Biology subjects

Peter, D.

Publications and source records attributed to Peter, D..

5 recordsLinked to original sources

bioRxiv2026

Reforestation under climate change - a cross-regional deadwood retention experiment to develop multifunctional forests on disturbed Norway spruce areas

The impact of extreme weather events such as droughts, heatwaves, storms and the associated intensification of bark beetle outbreaks in Norway spruce forests in recent years, has led to a large-scale forest loss in Central Europe. There are various options for post-disturbance management, from complete clearing to no intervention, but their pros and cons - in the context of multifunctional forest management - are not resolved. The "ResEt-Fi" project ("Pioneering reforestation: Regional management for establishing multifunctional forests on post-disturbed Norway spruce areas") consortium implemented a cross-regional field trial to test how specific practices of deadwood retention affect the ecological conditions and subsequent reforestation dynamics of natural regeneration and planted trees. It aims at generating climate-stable mixed forests within an ecological valuable transition, balancing ecosystem functioning and socio-economic benefits. As an outcome for stakeholders and forest practitioners, guidelines and showcase scenarios for facilitating the selection of management procedures will be created. In this article, we provide insight into (i) the applied post-disturbance deadwood management practices and the rationale for their selection, (ii) the experimental setup of our cross-regional field trial, (iii) the initial post-disturbance status and perspective with respect to regional site conditions and deadwood treatment. While the setup and site conditions will primarily serve as a reference for subsequent studies in our joint project, this is the first systematic, cross-regional study on the effects of the management options standing deadwood, high stumps and clearing on microclimate, biodiversity, and tree regeneration in the critical early stages of forest regeneration after disturbance.

ecology↗

bioRxiv2023

Structure of the minor spliceosomal U11 snRNP

The minor spliceosome catalyses the excision of U12-dependent introns from pre-mRNAs. These introns are rare, but their removal is critical for cell viability. We obtained a cryo-EM reconstruction of the 13-subunit U11 snRNP complex, revealing structures of U11 snRNA and five minor spliceosome-specific factors. U11 snRNP appears strikingly different from the equivalent major spliceosome U1 snRNP. SNRNP25 and SNRNP35 form a dimer, which specifically recognises U11 snRNA. PDCD7 forms extended helices, which bridge SNRNP25 and SNRNP48, located at the distal ends of the particle. SNRNP48 forms multiple interfaces with U11 snRNP and, together with ZMAT5, are positioned near the 5-end of the U11 snRNA and likely stabilise the binding of the incoming 5SS. Our structure provides mechanistic insights into U12-dependent intron recognition and the evolution of the splicing machinery.

biochemistry↗

bioRxiv2023

Targeting cancer with small molecule pan-KRAS degraders

Despite the high prevalence of cancers driven by KRAS mutations, to date only the G12C mutation has been clinically proven to be druggable via covalent targeting of the mutated cysteine amino acid residue (1). However, in many cancer indications other KRAS mutations, such as G12D and -V, are far more prevalent and small molecule concepts that can address a wider variety of oncogenic KRAS alleles are in high clinical demand (2). Here we show that a single small molecule can be used to simultaneously and potently degrade 13 out of 17 of the most prevalent oncogenic KRAS alleles, including those not yet tractable by inhibitors. Compared with inhibition, degradation of oncogenic KRAS results in more profound and sustained pathway modulation across a broad range of KRAS mutant cell lines. As a result, KRAS degraders inhibit growth of the majority of cancer cell lines driven by KRAS mutations while sparing models without genetic KRAS aberrations. Finally, we demonstrate that pharmacological degradation of oncogenic KRAS leads to tumour regression in vivo. Together, these findings unveil a new path towards addressing KRAS driven cancers with small molecule degraders. One-Sentence SummaryThe most prevalent KRAS variants which drive tumour growth in a major share of cancer patients can be targeted with a single small molecule degrader.

pharmacology and toxicology↗

bioRxiv2019

Exploring midwives understanding of respectful and non-abusive maternal care in Kumasi, Ghana: Qualitative Inquiry

BackgroundVarious aspects of disrespect and abusive maternity care have received scholarly attention because of frequent reports of the phenomenon in most healthcare facilities globally, especially in low- and middle-income countries. However, the perspectives of skilled providers on respectful maternal care have not been extensively studied. Midwives knowledge of respectful maternity care is critical in designing any interventive measures to address the menace of disrespect and abuse in maternity care. Therefore, the present study sought to explore the views of midwives on respectful maternity care at a Teaching Hospital in Kumasi, Ghana.\n\nMethodsPhenomenological qualitative research design was employed in the study. Data were generated through individual in-depth interviews, which were audio-recorded and transcribed verbatim. Data saturation was reached with fifteen midwives. Open Code 4.03 was used to manage and analyse the data.\n\nFindingsThe midwives understanding of respectful maternity care was comprised of the following components: non-abusive care, consented care, confidential care, non-violation of childbearing womens basic human rights, and non-discriminatory care. Probing questions to solicit midwives opinions on an evidenced-based component of respectful maternity care generated little information, suggesting that the midwives have a gap in knowledge regarding this component of respectful maternity care.\n\nConclusionMidwives reported an understanding of most components of respectful maternity care, but their gap in knowledge on evidenced-based care requires policy attention and in-service training. To understand the extent to which this gap in knowledge can be generalized for midwives across Ghana to warrant a redesign of the national midwifery curriculum, the authors recommend a nationwide cross-sectional quantitative study.

scientific communication and education↗

bioRxiv2019

A role for EP3 and its associated G protein, Gz, in negatively regulating beta-cell function and mass in the context of insulin resistance and obesity

When homozygous for the LeptinOb mutation (Ob), Black-and-Tan Brachyury (BTBR) mice become morbidly obese and severely insulin resistant, and by 10 weeks of age, frankly diabetic. Previous work has shown Prostaglandin EP3 Receptor (EP3) expression and activity is up-regulated in islets from BTBR-Ob mice as compared to lean controls, actively contributing to their beta-cell dysfunction. In this work, we aimed to test the impact of beta-cell-specific EP3 loss on the BTBR-Ob phenotype by crossing Ptger3 floxed mice with the Rat insulin promoter (RIP)-CreHerr driver strain. Instead, germline recombination of the floxed allele in the founder mouse - an event whose prevalence we identified as directly associated with underlying insulin resistance of the background strain - generated a full-body knockout. Full-body EP3 loss provided no diabetes protection to BTBR-Ob mice, but, unexpectedly, significantly worsened BTBR-lean insulin resistance and glucose tolerance. This in vivo phenotype was not associated with changes in beta-cell fractional area or markers of beta-cell replication ex vivo. Instead, EP3-null BTBR-lean islets had essentially uncontrolled insulin hypersecretion. The selective up-regulation of constitutively-active EP3 splice variants in islets from young, lean BTBR mice as compared to C57BL/6J, where no phenotype of EP3 loss has been observed, provides a potential explanation for the hypersecretion phenotype. In support of this, high islet EP3 expression in Balb/c females vs. Balb/c males was fully consistent with their sexually-dimorphic metabolic phenotype after loss of EP3-coupled Gz protein. Taken together, our findings provide a new dimension to the understanding of EP3 as a critical brake on insulin secretion. New and NoteworthyIslet Prostaglandin EP3 receptor (EP3) signaling is well-known as up-regulated in the pathophysiological conditions of type 2 diabetes, contributing to beta-cell dysfunction. Unexpected findings in mouse models of non-obese insulin sensitivity and resistance provide a new dimension to our understanding of EP3 as a key modulator of insulin secretion. A previously-unknown relationship between mouse insulin resistance and the penetrance of Rat insulin promoter-driven germline floxed allele recombination is critical to consider when creating beta-cell-specific knockouts. For Table of Contents Use Only O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=121 SRC="FIGDIR/small/671289v3_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@15cf1d5org.highwire.dtl.DTLVardef@108f565org.highwire.dtl.DTLVardef@126e479org.highwire.dtl.DTLVardef@61fdf8_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗