A High Through-Put Reverse Genetic Screen Identifies Two Genes Involved in Remote Memory in Mice

Previous studies have revealed that the initial stages of memory formation require several genes involved in synaptic, transcriptional and translational mechanisms. In contrast, very little is known about the molecular and cellular mechanisms underlying later stages of memory, including remote memory (i.e. 7-day memory). To identify genes required for remote memory, we screened randomly selected mouse strains harboring known mutations. In our primary reverse genetic screen, we identified 4 putative remote memory mutant strains out of a total of 54 lines analyzed. Additionally, we found 11 other mutant strains with other abnormal profiles. Secondary screens confirmed that mutations of integrin β2 (Itgβ2) and steryl-O-acyl transferase 1 (Soat1) specifically disrupted remote memory. This study identifies some of the first genes required for remote memory, and suggests that screens of targeted mutants may be an efficient strategy to identify molecular requirements for this process

Muscleblind-Like 1 Knockout Mice Reveal Novel Splicing Defects in the Myotonic Dystrophy Brain

Myotonic dystrophy type 1 (DM1) is a multi-systemic disorder caused by a CTG trinucleotide repeat expansion (CTGexp) in the DMPK gene. In skeletal muscle, nuclear sequestration of the alternative splicing factor muscleblind-like 1 (MBNL1) explains the majority of the alternative splicing defects observed in the HSALR transgenic mouse model which expresses a pathogenic range CTGexp. In the present study, we addressed the possibility that MBNL1 sequestration by CUGexp RNA also contributes to splicing defects in the mammalian brain. We examined RNA from the brains of homozygous Mbnl1ΔE3/ΔE3 knockout mice using splicing-sensitive microarrays. We used RT-PCR to validate a subset of alternative cassette exons identified by microarray analysis with brain tissues from Mbnl1ΔE3/ΔE3 knockout mice and post-mortem DM1 patients. Surprisingly, splicing-sensitive microarray analysis of Mbnl1ΔE3/ΔE3 brains yielded only 14 candidates for mis-spliced exons. While we confirmed that several of these splicing events are perturbed in both Mbnl1 knockout and DM1 brains, the extent of splicing mis-regulation in the mouse model was significantly less than observed in DM1. Additionally, several alternative exons, including Grin1 exon 4, App exon 7 and Mapt exons 3 and 9, which have previously been reported to be aberrantly spliced in human DM1 brain, were spliced normally in the Mbnl1 knockout brain. The sequestration of MBNL1 by CUGexp RNA results in some of the aberrant splicing events in the DM1 brain. However, we conclude that other factors, possibly other MBNL proteins, likely contribute to splicing mis-regulation in the DM1 brain

Bi-Directional Effect of Cholecystokinin Receptor-2 Overexpression on Stress-Triggered Fear Memory and Anxiety in the Mouse

Fear, an emotional response of animals to environmental stress/threats, plays an important role in initiating and driving adaptive response, by which the homeostasis in the body is maintained. Overwhelming/uncontrollable fear, however, represents a core symptom of anxiety disorders, and may disturb the homeostasis. Because to recall or imagine certain cue(s) of stress/threats is a compulsory inducer for the expression of anxiety, it is generally believed that the pathogenesis of anxiety is associated with higher attention (acquisition) selectively to stress or mal-enhanced fear memory, despite that the actual relationship between fear memory and anxiety is not yet really established. In this study, inducible forebrain-specific cholecystokinin receptor-2 transgenic (IF-CCKR-2 tg) mice, different stress paradigms, batteries of behavioral tests, and biochemical assays were used to evaluate how different CCKergic activities drive fear behavior and hormonal reaction in response to stresses with different intensities. We found that in IF-CCKR-2 tg mice, contextual fear was impaired following 1 trial of footshock, while overall fear behavior was enhanced following 36 trials of footshock, compared to their littermate controls. In contrast to a standard Yerkes-Dodson (inverted-U shaped) stress-fear relationship in control mice, a linearized stress-fear curve was observed in CCKR-2 tg mice following gradient stresses. Moreover, compared to 1 trial, 36 trials of footshock in these transgenic mice enhanced anxiety-like behavior in other behavioral tests, impaired spatial and recognition memories, and prolonged the activation of adrenocorticotropic hormone (ACTH) and glucocorticoids (CORT) following new acute stress. Taken together, these results indicate that stress may trigger two distinctive neurobehavioral systems, depending on both of the intensity of stress and the CCKergic tone in the brain. A “threshold theory” for this two-behavior system has been suggested

Antimicrobial susceptibility patterns and characterization of clinical isolates of Staphylococcus aureus in KwaZulu-Natal province, South Africa

BACKGROUND: Antimicrobial resistance of Staphylococcus aureus especially methicillin-resistant S. aureus (MRSA) continues to be a problem for clinicians worldwide. However, few data on the antibiotic susceptibility patterns of S. aureus isolates in South Africa have been reported and the prevalence of MRSA in the KwaZulu-Natal (KZN) province is unknown. In addition, information on the characterization of S. aureus in this province is unavailable. This study investigated the susceptibility pattern of 227 S. aureus isolates from the KZN province, South Africa. In addition, characterization of methicillin-sensitive S. aureus (MSSA) and MRSA are reported in this survey. METHODS: The in-vitro activities of 20 antibiotics against 227 consecutive non-duplicate S. aureus isolates from clinical samples in KZN province, South Africa were determined by the disk-diffusion technique. Isolates resistant to oxacillin and mupirocin were confirmed by PCR detection of the mecA and mup genes respectively. PCR-RFLP of the coagulase gene was employed in the characterization of MSSA and MRSA. RESULTS: All the isolates were susceptible to vancomycin, teicoplanin and fusidic acid, and 26.9% of isolates studied were confirmed as MRSA. More than 80% of MRSA were resistant to at least four classes of antibiotics and isolates grouped in antibiotype 8 appears to be widespread in the province. The MSSA were also susceptible to streptomycin, neomycin and minocycline, while less than 1% was resistant to chloramphenicol, ciprofloxacin, rifampicin and mupirocin. The inducible MLS(B )phenotype was detected in 10.8% of MSSA and 82% of MRSA respectively, and one MSSA and one MRSA exhibited high-level resistance to mupirocin. There was good correlation between antibiotyping and PCR-RFLP of the coagulase gene in the characterization of MRSA in antibiotypes 1, 5 and 12. CONCLUSION: In view of the high resistance rates of MRSA to gentamicin, erythromycin, clindamycin, rifampicin and trimethoprim, treatment of MRSA infections in this province with these antibacterial agents would be unreliable. There is an emerging trend of mupirocin resistance among S. aureus isolates in the province. PCR-RFLP of the coagulase gene was able to distinguish MSSA from MRSA and offers an attractive option to be considered in the rapid epidemiological analysis of S. aureus in South Africa. Continuous surveillance on resistance patterns and characterization of S. aureus in understanding new and emerging trends in South Africa is of utmost importance

Expenditures on education and situation on the local labor market in the light of the human capital theory

Celem badań była próba oceny istnienia zależności pomiędzy wydatkami na edukację ponoszonymi przez gminy a sytuacją na lokalnym wiejskim rynku pracy. Nawiązano do problematyki kapitału ludzkiego i jego wpływu na rozwój społeczno-gospodarczy regionów, ze szczególnym uwzględnieniem obszarów wiejskich Pomorza Środkowego w Polsce. Wyniki analizy potwierdziły, że inwestycje w kapitał ludzki podnoszą poziom PKB.This article refers to a human capital and his impact on social-economic development regions with a special focus on rural communities of the Koszalin county. The article try to evaluate, ifis the relation between education expenditures and situation on the local labour market. In order to do it, the coefficient of Pearson linear correlation and the coefficient ofregression were applied. The time taken for analysis are the years 2000-2013. The available literature, statistical data ofthe Central Statistical Office, ofthe BDL (the Bank of Local Data), census data and data of the WUP (Voivodeship Labour Office) in Szczecin. In this context, in the spectrum of the human capitaltheory and the development, job activity of rural regions, it is worth undertaking a discussion concerning this subject

Impact of education and professional activity and the diversity of human capital of rural area of Koszalin district

W artykule poruszono ważną kwestię aktywności rynku pracy obszarów wiejskich w kontekście wykształ- cenia jego uczestników. Jako szczególnie istotne uznano wykształcenie, gdyż jest ono kluczowym czynnikiem rozwoju kapitału ludzkiego, a także wpływa na aktywność zawodową ludności. Poziom wykształcenia oraz podejmowanie kształcenia przez całe życie są aktualnie priorytetowymi uwarunkowaniami rozwoju, gdyż od ich jakości zależy rozwój regionów, a także całych gospodarek.This article raises an important issue of labor market activity in rural areas. As education was particularly important as a key factor in the development human capital and economic activity the population. The level of education and making life-long learning is a key determinant of development because of its quality depends development regions and entire economies. This article presents a diversifi ed structure of human capital in rural communities Koszalin district, and to show the relationship between the rate of professional activity and education the population

Educational competencies vs human capital diversification on rural areas in the Zachodniopomorskie province

Celem artykułu jest określenie poziomu zróżnicowania i klasyfikacja obszarów wiejskich województwa zachodniopomorskiego pod względem zasobów kapitału ludzkiego definiowanego w obszarze edukacji. W badaniu zastosowano metodę porządkowania liniowego bezwzorcową i w efekcie każdej jednostce przestrzennej przypisano miarę syntetyczną, opisującą łączny poziom zasobu. Przyjęto założenie o nierównym rozkładzie kapitału ludzkiego na obszarach wiejskich. Uzyskane wyniki potwierdzają, że obszary wiejskie w województwie zachodniopomorskim są zróżnicowane pod względem kapitału ludzkiego, a poziom kapitału można wyrazić jakościowymi kompetencjami edukacyjnymi mieszkańców danej jednostki (także w obszarze edukacji poza formalnej). Przestrzenne rozmieszczenie kapitału ludzkiego jest zgodne z typologią obszarów wiejskich dokonaną w ramach Monitoringu Rozwoju Obszarów Wiejskich. Wyższa koncentracja kapitału występuje na obszarach silnie zurbanizowanych (gminy typu 7), podczas gdy deficyty kapitału ujawniają się na obszarach peryferyjnych opartych na rolnictwie wielkoobszarowym, zwłaszcza w tzw. gminach popegeerowskich (gminy typu 2). Badaniem objęto obszary wiejskie zdefiniowane jako gminy wiejskie i wiejsko-miejskie wyodrębnione w oparciu o kryterium administracyjne zgodnie z nomenklaturą GUS. Źródłem danych były Okręgowa Komisja Egzaminacyjna (OKE) w Poznaniu, Narodowy Spis Powszechny 2011, Bank Danych Lokalnych GUS oraz Monitoring Rozwoju Obszarów Wiejskich etap I.The aim of the paper was to determine the level of differentiation and classification of rural areas in the Zachodniopomorskie province in terms of human capital resources defined in the field of education. The linear ordering method in the study was applied, and as a result, each spatial unit the synthetic indicator was assigned, describing the total level of the resource. It was assumed the uneven spatial distribution of human capital. The obtained results confirm: a higher level of human capital cumulating on highly urbanized areas and the occurrence of deficits on peripheral areas characterized by qualitatively low educational competences (also outside the formal). The study encompasses rural areas defined as rural and rural-urban gminas distinguished according to the GUS administrative criterion. The Regional Examination Board (OKE) in Poznan, the National Census of 2011 (NSP), the Local Data Bank of the CSO and the data of Rural Development Monitoring stage 1 were the main data source

EU Countries Socio-Economic Development in the Context of Europe 2020 Strategy

This article discusses important and current issues of sustainable development of the EU countries in the context of the Europe 2020 strategy (a strategy for smart, sustainable and inclusive growth). The main objective of this article is to prepare hierarchy and classification of the EU countries (including Norway and Croatia), showing the degree of core indicators implemented as described in the framework of the Europe 2020 strategy. Authors attempt to isolate groups of the EU countries which present similar development levels on the basis of accepted development indicators. It was attempts to determine: - the level of sustainable development EU countries (based on synthetic indicator), - trends in changing of sustainable development level EU countries, - the main factors determining the level of sustainable development level EU countries. Based on estimated indicators following assumptions were verified: the development distance between EU countries has steadily decreased and the economical factors are the most strongly determining factors of sustainable development. Selected methods of multivariable objects hierarchy and classification have been used in the study. In order to measure the level of sustainable development of the EU countries, linear ordering has been applied based on the standardized sums method. As a result, a relative level indicator of development has been assigned to each country. The classification of the EU countries has been made mainly according to the Ward hierarchical agglomeration procedure. Thus, groups of countries appeared have been similar in terms of analyzed characteristics. It allowed an attempt to determine basic features of these countries’ groups in terms of factors determining their development. Analysis will be carried out in spatial and time dimension as a part of the research. The subject of spatial analysis will be the EU countries, in particular their socio-economic development indicators as described in the Europe 2020 strategy framework. The time range of the study includes 2004 and 2012. Eurostat has been the main data source. Based on the obtained results, it has turned out that the development distance between European countries has been reduced. Analyzing changes of the level of the European countries development in 2004 and 2012 has showed visible process of catching-up development by countries in Central and Eastern Europe (with the leading position of Poland). Strong spatial differentiation of the European countries in terms of socio-economic development persists still. Analyzes have allowed to distinguish three groups of countries (both in the resulting hierarchy and grouping method): the Scandinavian countries and the countries of the so-called "the core of the EU", characterized by the highest level of life and the best economic situation. The second group of countries, called "Eastern bloc" of the enlargement of the EU in 2004 (except Malta), that are currently on the way of approximating their richer neighbours. They characterized by relatively high growth, mainly in the social sphere. The third group consists of countries that are in the structures of the EU for years, the countries of southern Europe (mainly Spain, Greece and Italy), in which the progress has not been observed or has been negligible. As many as three out of five features under examination (two of economy pillar and one of the society pillar) comparatively strongly explain the level of sustainable development indicator. It was proven that an environmental component was of less importance

Educational activity of rural areas in terms of human capital theory

Podjęto próbę oceny problemu aktywności edukacyjnej mieszkańców obszarów wiejskich w świetle teorii kapitału ludzkiego. W sytuacji zmieniających się warunków funkcjonowania całych gospodarek zwrócono uwagę na konieczność systematycznego wzrostu przeciętnego poziomu wykształcenia jako jednej z determinant kapitału ludzkiego. Wskazano zmiany, jakie zaszły w ostatnich latach w rozwoju kapitału ludzkiego na polskiej wsi oraz zasugerowano, iż formalny poziom edukacji nie jest wystarczający do zmniejszenia dysproporcji rozwojowych pomiędzy miastem a wsią. Zwrócono uwagę, że ważna jest aktywność edukacyjna mieszkańców wsi, również ta podejmowana na drodze nieformalnej w celu utrzymania aktywności zawodowej w późniejszym wieku.The article addresses the problem of education among rural residents using the theory of human capital. The world’s changing economic conditions force an increase in the average level of education, as one of most important determinants of human capital. The article shows the changes, that have occurred in the development of human capital in the Polish countryside in recent years, and suggests that the formal level of education is insufficient to reduce disparities between urban and rural areas. It is important for rural residents to undertake training or educational program, both informal and formal, to maintain employability later in life. Given the importance of education for human capital development and its impact on economic activity of the region’s residents, the study’s main objective is to analyze and assess the level of human capital in Poland’s rural areas and the educational efforts of their residents. The goal is achieved through the use of the statistical data obtained from GUS and the published domestic and foreign studies and reports

Resources of human capital on rural areas in Poland

Podjęto próbę oszacowania zasobów kapitału ludzkiego dla obszarów wiejskich w Polsce oraz ich hierarchii na podstawie wskaźnika zasobów kapitału ludzkiego (WZKL). Poszukiwano odpowiedzi na pytania, jaki jest stan zasobów kapitału ludzkiego na obszarach wiejskich w Polsce, które regiony charakteryzują się najwyższym, a które najniższym potencjałem kapitału ludzkiego, jakie jest zróżnicowanie badanych obszarów pod względem zasobów kapitału ludzkiego. Wykorzystując dostępną literaturę oraz dane GUS zweryfikowano przyjęte założenia o istnieniu silnego zróżnicowania w zasobach kapitału ludzkiego na obszarach wiejskich w Polsce.The main aim of this article is to estimate human capital resources on rural areas in Poland based on the human capital indicator. Following questions were formed: What is the state of human capital resources on rural areas in Poland? Which regions posses the highest/ lowest of human capital resources? How are rural areas in Poland diversified in terms of human capital resources? The assumption of differences in the resources of human capital on rural areas in Poland was verified. The available literature, statistical data of the Central Statistical Office, of the BDL (the Bank of Local Data), census data were used to estimate HC resources indicato