bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kin selection underpins family dynamics in rural China
Authors: He Qiao-Qiao , Wang Ming-Yang , Wu Jia-Jia , Feng Tian-Jiao , Zheng Xiu-Deng , Yu Jie-Ru , Tang Song-Hua , Deng Ling-Ling , Fu Chang , Mace Ruth , Tao Yi , Ji Ting 
Published: September 2023

AbstractThe number of co-resident members is an important characteristic of human families and thus plays an important role in human evolution. However, an inclusive fitness model of how many members should co-reside has not been explicitly tested. Here we use an evolutionary game model and a decade of family dynamic data from a rural population of southwestern China (1,110 households) to show that the existence of an evolutionary stable family size can be understood by considering the average local relatedness and average inclusive fitness of the family. Empirical data analyses show that average relatednessdecreased with increasing family size, andwas associated with helping behavior (especially for the elders) in the family, so the family tended to keep a higher level of average relatedness by adjusting the number of co-resident members. These findings are helpful to understand the variation in family size in different cultures and to demonstrate the importance of kin selection in regulating family dynamics.
A developmental ontology for the colonial architecture of salps
Authors: Damian-Serrano Alejandro , Sutherland Kelly R. 
Published: September 2023

AbstractColonial animals are composed of clonal individuals that remain physically connected and physiologically integrated. Salps are urochordates with a dual life cycle including an asexual solitary stage that buds sexual colonies composed of jet-propelling zooids that efficiently swim together as a single unit by multi-jet propulsion. Colonies from different species develop distinct architectures characterized by their zooid arrangement patterns, but this diversity has received little attention. Thus, these architectures have never been formally defined using a framework of variables and axes that would allow comparative analyses. We set out to define an ontology of the salp colony architecture morphospace and describe the developmental pathways that build the different architectures. To inform these definitions, we collected and photographed live specimens of adult and developing colonies through offshore SCUBA diving. Since all salp colonies begin their development as a transversal double chain, we characterized each adult colonial architecture as a series of developmental transitions, such as rotations and translations of zooids, relative to their orientation at this early shared stage. We hypothesize that all adult architectures are either final or intermediate stages within three developmental pathways towards either bipinnate, cluster, or helical forms. This framework will enable comparative studies on the biomechanical implications, ecological functions, evolutionary history, and engineering applications of the diversity of salp colony architectures.
Defining RNA oligonucleotides that reverse deleterious phase transitions of RNA-binding proteins with prion-like domains
Authors: Guo Lin , Mann Jacob R. , Mauna Jocelyn C. , Copley Katie E. , Wang Hejia , Rubien Jack D. , Odeh Hana M. , Lin JiaBei , Lee Bo Lim , Ganser Laura , Robinson Emma , Kim Kevin M. , Murthy Anastasia C. , Paul Tapas , Portz Bede , Gleixner Amanda M. , Diaz Zamia , Carey Jenny L. , Smirnov Ashleigh , Padilla George , Lavorando Ellen , Espy Carolann , Shang Yulei , Huang Eric J. , Chesi Alessandra , Fawzi Nicolas L. , Myong Sua , Donnelly Christopher J. , Shorter James 
Published: September 2023

SummaryRNA-binding proteins with prion-like domains, such as FUS and TDP-43, condense into functional liquids, which can transform into pathological fibrils that underpin fatal neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD). Here, we define short RNAs (24-48 nucleotides) that prevent FUS fibrillization by promoting liquid phases, and distinct short RNAs that prevent and, remarkably, reverse FUS condensation and fibrillization. These activities require interactions with multiple RNA-binding domains of FUS and are encoded by RNA sequence, length, and structure. Importantly, we define a short RNA that dissolves aberrant cytoplasmic FUS condensates, restores nuclear FUS, and mitigates FUS proteotoxicity in optogenetic models and human motor neurons. Another short RNA dissolves aberrant cytoplasmic TDP-43 condensates, restores nuclear TDP-43, and mitigates TDP-43 proteotoxicity. Since short RNAs can be effectively delivered to the human brain, these oligonucleotides could have therapeutic utility for ALS/FTD and related disorders.
Eta-secretase-like processing of the amyloid precursor protein (APP) by RHBDL4
Authors: Ylauna Christine Megane Penalva , Paschkowsky Sandra , Recinto Sherilyn Junelle , Duchesne Anthony , Levet Clemence , Charron François , Freeman Matthew , McKinney R. Anne , Trempe Jean-Francois , Munter Lisa Marie 
Published: September 2023

AbstractThe amyloid precursor protein (APP) has been extensively studied with regards to its contribution to the pathology of Alzheimer’s disease. APP is an ubiquitously expressed type I transmembrane protein synthesized in the endoplasmic reticulum (ER) and translocated to the plasma membrane where it undergoes proteolytic cleavages by several identified proteases. Conversely to other known proteases, we previously elucidated human rhomboid protease RHBDL4 as a novel APP processing enzyme where several cleavages likely occur already in the ER. Interestingly, the pattern of RHBDL4-derived large APP C-terminal fragments resemble those generated by the η-secretase or MT5-MMP, which was described to generate so called Aη fragments. The similarity in large APP C-terminal fragments between both proteases raised the question whether RHBDL4 may contribute to η-secretase activity and Aη-like fragments. Here, we identified two cleavage sites of RHBDL4 in APP by mass spectrometry, which, intriguingly, lie in close proximity to the cleavage sites of MT5-MMP. Indeed, we observed that RHBDL4 generates Aη-like fragmentsin vitrowithout contributions of α-, β-, or γ-secretases. Such Aη-like fragments are likely generated in the ER since RHBDL4-derived APP-C-terminal fragments do not reach the cell surface. Inherited, familial APP mutations appear to not affect this processing pathway. In RHBDL4 knockout mice, we observed increased cerebral full length APP levels in comparison to WT brains in support of RHBDL4 being a physiologically relevant protease for APP. Furthermore, we found secreted Aη fragments in dissociated mixed cortical cultures from wild type mice, however significantly less Aη fragments in cultures from RHBDL4 knockout mice. Our data underscores that RHBDL4 contributes to η-secretease-like processing of APP and that RHBDL4 is a physiologically relevant protease for APP.
Investigating the genetic control of plant development under speed breeding conditions
Authors: Rossi Nicola , Powell Wayne , Mackay Ian , Hickey Lee , Maurer Andreas , Pillen Klaus , Halliday Karen , Sharma Rajiv 
Published: September 2023

AbstractSpeed breeding is a powerful tool to accelerate breeding and research programmes by shortening generation time and has been widely adopted for a range of crop species. Despite its success and growing popularity with breeders the genetic basis of plant development under speed breeding remains unknown. In this study, we explored how genotypes respond in terms of developmental advancement under different photoperiod regimes in the context of speed breeding. A subset of the barley HEB-25 Nested Association Mapping population was evaluated for days to heading and maturity under two contrasting photoperiod conditions: 1) Speed Breeding (SB) consisting of 22 hours of light and 2 hours of darkness), and 2) Normal Breeding (NB) consisting of 16 hours of light and 8 hours of darkness. GWAS revealed that developmental responses under both conditions were largely controlled by two loci:PPDH-1andELF3. Allelic variants at these genes determine whether plants display early flowering and maturity under both NB and SB. At key QTL regions, domesticated alleles were associated with late flowering and maturity in NB and early flowering and maturity in SB, whereas wild alleles were associated with early flowering under both conditions. We hypothesise that this may be related to the dark dependent repression ofPPD-H1byELF3which might be more prominent in NB conditions. Furthermore, by comparing development under two contrasting photoperiod regimes, we were able to derive an estimate of plasticity for the two traits. Interestingly, plasticity in development was largely attributed to allelic variation at ELF3. Our results have important implications for our understanding and optimisation of speed breeding protocols particularly when incorporating genetics from wild relatives into breeding programmes and the design of breeding programmes to support the delivery of climate resilient crops.
Palmitoylation of proteolipid protein M6 promotes tricellular junction assembly in epithelia ofDrosophila
Authors: Schleutker Raphael , Luschnig Stefan 
Published: September 2023

SummaryTricellular junctions (TCJs) provide essential adhesive and occluding functions at epithelial cell vertices and play key roles for tissue integrity and physiology, but how TCJs are assembled and maintained is poorly understood. InDrosophila, the transmembrane proteins Anakonda (Aka), Gliotactin (Gli), and M6 constitute tricellular occluding junctions. Aka and M6 localize in an interdependent manner to vertices and are required jointly to localize Gli, but how these proteins interact to assemble TCJs was not known. Here, we show that the tetraspan proteolipid protein M6 physically interacts with Aka and with itself. M6 is palmitoylated on a conserved juxta-membrane cysteine cluster. This modification promotes efficient vertex localization of M6 and binding to Aka, but not to itself, and becomes essential when TCJ protein levels are reduced. Abolishing M6 palmitoylation leads to delayed accumulation of M6 and Aka at vertices but does not affect the rate of TCJ growth or mobility of M6 or Aka. Our findings suggest that palmitoylation-dependent recruitment of Aka by M6 promotes initiation of TCJ assembly, while subsequent TCJ growth relies on different mechanisms independent of M6 palmitoylation.
High-throughput DNA extraction and cost-effective miniaturized metagenome and amplicon library preparation of soil samples for DNA sequencing
Authors: Jensen Thomas BN , Dall Sebastian M , Knutsson Simon , Karst Søren M , Albertsen Mads 
Published: September 2023

AbstractReductions in sequencing costs have enabled widespread use of shotgun metagenomics and amplicon sequencing, which have drastically improved our understanding of the microbial world. However, large sequencing projects are now hampered by the cost of library preparation and low sample throughput. Here, we benchmarked three high-throughput DNA extraction methods: ZymoBIOMICS™ 96 MagBead DNA Kit, MP BiomedicalsTMFastDNATM-96 Soil Microbe DNA Kit, and DNeasy® 96 PowerSoil® Pro QIAcube® HT Kit. The DNA extractions were evaluated based on length, quality, quantity, and the observed microbial community across five diverse soil types. DNA extraction of all soil types was successful for all kits, however DNeasy® 96 PowerSoil® Pro QIAcube® HT Kit excelled across all performance parameters. We further used the nanoliter dispensing robot I.DOT One to miniaturize Illumina amplicon and metagenomic library preparation volumes by a factor of 5 and 10, respectively, with no significant impact on the observed microbial communities. With these protocols, DNA extraction, metagenomic library preparation, or amplicon library preparation for one 96-well plate are approx. 3, 5, and 6 hours, respectively. Furthermore, the miniaturization of amplicon and metagenome library preparation reduces the chemical and plastic costs from 5.0 to 3.6 and 59 to 7.3 USD pr. sample.
Post-replicative lesion processing limits DNA damage-induced mutagenesis
Authors: Maslowska Katarzyna H. , Wong Ronald P. , Ulrich Helle D. , Pagès Vincent 
Published: September 2023

AbstractDNA lesions are a threat to genome stability. To cope with them during DNA replication, cells have evolved lesion bypass mechanisms: Translesion Synthesis (TLS), which allows the cell to insert a nucleotide directly opposite the lesion, with the risk of introducing a mutation, and error-free Damage Avoidance (DA), which uses homologous recombination to retrieve the genetic information from the sister chromatid.In this study, we investigate the timing of lesion bypass and its implications for the accuracy of the process. Our findings reveal that DNA polymerase η can bypass common, UV-induced TT-cyclobutane pyrimidine dimers at the fork, immediately after encountering the blocking lesion. In contrast, TLS at TT(6-4) photoproducts and bulky G-AAF adducts, mediated by Rev1 and Pol ζ, takes place behind the fork, at post-replicative gaps that are generated downstream of the lesion after repriming. We show that in this latter situation, TLS competes with the DA pathway, thus reducing overall mutagenicity of damage bypass. Additionally, our study demonstrates that Exo1 nuclease influences the balance between TLS and DA by modulating the size of the post-replicative gaps.
Alternative splicing coupled to nonsense-mediated decay coordinates downregulation of non-neuronal genes in developing neurons
Authors: Zhuravskaya Anna , Yap Karen , Hamid Fursham , Makeyev Eugene V. 
Published: September 2023

AbstractThe functional coupling between alternative pre-mRNA splicing (AS) and the mRNA quality control mechanism called nonsense-mediated decay (NMD) can modulate transcript abundance. Previous studies have identified several examples of such a regulation in developing neurons. However, the systems-level effects of AS-NMD in this context are poorly understood. We developed an R package, factR2, which offers a comprehensive suite of AS-NMD analysis functions. Using this tool, we conducted a longitudinal analysis of gene expression in pluripotent stem cells undergoing induced neuronal differentiation. Our analysis uncovered hundreds of AS-NMD events with significant potential to regulate gene expression. Notably, this regulation was significantly overrepresented in specific functional groups of developmentally downregulated genes. Particularly strong association with gene downregulation was detected for alternative cassette exons stimulating NMD (NS-CEs) upon their inclusion into mature mRNA. By combining bioinformatics analyses with CRISPR/Cas9 genome editing and other experimental approaches we show that NS-CEs regulated by the RNA-binding protein PTBP1 dampen the expression of their genes in developing neurons. We also provide evidence that the NS-CE activity is temporally coordinated with NMD-independent gene repression mechanisms. Our study provides an accessible workflow for the discovery and prioritization of AS-NMD targets. It further argues that the AS-NMD pathway plays a widespread role in developing neurons by facilitating the downregulation of functionally related non-neuronal genes.
A Stapled Peptide Inhibitor of METTL3-METTL14 for Cancer Therapy
Authors: Li Zenghui , Feng Yuqing , Han Hong , Jiang Xingyue , Chen Weiyu , Ma Xuezhen , Mei Yang , Yuan Dan , Zhang Dingxiao , Shi Junfeng 
Published: September 2023

AbstractMETTL3, a primary methyltransferase catalyzing RNA N6-methyladenosine (m6A) modification, has been identified as an oncogene in several cancer types and thus nominated as a potentially effective target for therapeutic inhibition, although current options using this strategy are limited. In this study, we targeted protein-protein interactions at the METTL3-METTL14 binding interface to inhibit complex formation and subsequent catalysis of RNA m6A modification. Among candidate peptides,RM3exhibited the highest anti-cancer potency, inhibiting METTL3 activity while also facilitating its proteasomal degradation. We then designed a stapled peptide inhibitor (RSM3) with enhanced peptide stability and formation of the α-helical secondary structure required for METTL3 interaction. Functional and transcriptomic analysisin vivoindicated thatRSM3induced upregulation of programmed cell death-related genes while inhibiting cancer-promoting signals. Furthermore, tumor growth was significantly suppressed while apoptosis was enhanced uponRSM3treatment, accompanied by in-creased METTL3 degradation, and reduced global RNA methylation levels in twoin vivotumor models. This peptide inhibitor thus exploits a mechanism distinct from other competitive-binding small molecules to inhibit oncogenic METTL3 activity. Our findings collectively highlight the potential of targeting METTL3 in cancer therapies through peptide-based inhibition of complex formation and proteolytic degradation.
HIF1A contributes to the survival of aneuploid and mosaic pre-implantation embryos
Authors: Sanchez-Vasquez Estefania , Bronner Marianne E. , Zernicka-Goetz Magdalena 
Published: September 2023

ABSTRACTHuman fertility is suboptimal, partly due to error-prone divisions in early cleavage-stages that result in aneuploidy. Most human pre-implantation are mosaics of euploid and aneuploid cells, however, mosaic embryos with a low proportion of aneuploid cells have a similar likelihood of developing to term as fully euploid embryos. How embryos manage aneuploidy during development is poorly understood. This knowledge is crucial for improving fertility treatments and reducing developmental defects. To explore these mechanisms, we established a new mouse model of chromosome mosaicism to study the fate of aneuploid cells during pre-implantation development. We previously used the Mps1 inhibitor reversine to generate aneuploidy in embryos. Here, we found that treatment with the more specific Mps1 inhibitor AZ3146 induced chromosome segregation defects in pre-implantation embryos, similar to reversine. However, AZ3146- treated embryos showed a higher developmental potential than reversine-treated embryos. Unlike reversine-treated embryos, AZ3146-treated embryos exhibited transient upregulation of Hypoxia Inducible-Factor-1A (HIF1A) and lacked p53 upregulation. Pre-implantation embryos develop in a hypoxic environmentin vivo, and hypoxia exposurein vitroreduced DNA damage in response to Mps1 inhibition and increased the proportion of euploid cells in the mosaic epiblast. Inhibiting HIF1A in mosaic embryos also decreased the proportion of aneuploid cells in mosaic embryos. Our work illuminates potential strategies to improve the developmental potential of mosaic embryos.
Human DCP1 is crucial for mRNA decapping and possesses paralog-specific gene regulating functions
Authors: Chen Ting-Wen , Liao Hsiao-Wei , Noble Michelle , Siao Jing-Yi , Cheng Yu-Hsuan , Chiang Wei-Chung , Lo Yi-Tzu , Chang Chung-Te 
Published: September 2023

ABSTRACTThe mRNA 5’-cap structure removal by the decapping enzyme DCP2 is a critical step in gene regulation. While DCP2 is the catalytic subunit in the decapping complex, its activity is strongly enhanced by multiple factors, particularly DCP1, which is the major activator in yeast. However, the precise role of DCP1 in metazoans has yet to be fully elucidated. Moreover, in humans, the specific biological functions of the two DCP1 paralogs, DCP1a and DCP1b, remain largely unknown. To investigate the role of human DCP1, we generated cell-lines that were deficient in DCP1a, DCP1b or both to evaluate the importance of DCP1 in the decapping machinery. Our results highlight the importance of human DCP1 in decapping process and show that the EVH1 domain of DCP1 enhances the mRNA-binding affinity of DCP2. Transcriptome and metabolome analyses outline the distinct functions of DCP1a and DCP1b in human cells, regulating specific endogenous mRNA targets and biological processes. Overall, our findings provide insights into the molecular mechanism of human DCP1 in mRNA decapping and shed light on the distinct functions of its paralogs.
Delineating the heterogeneity of senescence-induced-functional alterations in hepatocytes
Authors: Kumar Pavitra , Hassan Mohsin , Tacke Frank , Engelmann Cornelius 
Published: September 2023

AbstractBackground and AimCellular senescence of hepatocytes involves permanent cell cycle arrest, disrupted cellular bioenergetics, resistance to cell death, and the release of pro-inflammatory cytokines. This ’zombie-like’ state perpetuates harmful effects on tissues and holds potential implications for liver disease progression. Remarkably, senescence exhibits heterogeneity, stemming from two crucial factors: the inducing stressor and the cell type. As such, our present study endeavors to characterize stressor-specific changes in senescence phenotype, its related molecular patterns, and cellular bioenergetics in primary mouse hepatocytes (PMH) and hepatocyte-derived liver organoids (HepOrgs).MethodsPMH, isolated by collagenase-perfused mouse liver (C57B6/J; 18-23 weeks), were cultured overnight in William’s E-medium supplemented with 2% FBS, L-glutamine, and hepatocyte growth supplements. HepOrgs were developed by culturing cells in a 3D matrix for two weeks. The senescence was induced by DNA damage (doxorubicin, cisplatin, and etoposide), oxidative stress (H2O2, and ethanol), and telomere inhibition (BIBR-1532), p53 activation (nutlin-3a), DNA methyl transferase inhibition (5-azacitidine), and metabolism inhibitors (galactosamine and hydroxyurea). SA-β galactosidase activity, immunofluorescence, immunoblotting, and senescence-associated secretory phenotype (SASP), and cellular bioenergetics were used to assess the senescence phenotype.ResultsEach senescence inducer triggers a unique combination of senescence markers in hepatocytes. All senescence inducers, except hydroxyurea and ethanol, increased SA-β galactosidase activity, the most commonly used marker for cellular senescence. Among the SASP factors, CCL2 and IL-10 were consistently upregulated, while Plasminogen activator inhibitor-1 exhibited global downregulation across all modes of senescence. Notably, DNA damage response was activated by DNA damage inducers. Cell cycle markers were most significantly reduced by doxorubicin, cisplatin, and galactosamine. Additionally, DNA damage-induced senescence shifted cellular bioenergetics capacity from glycolysis to oxidative phosphorylation.ConclusionIn our study, we demonstrated that each senescence inducer activates a unique combination of senescence markers in PMH. Doxorubicin demonstrated the highest efficacy in inducing senescence, followed by cisplatin and H2O2, with no impact on apoptosis. Each inducer prompted DNA damage response and mitochondrial dysfunction, independent of MAPK/AKT.Graphical abstract