Immense Variation Research Articles

DIPG-23. SAFETY AND TECHNICAL YIELD OF BRAINSTEM BIOPSIES IN CHILDREN – AN UPDATED META-ANALYSIS OF 1000 CASES

Abstract BACKGROUND Brainstem tumors represent ~10% of pediatric brain tumors, ~80% of these are diffuse intrapontine gliomas (DIPG, primarily WHO Grade 4 midline glioma, H3 K27M-mutant). Given invariably poor prognosis in these cases, there continues to be immense variation (across the US and internationally) in performing biopsy of these lesions as opposed to making a presumptive diagnosis based on MRI. Several multi-center studies in recent years have aimed to show the safety profile of biopsy but an updated meta-analysis is lacking. METHODS We found 29 studies of pediatric brainstem biopsy in the last 20 years (2003-2023), representing data from 1002 children. We applied meta-analysis of proportions using a random-effects model to generate point estimates, confidence intervals, and measures of heterogeneity. RESULTS 87% of procedures were stereotactic needle biopsies (of these, 62% with a frame, 14% without frame, and 24% robotic.) Biopsy yield (i.e. the rate at which biopsy resulted in a tissue diagnosis) was 94% (95% CI 92-97). Temporary complications were seen in 6% (95 CI 4-8), most commonly including 1) radiographic evidence of bleeding or air without an associated fixed neurological deficit, 2) cranial nerve dysfunction, and 3) delayed awakening. Permanent complications (excluding death) were seen in 1% (95% CI 0.5-2), most commonly including cranial nerve dysfunction and limb weakness. 5 deaths were reported in the entire pooled cohort of 1002 children (0.5%). Gliomas represented 92% of tumors (95% CI 89-95). Of the gliomas for which WHO grading was provided, 68% were high grade (III/IV). CONCLUSION When counseling families on the merits of brainstem biopsy in children, it is reasonable to state that permanent morbidity is rare (< 2%). If biopsy is performed specifically to facilitate enrollment in clinical trials requiring a molecular diagnosis, the risks of biopsy outlined here should be weighed against potential benefits of trial enrollment.

Robust and Fast‐Ion Conducting Interphase Empowering SiOx Anode Toward High Energy Lithium–Ion Batteries

AbstractSilicon suboxides (SiOx) materials are highly desirable as anode for high energy Li‐ion batteries due to their much higher specific capacity than conventional graphite anode. However, the low initial Coulombic efficiency (ICE) and inadequate capacity retention of SiOx anode arising from its immense volume variation during repeated lithiation/delithiation process greatly hinder its practical applications. To address these drawbacks of SiOx, by a simple calcination method, a robust and fast‐ion conducting interphase enriched of LiF, Li2C2O4, LiBO2, and Li2B4O7 is rationally pre‐constructed With the assistance of this pre‐constructed artificial protective layer, the formed solid‐electrolyte interphase (SEI) layer possesses high Young's modulus and fast Li+ conducting, and thus can accommodate the plastic deformation of SiOx anode, alleviate the parasitic reactions, and maintain the electrode integrity upon cycling. Thus, the modified SiOx (M‐SiOx) anode exhibits higher ICE, better capacity retention and superior rate capability. More encouragingly, full cells pairing the M‐SiOx anode with LiNi0.8Mn0.1Co0.1O2 cathode show a high capacity retention of 80.6% for 200 cycles. This paper reveals the importance of pre‐constructing an artificial SEI layer and regulating interfacial chemistry in improving the performance of SiOx‐based anodes, which is a milestone work for boosting the large scale application of SiOx‐based anodes.

Broad-Scale Assessment of Methylmercury in Adult Amphibians.

Mercury (Hg) is a toxic contaminant that has been mobilized and distributed worldwide and is a threat to many wildlife species. Amphibians are facing unprecedented global declines due to many threats including contaminants. While the biphasic life history of many amphibians creates a potential nexus for methylmercury (MeHg) exposure in aquatic habitats and subsequent health effects, the broad-scale distribution of MeHg exposure in amphibians remains unknown. We used nonlethal sampling to assess MeHg bioaccumulation in 3,241 juvenile and adult amphibians during 2017-2021. We sampled 26 populations (14 species) across 11 states in the United States, including several imperiled species that could not have been sampled by traditional lethal methods. We examined whether life history traits of species and whether the concentration of total mercury in sediment or dragonflies could be used as indicators of MeHg bioaccumulation in amphibians. Methylmercury contamination was widespread, with a 33-fold difference in concentrations across sites. Variation among years and clustered subsites was less than variation across sites. Life history characteristics such as size, sex, and whether the amphibian was a frog, toad, newt, or other salamander were the factors most strongly associated with bioaccumulation. Total Hg in dragonflies was a reliable indicator of bioaccumulation of MeHg in amphibians (R2 ≥ 0.67), whereas total Hg in sediment was not (R2 ≤ 0.04). Our study, the largest broad-scale assessment of MeHg bioaccumulation in amphibians, highlights methodological advances that allow for nonlethal sampling of rare species and reveals immense variation among species, life histories, and sites. Our findings can help identify sensitive populations and provide environmentally relevant concentrations for future studies to better quantify the potential threats of MeHg to amphibians.

The Diversity in Grapes of Vitis labrusca Grown in Bolu (Türkiye) Assessed by Multivariate Approaches.

The grape is one of the most produced and processed horticultural crops. This study evaluated the grape genetic resource belonging to the Vitis labrusca species. The diversity was assessed according to morphometric, antioxidant, physicochemical, and colorimetric characteristics. The diversity was evaluated using a variation index and multivariate analyses. The bunch weight of the vines exhibited a range from 21.05 g to 162.46 g, with a coefficient of variation (CV) of 38.97%. The average bunch weight was 64.74 g. In terms of the berry properties, the highest CV was observed for the berry weight (21.95%). The peel thickness displayed a CV of 36.40%, and an average of 0.23 mm. The CVs for the juice characteristics in the berries of the studied vines were 7.11%, 16.61%, 19.41%, and 28.10% for the pH, TSS, must yield, and TA, respectively. The TPC of the accessions exhibited a notably low variation (CV = 4.63%). The color properties of the accessions displayed an immense variation, except for the L* values. The hierarchical clustering analysis divided the accessions into two main clusters, which both had two subclusters. The multivariate approaches separated individuals into different groups, and they were considered useful tools for utilization in the genetic diversity assessments. Further studies on the cultivation technique and crossbreeding with Vitis vinifera will provide more insights into the population, and this study will be a source for upcoming studies on V. labrusca in the region.

Local strategies towards 100% renewable energy cities and regions for West Nusa Tenggara, Indonesia

Much of the focus in the global transition towards renewable energy, a key steppingstone towards achieving the goals of the Paris Agreement, has been on the national and international levels. This focus tends to hide the immense variation present at the sub-national level. Local and regional governments are critical actors in the energy transition, and their involvement is crucial as they are ideally placed to guide their respective communities and to ensure that this transition is just, equitable and inclusive. Even though they may show the ability and ambition, the need for effective multilevel governance and enabling national policy frameworks to channel resources to the local and regional levels is more urgent than ever. Through the 100% Renewables Cities and Regions Roadmap project, the Province of West Nusa Tenggara (NTB) in Indonesia has chosen to aim to achieve one hundred percent renewable energy use in its territory by 2050 on the way to net-zero emissions. This paper discusses the results of the energy systems modelling conducted in NTB that presents a viable pathway towards this goal, which forms the basis of further recommendations and ways forward for the province in terms of priority sectors and actions.

The response to stressors in adulthood depends on the interaction between prenatal exposure to glucocorticoids and environmental context

Maternal stress during reproduction can influence how offspring respond to stress later in life. Greater lifetime exposure to glucocorticoid hormones released during stress is linked to greater risks of behavioral disorders, disease susceptibility, and mortality. The immense variation in individual’s stress responses is explained, in part, by prenatal glucocorticoid exposure. To explore the long-term effects of embryonic glucocorticoid exposure, we injected Japanese quail (Coturnix japonica) eggs with corticosterone. We characterized the endocrine stress response in offspring and measured experienced aggression at three different ages. We found that prenatal glucocorticoid exposure affected (1) the speed at which the stress response was terminated suggesting dysregulated negative feedback, (2) baseline corticosterone levels in a manner dependent on current environmental conditions with higher levels of experienced aggression associated with higher levels of baseline corticosterone, (3) the magnitude of an acute stress response based on baseline concentrations. We finish by proposing a framework that can be used to test these findings in future work. Overall, our findings suggest that the potential adaptive nature of prenatal glucocorticoid exposure is likely dependent on environmental context and may also be tempered by the negative effects of longer exposure to glucocorticoids each time an animal faces a stressor.

Which Factors Influence the Immensely Fluctuating CRT Implantation Rates in Europe? A Mixed Methods Approach Using Qualitative Content Analysis Based on Expert Interviews.

(1) Background: Cardiac resynchronisation therapy (CRT) is nowadays an indispensable treatment option for heart failure. Although the indication is subject to clear cross-national guidelines by the European Society of Cardiology (ESC), there is immense variation in the number of implantations per 100,000 inhabitants in Europe, especially in German-speaking countries (Germany, Austria and Switzerland). The aim of the present study was to identify possible factors for these differences using a qualitative research approach. (2) Methods: Semi-standardized interviews were conducted with 11 experts in the field of CRT therapy (3 experts from Germany, 4 from Austria and 4 from Switzerland) using a pre-prepared interview template and analysed according to Mayring's qualitative content analysis. (3) Results: The main factors identified were the costs of purchasing the devices and the financing systems of the respective healthcare systems, although cost pressure still seems to play a subordinate role in the German-speaking countries. Moreover, "lack of implementation of ESC guidelines", "insufficient training" and "lack of medical infrastructure" could be excluded as potential reasons. (4) Conclusions: Economic factors, but not a lack of adherence to ESC guidelines, seem to have a major influence on the fluctuating implantation figures in German-speaking countries, according to the unanimous assessment of renowned experts.

Deliberative democracy and the digital public sphere: Asymmetrical fragmentation as a political not a technological problem

Deliberative democracy and the digital public sphere: Asymmetrical fragmentation as a political not a technological problem

Characteristics of International Rotations for Undergraduate Medical Education at United States Medical Schools: A National Study.

Medical education is criticized that it does not prepare students to serve in an increasingly globalized society. Evidence that global educational experiences can alleviate these concerns have contributed to the rise in international medical education experiences. This study explores surrounding characteristics and institutional support for international rotations across medical schools in the US. The authors conducted a sequential mixed methods exploratory national survey of international rotation coordinators at 185 US medical schools and 15 semi-structured interviews in fall 2018. Quantitative data were analyzed with descriptive statistics and qualitative data were coded and analyzed using interpretive description to identify themes across data. There were 57 responses to the survey for an overall response rate of 31%, with 77% percent of respondents (n = 44) indicating that their medical school offered international rotations. Fifteen individuals representing 13 medical schools were identified as interviewees for the second stage of the study. International rotation coordinators described components of international rotations, including partnerships with host communities, use of third-party organizations, and supporting administrative and academic structures. Although international rotations are common in medical education, they are not positioned as core academic programming within medical schools. This leads to challenges in planning, implementation, and evaluation, and immense variation in rotation components across medical programs. Future research should explore best practices for pre-departure preparation, post-travel debriefing, and evaluation of student activity as well as impact on the host site. Additional research should include exploration of unique benefits of international versus domestic sites, and aspects of sustainable partnerships between medical schools and host communities.

Genomic insights into rapid speciation within the world’s largest tree genus Syzygium

Species radiations, despite immense phenotypic variation, can be difficult to resolve phylogenetically when genetic change poorly matches the rapidity of diversification. Genomic potential furnished by palaeopolyploidy, and relative roles for adaptation, random drift and hybridisation in the apportionment of genetic variation, remain poorly understood factors. Here, we study these aspects in a model radiation, Syzygium, the most species-rich tree genus worldwide. Genomes of 182 distinct species and 58 unidentified taxa are compared against a chromosome-level reference genome of the sea apple, Syzygium grande. We show that while Syzygium shares an ancient genome doubling event with other Myrtales, little evidence exists for recent polyploidy events. Phylogenomics confirms that Syzygium originated in Australia-New Guinea and diversified in multiple migrations, eastward to the Pacific and westward to India and Africa, in bursts of speciation visible as poorly resolved branches on phylogenies. Furthermore, some sublineages demonstrate genomic clines that recapitulate cladogenetic events, suggesting that stepwise geographic speciation, a neutral process, has been important in Syzygium diversification.

Graphical Image Region Extraction with K-Means Clustering and Watershed.

With a wide range of applications, image segmentation is a complex and difficult preprocessing step that plays an important role in automatic visual systems, which accuracy impacts, not only on segmentation results, but directly affects the effectiveness of the follow-up tasks. Despite the many advances achieved in the last decades, image segmentation remains a challenging problem, particularly, the segmenting of color images due to the diverse inhomogeneities of color, textures and shapes present in the descriptive features of the images. In trademark graphic images segmentation, beyond these difficulties, we must also take into account the high noise and low resolution, which are often present. Trademark graphic images can also be very heterogeneous with regard to the elements that make them up, which can be overlapping and with varying lighting conditions. Due to the immense variation encountered in corporate logos and trademark graphic images, it is often difficult to select a single method for extracting relevant image regions in a way that produces satisfactory results. Many of the hybrid approaches that integrate the Watershed and K-Means algorithms involve processing very high quality and visually similar images, such as medical images, meaning that either approach can be tweaked to work on images that follow a certain pattern. Trademark images are totally different from each other and are usually fully colored. Our system solves this difficulty given it is a generalized implementation designed to work in most scenarios, through the use of customizable parameters and completely unbiased for an image type. In this paper, we propose a hybrid approach to Image Region Extraction that focuses on automated region proposal and segmentation techniques. In particular, we analyze popular techniques such as K-Means Clustering and Watershedding and their effectiveness when deployed in a hybrid environment to be applied to a highly variable dataset. The proposed system consists of a multi-stage algorithm that takes as input an RGB image and produces multiple outputs, corresponding to the extracted regions. After preprocessing steps, a K-Means function with random initial centroids and a user-defined value for k is executed over the RGB image, generating a gray-scale segmented image, to which a threshold method is applied to generate a binary mask, containing the necessary information to generate a distance map. Then, the Watershed function is performed over the distance map, using the markers defined by the Connected Component Analysis function that labels regions on 8-way pixel connectivity, ensuring that all regions are correctly found. Finally, individual objects are labelled for extraction through a contour method, based on border following. The achieved results show adequate region extraction capabilities when processing graphical images from different datasets, where the system correctly distinguishes the most relevant visual elements of images with minimal tweaking.

Indian Monument Recognition Using Deep Learning

Monuments are physical structures built or created dedicated to a person or event. Their importance to the region they belong to makes their documentation and preservation important. Monuments being 3D objects, pose is an issue in terms of the difference in perception of the monument images. There can be an immense variation because of the viewpoint from which the image is being taken. To overcome this issue, Data Augmentation is used in this study. Random Flip, Random Rotation, Random Translation and Random Zoom, Random Contrast, Random Hue, Random Brightness, and Random Saturation operations under Data Augmentation are applied on the dataset. This research uses Deep Learning architectures on a hybrid dataset of “Indian Monument Recognition Dataset” and “Qutub Complex Monuments' Images Dataset.” InceptionV3, MobileNet, ResNet50, AlexNet, and VGG16 recognize the monuments with an accuracy of 97.79%, 93.73%, 86.47%, 68.88%, and 61.33% respectively.

Differential Regulation and Production of Secondary Metabolites among Isolates of the Fungal Wheat Pathogen Zymoseptoria tritici.

ABSTRACTThe genome of the wheat-pathogenic fungus Zymoseptoria tritici represents extensive presence-absence variation in gene content. Here, we addressed variation in biosynthetic gene cluster (BGC) content and biochemical profiles among three isolates. We analyzed secondary metabolite properties based on genome, transcriptome, and metabolome data. The isolates represent highly distinct genome architecture but harbor similar repertoires of BGCs. Expression profiles for most BGCs show comparable patterns of regulation among the isolates, suggesting a conserved biochemical infection program. For all three isolates, we observed a strong upregulation of a putative abscisic acid (ABA) gene cluster during biotrophic host colonization, indicating that Z. tritici interferes with host defenses by the biosynthesis of this phytohormone. Further, during in vitro growth, the isolates show similar metabolomes congruent with the predicted BGC content. We assessed if secondary metabolite production is regulated by histone methylation using a mutant impaired in formation of facultative heterochromatin (H3K27me3). In contrast to other ascomycete fungi, chromatin modifications play a less prominent role in regulation of secondary metabolites. In summary, we show that Z. tritici has a conserved program of secondary metabolite production, contrasting with the immense variation in effector expression, and some of these metabolites might play a key role during host colonization.IMPORTANCE Zymoseptoria tritici is one of the most devastating pathogens of wheat. So far the molecular determinants of virulence and their regulation are poorly understood. Previous studies have focused on proteinaceous virulence factors and their extensive diversity. In this study, we focus on secondary metabolites produced by Z. tritici. Using a comparative framework, we characterize core and noncore metabolites produced by Z. tritici by combining genome, transcriptome, and metabolome data sets. Our findings indicate highly conserved biochemical profiles with contrasting genetic and phenotypic diversity of the field isolates investigated here. This discovery has relevance for future crop protection strategies.

Green plant genomes: What we know in an era of rapidly expanding opportunities

Green plants play a fundamental role in ecosystems, human health, and agriculture. As de novo genomes are being generated for all known eukaryotic species as advocated by the Earth BioGenome Project, increasing genomic information on green land plants is essential. However, setting standards for the generation and storage of the complex set of genomes that characterize the green lineage of life is a major challenge for plant scientists. Such standards will need to accommodate the immense variation in green plant genome size, transposable element content, and structural complexity while enabling research into the molecular and evolutionary processes that have resulted in this enormous genomic variation. Here we provide an overview and assessment of the current state of knowledge of green plant genomes. To date fewer than 300 complete chromosome-scale genome assemblies representing fewer than 900 species have been generated across the estimated 450,000 to 500,000 species in the green plant clade. These genomes range in size from 12 Mb to 27.6 Gb and are biased toward agricultural crops with large branches of the green tree of life untouched by genomic-scale sequencing. Locating suitable tissue samples of most species of plants, especially those taxa from extreme environments, remains one of the biggest hurdles to increasing our genomic inventory. Furthermore, the annotation of plant genomes is at present undergoing intensive improvement. It is our hope that this fresh overview will help in the development of genomic quality standards for a cohesive and meaningful synthesis of green plant genomes as we scale up for the future.

Glucagon-Like Peptide-1 Is Associated With Systemic Inflammation in Pediatric Patients Treated With Hematopoietic Stem Cell Transplantation.

Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are challenged with severe side effects, which are propagated by mucosal barrier disruption, and the related microbial translocation and systemic inflammation. Glucagon-like peptide-1 (GLP-1), a well-known incretin hormone, possesses anti-inflammatory properties and promotes regeneration of damaged intestinal epithelium in animal studies. We hypothesized that the immense inter-individual variation in the degree of mucosal damage and systemic inflammation, seen after HSCT is influenced by endogenous GLP-1 and could be related to acute post-transplant complications. In this prospective study we measured serial weekly fasting plasma GLP-1, along with C-reactive protein (CRP), and citrulline in 82 pediatric patients during allogeneic HSCT together with a fasting plasma GLP-1 in sex- and age-matched healthy controls. Overall, GLP-1 levels were increased in the patients during the course of HSCT compared with the controls, but tended to decrease post-transplant, most pronounced in patients receiving high-intensity conditioning regimen. The increase in CRP seen in the early post-transplant phase was significantly lower from day +8 to +13 in patients with GLP-1 above the upper quartile (>10 pmol/L) at day 0 (all P ≤ 0.03). Similar findings were seen for peak CRP levels after adjusting for type of conditioning (-47.0%; 95% CI, -8.1 – -69.4%, P = 0.02). Citrulline declined significantly following the transplantation illustrating a decrease in viable enterocytes, most evident in patients receiving high-intensity conditioning regimen. GLP-1 levels at day 0 associated with the recovery rate of citrulline from day 0 to +21 (34 percentage points (pp)/GLP-1 doubling; 95% CI, 10 – 58pp; P = 0. 008) and day 0 to day +90 (48 pp/GLP-1 doubling; 95% CI, 17 – 79pp; P = 0. 004), also after adjustment for type of conditioning. This translated into a reduced risk of acute graft-versus-host disease (aGvHD) in patients with highest day 0 GLP-1 levels (>10 pmol/L) (cause-specific HR: 0.3; 95% CI, 0.2 – 0.9, P = 0.02). In conclusion, this study strongly suggests that GLP-1 influences regeneration of injured epithelial barriers and ameliorates inflammatory responses in the early post-transplant phase.

Estimates of global SARS-CoV-2 infection exposure, infection morbidity, and infection mortality rates in 2020.

We aimed to estimate, albeit crudely and provisionally, national, regional, and global proportions of respective populations that have been infected with SARS-CoV-2 in the first year after the introduction of this virus into human circulation, and to assess infection morbidity and mortality rates, factoring both documented and undocumented infections. The estimates were generated by applying mathematical models to 159 countries and territories. The percentage of the world's population that has been infected as of 31 December 2020 was estimated at 12.56% (95% CI: 11.17–14.05%). It was lowest in the Western Pacific Region at 0.66% (95% CI: 0.59–0.75%) and highest in the Americas at 41.92% (95% CI: 37.95–46.09%). The global infection fatality rate was 10.73 (95% CI: 10.21–11.29) per 10,000 infections. Globally per 1000 infections, the infection acute-care bed hospitalization rate was 19.22 (95% CI: 18.73–19.51), the infection ICU bed hospitalization rate was 4.14 (95% CI: 4.10–4.18). If left unchecked with no vaccination and no other public health interventions, and assuming circulation of only wild-type variants and no variants of concern, the pandemic would eventually cause 8.18 million deaths (95% CI: 7.30–9.18), 163.67 million acute-care hospitalizations (95% CI: 148.12–179.51), and 33.01 million ICU hospitalizations (95% CI: 30.52–35.70), by the time the herd immunity threshold is reached at 60–70% infection exposure. The global population remained far below the herd immunity threshold by end of 2020. Global epidemiology reveals immense regional variation in infection exposure and morbidity and mortality rates.

Ejaculate Allocation and Sperm Characteristics Differ among Alternative Male Types in a Species of Fish with Cooperation and Competition among Unrelated Males.

Sexual selection arising from sperm competition has driven the evolution of immense variation in ejaculate allocation and sperm characteristics not only among species, but also among males within a species. One question that has received little attention is how cooperation among males affects these patterns. Here we ask how male alternative reproductive types differ in testes size, ejaculate production, and sperm morphology in the ocellated wrasse, a marine fish in which unrelated males cooperate and compete during reproduction. Nesting males build nests, court females and provide care. Sneaker males only “sneak” spawn, while satellite males sneak, but also help by chasing away sneakers. We found that satellite males have larger absolute testes than either sneakers or nesting males, despite their cooperative role. Nesting males invested relatively less in testes than either sneakers or satellites. Though sneakers produced smaller ejaculates than either satellite or nesting males, we found no difference among male types in either sperm cell concentration or sperm number, implying sneakers may produce less seminal fluid. Sperm tail length did not differ significantly among male types, but sneaker sperm cells had significantly larger heads than either satellite or nesting male sperm, consistent with past research showing sneakers produce slower sperm. Our results highlight that social interactions among males can influence sperm and ejaculate production.

Making Sense of Corporate Water Usage Strategy and Performance

Access to high quality and reliable freshwater resources is a global concern as demand for water continues to grow while its sustainable supply is at risk. In the face of mounting pressures, the need for sustainable corporate water use practices is paramount, yet businesses continue to operate with immense variation in their water usage strategies and performance. Our research is driven by the desire to better understand why this variation continues to persist, especially within a highly water-dependent industry such as the craft brewing industry. Using an interview-based qualitative approach, we seek to better understand how corporate managers, from breweries in Alberta and California, are making sense of water issues. Our empirical findings reveal that novel cognitive frames pertinent to making sense of water management decisions help to explain why corporate water usage performance differs between breweries, thereby enriching the cognitive framing and sensemaking literatures, and extending these into the sustainability context. In so doing, we offer the first empirical inquiry into how corporate managers’ sensemaking processes are related to their firms’ water management strategies, and, by extension, their water usage performance.

Population consequences of climate change through effects on functional traits of lentic brown trout in the sub-Arctic

Climate-induced plasticity in functional traits has received recent attention due to the immense importance phenotypic variation plays in population level responses. Here, we explore the effect of different climate-change scenarios on lentic populations of a freshwater ectotherm, the brown trout (Salmo trutta L.), through climate effects on functional traits. We first parameterize models of climate variables on growth, spawning probability and fecundity. The models are utilized to inform a dynamic age-structured projection matrix, enabling long-term population viability projections under climate and population density variation. Ambient temperature and winter conditions had a substantial effect on population growth rate. In general, warmer summer temperatures resulted in faster growth rates for young fish but ended in smaller size at age as fish got older. Increasing summer temperatures also induced maturation at younger age and smaller size. In addition, we found effects of first-year growth on later growth trajectories for a fish, indicating that environmental conditions experienced the first year will also influence size at age later in life. At the population level, increasing temperatures average (up to 4 °C increase in areas with mean summer temperature at approximately 12 °C) resulted in a positive effect on population growth rate (i.e. smaller but more fish) during climate simulations including increasing and more variable temperatures.

Effect of Reduced Connexin43 Function on Nasal Bone Morphology and Remodelling in the G60S Mutant Mouse Model of Oculodentodigital Dysplasia

Connexin43 (Cx43), a gap-junctional protein, is known to play a role in bone development and remodelling. Our understanding of how Cx43 helps regulate bone remodelling has largely been gained through studies of long bones from a variety of Cx43 knockout mouse models, wherein disrupted osteoblast, osteoclast and osteocyte function cause altered bone morphology. However, clinically, altered Cx43 function manifests as the rare disorder oculodentodigital dysplasia (ODDD), caused by mutations in GJA1, the gene that encodes Cx43. Patients with ODDD display a suite of skeletal defects that are largely localized to craniofacial structures. While the important of Cx43 in long bone remodelling has been established, it is unknown if it plays a similar role in the skull. Thus here, using a mouse model of ODDD heterozygous for a mutation in Gja1 (G60S/+) and with known abnormal craniofacial morphology, we investigate the role of Cx43 in remodelling within the skull. Given that skeletally mature G60S/+ mice present with variable curvature of the nasal bones, we measure and compare phenotype and remodelling in nasal bones between G60S/+ and wildtype (WT) mice using micro-CT imaging, dynamic calcein histology, immunohistochemistry and tartrate-resistant acid phosphatase (TRAP) staining. Results from micro-CT imaging of G60S/+ and WT littermates over a post-natal developmental timeline from post-natal day 7, 14, 21 and three-months of age have shown that this craniofacial asymmetry is absent in younger mice, appears by post-natal day 21 and gets progressively worse with age. By three-months of age, one third of G60S/+ mice display the curved nasal bone phenotype whereas this phenotype is absent in WT mice, suggesting that the phenotype is caused by altered bone remodelling rather than disruption of initial development. Immunohistochemical staining for sclerostin and TRAP staining is greatly pronounced in G60S/+ nasal bones and corresponds to regions that display a concave curvature. These results suggest that the abnormal nasal bone curvature phenotype displayed in G60S/+ mice could be due to altered osteoclast activity and bone resorption and indicate that Cx43 does indeed help regulate bone remodelling in the skull. Our findings provide novel and exciting insights into the role of Cx43 in bone homeostasis and suggests that this protein serves a similar function in remodelling throughout the skeleton. Additionally, our results indicate that many of the skeletal manifestations of ODDD may be due to disrupted bone remodelling, which could underlie the immense phenotypic variation among patients with ODDD.