ANTI-CRISPR vs. CRISPR: The evolutionary arms race between microorganisms

CRISPR arrays are a defense mechanism employed by bacteria against viral invaders. Cas proteins do the work in detecting, capturing, and integrating the viral DNA into the CRISPR array (Barrangou et al., 2007). Anti-CRISPR proteins are produced by phages, viruses that infect bacteria, to stop the bacterial host’s CRISPR-Cas complex from interrupting the phage life cycle (Bondy-Denomy, et al., 2015). SEA-PHAGES is a course-based bacteriophage research network composed of 120 colleges and known at James Madison University as Viral Discovery. JMU uses the unsequenced Streptomyces griseus ATCC10137 as a host for bacteriophage discovery and propagation, and in this study we report the sequencing and analysis of this strain, including a search for CRISPR-Cas arrays. To determine if the S. griseus ATCC 10137 encodes CRISPR-Cas arrays, next generation sequencing and bioinformatic analyses were performed. DNA extraction and whole genome sequencing using an Illumina MiniSeq and Oxford MinION were used to obtain sequence data from S. griseus ATCC10137. The Illumina reads were trimmed using Trimmomatic, and the Nanopore data were filtered using Filtlong. A hybrid genome assembly using the Illumina reads and Nanopore reads was generated using Unicycler, resulting in a genome assembly that was 8,576,363 bp long. To determine if CRISPR-Cas arrays were present in the genome, the assembly fasta was uploaded to CRISPRfinder. CRISPRfinder identified 3 probable CRISPR arrays, and 10 questionable regions. Automated annotation methods Prokka and RAST were used to predict genes in the S. griseus genome, but they produced substantially different output. We therefore developed the novel bioinformatic tool, Prokkrastinator, to merge the two annotation methods. Prokkrastinator doubles as a genome browser and gene table. To search for anti-CRISPR proteins in the genome of bacteriophage Wipeout, protein models were generated using YASARA. Of the 62.57 % of the Wipeout gene products that were not able to be modeled, 13 gene products were in the same size range as all other phage-produced anti-CRISPR proteins, 50-150 amino acids long. These 13 gene products should be further studied to determine whether or not they could be potential anti-CRISPR proteins, as they are the only proteins of the appropriate size

Modifying memory for a museum tour in older adults: reactivation-related updating that enhances and distorts memory is reduced in ageing

Memory reactivation, the activation of a latent memory trace when we are reminded of a past experience, strengthens memory but can also contribute to distortions if new information present during reactivation is integrated with existing memory. In a previous study in young adults (St. Jacques & Schacter, 2013; Psychological Science) we found that the quality of memory reactivation, manipulated using the principle of encoding specificity and indexed by recollection ratings, modulated subsequent true and false memories for events experienced during a museum tour. Here, we examined age-related changes in the quality of memory reactivation on subsequent memory. Young and older adults reactivated memories for museum stops immediately followed by the presentation of a novel lure photo from an alternate tour version (i.e., reactivation plus new information). There was an increase in subsequent true memories for reactivated targets and for subsequent false memories for lures that followed reactivated targets, when compared to baseline target and lure photos. However, the influence of reactivation on subsequent memories was reduced in older adults. These data reveal that aging alters reactivation-related updating processes that allow memories to be strengthened and updated with new information- consequently reducing memory distortions in older compared to young adults

Book Reviews

Reviews of the following books: The Fathers of the Towns: Leadership and Community Structure in Eighteenth-century New England by Edward M. Cook, Jr.; Voyages by Alfred T. Hill; The Indians of Maine and the Atlantic Provinces: A Bibliographical Guide by Roger B. Ray; Sunday River Sketches: A New England Chronicle by Martha Fifield Wilkin

Influence of aging on the neural correlates of autobiographical, episodic, and semantic memory retrieval

We used fMRI to assess the neural correlates of autobiographical, semantic, and episodic memory retrieval in healthy young and older adults. Participants were tested with an eventrelated paradigm in which retrieval demand was the only factor varying between trials. A spatio-temporal partial least square analysis was conducted to identify the main patterns of activity characterizing the groups across conditions. We identified brain regions activated by all three memory conditions relative to a control condition. This pattern was expressed equally in both age groups and replicated previous findings obtained in a separate group of younger adults. We also identified regions whose activity differentiated among the different memory conditions. These patterns of differentiation were expressed less strongly in the older adults than in the young adults, a finding that was further confirmed by a barycentric discriminant analysis. This analysis showed an age-related dedifferentiation in autobiographical and episodic memory tasks but not in the semantic memory task or the control condition. These findings suggest that the activation of a common memory retrieval network is maintained with age, whereas the specific aspects of brain activity that differ with memory content are more vulnerable and less selectively engaged in older adults. Our results provide a potential neural mechanism for the well-known age differences in episodic/autobiographical memory, and preserved semantic memory, observed when older adults are compared with younger adults

Comparison of earthquake-triggered turbidites from the Saguenay (Eastern Canada) and Reloncavi (Chilean margin) Fjords: implications for paleoseismicity and sedimentology

International audienceHigh-resolution seismic profiles along with physical and sedimentological properties of sediment cores from the Saguenay (Eastern Canada) and Reloncavi (Chile) Fjords allowed the identification of several decimeter to meter-thick turbidites. In both fjords, the turbidites were associated with large magnitude historic and pre-historic earthquakes including the 1663 AD (M > 7) earthquake in the Saguenay Fjord, and the 1960 (M 9.5), 1837 (M ~ 8) and 1575 AD major Chilean subduction earthquakes in the Reloncavi Fjord. In addition, a sand layer with exoscopic characteristics typical of a tsunami deposit was observed immediately above the turbidite associated with the 1575 AD earthquake in the Reloncavi Fjord and supports both the chronology and the large magnitude of that historic earthquake. In the Saguenay Fjord, the earthquake-triggered turbidites are sometimes underlying a hyperpycnite associated with the rapid breaching and draining of a natural dam formed by earthquake-triggered landslides. Similar hyperpycnal floods were also recorded in historical and continental geological archives for the 1960 and 1575 AD Chilean subduction earthquakes, highlighting the risk of such flood events several weeks or months after main earthquake. In both fjords, as well as in other recently recognized earthquake-triggered turbidites, the decimeter-to meter-thick normally-graded turbidites are characterized by a homogeneous, but slightly fining upward tail. Finally, this paper also emphasizes the sensitivity of fjords to record historic and pre-historic seismicity

Age differences in brain activity during emotion processing: reflections of age-Related decline or increased emotion regulation?

Despite the fact that physical health and cognitive abilities decline with aging, the ability to regulate emotion remains stable and in some aspects improves across the adult life span. Older adults also show a positivity effect in their attention and memory, with diminished processing of negative stimuli relative to positive stimuli compared with younger adults. The current paper reviews functional magnetic resonance imaging studies investigating age-related differences in emotional processing and discusses how this evidence relates to two opposing theoretical accounts of older adults’ positivity effect. The aging-brain model [Cacioppo et al. in: Social Neuroscience: Toward Understanding the Underpinnings of the Social Mind. New York, Oxford University Press, 2011] proposes that older adults’ positivity effect is a consequence of age-related decline in the amygdala, whereas the cognitive control hypothesis [Kryla-Lighthall and Mather in: Handbook of Theories of Aging, ed 2. New York, Springer, 2009; Mather and Carstensen: Trends Cogn Sci 2005;9:496–502; Mather and Knight: Psychol Aging 2005;20:554–570] argues that the positivity effect is a result of older adults’ greater focus on regulating emotion. Based on evidence for structural and functional preservation of the amygdala in older adults and findings that older adults show greater prefrontal cortex activity than younger adults while engaging in emotion-processing tasks, we argue that the cognitive control hypothesis is a more likely explanation for older adults’ positivity effect than the aging-brain model

Quality of life and pain in premenopausal women with major depressive disorder: The POWER Study

BACKGROUND: Whereas it is established that organic pain may induce depression, it is unclear whether pain is more common in healthy subjects with depression. We assessed the prevalence of pain in premenopausal women with major depression (MDD). Subjects were 21- to 45-year-old premenopausal women with MDD (N = 70; age: 35.4 +/- 6.6; mean +/- SD) and healthy matched controls (N = 36; age 35.4 +/- 6.4) participating in a study of bone turnover, the P.O.W.E.R. (Premenopausal, Osteopenia/Osteoporosis, Women, Alendronate, Depression) Study. METHODS: Patients received a clinical assessment by a pain specialist, which included the administration of two standardized forms for pain, the Brief Pain Inventory – Short Form, and the Initial Pain Assessment Tool, and two scales of everyday stressors, the Hassles and Uplifts Scales. In addition, a quality-of-life instrument, the SF-36, was used. The diagnosis of MDD was established by a semi-structured interview, according to the DSM-IV criteria. Substance P (SP) and calcitonin-gene-related-peptide (CGRP), neuropeptides which are known mediators of pain, were measured every hour for 24 h in a subgroup of patients (N = 17) and controls (N = 14). RESULTS: Approximately one-half of the women with depression reported pain of mild intensity. Pain intensity was significantly correlated with the severity of depression (r(2 )= 0.076; P = 0.04) and tended to be correlated with the severity of anxiety, (r(2 )= 0.065; P = 0.07), and the number of depressive episodes (r(2 )= 0.072; P = 0.09). Women with MDD complained of fatigue, insomnia, and memory problems and experienced everyday negative stressors more frequently than controls. Quality of life was decreased in women with depression, as indicated by lower scores in the emotional and social well-being domains of the SF-36. SP (P < 0.0003) and CGRP (P < 0.0001) were higher in depressed subjects. CONCLUSION: Women with depression experienced pain more frequently than controls, had a lower quality of life, and complained more of daily stressors. Assessment of pain may be important in the clinical evaluation of women with MDD. SP and CGRP may be useful biological markers in women with MDD

Towards novel difluorinated sugar mimetrics; syntheses and conformational analyses of highly-functionalised difluorinated cyclooctenones

Highly-functionalised difluorinated cyclooctenones were synthesised from trifluoroethanol using either metallated difluoroenol acetal or carbamate chemistry, followed by a [2,3]-Wittig rearrangement or aldol reaction. Efficient RCM reactions afforded the title compounds which showed rather restricted fluxional behaviour by VT 19F NMR. Topological characterisation by molecular modelling and NOESY/ROESY experiments offered a number of challenges, but allowed the identification of two favoured boat-chair conformers which interconverted by pseudorotation with relatively large activation barriers

Elemental spatial and temporal association formation in left temporal lobe epilepsy

The mesial temporal lobe (MTL) is typically understood as a memory structure in clinical settings, with the sine qua non of MTL damage in epilepsy being memory impairment. Recent models, however, understand memory as one of a number of higher cognitive functions that recruit the MTL through their reliance on more fundamental processes, such as “self-projection” or “association formation”. We examined how damage to the left MTL influences these fundamental processes through the encoding of elemental spatial and temporal associations. We used a novel fMRI task to image the encoding of simple visual stimuli, either rich or impoverished, in spatial or spatial plus temporal information. Participants included 14 typical adults (36.4 years, sd. 10.5 years) and 14 patients with left mesial temporal lobe damage as evidenced by a clinical diagnosis of left temporal lobe epilepsy (TLE) and left MTL impairment on imaging (34.3 years, sd. 6.6 years). In-scanner behavioral performance was equivalent across groups. In the typical group whole-brain analysis revealed highly significant bilateral parahippocampal activation (right > left) during spatial associative processing and left hippocampal/parahippocampal deactivation in joint spatial-temporal associative processing. In the left TLE group identical analyses indicated patients used MTL structures contralateral to the seizure focus differently and relied on extra-MTL regions to a greater extent. These results are consistent with the notion that epileptogenic MTL damage is followed by reorganization of networks underlying elemental associative processes. In addition, they provide further evidence that task-related fMRI deactivation can meaningfully index brain function. The implications of these findings for clinical and cognitive neuropsychological models of MTL function in TLE are discussed

Grandi Byen-supporting child growth and development through integrated, responsive parenting, nutrition and hygiene: Study protocol for a randomized controlled trial

BACKGROUND: Poor child growth and development outcomes stem from complex relationships encompassing biological, behavioral, social, and environmental conditions. However, there is a dearth of research on integrated approaches targeting these interwoven factors. The Grandi Byen study seeks to fill this research gap through a three-arm longitudinal randomized controlled trial which will evaluate the impact of an integrated nutrition, responsive parenting, and WASH (water, sanitation and hygiene) intervention on holistic child growth and development. METHODS: We will recruit 600 mother-infant dyads living in Cap-Haitien, Haiti and randomize them equally into one of the following groups: 1) standard well-baby care; 2) nutritional intervention (one egg per day for 6 months); and 3) multicomponent Grandi Byen intervention (responsive parenting, nutrition, WASH + one egg per day for 6 months). Primary outcomes include child growth as well as cognitive, language, motor, and social-emotional development. The study also assesses other indicators of child health (bone maturation, brain growth, diarrheal morbidity and allergies, dietary intake, nutrient biomarkers) along with responsive parenting as mediating factors influencing the primary outcomes. An economic evaluation will assess the feasibility of large-scale implementation of the interventions. DISCUSSION: This study builds on research highlighting the importance of responsive parenting interventions on overall child health, as well as evidence demonstrating that providing an egg daily to infants during the complementary feeding period can prevent stunted growth. The multicomponent Grandi Byen intervention may provide evidence of synergistic or mediating effects of an egg intervention with instruction on psychoeducational parenting and WASH on child growth and development. Grandi Byen presents key innovations with implications for the well-being of children living in poverty globally. TRIAL REGISTRATION: NCT04785352 . Registered March 5, 2021 at https://clinicaltrials.gov/