Gene expression profiling of two fish helminths throughout their complex life cycles. Are parasite’s life stages genetically decoupled?

Komplexe Lebenszyklen sind eine häufige, aber anspruchsvolle Lebensweise von Parasiten. Parasiten mit komplexen Lebenszyklen infizieren nacheinander mehrere Wirte und passen sich an verschiedene ökologische Nischen an. Werden in diesem Szenario dieselben Gene in allen Wirten einheitlich exprimiert? Die Hypothese der adaptiven Entkopplung besagt, dass verschiedene Stadien in einem komplexen Lebenszyklus genetisch und evolutionär unabhängig sind, was bedeutet, dass die Selektion auf Parasitenmerkmale in einem Wirt keine Auswirkungen auf Merkmale in anderen Wirten hat. Wir haben diese Hypothese anhand von zwei Parasitenarten getestet: dem Bandwurm Schistocephalus solidus und dem Fadenwurm Camallanus lacustris. Die Transkriptomsequenzierung wurde an Proben während ihrer komplexen Lebenszyklen durchgeführt. Die Genexpressionsanalyse wurde durchgeführt, um Gene zu identifizieren, die zwischen den Wirten, zwischen den Funktionsstadien und zwischen den Bedingungen unterschiedlich exprimiert werden. Darüber hinaus wurde mit einer Analyse der Anreicherung von Gensätzen untersucht, ob ähnliche biologische Funktionen von ähnlichen Genen in verschiedenen Stadien kodiert werden. Unsere Ergebnisse zeigen signifikante Unterschiede in der Genexpression zwischen den verschiedenen Stadien, wobei keine positive Korrelation zwischen Stadien mit derselben Aufgabe oder demselben Wirt beobachtet wurde. Gene, die in einem Stadium hochreguliert (oder herunterreguliert) werden, werden in anderen Stadien nicht in ähnlicher Weise exprimiert. Dies spricht für die Unabhängigkeit der einzelnen Stadien bei der Genexpression, die es den Parasiten ermöglicht, ihren Phänotyp als Reaktion auf unterschiedlichen Selektionsdruck zu modulieren. Diese Ergebnisse bestätigen die Hypothese der adaptiven Entkopplung bei parasitären Würmern und bieten Einblicke in den evolutionären Erfolg dieser Lebensweise.Complex life cycles are a common but demanding lifestyle among parasites. Parasites with complex life cycles sequentially infect multiple hosts, adapting to various ecological niches using information encoded within a single genome. In this scenario, are the same genes expressed consistently across all hosts, as might occur when parasite stages perform similar functions? The adaptive decoupling hypothesis posits that different stages in a complex life cycle are genetically and evolutionarily independent, meaning selection on parasite traits in one host does not affect traits in other hosts. We tested this hypothesis using two species of parasites: the tapeworm Schistocephalus solidus and the nematode Camallanus lacustris, both of which have three-host life cycles. Transcriptome sequencing was performed on samples throughout their complex life cycles, generating transcriptomes from 10 stages of S. solidus and 7 stages of C. lacustris. Gene expression analysis was conducted to identify genes differentially expressed between hosts, between functional stages, and between conditions. Additionally, gene set enrichment analysis assessed whether similar biological functions are encoded by similar genes across stages. Our findings demonstrate significant differences in gene expression across stages, with no positive correlation observed between stages sharing the same task or host. The highest correlation occurred between stages sampled close in time. In conclusion, the lack of positive correlation between different life cycle stages indicates that genes up-regulated (or down-regulated) in one stage are not similarly expressed in other stages. This evidence supports the independence of each stage in gene expression, enabling parasites to modulate their phenotype in response to different selective pressures. These findings corroborate the adaptive decoupling hypothesis in parasitic worms with complex life cycles, offering insights into the evolutionary success of this lifestyle

Mexican petroleum since nationalization.

Thesis (M.A.)--Boston UniversityThe first successful commercial exploitation of Mexican petroleum took place during the last decade of Porfirio Diaz's regime (1900-1910). Favorable concessions were given to British and American oil companies. Under these conditions, Mexico by 1921 had become the world's second largest oil producing country. The Revolution of 1910-1920 brought about profound changes in Mexico. There emerged a highly nationalistic orientation toward subsoil wealth. As a result, Article 27 of the 1917 Constitution vested ownership and control of mineral and petroleum deposits in the nation. In addition, there arose in post-Revolutionary Mexico a strong labor movement generally backed by the government. Under these new conditions, friction developed between the labor movement and Mexican government, on the one hand, and the foreign petroleum companies on the other, leading to the expropriation of the oil companies by the Mexican government on March 18, 1938. [TRUNCATED

Proteomics and Mass Spectrometry: What Have We Learned About The Heart?

The emergence of new platforms for the discovery of innovative therapeutics has provided a means for diagnosing cardiac disease in its early stages. Taking into consideration the global health burden of cardiac disease, clinicians require innovations in medical diagnostics that can be used for risk stratification. Proteomic based studies offer an avenue for the discovery of proteins that are differentially regulated during disease; such proteins could serve as novel biomarkers of the disease state. For instance, in clinical practice, the abundance of such biomarkers in blood could be correlated with the severity of the disease state. As such, early detection of biomarkers would enable an improvement in patient prognosis. In this review, we outline advancements in various proteomic platforms used to study the disease proteome and their applications to the field of clinical medicine. Specifically, we highlight the contributions of proteomic-based profiling experiments to the analysis of cardiovascular diseases

No association between candidate genes for color determination and color phenotype in Hierophis viridiflavus, and characterization of a contact zone

Genetic and phenotypic differentiation in allopatric conditions can be explained either by neutral phenomena or adaptative processes driven by selection. In reptiles, coloration can affect aspects directly related to their survival, representing a classical character under selection. In this context, secondary contact areas are natural laboratory to understand evolutionary processes underlying genetic permeability, especially when populations differ in phenotypic traits such as coloration. The western whip snake Hierophis viridiflavus presents two divergent mitochondrial clades, characterized by the presence of one of two main color phenotypes, namely one with black and yellow stripes and a fully melanic one. Here, we investigated whether melanogenesis-linked genes are determinant of the chromatic differences observed across the phenotypic variation of the species. In addition, we used a multilocus dataset, including 134 original ND4 sequences, to better define the overall genetic structure and to provide a characterization of a contact zone identified in Central Italy by estimating the amount of nuclear gene exchange. While we found no evidence supporting a direct association between target genes and coloration, a non-synonymous substitution polymorphism, at high frequency, was detected in the β melanocyte-stimulating hormone whose possible function has been discussed. Concerning the genetic structure, both mtDNA and nuDNA were partly concordant indicating introgression events occurring at the contact zone. When we measured the nuclear gene flow, we found a significant amount of gene exchange, mainly guided from one clade to the other, that is, asymmetric. These results might suggest the presence of ecological and/or behavioral processes driving the observed directional gene flow

Distinct regions in the 3′ untranslated region are responsible for targeting and stabilizing utrophin transcripts in skeletal muscle cells

In this study, we have sought to determine whether utrophin transcripts are targeted to a distinct subcellular compartment in skeletal muscle cells, and have examined the role of the 3′ untranslated region (UTR) in regulating the stability and localization of utrophin transcripts. Our results show that utrophin transcripts associate preferentially with cytoskeleton-bound polysomes via actin microfilaments. Because this association is not evident in myoblasts, our findings also indicate that the localization of utrophin transcripts with cytoskeleton-bound polysomes is under developmental influences. Transfection of LacZ reporter constructs containing the utrophin 3′UTR showed that this region is critical for targeting chimeric mRNAs to cytoskeleton-bound polysomes and controlling transcript stability. Deletion studies resulted in the identification of distinct regions within the 3′UTR responsible for targeting and stabilizing utrophin mRNAs. Together, these results illustrate the contribution of posttranscriptional events in the regulation of utrophin in skeletal muscle. Accordingly, these findings provide novel targets, in addition to transcriptional events, for which pharmacological interventions may be envisaged to ultimately increase the endogenous levels of utrophin in skeletal muscle fibers from Duchenne muscular dystrophy (DMD) patients

Global phosphoproteomic profiling reveals perturbed signaling in a mouse model of dilated cardiomyopathy

Phospholamban (PLN) plays a central role in Ca2+ homeostasis in cardiac myocytes through regulation of the sarco(endo)plasmic reticulum Ca2+-ATPase 2A (SERCA2A) Ca2+ pump. An inherited mutation converting arginine residue 9 in PLN to cysteine (R9C) results in dilated cardiomyopathy (DCM) in humans and transgenic mice, but the downstream signaling defects leading to decompensation and heart failure are poorly understood. Here we used precision mass spectrometry to study the global phosphorylation dynamics of 1,887 cardiac phosphoproteins in early affected heart tissue in a transgenic R9C mouse model of DCM compared with wild-type littermates. Dysregulated phosphorylation sites were quantified after affinity capture and identification of 3,908 phosphopeptides from fractionated whole-heart homogenates. Global statistical enrichment analysis of the differential phosphoprotein patterns revealed selective perturbation of signaling pathways regulating cardiovascular activity in early stages of DCM. Strikingly, dysregulated signaling through the Notch-1 receptor, recently linked to cardiomyogenesis and embryonic cardiac stem cell development and differentiation but never directly implicated in DCM before, was a prominently perturbed pathway. We verified alterations in Notch-1 downstream components in early symptomatic R9C transgenic mouse cardiomyocytes compared with wild type by immunoblot analysis and confocal immunofluorescence microscopy. These data reveal unexpected connections between stress-regulated cell signaling networks, specific protein kinases, and downstream effectors essential for proper cardiac function

The predictive value of fruit juice in the esophagus-pleural fistula.

Esophageal-pleural fistula is a rare and challenging condition to diagnose and requires strong clinical suspicion in order to be recognized promptly. Chest computed tomography (CT) with contrast medium for explain abbreviation (OS) is the gold standard for diagnosis. The definitive therapy is purely surgical, except for a few selected cases that benefit from endoscopic therapy. Our case involves a 45-year-old woman who came to the Emergency Department with dyspnea and thoracalgia. Chest X-ray and high-resolution CT showed empyema and pleural effusion to the left hemithorax. The lack of improvement despite the therapy and a subsequent clinical finding gave rise to the suspicion of esophageal-pleural fistula, confirmed with CT with contrast medium for OS. In this case, we opted for endoscopy correction of the esophageal defects. The diagnostic delay and the pre-existing comorbidities (previous kidney transplant for chronic kidney disease from lupus nephritis, high blood pressure, familiarity with Ischemic cardiomyopathy) could justify the inauspicious course of our case

Envisioning Resilience & Revitalization in the Apremont Triangle Neighborhood

ENVISIONING RESILIENCE AND REVITALIZATION IN THE APREMONT TRIANGLE NEIGHBORHOOD This urban design studio partnered with the City of Springfield to investigate the complexity of issues facing the Apremont Triangle neighborhood within the metro district and develop a range of conceptual designs. The studio focused on developing ideas that improve the livability of the neighborhoods, walkability of streets, and improve the environmental and economic health of the neighborhood. Resiliency in this context means that the neighborhood strives for a social and physical balance. The Studio began by conducting an inventory and analysis of cultural, economic, and ecological factors that influence the neighborhood. A series of community engagement strategies were employed to gather input and perspective of neighborhood needs. These included an online survey, meetings with neighborhood organizations and key stakeholders, a storefront gallery display on Chestnut Street, and a findings presentation to the community. The proposed conceptual designs aim to revitalize and improve the neighborhood in a many ways including, walkability and connectivity of the neighborhood, employing green stormwater management practices, phytotechnologies, increasing urban agriculture, illustrating local education and business opportunities. Project Significance: This studio reached out to numerous community organizations and created new partnerships that will benefit future research and design work. This effort will strengthen the role of community organizations in the city and give them a stronger voice. The work reveals the underused potentials of a neglected and underused area in the city of Springfield

Cardiac-Specific Elevations in Thyroid Hormone Enhance Contractility and Prevent Pressure Overload-Induced Cardiac Dysfunction

Thyroid hormone (TH) is critical for cardiac development and heart function. In heart disease, TH metabolism is abnormal, and many biochemical and functional alterations mirror hypothyroidism. Although TH therapy has been advocated for treating heart disease, a clear benefit of TH has yet to be established, possibly because of peripheral actions of TH. To assess the potential efficacy of TH in treating heart disease, type 2 deiodinase (D2), which converts the prohormone thyroxine to active triiodothyronine (T3), was expressed transiently in mouse hearts by using the tetracycline transactivator system. Increased cardiac D2 activity led to elevated cardiac T3 levels and to enhanced myocardial contractility, accompanied by increased Ca(2+) transients and sarcoplasmic reticulum (SR) Ca(2+) uptake. These phenotypic changes were associated with up-regulation of sarco(endo)plasmic reticulum calcium ATPase (SERCA) 2a expression as well as decreased Na(+)/Ca(2+) exchanger, beta-myosin heavy chain, and sarcolipin (SLN) expression. In pressure overload, targeted increases in D2 activity could not block hypertrophy but could completely prevent impaired contractility and SR Ca(2+) cycling as well as altered expression patterns of SERCA2a, SLN, and other markers of pathological hypertrophy. Our results establish that elevated D2 activity in the heart increases T3 levels and enhances cardiac contractile function while preventing deterioration of cardiac function and altered gene expression after pressure overload