bluuebunny/crossref_metadata_2025_split huggingface dataset:
California’s forest carbon offsets buffer pool is severely undercapitalized
Authors: Badgley Grayson , Chay Freya , Chegwidden Oriana S. , Hamman Joseph J. , Freeman Jeremy , Cullenward Danny 
Published: May 2022

AbstractCalifornia operates a large forest carbon offsets program that credits carbon stored in forests across the continental United States and parts of coastal Alaska. These credits can be sold to buyers who wish to justify ongoing emissions, including in California’s cap-and-trade program. Although fossil CO2 emissions have effectively permanent atmospheric consequences, carbon stored in forests is inherently less durable because forests are subject to significant socioeconomic and physical risks that can cause temporarily stored carbon to be re-released into the atmosphere. To address these risks, California’s program is nominally designed to provide a 100-year guarantee on forest carbon claims based on a self-insurance program known as a buffer pool. Projects contribute credits to the buffer pool based on a suite of project-specific risk factors, with buffer pool credits retired as needed to cover carbon losses from events such as wildfire or drought. So long as the buffer pool remains solvent, the program’s permanence claim remains intact. Here, we perform an actuarial analysis of the performance of California’s buffer pool. We document how wildfires have depleted nearly one-fifth of the total buffer pool in less than a decade, equivalent to at least 95 percent of the program-wide contribution intended to manage all fire risks for 100 years. We also show that potential carbon losses from a single forest disease, sudden oak death, could fully encumber all credits set aside for disease and insect risks. These findings indicate that California’s buffer pool is severely undercapitalized and therefore unlikely to be able to guarantee the environmental integrity of California’s forest offsets program for 100 years.
Interphotoreceptor matrix proteoglycans IMPG1 and IMPG2 proteolyze in the SEA domain and reveal localization mutual dependency
Authors: Mitchell Benjamin , Coulter Chloe , Geldenhuys Werner J. , Rhodes Scott , Salido Ezequiel M. 
Published: May 2022

AbstractThe interphotoreceptor matrix (IPM) is a specialized extracellular mesh of molecules surrounding the inner and outer segments of photoreceptor neurons. Interphotoreceptor matrix proteoglycan 1 and 2 (IMPG1 and IMPG2) are major components of the IPM. Both proteoglycans possess SEA (sperm protein, enterokinase and agrin) domains, which may support proteolysis. Interestingly mutations in the SEA domains of IMPG1 and IMPG2 are associated with vision disease in humans. However, if SEA domains in IMPG molecules undergo proteolysis, and how this contributes to vision pathology is unknown. Therefore, we investigated SEA-mediated proteolysis of IMPG1 and IMPG2 and its significance to IPM physiology. Immunoblot analysis confirmed proteolysis of IMPG1 and IMPG2 in the retinas of wildtype mice. Point mutations mimicking human mutations in the SEA domain of IMPG1 that are associated with vision disease inhibited proteolysis. These findings demonstrate that proteolysis is part of the maturation of IMPG1 and IMPG2, in which deficits are associated with vision diseases. Further, immunohistochemical assays showed that proteolysis of IMPG2 generated two subunits, a membrane-attached peptide and an extracellular peptide. Notably, the extracellular portion of IMPG2 trafficked from the IPM around the inner segment toward the outer segment IPM by an IMPG1-dependent mechanism. This result provides the first evidence of a trafficking system that shuttles IMPG1 and IMPG2 from the inner to outer IPM in a co-dependent manner. In addition, these results suggest an interaction between IMPG1–IMPG2, and propose that mutations affecting one IMPG could affect the localization of the normal IMPG partner contributing to the disease mechanism of vision diseases associated with defective IMPG molecules.
A translational MRI approach to validate acute axonal damage detection
Authors: Toschi Nicola , Cerdá Antonio Cerdán , Treaba Constantina A , Barletta Valeria , Herranz Elena , Mehndiratta Ambica , Mainero Caterina , De Santis Silvia 
Published: May 2022

AbstractAxonal degeneration is a central pathological feature of neurodegenerative pathologies and is closely associated with irreversible clinical disability. Current noninvasive methods to detect axonal damage in vivo are limited in their specificity, clinical applicability, and lack of proper validation. We aimed to validate an MRI framework based on multicompartment modeling of the diffusion-weighted signal (AxCaliber) in rats in the presence of axonal pathology, achieved through injection of a neurotoxin damaging the neuronal terminal of axons. We then applied the same MRI protocol to map axonal integrity in the whole brain of multiple sclerosis relapsing-remitting patients and age-matched healthy controls, a pathology associated with a neurodegenerative component.AxCaliber is sensitive to microstructural axonal damage in rats, as demonstrated by a significant increase in the mean axonal caliber along the target tract, which correlated with the neurotoxin neurofilament staining. In humans, we uncovered a diffuse increase in mean axonal caliber in multiple sclerosis lesions and, importantly, in most areas of the normal-appearing white matter. Our results demonstrate that axonal diameter mapping is a sensitive and specific imaging biomarker able to link noninvasive imaging contrasts with the underlying biological substrate, supporting the key role of generalized axonal damage useful in diseases such as multiple sclerosis.
Environmental DNA from archived leaves reveals widespread temporal turnover and biotic homogenization in forest arthropod communities
Authors: Krehenwinkel Henrik , Weber Sven , Broekmann Rieke , Melcher Anja , Hans Julian , Wolf Ruediger , Hochkirch Axel , Kennedy Susan Rachel , Koschorreck Jan , Kuenzel Sven , Müller Christoph , Retzlaff Rebecca , Teubner Diana , Schanzer Sonja , Klein Roland , Paulus Martin , Udelhoven Thomas , Veith Michael 
Published: May 2022

AbstractA major limitation of current reports on insect declines is the lack of standardized, long-term, and taxonomically broad time series. Here, we demonstrate the utility of environmental DNA from archived leaf material to characterize plant-associated arthropod communities. We base our work on several multi-decadal leaf time series from tree canopies in four land use types, which were sampled as part of a long-term environmental monitoring program across Germany. Using these highly standardized and well-preserved samples, we analyze temporal changes in communities of several thousand arthropod species belonging to 23 orders using metabarcoding and quantitative PCR. Our data do not support widespread declines of α-diversity or genetic variation within sites. Instead, we find a gradual community turnover, which results in temporal and spatial biotic homogenization, across all land use types and all arthropod orders. Our results suggest that insect decline is more complex than mere α-diversity loss, but can be driven by β-diversity decay across space and time.
Centrally expressed Cav3.2 T-type calcium channel is critical for the initiation and maintenance of neuropathic pain
Authors: Fayad Sophie L. , Ourties Guillaume , Le Gac Benjamin , Jouffre Baptiste , Lamoine Sylvain , Fruquière Antoine , Laffray Sophie , Gasmi Laila , Cauli Bruno , Mallet Christophe , Bourinet Emmanuel , Bessaih Thomas , Lambert Régis C. , Leresche Nathalie 
Published: May 2022

AbstractCav3.2 T-type calcium channel is a major molecular actor of neuropathic pain in peripheral sensory neurons, but its involvement at the supra-spinal level is almost unknown. In the Anterior Pretectum (APT), a hub of connectivity of the somatosensory system involved in pain perception, we show that Cav3.2 channels are expressed in a sub-population of GABAergic neurons co-expressing parvalbumin (PV). In these PV-expressing neurons, Cav3.2 channels contribute to a high frequency bursting activity, which is increased in the spared nerve injury model of neuropathy. Specific deletion of Cav3.2 channels in APT neurons reduced both the initiation and maintenance of mechanical and cold allodynia. These data are a direct demonstration that centrally expressed Cav3.2 channels also play a fundamental role in pain pathophysiology.
Phorbolester-activated Munc13-1 and ubMunc13-2 exert opposing effects on dense-core vesicle secretion
Authors: Houy Sébastien , Martins Joana S. , Lipstein Noa , Sørensen Jakob B. 
Published: May 2022

AbstractMunc13 proteins are priming factors for SNARE-dependent exocytosis, which are activated by diacylglycerol (DAG)-binding to their C1-domain. Several Munc13 paralogs exist, but their differential roles are not well understood. We studied the interdependence of phorbolesters (DAG mimics) with Munc13-1 and ubMunc13-2 in mouse adrenal chromaffin cells. Although expression of either Munc13-1 or ubMunc13-2 stimulated secretion, phorbolester was only stimulatory for secretion when ubMunc13-2 expression dominated, but inhibitory when Munc13-1 dominated. Accordingly, phorbolester stimulated secretion in wildtype cells, or cells overexpressing ubMunc13-2, but inhibited secretion in Munc13-2/Unc13b knockout (KO) cells or in cells overexpressing Munc13-1. Phorbolester was more stimulatory in the Munc13-1/Unc13a KO than in WT littermates, showing that endogenous Munc13-1 limits the effects of phorbolester. Imaging showed that ubMunc13-2, but not Munc13-1, traffics to the plasma membrane with a time-course matching Ca2+-dependent secretion, and trafficking is independent of synaptotagmin-7 (syt7). However, in the absence of syt7, phorbolester became inhibitory for both Munc13-1 and ubMunc13-2 driven secretion, indicating that stimulatory phorbolester x Munc13-2 interaction depends obligatorily on functional pairing with syt7. Overall, DAG/phorbolester, ubMunc13-2 and syt7 form a stimulatory triad for dense-core vesicle priming.
Quality Control Framework of TCM Preparations based on Multi-type Fingerprints using a Source Proportion Estimation Model
Authors: Zha Yuguo , Yao Qi , Zhao Dan , Zhu Xue , Bai Hong , Ning Kang 
Published: May 2022

AbstractTraditional Chinese Medicine (TCM) preparations have been widely used in clinical practice for the treatment of various diseases. The quality of TCM preparations is related to clinical efficacy and safety and is highly valued by researchers. The authenticity of TCM preparation can be guaranteed objectively by accurate quality control according to the composition. Here, we proposed a quality control framework of TCM preparations, which is based on multi-type fingerprints using the source proportion estimation model (SPEM). The high-performance liquid chromatography (HPLC) analysis and the high-throughput sequencing analysis are employed to acquire the chemical and taxonomic fingerprints of samples, respectively. The quality of TCM preparations among different manufacturers or batches is evaluated by using SPEM, which is an unsupervised method for source identification of TCM samples. Results showed the good performance of the quality control framework, for example, SPEM achieved a mean accuracy of 0.778 based on the ITS2 taxonomic fingerprint when differentiating manufacturer of BazhenYimu Wan pill. Applications of the quality control framework revealed the batch effect in TCM samples, and environmental factors, such as geography have a profound impact on the consistency of TCM preparations. In summary, this study is an exploration in the field of digital development of TCM preparations and provide a new insight to quantify the batch effect among different batches of TCM samples.
Understanding Definitions and Reporting of Deaths Attributed to COVID-19 in the UK – Evidence from FOI Requests
Authors: Jefferson Tom , Dietrich Madeleine , Brassey Jon , Heneghan Carl 
Published: May 2022

AbstractDeath is a widely used outcome to assess the severity of pandemics. Accuracy in assigning the cause of death is of vital importance to define the impact of the agent, monitor its evolution, and compare its threat with those of other agents. Throughout the COVID-19 pandemic, there has been widespread reporting of aggregate death data with little attention paid to the accuracy of the assignment of causation.We aimed to analyse public authorities’ understanding of the assignment of cause of deaths during the SARS-CoV-2 pandemic in the UK by accessing Freedom of Information requests posed in three periods in 2020-21. By public authorities, we mean NHS Health Trusts, laboratories, and government agencies such as Public Health England and the Department of Health and Social Care. We searched WhatDoTheyKnow using the terms “covid and death”. We excluded those requests to bodies that cannot provide an answer (e.g. Councils) and those dealing with the effects of vaccines.We grouped questions into themes addressing the definitions and causes of death relevant to the pandemic. We looked at the responses to the questions of the definition of cause of death, the accuracy of the attribution, the role of other pre-existing pathologies and how these were reported and quantified.We found 800 requests from over 90 individuals. There was no consistency in the definition of cause of death or contributory cause of death across national bodies and in different bodies within the same nation. Nursing home providers, as well as medical practitioners, can assign a cause of death according to the Care Quality Commission. Post-mortem examinations were uncommon, the ONS did not incorporate their results in the summary of deaths by cause during the pandemic period. The meaning of the words “test” or “swab” was never clarified by any of the respondents. In care homes in England 1,304 out of 17,264 COVID-19 (7.6%, range 0% to 63%) mentioned COVID-19 in the absence of contributory or other factors in the death certificate, making it impossible to ascertain a chain of causality. The inconsistencies already noted hinder the ascertainment of the role of each factor leading to death and the quantification of the importance of infection. Some responses indicate that SARS-CoV-2 negative individuals or those whose death was not caused by COVID-19 were classified as “COVID-19 deaths”. We found 14 different ways of attributing the causes of death mentioned by respondents.The overall lack of consistency has confused the public and likely led to erroneous conclusions. We are unable to separate the effects on deaths of SARS-CoV-2 from those of human interventions. A coherent process based on consistent definitions across the devolved nations is required. Furthermore, to enhance the accuracy of causation in pandemics a subset of deaths should be verified using autopsies with full medical documentation.
Molecular architecture of the autoinhibited kinesin-1 lambda particle
Authors: Weijman Johannes F. , Yadav Sathish K.N. , Surridge Katherine J. , Cross Jessica A. , Borucu Ufuk , Mantell Judith , Woolfson Derek N. , Schaffitzel Christiane , Dodding Mark P. 
Published: May 2022

AbstractDespite continuing progress in kinesin enzyme mechanochemistry and emerging understanding of the cargo recognition machinery, it is not known how these functions are coupled and controlled by the alpha-helical coiled coils encoded by a large component of kinesin protein sequences. Here, we combine computational structure prediction with single-particle negative stain electron microscopy to reveal the coiled-coil architecture of heterotetrameric kinesin-1, in its compact state. An unusual flexion in the scaffold enables folding of the complex, bringing the kinesin heavy chain-light chain interface into close apposition with a tetrameric assembly formed from the region of the molecule previously assumed to be the folding hinge. This framework for autoinhibition is required to uncover how engagement of cargo and other regulatory factors drive kinesin-1 activation.Summary statementIntegration of computational structure prediction with electron microscopy reveals the coiled-coil architecture of the autoinhibited compact conformer of the microtubule motor, kinesin-1.
Long-term temporal trends in gastrointestinal parasite infection in wild Soay sheep
Authors: Hayward Adam D. , Behnke Jerzy M. , Childs Dylan Z. , Corripio-Miyar Yolanda , Fenton Andy , Fraser Mariecia D. , Kenyon Fiona , McNeilly Tom N. , Pakeman Robin J. , Pedersen Amy B. , Pemberton Josephine M. , Sweeny Amy R. , Wilson Ken , Pilkington Jill G. 
Published: May 2022

SummaryMonitoring the prevalence and abundance of parasites over time is important for addressing their potential impact on host life-histories, immunological profiles, and their influence as a selective force. Only long-term ecological studies have the potential to shed light on both the temporal trends in infection prevalence and abundance and the drivers of such trends, because of their ability to dissect drivers that may be confounded over shorter time scales. Despite this, only a relatively small number of such studies exist. Here, we analysed changes in the prevalence and abundance of gastrointestinal parasites in the wild Soay sheep population of St Kilda across 31 years. The host population density has increased across the study, and population density is known to increase parasite transmission, but we found that density and year explained temporal variation in parasite prevalence and abundance independently. Prevalence of both strongyle nematodes and coccidian microparasites increased during the study, and this effect varied between lambs, yearlings and adults. Meanwhile, abundance of strongyles was more strongly linked to host density than to temporal (yearly) dynamics, while abundance of coccidia showed a strong temporal trend without any influence of density. Strikingly, coccidian abundance increased threefold across the course of the study in lambs, while increases in yearlings and adults were negligible. Our decades-long, intensive, individual-based study will enable the role of environmental change and selection pressures in driving these dynamics to be determined, potentially providing unparalleled insight into the drivers of temporal variation in parasite dynamics in the wild.Key findingsWe studied temporal trends in gastrointestinal parasites of wild sheep over 31 yearsYear and host population density explained temporal variation in parasites independentlyPrevalence of both strongyle nematodes and coccidia varied across the study periodAbundance of strongyles was more closely linked to host density than yearAbundance of coccidia increased threefold over time in lambs, but did not vary in adults
Distributed and gradual microstructure changes track the emergence of behavioural benefit from memory reactivation
Authors: Rakowska Martyna , Lazari Alberto , Cercignani Mara , Bagrowska Paulina , Johansen-Berg Heidi , Lewis Penelope A. 
Published: May 2022

AbstractMemory traces develop gradually and link to neural plasticity. Memory reactivation during sleep is crucial for consolidation, but its precise impact on plasticity and contribution to long-term memory storage remains unclear. We used multimodal diffusion-weighted imaging to track the location and timescale of microstructural changes following Targeted Memory Reactivation (TMR) of a motor task. This showed continuous microstructure plasticity in precuneus across 10 days post-TMR, paralleling the gradual development of behavioural benefit. Both early (0 - 24 h post-TMR) and late (24 h - 10 days post-TMR) microstructural changes in striatum and sensorimotor cortex were associated with the emergence of behavioural effects of TMR at day 20. Furthermore, the baseline microstructural architecture of sensorimotor cortex predicted TMR susceptibility. These findings demonstrate that repeated reactivation of memory traces during sleep engenders microstructural plasticity which continues days after the stimulation night and is associated with the emergence of memory benefits at the behavioural level.
Argon plasma-modified bacterial cellulose filters for protection against respiratory pathogens
Authors: Żywicka Anna , Ciecholewska-Juśko Daria , Szymańska Magdalena , Drozd Radosław , Sobolewski Peter , Junka Adam , Gorgieva Selestina , El Fray Miroslawa , Fijałkowski Karol 
Published: May 2022

AbstractDue to the global spread of the SARS-CoV-2 virus and the resultant pandemic, there has been a major surge in the demand for surgical masks, respirators, and other air filtration devices. Unfortunately, the fact that these filters are made of petrochemical-derived, non-biodegradable polymers means that the surge in production has also led to a surge in plastic waste. In this work, we present novel, sustainable filters based on bacterial cellulose (BC) functionalized with low-pressure argon plasma (LPP-Ar). The “green” production process involved BC biosynthesis by Komagataeibacter xylinus, followed by simple purification, homogenization, lyophilization, and finally LPP-Ar treatment. The obtained LPP-Ar-functionalized BC-based material (LPP-Ar-BC-bM) showed excellent antimicrobial and antiviral properties, with no cytotoxicity versus murine fibroblasts in vitro. Further, filters consisting of three layers of LPP-Ar-BC-bM had >99% bacterial and viral filtration efficiency, while maintaining sufficiently low airflow resistance (6 mbar at an airflow of 95 L/min). Finally, as a proof-of-concept, we were able to prepare 80 masks with LPP-Ar-BC-bM filter and ~85% of volunteer medical staff assessed them as good or very good in terms of comfort. We conclude that our novel sustainable, biobased, biodegradable filters are suitable for respiratory personal protective equipment (PPE), such as surgical masks and respirators. Further, with scale-up, they may be adapted for indoor air handling filtration in hospitals or schools.Graphical abstract
Analysis of allelic cross-reactivity of monoclonal IgG antibodies by a multiplexed reverse FluoroSpot assay
Authors: Hoffmann-Veltung Henriette , Anabire Nsoh Godwin , Ofori Michael Fokuo , Janhmatz Peter , Ahlborg Niklas , Hviid Lars , Quintana Maria del Pilar 
Published: May 2022

AbstractThe issue of antibody cross-reactivity is of central importance in immunology, and not least in protective immunity to Plasmodium falciparum malaria, where key antigens show substantial allelic variation (polymorphism). However, serological analysis often does not allow the distinction between true cross-reactivity (one antibody recognizing multiple antigen variants) and apparent cross-reactivity (presence of multiple variant-specific antibodies), as it requires analysis at the single B-cell/monoclonal antibody level. ELISpot is an assay that enables that, and a recently developed multiplexed variant of ELISpot (FluoroSpot) facilitates simultaneous assessment of B-cell/antibody reactivity to several different antigens. In this study, we present a further enhancement of this assay that makes direct analysis of monoclonal antibody-level cross-reactivity with allelic variants feasible. Using VAR2CSA-type PfEMP1 – a notoriously polymorphic antigen involved in the pathogenesis of placental malaria – as a model, we demonstrate the robustness of the assay and its applicability to analysis of true cross-reactivity of monoclonal VAR2CSA-specific antibodies in naturally exposed individuals. The assay is adaptable to the analysis of other polymorphic antigens, rendering it a powerful tool in studies of immunity to malaria and many other diseases.