Geomorphological control on boulder transport and coastal erosion before, during and after an extreme extra-tropical cyclone

Extreme wave events in coastal zones are principal drivers of geomorphic change. Evidence of boulder entrainment and erosional impact during storms is increasing. However, there is currently poor time coupling between pre- and post-storm measurements of coastal boulder deposits. Importantly there are no data reporting shore platform erosion, boulder entrainment and/or boulder transport during storm events – rock coast dynamics during storm events are currently unexplored. Here, we use high-resolution (daily) field data to measure and characterise coastal boulder transport before, during and after the extreme Northeast Atlantic extra-tropical cyclone Johanna in March 2008. Forty-eight limestone fine-medium boulders (n = 46) and coarse cobbles (n = 2) were tracked daily over a 0.1 km2 intertidal area during this multi-day storm. Boulders were repeatedly entrained, transported and deposited, and in some cases broken down (n = 1) or quarried (n = 3), during the most intense days of the storm. Eighty-one percent (n = 39) of boulders were located at both the start and end of the storm. Of these, 92% were entrained where entrainment patterns were closely aligned to wave parameters. These data firmly demonstrate rock coasts are dynamic and vulnerable under storm conditions. No statistically significant relationship was found between boulder size (mass) and net transport distance. Graphical analyses suggest that boulder size limits the maximum longshore transport distance but that for the majority of boulders lying under this threshold, other factors influence transport distance. Paired analysis of 20 similar sized and shaped boulders in different morphogenic zones demonstrates that geomorphological control affects entrainment and transport distance – where net transport distances were up to 39 times less where geomorphological control was greatest. These results have important implications for understanding and for accurately measuring and modelling boulde

The Origin of the White Roman Goose

In order to avoid interference from nuclear copies of mitochondrial DNA (numts), mtDNA of the white Roman goose (domestic goose) was extracted from liver mitochondria. The mtDNA control region was amplified using a long PCR strategy and then sequenced. Neighbor-joining, maximum parsimony, and maximum-likelihood approaches were implemented using the 1,177 bp mtDNA control region sequences to compute the phylogenetic relationships of the domestic goose with other geese. The resulting identity values for the white Roman geese were 99.1% (1,166/1,177) with western graylag geese and 98.8% (1,163/1,177) with eastern graylag geese. In molecular phylogenetic trees, the white Roman goose was grouped in the graylag lineage, indicating that the white Roman goose came from the graylag goose (Anser anser). Thus, the scientific name of the white Roman goose should be Anser anser 'White Roman.'

Trophic niche overlap between native freshwater mussels (Order: Unionida) and the invasive Corbicula fluminea

Freshwater mussels (Order Unionida) are highly threatened. Interspecific competition for food sources with invasive alien species is considered to be one of the factors responsible for their decline because successful invaders are expected to have wider trophic niches and more flexible feeding strategies than their native counterparts. In this study, carbon (δ13C: 13C/12C) and nitrogen (δ15N: 15N/14N) stable isotopes were used to investigate the trophic niche overlap between the native freshwater mussel species, Anodonta anatina, Potomida littoralis, and Unio delphinus, and the invasive bivalve Corbicula fluminea living in sympatry in the Tua basin (south-west Europe). The species presenting the widest trophic niches were C. fluminea and A. anatina, which indicate that they have broader diets than U. delphinus and P. littoralis. Nonetheless, all the species assimilated microphytobenthos, sediment organic matter, and detritus derived from vascular plants, although with interspecific variability in the assimilated proportions of each source. The trophic niche of the invasive species overlapped with the trophic niche of all the native species, with the extent varying between sites and according to the species. From the three native species analysed, Potomida littoralis may be at a higher risk for competition for food with C. fluminea in the Tua basin, if food sources become limited, because this native mussel presented the narrowest trophic niche across sites and the highest probability of overlapping with the trophic niche of C. fluminea. Given the global widespread distribution of C. fluminea, the implementation of management measures devoted to the control or even eradication of this invasive alien species should be a conservation priority given its potential for competition with highly threatened native freshwater mussels.V.M. and P.C. were supported by doctoral grants SFRH/BD/108298/2015 and SFRH/BD/131814/2017, respectively, from the Portuguese Foundation for Science and Technology—FCT through POPH/FSE funds. FCT also supported M.L.L. under contract (2020.03608.CEECIND). This study was conducted within the project FRESHCO – Multiple implications of invasive species on Freshwater Mussel coextinction processes, supported by FCT and COMPETE funds (contract: PTDC/AGRFOR/1627/2014). This study was also supported by national funds through FCT – Foundation for Science and Technology within the scope of UIDB/04423/2020 and UIDP/04423/2020. We thank Jacinto Cunha for providing Figure 1.info:eu-repo/semantics/publishedVersio

Obesity, inflammation, and insulin resistance

White adipose tissue (WAT) is considered an endocrine organ. When present in excess, WAT can influence metabolism via biologically active molecules. Following unregulated production of such molecules, adipose tissue dysfunction results, contributing to complications associated with obesity. Previous studies have implicated pro- and anti-inflammatory substances in the regulation of inflammatory response and in the development of insulin resistance. In obese individuals, pro-inflammatory molecules produced by adipose tissue contribute to the development of insulin resistance and increased risk of cardiovascular disease. On the other hand, the molecules with anti-inflammatory action, that have been associated with the improvement of insulin sensitivity, have your decreased production. Imbalance of these substances contributes significantly to metabolic disorders found in obese individuals. The current review aims to provide updated information regarding the activity of biomolecules produced by WAT

Machine Learning Detects Pan-cancer Ras Pathway Activation in The Cancer Genome Atlas

Precision oncology uses genomic evidence to match patients with treatment but often fails to identify all patients who may respond. The transcriptome of these \u201chidden responders\u201d may reveal responsive molecular states. We describe and evaluate a machine-learning approach to classify aberrant pathway activity in tumors, which may aid in hidden responder identification. The algorithm integrates RNA-seq, copy number, and mutations from 33 different cancer types across The Cancer Genome Atlas (TCGA) PanCanAtlas project to predict aberrant molecular states in tumors. Applied to the Ras pathway, the method detects Ras activation across cancer types and identifies phenocopying variants. The model, trained on human tumors, can predict response to MEK inhibitors in wild-type Ras cell lines. We also present data that suggest that multiple hits in the Ras pathway confer increased Ras activity. The transcriptome is underused in precision oncology and, combined with machine learning, can aid in the identification of hidden responders. Way et al. develop a machine-learning approach using PanCanAtlas data to detect Ras activation in cancer. Integrating mutation, copy number, and expression data, the authors show that their method detects Ras-activating variants in tumors and sensitivity to MEK inhibitors in cell lines

Oncogenic Signaling Pathways in The Cancer Genome Atlas

Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in ten canonical pathways: cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGFb signaling, p53 and beta-catenin/Wnt. We charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity. Eighty-nine percent of tumors had at least one driver alteration in these one alteration potentially targetable by currently available drugs. Thirty percent of tumors had multiple targetable alterations, indicating opportunities for combination therapy

Genomic and Molecular Landscape of DNA Damage Repair Deficiency across The Cancer Genome Atlas

DNA damage repair (DDR) pathways modulate cancer risk, progression, and therapeutic response. We systematically analyzed somatic alterations to provide a comprehensive view of DDR deficiency across 33 cancer types. Mutations with accompanying loss of heterozygosity were observed in over 1/3 of DDR genes, including TP53 and BRCA1/2. Other prevalent alterations included epigenetic silencing of the direct repair genes EXO5, MGMT, and ALKBH3 in 3c20% of samples. Homologous recombination deficiency (HRD) was present at varying frequency in many cancer types, most notably ovarian cancer. However, in contrast to ovarian cancer, HRD was associated with worse outcomes in several other cancers. Protein structure-based analyses allowed us to predict functional consequences of rare, recurrent DDR mutations. A new machine-learning-based classifier developed from gene expression data allowed us to identify alterations that phenocopy deleterious TP53 mutations. These frequent DDR gene alterations in many human cancers have functional consequences that may determine cancer progression and guide therapy. Knijnenburg et al. present The Cancer Genome Atlas (TCGA) Pan-Cancer analysis of DNA damage repair (DDR) deficiency in cancer. They use integrative genomic and molecular analyses to identify frequent DDR alterations across 33 cancer types, correlate gene- and pathway-level alterations with genome-wide measures of genome instability and impaired function, and demonstrate the prognostic utility of DDR deficiency scores

Risks of seroconversion of hepatitis B, hepatitis C and human immunodeficiency viruses in children with multitransfused thalassaemia major

Objectives: To estimate the risks of seroconversion of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency viruses (HIV) in children with multitransfused thalassaemia at a thalassaemic clinic in Kuala Lumpur, Malaysia. Methods: Seventy-two children (39 males, median age 11.3 years, 2.5th-97.5th centile: 1.4-19.2 years) with thalassaemia major were studied. The risks of seroconversion of HBV, HCV and HIV were estimated by comparing the seroprevalences of hepatitis B surface antigen (HBsAg), anti-HCV and anti-HIV between a defined starting point and an end point. The end point was the point when latest serological results were available while the starting point was when regular transfusion was commenced, or approximately 5 years before the end point when the duration of transfusion was longer. Results: The median duration of the study was 49 months (range 8-69 months, total 2953 patient-months). There were 2605 transfusion episodes and 4154 units of blood transfused (0.88 transfusion episode/patient per month, 1.41 units of blood transfused/patient per month). There were three new seroconversions for anti-HCV but none for HBsAg and anti-HIV. The risk of seroconversion for HCV was one in 1384 units of blood transfused (95 CI: 4000-472). The seroprevalence rates at the starting and end points were: HBsAg (1, 1), anti-HCV (10, 13) and anti-HIV (0, 0), respectively. Conclusions: The estimated risk of acquiring HCV infection in children receiving multiple blood transfusions in this study is surprisingly higher than the generally accepted estimated risk. Other routes of transmission may be important. A prospective, multicentre study to estimate such risks more precisely is needed

Osthole Suppresses Hepatocyte Growth Factor (HGF)-Induced Epithelial-Mesenchymal Transition via Repression of the c-Met/Akt/mTOR Pathway in Human Breast Cancer Cells

Substantial activation of the HGF/c-Met signaling pathway is involved in the progression of several types of cancers and associated with increased tumor invasion and metastatic potential. Underlying HGF-induced tumorigenesis, epithelial to mesenchymal transition (EMT) shows a positive correlation with progression in patients. We previously determined that osthole is a potent fatty acid synthase (FASN) inhibitor. FASN is implicated in Cancer progression and may regulate lipid raft function. We therefore examined whether osthole could block HGF-induced tumorigenesis by disrupting lipid rafts. Here, we found that osthole could abrogate HGF-induced cell scattering, migration, and invasion in MCF-7 breast cancer cells. Osthole also effectively inhibited the HGF-induced decrease of E-cadherin and increase of vimentin via down-regulation of phosphorylated Akt and mTOR. Interestingly, osthole blocked HGF-induced c,,Met:phosphorylation and repressed the expression of total c-Met protein in MCF-7 cells. In addition, C75, a pharmacological inhibitor of FASN, repressed the expression of total c-Met protein in MCF-7 cells. Consistent with a role for FASN, loss of c-Met in cells treated with osthole was prevented by the exogenous addition of palmitate. Briefly, our result suggests a connection between FASN activity and c-Met, protein expression and that osthole is a potential compound for breast cancer therapy by targeting the major pathway of HGF/C-Met-induced EMT