Future challenges in colloid and interfacial science

This article deals with topics where I expect special future challenges, exemplifying these by experiments out of my own department. One area where I expect large progress also in view of many technical developments in the past concerns the understanding of the structure of fluid interfaces at the atomic level. It is shown by non-linear optical spectroscopies that the free water surface is ice-like and can be “liquefied” by ion adsorption. X-ray fluorescence from the interface demonstrates that ion binding is very specific which cannot be explained by existing theories. A second major area are nonequilibrium features, and one of the old and new ones here is nucleation and growth. This presentation concentrates on effects produced by ultrasound, a well-defined trigger of gas bubble formation. It exhibits high potential for chemistry at extreme conditions but with a reactor at normal conditions. It has special importance for treatment of surfaces that can be also manipulated via controlled surface energies. A third area will concern complex and smart systems with multiple functions in materials and biosciences. As next generation, I anticipate those with feedback control, and examples on this are self-repairing coatings

Preexisting and de novo humoral immunity to SARS-CoV-2 in humans

Zoonotic introduction of novel coronaviruses may encounter preexisting immunity in humans. Using diverse assays for antibodies recognizing SARS-CoV-2 proteins, we detect preexisting humoral immunity. SARS-CoV-2 spike glycoprotein (S)-reactive antibodies were detectable by a flow cytometry-based method in SARS-CoV-2-uninfected individuals and were particularly prevalent in children and adolescents. They were predominantly of the IgG class and targeted the S2 subunit. By contrast, SARS-CoV-2 infection induced higher titers of SARS-CoV-2 S-reactive IgG antibodies, targeting both the S1 and S2 subunits, and concomitant IgM and IgA antibodies, lasting throughout the observation period. Notably, SARS-CoV-2-uninfected donor sera exhibited specific neutralizing activity against SARS-CoV-2 and SARS-CoV-2 S pseudotypes. Distinguishing preexisting and de novo immunity will be critical for our understanding of susceptibility to and the natural course of SARS-CoV-2 infection

'Public administration in an age of austerity' : Positive lessons from policy studies

Peer reviewedPostprin

Identification of molecular markers for the early detection of human squamous cell carcinoma of the uterine cervix

To identify novel cellular genes that could potentially act as predictive molecular markers for human cervical cancer, we employed RT–PCR differential display, reverse Northern and Northern blot analysis to compare the gene expression profiles between squamous cell carcinoma biopsies and adjacent histo-pathological normal epithelium tissues. Twenty-eight cDNA clones were isolated that were demonstrated to be consistently over-expressed in squamous cell cervical cancer biopsies of FIGO stages 1B to 3B. Most importantly, it was observed that, in addition to their over-expression in cancer lesions, some of these genes are upregulated in the presumably histo-pathological normal adjacent tissues. Of particular interest is clone G30CC that has been identified to be the gene that encodes S12 ribosomal protein. When employed for RNA–RNA in situ hybridization experiments, expression of G30CC could be detected in the immature basal epithelial cells of histo-pathological normal tissues collected from cervical cancer patients of early FIGO stages. In comparison, the expression of G30CC was not detected in cervical tissues collected from patients admitted for surgery of non-malignant conditions. These results allow the distinct possibility of employing the ribosomal protein S12 gene as an early molecular diagnostic identifier for the screening of human cervical cancer and a potential target employed for cancer gene therapy trials

Search for supersymmetric particles in scenarios with a gravitino LSP and stau NLSP

Sleptons, neutralinos and charginos were searched for in the context of scenarios where the lightest supersymmetric particle is the gravitino. It was assumed that the stau is the next-to-lightest supersymmetric particle. Data collected with the DELPHI detector at a centre-of-mass energy near 189 GeV were analysed combining the methods developed in previous searches at lower energies. No evidence for the production of these supersymmetric particles was found. Hence, limits were derived at 95% confidence level.Comment: 31 pages, 14 figure

Male circumcision and prevalence of genital human papillomavirus infection in men : a multinational study

Background: Accumulated evidence from epidemiological studies and more recently from randomized controlled trials suggests that male circumcision (MC) may substantially protect against genital HPV infection in men. The purpose of this study was to assess the association between MC and genital HPV infection in men in a large multinational study. Methods: A total of 4072 healthy men ages 18-70 years were enrolled in a study conducted in Brazil, Mexico, and the United States. Enrollment samples combining exfoliated cells from the coronal sulcus, glans penis, shaft, and scrotum were analyzed for the presence and genotyping of HPV DNA by PCR and linear array methods. Prevalence ratios (PR) were used to estimate associations between MC and HPV detection adjusting for potential confounders. Results: MC was not associated with overall prevalence of any HPV, oncogenic HPV types or unclassified HPV types. However, MC was negatively associated with non-oncogenic HPV infections (PR 0.85, 95% confident interval: 0.76-0.95), in particular for HPV types 11, 40, 61, 71, and 81. HPV 16, 51, 62, and 84 were the most frequently identified genotypes regardless of MC status. Conclusions: This study shows no overall association between MC and genital HPV infections in men, except for certain non-oncogenic HPV types for which a weak association was found. However, the lack of association with MC might be due to the lack of anatomic site specific HPV data, for example the glans penis, the area expected to be most likely protected by MC

O-linked sialoglycans modulate the proteolysis of SARS-CoV-2 spike and likely contribute to the mutational trajectory in variants of concern.

The emergence of a polybasic cleavage motif for the protease furin in SARS-CoV-2 spike has been established as a major factor for human viral transmission. The region N-terminal to that motif is extensively mutated in variants of concern (VOCs). Besides furin, spikes from these variants appear to rely on other proteases for maturation, including TMPRSS2. Glycans near the cleavage site have raised questions about proteolytic processing and the consequences of variant-borne mutations. Here, we identify that sialic acid-containing O-linked glycans on Thr678 of SARS-CoV-2 spike influence furin and TMPRSS2 cleavage and posit O-linked glycosylation as a likely driving force for the emergence of VOC mutations. We provide direct evidence that the glycosyltransferase GalNAc-T1 primes glycosylation at Thr678 in the living cell, an event that is suppressed by mutations in the VOCs Alpha, Delta, and Omicron. We found that the sole incorporation of N-acetylgalactosamine did not impact furin activity in synthetic O-glycopeptides, but the presence of sialic acid reduced the furin rate by up to 65%. Similarly, O-glycosylation with a sialylated trisaccharide had a negative impact on TMPRSS2 cleavage. With a chemistry-centered approach, we substantiate O-glycosylation as a major determinant of spike maturation and propose disruption of O-glycosylation as a substantial driving force for VOC evolution

The relationship between self-awareness of attentional status, behavioral performance and oscillatory brain rhythms

High-level cognitive factors, including self-awareness, are believed to play an important role in human visual perception. The principal aim of this study was to determine whether oscillatory brain rhythms play a role in the neural processes involved in self-monitoring attentional status. To do so we measured cortical activity using magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) while participants were asked to self-monitor their internal status, only initiating the presentation of a stimulus when they perceived their attentional focus to be maximal. We employed a hierarchical Bayesian method that uses fMRI results as soft-constrained spatial information to solve the MEG inverse problem, allowing us to estimate cortical currents in the order of millimeters and milliseconds. Our results show that, during self-monitoring of internal status, there was a sustained decrease in power within the 7-13 Hz (alpha) range in the rostral cingulate motor area (rCMA) on the human medial wall, beginning approximately 430 msec after the trial start (p < 0.05, FDR corrected). We also show that gamma-band power (41-47 Hz) within this area was positively correlated with task performance from 40-640 msec after the trial start (r = 0.71, p < 0.05). We conclude: (1) the rCMA is involved in processes governing self-monitoring of internal status; and (2) the qualitative differences between alpha and gamma activity are reflective of their different roles in self-monitoring internal states. We suggest that alpha suppression may reflect a strengthening of top-down interareal connections, while a positive correlation between gamma activity and task performance indicates that gamma may play an important role in guiding visuomotor behavior. © 2013 Yamagishi et al

Neutralising antibodies after COVID-19 vaccination in UK haemodialysis patients

Vaccination against COVID-19 induces highly protective immune responses in most people. As some countries switch from suppression to acceptance of transmission of SARS-CoV-2 within a largely vaccinated adult population, vulnerable patient groups that have not mounted adequate immune responses to vaccination might experience significant morbidity and mortality. There is an urgent need to identify such patient groups and to optimise medical advice and vaccination strategies for them

Pain Reactivity and Plasma β-Endorphin in Children and Adolescents with Autistic Disorder

International audienceBackground: Reports of reduced pain sensitivity in autism have prompted opioid theories of autism and have practical care ramifications. Our objective was to examine behavioral and physiological pain responses, plasma β-endorphin levels and their relationship in a large group of individuals with autism.Methodology/Principal Findings: The study was conducted on 73 children and adolescents with autism and 115 normal individuals matched for age, sex and pubertal stage. Behavioral pain reactivity of individuals with autism was assessed in three observational situations (parents at home, two caregivers at day-care, a nurse and child psychiatrist during blood drawing), and compared to controls during venepuncture. Plasma β-endorphin concentrations were measured by radioimmunoassay. A high proportion of individuals with autism displayed absent or reduced behavioral pain reactivity at home (68.6%), at day-care (34.2%) and during venepuncture (55.6%). Despite their high rate of absent behavioral pain reactivity during venepuncture (41.3 vs. 8.7% of controls, P<0.0001), individuals with autism displayed a significantly increased heart rate in response to venepuncture (P<0.05). Moreover, this response (Δ heart rate) was significantly greater than for controls (mean±SEM; 6.4±2.5 vs. 1.3±0.8 beats/min, P<0.05). Plasma β-endorphin levels were higher in the autistic group (P<0.001) and were positively associated with autism severity (P<0.001) and heart rate before or after venepuncture (P<0.05), but not with behavioral pain reactivity.Conclusions/Significance: The greater heart rate response to venepuncture and the elevated plasma β-endorphin found in individuals with autism reflect enhanced physiological and biological stress responses that are dissociated from observable emotional and behavioral reactions. The results suggest strongly that prior reports of reduced pain sensitivity in autism are related to a different mode of pain expression rather than to an insensitivity or endogenous analgesia, and do not support opioid theories of autism. Clinical care practice and hypotheses regarding underlying mechanisms need to assume that children with autism are sensitive to pain