Anterograde trafficking of Toll-like receptors requires the cargo sorting adaptors TMED-2 and 7

Toll-Like Receptors (TLRs) play a pivotal role in immunity by recognising conserved structural features of pathogens and initiating the innate immune response. TLR signalling is subject to complex regulation that remains poorly understood. Here we show that two small type I transmembrane receptors, TMED2 and 7, that function as cargo sorting adaptors in the early secretory pathway are required for transport of TLRs from the ER to Golgi. Protein interaction studies reveal that TMED7 interacts with TLR2, TLR4 and TLR5 but not with TLR3 and TLR9. On the other hand, TMED2 interacts with TLR2, TLR4 and TLR3. Dominant negative forms of TMED7 suppress the export of cell surface TLRs from the ER to the Golgi. By contrast TMED2 is required for the ER-export of both plasma membrane and endosomal TLRs. Together, these findings suggest that association of TMED2 and TMED7 with TLRs facilitates anterograde transport from the ER to the Golgi.     

Mortality rates of desert vegetation during high-intensity drought at Uluru-Kata Tjuta National Park,Central Australia

Precipitation variability and heatwaves are expected to intensify over much of inland Australia under most projected climate change scenarios. This will undoubtedly have impacts on the biota of Australian dryland systems. However, accurate modelling of these impacts is presently impeded by a lack of empirical research on drought/heatwave effects on native arid flora and fauna. During the 2018–2021 Australian drought, many parts of the continent's inland experienced their hottest, driest period on record. Here, we present the results of a field survey in 2021 involving indigenous rangers, scientists and national parks staff who assessed plant dieback during this drought at Ulur u-Kata Tjut a National Park (UKTNP), central Australia. Spatially randomized quadrat sampling of eight common and culturally important plants indicated the following plant death rates across UKTNP (in order of drought susceptibility): desert myrtle (Aluta maisonneuvei subsp. maisonneuvei) (91%), yellow flame grevillea (Grevillea eriostachya) (79%), Maitland's wattle (Acacia maitlandii) (67%), waxy wattle (A. melleodora) (65%), soft spinifex grass (Triodia pungens) (53%), mulga (A. aneura) (42%), desert oak (Allocasuarina decaisneana) (22%) and quandong (Santalum acuminatum) (0%). The sampling also detected that seedling recruitment was absent or minimal for all plants except soft spinifex, while a generalized linear mixed model (GLMM) indicated two-way interactions among species, plant size and stand density as important predictors of drought survival of adult plants. A substantial loss of biodiversity has occurred at UKTNP during the recent drought, with likely drivers of widespread plant mortality being extreme multi-year rainfall deficit (2019 recorded the lowest-ever annual rainfall at UKTNP [27 mm]) and record high summer temperatures (December 2019 recorded the highest-ever temperature [47.1°C]). Our findings indicate that widespread plant death and extensive vegetation restructuring will occur across arid Australia if the severity and frequency of droughts increase under climate change.     

Juvenile proportion as a predictor of freshwater turtle population change

The extreme longevity of turtles and tortoises can make it difficult to determine the conservation status of their populations because high annual adult survival may mask gradual attrition due to low levels of recruitment. When long-term demographic trends are unknown and available data are insufficient for population modelling, it may be assumed that a scarcity of juveniles indicates low recruitment that will result in population ageing and numerical decline. However, the reliability with which the proportion of juveniles foreshadows demographic change is uncertain. We tested the hypothesis that a low proportion of juveniles in a turtle population presages its ageing by analysing over 20 years of survey data for five discrete populations of the Australian western saw-shelled turtle (Myuchelys bellii: Chelidae), a listed threatened species. The analysis tested whether the initial proportion of juvenile turtles in each population was related to its temporal trend in average body size. The five populations had varied structure and trends, with the initial proportion of juvenile turtles ranging from 10% to 39% and average body size increasing over time in some populations and decreasing in others. Contrary to expectation, the initial proportion of juveniles was unrelated to the trend in average body size and, by inference, average age, indicating that effective trend forecasting requires more detailed demographic information than merely population structure.     

Small-scale plant species turnover in a limestone grassland: the carousel model and some comments on the niche concept

Abstract. This study reports on small-scale changes in the distribution of plant species in a 2.5 m² plot of grazed, species-rich Veronica spicata - Avenula pratensis grassland on shallow, dry, nutrient-poor soil in the Great Alvar area (Stora Alvaret) of southern Öland, southeastern Sweden. Multivari-ate analysis of 0.001 m² and 0.25 m² quadrats within the plot showed that there is little floristic variation without any trend in the plot. Average species richness varied little throughout the study period from 1986 to 1991 with 1986 averages of 7.0 on 0.001m², 16.3 on 0.01 m², and 26.1 on 0.25 m². On 0.001 m²the highest species number found was 12, on 0.01 m², 27. However, cumulative species richness, i.e. species number in the first year plus new species appearing in later years (averaged over 40 quadrats) increased over the same period, on 0.001 m² from 7.0 in 1986 to 14.9 in 1991, and on 0.01 m² from 16.3 to 24.1. Cumulative frequency, i.e. number of quadrats out of 40 where a species occurred in the first year or/and in later years, increased as well; the number of cumulatively highly frequent (> 80%) species increased from 5 in 1986 to 18 in 1991. Species mobility on the scale of the small quadrats used implies both appearance and disappearance from these quadrats. Using six examples, species mobility is shown to vary individualistically, both in rate and degree. We postulate that in homogeneous, grazed, nutrient- and water-deficient environments many species can reach virtually all microsites within the plot, which we express through the idea of the ‘carousel model’. We also question the usefulness of the niche concept and re-interpret it by stating that all species of this plant community have the same habitat niche, while most of them are short-lived and have the same regeneration niche. The essential variation amongst the species is their individual ability to establish or re-establish by making use of favourable conditions appearing in microsites in an unknown, complex spatio-temporal pattern.     

Use of 31P magnetisation transfer magnetic resonance spectroscopy to measure ATP changes after 670 nm transcranial photobiomodulation in older adults

Mitochondrial function declines with age, and many pathological processes in neurodegenerative diseases stem from this dysfunction when mitochondria fail to produce the necessary energy required. Photobiomodulation (PBM), long-wavelength light therapy, has been shown to rescue mitochondrial function in animal models and improve human health, but clinical uptake is limited due to uncertainty around efficacy and the mechanisms responsible. Using ³¹P magnetisation transfer magnetic resonance spectroscopy (MT-MRS) we quantify, for the first time, the effects of 670 nm PBM treatment on healthy ageing human brains. We find a significant increase in the rate of ATP synthase flux in the brain after PBM in a cohort of older adults. Our study provides initial evidence of PBM therapeutic efficacy for improving mitochondrial function and restoring ATP flux with age, but recognises that wider studies are now required to confirm any resultant cognitive benefits.     

Knockdown resistance (kdr) to DDT and pyrethroid insecticides maps to a sodium channel gene locus in the housefly (Musca domestica)

The voltage-sensitive sodium channel is generally regarded as the primary target site of dichlorodiphenyl-trichloro-ethane (DDT) and pyrethroid insecticides, and has been implicated in the widely reported mechanism of nerve insensitivity to these compounds. This phenomenon is expressed as knockdown resistance (kdr) and has been best characterised in the housefly where several putative alleles, including the more potent super-kdr factor, have been identified. We report the isolation of cDNA clones containing part of a housefly sodium channel gene, designated Msc, which show close homology to the para sodium channel of Drosophila (99% amino acid identity within the region of overlap). Using Southern blots of insect DNA, restriction fragment length polymorphisms (RFLPs) at the Msc locus were identified in susceptible, kdr and super-kdr housefly strains. These RFLPs showed tight linkage to resistance in controlled crosses involving these strains, thus providing clear genetic evidence that kdr, and hence pyrethroid mode of action, is closely associated with the voltage-sensitive sodium channel.     

Apoptosis: suicide, execution or murder?

Apoptosis, a controlled form of cell death, appears to be regulated in several ways. Early studies indicated that de novo protein synthesis was required for apoptosis of thymocytes, but more recent studies have found that other cells can undergo apoptosis when protein synthesis is blocked or that inhibition of protein or RNA synthesis can induce apoptosis. Whether these findings reflect distinct forms of apoptosis or variations on a single pathway is not yet known. In this article the case for a single pathway to apoptosis, accessible at multiple points, is discussed.     

Protein folding in the cell: molecular chaperones pave the way

In vitro, many unfolded polypeptides are able to fold to the native state spontaneously, indicating that the amino acid sequence of a protein contains all the information necessary to specify its three-dimensional conformation. It had been assumed that protein folding in vivo also generally occurs in a spontaneous process. This view has changed only recently due to the discovery of a number of proteins, now commonly called 'molecular chaperones', which are essential for cellular protein folding and occur ubiquitously in eubacteria, archaebacteria and in eukaryotic cells.