Cortical function and the processing of sensory stimuli is remarkably robust against the continuous loss of neurons during aging, but also accelerated loss during prodromal stages of neurodegeneration. Population activity of neurons in sensory cortices builds a representation of the environment in form of a map that is structured in an informative way for guiding behavior. Here, we used the mouse auditory cortex as a model and probed the robustness of a representational map against the removal functionally characterized neurons. Specifically, we tested in how far the structure of the representational map is safeguarded by homeostatic network mechanisms. We combined longitudinal two-photon calcium imaging of population responses evoked by a diverse set of sound stimuli in the mouse auditory cortex with a targeted microablation of individual, functionally characterized neurons. Unilateral microablation of 30 - 40 selected sound-responsive layer 2/3 neurons led to a temporary collapse of the representational map that showed a subsequent recovery. At the level of individual neurons, we observed that the recovery was predominantly driven by neurons that were unresponsive to the sounds before microablation and gained responsiveness during the time course of several days. The remodeling of the spared network was mediated by a shift of the distribution of tuning curves towards the ablated neurons and was accompanied by a shift in the excitation/inhibition balance. Together, our findings provide a link between the plasticity of individual neurons and the population dynamics of sensory representations mediating robustness of cortical function. The dynamic reconstitution of the structure of activity patterns evoked by sensory stimuli despite a permanent loss of neurons in the network demonstrates a homeostatic maintenance of sensory representations in the neocortex.
Given the social and emotional tolls of the COVID-19 pandemic on college and university students, many students have become academically disengaged during the pandemic. Although some colleges and universities have the capacity to promote social support for their students, research has yet to comprehensively demonstrate the relationship between social support and academic engagement. To fill this gap, we leverage survey results from four universities across the United States and Israel. Through multi-group structural equation modelling, we explore (a) how perceived social support relates to being emotionally unavailable for learning, (b) how this relationship is partially explained through coping and COVID-19 concerns, and (c) how these relationships can differ across countries. We find that students who perceived higher levels of social support had lower rates of being emotionally unavailable for learning. Part of this relationship occurred through greater rates of coping and, subsequently, fewer concerns about the pandemic. We also noticed significant differences in these relationships between countries. We conclude with a discussion of study implications for higher education policies and practices.
Amanda B. Abildgaard, Voutsinos, Vasileios , Petersen, Søren D. , Larsen, Fia B. , Kampmeyer, Caroline , Johansson, Kristoffer E. , Stein, Amelie , Ravid, Tommer , Andréasson, Claes , Jensen, Michael K. , Lindorff-Larsen, Kresten , ו Hartmann-Petersen, Rasmus . 2023. “Hsp70-Binding Motifs Function As Protein Quality Control Degrons”, 80, 1, Pp. 32. . Publisher's Versionתקציר
Protein quality control (PQC) degrons are short protein segments that target misfolded proteins for proteasomal degradation, and thus protect cells against the accumulation of potentially toxic non-native proteins. Studies have shown that PQC degrons are hydrophobic and rarely contain negatively charged residues, features which are shared with chaperone-binding regions. Here we explore the notion that chaperone-binding regions may function as PQC degrons. When directly tested, we found that a canonical Hsp70-binding motif (the APPY peptide) functioned as a dose-dependent PQC degron both in yeast and in human cells. In yeast, Hsp70, Hsp110, Fes1, and the E3 Ubr1 target the APPY degron. Screening revealed that the sequence space within the chaperone-binding region of APPY that is compatible with degron function is vast. We find that the number of exposed Hsp70-binding sites in the yeast proteome correlates with a reduced protein abundance and half-life. Our results suggest that when protein folding fails, chaperone-binding sites may operate as PQC degrons, and that the sequence properties leading to PQC-linked degradation therefore overlap with those of chaperone binding.
Daniela Schiller, Yu, Alessandra NC, Alia-Klein, Nelly , Becker, Susanne , Cromwell, Howard C, Dolcos, Florin , Eslinger, Paul J, Frewen, Paul , Kemp, Andrew H, Pace-Schott, Edward F, Raber, Jacob , Silton, Rebecca L, Stefanova, Elka , Williams, Justin HG, Abe, Nobuhito , Aghajani, Moji , Albrecht, Franziska , Alexander, Rebecca , Anders, Silke , Aragón, Oriana R, Arias, Juan A, Arzy, Shahar , Aue, Tatjana , Baez, Sandra , Balconi, Michela , Ballarini, Tommaso , Bannister, Scott , Banta, Marlissa C, Barrett, Karen Caplovitz, Belzung, Catherine , Bensafi, Moustafa , Booij, Linda , Bookwala, Jamila , Boulanger-Bertolus, Julie , Boutros, Sydney Weber, Bräscher, Anne-Kathrin , Bruno, Antonio , Busatto, Geraldo , Bylsma, Lauren M, Caldwell-Harris, Catherine , Chan, Raymond CK, Cherbuin, Nicolas , Chiarella, Julian , Cipresso, Pietro , Critchley, Hugo , Croote, Denise E, Demaree, Heath A, Denson, Thomas F, Depue, Brendan , Derntl, Birgit , Dickson, Joanne M, Dolcos, Sanda , Drach-Zahavy, Anat , Dubljević, Olga , Eerola, Tuomas , Ellingsen, Dan-Mikael , Fairfield, Beth , Ferdenzi, Camille , Friedman, Bruce H, H Y Fu, Cynthia , Gatt, Justine M, deGelder, Beatrice , Gendolla, Guido HE, Gilam, Gadi , Goldblatt, Hadass , Gooding, Anne Elizabeth, Gosseries, Olivia , Hamm, Alfons O, Hanson, Jamie L, Hendler, Talma , Herbert, Cornelia , Hofmann, Stefan G, Ibanez, Agustin , Joffily, Mateus , Jovanovic, Tanja , Kahrilas, Ian J, Kangas, Maria , Katsumi, Yuta , Kensinger, Elizabeth , Kirby, Lauren AJ, Koncz, Rebecca , Koster, Ernst HW, Kozlowska, Kasia , Krach, Sören , Kret, Mariska E, Krippl, Martin , Kusi-Mensah, Kwabena , Ladouceur, Cecile D, Laureys, Steven , Lawrence, Alistair , Li, Chiang-Shan R, Liddell, Belinda J, Lidhar, Navdeep K, Lowry, Christopher A, Magee, Kelsey , Marin, Marie-France , Mariotti, Veronica , Martin, Loren J, Marusak, Hilary A, Mayer, Annalina V, Merner, Amanda R, Minnier, Jessica , Moll, Jorge , Morrison, Robert G, Moore, Matthew , Mouly, Anne-Marie , Mueller, Sven C, Mühlberger, Andreas , Murphy, Nora A, Muscatello, Maria Rosaria An, Musser, Erica D, Newton, Tamara L, Noll-Hussong, Michael , Norrholm, Seth Davin, Northoff, Georg , Nusslock, Robin , Okon-Singer, Hadas , Olino, Thomas M, Ortner, Catherine , Owolabi, Mayowa , Padulo, Caterina , Palermo, Romina , Palumbo, Rocco , Palumbo, Sara , Papadelis, Christos , Pegna, Alan J, Pellegrini, Silvia , Peltonen, Kirsi , Penninx, Brenda WJH, Pietrini, Pietro , Pinna, Graziano , Lobo, Rosario Pintos, Polnaszek, Kelly L, Polyakova, Maryna , Rabinak, Christine , HeleneRichter, S , Richter, Thalia , Riva, Giuseppe , Rizzo, Amelia , Robinson, Jennifer L, Rosa, Pedro , Sachdev, Perminder S, Sato, Wataru , Schroeter, Matthias L, Schweizer, Susanne , Shiban, Youssef , Siddharthan, Advaith , Siedlecka, Ewa , Smith, Robert C, Soreq, Hermona , Spangler, Derek P, Stern, Emily R, Styliadis, Charis , Sullivan, Gavin B, Swain, James E, Urben, Sébastien , Van den Stock, Jan , Kooij, Michael AVander, van Overveld, Mark , Van Rheenen, Tamsyn E, VanElzakker, Michael B, Ventura-Bort, Carlos , Verona, Edelyn , Volk, Tyler , Wang, Yi , Weingast, Leah T, Weymar, Mathias , Williams, Claire , Willis, Megan L, Yamashita, Paula , Zahn, Roland , Zupan, Barbra , Lowe, Leroy , Gabriela, Gan , F, Huggins Charlotte, ו Leonie, Loeffler . 2023. “The Human Affectome”. Neurosci Biobehav Rev, Pp. 105450. doi:10.1016/j.neubiorev.2023.105450. תקציר
Over the last decades, the interdisciplinary field of the affective sciences has seen proliferation rather than integration of theoretical perspectives. This is due to differences in metaphysical and mechanistic assumptions about human affective phenomena (what they are and how they work) which, shaped by academic motivations and values, have determined the affective constructs and operationalizations. An assumption on the purpose of affective phenomena can be used as a teleological principle to guide the construction of a common set of metaphysical and mechanistic assumptions-a framework for human affective research. In this capstone paper for the special issue "Towards an Integrated Understanding of the Human Affectome", we gather the tiered purpose of human affective phenomena to synthesize assumptions that account for human affective phenomena collectively. This teleologically-grounded framework offers a principled agenda and launchpad for both organizing existing perspectives and generating new ones. Ultimately, we hope Human Affectome brings us a step closer to not only an integrated understanding of human affective phenomena, but an integrated field for affective research.
Human milk oligosaccharides (HMOs) stimulate the growth of gut commensals, prevent the adhesion of enteropathogens and modulate host immunity. The major factors influencing variations in the HMO profile are polymorphisms in the secretor (Se) or Lewis (Le) gene, which affect the activity of the enzymes fucoslytransferase 2 and 3 (FUT2 and FUT3) that lead to the formation of four major fucosylated and non-fucosylated oligosaccharides (OS). This pilot study aimed to determine the HMO profile of Israeli breastfeeding mothers of 16 term and 4 preterm infants, from a single tertiary center in the Tel Aviv area. Fifty-two human milk samples were collected from 20 mothers at three-time points: colostrum, transitional milk and mature milk. The concentrations of nine HMOs were assessed using liquid chromatography coupled with mass spectra chromatograms. Fifty-five percent of the mothers were secretors and 45% were non-secretors. Infant sex affected HMO levels depending on the maternal secretor status. Secretor mothers to boys had higher levels of FUT2-dependent OS and higher levels of disialyllacto-N-tetraose in the milk of mothers to girls, whereas non-secretor mothers to girls had higher levels of 3′-sialyllactose. In addition, the season at which the human milk samples were obtained affected the levels of some HMOs, resulting in significantly lower levels in the summer. Our findings provide novel information on the irregularity in the HMO profile among Israeli lactating women and identify several factors contributing to this variability.
