Mitochondrial echoes of first settlement and genetic continuity in El Salvador

Background: From Paleo-Indian times to recent historical episodes, the Mesoamerican isthmus played an important role in the distribution and patterns of variability all around the double American continent. However, the amount of genetic information currently available on Central American continental populations is very scarce. In order to shed light on the role of Mesoamerica in the peopling of the New World, the present study focuses on the analysis of the mtDNA variation in a population sample from El Salvador. Methodology/Principal Findings: We have carried out DNA sequencing of the entire control region of the mitochondrial DNA (mtDNA) genome in 90 individuals from El Salvador. We have also compiled more than 3,985 control region profiles from the public domain and the literature in order to carry out inter-population comparisons. The results reveal a predominant Native American component in this region: by far, the most prevalent mtDNA haplogroup in this country (at ~90%) is A2, in contrast with other North, Meso- and South American populations. Haplogroup A2 shows a star-like phylogeny and is very diverse with a substantial proportion of mtDNAs (45%; sequence range 16090–16365) still unobserved in other American populations. Two different Bayesian approaches used to estimate admixture proportions in El Salvador shows that the majority of the mtDNAs observed come from North America. A preliminary founder analysis indicates that the settlement of El Salvador occurred about 13,400±5,200 Y.B.P.. The founder age of A2 in El Salvador is close to the overall age of A2 in America, which suggests that the colonization of this region occurred within a few thousand years of the initial expansion into the Americas. Conclusions/Significance: As a whole, the results are compatible with the hypothesis that today's A2 variability in El Salvador represents to a large extent the indigenous component of the region. Concordant with this hypothesis is also the observation of a very limited contribution from European and African women (~5%). This implies that the Atlantic slave trade had a very small demographic impact in El Salvador in contrast to its transformation of the gene pool in neighbouring populations from the Caribbean facade

Beringian Standstill and Spread of Native American Founders

Native Americans derive from a small number of Asian founders who likely arrived to the Americas via Beringia. However, additional details about the intial colonization of the Americas remain unclear. To investigate the pioneering phase in the Americas we analyzed a total of 623 complete mtDNAs from the Americas and Asia, including 20 new complete mtDNAs from the Americas and seven from Asia. This sequence data was used to direct high-resolution genotyping from 20 American and 26 Asian populations. Here we describe more genetic diversity within the founder population than was previously reported. The newly resolved phylogenetic structure suggests that ancestors of Native Americans paused when they reached Beringia, during which time New World founder lineages differentiated from their Asian sister-clades. This pause in movement was followed by a swift migration southward that distributed the founder types all the way to South America. The data also suggest more recent bi-directional gene flow between Siberia and the North American Arctic

Present and future evolution of advanced breast cancer therapy

Although the introduction of novel therapies and drug combinations has improved the prognosis of metastatic breast cancer, the disease remains incurable. Increased knowledge of the biology and the molecular alterations in breast cancer has facilitated the design of targeted therapies. These agents include receptor and nonreceptor tyrosine kinase inhibitors (epidermal growth factor receptor family), intracellular signaling pathways (phosphatidylinositol-3-kinase, AKT, mammalian target of rapamycin) angiogenesis inhibitors and agents that interfere with DNA repair (poly(ADP-ribose) polymerase inhibitors). In the present review, we present the most promising studies of these new targeted therapies and novel combinations of targeted therapies with cytotoxic agents

Temporal trends in disease-specific causes of cardiovascular mortality amongst patients with cancer in the USA between 1999 to 2019.

AIMS: We report disease-specific cardiovascular causes of mortality amongst cancer patients in the USA between 1999 to 2019, considering temporal trends by age, sex, and cancer site. METHODS AND RESULTS: We used the Multiple Cause of Death database, accessed through the CDC WONDER (Centres for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research) resource. We included 629,308 decedents with cardiovascular disease (CVD) recorded as the primary cause of death and active malignancy listed as a contributing cause of death. We created disease-specific CVD categories and grouped cancers by site. We calculated the proportion of CVD deaths attributed to each disease category stratified by sex, age, and cancer site. We also examined disease-specific temporal trends by cancer site. Ischaemic heart disease (IHD) was the most common cardiovascular cause of death across all cancer types (55.6%), being more common in men (59.8%), older ages, and in those with lung (67.8%) and prostate (58.3%) cancers. Cerebrovascular disease (12.9%) and hypertensive diseases (7.6%) were other common causes of death. The proportion of deaths due to heart failure was greatest in haematological (7.7%) and breast (6.3%) cancers. There was a decreasing temporal trend in the proportion of cardiovascular deaths attributed to IHD across all cancer types. The proportion of deaths due to hypertensive diseases showed the greatest percentage increase, with largest change in breast cancer patients (+191.1%). CONCLUSIONS: We demonstrate differential cardiovascular mortality risk by cancer site and demographics, providing insight into the evolving healthcare needs of this growing high cardiovascular risk population

The Emergence of Computing Disciplines in Communist Czechoslovakia: What’s in a (Sovietized) Name?

Part 1: Eastern EuropeInternational audienceDrawing upon archival evidence from the Czechoslovak government and its ministries from the 1970s, this paper presents a preliminary snapshot of the institutional processes that drove the emergence of computing disciplines separate from the rubric of Soviet cybernetics in Communist Czechoslovakia (nowadays, the Czech Republic and the Slovak Republic). We show that the new disciplines were created by a top-down order of the Czechoslovak government, which, in turn, was motivated by a larger scale initiative in the East Bloc. The disciplines created in the 1970s were as follows: Numerical Mathematics for an area of education akin to computer science, Electronic Computers for an area of education akin to computer engineering, and Automated Management/Control Systems for applied computing education. The evidence suggests that the cybernetics metaphor lost its organizing power in 1973 over the broad field of information processing in Czechoslovakia. This disciplinary shift, albeit not immediate, redistributed power between cybernetics and informatics. Indeed, it appears that even nowadays the distribution of power between the two disciplines in the Czech Republic is still in negotiation; what we term a “residual drift” has continued for almost 50 years as an impressive afterglow of the past fame of cybernetics in the east. In sum, the paper raises awareness of the fact that the emergence of computing disciplines behind the Iron Curtain was very different from the West. It also suggests that while academic research analogous to computer science thrived, other computing disciplines in Czechoslovakia were in more complicated positions. Although this paper focuses on Czechoslovakia, the method is generalizable and the data on enrollments may be compared to other countries. Thus, we provide a framework for the further study of similar disciplinary efforts in the remaining East Bloc countries

The blood indicators of Siberian sturgeon welfare

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