bluuebunny/crossref_metadata_2025_split huggingface dataset:
Organic compounds drive growth in phytoplankton taxa from different functional groups
Authors: Martens Nele , Ehlert Emilia , Putri Widhi , Sibbertsen Martje , Schaum C.-Elisa 
Published: October 2023

AbstractPhytoplankton are usually considered autotrophs by default, but an increasing number of studies shows that many taxa are able to also utilise organic carbon. Acquiring nutrients and energy from different sources might enable an efficient uptake of required substances and provide a strategy to deal with a varying resource availability, especially in highly dynamic ecosystems such as estuaries. In our study we investigated the effects of 31 organic carbon sources on the growth of 17 phytoplankton strains from the Elbe estuary spanning four functional groups. All of our strains were able to make use of at least 1 and up to 26 organic compounds for growth. Pico-sized green algae such asMychonastes, ChoricystisandChlorella, as well as nano-sized green algae from the genusMonoraphidiumin particular were positively affected by a high variety of substances. Reduced light availability, typically appearing in turbid estuaries and similar habitats, resulted in an overall poorer ability to utilise organic substances for growth, indicating that organic carbon acquisition was not primarily a specific strategy to deal with darkness. Our results give further evidence for mixotrophy being an ubiquitous ability of phytoplankton and highlight the importance to consider this trophic strategy in research.
Reduced nephron endowment in the commonSix2-TGCtgmouse line is due toSix3misexpression by aberrant enhancer-promoter interactions in the transgene
Authors: Perl Alison J. , Liu Han , Hass Matthew , Adhikari Nirpesh , Chaturvedi Praneet , Hu Yueh-Chiang , Jiang Rulang , Liu Yaping , Kopan Raphael 
Published: October 2023

AbstractLifelong kidney function relies on the complement of nephrons generated during mammalian development from a mesenchymal nephron progenitor cell (NPC) population. Low nephron endowment confers increased susceptibility to chronic kidney disease. We asked whether reduced nephron numbers in the popularSix2TGCtransgenic mouse line1was due to disruption of a regulatory gene at the integration site or to ectopic expression of a gene(s) contained within the transgene. Targeted locus amplification identified integration of theSix2TGCtransgene within an intron ofCntnap5aon chr1. We generated Hi-C datasets from NPCs isolated from theSix2TGCtg/+mice, theCited1CreERT2/+control mice, and theSix2TGCtg/+;Tsc1+/Flox,2mice that exhibited restored nephron number compared withSix2TGCtg/+mice, and mapped the precise integration ofSix2TGCandCited1CreERT2transgenes to chr1 and chr14, respectively. No changes in topology, accessibility, or expression were observed within the 50-megabase region centered onCntnap5ainSix2TGCtg/+mice compared with control mice. By contrast, we identified an aberrant regulatory interaction between aSix2distal enhancer and theSix3promoter contained within the transgene. Increasing theSix2TGCtgtoSix2locus ratio or removing oneSix2allele inSix2TGCtg/+mice, caused severe renal hypoplasia. Furthermore, CRISPR disruption ofSix3within the transgene (Six2TGCΔSix3CT) restored nephron endowment to wildtype levels and abolished the stoichiometric effect. Data from genetic and biochemical studies together suggest that inSix2TGC,SIX3 interferes with SIX2 function in NPC renewal through its C-terminal domain.SignificanceUsing high-resolution chromatin conformation and accessibility datasets we mapped the integration site of two popular transgenes used in studies of nephron progenitor cells and kidney development. Aberrant enhancer-promoter interactions drive ectopic expression ofSix3in theSix2TGCtgline which was correlated with disruption of nephrogenesis. Disruption ofSix3within the transgene restored nephron numbers to control levels; further genetic and biochemical studies suggest thatSix3interferes withSix2-mediated regulation of NPC renewal.
Reverse Correlation Characterizes More Complete Tinnitus Spectra in Patients
Authors: Barnett Nelson V. , Hoyland Alec , Chari Divya A. , Parrell Benjamin , Lammert Adam C. 
Published: October 2023

AbstractGoalWe validate a recent reverse correlation approach to tinnitus characterization by applying it to individuals with clinically-diagnosed tinnitus.MethodsTwo tinnitus patients assessed the subjective similarity of their non-tonal tinnitus percepts and random auditory stimuli. Regression of the responses onto the stimuli yielded reconstructions which were evaluated qualitatively by playing back resynthesized waveforms to the subjects and quantitatively by response prediction analysis.ResultsSubject 1 preferred their resynthesis to white noise; subject 2 did not. Response prediction balanced accuracies were significantly higher than chance across subjects: subject 1: 0.5963, subject 2: 0.6922.ConclusionReverse correlation can provide the foundation for reconstructing accurate representations of complex, non-tonal tinnitus in clinically diagnosed subjects. Further refinements may yield highly similar waveforms to individualized tinnitus percepts.Impact StatementCharacterization of tinnitus sounds can help clarify the heterogeneous nature of the condition and link etiology to subtypes and treatments.
FORMATION OF MALIGNANT, METASTATIC SMALL CELL LUNG CANCERS THROUGH OVERPRODUCTION OF cMYC PROTEIN IN TP53 AND RB1 DEPLETED PULMONARY NEUROENDOCRINE CELLS DERIVED FROM HUMAN EMBRYONIC STEM CELLS
Authors: Chen Huanhuan Joyce , Gardner Eric E. , Shah Yajas , Zhang Kui , Thakur Abhimanyu , Zhang Chen , Elemento Olivier , Varmus Harold 
Published: October 2023

AbstractWe recently described our initial efforts to develop a model for small cell lung cancer (SCLC) derived from human embryonic stem cells (hESCs) that were differentiated to form pulmonary neuroendocrine cells (PNECs), a putative cell of origin for neuroendocrine-positive SCLC. Although reduced expression of the tumor suppressor genesTP53andRB1allowed the induced PNECs to form subcutaneous growths in immune-deficient mice, the tumors did not display the aggressive characteristics of SCLC seen in human patients. Here we report that the additional, doxycycline-regulated expression of a transgene encoding wild-type or mutant cMYC protein promotes rapid growth, invasion, and metastasis of these hESC-derived cells after injection into the renal capsule. Similar to others, we find that the addition of cMYC encourages the formation of the SCLC-N subtype, marked by high levels ofNEUROD1RNA. Using paired primary and metastatic samples for RNA sequencing, we observe that the subtype of SCLC does not change upon metastatic spread and that production of NEUROD1 is maintained. We also describe histological features of these malignant, SCLC-like tumors derived from hESCs and discuss potential uses of this model in efforts to control and better understand this recalcitrant neoplasm.
Aboveground enemy release increases seedling survival in grasslands
Authors: Brian Joshua I. , Shepherd Harry E. R. , Pérez-Navarro María Ángeles , Catford Jane A. 
Published: October 2023

AbstractThe enemy release hypothesis is a popular hypothesis to explain the success of invasive plants. Enemy release studies typically focus on single species or types of communities, feature indirect experimental manipulations that apply pesticides to whole communities not individual species, and only examine responses of established plants or plant populations, limiting their generality. Using a novel species-specific approach, we examine whether enemy release can enhance seedling survival and recruitment of 16 grassland species by experimentally linking enemy release with enhanced plant performance.We planted seedlings of 16 native grassland species from two functional groups (C4 grasses and non-legume forbs) into two grassland sites (early and mid succession). We hand-painted 1,548 individual seedlings with pesticides (insecticide and fungicide) over the course of a growing season to enforce aboveground species-specific enemy release, and tested whether it enhanced survival relative to untreated controls. Using native species enabled us to directly test effects of enemy release, while avoiding confounding factors like unknown invasion histories. Of the 16 native study species, 13 are naturalised/invasive outside of their native ranges.Release from insects increased seedling survival by 80% on average, with no additional benefit of release from fungal pathogens. This effect was consistent across functional groups and community successional stages, and was strongest in resource-acquisitive species. The size of species’ performance benefits from enemy release were positively correlated with the number of regions globally where each species has been introduced and naturalised.Synthesis. Previous studies of enemy release have centred on adults and findings have varied among species. We found a positive effect of release from insect herbivores early in colonisation – a trend that held across functional groups and types of resident community. We posit that the consistent vulnerability of seedlings vis-à-vis later life stages leads to this more ubiquitous benefit of enemy release. Enemy release may therefore aid initial recruitment of most, if not all, plants during the invasion process, even if enemies rapidly accumulate. The positive correlations between the benefits of enemy release for seedlings, species’ life history strategies and global naturalisation patterns provide compelling hypotheses for future research.
On the contrast response function of adapted neural populations
Authors: Tring Elaine , Dipoppa Mario , Ringach Dario L. 
Published: October 2023

AbstractThe magnitude of neural responses in sensory cortex depends on the intensity of a stimulus and its probability of being observed within the environment. How these two variables combine to influence the overall response of cortical populations remains unknown. Here we show that, in primary visual cortex, the vector magnitude of the population response is described by a separable power-law that factors the intensity of a stimulus and its probability.
Cross-pathway integration of cAMP signals through cGMP and calcium-regulated phosphodiesterases in mouse striatal cholinergic interneurons
Authors: Bompierre Ségolène , Byelyayeva Yelyzaveta , Mota Elia , Lefevre Marion , Pumo Anna , Kehler Jan , Castro Liliana R.V. , Vincent Pierre 
Published: October 2023

AbstractAcetylcholine plays a key role in striatal function, yet the intricate dynamics of cyclic nucleotide signaling which govern the firing properties of cholinergic interneurons (ChINs) have remained elusive. Since phosphodiesterases determine the dynamics of cyclic nucleotides, in this study, we used FRET biosensors and pharmacological compounds to examine phosphodiesterase activity in ChINs in mouse brain slices. Intriguingly, these neurons displayed strikingly low levels and slow cAMP responsiveness compared to medium-sized spiny neurons (MSNs). Our experiments revealed that PDE1, PDE3 and PDE4 are important regulators of cAMP level in ChINs. Notably, the induction of cGMP production by nitric oxide (NO) donors increases cAMP by inhibiting PDE3 - a mechanism hitherto unexplored in neuronal context. Furthermore, the activation of NMDA or metabotropic glutamate receptors increases intracellular calcium, consequently activating PDE1 and thereby decreasing both cAMP and cGMP. This interplay of phosphodiesterases enables the control of cAMP by the neuromodulatory influences of glutamate and NO. Remarkably, the NO/cGMP signal results in different effects: NO enhances cAMP in ChINs by inhibiting PDE3, whereas it reduces cAMP levels in MSNs by activating PDE2A. These findings underscore the specificity of intracellular signaling in ChINs compared to MSNs and show how the NO-cGMP pathway affects these various neuronal types differently. These observations have significant implications for understanding the regulation of the striatal network and the integration of dopaminergic signals and suggest innovative therapeutic strategies for addressing basal ganglia disorders with unmet medical need.
Exploration of the Tunability of BRD4 Degradation by DCAF16Trans-labelling Covalent Glues
Authors: Hassan Muhammad Murtaza , Li Yen-Der , Ma Michelle W. , Teng Mingxing , Byun Woong Sub , Puvar Kedar , Lumpkin Ryan , Sandoval Brittany , Rutter Justine C. , Jin Cyrus Y. , Wang Michelle Y. , Xu Shawn , Schmoker Anna M. , Cheong Hakyung , Groendyke Brian J. , Qi Jun , Fischer Eric S. , Ebert Benjamin L. , Gray Nathanael S. 
Published: October 2023

ABSTRACTSmall molecules that can induce protein degradation by inducing proximity between a desired target and an E3 ligase have the potential to greatly expand the number of proteins that can be manipulated pharmacologically. Current strategies for targeted protein degradation are mostly limited in their target scope to proteins with preexisting ligands. Alternate modalities such as molecular glues, as exemplified by the glutarimide class of ligands for the CUL4CRBNligase, have been mostly discovered serendipitously. We recently reported atrans-labelling covalent glue mechanism which we named ‘Template-assisted covalent modification’, where an electrophile decorated small molecule binder of BRD4 was effectively delivered to a cysteine residue on an E3 ligase DCAF16 as a consequence of a BRD4-DCAF16 protein-protein interaction. Herein, we report our medicinal chemistry efforts to evaluate how various electrophilic modifications to the BRD4 binder, JQ1, affect DCAF16trans-labeling and subsequent BRD4 degradation efficiency. We discovered a decent correlation between the ability of the electrophilic small molecule to induce ternary complex formation between BRD4 and DCAF16 with its ability to induce BRD4 degradation. Moreover, we show that a more solvent-exposed warhead presentation is optimal for DCAF16 recruitment and subsequent BRD4 degradation. Unlike the sensitivity of CUL4CRBNglue degraders to chemical modifications, the diversity of covalent attachments in this class of BRD4 glue degraders suggests a high tolerance and tunability for the BRD4-DCAF16 interaction. This offers a potential new avenue for a rational design of covalent glue degraders by introducing covalent warheads to known binders.
Injury induced renal fibrosis promotes cystogenesis and cyst growth in adult mice with autosomal dominant polycystic kidney disease
Authors: Wu Ming , Chen Dongping , Wang Yanzhe , Lin Pinglan , Bai Yanfang , Xing Yufeng , Huang Di , Ye Chaoyang 
Published: October 2023

AbstractAutosomal dominant polycystic kidney disease (ADPKD) is a life-long disease and caused by mutations inPKD1orPKD2gene. Fibrosis is a hallmark of chronic kidney disease and is positively correlated with renal cyst growth, however the role of fibrosis in ADPKD is still controversial. In this study, we established renal fibrosis by toxic or surgical injuries in adult mice, andPkdgene was inactivated at different time point before or after renal injury according to the pattern of fibrosis progression in different injury models. Here we showed that renal injury before or afterPkdgene inactivation can both induce renal cysts in adultPkd1orPkd2mice, and the extent of cystic burden was tightly correlated with the baseline levels of fibrosis when three hits (injury and gene inactivation) occurred. Inactivation ofPkd1gene at the recovery stage after surgery induced less renal cysts in adultPkd1mice. Enhanced renal fibrosis by repeated toxic injuries before gene inactivation accelerated renal cyst growth inPkd1mice. We further showed that the rate of cyst formation at the early stage in adultPkd1mice was positively correlated with the baseline levels of renal fibrosis. Finally, we showed that conditional knockout ofEzh2gene attenuated renal fibrosis and cyst growth in adultPkd1mice with pre-existing renal fibrosis. We conclude that the fibrotic response after renal injury is a driving force for renal cyst formation and growth in adult kidneys and inhibition of renal fibrosis through targeting EZH2 might be new therapeutic strategy for adult ADPKD. Importantly, our study suggests that there is a time window for intervention upon acute kidney injury in adult ADPKD patients.Translational StatementAutosomal dominant polycystic kidney disease (ADPKD) is a life-long disease and caused by mutations inPKD1orPKD2gene. Fibrosis is a hallmark of chronic kidney disease and is positively correlated with renal cyst growth, however the role of renal fibrosis in ADPKD is controversial. In this study, we found that renal cysts were formed in adultPkd1orPkd2mice with established renal fibrosis induced by toxic or ischemia reperfusion injuries. Cyst formation or growth in adult ADPKD mice was tightly correlated with baseline levels of renal fibrosis after third hits. Enhanced renal fibrosis beforePkd1gene deletion in adult mice accelerated cyst growth. Inhibition of renal fibrosis through targeting EZH2 delayed cyst growth in adult ADPKD mice. Thus, renal fibrosis is a trigger of cyst formation and growth in adult ADPKD mice, and therapeutically targeting EZH2 might be new strategy to treat adult patients with ADPKD. Our study suggests that there is a time window for intervention upon acute kidney injury in adult ADPKD patients.
Bamboozling Interactions: Interspecific associations within mixed-species bird flocks in bamboo in the Eastern Himalaya
Authors: Srinivasan Sidharth , Biswakarma Aman , Pradhan D.K. , Rai Shambu , Srinivasan Umesh 
Published: October 2023

ABSTRACTBamboo, although widespread, is a globally understudied habitat, but supports significant biodiversity, including specialist bird species. Mixed-species bird flocks (flocks) are an important and regular feature of forest bird communities worldwide and have been well-studied. However, how and why flocks might differ between bamboo and non-bamboo habitats is unknown.We studied flocks and their arthropod prey in rainforest and bamboo stands across two seasons in the Eastern Himalaya. Using network analysis, we compared interspecific associations within flocks, and asked if resource availability (arthropod abundance) drives flocking.Bamboo and rainforest flocks were significantly different, with bamboo flocks being more cohesive, less modular and their species more interconnected. Further, bamboo flocks were more consistent in their composition across seasons whereas rainforest flocks partially disintegrated in spring, probably because of increased arthropod abundance. In bamboo, the loss of arthropods in an entire substrate and the increase in other substrates was potentially insufficient to cease flocking in spring.Resource availability and the unique foraging behaviour of the bamboo specialists likely drive flocking in the Eastern Himalaya bamboo. Our study is among the few to describe bamboo flocks and we emphasise conserving bamboo stands to ensure persistence of this unique flock in the Eastern Himalaya.
Complete suspension culture of human induced pluripotent stem cells supplemented with suppressors of spontaneous differentiation
Authors: Matsuo-Takasaki Mami , Kambayashi Sho , Hemmi Yasuko , Wakabayashi Tamami , Shimizu Tomoya , An Yuri , Ito Hidenori , Takeuchi Kazuhiro , Ibuki Masato , Kawashima Terasu , Masayasu Rio , Suzuki Manami , Nishishita Naoki , Kawai Yoshikazu , Umekage Masafumi , Kato Tomoaki M , Noguchi Michiya , Nakade Koji , Nakamura Yukio , Nakaishi Tomoyuki , Tsukahara Masayoshi , Hayashi Yohei 
Published: October 2023

AbstractHuman induced pluripotent stem cells (hiPSCs) are promising resources for producing various types of tissues in regenerative medicine; however, the improvement in a scalable culture system that can precisely control the cellular status of hiPSCs is needed. Utilizing suspension culture without microcarriers or special materials allows for massive production, automation, cost-effectiveness, and safety assurance in industrialized regenerative medicine. Here, we found that hiPSCs cultured in suspension conditions with continuous agitation without any microcarriers or extracellular matrix components were more prone to spontaneous differentiation than those cultured in conventional adherent conditions. Adding PKCβ and Wnt signaling pathway inhibitors in the suspension conditions suppressed the spontaneous differentiation of hiPSCs into ectoderm and mesendoderm, respectively. In these conditions, we successfully completed the culture processes of hiPSCs including the generation of hiPSCs from peripheral blood mononuclear cells with the expansion of bulk population and single-cell sorted clones, long-term culture with robust self-renewal characteristics, single-cell cloning, direct cryopreservation from suspension culture and their successful recovery, and efficient mass production of a clinical-grade hiPSC line. Our results demonstrate that precise control of the cellular status in suspension culture conditions paves the way for their stable and automated clinical application.
Developmental origin and local signals cooperate to determine septal astrocyte identity
Authors: Xie Yajun , Reid Christopher M. , Granados Alejandro A. , Garcia Miguel Turrero , Dale-Huang Fiona , Hanson Sarah M. , Mancia Walter , Liu Jonathan , Adam Manal , Mosto Olivia , Pisco Angela O. , Alvarez-Buylla Arturo , Harwell Corey C. 
Published: October 2023

ABSTRACTAstrocyte specification during development is influenced by both intrinsic and extrinsic factors, but the precise contribution of each remains poorly understood. Here we show that septal astrocytes from Nkx2.1 and Zic4 expressing progenitor zones are allocated into non-overlapping domains of the medial (MS) and lateral septal nuclei (LS) respectively. Astrocytes in these areas exhibit distinctive molecular and morphological features tailored to the unique cellular and synaptic circuit environment of each nucleus. Using single-nucleus (sn) RNA sequencing, we trace the developmental trajectories of cells in the septum and find that neurons and astrocytes undergo region and developmental stage-specific local cell-cell interactions. We show that expression of the classic morphogens Sonic hedgehog (Shh) and Fibroblast growth factors (Fgfs) by MS and LS neurons respectively, functions to promote the molecular specification of local astrocytes in each region. Finally, using heterotopic cell transplantation, we show that both morphological and molecular specifications of septal astrocytes are highly dependent on the local microenvironment, regardless of developmental origins. Our data highlights the complex interplay between intrinsic and extrinsic factors shaping astrocyte identities and illustrates the importance of the local environment in determining astrocyte functional specialization.