Spontaneous Echocardiographic Contrast (SPE) – An In-Vitro Study of the Impact of Cardiac-Output, Left-Ventricular DP/DT and Temperature

Recent clinical studies have indicated echocardiographic observations of gaseous emboli in the left ventricle (LV) and atrium (LA) during studies in patients with mechanical heart valves (MHV) in the mitral position. These reports have shown that the intensities of these gas bubbles in elderly patients are less than those in younger patients. These facts may indicate a correlation between formation of the gas bubbles and the LV functions. The goal was to utilize our pulse duplication system to create the corresponding physiologic conditions and to understand the impact of these parameters on SpE formation

Bi-allelic PAGR1 variants are associated with microcephaly and a severe neurodevelopmental disorder: genetic evidence from two families

Exome and genome sequencing were used to identify the genetic etiology of a severe neurodevelopmental disorder in two unrelated Ashkenazi Jewish families with three affected individuals. The clinical findings included a prenatal presentation of microcephaly, polyhydramnios and clenched hands while postnatal findings included microcephaly, severe developmental delay, dysmorphism, neurologic deficits, and death in infancy. A shared rare homozygous, missense variant (c.274A > G; p.Ser92Gly, NM_024516.4) was identified in PAGR1, a gene currently not associated with a Mendelian disease. PAGR1 encodes a component of the histone methyltransferase MLL2/MLL3 complex and may function in the DNA damage response pathway. Complete knockout of the murine Pagr1a is embryonic-lethal. Given the available evidence, PAGR1 is a strong candidate gene for a novel autosomal recessive severe syndromic neurodevelopmental disorder

Distribution and Extinction of Ungulates during the Holocene of the Southern Levant

BACKGROUND: The southern Levant (Israel, Palestinian Authority and Jordan) has been continuously and extensively populated by succeeding phases of human cultures for the past 15,000 years. The long human impact on the ancient landscape has had great ecological consequences, and has caused continuous and accelerating damage to the natural environment. The rich zooarchaeological data gathered at the area provide a unique opportunity to reconstruct spatial and temporal changes in wild species distribution, and correlate them with human demographic changes. METHODOLOGY: Zoo-archaeological data (382 animal bone assemblages from 190 archaeological sites) from various time periods, habitats and landscapes were compared. The bone assemblages were sorted into 12 major cultural periods. Distribution maps showing the presence of each ungulate species were established for each period. CONCLUSIONS: The first major ungulate extinction occurred during the local Iron Age (1,200-586 BCE), a period characterized by significant human population growth. During that time the last of the largest wild ungulates, the hartebeest (Alcelaphus buselaphus), aurochs (Bos primigenius) and the hippopotamus (Hippopotamus amphibius) became extinct, followed by a shrinking distribution of forest-dwelling cervids. A second major wave of extinction occurred only in the 19th and 20th centuries CE. Furthermore, a negative relationship was found between the average body mass of ungulate species that became extinct during the Holocene and their extinction date. It is thus very likely that the intensified human activity through habitat destruction and uncontrolled hunting were responsible for the two major waves of ungulate extinction in the southern Levant during the late Holocene

MiRNA-Mediated Control of HLA-G Expression and Function

HLA-G is a non-classical HLA class-Ib molecule expressed mainly by the extravillous cytotrophoblasts (EVT) of the placenta. The expression of HLA-G on these fetal cells protects the EVT cells from immune rejection and is therefore important for a healthy pregnancy. The mechanisms controlling HLA-G expression are largely unknown. Here we demonstrate that miR-148a and miR-152 down-regulate HLA-G expression by binding its 3′UTR and that this down-regulation of HLA-G affects LILRB1 recognition and consequently, abolishes the LILRB1-mediated inhibition of NK cell killing. We further demonstrate that the C/G polymorphism at position +3142 of HLA-G 3′UTR has no effect on the miRNA targeting of HLA-G. We show that in the placenta both miR-148a and miR-152 miRNAs are expressed at relatively low levels, compared to other healthy tissues, and that the mRNA levels of HLA-G are particularly high and we therefore suggest that this might enable the tissue specific expression of HLA-G