During the last centuries, humans have transformed global ecosystems. With their temporal dimension, herbaria provide the otherwise scarce long-termdata crucial for trackin gecological and ...evolutionary changes over this period of intense global change. The sheer size of herbaria, together with their increasing digitization and the possibility of sequencing DNA from the preserved plant material, makes them invaluable resources for understanding ecological and evolutionary species’ responses to global environmental change. Following the chronology of global change, we highlight how herbaria can inform about long-term effects on plants of at least four of the main drivers of global change: pollution, habitat change, climate change and invasive species. We summarize how herbarium specimens so far have been used in global change research, discuss future opportunities and challenges posed by the nature of these data, and advocate for an intensified use of these ‘windows into the past’ for global change research and beyond.
Genetic diversity loss in the Anthropocene Exposito-Alonso, Moises; Booker, Tom R; Czech, Lucas ...
Science (American Association for the Advancement of Science),
09/2022, Letnik:
377, Številka:
6613
Journal Article
Recenzirano
Odprti dostop
Anthropogenic habitat loss and climate change are reducing species' geographic ranges, increasing extinction risk and losses of species' genetic diversity. Although preserving genetic diversity is ...key to maintaining species' adaptability, we lack predictive tools and global estimates of genetic diversity loss across ecosystems. We introduce a mathematical framework that bridges biodiversity theory and population genetics to understand the loss of naturally occurring DNA mutations with decreasing habitat. By analyzing genomic variation of 10,095 georeferenced individuals from 20 plant and animal species, we show that genome-wide diversity follows a mutations-area relationship power law with geographic area, which can predict genetic diversity loss from local population extinctions. We estimate that more than 10% of genetic diversity may already be lost for many threatened and nonthreatened species, surpassing the United Nations' post-2020 targets for genetic preservation.
The RNA exosome is a key 3'-5' exoribonuclease with an evolutionarily conserved structure and function. Its cytosolic functions require the co-factors SKI7 and the Ski complex. Here we demonstrate by ...co-purification experiments that the ARM-repeat protein RESURRECTION1 (RST1) and RST1 INTERACTING PROTEIN (RIPR) connect the cytosolic Arabidopsis RNA exosome to the Ski complex. rst1 and ripr mutants accumulate RNA quality control siRNAs (rqc-siRNAs) produced by the post-transcriptional gene silencing (PTGS) machinery when mRNA degradation is compromised. The small RNA populations observed in rst1 and ripr mutants are also detected in mutants lacking the RRP45B/CER7 core exosome subunit. Thus, molecular and genetic evidence supports a physical and functional link between RST1, RIPR and the RNA exosome. Our data reveal the existence of additional cytosolic exosome co-factors besides the known Ski subunits. RST1 is not restricted to plants, as homologues with a similar domain architecture but unknown function exist in animals, including humans.
As regulators of gene expression in multicellular organisms, microRNAs (miRNAs) are crucial for growth and development. Although a plethora of factors involved in their biogenesis and action in ...Arabidopsis (Arabidopsis thaliana) has been described, these processes and their fine-tuning are not fully understood. Here, we used plants expressing an artificial miRNA target mimic (MIM) to screen for negative regulators of miR156. We identified a new mutant allele of the F-box gene HAWAIIAN SKIRT (HWS; At3G61590), hws-5, as a suppressor of the MIM156-induced developmental and molecular phenotypes. In hws plants, levels of some endogenous miRNAs are increased and their mRNA targets decreased. Plants constitutively expressing full-length HWS—but not a truncated version lacking the F-box domain—display morphological and molecular phenotypes resembling those of mutants defective in miRNA biogenesis and activity. In combination with such mutants, hws loses its delayed floral organ abscission ("skirt") phenotype, suggesting epistasis. Also, the hws transcriptome profile partially resembles those of well-known miRNA mutants hyl1-2, se-3, and ago1-27, pointing to a role in a common pathway. We thus propose HWS as a novel, F-box dependent factor involved in miRNA function.
Species’ responses at the genetic level are key to understanding the long‐term consequences of anthropogenic global change. Herbaria document such responses, and, with contemporary sampling, provide ...high‐resolution time‐series of plant evolutionary change. Characterizing genetic diversity is straightforward for model species with small genomes and a reference sequence. For nonmodel species—with small or large genomes—diversity is traditionally assessed using restriction‐enzyme‐based sequencing. However, age‐related DNA damage and fragmentation preclude the use of this approach for ancient herbarium DNA. Here, we combine reduced‐representation sequencing and hybridization‐capture to overcome this challenge and efficiently compare contemporary and historical specimens. Specifically, we describe how homemade DNA baits can be produced from reduced‐representation libraries of fresh samples, and used to efficiently enrich historical libraries for the same fraction of the genome to produce compatible sets of sequence data from both types of material. Applying this approach to both Arabidopsis thaliana and the nonmodel plant Cardamine bulbifera, we discovered polymorphisms de novo in an unbiased, reference‐free manner. We show that the recovered genetic variation recapitulates known genetic diversity in A. thaliana, and recovers geographical origin in both species and over time, independent of bait diversity. Hence, our method enables fast, cost‐efficient, large‐scale integration of contemporary and historical specimens for assessment of genome‐wide genetic trends over time, independent of genome size and presence of a reference genome.
•Vandetanib enhanced PDT-mediated cytotoxicity through the impairment of NHEJ repair of DNA double strand breaks.•Vandetanib inhibits PDT-induced EGFR-mediated DNA-PKcs activation.•Vandetanib + PDT ...modulates tumour microenvironment through vasculature shutdown, coupled with inhibition of EGFR signalling.•MAPK-ERK1/2 pathway is a potential target to overcome the eventual tumour regrowth post-vandetanib + PDT treatment in HNSCC.
Epidermal growth factor receptor (EGFR) overexpression is characteristic in head and neck cancers and is associated with tumour regrowth following photodynamic therapy (PDT).
We investigated vandetanib, which selectively blocks EGFR and vascular endothelial growth factor receptor-2 (VEGFR-2), to enhance the efficacy of PDT.
We assessed the in vitro therapeutic efficacy of: 1) vandetanib; 2) PDT with the photosensitizer Chlorin e6 (Fotolon®); and 3) combined PDT + vadetanib treatment in CAL-27 oral squamous cell carcinoma (OSCC) cell line by cell viability, γH2AX foci immunostaining, cell cycle arrest and western blot. We also performed in vivo tumour regression study and immunohistochemical staining of formalin-fixed paraffin-embedded (FFPE) regressed and regrown tumour tissues.
First, we observed significantly higher cytotoxicity and residual DNA damage in vandetanib + PDT-treated CAL-27 OSCC cells than tumour cells treated with PDT alone. This is due to impaired DNA DSB repair caused by downregulation of EGFR-mediated DNA-dependent protein kinase catalytic subunit (DNA-PKcs) activation. Next, combined vandetanib and PDT resulted in significant tumour growth delay in vivo that is linked to reduction of PDT-induced EGFR phosphorylation and cellular proliferation, along with loss of tumour vasculature. In particular, we observed significant revascularisation of the microenvironment that is associated with upregulated ERK1/2 phosphorylation in regrown tumours post-vandetanib + PDT, thereby corroborating the importance of microenvironmental modification for the observed drug-PDT synergistic interaction.
Taken together, our data suggests that vandetanib enhances the efficacy of PDT through both direct and indirect effects on the cellular DNA repair machinery and tumour microenvironment, respectively.
This study investigates preexisting and vaccine-induced vector immunity in 30 participants of a Phase-1 VSV-EBOV Ebola vaccine trial. No preexisting immunity was detected, however humoral and ...cell-mediated immunity against internal VSV proteins was observed in up to 36% of vaccines.
Abstract
In response to the Ebola virus (EBOV) crisis of 2013–2016, a recombinant vesicular stomatitis virus (VSV)–based EBOV vaccine was clinically tested (NCT02283099). A single-dose regimen of VSV-EBOV revealed a safe and immunogenic profile and demonstrated clinical efficacy. While EBOV-specific immune responses to this candidate vaccine have previously been investigated, limited human data on immunity to the VSV vector are available. Within the scope of a phase 1 study, we performed a comprehensive longitudinal analysis of adaptive immune responses to internal VSV proteins following VSV-EBOV immunization. While no preexisting immunity to the vector was observed, more than one-third of subjects developed VSV-specific cytotoxic T-lymphocyte responses and antibodies.
Background. The Depression Substudy of the Shingles Prevention Study (SPS) was designed to evaluate the association between major depression and immune responses to a high-titer live attenuated ...varicella zoster virus (VZV) vaccine (zoster vaccine), which boosts cell-mediated immunity (CMI) to VZV and decreases the incidence and severity of herpes zoster (HZ). The Depression Substudy was a 2-year longitudinal cohort study in 92 community-dwelling adults ≥60 years of age who were enrolled in the SPS, a large, double-blind, placebo-controlled Veterans Affairs Cooperative zoster vaccine efficacy study. Methods. Forty subjects with major depressive disorder, stratified by use of antidepressant medications, and 52 age- and sex-matched controls with no history of depression or other mental illness had their VZV-CMI measured prior to vaccination with zoster vaccine or placebo and at 6 weeks, 1 year, and 2 years postvaccination. Results. Depressed subjects who were not treated with antidepressant medications had lower levels of VZV-CMI following administration of zoster vaccine than nondepressed controls or depressed subjects receiving antidepressants even when antidepressant medications failed to alter depressive symptom severity (P < .005). Similar results were obtained taking into account the time-varying status of depression and use of antidepressant medications, as well as changes in depressive symptoms, during the postvaccination period. Conclusions. Depressed patients have diminished VZV-CMI responses to zoster vaccine, and treatment with antidepressant medication is associated with normalization of these responses. Because higher levels of VZV-CMI correlate with lower risk and severity of HZ, untreated depression may increase the risk and severity of HZ and reduce the efficacy of zoster vaccine.
HAWAIIAN SKIRT is a cofactor for Arabidopsis thaliana microRNA function and acts in an F
-
box
-
dependent manner.
As regulators of gene expression in multicellular organisms, microRNAs (miRNAs) are ...crucial for growth and development. Although a plethora of factors involved in their biogenesis and action in Arabidopsis (
Arabidopsis thaliana
) has been described, these processes and their fine-tuning are not fully understood. Here, we used plants expressing an artificial miRNA target mimic (MIM) to screen for negative regulators of miR156. We identified a new mutant allele of the F-box gene
HAWAIIAN SKIRT
(
HWS
; At3G61590),
hws
-
5
, as a suppressor of the
MIM156
-induced developmental and molecular phenotypes. In
hws
plants, levels of some endogenous miRNAs are increased and their mRNA targets decreased. Plants constitutively expressing full-length HWS—but not a truncated version lacking the F-box domain—display morphological and molecular phenotypes resembling those of mutants defective in miRNA biogenesis and activity. In combination with such mutants,
hws
loses its delayed floral organ abscission (“skirt”) phenotype, suggesting epistasis. Also, the
hws
transcriptome profile partially resembles those of well-known miRNA mutants
hyl1
-
2
,
se
-
3
, and
ago1
-
27
, pointing to a role in a common pathway. We thus propose HWS as a novel, F-box dependent factor involved in miRNA function.
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