Miracle-dz/UniFAR-FTUs huggingface dataset:
In silico and in vitro studies of transition metal complexes derived from curcumin–isoniazid Schiff base

Abstract A series of transition metal complexes have been synthesized from biologically active curcumin and isoniazid Schiff base. They are characterized by various spectral techniques like UV–Vis, Fourier transform infrared (FT-IR), nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR) and mass spectroscopies. Moreover, elemental analysis, magnetic susceptibility and molar conductivity measurements are also carried out. All these data evidence that the metal complexes acquire square planar except zinc(II) which adopts a tetrahedral geometry, and they are non-electrolytic in nature. Groove mode of binding between the calf thymus DNA (CT DNA) and metal complexes is confirmed by electronic absorption titration, viscosity and cyclic voltammetry studies. In addition to that, all the metal complexes are able to cleave pUC 19 DNA. Optimized geometry and ground-state electronic structure calculations of all the synthesized compounds are established out by density functional theory (DFT) using B3LYP method which theoretically reveals that copper(II) complex explores higher stability and higher biological accessibility. This is experimentally corroborated by antimicrobial studies. In silico Absorption, Distribution, Metabolism, Excretion (ADME) studies reveal the biological potential of all synthesized complexes, and also biological activity of the ligand is predicted by PASS online biological activity prediction software. Molecular docking studies are also carried out to confirm the groove mode of binding and receptor–complex interactions. Graphical Abstract Communicated by Ramaswamy H. Sarma
Isolation of compound microsatellite markers in Begonia fenicis (Begoniaceae) endemic to East and Southeast Asian islands.

PREMISE OF THE STUDY We developed compound microsatellite markers for Begonia fenicis, a species endemic to eastern and southeastern Asian islands, to investigate geographical genetic structure. METHODS AND RESULTS Using the compound microsatellite marker technique, 21 markers were developed and six polymorphic markers were characterized for samples from four islands in Taiwan and southern Japan. The number of alleles per locus ranged from two to six (mean = 4.33). Observed and expected heterozygosities were 0.125-0.725 (0.383) and 0.498-0.719 (0.641), and polymorphic information content was 0.371-0.664 (0.567). The interspecific transferability of the 21 markers was evaluated for eight species of the section Diploclinium from the Philippines; 15 markers were successfully amplified in one to eight species. CONCLUSIONS These results indicate the utility of the six microsatellite markers in B. fenicis to investigate geographical genetic structure. The transferable markers are potentially useful for other species of the section.
Efficient and extensible algorithms for multi query optimization

Complex queries are becoming commonplace, with the growing use of decision support systems. These complex queries often have a lot of common sub-expressions, either within a single query, or across multiple such queries run as a batch. Multiquery optimization aims at exploiting common sub-expressions to reduce evaluation cost. Multi-query optimization has hither-to been viewed as impractical, since earlier algorithms were exhaustive, and explore a doubly exponential search space. In this paper we demonstrate that multi-query optimization using heuristics is practical, and provides significant benefits. We propose three cost-based heuristic algorithms: Volcano-SH and Volcano-RU, which are based on simple modifications to the Volcano search strategy, and a greedy heuristic. Our greedy heuristic incorporates novel optimizations that improve efficiency greatly. Our algorithms are designed to be easily added to existing optimizers. We present a performance study comparing the algorithms, using workloads consisting of queries from the TPC-D benchmark. The study shows that our algorithms provide significant benefits over traditional optimization, at a very acceptable overhead in optimization time.
Protein biomarkers in serum and urine for determining presence or absence of hip dysplasia in a canine model

This study compares serum and urine concentrations of relevant protein biomarkers among adult dogs with or without radiographic canine hip dysplasia (CHD). Adult (≥2 years of age), client‐owned dogs (n = 74) radiographically categorized as having at least “good” hips (n = 49) or having “mild,” “moderate,” or “severe” hip dysplasia (n = 25) by the Orthopedic Foundation for Animals (OFA). Urine and serum samples were obtained from each dog at a single time‐point and processed and analyzed for relevant protein biomarkers. Urinary concentrations of CTX‐II (p < 0.001) and TIMP‐1 (p = 0.002) were significantly lower in dogs with CHD compared to dogs with no CHD. ROC curve analyses were successful in establishing a panel of four biomarkers (urinary CTX‐I and II, serum MMP‐9, and serum PIICP) with high discriminatory capability for the presence or absence of hip dysplasia in adult dogs (AUC = 0.89). Urine and serum biomarkers can distinguish adult dogs with radiographic CHD from those with no CHD with a sensitivity of 0.95 and specificity of 0.77 using ROC analysis with AUC 0.89. Clinical Significance: This finding suggests that this simple, minimally invasive diagnostic technique has potential for discriminating dysplastic dogs from dogs with normal hips, with possible translational application to humans based on similar etiopathogenesis. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 9999:1–5, 2019.
Synthesis and Biological Activity of Some Benzochromenoquinolinones: Tacrine Analogs as Potent Anti‐Alzheimer's Agents

Alzheimer's disease (AD) is a well‐known neurodegenerative disorder affecting millions of old people worldwide and the corresponding epidemiological data emphasize the importance of the disease. As AD is a multifactorial illness, various single target directed drugs that have reached clinical trials have failed. Therefore, various factors associated with outset of AD have been considered in targeted drug discovery. In this work, various benzochromenoquinolinones were synthesized and evaluated for their cholinesterase and BACE1 inhibitory activities as well as neuroprotective and metal‐chelating properties. Among the synthesized compounds, 14‐amino‐13‐(3‐nitrophenyl)‐2,3,4,13‐tetrahydro‐1H‐benzo[6,7]chromeno[2,3‐b]quinoline‐7,12‐dione (6m) depicted the best inhibitory activity toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50s of 0.86 and 6.03 μm, respectively. Also, the compound could inhibit β‐secretase 1 (BACE1) with IC50=19.60 μm and showed metal chelating ability toward Cu2+, Fe2+, and Zn2+. In addition, docking study demonstrated desirable interactions of compound 6m with amino acid residues characterizing AChE, BChE, and BACE1.
Goal-Oriented Attention Self-Regulation (GOALS) training in older adults

Abstract Abstract Objectives: A common cognitive complaint of older adulthood is distractibility, or decline in ability to concentrate and maintain focus, yet few evidence-based interventions exist to address these deficits. We implemented s pilot trial of an evidence-based executive function training program, to investigate whether training in applied goal-directed attention regulation and problem solving would enhance executive control abilities in a sample of cognitively normal older adults with self-reported complaints of concentration problems. Method: Consecutively recruited participants were placed into small groups and randomized to either Goal-Oriented Attentional Self-Regulation training (GOALS; N = 15) or a closely matched Brain Health Education program (BHE; N = 15). Results: GOALS participants significantly improved on: neurocognitive measures of mental flexibility (p = 0.03, partial eta squared = 0.23); real-world setting functional performance measures of: task failures (p = 0.02, Cohen’s d = 0.88), task rule breaks (p = 0.02, Cohen’s d = 1.06), and execution (p = 0.04, Cohen’s d = 0.76); and in-lab functional assessment of goal-directed behaviour divergent thinking scale (p = 0.03, Cohen’s d = 0.95). All participants improved on a neurocognitive measure of planning (p = 0.01, partial eta squared = 0.031). BHE participants’ improvement over and above GOALS participants was limited to: rule adherence on the real world task (p = 0.04, Cohen’s d = 0.99), and evaluator rating (p = 0.03, Cohen’s d = 0.56), and average score (p = 0.02, Cohen’s d = 0.71) on the in-lab functional task. Conclusion: Participation in GOALS training can enhance executive control, and lead to real-world functional improvements, for cognitively normal older adults with self-reported attention difficulties.
Association Between Fatty Acids of Blood Cell Membranes and Incidence of Coronary Heart Disease: A Case-Control Study Nested in the PREDIMED Trial

Objective— To examine the associations between baseline levels of fatty acids in blood cell membranes and their 1-year changes with the incidence of coronary heart disease (CHD) in older adults at high cardiovascular disease risk. Approach and Results— This is a case-control study nested in the PREDIMED trial (Prevención con Dieta Mediterránea), with 136 CHD cases and 272 controls (matched on age, sex, body mass index, intervention group, and time of permanence in the study to the time event). We used gas chromatography to measure the proportion of 22 fatty acids in blood cell membranes at baseline and after 1 year. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% CIs. After adjustment for classical CHD risk factors and multiple testing, 1 SD increase in baseline levels of C22:0, C24:0 and the sum of individual very long chain saturated fatty acids was associated with 56% (OR, 0.44 [95% CI, 0.28–0.69]), 59% (OR, 0.41 [95% CI, 0.25–0.65]), and 55% (OR, 0.45 [95% CI, 0.29–0.70]) a decreased odds of developing CHD, respectively. Baseline C20:1n9 was associated with higher odds of CHD (OR, 1.58 [95% CI, 1.25–2.00]). Conclusions— Higher levels of C22:0 and C24:0 were associated with a lower CHD incidence, whereas higher levels of C20:1n9 were associated with a higher risk. This study adds to the growing body of evidence suggesting potential differences in the cardiovascular disease effects of different types of circulating saturated fatty acids.
Functional outcome in subretinal electronic implants depends on foveal eccentricity.

PURPOSE An active microelectronic subretinal implant, developed to replace the photoreceptive function in hereditary degenerations of the outer retina, has been applied in a pilot and clinical study in patients with end-stage retinal degeneration. METHODS The study population comprised 20 blind patients, all of whom lost vision as result of a hereditary retinal disease. An active visual implant was placed surgically within the subretinal space of each patient: subfoveal placement in eight patients (group 1) and parafoveal placement in 12 (group 2). Standardized low-vision tests, including light perception, light localization, movement detection, grating acuity, and visual acuity by Landolt C-rings, were used under masked, randomized implant-OFF and implant-ON conditions. For the chip-mediated vision functional results of both subject groups were compared. RESULTS Three of 20 patients were excluded from analysis because of surgical or technical implant issues. Among patients with nonfoveal placement of the implant, 80% could perceive light, 10% recognized location, and 10% correctly distinguished stripe patterns up to a resolution of 0.33 cycles/degree. No nonfoveal placement patient passed the motion or Landolt C-ring tests. When the implant was placed subfoveally, 100% of patients could perceive light and determine light localization, 75% could resolve motion up to 35°/s, 88% correctly distinguished stripe patterns up to a resolution of 3.3 cycles/degree, and 38% passed a Landolt C-ring test with a decimal visual acuity of up to 20/546 (logMAR 1.43). CONCLUSIONS Subfoveal placement of active subretinal visual implants allows superior measurable outcomes compared to para- or nonfoveal placement locations. (ClinicalTrials.gov numbers, NCT01024803, NCT00515814.).
Selection and characterization of novel DNA aptamer against colorectal carcinoma Caco‐2 cells

Aptamers are short, single‐stranded nucleic acid (DNA or RNA) oligonucleotides that can be obtained by a technique called systematic evolution of ligands by exponential enrichment (SELEX) in vitro. Due to superior properties such as small size, high binding affinity, and stability, they are considered to be feasible tools for diagnosis and treatment of disease. In the current study, we attempted to screen a high‐affinity DNA aptamer to selectively target the colorectal carcinoma Caco‐2 cells by using cell‐based SELEX approach. After 14 consecutive rounds of selection, aptamer ApC1 was identified. Confocal microscopy results revealed that ApC1 could rapidly internalize into Caco‐2 cells but not HEK 293 cells. Moreover, it showed high specificity to Caco‐2 cells rather than other cell lines such as 293T, HeLa, MCF‐7, HL‐60, and NB4. Collectively, our results demonstrated that aptamer ApC1 has high specificity to colorectal carcinoma Caco‐2 cells, which could be further applied for targeted therapy of colorectal cancer in future studies.
TRA2A Promoted Paclitaxel Resistance and Tumor Progression in Triple-Negative Breast Cancers via Regulating Alternative Splicing

Treatment of triple-negative breast cancer (TNBC) has been challenging, and paclitaxel resistance is one of the major obstacles to the better prognosis. Deregulation of alternative splicing (AS) may contribute to tumor progression and chemotherapy resistance. Human AS factor TRA2 has two separate gene paralogs encoding TRA2A and TRA2B proteins. TRA2B is associated with cancer cell survival and therapeutic sensitivity. However, the individual role of TRA2A in cancer progression has not been reported. Here we report that TRA2A facilitates proliferation and survival and migration and invasion of TNBC cells. In addition, TRA2A promotes paclitaxel resistance of TNBC by specifically controlling cancer-related splicing, which is independent of other splicing factors. TRA2A overexpression could promote AS of CALU, RSRC2, and PALM during paclitaxel treatment of TNBC cells. The isoform shift of RSRC2 from RSRC2s to RSRC2l leads to a decreased RSRC2 protein expression, which could contribute to TNBC paclitaxel resistance. TRA2A can regulate RSRC2 AS by specifically binding upstream intronic sequence of exon4. Strikingly, TRA2A expression is increased dramatically in patients with TNBC, and has a close relationship with decreased RSRC2 expression; both are associated with poor survival of TNBC. Collectively, our findings suggest that paclitaxel targets the TRA2A–RSRC2 splicing pathway, and deregulated TRA2A and RSRC2 expression may confer paclitaxel resistance. In addition to providing a novel molecular mechanism of cancer-related splicing dysregulation, our study demonstrates that expression of TRA2A in conjunction with RSRC2 may provide valuable molecular biomarker evidence for TNBC clinical treatment decisions and patient outcome. Mol Cancer Ther; 16(7); 1377–88. ©2017 AACR.
Apolipoprotein E and gray matter volume loss in patients with mild cognitive impairment and Alzheimer disease.

PURPOSE To examine the influence of apoliprotein E ε4 allele (APOE4) carrier status on disease progression by evaluating the rate of regional gray matter (GM) volume loss and disease severity in patients with newly diagnosed Alzheimer disease (AD) and stable amnestic mild cognitive impairment (MCI). MATERIALS AND METHODS This study was approved by the institutional review board and was HIPAA compliant. All subjects or their legal representatives gave informed consent for participation. Ninety-five subjects (63 male; average age, 77.1 years; age range, 58-91 years; 51 APOE4 carriers; 44 noncarriers) with either documented MCI to AD conversion or stable amnestic MCI underwent three yearly magnetic resonance imaging examinations. Voxel-based morphometry for image postprocessing and Clinical Dementia Rating (CDR) scale for cognitive assessment were used. RESULTS In APOE4 carriers, GM volume loss affected the hippocampi, temporal and parietal lobes, right caudate nucleus, and insulae in patients with MCI to AD conversion and the insular and temporal lobes in patients in whom MCI was stable. In subjects who were not APOE4 carriers, there was no significant GM volume change. There were no differences in CDR scores between APOE4 carriers and noncarriers. CONCLUSION APOE4 carriers with cognitive decline undergo faster GM atrophy than do noncarriers. The involvement of APOE4 in the progression of hippocampal atrophy, neocortical atrophy, or both has potential important implications for diagnosis and therapeutic approaches in patients with AD and should be considered in clinical trials. The present results and the results of prior studies indicate that the rate of hippocampal and neocortical atrophy is greater in association with APOE4 in nondemented elderly subjects, subjects with MCI, and those with AD.
A novel isoform of myosin 18A (Myo18Aγ) is an essential sarcomeric protein in mouse heart

Whereas myosin 18B (Myo18B) is known to be a critical sarcomeric protein, the function of myosin 18A (Myo18A) is unclear, although it has been implicated in cell motility and Golgi shape. Here, we show that homozygous deletion (homozygous tm1a, tm1b, or tm1d alleles) of Myo18a in mouse is embryonic lethal. Reminiscent of Myo18b, Myo18a was highly expressed in the embryo heart, and cardiac-restricted Myo18a deletion in mice was embryonic lethal. Surprisingly, using Western blot analysis, we were unable to detect the known isoforms of Myo18A, Myo18Aα and Myo18Aβ, in mouse heart using a custom C-terminal antibody. However, alternative anti-Myo18A antibodies detected a larger than expected protein, and RNA-Seq analysis indicated that a novel Myo18A transcript is expressed in mouse ventricular myocytes (and human heart). Cloning and sequencing revealed that this cardiac isoform, denoted Myo18Aγ, lacks the PDZ-containing N terminus of Myo18Aα but includes an alternative N-terminal extension and a long serine-rich C terminus. EGFP-tagged Myo18Aγ expressed in ventricular myocytes localized to the level of A-bands in sarcomeres, and Myo18a knockout embryos at day 10.5 exhibited disorganized sarcomeres with wavy thick filaments. We additionally generated myeloid-restricted Myo18a knockout mice to investigate the role of Myo18A in nonmuscle cells, exemplified by macrophages, which express more Myo18Aβ than Myo18Aα, but no defects in cell shape, motility, or Golgi shape were detected. In summary, we have identified a previously unrecognized sarcomere component, a large novel isoform (denoted Myo18Aγ) of Myo18A. Thus, both members of class XVIII myosins are critical components of cardiac sarcomeres.
Paraquat Exposure Increases Oxidative Stress Within the Dorsal Striatum of Male Mice With a Genetic Deficiency in One-carbon Metabolism.

Paraquat is an herbicide that is commonly used worldwide. Exposure to paraquat results in Parkinson's disease (PD)-like symptoms including dopaminergic cell loss. Nutrition has also been linked in the pathogenesis of PD, such as reduced levels of folic acid, a B-vitamin, and component of one-carbon metabolism. Within one-carbon metabolism, methylenetetrahydrofolate reductase (MTHFR) catalyzes the irreversible conversion of 5, 10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. A polymorphism in MTHFR (677 C&→T) has been reported in 5%-15% of North American and European human populations. The MTHFR polymorphism is also prevalent in PD patients. The goal of this study was to investigate the impact of paraquat-induced PD-like pathology in the context of reduced levels of MTHFR. Three-month-old male Mthfr+/- mice, which model the MTHFR polymorphism observed in humans, were administered intraperitoneal injections of paraquat (10 mg/kg) or saline 6 times over 3 weeks. At the end of paraquat treatment, motor and memory function were assessed followed by collection of brain tissue for biochemical analysis. Mthfr+/- mice treated with paraquat showed impaired motor function. There was increased microglial activation within the substantia nigra (SN) of Mthfr+/- mice treated with paraquat. Additionally, all Mthfr+/- mice that were treated with paraquat showed increased oxidative stress within the dorsal striatum, but not the SN. The present results show that paraquat exposure increases PD-like pathology in mice deficient in one-carbon metabolism.
Development, validation of QuEChERS-based method for simultaneous determination of multiclass pesticide residue in milk, and evaluation of the matrix effect

Abstract Extraction and quantification of pesticide residue from the milk matrix at or below the established maximum residue limit (MRL) is a challenging task for both analytical chemists and the regulatory institutions to take corrective actions for the human health and safety. The main aim of the study is to develop a simple rapid and less expensive QuEChERS extraction and cleanup method for simultaneous analysis of 41 multiclass pesticide residue in milk by gas chromatography-electron capture detector (GC-ECD), followed by confirmation of the residues with gas chromatography-mass spectrometer (GC-MS). Effect of sorbent type, temperature, spiking concentration, matrix effect (ME), measurement uncertainty (MU), inter- and intra-assay repeatability, reproducibility of recovery, and trueness of the results were investigated to validate the effectiveness of the method. Limit of determination (LOD) and limit of quantitation (LOQ) for all the analytes ranged within 0.001–0.02 and 0.002–0.05 µg mL−1, respectively. The % recovery of all the pesticides ranged between 91.38 and 117.56% with relative standard deviation (RSD) below 2.79%. The MU for all the analytes was ≤29% of respective LOQs, and except for few pesticides, the ME was largely negative. The method fulfilled all the SANTE guidelines and thus can be extended for routine analysis of multiclass pesticide residue in milk.
Enhanced oxidative stability of meat by including tannin-rich leaves of woody plants in goat diet

Objective The aim of this study was to evaluate the effect of dietary incorporation of tannin-rich woody species on meat oxidative stability, carcass traits and meat quality in goats. Methods Two tannin-rich species were tested using a three-treatments feeding trial, where treatments consisted of: Larrea divaricata and Acacia aroma both at 12.5% in dry matter basis of the diet and a control diet (alfalfa hay). All feeding diets were iso-protein and iso-energy. Carcass conformation, carcass compactness, carcass fatness and subcutaneous fat deposition were evaluated. Intake, liveweigh, Longissimus thoracis et lumborum muscles of goats were analyzed in order to evaluate quality parameters such as pH value, instrumental color evaluation, water holding capacity, total phenolic content, antioxidant activity, meat oxidative stability and fatty acid profiles in meat. Results Feed intake, liveweight gain, carcass, and meat traits did not differ among treatments. Changes in meat lipid profile among treatments were observed for oleic and elaidic acid contents. Meat total phenolic content and antioxidant activity did not differ among treatments; although, meat oxidative status after storage at room temperature, as well as under refrigerated and frozen conditions were different between control and both supplemented groups. Conclusion The inclusion of Acacia aroma and Larrea divaricata leaves in goat diet enhanced meat oxidative stability. Modulation of the ruminal biohydrogenation of fatty acids produced by condensed tannins of these plant species need to be further investigated.