keyword
https://read.qxmd.com/read/38478018/snare-chaperone-sly1-directly-mediates-close-range-vesicle-tethering
#1
JOURNAL ARTICLE
Mengtong Duan, Rachael L Plemel, Tomoka Takenaka, Ariel Lin, Beatriz Marie Delgado, Una Nattermann, Daniel P Nickerson, Joji Mima, Elizabeth A Miller, Alexey J Merz
The essential Golgi protein Sly1 is a member of the Sec1/mammalian Unc-18 (SM) family of SNARE chaperones. Sly1 was originally identified through remarkable gain-of-function alleles that bypass requirements for diverse vesicle tethering factors. Employing genetic analyses and chemically defined reconstitutions of ER-Golgi fusion, we discovered that a loop conserved among Sly1 family members is not only autoinhibitory but also acts as a positive effector. An amphipathic lipid packing sensor (ALPS)-like helix within the loop directly binds high-curvature membranes...
June 3, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38477340/f-box-protein-fbxb-65-regulates-anterograde-transport-of-a-kinesin-3-motor-unc-104-through-a-ptm-near-its-cargo-binding-ph-domain
#2
JOURNAL ARTICLE
Vidur Sabharwal, Sri Padma Priya Boyanapalli, Amir Shee, Michael L Nonet, Amitabha Nandi, Debasish Chaudhuri, Sandhya P Koushika
Axonal transport in neurons is essential for cargo movement between the cell body and synapses. UNC-104/KIF1A, a Kinesin-3 motor in C. elegans that anterogradely transports precursors of synaptic vesicles (pre-SVs), is degraded at synapses. Touch neurons-specific knockdown of the E1 ubiquitin-activating enzyme, uba-1, leads to UNC-104 accumulation at neuronal ends and synapses. An RNAi screen identified fbxb-65, an F-box protein, that leads to UNC-104 accumulation at neuronal distal ends, alters UNC-104 net anterograde movement and levels of UNC-104 on cargo without changing synaptic UNC-104 levels...
March 13, 2024: Journal of Cell Science
https://read.qxmd.com/read/38473270/fear-of-recurrence-in-advanced-cancer-patients-sociodemographic-clinical-and-psychological-correlates
#3
JOURNAL ARTICLE
Caterina Calderon, Marina Gustems, Rocio Galán-Moral, Maria M Muñoz-Sánchez, Lorena Ostios-García, Paula Jiménez-Fonseca
Fear of cancer recurrence significantly impacts advanced cancer patients, prompting emotional distress and increased healthcare utilization. This present study aims to analyze the fear of recurrence among patients with advanced cancer undergoing systemic treatment and its relationship with sociodemographic, clinical, and psychological factors. A multicenter cross-sectional study was conducted in 15 oncology departments across Spain, involving patients with locally advanced, unresectable, or metastatic cancer eligible for systemic treatment...
February 23, 2024: Cancers
https://read.qxmd.com/read/38471256/sympathovagal-quotient-and-resting-state-functional-connectivity-of-control-networks-are-related-to-gut-ruminococcaceae-abundance-in-healthy-men
#4
JOURNAL ARTICLE
Ana L Miranda-Angulo, Juan D Sánchez-López, Daniel A Vargas-Tejada, Valentina Hawkins-Caicedo, Juan C Calderón, Jaime Gallo-Villegas, Juan F Alzate-Restrepo, Jazmin X Suarez-Revelo, Gabriel Castrillón
INTRODUCTION: Heart rate variability (HRV), brain resting-state functional connectivity (rsFC), and gut microbiota (GM) are three recognized indicators of health status, whose relationship has not been characterized. We aimed to identify the GM genera and families related to HRV and rsFC, the interaction effect of HRV and rsFC on GM taxa abundance, and the mediation effect of diet on these relationships. METHODS: Eighty-eight healthy, young Colombian men were included in this cross-sectional study...
February 24, 2024: Psychoneuroendocrinology
https://read.qxmd.com/read/38467475/preferential-transport-of-synaptic-vesicles-across-neuronal-branches-is-regulated-by-the-levels-of-the-anterograde-motor-unc-104-kif1a-in-vivo
#5
JOURNAL ARTICLE
Amruta Vasudevan, Neena Ratnakaran, Kaushalya Murthy, Shikha Kumari, David H Hall, Sandhya P Koushika
Asymmetric transport of cargo across axonal branches is a field of active research. Mechanisms contributing to preferential cargo transport along specific branches in vivo in wild type neurons are poorly understood. We find that anterograde synaptic vesicles preferentially enter the synaptic branch or pause at the branch point in C. elegans PLM neurons. The synaptic vesicle anterograde kinesin motor UNC-104/KIF1A regulates this vesicle behaviour at the branch point. Reduced levels of functional UNC-104 cause vesicles to predominantly pause at the branch point and lose their preference for turning into the synaptic branch...
February 14, 2024: Genetics
https://read.qxmd.com/read/38459884/rnf135-promotes-cell-proliferation-and-autophagy-in-lung-adenocarcinoma-by-promoting-the-phosphorylation-of-ulk1
#6
JOURNAL ARTICLE
Lichun Zhuang, Guanhui Shi, Yuejun Sun
OBJECTIVE: To detect the expression of RING finger protein 135 (RNF135) in lung adenocarcinoma tissues and explore its role in the progression of lung adenocarcinoma. METHODS: Bioinformation analysis, quantitative polymerase chain reaction, and immunoblotting technique discovered the expression of RNF135 in lung adenocarcinoma tissues. Cell counting kit-8 and colony formation, immunostaining, and immunoblot assays examined the effects of RNF135 on cell growth and autophagy...
2024: Allergologia et Immunopathologia
https://read.qxmd.com/read/38457207/polq-identifies-a-better-response-subset-to-immunotherapy-in-muscle-invasive-bladder-cancer-with-high-pd-l1
#7
JOURNAL ARTICLE
Ge Liu, Kaifeng Jin, Zhaopei Liu, Xiaohe Su, Ziyue Xu, Bingyu Li, Jingtong Xu, Yuan Chang, Yiwei Wang, Yu Zhu, Le Xu, Jiejie Xu, Zewei Wang, Hailong Liu, Weijuan Zhang
BACKGROUND: Though programmed cell death-ligand 1 (PD-L1) has been used in predicting the efficacy of immune checkpoint blockade (ICB), it is insufficient as a single biomarker. As a key effector of an intrinsically mutagenic microhomology-mediated end joining (MMEJ) pathway, DNA polymerase theta (POLQ) was overexpressed in various malignancies, whose expression might have an influence on genomic stability, therefore altering the sensitivity to chemotherapy and immunotherapy. METHODS: A total of 1304 patients with muscle-invasive bladder cancer (MIBC) from six independent cohorts were included in this study...
February 2024: Cancer Medicine
https://read.qxmd.com/read/38444141/-research-progress-on-the-role-of-tank-binding-kinase-1-in-pink1-parkin-dependent-and-independent-mitophagy
#8
JOURNAL ARTICLE
Hao Deng, Zhi Xia, Hua-Yu Shang
Mitophagy is a process that selectively removes excess or damaged mitochondria and plays an important role in regulating intracellular mitochondrial mass and maintaining mitochondrial energy metabolism. TANK-binding kinase 1 (TBK1) is a multifunctional serine/threonine protein kinase, which is involved in the regulation of PTEN-induced putative kinase 1 (PINK1)/Parkin-dependent and -independent mitophagy. Recent studies have shown that TBK1 phosphorylates the autophagy related proteins, such as optineurin (OPTN), p62/sequestosome-1, Ras-related GTP binding protein 7 (Rab7), and mediates the binding of nuclear dot protein 52 (NDP52) to UNC-51 like autophagy activating kinase 1 (ULK1) complex, as well as the binding of TAX1-binding protein 1 (TAX1BP1) to microtubule-associated protein 1 light chain 3 (LC3), thereby enhancing PINK1/Parkin-dependent mitophagy...
February 25, 2024: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://read.qxmd.com/read/38442891/autophagy-the-crossword-puzzle
#9
EDITORIAL
Daniel J Klionsky
It's April, so it is time to lighten up (think April Fools' Day). In this issue of the journal, I have two different sets of puzzles for you. Of course, these are not just for your amusement; there is an educational component as well. For example, the crossword puzzle requires you to think about autophagy and perhaps do some searching for names or terms that you are less familiar with (the Guidelines is always a good source of information in this regard). In addition, the crossword puzzle uses official HGNC nomenclature unless otherwise specified - another learning opportunity...
March 5, 2024: Autophagy
https://read.qxmd.com/read/38436129/protective-autophagy-enhances-antistress-ability-through-ampk-ulk1-signaling-pathway-in-human-immortalized-keratinocytes
#10
JOURNAL ARTICLE
Zhinan Shi, Jing Wang, Min Li, Li Gu, Zhiyi Xu, Xiaoyu Zhai, Shu Zhou, Jingting Zhao, Liqun Gu, Lin Chen, Linling Ju, Bingrong Zhou, Hui Hua
Keratinocytes, located in the outermost layer of human skin, are pivotal cells to resist environmental damage. Cellular autophagy plays a critical role in eliminating damaged organelles and maintaining skin cell homeostasis. Low-dose 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) has been demonstrated to enhance skin's antistress ability; however, the regulatory mechanisms of autophagy in keratinocytes remain unclear. In this study, we treated immortalized human keratinocytes (HaCaT cells) with low-dose ALA-PDT (0...
March 4, 2024: Cell Biology International
https://read.qxmd.com/read/38435720/new-approaches-for-understanding-the-potential-role-of-microbes-in-alzheimer-s-disease
#11
REVIEW
Heather E Whitson, William A Banks, Monica M Diaz, Bess Frost, Manolis Kellis, Richard Lathe, Kenneth E Schmader, Serena S Spudich, Rudolph Tanzi, Gwenn Garden
Alzheimer's disease (AD) involves a complex pathological process that evolves over years, and its etiology is understood as a classic example of gene-environment interaction. The notion that exposure to microbial organisms may play some role in AD pathology has been proposed and debated for decades. New evidence from model organisms and -omic studies, as well as epidemiological data from the recent COVID-19 pandemic and widespread use of vaccines, offers new insights into the "germ hypothesis" of AD. To review new evidence and identify key research questions, the Duke/University of North Carolina (Duke/UNC) Alzheimer's Disease Research Center hosted a virtual symposium and workshop: "New Approaches for Understanding the Potential Role of Microbes in Alzheimer's disease...
March 2024: Brain, behavior, & immunity health
https://read.qxmd.com/read/38432059/the-mechanism-of-unc-51-like-kinase-1-and-the-applications-of-small-molecule-modulators-in-cancer-treatment
#12
REVIEW
Dejuan Sun, Zhiqi Zhang, Xinbo Yu, Hua Li, Xiaobo Wang, Lixia Chen
Autophagy is a process of self-renewal in cells, which not only provides the necessary nutrients for cells, but also clears necrotic organelles. Autophagy disorders are closely related to diseases such as cancer. UNC-51-like kinase 1 (ULK1) is a serine/threonine protein kinase that plays a crucial role in receiving input from energy and nutrient sensors, activating autophagy to maintain cellular homeostasis under stressful conditions. In recent years, targeting ULK1 has become a highly promising strategy for cancer treatment...
February 27, 2024: European Journal of Medicinal Chemistry
https://read.qxmd.com/read/38432030/effect-of-sleep-disordered-breathing-severity-in-children-with-down-syndrome-on-parental-wellbeing-and-social-support
#13
JOURNAL ARTICLE
Miles Beng Hee Ong, Margot J Davey, Gillian M Nixon, Lisa M Walter, Rosemary Sc Horne
INTRODUCTION: Sleep disorders, particularly sleep disordered breathing (SDB), are common in children with Down syndrome (DS). We investigated the relationship between SDB severity and parental psychological wellbeing and their perception of social support. METHODS: 44 children with DS (3-19 years) underwent overnight polysomnography and were categorised into three groups: primary snoring, Mild and Moderate/Severe obstructive sleep apnoea (OSA). Parents completed questionnaires about their child's behaviour (Child Behavior Checklist), sleep symptoms (Pediatric Sleep Survey Instrument) and SDB-related quality of life (OSA-18), together with the DUKE-UNC Functional Social Support (DUKE) and Psychological General Well-Being Index (PGWBI) questionnaires for themselves...
February 26, 2024: Sleep Medicine
https://read.qxmd.com/read/38426898/ythdc1-crm1-facilitates-m6a-modified-circrna388-nuclear-export-to-induce-coelomocyte-autophagy-via-the-mir-2008-ulk-axis-in-apostichopus-japonicus
#14
JOURNAL ARTICLE
Jiqing Liu, Yina Shao, Chenghua Li
N 6-methyladenosine (m6A), the most prevalent internal modification in eukaryotic RNA, was able to mediate circular RNA (circRNA) function in many immune processes. Nevertheless, the functional role of m6A-modified circRNAs in innate immunity of invertebrates remained unclear. In this study, we identified m6A-modified circRNA388 from cultured sea cucumber (Apostichopus japonicus) coelomocytes, which was mainly detected in cytoplasm after Vibrio splendidus infection. A knockdown assay indicated that cytoplasm circRNA388 promoted coelomocyte autophagy and decreased the number of intracellular V...
March 1, 2024: Journal of Immunology
https://read.qxmd.com/read/38412547/does-paging-clinicians-about-tick-borne-disease-serological-results-impact-clinical-care-a-retrospective-analysis-of-70-cases-in-north-carolina
#15
JOURNAL ARTICLE
Neha V Mokashi, Amanda Brown Marusiak, Dana Giandomenico, Meghan Cleinmark, John L Schmitz, Ross M Boyce
Delayed treatment of Rocky Mountain spotted fever is associated with increased morbidity and mortality. Because the diagnosis cannot be established from a single serological test, guidelines recommend empirical antibiotic initiation in suspect patients. We evaluated a policy used by UNC Health of paging clinicians when acute testing for Rickettsia returned with a titer ≥ 1:256. Our objective was to assess the potential effect of paging on routine treatment practices. Notably, we found that a high proportion of cases (N = 28, 40%) were not prescribed antibiotics until the results were available...
February 27, 2024: American Journal of Tropical Medicine and Hygiene
https://read.qxmd.com/read/38405977/unc-30-pitx-coordinates-neurotransmitter-identity-with-postsynaptic-gaba-receptor-clustering
#16
Edgar Correa, Morgane Mialon, Mélissa Cizeron, Jean-Louis Bessereau, Berangere Pinan-Lucarre, Paschalis Kratsios
Terminal selectors are transcription factors that control neuronal identity by regulating the expression of key effector molecules, such as neurotransmitter (NT) biosynthesis proteins, ion channels and neuropeptides. Whether and how terminal selectors control neuronal connectivity is poorly understood. Here, we report that UNC-30 (PITX2/3), the terminal selector of GABA motor neuron identity in C. elegans , is required for NT receptor clustering, a hallmark of postsynaptic differentiation. Animals lacking unc-30 or madd-4B, the short isoform of the MN-secreted synapse organizer madd-4 ( Punctin/ADAMTSL ), display severe GABA receptor type A (GABA A R) clustering defects in postsynaptic muscle cells...
February 14, 2024: bioRxiv
https://read.qxmd.com/read/38405875/unc-16-interacts-with-lrk-1-and-wdfy-3-to-regulate-the-termination-of-axon-growth
#17
Cody J Drozd, Tamjid A Chowdhury, Christopher C Quinn
MAPK8IP3 (unc-16/JIP3) is a neurodevelopmental-disorder associated gene that can regulate the termination of axon growth. However, its role in this process is not well understood. Here, we report that UNC-16 promotes axon termination through a process that includes the LRK-1(LRRK-1/LRRK-2) kinase and the WDFY-3 (WDFY3/Alfy) selective autophagy protein. Genetic analysis suggests that UNC-16 promotes axon termination through an interaction between its RH1 domain and the dynein complex. Loss of unc-16 function causes accumulation of late endosomes specifically in the distal axon...
February 16, 2024: bioRxiv
https://read.qxmd.com/read/38405708/cell-non-autonomous-signaling-through-the-conserved-c-elegans-glycopeptide-hormone-receptor-fshr-1-regulates-cholinergic-neurotransmission
#18
Morgan Buckley, William P Jacob, Letitia Bortey, Makenzi McClain, Alyssa L Ritter, Amy Godfrey, Allyson S Munneke, Shankar Ramachandran, Signe Kenis, Julie C Kolnik, Sarah Olofsson, Ryan Adkins, Tanner Kutoloski, Lillian Rademacher, Olivia Heinecke, Alexandra Alva, Isabel Beets, Michael M Francis, Jennifer R Kowalski
Modulation of neurotransmission is key for organismal responses to varying physiological contexts such as during infection, injury, or other stresses, as well as in learning and memory and for sensory adaptation. Roles for cell autonomous neuromodulatory mechanisms in these processes have been well described. The importance of cell non-autonomous pathways for inter-tissue signaling, such as gut-to-brain or glia-to-neuron, has emerged more recently, but the cellular mechanisms mediating such regulation remain comparatively unexplored...
February 12, 2024: bioRxiv
https://read.qxmd.com/read/38400829/sequences-in-the-myosin-a-rod-interact-with-unc-89-obscurin-and-the-zinc-finger-protein-unc-98-during-thick-filament-assembly-and-m-line-formation-in-c-elegans-striated-muscle
#19
JOURNAL ARTICLE
Sarah A Almuhanna, Humayra Z Oishi, Kar Men Lee, Pamela E Hoppe
The M-line of striated muscle is a complex structure that anchors myosin-containing thick filaments and also participates in signaling and proteostasis. While the physical associations among many M-line components have been defined, the mechanism of thick filament attachment is not completely understood. In Caenorhabditis elegans, myosin A is essential for viability and forms the site of M-line attachment at the center of the filament, whereas myosin B forms the filament arms. Using a mutant myosin A that forms ectopic filaments, we examined interactions between myosin A and M-line proteins in intact muscle cells...
February 24, 2024: Cytoskeleton
https://read.qxmd.com/read/38396629/carnosic-acid-against-lung-cancer-induction-of-autophagy-and-activation-of-sestrin-2-lkb1-ampk-signalling
#20
JOURNAL ARTICLE
Eric J O'Neill, Newman Siu Kwan Sze, Rebecca E K MacPherson, Evangelia Tsiani
Non-small cell lung cancer (NSCLC) represents 80% of all lung cancer cases and is characterized by low survival rates due to chemotherapy and radiation resistance. Novel treatment strategies for NSCLC are urgently needed. Liver kinase B1 (LKB1), a tumor suppressor prevalently mutated in NSCLC, activates AMP-activated protein kinase (AMPK) which in turn inhibits mammalian target of rapamycin complex 1 (mTORC1) and activates unc-51 like autophagy activating kinase 1 (ULK1) to promote autophagy. Sestrin-2 is a stress-induced protein that enhances LKB1-dependent activation of AMPK, functioning as a tumor suppressor in NSCLC...
February 6, 2024: International Journal of Molecular Sciences
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