidation production in the aortic tissue during AAA development. In addition, quercetin-treated mice exhibited significantly lower expression of the p47phox subunit of nicotinamide adenine dinucleotide phosphate oxidase and inducible nitric oxide synthase, as well as coordinated downregulation of manganese-superoxide dismutase activities and glutathione peroxidase (GPx)-1 and GPx-3 expression. Quercetin also blunted the expression of c-Jun N-terminal kinase (JNK) and phospho-JNK and, in addition, diminished activation of the activator protein (AP)-1 transcription factor. Gelatin zymography showed that quercetin eliminated matrix metalloproteinase (MMP)-2 and MMP-9 activation during AAA formation. In conclusion, the inhibitory effects of quercetin on oxidative stress and MMP activation, through modulation of JNK/AP-1 signaling, may partly account for its benefit in CaCl2-induced AAA.
Effect of a Single Gemfibrozil Dose on the Pharmacokinetics of Rosuvastatin in Bile and Plasma in Healthy Volunteers

The effect of a single intrajejunal dose of gemfibrozil (600 mg) on the plasma pharmacokinetics and biliary excretion of a single intrajejunal dose of rosuvastatin (20 mg) was investigated by using a multichannel catheter positioned in the distal duodenum‐proximal jejunum in 8 healthy volunteers. Bile and plasma samples were collected every 20 minutes for 200 minutes, with additional plasma samples being drawn for up to 48 hours. Gemfibrozil did not affect the bioavailability of rosuvastatin, although it increased the apparent absorption phase during the initial 200 minutes (AUCplasma, 200min) by 1.56‐fold (95% confidence interval, 1.14–2.15). The interaction was less pronounced in this single‐dose study than in a previous report when gemfibrozil was administered repeatedly; nevertheless, the interaction coincided with the highest exposure to gemfibrozil. The plausible reason why the interaction in this investigation was only minor is the low exposure to gemfibrozil (and its metabolites), suggesting that the total plasma concentration of gemfibrozil needs to be above 20 μM to affect the disposition of rosuvastatin. This study demonstrates the value of monitoring the plasma pharmacokinetics of the inhibitor, and not only the drug under investigation, to improve the mechanistic interpretation.
Circulating Tumor Cells versus Imaging—Predicting Overall Survival in Metastatic Breast Cancer

Purpose: The presence of ≥5 circulating tumor cells (CTC) in 7.5 mL blood from patients with measurable metastatic breast cancer before and/or after initiation of therapy is associated with shorter progression-free and overall survival. In this report, we compared the use of CTCs to radiology for prediction of overall survival. Experimental Design: One hundred thirty-eight metastatic breast cancer patients had imaging studies done before and a median of 10 weeks after the initiation of therapy. All scans were centrally reviewed by two independent radiologists using WHO criteria to determine radiologic response. CTC counts were determined ∼4 weeks after initiation of therapy. Specimens were analyzed at one of seven laboratories and reviewed by a central laboratory. Results: Interreader variability for radiologic responses and CTC counts were 15.2% and 0.7%, respectively. The median overall survival of 13 (9%) patients with radiologic nonprogression and ≥5 CTCs was significantly shorter than that of the 83 (60%) patients with radiologic nonprogression and <5 CTCs (15.3 versus 26.9 months; P = 0.0389). The median overall survival of the 20 (14%) patients with radiologic progression and <5 CTCs was significantly longer than the 22 (16%) patients with ≥5 CTCs that showed progression by radiology (19.9 versus 6.4 months; P = 0.0039). Conclusions: Assessment of CTCs is an earlier, more reproducible indication of disease status than current imaging methods. CTCs may be a superior surrogate end point, as they are highly reproducible and correlate better with overall survival than do changes determined by traditional radiology.
Antimicrobial resistance to ceftazidime involving loss of penicillin-binding protein 3 in Burkholderia pseudomallei

Known mechanisms of resistance to β-lactam antibiotics include β-lactamase expression, altered drug target, decreased bacterial permeability, and increased drug efflux. Here, we describe a unique mechanism of β-lactam resistance in the biothreat organism Burkholderia pseudomallei (the cause of melioidosis), associated with treatment failure during prolonged ceftazidime therapy of natural infection. Detailed comparisons of the initial ceftazidime-susceptible infecting isolate and subsequent ceftazidime-resistant variants from six patients led us to identify a common, large-scale genomic loss involving a minimum of 49 genes in all six resistant strains. Mutational analysis of wild-type B. pseudomallei demonstrated that ceftazidime resistance was due to deletion of a gene encoding a penicillin-binding protein 3 (BPSS1219) present within the region of genomic loss. The clinical ceftazidime-resistant variants failed to grow using commonly used laboratory culture media, including commercial blood cultures, rendering the variants almost undetectable in the diagnostic laboratory. Melioidosis is notoriously difficult to cure and clinical treatment failure is common in patients treated with ceftazidime, the drug of first choice across most of Southeast Asia where the majority of cases are reported. The mechanism described here represents an explanation for ceftazidime treatment failure, and may be a frequent but undetected resistance event.
Ethnic and Gender Differences in Ambulatory Blood Pressure Trajectories: Results From a 15-Year Longitudinal Study in Youth and Young Adults

Background— Cross-sectional studies demonstrated ethnic and gender differences in ambulatory blood pressure patterns, but little is known about the longitudinal development of these differences. Methods and Results— Twenty-four-hour ambulatory blood pressure was measured up to 12 times (5 times on average) over a 15-year period in 312 African Americans (AAs) and 351 European Americans aged 7 to 30 years. Multivariate individual growth curves across age were created for daytime and nighttime blood pressure jointly. For both daytime and nighttime systolic blood pressure (SBP), AAs and males had higher levels (P<0.001) than European Americans and females. Males also showed a greater increase with age (P<0.001) than females. For nighttime SBP, a faster increase of SBP with age (P<0.01) in AAs was additionally observed. The ethnic difference in nighttime SBP levels and its increase with age were significantly larger than in daytime SBP. For daytime and nighttime diastolic blood pressure, AAs had higher levels than European Americans (P<0.001), and this difference was significantly larger at night. From late adolescence onward, males showed a greater increase in diastolic blood pressure with age than females. Ethnic and gender differences persisted after adjustment for height, body mass index, socioeconomic status, and stress-related coping styles. Family history of essential hypertension explained ethnic differences in daytime SBP. Conclusions— We observed significant ethnic and gender differences in longitudinal trajectories of ambulatory blood pressure in youth and young adults. The blunted nocturnal decline and its exacerbation with age in AAs corroborate and extend findings of cross-sectional studies.
Effect of central corneal thickness on intraocular pressure with the rebound tonometer and the applanation tonometer in normal dogs.

OBJECTIVE To evaluate the effect of central corneal thickness (CCT) on the measurement of intraocular pressure (IOP) with the rebound (TonoVet(®)) and applanation (TonoPen XL(®)) tonometers in beagle dogs. ANIMAL STUDIED Both eyes of 60 clinically normal dogs were used. PROCEDURES The IOP was measured by the TonoVet(®), followed by the TonoPen XL(®) in half of the dogs, while the other half was measured in the reverse order. All CCT measurements were performed 10 min after the use of the second tonometer. RESULTS The mean IOP value measured by the TonoVet(®) (16.9 ± 3.7 mmHg) was significantly higher than the TonoPen XL(®) (11.6 ± 2.7 mmHg; P < 0.001). The IOP values obtained by both tonometers were correlated in the regression analysis (γ(2) = 0.4393, P < 0.001). Bland-Altman analysis showed that the lower and upper limits of agreement between the two devices were -0.1 and +10.8 mmHg, respectively. The mean CCT was 549.7 ± 51.0 μm. There was a correlation between the IOP values obtained by the two tonometers and CCT readings in the regression analysis (TonoVet(®) : P = 0.002, TonoPen XL(®) : P = 0.035). The regression equation demonstrated that for every 100 μm increase in CCT, there was an elevation of 1 and 2 mmHg in IOP measured by the TonoPen XL(®) and TonoVet(®), respectively. CONCLUSIONS The IOP obtained by the TonoVet(®) and TonoPen XL(®) would be affected by variations in the CCT. Therefore, the CCT should be considered when interpreting IOP values measured by tonometers in dogs.
On Potential Energy Models for EA-based Ab Initio Protein Structure Prediction

Ab initio protein structure prediction involves determination of the three-dimensional (3D) conformation of proteins on the basis of their amino acid sequence, a potential energy (PE) model that captures the physics of the interatomic interactions, and a method to search for and identify the global minimum in the PE (or free energy) surface such as an evolutionary algorithm (EA). Many PE models have been proposed over the past three decades and more. There is currently no understanding of how the behavior of an EA is affected by the PE model used. The study reported here shows that the EA behavior can be profoundly affected: the EA performance obtained when using the ECEPP PE model is significantly worse than that obtained when using the Amber, OPLS, and CVFF PE models, and the optimal EA control parameter values for the ECEPP model also differ significantly from those associated with the other models.