Miracle-dz/UniFAR-FTUs huggingface dataset:
The Mechanism of the Negative Chronotropic and Dromotropic Actions of Adenosine 5'-triphosphate in the Heart: An Update

Adenosine 5'-triphosphate (ATP) plays a critical role in intracellular metabolism and energetics. Extracellular ATP is rapidly degraded to adenosine by ectoenzymes. Both ATP and adenosine suppress cardiac pacemakers' automaticity and atrioventricular nodal conduction, albeit via the different mechanism of actions. This historical update summarizes the current knowledge regarding the negative chronotropic and dromotropic actions of ATP and discusses the clinical implications regarding the utility of ATP as a diagnostic and therapeutic agent in the management of neutrally mediated syncope and paroxysmal supra ventricular tachycardia.
What controls polyspermy in mammals, the oviduct or the oocyte?

A block to polyspermy is required for successful fertilisation and embryo survival in mammals. A higher incidence of polyspermy is observed during in vitro fertilisation (IVF) compared with the in vivo situation in several species. Two groups of mechanisms have traditionally been proposed as contributing to the block to polyspermy in mammals: oviduct‐based mechanisms, avoiding a massive arrival of spermatozoa in the proximity of the oocyte, and egg‐based mechanisms, including changes in the membrane and zona pellucida (ZP) in reaction to the fertilising sperm. Additionally, a mechanism has been described recently which involves modifications of the ZP in the oviduct before the oocyte interacts with spermatozoa, termed “pre‐fertilisation zona pellucida hardening”. This mechanism is mediated by the oviductal‐specific glycoprotein (OVGP1) secreted by the oviductal epithelial cells around the time of ovulation, and is reinforced by heparin‐like glycosaminoglycans (S‐GAGs) present in oviductal fluid. Identification of the molecules contributing to the ZP modifications in the oviduct will improve our knowledge of the mechanisms of sperm‐egg interaction and could help to increase the success of IVF systems in domestic animals and humans.
The effects of mortality reminders on posttraumatic growth and finding benefits among patients with life-threatening illness and their caregivers

Individuals confronted with a life-threatening illness often report posttraumatic growth (PTG) or finding benefits in disease. These positive evaluations of personal strength, perceptions of improved personal relations and new possibilities may represent a defensive response (cf Janus-face model). Three studies investigated the effects of mortality reminders on reports of PTG or benefit findings among people living with life-threatening illness or their caregivers. 80 people living with HIV (Study 1), 164 breast cancer survivors (Study 2) and 50 family caregivers for a patient with Huntington Disease (Study 3) were randomly assigned to the experimental (mortality reminders) or control conditions. Across three studies, those exposed to mortality reminders reported lower PTG or benefit finding, compared to the controls. These effects were moderated by time elapsed since diagnosis: mortality reminders led to lower PTG/benefit finding among those who received the diagnosis more recently. The results provide an insight into the defensive character of PTG/finding benefits in illness and changes in the function of these beliefs over time elapsing since diagnosis.
Epigenetic mechanisms in senescence, immortalisation and cancer

Cancer is controlled not only by genetic events but also by epigenetic events. The active acquisition of epigenetic changes is a poorly understood but very important process in mammalian development, differentiation, and disease. It is well established that epigenetic events are controlled by a specific subgroup of proteins, such as DNA methyltransferases, histone acetylases histone lysine methyltransferases or histone deacetylases, that influence methylation or acetylation patterns to modulate gene expression. We and others have identified S‐adenosylhomocysteine hydrolase in a high‐throughput genetic screen focused on discovering novel genes whose inhibition induces immortalisation of primary cells. Herein, we address the importance of genes involved in epigenetic mechanisms during senescence and how their effects might determine senescence bypass and immortalisation. The ways in which genes that regulate epigenetic mechanisms might modulate senescence/immortalisation and how these pathways could influence cancer development are explored. Overall, epigenetic modifications seem to play a major role in cancer, influencing tumour outcome by interfering with key senescence pathways.
Inhibition of Secretory Phospholipase A2 Activity Attenuates Acute Cardiogenic Pulmonary Edema Induced by Isoproterenol Infusion in Mice After Myocardial Infarction

Several types of secretory phospholipase A2 (sPLA2) are expressed in lung tissue, yielding various eicosanoids that might cause pulmonary edema. This study examined whether inhibition of sPLA2 activity attenuates acute cardiogenic pulmonary edema in mice. Acute cardiogenic pulmonary edema was induced in C57BL/6J male mice by an increase in heart rate with continuous intravenous infusion of isoproterenol (ISP) (10 mg/kg/h) at 2 weeks after the creation of myocardial infarction by left coronary artery ligation. Just before ISP infusion, a single intraperitoneal injection of 100 mg/kg LY374388, a prodrug of LY329722 that inhibits sPLA2 activity, or vehicle was administered. The ISP infusion after myocardial infarction induced interstitial and alveolar edema on lung histology. Furthermore, it increased the lung-to-body weight ratio, pulmonary vascular permeability evaluated by the Evans blue extravasation method, lung activity of sPLA2, and lung content of thromboxane A2 and leukotriene B4. These changes were significantly attenuated by LY374388 treatment. In Kaplan-Meier analysis, the survival rate during the ISP infusion after myocardial infarction was significantly higher in LY374388- than in vehicle-treated mice. Similar results were obtained with another inhibitor of sPLA2 activity, para-bromophenacyl bromide. In conclusion, inhibition of sPLA2 activity suppressed acute cardiogenic pulmonary edema.
Egg size and offspring quality: a meta‐analysis in birds

Parents affect offspring fitness by propagule size and quality, selection of oviposition site, quality of incubation, feeding of dependent young, and their defence against predators and parasites. Despite many case studies on each of these topics, this knowledge has not been rigorously integrated into individual parental care traits for any taxon. Consequently, we lack a comprehensive, quantitative assessment of how parental care modifies offspring phenotypes. This meta‐analysis of 283 studies with 1805 correlations between egg size and offspring quality in birds is intended to fill this gap. The large sample size enabled testing of how the magnitude of the relationship between egg size and offspring quality depends on a number of variables. Egg size was positively related to nearly all studied offspring traits across all stages of the offspring life cycle. Not surprisingly, the relationship was strongest at hatching but persisted until the post‐fledging stage. Morphological traits were the most closely related to egg size but significant relationships were also found with hatching success, chick survival, and growth rate. Non‐significant effect sizes were found for egg fertility, chick immunity, behaviour, and life‐history or sexual traits. Effect size did not depend on whether chicks were raised by their natural parents or were cross‐fostered to other territories. Effect size did not depend on species‐specific traits such as developmental mode, clutch size, and relative size of the egg, but was larger if tested in captive compared to wild populations and between rather than within broods. In sum, published studies support the view that egg size affects juvenile survival. There are very few studies that tested the relationship between egg size and the fecundity component of offspring fitness, and no studies on offspring survival as adults or on global fitness. More data are also needed for the relationships between egg size and offspring behavioural and physiological traits. It remains to be established whether the relationship between egg size and offspring performance depends on the quality of the offspring environment. Positive effect sizes found in this study are likely to be driven by a causal effect of egg size on offspring quality. However, more studies that control for potential confounding effects of parental post‐hatching care, genes, and egg composition are needed to establish firmly this causal link.
Fracture in teeth—a diagnostic for inferring bite force and tooth function

Teeth are brittle and highly susceptible to cracking. We propose that observations of such cracking can be used as a diagnostic tool for predicting bite force and inferring tooth function in living and fossil mammals. Laboratory tests on model tooth structures and extracted human teeth in simulated biting identify the principal fracture modes in enamel. Examination of museum specimens reveals the presence of similar fractures in a wide range of vertebrates, suggesting that cracks extended during ingestion or mastication. The use of ‘fracture mechanics' from materials engineering provides elegant relations for quantifying critical bite forces in terms of characteristic tooth size and enamel thickness. The role of enamel microstructure in determining how cracks initiate and propagate within the enamel (and beyond) is discussed. The picture emerges of teeth as damage‐tolerant structures, full of internal weaknesses and defects and yet able to contain the expansion of seemingly precarious cracks and fissures within the enamel shell. How the findings impact on dietary pressures forms an undercurrent of the study.
Top predators as biodiversity regulators: the dingo Canis lupus dingo as a case study

Top‐order predators often have positive effects on biological diversity owing to their key functional roles in regulating trophic cascades and other ecological processes. Their loss has been identified as a major factor contributing to the decline of biodiversity in both aquatic and terrestrial systems. Consequently, restoring and maintaining the ecological function of top predators is a critical global imperative. Here we review studies of the ecological effects of the dingo Canis lupus dingo, Australia's largest land predator, using this as a case study to explore the influence of a top predator on biodiversity at a continental scale. The dingo was introduced to Australia by people at least 3500 years ago and has an ambiguous status owing to its brief history on the continent, its adverse impacts on livestock production and its role as an ecosystem architect. A large body of research now indicates that dingoes regulate ecological cascades, particularly in arid Australia, and that the removal of dingoes results in an increase in the abundances and impacts of herbivores and invasive mesopredators, most notably the red fox Vulpes vulpes. The loss of dingoes has been linked to widespread losses of small and medium‐sized native mammals, the depletion of plant biomass due to the effects of irrupting herbivore populations and increased predation rates by red foxes. We outline a suite of conceptual models to describe the effects of dingoes on vertebrate populations across different Australian environments. Finally, we discuss key issues that require consideration or warrant research before the ecological effects of dingoes can be incorporated formally into biodiversity conservation programs.
The Effect of Selective Antihypertensive drugs on the Vascular Remodeling‐associated Hypertension: Insights from a Profilin1 Transgenic Mouse Model

Hypertension represents a major risk factor for cardiovascular diseases. We have developed a novel transgenic mouse model by overexpressing the cDNA of human profilin1 in the blood vessels of transgenic mice which led to vascular hypertrophy and hypertension. We assessed the effects of losartan, amlodipine or atenolol on vascular hypertrophy‐associated hypertension, by treating the profilin1 transgenic mice for 4 weeks. Our myograph results showed improvement in the contraction response towards phenylephrine and in the relaxation response towards acetylcholine and sodium nitrite in losartan‐ and amlodipine‐treated profilin1 mice. Western blot analyses using mesenteric arteries of lasortan and amlodipine‐treated profilin1 mice showed significant decreases in their signaling respectively as follows: the expression of α1 integrin (104% and 93%) and β1 integrin (116% and 109%); p‐ERK1/2 (149% and 130%) and p‐JNK (171% and 137%); the phospho‐myosin light chain20 (p‐MLC20) (117% and 150%) and the ROCKII expression (125% and 180). Conversely, there were significant increases in the eNOS expression (82% and 80%) and activation (p‐eNOS) (78 and 76%). On the other hand, atenololtreated profilin1 mice showed no significant change in all measured parameters. In conclusion, Profilin1 gene may represent a new therapeutic target in the treatment of vascular hypertrophy‐associated hypertension.
Psychological intervention with couples coping with breast cancer: A systematic review

Objective: Information about psychological intervention with couples coping with breast cancer is not well-disseminated. This can be explained, at least in part, by the absence of knowledge about the efficacy of this kind of intervention. The aim of the present systematic review is to identify and describe psychological interventions for couples coping with breast cancer and evaluate their efficacy. Design: Studies identified by a searching multiple literature databases related to health and psychology between 1975 and 2013. Rigorous inclusion and exclusion criteria were utilised. Results: Of 129 abstracts, 13 were extracted for further analysis and a final ten studies were deemed eligible for inclusion. Data were extracted from each study regarding study sample characteristics, design, results and methodological limitations. The results obtained were mixed in regard to efficacy, although the overwhelming majority of studies (eight studies) found benefits for both women and their partners in some dimensions, such as quality of life, psychological distress, relationship functioning and physical symptoms associated with cancer. Conclusion: Psychological interventions for couples coping with breast cancer appear to be effective for both women and their partners. However, further studies are needed to evaluate the efficacy of couple-based interventions and, to identify for whom and how they are more effective.
Synthesis and supramolecular studies of chiral boronated platinum(II) complexes: insights into the molecular recognition of carboranes by β-cyclodextrin.

The synthesis and characterisation of a novel isomeric family of closo-carborane-containing Pt(II) complexes ((R/S)-(1-4)⋅2 NO(3)) are reported. Related complexes (5⋅NO(3) and 6⋅NO(3)) that contain the 7,8-nido-carborane cluster were obtained from the selective deboronation of the 1,2-closo-carborane analogues. The corresponding water-soluble supramolecular 1:1 host-guest β-cyclodextrin (β-CD) adducts ((R/S)-(1-4)⋅β-CD⋅2 NO(3)) were also prepared and fully characterised. HR-ESI-MS experiments confirmed the presence of the host-guest adducts, and 2D-(1) H{(11)B} ROESY NMR studies showed that the boron clusters enter the β-CD from the side of the wider annulus. Isothermal titration calorimetry (ITC) experiments revealed enthalpically driven 1:1 and higher-order supramolecular interactions between β-CD and (R/S)-(1-4)⋅2 NO(3) in aqueous solution. A comparison of the predominate 1:1 binding mode established that the affinity of β-CD for the guest molecule is mainly influenced by the pyridyl ring substitution pattern and chirality of the host, whilst the nature of the closo-carborane isomer also plays some role, with the most favourable structural features for β-CD binding being the presence of the 4-pyridyl ring, 1,12-closo-carborane, and an S configuration. The results reported here represent the first comprehensive calorimetric study of the supramolecular interactions between closo-carborane compounds and β-CD, and it provides fascinating insights into the structural features influencing the thermodynamics of this phenomenon.
DPP-4 (CD26) Inhibitor Alogliptin Inhibits Atherosclerosis in Diabetic Apolipoprotein E–Deficient Mice

Dipeptidyl peptidase-4 (DPP-4 or CD26) inhibitors, a new class of antidiabetic compounds, are effective in the treatment of hyperglycemia. Because atherosclerosis-related cardiovascular diseases are the major complications of diabetes, it is important to determine the effect of DPP-4 inhibitors on atherosclerosis. In this study, nondiabetic and diabetic apolipoprotein E-deficient mice were treated with DPP-4 inhibitor alogliptin for 24 weeks, and atherosclerotic lesions in aortic origins were examined. Results showed that diabetes significantly increased atherosclerotic lesions, but alogliptin treatment reduced atherosclerotic lesions in diabetic mice. Metabolic studies showed that diabetes increased plasma glucose and that alogliptin treatment reduced glucose. Furthermore, immunohistochemistry study showed that diabetes increased interleukin-6 (IL-6) and IL-1β protein expression in atherosclerotic plaques, but alogliptin treatment attenuated diabetes-augmented IL-6 and IL-1β expression. In consistence with the observations from the mouse models, our in vitro studies showed that alogliptin-inhibited toll-like receptor 4 (TLR-4)-mediated upregulation of IL-6, IL-1β, and other proinflammatory cytokines by mononuclear cells. Taken together, our findings showed that alogliptin-inhibited atherosclerosis in diabetic apolipoprotein E-deficient mice and that the actions of alogliptin on both glucose and inflammation may contribute to the inhibition.
Administration of Rosmarinic Acid Reduces Cardiopathology and Blood Pressure Through Inhibition of p22phox NADPH Oxidase in Fructose-Fed Hypertensive Rats

Abstract Rosmarinic acid (RA), a caffeic acid ester, has insulin-sensitizing and antioxidant effects in high fructose-fed model of insulin resistance (IR). This study investigated whether RA supplementation prevents cardiac abnormalities and hypertension in fructose-fed rats (FFR). Rats fed with fructose diet (60 g/100 g) for 60 days exhibited metabolic abnormalities and rise in plasma and cardiac lipids and whole body IR. The levels of cardiac antioxidants and plasma ferric reducing antioxidant power were significantly reduced in FFR concomitant with increased levels of lipid peroxidation and protein oxidation products. A significant rise in troponin T, creatine kinase-MB, aspartate transaminase, and lactate dehydrogenase in plasma of FFR was noted. RA supplementation to FFR (10 mg/kg from the 16th day) significantly improved insulin sensitivity, reduced lipid levels, oxidative damage, and the expression of p22phox subunit of nicotinamide adenine dinucleotide phosphate reduced oxidase, and prevented cardiac hypertrophy. Fructose-induced rise in blood pressure was also lowered by RA through decrease in endothelin-1 and angiotensin-converting enzyme activity and increase in nitric oxide levels. Histology revealed a reduction in myocardial damage in RA-supplemented FFR. These findings suggest that RA acts as a vasoactive substance and a cardioprotector through its antioxidant property. Thus, RA may be useful in reducing the cardiovascular risk associated with IR.
Qiliqiangxin Inhibits the Development of Cardiac Hypertrophy, Remodeling, and Dysfunction During 4 Weeks of Pressure Overload in Mice

Abstract Qiliqiangxin (QL), a traditional Chinese medicine, has been used in the treatment of chronic heart failure. However, whether QL can benefit cardiac remodeling in the hypertensive state is unknown. We here examined the effects of QL on the development of cardiac hypertrophy through comparing those of losartan in C57BL/6 mice underlying transverse aorta constriction for 4 weeks. QL and losartan were administrated at 0.6 mg and 13.4 mg·kg−1·d−1, respectively. Cardiac hypertrophy, function, and remodeling were evaluated by echocardiography, catheterization, histology, and examination of specific gene expression and ERK phosphorylation. Cardiac apoptosis, autophagy, tumor necrosis factor &agr;/insulin-like growth factor-1, and angiotensin II type 1 receptor expression and especially the proliferation of cardiomyocytes and phosphorylation of ErbB receptors were examined in vivo to elucidate the mechanisms. Transverse aorta constriction for 2 weeks resulted in a significant cardiac hypertrophy, which was significantly suppressed by either QL or losartan treatment. At 4 weeks after transverse aorta constriction, although the development of cardiac dysfunction and remodeling and the increases in apoptosis, autophagy, tumor necrosis factor &agr;/insulin-like growth factor-1, and angiotensin II type 1 receptor expression were abrogated comparably between QL and losartan treatments, QL, but not losartan, enhanced proliferation of cardiomyocytes, which was paralleled with dowregulation of CCAAT/enhancer-binding protein &bgr;, upregulation of CBP/p300-interacting transactivator with ED-rich carboxy-terminal domain 4, and increases in ErbB2 and ErbB4 phosphorylation. Furthermore, inhibition of either ErbB2 or CBP/p300-interacting transactivator with ED-rich carboxy-terminal domain 4 abolished the cardiac protective effects of QL. Thus, QL inhibits myocardial inflammation and cardiomyocyte death and promotes cardiomyocyte proliferation, leading to an ameliorated cardiac remodeling and function in a mouse model of pressure overload. The possible mechanisms may involve inhibition of angiotensin II type 1 receptor and activation of ErbB receptors.
Neuropsychiatry and Behavioral Neuroscience

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Output Signal Power Analysis in Erbium-Doped Fiber Amplifier with Pump Power and Length Variation Using Various Pumping Techniques

The scope of this paper is to analyze the output signal power with pump power and length variation in cascaded EDFA simulation model performance. This paper describes the simulation model of Erbium-Doped Fiber Amplifier (EDFA) of variable lengths (10 m, 50 m, and 120 m) with dual pumping techniques (dual forward pumping with two 980 nm wavelengths, dual forward and backward pumping with two 980 nm wavelengths) and Tri-pumping techniques. The simulation models consist of input source and pump power coupled by WDM coupler which gives optimized signal power in the above-mentioned simulation model. The simulation model consists of source with multiple wavelengths (1520 nm–1618 nm), pumping source with the wavelength 980 nm, isolator, and filter. The resulting models accurately represent EDFA optimized output signal power. Simulation results show that choosing careful fiber length 120 m and pump power 1 W in dual pumping provided 0.07 W optimized output signal power compared to other pumping techniques.