Label‐free imaging of healthy and infarcted fetal sheep hearts by two‐photon microscopy

Coronary heart disease is one of the largest causes of death worldwide, making this a significant health care issue. A critical problem for the adult human heart is that it does not undergo effective repair in response to damage, leaving patients with a poor prognosis. Unlike the adult, fetal hearts have the ability to repair after myocardial damage. Using two‐photon microscopy, we have visualised the morphological and metabolic changes following myocardial infarction in sheep fetuses, to characterise response to cardiac injury in a mammalian model. Following myocardial infarction, fetal hearts showed no significant increase in collagen deposition in the region of the infarction, when compared to either the surrounding tissue or shams. In contrast, metabolic activity (i. e. NAD(P)H and FAD) was significantly reduced in the region of myocardial infarction, when compared to either the surrounding tissue or sham hearts. For comparison, we also imaged two hearts from preadolescent sheep (sham and myocardial infarction) and showed highly ordered collagen deposition with decreased metabolic activity within the infarcted area. Therefore, two‐photon imaging had the capacity to image both morphological and metabolic changes in response to myocardial infarction and showed differences in the response with age. Picture : Two‐photon imaging of myocardial infarction ( b and d ) enabled the visualisation of increased collagen (blue; Em=431 nm) and changes in other tissue autofluorescence (green; Em=489–606 nm) in fetal ( a and b ) and preadolescent ( c and d ) hearts, compared to shams ( a and c ). The excitation wavelength was 840 nm. Scale bars: 10 μm.

     

Metakaryotic stem cell lineages in organogenesis of humans and other metazoans

A non-eukaryotic, metakaryotic cell with large, open mouthed, bell shaped nuclei represents an important stem cell lineage in fetal/juvenile organogenesis in humans and rodents. each human bell shaped nucleus contains the diploid human DNA genome as tested by quantitative Feulgen DNA cytometry and fluorescent in situ hybridization with human pan-telomeric, pan-centromeric and chromosome specific probes. From weeks ∼5–12 of human gestation the bell shaped nuclei are found in organ anlagen enclosed in sarcomeric tubular syncytia. Within syncytia bell shaped nuclear number increases binomially up to 16 or 32 nuclei; clusters of syncytia are regularly dispersed in organ anlagen. Syncytial bell shaped nuclei demonstrate two forms of symmetrical amitoses, facing or “kissing” bells and “stacking” bells resembling separation of two paper cups. Remarkably, DNA increase and nuclear fission occur coordinately. Importantly, syncytial bell shaped nuclei undergo asymmetrical amitoses creating organ specific ensembles of up to eight distinct closed nuclear forms, a characteristic required of a stem cell lineage. Closed nuclei emerging from bell shaped nuclei are eukaryotic as demonstrated by their subsequent increases by extra-syncytial mitoses populating the parenchyma of growing anlagen. From 9–14 weeks syncytia fragment forming single cells with bell shaped nuclei that continue to display both symmetrical and asymmetrical amitoses. These forms persist in the juvenile period and are specifically observed in bases of colonic crypts. Metakaryotic forms are found in organogenesis of humans, rats, mice and the plant Arabidopsis indicating an evolutionary origin prior to the divergence of plants and animals.     

Mutation of the PDK1 PH domain inhibits protein kinase B/Akt, leading to small size and insulin resistance

PDK1 activates a group of kinases, including protein kinase B (PKB)/Akt, p70 ribosomal S6 kinase (S6K), and serum and glucocorticoid-induced protein kinase (SGK), that mediate many of the effects of insulin as well as other agonists. PDK1 interacts with phosphoinositides through a pleckstrin homology (PH) domain. To study the role of this interaction, we generated knock-in mice expressing a mutant of PDK1 incapable of binding phosphoinositides. The knock-in mice are significantly small, insulin resistant, and hyperinsulinemic. Activation of PKB is markedly reduced in knock-in mice as a result of lower phosphorylation of PKB at Thr308, the residue phosphorylated by PDK1. This results in the inhibition of the downstream mTOR complex 1 and S6K1 signaling pathways. In contrast, activation of SGK1 or p90 ribosomal S6 kinase or stimulation of S6K1 induced by feeding is unaffected by the PDK1 PH domain mutation. These observations establish the importance of the PDK1-phosphoinositide interaction in enabling PKB to be efficiently activated with an animal model. Our findings reveal how reduced activation of PKB isoforms impinges on downstream signaling pathways, causing diminution of size as well as insulin resistance.     

A high-powered replication study finds no effect of starting or stopping hormonal contraceptive use on relationship quality

A number of recent studies have implicated that incongruent use of hormonal contraceptives (HCs) negatively affects various aspects of women's romantic relationships. It has been suggested that women with incongruent HC use (a discrepancy in HC use status between when they first met their current partner and the time of study participation) report less sexual satisfaction and higher jealousy scores compared to women with congruent HC use. A similar effect has also been hypothesized for general relationship satisfaction, and recent findings suggest that the association between HC incongruency and women's general relationship satisfaction is moderated by third-party ratings of facial attractiveness of the women's male partners. Using a large convenience sample (N = 948) of Finnish women, we attempted to replicate previously reported findings but found no support for the HC congruency hypothesis, despite excellent statistical power (≥98.7%) to detect previously reported effect sizes. Instead, after dividing our sample into four groups based on HC congruency/incongruency, we found that the largest differences in jealousy, sexual satisfaction, and relationship satisfaction scores tended to be found between women who were consistent HC users and consistent non-users (i.e., between women with different kinds of congruent HC use). We also detected a significant main effect of current HC use on jealousy. We conclude that HC congruency effects reported in previous studies may have spuriously arisen from unequal distributions of current HC users within congruent and incongruent HC user groups.     

Vandachostylis ‘Sri-Siam’: an intergeneric hybrid with superior qualities as evidenced by its biochemical fragrance and transcriptome profiles

Journal of Plant Biochemistry and Biotechnology - Vandachostylis ‘Sri-Siam’ is a fragrant orchid, suitable as a potted plant for the floriculture and perfumery industries due to its...     

Rift Valley fever knowledge,mitigation strategies and communication preferences among male and female livestock farmers in Eastern Province,Rwanda

The Government of Rwanda reported an outbreak of Rift Valley fever (RVF) in the Eastern Province in 2018. To respond to the outbreak, vaccination and education campaigns about the disease were carried out. Because RVF cases continue to be detected in Rwanda and the disease impacts livelihoods and health, accurate knowledge and communication are imperative. The objectives of this study were to evaluate knowledge and risk perceptions of RVF transmission among livestock farmers in Nyagatare District, Eastern Province, Rwanda, and to compare RVF knowledge, risk perceptions, and farming practices between male and female livestock farmers. This cross-sectional, quantitative study was conducted in selected sectors of Nyagatare District in the Eastern Province of Rwanda in June 2019. A 34-question survey was used to ask about demographics, livestock ownership, risk perceptions about zoonotic diseases and livestock management, RVF knowledge, preferred communication sources and information sharing strategies, and protective strategies for RVF mitigation while working with livestock. Livestock farmers were interviewed at three milk collection centers, two village meeting points, a farm cooperative meeting, and during door-to-door visits in villages. In total, 123 livestock farmers were interviewed. The survey found that most livestock farmers lacked knowledge about epizootic and zoonotic transmission of RVF, more male livestock farmers were familiar with RVF and risk mitigation strategies, and female livestock farmers are not viewed as reliable sources of information. Additionally, most livestock farmers had not vaccinated their animals against RVF despite past vaccination campaigns. Radio was the most popular communication channel. These findings show that RVF knowledge and information sharing are inadequate among livestock farmers in Eastern Province. Therefore, vaccination and education campaigns may need to be reevaluated within the context of these trends in order to prepare for future RVF outbreaks.     

Reaction of forest soil microflora to environmental stress along a moderate pollution gradient next to an oil refinery

Twenty-five study sites were established along a 57-km-long transect in order to estimate the impact of an oil refinery, mainly emitting sulphur dioxide (24000 t yr⁻¹), on forest soil (F/H-horizon) chemistry and microbiology. The study demonstrated the existence of a pollution gradient which was best represented by the logarithm of the concentration of vanadium in the analyzed F/H soil layer. Of the soil microbial characteristics measured, including length of fungal hyphae, soil respiration, microbial biomass C and N, and percentage mass loss of Scots pine (Pinus sylvestris) needle litter, only fungal hyphal length was suppressed by the pollution load. No reduction in basic cations (Ca, Mg, K, and Na) in the F/H-horizon, or enrichment of soluble aluminum in the F/H-horizon of the Scots pine forest could be detected to result from the deposition.     

How fast is fast? Eco‐evolutionary dynamics and rates of change in populations and phenotypes

It is increasingly recognized that evolution may occur in ecological time. It is not clear, however, how fast evolution – or phenotypic change more generally – may be in comparison with the associated ecology, or whether systems with fast ecological dynamics generally have relatively fast rates of phenotypic change. We developed a new dataset on standardized rates of change in population size and phenotypic traits for a wide range of species and taxonomic groups. We show that rates of change in phenotypes are generally no more than 2/3, and on average about 1/4, the concurrent rates of change in population size. There was no relationship between rates of population change and rates of phenotypic change across systems. We also found that the variance of both phenotypic and ecological rates increased with the mean across studies following a power law with an exponent of two, while temporal variation in phenotypic rates was lower than in ecological rates. Our results are consistent with the view that ecology and evolution may occur at similar time scales, but clarify that only rarely do populations change as fast in traits as they do in abundance.     

The peptide analogue of MCP-1 65-76 sequence is an inhibitor of inflammation

Inflammation plays an important role in vessel wall remodeling that occurs in atherosclerosis and postangioplasty restenosis. Monocytic chemoattractant protein-1 (MCP-1) is one of the main attractors of monocytes and some lymphocyte subsets to the damaged vessel. The aims of the study were to confirm MCP-1 participation in the development of acute coronary syndromes, to produce the potential MCP-1 peptide antagonist, and to investigate its effects in vitro and in vivo in different animal models of inflammation. MCP-1 plasma concentration was measured by ELISA (enzyme-linked immunosorbent assay). Chemokine receptor expression by cells isolated from human atherosclerotic lesions was assessed by direct immunofluorescence and flow cytometry. MCP-1 sequence was analyzed with Peptide Companion software and peptides were synthesized using Fmoc strategy. The peptide resistance to degradation was checked by 1H-NMR spectroscopy. The peptide effect on MCP-1-stimulated cell migration was studied in Boyden chamber and in mouse air pouch model, and its influence on lipopolysaccharide (LPS)-induced inflammatory cell recruitment was investigated in models of subcutaneous inflammation in rats and nonhuman primates. We revealed nearly a 2-fold increase of MCP-1 plasma level in patients with unstable angina in comparison with patients with stable angina. The atherosclerotic plaque specimens obtained from patients with unstable angina contained a significant amount of chemokine receptor-expressing leukocytes. Peptide from MCP-1 C-terminal 65-76 sequence (peptide X) inhibited MCP-1-stimulated monocytic cell migration in vitro and in vivo. Peptide X labeled with 99mTc accumulated specifically at sites of inflammation in rats. Peptide X administrated i.m and i.v. suppressed monocyte and granulocyte recruitment induced by subcutaneous injection of LPS in the back of rats and non-human primates. Our data demonstrate that MCP-1-mediated chemotaxis could be responsible for atherosclerotic plaque "destabilization". Peptide X may represent a new class of anti-inflammatory drugs to be used in cardiology.