Due to their stationery nature, plants are exposed to a diverse range of biotic and abiotic stresses, of which heavy metals stress poses as one of the most detrimental abiotic stresses, targeting crucial and vital processes. Heavy metals instigate the over-production of reactive oxygen species (ROS), and in order to mitigate the adverse effects of ROS, plants induce multiple defence mechanisms. Besides the negative implications of overproduction of ROS, these molecules play a multitude of signaling roles in plants, acting as a central player in the complex signaling network of cells. One of the signaling mechanisms it is involved in is the mitogen-activated protein kinase (MAPK) cascade, a signaling pathway used to transduce extracellular stimuli into intracellular responses. Plant MAPKs have been implicated in signaling of stresses, phytohormones and cell cycle cues. However, the influence of various heavy metals on MAPKs activation has not been well documented. In this review, we will attempt to address and summarize several aspects related to various heavy metal-induced ROS signaling, how these signals activate the MAPK cascade and the downstream transcription factors that instigates the plants response to these heavy metals. Moreover, we will highlight a modern research methodology that could characterize the novel genes associated with MAPKs and their roles in heavy metal stress.

Moniliophthora perniciosa causes the witches’ broom disease of cacao, and it can infect the tomato Micro-Tom (MT). Typical symptoms are stem swelling and shoot outgrowth, whereas reduction in root biomass is another side effect. We investigated whether the impairment of root growth derives from a hormonal imbalance or sink competition. Intense stem swelling coincided with a reduction in root biomass, predominantly of lateral roots. A few genes involved in hormone metabolism were activated; however, hormonal levels were not altered. Inoculation of the auxin highly-responsive entire genotype maintained the impaired root phenotype. Genes involved in root respiration, carbohydrate, amino acid and cell wall metabolism were repressed, whereas genes linked to water/nitrogen/phosphorous starvation were upregulated. Lower levels of sugars and amino acids suggested carbohydrate deprivation. Less 13C accumulated in roots of infected MT, but not in the symptomless low-cytokinin MT-transgenic line that overexpresses CYTOKININ OXIDASE-2 ( 35S::AtCKX2). We show evidence that the impairment of root development potentially derives from a reduction of photoassimilate supply by the establishment of a strong sink at the shoot symptomatic infection site, rather than hormonal imbalance. We speculate that this impact may contribute to the dramatic decrease in cocoa yields after M. perniciosa invasion.

Abstract Aim The U.S. Food and Drug Administration (FDA) has granted approval for the use of cyclin-dependent kinase 4 and 6 inhibitors (CDKIs) in the management of advanced and metastatic breast cancer. We evaluated the real-world data associated with safety in younger and older adults base on Adverse Event Reporting System (FAERS) database of the FDA. Methods We conducted disproportionality analysis to detect and compare CDKI-related adverse events (AEs) among the younger and older adults. Results The data used were from 3,851, 64,731, and 8,420 case reports on abemaciclib, palbociclib, and ribociclib, respectively Disproportionality analysis revealed 170, 397, and 626 AEs of abemaciclib, palbociclib, and ribociclib, respectively, in younger adults, and 113, 475, and 557 in older adults. The numbers of system organ classes for abemaciclib, palbociclib, and ribociclib were 27 each among younger adults, and 25, 27, and 27 among older adults. We found several expected AE signals same with drug instructions, such as diarrhea, neutropenia, and thromboembolic events. Furthermore, unexpected AE signals, such as campylobacter sepsis, enterococcal endocarditis, and atrioventricular block were identified. Conclusion Our results align with clinical observations, emphasizing possible AEs associated with CDKIs. It is essential to conduct future clinical research to confirm differences in CDKIs among younger and older individuals.

Food distribution and availability fundamentally shape foraging. Yet spatiotemporal distribution of mobile prey and its proximate effects on animals have rarely been assessed. The neotropical bat, Noctilio albiventris, forages on aquatic swarming insects which peak just one to two hours after dusk. We matched seasonal insect distribution at high spatiotemporal resolution to the foraging behavior of adult female bats. Surprisingly, insect abundance was lower in the wet season, and insect patches dispersed more rapidly. Correspondingly, bats emerged 45% earlier, foraged over 40% longer, and flew almost twice as far compared to the dry season. Wet season bats also spent less time at each patch, suggesting that patches, though the same size, were less dense and depleted more rapidly. Our results highlight the tight link between foraging and sharp seasonal shifts in the spatial unpredictability and temporal ephemerality of resources, shedding light on behavioral adaptations and plasticity in response to resource fluctuation.

Aims/Introduction: Phage display method is a crucial tool to find novel clinically valuable diabetes-associated autoantigens, and identify known autoantigen epitopes that are associated with diabetes; could providing scientific support and guidance for the artificial construction and synthesis of type I diabetes mellitus (T1DM) novel biomarkers. Materials and Methods: The phage display system was used for “bio-panning” of T1DM serum. Following by the sequencing of the phage DNAs, the homologous sequences of the above fusion heptapeptide were further investigated by BLAST to track the origin of the polypeptide sequences. The antibody spectrum revealed new T1DM-associated epitopes and antibodies. Results: A total of 1200 phage DNA were sequenced and 9 conserved polypeptide sequences were collected. It was confirmed that the zinc transporter and islet amyloid protease were among them.The conserved polypeptide sequence 8 and another three distinctive polypeptide sequences derived from Proteus were discovered. Furthermore, we expressed recombinant proteins with homologous polypeptide sequences for the human islet amyloid polypeptide (IAPP) polypeptide precursor human zinc transporter 8 (ZNT8). Through clinical sample detection for the serum from T1DM (n=100) and T2DM (n=200) patients, results demonstrate the importance and relevance of these polypeptides in the recognition and classification of various forms of diabetes. Conclusion：Human pancreatic and concurrent bacterial-derived protein antigens and their epitopes were identified in this research by phage display system, which is crucial for distinguishing different types of diabetes.

In recent years, China has become more closely connected with other countries, and Internet technology has developed rapidly. The new situation has put forward new requirements and challenges to the study of oral English. The disadvantages of traditional oral English teaching are gradually exposed. It is difficult for traditional teaching methods to adapt to the new situation of English learning. This paper analyzes the disadvantages of traditional oral English teaching, analyzes the significance of Internet-based oral English learning, and come up with the basic implementation strategies of independent learning, hoping to improve the efficiency of oral English learning.

Species distribution and habitat selection models frequently use data collected from a small geographic area over a short window of time to extrapolate patterns of relative abundance to unobserved areas or periods of time. However, these types of models often poorly predict how animals will use habitat beyond the place and time of data collection because space-use behaviors vary between individuals and are context-dependent. Here, we present a modelling workflow to advance predictive distribution performance by explicitly accounting for individual variability in habitat selection behavior and dependence on environmental context. Using global positioning system (GPS) data collected from 238 individual pronghorn, (Antilocapra americana), across 3 years in Utah, we combine individual-year-season-specific exponential habitat-selection models with weighted mixed-effects regressions to both draw inference about the drivers of habitat selection and predict space-use in areas/times where/when pronghorn were not monitored. We found a tremendous amount of variation in both the magnitude and direction of habitat selection behavior across seasons, but also across individuals, geographic regions, and years. We were able to attribute portions of this variation to season, movement strategy, sex, and regional variability in resources, conditions, and risks. We were also able to partition residual variation into inter- and intra-individual components. We then used the results to predict population-level, spatially and temporally dynamic, habitat-selection coefficients across Utah, resulting in a temporally dynamic map of pronghorn distribution at a 30x30m resolution but an extent of 220,000km2. We believe our transferable workflow can provide managers and researchers alike a way to turn limitations of traditional RSF models - variability in habitat selection - into a tool to improve understanding and predicting animal distribution across space and time.

High energy density Ni-rich layered oxide cathodes LiNi0.83Co0.12Mn0.05-xAlxO2 (x=0, 0.025, 0.05; NMC, NMCA, and NCA, respectively) are fabricated in two different microstructural forms: (i) nanoparticles (NP) and (ii) nanofibers (NF), to evaluate the morphology and compositional effect on the electrochemical properties using same precursors, with the latter fabricated by electrospinning process. Although all the cathodes exhibit a similar crystal structure as confirmed by X-ray diffraction and Raman spectroscopy, contrasting difference is observed in their electrochemical properties. XRD and XPS analyses indicate a higher amount of cationic disorder for the NP cathodes compared to their NF counterparts. Nanofibrous Ni-rich layered oxide cathodes exhibit higher discharge capacities at all C-rates in comparison to NP cathodes. When cycled at 1C-rate for 100 cycles, capacity retention of 81% is observed for NCA-NF, which is superior to all cathodes. Voltage decay as a function of the charge-discharge cycle is found to be low (0.2 mV/cycle) for nanofibrous cathodes compared to 1.5 mV/cycle for NP cathodes. The good rate capability and cyclic stability of nanofibrous Ni-rich layered oxide cathodes are attributed to a shorter pathway of Li+ diffusion and a large proportion of the active surface area.

Climate change is shifting the timing of organismal life-history events such as hatching, growth, reproduction, and migration. Although consequential food-web mismatches can emerge if predators and prey shift at different rates, research on phenological shifts has traditionally focused on single trophic levels. Here, we analyzed >2000 long-term, monthly time series of phytoplankton, zooplankton, and fish abundance or biomass for three major U.S. estuaries (San Francisco, Chesapeake, and Massachusetts bays). Phenological shifts occurred in over a quarter (27%) of the combined series and shifting taxa overwhelmingly advanced phenology. However, many (~34%-68%) taxa did not track the changing environment, and trends often diverged between predators and their potential prey. Notably, in the San Francisco Bay most fishes showed a delayed timing of peak abundance while many zooplankton peaked earlier, illustrating the potential for climate-driven trophic mismatch. Our results suggest that even if signatures of global climate change differ locally, widespread phenological change has the potential to disrupt estuarine food webs.

In the field of ecology, we are facing urgent challenges related to biodiversity loss, global change and ecosystem sustainability. In this context, the application of Foundation Models emerges as a powerful tool. These models have the potential to reshape our understanding of natural systems, incorporating large volumes of data from different sources and generating results with a more holistic view of ecosystem functioning. However, the application of foundational models in ecology presents challenges that will need to be addressed, such as model interpretation, training efficiency, and the ethical considerations due their implementation.

Tracking climatic conditions throughout the year is often assumed to be an adaptive behavior underlying seasonal migration patterns in animal populations. In this study, we investigate this hypothesis using genetic markers data to map migratory connectivity for 22 genetically distinct bird populations across 6 species. We found that the variation in seasonal climate tracking at a continental scale is more likely a consequence, rather than an underlying driver, of migratory connectivity, which is itself largely shaped by energy efficiency -- i.e. optimizing the balance between accessing available resources and the cost of movement. However, our results also suggest that regional-scale seasonal precipitation tracking affects migration destinations, thus revealing a potential scale-dependency of ecological processes driving migration. Our results have implications for the conservation of migratory species under climate change, as populations that track climate seasonally are potentially at higher risk if they adapt to a narrow range of climatic conditions.

A document by Guillermo Rodriguez-Nava. Click on the document to view its contents.

IntroductionLemierre’s syndrome is a systemic septic embolism caused by thrombophlebitis of the internal jugular vein and presenting with various distantly infected abscesses. Various diagnostic criteria exist, but there is no standardized definition. Lemierre’s syndrome is generally believed to be caused by infection with anaerobic bacteria around the oropharynx. Delayed diagnosis can lead to dyspnea and deep neck infections due to acute airway constriction, which can lead to fatal outcomes. Ophthalmologic complications of Lemierre’s syndrome are relatively rare. In this study, we report our experience with a patient with Lemierre’s syndrome who lost her sight.

A case for the use of chemotherapy in hereditary mitochondrial optic neuropathies: successful administration of cisplatin/etoposide in a male patient with testicular seminoma and Leber’s Hereditary Optic NeuropathyVrisakis J, Fraser C.L., Shahnam A, Nindra U, Grimison P

Island habitats are natural laboratories that offer unique opportunities to study speciation mechanisms. Recent work indicates that both anagenetic and cladogenetic speciation processes, driven by allopatric and sympatric modes, contribute to island species diversity. However, clear evidence of local adaptation of endemic plant species on islands requires in-depth studies, which are scarce. This study underscores the importance of local adaptation in maintaining species entity by examining how adaptive introgression, hybridization, and local adaptation contribute to genetic variation in island species. Specifically, multilocus genome scanning of 51 nuclear genes was used to investigate the evolutionary relationships of the Scutellaria species complex on Taiwan Island and assess the role of in situ diversification in generating high endemism and genetic diversity. Recurrent interspecies introgressions were detected by phylogenetic networks and ABBA-BABA-based analysis, suggesting ongoing or recent speciation processes. Approximate Bayesian computation identified hybrid speciation in S. taiwanensis and S. hsiehii, with evidence of hybridization between more than two parental species. Genotype-environment association studies revealed that the influence of climate, particularly precipitation- and temperature-related factors, contributed to adaptive genetic divergence between species. Additionally, adaptive introgressions related to environmental pressures that may have facilitated the colonization of new island habitats were identified. This research illustrates how hybridization, introgression, and adaptation shaped the evolutionary histories and divergence of this island-endemic plant species complex and sheds light on the multifaceted mechanisms of speciation on semi-isolated islands.

Pharmacometrics is instrumental in drug development, guiding decisions on dose selection, study design, formulation optimization, biomarker identification and commercial viability. While traditional Pharmacokinetic-Pharmacodynamic (PK/PD) modeling is widely embraced, Kinetic-Pharmacodynamic (KPD) modeling remains relatively underutilized. This paper introduces KPD modeling as an alternative approach for understanding dose-effect relationships in scenarios where conventional PK data is limited. KPD models use dose as the primary input to predict key parameters, offering a valuable tool for clinical applications. To explore KPD modeling’s scope and potential benefits, we conducted a systematic review following PRISMA guidelines. The research question was “Where can KPD modeling be applied, and what are the main outcomes from KPD models?”. We searched databases, including PubMed, Web of Science, Cochrane and EMBASE, using specific terms. Eligible articles had to be in english and discuss KPD modeling applications or its role in model development. Our review covered 132 articles published from January 2004 to October 2023, identifying 51 meeting inclusion criteria. Data included publication year, country, institution, study type, studied compounds, software tools, KPD applications, and outcomes. This paper presents a comprehensive analysis of reviewed studies, highlighting diverse KPD modeling applications in clinical and preclinical settings. It outlines limitations and suggests avenues for rational KPD integration into research, clinical trials, and regulatory approvals. By harnessing KPD modeling’s power, pharmacometrics can enhance decision-making, addressing challenges posed by limited PK data, ultimately advancing drug development and patient care.

Tacrolimus, a calcineurin inhibitor, is an effective immunosuppressant for solid organ transplants (SOT). However, its narrow therapeutic index and high variability in pharmacokinetics can lead to inefficacy, toxicities, and suboptimal outcomes. Genotyping for CYP3A5 gene prior to SOT can identify individuals at risk of high or low tacrolimus levels and guide first-dose dosing. Genotype-guided Bayesian dosing uses population pharmacokinetic data and individual patient characteristics to accurately predict the tacrolimus dose required to achieve a target concentration. This can help achieve target tacrolimus concentrations sooner and maintain them within range, reducing risk of organ rejection or tacrolimus toxicity. This review aims to assess the benefits of genotype-guided Bayesian dosing for tacrolimus and its ability to accurately predict tacrolimus dosing, leading to increased maintenance of therapeutic drug exposure in these individuals. This systematic review identified three studies that incorporated genotyping and Bayesian informed methods to predict tacrolimus dosing in the paediatric population post SOT. The studies included 369 kidney, 231 heart, 246 liver and 16 lung transplant individuals. The review found that combination of clinical, demographic, and genetic data has a significant influence on tacrolimus clearance. Combining these parameters allowed the prediction of first dose tacrolimus post SOT and ongoing therapeutic tacrolimus dosing to optimally maintain target tacrolimus levels. In conclusion, personalised tacrolimus dosing models in paediatric SOT can be developed using clinical, demographic, and genetic data to predict first dose and ongoing adjustments to meet therapeutic tacrolimus targets and reduce the risk of under- and over- exposure.

Wild pigs (Sus scrofa) are a highly destructive invasive species across the globe, making them subject to intensive management including lethal control. Robust estimates of population abundance are needed to assess and optimize the effectiveness of control efforts. Genetic capture mark-recapture (GCMR) offers considerable promise for monitoring invasive wild pigs. However, obtaining robust estimates from GCMR can be difficult due to low quality DNA, particularly in moist, hot environments that promote fast DNA degradation. To examine if GCMR is feasible for estimating wild pig abundance, we collected pig fecal samples in three sites (bottomland hardwoods, mixed forest, and upland pine) at the Savannah River Site, South Carolina, USA. Amplification success across nine microsatellite loci varied across habitats with bottomland hardwoods having the lowest success (18%) compared to the mixed forest (56%) and upland pine (65%). Resultant abundance and density estimates were relatively similar between field-based methods and GCMR in the bottomland hardwoods and upland habitats, but estimates for the bottomland hardwoods had larger confidence intervals. Tests with additional extraction methods in the bottomland hardwoods found low amplification, with a combination of Nucleospin soil kits and Zymo clean-up kits performing the best. While our study found reasonable estimates of density across three habitats, environmental conditions have a powerful influence on amplification success and the corresponding number of recaptures in wild pig GCMR, particularly in the bottomland hardwoods where flooding was frequent during sampling. Successful GCMR studies should, therefore, consider both sampling intensity and laboratory costs when designing studies because dryer habitats have higher amplification success but lower pig densities.

Australia’s national living guidelines for COVID-19 were launched in April 2020 and include over 200 recommendations to guide the clinical care of patients with COVID-19. Until the guidelines were retired in August 2023, new evidence was continually monitored through daily surveillance. This paper describes how evidence surveillance was established (at a time when efforts to collate information on the novel coronavirus were in their infancy and often duplicative) and how it evolved throughout the pandemic. Among the wide range of sources monitored, the collections of COVID-19 research from leading medical journals, medRxiv preprints and PubMed auto alerts proved the most enduring in identifying time-critical and impactful evidence. The paper also explores how evidence was tracked and surveillance integrated into the overall evidence workflow by using messaging apps and communication platforms. Several factors contributed to the feasibility of daily surveillance, including the clearly defined scope of the guidelines; focusing efforts on maximum impact; minimising duplication by partnering with others; setting up simple but effective processes for managing evidence; and the value of continuous involvement of personnel from the outset. The example of Australia’s living COVID-19 guidelines has demonstrated the feasibility and essential role of daily evidence surveillance in maintaining COVID-19 living guidelines for over 3 years.

The blasting excavation process during underground rock mass engineering can induce severe stress disturbance, resulting in spalling and damage to the surrounding rock mass in the tunnels, which can seriously compromise the underground engineering construction. In the present work, an experimental blast loading device was developed to study the dynamic response of rocks under explosive loads, which could vary the utilization of explosive gas energy by changing the constraint conditions. The device employed a high-speed camera to record the stress wave propagation and failure characteristics on the surface of the specimen and verified the reliability of the experimental results using an ultra-dynamic strain gauge. The developed apparatus was used to explore the failure characteristics and stress wave propagation laws in red sandstone under different explosion gas energies. The complete process of stress wave propagation in red sandstone was captured under different explosive gas energies, from an intact form to failure, and the attenuation law of stress waves was obtained. The experimental results showed that when the explosive stress wave traversed through the specimen, it primarily experienced tensile strain, with maximum tensile strain observed at the free surface. The stress wave propagation in the specimen varied under different explosive loads, leading to varying overall failure characteristics of the specimen. The larger the amplitude of the stress wave, the greater the spatial attenuation coefficients of the compression wave and the tensile wave. The thickness of the spalling fracture was determined based on the wave width of the stress wave λ 1, the attenuation coefficient of the stress wave α, and the longitudinal wave velocity C 0. The closer the crack is to the bottom of the specimen, the smaller the thickness. The experimental results provide theoretical guidance to understand the strong dynamic disturbance behavior and progressive instability failure phenomenon in deep underground engineering.

Agriculture is a cornerstone of India’s economy, supporting a vast majority of its population. However, farmers grapple with selecting the right crop due to diverse soil characteristics, environmental factors, plant diseases, and the need for consistent crop monitoring. This paper presents a smart system assisting farmers in specific crop selection, integrating plant diseases and consistent monitoring as vital features. By considering comprehensive data on environmental parameters(moisture), soil characteristics (including N, P, K levels), plant diseases, and consistent crop monitoring, the system recommends the most suitable crop for each season. Moreover, it offers fertilizer suggestions aligned with optimal nutrient requirements, particularly focusing on N, P, and K levels, aiming to enhance farming efficiency and sustainability.

This paper presents a design of a gyro-TWT operating in the large-orbit electron beam mode, with the aim of reducing the working magnetic field while ensuring operational efficiency. The periodic dielectric-loaded structure is adopted as the high-frequency interaction circuit, which has not been reported in the application of large-orbit gyro-TWT in literature, while this structure has been successfully applied in the development of small-orbit devices. This paper conducts a comprehensive study and analysis of this structure and achieves stable operation in the Ka-band after the optimization of the tube. This tube works at second harmonic of electron frequency in the mode of large-orbit electron beam. The required magnetic field is only 5100 Gauss, which can be generated using electromagnetic coils instead of superconducting magnets. The operational parameters include voltage of 75 kV, current of 9A, and velocity spread of 3.5%. Under these conditions, the device presents stable operation, with -3 dB bandwidth of 4.3 GHz, and maximum output power of 165 kW. This result meets the expected requirements for magnetic field and operational efficiency, thus validating the feasibility of practical fabrication of large-orbit gyro-TWT with periodic dielectric-loaded structure.

Experimental and observational studies have elucidated that an amalgamation of biotic (e.g., biodiversity, large trees) and abiotic factors (e.g., climate, soil) jointly determine tree aboveground carbon stock within forest ecosystems. Yet, a pivotal factor potentially influencing these carbon repositories might be the specific tree mycorrhizal associations, especially given that ectomycorrhizal (EM) tree species frequently comprise more large-sized trees, translating to an augmented carbon reserve, as opposed to arbuscular mycorrhizal (AM) counterpart. However, how biotic and abiotic factors determine forest carbon through regulating AM vs. EM tree carbon stock is still elusive across large regions. Here, we examined a forest inventory data consisting of over 90,000 trees from 631 forest plots (30m × 30m each). Our objective was to explore how biodiversity (i.e., species diversity and ecological uniqueness), large trees (top 1% tree diameters), and environmental factors (e.g., climate and soil nutrients) differently regulate AM and EM, and thus, total tree aboveground carbon stock of temperate forests in northeast China. Our findings illuminated that large trees had consistent enhancement effect on AM and EM tree carbon repositories. However, the effects of biodiversity and environmental factors on carbon stock were opposite between AM and EM trees. Specifically, the two components of biodiversity were positively associated with AM tree carbon stock while negatively associated with EM tree carbon stock. Environment heterogeneity (i.e. mean annual temperature and soil nutrients) also exhibited contrasting impacts on AM and EM tree carbon stock. Consequently, when integrating AM and EM tree carbon stock into total carbon stock, the consistent effect of large trees on AM vs. EM trees was strengthened and most important, while the opposite effect of biodiversity or environment factors was diluted. In summary, this study emphasized a mycorrhizal viewpoint to better understand the determinants of overarching aboveground carbon profile across regional forests.

Do vertical gradients structure temperate forest insect herbivore communities? We tested the hypothesis that the increase in light intensity from understory to forest canopy level drives differences in leaf physical traits and budburst phenology that impact insect herbivores and thus play a role in structuring both herbivore communities and the damage they cause to trees. Twelve sugar maple (Acer saccharum) trees were monitored in southern Quebec, examining herbivore patterns from understory to canopy. Three sampling sessions took place in the summers of 2020, 2021, and 2022, recording temperature, humidity, sun exposure, and leaf physical traits in three strata. In the first two years, we measured herbivory rates, quantifying affected leaf surface percentage by damage type. Overall, herbivory damage decreased from the understory to the shade canopy and sun canopy in 2020, driven by leaf cutters and skeletonizers. Leaf stipplers and blotch miners also followed this pattern in 2020. The 2021 sampling showed a similar, albeit weaker, pattern. Leaf cutters and skeletonizers consistently caused less damage with increasing height in the canopy. The abundance of insect herbivores collected in 2022 matched the observed damage trend. Leaf thickness increased along the vertical gradient, making leaves less accessible to herbivores. Variation in plant traits according to sun exposure thus contributes to explaining vertical stratification of insect herbivore damage. The average annual herbivory rate of 9.1% of leaf surface suggests limited evidence supporting an important contribution of background herbivory to the decline of sugar maple forests