Age-associated B cells predict impaired humoral immunity after COVID-19 vaccination in patients receiving immune checkpoint blockade

Age-associated B cells (ABC) accumulate with age and in individuals with different immunological disorders, including cancer patients treated with immune checkpoint blockade and those with inborn errors of immunity. Here, we investigate whether ABCs from different conditions are similar and how they impact the longitudinal level of the COVID-19 vaccine response. Single-cell RNA sequencing indicates that ABCs with distinct aetiologies have common transcriptional profiles and can be categorised according to their expression of immune genes, such as the autoimmune regulator (AIRE). Furthermore, higher baseline ABC frequency correlates with decreased levels of antigen-specific memory B cells and reduced neutralising capacity against SARS-CoV-2. ABCs express high levels of the inhibitory FcγRIIB receptor and are distinctive in their ability to bind immune complexes, which could contribute to diminish vaccine responses either directly, or indirectly via enhanced clearance of immune complexed-antigen. Expansion of ABCs may, therefore, serve as a biomarker identifying individuals at risk of suboptimal responses to vaccination

Amitriptyline-Mediated Cognitive Enhancement in Aged 3×Tg Alzheimer's Disease Mice Is Associated with Neurogenesis and Neurotrophic Activity

Approximately 35 million people worldwide suffer from Alzheimer's disease (AD). Existing therapeutics, while moderately effective, are currently unable to stem the widespread rise in AD prevalence. AD is associated with an increase in amyloid beta (Aβ) oligomers and hyperphosphorylated tau, along with cognitive impairment and neurodegeneration. Several antidepressants have shown promise in improving cognition and alleviating oxidative stress in AD but have failed as long-term therapeutics. In this study, amitriptyline, an FDA-approved tricyclic antidepressant, was administered orally to aged and cognitively impaired transgenic AD mice (3×TgAD). After amitriptyline treatment, cognitive behavior testing demonstrated that there was a significant improvement in both long- and short-term memory retention. Amitriptyline treatment also caused a significant potentiation of non-toxic Aβ monomer with a concomitant decrease in cytotoxic dimer Aβ load, compared to vehicle-treated 3×TgAD controls. In addition, amitriptyline administration caused a significant increase in dentate gyrus neurogenesis as well as increases in expression of neurosynaptic marker proteins. Amitriptyline treatment resulted in increases in hippocampal brain-derived neurotrophic factor protein as well as increased tyrosine phosphorylation of its cognate receptor (TrkB). These results indicate that amitriptyline has significant beneficial actions in aged and damaged AD brains and that it shows promise as a tolerable novel therapeutic for the treatment of AD

Clinical practice: Breastfeeding and the prevention of allergy

The increase in allergic disease prevalence has led to heightened interest in the factors determining allergy risk, fuelled by the hope that by influencing these factors one could reduce the prevalence of allergic conditions. The most important modifiable risk factors for allergy are maternal smoking behaviour and the type of feeding. A smoke-free environment for the child (to be), exclusive breastfeeding for 4–6 months and the postponement of supplementary feeding (solids) until 4 months of age are the main measures considered effective. There is no place for restricted diets during pregnancy or lactation. Although meta-analyses suggest that hypoallergenic formula after weaning from breastfeeding grants protection against the development of allergic disease, the evidence is limited and weak. Moreover, all current feeding measures aiming at allergy prevention fail to show effects on allergic manifestations later in life, such as asthma. In conclusion, the allergy preventive effect of dietary interventions in infancy is limited. Counselling of future parents on allergy prevention should pay attention to these limitations

Nanoscale Metallic Iron for Environmental Remediation: Prospects and Limitations

The amendment of the subsurface with nanoscale metallic iron particles (nano-Fe0) has been discussed in the literature as an efficient in situ technology for groundwater remediation. However, the introduction of this technology was controversial and its efficiency has never been univocally established. This unsatisfying situation has motivated this communication whose objective was a comprehensive discussion of the intrinsic reactivity of nano-Fe0 based on the contemporary knowledge on the mechanism of contaminant removal by Fe0 and a mathematical model. It is showed that due to limitations of the mass transfer of nano-Fe0 to contaminants, available concepts cannot explain the success of nano-Fe0 injection for in situ groundwater remediation. It is recommended to test the possibility of introducing nano-Fe0 to initiate the formation of roll-fronts which propagation would induce the reductive transformation of both dissolved and adsorbed contaminants. Within a roll-front, FeII from nano-Fe0 is the reducing agent for contaminants. FeII is recycled by biotic or abiotic FeIII reduction. While the roll-front concept could explain the success of already implemented reaction zones, more research is needed for a science-based recommendation of nano- Fe0 for subsurface treatment by roll-front

IFITM proteins inhibit HIV-1 protein synthesis

Interferon induced transmembrane proteins (IFITMs) inhibit the cellular entry of a broad range of viruses, but it has been suspected that for HIV-1 IFITMs may also inhibit a post-integration replicative step. We show that IFITM expression reduces HIV-1 viral protein synthesis by preferentially excluding viral mRNA transcripts from translation and thereby restricts viral production. Codon-optimization of proviral DNA rescues viral translation, implying that IFITM-mediated restriction requires recognition of viral RNA elements. In addition, we find that expression of the viral accessory protein Nef can help overcome the IFITM-mediated inhibition of virus production. Our studies identify a novel role for IFITMs in inhibiting HIV replication at the level of translation, but show that the effects can be overcome by the lentiviral protein Nef.Wellcome Trust-University of Edinburgh Institutional Strategic Support Fun

Red snapper excavate sediments around artificial reefs: observations of ecosystem-engineering behavior by a widely distributed lutjanid

Hard substrate and vertical relief are limited habitat resources for reef-associated species in many regions. On the West Florida Shelf (WFS) of the Gulf of Mexico, red grouper Epinephelus morio act as ecosystem engineers by excavating sediments to expose limestone bedrock. Excavations can exceed 25 m in diameter and 2 m in depth and are among the most abundant WFS seafloor features at depths between 40 and 110 m. As part of a survey of hard-bottom habitats and associated reef fish assemblages, 1203 excavations were identified in WFS waters along the Florida Panhandle between 2014 and 2019. These excavations often contained subsided artificial reef material within their interior and infrequently included E. morio among observed fishes. We video-identified red snapper Lutjanus campechanus excavating sediments around 2 subsided artificial reefs in 2015 and 2017 for a total of approximately 56 min of excavation activity. A total of 24 excavation events were documented around a tire pile in 2015, and 5 were documented around a pyramid-shaped reef module in 2017. These observations help to explain the subsidence of artificial reefs and apparent excavation around their bases despite the scarcity of previously known excavating species. This suggests that L. campechanus might be ecosystem engineers on the WFS

Safety issues in functional capacity evaluation: Findings from a trial of a new approach for evaluating clients with chronic back pain

Although safety is recognized as a critical issue in functional capacity evaluations (FCEs), it has rarely been investigated. This paper reports on the findings of a study which examined safety aspects of a new approach to FCE. Fourteen rehabilitation clients with chronic back pain participated in the study. Aspects examined included the pre-FCE screening procedures, the monitoring of performance and safety during the FCE, and the end of FCE measures and follow-up procedures. Support was found for the screening procedures of the approach, particularly blood pressure measurement, and for the combined approach to monitoring of the persons performance from biomechanical, physiological and psychophysical perspectives. Issues for FCE safety in general are identified and discussed, including the importance of screening procedures to determine readiness for FCEs and the issue of load handling in FCEs, especially in relation to clients with chronic back pain