The striped skunk (Mephitis mephitis) is an intermediate host for Sarcocystis neurona

Striped skunks, initially negative for antibodies to Sarcocystis neurona, formed sarcocysts in skeletal muscles after inoculation with S. neurona sporocysts collected from a naturally infected Virginia opossum (Didelphis virginiana). Skunks developed antibodies to S. neurona by immunoblot and muscles containing sarcocysts were fed to laboratory-reared opossums which then shed sporulated Sarcocystis sporocysts in their faeces. Mean dimensions for sporocysts were 11.0 x 7.5 microm and each contained four sporozoites and a residuum. Sarcocysts from skunks and sporocysts from opossums fed infected skunk muscle were identified as S. neurona using PCR and DNA sequence analysis. A 2-month-old, S. neurona-naive pony foal was orally inoculated with 5 x 10(5) sporocysts. Commercial immunoblot for antibodies to S. neurona performed using CSF collected from the inoculated pony was low positive at 4 weeks p.i., positive at 6 weeks p.i., and strong positive at 8 weeks p.i. Gamma-interferon gene knockout mice inoculated with skunk/opossum derived sporocysts developed serum antibodies to S. neurona and clinical neurologic disease. Merozoites of S. neurona present in the lung, cerebrum, and cerebellum of mice were detected by immunohistochemistry using polyclonal antibodies to S. neurona. Based on the results of this study, the striped skunk is an intermediate host of S. neurona.     

Distribution and Characterization of Salmonella enterica Isolates from Irrigation Ponds in the Southeastern United States

Irrigation water has been implicated as a likely source of produce contamination by Salmonella enterica. Therefore, the distribution of S. enterica was surveyed monthly in irrigation ponds (n = 10) located within a prime agricultural region in southern Georgia and northern Florida. All ponds and 28.2% of all samples (n = 635) were positive for Salmonella, with an overall geometric mean concentration (0.26 most probable number [MPN]/liter) that was relatively low compared to prior reports for rivers in this region. Salmonella peaks were seasonal; the levels correlated with increased temperature and rainfall (P < 0.05). The numbers and occurrence were significantly higher in water (0.32 MPN/liter and 37% of samples) than in sediment (0.22 MPN/liter and 17% of samples) but did not vary with depth. Representative isolates (n = 185) from different ponds, sample types, and seasons were examined for resistance to 15 different antibiotics; most strains were resistant to streptomycin (98.9%), while 20% were multidrug resistant (MDR) for 2 to 6 antibiotics. DiversiLab repetitive extragenic palindromic-element sequence-based PCR (rep-PCR) revealed genetic diversity and showed 43 genotypes among 191 isolates, as defined by >95% similarity. The genotypes did not partition by pond, season, or sample type. Genetic similarity to known serotypes indicated Hadar, Montevideo, and Newport as the most prevalent. All ponds achieved the current safety standards for generic Escherichia coli in agricultural water, and regression modeling showed that the E. coli level was a significant predictor for the probability of Salmonella occurrence. However, persistent populations of Salmonella were widely distributed in irrigation ponds, and the associated risks for produce contamination and subsequent human exposure are unknown, supporting continued surveillance of this pathogen in agricultural settings.     

The antigenic anatomy of SARS-CoV-2 receptor binding domain

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Out of Africa and back again: nested cladistic analysis of human Y chromosome variation

We surveyed nine diallelic polymorphic sites on the Y chromosomes of 1,544 individuals from Africa, Asia, Europe, Oceania, and the New World. Phylogenetic analyses of these nine sites resulted in a tree for 10 distinct Y haplotypes with a coalescence time of approximately 150,000 years. The 10 haplotypes were unevenly distributed among human populations: 5 were restricted to a particular continent, 2 were shared between Africa and Europe, 1 was present only in the Old World, and 2 were found in all geographic regions surveyed. The ancestral haplotype was limited to African populations. Random permutation procedures revealed statistically significant patterns of geographical structuring of this paternal genetic variation. The results of a nested cladistic analysis indicated that these geographical associations arose through a combination of processes, including restricted, recurrent gene flow (isolation by distance) and range expansions. We inferred that one of the oldest events in the nested cladistic analysis was a range expansion out of Africa which resulted in the complete replacement of Y chromosomes throughout the Old World, a finding consistent with many versions of the Out of Africa Replacement Model. A second and more recent range expansion brought Asian Y chromosomes back to Africa without replacing the indigenous African male gene pool. Thus, the previously observed high levels of Y chromosomal genetic diversity in Africa may be due in part to bidirectional population movements. Finally, a comparison of our results with those from nested cladistic analyses of human mtDNA and beta-globin data revealed different patterns of inferences for males and females concerning the relative roles of population history (range expansions) and population structure (recurrent gene flow), thereby adding a new sex-specific component to models of human evolution.      

Association of 25-Hydroxyvitamin D status and genetic variation in the vitamin D metabolic pathway with FEV1 in the Framingham Heart Study

Background

Vitamin D is associated with lung function in cross-sectional studies, and vitamin D inadequacy is hypothesized to play a role in the pathogenesis of chronic obstructive pulmonary disease. Further data are needed to clarify the relation between vitamin D status, genetic variation in vitamin D metabolic genes, and cross-sectional and longitudinal changes in lung function in healthy adults.

Methods

We estimated the association between serum 25-hydroxyvitamin D [25(OH)D] and cross-sectional forced expiratory volume in the first second (FEV₁) in Framingham Heart Study (FHS) Offspring and Third Generation participants and the association between serum 25(OH)D and longitudinal change in FEV₁ in Third Generation participants using linear mixed-effects models. Using a gene-based approach, we investigated the association between 241 SNPs in 6 select vitamin D metabolic genes in relation to longitudinal change in FEV₁ in Offspring participants and pursued replication of these findings in a meta-analyzed set of 4 independent cohorts.

Results

We found a positive cross-sectional association between 25(OH)D and FEV₁ in FHS Offspring and Third Generation participants (P = 0.004). There was little or no association between 25(OH)D and longitudinal change in FEV₁ in Third Generation participants (P = 0.97). In Offspring participants, the CYP2R1 gene, hypothesized to influence usual serum 25(OH)D status, was associated with longitudinal change in FEV₁ (gene-based P < 0.05). The most significantly associated SNP from CYP2R1 had a consistent direction of association with FEV₁ in the meta-analyzed set of replication cohorts, but the association did not reach statistical significance thresholds (P = 0.09).

Conclusions

Serum 25(OH)D status was associated with cross-sectional FEV₁, but not longitudinal change in FEV₁. The inconsistent associations may be driven by differences in the groups studied. CYP2R1 demonstrated a gene-based association with longitudinal change in FEV₁ and is a promising candidate gene for further studies.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-015-0238-y) contains supplementary material, which is available to authorized users.     

Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera

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The timing and sequence of the complete annual moult in the Dunnock(Prunella modularis) in Britain over an eleven year period

Summary Data from the British Trust for Ornithology's Moult Enquiry collected in Britain from 1960 to 1970 were analysed to discover for the adult Dunnock(Prunella modularis), the moulting period, the rate of moult in the individual, the sequence of feather replacement and the relative timing of moult in different tracts, excluding the small contour feathers. The feather scores recorded on the moult cards were used to produce scatter diagrams on which calculations were based. The various ways of using such diagrams are discussed briefly. It is suggested that the speed of moult can often be estimated by visual appraisal, but regression analysis if used should be of dates of capture against individual moult scores, not of moult scores against each date (see fig. 2). Retrapped birds were used to confirm calculated moulting rates.The sequence of moult is similar to that of most other small passerines but the rate is rather faster than might be expected for this species which is remarkably sedentary in Britain.The use of moult for ageing at certain times is suggested; Dunnocks in new plumage before mid-August are almost certainly juveniles as are birds in tail and body moult with new remiges.The timing and rate of moult in different years and parts of Britain were compared and statistically significant differences were found in some cases. Birds caught in moult in different years were found not to be inherently early or late moulters.The probable relationship between the end of breeding activity and the start of moult is discussed. The number of Dunnocks caught at different stages of moult was analysed to discover if birds in heavy moult are less readily caught.

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Zeitliche Einpassung und Ablauf der jährlichen Vollmauser der Heckenbraunelle(Prunella modularis) in Großbritannien, 1960–1970

Zusammenfassung Die Arbeit faßt die Ergebnisse der Mauserkarten des Brit. Trust for Ornithology zusammen. Einzelheiten zum zeitlichen Verlauf und zur Mauserfolge werden dargestellt.Mausernde Heckenbraunellen wurden in Großbritannien von Ende Juni bis Anfang Oktober festgestellt. Der Höhepunkt der Handschwingenmauser dauert von Mitte Juli bis in die zweite Septemberhälfte (Abb. 1) bei einer mittleren Dauer der gesamten Handschwingenmauser pro Individuum von 54 Tagen. Der Zeitraum, in dem 50 Vögel mind. 2mal während einer Mauser gefangen wurden, beträgt 60 Tage. Aufgrund des Zeitpunktes der Handschwingenmauser kann eine Heckenbraunelle im vollständig frischen Gefieder vor Mitte August ziemlich sicher als diesjährig angesprochen werden.Die Mauser der Armschwingen beginnt, wenn die 2–4 innersten Handschwingen wieder gewachsen sind, etwa zur selben Zeit, wenn die 5. oder 6. Handschwinge ausfällt. So entstehen eher zwei kleine Lücken im Flügel als eine große. Der Ersatz der Armschwingen ist meistens abgeschlossen, wenn die 8. Handschwinge vollständig nachgewachsen ist; einige Vögel beenden den Armschwingenwechsel erst nach der vollständigen Handschwingenmauser. Die innersten Armschwingen beginnen für gewöhnlich während der Handschwingenmauser auszufallen, aber nicht bevor diese etwa mit 10–25 (vgl. S. 266) bewertet werden können. Der Zeitpunkt der Schwanzmauser variiert stärker; die Schwanzfedern beginnen während der ersten Hälfte der Handschwingenmauser zu fallen, doch vor der Armschwingenmauser. Heckenbraunellen mit frischen Schwungfedern und mauserndem Schwanz sind fast mit Sicherheit diesjährige Vögel.Der Modus der Schwingenmauser ist derselbe wie bei der Mehrzahl der Passeres. Die Handschwingen werden descendent, die Armschwingen ascendent gemausert. Die Steuerfedern fallen in der überwiegenden Mehrzahl der Fälle zentrifugal, doch oft in sehr rascher Folge. Bis zu einem Viertel der Vögel mausert den Schwanz irregulär.Die Armschwingmauser erscheint als ein in sich beschleunigter Vorgang, wie dies bereits beim Gimpel nachgewiesen wurde. Armschwingen- und Schwanzmauser laufen dagegen mit Ausnahme der Extreme am Anfang und Ende relativ linear mit der Zeit ab.Im Mauserbeginn lassen sich regionale und jährliche Unterschiede feststellen. Von 1960–1970 war das mittlere Datum des Beginns im N und S Großbritanniens der 29. Juli, in Wales und in den mittleren Gebieten Englands dagegen der 3. August. Der Unterschied ist statistisch signifikant; 1963 lag der mittlere Beginn später als in den übrigen Jahren. Individuell besteht bei Heckenbraunellen keine Tendenz, konstant früh oder spät zu mausern; eher ist der Mauserbeginn möglicherweise korreliert mit dem Ende des individuellen Brutgeschäftes, wie dies auch bei einer Reihe anderer Arten nachgewiesen wurde.

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I should like to dedicate this paper to the memory of Prof.E. Stresemann, whose life's work was such an inspiration, especially to those interested in the study of moult.     

Substituted 2H-isoquinolin-1-ones as potent Rho-kinase inhibitors: Part 3, aryl substituted pyrrolidines

The discovery and SAR of a series of β-aryl substituted pyrrolidine 2H-isoquinolin-1-one inhibitors of Rho-kinase (ROCK) derived from 2 is herein described. SAR studies have shown that aryl groups in the β-position are optimal for potency. Our efforts focused on improving the ROCK potency of this isoquinolone class of inhibitors which led to the identification of pyrrolidine 32 which demonstrated a 10-fold improvement in aortic ring (AR) potency over 2.