bluuebunny/crossref_metadata_2025_split huggingface dataset:
SHIELD: Skull-shaped hemispheric implants enabling large-scale electrophysiology datasets in the mouse brain
Authors: Bennett Corbett , Ouellette Ben , Ramirez Tamina , Cahoon Alex , Cabasco Hannah , Browning Yoni , Lakunina Anna , Lynch Galen F. , McBride Ethan , Belski Hannah , Gillis Ryan , Grasso Conor , Howard Robert , Johnson Tye , Loeffler Henry , Smith Heston , Sullivan David , Williford Allison , Caldejon Shiella , Durand Severine , Gale Samuel , Guthrie Alan , Ha Vivian , Han Warren , Hardcastle Ben , Mochizuki Chris , Sridhar Arjun , Suarez Lucas , Swapp Jackie , Wilkes Joshua , Siegle Joshua H. , Farrell Colin , Groblewski Peter A. , Olsen Shawn R. 
Published: November 2023

AbstractTo understand the neural basis of behavior, it is essential to measure spiking dynamics across many interacting brain regions. While new technologies, such as Neuropixels probes, facilitate multi-regional recordings, significant surgical and procedural hurdles remain for these experiments to achieve their full potential. Here, we describe a novel 3D-printed cranial-replacement implant (SHIELD) enabling electrophysiological recordings from distributed areas of the mouse brain. This skull-shaped implant is designed with customizable insertion holes, allowing dozens of cortical and subcortical structures to be recorded in a single mouse using repeated multi-probe insertions over many days. We demonstrate the procedure’s high success rate, biocompatibility, lack of adverse effects on behavior, and compatibility with imaging and optogenetics. To showcase the scientific utility of the SHIELD implant, we use multi-probe recordings to reveal novel insights into how alpha rhythms organize spiking activity across visual and sensorimotor networks. Overall, this method enables powerful large-scale electrophysiological measurements for the study of distributed brain computation.
Stereotyped goal-directed manifold dynamics in the insular cortex
Authors: Talpir Itay , Livneh Yoav 
Published: November 2023

SummaryThe insular cortex is involved in diverse processes including bodily homeostasis, emotions, and cognition. Yet we lack a comprehensive understanding of how it processes information at the level of neuronal populations. We leveraged recent advances in unsupervised machine learning to study insular cortex population activity patterns (i.e., neuronal manifold) in mice performing goal-directed behaviors. We find that the insular cortex activity manifold is remarkably consistent across different animals and under different motivational states. Activity dynamics within the neuronal manifold are highly stereotyped during rewarded trials, enabling robust prediction of single-trial outcomes across different mice, and across various natural and artificial motivational states. Comparing goal-directed behavior with self-paced free consumption, we find that the stereotyped activity patterns reflect task-dependent goal-directed reward anticipation, and not licking, taste, or positive valence. These findings reveal a core computation in insular cortex that could explain its involvement in pathologies involving aberrant motivations.
Pyruvate Oxidation Sustains B Cell Antigen-Specific Activation to Exacerbate MASH
Authors: Barrow Fanta , Wang Haiguang , Fredrickson Gavin , Florczak Kira , Ciske Erin , Khanal Shalil , Parthiban Preethy , Nguyen Huy , Rios Enrique , Kostallari Enis , Revelo Xavier S. 
Published: November 2023

ABSTRACTB cells play a crucial role in the pathogenesis of metabolic dysfunction-associated steatohepatitis (MASH), a severe form of steatotic liver disease that if persistent can lead to cirrhosis, liver failure, and cancer. Chronic inflammation and fibrosis are key features of MASH that determine disease progression and outcomes. Recent advances have revealed that pathogenic B cell-derived cytokines and antibodies promote the development of MASH. However, the mechanisms through which B cells promote fibrosis and the metabolic adaptations underlying their pathogenic responses remain unclear. Here, we report that a subset of mature B cells with heightened cytokine responses accumulate in the liver and promote inflammation in MASH. To meet the increased energetic demand of effector responses, B cells increase their ATP production via oxidative phosphorylation (OXPHOS) fueled by pyruvate oxidation in a B cell receptor (BCR)-specific manner. Blocking pyruvate oxidation completely abrogated the inflammatory capacity of MASH B cells. Accordingly, the restriction of the BCR led to MASH attenuation, including reductions in steatosis, hepatic inflammation, and fibrosis. Mechanistically, BCR restriction decreased B cell maturation, activation, and effector responses in the liver, accompanied by decreased T cell- and macrophage-mediated inflammation. Notably, attenuated liver fibrosis in BCR-restricted mice was associated with lower IgG production and decreased expression of Fc-gamma receptors on hepatic stellate cells. Together, these findings indicate a key role for B cell antigen-specific responses in promoting steatosis, inflammation, and fibrosis during MASH.
Testing Times: Challenges in Disentangling Admixture Histories in Recent and Complex Demographies
Authors: Williams Matthew P. , Flegontov Pavel , Maier Robert , Huber Christian D. 
Published: November 2023

AbstractPaleogenomics has expanded our knowledge of human evolutionary history. Since the 2020s, the study of ancient DNA has increased its focus on reconstructing the recent past. However, the accuracy of paleogenomic methods in answering questions of historical and archaeological importance amidst the increased demographic complexity and decreased genetic differentiation within the historical period remains an open question. We used two simulation approaches to evaluate the limitations and behavior of commonly used methods, qpAdm and thef3-statistic, on admixture inference. The first is based on branch-length data simulated from four simple demographic models of varying complexities and configurations. The second, an analysis of Eurasian history composed of 59 populations using whole-genome data modified with ancient DNA conditions such as SNP ascertainment, data missingness, and pseudo-haploidization. We show that under conditions resembling historical populations, qpAdm can identify a small candidate set of true sources and populations closely related to them. However, in typical ancient DNA conditions, qpAdm is unable to further distinguish between them, limiting its utility for resolving fine-scaled hypotheses. Notably, we find that complex gene-flow histories generally lead to improvements in the performance of qpAdm and observe no bias in the estimation of admixture weights. We offer a heuristic for admixture inference that incorporates admixture weight estimate andP-values of qpAdm models, andf3-statistics to enhance the power to distinguish between multiple plausible candidates. Finally, we highlight the future potential of qpAdm through whole-genome branch-lengthf2-statistics, demonstrating the improved demographic inference that could be achieved with advancements inf-statistic estimations.
Generation of salivary glands derived from pluripotent stem cells via conditional blastocyst complementation
Authors: Tanaka Junichi , Miura Akihiro , Shimamura Yuko , Hwang Youngmin , Shimizu Dai , Kondo Yuri , Sawada Anri , Sarmah Hemanta , Ninish Zurab , Mishima Kenji , Mori Munemasa 
Published: November 2023

SummaryVarious patients suffer from dry mouth due to salivary gland dysfunction. Whole salivary gland generation and transplantation is a potential therapy to resolve this issue. However, the lineage permissible to design the entire salivary gland generation has been enigmatic. Here, we discovered Foxa2 as a lineage critical for generating a salivary gland via conditional blastocyst complementation (CBC). Foxa2 linage, but not Shh nor Pitx2, initiated to label between the boundary region of the endodermal and the ectodermal oral mucosa before primordial salivary gland formation, resulting in marking the entire salivary gland. The salivary gland was agenesis by depleting Fgfr2 under the Foxa2 lineage in the mice. We rescued this phenotype by injecting donor pluripotent stem cells into the mouse blastocysts. Those mice survived until adulthood with normal salivary glands compatible in size compared with littermate controls. These results indicated that CBC-based salivary gland generation is promising for next-generation cell-based therapy.
Chemical Tools for the Gid4 Subunit of the Human E3 Ligase C-terminal to LisH (CTLH) Degradation Complex
Authors: Yazdi Aliakbar Khalili , Perveen Sumera , Song Xiaosheng , Dong Aiping , Szewczyk Magdalena M. , Calabrese Matthew F. , Casimiro-Garcia Agustin , Chakrapani Subramanyam , Dowling Matthew S. , Ficici Emel , Lee Jisun , Montgomery Justin I. , O’Connell Thomas N. , Skrzypek Grzegorz J. , Tran Tuan P. , Troutman Matthew D. , Wang Feng , Young Jennifer A. , Min Jinrong , Barsyte-Lovejoy Dalia , Brown Peter J. , Santhakumar Vijayaratnam , Arrowsmith Cheryl H. , Vedadi Masoud , Owen Dafydd R. 
Published: November 2023

AbstractWe have developed a novel chemical handle (PFI-E3H1) and a chemical probe (PFI-7) as ligands for the Gid4 subunit of the human E3 ligase CTLH degradation complex. Through an efficient initial hit-ID campaign, structure-based drug design (SBDD) and leveraging the sizeable Pfizer compound library, we identified a 500 nM ligand for this E3 ligase through file screening alone. Further exploration identified a vector that is tolerant to addition of a linker for future chimeric molecule design. The chemotype was subsequently optimized to sub-100 nM Gid4 binding affinity for a chemical probe. These novel tools, alongside the suitable negative control also identified, should enable the interrogation of this complex human E3 ligase macromolecular assembly.
MdHY5 and MdHY5S form a positive transcription loop to regulate browning and phenolics synthesis in fresh-cut apple under purple LED light
Authors: Jin Juntong , Qi Liyong , Shen Shurong , Yang Shuran , Yuan Hui , Wang Aide 
Published: November 2023

ABSTRACTEnzymatic browning significantly affects the appearance and quality of fresh-cut fruit. Light treatment can effectively inhibit fresh-cut apple browning via unknown molecular mechanisms. Here, we found that the application of purple LED light decreased the browning index of fresh-cut apple, delaying browning as compared to that of fresh-cut apple placed in the dark, and suggesting that purple LED light suppresses browning. In addition, the expression levels ofMdHY5andMdHY5S, important BASIC LEUCINE ZIPPER DOMAIN (bZIP) transcription factors that are involved in the light signaling pathway, were increased by purple LED light treatment. SilencingMdHY5andMdHY5Sin apple meant that purple LED light treatment no longer inhibited fresh-cut apple browning, the expression levels of the browning-related genesPOLYPHENOL OXIDASE(MdPPO) andPEROXIDASE(MdPOD) increased, and the expression of the phenolic synthesis genePHENYLALANINE AMMONIALYASE(MdPAL) decreased. Further study revealed thatMdHY5andMdHY5Sbind to theMdPPOandMdPODpromoters, reducing their transcription. In contrast,MdHY5andMdHY5Sbind to theMdPALpromoter, enhancing transcription. Further research revealed that MdHY5 and MdHY5S also bind directly to each other’s promoters to form a positive transcriptional loop that activates their transcription. Our findings revealed that purple LED light inhibits browning and increases phenolics synthesis in fresh-cut apple by activatingMdHY5andMdHY5S. The results provide a theoretical basis upon which the new methods for improving the appearance and quality of fresh-cut apple can be based.
The Velvet transcription factor PnVeA regulates necrotrophic effectors and secondary metabolism in the wheat pathogenParastagonospora nodorum
Authors: Morikawa Shota , Verdonk Callum , John Evan , Lenzo Leon , Sbaraini Nicolau , Turo Chala , Li Hang , Jiang David , Chooi Yit-Heng , Tan Kar-Chun 
Published: November 2023

AbstractThe fungusParastagonospora nodorumcauses septoria nodorum blotch on wheat. The role of the fungal Velvet-family transcription factor VeA inP. nodorumdevelopment and virulence was investigated here. Deletion of theP. nodorum VeAortholog,PnVeA, resulted in growth abnormalities including pigmentation, abolished asexual sporulation and highly reduced virulence on wheat. Comparative RNA-Seq and RT-PCR analyses revealed that the deletion ofPnVeAalso decoupled the expression of major necrotrophic effector genes. In addition, the deletion ofPnVeAresulted in an up-regulation of four predicted secondary metabolite (SM) gene clusters. Using liquid-chromatography mass-spectrometry, it was observed that one of the SM gene clusters led to an accumulation of the mycotoxin alternariol. PnVeA is essential for asexual sporulation, full virulence, secondary metabolism and necrotrophic effector regulation.
An emerging clade of Chikungunya West African genotype discovered in real-time during 2023 outbreak in Senegal
Authors: Padane Abdou , Tegally Houriiyah , Ramphal Yajna , Seyni Ndiaye , Sarr Mariéma , Diop Mame Matar , Diedhiou Cyrille Kouligueul , Mboup Aminata , Diouf Ndèye Dieyna , Souaré Abdoulaye , Diagne Ndéye Diabou , Aza-Gnandji Marilyne , Dabo Ndèye Astou , Dia Yacine Amet , Diaw Ndeye Aminata , Leye Nafissatou , Diaw Papa Alassane , Ahouidi Ambroise , Cissé Badara , Diallo Abdoulaye Samba , Diop Ousmane , Diallo Abdou Aziz , Ndoye Souadou , Sanko Tomasz J. , Baxter Cheryl , Wilkinson Eduan , San James E. , Tshabuila Derek , Naidoo Yeshnee , Pillay Sureshnee , Lessells Richard , Cissé Khady , Leye Abdoulaye , Mbaye Khalifa Ababacar , Kania Dramane , Tinto Bachirou , Traoré Isidore , Kagone Sampawendé Thérèse , Ouedraogo Abdoul Salam , Gifford Robert J. , Lourenço José , Giovanetti Marta , Giandhari Jennifer , de Oliveira Tulio , Mboup Souleymane 
Published: November 2023

AbstractChikungunya (CHIKV) is a re-emerging endemic arbovirus in West Africa. Since July 2023, Senegal and Burkina Faso have been experiencing an ongoing outbreak, with over 300 confirmed cases detected so far in the regions of Kédougou and Tambacounda in Senegal, the largest recorded outbreak yet. CHIKV is typically maintained in a sylvatic cycle in Senegal but its evolution and factors contributing to re-emergence are so far unknown in West Africa, leaving a gap in understanding and responding to recurrent epidemics. We produced, in real-time, the first locally-generated and publicly available CHIKV whole genomes in West Africa, to characterize the genetic diversity of circulating strains, along with phylodynamic analysis to estimate time of emergence and population growth dynamics. A novel strain of the West African genotype, phylogenetically distinct from strains circulating in previous outbreaks, was identified. This suggests a likely new spillover from sylvatic cycles in rural Senegal and potential of seeding larger epidemics in urban settings in Senegal and elsewhere.
Association Between Beta Blocker and Clinical Outcome in Adult Patients with Sepsis or Septic Shock: Protocol of a Systematic Review and Meta- Analysis of Randomized Controlled Trials
Authors: Bhattacharjee Sulagna , Ernest Emmanuel Easterson , Maitra Souvik 
Published: November 2023

AbstractUse of beta-blockers as a part of heart rate control strategy is sepsis and septic shock patients is of great debate. Despite of early encouraging results, no large trial was performed and several subsequent small studies reported conflicting results. This meta-analysis and systematic review will be conducted and published as per PRISMA guidelines. In this review, randomized controlled trials comparing short-acting beta-blockers with ‘standard of care’ in adult patients with sepsis and septic shock will be included. Primary outcome will be 28-day mortality and secondary outcomes will be duration of intensive care unit stay, duration of hospital stay, ICU mortality, hospital mortality and reported adverse events. A random effect model will be used for all analysis.Source of SupportNilConflict of interestsNone
Midkine and Ptprz1b act upstream of Wnt planar cell polarity to establish a midline in the developing zebrafish hindbrain
Authors: Le Yao , Rajasekhar Kavitha , Loo Tricia Y.J. , Saunders Timothy E. , Wohland Thorsten , Winkler Christoph 
Published: November 2023

ABSTRACTA midline in the developing central nervous system (CNS) is essential for the symmetric distribution of neural progenitors that later establish functional, bilaterally symmetric neural circuits. In the zebrafish hindbrain, a midline forms early during neurulation and requires a coordinated interplay of cell convergence and midline-crossing cell divisions (C-divisions). These two processes are controlled by the Wnt/planar cell polarity (PCP) pathway. However, upstream cues that control the timely production of PCP components remain unknown. Midkine (Mdk) and pleiotrophin (Ptn) are structurally related heparin-binding growth factors that are dynamically expressed in the developing zebrafish hindbrain. We used proximity ligation assays (PLAs) and fluorescence cross correlation spectroscopy (FCCS)in vivoto show that two zebrafish Mdks, Mdka and Mdkb, as well as Ptn interact with protein tyrosine phosphatase receptors type Z1, Ptprz1a and Ptprz1b, with distinct affinities. Ligand binding triggered Ptprz1b internalization and thereby determined the availability of signaling receptor on cell membranes. In zebrafishmdka, ptnandptprz1bmutants, cell migration and convergence were significantly impaired during hindbrain neurulation. Impaired convergence led to misplaced C-divisions, defective cell polarity and consequently duplicated midlines. These duplications were rescued by overexpression ofDrosophilaPrickle, a key component of the Wnt/PCP pathway. Here, we provide evidence that zygotic Mdka controls the distribution of maternally provided Ptprz1b, which in turn is needed for transcription of zebrafishprickle1b. Our findings thus reveal a role for Mdka and Ptprz1b upstream of Wnt/PCP to coordinate neural plate convergence, neural progenitor positioning and midline formation.
Dietary restriction and life-history trade-offs: insights into mTOR pathway regulation and reproductive investment in Japanese quails
Authors: Reda Gebrehaweria Kidane , Ndunguru Sawadi Fransisco , Csernus Brigitta , Gulyás Gabriella , Knop Renáta , Szabó Csaba , Czeglédi Levente , Lendvai Ádám Z. 
Published: November 2023

AbstractResources are needed for growth, reproduction and survival, and organisms must trade-off limited resources among competing processes. Nutritional availability in organisms is sensed and monitored by nutrient-sensing pathways that can trigger physiological changes or alter gene expression. Previous studies have proposed that one such signalling pathway, the mechanistic target of rapamycin (mTOR), underpins a form of adaptive plasticity when individuals encounter constraints in their energy budget. Despite the fundamental importance of this process in evolutionary biology, how nutritional limitation is regulated through the expression of genes governing this pathway and its consequential effects on fitness remains understudied, particularly in birds. We used dietary restriction to simulate resource depletion and examined its effects on body mass, reproduction and gene expression in Japanese quails (Coturnix japonica). Quails were subjected toad libitum(ADL) feeding or 20%, 30%, and 40% restriction levels for two weeks. All restricted groups exhibited reduced body mass, whereas reductions in the number and mass of eggs were observed only under more severe restrictions. Dietary restriction led to decreased expression ofmTORand insulin-like growth factor 1 (IGF1), whereas the ribosomal protein S6 kinase 1 (RPS6K1) and autophagy-related genes (ATG9AandATG5) were upregulated. The pattern in which mTOR respond to restriction was similar to what has been seen in body mass. Regardless of the treatment, proportionally higher reproductive investment was associated with individual variation inmTORexpression. These findings reveal the connection between dietary intake and the expression ofmTORand related genes in this pathway.
Neopolyploidy-induced changes in the giant duckweed (Spirodela polyrhiza) alter herbivore preference, performance, and plant population performance
Authors: Assour Hannah R. , Ashman Tia-Lynn , Turcotte Martin M. 
Published: November 2023

ABSTRACTPremisePolyploidy is a widespread mutational process in angiosperms that may alter population performance of not only plants but also their animal associates. Yet, knowledge of whether ploidy affects plant-herbivore dynamics is scarce. Here, we test whether aphid herbivores exhibit preference for diploid or neopolyploid plants, whether ploidy impacts plant and herbivore performance, and whether these interactions depend on plant genetic background.MethodsUsing multiple pairs of independently synthesized neotetraploid greater duckweed (Spirodela polyrhiza) and their diploid progenitors, we evaluated the effect of neopolyploidy on duckweed’s interaction with the water-lily aphid (Rhopalosiphum nymphaeae). Using two-way choice experiments, we first evaluated feeding preference by the herbivore. We then evaluated the consequences of ploidy on aphid and plant performance by measuring population growth over multiple generations.Key ResultsAphids preferred neopolyploids over diploids when the plants were provided at equal abundances but not when they were provided at equal surface area, indicating the role of plant size in driving this preference. Additionally, neopolyploidy increased aphid population performance, but this result was highly dependent on the genetic lineage of the plant. Lastly, the impact of herbivory on neopolyploids vs. diploid duckweed varied greatly with genetic lineage, but overall, neopolyploids appeared to be generally less tolerant than diploids.ConclusionsWe conclude that polyploidization can impact the preference and performance of herbivores on their plant hosts, whereas plant performance depends on complex interactions between herbivory, ploidy, and genetic lineage. These results have significant implications for the establishment and persistence of plants and herbivores in nature.