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Funding: This study was supported by the Swiss National Science Foundation (grant P2BEP3_195232) and by the Academy of Finland (project 323527 and project 329251). Species' range shifts and local extinctions caused by climate change lead to community composition changes. At large spatial scales, ecological barriers, such as biome boundaries, coastlines, and elevation, can influence a community's ability to shift in response to climate change. Yet, ecological barriers are rarely considered in climate change studies, potentially hindering predictions of biodiversity shifts. We used data from two consecutive European breeding bird atlases to calculate the geographic distance and direction between communities in the 1980s and their compositional best match in the 2010s and modeled their response to barriers. The ecological barriers affected both the distance and direction of bird community composition shifts, with coastlines and elevation having the strongest influence. Our results underscore the relevance of combining ecological barriers and community shift projections for identifying the forces hindering community adjustments under global change. Notably, due to (macro)ecological barriers, communities are not able to track their climatic niches, which may lead to drastic changes, and potential losses, in community compositions in the future. Publisher PDF

Glyphosate is the most commonly used herbicide around the world, which led to its accumulation in the environment and consequent ubiquitous human exposure. Glyphosate is marketed in numerous glyphosate-based herbicide formulations (GBHs) that include co-formulants to enhance herbicidal effect of the active ingredient, but are declared as inert substances. However, these other ingredients can have biologic activity on their own and may interact with the glyphosate in synergistic toxicity. In this study, we focused to compare the cytogenetic effect of the active ingredient glyphosate and three marketed GBHs (Roundup Mega, Fozat 480, and Glyfos) by investigating cytotoxicity with fluorescent co-labeling and WST-1 cell viability assay as well as genotoxicity with cytokinesis block micronucleus assay in isolated human mononuclear white blood cells. Glyphosate had no notable cytotoxic activity over the tested concentration range (0-10,000 μM), whereas all the selected GBHs induced significant cell death from 1,000 μM regardless of metabolic activation (S9). Micronucleus (MN) formation induced by glyphosate and its formulations at sub-cytotoxic concentrations (0-100 μM) exhibited a diverse pattern. Glyphosate caused statistically significant increase of MN frequency at the highest concentration (100 μM) after 20-h exposure. Contrarily, Roundup Mega exerted a significant genotoxic effect at 100 μM both after 4- and 20-h exposures; moreover, Glyfos and Fozat 480 also resulted in a statistically significant increase of MN frequency from the concentration of 10 μM after 4-h and 20-h treatment, respectively. The presence of S9 had no effect on MN formation induced by either glyphosate or GBHs. The differences observed in the cytotoxic and genotoxic pattern between the active principle and formulations confirm the previous concept that the presence of co-formulants in the formulations or the interaction of them with the active ingredient is responsible for the increased toxicity of herbicide products, and draw attention to the fact that GBHs are still currently in use, the toxicity of which rivals that of POEA-containing formulations (e.g., Glyfos) already banned in Europe. Hence, it is advisable to subject them to further comprehensive toxicological screening to assess the true health risks of exposed individuals, and to reconsider their free availability to any users.

Supplementary methods, results and JAGS code

As main result we prove that Fej\'er means of Walsh-Kaczmarz-Fourier series are uniformly bounded operators from the Hardy martingale space $\ H_{p}$ to the Hardy martingale space $H_{p}$ for $ 0

Investigations on the impact of genetic factors on the development of obesity have been limited regarding the Roma population&mdash, the largest and most vulnerable ethnic minority in Europe of Asian origin. Genetic variants identified from genetic association studies are primarily from European populations. With that in mind, we investigated the applicability of data on selected obesity-related single nucleotide polymorphisms (SNPs), obtained from the Hungarian general (HG) population of European origin, on the Hungarian Roma (HR) population. Twenty preselected SNPs in susceptible alleles, known to be significantly associated with obesity-related phenotypes, were used to estimate the effect of these SNPs on body mass index (BMI) and waist circumference (WC) in HG (N = 1783) and HR (N = 1225) populations. Single SNP associations were tested using linear and logistic regression models, adjusted for known covariates. Out of 20 SNPs, four located in FTO (rs1121980, rs1558902, rs9939609, and rs9941349) showed strong association with BMI and WC as continuous variables in both samples. Computations based on Adult Treatment Panel III (ATPIII) and the International Diabetes Federation&rsquo, s (IDF) European and Asian criteria showed rs9941349 in FTO to be associated only with WC among both populations, and two SNPs (rs2867125, rs6548238) in TMEM18 associated with WC only in HG population. A substantial difference (both in direction and effect size) was observed only in the case of rs1801282 in PPAR&gamma, on WC as a continuous outcome. Findings suggest that genetic risk scores based on counting SNPs with relatively high effect sizes, defined based on populations with European ancestry, can sufficiently allow estimation of genetic susceptibility for Roma. Further studies are needed to clarify the role of SNP(s) with protective effect(s).

Chen and Hsiao gave the numerical solution of initial value problems of systems of linear differential equations with constant coefficients by Walsh polynomials approach. This result was improved by G\'at and Toledo for initial value problems of differential equations with variable coefficients on the interval $[0,1[$ and initial value $\xi=0$. In the present paper we discuss the general case while $\xi$ can take any arbitrary value in the interval $[0,1[$. We show the existence and uniform convergence of the numerical solution, as well.

The properties of the maximal operator of the $(C,\alpha)$-means ($\alpha=(\alpha_1,\ldots,\alpha_d)$) of the multi-dimensional Walsh-Kaczmarz-Fourier series are discussed, where the set of indices is inside a cone-like set. We prove that the maximal operator is bounded from $H_p^\gamma$ to $L_p$ for $p_0< p $ ($p_0=\max{1/(1+\alpha_k): k=1,\ldots, d}$) and is of weak type $(1,1)$. As a corollary we get the theorem of Simon \cite{S1} on the a.e. convergence of cone-restricted two-dimensional Fej\'er means of integrable functions. At the endpoint case $p=p_0$, we show that the maximal operator $\sigma^{\kappa,\alpha,*}_L$ is not bounded from the Hardy space $H_{p_0}^\gamma$ to the space $L_{p_0}$.

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Since the emergence of the acquired immune deficiency syndrome (AIDS), there has been a great deal of interest in identifying cofactors that accelerate progression of the disease elicit‐ ed by human immunodeficiency virus types 1 or 2 (HIV-1, HIV-2). Beside inherent factors and environmental agents, speculations led to the conclusion that infectious diseases fre‐ quently occur in HIV infected persons, might augment HIV replication, and consequently facilitate AIDS progression. HIV infection is followed by a long disease-free period, during which a low number of CD4+ immune cells contains transcriptionally silent provirus. Acti‐ vation of CD4+ cells by external factors, including heterologous viruses, terminates latency forcing towards a productive HIV infection. Transactivation of the HIV long terminal repeat (LTR) by cellular, nuclear transcriptional factors (e.g. NF-κB, Sp1) induced by mitogens, cy‐ tokines, chemokines, simultaneous virus infections is followed by gene expression including the synthesis of the HIV transactivator protein (TAT), which binds to the transactivating re‐ sponse (TAR) element of the genome, ultimately leading to large scale production of HIV and death of infected cells through apoptosis [1,2]. In vitro studies showed that products of immediate early (IE) or early (E) genes of several DNA viruses such as human herpesviruses (HHV) -1, 2, 3, 4, 5, 6A, 8, adenoviruses, as well as hepatitis B virus (HBV) X gene, human T lymphotropic virus type I (HTLV-I) tax gene upregulated production of these transcriptional factors and activate HIV-1 or HIV-2 in the same cells. Simultaneous infection in a single cell is relatively rare event in vivo; therefore such type of biological effects in nature could be minimal. On the contrary, cross-talk between immune cells carrying different viruses via cy‐ tokines, chemokines is more common. Heterologous viruses infect many types of cells, which are not targets of HIV, but release several immunomodulatory mediators, usually in

1.1 Latency and reactivation of HIV-1 Since the discovery of human immunodeficiency virus type 1 (HIV-1), there has been a great deal of interest in identifying cofactors that might accelerate the stages of development associated with acquired immunodeficiency syndrome (AIDS). Many environmental agents, namely inherent factors such as ethnicity and geographical location, were first implicated as risk factors in the study of HIV infection. However, speculation that infectious diseases may act as cofactors in HIV infection began to be studied soon thereafter. These speculations led to one of the early opinions that HIV plays a correlary role in AIDS, but not a causative role (Duesberg, 1989). AIDS patients have a history of both circumstantial serological and microbial evidence of increased exposure to a number of common and opportunistic infectious agents. It is difficult to ascertain, however, whether these various coinfections contribute anything to the progressive decline of the immune system (Pedersen et al., 1990). In vivo, infection with HIV-1 is followed by a long disease-free period, during which a low number of CD4+ mononuclear leukocytes (CCR5 coreceptor positive monocytes and CXCR4 coreceptor positive lymphocytes) containing transcriptionally silent integrated provirus can be found. HIV-1 replication can be demonstrated in only a small population of T cells without inducing clinical manifestations. This state of latency is partly due to low transcriptional activity of the integrated provirus in resting cells. Activation of CD4+ cells by antigens, mitogens (Tobiume et al., 1998) or superinfection by other viruses interacting with HIV-1 via viral and/or cellular transacting factors may terminate HIV-1 latency, leading to a productive HIV-1 infection. Transactivation of the HIV-1 long terminal repeat (LTR) in turn will induce gene expression, including the synthesis of the HIV-1 transactivator protein (TAT) (Arya et al., 1985). TAT will then independently amplify HIV-1 gene expression, ultimately leading to a high level of virus replication and death of infected cells. Onset and progression of AIDS correlates with augmented production of infectious virions parallel to a

Results of a retrospective study of patients who underwent pulmonary metastasectomies after colorectal surgery in the last five years are reported here. Prognostic factors are evaluated and analyzed in the context of current literature.37 lung resections were performed in 33 patients between 2001 and 2006, the male:female ratio was 19:14. The average age was 61.3 years (49-76). We analyzed the extent of lung resections, disease free intervals (DFI), laterality of the tumours, number and locations of metastases, lymph node involvements and the incidence of resection of hepatic metastases. Altogether, 20 solitary lung metastases were removed and 17 multiple resections were performed. 25 sublobar resections, 11 lobectomies and one pneumonectomy were carried out. 18 patients had right sided, eight patients had left sided and six patients had bilateral disease. 6 of the 33 patients underwent either synchronous or metachronous liver resection for hepatic metastases.Survivals were calculated by the Kaplan-Meier method. The average DFI was 27.6 months. When all patients were considered, the average survival was 28 months. 52% of the patients had a 3-year postoperative survival, if lung metastases were present only.Patients benefit from surgical removal of lung metastases of colorectal cancer. There were no differences in survival rates between patients who underwent resection of solitary or multiple lung metastases up to seven deposits. However, the average survival was 12 months shorter if hilar/mediastinal lymph nodes were involved. Furthermore, the average survival of six patients with hepatic metastases was 10 months shorter than the rest of the group. There was no benefit of DFI over 24 months. None of the other prognostic factors showed significant difference.

Kidney transplantation is a widely used method for the treatment o fend-stage renal disease. Between September 3, 1993 and December 2002 a total of 300 kidney transplantations were performed at the Department of Surgery at the Medical University of Pécs. In 24 patients simultaneous kidney and pancreas transplantation was performed. The mean age of the 189 male and 111 female patients was 42 years. The HLA B, Dr tissue antigen mismatches was 1.63. The average cold ischemic time was 1199 minutes whereas the average anastomotic time was 43 minutes. Early surgical complications happened to 16 patients. In spite of the immunosuppressive treatment 26 acute steroid resistant rejection have occurred, 9 of which were irreversible. In our opinion the meticulous surgical technique is as important as the postoperative care is. The early and late complications of 300 renal transplants are reviewed by the authors.

In this paper we investigate the norm convergence of Feje'r means of functions belonging to Lipschitz classes in that case when the orthonormal system is the unitary dyadic martingale différence system (UDMD system). We give an estimation of the order of norm convergence. The resuit of the paper shows a sharp constrast between the corresponding known Statement which relatives to the ordinary Walsh-Paley system.

Klebsiella pneumoniae is an important human pathogen, and causative agent of nosocomial infections. Clinical strains of K. pneumoniae can acquire antibiotic resistance to many commonly used beta-lactam antibiotics, including carbapenems, which are considered as one of the last resort antibiotics used for the treatment of multi-drug resistant (MDR) bacteria. The spread of MDR strains is a serious threat for public health. Therefore, it is important to use molecular typing of bacteria to trace the spread of MDR strains, especially in the hospital environment. We used pulsed field gel electrophoresis (PFGE) to determine the relatedness between ertapenem-resistant clinical isolates of K. pneumoniae, and reverse transcription quantitative polymerase chain reaction (RT-qPCR) to determine the expression of several genes coding for efflux pump components and porin channels in order to investigate the mechanisms of resistance to carbapenems and tigecycline in K. pneumoniae. The total of 70 ertapenem-resistant clinical isolates of K. pneumoniae was collected from different departments of Clinical Hospital Rijeka, Croatia during 2 years period. Antibiotic susceptibility to imipenem, meropenem, doripenem, tigecycline, colistin, ciprofloxacin, cefotaxime, and ceftazidime was determined by disk diffusion and E-test. All isolates were analyzed by PFGE after macrorestriction with Xba I restriction enzyme. PFGE data was analyzed by BioNumerics GelCompar II software, and dendogram showing genetic relationship between different isolates was created. RNA was isolated from a subset of ertapenem-resistant isolates, and reverse transcribed. Resulting cDNA was analyzed by RT-qPCR to determine if there is a difference in the expression of genes for efflux pump acrAB (acrA), outer membrane component of efflux pump tolC, and two porin channels, ompK35 and ompK36 between samples resistant to tigecycline, or carbapenems (imipenem, meropenem, and doripenem), and control strains that were susceptible to all carbapenems and tigecycline. All ertapenem-resistant isolates showed high-level resistance to broad-spectrum cephalosporins and ciprofloxacin, and eight isolates were also resistant to tigecycline, while five isolates showed reduced susceptibility or were resistant to at least one of the other carbapenems. All isolates were susceptible to colistin. Typeabilty by PFGE was 100%. All but one out of 70 isolates (98, 6 %) belonged to the same pulsogroup based on >80% similarity criterion, which implies that the isolates are the result of epidemic spread of single strain through the hospital. We did not find any statistically significant difference in the expression of acrA and tolC genes between resistant isolates and control group. However, we found significantly reduced expression of gene for ompK35 porin in isolates resistant to tigecycline compared to control strains, which implies that the downregulation of ompK35 porin might be one of the mechanisms of tigecycline resistance in K. pneumoniae.