Identification of two insecticide resistance markers in Ethiopian Anopheles stephensi mosquitoes using a multiplex amplicon sequencing assay
Holly Acford-Palmer, Jody E Phelan, Fitsum G Tadesse, Mojca Kristan, Emma Collins, Anton Spadar, Thomas Walker, Teun Bousema, Louisa A Messenger, Taane G Clark & Susana Campino
Since its first detection in 2012 in Djibouti, Anopheles stephensi has invaded and established in the Horn of Africa, and more recently Nigeria. The expansion of this vector poses a significant threat to malaria control and elimination efforts. Integrated vector management is the primary strategy used to interrupt disease transmission; however, growing insecticide resistance is threatening to reverse gains in global malaria control. We present a next-generation amplicon-sequencing approach, for high-throughput monitoring of insecticide resistance genes (ace1, GSTe2, vgsc and rdl), species identification and characterization of genetic diversity (its2 and cox1) in An. stephensi. Overall, we present a reliable, cost-effective strategy using amplicon-sequencing to monitor known insecticide resistance mutations, with the potential to identify new genetic variants, to assist in the high-throughput surveillance of insecticide resistance in An. stephensi populations.
RWP-RK Domain 3 (OsRKD3) induces somatic embryogenesis in black rice
Yekti Asih Purwestri, Yang-Seok Lee, Cathal Meehan, Windi Mose, Febri Adi Susanto, Putri Wijayanti, Anisa Nazera Fauzia, Tri Rini Nuringtyas, Nosheen Hussain, Hadi Lanang Putra & Jose Gutierrez-Marcos
Plants have the unique capability to form embryos from both gametes and somatic cells, with the latter process known as somatic embryogenesis. Somatic embryogenesis (SE) can be induced by exposing plant tissues to exogenous growth regulators or by the ectopic activation of embryogenic transcription factors. Our study demonstrates that the ectopic overexpression of OsRKD3, which is expressed preferentially in reproductive tissues, can trigger the formation of somatic embryos in an Indonesian black rice landrace (Cempo Ireng) that is normally resistant to somatic embryogenesis. Furthermore, OsRKD3 was shown to mediate the transcriptional activation of a discrete gene network, which includes several transcription factors such as APETALA 2-like (AP2-like)/ETHYLENE RESPONSE FACTOR (ERF), MYB and CONSTANS-like (COL), and chromatin remodeling factors associated with hormone signal transduction, stress responses and post-embryonic pathways. Our data show that OsRKD3 modulates an extensive gene network and its activation is associated with the initiation of a somatic embryonic program that facilitates genetic transformation in black rice. These findings hold substantial promise for improving crop productivity and advancing agricultural practices in black rice.
Bacterial catabolism of membrane phospholipids links marine biogeochemical cycles
Linda M. Westermann, Ian D. E. A. Lidbury Chun-Yang Li, Ning Wang, Andrew R. J. Murphy, Maria del Mar Aguilo Ferretjans, Mussa Quareshy, Muralidharan Shanmugan , Alberto Torcello-Requena, Eleonora Silvano, Yu-Zhong Zhang, Claudia A. Blindauer, Yin Chen, David J. Scanlan
In marine systems, the availability of inorganic phosphate can limit primary production leading to bacterial and phytoplankton utilization of the plethora of organic forms available. Among these are phospholipids that form the lipid bilayer of all cells as well as released extracellular vesicles. However, information on phospholipid degradation is almost nonexistent despite their relevance for biogeochemical cycling. Here, we identify complete catabolic pathways for the degradation of the common phospholipid headgroups phosphocholine (PC) and phosphorylethanolamine (PE) in marine bacteria.
The carbon footprint of products used in five common surgical operations: identifying contributing products and processes
Chantelle Rizan, Robert Lillywhite, Malcolm Reed, Mahmood F Bhutta
The aim of this study was to evaluate the carbon footprint of products used within five common operations, and to identify the biggest contributors (hotspots). We determined the carbon footprint of the products used in each of the five operations, alongside greatest contributors through analysis of individual products and of underpinning processesAcross the five operations, 23% of product types were responsible for 80% of the operation carbon footprint. Mean average contribution from production of single-use items was 54%, decontamination of reusables 20%, waste disposal of single-use items 8%, production of packaging for single-use items 6% and linen laundering 6%. Change in practice and policy should be targeted towards those products making greatest contribution, and should include reducing single-use items and switching to reusables, alongside optimising processes for decontamination and waste disposal, modelled to reduce carbon footprint of these operations by 23%-42%.
Penicillin Binding Protein Substitutions Cooccur with Fluoroquinolone Resistance in Epidemic Lineages of Multidrug-Resistant Clostridioides difficile
Dingle KE, Freeman J, Didelot X, Quan TP, Eyre DW, Swann J, Spittal WD, Clark EV, Jolley KA, Walker AS, Wilcox MH
Clostridioides difficile remains a key cause of healthcare-associated infection, with multidrug-resistant (MDR) lineages causing high-mortality (≥20%) outbreaks. Cephalosporin treatment is a long-established risk factor, and antimicrobial stewardship is a key control. A mechanism underlying raised cephalosporin MICs has not been identified in C. difficile, but among other species, this is often acquired via amino acid substitutions in cell wall transpeptidases (penicillin binding proteins [PBPs]). Here, we investigated five C. difficile transpeptidases (PBP1 to PBP5) for recent substitutions, associated cephalosporin MICs, and co-occurrence with fluoroquinolone resistance. Here, we identify a mechanism associated with raised cephalosporin MICs in C. difficile comprising amino acid substitutions in two cell wall transpeptidase enzymes (penicillin binding proteins). Our study identifies a mechanism that may explain the contribution of cephalosporin stewardship to resolving outbreak conditions. However, due to the co-occurrence of raised cephalosporin MICs and fluoroquinolone resistance, further work is needed to determine the relative importance of each.
Tau in cerebrospinal fluid induces neuronal hyperexcitability and alters hippocampal theta oscillations
Jessica Brown, Elena Camporesi, Juan Lantero-Rodriguez, Maria Olsson, Alice Wang, Blanca Medem, Henrik Zetterberg, Kaj Blennow, Thomas K. Karikari, Mark Wall and Emily Hill
Alzheimer’s disease (AD) and other tauopathies are characterized by the aggregation of tau into soluble and insoluble forms (including tangles and neuropil threads). In humans, a fraction of both phosphorylated and non-phosphorylated N-terminal to mid-domain tau species, are secreted into cerebrospinal fluid (CSF). Some of these CSF tau species can be measured as diagnostic and prognostic biomarkers, starting from early stages of disease. Here, we have developed and applied a novel approach to examine the electrophysiological effects of CSF from patients with a tau-positive biomarker profile. We demonstrate that CSF-tau mediates an increase in neuronal excitability in single cells. We then observed, at the network level, increased input–output responses and enhanced paired-pulse facilitation as well as an increase in long-term potentiation. Finally, we show that CSF-tau modifies the generation and maintenance of hippocampal theta oscillations, which have important roles in learning and memory and are known to be altered in AD patients. Together, we describe a novel method for screening human CSF-tau to understand functional effects on neuron and network activity, which could have far-reaching benefits in understanding tau pathology, thus allowing for the development of better targeted treatments for tauopathies in the future.