Stemness factor Sall4 is required for DNA damage response in embryonic stem cells.

Mouse embryonic stem cells (ESCs) are genetically more stable than somatic cells, thereby preventing the passage of genomic abnormalities to their derivatives including germ cells. The underlying mechanisms, however, remain largely unclear. In this paper, we show that the stemness factor Sall4 is required for activating the critical Ataxia Telangiectasia Mutated (ATM)-dependent cellular responses to DNA double-stranded breaks (DSBs) in mouse ESCs and confer their resistance to DSB-induced cytotoxicity. Sall4 is rapidly mobilized to the sites of DSBs after DNA damage. Furthermore, Sall4 interacts with Rad50 and stabilizes the Mre11-Rad50-Nbs1 complex for the efficient recruitment and activation of ATM. Sall4 also interacts with Baf60a, a member of the SWI/SNF (switch/sucrose nonfermentable) ATP-dependent chromatin-remodeling complex, which is responsible for recruiting Sall4 to the site of DNA DSB damage. Our findings provide novel mechanisms to coordinate stemness of ESCs with DNA damage response, ensuring genomic stability during the expansion of ESCs

Botulinum neurotoxin - Biochemical aspects and mechanism of action (Review)

Ботулиновият невротоксин (BoNT) е една от най-силните биологични субстанции, познати на човечеството. Продуцира се от спорообразуващи анаеробни бактерии Clostridium botulinum, които причиняват заболяването ботулизъм. BoNT блокира освобождаването на невротрансмитера ацетилхолин, провеждащ нервните импулси до мускулните влакна. По този начин токсинът косвено предизвиква мускулна парализа. Тази негова животозастрашаваща способност обаче се оказва изключително ефективна при терапия на редица заболявания, свързани с абнормна хиперактивация на мускули и жлези, естетически корекции на глаберални бръчки и други.Известни са девет серотипа на BoNT, наименовани с латинските букви от А-Н (BoNT-C е разделен на два типа), като типовете А, B, E и F причиняват ботулизъм при човека. Според някои автори са изследвани и изолати от хора, съдържащи BoNT-G.Изследват се и редица нови направления в медицинската практика, където BoNT може да се приложи ефективно - детска церебрална парализа, хронични анални фисури, урологични смущения и други.Botulinum neurotoxin (BoNT) is one of the most poisonous biological substances known to mankind. The toxin is produced by spore-forming anaerobic bacteria Clostridium botulinum, which causes botulism.BoNT blocks acetylcholine release - the principal neurotransmitter of the nerve impulses to muscle fibers. This indirectly causes muscle paralysis. This life-threatening ability, however, turns out to be extremely effective in the therapy of a number of diseases associated with hyperactivation of the muscles and glands, aesthetic corrections of glabellar wrinkles and others.There are nine serotypes of BoNT, named with the Latin letters from A to H (BoNT-C is separated into two types), as types A, B, E and F cause botulism in humans. According to some authors there are human isolates containing BoNT-G too.A number of new directions in the medical practice - cerebral palsy, chronic anal fissures, urological disorders and others - are currently under study for successful application of BoNT

Методически въпроси на икономическото изучаване на услугите на агроекоситемите

This study adapt a holistic interdisciplinary framework for analysis, assessment and improvement of the system of governance of agro-ecosystem services. A review is made on development of research on this "new" issue. Agroecosytems services and defined and classified. The management of agro-ecosystem services is defined, and principles modes of mechanisms affecting behaviours of agrarian and non-agrarian agents (institutional environment, market, private, collective, public and hybrid forms) characterised. Multiple personal, economic, political, international, natural, etc. factors for governing choice are identified. The stages for improvement of the governance of agro-ecosystem services are characterised. A framework for assessment of agro-ecosystem services is presented. Importance of organic agriculture as a major form of ecosystem management is analysed.Direction of application of client value in economic analysis are specified. An approach for analysing greed cities as a new perspective form for ecosystem services management is worked out. Multiple assessment of environmental pressure of agriculture in Bulgaria and analysed

Методически въпроси на икономическото изучаване на услугите на агроекоситемите

This study adapt a holistic interdisciplinary framework for analysis, assessment and improvement of the system of governance of agro-ecosystem services. A review is made on development of research on this "new" issue. Agroecosytems services and defined and classified. The management of agro-ecosystem services is defined, and principles modes of mechanisms affecting behaviours of agrarian and non-agrarian agents (institutional environment, market, private, collective, public and hybrid forms) characterised. Multiple personal, economic, political, international, natural, etc. factors for governing choice are identified. The stages for improvement of the governance of agro-ecosystem services are characterised. A framework for assessment of agro-ecosystem services is presented. Importance of organic agriculture as a major form of ecosystem management is analysed.Direction of application of client value in economic analysis are specified. An approach for analysing greed cities as a new perspective form for ecosystem services management is worked out. Multiple assessment of environmental pressure of agriculture in Bulgaria and analysed

Fractalkine Expression Induces Endothelial Progenitor Cell Lysis by Natural Killer Cells

BACKGROUND: Circulating CD34(+) cells, a population that includes endothelial progenitors, participate in the maintenance of endothelial integrity. Better understanding of the mechanisms that regulate their survival is crucial to improve their regenerative activity in cardiovascular and renal diseases. Chemokine-receptor cross talk is critical in regulating cell homeostasis. We hypothesized that cell surface expression of the chemokine fractalkine (FKN) could target progenitor cell injury by Natural Killer (NK) cells, thereby limiting their availability for vascular repair. METHODOLOGY/PRINCIPAL FINDINGS: We show that CD34(+)-derived Endothelial Colony Forming Cells (ECFC) can express FKN in response to TNF-α and IFN-γ inflammatory cytokines and that FKN expression by ECFC stimulates NK cell adhesion, NK cell-mediated ECFC lysis and microparticles release in vitro. The specific involvement of membrane FKN in these processes was demonstrated using FKN-transfected ECFC and anti-FKN blocking antibody. FKN expression was also evidenced on circulating CD34(+) progenitor cells and was detected at higher frequency in kidney transplant recipients, when compared to healthy controls. The proportion of CD34(+) cells expressing FKN was identified as an independent variable inversely correlated to CD34(+) progenitor cell count. We further showed that treatment of CD34(+) circulating cells isolated from adult blood donors with transplant serum or TNF-α/IFN-γ can induce FKN expression. CONCLUSIONS: Our data highlights a novel mechanism by which FKN expression on CD34(+) progenitor cells may target their NK cell mediated killing and participate to their immune depletion in transplant recipients. Considering the numerous diseased contexts shown to promote FKN expression, our data identify FKN as a hallmark of altered progenitor cell homeostasis with potential implications in better evaluation of vascular repair in patients

Оценка на устойчивостта на българското селско стопанство

This paper assesses the integral, governance, economic, social and environmental sustainability of Bulgarian agriculture. On the base official aggravate (statistical, etc.) and survey data approbation is made of elaborated holistic framework and evaluated sustainability level at different levels - national, sub sector, region, (agro)ecosystems, and farm. Website of the project: https://zem.alle.b

Case Report: Transthyretin Glu54Leu—a rare mutation with predominant cardiac phenotype

We report two unrelated Bulgarian families with hereditary transthyretin (ATTR) amyloidosis due to a rare p.Glu74Leu (Glu54Leu) pathogenic variant found in seven individuals—three of them symptomatic. Only one family with the same variant and with a Swedish origin has been clinically described so far. Our patients are characterized by predominant cardiac involvement, very much similar to the Swedish patients. Although the initial complaint was bilateral carpal tunnel syndrome, advanced amyloid cardiomyopathy was found in two symptomatic carriers at diagnosis with heart failure manifestations. The neurological involvement was considered as mild, with mainly sensory signs and symptoms being present. We followed a non-biopsy algorithm to confirm the diagnosis. Tafamidis 61 mg has been initiated as the only approved disease modifying treatment for ATTR cardiomyopathy. Clinical stability in the absence of adverse events has been observed at follow up

Устойчивост на селското стопанство в България

This paper gives answer to topical and debated research and practical questions at the current stage of development of Bulgarian agriculture - „what is sustainability of agriculture", „how to assess sustainability of agricultural in the conditions of EU CAP implementation in the country“, and „which are critical factors for improvement of socio-economic and environmental sustainability in the sector“. Evolution of the „concept“ of agrarian sustainability and the major approached for its assessment are discussed More precise definition of sustainability of Bulgarian agriculture is suggested and the requirements for the system of its assessment are characterised. For the first time a new „governance“ pillar of agrarian sustainability is included along with the universally accepted economic, social and environmental pillars (aspects). Practically applicable for the specific conditions of Bulgarian agriculture holistic framework for assessing sustainability level of agrarian systems of different types (sector, sub-sector, region, ecosystem, agricultural farm) is suggested. The later included 25 principles, 66 criteria, and 163 indicators and reference values for assessing integral, governance, economic, social and environmental sustainability as well as approach for their calculation, integration and interpretation. Approbation of the elaborated framework in assessment of agrarian sustainability at various levels (national, sub-sector, region, (agro)ecosystem, and farm) is made on the base of official statistical, etc, information and original farm surveys. Critical factors for improving sustainability of Bulgarian agriculture are identified, and recommendation made for amelioration of research and assessment practices, public policies and farming strategies for sustainable development. Website of the project: https://zem.alle.b

Устойчивост на селското стопанство в България

This paper gives answer to topical and debated research and practical questions at the current stage of development of Bulgarian agriculture - „what is sustainability of agriculture", „how to assess sustainability of agricultural in the conditions of EU CAP implementation in the country“, and „which are critical factors for improvement of socio-economic and environmental sustainability in the sector“. Evolution of the „concept“ of agrarian sustainability and the major approached for its assessment are discussed More precise definition of sustainability of Bulgarian agriculture is suggested and the requirements for the system of its assessment are characterised. For the first time a new „governance“ pillar of agrarian sustainability is included along with the universally accepted economic, social and environmental pillars (aspects). Practically applicable for the specific conditions of Bulgarian agriculture holistic framework for assessing sustainability level of agrarian systems of different types (sector, sub-sector, region, ecosystem, agricultural farm) is suggested. The later included 25 principles, 66 criteria, and 163 indicators and reference values for assessing integral, governance, economic, social and environmental sustainability as well as approach for their calculation, integration and interpretation. Approbation of the elaborated framework in assessment of agrarian sustainability at various levels (national, sub-sector, region, (agro)ecosystem, and farm) is made on the base of official statistical, etc, information and original farm surveys. Critical factors for improving sustainability of Bulgarian agriculture are identified, and recommendation made for amelioration of research and assessment practices, public policies and farming strategies for sustainable development. Website of the project: https://zem.alle.b