bluuebunny/crossref_metadata_2025 huggingface dataset:
Tyrosine kinase inhibitors trigger lysosomal damage-associated cell lysis to activate the NLRP3 inflammasome
Authors: Neuwirt Emilia , Magnani Giovanni , Ćiković Tamara , Kostina Anna , Wöhrle Svenja , Flemming Stephan , Fischer Larissa , Fischenich Nora J. , Saller Benedikt S. , Gorka Oliver , Renner Steffen , Agarinis Claudia , Parker Christian , Boettcher Andreas , Farady Christopher J. , Backofen Rolf , Rodriguez-Franco Marta , Tholen Martina , Reinheckel Thomas , Ott Thomas , Groß Christina J. , Jost Philipp J. , Groß Olaf
Published: February 2022

Inflammasomes are intracellular protein complexes that control proteolytic maturation and secretion of inflammatory interleukin-1 (IL-1) family cytokines and are thus important in host defense. While some inflammasomes are activated simply by binding to pathogen-derived molecules, others, including those nucleated by NLRP3 and NLRP1, have more complex activation mechanisms that are not fully understood. We screened a library of small molecules to identify new inflammasome activators that might shed light on activation mechanisms. In addition to validating dipeptidyl peptidase (DPP) inhibitors as NLRP1 activators, we find that clinical tyrosine kinase inhibitors (TKIs) including imatinib and masitinib activate the NLRP3 inflammasome. Mechanistically, these TKIs cause lysosomal swelling and damage, leading to cathepsin-mediated destabilization of myeloid cell membranes and cell lysis. This is accompanied by potassium (K+) efflux, which activates NLRP3. Both lytic cell death and NLRP3 activation but not lysosomal damage induced by TKIs are prevented by the cytoprotectant high molecular weight polyethylene glycol (PEG). Our study establishes a screening method that can be expanded for inflammasome research and immunostimulatory drug development, and provides new insight into immunological off-targets that may contribute to efficacy or adverse effects of TKIs.

One Sentence Summary

A functional small molecule screen identifies imatinib, masitinib and other tyrosine kinase inhibitors that destabilize myeloid cell lysosomes, leading to cell lysis and K+ efflux-dependent NLRP3 inflammasome activation.
Towards phage therapy for acne vulgaris: Topical application in a mouse model
Authors: Rimon Amit , Rakov Chani , Lerer Vanda , Sheffer-Levi Sivan , Alkalky-Oren Sivan , Shlomov Tehila , Shasha Lihi , Lubin Ruthi , Coppenhagen-Glazer Shunit , Molho-Pessach Vered , Hazan Ronen
Published: February 2022

Acne vulgaris is a common neutrophile-driven inflammatory skin disorder in whichCutibacterium acnes(C. acnes) bacteria play a significant role. Until now, antibiotics have been widely used to treat acne vulgaris, with the inevitable increase in bacterial antibiotic resistance. Phage therapy is a promising solution to the rising problem of antibiotic-resistant bacteria, utilizing viruses that specifically lyse bacteria.

Here, we explored the feasibility of phage therapy againstC. acnes. By combining eight novel phages we had isolated, together with commonly used antibiotics, we achieved 100% eradication of clinically isolatedC. acnesstrains. Using topical phage therapy in an acne mouse model resulted in significantly superior clinical scores, as well as a reduction in neutrophil infiltration compared to the control group. These results demonstrate the potential of phage therapy in acne vulgaris treatment, especially when antibiotic-resistant strains are involved.
Interplay between external inputs and recurrent dynamics during movement preparation and execution in a network model of motor cortex
Authors: Bachschmid-Romano Ludovica , Hatsopoulos Nicholas G. , Brunel Nicolas
Published: February 2022

The primary motor cortex has been shown to coordinate movement preparation and execution through computations in approximately orthogonal subspaces. The underlying network mechanisms, and the roles played by external and recurrent connectivity, are central open questions that need to be answered to understand the neural substrates of motor control. We develop a recurrent neural network model that recapitulates the temporal evolution of neuronal activity recorded from the primary motor cortex of a macaque monkey during an instructed delayed-reach task. In particular, it reproduces the observed dynamic patterns of covariation between neural activity and the direction of motion. We explore the hypothesis that the observed dynamics emerges from a synaptic connectivity structure that depends on the preferred directions of neurons in both preparatory and movement-related epochs, and we constrain the strength of both synaptic connectivity and external input parameters from data. While the model can reproduce neural activity for multiple combinations of the feedforward and recurrent connections, the solution that requires minimum external inputs is one where the observed patterns of covariance are shaped by external inputs during movement preparation, while they are dominated by strong direction-specific recurrent connectivity during movement execution, in agreement with recent experimental findings on the relationship between motor–cortical and motor–thalamic activity, both before and during movement execution. Our model also demonstrates that the way in which single-neuron tuning properties change over time can explain the level of orthogonality of preparatory and movement-related subspaces.
Improved pathogen and stress tolerance in tomato mutants of SET domain histone 3 lysine methyltransferases
Authors: Bvindi Carol , Lee Sanghun , Tang Liang , Mickelbart Michael V. , Li Ying , Mengiste Tesfaye
Published: February 2022

Histone lysine methylations (HLMs) are implicated in control of gene expression in different eukaryotes. However, the role of HLMs in regulating desirable crop traits and the enzymes involved in these modifications are poorly understood. We studied the functions of tomato histone H3 lysine methyltransferases Set Domain Group 33 (SDG33) and SDG34 in biotic and abiotic stress responses. SDG33 and SDG34 mutants were altered in H3K36 and H3K4 methylations, and expression of genes involved in diverse processes and responses to biotic and abiotic stimuli. The double but not the single mutants show resistance to the fungal pathogen Botrytis cinerea. Interestingly, single mutants were tolerant to drought and the double mutant showed superior tolerance consistent with independent and additive functions. Mutants maintained higher water status during drought and improved recovery and survival after lapse of drought. Notably, diminution of H3K4 and H3K36 trimethylation and expression of negative regulators in challenged plants contributes to stress tolerance of the mutants. Mutations in SDG33 and SDG34 remove predisposition to biotic and abiotic stress by disrupting permissive transcriptional context promoting expression of negative regulatory factors. These allows improvement of stress and pathogen tolerance through modification of histone epigenetic marks.
Accurate proteome-wide measurement of methionine oxidation in aging mouse brains
Authors: Bettinger John Q. , Simon Matthew , Korotkov Anatoly , Welle Kevin A. , Hryhorenko Jennifer R. , Seluanov Andrei , Gorbunova Vera , Ghaemmaghami Sina
Published: February 2022

The oxidation of methionine side chains has emerged as an important posttranslational modification of proteins. A diverse array of low-throughput and targeted studies have suggested that the oxidation of methionine residues in select proteins can have diverse impacts on cell physiology, ranging from detrimental effects on protein structure and stability to functional roles in cell signaling. Despite its importance, the large-scale investigation of methionine oxidation in a complex matrix, such as the cellular proteome, has been historically hampered by technical limitations. Herein we report a methodology, Methionine Oxidation by Blocking (MobB), that allows for accurate and precise quantification of low levels of methionine oxidation typically observed in vivo. To demonstrate the utility of this methodology, we applied MobB to the brain tissues of young (6 m.o.) and old (20 m.o.) mice and identified over 280 novel sites for in vivo methionine oxidation. We further demonstrated that oxidation stoichiometries for specific methionine residues are highly consistent between individual animals and methionine sulfoxides are enriched in clusters of functionally related gene products including membrane and extracellular proteins. However, we did not detect significant changes in methionine oxidation in brains of old mice. Our results suggest that under normal in vivo conditions methionine oxidation is a biologically regulated process rather than a result of stochastic chemical damage.
Resistance to EGFR inhibitors in lung cancer occurs through horizontal transfer and is associated with increased caveolins expression
Authors: Junqueira-Neto Susana , Oliveira Ana R. , Marques Joana F. , Oliveira Patrícia , Fernandes Maria G. , Hespanhol Venceslau , Barroso Ana , Pinheiro Jorge , Souto-Moura Conceição , Cavadas Bruno , Pereira Luísa , Adem Bárbara , Silva Miguel , Melo Sónia A. , Costa José L. , Machado José C.
Published: February 2022

Resistance to treatment is a major clinical problem and a major cause of cancer-related deaths. Understanding the biological basis of resistance acquisition is of utmost importance to improve the clinical management of cancer patients. NGS analysis of human lung cancer (LC) tumors from patients that relapsed after treatment with EGFR-tyrosine kinase inhibitors (TKI), revealed that the p.T790M resistance mutation is not present in all the relapsing tumor cells, suggesting that LC cells can become resistant even if not carrying the p.T790M mutation. Using in vitro treatments with conditioned medium (CM) and in vivo co-inoculation experiments, we show that LC cells sensitive to EGFR-TKIs (S cells) acquire resistance faster when treated with CM from LC cells resistant to EGFR-TKIs (R cells) or when co-inoculated with R cells in opposite flanks of the same animal. Importantly, we show that acquisition of resistance is not due to the emergence of subpopulations of cancer cells with new resistance mutations. Using transcriptomics, we show that acquisition of resistance is associated with upregulation of genes involved in endocytosis, namely caveolins CAV1 and CAV2. These findings were validated in human clinical samples, where an increase in CAV1 and CAV2 expression was associated with tumor relapse after treatment with EGFR-TKIs. Our results suggest that acquisition of resistance to targeted therapies results from the combined effect of selection of cells harboring specific resistance mutations and horizontal transfer of the resistance phenotype. These findings may pave the way to bring intercellular communication into the realm of cancer treatment.

One Sentence Summary

Resistance to EGFR inhibitors is transferred horizontally between lung cancer cells and is associated with gain of expression of caveolins.
The effects of brief heat during early booting on reproductive, developmental and physiological performance in common wheat (Triticum aestivum L.)
Authors: Xu Jiemeng , Lowe Claudia , Hernandez-Leon Sergio G. , Dreisigacker Susanne , Reynolds Matthew P. , Valenzuela-Soto Elisa M. , Paul Matthew J. , Heuer Sigrid
Published: February 2022

Rising temperatures due to climate change threaten agricultural crop productivity. As a cool-season crop wheat is heat sensitive, but often exposed to high temperatures during cultivation. In the current study, a bread wheat panel of spring wheat genotypes, including putatively heat-tolerant Australian and CIMMYT genotypes, was exposed to a 5-day mild (34°C/28°C, day/night) or extreme (37°C/27°C) heat stress during the sensitive pollen developmental stage. Worsening effects on anther morphology were observed as heat stress increased from mild to extreme. Even under mild heat a significant decrease in pollen viability and grain number per spike from primary spike was observed compared with the control (21°C/15°C), with Sunstar and two CIMMYT breeding lines performing well. A heat-specific positive correlation between the two traits indicates the important role of pollen fertility for grain setting. Interestingly, both mild and extreme heat induced development of new tillers after the heat stress, providing an alternative sink for accumulated photosynthates and significantly contributing to the final yield. Measurements of flag leaf maximum potential quantum efficiency of Photosystem II (Fv/Fm) showed an initial inhibition after the heat treatment, followed by a full recovery within a few days. Despite this, model fitting using chlorophyll SPAD measurements showed an earlier onset or faster senescence rate under heat stress. The data presented here provide interesting entry points for further research into pollen fertility, tillering dynamics and leaf senescence under heat. The identified tolerant wheat genotypes can be used to dissect the underlying mechanisms and breed climate-resilient wheat.
Molecular Insights into the Recognition of Acetylated Histone Modifications by the BRPF2 Bromodomain
Authors: Barman Soumen , Roy Anirban , Padhan Jyotirmayee , Sudhamalla Babu
Published: February 2022

HBO1 (HAT bound to ORC), a member of the MYST family of histone acetyltransferases (HATs), was initially identified as a binding partner of the origin recognition complex (ORC) that acetylates free histone H3, H4, and nucleosomal H3. It functions as a quaternary complex with the BRPF (BRPF1/2/3) scaffolding protein and two accessory proteins, ING4/5 and Eaf6. BRPF2 interaction with HBO1 has been shown to be important for regulating H3K14 acetylation during embryonic development. However, how the BRPF2 directs the HBO1 HAT complex to chromatin to regulate its HAT activity towards nucleosomal substrates remains unclear. Our findings reveal novel interacting partners of the BRPF2 bromodomain that recognizes different acetyllysine residues on the N-terminus of histone H4, H3, and H2A and preferentially binds to H4K5ac, H4K8ac, and H4K5acK12ac modifications. Further, mutational analysis of BRPF2 bromodomain coupled with ITC binding and pull-down assays on the histone substrates identified critical residues responsible for acetyllysine binding. Moreover, the BRPF2 bromodomain could enrich H4K5ac mark-bearing mononucleosomes compared to other acetylated H4 marks. Consistent with this, ChIP-seq analysis revealed that BRPF2 strongly co-localizes with HBO1 at histone H4K5ac and H4K8ac marks near the TSS in the genome. Together, our study provides novel insights into how the histone binding function of the BRPF2 bromodomain directs the recruitment of the HBO1 HAT complex to chromatin to regulate gene expression.
Regulation of Hedgehog Signaling Through Arih2-Mediated Smoothened Ubiquitination and Endoplasmic Reticulum-Associated Degradation
Authors: Lv Bo , Zhang Xiao-Ou , Pazour Gregory J.
Published: February 2022

During Hedgehog signaling, the ciliary levels of Ptch1 and Smo are regulated by pathway activity. At the basal state, Ptch1 localizes to cilia and prevents the ciliary accumulation and activation of Smo. Upon stimulation with Hedgehog ligand, Ptch1 exits cilia and relieves the inhibition of Smo. Uninhibited Smo concentrates in cilia, becomes activated, and activates the downstream steps of the pathway. Loss of the ubiquitin E3 ligase Arih2 elevates the cellular level of Smo, causes Smo to inappropriately localize to cilia at the at the basal state, and elevates basal expression of Hedgehog responsive genes. Mice express two isoforms of Arih2 with different N-termini, but neither isoform localizes to cilia. Instead, Arih2α is found in the nucleus and Arih2β is found on the cytoplasmic face of the endoplasmic reticulum. Re-expression of endoplasmic reticulum-localized Arih2β, but not nuclear-localized Arih2α returns the cellular Smo levels back to normal and rescues the ciliary Smo accumulation phenotype. When Arih2β is missing, protein aggregates accumulate in the endoplasmic reticulum and the unfolded protein response is activated. Inhibitor studies suggest that Arih2β functions to mark excess or misfolded Smo for degradation by endoplasmic reticulum-associated degradation. When Arih2β is defective, excess Smo, possibly misfolded, is delivered to the cell surface and cilium where it interferes with pathway regulation. These findings add another level of complexity to the Hedgehog pathway.
Differential roles of neural crest- and endothelial-derived FOXC2 in trabecular meshwork and Schlemm’s Canal in glaucomatous pathology
Authors: Norden Pieter R. , Beckmann Lisa , Fang Raymond , Ujiie Naoto , Cai Zhen , Zhang Xian , Kweon Junghun , Liu Ting , Aoto Kazushi , Quaggin Susan E. , Zhang Hao F. , Kume Tsutomu
Published: February 2022

Impaired development and maintenance of the Schlemm’s Canal (SC) is associated with perturbed aqueous humor outflow regulation and glaucoma progression. Key molecular mechanisms, such as ANGPT/TIE2, PROX1, and VEGF-C/VEGFR-3 regulate SC development and maintenance, but mechanisms of paracrine signaling from neighboring tissues, including the trabecular meshwork (TM) are poorly understood. Here, we show Foxc2 is critical within the neural crest (NC)-derived TM and SC endothelium for development of the aqueous humor outflow pathway. In mice, NC- specific deletion of Foxc2 results in abnormal anterior eye segment development, including impaired SC morphogenesis and functional maintenance, loss of SC identity, and impaired maintenance of intraocular pressure (IOP). Visible light optical coherence tomography angiography analysis also demonstrated functional impairment of the SC in response to changes in IOP in NC-Foxc2-/- mice, suggesting increased TM stiffness. Utilization of single-cell RNA-sequencing (scRNA-seq) analysis then identified that this phenotype is predominately characterized by transcriptional changes associated with extracellular matrix organization and stiffness in TM-associated cell clusters, including increased matrix metalloproteinase (MMP) expression, which can generate soluble TIE2 that acts as an ANGPT trap. As FOXC2 is also critically involved in development of the lymphatic vasculature in other tissues, we also show that endothelial-specific deletion of Foxc2 resulted in impaired SC morphogenesis due to loss of TIE2 expression, which was rescued by deletion of the TIE2 phosphatase VE-PTP. Thus, NC-Foxc2 is critical for development of the TM, and both NC- and endothelial-Foxc2 are key for maintenance of SC identity and its morphogenesis.
Improved Heat Tolerance in Heat-acclimated Mice: The Probable Role of the PD-L1 Pathway
Authors: Qiu Minyue , Zhou Yuxin , Ye Nan , Guo Hongxia , Zhou Xiaoyang , Ding Xiaoyan , Li Jintao
Published: February 2022

Heat stroke is a life-threatening illness and is related to systematic inflammation-induced multiple organ dysfunction. Available evidence indicates that the severity of the systematic inflammatory response in heat stroke may be related to the changes in immune regulation brought by heat acclimation. However, the mechanisms of heat acclimation are still unclear. Here, we assessed the differences in immunocyte subsets in the spleen and lymph nodes of heat-acclimated and unacclimated mice. A higher frequency of CD4+Foxp3+ Tregs was observed in heat-acclimated mice. Our results indicated that the improved heat tolerance exhibited during acute heat stress exposure was related to an increased number of Tregs. In heat-acclimated mice, an increase in the number of Tregs was able to mitigate the recruitment of neutrophils, inhibit the activation of neutrophils, and suppress the severity of acute inflammation. Increased differentiation and development of Tregs in peripheral immune organs in heat-acclimated mice might stem from enhanced expression of Foxp3 and PD-L1. Our results strongly suggest that the regulatory function of increased Tregs on neutrophils may be regulated through the PD-1/PD-L1 pathway. The anti-inflammatory effects of Tregs have never been studied in the context of heat stress-induced systemic inflammation. Thus, our results on immunoregulation involving Tregs in heat-acclimated mice might be significant for devising a potential treatment for systemic inflammatory response syndrome and heatstroke.
Mitotic bookmarking by CTCF controls selected genes during the fast post-mitotic genome reactivation of ES cells
Authors: Chervova Almira , Festuccia Nicola , Dubois Agnes , Navarro Pablo
Published: February 2022

Mitosis leads to a global downregulation of transcription that then needs to be efficiently restored. In somatic cells, this is mediated by a transient hyper-active state that first leads to the reactivation of genes necessary to rebuild the interphasic cell and then of those executing specific cell functions. Here, we hypothesized that cells displaying rapid cell cycles may display accelerated gene reactivation dynamics. To test this, we focused on mouse Embryonic Stem (ES) cells, which have a short cell cycle and spend a minor time in G1. Compared to previous studies, we observed a uniquely fast global reactivation, which displays little specificity towards housekeeping versus cell identity genes. Such lack of specificity may enable the restoration of the entirety of regulatory functions before the onset of DNA replication. Genes displaying the fastest reactivation dynamics are associated with binding of CTCF, a transcription factor that largely maintains binding to its targets on DNA during mitosis. Nevertheless, we show that the post-mitotic global burst is robust and largely insensitive to CTCF depletion. There are, however, around 350 genes that respond to CTCF depletion rapidly after mitotic exit. Remarkably, these are characterised by promoter-proximal mitotic bookmarking by CTCF. We propose that the structure of the cell cycle imposes distinct constrains to post-mitotic gene reactivation dynamics in different cell types, via mechanisms that are yet to be identified but that can be modulated by mitotic bookmarking factors.
Zn-dependent structural transition of SOD1 modulates its ability to undergo liquid-liquid phase separation
Authors: Das Bidisha , Roychowdhury Sumangal , Mohanty Priyesh , Rizuan Azamat , Mittal Jeetain , Chattopadhyay Krishnananda
Published: February 2022

The toxic gain of function of Cu/Zn superoxide dismutase (SOD1) associated with the neurodegenerative disease - Amyotrophic lateral sclerosis (ALS), is believed to occur via misfolding and/or aggregation. SOD1 is also associated with stress granules (SGs) which are a type of membraneless organelle believed to form via liquid-liquid phase separation (LLPS) of several proteins containing low-complexity, disordered regions. Using a combination of experiments and computer simulations, we report here that structural disorder in two loop regions of SOD1 induced by the absence of metal cofactor - Zn, triggers its LLPS. The phase-separated droplets give rise to aggregates which eventually form toxic amyloids upon prolonged incubation. The addition of exogenous Zn to immature, metal-free SOD1 and the severe ALS mutant - I113T, stabilized the loops and restored the folded structure, thereby inhibiting LLPS and subsequent aggregation. In contrast, the Zn-induced inhibition of LLPS and aggregation was found to be partial in the case of another severe ALS-associated mutant - G85R, which exhibits reduced Zn-binding. Moreover, a less-severe ALS mutant - G37R with perturbed Cu binding does not undergo LLPS. In conclusion, our work establishes a role for Zn-dependent modulation of SOD1 disorder and LLPS as a precursor phenomenon which may lead to the formation of toxic amyloids associated with ALS.

Significance Statement

The formation of membraneless organelles such as stress granules (SGs) is believed to occur through the process of liquid-liquid phase separation (LLPS) and involves numerous proteins containing intrinsically disordered regions. Whether SOD1, which is also associated with SGs and whose aggregation is associated with Amyotrophic lateral sclerosis (ALS), can independently undergo LLPS, is not known. SOD1 is a metalloenzyme which is stabilized by the metal co-factor - Zn. In this work, we utilize experimental and simulation techniques to highlight the modulation of SOD1 LLPS propensity in a Zn-dependent manner due to underlying conformational transitions between folded and partially disordered states. Our work establishes a link between SOD1 LLPS and aggregation, which is relevant to ALS pathogenesis.
Probabilistic inversions of electrical resistivity tomography data with a machine learning‐based forward operator
Authors: Aleardi Mattia , Vinciguerra Alessandro , Stucchi Eusebio , Hojat Azadeh
Published: February 2022

Casting a geophysical inverse problem into a Bayesian setting is often discouraged by the computational workload needed to run many forward modelling evaluations. Here we present probabilistic inversions of electrical resistivity tomography data in which the forward operator is replaced by a trained residual neural network that learns the non‐linear mapping between the resistivity model and the apparent resistivity values. The use of this specific architecture can provide some advantages over standard convolutional networks as it mitigates the vanishing gradient problem that might affect deep networks. The modelling error introduced by the network approximation is properly taken into account and propagated onto the estimated model uncertainties. One crucial aspect of any machine learning application is the definition of an appropriate training set. We draw the models forming the training and validation sets from previously defined prior distributions, while a finite element code provides the associated datasets. We apply the approach to two probabilistic inversion frameworks: A Markov chain Monte Carlo algorithm is applied to synthetic data, while an ensemble‐based algorithm is employed for the field measurements. For both the synthetic and field tests, the outcomes of the proposed method are benchmarked against the predictions obtained when the finite element code constitutes the forward operator. Our experiments illustrate that the network can effectively approximate the forward mapping even when a relatively small training set is created. The proposed strategy provides a forward operator that is three orders of magnitude faster than the accurate but computationally expensive finite element code. Our approach also yields the most likely solutions and uncertainty quantifications comparable to those estimated when the finite element modelling is employed. The presented method allows solving the Bayesian electrical resistivity tomography with a reasonable computational cost and limited hardware resources.
Reducing the income tax burden for households with children: an assessment of the child tax credit reform in Austria
Authors: Christl Michael , De Poli Silvia , Varga Janos
Published: February 2022

In this paper, we analyse the impact of the implementation of a child tax credit in Austria in 2018. We combine microsimulation techniques, labour supply modelling and dynamic general equilibrium modelling to make an ex ante evaluation of the reform, accounting also for behavioural responses of individuals. We show that although the macroeconomic effect of the Austrian reform is expected to be relatively small, accounting for feedback effects on a micro‐level is very important, especially when analysing socioeconomic and policy‐relevant indicators, such as poverty and inequality. When focusing on the distributional implications and the impact on poverty, our analysis highlights that the first‐round effects of the child tax credit substantially underestimate the increase in household income for households with children. Additionally, we find that when accounting for second‐round effects, the loss in tax revenues is partly offset. The estimated self‐financing effect of the reform is estimated to be about 13 per cent. Our results also indicate that part of the associated tax decrease can be potentially captured by the employer, meaning that gross wages are expected to fall slightly. Therefore, in the medium term, some households without children might suffer a small reduction in their disposable income. Overall, our analysis highlights the importance of accounting for second‐round effects when analysing tax reforms ex ante.
Unmanned aerial vehicles as a useful tool for investigating animal movements
Authors: Iwamoto Masamichi , Nogami Shonosuke , Ichinose Tomohiro , Takeda Keiji
Published: February 2022

Determining animal abundance is crucial for assessing the effectiveness of management measures against pest animals. Meanwhile, investigating animal movements has become important for conducting abundance estimations of unmarked animals since the random encounter model (REM) was published. REM is a camera trapping method that derives animal density by using contact ratio between camera traps and targeted animals that randomly move at a certain speed in a given area. However, it requires an independent value, which is animal speed. For investigating animal speed, camera traps with video recording and GPS tagging are the commonly used tools.

Unmanned aerial vehicles (UAVs) are currently used in wildlife monitoring to investigate the abundance of target species. It is evaluated as a tool that is non‐invasive and suitable for surveys in inaccessible landscapes. Considering these characteristics, we regarded a distant survey using this technology as suitable for investigating animal movements. Therefore, we proposed a method for estimating animal movements using UAVs and conducted a case study that aimed to investigate wild boars' movements.

We collected 11 video samples that successfully followed the movements of wild boars from 26 UAV flights in total, and the average speed of their movements derived from all the samples was 1.54 km/24 hr.

We found that issues can be improved, including species identification, video sample length, and animal behaviours or activity patterns. On the other hand, our method showed potential for applying to species with specific characteristics in their body size, shape or activity patterns. With improvements in the issues mentioned above, UAVs would become an alternative tool for investigating animal movements.
treetop: A Shiny‐based application and R package for extracting forest information from LiDAR data for ecologists and conservationists
Authors: Silva Carlos Alberto , Hudak Andrew T. , Vierling Lee A. , Valbuena Ruben , Cardil Adrian , Mohan Midhun , de Almeida Danilo Roberti Alves , Broadbent Eben N. , Almeyda Zambrano Angelica M. , Wilkinson Ben , Sharma Ajay , Drake Jason B. , Medley Paul B. , Vogel Jason G. , Prata Gabriel Atticciati , Atkins Jeff W. , Hamamura Caio , Johnson Daniel J. , Klauberg Carine
Published: February 2022

Individual tree detection (ITD) and crown delineation are two of the most relevant methods for extracting detailed and reliable forest information from LiDAR (Light Detection and Ranging) datasets. However, advanced computational skills and specialized knowledge have been normally required to extract forest information from LiDAR.

The development of accessible tools for 3D forest characterization can facilitate rapid assessment by stakeholders lacking a remote sensing background, thus fostering the practical use of LiDAR datasets in forest ecology and conservation. This paper introduces the treetop application, an open‐source web‐based and R package LiDAR analysis tool for extracting forest structural information at the tree level, including cutting‐edge analyses of properties related to forest ecology and management.

We provide case studies of how treetop can be used for different ecological applications, within various forest ecosystems. Specifically, treetop was employed to assess post‐hurricane disturbance in natural temperate forests, forest homogeneity in industrial forest plantations and the spatial distribution of individual trees in a tropical forest.

treetop simplifies the extraction of relevant forest information for forest ecologists and conservationists who may use the tool to easily visualize tree positions and sizes, conduct complex analyses and download results including individual tree lists and figures summarizing forest structural properties. Through this open‐source approach, treetop can foster the practical use of LiDAR data among forest conservation and management stakeholders and help ecological researchers to further understand the relationships between forest structure and function.
Outstanding challenges and future directions for biodiversity monitoring using citizen science data
Authors: Johnston Alison , Matechou Eleni , Dennis Emily B.
Published: February 2022

There is increasing availability and use of unstructured and semi‐structured citizen science data in biodiversity research and conservation. This expansion of a rich source of ‘big data’ has sparked numerous research directions, driving the development of analytical approaches that account for the complex observation processes in these datasets.

We review outstanding challenges in the analysis of citizen science data for biodiversity monitoring. For many of these challenges, the potential impact on ecological inference is unknown. Further research can document the impact and explore ways to address it. In addition to outlining research directions, describing these challenges may be useful in considering the design of future citizen science projects or additions to existing projects.

We outline challenges for biodiversity monitoring using citizen science data in four partially overlapping categories: challenges that arise as a result of (a) observer behaviour; (b) data structures; (c) statistical models; and (d) communication. Potential solutions for these challenges are combinations of: (a) collecting additional data or metadata; (b) analytically combining different datasets; and (c) developing or refining statistical models.

While there has been important progress to develop methods that tackle most of these challenges, there remain substantial gains in biodiversity monitoring and subsequent conservation actions that we believe will be possible by further research and development in these areas. The degree of challenge and opportunity that each of these presents varies substantially across different datasets, taxa and ecological questions. In some cases, a route forward to address these challenges is clear, while in other cases there is more scope for exploration and creativity.
Flouroscopic versus conventional epidural blood patch in obstetrics: A retrospective cohort study
Authors: Orbach‐Zinger Sharon , Lekar Leibzon Margarita , Gonen Ophir , Zribi Benjamin , Wazwaz Susan A. , Binyamin Yair , Heesen Michael , Matatov Yuri , Shimon Orit , Eidelman Leonid A.
Published: February 2022

Background

Epidural blood patch is a common effective treatment for postdural puncture headache after accidental dural puncture during labor and may be done in conventional or fluoroscopy‐guided methods. The aim of this study was to compare intensity of headache at the time of discharge from the hospital and to compare blood volumes injected in conventional epidural blood patches versus fluoroscopic‐guided blood patches and evaluate the side effects of both method of treatment.

Methods

Between the years 2010 and 2020, 84 patients who were diagnosed with postdural puncture headache received either a conventional epidural blood patch or a fluoroscopic‐guided blood patch. Blood volumes were compared and evaluation of side effects was made based on data collected during and after the procedure.

Results

Eighty‐four patients were included in this study. Fifty‐two women in the conventional epidural blood patch group and 32 in the fluoroscopic‐guided blood patch group. Women in the conventional epidural blood patch group received statistically significantly higher doses of blood than women in the fluoroscopic‐guided blood patch group: conventional method 29 ml IQR [23‐36] versus fluoroscopic method 16 ml, IQR [12‐18], p < .001 with no difference in headache pain intensity at hospital release. There was no difference between groups in hospital length of stay, or persistent PDPH. There was also no difference chronic headache or backache between the two groups.

Conclusions

Women who received fluoroscopic epidural blood patch required a much lower volume of blood injected while there was no difference between groups in headache pain intensity at discharge.
Point‐of‐care ultrasound‐first for the evaluation of small bowel obstruction: National cost savings, length of stay reduction, and preventable radiation exposure
Authors: Brower Charles H. , Baugh Christopher W. , Shokoohi Hamid , Liteplo Andrew S. , Duggan Nicole , Havens Joaquim , Askari Reza , Rehani Madan M. , Kapur Tina , Goldsmith Andrew J.
Published: February 2022

Objectives

Computed tomography (CT) has long been the gold standard in diagnosing patients with suspected small bowel obstruction (SBO). Recently, point‐of‐care ultrasound (POCUS) has demonstrated comparable test characteristics to CT imaging for the diagnosis of SBO. Our primary objective was to estimate the annual national cost saving impact of a POCUS‐first approach for the evaluation of SBO. Our secondary objectives were to estimate the reduction in radiation exposure and emergency department (ED) length of stay (LOS).

Methods

We created and ran 1000 trials of a Monte Carlo simulation. The study population included all patients presenting to the ED with abdominal pain who were diagnosed with SBO. Using this simulation, we modeled the national annual cost savings in averted advanced imaging from a POCUS‐first approach for SBO. The model assumes that all patients who require surgery or have non‐diagnostic POCUS exams undergo CT imaging. The model also conservatively assumes that a subset of patients with diagnostic POCUS exams undergo additional confirmatory CT imaging. We used the same Monte Carlo model to estimate the reduction in radiation exposure and total ED bed hours saved.

Results

A POCUS‐first approach for diagnosing SBO was estimated to save a mean (±SD) of $30.1 million (±8.9 million) by avoiding 143,000 (±31,000) CT scans. This resulted in a national cumulative decrease of 507,000 bed hours (±268,000) in ED LOS. The reduction in radiation exposure to patients could potentially prevent 195 (±56) excess annual cancer cases and 98 (±28) excess annual cancer deaths.

Conclusions

If adopted widely and used consistently, a POCUS‐first algorithm for SBO could yield substantial national cost savings by averting advanced imaging, decreasing ED LOS, and reducing unnecessary radiation exposure in patients. Clinical decision tools are needed to better identify which patients would most benefit from CT imaging for SBO in the ED.
Five‐year trends in induction of labour in a large Australian metropolitan maternity service
Authors: O’ Sullivan Caoimhe , Wilson Erin , Beckmann Michael
Published: February 2022

Background

The World Health Organisation recommends that induction of labour (IOL) be performed only with a clear medical indication. Australian rates of IOL appear to be rising, with more than one‐third of women having labour induced. This may reflect changing clinician and consumer perceptions of the benefits and potential harms of term IOL.

Aims

To understand recent trends in the rates and indications for IOL.

Materials and Methods

A retrospective cohort study was undertaken in a Level 6 maternity facility, in metropolitan South‐East Queensland, Australia. Routinely collected data were gathered between 2015 and 2020. Exclusion criteria were multiple pregnancies, stillbirth and pre‐labour rupture of membranes. Pre‐labour rupture of membranes was excluded due to inability to assess if IOL for this indication was a true induction or augmentation of labour. Indications for induction were grouped into maternal, fetal, elective indications, ‘post‐dates’ and decreased fetal movements (DFM). Rates of IOL and frequency of the various indications were compared over time.

Results

About 46 530 livebirths occurred during the study period, with labour induced in 31.7%. The proportion of women undergoing IOL increased from 29.8% in 2015 to 33.4% in 2019 (P < 0.001). The proportion of inductions for DFM and elective indications increased over time, with a substantial decrease in ‘post‐dates’ IOL.

Conclusions

This large contemporary analysis of IOL trends in Australia has demonstrated rising rates and changing indications for IOL. There remain large knowledge gaps in areas such as care of women with DFM, definitions and management of ‘post‐term pregnancy’, and the economic and service impacts of rising trends in the rate of IOL.
Anti‐KIT monoclonal antibody CDX‐0159 induces profound and durable mast cell suppression in a healthy volunteer study
Authors: Alvarado Diego , Maurer Marcus , Gedrich Richard , Seibel Scott B. , Murphy Michael B. , Crew Linda , Goldstein Joel , Crocker Andrea , Vitale Laura A. , Morani Pamela A. , Thomas Lawrence J. , Hawthorne Thomas R. , Keler Tibor , Young Diane , Crowley Elizabeth , Kankam Martin , Heath‐Chiozzi Margo
Published: February 2022

Background

Mast cells (MC) are powerful inflammatory immune sentinel cells that drive numerous allergic, inflammatory, and pruritic disorders when activated. MC‐targeted therapies are approved in several disorders, yet many patients have limited benefit suggesting the need for approaches that more broadly inhibit MC activity. MCs require the KIT receptor and its ligand stem cell factor (SCF) for differentiation, maturation, and survival. Here we describe CDX‐0159, an anti‐KIT monoclonal antibody that potently suppresses MCs in human healthy volunteers.

Methods

CDX‐0159‐mediated KIT inhibition was tested in vitro using KIT‐expressing immortalized cells and primary human mast cells. CDX‐0159 safety and pharmacokinetics were evaluated in a 13‐week good laboratory practice (GLP)‐compliant cynomolgus macaque study. A single ascending dose (0.3, 1, 3, and 9 mg/kg), double‐blinded placebo‐controlled phase 1a human healthy volunteer study (n = 32) was conducted to evaluate the safety, pharmacokinetics, and pharmacodynamics of CDX‐0159.

Results

CDX‐0159 inhibits SCF‐dependent KIT activation in vitro. Fc modifications in CDX‐0159 led to elimination of effector function and reduced serum clearance. In cynomolgus macaques, multiple high doses were safely administered without a significant impact on hematology, a potential concern for KIT inhibitors. A single dose of CDX‐0159 in healthy human subjects was generally well tolerated and demonstrated long antibody exposure. Importantly, CDX‐0159 led to dose‐dependent, profound suppression of plasma tryptase, a MC‐specific protease associated with tissue MC burden, indicative of systemic MC suppression or ablation.

Conclusion

CDX‐0159 administration leads to systemic mast cell ablation and may represent a safe and novel approach to treat mast cell‐driven disorders.
Camp methodologies: The “how” of studying camps
Authors: Weima Yolanda , Brankamp Hanno
Published: February 2022

This special section contributes to the growing interdisciplinary field of camp studies by examining the ways in which scholars methodologically approach and study camps and camp‐like spaces. The characteristics of camps, which render them of interest to scholarship in the first place, simultaneously generate methodological, ethical, and practical questions for research. Yet comparatively few studies have explicitly addressed the methods and methodologies in camp research. How do camp contexts shape our underlying research philosophies and how do particular ways of doing research impact our conceptualisations of camps? The contributors to this special section provide a variety of answers to these questions, drawing on empirical research in/on current and historical camp settings. Overall, we gesture towards “camp methodologies” not as a set of prescribed tools, techniques, or epistemologies to be followed when studying camps but as a shorthand for approaches that consider first, how camp geographies delimit research activities and second, how methodological choices in turn (re)construct the camp conceptually in different ways. Ultimately, this collection aims to encourage critical debates and reflections to shed more light on the methodological effects, positionalities, responsibilities, complicities, and continuing necessities of studying camps.
How to measure flower ultraviolet reflectance using digital photography
Authors: Napoleone Francesca , Manzini Davide , Burrascano Sabina
Published: February 2022

Aims

Flower ultraviolet (UV) reflectance strongly influences insects’ ability to detect flowers and locate pollen/nectar sources. Although included in the TRY database, the lack of a cost‐effective standardised method of measurement hampers the availability of information on this key floral trait. Digital photography and image processing allow for a novel approach to flower UV reflectance measurement that is both accessible and accurate.

Location

European semi‐natural grasslands.

Methods

We used a UV‐LED light and a mirrorless camera with a filter, which represents a low‐cost equipment for narrow emission/reflection photography (350–380 nm). Flowers were photographed with two standards of known reflection, and UV reflectance values were obtained using open‐source image processing software. We measured UV reflectance for 57 plant species typical of European semi‐natural grasslands.

Results

Our values substantially matched the categorical classes obtained by analogue photography available in TRY and showed a highly significant relationship with spectrophotometric measures.

Conclusions

The method proposed here overcomes the one based on analogue photography and subjective visual estimates, and represents an easy and low‐cost alternative to spectrophotometry. It may promote the standardised measurement of flower UV reflectance and broaden the information of this trait globally, meeting the needs of functional ecology and trait‐based community assembly studies.
Do experimental drought stress and species' drought sensitivity influence herbivory in tropical tree seedlings?
Authors: Muehleisen Andrew J. , Manzané‐Pinzón Eric , Engelbrecht Bettina M. J. , Jones F. Andrew , Comita Liza S.
Published: February 2022

In tropical forests, drought and herbivory represent two potent stresses on seedlings. Climate change is expected to increase the frequency of severe droughts in many tropical forests, which may influence seedling vulnerability to herbivores if drought stress affects seedling palatability. Furthermore, contrasting selective pressures in wetter vs drier forests could mean that species well‐adapted to herbivores are less drought resistant and vice versa. In this study, we measured seedling performance and herbivory in a common garden experiment where seedlings of 15 tree species were subjected to irrigation or rainfall exclusion treatments across two dry seasons in Panama. Water manipulation had no effects on foliar herbivory during the experiment for all species combined and for 14 of the 15 focal species when analyzed separately. There was large variation among species in herbivore damage, but no relationship between the sensitivity of species to drought and the amount of herbivory they experienced. Altogether, our findings suggest that increasing drought stress is unlikely to directly alter tropical tree seedling susceptibility to herbivore attack in this forest. Additional studies are needed to determine whether drought alters tropical plant‐herbivore interactions via other mechanisms, such as through changes in herbivorous insect communities and/or increases in fitness costs of herbivory.

Abstract in Spanish is available with online material.