Genetic structure and diversity of the Chilean flat oyster Ostrea chilensis (Bivalvia: Ostreidae) along its natural distribution from natural beds subject to different fishing histories

Ostrea chilensis (Küster, 1844), the flat oyster, is native to Chile and New Zealand. In Chile, it occurs in a few natural beds, from the northern part of Chiloé Island (41 ºS) to the Guaitecas Archipelago (45 ºS). This bivalve is slow growing, broods its young, and has very limited dispersal potential. The Ostrea chilensis fishery has been over-exploited for a number of decades such that in some locations oysters no longer exist. The aim of this study was to study the genetic diversity of the Chilean flat oyster along its natural distribution to quantify the possible impact of the dredge fishery on wild populations. The genetic structure and diversity of Ostrea chilensis from six natural beds with different histories of fishing activity were estimated. Based on mitochondrial (Cytb) and nuclear (ITS1) DNA sequence variation, our results provide evidence that genetic diversity is different among populations with recent history of wild dredge fishery efforts. We discuss the possible causes of these results. Ultimately, such new information may be used to develop and apply new management measures to promote the sustainable use of this valuable marine resource.     

Prevalence rate and risk factors of human cystic echinococcosis: A cross-sectional,community-based,abdominal ultrasound study in rural and urban north-central Chile

BackgroundCystic echinococcosis (CE) caused by Echinococcus granulosus sensu lato (s.l.) is a neglected and underdiagnosed parasitic zoonosis that has a significant socioeconomic impact on rural communities relying on livestock farming. CE is endemic across Latin America, including Chile, where the Coquimbo region exhibits a relatively high record of hospital-based human cases and infected animals. However, the incidence of hospitalized CE cases may underestimate the real burden of infection in a population, since the majority of cases never reach medical attention or official disease records.Methodology/Principal findingsIn 2019, a cross-sectional, community-based study was conducted with the objectives of estimating for the first time the prevalence of human abdominal CE using abdominal ultrasound (US) screening in volunteers residing in urban and rural localities of the Monte Patria municipality located in Limarí province, Coquimbo region, Chile, and identifying the risk factors associated with human infection. Pre-screening activities included a 16-h lecture/hands-on training aimed at rural physicians that focused on the diagnosis of CE by US, based on current WHO recommendations. A total of 2,439 (~8% of municipality inhabitants) people from thirteen target localities were screened by abdominal US in June-July 2019. We found an overall CE prevalence of 1.6% (95% CI 1.1–2.2) with a significantly higher likelihood of infection in rural localities, older age classes and people drinking non-potable water; 84.6% of infected volunteers were newly diagnosed with CE. Cysts were either in active or inactive stages in equal proportions; active cysts were detected in all age classes, while 95.7% of inactive cysts occurred in >40 years-old subjects.Conclusions/SignificanceThis is the first US survey aimed at detecting human infection caused by Echinococcus granulosus s.l. in Chile. Our findings indicate a high CE prevalence in the area, and contribute to define the demographic and behavioral risk factors promoting the transmission of the parasitic infection within target communities. Our results support the implementation of cost-effective strategies for the diagnosis, treatment and control of CE, and the need to improve the epidemiological surveillance system in Chile.     

A network-based approach to integrate nutrient microenvironment in the prediction of synthetic lethality in cancer metabolism

Synthetic Lethality (SL) is currently defined as a type of genetic interaction in which the loss of function of either of two genes individually has limited effect in cell viability but inactivation of both genes simultaneously leads to cell death. Given the profound genomic aberrations acquired by tumor cells, which can be systematically identified with -omics data, SL is a promising concept in cancer research. In particular, SL has received much attention in the area of cancer metabolism, due to the fact that relevant functional alterations concentrate on key metabolic pathways that promote cellular proliferation. With the extensive prior knowledge about human metabolic networks, a number of computational methods have been developed to predict SL in cancer metabolism, including the genetic Minimal Cut Sets (gMCSs) approach. A major challenge in the application of SL approaches to cancer metabolism is to systematically integrate tumor microenvironment, given that genetic interactions and nutritional availability are interconnected to support proliferation. Here, we propose a more general definition of SL for cancer metabolism that combines genetic and environmental interactions, namely loss of gene functions and absence of nutrients in the environment. We extend our gMCSs approach to determine this new family of metabolic synthetic lethal interactions. A computational and experimental proof-of-concept is presented for predicting the lethality of dihydrofolate reductase (DHFR) inhibition in different environments. Finally, our approach is applied to identify extracellular nutrient dependences of tumor cells, elucidating cholesterol and myo-inositol depletion as potential vulnerabilities in different malignancies.     

Expression of the high molecular weight fibroblast growth factor-2 isoform of 210 amino acids is associated with modulation of protein kinases C delta and epsilon and ERK activation

The high molecular weight (HMW) fibroblast growth factor (FGF)-2 isoform of 210 amino acids initiated at a CUG start codon possesses a nuclear localization sequence and is not secreted. In contrast, the low molecular weight (LMW) isoform of 155 amino acids initiated at the AUG start codon can be secreted and activates the cell surface FGF receptors. The two isoforms possess different biological properties; however, little is known about the intracrine regulatory mechanisms involved in the biological effects of the HMW FGF-2 isoform. Using pancreatic cells stably transfected with cDNAs leading to the expression of either the HMW FGF-2 (A3 cells) or the LMW form (A5 cells), we provide evidence that the two FGF-2 isoforms differentially modulate PKC levels. The LMW FGF-2 up-regulated the PKC epsilon levels by 1.6-fold; by contrast the HMW isoform down-regulated the level of this PKC isotype by about 3-fold and increased the amount of PKC delta by 1.7-fold. PKC mRNAs were also modified, suggesting that PKC expression was regulated at a pretranslational level. Additionally, expression of different levels of the HMW FGF-2 with an inducible expression system confirmed the role of this isoform on PKC delta and epsilon expressions. Increased activation of ERK-1 and -2 was also observed in cells expressing the HMW FGF-2. By using different PKC inhibitors and a dominant negative PKC delta, it was found that ERK activation was PKC delta-dependent. These data indicate that expression of HMW FGF-2 can modify PKC levels by acting at the intracellular level and that the overexpression of PKC delta induces ERK-1/2 activation. The expression of a dominant negative FGFR1 did not reduce ERK-1/2 activation by the HMW FGF-2, suggesting that ERK activation does not require FGFR activity. The signaling cascade downstream of ERK might be involved in the known mitogenic effect exerted by this FGF-2 isoform.     

Neuronal nicotinic receptors: from protein structure to function

Neuronal nicotinic acetylcholine receptors are a prototype of ligand-gated channels that mediate transmission in the central and peripheral nervous system. Structure-function studies performed at the amino acid level are now unraveling the determinant residues either for the properties of the ligand-binding domain or the ionic pore. In this work we review, in the light of the latest finding, the structure-function relationship of these receptors and their implication in neurological diseases.     

Comparative study of physical properties of three suture materials: silk, e-PTFE (Gore-Tex), and PLA/PGA (Vicryl)

The aim of this in-vitro study was to compare the physical properties of three suture materials used in periodontal surgery: silk, expanded polytetrafluoroethylene (e-PTFE), and polylactic acid/polyglycolic and (PLA/PGA). Five physical tests were carried out on each of the three suture materials: strain to failure, tensile strength, knot tensile strength, knot slippage, and capillarity. For each test, 30 samples of each suture material were used. In all cases, the statistical results showed that the e-PTFE and the PLA/PGA threads were superior.     

Proteomic analysis identifies a new complex required for nuclear pre-mRNA retention and splicing

Using the proteomic tandem affinity purification (TAP) method, we have purified the Saccharomyces cerevisie U2 snRNP-associated splicing factors SF3a and SF3b. While SF3a purification revealed only the expected subunits Prp9p, Prp11p and Prp21p, yeast SF3b was found to contain only six subunits, including previously known components (Rse1p, Hsh155p, Cus1p, Hsh49p), the recently identified Rds3p factor and a new small essential protein (Ysf3p) encoded by an unpredicted split ORF in the yeast genome. Surprisingly, Snu17p, the proposed yeast orthologue of the seventh human SF3b subunit, p14, was not found in the yeast complex. TAP purification revealed that Snu17p, together with Bud13p and a newly identified factor, Pml1p/Ylr016c, form a novel trimeric complex. Subunits of this complex were not essential for viability. However, they are required for efficient splicing in vitro and in vivo. Furthermore, inactivation of this complex causes pre-mRNA leakage from the nucleus. The corresponding complex was named pre-mRNA REtention and Splicing (RES). The presence of RES subunit homologues in numerous eukaryotes suggests that its function is evolutionarily conserved.