Cardioprotective and anti-hypertensive effects of Prosopis glandulosa in rat models of pre-diabetes

AIM: Obesity and type 2 diabetes present with two debilitating complications, namely, hypertension and heart disease. The dried and ground pods of Prosopis glandulosa (commonly known as the Honey mesquite tree) which is part of the Fabaceae (or legume) family are currently marketed in South Africa as a food supplement with blood glucose-stabilising and anti-hypertensive properties. We previously determined its hypoglycaemic effects, and in the current study we determined the efficacy of P glandulosa as anti-hypertensive agent and its myocardial protective ability. METHODS: Male Wistar rats were rendered either pre-diabetic (diet-induced obesity: DIO) or hypertensive (high-fat diet: HFD). DIO animals were treated with P glandulosa (100 mg/kg/day for the last eight weeks of a 16-week period) and compared to age-matched controls. Hearts were perfused ex vivo to determine infarct size. Biometric parameters were determined at the time of sacrifice. Cardiac-specific insulin receptor knock-out (CIRKO) mice were similarly treated with P glandulosa and infarct size was determined. HFD animals were treated with P glandulosa from the onset of the diet or from weeks 12–16, using captopril (50 mg/kg/day) as the positive control. Blood pressure was monitored weekly. RESULTS: DIO rats and CIRKO mice: P glandulosa ingestion significantly reduced infarct size after ischaemia–reperfusion. Proteins of the PI-3-kinase/PKB/Akt survival pathway were affected in a manner supporting cardioprotection. HFD model: P glandulosa treatment both prevented and corrected the development of hypertension, which was also reflected in alleviation of water retention. CONCLUSION: P glandulosa was cardioprotective and infarct sparing as well as anti-hypertensive without affecting the body weight or the intra-peritoneal fat depots of the animals. Changes in the PI-3-kinase/PKB/Akt pathway may be causal to protection. Results indicated water retention, possibly coupled to vasoconstriction in the HFD animals, while ingestion of P glandulosa alleviated both. We concluded that treatment of pre-diabetes, type 2 diabetes or hypertension with P glandulosa poses possible beneficial health effects.Department of HE and Training approved lis

Genomic Fingerprints of Palaeogeographic History: The Tempo and Mode of Rift Tectonics Across Tropical Africa Has Shaped the Diversification of the Killifish Genus Nothobranchius (Teleostei: Cyprinodontiformes)

This paper reports a phylogeny of the African killifishes (Genus Nothobranchius, Order Cyprinodontiformes) informed by five genetic markers (three nuclear, two mitochondrial) of 80 taxa (seven undescribed and 73 of the 92 recognized species). These short-lived annual fishes occupy seasonally wet habitats in central and eastern Africa, and their distribution coincides largely with the East African Rift System (EARS). The fossil dates of sister clades used to constrain a chronometric tree of all sampled Nothobranchius recovered the origin of the genus at ~13.27 Mya. It was followed by the radiations of six principal clades through the Neogene. An ancestral area estimation tested competing biogeographical hypotheses to constrain the ancestral origin of the genus to the Nilo-Sudan Ecoregion, which seeded a mid-Miocene dispersal event into the Coastal ecoregion, followed closely (~10 Mya) by dispersals southward across the Mozambique coastal plain into the Limpopo Ecoregion. Extending westwards across the Tanzanian plateau, a pulse of radiations through the Pliocene were associated with dispersals and fragmentation of wetlands across the Kalahari and Uganda Ecoregions. We interpret this congruence of drainage rearrangements with dispersals and cladogenic events of Nothobranchius to reflect congruent responses to recurrent uplift and rifting. The coevolution of these freshwater fishes and wetlands is attributed to ultimate control by tectonics, as the EARS extended southwards during the Neogene. Geobiological consilience of the combined evidence supports a tectonic hypothesis for the evolution of Nothobranchius

The structure of Chariklo's rings from stellar occultations

Two narrow and dense rings (called C1R and C2R) were discovered around the Centaur object (10199) Chariklo during a stellar occultation observed on 2013 June 3. Following this discovery, we planned observations of several occultations by Chariklo's system in order to better characterize the physical properties of the ring and main body. Here, we use 12 successful occulations by Chariklo observed between 2014 and 2016. They provide ring profiles (physical width, opacity, edge structure) and constraints on the radii and pole position. Our new observations are currently consistent with the circular ring solution and pole position, to within the $\pm 3.3$ km formal uncertainty for the ring radii derived by Braga-Ribas et al. The six resolved C1R profiles reveal significant width variations from $\sim 5$ to 7.5 km. The width of the fainter ring C2R is less constrained, and may vary between 0.1 and 1 km. The inner and outer edges of C1R are consistent with infinitely sharp boundaries, with typical upper limits of one kilometer for the transition zone between the ring and empty space. No constraint on the sharpness of C2R's edges is available. A 1$\sigma$ upper limit of $\sim 20$ m is derived for the equivalent width of narrow (physical width <4 km) rings up to distances of 12,000 km, counted in the ring plane

Wavelength-resolved reverberation mapping of intermediate redshift quasars HE 0413-4031 and HE 0435-4312: Dissecting Mg II, optical Fe II, and UV Fe II emission regions

We present the wavelength-resolved reverberation mapping (RM) of combined MgII and UV FeII broad-line emissions for two intermediate redshifts (z$\sim$1), luminous quasars - HE 0413-4031 and HE 0435-4312, monitored by the SALT and 1-m class telescopes between 2012-2022. Through this technique, we aim to disentangle the Mg II and FeII emission regions and to build a radius-luminosity relation for UV FeII emission, which has so far remained unconstrained. Several methodologies have been applied to constrain the time delays for total MgII and FeII emissions. In addition, this technique is performed to quantify the inflow or outflow of broad-line region gas around the supermassive black hole and to disentangle the emission/emitting regions from lines produced in proximity to each other. The mean total FeII time delay is nearly equal to the mean total Mg II time delay for HE 0435-4312 suggesting a co-spatiality of their emissions. However, in HE 0413-4031, the mean FeII time delay is found to be longer than the mean MgII time delay, suggesting that FeII is produced at longer distances from the black hole. The UV Fe II R-L relation is updated with these two quasars and compared with the optical FeII relation, which suggests that the optical FeII region is located further than the UV FeII by a factor of 1.7-1.9 i.e. $R_{\rm FeII-opt}\sim(1.7-1.9)R_{\rm FeII-UV}$. We detected a weak pattern in the time delay vs. wavelength relation, suggesting that the MgII broad-line originates a bit closer to the SMBH than the UV FeII, however, the difference is not very significant. Comparison of MgII, UV, and optical FeII R-L relations suggests that the difference may be larger for lower-luminosity sources, possibly with the MgII emission originating further from the SMBH. In the future, more RM data will be acquired to put better constraints on these trends, in particular the UV FeII R-L relation.Comment: 24 pages, 16 figures, 5 tables, Accepted for publication in A&A, in Pres

Wavelength-resolved Reverberation Mapping of quasar CTSC30.10: Dissecting MgII and FeII emission regions

We present the results of the reverberation monitoring aimed at MgII broad line and FeII pseudocontinuum for the luminous quasar CTS C30.10 (z = 0.90052) with the Southern African Large Telescope covering the years 2012-2021. We aimed at disentangling the MgII and UV FeII variability and the first measurement of UV FeII time delay for a distant quasar. We used several methods for time-delay measurements and determined both FeII and MgII time delays as well as performed a wavelength-resolved time delay study for a combination of MgII and FeII in the 2700 - 2900 \AA restframe wavelength range. We obtain the time delay for MgII of $275.5^{+12.4}_{-19.5}$ days in the rest frame, while for FeII we have two possible solutions of $270.0^{+13.8}_{-25.3}$ days and $180.3^{+26.6}_{-30.0}$ in the rest frame. Combining this result with the old measurement of FeII UV time delay for NGC 5548 we discuss for the first time the radius-luminosity relation for UV FeII with the slope consistent with $0.5$ within uncertainties. Since FeII time delay has a shorter time-delay component but lines are narrower than MgII, we propose that the line delay measurement is biased towards the BLR part facing the observer, with the bulk of the Fe II emission may arise from the more distant BLR region, one that is shielded from the observer.Comment: 22 pages, 19 Figures, 6 Tables, Submitted to Astronomy and Astrophysics, Comments are welcom

Gender Separation Increases Somatic Growth in Females but Does Not Affect Lifespan in Nothobranchius furzeri

According to life history theory, physiological and ecological traits and parameters influence an individual's life history and thus, ultimately, its lifespan. Mating and reproduction are costly activities, and in a variety of model organisms, a negative correlation of longevity and reproductive effort has been demonstrated. We are employing the annual killifish Nothobranchius furzeri as a vertebrate model for ageing. N. furzeri is the vertebrate displaying the shortest known lifespan in captivity with particular strains living only three to four months under optimal laboratory conditions. The animals show explosive growth, early sexual maturation and age-dependent physiological and behavioural decline. Here, we have used N. furzeri to investigate a potential reproduction-longevity trade-off in both sexes by means of gender separation. Though female reproductive effort and offspring investment were significantly reduced after separation, as investigated by analysis of clutch size, eggs in the ovaries and ovary mass, the energetic surplus was not reallocated towards somatic maintenance. In fact, a significant extension of lifespan could not be observed in either sex. This is despite the fact that separated females, but not males, grew significantly larger and heavier than the respective controls. Therefore, it remains elusive whether lifespan of an annual species evolved in periodically vanishing habitats can be prolonged on the cost of reproduction at all

Quantifiable Biomarkers of Normal Aging in the Japanese Medaka Fish (Oryzias latipes)

BACKGROUND: Small laboratory fish share many anatomical and histological characteristics with other vertebrates, yet can be maintained in large numbers at low cost for lifetime studies. Here we characterize biomarkers associated with normal aging in the Japanese medaka (Oryzias latipes), a species that has been widely used in toxicology studies and has potential utility as a model organism for experimental aging research. PRINCIPAL FINDINGS: The median lifespan of medaka was approximately 22 months under laboratory conditions. We performed quantitative histological analysis of tissues from age-grouped individuals representing young adults (6 months old), mature adults (16 months old), and adults that had survived beyond the median lifespan (24 months). Livers of 24-month old individuals showed extensive morphologic changes, including spongiosis hepatis, steatosis, ballooning degeneration, inflammation, and nuclear pyknosis. There were also phagolysosomes, vacuoles, and residual bodies in parenchymal cells and congestion of sinusoidal vessels. Livers of aged individuals were characterized by increases in lipofuscin deposits and in the number of TUNEL-positive apoptotic cells. Some of these degenerative characteristics were seen, to a lesser extent, in the livers of 16-month old individuals, but not in 6-month old individuals. The basal layer of the dermis showed an age-dependent decline in the number of dividing cells and an increase in senescence-associated β-galactosidase. The hearts of aged individuals were characterized by fibrosis and lipofuscin deposition. There was also a loss of pigmented cells from the retinal epithelium. By contrast, age-associated changes were not apparent in skeletal muscle, the ocular lens, or the brain. SIGNIFICANCE: The results provide a set of markers that can be used to trace the process of normal tissue aging in medaka and to evaluate the effect of environmental stressors

Asymmetric Reproductive Isolation between Two Sympatric Annual Killifish with Extremely Short Lifespans

BACKGROUND: Interspecific reproductive isolation is typically achieved by a combination of intrinsic and extrinsic barriers. Behavioural isolating barriers between sympatric, closely related species are often of primary importance and frequently aided by extrinsic factors causing spatial and temporal interspecific separation. Study systems with a severely limited role of extrinsic factors on reproductive isolation may provide valuable insights into how reproductive isolation between sympatric species is maintained. We used no-choice experimental set-up to study reproductive barriers between two closely related sympatric African killifish species, Nothobranchius furzeri and Nothobranchius orthonotus. These fish live in small temporary savannah pools and have complete spatial and temporal overlap in reproductive activities and share a similar ecology. PRINCIPAL FINDINGS: We found that the two species display largely incomplete and asymmetric reproductive isolation. Mating between N. furzeri males and N. orthonotus females was absent under standard experimental conditions and eggs were not viable when fish were forced to mate in a modified experimental setup. In contrast, male N. orthonotus indiscriminately mated with N. furzeri females, the eggs were viable, and offspring successfully hatched. Most spawnings, however, were achieved by male coercion and egg production and embryo survival were low. Behavioural asymmetry was likely facilitated by mating coercion from larger males of N. orthonotus and at relatively low cost to females. Interestingly, the direction of asymmetry was positively associated with asymmetry in post-mating reproductive barriers. SIGNIFICANCE: We showed that, in fish species with a promiscuous mating system and multiple matings each day, selection for strong mate preferences was relaxed. This effect was likely due to the small proportion of resources allocated to each single mating and the high potential cost to females from mating refusal. We highlight and discuss the fact that males of rarer species may often coercively mate with females of a related, more abundant species

The Identification of Zebrafish Mutants Showing Alterations in Senescence-Associated Biomarkers

There is an interesting overlap of function in a wide range of organisms between genes that modulate the stress responses and those that regulate aging phenotypes and, in some cases, lifespan. We have therefore screened mutagenized zebrafish embryos for the altered expression of a stress biomarker, senescence-associated β-galactosidase (SA-β-gal) in our current study. We validated the use of embryonic SA-β-gal production as a screening tool by analyzing a collection of retrovirus-insertional mutants. From a pool of 306 such mutants, we identified 11 candidates that showed higher embryonic SA-β-gal activity, two of which were selected for further study. One of these mutants is null for a homologue of Drosophila spinster, a gene known to regulate lifespan in flies, whereas the other harbors a mutation in a homologue of the human telomeric repeat binding factor 2 (terf2) gene, which plays roles in telomere protection and telomere-length regulation. Although the homozygous spinster and terf2 mutants are embryonic lethal, heterozygous adult fish are viable and show an accelerated appearance of aging symptoms including lipofuscin accumulation, which is another biomarker, and shorter lifespan. We next used the same SA-β-gal assay to screen chemically mutagenized zebrafish, each of which was heterozygous for lesions in multiple genes, under the sensitizing conditions of oxidative stress. We obtained eight additional mutants from this screen that, when bred to homozygosity, showed enhanced SA-β-gal activity even in the absence of stress, and further displayed embryonic neural and muscular degenerative phenotypes. Adult fish that are heterozygous for these mutations also showed the premature expression of aging biomarkers and the accelerated onset of aging phenotypes. Our current strategy of mutant screening for a senescence-associated biomarker in zebrafish embryos may thus prove to be a useful new tool for the genetic dissection of vertebrate stress response and senescence mechanisms