@article{14826,
abstract = {The plant-signaling molecule auxin triggers fast and slow cellular responses across land plants and algae. The nuclear auxin pathway mediates gene expression and controls growth and development in land plants, but this pathway is absent from algal sister groups. Several components of rapid responses have been identified in Arabidopsis, but it is unknown if these are part of a conserved mechanism. We recently identified a fast, proteome-wide phosphorylation response to auxin. Here, we show that this response occurs across 5 land plant and algal species and converges on a core group of shared targets. We found conserved rapid physiological responses to auxin in the same species and identified rapidly accelerated fibrosarcoma (RAF)-like protein kinases as central mediators of auxin-triggered phosphorylation across species. Genetic analysis connects this kinase to both auxin-triggered protein phosphorylation and rapid cellular response, thus identifying an ancient mechanism for fast auxin responses in the green lineage.},
author = {Kuhn, Andre and Roosjen, Mark and Mutte, Sumanth and Dubey, Shiv Mani and Carrillo Carrasco, Vanessa Polet and Boeren, Sjef and Monzer, Aline and Koehorst, Jasper and Kohchi, Takayuki and Nishihama, Ryuichi and Fendrych, Matyas and Sprakel, Joris and Friml, Jiří and Weijers, Dolf},
issn = {1097-4172},
journal = {Cell},
keywords = {General Biochemistry, Genetics and Molecular Biology},
number = {1},
pages = {130--148.e17},
publisher = {Elsevier},
title = {{RAF-like protein kinases mediate a deeply conserved, rapid auxin response}},
doi = {10.1016/j.cell.2023.11.021},
volume = {187},
year = {2024},
}
@article{14850,
abstract = {Elaborate sexual signals are thought to have evolved and be maintained to serve as honest indicators of signaller quality. One measure of quality is health, which can be affected by parasite infection. Cnemaspis mysoriensis is a diurnal gecko that is often infested with ectoparasites in the wild, and males of this species express visual (coloured gular patches) and chemical (femoral gland secretions) traits that receivers could assess during social interactions. In this paper, we tested whether ectoparasites affect individual health, and whether signal quality is an indicator of ectoparasite levels. In wild lizards, we found that ectoparasite level was negatively correlated with body condition in both sexes. Moreover, some characteristics of both visual and chemical traits in males were strongly associated with ectoparasite levels. Specifically, males with higher ectoparasite levels had yellow gular patches with lower brightness and chroma, and chemical secretions with a lower proportion of aromatic compounds. We then determined whether ectoparasite levels in males influence female behaviour. Using sequential choice trials, wherein females were provided with either the visual or the chemical signals of wild-caught males that varied in ectoparasite level, we found that only chemical secretions evoked an elevated female response towards less parasitised males. Simultaneous choice trials in which females were exposed to the chemical secretions from males that varied in parasite level further confirmed a preference for males with lower parasites loads. Overall, we find that although health (body condition) or ectoparasite load can be honestly advertised through multiple modalities, the parasite-mediated female response is exclusively driven by chemical signals.},
author = {Pal, Arka and Joshi, Mihir and Thaker, Maria},
issn = {0022-0949},
journal = {Journal of Experimental Biology},
keywords = {Insect Science, Molecular Biology, Animal Science and Zoology, Aquatic Science, Physiology, Ecology, Evolution, Behavior and Systematics},
number = {1},
publisher = {The Company of Biologists},
title = {{Too much information? Males convey parasite levels using more signal modalities than females utilise}},
doi = {10.1242/jeb.246217},
volume = {227},
year = {2024},
}
@article{14979,
abstract = {Poxviruses are among the largest double-stranded DNA viruses, with members such as variola virus, monkeypox virus and the vaccination strain vaccinia virus (VACV). Knowledge about the structural proteins that form the viral core has remained sparse. While major core proteins have been annotated via indirect experimental evidence, their structures have remained elusive and they could not be assigned to individual core features. Hence, which proteins constitute which layers of the core, such as the palisade layer and the inner core wall, has remained enigmatic. Here we show, using a multi-modal cryo-electron microscopy (cryo-EM) approach in combination with AlphaFold molecular modeling, that trimers formed by the cleavage product of VACV protein A10 are the key component of the palisade layer. This allows us to place previously obtained descriptions of protein interactions within the core wall into perspective and to provide a detailed model of poxvirus core architecture. Importantly, we show that interactions within A10 trimers are likely generalizable over members of orthopox- and parapoxviruses.},
author = {Datler, Julia and Hansen, Jesse and Thader, Andreas and Schlögl, Alois and Bauer, Lukas W and Hodirnau, Victor-Valentin and Schur, Florian KM},
issn = {1545-9985},
journal = {Nature Structural & Molecular Biology},
keywords = {Molecular Biology, Structural Biology},
publisher = {Springer Nature},
title = {{Multi-modal cryo-EM reveals trimers of protein A10 to form the palisade layer in poxvirus cores}},
doi = {10.1038/s41594-023-01201-6},
year = {2024},
}
@article{15033,
abstract = {The GNOM (GN) Guanine nucleotide Exchange Factor for ARF small GTPases (ARF-GEF) is among the best studied trafficking regulators in plants, playing crucial and unique developmental roles in patterning and polarity. The current models place GN at the Golgi apparatus (GA), where it mediates secretion/recycling, and at the plasma membrane (PM) presumably contributing to clathrin-mediated endocytosis (CME). The mechanistic basis of the developmental function of GN, distinct from the other ARF-GEFs including its closest homologue GNOM-LIKE1 (GNL1), remains elusive. Insights from this study largely extend the current notions of GN function. We show that GN, but not GNL1, localizes to the cell periphery at long-lived structures distinct from clathrin-coated pits, while CME and secretion proceed normally in gn knockouts. The functional GN mutant variant GNfewerroots, absent from the GA, suggests that the cell periphery is the major site of GN action responsible for its developmental function. Following inhibition by Brefeldin A, GN, but not GNL1, relocates to the PM likely on exocytic vesicles, suggesting selective molecular associations en route to the cell periphery. A study of GN-GNL1 chimeric ARF-GEFs indicates that all GN domains contribute to the specific GN function in a partially redundant manner. Together, this study offers significant steps toward the elucidation of the mechanism underlying unique cellular and development functions of GNOM.},
author = {Adamowski, Maciek and Matijevic, Ivana and Friml, Jiří},
issn = {2050-084X},
journal = {eLife},
keywords = {General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, General Medicine, General Neuroscience},
publisher = {eLife Sciences Publications},
title = {{Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery}},
doi = {10.7554/elife.68993},
volume = {13},
year = {2024},
}
@article{14613,
abstract = {Many insects carry an ancient X chromosome - the Drosophila Muller element F - that likely predates their origin. Interestingly, the X has undergone turnover in multiple fly species (Diptera) after being conserved for more than 450 MY. The long evolutionary distance between Diptera and other sequenced insect clades makes it difficult to infer what could have contributed to this sudden increase in rate of turnover. Here, we produce the first genome and transcriptome of a long overlooked sister-order to Diptera: Mecoptera. We compare the scorpionfly Panorpa cognata X-chromosome gene content, expression, and structure, to that of several dipteran species as well as more distantly-related insect orders (Orthoptera and Blattodea). We find high conservation of gene content between the mecopteran X and the dipteran Muller F element, as well as several shared biological features, such as the presence of dosage compensation and a low amount of genetic diversity, consistent with a low recombination rate. However, the two homologous X chromosomes differ strikingly in their size and number of genes they carry. Our results therefore support a common ancestry of the mecopteran and ancestral dipteran X chromosomes, and suggest that Muller element F shrank in size and gene content after the split of Diptera and Mecoptera, which may have contributed to its turnover in dipteran insects.},
author = {Lasne, Clementine and Elkrewi, Marwan N and Toups, Melissa A and Layana Franco, Lorena Alexandra and Macon, Ariana and Vicoso, Beatriz},
issn = {1537-1719},
journal = {Molecular Biology and Evolution},
keywords = {Genetics, Molecular Biology, Ecology, Evolution, Behavior and Systematics},
number = {12},
publisher = {Oxford University Press},
title = {{The scorpionfly (Panorpa cognata) genome highlights conserved and derived features of the peculiar dipteran X chromosome}},
doi = {10.1093/molbev/msad245},
volume = {40},
year = {2023},
}
@article{14639,
abstract = {Background: Biallelic variants in OGDHL, encoding part of the α-ketoglutarate dehydrogenase complex, have been associated with highly heterogeneous neurological and neurodevelopmental disorders. However, the validity of this association remains to be confirmed. A second OGDHL patient cohort was recruited to carefully assess the gene-disease relationship.
Methods: Using an unbiased genotype-first approach, we screened large, multiethnic aggregated sequencing datasets worldwide for biallelic OGDHL variants. We used CRISPR/Cas9 to generate zebrafish knockouts of ogdhl, ogdh paralogs, and dhtkd1 to investigate functional relationships and impact during development. Functional complementation with patient variant transcripts was conducted to systematically assess protein functionality as a readout for pathogenicity.
Results: A cohort of 14 individuals from 12 unrelated families exhibited highly variable clinical phenotypes, with the majority of them presenting at least one additional variant, potentially accounting for a blended phenotype and complicating phenotypic understanding. We also uncovered extreme clinical heterogeneity and high allele frequencies, occasionally incompatible with a fully penetrant recessive disorder. Human cDNA of previously described and new variants were tested in an ogdhl zebrafish knockout model, adding functional evidence for variant reclassification. We disclosed evidence of hypomorphic alleles as well as a loss-of-function variant without deleterious effects in zebrafish variant testing also showing discordant familial segregation, challenging the relationship of OGDHL as a conventional Mendelian gene. Going further, we uncovered evidence for a complex compensatory relationship among OGDH, OGDHL, and DHTKD1 isoenzymes that are associated with neurodevelopmental disorders and exhibit complex transcriptional compensation patterns with partial functional redundancy.
Conclusions: Based on the results of genetic, clinical, and functional studies, we formed three hypotheses in which to frame observations: biallelic OGDHL variants lead to a highly variable monogenic disorder, variants in OGDHL are following a complex pattern of inheritance, or they may not be causative at all. Our study further highlights the continuing challenges of assessing the validity of reported disease-gene associations and effects of variants identified in these genes. This is particularly more complicated in making genetic diagnoses based on identification of variants in genes presenting a highly heterogenous phenotype such as “OGDHL-related disorders”.},
author = {Lin, Sheng-Jia and Vona, Barbara and Lau, Tracy and Huang, Kevin and Zaki, Maha S. and Aldeen, Huda Shujaa and Karimiani, Ehsan Ghayoor and Rocca, Clarissa and Noureldeen, Mahmoud M. and Saad, Ahmed K. and Petree, Cassidy and Bartolomaeus, Tobias and Abou Jamra, Rami and Zifarelli, Giovanni and Gotkhindikar, Aditi and Wentzensen, Ingrid M. and Liao, Mingjuan and Cork, Emalyn Elise and Varshney, Pratishtha and Hashemi, Narges and Mohammadi, Mohammad Hasan and Rad, Aboulfazl and Neira, Juanita and Toosi, Mehran Beiraghi and Knopp, Cordula and Kurth, Ingo and Challman, Thomas D. and Smith, Rebecca and Abdalla, Asmahan and Haaf, Thomas and Suri, Mohnish and Joshi, Manali and Chung, Wendy K. and Moreno-De-Luca, Andres and Houlden, Henry and Maroofian, Reza and Varshney, Gaurav K.},
issn = {1756-994X},
journal = {Genome Medicine},
keywords = {Genetics (clinical), Genetics, Molecular Biology, Molecular Medicine},
publisher = {Springer Nature},
title = {{Evaluating the association of biallelic OGDHL variants with significant phenotypic heterogeneity}},
doi = {10.1186/s13073-023-01258-4},
volume = {15},
year = {2023},
}
@article{14683,
abstract = {Mosaic analysis with double markers (MADM) technology enables the generation of genetic mosaic tissue in mice and high-resolution phenotyping at the individual cell level. Here, we present a protocol for isolating MADM-labeled cells with high yield for downstream molecular analyses using fluorescence-activated cell sorting (FACS). We describe steps for generating MADM-labeled mice, perfusion, single-cell suspension, and debris removal. We then detail procedures for cell sorting by FACS and downstream analysis. This protocol is suitable for embryonic to adult mice.
For complete details on the use and execution of this protocol, please refer to Contreras et al. (2021).1},
author = {Amberg, Nicole and Cheung, Giselle T and Hippenmeyer, Simon},
issn = {2666-1667},
journal = {STAR Protocols},
keywords = {General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, General Neuroscience},
number = {1},
publisher = {Elsevier},
title = {{Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry}},
doi = {10.1016/j.xpro.2023.102771},
volume = {5},
year = {2023},
}
@article{14742,
abstract = {Chromosomal rearrangements (CRs) have been known since almost the beginning of genetics.
While an important role for CRs in speciation has been suggested, evidence primarily stems
from theoretical and empirical studies focusing on the microevolutionary level (i.e., on taxon
pairs where speciation is often incomplete). Although the role of CRs in eukaryotic speciation at
a macroevolutionary level has been supported by associations between species diversity and
rates of evolution of CRs across phylogenies, these findings are limited to a restricted range of
CRs and taxa. Now that more broadly applicable and precise CR detection approaches have
become available, we address the challenges in filling some of the conceptual and empirical
gaps between micro- and macroevolutionary studies on the role of CRs in speciation. We
synthesize what is known about the macroevolutionary impact of CRs and suggest new research avenues to overcome the pitfalls of previous studies to gain a more comprehensive understanding of the evolutionary significance of CRs in speciation across the tree of life.},
author = {Lucek, Kay and Giménez, Mabel D. and Joron, Mathieu and Rafajlović, Marina and Searle, Jeremy B. and Walden, Nora and Westram, Anja M and Faria, Rui},
issn = {1943-0264},
journal = {Cold Spring Harbor Perspectives in Biology},
keywords = {General Biochemistry, Genetics and Molecular Biology},
number = {11},
publisher = {Cold Spring Harbor Laboratory},
title = {{The impact of chromosomal rearrangements in speciation: From micro- to macroevolution}},
doi = {10.1101/cshperspect.a041447},
volume = {15},
year = {2023},
}
@article{14770,
abstract = {We developed LIONESS, a technology that leverages improvements to optical super-resolution microscopy and prior information on sample structure via machine learning to overcome the limitations (in 3D-resolution, signal-to-noise ratio and light exposure) of optical microscopy of living biological specimens. LIONESS enables dense reconstruction of living brain tissue and morphodynamics visualization at the nanoscale.},
author = {Danzl, Johann G and Velicky, Philipp},
issn = {1548-7105},
journal = {Nature Methods},
keywords = {Cell Biology, Molecular Biology, Biochemistry, Biotechnology},
number = {8},
pages = {1141--1142},
publisher = {Springer Nature},
title = {{LIONESS enables 4D nanoscale reconstruction of living brain tissue}},
doi = {10.1038/s41592-023-01937-5},
volume = {20},
year = {2023},
}
@article{14774,
abstract = {Morphogen gradients impart positional information to cells in a homogenous tissue field. Fgf8a, a highly conserved growth factor, has been proposed to act as a morphogen during zebrafish gastrulation. However, technical limitations have so far prevented direct visualization of the endogenous Fgf8a gradient and confirmation of its morphogenic activity. Here, we monitor Fgf8a propagation in the developing neural plate using a CRISPR/Cas9-mediated EGFP knock-in at the endogenous fgf8a locus. By combining sensitive imaging with single-molecule fluorescence correlation spectroscopy, we demonstrate that Fgf8a, which is produced at the embryonic margin, propagates by diffusion through the extracellular space and forms a graded distribution towards the animal pole. Overlaying the Fgf8a gradient curve with expression profiles of its downstream targets determines the precise input-output relationship of Fgf8a-mediated patterning. Manipulation of the extracellular Fgf8a levels alters the signaling outcome, thus establishing Fgf8a as a bona fide morphogen during zebrafish gastrulation. Furthermore, by hindering Fgf8a diffusion, we demonstrate that extracellular diffusion of the protein from the source is crucial for it to achieve its morphogenic potential.},
author = {Harish, Rohit K and Gupta, Mansi and Zöller, Daniela and Hartmann, Hella and Gheisari, Ali and Machate, Anja and Hans, Stefan and Brand, Michael},
issn = {1477-9129},
journal = {Development},
keywords = {Developmental Biology, Molecular Biology},
number = {19},
publisher = {The Company of Biologists},
title = {{Real-time monitoring of an endogenous Fgf8a gradient attests to its role as a morphogen during zebrafish gastrulation}},
doi = {10.1242/dev.201559},
volume = {150},
year = {2023},
}
@article{14776,
abstract = {Soluble chaperones residing in the endoplasmic reticulum (ER) play vitally important roles in folding and quality control of newly synthesized proteins that transiently pass through the ER en route to their final destinations. These soluble residents of the ER are themselves endowed with an ER retrieval signal that enables the cell to bring the escaped residents back from the Golgi. Here, by using purified proteins, we showed that Nicotiana tabacum phytaspase, a plant aspartate-specific protease, introduces two breaks at the C-terminus of the N. tabacum ER resident calreticulin-3. These cleavages resulted in removal of either a dipeptide or a hexapeptide from the C-terminus of calreticulin-3 encompassing part or all of the ER retrieval signal. Consistently, expression of the calreticulin-3 derivative mimicking the phytaspase cleavage product in Nicotiana benthamiana cells demonstrated loss of the ER accumulation of the protein. Notably, upon its escape from the ER, calreticulin-3 was further processed by an unknown protease(s) to generate the free N-terminal (N) domain of calreticulin-3, which was ultimately secreted into the apoplast. Our study thus identified a specific proteolytic enzyme capable of precise detachment of the ER retrieval signal from a plant ER resident protein, with implications for the further fate of the escaped resident.},
author = {Teplova, Anastasiia and Pigidanov, Artemii A. and Serebryakova, Marina V. and Golyshev, Sergei A. and Galiullina, Raisa A. and Chichkova, Nina V. and Vartapetian, Andrey B.},
issn = {1422-0067},
journal = {International Journal of Molecular Sciences},
keywords = {Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Computer Science Applications, Spectroscopy, Molecular Biology, General Medicine, Catalysis},
number = {22},
publisher = {MDPI},
title = {{Phytaspase Is capable of detaching the endoplasmic reticulum retrieval signal from tobacco calreticulin-3}},
doi = {10.3390/ijms242216527},
volume = {24},
year = {2023},
}
@article{14781,
abstract = {Germ granules, condensates of phase-separated RNA and protein, are organelles that are essential for germline development in different organisms. The patterning of the granules and their relevance for germ cell fate are not fully understood. Combining three-dimensional in vivo structural and functional analyses, we study the dynamic spatial organization of molecules within zebrafish germ granules. We find that the localization of RNA molecules to the periphery of the granules, where ribosomes are localized, depends on translational activity at this location. In addition, we find that the vertebrate-specific Dead end (Dnd1) protein is essential for nanos3 RNA localization at the condensates’ periphery. Accordingly, in the absence of Dnd1, or when translation is inhibited, nanos3 RNA translocates into the granule interior, away from the ribosomes, a process that is correlated with the loss of germ cell fate. These findings highlight the relevance of sub-granule compartmentalization for post-transcriptional control and its importance for preserving germ cell totipotency.},
author = {Westerich, Kim Joana and Tarbashevich, Katsiaryna and Schick, Jan and Gupta, Antra and Zhu, Mingzhao and Hull, Kenneth and Romo, Daniel and Zeuschner, Dagmar and Goudarzi, Mohammad and Gross-Thebing, Theresa and Raz, Erez},
issn = {1534-5807},
journal = {Developmental Cell},
keywords = {Developmental Biology, Cell Biology, General Biochemistry, Genetics and Molecular Biology, Molecular Biology},
number = {17},
pages = {1578--1592.e5},
publisher = {Elsevier},
title = {{Spatial organization and function of RNA molecules within phase-separated condensates in zebrafish are controlled by Dnd1}},
doi = {10.1016/j.devcel.2023.06.009},
volume = {58},
year = {2023},
}
@article{13989,
abstract = {Characterizing and controlling entanglement in quantum materials is crucial for the development of next-generation quantum technologies. However, defining a quantifiable figure of merit for entanglement in macroscopic solids is theoretically and experimentally challenging. At equilibrium the presence of entanglement can be diagnosed by extracting entanglement witnesses from spectroscopic observables and a nonequilibrium extension of this method could lead to the discovery of novel dynamical phenomena. Here, we propose a systematic approach to quantify the time-dependent quantum Fisher information and entanglement depth of transient states of quantum materials with time-resolved resonant inelastic x-ray scattering. Using a quarter-filled extended Hubbard model as an example, we benchmark the efficiency of this approach and predict a light-enhanced many-body entanglement due to the proximity to a phase boundary. Our work sets the stage for experimentally witnessing and controlling entanglement in light-driven quantum materials via ultrafast spectroscopic measurements.},
author = {Hales, Jordyn and Bajpai, Utkarsh and Liu, Tongtong and Baykusheva, Denitsa Rangelova and Li, Mingda and Mitrano, Matteo and Wang, Yao},
issn = {2041-1723},
journal = {Nature Communications},
keywords = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary},
publisher = {Springer Nature},
title = {{Witnessing light-driven entanglement using time-resolved resonant inelastic X-ray scattering}},
doi = {10.1038/s41467-023-38540-3},
volume = {14},
year = {2023},
}
@article{14077,
abstract = {The regulatory architecture of gene expression is known to differ substantially between sexes in Drosophila, but most studies performed
so far used whole-body data and only single crosses, which may have limited their scope to detect patterns that are robust across tissues
and biological replicates. Here, we use allele-specific gene expression of parental and reciprocal hybrid crosses between 6 Drosophila
melanogaster inbred lines to quantify cis- and trans-regulatory variation in heads and gonads of both sexes separately across 3 replicate
crosses. Our results suggest that female and male heads, as well as ovaries, have a similar regulatory architecture. On the other hand,
testes display more and substantially different cis-regulatory effects, suggesting that sex differences in the regulatory architecture that
have been previously observed may largely derive from testis-specific effects. We also examine the difference in cis-regulatory variation
of genes across different levels of sex bias in gonads and heads. Consistent with the idea that intersex correlations constrain expression
and can lead to sexual antagonism, we find more cis variation in unbiased and moderately biased genes in heads. In ovaries, reduced cis
variation is observed for male-biased genes, suggesting that cis variants acting on these genes in males do not lead to changes in ovary
expression. Finally, we examine the dominance patterns of gene expression and find that sex- and tissue-specific patterns of inheritance
as well as trans-regulatory variation are highly variable across biological crosses, although these were performed in highly controlled
experimental conditions. This highlights the importance of using various genetic backgrounds to infer generalizable patterns.},
author = {Puixeu Sala, Gemma and Macon, Ariana and Vicoso, Beatriz},
issn = {2160-1836},
journal = {G3: Genes, Genomes, Genetics},
keywords = {Genetics (clinical), Genetics, Molecular Biology},
number = {8},
publisher = {Oxford University Press},
title = {{Sex-specific estimation of cis and trans regulation of gene expression in heads and gonads of Drosophila melanogaster}},
doi = {10.1093/g3journal/jkad121},
volume = {13},
year = {2023},
}
@article{12163,
abstract = {Small GTPases play essential roles in the organization of eukaryotic cells. In recent years, it has become clear that their intracellular functions result from intricate biochemical networks of the GTPase and their regulators that dynamically bind to a membrane surface. Due to the inherent complexities of their interactions, however, revealing the underlying mechanisms of action is often difficult to achieve from in vivo studies. This review summarizes in vitro reconstitution approaches developed to obtain a better mechanistic understanding of how small GTPase activities are regulated in space and time.},
author = {Loose, Martin and Auer, Albert and Brognara, Gabriel and Budiman, Hanifatul R and Kowalski, Lukasz M and Matijevic, Ivana},
issn = {1873-3468},
journal = {FEBS Letters},
keywords = {Cell Biology, Genetics, Molecular Biology, Biochemistry, Structural Biology, Biophysics},
number = {6},
pages = {762--777},
publisher = {Wiley},
title = {{In vitro reconstitution of small GTPase regulation}},
doi = {10.1002/1873-3468.14540},
volume = {597},
year = {2023},
}
@article{12802,
abstract = {Little is known about the critical metabolic changes that neural cells have to undergo during development and how temporary shifts in this program can influence brain circuitries and behavior. Inspired by the discovery that mutations in SLC7A5, a transporter of metabolically essential large neutral amino acids (LNAAs), lead to autism, we employed metabolomic profiling to study the metabolic states of the cerebral cortex across different developmental stages. We found that the forebrain undergoes significant metabolic remodeling throughout development, with certain groups of metabolites showing stage-specific changes, but what are the consequences of perturbing this metabolic program? By manipulating Slc7a5 expression in neural cells, we found that the metabolism of LNAAs and lipids are interconnected in the cortex. Deletion of Slc7a5 in neurons affects the postnatal metabolic state, leading to a shift in lipid metabolism. Additionally, it causes stage- and cell-type-specific alterations in neuronal activity patterns, resulting in a long-term circuit dysfunction.},
author = {Knaus, Lisa and Basilico, Bernadette and Malzl, Daniel and Gerykova Bujalkova, Maria and Smogavec, Mateja and Schwarz, Lena A. and Gorkiewicz, Sarah and Amberg, Nicole and Pauler, Florian and Knittl-Frank, Christian and Tassinari, Marianna and Maulide, Nuno and Rülicke, Thomas and Menche, Jörg and Hippenmeyer, Simon and Novarino, Gaia},
issn = {0092-8674},
journal = {Cell},
keywords = {General Biochemistry, Genetics and Molecular Biology},
number = {9},
pages = {1950--1967.e25},
publisher = {Elsevier},
title = {{Large neutral amino acid levels tune perinatal neuronal excitability and survival}},
doi = {10.1016/j.cell.2023.02.037},
volume = {186},
year = {2023},
}
@article{10787,
abstract = {A species distributed across diverse environments may adapt to local conditions. We ask how quickly such a species changes its range in response to changed conditions. Szép et al. (Szép E, Sachdeva H, Barton NH. 2021 Polygenic local adaptation in metapopulations: a stochastic eco-evolutionary model. Evolution75, 1030–1045 (doi:10.1111/evo.14210)) used the infinite island model to find the stationary distribution of allele frequencies and deme sizes. We extend this to find how a metapopulation responds to changes in carrying capacity, selection strength, or migration rate when deme sizes are fixed. We further develop a ‘fixed-state’ approximation. Under this approximation, polymorphism is only possible for a narrow range of habitat proportions when selection is weak compared to drift, but for a much wider range otherwise. When rates of selection or migration relative to drift change in a single deme of the metapopulation, the population takes a time of order m−1 to reach the new equilibrium. However, even with many loci, there can be substantial fluctuations in net adaptation, because at each locus, alleles randomly get lost or fixed. Thus, in a finite metapopulation, variation may gradually be lost by chance, even if it would persist in an infinite metapopulation. When conditions change across the whole metapopulation, there can be rapid change, which is predicted well by the fixed-state approximation. This work helps towards an understanding of how metapopulations extend their range across diverse environments.
This article is part of the theme issue ‘Species’ ranges in the face of changing environments (Part II)’.},
author = {Barton, Nicholas H and Olusanya, Oluwafunmilola O},
issn = {1471-2970},
journal = {Philosophical Transactions of the Royal Society B: Biological Sciences},
keywords = {General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology},
number = {1848},
publisher = {The Royal Society},
title = {{The response of a metapopulation to a changing environment}},
doi = {10.1098/rstb.2021.0009},
volume = {377},
year = {2022},
}
@article{11160,
abstract = {Mutations in the chromodomain helicase DNA-binding 8 (CHD8) gene are a frequent cause of autism spectrum disorder (ASD). While its phenotypic spectrum often encompasses macrocephaly, implicating cortical abnormalities, how CHD8 haploinsufficiency affects neurodevelopmental is unclear. Here, employing human cerebral organoids, we find that CHD8 haploinsufficiency disrupted neurodevelopmental trajectories with an accelerated and delayed generation of, respectively, inhibitory and excitatory neurons that yields, at days 60 and 120, symmetrically opposite expansions in their proportions. This imbalance is consistent with an enlargement of cerebral organoids as an in vitro correlate of patients’ macrocephaly. Through an isogenic design of patient-specific mutations and mosaic organoids, we define genotype-phenotype relationships and uncover their cell-autonomous nature. Our results define cell-type-specific CHD8-dependent molecular defects related to an abnormal program of proliferation and alternative splicing. By identifying cell-type-specific effects of CHD8 mutations, our study uncovers reproducible developmental alterations that may be employed for neurodevelopmental disease modeling.},
author = {Villa, Carlo Emanuele and Cheroni, Cristina and Dotter, Christoph and López-Tóbon, Alejandro and Oliveira, Bárbara and Sacco, Roberto and Yahya, Aysan Çerağ and Morandell, Jasmin and Gabriele, Michele and Tavakoli, Mojtaba and Lyudchik, Julia and Sommer, Christoph M and Gabitto, Mariano and Danzl, Johann G and Testa, Giuseppe and Novarino, Gaia},
issn = {2211-1247},
journal = {Cell Reports},
keywords = {General Biochemistry, Genetics and Molecular Biology},
number = {1},
publisher = {Elsevier},
title = {{CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories}},
doi = {10.1016/j.celrep.2022.110615},
volume = {39},
year = {2022},
}
@article{11167,
abstract = {Complex I is one of the major respiratory complexes, conserved from bacteria to mammals. It oxidises NADH, reduces quinone and pumps protons across the membrane, thus playing a central role in the oxidative energy metabolism. In this review we discuss our current state of understanding the structure of complex I from various species of mammals, plants, fungi, and bacteria, as well as of several complex I-related proteins. By comparing the structural evidence from these systems in different redox states and data from mutagenesis and molecular simulations, we formulate the mechanisms of electron transfer and proton pumping and explain how they are conformationally and electrostatically coupled. Finally, we discuss the structural basis of the deactivation phenomenon in mammalian complex I.},
author = {Kampjut, Domen and Sazanov, Leonid A},
issn = {0959-440X},
journal = {Current Opinion in Structural Biology},
keywords = {Molecular Biology, Structural Biology},
publisher = {Elsevier},
title = {{Structure of respiratory complex I – An emerging blueprint for the mechanism}},
doi = {10.1016/j.sbi.2022.102350},
volume = {74},
year = {2022},
}
@article{11351,
abstract = {One hallmark of plant cells is their cell wall. They protect cells against the environment and high turgor and mediate morphogenesis through the dynamics of their mechanical and chemical properties. The walls are a complex polysaccharidic structure. Although their biochemical composition is well known, how the different components organize in the volume of the cell wall and interact with each other is not well understood and yet is key to the wall’s mechanical properties. To investigate the ultrastructure of the plant cell wall, we imaged the walls of onion (Allium cepa) bulbs in a near-native state via cryo-focused ion beam milling (cryo-FIB milling) and cryo-electron tomography (cryo-ET). This allowed the high-resolution visualization of cellulose fibers in situ. We reveal the coexistence of dense fiber fields bathed in a reticulated matrix we termed “meshing,” which is more abundant at the inner surface of the cell wall. The fibers adopted a regular bimodal angular distribution at all depths in the cell wall and bundled according to their orientation, creating layers within the cell wall. Concomitantly, employing homogalacturonan (HG)-specific enzymatic digestion, we observed changes in the meshing, suggesting that it is—at least in part—composed of HG pectins. We propose the following model for the construction of the abaxial epidermal primary cell wall: the cell deposits successive layers of cellulose fibers at −45° and +45° relative to the cell’s long axis and secretes the surrounding HG-rich meshing proximal to the plasma membrane, which then migrates to more distal regions of the cell wall.},
author = {Nicolas, William J. and Fäßler, Florian and Dutka, Przemysław and Schur, Florian KM and Jensen, Grant and Meyerowitz, Elliot},
issn = {0960-9822},
journal = {Current Biology},
keywords = {General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology},
number = {11},
pages = {P2375--2389},
publisher = {Elsevier},
title = {{Cryo-electron tomography of the onion cell wall shows bimodally oriented cellulose fibers and reticulated homogalacturonan networks}},
doi = {10.1016/j.cub.2022.04.024},
volume = {32},
year = {2022},
}