Flavoured soft leptogenesis and natural values of the B term

We revisit flavour effects in soft leptogenesis relaxing the assumption of universality for the soft supersymmetry breaking terms. We find that with respect to the case in which the heavy sneutrinos decay with equal rates and equal CP asymmetries for all lepton flavours, hierarchical flavour configurations can enhance the efficiency by more than two orders of magnitude. This translates in more than three order of magnitude with respect to the one-flavour approximation. We verify that lepton flavour equilibration effects related to off-diagonal soft slepton masses are ineffective for damping these large enhancements. We show that soft leptogenesis can be successful for unusual values of the relevant parameters, allowing for $B\sim {\cal O}({\rm TeV})$ and for values of the washout parameter up to $m_{\rm eff}/m_* \sim 5\times 10^{3}$.Comment: 23 pages, 5 figures postscript, Minor changes to match the published version in JHE

Prion Protein Amino Acid Determinants of Differential Susceptibility and Molecular Feature of Prion Strains in Mice and Voles

The bank vole is a rodent susceptible to different prion strains from humans and various animal species. We analyzed the transmission features of different prions in a panel of seven rodent species which showed various degrees of phylogenetic affinity and specific prion protein (PrP) sequence divergences in order to investigate the basis of vole susceptibility in comparison to other rodent models. At first, we found a differential susceptibility of bank and field voles compared to C57Bl/6 and wood mice. Voles showed high susceptibility to sheep scrapie but were resistant to bovine spongiform encephalopathy, whereas C57Bl/6 and wood mice displayed opposite features. Infection with mouse-adapted scrapie 139A was faster in voles than in C57Bl/6 and wood mice. Moreover, a glycoprofile change was observed in voles, which was reverted upon back passage to mice. All strains replicated much faster in voles than in mice after adapting to the new species. PrP sequence comparison indicated a correlation between the transmission patterns and amino acids at positions 154 and 169 (Y and S in mice, N and N in voles). This correlation was confirmed when inoculating three additional rodent species: gerbils, spiny mice and oldfield mice with sheep scrapie and 139A. These rodents were chosen because oldfield mice do have the 154N and 169N substitutions, whereas gerbil and spiny mice do not have them. Our results suggest that PrP residues 154 and 169 drive the susceptibility, molecular phenotype and replication rate of prion strains in rodents. This might have implications for the assessment of host range and molecular traceability of prion strains, as well as for the development of improved animal models for prion diseases

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

Antihypertensives for combating dementia? A perspective on candidate molecular mechanisms and population-based prevention

Age-related increases in prevalent dementia over the next 30–40 years risk collapsing medical resources or radically altering the way we treat patients. Better prevention of dementia therefore needs to be one of our highest medical priorities. We propose a perspective on the pathological basis of dementia based on a cerebrovascular-Alzheimer disease spectrum that provides a more powerful explanatory framework when considering the impact of possible public health interventions. With this in mind, a synthesis of evidence from basic, clinical and epidemiological studies indeed suggests that the enhanced treatment of hypertension could be effective for the primary prevention of dementia of either Alzheimer or vascular etiology. In particular, we focus on candidate preventative mechanisms, including reduced cerebrovascular disease, disruption of hypoxia-dependent amyloidogenesis and the potential neuroprotective properties of calcium channel blockers. Following the successful translation of large, long-term and resource-intense trials in cardiology into improved vascular health outcomes in many countries, new multinational prevention trials with dementia-related primary outcomes are now urgently required

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses

On 24th November 2021, the sequence of a new SARS-CoV-2 viral isolate Omicron-B.1.1.529 was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titers of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic Alpha, Beta, Gamma, or Delta are substantially reduced, or the sera failed to neutralize. Titers against Omicron are boosted by third vaccine doses and are high in both vaccinated individuals and those infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of the large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses and uses mutations that confer tight binding to ACE2 to unleash evolution driven by immune escape. This leads to a large number of mutations in the ACE2 binding site and rebalances receptor affinity to that of earlier pandemic viruses

Engineering of Functional Cartilage Tissue Using Stem Cells from Synovial Lining: A Preliminary Study

Stem cells derived from synovial lining—synovial lining-derived stem cells or SDSCs—are a promising cell source for cartilage tissue engineering. We hypothesized that negatively selected SDSCs would form cartilage constructs and conventionally passaged SDSCs would be contaminated with macrophages, inhibiting SDSC-based chondrogenesis. We mixed SDSCs with fibrin gel and seeded the cells into polyglycolic acid scaffolds. After 3 days of incubation with a proliferative growth factor cocktail (containing transforming growth factor β1 [TGF-β1], insulin-like growth factor I [IGF-I], and basic fibroblast growth factor [FGF-2]), the cell-fibrin-polyglycolic acid constructs were transferred into rotating bioreactor systems and cultured with a chondrogenic growth factor cocktail (TGF-β1/IGF-I) for up to 4 weeks. Tissue constructs based on negatively selected SDSCs had cartilaginous characteristics; were rich in glycosaminoglycans and collagen II; exhibited high expression of mRNA and protein for collagen II, aggrecan, and Sox 9; exhibited a negligible level of mRNA and protein for collagens I and X; and had an equilibrium modulus in the range of values measured for native human cartilage. Conventional passage yielded SDSCs with contaminating macrophages, which adversely affected the quality of tissue-engineered cartilage. We thus propose functional cartilage constructs could be engineered in vitro through the use of negatively isolated SDSCs