Miracle-dz/UniFAR-FTUs huggingface dataset:
Intraspecific divergence in floral-tube length promotes asymmetric pollen movement and reproductive isolation.

The causative link between phenotypic divergence and reproductive isolation is an important but poorly understood part of ecological speciation. We studied the effects of floral-tube length variation on pollen placement/receipt positions and reproductive isolation. In a population of Lapeirousia anceps (Iridaceae) with bimodal floral-tube lengths, we labelled pollen of short- and long-tubed flowers with different color fluorescent nano-particles (quantum dots). This enabled us to map pollen placement by long- and short-tubed flowers on the only floral visitor, a long-proboscid fly. Furthermore, it allowed us to quantify pollen movement within and between floral-tube lengths. Short- and long-tubed flowers placed pollen on different parts of the pollinator, and long-tubed flowers placed more pollen per visit than short-tubed flowers. This resulted in assortative pollen receipt (most pollen received comes from the same phenotype) and strong but asymmetric reproductive isolation, where short-tubed plants are more reproductively isolated than long-tubed plants. These results suggest that floral-tube length divergence can promote mechanical isolation in plants through divergence in pollen placement sites on pollinators. Consequently, in concert with other reproductive isolation mechanisms, selection for differences in floral-tube length can play an important role in ecological speciation of plants. This article is protected by copyright. All rights reserved.
Design and synthesis of phenylpiperazine derivatives as potent anticancer agents for prostate cancer

Novel thiourea (5a, 5b) and thiazolidinone derivatives (6a, 6b) were synthesized by hybridizing molecules starting from the compound 6‐(4‐phenylpiperazin‐1‐yl)pyridin‐3‐amine (4) which is known to show anticancer activity. The synthesis of the leading compound was carried out by using 1‐(5‐nitropyridin‐2‐yl)‐4‐phenylpiperazine (3) which was obtained by a novel method of the reaction of 2‐chloro‐5‐nitropyridine (1) and N‐phenylpiperazine (2). The structures of the compounds were confirmed using FTIR, 1H NMR, 13C NMR, HRMS spectroscopic methods and elemental analysis. The organic molecules were tested for their anticancer activities against prostate cancer (PC) cell lines: DU 145, PC‐3 and LNCaP. As the compound 5a exerted the highest cytotoxic activity, IC50 concentrations of compound 5a were further investigated in terms of morphology, colony‐forming ability, RNA expression, fragmented DNA and cell cycle distributions of PC cell lines. Overall data revealed that compound 5a treatment induces apoptosis and DNA fragmentation in PC cell lines and inhibits cell cycle progression resulting in the accumulation of cells in either the G1 or the S phases.
A kinetochore-based ATM/ATR-independent DNA damage checkpoint maintains genomic integrity in trypanosomes

Abstract DNA damage-induced cell cycle checkpoints serve as surveillance mechanisms to maintain genomic stability, and are regulated by ATM/ATR-mediated signaling pathways that are conserved from yeast to humans. Trypanosoma brucei, an early divergent microbial eukaryote, lacks key components of the conventional DNA damage-induced G2/M cell cycle checkpoint and the spindle assembly checkpoint, and nothing is known about how T. brucei controls its cell cycle checkpoints. Here we discover a kinetochore-based, DNA damage-induced metaphase checkpoint in T. brucei. MMS-induced DNA damage triggers a metaphase arrest by modulating the abundance of the outer kinetochore protein KKIP5 in an Aurora B kinase- and kinetochore-dependent, but ATM/ATR-independent manner. Overexpression of KKIP5 arrests cells at metaphase through stabilizing the mitotic cyclin CYC6 and the cohesin subunit SCC1, mimicking DNA damage-induced metaphase arrest, whereas depletion of KKIP5 alleviates the DNA damage-induced metaphase arrest and causes chromosome mis-segregation and aneuploidy. These findings suggest that trypanosomes employ a novel DNA damage-induced metaphase checkpoint to maintain genomic integrity.
Prolonged Perioperative Use of Pregabalin and Ketamine to Prevent Persistent Pain after Cardiac Surgery.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC Cardiac surgery is associated with a significant rate of chronic postoperative painFew proven strategies exist to reduce chronic postoperative pain WHAT THIS ARTICLE TELLS US THAT IS NEW: The administration of pregabalin (14 days) with or without ketamine (2 days) postoperatively reduced the prevalence of pain at 3 and 6 monthsSide effects from pregabalin and ketamine administration were generally mild BACKGROUND:: Persistent postsurgical pain is common and affects quality of life. The hypothesis was that use of pregabalin and ketamine would prevent persistent pain after cardiac surgery. METHODS This randomized, double-blind, placebo-controlled trial was undertaken at two cardiac surgery centers in the United Kingdom. Adults without chronic pain and undergoing any elective cardiac surgery patients via sternotomy were randomly assigned to receive either usual care, pregabalin (150 mg preoperatively and twice daily for 14 postoperative days) alone, or pregabalin in combination with a 48-h postoperative infusion of intravenous ketamine at 0.1 mg · kg · h. The primary endpoints were prevalence of clinically significant pain at 3 and 6 months after surgery, defined as a pain score on the numeric rating scale of 4 or higher (out of 10) after a functional assessment of three maximal coughs. The secondary outcomes included acute pain, opioid use, and safety measures, as well as long-term neuropathic pain, analgesic requirement, and quality of life. RESULTS In total, 150 patients were randomized, with 17 withdrawals from treatment and 2 losses to follow-up but with data analyzed for all participants on an intention-to-treat basis. The prevalence of pain was lower at 3 postoperative months for pregabalin alone (6% [3 of 50]) and in combination with ketamine (2% [1 of 50]) compared to the control group (34% [17 of 50]; odds ratio = 0.126 [0.022 to 0.5], P = 0.0008; and 0.041 [0.0009 to 0.28], P < 0.0001, respectively) and at 6 months for pregabalin alone (6% [3 of 50]) and in combination with ketamine 0% (0 of 5) compared to the control group (28% [14 of 50]; odds ratio = 0.167 [0.029 to 0.7], P = 0.006; and 0.000 [0 to 0.24], P < 0.0001). Diplopia was more common in both active arms. CONCLUSIONS Preoperative administration of 150 mg of pregabalin and postoperative continuation twice daily for 14 days significantly lowered the prevalence of persistent pain after cardiac surgery.
Exploration of the Stanford Integrated Psychosocial Assessment for Transplantation With Psychosocial and Medical Outcomes in Kidney and Kidney–Pancreas Transplant Recipients

Introduction: The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) is a psychometric instrument designed to assess patient risk for transplant. We investigated the association between SIPAT scores and demographic data with psychosocial and medical outcomes within a diverse kidney/kidney–pancreas transplant population. Design: The SIPAT was administered to all pretransplant candidates. A retrospective review of transplanted patients who had at least 6 months of follow-up was completed. Results: The sample included 136 patients: male (n = 77 [57%]) with a mean age of 47 years old. Thirty-eight percent were black (n = 51), 55% had less than a high school education (n = 74), and 65% had low socioeconomic status (n = 89). Statistical difference was found among SIPAT scores and substance use and support system instability (P = .035, P = .012). Females (P = .012) and patients with a history of psychopathology (P = .002) developed or had a relapse of psychopathology following transplant. Patients with more than a high school education (P = .025) and who were less than 30 years (P = .026) had higher rejection incidence rates. Risk factors for rehospitalizations included Hispanic race, diabetes, and low socioeconomic status (P = .036, P = .038, P = .014). African American/Black and male patients had higher incidence of infection events (P = .032, P = .049). Mortality and treatment nonadherence were not significantly associated with SIPAT scores or demographic variables. Conclusion: The SIPAT was associated with posttransplant substance use and support system instability, while demographic variables were associated with the development and/or relapse of psychopathology, graft loss, rejection, infection events, and medical rehospitalizations. Revision of the SIPAT to include additional demographic components may lend to improved prediction of transplant outcomes.
Protective effect of Curcuma amada acetone extract against high-fat and high-sugar diet-induced obesity and memory impairment

ABSTRACT Objectives: Curcuma amada Roxb. (Mango ginger) was evaluated for anti-obesity, anti-amnesic and neuroprotection using high-fat and high-sugar diet (HFHS)-induced obesity and cognitive impairment in rats. Methods: Animals were exposed to HFHS diet to evaluate lipid parameters and subjected to Y maze test and Pole climbing test to evaluate the memory. In addition, oxidative stress parameters, acetyl cholinesterase activity (AChE), neurochemicals and histopathology were assessed in the brain. Results: HFHS diet led to increased body weight and lipid parameters (total cholesterol, low-density lipoprotein [LDL], and very low-density lipoprotein [VLDL], triglycerides [TG]) but not high-density lipoprotein (HDL). Elevated serum glutamate oxalate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT), oxidative biomarker, decreased enzymatic and non-enzymatic antioxidants, Acetylcholinesterase (AChE) activity and reduced percentage of spontaneous alternation behaviour (% SAB in Y-maze test) as well as reduced serotonin and dopamine levels and neurodegeneration were observed in HFHS diet-fed rats. Curcuma amada (CAAE1, 100 mg/kg and CAAE2, 300 mg/kg) treatment to HFHS diet-fed rats (21 days after HFHS diet feeding alone) showed dose-dependent activity and ameliorated the HFHS diet-induced alterations in lipid parameters related to obesity, hepatological parameters, memory, oxidative stress, neurochemicals and neurodegeneration. Furthermore, 300 mg/kg of C. amada (CAAE2) augmented the memory by inhibiting acetylcholinesterase (AChE) activity; it also ameliorated the effect of antioxidants such as glutathione, superoxide dismutase (SOD), and total thiol and mitigated the effect of malondialdehyde (MDA). CAAE2 also controlled the level of dopamine and serotonin and reduced the neurodegeneration in the hippocampus CA1 region. Discussion: The results of the present study indicated that treatment with C. amada 300 mg/kg (CAAE2) attenuated the HFHS diet-induced obesity, memory loss, oxidative stress, and neurodegeneration. These study results indicated that the administration of C. amada offers a potential treatment option for obesity and memory loss, and it requires further preclinical and clinical evaluations.
Vascular Adhesion Protein-1 (VAP-1) as Predictor of Radiographic Severity in Symptomatic Knee Osteoarthritis in the New York University Cohort

Background: To investigate the expression of vascular adhesion protein-1 (VAP-1) in joint tissues and serum in symptomatic knee osteoarthritis (SKOA) patients and examine whether VAP-1 levels predict increased risk of disease severity in a cross-sectional study. Methods: Baseline VAP-1 expression and soluble VAP-1 (sVAP-1) levels were assessed in the synovium synovial fluid and in the serum in cohorts of patients with tibiofemoral medial knee OA and healthy subjects. Standardized fixed-flexion poster anterior knee radiographs scored for Kellgren–Lawrence (KL) grade (0–4) and medial joint space width (JSW). KL1/2 vs. KL3/4 scores defined early and advanced radiographic severity, respectively. Biochemical markers assessed in serum or synovial fluids (SF) comprised sVAP-1, interleukin 1 receptor antagonist (IL-1Ra), interleukin 6 (IL-6), soluble receptor for advanced glycation end-products (sRAGE), C-C motif chemokine ligand 2 (CCL2), C-C motif chemokine ligand 4 (CCL4), cluster of differentiation 163 (CD163), high sensitivity C-reactive protein (hsCRP), and matrix metalloproteinases (MMPs)-1,-3,-9. Associations between biomarkers and radiographic severity KL1/2 vs. KL3/4 (logistic regression controlling for covariates) and pain (Spearman correlation) were evaluated. Results: Elevated levels of sVAP-1 observed in OA synovial fluid and VAP-1 expression in synovium based on immunohistochemical, microarray, and real-time quantitative polymerase chain reaction (qRT-PCR) analyses. However, serum sVAP-1 levels in OA patients were lower than in controls and inversely correlated with pain and inflammation markers (hsCRP and soluble RAGE). Soluble VAP-1 levels in serum were also lower in radiographically advanced (KL3/4) compared with early KL1/2 knee SKOA patients. Conclusion: Local (synovial fluid) semicarbazide-sensitive amine oxidase (SSAO)/sVAP-1 levels were elevated in OA and correlated with radiographic severity. However, systemic (serum) sVAP-1 levels were lower in SKOA patients than normal and inversely correlated with pain and inflammation markers. Serum sVAP-1 levels were higher in early (KL1/2) compared with advanced (KL3/4) SKOA patients.
Molecular Basis of Glycosaminoglycan Heparin Binding to the Chemokine CXCL1 Dimer*

Background: Glycosaminoglycan (GAG)-chemokine dimer interactions regulate neutrophil trafficking, but the molecular basis underlying their interactions is not well understood. Results: NMR studies of murine CXCL1 indicate that heparin spans the dimer interface and enhances its structural integrity and stability. Conclusion: Heparin binding modulates multiple structural properties of the chemokine dimer. Significance: This study provides novel structural insights into how chemokine dimers orchestrate neutrophil recruitment. Glycosaminoglycan (GAG)-bound and soluble chemokine gradients in the vasculature and extracellular matrix mediate neutrophil recruitment to the site of microbial infection and sterile injury in the host tissue. However, the molecular principles by which chemokine-GAG interactions orchestrate these gradients are poorly understood. This, in part, can be directly attributed to the complex interrelationship between the chemokine monomer-dimer equilibrium and binding geometry and affinities that are also intimately linked to GAG length. To address some of this missing knowledge, we have characterized the structural basis of heparin binding to the murine CXCL1 dimer. CXCL1 is a neutrophil-activating chemokine and exists as both monomers and dimers (Kd = 36 μm). To avoid interference from monomer-GAG interactions, we designed a trapped dimer (dCXCL1) by introducing a disulfide bridge across the dimer interface. We characterized the binding of GAG heparin octasaccharide to dCXCL1 using solution NMR spectroscopy. Our studies show that octasaccharide binds orthogonally to the interhelical axis and spans the dimer interface and that heparin binding enhances the structural integrity of the C-terminal helical residues and stability of the dimer. We generated a quadruple mutant (H20A/K22A/K62A/K66A) on the basis of the binding data and observed that this mutant failed to bind heparin octasaccharide, validating our structural model. We propose that the stability enhancement of dimers upon GAG binding regulates in vivo neutrophil trafficking by increasing the lifetime of “active” chemokines, and that this structural knowledge could be exploited for designing inhibitors that disrupt chemokine-GAG interactions and neutrophil homing to the target tissue.
The Association between Whole Grain Products Consumption and Successful Aging: A Combined Analysis of MEDIS and ATTICA Epidemiological Studies

The quality of carbohydrates in the diet, including whole grains, matters greatly to health. There is emerging evidence supporting various protective effects from whole grain consumption against certain chronic diseases. However, being free of disease is not a requirement for healthy ageing, as many older adults have one or more health conditions but, when well controlled, have little influence on their wellbeing. The present study aimed to evaluate the association between whole grain consumption on successful aging, through an analysis of a sample of n = 3349, over-50-years-old men and women participating in the ATTICA and MEDIS population-based cross-sectional studies. Successful aging was evaluated using the validated successful aging index (SAI, range 0–10) comprising of health-related social, lifestyle and clinical components. High whole grain intake was positively associated with SAI as compared with low (b ± SE: 0.278 ± 0.091, p = 0.002), whereas no significant associations were observed between moderate whole grain consumption and SAI (p > 0.05). Increased whole grain intake has been associated with several health benefits, and, as is shown here, with higher successful aging levels. Therefore, consumption of whole grains should be encouraged, especially by replacing refined grains, without increasing total energy intake.
Dual Epigenetic Regulation of ERα36 Expression in Breast Cancer Cells

Breast cancer remains the major cause of cancer-induced morbidity and mortality in women. Among the different molecular subtypes, luminal tumors yet considered of good prognosis often develop acquired resistance to endocrine therapy. Recently, misregulation of ERα36 was reported to play a crucial role in this process. High expression of this ERα isoform was associated to preneoplastic phenotype in mammary epithelial cells, disease progression, and enhanced resistance to therapeutic agents in breast tumors. In this study, we identified two mechanisms that could together contribute to ERα36 expression regulation. We first focused on hsa-miR-136-5p, an ERα36 3’UTR-targeting microRNA, the expression of which inversely correlated to the ERα36 one in breast cancer cells. Transfection of hsa-miR136-5p mimic in MCF-7 cells resulted in downregulation of ERα36. Moreover, the demethylating agent decitabine was able to stimulate hsa-miR-136-5p endogenous expression, thus indirectly decreasing ERα36 expression and counteracting tamoxifen-dependent stimulation. The methylation status of ERα36 promoter also directly modulated its expression level, as demonstrated after decitabine treatment of breast cancer cell and confirmed in a set of tumor samples. Taken together, these results open the way to a direct and an indirect ERα36 epigenetic modulation by decitabine as a promising clinical strategy to counteract acquired resistance to treatment and prevent relapse.
First-inHuman Evaluation of 18 F-Mefway , a PET Radioligand Specific to Serotonin-1 A Receptors

1Department of Medical Physics, University of Wisconsin, Madison, Wisconsin; 2Waisman Center for Brain Imaging and Behavior, University of Wisconsin, Madison, Wisconsin; 3Department of Radiological Sciences, University of California, Irvine, California; 4Department of Radiology, University of Wisconsin, Madison, Wisconsin; 5Department of Medicine, University of Wisconsin, Madison, Wisconsin; 6Department of Geriatrics, University of Wisconsin, Madison, Wisconsin; and 7Department of Psychiatry, University of Wisconsin, Madison, Wisconsin
It is over three decades of graduate education in Epizootiology at the University of Ibadan, Nigeria (1975–2011): is there a need to revise the curriculum?

Epizootiology is the study of variable factors, events, forces and circumstances that contribute to the occurrence, distribution, control and prevention of ill-health, diseases and other problems in animal groups. It is a key component of veterinary medicine education at the University of Ibadan, Nigeria since 1975. It started as a Graduate Certificate in Epizootiology (GCE) in 1976. Later it was revised into M.Sc. Epizootiology in 1986. At graduate level, epizootiology curriculum has supported the M.Sc. Epizootiology programme. It compliments training in Veterinary Public Health and Preventive Medicine. This epizootiology curriculum has been operational at graduate level for more than three decades. Now in 2011, a consortium of English speaking West African Universities is committed to review the current curriculum at the University of Ibadan to strengthen health systems in an interdependent world with scope for internationalized practicum in disease investigation. Emphases are made towards skills development in molecular studies on disease causal agents and the mapping of associated geographic risk factors, including indigenous knowledge and practices. It is notable that most English-speaking West African countries including Ghana, Liberia, Sierra Leone and Gambia either lack a Veterinary School or just started some, but do not have graduate programme in Epizootiology. Thus, the curriculum at Ibadan is positioned to make impact in three key areas, namely, sub-regional ecosystem health studies, improving human-animal disease surveillance programmes, and in indigenization of bio-technology for monitoring and evaluation of trans-boundary animal disease control interventions for global health in West Africa.
Strategic and structural barriers to the development of electronic banking: The case study of Sepah Bank in Isfahan

Technology development along with extensive developments in electronic commerce has not only changed the traditional commerce but also revolutionized communities' lives. Electronic banking is also no exception since it has been influenced by these developments. These developments; however, have been confronted with challenges and barriers in areas such as cultural, economic and social, strategic and structural field, in every society. In this study, strategic and structural barriers as the main factors influencing the development of electronic banking in Iran will be identified and analyzed. The study was a cross-sectional survey and the sample of the study was 70 employees of Sepah Bank branches in Isfahan. The distributed questionnaire had the reliability of 0.94. The result of the questionnaire's analysis indicated that customers' satisfaction, employees' satisfaction, government benefit and society benefit are the indicators of strategic barriers. Moreover, formality, centralization and complexity are the investigated indicators in structural barriers. All of the above mentioned factors have a meaningful relationship with development of electronic banking.
Genetic characterization of Echinococcus isolates from various intermediate hosts in the Qinghai-Tibetan Plateau Area, China

Abstract This study examined Echinococcus spp. genotypes and genetic variants isolated from humans as well as domestic and wild animals from the Qinghai-Tibetan Plateau Area using the cox1 gene. All samples except the pika isolates were identified as the Echinococcus granulosus sensu stricto. Sixteen different haplotypes with considerable intraspecific variation were detected and characterized in mitochondrial cox1 sequences. The parsimonious network of cox1 haplotypes showed star-like features, and the neutrality indexes computed via Tajima's D and Fu's Fs tests showed high negative values in E. granulosus s. s. , indicating deviations from neutrality; the Fst values were low among the populations, implying that the populations were not genetically differentiated. The pika isolates were identified as E. multilocularis and E. shiquicus. Only one haplotype was recognized in the pika isolates. E. granulosus s. s. was the predominant species found in animals and humans, followed by E. multilocularis and E. shiquicus, with high genetic diversity circulating among the animals and humans in this area. Further studies are needed to cover many sample collection sites and larger numbers of pathogen isolates, which may reveal abundant strains and/or other haplotypes in the hydatid cysts infecting human and animal populations of the QTPA, China.