UDP-glucose dehydrogenase expression is upregulated following EMT and differentially affects intracellular glycerophosphocholine and acetylaspartate levels in breast mesenchymal cell lines

Funding Information: The study received funding from Icelandic centre for research award number: 163254‐051; Recipient: Ottar Rolfsson and Doktorsstyrkir Háskóla Ísland; Doktorsstyrkir 2020; Recipient: Qiong Wang. Publisher Copyright: © 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.Metabolic rewiring is one of the indispensable drivers of epithelial–mesenchymal transition (EMT) involved in breast cancer metastasis. In this study, we explored the metabolic changes during spontaneous EMT in three separately established breast EMT cell models using a proteomic approach supported by metabolomic analysis. We identified common proteomic changes, including the expression of CDH1, CDH2, VIM, LGALS1, SERPINE1, PKP3, ATP2A2, JUP, MTCH2, RPL26L1 and PLOD2. Consistently altered metabolic enzymes included the following: FDFT1, SORD, TSTA3 and UDP-glucose dehydrogenase (UGDH). Of these, UGDH was most prominently altered and has previously been associated with breast cancer patient survival. siRNA-mediated knock-down of UGDH resulted in delayed cell proliferation and dampened invasive potential of mesenchymal cells and downregulated expression of the EMT transcription factor SNAI1. Metabolomic analysis revealed that siRNA-mediated knock-down of UGDH decreased intracellular glycerophosphocholine (GPC), whereas levels of acetylaspartate (NAA) increased. Finally, our data suggested that platelet-derived growth factor receptor beta (PDGFRB) signalling was activated in mesenchymal cells. siRNA-mediated knock-down of PDGFRB downregulated UGDH expression, potentially via NFkB-p65. Our results support an unexplored relationship between UGDH and GPC, both of which have previously been independently associated with breast cancer progression.Peer reviewe

ANÁLISE DA INFLUÊNCIA DA HIPERTENSÃO ARTERIAL SISTÊMICA E DA INSUFICIÊNCIA CARDÍACA NO AGRAVO DO QUADRO CLÍNICO DE PACIENTES COM DOENÇA RENAL CRÔNICA: uma revisão de literatura

Introduction: systemic arterial hypertension (SAH) and heart failure, epidemiologically, are diseases that model consequences for other systems of the human body, for example chronic kidney disease (CKD). The development of this appears to be a social consequence of lack of knowledge, as its secondary outcomes are controllable and treatable. Countries like Brazil have exorbitant expenses when it comes to financing dialysis and transplant procedures, with an increase in these numbers, especially in young patients decompensated for their underlying diseases. The objective of this work is to observe the incidence in the literature of SAH and heart failure in patients related to the worsening of CKD. Methodology: descriptive study in narrative review, which seeks to answer the PICO acromion “What is the influence of systemic arterial hypertension and heart failure on the worsening of the clinical condition of patients with chronic kidney disease? ”. Discussion: CKD's pathophysiology is the loss of kidney function, where they lose functionality and destroy their specific cells, resulting in the inability to maintain metabolic balance. It proves to be a problem of public responsibility, where more and more deaths in the population are reported. The main risk factors for CKD are highly prevalent chronic diseases such as hypertension and heart failure, the first being the most described in the literature as a triggering factor. Thus resulting in worsening of renal function laboratory results, resulting in chronic kidney injury (CRF). Results: Analyzing the databases, articles in the last 10 years were observed, where 38.6% had the descriptors systemic arterial hypertension and heart failure, describing them as their main secondary outcome. Conclusion: to the scientific society, it contributes summarized and updated indexes reporting the relationship between these precursor pathologies. To society, it informs the problem and a way to inform the patient about their health condition and better understanding.Introdução: hipertensão arterial sistêmica (HAS) e Insuficiência cardíaca, epidemiologicamente são doenças modeladoras de consequências a outros sistemas do corpo humano, por exemplo a doença renal crônica (DRC). O desenvolvimento desta mostra-se como consequência social a falta de conhecimento, pois seus desfechos secundários são controláveis e tratáveis. Países como o Brasil, possuem gastos exorbitantes quando ao custeio de procedimentos de diálise e transplante, sendo observado uma crescente nestes números, principalmente em pacientes jovens descompensados das doenças de base. O objetivo deste trabalho são observar a incidência na literatura, sobre a HAS e insuficiência cardíaca em pacientes relacionadas ao agravo da DRC. Metodologia: estudo descritivo em revisão de narrativa, que procura responder ao acrômio PICO “Qual é a influência da hipertensão arterial sistêmica e da insuficiência cardíaca no agravo do quadro clínico de pacientes com doença renal crônica? ”. Discussão: DRC tem como fisiopatologia a perda da função renal, onde estes perdem a funcionalidade e destroem suas células especificas, resultando na incapacidade em manter o equilíbrio metabólico. Mostra-se uma mazela de responsabilidade pública, onde cada vez mais relados de morte na população são relatados. Os principais fatores de risco para a DRC são doenças crônicas de alta prevalência como HAS e insuficiência cardíaca, sendo a primeira a mais descrita na literatura como fator desencadeante. Assim resultando na piora dos resultados laboratoriais de função renal, resultando em uma injúria renal crônica (IRC). Resultados: Analisando as bases de dados, foi observado artigos nos últimos 10 anos, onde 38,6% tinham os descritores hipertensão Arterial sistêmica e insuficiência cardíaca, descrevendo como seu principal desfecho secundário. Conclusão: à sociedade científica, contribui com índices resumidos e atualizados relatando a relação entre estas patologias precursoras. À sociedade, informa sua problemática e uma maneira em informar o paciente sobre a sua condição de saúde e melhor compreensão

ATLANTIC EPIPHYTES: a data set of vascular and non-vascular epiphyte plants and lichens from the Atlantic Forest

Epiphytes are hyper-diverse and one of the frequently undervalued life forms in plant surveys and biodiversity inventories. Epiphytes of the Atlantic Forest, one of the most endangered ecosystems in the world, have high endemism and radiated recently in the Pliocene. We aimed to (1) compile an extensive Atlantic Forest data set on vascular, non-vascular plants (including hemiepiphytes), and lichen epiphyte species occurrence and abundance; (2) describe the epiphyte distribution in the Atlantic Forest, in order to indicate future sampling efforts. Our work presents the first epiphyte data set with information on abundance and occurrence of epiphyte phorophyte species. All data compiled here come from three main sources provided by the authors: published sources (comprising peer-reviewed articles, books, and theses), unpublished data, and herbarium data. We compiled a data set composed of 2,095 species, from 89,270 holo/hemiepiphyte records, in the Atlantic Forest of Brazil, Argentina, Paraguay, and Uruguay, recorded from 1824 to early 2018. Most of the records were from qualitative data (occurrence only, 88%), well distributed throughout the Atlantic Forest. For quantitative records, the most common sampling method was individual trees (71%), followed by plot sampling (19%), and transect sampling (10%). Angiosperms (81%) were the most frequently registered group, and Bromeliaceae and Orchidaceae were the families with the greatest number of records (27,272 and 21,945, respectively). Ferns and Lycophytes presented fewer records than Angiosperms, and Polypodiaceae were the most recorded family, and more concentrated in the Southern and Southeastern regions. Data on non-vascular plants and lichens were scarce, with a few disjunct records concentrated in the Northeastern region of the Atlantic Forest. For all non-vascular plant records, Lejeuneaceae, a family of liverworts, was the most recorded family. We hope that our effort to organize scattered epiphyte data help advance the knowledge of epiphyte ecology, as well as our understanding of macroecological and biogeographical patterns in the Atlantic Forest. No copyright restrictions are associated with the data set. Please cite this Ecology Data Paper if the data are used in publication and teaching events. © 2019 The Authors. Ecology © 2019 The Ecological Society of Americ

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Swelling transition of a clay induced by heating

Clays are of paramount importance for soil stability, but also in applications ranging from oil recovery to composites and hydrogels. Generically, clays are divided into two subclasses: macroscopically swelling, ‘active’ clays that have the capacity for taking up large amounts of water to form stable gels, and ‘passive’ or non-swelling clays; the former stabilize soils whereas the latter are known to lead to landslides. However, it has been unclear so far what mechanisms underlie clay swelling. Here, we report the first observation of a temperature-induced transition from a passive to an active, swelling clay. We propose a simple description of the swelling transition; while net attractive interactions are dominant at low temperatures so that the clay particles remain attached to each other in stacks, at higher temperatures it is energetically favourable for the clay to swell due to the entropy that is gained by counterions which are liberated during swelling

Monitoring of the spatial and temporal dynamics of BER/SSBR pathway proteins, including MYH, UNG2, MPG, NTH1 and NEIL1-3, during DNA replication.

Base lesions in DNA can stall the replication machinery or induce mutations if bypassed. Consequently, lesions must be repaired before replication or in a post-replicative process to maintain genomic stability. Base excision repair (BER) is the main pathway for repair of base lesions and is known to be associated with DNA replication, but how BER is organized during replication is unclear. Here we coupled the iPOND (isolation of proteins on nascent DNA) technique with targeted mass-spectrometry analysis, which enabled us to detect all proteins required for BER on nascent DNA and to monitor their spatiotemporal orchestration at replication forks. We demonstrate that XRCC1 and other BER/single-strand break repair (SSBR) proteins are enriched in replisomes in unstressed cells, supporting a cellular capacity of post-replicative BER/SSBR. Importantly, we identify for the first time the DNA glycosylases MYH, UNG2, MPG, NTH1, NEIL1, 2 and 3 on nascent DNA. Our findings suggest that a broad spectrum of DNA base lesions are recognized and repaired by BER in a post-replicative process

X-ray Studies of Carbon Dioxide Intercalation in Na-Fluorohectorite Clay at Near-Ambient Conditions

We show experimentally that gaseous CO2 intercalates into the interlayer space of the synthetic smectite clay Na-fluorohectorite at conditions not too far from ambient. The mean interlayer repetition distance of the clay when CO2 is intercalated is found to be 12.5 Å for the conditions −20 °C and 15 bar. The magnitude of the expansion of the interlayer upon intercalation is indistinguishable from that observed in the dehydrated–monohydrated transition for H2O, but the possibility of water intercalation is ruled out by a careful analysis of the experimental conditions and repeating the measurements exposing the clay to nitrogen gas. The dynamics of the process is observed to be dependent on the pressure, with a higher intercalation rate at increased pressure. The rate of CO2 intercalation at the studied conditions is found to be several orders of magnitude slower than the intercalation rate of water or humidity at ambient pressure and temperature

Swelling transition of a clay induced by heating

Clays are of paramount importance for soil stability, but also in applications ranging from oil recovery to composites and hydrogels. Generically, clays are divided into two subclasses: macroscopically swelling, ‘active’ clays that have the capacity for taking up large amounts of water to form stable gels, and ‘passive’ or non-swelling clays; the former stabilize soils whereas the latter are known to lead to landslides. However, it has been unclear so far what mechanisms underlie clay swelling. Here, we report the first observation of a temperature-induced transition from a passive to an active, swelling clay. We propose a simple description of the swelling transition; while net attractive interactions are dominant at low temperatures so that the clay particles remain attached to each other in stacks, at higher temperatures it is energetically favourable for the clay to swell due to the entropy that is gained by counterions which are liberated during swelling

Swelling transition of a clay induced by heating

-Clays are of paramount importance for soil stability, but also in applications ranging from oil recovery to composites and hydrogels. Generically, clays are divided into two subclasses: macroscopically swelling, ‘active’ clays that have the capacity for taking up large amounts of water to form stable gels, and ‘passive’ or non-swelling clays; the former stabilize soils whereas the latter are known to lead to landslides. However, it has been unclear so far what mechanisms underlie clay swelling. Here, we report the first observation of a temperature-induced transition from a passive to an active, swelling clay. We propose a simple description of the swelling transition; while net attractive interactions are dominant at low temperatures so that the clay particles remain attached to each other in stacks, at higher temperatures it is energetically favourable for the clay to swell due to the entropy that is gained by counterions which are liberated during swelling

UDP-glucose dehydrogenase expression is upregulated following EMT and differentially affects intracellular glycerophosphocholine and acetylaspartate levels in breast mesenchymal cell lines

Metabolic rewiring is one of the indispensable drivers of epithelial-mesenchymal transition (EMT) involved in breast cancer metastasis. In this study, we explored the metabolic changes during spontaneous EMT in three separately established breast EMT cell models using a proteomics approach supported by metabolomic analysis. We identified common proteomic changes, including in the expression of CDH1, CDH2, VIM, LGALS1, SERPINE1, PKP3, ATP2A2, JUP, MTCH2, RPL26L1 and PLOD2. Consistently altered metabolic enzymes included: FDFT1, SORD, TSTA3 and UDP-glucose dehydrogenase (UGDH). Of these, UGDH was most prominently altered and has previously been associated with breast cancer patient survival. siRNA-mediated knockdown of UGDH resulted in delayed cell proliferation and dampened invasive potential of mesenchymal cells, and downregulated expression of the EMT transcription factor SNAI1. Metabolomic analysis revealed that siRNA-mediated knockdown of UGDH decreased intracellular glycerophosphocholine (GPC), whereas levels of acetyl aspartate (NAA) increased. Finally, our data suggested that platelet-derived growth factor receptor beta (PDGFRB) signaling was activated in mesenchymal cells. siRNA-mediated knockdown of PDGFRB downregulated UGDH expression, potentially via NFkB-p65. Our results support an unexplored relationship between UGDH and GPC, both of which have previously been independently associated with breast cancer progression