bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomic analyses reveal prenatal stress promotes late-onset neural stem cell proliferation in adult male offspring
Authors: Wang Z. , Zhou L.Q. , Lee C.M. , Shi J.Y. , Liu L. , Yang X.J. , Deng Y.X. , Liu J.P. , Wang J.B. , Zhu W.M. , Sun Y.E. , Lin Q. 
Published: December 2022

AbstractPerturbations during critical time windows during embryonic development can lead to adverse functional consequences that manifest later in life. Here, we report that prenatal maternal stress (PNS) during the peak of embryonic neurogenesis (E14-delivery) dramatically increased numbers of proliferating neural stem/progenitor cells (NSC/NPCs) in the ependymal-subventricular zone (E-SVZ) and neuroblasts (NBs) in the rostral migratory stream and newborn neurons in the olfactory bulb (OB) of male mouse offspring without causing significant cell death or a deficit in cell migration to the OB. Mechanistically, bulk and single-nucleus transcriptomic analyses showed that PNS affected gene regulatory networks controlling cell cycle progression and stem cell maintenance, maturation of neural circuits, and gliogenesis in prenatally stressed (STR) offspring. More specifically, we found that prenatal exposure to mild maternal restraint-stress sustained MAPK (ERK) activity in the E-SVZ and thus prolonged NSC/NPC/NB proliferation in stressed brains. Moreover, we found PNS disorganized the cytoarchitecture of the glomerular layer of the OB, which may directly relate to the deficit in discriminating different social orders in stressed offspring. Compared to STR males, their female littermates showed less change in the number of proliferating cells in the E-SVZ.
A MTA2-SATB2 chromatin complex restrains colonic plasticity toward small intestine by retaining HNF4A at colonic chromatin
Authors: Gu Wei , Huang Xiaofeng , Singh Pratik N. P. , Lan Ying , Gomez-Salinero Jesus M , Rafii Shahin , Verzi Mike , Shivdasani Ramesh , Zhou Qiao 
Published: December 2022

SummaryPlasticity between cell lineages is a fundamental but poorly understood property of regenerative tissues. In the gut tube, small intestine absorbs nutrients whereas colon absorbs electrolytes. In a striking display of inherent plasticity, adult colonic mucosa lacking the chromatin factor SATB2 is converted to small intestine. Using proteomics and CRISPR-Cas9 screen, we identified MTA2 as a crucial component of the molecular machinery that, together with SATB2, restrain colonic plasticity. MTA2 loss in adult mouse colon activated lipid absorptive genes and functional lipid uptake. Mechanistically, MTA2 co-binds with HNF4A, an activating pan-intestine transcription factor (TF), on colonic chromatin. MTA2 loss leads to HNF4A release from colonic and gain on small intestinal chromatin. SATB2 similarly restrains colonic plasticity through a HNF4A-dependent mechanism. Our study provides a generalizable model of lineage plasticity in which broadly-expressed TFs are retained on tissue-specific enhancers to maintain cell identity and prevent activation of alternative lineages; their release unleashes plasticity.
Mapping Typical and Altered Neurodevelopment with Sleep Macro- and Micro-Architecture
Authors: Kozhemiako N , Buckley AW , Chervin RD , Redline S , Purcell SM 
Published: December 2022

AbstractProfiles of sleep duration and timing and corresponding electroencephalographic activity reflect brain changes that support cognitive and behavioral maturation and may provide practical markers for tracking typical and atypical neurodevelopment. To build and evaluate a sleep-based, quantitative metric of brain maturation, we used whole-night polysomnography data, initially from two large National Sleep Research Resource samples, spanning childhood and adolescence (totalN= 4,013, aged 2.5 to 17.5 years): the Childhood Adenotonsillectomy Trial (CHAT), a research study of children with snoring without neurodevelopmental delay, and NCH, a pediatric sleep clinic cohort. Among children without developmental disorders, sleep metrics derived from the electroencephalogram (EEG) displayed robust age-related changes consistently across datasets. Prominent stage-, band- and channel-specific developmental trajectories in spectral power were found. During non-rapid eye movement (NR) sleep, spindles and slow oscillations further exhibited characteristic developmental patterns, with respect to their rate of occurrence, temporal coupling and morphology. Based on these metrics in NCH, we constructed a model to predict an individual’s chronological age. The model performed with high accuracy (r= 0.95 in the held-out NCH testing sample andr= 0.88 in a second independent replication sample (PATS) with a broadly comparable age range). EEG-based age predictions reflected clinically meaningful neurodevelopmental differences; for example, compared to typically developing children, those with neurodevelopmental diagnoses (NDD) showed greater variability in predicted age, and children with Down syndrome or intellectual disability had significantly younger brain age predictions (respectively, 2.2 and 0.59 years less than their chronological age) compared to age-matched non-NDD children. Overall, our results indicate that sleep architecture offers a sensitive window for characterizing brain maturation, suggesting the potential for scalable, objective sleep-based biomarkers to measure typical and atypical neurodevelopment.
Circadian clock factors regulate seed oil accumulation by promoting fatty acid synthesis in Arabidopsis
Authors: Kim Sang-Chul , Edgeworth Kristen N. , Nusinow Dmitri A. , Wang Xuemin 
Published: December 2022

ABSTRACTThe circadian clock regulates temporal metabolic activities, enabling organisms to adapt to cyclic environmental changes, but how it affects lipid metabolism in plants is poorly understood. Our previous finding showed that the central clock transcription factors LATE ELONGATED HYPOCOTYL (LHY) and CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) increased seed oil contents in Arabidopsis. Here we investigated the molecular and metabolic mechanism underlying the LHY and CCA1 regulated oil accumulation. Triacylglycerol (TAG) accumulation in Arabidopsis developing seeds was increased inLHY-overexpressing (LHY-OE) and decreased inlhycca1plants compared to wild-type (WT). Metabolic tracking of lipids in developing seeds indicated that fatty acids (FAs) of major lipid precursors for TAG production increased more rapidly in LHY-OE and slowly inlhycca1than in WT, suggesting that LHY enhanced FA synthesis. Transcript analysis revealed that the expression of genes involved in FA synthesis, including the one encoding β-ketoacyl-ACP synthase III (KASIII), was oppositely changed in developing seeds of LHY/CCA1-OEs and those oflhycca1. Chromatin immunoprecipitation, electrophoretic mobility shift, and transactivation assays indicated that LHY directly bound and activated the promoter ofKASIII. Furthermore, phosphatidic acid, a metabolic precursor to TAG, inhibited LHY binding toKASIIIpromoter elements. Our data reveal a new regulatory mechanism by the core clock regulators for storage lipid production during plant seed development.
Cellular integration with a subretinal honeycomb-shaped prosthesis
Authors: Bhuckory Mohajeet B. , Chen Zhijie , Wang Bing-Yi , Shin Andrew , Huang Tiffany , Galambos Ludwig , Vounotrypidis Efstathios , Mathieson Keith , Kamins Theodore , Palanker Daniel 
Published: December 2022

AbstractIn patients blinded by geographic atrophy, subretinal photovoltaic implant with 100µm pixels provided visual acuity closely matching the pixel pitch. However, such flat bipolar pixels cannot be scaled below 75µm, limiting the attainable visual acuity. This limitation can be overcome by shaping the electric field with 3-dimensional electrodes. In particular, elevating the return electrode on top of honeycomb-shaped vertical walls surrounding each pixel extends the electric field vertically and decouples its penetration into tissue from the pixel width. This approach relies on migration of the retinal cells into the honeycomb wells. Here, we demonstrate that the majority of the inner retinal neurons migrate into 25µm deep wells, leaving the third-order neurons, such as amacrine and ganglion cells, outside. This is important for selective stimulation of the second-order neurons to preserve the retinal signal processing in prosthetic vision. Comparable glial response to that with flat implants suggests that migration and separation of the retinal cells by the walls does not cause additional stress. Furthermore, retinal migration into the honeycombs does not negatively affect its electrical excitability.
The protooncogene Ski regulates the neuron-glia switch during development of the mammalian cerebral cortex
Authors: Grison Alice , Karimaddini Zahra , Breda Jeremie , Mukhtar Tanzila , Boareto Marcelo , Eschbach Katja , Beisel Christian , Iber Dagmar , van Nimwegen Erik , Taylor Verdon , Atanasoski Suzana 
Published: December 2022

ABSTRACTThe brain is the most complex organ in mammals and understanding the origin of this complexity is a major challenge for developmental biologists. Crucial to the size and morphology of the cortex is the timing and transition of neural stem cell (NSC) fate. An interesting candidate for modulating and fine tuning these processes is the transcriptional regulator Ski, a protooncogene expressed in cortical cells. Ski is involved in diverse cellular processes and epigenetic programs, and mice deficient in Ski exhibit complex central nervous system defects that resemble some of the features observed in patients with 1p36 deletion syndrome and Shprintzen–Goldberg syndrome. Here, we took advantage ofin vivotransgenic labeling and next-generation sequencing to analyze the gene expression profiles of NSCs, basal progenitor (BP) cells, and newborn neurons (NBNs) from wildtype and Ski-deficient embryos throughout cortical development. We created a unique database that allowed us to identify and compare signaling pathways and transcriptional networks within each progenitor population in the presence and absence of Ski. We find that NSCs are the most affected cell population and uncover that mutant NSCs fail to switch to a gliogenic fate in time. We show that Ski functions in concert with the Bone Morphogenetic Protein (BMP) signaling pathway to alter the cell differentiation fate of NSCs from neurons to glia, which is key to generating adequate numbers of specific cell types during corticogenesis. Thus, by combining genetic tools and bioinformatic analysis, our work not only deepens the knowledge of how Ski functions in the brain, but also provides an immense resource for studying neurodevelopmental disorders.
Cholesterol and ceramide facilitate SARS-CoV-2 Spike protein-mediated membrane fusion
Authors: Niort Kristina , Dancourt Julia , Boedec Erwan , Amir Dache Zahra Al , Lavieu Grégory , Tareste David 
Published: December 2022

AbstractSARS-CoV-2 entry into host cells is mediated by the Spike (S) protein of the viral envelope. The S protein is composed of two subunits: S1 that induces binding to the host cellviaits interaction with the ACE2 receptor of the cell surface and S2 that triggers fusion between viral and cellular membranes. Fusion by S2 depends on its heptad repeat domains that bring membranes close together, and its fusion peptide (FP) that interacts with and perturb the membrane structure to trigger fusion. Recent studies suggest that cholesterol and ceramide lipids from the cell surface may facilitate SARS-CoV-2 entry into host cells, but their exact mode of action remains unknown. We have used a combination ofin vitroliposome-liposome andin situcell-cell fusion assays to study the lipid determinants of S-mediated membrane fusion. We found that cholesterol and ceramide both facilitated fusion, suggesting that targeting lipids could be effective against SARS-CoV-2. As proof of concept, we examined the effect of chlorpromazine (CPZ), an antipsychotic drug known to perturb membrane structure. We found that CPZ inhibited S-mediated membrane fusion and thus potentially SARS-CoV-2 entry.
Cortical Reactivation of Non-Spatial and Spatial Memory Representations Coordinate with Hippocampus to Form a Memory Dialogue
Authors: Chang HaoRan , Esteves Ingrid M. , Neumann Adam R. , Mohajerani Majid H. , McNaughton Bruce L. 
Published: December 2022

AbstractEpisodic memory depends on the association of diverse attribute representations that are distributed across the neocortex, and evidence suggests that these attributes are linked, at least initially, by the hippocampus, which orchestrates retrieval and the offline replay of experience during memory consolidation. The dynamics that characterize this hippocampal-cortical dialogue, however, are only partly understood. Although it was originally proposed that replay is initiated in CA3, with the spontaneous emission of sharp-wave ripple (SWR) bursts, increasing evidence suggests that cortex may seed the process with partial information, leading to pattern completion in CA3 and subsequent global reactivation of the episode. A recent study has shown that the secondary motor cortex (M2), among other areas, carries two distinct types of representations: place cell-like activity, which relies on an intact hippocampus for its development, and responses tied to visuo-tactile cues — the ‘attributes’ of the experience, which do not require the hippocampus. Using two-photon Ca2+imaging, while simultaneously acquiring LFP from the ipsilateral CA1, we assessed the interactions among cortical retrieval of visuo-tactile attributes of previous experiences in a virtual environment, hippocampal SWR, and the cortical reinstatement of the spatial aspects of the same experiences. During rest after the experience, two types of reactivation events occurred, which separately conveyed information about spatial trajectories and visuo-tactile attributes. Reactivation of attribute information preceded that of trajectories in relation to hippocampal SWRs. Furthermore, paired reactivations of cue and trajectory information supported similar features of previous experiences. These results are consistent with the hypothesis that cortical retrieval of non-spatial attributes of recent experience seeds hippocampal reactivation of associated spatial sequences, which is followed by retrieval of episodic memory traces.
Chelerythrine as an anti-Zika virus agent: therapeutic potential and mode of action
Authors: Españo Erica , Kim Jiyeon , Lee Chong-Kil , Webster Robert G. , Webby Richard J. , Kim Jeong-Ki 
Published: December 2022

AbstractZika virus (ZIKV) is a mosquito-borne virus that has been associated with adult and neonatal neurological conditions. So far, there is no approved drug or vaccine against ZIKV infection; thus, ZIKV remains a global health threat. Here, we explored the effects of chelerythrine (CTC), a known protein kinase C (PKC) inhibitor, against ZIKV infection in cell culture models to determine its potential as a therapeutic agent for ZIKV infection. We found that CTC protected Vero cells from ZIKV-induced cytopathic effects in a dose-dependent manner. It also reduced the production of ZIKV in Vero and A549 cells. In contrast, other PKC inhibitors failed to protect Vero cells from ZIKV-induced cytopathic effects, indicating PKC-independent mechanisms underlying the effects of CTC on ZIKV. Further investigation suggested that CTC inhibited ZIKV attachment/binding rather than internalization in the host cells. Pretreatment of cell-free ZIKV particles rather than pretreatment of cells with CTC resulted in reduced ZIKV infectivityin vitro, indicating that CTC blocked the attachment/binding of the ZIKV particles to host factors.In silicoanalyses suggested that these effects are potentially due to the binding of CTC to the ZIKV E protein, which may occlude the interaction of the E protein with attachment factors or receptors on the host cell surface. Overall, our findings suggest that CTC reduces the infectivity of ZIKV particles through PKC- and cell-independent mechanisms. Our findings also support further exploration of CTC as an anti-ZIKV agent.
Parallel motion vision pathways in the brain of a tropical bee
Authors: Honkanen Anna , Hensgen Ronja , Kannan Kavitha , Adden Andrea , Warrant Eric , Wcislo William , Heinze Stanley 
Published: December 2022

AbstractSpatial orientation is a prerequisite for most behaviors. In insects, the underlying neural computations take place in the central complex (CX), the brain’s navigational center. In this region different streams of sensory information converge to enable context-dependent navigational decisions. Accordingly, a variety of CX input neurons deliver information about different navigation-relevant cues. In bees, direction encoding polarized light signals converge with translational optic flow signals that are suited to encode the flight speed of the animals. The continuous integration of speed and directions in the CX can be used to generate a vector memory of the bee’s current position in space in relation to its nest, i.e. perform path integration. This process depends on specific, complex features of the optic flow encoding CX input neurons, but it is unknown how this information is derived from the visual periphery. Here, we thus aimed at gaining insight into how simple motion signals are reshaped upstream of the speed encoding CX input neurons to generate their complex features. Using electrophysiology and anatomical analyses of the halictic beesMegalopta genalisandMegalopta centralis, we identified a wide range of motion-sensitive neurons connecting the optic lobes with the central brain. While most neurons formed pathways with characteristics incompatible with CX speed neurons, we showed that one group of lobula projection neurons possess some physiological and anatomical features required to generate the visual responses of CX optic-flow encoding neurons. However, as these neurons cannot explain all features of CX speed cells, local interneurons of the central brain or alternative input cells from the optic lobe are additionally required to construct inputs with sufficient complexity to deliver speed signals suited for path integration in bees.
Quantifying the deformability of malaria-infected red blood cells using deep learning trained on synthetic cells
Authors: Rademaker Daniel T. , Koopmans Joshua J. , Thyen Gwendolyn M.S.M. , Piruska Aigars , Huck Wilhelm T.S. , Vriend Gert , ‘t Hoen Peter A.C. , Kooij Taco W.A. , Huynen Martijn A. , Proellochs Nicholas I. 
Published: December 2022

AbstractSeveral haematologic diseases, including malaria, diabetes, and sickle cell anaemia, result in a reduced red blood cell deformability. This deformability can be measured using a microfluidic device with channels of varying width. Nevertheless, it is challenging to algorithmically recognise large numbers of red blood cells and quantify their deformability from image data. Deep learning has become the method of choice to handle noisy and complex image data. However, it requires a significant amount of labelled data to train the neural networks. By creating images of cells and mimicking noise and plasticity in those images, we generate synthetic data to train a network to detect and segment red blood cells from video-recordings, without the need for manually annotated labels. Using this new method, we uncover significant differences between the deformability of RBCs infected with different strains ofPlasmodium falciparum, providing clues to the variation in virulence of these strains.
Transposable elements as tissue-specific enhancers in cancers of endodermal lineage
Authors: Karttunen Konsta , Patel Divyesh , Xia Jihan , Fei Liangru , Palin Kimmo , Aaltonen Lauri , Sahu Biswajyoti 
Published: December 2022

AbstractTransposable elements (TE) are repetitive genomic elements that harbor binding sites for human transcription factors (TF). A regulatory role for TEs has been suggested in embryonal development and diseases such as cancer but systematic investigation of their functions has been limited by their widespread silencing in the genome. Here, we have utilized unbiased massively parallel reporter assay data using whole human genome library to identify TEs with functional enhancer activity in two human cancer types of endodermal lineage, colorectal and liver cancers. We show that the identified TE enhancers are characterized by genomic features associated with active enhancers, such as epigenetic marks and TF binding. Importantly, we identified distinct TE subfamilies that function as tissue-specific enhancers, namely MER11- and LTR12-elements in colon and liver cancers, respectively. These elements are bound by distinct TFs in each cell type, and they have predicted associations to differentially expressed genes. In conclusion, these data demonstrate how different cancer types can utilize distinct TEs as tissue-specific enhancers, paving the way for comprehensive understanding of the role of TEs as bona fide enhancers in the cancer genomes.
AB668, a novel highly selective protein kinase CK2 inhibitor with a distinct anti-tumor mechanism as compared to CX-4945 and SGC-CK2-1
Authors: Bancet Alexandre , Frem Rita , Jeanneret Florian , Mularoni Angélique , Bazelle Pauline , Roelants Caroline , Delcros Jean-Guy , Guichou Jean-François , Pillet Catherine , Coste Isabelle , Renno Toufic , Battail Christophe , Cochet Claude , Lomberget Thierry , Filhol Odile , Krimm Isabelle 
Published: December 2022

AbstractAlthough the involvement of protein kinase CK2 in cancer is well-documented, there is a need for selective CK2 inhibitors suitable for investigating CK2 specific roles in cancer-related biological pathways and further explore its therapeutic potential. Here we have discovered AB668, a new bivalent inhibitor that binds both at the ATP site and an allosteric αD pocket unique to CK2. The molecule inhibits CK2 activity with an outstanding selectivity over other kinases. Using caspase activation assay, live-cell imaging and transcriptomic analysis, we have compared the effects of this bivalent inhibitor to the non-selective ATP-competitive inhibitor CX-4945 that reached clinic and to the selective ATP-competitive SGC-CK2-1 molecule. Our results show that in contrast to CX-4945 or SGC-CK2-1, AB668 has a distinct mechanism of action regarding its anti-cancer activity, inducing apoptotic cell death and stimulating distinct biological pathways in several cancer cell lines while sparing healthy cells. Our data suggest that targeting a cryptic CK2 αD pocket validates an allosteric approach to targeting CK2 and provides a starting point for creating drug-like CK2 inhibitors for aggressive cancers.