Cancer prevention by targeting angiogenesis

Healthy individuals can harbour microscopic tumours and dysplastic foci in different organs in an undetectable and asymptomatic state for many years. These lesions do not progress in the absence of angiogenesis or inflammation. Targeting both processes before clinical manifestation can prevent tumour growth and progression. Angioprevention is a chemoprevention approach that interrupts the formation of new blood vessels when tumour cell foci are in an indolent state. Many efficacious chemopreventive drugs function by preventing angiogenesis in the tumour microenvironment. Blocking the vascularization of incipient tumours should maintain a dormancy state such that neoplasia or cancer exist without disease. The current limitations of antiangiogenic cancer therapy may well be related to the use of antiangiogenic agents too late in the disease course. In this Review, we suggest mechanisms and strategies for using antiangiogenesis agents in a safe, preventive clinical angioprevention setting, proposing different levels of clinical angioprevention according to risk, and indicate potential drugs to be employed at these levels. Finally, angioprevention may go well beyond cancer in the prevention of a range of chronic disorders where angiogenesis is crucial, including different forms of inflammatory or autoimmune diseases, ocular disorders, and neurodegeneration

Multilocus phylogenetics in a widespread African anuran lineage (Brevicipitidae: Breviceps) reveals patterns of diversity reflecting geoclimatic change

AimTo investigate models assessing the influence of geomorphology and climatic shifts on species diversification in sub‐Saharan Africa by reconstructing the pattern and timing of phylogenetic relationships of rain frogs (Brevicipitidae: Breviceps).LocationSub‐Saharan Africa, south of the Congo Basin.MethodsMultilocus sequence data were generated for near complete species‐level sampling of the genus Breviceps. Phylogenetic relationships were inferred via Bayesian inference and maximum likelihood analyses on both concatenated and single‐gene datasets. Network analyses identified locus‐specific reticulate relationships among taxa. Bayesian methods were used to infer dates of divergence among Breviceps lineages, and niche modelling was used to identify possible adaptive divergence.ResultsBreviceps is monophyletic and comprised of two major, largely allopatric subclades. Diversity within each subclade is concentrated in two areas with contrasting geologic and climatic histories: the arid/semiarid winter rainfall zone in the south‐western (SW) Cape, and the semitropical East Coast that receives predominantly summer rainfall. Recognized species diversity in the SW Cape based on phenotypic variation is consistent with observed genetic patterns whereas the East Coast is shown to harbour unexpectedly high genetic diversity and up to seven putative, cryptic species. Niche models show significant overlap between closely related species.Main conclusionsDating analyses indicate that diversification of Breviceps occurred rapidly within the Miocene, with only a moderate decline over the Plio‐Pleistocene, suggesting that this process might be slowed but ongoing. Our findings suggest that a combination of two models, a landscape barrier model and climate fluctuation model, can explain patterns of diversification in Breviceps. This demonstrates that Miocene epeirogenic events and climatic shifts may have had a considerable influence on contemporary patterns of biodiversity. Topographic complexity and relative geoclimatic stability in the East have promoted cryptic diversification in allopatry, and this area clearly harbours numerous undescribed taxa and is in need of detailed biotic investigation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145569/1/jbi13394.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145569/2/jbi13394_am.pd

VET Leadership for the Future: contexts, characteristics and capabilities

This study examines leadership in Australia’s vocational education and training (VET) sector. VET leaders make a vital and growing contribution to learners, industry and society, yet research on their work is limited. This has direct implications for ensuring leadership is most effective, and for framing evidence-based capacity development. To assist the sector, and in particular the people who find themselves running large and complex training organisations, this study paints a picture of what VET leaders do, and of how they can do it best

Cryptic diversity among Yazoo Darters (Percidae: Etheostoma raneyi) in disjunct watersheds of northern Mississippi

© Copyright 2020 Nasser et al. The Yazoo Darter, Etheostoma raneyi (Percidae), is an imperiled freshwater fish species endemic to tributaries of the Yocona and Little Tallahatchie rivers of the upper Yazoo River basin, in northern Mississippi, USA. The two populations are allopatric, isolated by unsuitable lowland habitat between the two river drainages. Relevant literature suggests that populations in the Yocona River represent an undescribed species, but a lack of data prevents a thorough evaluation of possible diversity throughout the range of the species. Our goals were to estimate phylogenetic relationships of the Yazoo Darter across its distribution and identify cryptic diversity for conservation management purposes. Maximum likelihood (ML) phylogenetic analyses of the mitochondrial cytochrome b (cytb) gene returned two reciprocally monophyletic clades representing the two river drainages with high support. Bayesian analysis of cytb was consistent with the ML analysis but with low support for the Yocona River clade. Analyses of the nuclear S7 gene yielded unresolved relationships among individuals in the Little Tallahatchie River drainage with mostly low support, but returned a monophyletic clade for individuals from the Yocona River drainage with high support. No haplotypes were shared between the drainages for either gene. Additional cryptic diversity within the two drainages was not indicated. Estimated divergence between Yazoo Darters in the two drainages occurred during the Pleistocene (\u3c1 million years ago) and was likely linked to repeated spatial shifts in suitable habitat and changes in watershed configurations during glacial cycles. Individuals from the Yocona River drainage had lower genetic diversity consistent with the literature. Our results indicate that Yazoo Darters in the Yocona River drainage are genetically distinct and that there is support for recognizing Yazoo Darter populations in the Yocona River drainage as a new species under the unified species concept

Injury-induced Foxm1 expression in the mouse kidney drives epithelial proliferation by a cyclin F-dependent mechanism

Acute kidney injury (AKI) strongly upregulates the transcription factor Foxm1 in the proximal tubule in vivo, and Foxm1 drives epithelial proliferation in vitro. Here, we report that deletion of Foxm1 either with a nephron-specific Cre driver or by inducible global deletion reduced proximal tubule proliferation after ischemic injury in vivo. Foxm1 deletion led to increased AKI to chronic kidney disease transition, with enhanced fibrosis and ongoing tubule injury 6 weeks after injury. We report ERK mediated FOXM1 induction downstream of the EGFR in primary proximal tubule cells. We defined FOXM1 genomic binding sites by cleavage under targets and release using nuclease (CUT&RUN) and compared the genes located near FOXM1 binding sites with genes downregulated in primary proximal tubule cells after FOXM1 knockdown. The aligned data sets revealed the cell cycle regulator cyclin F (CCNF) as a putative FOXM1 target. We identified 2 cis regulatory elements that bound FOXM1 and regulated CCNF expression, demonstrating that Ccnf is strongly induced after kidney injury and that Foxm1 deletion abrogates Ccnf expression in vivo and in vitro. Knockdown of CCNF also reduced proximal tubule proliferation in vitro. These studies identify an ERK/FOXM1/CCNF signaling pathway that regulates injury-induced proximal tubule cell proliferation

Gravitational radiospectrometer

Gravitational lensing is predicted by general relativity and is found in observations. When a gravitating body is surrounded by a plasma, the lensing angle depends on a frequency of the electromagnetic wave due to refraction properties, and the dispersion properties of the light propagation in plasma. The last effect leads to dependence, even in the uniform plasma, of the lensing angle on the frequency, what resembles the properties of the refractive prism spectrometer. The strongest action of this spectrometer is for the frequencies slightly exceeding the plasma frequency, what corresponds to very long radiowaves.Comment: 11 pages, 2 figure

A New Class of Exact Hairy Black Hole Solutions

We present a new class of black hole solutions with minimally coupled scalar field in the presence of a negative cosmological constant. We consider a one-parameter family of self-interaction potentials parametrized by a dimensionless parameter $g$. When $g=0$, we recover the conformally invariant solution of the Martinez-Troncoso-Zanelli (MTZ) black hole. A non-vanishing $g$ signals the departure from conformal invariance. All solutions are perturbatively stable for negative black hole mass and they may develop instabilities for positive mass. Thermodynamically, there is a critical temperature at vanishing black hole mass, where a higher-order phase transition occurs, as in the case of the MTZ black hole. Additionally, we obtain a branch of hairy solutions which undergo a first-order phase transition at a second critical temperature which depends on $g$ and it is higher than the MTZ critical temperature. As $g\to 0$, this second critical temperature diverges.Comment: 18 pages, 6 figures, minor changes, references added, published versio

Inclusive b-hadron production cross section with muons in pp collisions at s√=7TeV

A measurement of the b-hadron production cross section in proton-proton collisions at s√=7TeVs=7TeV is presented. The dataset, corresponding to 85 nb−1, was recorded with the CMS experiment at the LHC using a low-threshold single-muon trigger. Events are selected by the presence of a muon with transverse momentum pμT>6GeVpTμ>6GeV with respect to the beam direction and pseudorapidity |η μ | < 2.1. The transverse momentum of the muon with respect to the closest jet discriminates events containing b hadrons from background. The inclusive b-hadron production cross section is presented as a function of muon transverse momentum and pseudorapidity. The measured total cross section in the kinematic acceptance is σ(pp → b + X → μ + X′) = 1.32 ± 0.01(stat) ± 0.30(syst) ± 0.15(lumi)μb

A dynastic elite in monumental Neolithic society

The nature and distribution of political power in Europe during the Neolithic era remains poorly understood. During this period, many societies began to invest heavily in building monuments, which suggests an increase in social organization. The scale and sophistication of megalithic architecture along the Atlantic seaboard, culminating in the great passage tomb complexes, is particularly impressive. Although co-operative ideology has often been emphasised as a driver of megalith construction, the human expenditure required to erect the largest monuments has led some researchers to emphasize hierarchy—of which the most extreme case is a small elite marshalling the labour of the masses. Here we present evidence that a social stratum of this type was established during the Neolithic period in Ireland. We sampled 44 whole genomes, among which we identify the adult son of a first-degree incestuous union from remains that were discovered within the most elaborate recess of the Newgrange passage tomb. Socially sanctioned matings of this nature are very rare, and are documented almost exclusively among politico-religious elites—specifically within polygynous and patrilineal royal families that are headed by god-kings. We identify relatives of this individual within two other major complexes of passage tombs 150 km to the west of Newgrange, as well as dietary differences and fine-scale haplotypic structure (which is unprecedented in resolution for a prehistoric population) between passage tomb samples and the larger dataset, which together imply hierarchy. This elite emerged against a backdrop of rapid maritime colonization that displaced a unique Mesolithic isolate population, although we also detected rare Irish hunter-gatherer introgression within the Neolithic population