Genetic diversity of the Plasmodium falciparum GTP-cyclohydrolase 1, dihydrofolate reductase and dihydropteroate synthetase genes reveals new insights into sulfadoxine-pyrimethamine antimalarial drug resistance

Plasmodium falciparum parasites resistant to antimalarial treatments have hindered malaria disease control. Sulfadoxine-pyrimethamine (SP) was used globally as a first-line treatment for malaria after wide-spread resistance to chloroquine emerged and, although replaced by artemisinin combinations, is currently used as intermittent preventive treatment of malaria in pregnancy and in young children as part of seasonal malaria chemoprophylaxis in sub-Saharan Africa. The emergence of SP-resistant parasites has been predominantly driven by cumulative build-up of mutations in the dihydrofolate reductase (pfdhfr) and dihydropteroate synthetase (pfdhps) genes, but additional amplifications in the folate pathway rate-limiting pfgch1 gene and promoter, have recently been described. However, the genetic make-up and prevalence of those amplifications is not fully understood. We analyse the whole genome sequence data of 4,134 P. falciparum isolates across 29 malaria endemic countries, and reveal that the pfgch1 gene and promoter amplifications have at least ten different forms, occurring collectively in 23% and 34% in Southeast Asian and African isolates, respectively. Amplifications are more likely to be present in isolates with a greater accumulation of pfdhfr and pfdhps substitutions (median of 1 additional mutations; P<0.00001), and there was evidence that the frequency of pfgch1 variants may be increasing in some African populations, presumably under the pressure of SP for chemoprophylaxis and anti-folate containing antibiotics used for the treatment of bacterial infections. The selection of P. falciparum with pfgch1 amplifications may enhance the fitness of parasites with pfdhfr and pfdhps substitutions, potentially threatening the efficacy of this regimen for prevention of malaria in vulnerable groups. Our work describes new pfgch1 amplifications that can be used to inform the surveillance of SP drug resistance, its prophylactic use, and future experimental work to understand functional mechanisms.     

The historical context of contemporary climatic adaptation: a case study in the climatically dynamic and environmentally complex southwestern United States

The process of adaptation can be highly dependent upon historical and contemporary factors, especially in environmentally and topographically complex regions affected by Pleistocene glaciations. Here, we investigate Hilaria jamesii (Poaceae), a dryland C₄ graminoid, to test how patterns of adaptive genetic variation are linked to its glacial and post-glacial history. We show that the species persisted in a single, southern refugium during the last glacial period and subsequently migrated throughout its current distribution concurrent with post-glacial warming. The species’ putative adaptive genetic variation correlates with climatic gradients (e.g. monsoon precipitation and mean diurnal temperature range) that covary with the species’ probable route of demographic expansion. The short timescale and multiple climatic dimensions of adaptation imply that natural selection acted primarily upon standing genetic variation. These findings suggest that restoration and conservation practices should prioritize the maintenance of standing genetic variation to ensure that species have the capacity to respond to future environmental changes.     

Assessing land use and land cover change in coastal urban wetlands of international importance in Ghana using Intensity Analysis

Wetlands Ecology and Management - In the era of global environmental change, land transformation is acknowledged as a critical subject that needs to be addressed. Even though some studies have been...     

Intraspecific competition and aggression for shells in the hermit crab Pagurus samuel1s

Many studies have investigated shell‐related behaviour in hermit crabs. Few studies, however, have focused specifically on the intraspecies aggression associated with shell competition. We examined intraspecies aggression in hermit crab (Pagurus samuelis) pairs as it relates to competition for a limiting resource, gastropod shells. Pairs of hermit crabs were observed in the laboratory in four different treatments that varied the presence or absence of shells for one or both of the crabs. Measurements of the latency to respond, the number of bouts, and the fight durations were recorded. There was a significant difference among treatments for all three measurements, and naked hermit crabs were much more aggressive than housed hermit crabs. There was no significant difference in aggression between males and females in any of the three treatments. The heightened aggression observed in naked P. samuelis is likely in service of acquiring a protective shell.     

Neighboring Parenchyma Cells Contribute to Arabidopsis Xylem Lignification,while Lignification of Interfascicular Fibers Is Cell Autonomous

Lignin is a critical structural component of plants, providing vascular integrity and mechanical strength. Lignin precursors (monolignols) must be exported to the extracellular matrix where random oxidative coupling produces a complex lignin polymer. The objectives of this study were twofold: to determine the timing of lignification with respect to programmed cell death and to test if nonlignifying xylary parenchyma cells can contribute to the lignification of tracheary elements and fibers. This study demonstrates that lignin deposition is not exclusively a postmortem event, but also occurs prior to programmed cell death. Radiolabeled monolignols were not detected in the cytoplasm or vacuoles of tracheary elements or neighbors. To experimentally define which cells in lignifying tissues contribute to lignification in intact plants, a microRNA against CINNAMOYL CoA-REDUCTASE1 driven by the promoter from CELLULOSE SYNTHASE7 (ProCESA7:miRNA CCR1) was used to silence monolignol biosynthesis specifically in cells developing lignified secondary cell walls. When monolignol biosynthesis in ProCESA7:miRNA CCR1 lines was silenced in the lignifying cells themselves, but not in the neighboring cells, lignin was still deposited in the xylem secondary cell walls. Surprisingly, a dramatic reduction in cell wall lignification of extraxylary fiber cells demonstrates that extraxylary fibers undergo cell autonomous lignification.     

Voltage-sensitive chloride ion channels in Anopheles gambiae Sua-1B cells

In this study, we performed electrophysiological analysis of Anopheles gambiae Sua-1B cells having “neuron-like” morphologies using the patch clamp method. The recorded cells (n = 79) had processes resembling axons/dendrites, with 63 % unipolar, 22 % bipolar, and 15 % multipolar. While no inward currents were observed following step depolarizations (holding potential = ?80 mV), a slowly activating outward current was observed in 96 % of the cells, especially at depolarized potentials. The amplitude of the current was attenuated nearly 70 % by reducing extracellular Cl^? ion concentration, or by incubating with 100 μM DIDS, a known voltage-sensitive chloride channel blocker, suggesting that the current was mediated by chloride ions. No qualitative difference was found between recordings made with Cs⁺ ions in the intracellular pipette solution (inhibits K⁺ currents) and those made with normal physiological solution, indicating a deficiency of potassium channels. Additionally, recordings made with Ca²⁺-free extracellular bath solution eliminated the slowly activating outward current. A subset of cells (n = 3) lacked this current, but had outward currents with voltage-dependent properties similar to those of volume-regulated chloride channels. Taken together, our results suggest that the voltage-sensitive currents observed in the majority of Sua-1B cells are mediated primarily by chloride channels of the calcium-dependent subtype.