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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.

[This corrects the article DOI: 10.1371/journal.pbio.1002557.].

The mitochondrial ribosome, which translates all mitochondrial DNA (mtDNA)-encoded proteins, should be tightly regulated pre- and post-transcriptionally. Recently, we found RNA-DNA differences (RDDs) at human mitochondrial 16S (large) rRNA position 947 that were indicative of post-transcriptional modification. Here, we show that these 16S rRNA RDDs result from a 1-methyladenosine (m1A) modification introduced by TRMT61B, thus being the first vertebrate methyltransferase that modifies both tRNA and rRNAs. m1A947 is conserved in humans and all vertebrates having adenine at the corresponding mtDNA position (90% of vertebrates). However, this mtDNA base is a thymine in 10% of the vertebrates and a guanine in the 23S rRNA of 95% of bacteria, suggesting alternative evolutionary solutions. m1A, uridine, or guanine may stabilize the local structure of mitochondrial and bacterial ribosomes. Experimental assessment of genome-edited Escherichia coli showed that unmodified adenine caused impaired protein synthesis and growth. Our findings revealed a conserved mechanism of rRNA modification that has been selected instead of DNA mutations to enable proper mitochondrial ribosome function.

RNA-seq is becoming a preferred tool for genomics studies of model and non-model organisms. However, DNA-based analysis of organisms lacking sequenced genomes cannot rely on RNA-seq data alone to isolate most genes of interest, as DNA codes both exons and introns. With this in mind, we designed a novel tool, LEMONS, that exploits the evolutionary conservation of both exon/intron boundary positions and splice junction recognition signals to produce high throughput splice-junction predictions in the absence of a reference genome. When tested on multiple annotated vertebrate mRNA data, LEMONS accurately identified 87% (average) of the splice-junctions. LEMONS was then applied to our updated Mediterranean chameleon transcriptome, which lacks a reference genome, and predicted a total of 90,820 exon-exon junctions. We experimentally verified these splice-junction predictions by amplifying and sequencing twenty randomly selected genes from chameleon DNA templates. Exons and introns were detected in 19 of 20 of the positions predicted by LEMONS. To the best of our knowledge, LEMONS is currently the only experimentally verified tool that can accurately predict splice-junctions in organisms that lack a reference genome.

The Levant is an important migration bridge, harboring border-zones between Afrotropical and palearctic species. Accordingly, Chameleo chameleon, a common species throughout the Mediterranean basin, is morphologically divided in the southern Levant (Israel) into two subspecies, Chamaeleo chamaeleon recticrista (CCR) and C. c. musae (CCM). CCR mostly inhabits the Mediterranean climate (northern Israel), while CCM inhabits the sands of the north-western Negev Desert (southern Israel). AFLP analysis of 94 geographically well dispersed specimens indicated moderate genetic differentiation (PhiPT = 0.097), consistent with the classical division into the two subspecies, CCR and CCM. In contrast, sequence analysis of a 637 bp coding mitochondrial DNA (mtDNA) fragment revealed two distinct phylogenetic clusters which were not consistent with the morphological division: one mtDNA cluster consisted of CCR specimens collected in regions northern of the Jezreel Valley and another mtDNA cluster harboring specimens pertaining to both the CCR and CCM subspecies but collected southern of the Jezreel Valley. AMOVA indicated clear mtDNA differentiation between specimens collected northern and southern to the Jezreel Valley (PhiPT = 0.79), which was further supported by a very low coalescent-based estimate of effective migration rates. Whole chameleon mtDNA sequencing (∼17,400 bp) generated from 11 well dispersed geographic locations revealed 325 mutations sharply differentiating the two mtDNA clusters, suggesting a long allopatric history further supported by BEAST. This separation correlated temporally with the existence of an at least 1 million year old marine barrier at the Jezreel Valley exactly where the mtDNA clusters meet. We discuss possible involvement of gender-dependent life history differences in maintaining such mtDNA genetic differentiation and suggest that it reflects (ancient) local adaptation to mitochondrial-related traits.

There is a considerable gap between investigating the dynamics of single neurons and the computational aspects of neural networks. A growing number of studies have attempted to overcome this gap using the excitation in brain slices elicited by various chemical manipulations of the bath solution. However, there has been no quantitative study on the effects of these manipulations on the cellular and network factors controlling excitability. Using the whole-cell configuration of the patch-clamp technique we recorded the membrane potential from the soma of layer 5 pyramidal neurons in acute brain slices from the somatosensory cortex of young rats at 22 degrees C and 35 degrees C. Using blockers of synaptic transmission, we show distinct changes in cellular properties following modification of the ionic composition of the artificial cerebrospinal fluid (ACSF). Thus both cellular and network changes may contribute to the observed effects of slice excitation solutions on the physiology of single neurons. Furthermore, our data suggest that the difference in the ionic composition of current standard ACSF from that of CSF measured in vivo cause ACSF to depress network activity in acute brain slices. This may affect outcomes of experiments investigating biophysical and physiological properties of neurons in such preparations. Our results strongly advocate the necessity of redesigning experiments routinely carried out in the quiescent acute brain slice preparation.

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.

Background: The posterior approach to the humeral shaft is commonly used for surgical procedures on the humeral shaft. We present our experiences using the modification of the surgical exposure described by Gerwin M. which we have found useful at the time of revision surgery. Methods: Between 2014 and 2019, six patients who underwent a revision surgical procedure for a nonunion of the humeral shaft where a prior surgical procedure was performed through a posterior incision were included. The approach used a modification of the posterior approach described by Gerwin M. where the lower lateral cutaneous nerve branch of the radial nerve is used to identify trace, mobilize, retract, and protect the radial nerve to achieve adequate exposure of the humeral shaft. Results and Discussion: None of the patients had a postoperative nerve deficit.Adequate exposure to aid hardware removal, osteosynthesis, and bone grafting was achieved in all patients. Conclusion: The modification of the posterior approach described by Gerwin M. is useful at the time of revision or redo surgery on the humeral shaft where other bony and soft tissue landmarks are altered to prevent an iatrogenic injury to the radial nerve while providing adequate exposure to treat a nonunion.

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.

AbstractNamed Entity Recognition (NER) is a fundamental NLP task, commonly formulated as classification over a sequence of tokens. Morphologically rich languages (MRLs) pose a challenge to this basic formulation, as the boundaries of named entities do not necessarily coincide with token boundaries, rather, they respect morphological boundaries. To address NER in MRLs we then need to answer two fundamental questions, namely, what are the basic units to be labeled, and how can these units be detected and classified in realistic settings (i.e., where no gold morphology is available). We empirically investigate these questions on a novel NER benchmark, with parallel token- level and morpheme-level NER annotations, which we develop for Modern Hebrew, a morphologically rich-and-ambiguous language. Our results show that explicitly modeling morphological boundaries leads to improved NER performance, and that a novel hybrid architecture, in which NER precedes and prunes morphological decomposition, greatly outperforms the standard pipeline, where morphological decomposition strictly precedes NER, setting a new performance bar for both Hebrew NER and Hebrew morphological decomposition tasks.

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.

Subjective listening tests are routinely conducted by academic researchers and industry professionals to assess the quality of various speech and audio processing algorithms and transmission services. Listening tests often take place in controlled environments for the sake of consistency, but in many cases, listening tests could be undertaken remotely using a suitable web interface. Despite the work of several projects in the past, there is no publicly available, fully hosted listening test platform which allows for easy test creation, deployment and data collection. Here, we present a fully functional end-to-end listening test platform which allows a user to create and share MUSHRA, ACR and A/B tests within minutes. Collected data can then be downloaded in various forms. For users who would prefer to host the system on their own servers, we provide Docker and AWS images for easy installation.

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.

Previous cross-sectional imaging studies found differences in brain structure and in resting state networks between presymptomatic carriers of mutations in C9orf72 (C9+) and healthy controls. We carried out a prospective longitudinal study of clinical and resting state functional imaging in a cohort of 15 presymptomatic C9+ carriers to determine whether differences in resting state connectivity prior to developing symptoms reflect static developmental differences or ongoing low-grade degenerative changes. Presymptomatic C9+ carriers were scanned at baseline with follow-up scanning at 6- and 18-months and compared to a cohort of 14 healthy controls scanned longitudinally. Resting state networks associated with manifest disease were visualized by comparing 27 symptomatic C9+ carriers to 34 healthy controls. Motor, salience, thalamic, and speech production networks were visualized using a seed-based analysis. Neurofilament light chain was measured in serum obtained at the time of the scans. Neither clinical measures of motor, cognitive, and behavioral function nor neurofilament levels changed over follow-up in presymptomatic C9+ carriers. In thalamic networks, there was a reduction in connectivity in presymptomatic carriers at all timepoints with a constant difference compared to healthy controls. In contrast, precuneus/posterior cingulate regions exhibited declining functional connectivity compared to controls over the 18-month follow-up, particularly in motor networks. These were regions that also exhibited reduced functional connectivity in symptomatic C9+ carriers. Reduced connectivity over time also occurred in small regions of frontal and temporal cortex within salience and thalamic networks in presymptomatic C9+ carriers. A few areas of increased connectivity occurred, including cortex near the motor seed and within the speech production network. Overall, changes in functional connectivity over time favor the explanation of ongoing low-grade alterations in presymptomatic C9+ carriers in most networks, with the exception of thalamic networks where functional connectivity reductions were stable over time. The loss of connectivity to parietal cortex regions in several different networks may be a distinct feature of C9orf72-related degeneration. Longitudinal studies of carriers who phenoconvert will be important to determine the prognostic significance of presymptomatic functional connectivity alterations.

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.

The Levant is an important migration bridge, harboring border-zones between Afrotropical and palearctic species. Accordingly, Chameleo chameleon, a common species throughout the Mediterranean basin, is morphologically divided in the southern Levant (Israel) into two subspecies, Chamaeleo chamaeleon recticrista (CCR) and C. c. musae (CCM). CCR mostly inhabits the Mediterranean climate (northern Israel), while CCM inhabits the sands of the north-western Negev Desert (southern Israel). AFLP analysis of 94 geographically well dispersed specimens indicated moderate genetic differentiation (PhiPT = 0.097), consistent with the classical division into the two subspecies, CCR and CCM. In contrast, sequence analysis of a 637 bp coding mitochondrial DNA (mtDNA) fragment revealed two distinct phylogenetic clusters which were not consistent with the morphological division: one mtDNA cluster consisted of CCR specimens collected in regions northern of the Jezreel Valley and another mtDNA cluster harboring specimens pertaining to both the CCR and CCM subspecies but collected southern of the Jezreel Valley. AMOVA indicated clear mtDNA differentiation between specimens collected northern and southern to the Jezreel Valley (PhiPT = 0.79), which was further supported by a very low coalescent-based estimate of effective migration rates. Whole chameleon mtDNA sequencing (∼17,400 bp) generated from 11 well dispersed geographic locations revealed 325 mutations sharply differentiating the two mtDNA clusters, suggesting a long allopatric history further supported by BEAST. This separation correlated temporally with the existence of an at least 1 million year old marine barrier at the Jezreel Valley exactly where the mtDNA clusters meet. We discuss possible involvement of genderdependent life history differences in maintaining such mtDNA genetic differentiation and suggest that it reflects (ancient) local adaptation to mitochondrial-related traits. [ABSTRACT FROM AUTHOR]

Abstract  In vivo inhibition of Ras by its antagonist farnesylthiosalicylic acid (FTS) prevents and reverses liver fibrosis in a rat model. In this study we showed the in vitro effects of Ras inhibition in a rat hepatic stellate cell line, HSC-T6. The IC50 of FTS that inhibited PDGF-induced proliferation was 15 μM. FTS, by itself or in combination with PDGF, induced a three- to fivefold increase in the number of apoptotic stellate cells but did not induce apoptosis in cells cultured with TGFβ1. We observed increased activity of MMP-9 and MMP-2 induced by FTS in combination with PDGF or TGFβ. FTS, alone or in the presence of PDGF and TGFβ, reduced collagen I mRNA expression. In conclusion, the in vivo amelioration of liver fibrosis by FTS may be explained by its ability to inhibit hepatic stellate cell proliferation, induce apoptosis and MMP-2 and MMP-9 activity, and decrease collagen I expression. [ABSTRACT FROM AUTHOR]

The voltage-clamp technique is applicable only to spherical cells. In nonspherical cells, such as neurons, the membrane potential is not clamped distal to the voltage-clamp electrode. This means that the current recorded by the voltage-clamp electrode is the sum of the local current and of axial currents from locations experiencing different membrane potentials. Furthermore, voltage-gated currents recorded from a nonspherical cell are, by definition, severely distorted due to the lack of space clamp. Justifications for voltage clamping in nonspherical cells are, first, that the lack of space clamp is not severe in neurons with short dendrites. Second, passive cable theory may be invoked to justify application of voltage clamp to branching neurons, suggesting that the potential decay is sufficiently shallow to allow spatial clamping of the neuron. Here, using numerical simulations, we show that the distortions of voltage-gated K+and Ca2+currents are substantial even in neurons with short dendrites. The simulations also demonstrate that passive cable theory cannot be used to justify voltage clamping of neurons due to significant shunting to the reversal potential of the voltage-gated conductance during channel activation. Some of the predictions made by the simulations were verified using somatic and dendritic voltage-clamp experiments in rat somatosensory cortex. Our results demonstrate that voltage-gated K+and Ca2+currents recorded from branching neurons are almost always severely distorted. [ABSTRACT FROM AUTHOR]

Purpose: Fractures of the humeral shaft are common and account for 3%–5% of all orthopedic injuries. This study aims to estimate the incidence of radial nerve palsy and its outcome when the anterior approach is employed and to analyze the predictive factors. Methods: The study was performed in the department of orthopaedics unit of a tertiary care trauma referral center. Patients who underwent surgery for acute fractures and nonunions of humerus shaft through an anterior approach from January 2007 to December 2012 were included. We retrospectively analyzed medical records, including radiographs and discharge summaries, demographic data, surgical procedures prior to our index surgery, AO fracture type and level of fracture or nonunion, experience of the operating surgeon, time of the day when surgery was performed, and radial nerve palsy with its recovery condition. The level of humerus shaft fracture or nonunion was divided into upper third, middle third and lower third. Irrespective of prior surgeries done elsewhere, the first surgery done in our institute through an anterior approach was considered as the index surgery and subsequent surgical exposures were considered as secondary procedures. Results: Of 85 patients included, 19 had preoperative radial nerve palsy. Eleven (16%) patients developed radial nerve palsy after our index procedure. Surgeons who have two or less than two years of surgical experience were 9.2 times more likely to induce radial nerve palsy (p = 0.002). Patients who had surgery between 8 p.m. and 8 a.m. were about 8 times more likely to have palsy (p = 0.004). The rest risk factor is AO type A fractures, whose incidence of radial nerve palsy was 1.3 times as compared with type B fractures (p = 0.338). For all the 11 patients, one was lost to follow-up and the others recovered within 6 months. Conclusion: Contrary to our expectations, secondary procedures and prior multiple surgeries with failed implants and poor soft tissue were not predictive factors of postoperative deficit. From our study, we also conclude that radial nerve recovery can be reasonably expected in all patients with a postoperative palsy following the anterolateral approach.

Spatial audio is essential for creating a sense of immersion in virtual environments. Efficient encoding methods are required to deliver spatial audio over networks without compromising Quality of Service (QoS). Streaming service providers such as YouTube typically transcode content into various bit rates and need a perceptually relevant audio quality metric to monitor users’ perceived quality and spatial localization accuracy. The aim of the paper is two-fold. First, it is to investigate the effect of Opus codec compression on the quality of spatial audio as perceived by listeners using subjective listening tests. Secondly, it is to introduce AMBIQUAL, a full reference objective metric for spatial audio quality, which derives both listening quality and localization accuracy metrics directly from the B-format Ambisonic audio. We compare AMBIQUAL quality predictions with subjective quality assessments across a variety of audio samples which have been compressed using the Opus 1.2 codec at various bit rates. Listening quality and localization accuracy of first and third-order Ambisonics were evaluated. Several fixed and dynamic audio sources (single and multiple) were used to evaluate localization accuracy. Results show good correlation regarding listening quality and localization accuracy between objective quality scores using AMBIQUAL and subjective scores obtained during listening tests.

Bacteriophage modulation of microbial populations impacts critical processes in ocean, soil, and animal ecosystems. However, the role of bacteriophages with RNA genomes (RNA bacteriophages) in these processes is poorly understood, in part because of the limited number of known RNA bacteriophage species. Here, we identify partial genome sequences of 122 RNA bacteriophage phylotypes that are highly divergent from each other and from previously described RNA bacteriophages. These novel RNA bacteriophage sequences were present in samples collected from a range of ecological niches worldwide, including invertebrates and extreme microbial sediment, demonstrating that they are more widely distributed than previously recognized. Genomic analyses of these novel bacteriophages yielded multiple novel genome organizations. Furthermore, one RNA bacteriophage was detected in the transcriptome of a pure culture of Streptomyces avermitilis, suggesting for the first time that the known tropism of RNA bacteriophages may include gram-positive bacteria. Finally, reverse transcription PCR (RT-PCR)-based screening for two specific RNA bacteriophages in stool samples from a longitudinal cohort of macaques suggested that they are generally acutely present rather than persistent.

This is a case study on the influence of the lower part of road vehicles on the global drag characteristics. Reducing overall drag by redesigning the lower part of the road vehicles has a potential of almost 20% in the overall drag breakdown, mainly due to the viscous effects and the fluidic interaction of the flow under the car with the typical bluff body flow pattern behind the vehicle. A special parameterization is proposed for the global shape of the sedan car, with respect to the lower part of the body, taking into account most of the specificities of the system. For such a complex interaction, CFD analysis is probably the only efficient tool in order to assess specific design parameterization of a generic car shape. Building on the credibility of such instruments is one of the major goals of this paper. Also, with respect to a target sedan car configuration, examples of successful design strategies are presented. Based on the CFD results, possible strategies to be used in order to reduce viscous drag and global drag characteristics are proposed.

The accurate measurement of acoustic nonlinearity parameter β for fluids or solids generally requires making corrections for diffraction effects due to finite size geometry of transmitter and receiver. These effects are well known in linear acoustics, while those for second harmonic waves have not been well addressed and therefore not properly considered in previous studies. In this work, we explicitly define the attenuation and diffraction corrections using the multi-Gaussian beam (MGB) equations which were developed from the quasilinear solutions of the KZK equation. The effects of making these corrections are examined through the simulation of β determination in water. Diffraction corrections are found to have more significant effects than attenuation corrections, and the β values of water can be estimated experimentally with less than 5% errors when the exact second harmonic diffraction corrections are used together with the negligible attenuation correction effects on the basis of linear frequency dependence between attenuation coefficients, α2 ≃ 2α1.

Hemophilic pseudotumor is a rare complication of hemophilia, occurring in 1 to 2 percent of individuals with severe factor VIII or factor IX deficiency. A 35-year-old male presented with a swelling in the right lower abdomen for 3 months. There was no history of trauma. Examination revealed a swelling over the right iliac fossa. Right hip showed 30° flexion deformity. Blood investigations like complete blood count, APTT, PT, bleeding and clotting time, and fibrinogen were all normal. Plain radiograph and MRI showed a lytic lesion in the right iliac wing. Excision biopsy of the swelling showed organized hematoma with a fibrous capsule suggestive of a pseudotumor. Further haematological workup like factors VIII and IX was normal. At 2 years follow-up, there was no recurrence. We report this case of pseudotumour in patient without any bleeding disorder. Such case has not been reported in literature to the best of our knowledge.

Considering two given real parameters \(\alpha, \beta\) satisfying the conditions \(0\leq\alpha\leq\beta\), D. D. Stancu [7] constructed and studied the linear positive operators \(P^{(\alpha,\beta)}_m:C([0,1])\to C([0,1])\), defined for any \(f\in C([0,1])\) and any positive integer \(m\) by (1). In this paper we are dealing with the Durrmeyer form of Stancu's operators. Some approximation properties of these Durrmeyer-Stancu operators are established. As a particular case, we retrieve approximation properties for the classical Durrmeyer operators [5].

Recently, C. Mortici defined a class of linear and positive operators depending on a certain function \(\varphi\). These operators generalize the well known Szász-Mirakjan operators. A convergence theorem for the defined sequence by the mentioned operators was given.Other interesting approximation properties of these generalized Szász-Mirakjan operators and also their bivariate form were obtained by D. Bărbosu, O. T. Pop and D. Miclăuș.In the present paper we are dealing with the Kantorovich form of the generalized Szász-Mirakjan operators. We construct the Kantorovich associated operators and then we establish a convergence theorem for the defined operators. The degree of approximation is expressed in terms of the modulus of continuity. Next, we construct the bivariate and respectively the GBS corresponding operators and we establish some of their approximation properties.

Considering a given function \(f\in C[0,1]\), the interval \([0,1]\) is divided in \(m\) equally spaced subintervals \(\left[\tfrac{k-1}{m},\tfrac{k}{m}\right]\), \(k=\overline{1,m}\). On each of such type of interval the Bernstein approximation formula is applied and a corresponding Bernstein type quadrature formula is obtained. Making the sum of mentioned quadrature formulas, the composite Bernstein type quadrature formula is obtained.

An extension of Stancu's operator \(P_{m}^{(\alpha ,\beta )}\) to the case of bivariate functions is presented and some approximation properties of this operator are discussed.

The sequence of bivariate operators of Bernstein-Schurer is constructed and some approximation properties of this sequence are studied.

The Voronovskaja theorem for the Bernstein-Schurer bivariate operatos is established.

Not available.