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Abstract Background Mitochondrial DNA (mtDNA) is present at high copy numbers in animal cells, and though characterized by a single haplotype in each individual due to maternal germline inheritance, deleterious mutations and intact mtDNA molecules frequently co-exist (heteroplasmy). A number of factors, such as replicative segregation, mitochondrial bottlenecks, and selection, may modulate the exitance of heteroplasmic mutations. Since such mutations may have pathological consequences, they likely survive and are inherited due to functional complementation via the intracellular mitochondrial network. Here, we hypothesized that compromised mitochondrial fusion would hamper such complementation, thereby affecting heteroplasmy inheritance. Results We assessed heteroplasmy levels in three Caenorhabditis elegans strains carrying different heteroplasmic mtDNA deletions (ΔmtDNA) in the background of mutant mitofusin (fzo-1). Animals displayed severe embryonic lethality and developmental delay. Strikingly, observed phenotypes were relieved during subsequent generations in association with complete loss of ΔmtDNA molecules. Moreover, deletion loss rates were negatively correlated with the size of mtDNA deletions, suggesting that mitochondrial fusion is essential and sensitive to the nature of the heteroplasmic mtDNA mutations. Introducing the ΔmtDNA into a fzo-1;pdr-1;+/ΔmtDNA (PARKIN ortholog) double mutant resulted in a skewed Mendelian progeny distribution, in contrast to the normal distribution in the fzo-1;+/ΔmtDNA mutant, and severely reduced brood size. Notably, the ΔmtDNA was lost across generations in association with improved phenotypes. Conclusions Taken together, our findings show that when mitochondrial fusion is compromised, deleterious heteroplasmic mutations cannot evade natural selection while inherited through generations. Moreover, our findings underline the importance of cross-talk between mitochondrial fusion and mitophagy in modulating the inheritance of mtDNA heteroplasmy.

ADARs (adenosine deaminases acting on RNA) are known for their adenosine-to-inosine RNA editing activity, and most recently, for their role in preventing aberrant dsRNA-response by activation of dsRNA sensors (i.e., RIG-I-like receptor homologs). However, it is still unclear whether suppressing spurious dsRNA-response represents the ancestral role of ADARs in bilaterians. As a first step to address this question, we identified ADAR1 and ADAR2 homologs in the planarian Schmidtea mediterranea, which is evolutionarily distant from canonical lab models (e.g., flies and nematodes). Our results indicate that knockdown of either planarian adar1 or adar2 by RNA interference (RNAi) resulted in upregulation of dsRNA-response genes, including three planarian rig-I-like receptor (prlr) homologs. Furthermore, independent knockdown of adar1 and adar2 reduced the number of infected cells with a dsRNA virus, suggesting they suppress a bona fide anti-viral dsRNA-response activity. Knockdown of adar1 also resulted in lesion formation and animal lethality, thus attesting to its essentiality. Simultaneous knockdown of adar1 and prlr1 rescued adar1(RNAi)-dependent animal lethality and rescued the dsRNA-response, suggesting that it contributes to the deleterious effect of adar1 knockdown. Finally, we found that ADAR2, but not ADAR1, mediates mRNA editing in planarians, suggesting at least in part non-redundant activities for planarians ADARs. Our results underline the essential role of ADARs in suppressing activation of harmful dsRNA-response in planarians, thus supporting it as their ancestral role in bilaterians. Our work also set the stage to study further and better understand the regulatory mechanisms governing anti-viral dsRNA-responses from an evolutionary standpoint using planarians as a model.

Introduction The burden of open extremity fractures is well recognized in placing a burgeoning demand on an already exhausted medical facility in low- and middle-income countries. This study aims to evaluate the functional outcome following “orthoplastic management” by orthopedic surgeons trained in limb reconstruction surgery. Methodology Adult patients with open lower limb injuries treated from January 1, 2022, to December 30, 2022, who underwent single or staged fixation and reconstruction procedures were identified. Patients with Gustilo–Anderson type IIIB fractures requiring skeletal stabilization with soft-tissue cover were included. Polytrauma patients requiring multidisciplinary surgical attention were excluded. A team of orthopedic surgeons trained in limb reconstruction was involved in the management. Inpatient and outpatient department follow-up by the treating team was done to document complications (infections, reoperations, and graft failures) and functional outcomes using the Lower Extremity Function Score. The duration of mean follow-up was 1 year since index surgery. Results A total of 24 adult patients with open lower limb injuries with preoperative Ganga Hospital Score (GHS) were included. Decision toward fixation with primary closure or further reconstruction was made collectively. The gray zone (GHS score of 15–16) of patients was more aggressively managed with emphasis on salvage. Additional reconstructive procedures were carried out based on the assessment at consequent follow-up. Three patients had a suboptimal joint function (less than functional range of motion for the involved joint) due to the resultant loss of compartment(s) and joint contracture. Five patients were retaken to the theater for further supplementary or corrective procedures following the index, definitive surgical procedure (bone grafting, partial flap loss, and fixator readjustment). Conclusion Good-to-excellent functional outcome was demonstrated with the “orthoplastic approach” where skeletal stabilization as well as soft-tissue reconstruction was performed by trained orthopedic surgeons. This study demonstrated that orthoplastic surgery is a safe and effective method of limb salvage.

Abstract Differential diagnosis is a crucial aspect of medical practice, as it guides clinicians to accurate diagnoses and effective treatment plans. Traditional resources, such as medical books and services like UpToDate, are constrained by manual curation, potentially missing out on novel or less common findings. This paper introduces and analyzes two novel methods to mine etiologies from scientific literature. The first method employs a traditional Natural Language Processing (NLP) approach based on syntactic patterns. By using a novel application of human-guided pattern bootstrapping patterns are derived quickly, and symptom etiologies are extracted with significant coverage. The second method utilizes generative models, specifically GPT-4, coupled with a fact verification pipeline, marking a pioneering application of generative techniques in etiology extraction. Analyzing this second method shows that while it is highly precise, it offers lesser coverage compared to the syntactic approach. Importantly, combining both methodologies yields synergistic outcomes, enhancing the depth and reliability of etiology mining.

The ever-increasing ageing of the world population is demanding superior orthopedic devices. Issues such as implant infection, poor osseointegration, or chronic inflammation remain problematic to the lifespan and long-term efficacy of implants. Fabrication of materials with bioinspired nanostructures is one emerging antibacterial strategy to prevent implant infection, however their interactions with blood components, and whether they retain their bactericidal properties in an environment displaying a complex protein corona, remains largely unexplored. In the present study, titanium alloy, commercially pure and plasma-sprayed titania were hydrothermally etched, passivated with human native plasma to develop a protein corona, and then incubated with either Staphylococcus aureus, Pseudomonas aeruginosa or human platelets. Surface analysis was first used to characterize the topography, chemical composition or crystallinity of each material. Fluorescence staining and SEM were performed to evaluate the nanostructure bactericidal properties, as well as to study platelet attachment and morphology. Composition of platelet supernatant was studied using ELISA and flow cytometry. Overall, our study showed that the bioinspired nanostructured surfaces displayed both impressive antibacterial properties in a complex environment, and a superior blood biocompatibility profile in terms of platelet activation (particularly for titanium alloy). Additionally, the amount of pro-inflammatory cytokines released by platelets was found to be no different to that found in native plasma (background levels) and, in some cases, presented a more pro-healing profile with an increased secretion of factors such as TGF-β, PDGF-BB or BMP-2. The nanostructured surfaces performed equally, or better, than hydroxyapatite-coated titanium which is one of the current gold standards in orthopedics. Although further in vivo studies are required to validate these results, such bioinspired nanostructured surfaces certainly show promise to be safely applied to medical device surfaces used in orthopedics and other areas.

Abstract Bacterial colonization of implantable biomaterials is an ever-pervasive threat that causes devastating infections, yet continues to elude resolution. In the present study, we report how a rationally designed antibacterial surface containing sharp nanospikes can enhance the susceptibility of pathogenic bacteria to antibiotics used in prophylactic procedures. We show that Staphylococcus aureus, once adhered to a titanium surface, changes its cell-surface charge to increase its tolerance to vancomycin. However, if the Ti surface is modified to bear sharp nanospikes, the activity of vancomycin is rejuvenated, leading to increased bacterial cell death through synergistic activity. Analysis of differential gene expression provided evidence of a set of genes involved with the modification of cell surface charge. Synchrotron-sourced attenuated Fourier-transform infrared microspectroscopy (ATR-FTIR), together with multivariate analysis, was utilized to further elucidate the biochemical changes of S. aureus adhered to nanospikes. By inhibiting the ability of the pathogen to reduce its net negative charge, the nanoengineered surface renders S. aureus more susceptible to positively charged antimicrobials such as vancomycin. This finding highlights the opportunity to enhance the potency of prophylactic antibiotic treatments during implant placement surgery by employing devices having surfaces modified with spike-like nanostructures.

Urban natural parks represent a remarkable concept that evokes the coexistence of human habitation with a wild environment, and the associated interactions between human and natural territories. In this context, urban noise infringes upon the natural soundscape, leading to various consequences for both realms. This study seeks to characterize the impact of anthropic noise levels on biodiversity in the urban natural Văcărești Park (Bucharest, Romania), utilizing on-site measurements and software simulation techniques. The study seeks to develop a method for evaluating integrative strategies to mitigate the impact of traffic noise on wildlife in an urban wild park, without addressing the specific effects of noise on the perception and communication of individual species. By calibrating field measurements with laboratory results, a more reliable data set will be used to identify areas where the biophonic environment is impacted by anthropogenic noise. Since human-generated noise in an urban natural park predominantly originates from road traffic and industrial sites, managing traffic noise and its propagation pathways could substantially improve the park’s soundscape. Additionally, this study will apply software simulations for noise reduction strategies, such as vegetation planting and earthen embankments, to obtain suitable solutions and propose plausible and effective actions to authorities for improving the biophonic environment. This research could also serve as the basis for long-term monitoring, allowing for the assessment of the evolution and impact of implemented measures over time.

Abstract Marine multichannel and wide‐angle seismic data constrain the distribution of seamounts, sediment cover sequence and crustal structure along a 460 km margin‐parallel transect of the Hikurangi Plateau. Seismic reflection data reveals five seamount up‐to 4.5 km high and 35–75 km wide, with heterogeneous internal velocity structure. Sediment cover decreases south‐to‐north from ∼4.5 km to ∼1–2 km. The Hikurangi Plateau crust (VP 5.5–7.5 km/s) is 11 ± 1 km thick in the south, but thins by 3–4 km further north (∼7–8 km). Gravity models constructed along two seismic lines show the reduction in crustal thickness persists further east, coinciding with a bathymetric scarp. Gravity data suggest the transition in crustal thickness may reflect spatial variability in deformation and lithospheric extension associated with plateau breakup. Variability in the thickness of subducting crust may contribute to differences in megathrust geometry, upper‐plate stress state and high‐rates of contraction and uplift along the southern Hikurangi margin.

Abstract Background West Nile virus (WNV), primarily vectored by mosquitoes of the genus Culex, is the most important mosquito-borne pathogen in North America, having infected thousands of humans and countless wildlife since its arrival in the USA in 1999. In locations with dedicated mosquito control programs, surveillance methods often rely on frequent testing of mosquitoes collected in a network of gravid traps (GTs) and CO2-baited light traps (LTs). Traps specifically targeting oviposition-seeking (e.g. GTs) and host-seeking (e.g. LTs) mosquitoes are vulnerable to trap bias, and captured specimens are often damaged, making morphological identification difficult. Methods This study leverages an alternative mosquito collection method, the human landing catch (HLC), as a means to compare sampling of potential WNV vectors to traditional trapping methods. Human collectors exposed one limb for 15 min at crepuscular periods (5:00–8:30 am and 6:00–9:30 pm daily, the time when Culex species are most actively host-seeking) at each of 55 study sites in suburban Chicago, Illinois, for two summers (2018 and 2019). Results A total of 223 human-seeking mosquitoes were caught by HLC, of which 46 (20.6%) were mosquitoes of genus Culex. Of these 46 collected Culex specimens, 34 (73.9%) were Cx. salinarius, a potential WNV vector species not thought to be highly abundant in upper Midwest USA. Per trapping effort, GTs and LTs collected > 7.5-fold the number of individual Culex specimens than HLC efforts. Conclusions The less commonly used HLC method provides important insight into the complement of human-biting mosquitoes in a region with consistent WNV epidemics. This study underscores the value of the HLC collection method as a complementary tool for surveillance to aid in WNV vector species characterization. However, given the added risk to the collector, novel mitigation methods or alternative approaches must be explored to incorporate HLC collections safely and strategically into control programs. Graphical Abstract

The atomic force microscope is a versatile tool for assessing the topography, friction, and roughness of a broad spectrum of surfaces, encompassing anti-bacterial nanostructure arrays. Measuring and comparing all these values with one instrument allows clear comparisons of many nanomechanical reactions and anomalies. Increasing nano-Newton-level forces through the cantilever tip allows for the testing and measuring of failure points, damage behavior, and functionality under unfavorable conditions. Subjecting a grade 5 titanium alloy to hydrothermally etched nanostructures while applying elevated cantilever tip forces resulted in the observation of irreversible damage through atomic force microscopy. Despite the damage, a rough and non-uniform morphology remained that may still allow it to perform in its intended application as an anti-bacterial implant surface. Utilizing an atomic force microscope enables the evaluation of these surfaces before their biomedical application.

The volcanic Intersalar Range of western Bolivia provides a unique opportunity to examine geochemical variations spanning the arc and reararc regions of the Central Andean Plateau. In this study we report 23 new 40Ar/39Ar ages, 15 whole-rock Sr-Nd-Pb isotope analyses, and 50 whole-rock major and trace element analyses from samples collected across ∼115 km of the Intersalar Range. Most samples are classified as trachyandesites and trachydacites, with the most mafic lavas (slightly alkaline, basaltic trachyandesites) erupting from the Pliocene Coracora volcano in the central Altiplano. We identify two distinct pulses of reararc magmatism: a Miocene phase between 20 Ma and 14 Ma that corresponds with local compressional shortening, and a Plio-Pleistocene phase between 5 and 1 Ma that postdates observed structural deformation in the region. 87Sr/86Sr values (0.70512–0.70600) and 143Nd/144Nd values (0.51226–0.51255) are generally higher, and lower, respectively, in the younger phase, whereas Pb isotopes (206Pb/204Pb = 17.7315–18.5095; 207Pb/204Pb = 15.5714–15.6279; 208Pb/204Pb = 37.7862–38.6156) show little variation with age. Isotope values are only loosely correlated with distance from the modern Central Volcanic Zone. Higher Sr/Y, Dy/Yb, and [La/Yb]N values in the Plio-Pleistocene samples are consistent with homogenization at the base of a thicker continental crust compared to the Miocene samples. Nb concentrations show the strongest correlation with distance into the reararc compared to all other trace elements (arc Nb = 6–16 ppm; reararc Nb = 12–26 ppm). Nb/Nb* values (a measurement of the depth of the negative Nb anomaly) correspondingly increase into the reararc (indicating smaller anomalies), reaching a maximum at Coracora volcano before decreasing in the far rear arc region. Compiled data across the Central Andean Plateau reveal a strong correlation between Nb/Nb* and the presence of intact mantle lithosphere beneath the central Altiplano. We interpret this distinct Nb signal to reflect melting triggered by the breakdown of Nb-rich hydrous minerals within foundering (delaminating) mantle lithosphere. In conjunction with spatiotemporal data, Nb systematics provide the clearest indication of mantle lithosphere in regions where mafic samples are not present.

New strategies and market segments considering integrated approaches have emerged as critical components in the energy transition. Agrivoltaics is one approach that has shown a lot of promise for offering advantages in the food-energy-water nexus. The agrivoltaic system involves the installation of photovoltaic panels above agricultural lands to generate electricity while also allowing for crop production. The paper “SWOT and TOWS Matrix Analysis of Agrivoltaic System” comprehensively analyses the potential strengths, weaknesses, opportunities, and threats (SWOT) associated with implementing an agrivoltaic system. This study utilizes a SWOT analysis framework to identify and evaluate the internal and external factors that could impact the implementation and success of the agrivoltaic system. A TOWS matrix analysis is also conducted to formulate strategic recommendations based on the identified SWOT factors. The analysis results reveal that the agrivoltaic system has numerous strengths, including its potential to generate renewable energy, increase crop yield, and provide economic benefits to farmers. However, the system also faces several weaknesses and threats, such as high initial investment costs, land use conflicts, and potential environmental impacts. Based on the TOWS matrix analysis, this study provides strategic recommendations to maximize the potential of the agrivoltaic system while mitigating its weaknesses and threats. These recommendations include adopting a flexible pricing strategy, researching the system’s environmental impact, promoting collaboration between various stakeholders like government agencies, farmers, and energy service companies. Overall, this study provides valuable insights into the potential of agrivoltaic systems and the factors that should be considered when implementing such a system. The findings can help stakeholders make informed decisions and take appropriate actions to ensure the integration of agrivoltaic systems into agricultural practices.

The demand for joint replacement and other orthopedic surgeries involving titanium implants is continuously increasing; however, 1%–2% of surgeries result in costly and devastating implant associated infections (IAIs). Pseudomonas aeruginosa and Staphylococcus aureus are two common pathogens known to colonise implants, leading to serious complications. Bioinspired surfaces with spike-like nanotopography have previously been shown to kill bacteria upon contact; however, the longer-term potential of such surfaces to prevent or delay biofilm formation is unclear. Hence, we monitored biofilm formation on control and nanostructured titanium disc surfaces over 21 days following inoculation with Pseudomonas aeruginosa and Staphylococcus aureus. We found a consistent 2-log or higher reduction in live bacteria throughout the time course for both bacteria. The biovolume on nanostructured discs was also significantly lower than control discs at all time points for both bacteria. Analysis of the biovolume revealed that for the nanostructured surface, bacteria was killed not just on the surface, but at locations above the surface. Interestingly, pockets of bacterial regrowth on top of the biomass occurred in both bacterial species, however this was more pronounced for S. aureus cultures after 21 days. We found that the nanostructured surface showed antibacterial properties throughout this longitudinal study. To our knowledge this is the first in vitro study to show reduction in the viability of bacterial colonisation on a nanostructured surface over a clinically relevant time frame, providing potential to reduce the likelihood of implant associated infections.

Although conservation and development are two facets of sustainability, they are often placed in contradictory positions. In this context, planning systems are able to respond to investment pressure, especially in countries with underdeveloped institutional solutions for this purpose, and are consequently characterized by a shifting relationship between spatial planning and environmental protection. Although these issues have been relatively well conceptualized, the literature still lacks more in-depth analyses of selected case studies. In order to fill the gap, this study aimed to identify potential ways to protect the environment and natural values in urban areas from investment pressures in countries with less developed planning systems, based on a comparative Polish-Romanian perspective. The method consisted of comparing the national legal frameworks for environmental protection and spatial development and analyzing in detail two case studies from each country. The findings indicate that national protection is required in both countries to ensure the effective protection of natural areas situated within city administrative limits that provide important ecosystem services. Moreover, the results reveal the need for more research on similar areas using multi-scale interdisciplinary approaches and reviewing planning theory with respect to its efficiency in protecting nature.

In a courtroom, it is essential that the scientific evidence is both understandable and understood, so that the strengths and limitations of that evidence, within the context of a legal case, can inform decision making. The Evidence Chamber brings together entertainment, public engagement with science and research into a public performance activity that is centred around digital storytelling and science communication. This experience engages public audiences with science and allows a better understanding of how people interpret scientific evidence. In this paper, we discuss how we created this experience as an in-person and fully virtual performance through successful collaboration between forensic science research, public audiences, public engagement professionals, the legal profession, and digital performance artists.

The GLOBE Program’s GLOBE Observer Mosquito Habitat Mapper is a no-cost citizen scientist data collection tool compatible with Android and iOS devices. Available in 14 languages and 126 countries, it supports mosquito vector surveillance, mitigation, and education by interested individuals and as part of participatory community surveillance programs. For low-resource communities where mosquito control services are inadequate, the Mosquito Habitat Mapper supports local health action, empowerment, and environmental justice. The tangible benefits to human health supported by the Mosquito Habitat Mapper have encouraged its wide adoption, with more than 32,000 observations submitted from 84 countries. The Mosquito Habitat Mapper surveillance and data collection tool is complemented by an open database, a map visualization interface, data processing and analysis tools, and a supporting education and outreach campaign. The mobile app tool and associated research and education assets can be rapidly deployed in the event of a pandemic or local disease outbreak, contributing to global readiness and resilience in the face of mosquito-borne disease. Here, we describe the app, the Mosquito Habitat Mapper information system, examples of Mosquito Habitat Mapper deployment in scientific research, and the outreach campaign that supports volunteer training and STEM education of students worldwide.

Inspired by observations that the natural topography observed on cicada and dragonfly wings may be lethal to bacteria, researchers have sought to reproduce these nanostructures on biomaterials with the goal of reducing implant-associated infections. Titanium and its alloys are widely employed biomaterials with excellent properties but are susceptible to bacterial colonisation. Hydrothermal etching is a simple, cost-effective procedure which fabricates nanoscale protrusions of various dimensions upon titanium, depending on the etching parameters used. We investigated the role of etching time and the choice of cation (sodium and potassium) in the alkaline heat treatment on the topographical, physical, and bactericidal properties of the resulting modified titanium surfaces. Optimal etching times were 4 h for sodium hydroxide (NaOH) and 5 h for potassium hydroxide (KOH). NaOH etching for 4 h produced dense, but somewhat ordered, surface nanofeatures with 75 nanospikes per µm2. In comparison, KOH etching for 5 h resulted sparser but nonetheless disordered surface morphology with only 8 spikes per µm2. The NaOH surface was more effective at eliminating Gram-negative pathogens, while the KOH surface was more effective against the Gram-positive strains. These findings may guide further research and development of bactericidal titanium surfaces which are optimised for the predominant pathogens associated with the intended application.