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1.
Evolution ; 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39283731

RESUMO

The iconic marine raptorial predators Ichthyosauria and Eosauropterygia co-existed in the same ecosystems throughout most of the Mesozoic Era, facing similar evolutionary pressures and environmental perturbations. Both groups seemingly went through a massive macroevolutionary bottleneck across the Triassic-Jurassic (T/J) transition that greatly reduced their morphological diversity, leaving pelagic lineages as the only survivors. However, analyses of marine reptile disparity across the T/J transition have usually employed coarse morphological and temporal data. We comprehensively compare the evolution of ichthyosaurian and eosauropterygian morphology and body size across the Middle Triassic to Early Jurassic interval and find contrasting macroevolutionary patterns. The ecomorphospace of eosauropterygians predominantly reflects a strong phylogenetic signal, resulting in the clustering of three clades with clearly distinct craniodental phenotypes, suggesting 'leaps' towards novel feeding ecologies. Ichthyosaurian diversification lacks a discernible evolutionary trend, as we find evidence for a wide overlap of craniodental morphologies between Triassic and Early Jurassic forms. The temporal evolution of ecomorphological disparity, fin shape and body size of eosauropterygians and ichthyosaurians during the Late Triassic does not support the hypothesis of an abrupt macroevolutionary bottleneck near the T/J transition. Rather, an important turnover event should be sought earlier, during times of rapid sea level falls.

2.
BMC Med Educ ; 24(1): 834, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39095903

RESUMO

BACKGROUND: Medical Foundation Year (FY) doctors demonstrate greater psychological distress compared with the general population and other student groups. This feasibility study investigated FY doctors' perceptions of mindfulness and the impact of a mindful resilience and effectiveness training (MRET) programme on stress, wellbeing, and performance. METHODS: Mixed-methods study utilising a questionnaire (study 1, N = 144) and a pre-post analysis design of MRET programme (study 2, N = 13), along with focus groups (N = 7). RESULTS: In study 1 28.5% of FY's reported using mindfulness. All five mindfulness facets were significantly, and positively, associated with mental wellbeing (p < 0.05). Acting with awareness (AA) and non-reactivity (NR) were significantly, positively associated with a challenge responses to stress (p < 0.05). Threat and loss appraisals were negatively associated with AA, NR, and non-judging (p < 0.01). Perceived productivity was positively associated with mindfulness facets: describing, AA, and NR (p < 0.001). In study 2, there were significant increases in wellbeing and mindfulness facets observing, describing, AA, and NR, and threat appraisals decreased (p < 0.05). The main themes identified across the focus group included Reframed Mindset, Values-Based Action, Embodied Leadership and Pedagogy. CONCLUSIONS: There exists a relationship between mindfulness, psychological wellbeing, and performance in FYs. The MRET prorgamme improved psychological wellbeing and reduced threat appraisals. Future work could focus resources on enhancing the skills of AA and NR, as this may be sufficient to bring about meaningful improvements in wellbeing, percieved productivity and cognitive reappraisal of stressful life events.


Assuntos
Estudos de Viabilidade , Atenção Plena , Resiliência Psicológica , Humanos , Masculino , Feminino , Adulto , Médicos/psicologia , Estresse Psicológico , Grupos Focais , Inquéritos e Questionários , Eficiência , Saúde Mental
3.
Anat Rec (Hoboken) ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39039747

RESUMO

Late Jurassic rhynchocephalians from the Solnhofen Archipelago have been known for almost two centuries. The number of specimens and taxa is constantly increasing, but little is known about the ontogeny of these animals. The well-documented marine taxon Pleurosaurus is one of such cases. With over 15 described (and many more undescribed) specimens, there were no unambiguous juveniles so far. Some authors have argued that Acrosaurus, another common component of the Solnhofen Archipelago herpetofauna, might represent an early ontogenetic stage of Pleurosaurus, but the lack of proper descriptions for this taxon makes this assignment tentative, at best. Here, we describe the first unambiguous post-hatchling juvenile of Pleurosaurus and tentatively attribute it to Pleurosaurus cf. P. ginsburgi. The new specimen comes from the Lower Tithonian of the Mörnsheim Formation, Germany. This specimen is small, disarticulated, and incomplete, but preserves several of its craniomandibular bones and presacral vertebrae. It shares with Pleurosaurus a set of diagnostic features, such as an elongated and triangular skull, a low anterior flange in its dentition, and an elongated axial skeleton. It can be identified as a juvenile due to the presence of an unworn dentition, well-spaced posteriormost dentary teeth, a large gap between the last teeth and the coronoid process of the dentary, and poorly ossified vertebrae with unfused neural arches. Acrosaurus shares many anatomical features with both this specimen and Pleurosaurus, which could indicate that the two genera are indeed synonyms. The early ontogenetic stage inferred for the new Pleurosaurus specimen argues for an even earlier ontogenetic placement for specimens referred to Acrosaurus, the latter possibly pertaining to hatchlings.

4.
Science ; 383(6685): 918-923, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38386744

RESUMO

Snakes and lizards (Squamata) represent a third of terrestrial vertebrates and exhibit spectacular innovations in locomotion, feeding, and sensory processing. However, the evolutionary drivers of this radiation remain poorly known. We infer potential causes and ultimate consequences of squamate macroevolution by combining individual-based natural history observations (>60,000 animals) with a comprehensive time-calibrated phylogeny that we anchored with genomic data (5400 loci) from 1018 species. Due to shifts in the dynamics of speciation and phenotypic evolution, snakes have transformed the trophic structure of animal communities through the recurrent origin and diversification of specialized predatory strategies. Squamate biodiversity reflects a legacy of singular events that occurred during the early history of snakes and reveals the impact of historical contingency on vertebrate biodiversity.


Assuntos
Evolução Biológica , Serpentes , Animais , Biodiversidade , Genômica , Lagartos/classificação , Locomoção , Filogenia , Serpentes/classificação , Serpentes/genética
5.
Anat Rec (Hoboken) ; 307(4): 1366-1389, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36951279

RESUMO

Understanding the origins of the vertebrate brain is fundamental for uncovering evolutionary patterns in neuroanatomy. Regarding extinct species, the anatomy of the brain and other soft tissues housed in endocranial spaces can be approximated by casts of these cavities (endocasts). The neuroanatomical knowledge of Rhynchocephalia, a reptilian clade exceptionally diverse in the early Mesozoic, is restricted to the brain of its only living relative, Sphenodon punctatus, and unknown for fossil species. Here, we describe the endocast and the reptilian encephalization quotient (REQ) of the Triassic rhynchocephalian Clevosaurus brasiliensis and compare it with an ontogenetic series of S. punctatus. To better understand the informative potential of endocasts in Rhynchocephalia, we also examine the brain-endocast relationship in S. punctatus. We found that the brain occupies 30% of its cavity, but the latter recovers the general shape and length of the brain. The REQ of C. brasiliensis (0.27) is much lower than S. punctatus (0.84-1.16), with the tuatara being close to the mean for non-avian reptiles. The endocast of S. punctatus is dorsoventrally flexed and becomes more elongated throughout ontogeny. The endocast of C. brasiliensis is mostly unflexed and tubular, possibly representing a more plesiomorphic anatomy in relation to S. punctatus. Given the small size of C. brasiliensis, the main differences may result from allometric and heterochronic phenomena, consistent with suggestions that S. punctatus shows peramorphic anatomy compared to Mesozoic rhynchocephalians. Our results highlight a previously undocumented anatomical diversity among rhynchocephalians and provide a framework for future neuroanatomical comparisons among lepidosaurs.


Assuntos
Neuroanatomia , Répteis , Animais , Filogenia , Répteis/anatomia & histologia , Evolução Biológica , Encéfalo/anatomia & histologia , Fósseis , Crânio/anatomia & histologia
6.
Mil Psychol ; : 1-13, 2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37921638

RESUMO

Defense and Security Personnel (DSP) often have to operate in the presence of stressful demands. Prior research has identified factors and processes associated with DSP being able to perform resiliently in demanding situations and settings. The aim of the present study was to develop a resilient performance training programme for UK defense and security operators. An intervention mapping (IM) method was used to guide the development of the programme. Typically, IM follows six sequential phases. In the present work, these phases were shaped by insights from prior research (e.g. systematic review and end user interviews), the input of a dedicated working group (N = 13) and from practitioner focus groups. During the IM process, the importance of programme flexibility was emphasized by practitioners. As such, the enAbling REsilieNt performAnce (ARENA) training programme was designed to be agile and include both face-to-face training and online learning modules. Theoretical behavior change principles, closely aligned to findings of earlier work on resilient defense and security performance, were used to underpin programme content and delivery. Future research should seek to gather data on the impact of the ARENA programme, in the targeted biological, psychological and social factors that previously been associated with resilient performances.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38016487

RESUMO

OBJECTIVE: The development of serious games for mental wellbeing is a topic of growing interest. The increase in acceptance of games as a mainstream entertainment medium combined with the immersive qualities of games provides opportunities for meaningful support and intervention in mental wellbeing. METHOD: We conducted a systematic review and exploratory meta-analysis to examine if aspects of the interventions influenced outcomes as measured via overall effect sizes. We employed a multilevel meta-analytic approach to accommodate the interdependency of effect sizes (18 effect sizes from 14 studies, with 2027 participants). RESULTS: Overall, the main effect for gaming interventions on any outcome variable was small to medium sized, d = .35 (confidence interval [.23, 47], p < .001). Results revealed that the only significant moderator was the nature of the intervention. Specifically, only interventions that included a rational emotional behavioural focus significantly predicted an improvement in depression and/or anxiety in participants. CONCLUSION: The findings reveal promising effects for therapeutic games for mental health, but replications are needed, alongside the addressing of methodological and procedural concerns.

8.
Stress Health ; 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37818925

RESUMO

To successfully complete a Polar expedition individuals and teams must respond resiliently to the environmental, psychological, and social demands they face. In this study we examined profiles of resilient function in seven people from three expeditions in the High Arctic. Using a structured daily diary, participants reported on experiences of physical health (morning and evening), affect, team cohesion, performance, and potential explanatory factors including sleep, demand appraisals, events, and coping strategies. Notable intra- and inter-individual variability was observed in daily reports and all profiles could be interpreted as representing resilient function. A number of significant relationships were found between markers of resilient physical and psychosocial function and potential explanatory variables. For example, there was much more daily variability in an individual's reporting of positive affect than prior research might imply, and what prior research designs could capture. Further, while negative affect tended to remain low and stable, our findings reveal that even minor and infrequent increases in negative emotions were significantly associated with other variables in the network. Finally, across the expedition period individual coping resources consistently exceeded demands, suggesting that individuals viewed the expedition as a challenge and not a threat. More broadly, these findings inform efforts to monitor, and maintain resilience when operating in Polar and other extreme settings.

9.
J Clin Virol ; 167: 105574, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37639778

RESUMO

BACKGROUND: The challenges of rapid upscaling of testing capacity were a major lesson from the COVID-19 pandemic response. The need for process adjustments in high-throughput testing laboratories made sample pooling a challenging option to implement. OBJECTIVE: This study aimed to evaluate whether pooling samples at source (swab pooling) was as effective as qRT-PCR testing of individuals in identifying cases of SARS-CoV-2 in real-world community testing conditions using the same high-throughput pipeline. METHODS: Two cohorts of 10 (Pool10: 1,030 participants and 103 pools) and 6 (Pool6: 1,284 participants and 214 pools) samples per pool were tested for concordance, sensitivity, specificity, and Ct value differences with individual testing as reference. RESULTS: Swab pooling allowed unmodified application of an existing high-throughput SARS-Cov-2 testing pipeline with only marginal loss of accuracy. For Pool10, concordance was 98.1% (95% Confidence interval: 93.3-99.8%), sensitivity was 95.7% (85.5-99.5%), and specificity was 100.0% (93.6-100.0%). For Pool6, concordance was 97.2% (94.0-99.0%), sensitivity was 97.5% (93.7-99.3%), and specificity was 96.4% (87.7-99.6%). Differences of outcomes measure between pool size were not significant. Most positive individual samples, which were not detected in pools, had very low viral concentration. If only individual samples with a viral concentration > 400 copies/ml (i.e. Ct value < 30) were considered positive, the overall sensitivity of pooling increased to 99.5%. CONCLUSION: The study demonstrated high sensitivity and specificity by swab pooling and the immediate capability of high-throughput laboratories to implement this method making it an option in planning of rapid upscaling of laboratory capacity for future pandemics.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , Teste para COVID-19 , Pandemias , Laboratórios
10.
Evolution ; 77(9): 1930-1944, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37288542

RESUMO

Evolutionary shifts in chromosome compositions (karyotypes) are major drivers of lineage and genomic diversification. Fusion of ancestral chromosomes is one hypothesized mechanism for the evolutionary reduction of the total chromosome number, a frequently implied karyotypic shift. Empirical tests of this hypothesis require model systems with variable karyotypes, known chromosome features, and a robust phylogeny. Here we used chameleons, diverse lizards with exceptionally variable karyotypes ($2n=20\text{-}62$), to test whether chromosomal fusions explain the repeated evolution of karyotypes with fewer chromosomes than ancestral karyotypes. Using a multidisciplinary approach including cytogenetic analyses and phylogenetic comparative methods, we found that a model of constant loss through time best explained chromosome evolution across the chameleon phylogeny. Next, we tested whether fusions of microchromosomes into macrochromosomes explained these evolutionary losses using generalized linear models. Multiple comparisons supported microchromosome fusions as the predominant agent of evolutionary loss. We further compared our results to various natural history traits and found no correlations. As such, we infer that the tendency of microchromosomes to fuse was a quality of the ancestral chameleon genome and that the genomic predisposition of ancestors is a more substantive predictor of chromosome change than the ecological, physiological, and biogeographical factors involved in their diversification.


Assuntos
Evolução Molecular , Genoma , Cariótipo , Cariotipagem , Filogenia
11.
Int Arch Occup Environ Health ; 96(7): 1015-1027, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37269341

RESUMO

OBJECTIVE: Taking regular rest breaks while working positively impacts productivity and wellbeing. While home and hybrid working styles have become a popular choice for employees, the impact of, and perceptions towards, taking breaks while working at home is poorly understood. The current research aimed to explore attitudes towards taking rest breaks while working from home and capture levels of breaks taken, wellbeing and productivity in a sample of UK white-collar workers. METHODS: A mixed method approach was applied where self-report data from an online survey were gathered from individuals (N = 140) from one organisation. Open-ended questions regarding attitudes and perceptions towards rest break behaviours were obtained. Further quantitative measures included the number of breaks taken while working from home, levels of productivity (measured by the Health and performance Presenteeism subscale) and mental wellbeing (measured by the Short Warwick-Edinburgh Mental wellbeing scale). Both quantitative and qualitative analysis approaches were applied. RESULTS: Qualitative responses indicated two overarching themes (1) Personal and (2) Organisational sat above four further themes including Movement outside, Structure of home working, Home environment and Digital presence. Additionally, quantitative findings indicated that the number of breaks taken outside was associated with positive changes in wellbeing. CONCLUSION: Employers could aim to support employees working from home in taking outside breaks through flexible working patterns, authentic leadership, and a change in company social norms around break behaviours. Such organisational changes could help to improve workforce productivity and wellbeing.


Assuntos
Atitude , Humanos , Inquéritos e Questionários , Autorrelato
12.
Artigo em Inglês | MEDLINE | ID: mdl-36905624

RESUMO

BACKGROUND: Historically, distal fifth metatarsal diaphyseal fractures have been treated with conservative management, with only limited research evaluating surgical treatment of these fractures. This study was performed to compare surgical versus conservative treatment of distal fifth metatarsal diaphyseal fractures in athletes and nonathletes. METHODS: A retrospective review of 53 patients with surgical or conservative treatment of isolated fifth metatarsal diaphyseal fractures was performed. Data recorded included age, sex, tobacco use, diagnosis of diabetes mellitus, time to clinical union, time to radiographic union, athletic versus nonathletic status, time to return to full activity, surgical fixation method, and complications. RESULTS: Patients treated surgically had a mean clinical union time of 8.2 weeks, radiographic union time of 13.5 weeks, and return to activity time of 12.9 weeks. Patients treated conservatively had a mean clinical union time of 16.3 weeks, radiographic union time of 25.2 weeks, and return to activity time of 20.7 weeks. Delayed unions and nonunions occurred in 27.0% of patients (10 of 37) treated conservatively and in none in the surgical group. CONCLUSIONS: Surgical treatment significantly decreased time to radiographic union, clinical union, and return to activity by an average of 8 weeks compared with conservative treatment. We suggest that surgical treatment of distal fifth metatarsal fractures is a viable option that may significantly decrease the patient's time to clinical union, radiographic union, and return to activity.


Assuntos
Traumatismos do Pé , Fraturas Ósseas , Ossos do Metatarso , Humanos , Ossos do Metatarso/cirurgia , Estudos Retrospectivos , Fraturas Ósseas/cirurgia , , Fixação Interna de Fraturas/métodos , Traumatismos do Pé/cirurgia
13.
Curr Biol ; 33(3): 557-565.e7, 2023 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-36603586

RESUMO

The extent to which evolution is deterministic is a key question in biology,1,2,3,4,5,6,7,8,9 with intensive debate on how adaptation6,10,11,12,13 and constraints14,15,16 might canalize solutions to ecological challenges.4,5,6 Alternatively, unique adaptations1,9,17 and phylogenetic contingency1,3,18 may render evolution fundamentally unpredictable.3 Information from the fossil record is critical to this debate,1,2,11 but performance data for extinct taxa are limited.7 This knowledge gap is significant, as general morphology may be a poor predictor of biomechanical performance.17,19,20 High-fiber herbivory originated multiple times within ornithischian dinosaurs,21 making them an ideal clade for investigating evolutionary responses to similar ecological pressures.22 However, previous biomechanical modeling studies on ornithischian crania17,23,24,25 have not compared early-diverging taxa spanning independent acquisitions of herbivory. Here, we perform finite-element analysis on the skull of five early-diverging members of the major ornithischian clades to characterize morphofunctional pathways to herbivory. Results reveal limited functional convergence among ornithischian clades, with each instead achieving comparable performance, in terms of reconstructed patterns and magnitudes of functionally induced stress, through different adaptations of the feeding apparatus. Thyreophorans compensated for plesiomorphic low performance through increased absolute size, heterodontosaurids expanded jaw adductor muscle volume, ornithopods increased jaw system efficiency, and ceratopsians combined these approaches. These distinct solutions to the challenges of herbivory within Ornithischia underpinned the success of this diverse clade. Furthermore, the resolution of multiple solutions to equivalent problems within a single clade through macroevolutionary time demonstrates that phenotypic evolution is not necessarily predictable, instead arising from the interplay of adaptation, innovation, contingency, and constraints.1,2,3,7,8,9,18.


Assuntos
Evolução Biológica , Dinossauros , Animais , Filogenia , Herbivoria , Crânio/anatomia & histologia , Fósseis , Dinossauros/anatomia & histologia
14.
PLoS One ; 17(10): e0273015, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36190945

RESUMO

A narrative systematic literature review was conducted to explore resilient performance in defence and security settings. A search strategy was employed across a total of five databases, searching published articles from 2001 onwards that assessed performance and optimal function in relation to resilience, in defence and security personnel. Following narrative synthesis, studies were assessed for quality. Thirty-two articles met inclusion criteria across a range of performance domains, including, but not limited to, course selection, marksmanship, land navigation, and simulated captivity. Some of the key findings included measures of mental toughness, confidence, and a stress-is-enhancing mindset being positively associated with performance outcomes. There was mixed evidence for the predictive value of biomarkers, although there was some support for cortisol, dehydroepiandrosterone sulfate (DHEA-S) and neuropeptide-y (NPY), and vagal reactivity. Interventions to improve resilient performance were focused on mindfulness or general psychological skills, with effects generally clearer on cognitive tasks rather than direct performance outcomes in the field. In sum, no single measure, nor intervention was consistently associated with performance over a range of domains. To inform future work, findings from the present review have been used to develop a framework of resilient performance, with the aim to promote theoretically informed work.


Assuntos
Atenção Plena , Neuropeptídeos , Biomarcadores , Sulfato de Desidroepiandrosterona , Hidrocortisona
15.
Proc Natl Acad Sci U S A ; 119(30): e2114100119, 2022 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-35858401

RESUMO

Salamanders are an important group of living amphibians and model organisms for understanding locomotion, development, regeneration, feeding, and toxicity in tetrapods. However, their origin and early radiation remain poorly understood, with early fossil stem-salamanders so far represented by larval or incompletely known taxa. This poor record also limits understanding of the origin of Lissamphibia (i.e., frogs, salamanders, and caecilians). We report fossils from the Middle Jurassic of Scotland representing almost the entire skeleton of the enigmatic stem-salamander Marmorerpeton. We use computed tomography to visualize high-resolution three-dimensional anatomy, describing morphologies that were poorly characterized in early salamanders, including the braincase, scapulocoracoid, and lower jaw. We use these data in the context of a phylogenetic analysis intended to resolve the relationships of early and stem-salamanders, including representation of important outgroups alongside data from high-resolution imaging of extant species. Marmorerpeton is united with Karaurus, Kokartus, and others from the Middle Jurassic-Lower Cretaceous of Asia, providing evidence for an early radiation of robustly built neotenous stem-salamanders. These taxa display morphological specializations similar to the extant cryptobranchid "giant" salamanders. Our analysis also demonstrates stem-group affinities for a larger sample of Jurassic species than previously recognized, highlighting an unappreciated diversity of stem-salamanders and cautioning against the use of single species (e.g., Karaurus) as exemplars for stem-salamander anatomy. These phylogenetic findings, combined with knowledge of the near-complete skeletal anatomy of Mamorerpeton, advance our understanding of evolutionary changes on the salamander stem-lineage and provide important data on early salamanders and the origins of Batrachia and Lissamphibia.


Assuntos
Evolução Biológica , Fósseis , Urodelos , Animais , Filogenia , Crânio/anatomia & histologia , Urodelos/anatomia & histologia , Urodelos/classificação
16.
Proc Biol Sci ; 289(1969): 20212493, 2022 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-35193399

RESUMO

Performance traits are tightly linked to the fitness of organisms. However, because studies of variation in performance traits generally focus on just one or several closely related species, we are unable to draw broader conclusions about how and why these traits vary across clades. One important performance trait related to many aspects of an animal's life history is bite-force. Here, we use a clade-wide phylogenetic comparative approach to investigate relationships between size, head dimensions and bite-force among lizards and tuatara (lepidosaurs), using the largest bite-force dataset collated to date for any taxonomic group. We test four predictions: that bite-force will be greater in larger species, and for a given body size, bite-force will be greatest in species with acrodont tooth attachment, herbivorous diets, and non-burrowing habits. We show that bite-force is strongly related to body and head size across lepidosaurs and, as predicted, larger species have the greatest bite-forces. Contrary to our other predictions, tooth attachment, diet and habit have little predictive power when accounting for size. Herbivores bite more forcefully simply because they are larger. Our results also highlight priorities for future sampling to further enhance our understanding of broader evolutionary patterns.


Assuntos
Força de Mordida , Lagartos , Animais , Evolução Biológica , Ecologia , Filogenia
17.
J Exp Biol ; 224(Pt 5)2021 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-33504585

RESUMO

Cranial morphology in lepidosaurs is highly disparate and characterised by the frequent loss or reduction of bony elements. In varanids and geckos, the loss of the postorbital bar is associated with changes in skull shape, but the mechanical principles underlying this variation remain poorly understood. Here, we sought to determine how the overall cranial architecture and the presence of the postorbital bar relate to the loading and deformation of the cranial bones during biting in lepidosaurs. Using computer-based simulation techniques, we compared cranial biomechanics in the varanid Varanus niloticus and the teiid Salvator merianae, two large, active foragers. The overall strain magnitude and distribution across the cranium were similar in the two species, despite lower strain gradients in V. niloticus In S. merianae, the postorbital bar is important for resistance of the cranium to feeding loads. The postorbital ligament, which in varanids partially replaces the postorbital bar, does not affect bone strain. Our results suggest that the reduction of the postorbital bar impaired neither biting performance nor the structural resistance of the cranium to feeding loads in V. niloticus Differences in bone strain between the two species might reflect demands imposed by feeding and non-feeding functions on cranial shape. Beyond variation in cranial bone strain related to species-specific morphological differences, our results reveal that similar mechanical behaviour is shared by lizards with distinct cranial shapes. Contrary to the situation in mammals, the morphology of the circumorbital region, calvaria and palate appears to be important for withstanding high feeding loads in these lizards.


Assuntos
Lagartos , Animais , Fenômenos Biomecânicos , Simulação por Computador , Crânio/anatomia & histologia , Especificidade da Espécie
18.
Gastroenterology ; 160(1): 362-377.e13, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33039466

RESUMO

BACKGROUND & AIMS: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress, and novel therapeutic response in PC to develop a biomarker-driven therapeutic strategy targeting DDR and replication stress in PC. METHODS: We interrogated the transcriptome, genome, proteome, and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient-derived xenografts and human PC organoids. RESULTS: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors, including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, cosegregates with response to platinum (P < .001) and PARP inhibitor therapy (P < .001) in vitro and in vivo. We generated a novel signature of replication stress that predicts response to ATR (P < .018) and WEE1 inhibitor (P < .029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < .001) but was not associated with DDR deficiency. CONCLUSIONS: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR-proficient PC and after platinum therapy.


Assuntos
Adenocarcinoma/patologia , Dano ao DNA/genética , Reparo do DNA/genética , Replicação do DNA/genética , Neoplasias Pancreáticas/patologia , Adenocarcinoma/genética , Adenocarcinoma/terapia , Biomarcadores , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Humanos , Terapia de Alvo Molecular , Organoides , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Ensaios Antitumorais Modelo de Xenoenxerto
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