Aging with Elevated Autistic Traits: Cognitive Functioning Among Older Adults with the Broad Autism Phenotype

Background: Little is known about the impact of aging with autism spectrum disorder (ASD) on cognition. As a first step in addressing this gap in our knowledge, the current study examined cognitive functioning among older adults with elevated, but subclinical levels of autistic traits (i.e., the Broad Autism Phenotype; BAP) compared to older adults without the BAP. Method: Forty older adults (aged 60-91, M=73 years) were recruited and classified as meeting criteria for the BAP (n=20) or not (control older adults, COA; n=20). Different components of executive function as well as episodic memory were measured using standardized performance-based neuropsychological assessments in addition to a self-report questionnaire of executive function difficulties. Results: Despite no differences in age, sex ratio, educational history or IQ, the BAP group demonstrated poorer performance on measures of executive function and episodic memory compared to the COA group. The BAP group also self-reported more executive function difficulties in everyday settings. Moreover, differences in working memory and attentional shifting were maintained after accounting for the influences of IQ and both depression and anxiety symptoms. Conclusions: These findings suggest that aging with the BAP confers additional risk to cognitive function for older adults. As the BAP forms a bridge in the continuum from typical to atypical levels of autistic traits, these findings suggest that individuals with ASD might also incur cognitive costs as they age into older adulthood

Black Hole Thermodynamics and Heavy Fermion Metals

Heavy fermion alloys at critical doping typically exhibit non-Fermi-liquid behavior at low temperatures, including a logarithmic or power law rise in the ratio of specific heat to temperature as the temperature is lowered. Anomalous specific heat of this type is also observed in a simple class of gravitational dual models that exhibit anisotropic scaling with dynamical critical exponent z > 1.Comment: 17 pages, 4 figures; v2: added references; v3: matches published versio

Gauss-Bonnet Black Holes and Heavy Fermion Metals

We consider charged black holes in Einstein-Gauss-Bonnet Gravity with Lifshitz boundary conditions. We find that this class of models can reproduce the anomalous specific heat of condensed matter systems exhibiting non-Fermi-liquid behaviour at low temperatures. We find that the temperature dependence of the Sommerfeld ratio is sensitive to the choice of Gauss-Bonnet coupling parameter for a given value of the Lifshitz scaling parameter. We propose that this class of models is dual to a class of models of non-Fermi-liquid systems proposed by Castro-Neto et.al.Comment: 17 pages, 6 figures, pdfLatex; small corrections to figure 10 in this versio

The Balance of Apoptotic and Necrotic Cell Death in Mycobacterium tuberculosis Infected Macrophages Is Not Dependent on Bacterial Virulence

An important mechanism of Mycobacterium tuberculosis pathogenesis is the ability to control cell death pathways in infected macrophages: apoptotic cell death is bactericidal, whereas necrotic cell death may facilitate bacterial dissemination and transmission

Tetracycline-inducible gene regulation in mycobacteria

A system for the tetracycline-inducible regulation of gene expression in mycobacteria has been developed. We have sub-cloned the tetRO region from the Corynebacterium glutamicum TetZ locus into a mycobacterial shuttle plasmid, making expression of genes cloned downstream of tetRO responsive to tetracycline. Using the luxAB-encoded luciferase from Vibrio harveyi as a reporter (pMind-Lx), we observed a 40-fold increase in light output from Mycobacterium smegmatis cultures 2 h after adding 20 ng ml(−1) of tetracycline. Similarly, exposure to the drug resulted in up to 20-fold increase in relative light units from M.bovis BCG carrying the reporter construct, and a 10-fold increase for M.tuberculosis. Tetracycline induction was demonstrated in log and stationary phase cultures. To evaluate whether this system is amenable to use in vivo, J774 macrophages were infected with M.bovis BCG[pMind-Lx], treated with amikacin to kill extracellular bacteria, and then incubated with tetracycline. A 10-fold increase in light output was measured after 24 h, indicating that intracellular bacteria are accessible and responsive to exogenously added tetracycline. To test the use of the tetracycline-inducible system for conditional gene silencing, mycobacteria were transformed with a pMind construct with tetRO driving expression of antisense RNA for the ftsZ gene. Bacterial cells containing the antisense construct formed filaments after 24 h exposure to tetracycline. These results demonstrate the potential of this tetracycline-regulated system for the manipulation of mycobacterial gene expression inside and outside cells

The core phageome and its interrelationship with preterm human milk lipids

\ua9 2023 The AuthorsPhages and lipids in human milk (HM) may benefit preterm infant health by preventing gastrointestinal pathobiont overgrowth and microbiome modulation. Lipid association may promote vertical transmission of phages to the infant. Despite this, interrelationships between lipids and phages are poorly characterized in preterm HM. Shotgun metagenomics and untargeted lipidomics of phage and lipid profiles from 99 preterm HM samples reveals that phages are abundant and prevalent from the first week and throughout the first 100 days of lactation. Phage-host richness of preterm HM increases longitudinally. Core phage communities characterized by Staphylococcus- and Propionibacterium-infecting phages are significantly correlated with long-chain fatty acid abundances over lactational age. We report here a phage-lipid interaction in preterm HM, highlighting the potential importance of phage carriage in preterm HM. These results reveal possible strategies for phage carriage in HM and their importance in early-life microbiota development

Comparative prebiotic activity of mixtures of cereal grain polysaccharides

The main components of the non-starch polysaccharide (NSP) fraction of wheat flour are arabinoxylan (AX) and β-glucan. These are also present in other cereal grains, but their proportions vary with AX being the major component in wheat and rye and β-glucan in barley and oats. Therefore, it was hypothesised that these NSPs could act synergistically when fermented in vitro at the ratios present in the major foods consumed, resulting in increased prebiotic activity. AX and β-glucan were therefore tested in in vitro fermentation studies to assess their prebiotic activity when used individually and/or in different ratios. Short-chain fatty-acids (SCFAs) produced from in vitro fermentation were measured using HPLC and bacterial populations were measured using flow cytometry with fluorescence in situ hybridisation (Flow-FISH). Fermentation of AX alone resulted in a significant bifidogenic activity and increased concentrations of SCFAs, mainly acetate, after 8-24 h of fermentation, however β-glucan alone did not show prebiotic activity. The greatest prebiotic activity, based on concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups, was observed when AX and β-glucan were combined at a 3:1 ratio, which corresponds to their ratios in wheat flour which is major source of cereal fibre in the diet. This indicates that the population of bacteria in the human GI tract may be modulated by the composition of the fibre in the diet, to maximise the prebiotic potential

Design and evaluation of the immunogenicity and efficacy of a biomimetic particulate formulation of viral antigens

Subunit viral vaccines are typically not as efficient as live attenuated or inactivated vaccines at inducing protective immune responses. This paper describes an alternative 'biomimetic' technology; whereby viral antigens were formulated around a polymeric shell in a rationally arranged fashion with a surface glycoprotein coated on to the surface and non-structural antigen and adjuvant encapsulated. We evaluated this model using BVDV E2 and NS3 proteins formulated in poly-(D, L-lactic-co-glycolic acid) (PLGA) nanoparticles adjuvanted with polyinosinic:polycytidylic acid (poly(I:C) as an adjuvant (Vaccine-NP). This Vaccine-NP was compared to ovalbumin and poly(I:C) formulated in a similar manner (Control-NP) and a commercial adjuvanted inactivated BVDV vaccine (IAV), all inoculated subcutaneously and boosted prior to BVDV-1 challenge. Significant virus-neutralizing activity, and E2 and NS3 specific antibodies were observed in both Vaccine-NP and IAV groups following the booster immunisation. IFN-γ responses were observed in ex vivo PBMC stimulated with E2 and NS3 proteins in both vaccinated groups. We observed that the protection afforded by the particulate vaccine was comparable to the licenced IAV formulation. In conclusion, the biomimetic particulates showed a promising immunogenicity and efficacy profile that may be improved by virtue of being a customisable mode of delivery

Mycobacterium leprae genomes from a British medieval leprosy hospital: towards understanding an ancient epidemic.

BACKGROUND: Leprosy has afflicted humankind throughout history leaving evidence in both early texts and the archaeological record. In Britain, leprosy was widespread throughout the Middle Ages until its gradual and unexplained decline between the 14th and 16th centuries. The nature of this ancient endemic leprosy and its relationship to modern strains is only partly understood. Modern leprosy strains are currently divided into 5 phylogenetic groups, types 0 to 4, each with strong geographical links. Until recently, European strains, both ancient and modern, were thought to be exclusively type 3 strains. However, evidence for type 2 strains, a group normally associated with Central Asia and the Middle East, has recently been found in archaeological samples in Scandinavia and from two skeletons from the medieval leprosy hospital (or leprosarium) of St Mary Magdalen, near Winchester, England. RESULTS: Here we report the genotypic analysis and whole genome sequencing of two further ancient M. leprae genomes extracted from the remains of two individuals, Sk14 and Sk27, that were excavated from 10th-12th century burials at the leprosarium of St Mary Magdalen. DNA was extracted from the surfaces of bones showing osteological signs of leprosy. Known M. leprae polymorphisms were PCR amplified and Sanger sequenced, while draft genomes were generated by enriching for M. leprae DNA, and Illumina sequencing. SNP-typing and phylogenetic analysis of the draft genomes placed both of these ancient strains in the conserved type 2 group, with very few novel SNPs compared to other ancient or modern strains. CONCLUSIONS: The genomes of the two newly sequenced M. leprae strains group firmly with other type 2F strains. Moreover, the M. leprae strain most closely related to one of the strains, Sk14, in the worldwide phylogeny is a contemporaneous ancient St Magdalen skeleton, vividly illustrating the epidemic and clonal nature of leprosy at this site. The prevalence of these type 2 strains indicates that type 2F strains, in contrast to later European and associated North American type 3 isolates, may have been the co-dominant or even the predominant genotype at this location during the 11th century

Field-induced quantum fluctuations in the heavy fermion superconductor CeCu2Ge2

Quantum-mechanical fluctuations in strongly correlated electron systems cause unconventional phenomena such as non-Fermi liquid behavior, and arguably high temperature superconductivity. Here we report the discovery of a field-tuned quantum critical phenomenon in stoichiometric CeCu2Ge2, a spin density wave ordered heavy fermion metal that exhibits unconventional superconductivity under ~ 10 GPa of applied pressure. Our finding of the associated quantum critical spin fluctuations of the antiferromagnetic spin density wave order, dominating the local fluctuations due to single-site Kondo effect, provide new information about the underlying mechanism that can be important in understanding superconductivity in this novel compound.Comment: Heavy Fermion, Quantum Critical Phenomeno