Biology subjects

Lopes, K.

Publications and source records attributed to Lopes, K..

3 recordsLinked to original sources

bioRxiv2025

Cytokine expression profile in the human brain of older adults

Alzheimers disease (AD) is a complex neurodegenerative condition linked to chronic neuroinflammation. This study investigates the cytokine gene expression profile in cortical tissue samples from elderly individuals with and without AD to identify potential biomarkers and enhance our understanding of disease pathogenesis. Utilizing high-depth RNA sequencing data, we identified a set of cytokines whose expression significantly associated with different aspects of the AD phenotype, including measures of neurofibrillary tangles, amyloid-{beta} deposition, and a person-specific rate of cognitive decline. Single-nucleus transcriptomics data facilitated the identification of specific cell types, such as microglia and oligodendrocytes, that significantly contribute to the inflammatory response in AD. Additionally, we observed a strong correlation between the expression of certain cytokines and genetic risk for the disease. Our findings indicate that cytokine-mediated neuroinflammation plays a vital role in AD progression and that modulating the immune response may offer a promising strategy for developing new therapies.

molecular biology↗

bioRxiv2024

Membrane fusion reactions limited by defective SNARE zippering or stiff lipid fatty acyl composition have distinct requirements for Sec17, Sec18, and adenine nucleotide

Intracellular membrane fusion is catalyzed by SNAREs, Rab GTPases, SM proteins, tethers, Sec18/NSF and Sec17/SNAP. Membrane fusion has been reconstituted with purified vacuolar proteins and lipids to address 3 salient questions: whether ATP hydrolysis by Sec18 affects its promotion of fusion, whether fusion promotion by Sec17 and Sec18 is only seen with mutant SNAREs or can also be seen with wild-type SNAREs, and whether Sec17 and Sec18 only promote fusion when they work together or whether they can each work separately. Fusion is driven by two engines, completion of SNARE zippering (which does not need Sec17/Sec18) and Sec17/Sec18-mediated fusion (needing SNAREs but not the energy from their complete zippering). Sec17 is required to rescue fusion that is blocked by incomplete zippering, though optimal rescue also needs the ATPase Sec18. ATP is an essential Sec18 ligand, but at limiting Sec17 levels Sec18 ATP hydrolysis also drives release of Sec17 without concomitant trans-SNARE complex disassembly. At higher (physiological) Sec17 levels, or without ATP hydrolysis, fusion prevails over Sec17 release. Stiff 16:0, 18:1 fatty acyl chain lipids provide an alternative route to suppressing fusion, with entirely wild-type SNAREs and without impediment to zippering. In this case, Sec17 and Sec18 restore comparable fusion with either ATP or a nonhydrolyzable analog. Fusion blocked by impaired zippering can be restored by concentrated Sec17 alone (but not by Sec18), while fusion inhibited by stiff fatty acyl chains is partially restored by Sec18 alone (but not by Sec17). With distinct fusion impediments, Sec18 and Sec17 have both shared roles and independent roles in promoting fusion. SignificanceSec17/SNAP and Sec18/NSF catalyze cis-SNARE complex disassembly through ATP hydrolysis, but also drive fusion itself without ATP hydrolysis. Fusion can be inhibited by either "stiff" fatty acyl chains while allowing full zippering of entirely wild-type SNAREs or by incomplete SNARE zippering. In either case, Sec17 and Sec18 restore full fusion, but with clear differences. With defective zippering, high levels of Sec17 can restore fusion without Sec18. With stiff fatty acyl chains, Sec18 alone can restore fusion but Sec17 alone will not. In both cases, Sec17 and Sec18 are more efficient together. SNARE-dependent membrane fusion thus relies on two energy sources, complete SNARE zippering and interactions with Sec17 and Sec18.

biochemistry↗

bioRxiv2018

Modulation of defence and iron homeostasis genes in rice roots by the diazotrophic endophyte Herbaspirillum seropedicae

Rice is staple food of nearly half the worlds population. Rice yields must therefore increase to feed ever larger populations. By colonising rice and other plants, Herbaspirillum spp. stimulate plant growth and productivity. However the molecular factors involved are largely unknown. To further explore this interaction, the transcription profiles of Nipponbare rice roots inoculated with Herbaspirillum seropedicae were determined by RNA-seq. Mapping the 104 million reads against the Oryza sativa cv. Nipponbare genome produced 65 million unique mapped reads that represented 13,840 transcripts each with at least two-times coverage. About 7.4 % (1,019) genes were differentially regulated and of these 256 changed expression levels more than two times. Several of the modulated genes encoded proteins related to plant defence (e.g. a putative probenazole inducible protein), plant disease resistance as well as enzymes involved in flavonoid and isoprenoid synthesis. Genes related to the synthesis and efflux of phytosiderophores (PS) and transport of PS-iron complexes were also induced by the bacteria. These data suggest that the bacterium represses the rice defence system while concomitantly activating iron uptake. Transcripts of H. seropedicae were also detected amongst which genes involved in nitrogen fixation, cell motility and cell wall synthesis were the most expressed.\n\nHighlightsRNASeq of H. seropedicae colonised rice roots showed remarkable regulation of defence, metal transport, stress and signalling genes. Fe-uptake genes were highly induced with implications in plant nutrition and immunity.

plant biology↗