Linear enamel hypoplasia in Homo naledi re-appraised in light of new Retzius periodicities

Objectives: Among low latitude apes, developmental defects of enamel often recur twice yearly, linkable to environmental cycles. Surprisingly, teeth of Homo naledi from Rising Star in South Africa (241-335 kya), a higher latitude site with today a single rainy season, also exhibit bimodally distributed hypoplastic enamel defects, but with uncertain timing and etiology. Newly-determined Retzius periodicities for enamel formation in this taxon enable a reconstruction of the temporal patterning of childhood stress. Methods: Using high resolution casts of 31 isolated anterior teeth from Homo naledi, 82 enamel defects (linear enamel hypoplasia-LEH) were identified. 17 teeth are assigned to three individuals. Perikymata in the occlusal wall of enamel furrows and between the onsets of successive LEH were visualized with scanning electron microscopy, and counted. Defects were measured with an optical scanner. Conversion of perikymata counts to estimates of LEH duration and inter-LEH interval draws upon Retzius periodicities of 9 and 11 days. Results: Anterior teeth record more than a year of developmental distress, expressed as two asymmetric intervals centered on 4.5 and 7.5-months bounded by 3 LEH. Durations, also, show bimodal distributions, lasting three or 12 weeks. Short duration LEH are more severe than long duration. Relative incisor/canine rates of formation are indistinguishable from modern humans. Discussion: We invoke a disease and dearth model, with short episodes of distress reflecting onset of disease in young infants, lasting about three weeks, followed by a season of undernutrition, possibly intensified by secondary plant compounds, spanning about 12 weeks, inferably coincident with austral winter

Live-Cell Monitoring of Periodic Gene Expression in Synchronous Human Cells Identifies Forkhead Genes involved in Cell Cycle Control

We developed a system to monitor periodic luciferase activity from cell cycle-regulated promoters in synchronous cells. Reporters were driven by a minimal human E2F1 promoter with peak expression in G1/S or a basal promoter with six Forkhead DNA-binding sites with peak expression at G2/M. After cell cycle synchronization, luciferase activity was measured in live cells at 10-min intervals across three to four synchronous cell cycles, allowing unprecedented resolution of cell cycle-regulated gene expression. We used this assay to screen Forkhead transcription factors for control of periodic gene expression. We confirmed a role for FOXM1 and identified two novel cell cycle regulators, FOXJ3 and FOXK1. Knockdown of FOXJ3 and FOXK1 eliminated cell cycle-dependent oscillations and resulted in decreased cell proliferation rates. Analysis of genes regulated by FOXJ3 and FOXK1 showed that FOXJ3 may regulate a network of zinc finger proteins and that FOXK1 binds to the promoter and regulates DHFR, TYMS, GSDMD, and the E2F binding partner TFDP1. Chromatin immunoprecipitation followed by high-throughput sequencing analysis identified 4329 genomic loci bound by FOXK1, 83% of which contained a FOXK1-binding motif. We verified that a subset of these loci are activated by wild-type FOXK1 but not by a FOXK1 (H355A) DNA-binding mutant

Blackcurrants Reduce the Risk of Postmenopausal Osteoporosis: A Pilot Double-Blind, Randomized, Placebo-Controlled Clinical Trial.

Beneficial effects of blackcurrant supplementation on bone metabolism in mice has recently been demonstrated, but no studies are available in humans. The current study aimed to examine the dose-dependent effects of blackcurrant in preventing bone loss and the underlying mechanisms of action in adult women. Forty peri- and early postmenopausal women were randomly assigned into one of three treatment groups for 6 months: (1) a placebo (control group, n = 13); (2) 392 mg/day of blackcurrant powder (low blackcurrant, BC, group, n = 16); and (3) 784 mg/day of blackcurrant powder (high BC group, n = 11). The significance of differences in outcome variables was tested by repeated-measures ANOVA with treatment and time as between- and within-subject factors, respectively. Overall, blackcurrant supplementation decreased the loss of whole-body bone mineral density (BMD) compared to the control group (p \u3c 0.05), though the improvement of whole-body BMD remained significant only in the high BC group (p \u3c 0.05). Blackcurrant supplementation also led to a significant increase in serum amino-terminal propeptide of type 1 procollagen (P1NP), a marker of bone formation (p \u3c 0.05). These findings suggest that daily consumption of 784 mg of blackcurrant powder for six months mitigates the risk of postmenopausal bone loss, potentially through enhancing bone formation. Further studies of larger samples with various skeletal conditions are warranted to confirm these findings

Informing mHealth and Web-Based Eating Disorder Interventions: Combining Lived Experience Perspectives With Design Thinking Approaches

Background: App-based interventions designed to prevent and treat eating disorders have considerable potential to overcome known barriers to treatment seeking. Existing apps have shown efficacy in terms of symptom reduction; however, uptake and retention issues are common. To ensure that apps meet the needs and preferences of those for whom they were designed, it is critical to understand the lived experience of potential users and involve them in the process of design, development, and delivery. However, few app-based interventions are pretested on and co-designed with end users before randomized controlled trials. Objective: To address the issue, this study used a highly novel design thinking approach to provide the context and a lived experience perspective of the end user, thus allowing for a deeper level of understanding. Methods: In total, 7 young women (mean age 25.83, SD 5.34, range 21-33 years) who self-identified as having a history of body image issues or eating disorders were recruited. Participants were interviewed about their lived experience of body image and eating disorders and reported their needs and preferences for app-based eating disorder interventions. Traditional (thematic analysis) and novel (empathy mapping; visually depicting and empathizing with the user’s personal experience) analyses were performed, providing a lived experience perspective of eating disorders and identifying the needs and preferences of this population in relation to app-based interventions for eating disorders. Key challenges and opportunities for app-based eating disorder interventions were also identified. Results: Findings highlighted the importance of understanding and identifying problematic eating disorder symptoms for the user, helpful practices for recovery that identify personal values and goals, the role of social support in facilitating hope, and aspects of usability to promote continued engagement and recovery. Conclusions: Practical guidance and recommendations are described for those developing app-based eating disorder interventions. These findings have the potential to inform practices to enhance participant uptake and retention in the context of app-based interventions for this population

A genetic locus complements resistance to Bordetella pertussis-induced histamine sensitization.

Histamine plays pivotal role in normal physiology and dysregulated production of histamine or signaling through histamine receptors (HRH) can promote pathology. Previously, we showed that Bordetella pertussis or pertussis toxin can induce histamine sensitization in laboratory inbred mice and is genetically controlled by Hrh1/HRH1. HRH1 allotypes differ at three amino acid residues with

Cerebellar Integrity in the Amyotrophic Lateral Sclerosis - Frontotemporal Dementia Continuum

Amyotrophic lateral sclerosis (ALS) and behavioural variant frontotemporal dementia (bvFTD) are multisystem neurodegenerative disorders that manifest overlapping cognitive, neuropsychiatric and motor features. The cerebellum has long been known to be crucial for intact motor function although emerging evidence over the past decade has attributed cognitive and neuropsychiatric processes to this structure. The current study set out i) to establish the integrity of cerebellar subregions in the amyotrophic lateral sclerosis-behavioural variant frontotemporal dementia spectrum (ALS-bvFTD) and ii) determine whether specific cerebellar atrophy regions are associated with cognitive, neuropsychiatric and motor symptoms in the patients. Seventy-eight patients diagnosed with ALS, ALS-bvFTD, behavioural variant frontotemporal dementia (bvFTD), most without C9ORF72 gene abnormalities, and healthy controls were investigated. Participants underwent cognitive, neuropsychiatric and functional evaluation as well as structural imaging using voxel-based morphometry (VBM) to examine the grey matter subregions of the cerebellar lobules, vermis and crus. VBM analyses revealed: i) significant grey matter atrophy in the cerebellum across the whole ALS-bvFTD continuum; ii) atrophy predominantly of the superior cerebellum and crus in bvFTD patients, atrophy of the inferior cerebellum and vermis in ALS patients, while ALS-bvFTD patients had both patterns of atrophy. Post-hoc covariance analyses revealed that cognitive and neuropsychiatric symptoms were particularly associated with atrophy of the crus and superior lobule, while motor symptoms were more associated with atrophy of the inferior lobules. Taken together, these findings indicate an important role of the cerebellum in the ALS-bvFTD disease spectrum, with all three clinical phenotypes demonstrating specific patterns of subregional atrophy that associated with different symptomology

Restaurant outbreak of Legionnaires' disease associated with a decorative fountain: an environmental and case-control study

BACKGROUND: From June to November 2005, 18 cases of community-acquired Legionnaires' disease (LD) were reported in Rapid City South Dakota. We conducted epidemiologic and environmental investigations to identify the source of the outbreak. METHODS: We conducted a case-control study that included the first 13 cases and 52 controls randomly selected from emergency department records and matched on underlying illness. We collected information about activities of case-patients and controls during the 14 days before symptom onset. Environmental samples (n = 291) were cultured for Legionella. Clinical and environmental isolates were compared using monoclonal antibody subtyping and sequence based typing (SBT). RESULTS: Case-patients were significantly more likely than controls to have passed through several city areas that contained or were adjacent to areas with cooling towers positive for Legionella. Six of 11 case-patients (matched odds ratio (mOR) 32.7, 95% CI 4.7-infinity) reported eating in Restaurant A versus 0 controls. Legionella pneumophila serogroup 1 was isolated from four clinical specimens: 3 were Benidorm type strains and 1 was a Denver type strain. Legionella were identified from several environmental sites including 24 (56%) of 43 cooling towers tested, but only one site, a small decorative fountain in Restaurant A, contained Benidorm, the outbreak strain. Clinical and environmental Benidorm isolates had identical SBT patterns. CONCLUSION: This is the first time that small fountain without obvious aerosol-generating capability has been implicated as the source of a LD outbreak. Removal of the fountain halted transmission