bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biosynthesis of the redox cofactor mycofactocin comprises oligoglycosylation by MftF in Mycolicibacterium smegmatis
Authors: Peña-Ortiz Luis , Graça Ana Patrícia , Guo Huijuan , Braga Daniel , Köllner Tobias G. , Regestein Lars , Beemelmanns Christine , Lackner Gerald 
Published: October 2019

AbstractMycofactocin (MFT) is a redox cofactor involved in alcohol metabolism of mycobacteria including Mycobacterium tuberculosis. In recent years, a preliminary biosynthetic model of MFT has been established by in-vitro studies, while the final structure of MFT remained elusive. Here, we report the discovery of MFT by metabolomics and establish a model of its biosynthesis in Mycolicibacterium smegmatis. Structure elucidation revealed that MFT is decorated with up to nine β-1,4-linked glucose residues. Dissection of biosynthetic genes demonstrated that the oligoglycosylation is catalyzed by the glycosyltransferase MftF. Furthermore, we confirm the cofactor function of MFT by activity-based metabolic profiling using the carveol dehydrogenase LimC and show that the MFT pool expands during cultivation on ethanol. Our results close an important gap of knowledge, will guide future studies into the physiological roles of MFT in bacteria and may inspire its utilization as a biomarker or potential drug target to combat mycobacterial diseases.
Ten-eleven translocation 1 Mediated-DNA Hydroxymethylation is Required for Myelination and Remyelination in the Mouse Brain
Authors: Zhang Ming , Wang Jian , Zhang Kaixiang , Lu Guozhen , Liu Yuming , Ren Keke , Wang Wenting , Xin Dazhuan , Xu Lingli , Mao Honghui , Xing Junlin , Gao Xingchun , Jin Weilin , Berry Kalen , Mikoshiba Katsuhiko , Wu Shengxi , Lu Q. Richard , Zhao Xianghui 
Published: October 2019

AbstractTen-eleven translocation (TET) proteins, the dioxygenase for DNA hydroxymethylation, are important players in nervous system development and diseases. However, their role in myelination and remyelination after injury remains elusive. Here, we identify a genome-wide and locus-specific DNA hydroxymethylation landscape shift during differentiation of oligodendrocyte-progenitor cells (OPC). Ablation of Tet1 results in stage-dependent defects in oligodendrocyte (OL) development and myelination in the mouse brain. The mice lacking Tet1 in the oligodendrocyte lineage develop behavioral deficiency. We also show that TET1 is required for remyelination in adulthood. Transcriptomic, genomic occupancy, and DNA hydroxymethylation profiling reveal a critical TET1-regulated epigenetic program for oligodendrocyte differentiation that includes genes associated with myelination, cell division, and calcium transport. Tet1-deficient OPCs exhibit reduced calcium activity, increasing calcium activity rescues the differentiation defects in vitro. Deletion of a TET1-5hmC target gene, Itpr2 impairs the onset of OPC differentiation. Together, our results suggest that stage-specific TET1-mediated epigenetic programming and intracellular signaling are important for proper myelination and remyelination in mice.
Dual Histone Methyl Reader ZCWPW1 Facilitates Repair of Meiotic Double Strand Breaks
Authors: Mahgoub Mohamed , Paiano Jacob , Bruno Melania , Wu Wei , Pathuri Sarath , Zhang Xing , Ralls Sherry , Cheng Xiaodong , Nussenzweig Andre , Macfarlan Todd 
Published: October 2019

SummaryMeiotic crossovers result from homology-directed repair of double strand breaks (DSBs). Unlike yeast and plants, where DSBs are generated near gene promoters, in many vertebrates, DSBs are enriched at hotspots determined by the DNA binding activity of the rapidly evolving zinc finger array of PRDM9 (PR domain zinc finger protein 9). PRDM9 subsequently catalyzes tri-methylation of lysine 4 and lysine 36 of Histone H3 in nearby nucleosomes. Here, we identify the dual histone methylation reader ZCWPW1, which is tightly co-expressed during spermatogenesis withPrdm9and co-evolved withPrdm9in vertebrates, as an essential meiotic recombination factor required for efficient synapsis and repair of PRDM9-dependent DSBs. In sum, our results indicate that the evolution of a dual histone methylation writer/reader system in vertebrates facilitated a shift in genetic recombination away from a static pattern near genes towards a flexible pattern controlled by the rapidly evolving DNA binding activity of PRDM9.
Prostaglandins regulate invasive, collective border cell migration
Authors: Fox Emily F. , Lamb Maureen C. , Mellentine Samuel Q. , Tootle Tina L. 
Published: October 2019

AbstractWhile prostaglandins (PGs), short-range lipid signals, regulate cell migration, their mechanisms of action are poorly understood in collective migration. To address this, we useDrosophilaborder cell migration during Stage 9 of oogenesis. The border cells delaminate from the epithelium, and migrate collectively and invasively between the nurse cells. Pxt is theDrosophilacyclooxygenase-like enzyme responsible for all PG synthesis. Loss of Pxt results in both a significant delay in border cell migration during Stage 9 and an increase in cluster length compared to wild-type controls. Contributing to these phenotypes is altered integrin localization. Integrins are enriched on the border cell membranes, and this enrichment is lost inpxtmutants. Active integrins require interaction with the actin cytoskeleton. As we previously found PGs regulate the actin bundler Fascin and Fascin is required for border cell migration, we hypothesized PGs regulate Fascin to control integrins. Supporting this, loss of Fascin results in apxt-like integrin localization, and dominant genetic interaction studies reveal that co-reduction of Pxt and Fascin results in delayed and elongated border cell clusters. Together these data lead to the model that PG signaling controls Fascin, and thereby integrins, to mediate on-time border cell migration and maintain cluster cohesion.
EEG state-trajectory instability and speed reveal global rules of intrinsic spatiotemporal neural dynamics
Authors: Menceloglu Melisa , Grabowecky Marcia , Suzuki Satoru 
Published: October 2019

AbstractSpatiotemporal dynamics of EEG/MEG (electro-/magneto-encephalogram) have typically been investigated by applying time-frequency decomposition and examining amplitude-amplitude, phase-phase, or phase-amplitude associations between combinations of frequency bands and scalp sites, primarily to identify neural correlates of behaviors and traits. Instead, we directly extracted global EEG spatiotemporal dynamics as trajectories of k-dimensional state vectors (k = the number of estimated current sources) to investigate potential global rules governing neural dynamics. We chose timescale-dependent measures of trajectory instability (approximately the 2nd temporal derivative) and speed (approximately the 1st temporal derivative) as state variables, that succinctly characterized trajectory forms. We compared trajectories across posterior, central, anterior, and lateral scalp regions as the current sources under those regions may serve distinct functions. We recorded EEG while participants rested with their eyes closed (likely engaged in spontaneous thoughts) to investigate intrinsic neural dynamics. Some potential global rules emerged. Time-averaged trajectory instability from all five regions tightly converged (with their variability minimized) at the level of generating nearly unconstrained but slightly conservative turns (∼100° on average) on the timescale of ∼25 ms, suggesting that spectral-amplitude profiles are globally adjusted to maintain this convergence. Further, within-frequency and cross-frequency phase relations appear to be independently coordinated to reduce average trajectory speed and increase the variability in trajectory speed and instability in a relatively timescale invariant manner, and to make trajectories less oscillatory. Future research may investigate the functional relevance of these intrinsic global-dynamics rules by examining how they adjust to various sensory environments and task demands or remain invariant. The current results also provide macroscopic constraints for quantitative modeling of neural dynamics as the timescale dependencies of trajectory instability and speed are relatable to oscillatory dynamics.
Nanog safeguards early embryogenesis against global activation of maternal β-catenin activity by interfering with TCF factors
Authors: He Mudan , Zhang Ru , Zhang Fenghua , Jiao Shengbo , Ye Ding , Wang Houpeng , Sun Yonghua 
Published: October 2019

SummaryMaternal β-catenin activity is essential and critical for dorsal induction and its dorsal activation has been thoroughly studied. However, how the maternal β-catenin activity is suppressed in the non-dorsal cells remains poorly understood. Nanog is known to play a central role for maintenance of the pluripotency and maternal-to-zygotic transition. Here we reveal a novel role of Nanog as a strong repressor of maternal Wnt/β-catenin signaling to safeguard the embryo against hyper-activation of maternal β-catenin activity and hyper-dorsalization. Knockdown ofnanogat different levels led to either posteriorization or dorsalization, mimicking zygotic or maternal activation of Wnt/β-catenin activities, and the maternal-zygotic mutant ofnanog(MZnanog) showed strong activation of maternal β-catenin and hyper-dorsalization. Although a constitutive-activator-type Nanog (Vp16-Nanog, lacking the N-terminal) perfectly rescued the defects of maternal to zygotic transition in MZnanog, it did not rescue the phenotypes resulting from β-catenin activation. Mechanistically, the N-terminal of Nanog directly interacts with TCF and interferes with the binding of β-catenin to TCF, thereby attenuating the transcriptional activity of β-catenin. Therefore, our study establishes a novel role for Nanog in repressing maternal β-catenin activity and demonstrates a transcriptional switch between β-catenin/TCF and Nanog/TCF complexes, which safeguards the embryo from global activation of maternal β-catenin activity.
Neuronal transcriptome analyses reveal novel neuropeptide modulators of excitation and inhibition imbalance in C. elegans
Authors: McCulloch Katherine A. , Zhou Kingston , Jin Yishi 
Published: October 2019

ABSTRACTNeuropeptides are secreted molecules that have conserved roles modulating many processes, including mood, reproduction, and feeding. Dysregulation of neuropeptide signaling is also implicated in neurological disorders such as epilepsy. However, much is unknown about the mechanisms regulating specific neuropeptides to mediate behavior. Here, we report that the expression levels of dozens of neuropeptides are up-regulated in response to circuit activity imbalance in C. elegans. acr-2 encodes a homolog of human nicotinic receptors, and functions in the cholinergic motoneurons. A hyperactive mutation, acr-2(gf), causes an activity imbalance in the motor circuit. We performed cell-type specific transcriptomic analysis and identified genes differentially expressed in acr-2(gf), compared to wild type. The most over-represented class of genes are neuropeptides, with insulin-like-peptides (ILPs) the most affected. Moreover, up-regulation of neuropeptides occurs in motoneurons, as well as sensory neurons. In particular, the induced expression of the ILP ins-29 occurs in the BAG neurons, which are previously shown to function in gas-sensing. We also show that this up-regulation of ins-29 in acr-2(gf) animals is activity-dependent. Our genetic and molecular analyses support cooperative effects for ILPs and other neuropeptides in promoting motor circuit activity in the acr-2(gf) background. Together, this data reveals that a major transcriptional response to motor circuit dysregulation is in up-regulation of multiple neuropeptides, and suggests that BAG sensory neurons can respond to intrinsic activity states to feedback on the motor circuit.AUTHOR SUMMARYNeuropeptides are secreted small molecules that regulate a variety of neuronal functions and are also implicated in many diseases. However, it remains poorly understood how expression of neuropeptides is regulated, particularly in disease states. Using a genetic animal model that mimics epilepsy, we identified dozens of neuropeptides that are up-regulated when neuronal activities are altered. Some of these neuropeptides share similarity to insulin-like properties (ILPs). Strikingly, one of these ILPs is expressed in sensory neurons that normally respond to acute carbon dioxide exposure. We show that the mis-regulation of this ILP expression is activity-dependent. Moreover, these neuropeptides act in concert to modulate animal behaviors. The findings in this study provide further evidence that neuropeptides are key mediators of aberrant cholinergic signaling, and suggest complex neural network effects from sensory neurons onto motor function.
Land productivity dynamics in and around protected areas globally from 1999 to 2013
Authors: de la Fuente Begoña , Weynants Mélanie , Bertzky Bastian , Delli Giacomo , Mandrici Andrea , Bendito Eduardo Garcia , Dubois Grégoire 
Published: October 2019

AbstractTracking changes in total biomass production or land productivity is an essential part of monitoring land transformations and long-term alterations of the health and productive capacity of land that are typically associated with land degradation. Persistent declines in land productivity impact many terrestrial ecosystem services that form the basis for sustainable livelihoods of human communities. Protected areas (PAs) are a key strategy in global efforts to conserve biodiversity and ecosystem services that are critical for human well-being, and cover about 15% of the land worldwide. Here we globally assess the trends in land productivity in PAs of at least 10 km2and in their unprotected surroundings (10 km buffers) from 1999 to 2013. We quantify the percentage of the protected and unprotected land that shows stable, increasing or decreasing trends in land productivity, quantified as long-term (15 year) changes in above-ground biomass derived from satellite-based observations with a spatial resolution of 1 km. We find that 44% of the land in PAs globally has retained the productivity at stable levels from 1999 to 2013, compared to 42% of stable productivity in the unprotected land around PAs. Persistent increases in productivity are more common in the unprotected lands around PAs (32%) than within PAs (18%) globally, which may be related to more active management and vegetation cover changes in some of these unprotected lands. About 14% of the protected land and 12% of the unprotected land around PAs has experienced declines in land productivity from 1999 to 2013 globally. Oceania has the highest percentage of land with stable productivity in PAs (57%) followed by Asia (52%). Europe is the continent with the lowest percentage of land with stable productivity levels in PAs (38%) and with the largest share of protected land with increasing land productivity (32%), which may be related to the high population density and share of agricultural land within PAs as well as to rural land abandonment processes in many regions of Europe. In conclusion, we provide a relevant indicator and assessment of land productivity dynamics that contributes to characterise the state, pressures and changes in and around protected areas globally. Further research may focus on more detailed analyses to disentangle the relative contribution of specific drivers (from climate change to land use change) and their interaction with land productivity dynamics and potential land degradation in different regions of the world.
Anlotinib overcomes multiple drug resistant of the colorectal cancer cells via inactivating PI3K/AKT pathway
Authors: Lan Weilan , Zhao Jinyan , Shang Haixia , Peng Jun , Chen Wujin , Lin Jiumao 
Published: October 2019

AbstractBackgroundAnlotinib is a multi-tyrosine kinase inhibitor that has been reported to have activity against colorectal cancer. However, the functional mechanisms whereby anlotinib mediates against deadly drug-resistant colorectal cancer (CRC) has not been fully described-specifically, the potential mechanisms that inhibit proliferation and induce apoptosis remain largely unknown.MethodsMTT assays were used to detect cell viability and calculate the resistance index. Colony formation was used to evaluate the proliferation of resistant cells. DAPI staining was used to detect cell apoptosis morphologically. Annexin V-FITC with PI staining was used to detect early and late-stage apoptosis of cells. Cell cycle distribution was determined by Flow cytometry. Transwell assays were performed to examine the ability of migration and invasion. Cyclin D1 Survivin, CDK4, Bcl-2, Bax and changes of PI3K/AKT pathway were detected by Western blotting. Compared as a single agent or combined with anlotinib or LY294002, PI3K inhibitor (LY294002) was used to verify whether it inhibited drug-resistant CRC cells by lowering PI3K/AKT.ResultsHCT-8/5-FU cells showed multiple drug resistance. Drug resistance index of 5-FU, ADM and DDP were 390.27, 2.55 and 4.57, respectively. Anlotinib was shown to inhibit cell viability on HCT-8/5-FU and HCT-8 cells for 24 h and 48 h in a dosage- and time-dependent pattern. Compared with 48 h, intervened with anlotinib (0 μM, 10 μM, 20 μM and 40 μM) for 24 h, the HCT-8/5-FU cells were sensitive to anlotinib, and their sensitivity was greater than that of the parent cell line (HCT-8) at 24 h. Further, anlotinib inhibited the number of cloned cells significantly and had a significant inhibitory effect on cell cycle, mainly by blocking G1 transferring to S phase. Moreover, anlotinib could down-regulate the expression of survivin, cyclin D1, CDK4, caspase-3, Bcl-2, MMP-2, vimentin, MMP-9, and N-cadherin, while up-regulating cleaved-caspase-3, Bax and E-cadherin. Anlotinib inhibited the activity of the PI3K/AKT pathway and induced apoptosis in HCT-8/5-FU cells. Using LY294002, a specific PI3K inhibitor, our experiment found anlotinib can inhibit drug-resistant CRC cells by reducing PI3K and p-AKT activity-induce apoptosis.ConclusionsAnlotinib inhibited the proliferation, metastasis and induced apoptosis of HCT-8 / 5-FU cells; and the mechanism could be that anlotinib overcomes multiple drug resistant of the colorectal cancer cells via inactivating PI3K/AKT pathway.
Torsin ATPases are required to complete nuclear pore complex biogenesis in interphase
Authors: Rampello Anthony J. , Laudermilch Ethan , Vishnoi Nidhi , Prohet Sarah M. , Shao Lin , Zhao Chenguang , Lusk C. Patrick , Schlieker Christian 
Published: October 2019

AbstractNuclear envelope herniations (blebs) containing FG-nucleoporins and ubiquitin are the phenotypic hallmark of Torsin ATPase manipulation. Both the dynamics of blebbing and the connection to nuclear pore biogenesis remain poorly understood. We employ a proteomics-based approach to identify MLF2 as a luminal component of the bleb. Using an MLF2-based live cell imaging platform, we demonstrate that NE blebbing occurs rapidly and synchronously immediately after nuclear envelope reformation during mitosis. Bleb formation is independent of ubiquitin conjugation within the bleb, but strictly dependent on POM121, a transmembrane nucleoporin essential for interphase nuclear pore biogenesis. Nup358, a late marker for interphase nuclear pore complex (NPC) biogenesis, is underrepresented relative to FG nucleoporins in nuclear envelopes of Torsin-deficient cells. The kinetics of bleb formation, its dependence on POM121, and a reduction of mature NPCs in Torsin deficient cells lead us to conclude that the hallmark phenotype of Torsin manipulation represents the accumulation of stalled NPC assembly intermediates.
Low-cost open hardware system for behavioural experiments simultaneously with electrophysiological recordings
Authors: Aguiar Leandro A. A. , de Vasconcelos Nivaldo A P , Tunes Gabriela Chiuffa , Fontenele Antonio J. , de Albuquerque Nogueira Romildo , Reyes Marcelo Bussotti , Carelli Pedro V. 
Published: October 2019

AbstractA major frontier in neuroscience is to find neural correlates of perception, learning, decision making, and a variety of other types of behavior. In the last decades, modern devices allow simultaneous recordings of different operant responses and the electrical activity of large neuronal populations. However, the commercially available instruments for studying operant conditioning are expensive, and the design of low-cost chambers has emerged as an appealing alternative to resource-limited laboratories engaged in animal behavior. In this article, we provide a full description of a platform that records the operant behavior and synchronizes it with the electrophysiological activity. The programming of this platform is open source, flexible and adaptable to a wide range of operant conditioning tasks. We also show results of operant conditioning experiments with freely moving rats with simultaneous electrophysiological recordings.Specifications table
Quantitative modeling of the function of kinetically driven transcriptional riboswitches
Authors: Parra-Rojas César , Fürtig Boris , Schwalbe Harald , Hernandez-Vargas Esteban A. 
Published: October 2019

AbstractWe propose a generalized modeling framework for the kinetic mechanisms of transcriptional riboswitches. The formalism accommodates time-dependent transcription rates and changes of metabolite concentration and permits incorporation of variations in transcription rate depending on transcript length. We derive explicit analytical expressions for the fraction of transcripts that determine repression or activation of gene expression, pause site location and its slowing down of transcription for the case of the (2’dG)-sensing riboswitch fromMesoplasma florum. Our modeling challenges the current view on the exclusive importance of metabolite binding to transcripts containing only the aptamer domain. Numerical simulations of transcription proceeding in a continuous manner under time-dependent changes of metabolite concentration further suggest that rapid modulations in concentration result in a reduced dynamic range for riboswitch function regardless of transcription rate, while a combination of slow modulations and small transcription rates ensures a wide range of finely tuneable regulatory outcomes.