Cell lineage-specific mitochondrial resilience during mammalian organogenesis.

Mitochondrial activity differs markedly between organs, but it is not known how and when this arises. Here we show that cell lineage-specific expression profiles involving essential mitochondrial genes emerge at an early stage in mouse development, including tissue-specific isoforms present before organ formation. However, the nuclear transcriptional signatures were not independent of organelle function. Genetically disrupting intra-mitochondrial protein synthesis with two different mtDNA mutations induced cell lineage-specific compensatory responses, including molecular pathways not previously implicated in organellar maintenance. We saw downregulation of genes whose expression is known to exacerbate the effects of exogenous mitochondrial toxins, indicating a transcriptional adaptation to mitochondrial dysfunction during embryonic development. The compensatory pathways were both tissue and mutation specific and under the control of transcription factors which promote organelle resilience. These are likely to contribute to the tissue specificity which characterizes human mitochondrial diseases and are potential targets for organ-directed treatments.

Inflammation-induced formation of fat-associated lymphoid clusters.

Fat-associated lymphoid clusters (FALCs) are a type of lymphoid tissue associated with visceral fat. Here we found that the distribution of FALCs was heterogeneous, with the pericardium containing large numbers of these clusters. FALCs contributed to the retention of B-1 cells in the peritoneal cavity through high expression of the chemokine CXCL13, and they supported B cell proliferation and germinal center differentiation during peritoneal immunological challenges. FALC formation was induced by inflammation, which triggered the recruitment of myeloid cells that expressed tumor-necrosis factor (TNF) necessary for signaling via the TNF receptors in stromal cells. Natural killer T cells (NKT cells) restricted by the antigen-presenting molecule CD1d were likewise required for the inducible formation of FALCs. Thus, FALCs supported and coordinated the activation of innate B cells and T cells during serosal immune responses.

Stochastic survival of the densest and mitochondrial DNA clonal expansion in aging.

The expansion of mitochondrial DNA molecules with deletions has been associated with aging, particularly in skeletal muscle fibers; its mechanism has remained unclear for three decades. Previous accounts have assigned a replicative advantage (RA) to mitochondrial DNA containing deletion mutations, but there is also evidence that cells can selectively remove defective mitochondrial DNA. Here we present a spatial model that, without an RA, but instead through a combination of enhanced density for mutants and noise, produces a wave of expanding mutations with speeds consistent with experimental data. A standard model based on RA yields waves that are too fast. We provide a formula that predicts that wave speed drops with copy number, consonant with experimental data. Crucially, our model yields traveling waves of mutants even if mutants are preferentially eliminated. Additionally, we predict that mutant loads observed in single-cell experiments can be produced by de novo mutation rates that are drastically lower than previously thought for neutral models. Given this exemplar of how spatial structure (multiple linked mtDNA populations), noise, and density affect muscle cell aging, we introduce the mechanism of stochastic survival of the densest (SSD), an alternative to RA, that may underpin other evolutionary phenomena.

Lumbar Bone Stress Injuries and Nonunited Defects in Elite Australian Cricket Players.

OBJECTIVE: To describe the presentation and management of lumbar bone stress injuries (LBSI), recurrent LBSI, and lumbar nonunited defects in elite Australian male and female cricket players. DESIGN: Retrospective case series. SETTING: Professional domestic and international cricket teams over 13 seasons. PARTICIPANTS: Elite Australian cricket players. INDEPENDENT VARIABLES: Symptomatic LBSI requiring time off cricket and lumbar nonunited defects, both confirmed by imaging. MAIN OUTCOME MEASURES: Incidence, presentation, history, healing, and management. RESULTS: 211 LBSI were identified at an average incidence of 5.4 per 100 players per season. LBSI were most common in male pace bowlers younger than 20 years of age (58.1 per 100 players per season), however, were also observed in older players, females, and non-pace bowlers. Recurrent LBSI accounted for 33% (27%-40%) of all LBSI. Median days to return to match availability was 182 (128-251) days for all LBSI, with a shorter time frame observed for new and less severe injuries, and male spin bowlers. Healing was demonstrated in 87% (81%-91%) of all LBSI cases. 29 nonunited defects were identified and predisposed subsequent pain, LBSI, and spondylolisthesis. CONCLUSIONS: LBSI are experienced by approximately 5.4 in every 100 elite Australian cricket players per season, with a high time cost of approximately 4 to 8 months. Nonunited defects also have a high time cost with associated subsequent lumbar spine issues. The findings of this study reinforce the importance of early detection and conservative management of LBSI, particularly for younger male pace bowlers and players with recurrent LBSI, which may be supported by MRI.

Path to autonomous soil sampling and analysis by ground-based robots.

Good site characterization is essential for the selection of remediation alternatives for impacted soils. The value of site characterization is critically dependent on the quality and quantity of the data collected. Current methods for characterizing impacted soils rely on expensive manual sample collection and off-site analysis. However, recent advances in terrestrial robotics and artificial intelligence offer a potentially revolutionary set of tools and methods that will help to autonomously explore natural environments, select sample locations with the highest value of information, extract samples, and analyze the data in real-time without exposing humans to potentially hazardous conditions. A fundamental challenge to realizing this potential is determining how to design an autonomous system for a given investigation with many, and often conflicting design criteria. This work presents a novel design methodology to navigate these criteria. Specifically, this methodology breaks the system into four components - sensing, sampling, mobility, and autonomy - and connects design variables to the investigation objectives and constraints. These connections are established for each component through a survey of existing technology, discussion of key technical challenges, and highlighting conditions where generality can promote multi-application deployment. An illustrative example of this design process is presented for the development and deployment of a robotic platform characterizing salt-impacted oil & gas reserve pits. After calibration, the relationship between the in situ robot chloride measurements and laboratory-based chloride measurements had a good linear relationship (R2-value = 0.861) and statistical significance (p-value = 0.003).

Soft Tissue Infection of Immunocompetent Man with Cat-Derived Globicatella Species.

We report a novel Globicatella species causing extensive soft tissue infection in a man bitten by a stray domestic cat in the United Kingdom. We identified this bacterium by 16S rRNA gene sequencing, whole-genome sequencing, and biochemical profiling and determined antimicrobial drug susceptibility.

A2B-COVID: A Tool for Rapidly Evaluating Potential SARS-CoV-2 Transmission Events.

Identifying linked cases of infection is a critical component of the public health response to viral infectious diseases. In a clinical context, there is a need to make rapid assessments of whether cases of infection have arrived independently onto a ward, or are potentially linked via direct transmission. Viral genome sequence data are of great value in making these assessments, but are often not the only form of data available. Here, we describe A2B-COVID, a method for the rapid identification of potentially linked cases of COVID-19 infection designed for clinical settings. Our method combines knowledge about infection dynamics, data describing the movements of individuals, and evolutionary analysis of genome sequences to assess whether data collected from cases of infection are consistent or inconsistent with linkage via direct transmission. A retrospective analysis of data from two wards at Cambridge University Hospitals NHS Foundation Trust during the first wave of the pandemic showed qualitatively different patterns of linkage between cases on designated COVID-19 and non-COVID-19 wards. The subsequent real-time application of our method to data from the second epidemic wave highlights its value for monitoring cases of infection in a clinical context.

Bulk-Boundary Correspondence and Singularity-Filling in Long-Range Free-Fermion Chains.

The bulk-boundary correspondence relates topologically protected edge modes to bulk topological invariants and is well understood for short-range free-fermion chains. Although case studies have considered long-range Hamiltonians whose couplings decay with a power-law exponent α, there has been no systematic study for a free-fermion symmetry class. We introduce a technique for solving gapped, translationally invariant models in the 1D BDI and AIII symmetry classes with α>1, linking together the quantized winding invariant, bulk topological string-order parameters, and a complete solution of the edge modes. The physics of these chains is elucidated by studying a complex function determined by the couplings of the Hamiltonian: in contrast to the short-range case where edge modes are associated to roots of this function, we find that they are now associated to singularities. A remarkable consequence is that the finite-size splitting of the edge modes depends on the topological winding number, which can be used as a probe of the latter. We furthermore generalize these results by (i) identifying a family of BDI chains with α<1 where our results still hold and (ii) showing that gapless symmetry-protected topological chains can have topological invariants and edge modes when α-1 exceeds the dynamical critical exponent.

One-dimensional and comprehensive two-dimensional gas chromatographic approaches for the characterization of post-consumer recycled plastic materials.

In September 2022, the European Commission published its new regulation on recycled plastic materials for food contact. It allows newly developed, non-authorized technologies and approaches, or so-called novel technologies, to be deployed in the field to generate the data needed for establishing regulatory and/or fit for purpose processes. The data shall be generated by using suitable methods, but the regulation does not give a more detailed description on those. In this study, commercially purchased buckets made of post-consumer recycled polypropylene were screened, using a number of different analytical approaches. Sample preparation methods, analysis techniques, and the data and information generated were compared. The results clearly demonstrate the need for a detailed characterization of such materials and the advantages and disadvantages of the analysis using conventional gas chromatography with flame ionization detection and mass spectrometery as well as two-dimensional comprehensive gas chromatography with time of flight mass spectrometry.

Characterizing soundscapes across diverse ecosystems using a universal acoustic feature set.

Natural habitats are being impacted by human pressures at an alarming rate. Monitoring these ecosystem-level changes often requires labor-intensive surveys that are unable to detect rapid or unanticipated environmental changes. Here we have developed a generalizable, data-driven solution to this challenge using eco-acoustic data. We exploited a convolutional neural network to embed soundscapes from a variety of ecosystems into a common acoustic space. In both supervised and unsupervised modes, this allowed us to accurately quantify variation in habitat quality across space and in biodiversity through time. On the scale of seconds, we learned a typical soundscape model that allowed automatic identification of anomalous sounds in playback experiments, providing a potential route for real-time automated detection of irregular environmental behavior including illegal logging and hunting. Our highly generalizable approach, and the common set of features, will enable scientists to unlock previously hidden insights from acoustic data and offers promise as a backbone technology for global collaborative autonomous ecosystem monitoring efforts.

A Retrospective Analysis of Pinnaplasty Outcomes: The Welsh Experience.

Prominent ears (PEs) are the most frequent congenital external ear deformity, occurring in ∼5% of the population. Although the deformity does not usually cause functional difficulties, it can significantly affect the patient's psychological and social health. The authors aim to present the Welsh experience of pinnaplasty, reviewing our outcomes and complications. A retrospective cross-sectional study was performed of all patients undergoing pinnaplasty in Morriston Hospital, Swansea, Wales. We represent the tertiary plastic surgery referral unit across Wales. We included all patients undergoing pinnaplasty between 2015 and 2022 inclusive. We excluded patients undergoing revision procedures or those who had no follow-up. Over the 7-year period, 236 pinnaplasties were performed and 203 were included in the analysis. Ninety-six percent of cases were performed using a cartilage-sparing approach, which represents the mainstay in our unit. The mean follow-up length for our cases was 12 months. Revision procedures were required in 4% of cases. Three hematomas (1.5%) and one (0.5%) wound dehiscence due to infection were recorded and required a return to the operating room. Suture extrusion was noted in 5% of cases (10 patients); 4.5% (9) cases were affected by either hypertrophic or keloid scarring. Across the United Kingdom, cosmetic procedures have come under scrutiny, namely, because of a difficult economic climate. In the era of tight fiscal control in health care, it is pertinent to analyze the outcomes and performance metrics of our operations regularly, thus aiding in the development of an established evidence base to advocate for our respective patients.

Maze design: size and number of choices impact fish performance in cognitive assays.

Although studies on fish cognition are increasing, consideration of how methodological details influence the ability to detect and measure performance is lagging. Here, in two separate experiments the authors compared latency to leave the start position, latency to make a decision, levels of participation and success rates (whether fish entered the rewarded chamber as first choice) across different physical designs. Experiments compared fish performance across (a) two sizes of T-mazes, large and standard, and a plus-maze, and (b) open choice arenas with either two or four doors. Fish in T-mazes with longer arms took longer to leave the start chamber and were less likely to participate in a trial than fish in T-mazes with shorter arms. The number of options, or complexity, in a maze significantly impacted success but did not necessarily impact behavioural measures, and did not impact the number of fish that reached a chamber. Fish in the plus-maze had similar latencies to leave the start box and time to reach any chamber as fish in the same-sized T-maze but exhibited lower overall success. Similarly, in an open choice arena, increasing the number of options - doors to potential reward chambers - resulted in lower probability of success. There was an influence of reward position in the choice arena, with rewarded chambers closest to the sides of the arena resulting in lower latencies to enter and higher probability of decision success. Together the results allow the authors to offer practical suggestions towards optimal maze design for studies of fish cognition.

The homeostatic dynamics of feeding behaviour identify novel mechanisms of anorectic agents.

Better understanding of feeding behaviour will be vital in reducing obesity and metabolic syndrome, but we lack a standard model that captures the complexity of feeding behaviour. We construct an accurate stochastic model of rodent feeding at the bout level in order to perform quantitative behavioural analysis. Analysing the different effects on feeding behaviour of peptide YY3-36 (PYY3-36), lithium chloride, glucagon-like peptide 1 (GLP-1), and leptin shows the precise behavioural changes caused by each anorectic agent. Our analysis demonstrates that the changes in feeding behaviour evoked by the anorectic agents investigated do not mimic the behaviour of well-fed animals and that the intermeal interval is influenced by fullness. We show how robust homeostatic control of feeding thwarts attempts to reduce food intake and how this might be overcome. In silico experiments suggest that introducing a minimum intermeal interval or modulating upper gut emptying can be as effective as anorectic drug administration.

Flow-modulated comprehensive two-dimensional gas chromatography combined with time-of-flight mass spectrometry: use of hydrogen as a more sustainable alternative to helium.

The present research is focused on the use and evaluation of hydrogen, as a more sustainable alternative to helium, within the context of fast flow modulation comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry. In such a respect, a comparison was made between the two mobile phases in terms of speed and overall chromatography performance. All experiments were carried out by using the following column set: low polarity with dimensions 10 m × 0.25 mm ID × 0.25 µm df and medium polarity with dimensions 2 m × 0.10 mm ID × 0.10 µm df. Fundamental gas chromatography parameters (efficiency, resolution) were measured under different experimental conditions, using the two carrier gases. Efficiency was measured in both the first and second dimensions, using a probe compound under isothermal conditions; after defining the optimum carrier gas conditions, a mixture containing 20 pesticides was analyzed to measure resolution, again in the first and second dimensions, using a temperature program. It was found (as expected) that a similar chromatography performance could be attained when using hydrogen, albeit with a circa 25% reduction in analysis time. Signal-to-noise ratios of the pesticides were calculated, using both carrier gases, with such values generally reduced (on average by 14%) when using hydrogen. Finally, a comparison was made between mass spectral profiles obtained analyzing the pesticides and fatty acid methyl esters using the two mobile phases. Even though mass spectral differences were observed, the ion profiles could be considered generally similar.

Visualizing, quantifying, and manipulating mitochondrial DNA in vivo.

Mitochondrial DNA (mtDNA) encodes proteins and RNAs that support the functions of mitochondria and thereby numerous physiological processes. Mutations of mtDNA can cause mitochondrial diseases and are implicated in aging. The mtDNA within cells is organized into nucleoids within the mitochondrial matrix, but how mtDNA nucleoids are formed and regulated within cells remains incompletely resolved. Visualization of mtDNA within cells is a powerful means by which mechanistic insight can be gained. Manipulation of the amount and sequence of mtDNA within cells is important experimentally and for developing therapeutic interventions to treat mitochondrial disease. This review details recent developments and opportunities for improvements in the experimental tools and techniques that can be used to visualize, quantify, and manipulate the properties of mtDNA within cells.

Short-range hunters: exploring the function and constraints of water shooting in dwarf gouramis.

Ballistic predation is a rare foraging adaptation: in fishes, most attention has focused on a single genus, the archerfish, known to manipulate water to shoot down prey above the water surface. However, several gourami species also exhibit apparently similar 'shooting' behaviour, spitting water up to 5 cm above the surface. In a series of experiments, we explored the shooting behaviour and aspects of its significance as a foraging ability in the dwarf gourami (Trichogaster lalius). We investigated sex differences in shooting abilities to determine whether gourami shooting is related to the sex-specific bubble nest manufacture where males mix air and water at the surface to form bubbles. We found that, actually, both sexes were equally able to shoot and could learn to shoot a novel target. In a second experiment, we presented untrained gouramis with opportunities to shoot at live prey and found they successfully shot down both fruit flies and crickets. Finally, we explored the effect of target height on shooting performance to establish potential constraints of shooting as a foraging ability. The frequency of attempted shots and success of hitting targets decreased with height, whereas latency to shoot increased. We also observed that repeatable individual differences account for variation in these measures of shooting performance. Together, our results provide evidence that gourami shooting has a foraging function analogous to that of archerfish. Gourami shooting may serve as an example of convergent evolution and provide opportunities for comparative studies into the, as yet unexplored, ecology and evolution of shooting in fishes.

Physical enrichment research for captive fish: Time to focus on the DETAILS.

Growing research effort has shown that physical enrichment (PE) can improve fish welfare and research validity. However, the inclusion of PE does not always result in positive effects and conflicting findings have highlighted the many nuances involved. Effects are known to depend on species and life stage tested, but effects may also vary with differences in the specific items used as enrichment between and within studies. Reporting fine-scale characteristics of items used as enrichment in studies may help to reveal these factors. We conducted a survey of PE-focused studies published in the last 5 years to examine the current state of methodological reporting. The survey results suggest that some aspects of enrichment are not adequately detailed. For example, the amount and dimensions of objects used as enrichment were frequently omitted. Similarly, the ecological relevance, or other justification, for enrichment items was frequently not made explicit. Focusing on ecologically relevant aspects of PE and increasing the level of detail reported in studies may benefit future work and we propose a framework with the acronym DETAILS (Dimensions, Ecological rationale, Timing of enrichment, Amount, Inputs, Lighting and Social environment). We outline the potential importance of each of the elements of this framework with the hope it may aid in the level of reporting and standardization across studies, ultimately aiding the search for more beneficial types of PE and the development of our understanding and ability to improve the welfare of captive fish and promote more biologically relevant behaviour.

C-reactive protein as a potential biomarker for disease progression in dengue: a multi-country observational study.

BACKGROUND: Dengue infection can cause a wide spectrum of clinical outcomes. The severe clinical manifestations occur sufficiently late in the disease course, during day 4-6 of illness, to allow a window of opportunity for risk stratification. Markers of inflammation may be useful biomarkers. We investigated the value of C-reactive protein (CRP) measured early on illness days 1-3 to predict dengue disease outcome and the difference in CRP levels between dengue and other febrile illnesses (OFI). METHOD: We performed a nested case-control study using the clinical data and samples collected from the IDAMS-consortium multi-country study. This was a prospective multi-center observational study that enrolled almost 8000 participants presenting with a dengue-like illness to outpatient facilities in 8 countries across Asia and Latin America. Predefined severity definitions of severe and intermediate dengue were used as the primary outcomes. A total of 281 cases with severe/intermediate dengue were compared to 836 uncomplicated dengue patients as controls (ratio 1:3), and also 394 patients with OFI. RESULTS: In patients with confirmed dengue, median (interquartile range) of CRP level within the first 3 days was 30.2 mg/L (12.4-61.2 mg/L) (uncomplicated dengue, 28.6 (10.5-58.9); severe or intermediate dengue, 34.0 (17.4-71.8)). Higher CRP levels in the first 3 days of illness were associated with a higher risk of severe or intermediate outcome (OR 1.17, 95% CI 1.07-1.29), especially in children. Higher CRP levels, exceeding 30 mg/L, also associated with hospitalization (OR 1.37, 95% CI 1.14-1.64) and longer fever clearance time (HR 0.84, 95% CI 0.76-0.93), especially in adults. CRP levels in patients with dengue were higher than patients with potential viral infection but lower than patients with potential bacterial infection, resulting in a quadratic association between dengue diagnosis and CRP, with levels of approximately 30 mg/L associated with the highest risk of having dengue. CRP had a positive correlation with total white cell count and neutrophils and negative correlation with lymphocytes, but did not correlate with liver transaminases, albumin, or platelet nadir. CONCLUSIONS: In summary, CRP measured in the first 3 days of illness could be a useful biomarker for early dengue risk prediction and may assist differentiating dengue from other febrile illnesses.

Energetic costs of cellular and therapeutic control of stochastic mitochondrial DNA populations.

The dynamics of the cellular proportion of mutant mtDNA molecules is crucial for mitochondrial diseases. Cellular populations of mitochondria are under homeostatic control, but the details of the control mechanisms involved remain elusive. Here, we use stochastic modelling to derive general results for the impact of cellular control on mtDNA populations, the cost to the cell of different mtDNA states, and the optimisation of therapeutic control of mtDNA populations. This formalism yields a wealth of biological results, including that an increasing mtDNA variance can increase the energetic cost of maintaining a tissue, that intermediate levels of heteroplasmy can be more detrimental than homoplasmy even for a dysfunctional mutant, that heteroplasmy distribution (not mean alone) is crucial for the success of gene therapies, and that long-term rather than short intense gene therapies are more likely to beneficially impact mtDNA populations.

Looplessness in networks is linked to trophic coherence.

Many natural, complex systems are remarkably stable thanks to an absence of feedback acting on their elements. When described as networks these exhibit few or no cycles, and associated matrices have small leading eigenvalues. It has been suggested that this architecture can confer advantages to the system as a whole, such as "qualitative stability," but this observation does not in itself explain how a loopless structure might arise. We show here that the number of feedback loops in a network, as well as the eigenvalues of associated matrices, is determined by a structural property called trophic coherence, a measure of how neatly nodes fall into distinct levels. Our theory correctly classifies a variety of networks-including those derived from genes, metabolites, species, neurons, words, computers, and trading nations-into two distinct regimes of high and low feedback and provides a null model to gauge the significance of related magnitudes. Because trophic coherence suppresses feedback, whereas an absence of feedback alone does not lead to coherence, our work suggests that the reasons for "looplessness" in nature should be sought in coherence-inducing mechanisms.