Response to comment by Dr. R. Cornish concerning the publication by Palmer et al.(2020)

Published On 2022/2

We thank Dr. Cornish for his' comment'piece prompted by our revised model for the timing of ice build-up and retreat during the Loch Lomond ('Younger Dryas') Stadial (LLS) in Glens Roy and Spean (Palmer et al., 2020), iconic valleys that contain suites of landforms that have stimulated debate for over two centuries. Our new interpretations are based on a high-precision varve chronology (the Lochaber Varve Chronology, or LMVC19) anchored to an absolute timescale by the Vedde Ash, a tephra isochron widely-employed in NW Europe which was detected within the varve sequence. These new results led us to challenge the model initially established by Sissons (1978, 1979a) concerning the relative timing of:(i) the expansion of glacier ice into the Spean and Roy catchments, and (ii) the order of the subsequent retreat of the ice margins. In responding to Cornish's comments we are mindful of the complexity of the …

Published On

2022/2

Volume

277

Page

107353

Authors

John Lowe

John Lowe

Royal Holloway, University of London

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62

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26

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0

I-10 Index(since 2020)

0

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0

Citation(since 2020)

0

Cited By

0

Research Interests

Quaternary science

Palaeoclimates

Tephrochronology

Dating methods

Annette MacLeod

Annette MacLeod

University of Glasgow

Position

Wellcome Trust Senior Fellow IBAHCM

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47

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23

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0

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0

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0

Citation(since 2020)

0

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Research Interests

Population Genomics

Molecular Parasitology

host parasite interactions

University Profile Page

Ian Matthews

Ian Matthews

Royal Holloway, University of London

Position

Senior Lecturer in Quaternary Science

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25

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20

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0

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0

Citation(since 2020)

0

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0

Research Interests

Quaternary Science

Alison MacLeod

Alison MacLeod

Royal Holloway, University of London

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21

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16

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0

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0

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0

Citation(since 2020)

0

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Research Interests

Geography

Quaternary Science

Abrupt environmental change

varves

tephrochronology

Other Articles from authors

Annette MacLeod

Annette MacLeod

University of Glasgow

EBioMedicine

Phenome-wide analysis reveals epistatic associations between APOL1 variants and chronic kidney disease and multiple other disorders

BackgroundAPOL1 variants G1 and G2 are common in populations with recent African ancestry. They are associated with protection from African sleeping sickness, however homozygosity or compound heterozygosity for these variants is associated with chronic kidney disease (CKD) and related conditions. What is not clear is the extent of associations with non-kidney-related disorders, and whether there are clusters of diseases associated with individual APOL1 genotypes.MethodsUsing a cohort of 7462 UK Biobank participants with recent African ancestry, we conducted a phenome-wide association study investigating associations between individual APOL1 genotypes and conditions identified by the International Classification of Disease phenotypes.FindingsWe identified 27 potential associations between individual APOL1 genotypes and a diverse range of conditions. G1/G2 compound heterozygotes were …

Annette MacLeod

Annette MacLeod

University of Glasgow

Parasites & vectors

Impact of environmental factors on Biomphalaria pfeifferi vector capacity leading to human infection by Schistosoma mansoni in two regions of western Côte d'Ivoire

A bstractBackgroundIntestinal schistosomiasis remains a worrying health problem, particularly in western Côte d'Ivoire, despite control efforts. It is therefore necessary to understand all the factors involved in the development of the disease, including biotic and abiotic factors. The aim of this study was to examine the factors that could support the maintenance of the intermediate host and its vectorial capacity in western Côte d'Ivoire.MethodsData on river physicochemical, microbiological, and climatic parameters, the presence or absence of snails with Schistosoma mansoni, and human infections were collected between January 2020 and February 2021. Spearman rank correlation tests, Mann–Whitney, analysis of variance (ANOVA), and an appropriate model selection procedure were used to analyze the data.ResultsThe overall prevalence of infected snails was 56.05%, with infection reaching 100% in some …

Ian Matthews

Ian Matthews

Royal Holloway, University of London

Earth System Science Data

Tephra data from varved lakes of the Last Glacial–Interglacial Transition: towards a global inventory and better chronologies on the Varved Sediments Database (VARDA)

The Varved Sediments Database (VARDA) was launched in 2020 and aimed to establish a community database for annually resolved chronological archives with their associated high-resolution proxy records. This resource would support reproducibility through accessible data for the paleoclimate and modelling communities. In this paper, VARDA has been extended by a dataset of European tephra geochemical data and metadata to enable the synchronisation of varve records during the Last Glacial–Interglacial Transition (LGIT; here defined as 25 to 8 ka; Beckett et al., 2022). Geochemical data from 49 known individual tephra layers across 19 lake records have been included, with Lago di Grande Monticchio being the single biggest contributor of geochemical data with 28 tephra layers. The Vedde Ash and Laacher See tephra are the most common layers found in six different records. This highlights the potential of refining the absolute age estimates for these tephra layers using varve chronologies and for synchronising regional paleoclimate archives. This is the first stage in a 5-year plan funded by the Past Global Changes (PAGES) Data Stewardship Scholarship to incorporate a global dataset of tephra geochemical data into varve records. Further stages of this project will focus on different regions and timescales. Data collated for this project are available open access at https://doi. org/10.5880/fidgeo. 2023.015 (Beckett et al., 2022).

Annette MacLeod

Annette MacLeod

University of Glasgow

medRxiv

APOL1 variants G1, G2 and N264K affect APOL1 plasma protein concentration: a UK Biobank study

Background APOL1 variants G1 and G2 are common in populations with recent sub-Saharan African ancestry. They are known to influence health conditions: most notably being associated with protection from human African trypanosomiasis and increased risk of susceptibility to chronic kidney disease. Association studies have often considered G1 and G2 as equivalent, however we recently presented evidence of substantial phenotypic differences between carriers of the two variants. An additional APOL1 variant, N264K, has previously been shown to modify the damaging effect of G2 on the kidney. Here, we examine the influence of these variants on APOL1 protein concentration. Methods Using a cohort of 1,050 UK Biobank participants with recent African ancestry, we compared APOL1 protein concentration in carriers of variants G1, G2, and N264K and performed a genome-wide association study to identify additional modifiers of APOL1 concentration. We also compared APOL1 concentration across self-reported ethnicities for all 43,330 UK Biobank participants for whom APOL1 concentration data was available. Findings APOL1 G1 and G2 are both associated with increased APOL1 protein concentration, however the effect of G2 is more marked, and it was the only locus that reached genome-wide significance in terms of association with APOL1 concentration (p = 3x10-155). In a G2 background, the presence of N264K is associated with a reduction in APOL1 concentration (p = 6 x 10-5). People with self-reported Black or Black British ethnicity have higher APOL1 concentrations all other self-reported ethnicities in the UK Biobank …

Annette MacLeod

Annette MacLeod

University of Glasgow

Scientific Reports

An easy to use tool for the analysis of subcellular mRNA transcript colocalisation in smFISH data

Single molecule fluorescence in situ hybridisation (smFISH) has become a valuable tool to investigate the mRNA expression of single cells. However, it requires a considerable amount of programming expertise to use currently available open-source analytical software packages to extract and analyse quantitative data about transcript expression. Here, we present FISHtoFigure, a new software tool developed specifically for the analysis of mRNA abundance and co-expression in QuPath-quantified, multi-labelled smFISH data. FISHtoFigure facilitates the automated spatial analysis of transcripts of interest, allowing users to analyse populations of cells positive for specific combinations of mRNA targets without the need for computational image analysis expertise. As a proof of concept and to demonstrate the capabilities of this new research tool, we have validated FISHtoFigure in multiple biological systems. We used …

Annette MacLeod

Annette MacLeod

University of Glasgow

Nature Communications

Publisher Correction: IL-17 signalling is critical for controlling subcutaneous adipose tissue dynamics and parasite burden during chronic murine Trypanosoma brucei infection

Publisher Correction: IL-17 signalling is critical for controlling subcutaneous adipose tissue dynamics and parasite burden during chronic murine Trypanosoma brucei infection - PMC Back to Top Skip to main content NIH NLM Logo Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation Search PMC Full-Text Archive Search in PMC Advanced Search User Guide Journal List Nat Commun PMC10901872 Other Formats PDF (373K) Actions Cite Collections Share Permalink Copy RESOURCES Similar articles Cited by other articles Links to NCBI Databases Journal List Nat Commun PMC10901872 As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply endorsement of, or agreement with, the contents by NLM or the National Institutes of Health. Learn more: PMC Disclaimer | PMC Copyright Notice Logo of ncomms Nat Commun. 2024; 15: 1833. …

Annette MacLeod

Annette MacLeod

University of Glasgow

Obesity and Inflammatory Factors in the Progression of Early-Onset Colorectal Cancer

Simple Summary The incidence of colorectal cancer (CRC) in the United States (US) has decreased significantly over the last several decades, but primarily in those 65 years of age and older. However, there has been a dramatic global increase in the incidence of colorectal cancer in patients younger than 50 years old. This cohort is known as early-onset colorectal cancer (EOCRC) and is projected to rise in incidence. This epidemiologic change is poorly understood, but the sharp increase in the incidence of obesity and metabolic dysfunction have been linked to this phenomenon. The aim of our study is to examine the complex inflammatory mechanisms affecting EOCRC, including obesity, hormonal effects, inflammatory processes, and the tumor environment. With an improved understanding of these interactions, new methods to prevent and treat EOCRC could reduce its incidence and prolong survival in affected patients. Abstract Metabolic dysfunction associated with obesity leads to a chronic pro-inflammatory state with systemic effects, including the alteration of macrophage metabolism. Tumor-associated macrophages have been linked to the formation of cancer through the production of metabolites such as itaconate. Itaconate downregulates peroxisome proliferator-activated receptor gamma as a tumor-suppressing factor and upregulates anti-inflammatory cytokines in M2-like macrophages. Similarly, leptin and adiponectin also influence macrophage cytokine expression and contribute to the progression of colorectal cancer via changes in gene expression within the PI3K/AKT pathway. This pathway …

Annette MacLeod

Annette MacLeod

University of Glasgow

Surgery

Long-term behavior and functional outcomes of ileal-pouch anal anastomosis in inflammatory bowel disease with changing phenotype

BackgroundIleal-pouch-anal anastomosis is the operation of choice after proctocolectomy for ulcerative colitis; some patients will develop Crohn’s disease. We aim to determine long-term behavior and outcomes of inflammatory bowel disease–ileal-pouch-anal anastomosis after colectomy, where a specialist gastrointestinal pathologist re-evaluated the initial colectomy specimen.MethodsPatients with inflammatory bowel disease–ileal-pouch-anal anastomosis were identified from a single-surgeon prospective database containing 1,165 patients accrued from 1991 to 2017 and invited to complete pouch-function and quality-of-life assessments. Medical records were used to obtain clinical outcomes and subjective functional assessments for those unable to be contacted. Data were compared between patients with and without histological assessment disagreement and subsequent inflammatory bowel disease …

Annette MacLeod

Annette MacLeod

University of Glasgow

PLoS neglected tropical diseases

Differences in gene expression profiles in early and late stage rhodesiense HAT individuals in Malawi

T. b. rhodesiense is the causative agent of Rhodesian human African trypanosomiasis (r-HAT) in Malawi. Clinical presentation of r-HAT in Malawi varies between foci and differs from East African HAT clinical phenotypes. The purpose of this study was to gain more insights into the transcriptomic profiles of patients with early stage 1 and late stage 2 HAT disease in Malawi. Whole blood from individuals infected with T. b. rhodesiense was used for RNA-Seq. Control samples were from healthy trypanosome negative individuals matched on sex, age range, and disease foci. Illumina sequence FASTQ reads were aligned to the GRCh38 release 84 human genome sequence using HiSat2 and differential analysis was done in R Studio using the DESeq2 package. XGR, ExpressAnalyst and InnateDB algorithms were used for functional annotation and gene enrichment analysis of significant differentially expressed genes. RNA-seq was done on 23 r-HAT case samples and 28 healthy controls with 7 controls excluded for downstream analysis as outliers. A total of 4519 genes were significant differentially expressed (p adjusted <0.05) in individuals with early stage 1 r-HAT disease (n = 12) and 1824 genes in individuals with late stage 2 r-HAT disease (n = 11) compared to controls. Enrichment of innate immune response genes through neutrophil activation was identified in individuals with both early and late stages of the disease. Additionally, lipid metabolism genes were enriched in late stage 2 disease. We further identified uniquely upregulated genes (log2 Fold Change 1.4–2.0) in stage 1 (ZNF354C) and stage 2 (TCN1 and MAGI3) blood. Our data add …

Annette MacLeod

Annette MacLeod

University of Glasgow

FLAgellum Member 8 modulates extravasation and extravascular distribution of African trypanosomes

In the mammalian host, the biology of tissue-dwelling Trypanosoma brucei parasites is not completely understood, especially the mechanisms involved in their extravascular colonization. The trypanosome flagellum is an essential organelle in multiple aspects of the parasites’ development. The flagellar protein termed FLAgellar Member 8 (FLAM8) acts as a docking platform for a pool of Cyclic AMP response protein 3 (CARP3) that is involved in signaling. FLAM8 exhibits a stage-specific distribution suggesting specific functions in the mammalian and vector stages of the parasite. Analyses of knockdown and knockout trypanosomes in their mammalian forms demonstrated that FLAM8 is not essential in vitro for survival, growth, motility and stumpy differentiation. Functional investigations in experimental infections showed that FLAM8-deprived trypanosomes can establish and maintain an infection in the blood circulation and differentiate into insect transmissible forms. However, quantitative bioluminescence imaging and gene expression analysis revealed that FLAM8-null parasites exhibit a significantly impaired dissemination in the extravascular compartment, that is restored by the addition of a single rescue copy of FLAM8. In vitro trans-endothelial migration assays revealed significant defects in trypanosomes lacking FLAM8, possibly due to cAMP signaling impairments when a pool of CARP3 is not stabilized within FLAM8-related scaffold. FLAM8 is the first flagellar component shown to modulate T. brucei distribution in the host tissues, possibly through sensing functions, contributing to the maintenance of extravascular parasite populations in …

Annette MacLeod

Annette MacLeod

University of Glasgow

Unmet Challenges in Patients with Crohn’s Disease

Patients with Crohn’s disease can present with a variety of clinical manifestations; treatment strategies should focus on long-term remission and improvement of quality of life. There is no standardized process of diagnosing, predicting prognosis, and treating the disease. This narrative review was based on a literature search using PubMed, Embase, and Science Direct. Data on unmet challenges in patients with Crohn’s disease were extracted from identified manuscripts. The aim was to discuss present research on standardized processes in the management of patients with Crohn’s disease and to identify the unmet needs in clinical evaluation and treatment approaches. There is no consensus on standardized diagnostic, treatment, and surveillance algorithms, particularly in assessing complications of Crohn’s, such as stricturing disease, intestinal cancer risk, and cutaneous manifestations. Complications and treatment failure rates of conventional, interventional, and surgical therapy place emphasis on the need for standardized treatment algorithms, particularly in the case of acute complications of the disease. Research on standardized clinical approaches, reliable biomarkers for disease diagnosis and therapy monitoring, and new treatment agents is necessary to improve therapy and reduce complications in patients with Crohn’s disease.

Annette MacLeod

Annette MacLeod

University of Glasgow

Cancer Medicine

Anti‐inflammatory mechanisms in cancer research: Characterization of a distinct M2‐like macrophage model derived from the THP‐1 cell line

Aims Macrophages play an essential role in cancer development. Tumor‐associated macrophages (TAMs) have predominantly M2‐like attributes that are associated with tumor progression and poor patient survival. Numerous methods have been reported for differentiating and polarizing macrophages in vitro, but there is no standardized and validated model for creating TAMs. Primary cells show varying cytokine responses depending on their origin and functional studies utilizing these cells may lack generalization and validity. A distinct cell line‐derived TAM‐like M2 subtype is required to investigate the mechanisms mediated by anti‐inflammatory TAMs in vitro. Our previous work demonstrated a standardized protocol for creating an M2 subtype derived from a human THP‐1 cell line. The cell expression profile, however, has not been validated. The aim of this study was to characterize and validate the TAM‐like …

Annette MacLeod

Annette MacLeod

University of Glasgow

The Lancet Gastroenterology & Hepatology

Neutralising antibody potency against SARS-CoV-2 wild-type and omicron BA. 1 and BA. 4/5 variants in patients with inflammatory bowel disease treated with infliximab and …

BackgroundAnti-TNF drugs, such as infliximab, are associated with attenuated antibody responses after SARS-CoV-2 vaccination. We aimed to determine how the anti-TNF drug infliximab and the anti-integrin drug vedolizumab affect vaccine-induced neutralising antibodies against highly transmissible omicron (B.1.1.529) BA.1, and BA.4 and BA.5 (hereafter BA.4/5) SARS-CoV-2 variants, which possess the ability to evade host immunity and, together with emerging sublineages, are now the dominating variants causing current waves of infection.MethodsCLARITY IBD is a prospective, multicentre, observational cohort study investigating the effect of infliximab and vedolizumab on SARS-CoV-2 infection and vaccination in patients with inflammatory bowel disease (IBD). Patients aged 5 years and older with a diagnosis of IBD and being treated with infliximab or vedolizumab for 6 weeks or longer were recruited from …

Annette MacLeod

Annette MacLeod

University of Glasgow

Infection, Genetics and Evolution

Association between polymorphisms of IL4, IL13, IL10, STAT6 and IFNG genes, cytokines and immunoglobulin E levels with high burden of Schistosoma mansoni in children from …

Eliminating schistosomiasis as a public health problem by 2030 requires a better understanding of the disease transmission, especially the asymmetric distribution of worm burden in individuals living and sharing the same environment. It is in this light that this study was designed to identify human genetic determinants associated with high burden of S. mansoni and also with the plasma concentrations of IgE and four cytokines in children from two schistosomiasis endemic areas of Cameroon. In school-aged children of schistosomiasis endemic areas of Makenene and Nom-Kandi of Cameroon, S. mansoni infections and their infection intensities were evaluated in urine and stool samples using respectively the Point-of-care Circulating Cathodic Antigen test (POC-CCA) and the Kato Katz (KK) test. Thereafter, blood samples were collected in children harbouring high burden of schistosome infections as well as in their …

Annette MacLeod

Annette MacLeod

University of Glasgow

PLoS Biology

The murine meninges acquire lymphoid tissue properties and harbour autoreactive B cells during chronic Trypanosoma brucei infection

The meningeal space is a critical brain structure providing immunosurveillance for the central nervous system (CNS), but the impact of infections on the meningeal immune landscape is far from being fully understood. The extracellular protozoan parasite Trypanosoma brucei, which causes human African trypanosomiasis (HAT) or sleeping sickness, accumulates in the meningeal spaces, ultimately inducing severe meningitis and resulting in death if left untreated. Thus, sleeping sickness represents an attractive model to study immunological dynamics in the meninges during infection. Here, by combining single-cell transcriptomics and mass cytometry by time-of-flight (CyTOF) with in vivo interventions, we found that chronic T. brucei infection triggers the development of ectopic lymphoid aggregates (ELAs) in the murine meninges. These infection-induced ELAs were defined by the presence of ER-TR7+ fibroblastic reticular cells, CD21/35+ follicular dendritic cells (FDCs), CXCR5+ PD1+ T follicular helper-like phenotype, GL7+ CD95+ GC-like B cells, and plasmablasts/plasma cells. Furthermore, the B cells found in the infected meninges produced high-affinity autoantibodies able to recognise mouse brain antigens, in a process dependent on LTβ signalling. A mid-throughput screening identified several host factors recognised by these autoantibodies, including myelin basic protein (MBP), coinciding with cortical demyelination and brain pathology. In humans, we identified the presence of autoreactive IgG antibodies in the cerebrospinal fluid (CSF) of second stage HAT patients that recognised human brain lysates and MBP, consistent with our …

2023/11/20

Article Details
Annette MacLeod

Annette MacLeod

University of Glasgow

bioRxiv

Transcriptome profiles of Tb rhodesiense in Malawi reveal focus specific gene expression Profiles associated with pathology

Background Sleeping sickness caused by T.b. rhodesiense is a fatal disease and endemic in Southern and Eastern Africa. There is an urgent need to develop novel diagnostic and control tools in order to achieve elimination of rhodesiense sleeping sickness which might be achieved through a better understanding of trypanosome gene expression and genetics using endemic isolates. Here, we describe transcriptome profiles and population structure of endemic T.b. rhodesienseisolates in human blood in Malawi. Methodology Blood samples of r-HAT cases from Nkhotakota and Rumphi foci were collected in PaxGene tubes for RNA extraction before initiation of r-HAT treatment. 100 million reads were obtained per sample, reads were initially mapped to the human genome reference GRCh38 using HiSat2 and then the unmapped reads were mapped against Trypanosoma brucei reference transcriptome …

Annette MacLeod

Annette MacLeod

University of Glasgow

State-of-the-art surgery for Crohn’s disease: part III-perianal Crohn’s disease

PurposeDiagnosis and treatment of perianal Crohn’s disease is challenging and requires its own domain of therapy. Different types of perianal disease require a spectrum of treatment strategies. Treatment options range from conservative therapy, including immunosuppressives, biologics, or stem cell therapy, to surgical treatment with specific indications depending on the underlying lesion. This is part III of the series “state-of-the-art surgery for Crohn’s disease,” focusing on the management of perianal disease. We discuss the definition and diagnosis of perianal Crohn’s disease, the treatment of perianal lesions, and specific surgical indications and techniques.Results and conclusionPitfalls and complications play a substantial role in the treatment of perianal Crohn’s disease, and surgical therapy may fail. Realistic treatment goals and an individual patient-oriented treatment approach are crucial in the treatment of …

John Lowe

John Lowe

Royal Holloway, University of London

BMC medical research methodology

The development and acceptability of an educational and training intervention for recruiters to neonatal trials: the TRAIN project

BackgroundSuboptimal or slow recruitment affects 30–50% of trials. Education and training of trial recruiters has been identified as one strategy for potentially boosting recruitment to randomised controlled trials (hereafter referred to as trials). The Training tRial recruiters, An educational INtervention (TRAIN) project was established to develop and assess the acceptability of an education and training intervention for recruiters to neonatal trials. In this paper, we report the development and acceptability of TRAIN.MethodsTRAIN involved three sequential phases, with each phase contributing information to the subsequent phase(s). These phases were 1) evidence synthesis (systematic review of the effectiveness of training interventions and a content analysis of the format, content, and delivery of identified interventions), 2) intervention development using a Partnership (co-design/co-creation) approach, and 3 …

2023/11/11

Article Details
John Lowe

John Lowe

Royal Holloway, University of London

Land

Testing the effect of relative pollen productivity on the REVEALS model: A validated reconstruction of Europe-Wide Holocene vegetation

Reliable quantitative vegetation reconstructions for Europe during the Holocene are crucial to improving our understanding of landscape dynamics, making it possible to assess the past effects of environmental variables and land-use change on ecosystems and biodiversity, and mitigating their effects in the future. We present here the most spatially extensive and temporally continuous pollen-based reconstructions of plant cover in Europe (at a spatial resolution of 1° × 1°) over the Holocene (last 11.7 ka BP) using the ‘Regional Estimates of VEgetation Abundance from Large Sites’ (REVEALS) model. This study has three main aims. First, to present the most accurate and reliable generation of REVEALS reconstructions across Europe so far. This has been achieved by including a larger number of pollen records compared to former analyses, in particular from the Mediterranean area. Second, to discuss methodological issues in the quantification of past land cover by using alternative datasets of relative pollen productivities (RPPs), one of the key input parameters of REVEALS, to test model sensitivity. Finally, to validate our reconstructions with the global forest change dataset. The results suggest that the RPPs.st1 (31 taxa) dataset is best suited to producing regional vegetation cover estimates for Europe. These reconstructions offer a long-term perspective providing unique possibilities to explore spatial-temporal changes in past land cover and biodiversity.

John Lowe

John Lowe

Royal Holloway, University of London

Acknowledgment to the Reviewers of Quaternary in 2022

High-quality academic publishing is built on rigorous peer review. Quaternary was able to uphold its high standards for published papers due to the outstanding efforts of our reviewers. Thanks to the efforts of our reviewers in 2022, the median time to first decision was 28.5 days and the median time to publication was 94 days. Regardless of whether the articles they examined were ultimately published, the editors would like to express their appreciation and thank the following reviewers for the time and dedication that they have shown Quaternary: