Bovine milk oligosaccharides as anti-adhesives against the respiratory tract pathogen Streptococcus pneumoniae

peer-reviewedStreptococcus pneumoniae is a Gram-positive pathogen, which is regularly found in the upper respiratory tract of healthy individuals. Increased numbers of S. pneumoniae have been observed colonising the upper respiratory tract of children affected by respiratory tract infections. Galβ1-4GlcNAcβ1-3Gal has been previously identified as one of the receptors involved in the adherence and translocation of S. pneumoniae. As this structure is similar to the milk oligosaccharide lacto-N-neoTetraose, many studies have investigated if free milk oligosaccharides can inhibit the adhesion of S. pneumoniae to epithelial cells of the respiratory tract. Here, we demonstrate that bovine oligosaccharides, which were extracted from demineralised whey, using a combination of membrane filtration and chromatography, were capable of reducing S. pneumoniae adhesion to pharynx and lung cells in vitro when tested at physiological concentrations. This study strengthens the potential use of bovine derived milk oligosaccharides as functional ingredients to reduce the incidence of infectious diseases

Allele-specific expression assays using Solexa

<p>Abstract</p> <p>Background</p> <p>Allele-specific expression (ASE) assays can be used to identify <it>cis</it>, <it>trans</it>, and <it>cis</it>-by-<it>trans </it>regulatory variation. Understanding the source of expression variation has important implications for disease susceptibility, phenotypic diversity, and adaptation. While ASE is commonly measured via relative fluorescence at a SNP, next generation sequencing provides an opportunity to measure ASE in an accurate and high-throughput manner using read counts.</p> <p>Results</p> <p>We introduce a Solexa-based method to perform large numbers of ASE assays using only a single lane of a Solexa flowcell. In brief, transcripts of interest, which contain a known SNP, are PCR enriched and barcoded to enable multiplexing. Then high-throughput sequencing is used to estimate allele-specific expression using sequencing counts. To validate this method, we measured the allelic bias in a dilution series and found high correlations between measured and expected values (r>0.9, p < 0.001). We applied this method to a set of 5 genes in a <it>Drosophila simulans </it>parental mix, F1 and introgression and found that for these genes the majority of expression divergence can be explained by <it>cis</it>-regulatory variation.</p> <p>Conclusion</p> <p>We present a new method with the capacity to measure ASE for large numbers of assays using as little as one lane of a Solexa flowcell. This will be a valuable technique for molecular and population genetic studies, as well as for verification of genome-wide data sets.</p

Exploring sexual dimorphism of the modern human talus through geometric morphometric methods

Sex determination is a pivotal step in forensic and bioarchaeological fields. Generally, scholars focus on metric or qualitative morphological features, but in the last few years several contributions have applied geometric-morphometric (GM) techniques to overcome limitations of traditional approaches. In this study, we explore sexual dimorphism in modern human tali from three early 20th century populations (Sassari and Bologna, Italy; New York, USA) at intra- and interspecific population levels using geometric morphometric (GM) methods. Statistical analyses were performed using shape, form, and size variables. Our results do not show significant differences in shape between males and females, either considering the pooled sample or the individual populations. Differences in talar morphology due to sexual dimorphism are mainly related to allometry, i.e. size-related changes of morphological traits. Discriminant function analysis using form space Principal Components and centroid size correctly classify between 87.7% and 97.2% of the individuals. The result is similar using the pooled sample or the individual population, except for a diminished outcome for the New York group (from 73.9% to 78.2%). Finally, a talus from the Bologna sample (not included in the previous analysis) with known sex was selected to run a virtual resection, followed by two digital reconstructions based on the mean shape of both the pooled sample and the Bologna sample, respectively. The reconstructed talus was correctly classified with a Ppost between 99.9% and 100%, demonstrating that GM is a valuable tool to cope with fragmentary tali, which is a common occurrence in forensic and bioarchaeological contexts

Bronchopulmonary Dysplasia: Executive Summary of a Workshop

Comment in Bronchopulmonary Dysplasia: The Ongoing Search for One Definition to Rule Them All. [J Pediatr. 2018] Midlife crisis? In its 50th year, BPD redefines itself. [J Pediatr. 2018

A rapid phenotype change in the pathogen Perkinsus marinus was associated with a historically significant marine disease emergence in the eastern oyster

The protozoan parasite Perkinsus marinus, which causes dermo disease in Crassostrea virginica, is one of the most ecologically important and economically destructive marine pathogens. The rapid and persistent intensification of dermo in the USA in the 1980s has long been enigmatic. Attributed originally to the effects of multi-year drought, climatic factors fail to fully explain the geographic extent of dermo’s intensification or the persistence of its intensified activity. Here we show that emergence of a unique, hypervirulent P. marinus phenotype was associated with the increase in prevalence and intensity of this disease and associated mortality. Retrospective histopathology of 8355 archival oysters from 1960 to 2018 spanning Chesapeake Bay, South Carolina, and New Jersey revealed that a new parasite phenotype emerged between 1983 and 1990, concurrent with major historical dermo disease outbreaks. Phenotypic changes included a shortening of the parasite’s life cycle and a tropism shift from deeper connective tissues to digestive epithelia. The changes are likely adaptive with regard to the reduced oyster abundance and longevity faced by P. marinus after rapid establishment of exotic pathogen Haplosporidium nelsoni in 1959. Our findings, we hypothesize, illustrate a novel ecosystem response to a marine parasite invasion: an increase in virulence in a native parasite

Ecology under lake ice

Winter conditions are rapidly changing in temperate ecosystems, particularly for those that experience periods of snow and ice cover. Relatively little is known of winter ecology in these systems, due to a historical research focus on summer ‘growing seasons’. We executed the first global quantitative synthesis on under‐ice lake ecology, including 36 abiotic and biotic variables from 42 research groups and 101 lakes, examining seasonal differences and connections as well as how seasonal differences vary with geophysical factors. Plankton were more abundant under ice than expected; mean winter values were 43.2% of summer values for chlorophyll a, 15.8% of summer phytoplankton biovolume and 25.3% of summer zooplankton density. Dissolved nitrogen concentrations were typically higher during winter, and these differences were exaggerated in smaller lakes. Lake size also influenced winter‐summer patterns for dissolved organic carbon (DOC), with higher winter DOC in smaller lakes. At coarse levels of taxonomic aggregation, phytoplankton and zooplankton community composition showed few systematic differences between seasons, although literature suggests that seasonal differences are frequently lake‐specific, species‐specific, or occur at the level of functional group. Within the subset of lakes that had longer time series, winter influenced the subsequent summer for some nutrient variables and zooplankton biomass

The Dual Impact of HIV-1 Infection and Aging on Naïve CD4+ T-Cells: Additive and Distinct Patterns of Impairment

HIV-1-infected adults over the age of 50 years progress to AIDS more rapidly than adults in their twenties or thirties. In addition, HIV-1-infected individuals receiving antiretroviral therapy (ART) present with clinical diseases, such as various cancers and liver disease, more commonly seen in older uninfected adults. These observations suggest that HIV-1 infection in older persons can have detrimental immunological effects that are not completely reversed by ART. As naïve T-cells are critically important in responses to neoantigens, we first analyzed two subsets (CD45RA+CD31+ and CD45RA+CD31-) within the naïve CD4+ T-cell compartment in young (20–32 years old) and older (39–58 years old), ART-naïve, HIV-1 seropositive individuals within 1–3 years of infection and in age-matched seronegative controls. HIV-1 infection in the young cohort was associated with lower absolute numbers of, and shorter telomere lengths within, both CD45RA+CD31+CD4+ and CD45RA+CD31-CD4+ T-cell subsets in comparison to age-matched seronegative controls, changes that resembled seronegative individuals who were decades older. Longitudinal analysis provided evidence of thymic emigration and reconstitution of CD45RA+CD31+CD4+ T-cells two years post-ART, but minimal reconstitution of the CD45RA+CD31-CD4+ subset, which could impair de novo immune responses. For both ART-naïve and ART-treated HIV-1-infected adults, a renewable pool of thymic emigrants is necessary to maintain CD4+ T-cell homeostasis. Overall, these results offer a partial explanation both for the faster disease progression of older adults and the observation that viral responders to ART present with clinical diseases associated with older adults

Becoming adults: Exploring the late ontogeny of the human talus

Introduction: The talus plays an important role in receiving and dissipating the forces and linking the leg and the foot. As such, it is of paramount importance to analyze how its morphology, internal and external, changes during late ontogeny and through adolescence. Method: To explore both the external shape and the internal architecture of the talus, Geometric Morphometrics and trabecular analysis have been applied to a sample of 35 tali from modern human juveniles aged between 5 and 15 years old (Middle Neolithic (4800-4500 BCE) to mid-20th century). Results: Results show that, as the overall size of the talus increases, the shape and orientation of talar facets also change. The youngest individuals exhibit a functional talus that is still characterized by a relatively immature shape (e.g., subtly expressed margins of articular surfaces) with articular facets only minimally rotated towards an adult configuration. In adolescents, talar shape has achieved adult form after the age of 11, with all the articular facets and posterior processes well-developed. Considering internal morphology, trabecular bone varies between age classes. While Bone Volume Fraction shifts during the age 5-15 range, Degree of Anisotropy is relatively more stable over the developmental period examined in the study since it exhibits smaller variations between age classes. Discussion: This study examined the late ontogeny of the human talus by considering both internal and external morphology. Results suggest that, although the locomotion has already assumed an adult-like pattern, the exploration of late talar growth may help understand how the talus adapts to changes in locomotor activity and how it responds to the increase in weight. Present results can be used to a better understanding of talar plasticity, improving interpretations of adult human talar form

Clinical phenotype and genetic associations in autosomal dominant familial Alzheimer's disease: a case series.

BACKGROUND: The causes of phenotypic heterogeneity in familial Alzheimer's disease with autosomal dominant inheritance are not well understood. We aimed to characterise clinical phenotypes and genetic associations with APP and PSEN1 mutations in symptomatic autosomal dominant familial Alzheimer's disease (ADAD). METHODS: We retrospectively analysed genotypic and phenotypic data (age at symptom onset, initial cognitive or behavioural symptoms, and presence of myoclonus, seizures, pyramidal signs, extrapyramidal signs, and cerebellar signs) from all individuals with ADAD due to APP or PSEN1 mutations seen at the Dementia Research Centre in London, UK. We examined the frequency of presenting symptoms and additional neurological features, investigated associations with age at symptom onset, APOE genotype, and mutation position, and explored phenotypic differences between APP and PSEN1 mutation carriers. The proportion of individuals presenting with various symptoms was analysed with descriptive statistics, stratified by mutation type. FINDINGS: Between July 1, 1987, and Oct 31, 2015, age at onset was recorded for 213 patients (168 with PSEN1 mutations and 45 with APP mutations), with detailed history and neurological examination findings available for 121 (85 with PSEN1 mutations and 36 with APP mutations). We identified 38 different PSEN1 mutations (four novel) and six APP mutations (one novel). Age at onset differed by mutation, with a younger onset for individuals with PSEN1 mutations than for those with APP mutations (mean age 43·6 years [SD 7·2] vs 50·4 years [SD 5·2], respectively, p<0·0001); within the PSEN1 group, 72% of age at onset variance was explained by the specific mutation. A cluster of five mutations with particularly early onset (mean age at onset <40 years) involving PSEN1's first hydrophilic loop suggests critical functional importance of this region. 71 (84%) individuals with PSEN1 mutations and 35 (97%) with APP mutations presented with amnestic symptoms, making atypical cognitive presentations significantly more common in PSEN1 mutation carriers (n=14; p=0·037). Myoclonus and seizures were the most common additional neurological features; individuals with myoclonus (40 [47%] with PSEN1 mutations and 12 [33%] with APP mutations) were significantly more likely to develop seizures (p=0·001 for PSEN1; p=0·036 for APP), which affected around a quarter of the patients in each group (20 [24%] and nine [25%], respectively). A number of patients with PSEN1 mutations had pyramidal (21 [25%]), extrapyramidal (12 [14%]), or cerebellar (three [4%]) signs. INTERPRETATION: ADAD phenotypes are heterogeneous, with both age at onset and clinical features being influenced by mutation position as well as causative gene. This highlights the importance of considering genetic testing in young patients with dementia and additional neurological features in order to appropriately diagnose and treat their symptoms, and of examining different mutation types separately in future research. FUNDING: Medical Research Council and National Institute for Health Research