Effect of hypokinesia on contractile function of cardiac muscle

Rats were subjected to hypokinesia for two months and the contractile function of isolated papillary muscle was studied. Hypokinesia reduced significantly the isotonic contraction rate which depended on the ATPase activity of the myofibrils; it also reduced the rate and index of relaxation which depended on the functional capacity of the Ca(++) pump of the sarcoplasmic reticulum. The maximum force of isometric contraction determined by the quantity of actomyosin bridges in the myofibrils did not change after hypokinesia. This complex of changes is contrary to that observed in adaptation to exercise when the rate of isotonic contraction and relaxation increases while the force of isometric contraction does not change. The possible mechanism of this stability of the contractile force during adaptation and readaptation of the heart is discussed

Effect of hypokinesia on cardiac contractile function and nervous regulation of the heart

Longterm hypokinesia caused cardiac deadaptation in rabbits, which resulted in the diminishing of the left ventricular rate of contraction and relaxation, joined later by decreased vascular resistance. As a results, the ejection rate as well as stroke volume and cardiac output were normal. The decrease of the relaxation speed was more obvious at a high heart rate and results in shortening of the diastolic pause and diminishing of cardiac output. Hearts of the hypokinetic animals were characterized by normal maximal pressure developed by a unit of muccardial mass aorta clamping, decreased adrenoreactivity, and increased cholinoreactivity. This complex of changes is contrary to changes observed in adaptation to exercise, but is similar to changes observed in compensatory hypertrophy of the heart

Hybridization of Common Reed in North America? The Answer is Blowing in the Wind

Background and aims: We review evidence for hybridization of Phragmites australis in North America and the implications for the persistence of native P. australis ssp. americanus populations in North America. We also highlight the need for an updated classification system, which takes P. australis intraspecific variation and hybridization into account. Methodology: We reviewed available published, in press, and in preparation literature to assess the likelihood of hybridization and interbreeding in genotypes of Phragmites australis present in North America. Principal results: Experimental results demonstrate that hybridization among introduced and native haplotypes is possible within the genus Phragmites, yet evidence that hybridization has naturally occurred is only starting to emerge. The lag in identifying hybridization in Phragmites in North America may be related to undersampling in some parts of North America and to a lack of molecular tools that provide the capability to recognize hybrids. Conclusions: Our understanding of the gene flow within and between species in the genus Phragmites is moving at a fast pace, especially on the east and Gulf coasts of North America. More attention should also be focused on the Great Lakes region, the southwestern and the west coast of the U.S. where sympatry has created opportunities for hybridization. Where hybridizations have been detected, there is currently no published data on how hybridization affects plant vigor, morphology, invasiveness, or conservation of the genetic integrity of the North American native subspecies. We conclude that detection of more hybridization is highly likely and that there is a need to develop new markers for the different Phragmites species and lineages to fill current knowledge gaps. Finally, we suggest that the classification system for P. australis should be updated and published to help clarify the nomenclature

DNA assays for genetic discrimination of three Phragmites australis subspecies in the United States

Premise: To genetically discriminate subspecies of the common reed (Phragmites australis), we developed real-time quantitative (qPCR) assays for identifying P. australis subsp. americanus, P. australis subsp. australis, and P. australis subsp. berlandieri. Methods and Results: Utilizing study-generated chloroplast DNA sequences, we developed three novel qPCR assays. Assays were verified on individuals of each subspecies and against two non-target species, Arundo donax and Phalaris arundinacea. One assay amplifies only P. australis subsp. americanus, one amplifies P. australis subsp. australis and/or P. australis subsp. berlandieri, and one amplifies P. australis subsp. americanus and/or P. australis subsp. australis. This protocol enhances currently available rapid identification methods by providing genetic discrimination of all three subspecies. Conclusions: The newly developed assays were validated using P. australis samples from across the United States. Application of these assays outside of this geographic range should be preceded by additional testing

Oncogenic RIT1 mutations in lung adenocarcinoma

Lung adenocarcinoma is comprised of distinct mutational subtypes characterized by mutually exclusive oncogenic mutations in RTK/RAS pathway members KRAS, EGFR, BRAF and ERBB2, and translocations involving ALK, RET and ROS1. Identification of these oncogenic events has transformed the treatment of lung adenocarcinoma via application of therapies targeted toward specific genetic lesions in stratified patient populations. However, such mutations have been reported in only ∼55% of lung adenocarcinoma cases in the United States, suggesting other mechanisms of malignancy are involved in the remaining cases. Here we report somatic mutations in the small GTPase gene RIT1 in ∼2% of lung adenocarcinoma cases that cluster in a hotspot near the switch II domain of the protein. RIT1 switch II domain mutations are mutually exclusive with all other known lung adenocarcinoma driver mutations. Ectopic expression of mutated RIT1 induces cellular transformation in vitro and in vivo, which can be reversed by combined PI3K and MEK inhibition. These data identify RIT1 as a driver oncogene in a specific subset of lung adenocarcinomas and suggest PI3K and MEK inhibition as a potential therapeutic strategy in RIT1-mutated tumors

Trust and reputation policy-based mechanisms for self-protection in autonomic communications

Currently, there is an increasing tendency to migrate the management of communications and information systems onto the Web. This is making many traditional service support models obsolete. In addition, current security mechanisms are not sufficiently robust to protect each management system and/or subsystem from web-based intrusions, malware, and hacking attacks. This paper presents research challenges in autonomic management to provide self-protection mechanisms and tools by using trust and reputation concepts based on policy-based management to decentralize management decisions. This work also uses user-based reputation mechanisms to help enforce trust management in pervasive and communications services. The scope of this research is founded in social models, where the application of trust and reputation applied in communication systems helps detect potential users as well as hackers attempting to corrupt management operations and services. These so-called “cheating services” act as “attacks”, altering the performance and the security in communication systems by consumption of computing or network resources unnecessarily

Global effects of DNA replication and DNA replication origin activity on eukaryotic gene expression

This report provides a global view of how gene expression is affected by DNA replication. We analyzed synchronized cultures of Saccharomyces cerevisiae under conditions that prevent DNA replication initiation without delaying cell cycle progression. We use a higher-order singular value decomposition to integrate the global mRNA expression measured in the multiple time courses, detect and remove experimental artifacts and identify significant combinations of patterns of expression variation across the genes, time points and conditions. We find that, first, ∼88% of the global mRNA expression is independent of DNA replication. Second, the requirement of DNA replication for efficient histone gene expression is independent of conditions that elicit DNA damage checkpoint responses. Third, origin licensing decreases the expression of genes with origins near their 3′ ends, revealing that downstream origins can regulate the expression of upstream genes. This confirms previous predictions from mathematical modeling of a global causal coordination between DNA replication origin activity and mRNA expression, and shows that mathematical modeling of DNA microarray data can be used to correctly predict previously unknown biological modes of regulation

Genome-scale analysis identifies paralog lethality as a vulnerability of chromosome 1p loss in cancer.

Functional redundancy shared by paralog genes may afford protection against genetic perturbations, but it can also result in genetic vulnerabilities due to mutual interdependency1-5. Here, we surveyed genome-scale short hairpin RNA and CRISPR screening data on hundreds of cancer cell lines and identified MAGOH and MAGOHB, core members of the splicing-dependent exon junction complex, as top-ranked paralog dependencies6-8. MAGOHB is the top gene dependency in cells with hemizygous MAGOH deletion, a pervasive genetic event that frequently occurs due to chromosome 1p loss. Inhibition of MAGOHB in a MAGOH-deleted context compromises viability by globally perturbing alternative splicing and RNA surveillance. Dependency on IPO13, an importin-β receptor that mediates nuclear import of the MAGOH/B-Y14 heterodimer9, is highly correlated with dependency on both MAGOH and MAGOHB. Both MAGOHB and IPO13 represent dependencies in murine xenografts with hemizygous MAGOH deletion. Our results identify MAGOH and MAGOHB as reciprocal paralog dependencies across cancer types and suggest a rationale for targeting the MAGOHB-IPO13 axis in cancers with chromosome 1p deletion

Policy language in restoration ecology

elating restoration ecology to policy is one of the aims of the Society for Ecological Restoration and its journal Restoration Ecology. As an interdisciplinary team of researchers in both ecological science and political science, we have struggled with how policy-relevant language is and could be deployed in restoration ecology. Using language in scientific publications that resonates with overarching policy questions may facilitate linkages between researcher investigations and decision-makers' concerns on all levels. Climate change is the most important environmental problem of our time and to provide policymakers with new relevant knowledge on this problem is of outmost importance. To determine whether or not policy-specific language was being included in restoration ecology science, we surveyed the field of restoration ecology from 2008 to 2010, identifying 1,029 articles, which we further examined for the inclusion of climate change as a key element of the research. We found that of the 58 articles with “climate change” or “global warming” in the abstract, only 3 identified specific policies relevant to the research results. We believe that restoration ecologists are failing to include themselves in policy formation and implementation of issues such as climate change within journals focused on restoration ecology. We suggest that more explicit reference to policies and terminology recognizable to policymakers might enhance the impact of restoration ecology on decision-making processes