In Conversation with Mubin Shaikh: From Salafi Jihadist to Undercover Agent inside the "Toronto 18" Terrorist Group

This interview with former undercover agent Mubin Shaikh can help academics and security practitioners understand the key role played and the challenges faced by covert human intelligence sources within domestic terrorist groups. The interview highlights the identity crisis, the personal factors, and the allure of jihadi militancy that initially drove Shaikh to join a Salafi jihadist group. It investigates Shaikh’s process of disengagement from the Salafi jihadist belief system and his rediscovery of a moderate, inclusive, and benevolent form of Islam. It explores his work as an undercover agent for the Canadian Security Intelligence Service, the Royal Canadian Mounted Police, and the Integrated National Security Enforcement Team responsible for disrupting domestic terrorist groups. The “Toronto 18” terrorist cell, the key role played by undercover agents in preventing terrorist action, and the challenges posed by entrapment are also discussed

Microbial environment shapes immune function and cloacal microbiota dynamics in zebra finches <i>Taeniopygia guttata</i>

BACKGROUND: The relevance of the host microbiota to host ecology and evolution is well acknowledged. However, the effect of the microbial environment on host immune function and host microbiota dynamics is understudied in terrestrial vertebrates. Using a novel experimental approach centered on the manipulation of the microbial environment of zebra finches Taeniopygia guttata, we carried out a study to investigate effects of the host's microbial environment on: 1) constitutive immune function, 2) the resilience of the host cloacal microbiota; and 3) the degree to which immune function and host microbiota covary in microbial environments that differ in diversity. RESULTS: We explored immune indices (hemagglutination, hemolysis, IgY levels and haptoglobin concentration) and host-associated microbiota (diversity and composition) in birds exposed to two experimental microbial environments differing in microbial diversity. According to our expectations, exposure to experimental microbial environments led to differences related to specific antibodies: IgY levels were elevated in the high diversity treatment, whereas we found no effects for the other immune indices. Furthermore, according to predictions, we found significantly increased richness of dominant OTUs for cloacal microbiota of birds of the high diversity compared with the low diversity group. In addition, cloacal microbiota of individual females approached their baseline state sooner in the low diversity environment than females in the high diversity environment. This result supported a direct phenotypically plastic response of host microbiota, and suggests that its resilience depends on environmental microbial diversity. Finally, immune indices and cloacal microbiota composition tend to covary within treatment groups, while at the same time, individuals exhibited consistent differences of immune indices and microbiota characteristics. CONCLUSION: We show that microbes in the surroundings of terrestrial vertebrates can influence immune function and host-associated microbiota dynamics over relatively short time scales. We suggest that covariation between immune indices and cloacal microbiota, in addition to large and consistent differences among individuals, provides potential for evolutionary adaptation. Ultimately, our study highlights that linking environmental and host microbiotas may help unravelling immunological variation within and potentially among species, and together these efforts will advance the integration of microbial ecology and ecological immunology

Biological Oxygen-dosed Activated Carbon (BODAC) filters – A bioprocess for ultrapure water production removing organics, nutrients and micropollutants

Biological oxygen-dosed activated carbon (BODAC) filters in an Ultrapure water plant were demonstrated to have the potential to further treat secondary wastewater treatment effluent. The BODAC filters were operated for 11 years without carbon regeneration or replacement, while still functioning as pre-treatment step to reverse osmosis (RO) membranes by actively removing organic micropollutants (OMPs) and foulants. In this study, the removal of nutrients and 13 OMPs from secondary wastewater treatment effluent was investigated for 2 years and simultaneously, the granules’ characterization and microbial community analysis were conducted to gain insights behind the stable long-term operation of the BODAC filters. The results showed that the BODAC granules' surface area was reduced by ∼70 % of what is in virgin carbon granules and covered by biofilm and inorganic depositions. The BODAC filters reduced the concentration of soluble organics, mainly proteins, performed as an effective nitrification system, and almost completely removed manganese. During the 2 years of observation, the filters consistently removed some OMPs such as hydrochlorothiazide, metoprolol, sotalol, and trimethoprim by at least 70 %. Finally, through microbial community analysis, we found that nitrifying and manganese-oxidizing bacteria were detected in high relative abundance on BODAC granules, supporting BODAC performance in removing OMPs and manganese as well as converting nitrogenous species in the water.</p

Measuring echogenicity and area of the puborectalis muscle:method and reliability

OBJECTIVES: To develop a semi-automated method to assess puborectalis muscle echogenicity on three-dimensional/four-dimensional (3D/4D) volume transperineal ultrasound images using 4D View and Matlab® software and evaluate its intra- and interobserver reliability. METHOD: The data of 23 women in their first trimester were included. 3D/4D volume datasets were obtained at rest. Two inexperienced observers were trained by an experienced observer to construct tomographic ultrasound images (TUI) from the original data and to delineate all structures. Puborectalis muscle area (PMA) and the mean echogenicity of the puborectalis muscle (MEP) were calculated offline. Intra- and interobserver reliability were determined by intraclass correlation coefficients (ICC) and their 95% CIs. RESULTS: The development of a semi-automated method to calculate puborectalis area and echogenicity is described in detail. PMA and MEP measurements in pregnant women demonstrated almost perfect intraobserver reliability for both inexperienced observers, with ICC values ranging from 0.88 to 0.99. The interobserver reliability showed ICCs of 0.63 for PMA and almost perfect ICC values, of 0.96-0.98, for echogenicity. The majority of intraobserver mismatch between two delineations of PMA occurred near the borders. CONCLUSIONS: Matlab software can be used to provide reliable measurements of the area and echogenicity of the puborectalis muscle. As the latter can be used to assess structural changes in the puborectalis muscle, it appears a promising new tool for studying pelvic floor structural anatomy

The microbial environment modulates non-genetic maternal effects on egg immunity

BACKGROUND: In a diverse microbial world immune function of animals is essential. Diverse microbial environments may contribute to extensive variation in immunological phenotypes of vertebrates, among and within species and individuals. As maternal effects benefit offspring development and survival, whether females use cues about their microbial environment to prime offspring immune function is unclear. To provide microbial environmental context to maternal effects, we asked if the bacterial diversity of the living environment of female zebra finches Taeniopygia guttata shapes maternal effects on egg immune function. We manipulated environmental bacterial diversity of birds and tested if females increased immunological investment in eggs in an environment with high bacterial diversity (untreated soil) versus low (gamma-sterilized soil). We quantified lysozyme and ovotransferrin in egg albumen and IgY in egg yolk and in female blood, and we used 16S rRNA gene sequencing to profile maternal cloacal and eggshell microbiotas. RESULTS: We found a maternal effect on egg IgY concentration that reflected environmental microbial diversity: females who experienced high diversity deposited more IgY in their eggs, but only if maternal plasma IgY levels were relatively high. We found no effects on lysozyme and ovotransferrin concentrations in albumen. Moreover, we uncovered that variation in egg immune traits could be significantly attributed to differences among females: for IgY concentration in yolk repeatability R = 0.80; for lysozyme concentration in albumen R = 0.27. Furthermore, a partial least squares path model (PLS-PM) linking immune parameters of females and eggs, which included maternal and eggshell microbiota structures and female body condition, recapitulated the treatment-dependent yolk IgY response. The PLS-PM additionally suggested that the microbiota and physical condition of females contributed to shaping maternal effects on egg immune function, and that (non-specific) innate egg immunity was prioritized in the environment with low bacterial diversity. CONCLUSIONS: The microbial environment of birds can shape maternal effects on egg immune function. Since immunological priming of eggs benefits offspring, we highlight that non-genetic maternal effects on yolk IgY levels based on cues from the parental microbial environment may prove important for offspring to thrive in the microbial environment that they are expected to face

Mean echogenicity and area of puborectalis muscle in women with stress urinary incontinence during pregnancy and after delivery

INTRODUCTION AND HYPOTHESIS: Pregnancy and childbirth are risk factors for the development of stress urinary incontinence (SUI). Urinary continence depends on normal urethral support, which is provided by normal levator ani muscle function. Our objective was to compare mean echogenicity and the area of the puborectalis muscle between women with and those without SUI during and after their first pregnancy. METHODS: We examined 280 nulliparous women at a gestational age of 12 weeks, 36 weeks, and 6 months after delivery. They filled out the validated Urogenital Distress Inventory and underwent perineal ultrasounds. SUI was considered present if the woman answered positively to the question "do you experience urine leakage related to physical activity, coughing, or sneezing?" Mean echogenicity of the puborectalis muscle (MEP) and puborectalis muscle area (PMA) were calculated. The MEP and PMA during pregnancy and after delivery in women with and without SUI were compared using independent Student's t test. RESULTS: After delivery the MEP was higher in women with SUI if the pelvic floor was at rest or in contraction, with effect sizes of 0.30 and 0.31 respectively. No difference was found in the area of the puborectalis muscle between women with and those without SUI. CONCLUSIONS: Women with SUI after delivery had a statistically significant higher mean echogenicity of the puborectalis muscle compared with non-SUI women when the pelvic floor was at rest and in contraction; the effect sizes were small. This higher MEP is indicative of a relatively higher intramuscular extracellular matrix component and could represent diminished contractile function

Exploring the versatility of the covalent thiol-alkyne reaction with substituted propargyl warheads: a deciding role for the cysteine protease

Terminal unactivated alkynes are nowadays considered the golden standard for cysteine-reactive warheads in activity-based probes (ABPs) targeting cysteine deubiquitinating enzymes (DUBs). In this work, we study the versatility of the thiol-alkyne addition reaction in more depth. Contrary to previous findings with UCHL3, we now show that covalent adduct formation can progress with substituents on the terminal or internal alkyne position. Strikingly, acceptance of alkyne substituents is strictly DUB-specific as this is not conserved among members of the same subfamily. Covalent adduct formation with the catalytic cysteine residue was validated by gel analysis and mass spectrometry of intact ABP-treated USP16CD(WT) and catalytically inactive mutant USP16CD(C205A). Bottom-up mass spectrometric analysis of the covalent adduct with a deuterated propargyl ABP provides mechanistic understanding of the in situ thiol-alkyne reaction, identifying the alkyne rather than an allenic intermediate as the reactive species. Furthermore, kinetic analysis revealed that introduction of (bulky/electron-donating) methyl substituents on the propargyl moiety decreases the rate of covalent adduct formation, thus providing a rational explanation for the commonly lower level of observed covalent adduct compared to unmodified alkynes. Altogether, our work extends the scope of possible propargyl derivatives in cysteine targeting ABPs from unmodified terminal alkynes to internal and substituted alkynes, which we anticipate will have great value in the development of ABPs with improved selectivity profiles.Proteomic

Genetic diversity, demographic history and neo-sex chromosomes in the Critically Endangered Raso lark

Small effective population sizes could expose island species to inbreeding and loss of genetic variation. Here, we investigate factors shaping genetic diversity in the Raso lark, which has been restricted to a single islet for approximately 500 years, with a population size of a few hundred. We assembled a reference genome for the related Eurasian skylark and then assessed diversity and demographic history using RAD-seq data (75 samples from Raso larks and two related mainland species). We first identify broad tracts of suppressed recombination in females, indicating enlarged neo-sex chromosomes. We then show that genetic diversity across autosomes in the Raso lark is lower than in its mainland relatives, but inconsistent with long-term persistence at its current population size. Finally, we find that genetic signatures of the recent population contraction are overshadowed by an ancient expansion and persistence of a very large population until the human settlement of Cape Verde. Our findings show how genome-wide approaches to study endangered species can help avoid confounding effects of genome architecture on diversity estimates, and how present-day diversity can be shaped by ancient demographic events

The nonpolymorphic MHC Qa-1b mediates CD8+ T cell surveillance of antigen-processing defects

The nonclassical major histocompatibility complex (MHC) Qa-1b accommodates monomorphic leader peptides and functions as a ligand for germ line receptors CD94/NKG2, which are expressed by natural killer cells and CD8+ T cells. We here describe that the conserved peptides are replaced by a novel peptide repertoire of surprising diversity as a result of impairments in the antigen-processing pathway. This novel peptide repertoire represents immunogenic neoantigens for CD8+ T cells, as we found that these Qa-1b–restricted T cells dominantly participated in the response to tumors with processing deficiencies. A surprisingly wide spectrum of target cells, irrespective of transformation status, MHC background, or type of processing deficiency, was recognized by this T cell subset, complying with the conserved nature of Qa-1b. Target cell recognition depended on T cell receptor and Qa-1b interaction, and immunization with identified peptide epitopes demonstrated in vivo priming of CD8+ T cells. Our data reveal that Qa-1b, and most likely its human homologue human leukocyte antigen-E, is important for the defense against processing-deficient cells by displacing the monomorphic leader peptides, which relieves the inhibition through CD94/NKG2A on lymphocytes, and by presenting a novel repertoire of immunogenic peptides, which recruits a subset of cytotoxic CD8+ T cells