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This paper uses an autoethnographic case study to analyse the difficulties inherent in the professional journey from bioscience researcher to research-informed, reflective bioscience teacher. This is viewed through a philosophy of becoming. The major demand placed upon the academic to achieve this transition is seen as the conscious adoption of a perspective that embraces epistemological pluralism -- also described as post-abyssal thinking. This recognises the value of alternative epistemological views and the way they can contribute to professional development. An explicit recognition of this challenge may provide a tool to support bioscience researchers to become integrated academics and relieve some of the tensions that exist, for example between teaching and research.

Lung cancer mortality largely results from metastasis. Despite curative surgery many patients with early-stage non-small cell lung cancer ultimately succumb to metastatic relapse. Current risk reduction strategies based on cytotoxic chemotherapy and radiation have only modest activity. Against this background, we functionally screened for novel metastasis modulators using a barcoded shRNA library and an orthotopic lung cancer model. We identified aryl hydrocarbon receptor (AHR), a sensor of xenobiotic chemicals and transcription factor, as suppressor of lung cancer metastasis. Knockdown of endogenous AHR induces epithelial-mesenchymal transition signatures, increases invasiveness of lung cancer cells in vitro and metastasis formation in vivo. Low intratumoral AHR expression associates with inferior outcome of patients with resected lung adenocarcinomas. Mechanistically, AHR triggers ATF4 signaling and represses matrix metalloproteinase activity, both counteracting metastatic programs. These findings link the xenobiotic defense system with control of lung cancer progression. AHR-regulated pathways are promising targets for innovative anti-metastatic strategies.

Cutaneous sensation is vital to controlling our hands and upper limbs. It helps close the motor control loop by informing adjustments of grasping forces during object manipulations and provides much of the information the brain requires to perceive our limbs as a part of our bodies. This sensory information is absent to upper-limb prosthesis users. Although robotic prostheses are becoming increasingly sophisticated, the absence of feedback imposes a reliance on open-loop control and limits the functional potential as an integrated part of the body. Experimental systems to restore physiologically relevant sensory information to prosthesis users are beginning to emerge. However, the impact of their long-term use on functional abilities, body image, and neural adaptation processes remains unclear. Understanding these effects is essential to transition sensate prostheses from sophisticated assistive tools to integrated replacement limbs. We recruited three participants with high-level upper-limb amputation who previously received targeted reinnervation surgery. Each participant was fit with a neural-machine-interface prosthesis that allowed participants to operate their device by thinking about moving their missing limb. Additionally, we fit a sensory feedback system that allowed participants to experience touch to the prosthesis as touch on their missing limb. All three participants performed a long-term take-home trial. Two participants used their neural-machine-interface systems with touch feedback and one control participant used his prescribed, insensate prosthesis. A series of functional outcome metrics and psychophysical evaluations were performed using sensate neural-machine-interface prostheses before and after the take-home period to capture changes in functional abilities, limb embodiment, and neural adaptation. Our results demonstrated that the relationship between users and sensate neural-machine-interface prostheses is dynamic and changes with long-term use. The presence of touch sensation had a near-immediate impact on how the users operated their prostheses. In the multiple independent measures of users' functional abilities employed, we observed a spectrum of performance changes following long-term use. Furthermore, after the take-home period, participants more appropriately integrated their prostheses into their body images and psychophysical tests provided strong evidence that neural and cortical adaptation occurred.

Object stiffness discrimination is fundamental to shaping the way we interact with our environment. Investigating the sensorimotor mechanisms underpinning stiffness discrimination may help further our understanding of healthy and sensory-impaired upper limb function. We developed a metric that leverages sensory discrimination techniques and a foraging-based analysis to characterize participant accuracy and discrimination processes of sensorimotor control. Our metric required searching and discriminating two variants of test-object: rubber blocks and spring cells, which emphasized cutaneous-force and proprioceptive feedback, respectively. We measured the number of test-objects handled, selection accuracy, and foraging duration. These values were used to derive six indicators of performance. We observed higher discrimination accuracies, with quicker search and handling durations, for blocks compared to spring cells. Correlative analyses of accuracy, error rates, and foraging times suggested that the block and spring variants were, in fact, unique sensory tasks. These results provide evidence that our metric is sensitive to the contributions of sensory feedback, motor control, and task performance strategy, and will likely be effective in further characterizing the impact of sensory feedback on motor control in healthy and sensory-impaired populations.

Abstract Radiotherapy is an important modality in lung cancer treatment. Despite advances in treatment planning and dose delivery, patient benefit is still limited by in-field relapse and metastatic recurrence. Simultaneous application of cisplatinum-based chemotherapy leads to moderately improved outcomes, thus providing proof-of-concept for radiosensitization strategies in lung cancer. In an unbiased functional genetic screen for radiosensitization targets in lung cancer, we identified syntaxin 18, a protein involved in retrograde vesicular transport between the Golgi apparatus and endoplasmic reticulum, as mediator of radioresistance. Downregulation of endogenous syntaxin 18 specifically reduced clonogenic survival of radioresistant and radiosensitive lung cancer cells following X-radiation. Gene expression programs regulating DNA repair, mitotic checkpoints and mitosis were altered in isogenic cells with reduced syntaxin 18 expression. Functionally, this translated into impaired DNA damage-induced cell cycle checkpoints leading to cell death by mitotic catastrophe. Interestingly, downregulation of syntaxin 18 in lung cancer cells also impaired expression of markers of epithelial-mesenchymal-transition, and reduced migration and invasion capacity. These findings suggest that syntaxin 18 is a key player regulating genes responsible for controlling the growth of the primary tumor as well as metastases upon radiotherapy of lung cancer. They provide a promising lead for biologically rational radiosensitization strategies impacting on radiation-induced cell death as well as metastasis.

BackgroundIndices of inter-evaluator reliability are used in many fields such as computational linguistics, psychology, and medical science; however, the interpretation of resulting values and determination of appropriate thresholds lack context and are often guided only by arbitrary "rules of thumb" or simply not addressed at all. Our goal for this work was to develop a method for determining the relationship between inter-evaluator agreement and error to facilitate meaningful interpretation of values, thresholds, and reliability.MethodsThree expert human evaluators completed a video analysis task, and averaged their results together to create a reference dataset of 300 time measurements. We simulated unique combinations of systematic error and random error onto the reference dataset to generate 4900 new hypothetical evaluators (each with 300 time measurements). The systematic errors and random errors made by the hypothetical evaluator population were approximated as the mean and variance of a normally-distributed error signal. Calculating the error (using percent error) and inter-evaluator agreement (using Krippendorff's alpha) between each hypothetical evaluator and the reference dataset allowed us to establish a mathematical model and value envelope of the worst possible percent error for any given amount of agreement.ResultsWe used the relationship between inter-evaluator agreement and error to make an informed judgment of an acceptable threshold for Krippendorff's alpha within the context of our specific test. To demonstrate the utility of our modeling approach, we calculated the percent error and Krippendorff's alpha between the reference dataset and a new cohort of trained human evaluators and used our contextually-derived Krippendorff's alpha threshold as a gauge of evaluator quality. Although all evaluators had relatively high agreement (> 0.9) compared to the rule of thumb (0.8), our agreement threshold permitted evaluators with low error, while rejecting one evaluator with relatively high error.ConclusionsWe found that our approach established threshold values of reliability, within the context of our evaluation criteria, that were far less permissive than the typically accepted "rule of thumb" cutoff for Krippendorff's alpha. This procedure provides a less arbitrary method for determining a reliability threshold and can be tailored to work within the context of any reliability index.

To effortlessly complete an intentional movement, the brain needs feedback from the body regarding the movement's progress. This largely nonconscious kinesthetic sense helps the brain to learn relationships between motor commands and outcomes to correct movement errors. Prosthetic systems for restoring function have predominantly focused on controlling motorized joint movement. Without the kinesthetic sense, however, these devices do not become intuitively controllable. We report a method for endowing human amputees with a kinesthetic perception of dexterous robotic hands. Vibrating the muscles used for prosthetic control via a neural-machine interface produced the illusory perception of complex grip movements. Within minutes, three amputees integrated this kinesthetic feedback and improved movement control. Combining intent, kinesthesia, and vision instilled participants with a sense of agency over the robotic movements. This feedback approach for closed-loop control opens a pathway to seamless integration of minds and machines.

Robert Jütte, von 1990 bis 2020 Leiter des Instituts für Geschichte der Medizin der Robert Bosch Stiftung in Stuttgart, hat im Jahr 2000 das Buch "Geschichte der Sinne" veröffentlicht und gilt damit im deutschen Sprachraum als Pionier der historischen Sinnesforschung. Im Rahmen des Workshops „Sinnesräume. Sensory Studies and Spatial Concepts: Schall (aus)messen, Grenzen (er)tasten, Gerüche (ein)ordnen, Zeiten (ab)schmecken …“ an der Universität Innsbruck, 27./28. Mai 2021, hielt er die Keynote mit dem Titel „Der Krieg und die Sinne. Vom Ersten zum Zweiten Weltkrieg“. Am Rande des Workshops führten Ellinor Forster und Regina Thumser-Wöhs das Gespräch mit Robert Jütte, zu dessen Schwerpunkten neben Medizingeschichte auch Alltags- und Kulturgeschichte der Frühen Neuzeit sowie jüdische Geschichte gehören.

Die Beiträge beziehen sich auf die raumkonstituierende Funktion von Sehen, Hören, Riechen, Schmecken und Tasten, darauf also, wie Raum durch die menschliche Wahrnehmung konstruiert und mit Wissensbeständen verknüpft wird. Dabei spielen sowohl visuelle Reize und haptische Eindrücke als auch die Klassifizierung von Geräuschen und Gerüchen eine Rolle. Ein besonderer Fokus liegt auf dem Zusammenspiel mehrerer Sinne. Häufig handelt es sich bei historischen Beschreibungen von Sinneswahrnehmungen um Ausnahmesituationen, wie das Erleben einer angstbesetzten Situation oder die Wahrnehmung einer neuen, ungewöhnlichen Umgebung. Es lassen sich aber auch Alltagssituationen untersuchen, wenn etwa sinnesspezifische Verortungen zur Fortführung von mentalen Zuschreibungen dienen, Geräusche wie der Straßenlärm oder der ‚Geschmack des Kolonialismus‘ beschrieben werden.

Purpose – Concept maps have been described as a valuable tool for exploring curriculum knowledge. However, less attention has been given to the use of them to visualise contested and tacit knowledge, i.e. the values and perceptions of teachers that underpin their practice. This paper aims to explore the use of concept mapping to uncover academics’ views and help them articulate their perspectives within the framework provided by the concepts of pedagogic frailty and resilience in a collaborative environment. Design/methodology/approach – Participants were a group of five colleagues within a Biochemical Science Department, working on the development of a new undergraduate curriculum. A qualitative single-case study was conducted to get some insights on how concept mapping might scaffold each step of the collaborative process. They answered the online questionnaire; their answers were “translated” into an initial expert-constructed concept map, which was offered as a starting point to articulate their views during a group session, resulting in a consensus map. Findings – Engaging with the questionnaire was useful for providing the participants with an example of an “excellent” map, sensitising them to the core concepts and the possible links between them, without imposing a high level of cognitive load. This fostered dialogue of complex ideas, introducing the potential benefits of consensus maps in team-based projects. Originality/value – An online questionnaire may facilitate the application of the pedagogic frailty model for academic development by scaling up the mapping process. The map-mediated facilitation of dialogue within teams of academics may facilitate faculty development by making explicit the underpinning values held by team members.

When developing meaningful curricula, institutions must engage with the desired disciplinary attributes of their graduates. Successfully employed in several areas, including psychology and chemistry, disciplinary literacies provide structure for the development of core competencies‐pursuing progressive education. To this end, we have sought to develop a comprehensive blueprint of a graduate biochemist, providing detailed insight into the development of skills in the context of disciplinary knowledge. The Biochemical Literacy Framework (BCLF) aspires to encourage innovative course design in both the biochemical field and beyond through stimulating discussion among individuals developing undergraduate biochemistry degree courses based on pedagogical best practice. Here, we examine the concept of biochemical literacy aiming to start answering the question: What must individuals do and know to approach and transform ideas in the context of the biochemical sciences? The BCLF began with the guidance published by relevant learned societies – including the Royal Society of Biology, the Biochemical Society, the American Society for Biochemistry and Molecular Biology and the Quality Assurance Agency, before considering relevant pedagogical literature. We propose that biochemical literacy is comprised of seven key skills: critical thinking, self‐management, communication, information literacy, visual literacy, practical skills and content knowledge. Together, these form a dynamic, highly interconnected and interrelated meta‐literacy supporting the use of evidence‐based, robust learning techniques. The BCLF is intended to form the foundation for discussion between colleagues, in addition to forming the groundwork for both pragmatic and exploratory future studies into facilitating and further defining biochemical literacy.

Abstract Opioid receptor activation was shown to enhance the efficacy of anti‐neoplastic drugs in several human cancer cell lines. In these cell lines, doxorubicin increased the number of opioid receptors and methadone concurrently enhanced cellular doxorubicin uptake. Triggered through lay press and media, animal owners started to challenge veterinary oncologists with questions about methadone use in anti‐cancer therapy. Especially in veterinary medicine, where side effects of chemotherapy are tolerated to a lesser extent and hence smaller doses are given, agents potentiating chemotherapeutic agents would be an optimal approach to treatment. Canine transitional cell carcinoma cells (TCC, K9TCC), canine osteosarcoma cells (OSA, Abrams) and canine hemangiosarcoma cells (HSA, DAL‐4) were incubated with different combinations of methadone, buprenorphine and doxorubicin, in order to test inhibition of cell proliferation. Opioid receptor density was assessed with fluorescence‐activated cell sorting in drug native and doxorubicin pretreated cells. In TCC and OSA cell lines opioid receptor density increased after doxorubicin pretreatment. In combination treatment, however, we did not find significant potentiation of doxorubicin's inhibitory effect on proliferation in these cell lines. Neither was there a significant increase of the effect of doxorubicin when the opioids were added 24 hr before doxorubicin. Hence, we could not confirm the hypothesis that opioids increase the anti‐proliferative effect of the anti‐neoplastic drug doxorubicin in any of these canine tumour cell lines. The lack of effect on a cellular level does not warrant a clinical approach to use opioids together with doxorubicin in dogs with cancer.

Abstract Dogs develop cancer spontaneously with age, with breed-specific risk underlying differences in genetics. Mammary tumors are reported as the most frequent neoplasia in intact female dogs. Their high prevalence in certain breeds suggests a genetic component, as it is the case in human familial breast cancer, distinctly in BRCA2-associated cancers. However, the molecular genetics of BRCA2 in the pathogenesis of canine cancer are still under investigation. Genetic variations of canine BRCA2 comprised single nucleotide polymorphisms, insertions and deletions. The BRCA2 level has been shown to be reduced in tumor gland samples, suggesting that low expression of BRCA2 is contributing to mammary tumor development in dogs. Additionally, specific variations of the BRCA2 gene affect RAD51 binding strength, critically damage the BRCA2-RAD51 binding and further provoke a defective repair. In humans, preclinical and clinical data revealed a synthetic lethality interaction between BRCA2 mutations and PARP inhibition. PARP inhibitors are successfully used to increase chemo- and radiotherapy sensitivity, although they are also associated with numerous side effects and acquired resistance. Cancer treatment of canine patients could benefit from increased chemo- and radiosensitivity, as their cancer therapy protocols usually include only low doses of drugs or radiation. Early investigations show tolerability of iniparib in dogs. PARP inhibitors also imply higher therapy costs and consequently are less likely to be accepted by pet owners. We summarized the current evidence of canine BRCA2 gene alterations and their association with mammary tumors. Mutations in the canine BRCA2 gene have the potential to be exploited in clinical therapy through the usage of PARP inhibitors. However, further investigations are needed before introducing PARP inhibitors in veterinary clinical practice.

Stroke patients often have difficulty completing motor tasks even after substantive rehabilitation. Poor recovery of motor function can often be linked to stroke-induced damage to motor pathways. However, stroke damage in pathways that impact effective integration of sensory feedback with motor control may represent an unappreciated obstacle to smooth motor coordination. In this study we investigated the effects of augmenting movement proprioception during a reaching task in six stroke patients as a proof of concept. We used a wearable neurorobotic proprioceptive feedback system to induce illusory kinaesthetic sensation by vibrating participants' upper arm muscles over active limb movements. Participants were instructed to extend their elbow to reach-and-point to targets of differing sizes at various distances, while illusion-inducing vibration (90 Hz), sham vibration (25 Hz), or no vibration was applied to the distal tendons of either their biceps brachii or their triceps brachii. To assess the impact of augmented kinaesthetic feedback on motor function we compared the results of vibrating the biceps or triceps during arm extension in the affected arm of stroke patients and able-bodied participants. We quantified performance across conditions and participants by tracking limb/hand kinematics with motion capture, and through Fitts' law analysis of reaching target acquisition. Kinematic analyses revealed that injecting 90 Hz illusory kinaesthetic sensation into the actively contracting (agonist) triceps muscle during reaching increased movement smoothness, movement directness, and elbow extension. Conversely, injecting 90 Hz illusory kinaesthetic sensation into the antagonistic biceps during reaching negatively impacted those same parameters. The Fitts' law analyses reflected similar effects with a trend toward increased throughput with triceps vibration during reaching. Across all analyses, able-bodied participants were largely unresponsive to illusory vibrational augmentation. These findings provide evidence that vibration-induced movement illusions delivered to the primary agonist muscle involved in active movement may be integrated into rehabilitative approaches to help promote functional motor recovery in stroke patients.

Die Beiträge des Bandes beschäftigen sich mit Begutachtungspraktiken verschiedener Epochen und zeigen die Entwicklung des Gutachtens als einen Prozess auf, der zunehmend der Diskussion, Ausverhandlung und dem Einfluss von Wissen und Gegenwissen um soziokulturelle Normen unterliegt. Ausgehend von der Annahme, dass der Medizin in der Klassifikation, Bewertung und Einschätzung bzw. in der Subjektivierung von Einzelnen und Gruppen eine besondere Bedeutung zukommt, rückt insbesondere jenes Verhältnis in den Fokus, das durch die Tätigkeit des Gutachtens zwischen und für Menschen hergestellt wird.

Cutaneous sensation is vital to controlling our hands and upper limbs. It helps close the motor control loop by informing adjustments of grasping forces during object manipulations and provides much of the information the brain requires to perceive our limbs as a part of our bodies. This sensory information is absent to upper-limb prosthesis users. Although robotic prostheses are becoming increasingly sophisticated, the absence of feedback imposes a reliance on open-loop control and limits the functional potential as an integrated part of the body. Experimental systems to restore physiologically relevant sensory information to prosthesis users are beginning to emerge. However, the impact of their long-term use on functional abilities, body image, and neural adaptation processes remains unclear. Understanding these effects is essential to transition sensate prostheses from sophisticated assistive tools to integrated replacement limbs. We recruited three participants with high-level upper-limb amputation who previously received targeted reinnervation surgery. Each participant was fit with a neural-machine-interface prosthesis that allowed participants to operate their device by thinking about moving their missing limb. Additionally, we fit a sensory feedback system that allowed participants to experience touch to the prosthesis as touch on their missing limb. All three participants performed a long-term take-home trial. Two participants used their neural-machine-interface systems with touch feedback and one control participant used his prescribed, insensate prosthesis. A series of functional outcome metrics and psychophysical evaluations were performed using sensate neural-machine-interface prostheses before and after the take-home period to capture changes in functional abilities, limb embodiment, and neural adaptation. Our results demonstrated that the relationship between users and sensate neural-machine-interface prostheses is dynamic and changes with long-term use. The presence of touch sensation had a near-immediate impact on how the users operated their prostheses. In the multiple independent measures of users’ functional abilities employed, we observed a spectrum of performance changes following long-term use. Furthermore, after the take-home period, participants more appropriately integrated their prostheses into their body images and psychophysical tests provided strong evidence that neural and cortical adaptation occurred.

Abstract Background Indices of inter-evaluator reliability are used in many fields such as computational linguistics, psychology, and medical science; however, the interpretation of resulting values and determination of appropriate thresholds lack context and are often guided only by arbitrary “rules of thumb” or simply not addressed at all. Our goal for this work was to develop a method for determining the relationship between inter-evaluator agreement and error to facilitate meaningful interpretation of values, thresholds, and reliability. Methods Three expert human evaluators completed a video analysis task, and averaged their results together to create a reference dataset of 300 time measurements. We simulated unique combinations of systematic error and random error onto the reference dataset to generate 4900 new hypothetical evaluators (each with 300 time measurements). The systematic errors and random errors made by the hypothetical evaluator population were approximated as the mean and variance of a normally-distributed error signal. Calculating the error (using percent error) and inter-evaluator agreement (using Krippendorff’s alpha) between each hypothetical evaluator and the reference dataset allowed us to establish a mathematical model and value envelope of the worst possible percent error for any given amount of agreement. Results We used the relationship between inter-evaluator agreement and error to make an informed judgment of an acceptable threshold for Krippendorff’s alpha within the context of our specific test. To demonstrate the utility of our modeling approach, we calculated the percent error and Krippendorff’s alpha between the reference dataset and a new cohort of trained human evaluators and used our contextually-derived Krippendorff’s alpha threshold as a gauge of evaluator quality. Although all evaluators had relatively high agreement (> 0.9) compared to the rule of thumb (0.8), our agreement threshold permitted evaluators with low error, while rejecting one evaluator with relatively high error. Conclusions We found that our approach established threshold values of reliability, within the context of our evaluation criteria, that were far less permissive than the typically accepted “rule of thumb” cutoff for Krippendorff’s alpha. This procedure provides a less arbitrary method for determining a reliability threshold and can be tailored to work within the context of any reliability index.

Photoisomerization mechanisms govern important (bio)catalytic reactions and lie at the core of many functional materials. Here, the authors report a molecular setup that allows for the direct and separate observation of three fundamental photoreactions, namely the hula twist, single-bond rotation, as well as double-bond isomerization.

Controlling complex photoresponsive systems while minimizing light input is highly challenging. Here, the authors report two photoswitchable molecular tweezers responding to the same light signals with opposite changes in their binding affinities towards a guest molecule allowing for its “light-economic” relocation.