Application of a seismic network to baleen whale call detection and localization in the Panama basin-a Bryde's whale example.

Baleen whales use sounds of various characteristics for different tasks and interactions. This study focuses on recordings from the Costa Rica Rift, in the Eastern Tropical Pacific Ocean, made by 25 ocean-bottom seismographs and a vertical array of 12 hydrophones between January and February 2015. The whale calls observed are of two kinds: more commonly, repetitive 4-5 s-long signals separated into two frequency bands centered at ∼20 and ∼36 Hz; less commonly, a series of ∼0.5 to 1.0 s-long, lower amplitude signals with frequencies between 80 and 160 Hz. These characteristics are similar to calls attributed to Bryde's whales which are occasionally sighted in this region. In this study, the repetitive calls are detected using both the short-term average/long-term average approach and a network empirical subspace detector. In total, 188 and 1891 calls are obtained for each method, demonstrating the value of the subspace detector for highly similar signals. These signals are first localized using a non-linear grid search algorithm and then further relocalized using the double-difference technique. The high-resolution localizations reveal the presence of at least seven whales during the recording period, often crossing the instrument network from southwest to northeast.

Biocatalytic synthesis of 2'-deoxynucleotide 5'-triphosphates from bacterial genomic DNA: Proof of principle.

2'-deoxynucleoside 5'-triphosphates (dNTPs) are the building blocks of DNA and are key reagents which are incorporated by polymerase enzymes during nucleic acid amplification techniques, such as polymerase chain reaction (PCR). These techniques are of high importance, not only in molecular biology research, but also in molecular diagnostics. dNTPs are generally produced by a bottom-up technique which relies on synthesis or isolation of purified small molecules like deoxynucleosides. However, the disproportionately high cost of dNTPs in low- and middle-income countries (LMICs) and the requirement for cold chain storage during international shipping makes an adequate supply of these molecules challenging. To reduce supply chain dependency and promote domestic manufacturing in LMICs, a unique top-down biocatalytic synthesis method is described to produce dNTPs. Readily available bacterial genomic DNA provides a crude source material to generate dNTPs and is extracted directly from Escherichia coli (step 1). Nuclease enzymes are then used to digest the genomic DNA creating monophosphorylated deoxynucleotides (dNMPs) (step 2). Design and recombinant production and characterization of E. coli nucleotide kinases is presented to further phosphorylate the monophosphorylated products to generate dNTPs (step 3). Direct use of the in-house produced dNTPs in nucleic acid amplification is shown (step 4) and their successful use as reagents in the application of PCR, thereby providing proof of principle for the future development of recombinant nucleases and design of a recombinant solid-state bioreactor for on-demand dNTP production.

Study protocol for Healthy Conversations @ Playgroup: a multi-site cluster randomized controlled trial of an intervention to promote healthy lifestyle behaviours in young children attending community playgroups.

BACKGROUND: Early childhood is a critical window for preventing obesity and chronic disease. Yet, 1 in 4 Australian children aged 5 years and under are affected by overweight or obesity; and significant proportions of children under 5 years fail to meet guidelines for diet quality, physical activity (PA), screen time, and sleep. Consequently, effective interventions to promote healthy lifestyle behaviors and prevent obesity during early childhood are needed. Community playgroups provide an opportunity for parents, carers, and children to meet in a safe and relaxed environment to play and share information. The structure, low cost and reach of playgroups provide a unique platform to engage parents in a scalable program to promote healthful lifestyle behaviors and prevent childhood obesity. However, the evidence base for the effectiveness of health promotion programs delivered in community playgroup settings is limited and lacking credible evidence from rigorously conducted randomized controlled trials. METHODS: The Healthy Conversations @ Playgroup randomized controlled trial (RCT) aims to address the underlying behavioral risk factors for obesity by helping parents take effective steps to improve their child's dietary, PA, screen time, and sleep behaviors. The intervention program comprises 10 "healthy conversations" led by a trained peer facilitator, designed to increase parents' behavioral capability and self-efficacy to implement autonomy-supportive parenting practices. The program will be delivered biweekly during regularly scheduled playgroup sessions over 10-weeks. Effectiveness will be tested in a 2-arm cluster RCT involving 60 community playgroups in three states across Australia. After baseline assessments, participating playgroups will be randomly allocated to either intervention or wait-list control conditions. Primary outcomes (vegetable intake, discretionary foods, daily PA, screen time, sleep duration, and body mass index [BMI] z-score) will be assessed at baseline, immediately post-intervention (10-weeks; T2) and 6-months post-intervention (T3). Outcomes will be assessed for differential change at T2 and T3. DISCUSSION: The Healthy Conversations @ Playgroup trial will rigorously evaluate a novel peer-led intervention program to promote healthful lifestyle behaviors and prevent obesity in children and families attending community playgroups. If effective, the program could be immediately scaled-up and delivered in community playgroups across Australia. TRIAL REGISTRATION: Trial registered 22nd January 2021 with the Australian and New Zealand Clinical Trials Registry ( ACTRN12621000055808 ).

Dietary inflammatory index and the aging kidney in older women: a 10-year prospective cohort study.

PURPOSE: Chronic inflammation plays a role in the pathogenesis of age-related renal disease and the diet can moderate systemic inflammation. The primary objective of this study was to examine the associations between a dietary inflammatory index (DII®) score and renal function, the trajectory of renal function decline, and renal disease-related hospitalizations and/or mortality over 10 years. METHODS: The study was conducted in 1422 Western Australian women without prevalent chronic kidney disease and aged ≥ 70 years. Baseline dietary data, obtained from a validated food frequency questionnaire, were used to calculate a DII score for each individual. RESULTS: In this cohort, the mean [range] DII score was 0.19 [- 6.14 to 6.39]. A higher DII score was associated with poorer renal function at baseline and a greater renal function decline over 10 years; after multivariable adjustments, a one-unit higher DII score was associated with a 0.55 mL/min/1.73 m2 lower eGFR at baseline (p = 0.01) and a 0.06 mL/min/1.73 m2 greater annual decline in eGFR over 10 years (p = 0.05). Restricted cubic splines provide evidence of a non-linear association between baseline DII score and risk of a renal disease-related event. Compared to participants in the lowest quintile, those in the highest quintile of DII score were at a higher risk of experiencing a renal disease-related event (adjusted HR 2.06, 95% CI 0.97, 4.37). CONCLUSION: Recommending an increased consumption of foods with a higher anti-inflammatory potential could form part of a multifaceted approach to reduce the risk of renal disease through diet and lifestyle changes.

Transitional B cells in quiescent SLE: An early checkpoint imprinted by IFN.

Systemic lupus (SLE) is characterized by a break of B cell tolerance that plays a central role in disease pathophysiology. An early checkpoint defect occurs at the transitional stage leading to the survival of autoreactive B cells and consequently the production of pathogenic autoantibodies. The main purpose of our work was to determine whether transitional B cells, as the most immature naïve B cell subset upstream of pathogenic B cells, display specific features compared to healthy non SLE subjects. Through extensive analysis of transitional B cells from untreated or low treated, mostly Caucasian, SLE patients, we demonstrated that transitional (T1 and T2) B cell frequencies were increased in SLE and positively correlated with disease activity. SLE transitional B cells displayed defects in two closely inter-related molecules (i.e. TLR9 defective responses and CD19 downregulation). RNA sequencing of sorted transitional B cells from untreated patients revealed a predominant overexpression of interferon stimulated genes (ISGs) even out of flares. In addition, early transitional B cells from the bone marrow displayed the highest interferon score, reflecting a B cell interferon burden of central origin. Hence, the IFN signature in transitional B cells is not confined to African American SLE patients and exists in quiescent disease since the medullary stage. These results suggest that in SLE these 3 factors (i.e. IFN imprintment, CD19 downregulation and TLR9 responses impairment) could take part at the early transitional B cell stage in B cell tolerance by-pass, ultimately leading in periphery to the expansion of autoantibodies-secreting cells.

Neutrophils Slow Disease Progression in Murine Lupus via Modulation of Autoreactive Germinal Centers.

Neutrophils are well characterized as mediators of peripheral tissue damage in lupus, but it remains unclear whether they influence loss of self-tolerance in the adaptive immune compartment. Lupus neutrophils produce elevated levels of factors known to fuel autoantibody production, including IL-6 and B cell survival factors, but also reactive oxygen intermediates, which can suppress lymphocyte proliferation. To assess whether neutrophils directly influence the progression of autoreactivity in secondary lymphoid organs (SLOs), we characterized the localization and cell-cell contacts of splenic neutrophils at several stages in the progression of disease in the NZB/W murine model of lupus. Neutrophils accumulate in SLO over the course of lupus progression, preferentially localizing near T lymphocytes early in disease and B cells with advanced disease. RNA sequencing reveals that the splenic neutrophil transcriptional program changes significantly over the course of disease, with neutrophil expression of anti-inflammatory mediators peaking during early-stage and midstage disease, and evidence of neutrophil activation with advanced disease. To assess whether neutrophils exert predominantly protective or deleterious effects on loss of B cell self-tolerance in vivo, we depleted neutrophils at different stages of disease. Neutrophil depletion early in lupus resulted in a striking acceleration in the onset of renal disease, SLO germinal center formation, and autoreactive plasma cell production. In contrast, neutrophil depletion with more advanced disease did not alter systemic lupus erythematosus progression. These results demonstrate a surprising temporal and context-dependent role for neutrophils in restraining autoreactive B cell activation in lupus.

Neutrophil-mediated IFN activation in the bone marrow alters B cell development in human and murine systemic lupus erythematosus.

Inappropriate activation of type I IFN plays a key role in the pathogenesis of autoimmune disease, including systemic lupus erythematosus (SLE). In this study, we report the presence of IFN activation in SLE bone marrow (BM), as measured by an IFN gene signature, increased IFN regulated chemokines, and direct production of IFN by BM-resident cells, associated with profound changes in B cell development. The majority of SLE patients had an IFN signature in the BM that was more pronounced than the paired peripheral blood and correlated with both higher autoantibodies and disease activity. Pronounced alterations in B cell development were noted in SLE in the presence of an IFN signature with a reduction in the fraction of pro/pre-B cells, suggesting an inhibition in early B cell development and an expansion of B cells at the transitional stage. These B cell changes strongly correlated with an increase in BAFF and APRIL expression in the IFN-high BM. Furthermore, we found that BM neutrophils in SLE were prime producers of IFN-α and B cell factors. In NZM lupus-prone mice, similar changes in B cell development were observed and mediated by IFN, given abrogation in NZM mice lacking type-I IFNR. BM neutrophils were abundant, responsive to, and producers of IFN, in close proximity to B cells. These results indicate that the BM is an important but previously unrecognized target organ in SLE with neutrophil-mediated IFN activation and alterations in B cell ontogeny and selection.

New insights into B cell biology in systemic lupus erythematosus and Sjögren's syndrome.

PURPOSE OF REVIEW: Our understanding of the physiological and pathogenic functions of B cells in systemic lupus erythematosus (SLE) and Primary Sjögren's syndrome (pSS) continues to expand. In this review, we discuss novel insights published in the last 18 months into the roles of B cells in systemic autoimmunity. RECENT FINDINGS: Data have continued to expand regarding the diverse mechanisms by which innate immune signals including Toll-like receptors (TLRs) regulate the B cell compartment. Localized B cells and long-lived plasma cells have been identified as playing an important role in target tissue including the development of ectopic lymphoid structures in kidney and salivary gland. In addition to pathogenic roles for B cells, there is mounting evidence for regulatory B cell subsets that play a protective role and new insights into the signals that regulate their development. SUMMARY: The past few years have provided insights into the multiple paths by which innate immune signals can lead to B cell activation in SLE and pSS and the increasingly diverse ways in which B cells contribute to disease expression. Further understanding the imbalance between protective and pathogenic functions for B cells in disease including in understudied target tissue should yield new treatment approaches.

Large-number detrital zircon U-Pb ages reveal global cooling caused the formation of the Chinese Loess Plateau during Late Miocene.

The formation and evolution of the landscape of the Chinese Loess Plateau (CLP) is debated because of uncertainties regarding dust provenance. We present a quantitative estimation of dust source contributions to the CLP, based on more than 37,100 detrital zircon U-Pb ages, combined with mineral assemblages and isotope analyses. Our results reveal that the CLP was stepwise formed by ~8 million years (Ma) and is mainly composed of material from the Northeastern Qinghai-Tibetan Plateau, with stepwise shifts in relative contributions of different eolian silt sources occurring at ~2.6 Ma and 1.5 to 1.2 Ma. We infer that these changes were driven by stepwise global cooling, which induced aridification and enhanced silt production in glaciated-cold climate dust source regions, as well as dust ablation in the expanded arid regions. We propose that global cooling, rather than regional tectonic deformation, was the main driver of the formation and evolution of the CLP during late Cenozoic.

Effectiveness of Foodbank Western Australia's Food Sensations® for Adults Food Literacy Program in Regional Australia.

BACKGROUND: Food Sensations for Adults, funded by the Western Australian Department of Health, is a four-week nutrition education program focused on food literacy, with demonstrated success amongst Western Australians. In the last two years, 25% of programs have been in regional and remote areas and therefore the aim of this research is to explore the impact of the program in regional areas. METHODS: Participants answered validated pre- and post-questionnaires to assess change in food literacy behaviours (2016-2018). RESULTS: Regional participants (n = 451) were more likely to live in low income areas, have lower education levels, and identify as Aboriginal, than metropolitan participants (n = 1398). Regional participants had statistically significantly higher food literacy behaviours in the plan and manage and preparation domains, and lower selection behaviours at baseline than metropolitan participants. Post program, regional participants showed matched improvements with metropolitan participants in the plan and manage, and preparation domains. Food selection behaviour results increased in both groups but were significantly higher in regional participants. CONCLUSIONS: The program demonstrates effective behaviour change in all participants; however, the increased disadvantage experienced by people residing outside of major cities highlights the need for additional government support in addressing regional specific barriers, such as higher food costs, to ensure participants gain maximum benefit from future food literacy programs.

Developing National Conceptual Understanding to Describe Entry-to-Practice Dietetics Competence.

OBJECTIVE: Develop consensus on entrustable professional activities (EPAs) and milestones for students, practice educators, and academics that need shared understanding to assess entry-level competence in dietetics. DESIGN: An iterative, pragmatic, 3 key-phase approach involving workshops, a consensus survey with job description and consultation. SETTING: Australia. PARTICIPANTS: A total of 58 academics and 43 practitioners with expertise in competency-based assessment in dietetics were purposefully selected to participate in 4 national workshops. Of those selected, 36 completed a survey that sought consensus on the EPAs and milestones drafted at the workshops (36% response rate). PHENOMENON OF INTEREST: Support for competency-based assessment. ANALYSIS: Level of agreement on the survey was set at ≥70%. These comments were triangulated with content analysis from 98 entry-level job descriptions. RESULTS: Consensus on 4 key tasks of the profession with associated descriptions of the level of performance were included to implement a nutrition intervention; facilitate a food, nutrition, and/or lifestyle conversation; perform professional activities and projects; and work as part of a team. CONCLUSIONS AND IMPLICATIONS: Identification of the key minimum tasks of a dietitian upon entry-to-practice, together with developmental descriptors of performance, provides clarity in the expected progression and end point of assessment. This resource will support competency-based assessment decisions. The international transferability of this warrants further investigation.

Fully Dried Two-Dimensional Paper Network for Enzymatically Enhanced Detection of Nucleic Acid Amplicons.

Two-dimensional paper networks (2DPNs) have enabled the use of paper-based platforms to perform multistep immunoassays for detection of pathogenic diseases at the point-of-care. To date, however, detection has required the user to provide multiple signal enhancement solutions and been limited to protein targets. We solve these challenges by using mathematical equations to guide the device design of a novel 2DPN, which leverages multiple fluidic inputs to apply fully dried solutions of hydrogen peroxide, diaminobenzidine, and horseradish peroxidase signal enhancement reagents to enhance the limit-of-detection of numerous nucleic acid products. Upon rehydration in our unique 2DPN design, the dried signal enhancement solution reduces the limit-of-detection (LOD) of the device to 5 × 1011 nucleic acid copies/mL without increasing false positive detection. Our easy-to-use device retains activity after 28 days of dry storage and produces reliable signal enhancement 40 min after sample application. The fully integrated device demonstrated versatility in its ability to detect double-stranded and single-stranded DNA samples, as well as peptide nucleic acids.

Macromechanics and polycaprolactone fiber organization drive macrophage polarization and regulate inflammatory activation of tendon in vitro and in vivo.

Appropriate macrophage response to an implanted biomaterial is crucial for successful tissue healing outcomes. In this work we investigated how intrinsic topological cues from electrospun biomaterials and extrinsic mechanical loads cooperate to guide macrophage activation and macrophage-tendon fibroblast cross-talk. We performed a series of in vitro and in vivo experiments using aligned or randomly oriented polycaprolactone nanofiber substrates in both mechanically loaded and unloaded conditions. Across all experiments a disorganized biomaterial fiber topography was alone sufficient to promote a pro-inflammatory signature in macrophages, tendon fibroblasts, and tendon tissue. Extrinsic mechanical loading was found to strongly regulate the character of this signature by reducing pro-inflammatory markers both in vitro and in vivo. We observed that macrophages generally displayed a stronger response to biophysical cues than tendon fibroblasts, with dominant effects of cross-talk between these cell types observed in mechanical co-culture models. Collectively our data suggest that macrophages play a potentially important role as mechanosensory cells in tendon repair, and provide insight into how biological response might be therapeutically modulated by rational biomaterial designs that address the biomechanical niche of recruited cells.

Bone Marrow-Derived Mesenchymal Stem Cells From Patients With Systemic Lupus Erythematosus Have a Senescence-Associated Secretory Phenotype Mediated by a Mitochondrial Antiviral Signaling Protein-Interferon-ß Feedback Loop.

OBJECTIVE: Bone marrow-derived mesenchymal stem cells (BM-MSCs) create a special microenvironment for hematopoiesis and immunity and display robust immunomodulatory properties that are impaired in systemic lupus erythematosus (SLE). This study was undertaken to identify the mechanisms of defects in human SLE BM-MSCs. METHODS: Patients fulfilling SLE classification criteria and healthy controls (n = 6 per group) were recruited according to an institutional review board-approved protocol. BM-MSCs were isolated with low-density Ficoll-Hypaque, verified by flow cytometry, and studied using immunocytochemistry, real-time polymerase chain reaction, Western blotting, comet assay, ß-galactosidase assay, and RNA interference. RESULTS: SLE BM-MSCs had a senescent phenotype characterized by a reduced proliferation rate, increased production of reactive oxygen species, increased DNA damage and repair, increased expression of p53 and p16, which block the cell cycle, and altered cytokine production (increased proinflammatory cytokine production and decreased immunomodulatory cytokine production). Moreover, SLE BM-MSCs had a 5-fold increase in interferon-ß (IFNß) levels (P < 0.05 versus healthy controls) and increased IFNß-induced messenger RNAs (mRNAs), including mRNA for the intracellular nucleic acid-sensing adaptor protein mitochondrial antiviral signaling protein (MAVS), whose expression was highly correlated with IFNß levels (r > 0.9, P < 0.01). Since MAVS is known to induce IFNß production, we hypothesized that there is a positive feedback loop between MAVS and IFNß. Notably, silencing of MAVS markedly decreased IFNß, p53, and p16 protein levels and expression of mRNAs for proinflammatory cytokines. CONCLUSION: This study demonstrates a novel pathway for elevated IFNß signaling in SLE that is not dependent on stimulation by immune complexes but rather is cell intrinsic and critically mediated by IFNß and MAVS, implicating new pathways as potential therapeutic targets.

Probiotics for the Treatment of Infantile Colic: A Systematic Review.

OBJECTIVE: To evaluate whether clinical data support the safety and efficacy of probiotics for the management of infantile colic. BACKGROUND: Probiotics have been suggested as a potential strategy for infantile colic, and the specific species that have been studied in healthy infants are considered to be safe. METHODOLOGY: A systematic review was conducted to identify randomized controlled trials (RCTs) evaluating the use of probiotic supplementation in infants with colic. RCTs with a primary end point assessing crying or fussing time were selected. A meta-analysis comparing "responders" to "nonresponders" in infants receiving probiotic versus control was conducted. The quality of trials selected was assessed. RESULTS: Five RCTs assessing 2 different strains of the probiotic Lactobacillus reuteri in mostly breastfed infants were identified. Analysis of response rates showed that infants receiving probiotics had a 2.3-fold greater chance of having a 50% or greater decrease in crying/fussing time compared to controls ( P = .01). Probiotic supplementation was not associated with any adverse events. CONCLUSION: Supplementation with the probiotic L. reuteri in breastfed infants appears to be safe and effective for the management of infantile colic. Further research is needed to determine the role of probiotics in infants who are formula-fed.

Loess Plateau storage of Northeastern Tibetan Plateau-derived Yellow River sediment.

Marine accumulations of terrigenous sediment are widely assumed to accurately record climatic- and tectonic-controlled mountain denudation and play an important role in understanding late Cenozoic mountain uplift and global cooling. Underpinning this is the assumption that the majority of sediment eroded from hinterland orogenic belts is transported to and ultimately stored in marine basins with little lag between erosion and deposition. Here we use a detailed and multi-technique sedimentary provenance dataset from the Yellow River to show that substantial amounts of sediment eroded from Northeast Tibet and carried by the river's upper reach are stored in the Chinese Loess Plateau and the western Mu Us desert. This finding revises our understanding of the origin of the Chinese Loess Plateau and provides a potential solution for mismatches between late Cenozoic terrestrial sedimentation and marine geochemistry records, as well as between global CO2 and erosion records.