Single-molecule tracking reveals dual front door/back door inhibition of Cel7A cellulase by its product cellobiose.

Degrading cellulose is a key step in the processing of lignocellulosic biomass into bioethanol. Cellobiose, the disaccharide product of cellulose degradation, has been shown to inhibit cellulase activity, but the mechanisms underlying product inhibition are not clear. We combined single-molecule imaging and biochemical investigations with the goal of revealing the mechanism by which cellobiose inhibits the activity of Trichoderma reesei Cel7A, a well-characterized exo-cellulase. We find that cellobiose slows the processive velocity of Cel7A and shortens the distance moved per encounter; effects that can be explained by cellobiose binding to the product release site of the enzyme. Cellobiose also strongly inhibits the binding of Cel7A to immobilized cellulose, with a Ki of 2.1 mM. The isolated catalytic domain (CD) of Cel7A was also inhibited to a similar degree by cellobiose, and binding of an isolated carbohydrate-binding module to cellulose was not inhibited by cellobiose, suggesting that cellobiose acts on the CD alone. Finally, cellopentaose inhibited Cel7A binding at micromolar concentrations without affecting the enzyme's velocity of movement along cellulose. Together, these results suggest that cellobiose inhibits Cel7A activity both by binding to the "back door" product release site to slow activity and to the "front door" substrate-binding tunnel to inhibit interaction with cellulose. These findings point to strategies for engineering cellulases to reduce product inhibition and enhance cellulose degradation, supporting the growth of a sustainable bioeconomy.

Nationwide law enforcement impact on the pet bird trade in China.

Conservation enforcement is a direct strategy to combat illegal wildlife trade in open markets. Yet, its large-scale effectiveness has not been widely assessed due to the lack of extensive market data. Between August 2016 and June 2017, a national coordinated enforcement campaign led by the leading Chinese authority to combat illegal migratory bird trade coincided with the largest-ever pet bird market survey across China by voluntary birdwatchers before and after the enforcement, which served as a unique natural experiment. Across 73 markets from 22 Chinese provinces, the dataset contains 140,723 birds of 346 species from 48 families and recorded a drastic decline in bird abundance traded after enforcement. Notably, species protected under China's Wildlife Protection Law declined significantly, while commercially bred species increased, although responses to enforcement were spatially heterogeneous. Our model showed that the national protection level was the best predictor for the trend of traded species, even after accounting for confounding factors such as regional baseline enforcement pressure and wild native bird populations. However, the widely traded native songbirds were not offered adequate national protection. Future policies should consider the pet bird trade patterns, target key areas of trade, and develop a more systematic market survey design to monitor trade.

Insights into the coexistence of birds and humans in cropland through meta-analyses of bird exclosure studies, crop loss mitigation experiments, and social surveys.

Birds share lands with humans at a substantial scale and affect crops. Yet, at a global scale, systematic evaluations of human-bird coexistence in croplands are scarce. Here, we compiled and used meta-analysis approaches to synthesize multiple global datasets of ecological and social dimensions to understand this complex coexistence system. Our result shows that birds usually increase woody, but not herbaceous, crop production, implying that crop loss mitigation efforts are critical for a better coexistence. We reveal that many nonlethal technical measures are more effective in reducing crop loss, e.g., using scaring devices and changing sow practices, than other available methods. Besides, we find that stakeholders from low-income countries are more likely to perceive the crop losses caused by birds and are less positive toward birds than those from high-income ones. Based on our evidence, we identified potential regional clusters, particularly in tropical areas, for implementing win-win coexistence strategies. Overall, we provide an evidence-based knowledge flow and solutions for stakeholders to integrate the conservation and management of birds in croplands.

Quantifying species biases among multidata sources on illegal wildlife trade and its implications for conservation.

Unsustainable wildlife consumption and illegal wildlife trade (IWT) threaten biodiversity worldwide. Although publicly accessible data sets are increasingly used to generate insights into IWT, little is known about their potential bias. We compared three typical and temporally corresponding data sets (4204 court verdicts, 926 seizure news reports, and 219 bird market surveys) on traded birds native to China and evaluated their possible species biases. Specifically, we evaluated bias and completeness of sampling for species richness, phylogeny, conservation status, spatial distribution, and life-history characteristics among the three data sets when determining patterns of illegal trade. Court verdicts contained the largest species richness. In bird market surveys and seizure news reports, phylogenetic clustering was greater than that in court verdicts, where songbird species (i.e., Passeriformes) were detected in higher proportions in market surveys. The seizure news data set contained the highest proportion of species of high conservation priority but the lowest species coverage. Across the country, all data sets consistently reported relatively high species richness in south and southwest regions, but markets revealed a northern geographic bias. The species composition in court verdicts and markets also exhibited distinct geographical patterns. There was significant ecological trait bias when we modeled whether a bird species is traded in the market. Our regression model suggested that species with small body masses, large geographical ranges, and a preference for anthropogenic habitats and those that are not nationally protected were more likely to be traded illegally. The species biases we found emphasize the need to know the constraints of each data set so that they can optimally inform strategies to combat IWT.

Cuantificación del sesgo por especies entre fuentes de datos múltiples para el mercado ilegal de fauna y lo que implica para la conservación Resumen El consumo insostenible y el comercio ilegal de fauna y flora silvestres amenazan la biodiversidad en todo el mundo. Aunque los conjuntos de datos de acceso público se utilizan cada vez más para obtener información sobre el mercado ilegal de especies silvestres, se sabe poco sobre su posible sesgo. Comparamos tres conjuntos de datos típicos con correspondencia temporal (4,204 sentencias judiciales, 926 informes de noticias sobre incautaciones y 219 encuestas sobre mercados de aves) de aves autóctonas de China objeto de comercio y evaluamos sus posibles sesgos por especie. En concreto, evaluamos el sesgo y la exhaustividad del muestreo de la riqueza de especies, la filogenia, el estado de conservación, la distribución espacial y las características del ciclo vital entre los tres conjuntos de datos a la hora de determinar los patrones del mercado ilegal. Las sentencias judiciales contenían la mayor riqueza de especies. En los estudios de mercado de aves y en los informes de noticias sobre incautaciones, la agrupación filogenética fue mayor que en las sentencias judiciales, donde las especies de aves canoras (Passeriformes) se detectaron en mayor proporción en los estudios de mercado. El conjunto de datos de noticias sobre decomisos contenía la mayor proporción de especies de alta prioridad para la conservación, pero la menor cobertura de especies. En todo el país, todos los conjuntos de datos informaron sistemáticamente de una riqueza de especies relativamente alta en las regiones sur y suroeste, pero los mercados revelaron un sesgo geográfico septentrional. La composición por especies en los veredictos judiciales y en los mercados también mostró patrones geográficos distintos. Hubo un sesgo significativo de rasgos ecológicos cuando modelamos si una especie de ave se comercializa en el mercado. Nuestro modelo de regresión sugería que las especies con masas corporales pequeñas, grandes áreas de distribución geográfica y preferencia por los hábitats antropogénicos y las especies que no están protegidas a nivel nacional tenían más probabilidades de ser objeto de comercio ilegal. Los sesgos de las especies que hallamos resaltan la necesidad de conocer las limitaciones de cada conjunto de datos para poder informar de manera óptima las estrategias de lucha contra el comercio ilegal de especies silvestres.

Use of consumer insights to inform behavior change interventions aimed at illegal pet turtle trade in China.

Illegal poaching and overexploitation for the international pet trade are among the greatest threats to freshwater turtles in Southeast Asia. Expanding consumer research in China is crucial to filling knowledge gaps about the scale and structure of illegal trade and developing audience-targeted and relevant interventions that may reduce demand for illegal turtles as pets. We applied mixed methods to provide a detailed understanding of the consumer side of the illegal pet turtle trade in China. We conducted 30 interviews with key stakeholders and online surveys (n = 2456) of turtle keepers via community forums. From these, we identified 3 core consumer groups based on their prior turtle-keeping experience, species exposure, and potential for future purchases. We conducted a thematic qualitative analysis of concepts related to the capability, opportunity, motivation, and behavior (COM-B) model to determine the factors influencing the illegal pet turtle trade and to identify barriers to illegal purchases. Specifically, we identified purchasers' capabilities, opportunities, and motivations in the context of legality, enforcement risk, captive breeding, and impacts on wild population. We developed consumer journey maps (i.e., visual representations of customer's experiences throughout their buying journey) for core consumer groups. These maps illustrate the sequential behaviors and processes that consumers undertake when purchasing turtles, from initial exposure to sourcing, keeping, and providing a new home. Key factors influencing illegal purchases included convenient purchase channels, misguided cognition and motivations for pet keeping, and weak law enforcement. Effective interventions included messages focusing on shifting cognition and beliefs, increasing legal risk perception, and emphasizing stringent law enforcement, primarily delivered through online channels. Our results underscore the necessity for adaptable, audience-tailored interventions to reduce consumer demand for illegal wildlife products. The mixed-methods approach, combining quantitative and qualitative data, provided a comprehensive understanding of the target behavior and can inform the development of effective intervention strategies.

Uso de las percepciones del consumidor para guiar las intervenciones de cambio conductual enfocadas en el mercado ilegal de tortugas en China Resumen La caza furtiva y la sobreexplotación por el comercio internacional de mascotas son algunas de las mayores amenazas para las tortugas de agua dulce del sudeste asiático. Es esencial conocer más sobre los consumidores en China para llenar los vacíos en el conocimiento sobre la escala y la estructura del comercio ilegal y desarrollar intervenciones pertinentes y dirigidas al público que puedan reducir la demanda de tortugas como mascotas ilegales. Aplicamos métodos mixtos para conocer en detalle la percepción del consumidor del comercio ilegal de tortugas como mascotas en China. Realizamos 30 entrevistas a actores clave y encuestas en línea (n=2456) a cuidadores de tortugas a través de foros comunitarios. A partir de ellas, identificamos tres grupos principales de consumidores en función de su experiencia previa en la cría de tortugas, su exposición a las especies y su potencial para futuras compras. Realizamos un análisis cualitativo temático de conceptos relacionados con el modelo de capacidad, oportunidad, motivación y comportamiento (COM­B) para determinar los factores que influyen en el comercio ilegal de tortugas e identificar las barreras para las compras ilegales. En concreto, identificamos las capacidades, oportunidades y motivaciones de los compradores en el contexto de la legalidad, el riesgo de aplicación de la ley, la cría en cautiverio y el impacto sobre la población silvestre. Elaboramos mapas de viaje del consumidor (representaciones visuales de las experiencias del cliente a lo largo de su compra) para los principales grupos de consumidores. Estos mapas ilustran los comportamientos y procesos secuenciales que llevan a cabo los consumidores cuando compran tortugas, desde la exposición inicial hasta la adquisición, el mantenimiento y la asignación de un nuevo hogar. Entre los factores clave que influyen en las compras ilegales se encuentran la conveniencia de los canales de compra, los conocimientos y motivaciones erróneos para mantener mascotas y la debilidad de la aplicación de la ley. Las intervenciones eficaces incluyeron mensajes centrados en cambiar los conocimientos y las creencias, aumentar la percepción del riesgo legal y hacer hincapié en la aplicación rigurosa de la ley, principalmente a través de canales virtuales. Nuestros resultados destacan la necesidad de intervenciones adaptables y adaptadas al público para reducir la demanda de productos ilegales de fauna silvestre por parte de los consumidores. El enfoque de métodos mixtos, que combina datos cuantitativos y cualitativos, proporcionó una comprensión exhaustiva del comportamiento objetivo y puede servir de base para el desarrollo de estrategias de intervención eficaces.

Urinary cadmium concentration is associated with the severity and clinical outcomes of COVID-19: a bicenter observational cohort study.

BACKGROUND: Cadmium and nickel exposure can cause oxidative stress, induce inflammation, inhibit immune function, and therefore has significant impacts on the pathogenesis and severity of many diseases. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can also provoke oxidative stress and the dysregulation of inflammatory and immune responses. This study aimed to assess the potential associations of cadmium and nickel exposure with the severity and clinical outcomes of patients with coronavirus disease 2019 (COVID-19). METHODS: We performed a retrospective, observational, bicenter cohort analysis of patients with SARS-CoV-2 infection in Taiwan between June 2022 and July 2023. Cadmium and nickel concentrations in blood and urine were measured within 3 days of the diagnosis of acute SARS-CoV-2 infection, and the severity and clinical outcomes of patients with COVID-19 were analyzed. RESULTS: A total of 574 patients were analyzed and divided into a severe COVID-19 group (hospitalized patients) (n = 252; 43.9%), and non-severe COVID-19 group (n = 322; 56.1%). The overall in-hospital mortality rate was 11.8% (n = 68). The severe COVID-19 patients were older, had significantly more comorbidities, and significantly higher neutrophil/lymphocyte ratio, C-reactive protein, and interleukin-6 than the non-severe COVID-19 patients (all p < 0.05). Blood and urine cadmium and urine nickel concentrations were significantly higher in the severe COVID-19 patients than in the non-severe COVID-19 patients. Among the severe COVID-19 patients, those in higher urine cadmium/creatinine quartiles had a significantly higher risk of organ failure (i.e., higher APACHE II and SOFA scores), higher neutrophil/lymphocyte ratio, lower PaO2/FiO2 requiring higher invasive mechanical ventilation support, higher risk of acute respiratory distress syndrome, and higher 60-, 90-day, and all-cause hospital mortality (all p < 0.05). Multivariable logistic regression models revealed that urine cadmium/creatinine was independently associated with severe COVID-19 (adjusted OR 1.643 [95% CI 1.060-2.547], p = 0.026), and that a urine cadmium/creatinine value > 2.05 µg/g had the highest predictive value (adjusted OR 5.349, [95% CI 1.118-25.580], p = 0.036). CONCLUSIONS: Urine cadmium concentration in the early course of COVID-19 could predict the severity and clinical outcomes of patients and was independently associated with the risk of severe COVID-19.

Dirac Nodal Line in Hourglass Semimetal Nb3SiTe6.

Glide-mirror symmetry in nonsymmorphic crystals can foster the emergence of novel hourglass nodal loop states. Here, we present spectroscopic signatures from angle-resolved photoemission of a predicted topological hourglass semimetal phase in Nb3SiTe6. Linear band crossings are observed at the zone boundary of Nb3SiTe6, which could be the origin of the nontrivial Berry phase and are consistent with a predicted glide quantum spin Hall effect; such linear band crossings connect to form a nodal loop. Furthermore, the saddle-like Fermi surface of Nb3SiTe6 observed in our results helps unveil linear band crossings that could be missed. In situ alkali-metal doping of Nb3SiTe6 also facilitated the observation of other band crossings and parabolic bands at the zone center correlated with accidental nodal loop states. Overall, our results complete the system's band structure, help explain prior Hall measurements, and suggest the existence of a nodal loop at the zone center of Nb3SiTe6.

Fetal-neonatal and maternal outcomes in women with Sjögren syndrome: a population-based registry linkage study.

OBJECTIVE: To provide better preconceptional and prenatal counselling to patients with sjögren syndrome (SS). METHODS: In total, 2 100 143 pregnancies between 2004 and 2014 were identified in the Taiwan National Health Insurance database and birth registry. The maternal history of SS was ascertained, and data were compared between pregnant women with and without SS. We assessed the odds ratios and 95% CIs of fetal-neonatal and maternal outcomes. RESULTS: There were 449 pregnancies in women with SS and 2 099 694 pregnancies in women without SS. The risks of still birth [odds ratio (OR) = 2.14, 95% CI = 1.01, 4.55], low birth weight (<2500 g, OR = 2.53, 95% CI = 1.92, 3.33), small for gestational age (OR = 2.03, 95% CI = 1.57, 2.03) and fetal distress (OR = 1.72, 95% CI = 1.2, 2.45) as well as maternal risks of pulmonary oedema (OR = 11.64, 95% CI = 1.62, 83.48), shock (OR = 6.07, 95% CI = 1.51, 24.3) and respiratory distress (OR = 5.61, 95% CI = 1.39, 22.6) were higher in the SS group than in the non-SS group. CONCLUSION: Women with SS have significant risks of adverse fetal-neonatal and maternal outcomes and must undergo prenatal counselling to understand the risks involved before conception.

Implications for biological invasion of non-native plants for sale in the world's largest online market.

Internet trade is increasingly recognized as a dispersal pathway of non-native plant species that is difficult to monitor. We sought to identify non-native flora present in the Chinese online market, the largest e-commerce market globally, and to decipher the effect of existing trade regulations, among other variables, on e-trading patterns and to inform policy. We used a comprehensive list of 811 non-native plant species in China present in 1 of the 3 phases of the invasion continuum (i.e., introduced, naturalized, and invasive). The price, propagule types, and quantities of the species offered for sale were retrieved from 9 online stores, including 2 of the largest platforms. Over 30% of the non-native species were offered for sale in the online marketplaces; invasive non-native species dominated the list (45.53%). No significant price difference was observed across the non-native species of the 3 invasion categories. Among the 5 propagule types, a significantly higher number of non-native species were offered for sale as seeds. The regression models and path analyses consistently revealed a direct positive effect of the number of uses and species' minimum residence time and an indirect effect of biogeography on the pattern of trade in non-native plant species when minimal phylogenetic signal was detected. A review of the existing phytosanitary regulations in China revealed their inadequacy in managing e-trading of non-native plant species. To address the problem, we propose integration of a standardized risk assessment framework that considers perceptions of stakeholders and is adaptable based on continuous surveillance of the trade network. If implemented successfully, the measures could provide a template for other countries to strengthen trading regulations for non-native plant species and take proactive management measures.

La venta de plantas no nativas en el mercado virtual más grande y sus implicaciones para la invasión biológica Resumen El mercado virtual en internet se reconoce cada vez más como una vía de dispersión de especies vegetales no nativas difícil de controlar. Intentamos identificar la flora no nativa presente en el mercado virtual chino, el mayor mercado de comercio electrónico del mundo, para descifrar el efecto de las regulaciones comerciales vigentes, entre otras variables, en los patrones de comercio electrónico e informar a las políticas. Utilizamos una lista integral de 811 especies de plantas no nativas de China presentes en una de las tres fases de invasión (es decir, introducidas, naturalizadas o invasoras). El precio, los tipos de propágulos y las cantidades de las especies puestas a la venta se recuperaron de nueve tiendas en línea, incluidas dos de las mayores plataformas. Más del 30% de las especies no nativas se pusieron a la venta en los mercados en línea; las especies no nativas invasoras dominaron esta lista (45,53%). No se observaron diferencias significativas de precio entre las especies no nativas en las tres categorías de invasión. Entre los cinco tipos de propágulos, se puso a la venta un número significativamente mayor de especies no nativas en forma de semillas. Los modelos de regresión y los análisis de trayectoria revelaron un efecto positivo directo y constante del número de usos y del tiempo mínimo de residencia de las especies y un efecto indirecto de la biogeografía sobre el patrón de comercio de especies vegetales no nativas cuando se detectó una señal filogenética mínima. Una revisión de la normativa fitosanitaria vigente en China reveló su insuficiencia para gestionar el comercio electrónico de las especies vegetales no nativas. Para abordar el problema, proponemos la integración de un marco normalizado de evaluación de riesgos que tenga en cuenta las percepciones de los actores y sea adaptable en función de la vigilancia continua de la red comercial. Si se aplican con éxito, las medidas podrían servir de modelo para que otros países refuercen la normativa sobre comercio de especies vegetales no nativas y adopten medidas proactivas de gestión.

Effect of Mobile Phone Text Messaging Self-Management Support for Patients With Diabetes or Coronary Heart Disease in a Chronic Disease Management Program (SupportMe) on Blood Pressure: Pragmatic Randomized Controlled Trial.

BACKGROUND: Maintaining engagement and support for patients with chronic diseases is challenging. SMS text messaging programs have complemented patient care in a variety of situations. However, such programs have not been widely translated into routine care. OBJECTIVE: We aimed to examine the implementation and utility of a customized SMS text message-based support program for patients with type 2 diabetes (T2D), coronary heart disease, or both within a chronic disease integrated care program. METHODS: We conducted a 6-month pragmatic parallel-group, single-blind randomized controlled trial that recruited people with T2D or coronary heart disease. Intervention participants received 4 semipersonalized SMS text messages per week providing self-management support to supplement standard care. Preprogrammed algorithms customized content based on participant characteristics, and the messages were sent at random times of the day and in random order by a fully automated SMS text messaging engine. Control participants received standard care and only administrative SMS text messages. The primary outcome was systolic blood pressure. Evaluations were conducted face to face whenever possible by researchers blinded to randomization. Participants with T2D were evaluated for glycated hemoglobin level. Participant-reported experience measures were evaluated using questionnaires and focus groups and summarized using proportions and thematic analysis. RESULTS: A total of 902 participants were randomized (n=448, 49.7% to the intervention group and n=454, 50.3% to the control group). Primary outcome data were available for 89.5% (807/902) of the participants. At 6 months, there was no difference in systolic blood pressure between the intervention and control arms (adjusted mean difference=0.9 mm Hg, 95% CI -1.1 to 2.1; P=.38). Of 642 participants with T2D, there was no difference in glycated hemoglobin (adjusted mean difference=0.1%, 95% CI -0.1% to 0.3%; P=.35). Self-reported medication adherence was better in the intervention group (relative risk=0.82, 95% CI 0.68-1.00; P=.045). Participants reported that the SMS text messages were useful (298/344, 86.6%) and easily understood (336/344, 97.7%) and motivated change (217/344, 63.1%). The lack of bidirectional messaging was identified as a barrier. CONCLUSIONS: The intervention did not improve blood pressure in this cohort, possibly because of high clinician commitment to improved routine patient care as part of the chronic disease management program as well as favorable baseline metrics. There was high program engagement, acceptability, and perceived value. Feasibility as part of an integrated care program was demonstrated. SMS text messaging programs may supplement chronic disease management and support self-care. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12616001689460; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371769&isReview=true. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2018-025923.

Parabolic Potential Surfaces Localize Charge Carriers in Nonblinking Long-Lifetime "Giant" Colloidal Quantum Dots.

Materials for studying biological interactions and for alternative energy applications are continuously under development. Semiconductor quantum dots are a major part of this landscape due to their tunable optoelectronic properties. Size-dependent quantum confinement effects have been utilized to create materials with tunable bandgaps and Auger recombination rates. Other mechanisms of electronic structural control are under investigation as not all of a material's characteristics are affected by quantum confinement. Demonstrated here is a new structure-property concept that imparts the ability to spatially localize electrons or holes within a core/shell heterostructure by tuning the charge carrier's kinetic energy on a parabolic potential energy surface. This charge carrier separation results in extended radiative lifetimes and in continuous emission at the single-nanoparticle level. These properties enable new applications for optics, facilitate novel approaches such as time-gated single-particle imaging, and create inroads for the development of other new advanced materials.

Coexisting Nodular Sclerosis Hodgkin Lymphoma and Kimura's Disease: A Case Report and Literature Review.

Kimura's disease (KD) is a rare lymphoproliferative fibroinflammatory disorder that commonly affects the subcutaneous tissue and lymph nodes of the head and neck. The condition is a reactive process involving T helper type 2 cytokines. Concurrent malignancies have not been described. Differential diagnosis with lymphoma can be challenging without tissue biopsy. Here, we present the first reported case of coexisting KD and eosinophilic nodular sclerosis Hodgkin lymphoma of the right cervical lymphatics in a 72-year-old Taiwanese man.

Altitude dependence of alpine grassland ecosystem multifunctionality across the Tibetan Plateau.

While altitude affects climatic characteristics, terrestrial plant habitats, and species composition, few studies considered the effects of altitude on ecosystem multifunctionality (EMF). Here, we teased apart the EMF at different altitude with a linear piecewise quantile regression and explore ecosystem functions and environmental factors with EMF along the altitudinal gradient across the Tibetan Plateau. Then, we estimated the response of ecosystem functions to environmental factors, and explain the impact of environmental factors on EMF through the structural equation model. Our data revealed an EMF changepoint at an altitude of about 3900 m where the EMF could be segregated into low- and high-altitude patterns. Our results indicate that water availability drives the EMF mainly through improving soil nutrients and microbe cycling functions in low-altitude regions; conversely, water-heat and phenological conditions regulate the EMF through the role of plant productivity and soil nutrients in high-altitude regions. As such, our EMF analysis suggests that to maintain the long-term stability of the grassland ecosystem, it becomes critical to fully consider the differences in the altitudinal patterns and mechanisms, particularly under the ongoing climate change.

Nanoscale dynamics of cellulose digestion by the cellobiohydrolase TrCel7A.

Understanding the mechanism by which cellulases from bacteria, fungi, and protozoans catalyze the digestion of lignocellulose is important for developing cost-effective strategies for bioethanol production. Cel7A from the fungus Trichoderma reesei is a model exoglucanase that degrades cellulose strands from their reducing ends by processively cleaving individual cellobiose units. Despite being one of the most studied cellulases, the binding and hydrolysis mechanisms of Cel7A are still debated. Here, we used single-molecule tracking to analyze the dynamics of 11,116 quantum dot-labeled TrCel7A molecules binding to and moving processively along immobilized cellulose. Individual enzyme molecules were localized with a spatial precision of a few nanometers and followed for hundreds of seconds. Most enzyme molecules bound to cellulose in a static state and dissociated without detectable movement, whereas a minority of molecules moved processively for an average distance of 39 nm at an average speed of 3.2 nm/s. These data were integrated into a three-state model in which TrCel7A molecules can bind from solution into either static or processive states and can reversibly switch between states before dissociating. From these results, we conclude that the rate-limiting step for cellulose degradation by Cel7A is the transition out of the static state, either by dissociation from the cellulose surface or by initiation of a processive run. Thus, accelerating the transition of Cel7A out of its static state is a potential avenue for improving cellulase efficiency.

The impact of type 1 diabetes mellitus in childhood on academic performance: A matched population-based cohort study.

BACKGROUND AND OBJECTIVE: The impact of type 1 diabetes mellitus (T1D) on academic performance is inconclusive. This study aims to compare scholastic performance and high-school completion in young people hospitalized with T1D compared to matched peers not hospitalized with diabetes. RESEARCH DESIGN: Retrospective case-comparison cohort study. METHOD: A population-level matched case-comparison study of people aged ≤18 hospitalized with T1D during 2005-2018 in New South Wales, Australia using linked health-related and education records. The comparison cohort was matched on age, gender, and residential postcode. Generalized linear mixed modeling examined risk of school performance below the national minimum standard (NMS) and generalized linear regression examined risk of not completing high school for young people hospitalized with T1D compared to peers. Adjusted relative risks (ARR) were calculated. RESULTS: Young females and males hospitalized with T1D did not have a higher risk of not achieving the NMS compared to peers for numeracy (ARR: 1.19; 95%CI 0.77-1.84 and ARR: 0.74; 95%CI 0.46-1.19) or reading (ARR: 0.98; 95%CI 0.63-1.50 and ARR: 0.85; 95%CI 0.58-1.24), respectively. Young T1D hospitalized females had a higher risk of not completing year 11 (ARR: 1.73; 95%CI 1.19-2.53) or 12 (ARR: 1.65; 95%CI 1.17-2.33) compared to peers, while hospitalized T1D males did not. CONCLUSIONS: There was no difference in academic performance in youth hospitalized with T1D compared to peers. Improved glucose control and T1D management may explain the absence of school performance decrements in students with T1D. However, females hospitalized with T1D had a higher risk of not completing high school. Potential associations of this increased risk, with attention to T1D and psycho-social management, should be investigated.

Hospital service use for young people with chronic health conditions: A population-based matched retrospective cohort study.

AIM: This study aims to identify the hospitalised morbidity associated with three common chronic health conditions among young people using a population-based matched cohort. METHODS: A population-level matched case-comparison retrospective cohort study of young people aged ≤18 years hospitalised with asthma, type 1 diabetes (T1D) or epilepsy during 2005-2018 in New South Wales, Australia using linked birth, health and mortality records. The comparison cohort was matched on age, sex and residential postcode. Adjusted rate ratios (ARR) were calculated by sex and age group. RESULTS: There were 65 055 young people hospitalised with asthma, 6648 with epilepsy, and 2209 with T1D. Young people with epilepsy (ARR 10.95; 95% confidence interval (CI) 9.98-12.02), T1D (ARR 8.64; 95% CI 7.72-9.67) or asthma (ARR 4.39; 95% CI 4.26-4.53) all had a higher risk of hospitalisation than matched peers. Admission risk was highest for males (ARR 11.00; 95% CI 9.64-12.56) and females with epilepsy (ARR 10.83; 95% CI 9.54-12.29) compared to peers. The highest admission risk by age group was for young people aged 10-14 years (ARR 5.50; 95% CI 4.77-6.34) living with asthma, children aged ≤4 years (ARR 12.68; 95% CI 11.35-14.17) for those living with epilepsy, and children aged 5-9 years (ARR 9.12; 95% CI 7.69-10.81) for those living with T1D compared to peers. CONCLUSIONS: The results will guide health service planning and highlight opportunities for better management of chronic health conditions, such as further care integration between acute, primary and community health services for young people.

EGFR T751_I759delinsN Mutation in Exon19 Detected by NGS but Not by Real-Time PCR in a Heavily-Treated Patient with NSCLC.

The detection of driver gene mutations can determine appropriate treatment strategies for non-small cell lung cancer (NSCLC) by identifying the presence of an effective druggable target. Mutations in the gene encoding the epidermal growth factor receptor (EGFR) are common driver mutations in NSCLC that can be effectively targeted by the use of EGFR tyrosine kinase inhibitors (EGFR-TKIs). However, without the detection of driver mutations, appropriate therapeutic decisions cannot be made. The most commonly applied methods for detecting driver gene mutations are assays based on polymerase chain reaction (PCR). However, the underlying mechanism of PCR-based assays limits the detection of rare mutations. Therefore, patients harboring rare mutations may not receive optimal treatment. We report a heavily-treated patient with NSCLC who harbored a T751_I759delinsN mutation in exon 19 of EGFR that was not detected by real-time PCR but was successfully detected by next-generation sequencing (NGS). The detection of a driver mutation using NGS resulted in the administration of targeted therapy, leading to favorable progression-free survival for the patient. Our report highlights the importance and potential of routine NGS testing among NSCLC patients for whom traditional assays fail to detect driver mutations when determining treatment options.

Paediatric Cerebral Arteriovenous Malformation: Outcomes from a Singapore Children's Hospital.

OBJECTIVES: Paediatric brain arteriovenous malformation (bAVM) is a rare and distinct clinical entity. There is a growing body of literature that support the success of multimodality approaches for this difficult condition. The authors aim to firstly, describe our institutional experience with a consecutive series of patients and next, corroborate our results with current literature. MATERIAL AND METHODS: This is a single institution, retrospective study conducted over a 20-year period. Patients less than 19 years old with bAVM were included. Variables of interest included patient demographics, clinical presentation, neuroimaging features, bAVM characteristics and treatment modality. Functional outcomes were measured with modified Rankin scale (mRS). RESULTS: There were 58 paediatric bAVMs, presenting at a mean age of 8.7 ± 4.2 years, and followed up for a mean duration of 7.7 years. Thirty-six patients (62.1%) underwent microsurgical resection, 10 patients had stereotactic radiosurgery (17.2%) and 2 patients had endovascular treatment (3.4%). 50 patients (86.2%) had a favourable outcome at 1-year follow up. Microsurgical resection and SRS had similar obliteration rates (resection 83.3%; SRS 80.0%) and recurrence (resection 10.0%; SRS 12.5%). There were 6 cases of bAVM recurrence (12.8%). This subgroup was noted to be less than 7.5 years old at presentation (OR 15.0, 95% CI 1.56 - 144), and less likely to present with bAVM rupture (OR 0.11, 95% CI 0.01 - 0.96). CONCLUSION: This study describes our experience in managing paediatric bAVM, whereby monomodal therapy can still be effective. Of note, we also demonstrate the role of extended surveillance to detect recurrence.

Motivations for the use and consumption of wildlife products.

The dominant approach to combating the illegal wildlife trade has traditionally been to restrict the supply of wildlife products. Yet conservationists increasingly recognize the importance of implementing demand-side interventions that target the end consumers in the trade chain. Their aim is to curb the consumption of wildlife or shift consumption to more sustainable alternatives. However, there are still considerable knowledge gaps in understanding of the diversity of consumer motivations in the context of illegal wildlife trade, which includes hundreds of thousands of species, different uses, and diverse contexts. Based on consultation with multiple experts from a diversity of backgrounds, nationalities, and focal taxa, we developed a typology of common motivations held by wildlife consumers that can be used to inform conservation interventions. We identified 5 main motivational categories for wildlife use: experiential, social, functional, financial, and spiritual, each containing subcategories. This framework is intended to facilitate the segmentation of consumers based on psychographics and allow the tailoring of interventions-whether behavior change campaigns, enforcement efforts, or incentive programs-to the specific context in which they will be used. Underlining the importance of consumer research and collaborating with local actors is an important step toward promoting a more systematic approach to the design of demand reduction interventions.

Motivaciones para el Uso y Consumo de Productos de Fauna Resumen Tradicionalmente, la estrategia dominante para combatir el mercado ilegal de fauna ha sido restringir la oferta de productos de fauna. Aun así, los conservacionistas cada vez reconocen más la importancia de implementar intervenciones por el lado de la demanda que se enfoquen en los consumidores finales en la cadena de mercado. Su objetivo es reducir el consumo de fauna o redirigir ese consumo hacia alternativas más sustentables. Sin embargo, todavía existen vacíos de conocimiento en el entendimiento de la diversidad de motivos para los consumidores dentro del contexto del mercado ilegal de fauna, el cual incluye cientos de miles de especies, diferentes usos y contextos diversos. Con base en consultas a varios expertos con una diversidad de antecedentes, nacionalidades y taxones de enfoque desarrollamos una tipología de motivos comunes que tienen los consumidores de fauna que pueden usarse para orientar las intervenciones de conservación. Identificamos cinco categorías principales de motivos para el uso de fauna: vivencial, social, funcional, financiero y espiritual, cada uno con subcategorías. Este marco de trabajo tiene la intención de facilitar la segmentación de consumidores con base en psicográficos y permitir la personalización de las intervenciones - sean campañas de cambios en el comportamiento, esfuerzos por hacer cumplir las reglas o programas de incentivos - al contexto específico en el que serán utilizadas. Resaltar la importancia de los estudios de mercado y la colaboración con los actores locales es un paso importante hacia la promoción de una estrategia más sistemática para el diseño de intervenciones para reducir la demanda.

Leveraging lifetime information to perform real-time 3D single-particle tracking in noisy environments.

A microscopy platform that leverages the arrival time of individual photons to enable 3D single-particle tracking of fast-moving (translational diffusion coefficient of ≃3.3 µm2/s) particles in high-background environments is reported here. It combines a hardware-based time-gating module, which enables the rate of photon processing to be as high as 100 MHz, with a two-photon-excited 3D single-particle tracking confocal microscope to enable high sample penetration depth. Proof-of-principle experiments where single quantum dots are tracked in solutions containing dye-stained cellulose, are shown with tracking performance markedly improved using the hardware-based time-gating module. Such a microscope design is anticipated to be of use to a variety of communities who wish to track single particles in cellular environments, which commonly have high fluorescence and scattering background.