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Since December 2019, the global pandemic caused by the highly infectious novel coronavirus 2019-nCoV (COVID-19) has been rapidly spreading. As of April 2020, the outbreak has spread to over 210 countries, with over 2,400,000 confirmed cases and over 170,000 deaths [1]. COVID-19 causes a severe pneumonia characterized by fever, cough, and shortness of breath. Similar coronavirus outbreaks have occurred in the past causing severe pneumonia like COVID-19, most recently, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). However, over time, SARS-CoV and MERS-CoV were shown to cause extra-pulmonary signs and symptoms including hepatitis, acute renal failure, encephalitis, myositis, and gastroenteritis. Similarly, sporadic reports of COVID-19 related extrapulmonary manifestations emerge. Unfortunately, there is no comprehensive summary of the multi-organ manifestations of COVID-19, making it difficult for clinicians to quickly educate themselves about this highly contagious and deadly pathogen. What's more, is that SARS-CoV and MERS-CoV are the closest humanity has come to combating something similar to COVID-19, however, there exists no comparison between the manifestations of any of these novel coronaviruses. In this review, we summarize the current knowledge of the manifestations of the novel coronaviruses SARS-CoV, MERS-CoV, and COVID-19, with a particular focus on the latter, and highlight their differences and similarities.

How common polymorphisms in noncoding genome regions can regulate cellular function remains largely unknown. Here we show that cardiac fibrosis, mimicked using a hydrogel with controllable stiffness, affects the regulation of the phenotypes of human cardiomyocytes by a portion of the long noncoding RNA ANRIL, the gene of which is located in the disease-associated 9p21 locus. In a physiological environment, cultured cardiomyocytes derived from induced pluripotent stem cells obtained from patients who are homozygous for cardiovascular-risk alleles (R/R cardiomyocytes) or from healthy individuals who are homozygous for nonrisk alleles contracted synchronously, independently of genotype. After hydrogel stiffening to mimic fibrosis, only the R/R cardiomyocytes exhibited asynchronous contractions. These effects were associated with increased expression of the short ANRIL isoform in R/R cardiomyocytes, which induced a c-Jun N-terminal kinase (JNK) phosphorylation-based mechanism that impaired gap junctions (particularly, loss of connexin-43 expression) following stiffening. Deletion of the risk locus or treatment with a JNK antagonist was sufficient to maintain gap junctions and prevent asynchronous contraction of cardiomyocytes. Our findings suggest that mechanical changes in the microenvironment of cardiomyocytes can activate the regulation of their function by noncoding loci.

Carbapenem resistance in Enterobacterales is a public health threat. Klebsiella pneumoniae carbapenemase (encoded by alleles of the bla KPC family) is one of the most common transmissible carbapenem resistance mechanisms worldwide. The dissemination of bla KPC historically has been associated with distinct K. pneumoniae lineages (clonal group 258 [CG258]), a particular plasmid family (pKpQIL), and a composite transposon (Tn4401). In the United Kingdom, bla KPC has represented a large-scale, persistent management challenge for some hospitals, particularly in North West England. The dissemination of bla KPC has evolved to be polyclonal and polyspecies, but the genetic mechanisms underpinning this evolution have not been elucidated in detail; this study used short-read whole-genome sequencing of 604 bla KPC-positive isolates (Illumina) and long-read assembly (PacBio)/polishing (Illumina) of 21 isolates for characterization. We observed the dissemination of bla KPC (predominantly bla KPC-2; 573/604 [95%] isolates) across eight species and more than 100 known sequence types. Although there was some variation at the transposon level (mostly Tn4401a, 584/604 [97%] isolates; predominantly with ATTGA-ATTGA target site duplications, 465/604 [77%] isolates), bla KPC spread appears to have been supported by highly fluid, modular exchange of larger genetic segments among plasmid populations dominated by IncFIB (580/604 isolates), IncFII (545/604 isolates), and IncR (252/604 isolates) replicons. The subset of reconstructed plasmid sequences (21 isolates, 77 plasmids) also highlighted modular exchange among non-bla KPC and bla KPC plasmids and the common presence of multiple replicons within bla KPC plasmid structures (>60%). The substantial genomic plasticity observed has important implications for our understanding of the epidemiology of transmissible carbapenem resistance in Enterobacterales for the implementation of adequate surveillance approaches and for control.

Usutu virus (USUV) is an emerging mosquitoborne flavivirus with an increasing number of reports from several countries in Europe, where USUV infection has caused high avian mortality rates. However, 20 years after the first observed outbreak of USUV in Europe, there is still no reliable assessment of the large-scale impact of USUV outbreaks on bird populations. In this study, we identified the areas suitable for USUV circulation in Germany and analyzed the effects of USUV on breeding bird populations. We calculated the USUV-associated additional decline of common blackbird (Turdus merula) populations as 15.7% inside USUV-suitable areas but found no significant effect for the other 14 common bird species investigated. Our results show that the emergence of USUV is a further threat for birds in Europe and that the large-scale impact on population levels, at least for common blackbirds, must be considered.

Japanese encephalitis virus (JEV) is a substantial cause of viral encephalitis, morbidity, and mortality in South-East Asia and the Western Pacific. World Health Organization recognized Japanese Encephalitis (JE) as a public health priority in demands to initiate active vaccination programs. Recently, the geographic distribution of JEV has apparently expanded into other areas in the Pacific islands and northern Australia; however, major gaps exist in knowledge in regard to its current distribution. Here, we mapped the potential distribution of mosquito vectors of JEV (Culex tritaeniorhynchus, Cx. pseudovishnui, Cx. vishnui, Cx. fuscocephala, Cx. gelidus), and reservoirs (Egretta garzetta, E. intermedia, Nycticorax nycticorax) based on ecological niche modeling approach. Ecological niche models predicted all species to occur across Central, South and South East Asia; however, Cx. tritaeniorhynchus, E. garzetta, E. intermedia, and N. nycticorax had broader potential distributions extending west to parts of the Arabian Peninsula. All predictions were robust and significantly better than random (P

Purpose: To identify the incidence, risk factors and impact on long-term survival of invasive pulmonary aspergillosis (IPA) and Aspergillus colonisation in patients receiving vv-extracorporeal membrane oxygenation (ECMO).Methods: A retrospective evaluation was performed of patients receiving vv-ECMO at a tertiary hospital in Manchester (UK) between January 2012 and December 2016. Data collected included epidemiological data, microbiological cultures, radiographic findings and outcomes. Cases were classified as proven IPA, putative IPA or Aspergillus colonisation according to a validated clinical algorithm.Results: 134 patients were supported with vv-ECMO, median age of 45.5 years (range: 16.4- 73.4). Ten (7%) patients had putative IPA and 9 (7%) had Aspergillus colonisation. Half of the patients with putative IPA lacked classical host risk factors for IPA. Median number of days on ECMO prior to Aspergillus isolation was 5 days. Immunosuppression and influenza A infection were significantly associated with developing IPA in a logistic regression model. Cox regression model demonstrates a three times greater hazard of death associated with IPA. Overall 6-month mortality rate was 38%. Patients with putative IPA and colonized patients had a 6-month mortality rate of 80% and 11%, respectively. Conclusions: Immunosuppression and Influenza A infection are independent risk factors for IPA. IPA, but not Aspergillus colonisation, is associated with high long-term mortality in patients supported with vv-ECMO.

Actinobacterium strain S63T isolated from a soil sample collected from Spindrift Col on Signy Island (South Orkney Islands, maritime Antarctic) is a new species of the Intrasporangiaceae family. Here we report a draft genome sequence with an approximate size of 5 Mbp contained in 54 contigs (69.33% GC content). Preliminary analysis revealed the presence of cold active protein coding sequences, which may indicate an adaptation to the harsh polar environment from which the strain was isolated.

The occurrence of ectotherm disease vectors outside of their previous distribution area and the emergence of vector-borne diseases can be increasingly observed at a global scale and are accompanied by a growing number of studies which investigate the vast range of determining factors and their causal links. Consequently, a broad span of scientific disciplines is involved in tackling these complex phenomena. First, we evaluate the citation behaviour of relevant scientific literature in order to clarify the question “do scientists consider results of other disciplines to extend their expertise?” We then highlight emerging tools and concepts useful for risk assessment. Correlative models (regression-based, machine-learning and profile techniques), mechanistic models (basic reproduction number R 0) and methods of spatial regression, interaction and interpolation are described. We discuss further steps towards multidisciplinary approaches regarding new tools and emerging concepts to combine existing approaches such as Bayesian geostatistical modelling, mechanistic models which avoid the need for parameter fitting, joined correlative and mechanistic models, multi-criteria decision analysis and geographic profiling. We take the quality of both occurrence data for vector, host and disease cases, and data of the predictor variables into consideration as both determine the accuracy of risk area identification. Finally, we underline the importance of multidisciplinary research approaches. Even if the establishment of communication networks between scientific disciplines and the share of specific methods is time consuming, it promises new insights for the surveillance and control of vector-borne diseases worldwide.

Mutations within cytotoxic T lymphocyte (CTL) epitopes impair T cell recognition, but escape mutations arising in flanking regions that alter antigen processing have not been defined in natural human infections. In human histocompatibility leukocyte antigen (HLA)-B57+ HIV-infected persons, immune selection pressure leads to a mutation from alanine to proline at Gag residue 146 immediately preceding the NH2 terminus of a dominant HLA-B57–restricted epitope, ISPRTLNAW. Although N-extended wild-type or mutant peptides remained well-recognized, mutant virus–infected CD4 T cells failed to be recognized by the same CTL clones. The A146P mutation prevented NH2-terminal trimming of the optimal epitope by the endoplasmic reticulum aminopeptidase I. These results demonstrate that allele-associated sequence variation within the flanking region of CTL epitopes can alter antigen processing. Identifying such mutations is of major relevance in the construction of vaccine sequences.

Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) at gene loci that affect cardiovascular function, and while mechanisms in protein-coding loci are obvious, those in non-coding loci are difficult to determine. 9p21 is a recently identified locus associated with increased risk of coronary artery disease (CAD) and myocardial infarction. Associations have implicated SNPs in altering smooth muscle and endothelial cell properties but have not identified adverse effects in cardiomyocytes (CMs) despite enhanced disease risk. Using induced pluripotent stem cell-derived CMs from patients that are homozygous risk/risk (R/R) and non-risk/non-risk (N/N) for 9p21 SNPs and either CAD positive or negative, we assessed CM function when cultured on hydrogels capable of mimicking the fibrotic stiffening associated with disease post-heart attack, i.e. “heart attack-in-a-dish” stiffening from 11 kiloPascals (kPa) to 50 kPa. While all CMs independent of genotype and disease beat synchronously on soft matrices, R/R CMs cultured on dynamically stiffened hydrogels exhibited asynchronous contractions and had significantly lower correlation coefficients versus N/N CMs in the same conditions. Dynamic stiffening reduced connexin 43 expression and gap junction assembly in R/R CMs but not N/N CMs. To eliminate patient-to-patient variability, we created an isogenic line by deleting the 9p21 gene locus from a R/R patient using TALEN-mediated gene editing, i.e. R/R KO. Deletion of the 9p21 locus restored synchronous contractility and organized connexin 43 junctions. As a non-coding locus, 9p21 appears to repress connexin transcription, leading to the phenotypes we observe, but only when the niche is stiffened as in disease. These data are the first to demonstrate that disease-specific niche remodeling, e.g. a “heart attack-in-a-dish” model, can differentially affect CM function depending on SNPs within a non-coding locus.

During the last decades the disease vector Aedes albopictus ( Ae . albopictus ) has rapidly spread around the globe. The spread of this species raises serious public health concerns. Here, we model the present distribution and the future climatic suitability of Europe for this vector in the face of climate change. In order to achieve the most realistic current prediction and future projection, we compare the performance of four different modelling approaches, differentiated by the selection of climate variables (based on expert knowledge vs. statistical criteria) and by the geographical range of presence records (native range vs. global range). First, models of the native and global range were built with MaxEnt and were either based on (1) statistically selected climatic input variables or (2) input variables selected with expert knowledge from the literature. Native models show high model performance (AUC: 0.91–0.94) for the native range, but do not predict the European distribution well (AUC: 0.70–0.72). Models based on the global distribution of the species, however, were able to identify all regions where Ae . albopictus is currently established, including Europe (AUC: 0.89–0.91). In a second step, the modelled bioclimatic envelope of the global range was projected to future climatic conditions in Europe using two emission scenarios implemented in the regional climate model COSMO-CLM for three time periods 2011–2040, 2041–2070, and 2071–2100. For both global-driven models, the results indicate that climatically suitable areas for the establishment of Ae . albopictus will increase in western and central Europe already in 2011–2040 and with a temporal delay in eastern Europe. On the other hand, a decline in climatically suitable areas in southern Europe is pronounced in the Expert knowledge based model. Our projections appear unaffected by non-analogue climate, as this is not detected by Multivariate Environmental Similarity Surface analysis. The generated risk maps can aid in identifying suitable habitats for Ae . albopictus and hence support monitoring and control activities to avoid disease vector establishment.

During the last decades dengue incidences are emerging significantly around the globe. Currently, about one fifth of the human population lives in dengue risk zones, which are mainly located in (sub-) tropical regions of Southeast Asia and the Western Pacific. Dengue infections in European population mainly referred to returning travellers from tropical endemic regions. Nevertheless, vector establishment in Europe already took place and therefore the risk increases. Currendy, autochthonous cases of dengue fever have been reported in Europe. Studies estimating the risk of dengue epidemics regard ing changing climatic conditions in Europe are missing. Therefore, we close this gap by using the temperature constraints for virus amplification within the vector Aedes aegypti from two laboratory experiments. We transfer these findings to the changing European climate based on data provided from a regional climate model (COSMO-CLM; A1B and B1 scenario). Daily mean temperature were averaged for the time-steps 2011—2040, 2041—2070 and 2071-2100 in order to reduce natural variability but rather point out climatic trends for risk assessments. For both scenarios the strongest increase of temperature is projected after mid-century. Results indicate a growing threat of virus amplification in Europe especially towards the end of this century. Larger parts of the Mediterranean will be at risk. The southwest of the Iberian Peninsular appears to be especially threatened. Even in some parts of Central Europe, such as Southwest Germany, dengue virus amplification can no longer be excluded at the end of the century. However, it is unlikely that Aedes aegypti will serve as an efficient vector in Europe. In fact, it is Aedes albopictus that is an invasive species in Europe and potential differences in extrinsic incubation period between Ae. aegypti and Ae. albopictus have to be identified. Policy and public health authorities have to consider these emerging biorisks in order to establish surveillance systems and develop counteraction strategies. Hence, we strongly empha size the need for a growing European awareness in the face of biological hazards that are responding to climatic changes.

Climate change is thought to assist spreading vector-borne diseases. During the last years, ecological niche modelling has been increasingly applied to predict the current distribution of disease vectors and their potential responses to climate change. However, sandflies and their transmitted diseases are only scarcely investigated via niche modelling. Here, we propose a methodological approach to combine specific dispersal pathways for a sandfly species (Phlebotomus perniciosus) with the shifting climatic niche in the face of climate change. Current climatic suitability for the species was determined. Future projection is based on data of a regional climate change model. We defined a cost-surface assigned by the changing climatic suitability and expert knowledge on species dispersal ability. The derived travel costs correspond to the effort for the species to move across the landscape to climatically suitable habitats. In future steps, least-cost paths will be calculated for this and further sandfly species with assumed spreading tendencies to Central Europe in the 21st century. Challenges are the integration of wind speed and biotic interactions.

Introduction: The Legionellaceae are fastidious Gram‐negative bacteria that reside in aquatic environments. They are a cause of severe community acquired pneumonia. Legionella pneumophila serogroup 1 is responsible for 70–90 % of human infection, with cases caused by some of the other 15 serogroups accounting for the rest. Most hospitals use the Legionella urinary antigen test for detection of legionellosis; however, this will only reliably detect L. pneumophila serogroup 1. Case presentation: We report two cases of severe community acquired pneumonia in patients requiring extracorporeal membrane oxygenation, referred to our adult Severe Respiratory Failure Unit. Legionella urinary antigen was negative in both cases. As clinical presentation strongly suggested Legionnaires’ disease (LD), respiratory samples were sent to the reference laboratory for PCR, which confirmed L. pneumophila non‐serogroup 1 in both cases. Case 1 was subsequently confirmed by culture and confirmed as L. pneumophila serogroup 5. Case 2 was culture‐negative. Conclusion: Legionella is an important pathogen. Recognition of the potential for non‐serogroup 1 strains to cause severe LD should prompt requests for further investigations including Legionella PCR in patients who present with suggestive symptoms when the urine antigen is negative. Reliance on the urine antigen test may result in a potentially serious under‐recognition of L. pneumophila non‐serogroup 1 and lead to mis‐diagnoses and inappropriate antimicrobial treatment.

Models of Golgi apparatus biogenesis and maintenance are focused on two possibilities: one is self-assembly from the endoplasmic reticulum, and the other is nucleation by a stable template. Here, we asked in three different experimental situations whether assembly of the Golgi apparatus might be dynamically nucleated. During microtubule depolymerization, the integral membrane protein p27 and the peripheral Golgi protein GM130, appeared in newly formed, scattered Golgi elements before three different Golgi apparatus cisternal enzymes, whereas GRASP55, a medial peripheral Golgi protein, showed, if anything, a tendency to accumulate in scattered Golgi elements later than a cisternal enzyme. During Golgi formation after brefeldin A washout, endoplasmic reticulum exit of Golgi resident enzymes could be completely separated from that of p27 and GM130. p27 and GM130 accumulation was onto newly organized perinuclear structures, not brefeldin A remnants, and preceded that of a cisternal enzyme. Reassembly was completely sensitive to guanosine 5'-diphosphate-restricted Sar1p. When cells were microinjected with Sar1pWT DNA to reverse a guanosine 5'-diphosphate-restricted Sar1p endoplasmic reticulum-exit block phenotype, GM130 and p27 collected perinuclearly with little to no exit of a cisternal enzyme from the endoplasmic reticulum. The overall data strongly indicate that the assembly of the Golgi apparatus can be nucleated dynamically by GM130/p27 associated structures. We define dynamic nucleation as the first step in a staged organelle assembly process in which new component association forms a microscopically visible structure onto which other components add later, e.g. Golgi cisternae.

Many studies have evaluated the role of Cryptosporidium spp. in outbreaks of enteric illness, but few studies have evaluated sporadic cryptosporidiosis in the United States. To assess the risk factors for sporadic cryptosporidiosis among immunocompetent persons, a matched case-control study was conducted in seven sites of the Foodborne Diseases Active Surveillance Network (FoodNet) involving 282 persons with laboratory-identified cryptosporidiosis and 490 age-matched and geographically matched controls. Risk factors included international travel (odds ratio [OR] = 7.7; 95% confidence interval [95% CI] = 2.7 to 22.0), contact with cattle (OR = 3.5; 95% CI = 1.8 to 6.8), contact with persons >2 to 11 years of age with diarrhea (OR = 3.0; 95% CI = 1.5 to 6.2), and freshwater swimming (OR = 1.9; 95% CI = 1.049 to 3.5). Eating raw vegetables was protective (OR = 0.5; 95% CI = 0.3 to 0.7). This study underscores the need for ongoing public health education to prevent cryptosporidiosis, particularly among travelers, animal handlers, child caregivers, and swimmers, and the need for further assessment of the role of raw vegetables in cryptosporidiosis.

Parkinson's disease (PD) is a common neurodegenerative disorder in humans with wide variability in the age of disease onset. Although the disease has been thought previously to occur sporadically in most patients, there is increasing evidence of a genetic contribution to the disorder. Recently, a polymorphic variant within intron 6 of the Nurr1 gene was reported to be associated with sporadic and familial PD. In an effort to identify susceptibility genes for PD, we have collected 783 PD patients from 372 families and 397 healthy controls from 217 families. PD patients and healthy controls were genotyped for the intron 6 insertion polymorphism by BseRI restriction endonuclease digestion. No significant difference in either homozygosity or heterozygosity for the 7048G7049 (IVS6 1361 +16insG) polymorphism was detected in the PD patient cohort as compared with the panel of healthy controls. Moreover, direct sequencing of exon 1 of the Nurr1 gene in PD patients failed to detect either of the two recently reported Nurr1 mutations identified in a small subset of a PD patient cohort. Taken together, these data suggest that genetic alteration at the Nurr1 locus is not a significant risk factor for the development of Parkinson's disease in our large sample of familial PD patients.

Mutations in LRRK2 were first reported as causing Parkinson's disease (PD) in late 2004. Since then, approximately a dozen LRRK2 substitutions have been identified that are believed to be pathogenic mutations. The substitution of adenine for guanine at nucleotide 4541 (4541G>A) in LRRK2 was recently reported. This substitution resulted in the replacement of an arginine at position 1514 with a glutamine (R1514Q). Although this substitution was not found in a large cohort of controls, its pathogenicity could not be verified. We have now genotyped the R1514Q substitution in a sample of 954 PD patients from 429 multiplex PD families. This substitution was identified in 1.8% of the PD patients; however, the majority of the PD sibships segregating this substitution were discordant for this putative mutation. In addition, the R1514Q substitution was detected in 1.4% of neurologically evaluated, control individuals. These data suggest that the R1514Q variant is not a pathogenic LRRK2 mutation. We believe it is imperative that the causative nature of any newly identified genetic variant be determined before it is included in any panel for diagnostic testing.

Summary of the dataobtained from the literature. Thistable provides information about the diffe-rent experimental studies, including studymaterial used and methodological details.The duration until the first observedtransmission or infection of SG at a giventemperature is given for each study.(XLS) References 1. World Health Organization (2012) Dengue andsevere dengue. Available: http://www.who.int/mediacentre/factsheets/fs117/en/. Accessed 11July 2012.2. Louis C (2012) Daily newspaper view of denguefever epidemic, Athens, Greece, 1927–1931.Emerg Infect Dis 18: 78–82.3. Schmidt-Chanasit J, Haditsch M, Scho¨neberg I,Gu¨nther S, Stark K, et al. (2010) Dengue virusinfection in a traveller returning from Croatia toGermany. Euro Surveill 15: 2–3.4. LaRucheG,Souare`s Y, Armengaud A, Peloux-Petiot F, Delaunay P, et al. (2010) First twoautochthonous dengue virus infections in metropol-itan France, September 2010. Euro Surveill 15: 2–6.5. Sousa C, Clairouin M, Seixas G, Viveiros B,Novo M, et al. (2012) Ongoing outbreak ofdengue type 1 in the autonomous region ofMadeira, Portugal: preliminary report. EuroSurveill 17: 20333.6. Editors of theAmerican Heritage Dictionaries (2007)The American heritage medical dictionary, revisededition. Boston: Houghton Mifflin Harcourt.7. Dietz K (1993) The estimation of the basicreproduction number for infectious diseases. StatMethods Med Res 2: 23–41.8. Barbazan P, Guiserix M, Boonyuan W, Tunta-prasart W, Pontier D, et al. (2010) Modelling theeffect of temperature on transmission of dengue.Med Vet Entomol 24: 66–73.9. Luz PM, Codec¸o CT, Massad E, Struchiner CJ(2003) Uncertainties regarding dengue modelingin Rio de Janeiro, Brazil. Mem Inst OswaldoCruz 98: 871–878.10. Christofferson RC, Mores CN (2011) Estimatingthe magnitude and direction of altered arbovirustransmission due to viral phenotype. PLoS ONE6: e16298. doi:10.1371/journal.pone.001629811. Paaijmans KP, Read AF, Thomas MB (2009)Understanding the link between malaria risk andclimate.ProcNatlAcadSciUSA106:13844–13849.12. Gubbins S, Carpenter S, Baylis M, Wood JLN,Mellor PS (2008) Assessing the risk of bluetongueto UK livestock: uncertainty and sensitivityanalyses of a temperature-dependent model forthe basic reproduction number. J R Soc Interface5: 363–371.13. Thomas S, Fischer D, Fleischmann S, Bittner T,Beierkuhnlein C (2011) Risk assessment of denguevirus amplification in Europe based on spatio-temporal high resolution climate change projec-tions. Erdkunde 65: 137–150.14. Blanc G, Caminopetros J (1930) Recherchesexperimentales sur la dengue. Ann Inst Pasteur44: 367–436.15. McLean DM, Clarke AM, Coleman JC, Mon-talbetti CA, Skidmore AG, et al. (1974) Vectorcapability of Aedes aegypti mosquitoes for Californiaencephalitis and dengue viruses at various tem-peratures. Can J Microbiol 20: 255–262.16. McLean DM, Miller MA, Grass PN (1975)Dengue virus transmission by mosquitoes incubat-ed at low temperatures. Mosq News 35: 322–327.17. Watts DM, Burke DS, Harrison BA, WhitmireRE, Nisalak A (1987) Effect of temperature on thevector efficiency of Aedes aegypti for dengue 2 virus.Am J Trop Med Hyg 36: 143–152.18. Rohani A, Wong YC, Zamre I, Lee HL, ZuraineeMN (2009) The effect of extrinsic incubationtemperature on development of dengue serotype2 and 4 viruses in Aedes aegypti (L.). SoutheastAsian J Trop Med Public Health 40: 942–950.19. Salazar MI, Richardson JH, Sa´nchez-Vargas I,Olson KE, Beaty BJ (2007) Dengue virus type 2:replication and tropisms in orally infected Aedesaegypti mosquitoes. BMC Microbiol 7: 9.20. Anderson JR, Rico-Hesse R (2006) Aedes aegyptivectorial capacity is determined by the infecting

Objective To study adipokines as a potential link between obesity and male subfertility. Design Cross-sectional study of subjects stratified into subgroups according to body mass index (BMI): normal-weight (18.50–24.99 kg/m 2 ), overweight (25–29.99 kg/m 2 ), and obese (>30 kg/m 2 ). Setting Leipzig, Germany from 2007 to 2011. Patient(s) Ninety-six male volunteers without spermatogenesis-associated diseases. Intervention(s) None. Main Outcome Measure(s) Semen parameters, reproductive hormones in serum, and leptin, adiponectin, resistin, chemerin, progranulin, vaspin, and visfatin concentrations in serum and seminal plasma. Result(s) All measured adipokines were detectable in human seminal plasma. The levels of progranulin, visfatin, and vaspin were statistically significantly higher in seminal plasma than in serum. An increase in body weight was associated with decreased levels of seminal plasma progranulin. Additionally, overweight/obese men had statistically significantly lower progranulin levels in seminal plasma than normal weight men. Adiponectin and progranulin concentrations in seminal plasma statistically significantly positively correlated with sperm concentration, sperm count, and total normomorphic spermatozoa. Conclusion(s) Adipokines are differently regulated in human male reproductive tract compared with the peripheral blood, and they could influence sperm functionality.

Background The interplay between global warming and invasive arthropods in temperate zones is of utmost interest in terms of the potential expansions of vector-borne diseases. Up to now, investigations on the recent establishment of mosquito vectors have focused on temperatures during their phases of activity. However, cold temperatures may also act as a strong ecological constraint. Projected changes in winter climate indicate an increase of mean minimum temperatures of the coldest quarter, less frequent days with frost and a shorter frost-season in Europe at the end of the century. Nevertheless, single cold extremes are also expected to persist under warming scenarios, which have a strong impact on reproduction success. Methods Here, the temperature constraints of European Aedes albopictus eggs, which had passed through a diapause, compared to non-diapausing eggs were examined systematically under controlled laboratory conditions. Additionally, one tropical strain of Ae. albopictus and of Ae. aegypti was used in the comparison. Results The lower temperature threshold tolerated by the European eggs of Ae. albopictus which have undergone a diapause, was -10°C for long term exposures (12 and 24h) and -12°C for 1h exposure. Non-diapausing eggs of European Ae. albopictus were found to hatch after a -7°C cold treatment (8, 12 and 24h exposure). Both tropical aedine species only tolerated the long term treatment at -2°C. Neither Ae. albopictus nor Ae. aegypti eggs hatched after being exposed to -15°C. Survival was mainly influenced by temperature (F = 329.2, df = 1, p Conclusions Here, low temperature thresholds for aedine mosquito egg survival were detected. The compilation of risk maps for temperate regions can substantially be improved by considering areas where an establishment of a vector population is unlikely due to winter conditions.

Background In the Old World, sandfly species of the genus Phlebotomus are known vectors of Leishmania, Bartonella and several viruses. Recent sandfly catches and autochthonous cases of leishmaniasis hint on spreading tendencies of the vectors towards Central Europe. However, studies addressing potential future distribution of sandflies in the light of a changing European climate are missing. Methodology Here, we modelled bioclimatic envelopes using MaxEnt for five species with proven or assumed vector competence for Leishmania infantum, which are either predominantly located in (south-) western (Phlebotomus ariasi, P. mascittii and P. perniciosus) or south-eastern Europe (P. neglectus and P. perfiliewi). The determined bioclimatic envelopes were transferred to two climate change scenarios (A1B and B1) for Central Europe (Austria, Germany and Switzerland) using data of the regional climate model COSMO-CLM. We detected the most likely way of natural dispersal (“least-cost path”) for each species and hence determined the accessibility of potential future climatically suitable habitats by integrating landscape features, projected changes in climatic suitability and wind speed. Results and Relevance Results indicate that the Central European climate will become increasingly suitable especially for those vector species with a current south-western focus of distribution. In general, the highest suitability of Central Europe is projected for all species in the second half of the 21st century, except for P. perfiliewi. Nevertheless, we show that sandflies will hardly be able to occupy their climatically suitable habitats entirely, due to their limited natural dispersal ability. A northward spread of species with south-eastern focus of distribution may be constrained but not completely avoided by the Alps. Our results can be used to install specific monitoring systems to the projected risk zones of potential sandfly establishment. This is urgently needed for adaptation and coping strategies against the emerging spread of sandfly-borne diseases., Author Summary Growing evidence exists on the emergence of sandfly-borne diseases in the light of climate change. Determining the principle responses of phlebotomine sandflies to climatic changes supports our understanding of future regions that will be threatened by new-establishments of this important group of disease vectors. The aim of this paper is to combine projected climatic suitability for five Phlebotomus species in Central Europe (Austria, Germany and Switzerland) for different time-periods during the 21st century with their potential spreading capacity to disperse to climatically suitable areas. We indicate that the Central European climate will develop toward the preferred bioclimatic niche of the species, especially from mid-century onwards. Nevertheless, we also elucidate within this study that sandflies will hardly be able to occupy the whole areas that will provide suitable climatic conditions due to their limited natural dispersal ability. Our approach provides a framework to combine statistical modelling techniques with expert knowledge on species ecology. Indications of future occurrences of disease vectors may help to initiate surveillance systems in specific regions at an early stage of risk exposure. Hence, the threat of the climate-driven spatial extension of disease vectors and consequently of potentially emerging vector-borne diseases can be counteracted.

Climate change is expected to manifest in the shift of organisms to regions where they were not present in the past, potentially entailing previously unseen biological risks. However, studies evaluating these future trends are scarce. Here, an important group of vectors (sandflies) and the pathogen transmitted (Leishmania infantum complex) causing the infectious disease visceral leishmaniasis is investigated, focussing on potential establishment in Germany during the 21st century. As the most important habitat factor, temperature requirements of pathogen and vector were derived from the literature and compared with recent climate records - provided by worldclim - and climate change scenarios. Climate data from the Regional Climate Model REMO were obtained and averaged over the time periods 2011- 2040, 2041-2070 and 2071-2100. Projected temperature changes (based on the A1B and A2 scenarios) were correlated with the constraints of vector and pathogen. Simulated potentially suitable habitat areas for vector and pathogen were merged to generate a temperature-derived risk map of visceral leishmaniasis. Temperature conditions seem to become suitable for the vector across large swaths of Germany. Nevertheless, temperature constraints for the pathogen may defer the establishment of the parasitic disease, particularly during the first half of the 21st century. Long-lasting epidemics of visceral leishmaniasis are therefore not expected in Germany during the next few decades, although during extremely warm years an increase in autochthonous cases of leishmaniasis may occur. The southwest (Upper Rhine Valley) and west (Cologne Bight) of Germany are identified as risk areas. The time of potential establishment and corresponding rise in biological risk varies between scenarios, due to differences in the predicted rate of temperature increase.

Background: The vast majority of the parkin mutations previously identified have been found in individuals with juvenile or early onset PD. Previous screening of later onset PD cohorts has not identified substantial numbers of parkin mutations. Methods: Families with at least two siblings with PD were ascertained to identify genes contributing to PD susceptibility. Screening of the parkin gene, by both quantitative PCR and exon sequencing, was performed in those families with either early onset PD (age onset ≤50 years) or positive lod score with a marker in intron 7 of the parkin gene. Results: A total of 25 different mutations in the parkin gene were identified in 103 individuals from 47 families. Mutations were found in both parkin alleles in 41 of the individuals, whereas a single mutation in only one of the two parkin alleles was observed in 62 individuals. Thirty-five of the subjects (34%) with a parkin mutation had an age at onset of 60 years or above with 30 of these 35 (86%) having a detectable mutation on only one parkin allele. Few significant clinical differences were observed among the individuals with two, one, or no mutated copies of the parkin gene. Conclusion: Mutations in the parkin gene occur among individuals with PD with an older age at onset (≥60 years) who have a positive family history of the disease. In addition, the clinical findings of parkin -positive individuals are remarkably similar to those without mutations.

Leishmaniasis is caused by protozoa of the genus Leishmania and transmitted by sand flies from mammalian reservoirs to humans. In recent years, a northward spread of L. infantum from highly endemic Mediterranean countries into previously non-endemic Central European areas has been suspected based on presumed sporadic cases of autochthonous leishmaniasis. Here, we investigated whether sand flies are prevalent in Bavaria in Southern Germany, a federal state in which autochthonous cases have previously been reported. Considering the present and future climatic conditions, we determined whether Bavaria is suitable for five sand fly species with assumed spreading tendencies towards Central Europe: Phlebotomus ariasi, P. neglectus, P. perfiliewi and P. perniciosus that are known vectors for Leishmania in Europe, and P. mascittii, a suspected but not proven vector. Within Bavaria we defined sampling regions based on their climatic suitability and their spatial distance to the sites of the autochthonous cases and/or to areas of reported sand fly detection in states adjacent to Bavaria. At 155 locations in 7 sampling regions, CDC light traps were placed during 38 nights in the summers of 2009 and 2010, resulting in 202 trap-nights. All traps were negative for sand flies. The results suggest that Bavaria is not yet endemic for sand flies, but do not exclude the possibility of sporadic cases of autochthonous human or zoonotic Leishmania infections. This study, which combined methodological approaches from different disciplines, serves as reference for future surveys and risk analyses of sand flies and leishmaniasis in so far non-endemic areas of Europe.

Parkinson disease (PD) is the second most common neurodegenerative disorder, surpassed in frequency only by Alzheimer disease. Elsewhere we have reported linkage to chromosome 2q in a sample of sibling pairs with PD. We have now expanded our sample to include 150 families meeting our strictest diagnostic definition of verified PD. To further delineate the chromosome 2q linkage, we have performed analyses using only those pedigrees with the strongest family history of PD. Linkage analyses in this subset of 65 pedigrees generated a LOD score of 5.1, which was obtained using an autosomal dominant model of disease transmission. This result strongly suggests that variation in a gene on chromosome 2q36-37 contributes to PD susceptibility.

The Asian tiger mosquito, Aedes albopictus, is capable of transmitting a broad range of viruses to humans. Since its introduction at the end of the 20th century, it has become well established in large parts of southern Europe. As future expansion as a result of climate change can be expected, determining the current and projected future climatic suitability of this invasive mosquito in Europe is of interest. Several studies have tried to detect the potential habitats for this species, but differing data sources and modelling approaches must be considered when interpreting the findings. Here, various modelling methodologies are compared with special emphasis on model set-up and study design. Basic approaches and model algorithms for the projection of spatio-temporal trends within the 21st century differ substantially. Applied methods range from mechanistic models (e.g. overlay of climatic constraints based on geographic information systems or rather process-based approaches) to correlative niche models. We conclude that spatial characteristics such as introduction gateways and dispersal pathways need to be considered. Laboratory experiments addressing the climatic constraints of the mosquito are required for improved modelling results. However, the main source of uncertainty remains the insufficient knowledge about the species' ability to adapt to novel environments.