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Functional Notch signaling is required for BMP4-induced inhibition of myogenic differentiation

The bone morphogenetic protein (BMP) and Notch signaling pathways are crucial for cellular differentiation. In many cases, the two pathways act similarly; for example, to inhibit myogenic differentiation. It is not known whether this inhibition is caused by distinct mechanisms or by an interplay between Notch and BMP signaling. Here we demonstrate that functional Notch signaling is required for BM

SARs for the antiparasitic plant metabolite pulchrol. : 3. Combinations of new substituents in A/B-rings and A/C-rings

The natural products pulchrol and pulchral, isolated from the roots of the Mexican plant Bourreria pulchra, have previously been shown to possess an antiparasitic activity toward Trypanosoma cruzi, Leishmania braziliensis and L. amazonensis, protozoa responsible for the Chagas disease and leishmaniasis. These infections have been classified as neglected diseases, and still require the development

Advancing the implementation of nature-based solutions in cities: A review of frameworks

Nature-based solutions (NBS) can help tackle climate change and advance urban sustainability by using nature to deliver social, ecological and economic benefits. However, their success largely depend on implementation for which several barriers exist. For NBS to be meaningful in terms of delivering positive impacts in cities, we need better understanding of how implementation is embedded in NBS fr

Effects of a Four-day Spaceflight and Recombinant Human Growth Hormone on Cancellous Bone Microarchitecture in Femoral Head of Rapidly Growing Male Rats

Spaceflight results in reduced bone accrual and muscle atrophy in growing rodents. Some studies suggest that the detrimental effects of spaceflight are due, in part, to impaired growth hormone (GH) signaling. An experiment flown aboard STS-41 (October 6–10, 1990) evaluated the efficacy of recombinant human growth hormone (rhGH) in ameliorating the detrimental effects of spaceflight on the musculos

Restricted cortical and amygdaloid removal of vesicular glutamate transporter 2 in preadolescent mice impacts dopaminergic activity and neuronal circuitry of higher brain function

A major challenge in neuroscience is to resolve the connection between gene functionality, neuronal circuits, and behavior. Most, if not all, neuronal circuits of the adult brain contain a glutamatergic component, the nature of which has been difficult to assess because of the vast cellular abundance of glutamate. In this study, we wanted to determine the role of a restricted subpopulation of glut

Reactivating Fetal Hemoglobin Expression in Human Adult Erythroblasts Through BCL11A Knockdown Using Targeted Endonucleases

We examined the efficiency, specificity, and mutational signatures of zinc finger nucleases (ZFNs), transcriptional activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 systems designed to target the gene encoding the transcriptional repressor BCL11A, in human K562 cells and human CD34+progenitor cells. ZFNs and TALENs were delivere

Remarkably low affinity of CD4/peptide-major histocompatibility complex class II protein interactions

The αβ T-cell coreceptor CD4 enhances immune responses more than 1 million-fold in some assays, and yet the affinity of CD4 for its ligand, peptide-major histocompatibility class II (pMHC II) on antigen-presenting cells, is so weak that it was previously unquantifiable. Here, we report that a soluble form of CD4 failed to bind detectably to pMHC II in surface plasmon resonance-based assays, establ

Rereading a tree-ring database to illustrate depositional histories of subfossil trees

Late Quaternary tree-ring chronologies have been constructed using data collected from subfossil trees preserved under favourable conditions in lake sediments and peat deposits. Tree-ring widths and densities are commonly used for reconstructions of past climate variability. An alternative way of using these data is to explore the replication curves of these chronologies. Here, we make use of prev

Two mechanisms for dissipation of excess light in monomeric and trimeric light-harvesting complexes

Oxygenic photoautotrophs require mechanisms for rapidly matching the level of chlorophyll excited states from light harvesting with the rate of electron transport from water to carbon dioxide. These photoprotective reactions prevent formation of reactive excited states and photoinhibition. The fastest response to excess illumination is the so-called non-photochemical quenching which, in higher pla

Mechanism for Burgess Shale-type preservation

Exceptionally preserved fossil biotas of the Burgess Shale and a handful of other similar Cambrian deposits provide rare but critical insights into the early diversification of animals. The extraordinary preservation of labile tissues in these geographically widespread but temporally restricted soft-bodied fossil assemblages has remained enigmatic since Walcott's initial discovery in 1909. Here, w

Association analysis identifies 65 new breast cancer risk loci

Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of

Widespread Increases in Iron Concentration in European and North American Freshwaters

Recent reports of increasing iron (Fe) concentrations in freshwaters are of concern, given the fundamental role of Fe in biogeochemical processes. Still, little is known about the frequency and geographical distribution of Fe trends or about the underlying drivers. We analyzed temporal trends of Fe concentrations across 340 water bodies distributed over 10 countries in northern Europe and North Am

"Everybody knows every child should be educated" : The Strive Towards Universal Primary Education in Tanzania

År 2001 deklarerade den tanzaniska regeringen den första Primary Education Development Plan och därmed avskaffades den tidigare obligatoriska skolavgiften för grundskolan. I och med avskaffandet av skolavgiften förväntades andelen barn i grundskola att öka. Syftet med avhandlingen är att förstå hur reformen och dess fokus på avskaffandet av skolavgiften har påverkat föräldrars och vårdnadshavares In 2001, the first Primary Education Development Plan declared that the previous obligatory primary education fee was to be abolished in Tanzania. This was an attempt to increase the access to public primary education for all children. This thesis aims to understand how the reform and its focus on the abolition of school fee influences parents’ and caregivers’ support for primary education and imp

SHARPIN stabilizes estrogen receptor a and promotes breast cancer cell proliferation

Estrogen receptor a is expressed in the majority of breast cancers and promotes estrogen-dependent cancer progression. In our study, we identified the novel E3 ubiquitin ligase SHARPIN function to facilitate ERα signaling. SHARPIN is highly expressed in human breast cancer and correlates with ERα protein level by immunohistochemistry. SHARPIN expression level correlates with poor prognosis in ERα

A membrane-bound NAC transcription factor, ANAC017, mediates mitochondrial retrograde signaling in Arabidopsis

Plants require daily coordinated regulation of energy metabolism for optimal growth and survival and therefore need to integrate cellular responses with both mitochondrial and plastid retrograde signaling. Using a forward genetic screen to characterize regulators of alternative oxidase1a (rao) mutants, we identified RAO2/Arabidopsis NAC domain-containing protein17 (ANAC017) as a direct positive re

The transcription factor ABI4 is a regulator of mitochondrial retrograde expression of ALTERNATIVE OXIDASE1a

Plant cells integrate signals from external sources and from organelles to regulate gene expression, referred to as anterograde and retrograde signaling, respectively. Functional characterization of the promoter of ALTERNATIVE OXIDASE1a (AOX1a) from Arabidopsis (Arabidopsis thaliana), a marker for mitochondrial retrograde response, was carried out by testing the ability of the AOX1a promoter to dr

Breaking down seasonality : Androgen modulation and stress response in a highly stable environment

Previous studies show that most birds inhabiting temperate regions have well defined life history stages, and they modulate the production of testosterone (T) and corticosterone (CORT) in response to changes in seasonality. In this study we aimed to examine baseline and stress-induced levels of CORT and circulating T in relation with life history stages in the rufous-collared sparrow, Zonotrichia