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Blackman, J.

Publications and source records attributed to Blackman, J..

5 recordsLinked to original sources

Are infraslow oscillations the missing link between sleep and Alzheimer's?

INTRODUCTIONLocus coeruleus and glymphatic dysfunction are linked both to Alzheimers disease (AD) and, recently, to infraslow oscillation in sleep spindle (sigma) activity (ISO). Here we hypothesise ISO integrity is a critical link between sleep and AD. METHODSWe analyzed non-rapid eye movement sleep EEG from AD and controls, extracting ISO peak amplitude, intrinsic frequency, and bandwidth from the sigma-power time course. We assessed group differences and correlations with plasma biomarkers (A{beta}42/40, pTau181 and 217, NfL, GFAP). RESULTSISO peak amplitude was significantly reduced in AD, while intrinsic frequency and bandwidth were preserved. ISO peak amplitude positively correlated with A{beta}42/40 ratio, and ISO bandwidth correlated with GFAP and NfL levels, and with lower verbal memory retention. DISCUSSIONSuch selective weakening of ISO in AD is consistent with LC dysfunction and impaired glymphatic cycling. ISO may be a novel mechanism and electrophysiological marker linking sleep microarchitecture to AD pathology.

neuroscience↗

Variable responses of individual species to tropical forest degradation

The functional stability of ecosystems depends greatly on interspecific differences in responses to environmental perturbation. However, responses to perturbation are not necessarily invariant among populations of the same species, so intraspecific variation in responses might also contribute. Such inter-population response diversity has recently been shown to occur spatially across species ranges, but we lack estimates of the extent to which individual populations across an entire community might have perturbation responses that vary through time. We assess this using 524 taxa that have been repeatedly surveyed for the effects of tropical forest logging at a focal landscape in Sabah, Malaysia. Just 39 % of taxa - all with non-significant responses to forest degradation - had invariant responses. All other taxa (61 %) showed significantly different responses to the same forest degradation gradient across surveys, with 6 % of taxa responding to forest degradation in opposite directions across multiple surveys. Individual surveys had low power (< 80 %) to determine the correct direction of response to forest degradation for one-fifth of all taxa. Recurrent rounds of logging disturbance increased the prevalence of intra-population response diversity, while uncontrollable environmental variation and/or turnover of intraspecific phenotypes generated variable responses in at least 44 % of taxa. Our results show that the responses of individual species to local environmental perturbations are remarkably flexible, likely providing an unrealised boost to the stability of disturbed habitats such as logged tropical forests.

ecology↗

Selective logging shows no impact on the dietary breadth of the fawn leaf-nosed bat (Hipposideros cervinus)

Logging activities degrade forest habitats across large areas of the tropics, but the impacts on trophic interactions that underpin forest ecosystems are poorly understood. DNA metabarcoding provides an invaluable tool to investigate such interactions, allowing analysis at a far greater scale and resolution than has previously been possible. We analysed the diet of the insectivorous fawn leaf-nosed bat Hipposideros cervinus across a forest disturbance gradient in Borneo, using a dataset of ecological interactions from an unprecedented number of bat-derived faecal samples. Bats predominantly consumed insects from the orders Lepidoptera, Blattodea, Diptera and Coleoptera, and the taxonomic composition of their diet remained relatively consistent across sites regardless of logging disturbance. There was little difference in the richness of prey consumed in each logging treatment, indicating potential resilience of this species to habitat degradation. In fact, bats consumed a high richness of prey items, and intensive sampling is needed to reliably compare feeding ecology over multiple sites regardless of the bioinformatic procedures used.

ecology↗

Altered structure and stability of bat-prey interaction networks in logged tropical forests revealed by metabarcoding

O_LIHabitat degradation is pervasive across the tropics and is particularly acute in Southeast Asia, with major implications for biodiversity. Much research has addressed the impact of degradation on species diversity; however, little is known about how ecological interactions are altered, including those that constitute important ecosystem functions such as pest consumption. C_LIO_LIWe examined how rainforest degradation alters trophic interaction networks linking insectivorous bats and their prey. We used DNA metabarcoding to study the diets of forest-dwelling insectivorous bat species, and compared bat-prey interaction networks between old growth forest and forest degraded by logging in Sabah, Borneo. C_LIO_LIWe predicted that rainforest degradation would cause measurable reductions in the numbers of prey consumed by individual bats, and that this degradation would yield networks in logged forest with lower functional complementarity, modularity and nestedness than those in old growth forest. C_LIO_LICompared to bats in old growth rainforest, bats in logged sites consumed a lower diversity of prey. Their interaction networks were less nested and had a more modular structure in which bat species had lower closeness centrality scores than in old growth forest. These network structures were associated with reduced network redundancy and thus increased vulnerability to perturbations in logged forests. C_LIO_LIOur results show how ecological interactions change between old growth and logged forests, with potentially negative implications for ecosystem function and network stability. We also highlight the potential importance of insectivorous bats in consuming invertebrate pests. C_LI Malay abstractO_LIDegradasi habitat merupakan suatu fenomena yang berleluasa dikawasan tropika, terutamanya di Asia Tenggara dengan implikasi yang besar ke atas biodiversiti. Banyak kajian telahpun meneliti impak degradasi habitat atas kepelbagaian spesis. Walau bagaimanapun, dari segi mana interaksi ekologi diubah suai kurang diselidik, termasuk interaksi yang membentuk fungsi ekosistem yang penting seperti pemakanan binatang perosak. C_LIO_LIKami telah memeriksa bagaimana degradasi hutan hujan tropika dapat mengubah suai interaksi antara tahap trofik yang menghubungkan kelawar yang memakan serangga dan mangsa mereka. Kami telah menggunakan "DNA metabarcoding" untuk mengenal pasti kandungan artropod dalam sampel najis kelawar and membandingkan jaringan interaksi kelawar dan mangsa mereka diantara hutan dara dan hutan yang telah dibalak di Sabah, Borneo. C_LIO_LIKami meramalkan bahawa degradasi hutan hujan akan menyebabkan kekurangan dalam bilangan nod mangsa yang dimakan oleh setiap individu kelawar yang dapat diukur. Degradasi ini pula boleh menghasilkan jaringan yang mempunyai fungsi saling melengkapi dan modulariti yang rendah, dan lebih berkelompok atau "mempunyai "nestedness" yang lebih tinggi di hutan yang dibalak berbanding hutan dara. C_LIO_LIKelawar di kawasan hutan yang dibalak memakan diversiti mangsa yang lebih rendah dengan kelawar di habitat hutan hujan dara. Jaringan-jaringan interaksi mereka kurang berkelompok dan mempunyai stuktur yang lebih modular dimana spesis kelawar mempunyai pemarkahan kerapatan berpusat yang lebih rendah daripada sepesis kelawar di hutan dara. Struktur-struktur jaringan ini berkait dengan lebihan jaringan atau "network redundancy" yang lebih rendah and ini membawa kepada kerentantan yang meningkat terhadap gangguan luar di hutan yang telah dibalak. C_LIO_LIKeputusan kami menunjukkan bagaimana interaksi ekologi berubah diantara hutan dara dan hutan yang dibalak, dengan potensi implikasi negatif untuk fungsi ekosistem dan kestabilan jaringan. Kami juga telah menunjukkan potensi kepentingan kelawar yang memakan serangga dalam fungsi mereka untuk makan perosak invertebrat. C_LI Data Accessibility StatementData are currently archived at the Centre for Ecology and Hydrology Environmental Information Data Centre (https://doi.org/10.5285/8b106445-d8e0-482c-b517-5a372a09dc91) and will be released from embargo following publication. Specific analysis scripts are available on GitHub with links given in the manuscript and will be archived on Zenodo prior to publication. Statement of authorshipSR, EC, DHB, MS and OTL conceived the project, DHB, VK and JB undertook field collections and laboratory work, DHB analysed the data with input from EC, and DHB wrote the manuscript with input from all authors.

ecology↗

Chemogenomic screening Identifies the Hsp70 Co-chaperone HDJ2 as a Hub for Anticancer Drug Resistance

Heat shock protein 70 (Hsp70) is an important molecular chaperone that regulates oncoprotein stability and tumorigenesis. However, attempts to develop anti-chaperone drugs targeting molecules such as Hsp70 have been hampered by toxicity issues. Hsp70 is regulated by a suite of co-chaperone molecules that bring \"clients\" to the primary chaperone for efficient folding. Therefore, rather than targeting Hsp70 itself, here we have examined the feasibility of inhibiting the co-chaperone HDJ2, a member of the J domain protein family, as a novel anticancer strategy. We found HDJ2 to be upregulated in a variety of cancers, suggesting a role in malignancy. To confirm this role, we screened the NIH Approved Oncology collection for chemical-genetic interactions with loss of HDJ2 in cancer. 41 compounds showed strong synergy with HDJ2 loss, whereas 18 dramatically lost potency. Several of these hits were validated using a HDJ2 inhibitor (116-9e) in castration-resistant prostate cancer cell (CRPC) and spheroid models. Taken together, these results confirmed that HDJ2 is a hub for anticancer drug resistance and that HDJ2 inhibition may be a potent strategy to sensitize cancer cells to current and future therapeutics.\n\nGraphical AbstractHDJ2 knockout or inhibition via small molecule impacts cellular resistance to anticancer therapeutics.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC=\"FIGDIR/small/818427v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (86K):\norg.highwire.dtl.DTLVardef@cc1f42org.highwire.dtl.DTLVardef@1184229org.highwire.dtl.DTLVardef@19f9b8aorg.highwire.dtl.DTLVardef@19c9037_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗