bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kinesin-7 CENP-E regulates chromosome alignment and genome stability of spermatogenic cells
Authors: She Zhen-Yu , Yu Kai-Wei , Zhong Ning , Xiao Yu , Wei Ya-Lan , Lin Yang , Li Yue-Ling , Lu Ming-Hui 
Published: April 2020

AbstractKinesin-7 CENP-E is an essential kinetochore motor required for chromosome alignment and congression. However, the specific functions of CENP-E in the spermatogenic cells during spermatogenesis remain unknown. In this study, we find that CENP-E proteins are expressed in the spermatogonia, spermatocytes, and the elongating spermatids. CENP-E inhibition by specific inhibitor GSK923295 results in the disruption of spermatogenesis and cell cycle arrest of spermatogenic cells. Both spermatogonia and spermatocytes are arrested in metaphase and several chromosomes are not aligned at the equatorial plate. We find that CENP-E inhibition leads to chromosome misalignment, the spindle disorganization, and the formation of the aneuploidy cells. Furthermore, the inhibition of CENP-E results in the defects in the formation of spermatids, including the sperm head condensation and the sperm tail formation. We have revealed that kinesin-7 CENP-E is essential for chromosome alignment and genome stability of the spermatogenic cells.
Genetic characterization of a unique neuroendocrine transdifferentiation prostate circulating tumor cell-derived eXplant model
Authors: Faugeroux Vincent , Pailler Emma , Oulhen Marianne , Deas Olivier , Brulle-Soumare Laura , Hervieu Céline , Marty Virginie , Alexandrova Kamelia , Andree Kiki C. , Stoecklein Nikolas H. , Tramalloni Dominique , Cairo Stefano , NgoCamus Maud , Nicotra Claudio , Terstappen Leon W. M. M. , Manaresi Nicolo , Lapierre Valérie , Fizazi Karim , Scoazec Jean-Yves , Loriot Yohann , Judde Jean-Gabriel , Farace Françoise 
Published: April 2020

AbstractTransformation of castration-resistant prostate cancer (CRPC) into an aggressive neuroendocrine disease (CRPC-NE) represents a major clinical challenge and experimental models are lacking. A CTC-derived eXplant (CDX) and a CDX-derived cell line are established using circulating tumor cells (CTCs) obtained by diagnostic leukapheresis from a CRPC patient resistant to enzalutamide. The CDX and the derived-cell line conserve 16% of primary tumor (PT) and 56% of CTC mutations, as well as 83% of PT copy-number aberrations including clonal TMPRSS2-ERG fusion and NKX3.1 loss. Both harbor an androgen receptor-null neuroendocrine phenotype, TP53, PTEN and RB1 loss. While PTEN and RB1 loss are acquired in CTCs, evolutionary analysis suggest that a PT subclone harboring TP53 loss is the driver of the metastatic event leading to the CDX. This CDX model provides insights on the sequential acquisition of key drivers of neuroendocrine transdifferentiation and offers a unique tool for effective drug screening in CRPC-NE management.
Cryo-EM structures reveal intricate Fe-S cluster arrangement and charging in Rhodobacter capsulatus formate dehydrogenase
Authors: Radon Christin , Mittelstädt Gerd , Duffus Benjamin R. , Bürger Jörg , Hartmann Tobias , Mielke Thorsten , Teutloff Christian , Leimkühler Silke , Wendler Petra 
Published: April 2020

AbstractMetal-containing formate dehydrogenases (FDH) catalyse the reversible oxidation of formate to carbon dioxide at their molybdenum or tungsten active site. They display a diverse subunit and cofactor composition, but structural information on these enzymes is limited. Here we report the cryo-electron microscopic structures of the soluble Rhodobacter capsulatus FDH (RcFDH) as isolated and in the presence of reduced nicotinamide adenine dinucleotide (NADH). RcFDH assembles into a 360 kDa dimer of heterotetramers revealing a putative interconnection of electron pathway chains. In the presence of NADH, the RcFDH structure shows charging of cofactors, indicative of an increased electron load.
The endoplasmic reticulum stress-autophagy pathway controls hypothalamic development and energy balance regulation in leptin-deficient neonates
Authors: Park Soyoung , Aintablian Aleek , Coupe Berengere , Bouret Sebastien G. 
Published: April 2020

AbstractObesity is associated with the activation of cellular responses, such as endoplasmic reticulum (ER) stress. Here, we show that leptin-deficient ob/ob mice display elevated hypothalamic ER stress as early as postnatal day 10, i.e., prior to the development of obesity in this mouse model. Neonatal treatment of ob/ob mice with the ER stress-relieving drug tauroursodeoxycholic acid (TUDCA) causes long-term amelioration of body weight, food intake, glucose homeostasis, and pro-opiomelanocortin (POMC) projections. Cells exposed to ER stress often activate autophagy. Accordingly, we report that in vitro induction of ER stress and neonatal leptin deficiency in vivo activate hypothalamic autophagy-related genes. Furthermore, genetic deletion of autophagy in pro-opiomelanocortin neurons of ob/ob mice worsens their glucose homeostasis, adiposity, hyperphagia, and POMC neuronal projections, all of which are ameliorated with neonatal TUDCA treatment. Together, our data highlight the importance of early life ER stress-autophagy pathway in influencing hypothalamic circuits and metabolic regulation.
Structural basis of astrocytic Ca2+ signals at tripartite synapses
Authors: Arizono Misa , Inavalli V. V. G. Krishna , Panatier Aude , Pfeiffer Thomas , Angibaud Julie , Levet Florian , Ter Veer Mirelle J. T. , Stobart Jillian , Bellocchio Luigi , Mikoshiba Katsuhiko , Marsicano Giovanni , Weber Bruno , Oliet Stéphane H. R. , Nägerl U. Valentin 
Published: April 2020

AbstractAstrocytic Ca2+ signals can be fast and local, supporting the idea that astrocytes have the ability to regulate single synapses. However, the anatomical basis of such specific signaling remains unclear, owing to difficulties in resolving the spongiform domain of astrocytes where most tripartite synapses are located. Using 3D-STED microscopy in living organotypic brain slices, we imaged the spongiform domain of astrocytes and observed a reticular meshwork of nodes and shafts that often formed loop-like structures. These anatomical features were also observed in acute hippocampal slices and in barrel cortex in vivo. The majority of dendritic spines were contacted by nodes and their sizes were correlated. FRAP experiments and Ca2+ imaging showed that nodes were biochemical compartments and Ca2+ microdomains. Mapping astrocytic Ca2+ signals onto STED images of nodes and dendritic spines showed they were associated with individual synapses. Here, we report on the nanoscale organization of astrocytes, identifying nodes as a functional astrocytic component of tripartite synapses that may enable synapse-specific communication between neurons and astrocytes.
Impact of visual callosal pathway is dependent upon ipsilateral thalamus
Authors: Ramachandra Vishnudev , Pawlak Verena , Wallace Damian J. , Kerr Jason N. D. 
Published: April 2020

AbstractThe visual callosal pathway, which reciprocally connects the primary visual cortices, is thought to play a pivotal role in cortical binocular processing. In rodents, the functional role of this pathway is largely unknown. Here, we measure visual cortex spiking responses to visual stimulation using population calcium imaging and functionally isolate visual pathways originating from either eye. We show that callosal pathway inhibition significantly reduced spiking responses in binocular and monocular neurons and abolished spiking in many cases. However, once isolated by blocking ipsilateral visual thalamus, callosal pathway activation alone is not sufficient to drive evoked cortical responses. We show that the visual callosal pathway relays activity from both eyes via both ipsilateral and contralateral visual pathways to monocular and binocular neurons and works in concert with ipsilateral thalamus in generating stimulus evoked activity. This shows a much greater role of the rodent callosal pathway in cortical processing than previously thought.
Hepatic saturated fatty acid fraction is associated with de novo lipogenesis and hepatic insulin resistance
Authors: Roumans Kay H. M. , Lindeboom Lucas , Veeraiah Pandichelvam , Remie Carlijn M. E. , Phielix Esther , Havekes Bas , Bruls Yvonne M. H. , Brouwers Martijn C. G. J. , Ståhlman Marcus , Alssema Marjan , Peters Harry P. F. , de Mutsert Renée , Staels Bart , Taskinen Marja-Riitta , Borén Jan , Schrauwen Patrick , Schrauwen-Hinderling Vera B. 
Published: April 2020

AbstractHepatic steatosis is associated with poor cardiometabolic health, with de novo lipogenesis (DNL) contributing to hepatic steatosis and subsequent insulin resistance. Hepatic saturated fatty acids (SFA) may be a marker of DNL and are suggested to be most detrimental in contributing to insulin resistance. Here, we show in a cross-sectional study design (ClinicalTrials.gov ID: NCT03211299) that we are able to distinguish the fractions of hepatic SFA, mono- and polyunsaturated fatty acids in healthy and metabolically compromised volunteers using proton magnetic resonance spectroscopy (1H-MRS). DNL is positively associated with SFA fraction and is elevated in patients with non-alcoholic fatty liver and type 2 diabetes. Intriguingly, SFA fraction shows a strong, negative correlation with hepatic insulin sensitivity. Our results show that the hepatic lipid composition, as determined by our 1H-MRS methodology, is a measure of DNL and suggest that specifically the SFA fraction may hamper hepatic insulin sensitivity.
Synthesis and evaluation of designed PKC modulators for enhanced cancer immunotherapy
Authors: Hardman Clayton , Ho Stephen , Shimizu Akira , Luu-Nguyen Quang , Sloane Jack L. , Soliman Mohamed S. A. , Marsden Matthew D. , Zack Jerome A. , Wender Paul A. 
Published: April 2020

AbstractBryostatin 1 is a marine natural product under investigation for HIV/AIDS eradication, the treatment of neurological disorders, and enhanced CAR T/NK cell immunotherapy. Despite its promising activity, bryostatin 1 is neither evolved nor optimized for the treatment of human disease. Here we report the design, synthesis, and biological evaluation of several close-in analogs of bryostatin 1. Using a function-oriented synthesis approach, we synthesize a series of bryostatin analogs designed to maintain affinity for bryostatin’s target protein kinase C (PKC) while enabling exploration of their divergent biological functions. Our late-stage diversification strategy provides efficient access to a library of bryostatin analogs, which per our design retain affinity for PKC but exhibit variable PKC translocation kinetics. We further demonstrate that select analogs potently increase cell surface expression of CD22, a promising CAR T cell target for the treatment of leukemias, highlighting the clinical potential of bryostatin analogs for enhancing targeted immunotherapies.
Fasting inhibits aerobic glycolysis and proliferation in colorectal cancer via the Fdft1-mediated AKT/mTOR/HIF1α pathway suppression
Authors: Weng Mei-lin , Chen Wan-kun , Chen Xiang-yuan , Lu Hong , Sun Zhi-rong , Yu Qi , Sun Peng-fei , Xu Ya-jun , Zhu Min-min , Jiang Nan , Zhang Jin , Zhang Jian-ping , Song Yuan-lin , Ma Duan , Zhang Xiao-ping , Miao Chang-hong 
Published: April 2020

AbstractEvidence suggests that fasting exerts extensive antitumor effects in various cancers, including colorectal cancer (CRC). However, the mechanism behind this response is unclear. We investigate the effect of fasting on glucose metabolism and malignancy in CRC. We find that fasting upregulates the expression of a cholesterogenic gene, Farnesyl-Diphosphate Farnesyltransferase 1 (FDFT1), during the inhibition of CRC cell aerobic glycolysis and proliferation. In addition, the downregulation of FDFT1 is correlated with malignant progression and poor prognosis in CRC. Moreover, FDFT1 acts as a critical tumor suppressor in CRC. Mechanistically, FDFT1 performs its tumor-inhibitory function by negatively regulating AKT/mTOR/HIF1α signaling. Furthermore, mTOR inhibitor can synergize with fasting in inhibiting the proliferation of CRC. These results indicate that FDFT1 is a key downstream target of the fasting response and may be involved in CRC cell glucose metabolism. Our results suggest therapeutic implications in CRC and potential crosstalk between a cholesterogenic gene and glycolysis.
Physical drivers of the summer 2019 North Pacific marine heatwave
Authors: Amaya Dillon J. , Miller Arthur J. , Xie Shang-Ping , Kosaka Yu 
Published: April 2020

AbstractSummer 2019 observations show a rapid resurgence of the Blob-like warm sea surface temperature (SST) anomalies that produced devastating marine impacts in the Northeast Pacific during winter 2013/2014. Unlike the original Blob, Blob 2.0 peaked in the summer, a season when little is known about the physical drivers of such events. We show that Blob 2.0 primarily results from a prolonged weakening of the North Pacific High-Pressure System. This reduces surface winds and decreases evaporative cooling and wind-driven upper ocean mixing. Warmer ocean conditions then reduce low-cloud fraction, reinforcing the marine heatwave through a positive low-cloud feedback. Using an atmospheric model forced with observed SSTs, we also find that remote SST forcing from the central equatorial and, surprisingly, the subtropical North Pacific Ocean contribute to the weakened North Pacific High. Our multi-faceted analysis sheds light on the physical drivers governing the intensity and longevity of summertime North Pacific marine heatwaves.
Overcoming the exciton binding energy in two-dimensional perovskite nanoplatelets by attachment of conjugated organic chromophores
Authors: Gélvez-Rueda María C. , Fridriksson Magnus B. , Dubey Rajeev K. , Jager Wolter F. , van der Stam Ward , Grozema Ferdinand C. 
Published: April 2020

AbstractIn this work we demonstrate a novel approach to achieve efficient charge separation in dimensionally and dielectrically confined two-dimensional perovskite materials. Two-dimensional perovskites generally exhibit large exciton binding energies that limit their application in optoelectronic devices that require charge separation such as solar cells, photo-detectors and in photo-catalysis. Here, we show that by incorporating a strongly electron accepting moiety, perylene diimide organic chromophores, on the surface of the two-dimensional perovskite nanoplatelets it is possible to achieve efficient formation of mobile free charge carriers. These free charge carriers are generated with ten times higher yield and lifetimes of tens of microseconds, which is two orders of magnitude longer than without the peryline diimide acceptor. This opens a novel synergistic approach, where the inorganic perovskite layers are combined with functional organic chromophores in the same material to tune the properties for specific applications.
Deeply conserved synteny resolves early events in vertebrate evolution
Authors: Simakov Oleg , Marlétaz Ferdinand , Yue Jia-Xing , O’Connell Brendan , Jenkins Jerry , Brandt Alexander , Calef Robert , Tung Che-Huang , Huang Tzu-Kai , Schmutz Jeremy , Satoh Nori , Yu Jr-Kai , Putnam Nicholas H. , Green Richard E. , Rokhsar Daniel S. 
Published: April 2020

AbstractAlthough it is widely believed that early vertebrate evolution was shaped by ancient whole-genome duplications, the number, timing and mechanism of these events remain elusive. Here, we infer the history of vertebrates through genomic comparisons with a new chromosome-scale sequence of the invertebrate chordate amphioxus. We show how the karyotypes of amphioxus and diverse vertebrates are derived from 17 ancestral chordate linkage groups (and 19 ancestral bilaterian groups) by fusion, rearrangement and duplication. We resolve two distinct ancient duplications based on patterns of chromosomal conserved synteny. All extant vertebrates share the first duplication, which occurred in the mid/late Cambrian by autotetraploidization (that is, direct genome doubling). In contrast, the second duplication is found only in jawed vertebrates and occurred in the mid–late Ordovician by allotetraploidization (that is, genome duplication following interspecific hybridization) from two now-extinct progenitors. This complex genomic history parallels the diversification of vertebrate lineages in the fossil record.
Imaging-assisted hydrogel formation for single cell isolation
Authors: Oldenhof Sander , Mytnyk Serhii , Arranja Alexandra , de Puit Marcel , van Esch Jan H. 
Published: April 2020

AbstractWe report a flexible single-cell isolation method by imaging-assisted hydrogel formation. Our approach consists of imaging-aided selective capture of cells of interest by encasing them into a polymeric hydrogel, followed by removal of unwanted cells and subsequent release of isolated cells by enzymatic hydrogel degradation, thus offering an opportunity for further analysis or cultivation of selected cells. We achieved high sorting efficiency and observed excellent viability rates (>98%) for NIH/3T3 fibroblasts and A549 carcinoma cells isolated using this procedure. The method presented here offers a mask-free, cost-efficient and easy-to-use alternative to many currently existing surface-based cell-sorting techniques, and has the potential to impact the field of cell culturing and isolation, e.g. single cell genomics and proteomics, investigation of cellular heterogeneity and isolation of best performing mutants for developing new cell lines.
The effect of Palm Oil Mill Effluent Final Discharge on the Characteristics of Pennisetum purpureum
Authors: Osman Nurul Atiqah , Ujang Farhana Aziz , Roslan Ahmad Muhaimin , Ibrahim Mohamad Faizal , Hassan Mohd Ali 
Published: April 2020

AbstractPhytoremediation is one of the environmental-friendly and cost-effective systems for the treatment of wastewater, including industrial wastewater such as palm oil mill effluent final discharge (POME FD). However, the effects of the wastewater on the phytoremediator plants, in term of growth performance, lignocellulosic composition, and the presence of nutrients and heavy metals in the plants are not yet well studied. In the present work, we demonstrated that POME FD increased the growth of P. purpureum. The height increment of P. purpureum supplied with POME FD (treatment) was 61.72% as compared to those supplied with rain water (control) which was 14.42%. For lignocellulosic composition, the cellulose percentages were 38.77 ± 0.29% (treatment) and 34.16 ± 1.01% (control), and the difference was significant. These results indicated that POME FD could be a source of plant nutrients, which P. purpureum can absorb for growth. It was also found that the heavy metals (Al, As, Cd, Co, Cr, Ni and Pb) inside the plant were below the standard limit of the World Health Organization (WHO). Since POME FD was shown to have no adverse effects on P. purpureum, further research regarding the potential application of P. purpureum following phytoremediation of POME FD such as biofuel production is warranted to evaluate its potential use to fit into the waste-to-wealth agenda.
Combination of Simultaneous Artificial Sensory Percepts to Identify Prosthetic Hand Postures: A Case Study
Authors: Segil Jacob L. , Cuberovic Ivana , Graczyk Emily L. , Weir Richard F. ff. , Tyler Dustin 
Published: April 2020

AbstractMultiple sources of sensory information are combined to develop hand posture percepts in the intact system, but the combination of multiple artificial somatosensory percepts by human prosthesis users has not been studied. Here, we report on a case study in which a person with transradial amputation identified prosthetic hand postures using artificial somatosensory feedback. He successfully combined five artificial somatosensory percepts to achieve above-chance performance of 95.0% and 75.7% in identifying four and seven postures, respectively. We studied how artificial somatosensation and the extant hand representation are combined in the decision-making process by providing two mappings between the prosthetic sensor and the location of the sensory percept: (1) congruent, and (2) incongruent. The participant’s ability to combine and engage with the sensory feedback significantly differed between the two conditions. The participant was only able to successfully generalize prior knowledge to novel postures in the congruent mapping. Further, he learned postures more accurately and quickly in the congruent mapping. Finally, he developed an understanding of the relationships between postures in the congruent mapping instead of simply memorizing each individual posture. These experimental results are corroborated by a Bayesian decision-making model which tracked the participant’s learning.
RAC1-Dependent ORAI1 Translocation to the Leading Edge Supports Lamellipodia Formation and Directional Persistence
Authors: Lopez-Guerrero Aida M. , Espinosa-Bermejo Noelia , Sanchez-Lopez Irene , Macartney Thomas , Pascual-Caro Carlos , Orantos-Aguilera Yolanda , Rodriguez-Ruiz Lola , Perez-Oliva Ana B. , Mulero Victoriano , Pozo-Guisado Eulalia , Martin-Romero Francisco Javier 
Published: April 2020

AbstractTumor invasion requires efficient cell migration, which is achieved by the generation of persistent and polarized lamellipodia. The generation of lamellipodia is supported by actin dynamics at the leading edge where a complex of proteins known as the WAVE regulatory complex (WRC) promotes the required assembly of actin filaments to push the front of the cell ahead. By using an U2OS osteosarcoma cell line with high metastatic potential, proven by a xenotransplant in zebrafish larvae, we have studied the role of the plasma membrane Ca2+ channel ORAI1 in this process. We have found that epidermal growth factor (EGF) triggered an enrichment of ORAI1 at the leading edge, where colocalized with cortactin (CTTN) and other members of the WRC, such as CYFIP1 and ARP2/3. ORAI1-CTTN co-precipitation was sensitive to the inhibition of the small GTPase RAC1, an upstream activator of the WRC. RAC1 potentiated ORAI1 translocation to the leading edge, increasing the availability of surface ORAI1 and increasing the plasma membrane ruffling. The role of ORAI1 at the leading edge was studied in genetically engineered U2OS cells lacking ORAI1 expression that helped us to prove the key role of this Ca2+ channel on lamellipodia formation, lamellipodial persistence, and cell directness, which are required for tumor cell invasiveness in vivo.
Prion protein N1 cleavage peptides stimulate microglial interaction with surrounding cells
Authors: Carroll J. A. , Groveman B. R. , Williams K. , Moore R. , Race B. , Haigh C. L. 
Published: April 2020

AbstractMicroglia act as the protective immune cell of the brain. By surveying the tissue to identify and rectify problems, they function to maintain the health of brain cells. The prion protein N-terminal cleavage fragment, N1, has demonstrated neuroprotective activities in vitro and in vivo. This study aimed to elucidate whether N1 could modulate microglial function and, if so, determine the consequences for the surrounding tissue. Using a mixed neuronal lineage and microglia co-culture system, we showed that N1 stimulation changed overall morphology and metabolism, suggesting enhanced cellular viability. Furthermore, N1 induced an increase in Cxcl10 secretion in the co-cultures. Recombinant Cxcl10, administered exogenously, mediated the changes in the mixed neuronal lineage culture morphology and metabolism in the absence of microglia, but no effect of Cxcl10 was observed on microglia cultured on their own. Direct cell-to-cell contact was required for N1 to influence microglia in the co-cultures, and this was linked with restructuring of microglial membrane composition to include a higher GM1 content at interaction sites with surrounding cells. Our findings show that N1 can play a regulatory role in microglial function in the context of an inter-connected network of cells by changing both cellular interaction sites and cytokine secretion.