First Observation of the ß3αp Decay of

The ß-delayed proton decay of ^{13}O has previously been studied, but the direct observation of ß-delayed 3αp decay has not been reported. Rare 3αp events from the decay of excited states in ^{13}N^{⋆} provide a sensitive probe of cluster configurations in ^{13}N. To measure the low-energy products following ß-delayed 3αp decay, the Texas Active Target (TexAT) time projection chamber was employed using the one-at-a-time ß-delayed charged-particle spectroscopy technique at the Cyclotron Institute, Texas A&M University. A total of 1.9×10^{5} ^{13}O implantations were made inside the TexAT time projection chamber. A total of 149 3αp events were observed, yielding a ß-delayed 3αp branching ratio of 0.078(6)%. Four previously unknown α-decaying excited states were observed in ^{13}N at 11.3, 12.4, 13.1, and 13.7 MeV decaying via the 3α+p channel.

Theoretical Schemas to Guide Back Pain Consortium (BACPAC) Chronic Low Back Pain Clinical Research.

BACKGROUND: Chronic low back pain (cLBP) is a complex with a heterogenous clinical presentation. A better understanding of the factors that contribute to cLBP is needed for accurate diagnosis, optimal treatment, and identification of mechanistic targets for new therapies. The Back Pain Consortium (BACPAC) Research Program provides a unique opportunity in this regard, as it will generate large clinical datasets, including a diverse set of harmonized measurements. The Theoretical Model Working Group was established to guide BACPAC research and to organize new knowledge within a mechanistic framework. This article summarizes the initial work of the Theoretical Model Working Group. It includes a three-stage integration of expert opinion and an umbrella literature review of factors that affect cLBP severity and chronicity. METHODS: During Stage 1, experts from across BACPAC established a taxonomy for risk and prognostic factors (RPFs) and preliminary graphical depictions. During Stage 2, a separate team conducted a literature review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to establish working definitions, associated data elements, and overall strength of evidence for identified RPFs. These were subsequently integrated with expert opinion during Stage 3. RESULTS: The majority (∼80%) of RPFs had little strength-of-evidence confidence, whereas seven factors had substantial confidence for either a positive association with cLBP (pain-related anxiety, serum C-reactive protein, diabetes, and anticipatory/compensatory postural adjustments) or no association with cLBP (serum interleukin 1-beta / interleukin 6, transversus muscle morphology/activity, and quantitative sensory testing). CONCLUSION: This theoretical perspective will evolve over time as BACPAC investigators link empirical results to theory, challenge current ideas of the biopsychosocial model, and use a systems approach to develop tools and algorithms that disentangle the dynamic interactions among cLBP factors.

Genetic diversity of Ethiopian sorghum reveals signatures of climatic adaptation.

KEY MESSAGE: A large collection of Ethiopian sorghum landraces, characterized by agro-ecology and racial-group, was found to contain high levels of diversity and admixture, with significant SNP associations identified for environmental adaptation. Sorghum [Sorghum bicolor L. (Moench)] is a major staple food crop in Ethiopia, exhibiting extensive genetic diversity with adaptations to diverse agroecologies. The environmental and climatic drivers, as well as the genomic basis of adaptation, are poorly understood in Ethiopian sorghum and are critical elements for the development of climate-resilient crops. Exploration of the genome-environment association (GEA) is important for identifying adaptive loci and predicting phenotypic variation. The current study aimed to better understand the GEA of a large collection of Ethiopian sorghum landraces (n = 940), characterized with genome-wide SNP markers, to investigate key traits related to adaptation to temperature, precipitation and altitude. The Ethiopian sorghum landrace collection was found to consist of 12 subpopulations with high levels of admixture (47%), representing all the major racial groups of cultivated sorghum with the exception of kafir. Redundancy analysis indicated that agroecology explained up to 10% of the total SNP variation, and geographical location up to 6%. GEA identified 18 significant SNP markers for environmental variables. These SNPs were found to be significantly enriched (P < 0.05) for a priori QTL for drought and cold adaptation. The findings from this study improve our understanding of the genetic control of adaptive traits in Ethiopian sorghum. Further, the Ethiopian sorghum germplasm collection provides sources of adaptation to harsh environments (cold and/or drought) that could be deployed in breeding programs globally for abiotic stress adaptation.

Contrasting model mechanisms of alanine aminotransferase (ALT) release from damaged and necrotic hepatocytes as an example of general biomarker mechanisms.

Interpretations of elevated blood levels of alanine aminotransferase (ALT) for drug-induced liver injury often assume that the biomarker is released passively from dying cells. However, the mechanisms driving that release have not been explored experimentally. The usefulness of ALT and related biomarkers will improve by developing mechanism-based explanations of elevated levels that can be expanded and elaborated incrementally. We provide the means to challenge the ability of closely related model mechanisms to generate patterns of simulated hepatic injury and ALT release that scale (or not) to be quantitatively similar to the wet-lab validation targets, which are elevated plasma ALT values following acetaminophen (APAP) exposure in mice. We build on a published model mechanism that helps explain the generation of characteristic spatiotemporal features of APAP hepatotoxicity within hepatic lobules. Discrete event and agent-oriented software methods are most prominent. We instantiate and leverage a small constellation of concrete model mechanisms. Their details during execution help bring into focus ways in which particular sources of uncertainty become entangled with cause-effect details within and across several levels. We scale ALT amounts in virtual mice directly to target plasma ALT values in individual mice. A virtual experiment comprises a set of Monte Carlo simulations. We challenge the sufficiency of four potentially explanatory theories for ALT release. The first of the tested model theories failed to achieve the initial validation target, but each of the three others succeeded. Results for one of the three model mechanisms matched all target ALT values quantitatively. It explains how ALT externalization is the combined consequence of lobular-location-dependent drug-induced cellular damage and hepatocyte death. Falsification of one (or more) of the model mechanisms provides new knowledge and incrementally shrinks the constellation of model mechanisms. The modularity and biomimicry of our explanatory models enable seamless transition from mice to humans.

Changing paradigm of sacral neuromodulation and external anal sphincter repair for faecal incontinence in specialist centres.

AIM: The aim of this study was to determine whether the paradigm of surgical intervention for faecal incontinence (FI) has changed between 2000 and 2013. METHOD: This was a multi-centre retrospective study of patients who had undergone either sacral neuromodulation (SNM) or delayed sphincter repair or sphincteroplasty (SR) as a primary surgical intervention for FI in five centres in Europe and one in the United States. The flow of patients according to the intervention, sustainability of the treatment at a minimum follow-up of 5 years, complications and requirement for further interventions were recorded. RESULTS: A total of 461 patients (median age 56 years, range 24-90 years, 41 men) had either SNM or SR as an index operation during the study period [SNM 284 (61.6%), SR 177 (38.4%)]. Among SNM patients, there were 169 revisional operations (change of battery and/or lead, re-siting or removal). At the time of last follow-up 203 patients (71.4%) continued to use SNM. Among SR patients, 30 (16.9%) had complications, most notably wound infection (22, 12.4%). During follow-up 32 patients (18.1%) crossed over to SNM. Comparing two 4-year periods (2000-2003 and 2007-2010), the proportion of patients operated on who had a circumferential sphincter defect of less than 90° was 48 (68%) and 45 (46%), respectively (P = 0.03), while those who had SNM as the primary intervention increased from 29% to 89% (P < 0.05). CONCLUSION: The paradigm of surgical intervention for FI has changed with increasing use of SNM.

Cryopreservation of the common carotid artery of the rabbit: Optimization of dimethyl sulfoxide concentration and cooling rate.

This paper describes the continuation of studies that demonstrated the suitability of CP-Tes solution as a medium for the introduction and removal of dimethyl sulfoxide in rabbit common carotid arteries and established the kinetics of cryoprotectant permeation in that tissue. In this paper we report the tolerance of rabbit common carotid artery to dimethyl sulfoxide, in concentrations up to 30% (w/w), using a technique of exposure that was designed to control osmotic stress. The maximum concentration achieved without damage was 15% (w/w). Vessels were then equilibrated with 15% dimethyl sulfoxide and cooled to -80 °C at 0.22, 0.69, 2.15, or 9.63 °C/min: they were then transferred to the gas phase of a liquid nitrogen refrigerator {temperature below -160 °C) for storage. Thawing was carried out in a 37 °C water bath. The optimum rate of cooling for these conditions was found to be 0.69 °C/min. The maximal recovery of contractile force in response to 10-6 M norepinephrine was 30-40%; relaxation to acetylcholine (an endothelium-mediated function) was 80% of control, and an estimated 71% of endothelial cells survived with minimal ultrastructural change.

A case study approach to high-containment laboratory workflows promoting sustainability, networking and innovation.

Advances in information technologies (ITs) and operational technologies (OTs) offer high-containment laboratories opportunities to evolve scientific and operational approaches, while increasing efficiency. Emerging technologies steadily introduce changes in data generation and management practices. United States (US) government agencies and partners operate high-containment laboratories that rely on ITs/OTs to provide critical scientific functions that support prevention, detection, response and recovery for catastrophic events. These unique operating environments provide an opportunity for implementation of ITs/OTs that can facilitate both efficiency and deeper or parallel study of disease and associated biological phenomena. Operational study by subject matter experts can aid in identification of requirements and challenges pertaining to emerging ITs/OTs, examination of use cases, refinement of technical specifications and optimisation of workflows. The National Bio and Agro-Defense Facility (NBAF) in the United States of America (USA), slated to be fully operational by 2023, will be a state-of-the-art research and diagnostic facility with Biosafety Level 2, 3 and 4 laboratories for the study of high-consequence transboundary animal pathogens and zoonotic diseases impacting public health. The NBAF will support the diagnosis of emerging diseases, development of countermeasures and transboundary animal disease training. Given the rapid emergence of IT/OT solutions, the authors used a case study approach to analyse and assess real-world, high-containment laboratory functions to help maximise efficiency in mission delivery for the NBAF and the broader high-containment laboratory network. The case study approach described here could be widely adapted to diverse situations characterised by a high rate of change to provide accurate, relevant workflow analyses and optimised recommendations.

Les progrès enregistrés dans les domaines des technologies de l'information (IT) et des technologies opérationnelles (OT) offrent aux laboratoires de confinement à haute sécurité la possibilité de faire évoluer leurs approches scientifiques et opérationnelles tout en gagnant en efficacité. Grâce à ces technologies émergentes, les pratiques de production et de gestion des données sont régulièrement affinées. Les organismes gouvernementaux étatsuniens et leurs partenaires exploitent des laboratoires de confinement à haute sécurité qui font appel aux IT/OT pour mettre en oeuvre des fonctionnalités scientifiques cruciales en appui de la prévention, la détection, l'intervention et le rétablissement en cas de catastrophes. Ces environnements opérationnels uniques offrent la possibilité d'introduire des applications IT/OT afin de faciliter aussi bien l'efficacité des opérations que l'étude plus approfondie ou concomitante d'une maladie et des phénomènes biologiques qui lui sont associés. Des études opérationnelles menées par des spécialistes peuvent contribuer à identifier les exigences et les défis liés aux IT/OT émergentes, à vérifier leurs utilisations concrètes, à affiner les spécifications techniques et à optimiser l'ordonnancement des opérations. Le National Bio and Agro-Defense Facility (NBAF) des états-Unis d'Amérique, qui devrait être pleinement opérationnel d'ici 2023, sera une institution de recherche et de diagnostic de pointe dotée de laboratoires de niveaux de biosécurité 2, 3 et 4 pour l'étude des agents pathogènes responsables de maladies animales transfrontalières à haut risque et des agents zoonotiques à fort impact sur la santé publique. Le NBAF contribuera au diagnostic des maladies émergentes et à l'élaboration de mesures de lutte ; il dispensera également des formations sur les maladies animales transfrontalières. Compte tenu du développement rapide des nouvelles solutions IT/OT, les auteurs ont mis au point une méthode d'études de cas pour l'analyse et l'évaluation des fonctionnalités concrètes des laboratoires de confinement à haute sécurité, destinée à maximiser l'efficacité des prestations du NBAF et du réseau plus large de laboratoires de confinement à haute sécurité. La méthode par études de cas décrite ici pourrait être largement adaptée à diverses situations caractérisées par un niveau élevé de changement, afin de fournir des analyses précises et pertinentes de l'ordonnancement des opérations et d'élaborer des recommandations optimisées.

Los adelantos de las tecnologías de la información (TI) y las tecnologías operativas (TO) ofrecen a los laboratorios de alta contención la posibilidad de transformar sus lógicas y procedimientos de trabajo científico y al mismo tiempo ganar en eficiencia. Progresivamente, a la estela de las nuevas tecnologías, los métodos empleados para generar y gestionar datos van evolucionando. Ciertos organismos públicos estadounidenses administran, junto con entidades colaboradoras, laboratorios de alta contención que dependen de las TI/TO para cumplir una serie de cometidos científicos fundamentales en apoyo de la prevención y detección de sucesos catastróficos, de la respuesta a ellos y de los subsiguientes procesos de recuperación. Estos excepcionales entornos de trabajo ofrecen la posibilidad de implantar TI/TO que a la vez aporten más eficiencia y faciliten un estudio más a fondo o en paralelo de as enfermedades y los fenómenos biológicos asociados a ellas. La realización de estudios operativos a cargo de especialistas en el tema puede ayudar a determinar las necesidades y dificultades que plantean las nuevas TI/TO, a examinar ejemplos de utilización, a afinar las especificaciones técnicas y a optimizar los procesos de trabajo. El órgano nacional de defensa biológica y agrícola (National Bio and Agro-Defense Facility, NBAF) de los Estados Unidos de América, que según las previsiones funcionará a pleno rendimiento en 2023, constituirá un avanzado dispositivo de investigación y diagnóstico al que estarán adscritos laboratorios de nivel 2, 3 y 4 de seguridad biológica para el estudio de agentes patógenos de los animales y enfermedades zoonóticas de carácter transfronterizo y de gran repercusión que afecten a la salud pública. El NBAF secundará el diagnóstico de enfermedades emergentes, la preparación de medidas de lucha y la formación sobre enfermedades animales transfronterizas. Teniendo en cuenta la velocidad a la que surgen soluciones de TI/TO, los autores recurrieron al estudio de ejemplos concretos para analizar y evaluar las funciones que cumplen en el mundo real los laboratorios de alta contención con el objetivo de ayudar al NBAF y a la red general de laboratorios de alta contención a ejercer su cometido con la máxima eficiencia. El método de trabajo aquí descrito, basado en el estudio de casos concretos, podría ser adaptado a diversas situaciones que se caractericen por un alto ritmo de transformaciones para efectuar análisis precisos y pertinentes de los procesos de trabajo y formular recomendaciones optimizadas.

Simulation enabled search for explanatory mechanisms of the fracture healing process.

A significant portion of bone fractures fail to heal properly, increasing healthcare costs. Advances in fracture management have slowed because translation barriers have limited generation of mechanism-based explanations for the healing process. When uncertainties are numerous, analogical modeling can be an effective strategy for developing plausible explanations of complex phenomena. We demonstrate the feasibility of engineering analogical models in software to facilitate discovery of biomimetic explanations for how fracture healing may progress. Concrete analogical models-Callus Analogs-were created using the MASON simulation toolkit. We designated a Target Region initial state within a characteristic tissue section of mouse tibia fracture at day-7 and posited a corresponding day-10 Target Region final state. The goal was to discover a coarse-grain analog mechanism that would enable the discretized initial state to transform itself into the corresponding Target Region final state, thereby providing an alternative way to study the healing process. One of nine quasi-autonomous Tissue Unit types is assigned to each grid space, which maps to an 80×80 µm region of the tissue section. All Tissue Units have an opportunity each time step to act based on individualized logic, probabilities, and information about adjacent neighbors. Action causes transition from one Tissue Unit type to another, and simulation through several thousand time steps generates a coarse-grain analog-a theory-of the healing process. We prespecified a minimum measure of success: simulated and actual Target Region states achieve ≥ 70% Similarity. We used an iterative refinement protocol to explore many combinations of Tissue Unit logic and action constraints. Workflows progressed through four stages of analog mechanisms. Similarities of 73-90% were achieved for Mechanisms 2-4. The range of Upper-Level similarities increased to 83-94% when we allowed for uncertainty about two Tissue Unit designations. We have demonstrated how Callus Analog experiments provide domain experts with a fresh medium and tools for thinking about and understanding the fracture healing process.

A Model Mechanism-Based Explanation of an In Vitro-In Vivo Disconnect for Improving Extrapolation and Translation.

An improved understanding of in vivo-to-in vitro hepatocyte changes is crucial to interpreting in vitro data correctly and further improving hepatocyte-based in vitro-to-in vivo extrapolations to human targets. We demonstrate using virtual experiments as a means of helping to untangle plausible causes of inaccurate extrapolations. We start with virtual mice that use biomimetic software livers. Previously, using these mice, we discovered model mechanisms that enabled achieving quantitative validation targets while also providing plausible causal explanations for temporal characteristics of acetaminophen hepatotoxicity. We isolated virtual hepatocytes, created a virtual culture, and then conducted dose-response experiments in both culture and mice. We expected to see differences between the two dose-response curves but were somewhat surprised that they crossed because it evidenced that simulated acetaminophen metabolism and toxicity are different for virtual culture and mouse contexts even though individual hepatocyte mechanisms were unchanged. Differences in dose-response curves provide a virtual example of an in vivo-to-in vitro disconnect. We use detailed results of experiments to explain this disconnect. Individual hepatocytes contribute differently to system-level phenomena. In liver, hepatocytes are exposed to acetaminophen sequentially. Relative production of the reactive acetaminophen metabolite is largest (smallest) in pericentral (periportal) hepatocytes. Because that sequential exposure is absent in culture, hepatocytes from different lobular locations do not respond the same. A virtual culture-to-mouse translation can stand as a scientifically challengeable hypothesis explaining an in vivo-to-in vitro disconnect. It provides a framework to develop more reliable interpretations of in vitro observations, which then may be used to improve extrapolations.

Competing Mechanistic Hypotheses of Acetaminophen-Induced Hepatotoxicity Challenged by Virtual Experiments.

Acetaminophen-induced liver injury in mice is a model for drug-induced liver injury in humans. A precondition for improved strategies to disrupt and/or reverse the damage is a credible explanatory mechanism for how toxicity phenomena emerge and converge to cause hepatic necrosis. The Target Phenomenon in mice is that necrosis begins adjacent to the lobule's central vein (CV) and progresses outward. An explanatory mechanism remains elusive. Evidence supports that location dependent differences in NAPQI (the reactive metabolite) formation within hepatic lobules (NAPQI zonation) are necessary and sufficient prerequisites to account for that phenomenon. We call that the NZ-mechanism hypothesis. Challenging that hypothesis in mice is infeasible because 1) influential variables cannot be controlled, and 2) it would require sequential intracellular measurements at different lobular locations within the same mouse. Virtual hepatocytes use independently configured periportal-to-CV gradients to exhibit lobule-location dependent behaviors. Employing NZ-mechanism achieved quantitative validation targets for acetaminophen clearance and metabolism but failed to achieve the Target Phenomenon. We posited that, in order to do so, at least one additional feature must exhibit zonation by decreasing in the CV direction. We instantiated and explored two alternatives: 1) a glutathione depletion threshold diminishes in the CV direction; and 2) ability to repair mitochondrial damage diminishes in the CV direction. Inclusion of one or the other feature into NZ-mechanism failed to achieve the Target Phenomenon. However, inclusion of both features enabled successfully achieving the Target Phenomenon. The merged mechanism provides a multilevel, multiscale causal explanation of key temporal features of acetaminophen hepatotoxicity in mice. We discovered that variants of the merged mechanism provide plausible quantitative explanations for the considerable variation in 24-hour necrosis scores among 37 genetically diverse mouse strains following a single toxic acetaminophen dose.

Evaluation of a pilot school-based physical activity challenge for primary students.

Issue addressed Physical inactivity and sedentary behaviour among children are growing public health concerns. The Culture Health Communities Activity Challenge (hereafter known as the Challenge) is a school-based pedometer program in which classes compete to achieve the highest class average daily steps in an 8-week period. The Challenge aims to encourage physical activity in primary school students, with a focus on engaging Aboriginal students. The program was piloted in 15 classes in New South Wales in 2014. Methods The evaluation aimed to explore students' and teachers' experiences of the Challenge, and assess its impact on the students' physical activity levels. Data sources were a pre- and post-intervention survey of students' physical activity levels and sedentary time (n=209), qualitative interviews with teachers (n=11) and discussions with 10 classes. Results Fifteen Year 5 and 6 classes comprising 318 students participated. Fifty percent of participants were girls, the average age was 11 years and the majority (57%) were Aboriginal students. Participation in the Challenge was associated with a slight but statistically significant increase in students' physical activity levels (P<0.05), and a significant decrease in weekend screen time (P<0.05). However, when stratified by Aboriginality these changes were not statistically significant for Aboriginal students. Qualitative feedback from teachers and students indicated high levels of engagement and satisfaction with the Challenge. Teachers and students reported positive impacts, including increased motivation to be physically active, and improved student attendance and engagement in class activities and teamwork. Conclusions Participation in the Challenge was associated with increased physical activity and decreased screen time for some students. Students and teachers also reported a range of positive social and educational outcomes. So what? The findings highlight the importance of primary schools as a setting for health promotion activities, and demonstrate that school-based physical activity programs can be engaging and appropriate for classes with high proportions of Aboriginal students.

A cell-centered, agent-based framework that enables flexible environment granularities.

BACKGROUND: Mechanistic explanations of cell-level phenomena typically adopt an observer perspective. Explanations developed from a cell's perspective may offer new insights. Agent-based models lend themselves to model from an individual perspective, and existing agent-based models generally utilize a regular lattice-based environment. A framework which utilizes a cell's perspective in an off-lattice environment could improve the overall understanding of biological phenomena. RESULTS: We present an agent-based, discrete event framework, with a demonstrative focus on biomimetic agents. The framework was first developed in 2-dimensions and then extended, with a subset of behaviors, to 3-dimensions. The framework is expected to facilitate studies of more complex biological phenomena through exploitation of a dynamic Delaunay and Voronoi off-lattice environment. We used the framework to model biological cells and to specifically demonstrate basic biological cell behaviors in two- and three-dimensional space. Potential use cases are highlighted, suggesting the utility of the framework in various scenarios. CONCLUSIONS: The framework presented in this manuscript expands on existing cell- and agent-centered methods by offering a new perspective in an off-lattice environment. As the demand for biomimetic models grows, the demand for new methods, such as the presented Delaunay and Voronoi framework, is expected to increase.

Optically enhanced coherent transport in YBa2Cu3O6.5 by ultrafast redistribution of interlayer coupling.

Nonlinear optical excitation of infrared active lattice vibrations has been shown to melt magnetic or orbital orders and to transform insulators into metals. In cuprates, this technique has been used to remove charge stripes and promote superconductivity, acting in a way opposite to static magnetic fields. Here, we show that excitation of large-amplitude apical oxygen distortions in the cuprate superconductor YBa2Cu3O6.5 promotes highly unconventional electronic properties. Below the superconducting transition temperature (Tc = 50 K) inter-bilayer coherence is transiently enhanced at the expense of intra-bilayer coupling. Strikingly, even above Tc a qualitatively similar effect is observed up to room temperature, with transient inter-bilayer coherence emerging from the incoherent ground state and similar transfer of spectral weight from high to low frequency. These observations are compatible with previous reports of an inhomogeneous normal state that retains important properties of a superconductor, in which light may be melting competing orders or dynamically synchronizing the interlayer phase. The transient redistribution of coherence discussed here could lead to new strategies to enhance superconductivity in steady state.

Printed three-dimensional airway model assists planning of single-lung ventilation in a small child.

BACKGROUND: Single-lung ventilation in infants and small children is challenging because suitable sizes of double-lumen cuffed tracheal tubes are not available. A 6-yr-old child required pulmonary saline washout for primary alveolar proteinosis, and therefore needed sequential single-lung ventilation in order to achieve safe oxygenation. Before undertaking this potentially hazardous procedure, we practised bronchial intubation on an anatomical model of her airway constructed from computed tomography (CT) data. METHODS: We created a full-scale, anatomically accurate, transparent plastic model of the trachea and main bronchi on a three-dimensional printer using data from a CT scan. We then performed several different airway approaches to identify those likely to be most suitable, ex vivo, before the clinical procedure was carried out on the patient. RESULTS: The model helped us to choose the type and size of bronchial tubes and to practise their insertion beforehand. Subsequently, during anaesthesia, the chosen technique was successful. CONCLUSIONS: Three-dimensional printing of a model of the airway of a small child aided planning of bronchial intubation and single-lung ventilation. Three-dimensional printing of airway structures may have wider application in anaesthesia practice.

Association mapping of resistance to Puccinia hordei in Australian barley breeding germplasm.

KEY MESSAGE: "To find stable resistance using association mapping tools, QTL with major and minor effects on leaf rust reactions were identified in barley breeding lines by assessing seedlings and adult plants." Three hundred and sixty (360) elite barley (Hordeum vulgare L.) breeding lines from the Northern Region Barley Breeding Program in Australia were genotyped with 3,244 polymorphic diversity arrays technology markers and the results used to map quantitative trait loci (QTL) conferring a reaction to leaf rust (Puccinia hordei Otth). The F3:5 (Stage 2) lines were derived or sourced from different geographic origins or hubs of international barley breeding ventures representing two breeding cycles (2009 and 2011 trials) and were evaluated across eight environments for infection type at both seedling and adult plant stages. Association mapping was performed using mean scores for disease reaction, accounting for family effects using the eigenvalues from a matrix of genotype correlations. In this study, 15 QTL were detected; 5 QTL co-located with catalogued leaf rust resistance genes (Rph1, Rph3/19, Rph8/14/15, Rph20, Rph21), 6 QTL aligned with previously reported genomic regions and 4 QTL (3 on chromosome 1H and 1 on 7H) were novel. The adult plant resistance gene Rph20 was identified across the majority of environments and pathotypes. The QTL detected in this study offer opportunities for breeding for more durable resistance to leaf rust through pyramiding multiple genomic regions via marker-assisted selection.

QTL analysis in multiple sorghum populations facilitates the dissection of the genetic and physiological control of tillering.

KEY MESSAGE: A QTL model for the genetic control of tillering in sorghum is proposed, presenting new opportunities for sorghum breeders to select germplasm with tillering characteristics appropriate for their target environments. Tillering in sorghum can be associated with either the carbon supply-demand (S/D) balance of the plant or an intrinsic propensity to tiller (PTT). Knowledge of the genetic control of tillering could assist breeders in selecting germplasm with tillering characteristics appropriate for their target environments. The aims of this study were to identify QTL for tillering and component traits associated with the S/D balance or PTT, to develop a framework model for the genetic control of tillering in sorghum. Four mapping populations were grown in a number of experiments in south east Queensland, Australia. The QTL analysis suggested that the contribution of traits associated with either the S/D balance or PTT to the genotypic differences in tillering differed among populations. Thirty-four tillering QTL were identified across the populations, of which 15 were novel to this study. Additionally, half of the tillering QTL co-located with QTL for component traits. A comparison of tillering QTL and candidate gene locations identified numerous coincident QTL and gene locations across populations, including the identification of common non-synonymous SNPs in the parental genotypes of two mapping populations in a sorghum homologue of MAX1, a gene involved in the control of tiller bud outgrowth through the production of strigolactones. Combined with a framework for crop physiological processes that underpin genotypic differences in tillering, the co-location of QTL for tillering and component traits and candidate genes allowed the development of a framework QTL model for the genetic control of tillering in sorghum.

Supermodels: sorghum and maize provide mutual insight into the genetics of flowering time.

Nested association mapping (NAM) offers power to dissect complex, quantitative traits. This study made use of a recently developed sorghum backcross (BC)-NAM population to dissect the genetic architecture of flowering time in sorghum; to compare the QTL identified with other genomic regions identified in previous sorghum and maize flowering time studies and to highlight the implications of our findings for plant breeding. A subset of the sorghum BC-NAM population consisting of over 1,300 individuals from 24 families was evaluated for flowering time across multiple environments. Two QTL analysis methodologies were used to identify 40 QTLs with predominately small, additive effects on flowering time; 24 of these co-located with previously identified QTL for flowering time in sorghum and 16 were novel in sorghum. Significant synteny was also detected with the QTL for flowering time detected in a comparable NAM resource recently developed for maize (Zea mays) by Buckler et al. (Science 325:714-718, 2009). The use of the sorghum BC-NAM population allowed us to catalogue allelic variants at a maximal number of QTL and understand their contribution to the flowering time phenotype and distribution across diverse germplasm. The successful demonstration of the power of the sorghum BC-NAM population is exemplified not only by correspondence of QTL previously identified in sorghum, but also by correspondence of QTL in different taxa, specifically maize in this case. The unification across taxa of the candidate genes influencing complex traits, such as flowering time can further facilitate the detailed dissection of the genetic control and causal genes.

An exploration of knowledge-organizing technologies to advance transdisciplinary back pain research.

Chronic low back pain (LBP) is influenced by a broad spectrum of patient-specific factors as codified in domains of the biopsychosocial model (BSM). Operationalizing the BSM into research and clinical care is challenging because most investigators work in silos that concentrate on only one or two BSM domains. Furthermore, the expanding, multidisciplinary nature of BSM research creates practical limitations as to how individual investigators integrate current data into their processes of generating impactful hypotheses. The rapidly advancing field of artificial intelligence (AI) is providing new tools for organizing knowledge, but the practical aspects for how AI may advance LBP research and clinical are beginning to be explored. The goals of the work presented here are to: (1) explore the current capabilities of knowledge integration technologies (large language models (LLM), similarity graphs (SGs), and knowledge graphs (KGs)) to synthesize biomedical literature and depict multimodal relationships reflected in the BSM, and; (2) highlight limitations, implementation details, and future areas of research to improve performance. We demonstrate preliminary evidence that LLMs, like GPT-3, may be useful in helping scientists analyze and distinguish cLBP publications across multiple BSM domains and determine the degree to which the literature supports or contradicts emergent hypotheses. We show that SG representations and KGs enable exploring LBP's literature in novel ways, possibly providing, trans-disciplinary perspectives or insights that are currently difficult, if not infeasible to achieve. The SG approach is automated, simple, and inexpensive to execute, and thereby may be useful for early-phase literature and narrative explorations beyond one's areas of expertise. Likewise, we show that KGs can be constructed using automated pipelines, queried to provide semantic information, and analyzed to explore trans-domain linkages. The examples presented support the feasibility for LBP-tailored AI protocols to organize knowledge and support developing and refining trans-domain hypotheses.

QTL for nodal root angle in sorghum (Sorghum bicolor L. Moench) co-locate with QTL for traits associated with drought adaptation.

Nodal root angle in sorghum influences vertical and horizontal root distribution in the soil profile and is thus relevant to drought adaptation. In this study, we report for the first time on the mapping of four QTL for nodal root angle (qRA) in sorghum, in addition to three QTL for root dry weight, two for shoot dry weight, and three for plant leaf area. Phenotyping was done at the six leaf stage for a mapping population (n = 141) developed by crossing two inbred sorghum lines with contrasting root angle. Nodal root angle QTL explained 58.2% of the phenotypic variance and were validated across a range of diverse inbred lines. Three of the four nodal root angle QTL showed homology to previously identified root angle QTL in rice and maize, whereas all four QTL co-located with previously identified QTL for stay-green in sorghum. A putative association between nodal root angle QTL and grain yield was identified through single marker analysis on field testing data from a subset of the mapping population grown in hybrid combination with three different tester lines. Furthermore, a putative association between nodal root angle QTL and stay-green was identified using data sets from selected sorghum nested association mapping populations segregating for root angle. The identification of nodal root angle QTL presents new opportunities for improving drought adaptation mechanisms via molecular breeding to manipulate a trait for which selection has previously been very difficult.

Kinetics of adsorption, desorption, and re-adsorption of a commercial endoglucanase in lignocellulosic suspensions.

This study conducted quantitative kinetic modeling and in situ and temporally resolved measurements of adsorption, desorption, and re-adsorption of a commercial endoglucanase in lignocellulosic suspensions. The study defined a cellulase adsorption and desorption competition parameter, a pseudo rate of binding and desorption, binding and desorption capacity, as well as cellulase-binding reversibility (a thermodynamic property) and recyclability (a engineering parameter). The results indicate that both substrate chemical and physical structures play important roles in cellulase binding and desorption. Binding of a commercial cellulase onto a cellulosic substrate was reversible. Bindings to two different lignocellulosic substrates were almost irreversible. While lignin and its structure positively affect binding capacity to substrate, they negatively affect cellulase recyclability. Collapsing of substrate pores reduced cellulose accessibility and cellulase-binding capacity and increased reversibility and recyclability. Increasing temperature and pH increase cellulase desorption and increased binding reversibility and capacity. This study lays the foundation for developing effective cellulase recycling strategies.