Minocycline in Severe Cerebral Amyloid Angiopathy: A Single-Center Cohort Study

BACKGROUND: Evidence from animal studies suggests that minocycline may reduce lobar intracerebral hemorrhage (ICH) recurrence in cerebral amyloid angiopathy, possibly by inhibiting perivascular extracellular matrix degradation in cerebral small vessels. There is currently no evidence of its safety or efficacy in humans with cerebral amyloid angiopathy. METHODS AND RESULTS: To provide preliminary data to support future studies of minocycline’s efficacy, the authors performed a retrospective single-center cohort study to assess the incidence of recurrent ICH in patients with an aggressive clinical course of probable cerebral amyloid angiopathy who had been prescribed minocycline off-label via shared decision-making. Crude incidence rate ratios were calculated to compare incidence rates before versus after treatment. Sixteen patients (mean age at minocycline initiation, 66.3±3.5 years; women 62.5%; median of 3 lobar ICHs [range, 1–6]) were initiated on minocycline and followed for a median of 12.4 months (range, 1.8–61.4 months). Adverse events were reported in 4 of 16 patients (gastroenteric, n=3; dizziness, n=1) and were considered mild. ICH incidence sharply increased the year before minocycline initiation compared with the preceding years (2.18 [95% CI, 1.50–3.07] versus 0.40 [95% CI, 0.25–0.60] events per patient-year) and fell to 0.46 (95% CI, 0.23–0.83) events per patient-year afterwards. Incidence rate ratios of recurrent ICH after minocycline was lower (0.21 [95% CI, 0.11–0.42], P<0.0001) compared with the year before initiation. CONCLUSIONS: Minocycline appeared safe and generally tolerated in a small group of patients with clinically aggressive cerebral amyloid angiopathy and was associated with reduced ICH recurrence. Determining whether this reduction represents a biological response to minocycline rather than a regression to the mean, however, will require a future controlled treatment trial

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Eusocial Transition in Blattodea: Transposable Elements and Shifts of Gene Expression

(1) Unravelling the molecular basis underlying major evolutionary transitions can shed light on how complex phenotypes arise. The evolution of eusociality, a major evolutionary transition, has been demonstrated to be accompanied by enhanced gene regulation. Numerous pieces of evidence suggest the major impact of transposon insertion on gene regulation and its role in adaptive evolution. Transposons have been shown to be play a role in gene duplication involved in the eusocial transition in termites. However, evidence of the molecular basis underlying the eusocial transition in Blattodea remains scarce. Could transposons have facilitated the eusocial transition in termites through shifts of gene expression? (2) Using available cockroach and termite genomes and transcriptomes, we investigated if transposons insert more frequently in genes with differential expression in queens and workers and if those genes could be linked to specific functions essential for eusocial transition. (3) The insertion rate of transposons differs among differentially expressed genes and displays opposite trends between termites and cockroaches. The functions of termite transposon-rich queen- and worker-biased genes are related to reproduction and ageing and behaviour and gene expression, respectively. (4) Our study provides further evidence on the role of transposons in the evolution of eusociality, potentially through shifts in gene expression

Non-linear transient models and transient corrections methods for IR low-background photo-detectors

Abstract. Physical models are used to reproduce and correct transient effects of infrared (IR) photo-detectors in time series after incoming illumination changes. Such photo-detectors, working at low background for IR astronomy in space, cover the ranges 6-15 µm (Si:Ga), 40-110 µm (unstressed Ge:GA) and 120-210 µm (stressed Ge:Ga) and are working at low temperature. We discuss detectors models (direct models) and transients corrections (inversion methods). Some have been successfully applied to ISO data, others are in preparation for SIRT

Live-bearing cockroach genome reveals convergent evolutionary mechanisms linked to viviparity in insects and beyond

Insects provide an unparalleled opportunity to link genomic changes with the rise of novel phenotypes, given tremendous variation in the numerous and complex adaptations displayed across the group. Among these numerous and complex adaptations, live-birth has arisen repeatedly and independently in insects and across the tree of life, suggesting this is one of the most common types of convergent evolution among animals. We sequenced the genome and transcriptome of the Pacific beetle-mimic cockroach, the only truly viviparous cockroach, and performed comparative analyses including two other viviparous insect lineages, the tsetse and aphids, to unravel the genomic basis underlying the transition to viviparity in insects. We identified pathways experiencing adaptive evolution, common in all viviparous insects surveyed, involved in uro-genital remodeling, maternal control of embryo development, tracheal system, and heart development. Our findings suggest the essential role of those pathways for the development of placenta-like structure enabling embryo development and nutrition. Viviparous transition seems also to be accompanied by the duplication of genes involved in eggshell formation. Our findings from the viviparous cockroach and tsetse reveal that genes involved in uterine remodeling are up-regulated and immune genes are down-regulated during the course of pregnancy. These changes may facilitate structural changes to accommodate developing young and protect them from the mothers immune system. Our results denote a convergent evolution of live-bearing in insects and suggest similar adaptive mechanisms occurred in vertebrates, targeting pathways involved in eggshell formation, uro-genital remodeling, enhanced tracheal and heart development, and reduced immunity

Live-bearing cockroach genome reveals convergent evolutionary mechanisms linked to viviparity in insects and beyond

Live birth (viviparity) has arisen repeatedly and independently among animals. We sequenced the genome and transcriptome of the viviparous Pacific beetle-mimic cockroach and performed comparative analyses with two other viviparous insect lineages, tsetse flies and aphids, to unravel the basis underlying the transition to viviparity in insects. We identified pathways undergoing adaptive evolution for insects, involved in urogenital remodeling, tracheal system, heart development, and nutrient metabolism. Transcriptomic analysis of cockroach and tsetse flies revealed that uterine remodeling and nutrient production are increased and the immune response is altered during pregnancy, facilitating structural and physiological changes to accommodate and nourish the progeny. These patterns of convergent evolution of viviparity among insects, together with similar adaptive mechanisms identified among vertebrates, highlight that the transition to viviparity requires changes in urogenital remodeling, enhanced tracheal and heart development (corresponding to angiogenesis in vertebrates), altered nutrient metabolism, and shifted immunity in animal systems.</p