bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Satellite III long non-coding RNA imparts survival benefits to cancer cells
Authors: Chatterjee Manjima , Sengupta Sonali 
Published: October 2021

ABSTRACTLong non-coding RNAs are heterogeneous group of transcripts that lack coding potential and have crucial roles in gene regulations. Recent days have seen an increasing association of non-coding RNAs with human diseases, especially cancers. Satellite III (SatIII) lncRNAs are transcribed from pericentromeric heterochromatic region of the human chromosome. Though transcriptionally silent in normal conditions, SatIII is actively transcribed under condition of stress, mainly heat shock. SatII repeat, another component of pericentromeric region of human chromosome, has been associated with wide variety of epithelial cancer. Overexpression of Satellite RNAs induces breast cancer in mice. Though much is known about Satellite RNAs, which includes alpha satellites and SatII repeats, however little is known about SatIII in human cancers. Hence we directed our study to understand the role of human Satellite III repeats in cancerous conditions. In the present study, we show that colon and breast cancer cells transcribe SatIII independent of heat shock, in an HSF1-independent manner. Our study also reveals that, overexpression of SatIII RNA favours cancer cell survival by overriding chemo drug-induced cell death. Knockdown of SatIII sensitizes cells towards chemotherapeutic drugs. SatIII transcript knockdown restores the expression of p53 protein, which in turn facilitates cell death. Heat shock however helps SatIII to continue with its pro-cell survival function. Our results, therefore suggest SatIII to be an important regulator of human cancers. Induction of SatIII is not only a response to the oncogenic stress but also facilitates cancer progression by a distinct pathway that is different from heat stress pathway.
Functional characterisation of single nucleotide variants of the psychiatric risk gene cacna1c in the zebrafish
Authors: Banono Nancy Saana , Gawel Kinga , Mäki-Marttunen Tuomo , van der Ent Wietske , Kukula-Koch Wirginia , Fyhn Marianne , Einevoll Gaute T. , Andreassen Ole A. , Esguerra Camila V. 
Published: October 2021

AbstractSeveral genome-wide association studies have associated CACNA1C variants with psychiatric disorders. The molecular mechanisms involved are poorly understood. Taking advantage of the zebrafish larva as a model, we investigated how two different mutations in cacna1c – sa10930 (nonsense mutation) and sa15296 (splice site mutation), affect neuronal function. We characterized changes in cacna1c mRNA, neurotransmitter levels and behaviour, as well as whole-brain activity using single electrode local field potential recordings. Both point mutations resulted in a significant reduction in cacna1c mRNA, as well as social behaviour and prepulse inhibition deficits. Whereas sa15296 mutants displayed abnormal locomotor and open-field behaviour, we observed normal behaviour in the sa10930 mutants. Brain recordings from both mutants had lower spectral power while sa15296 displayed significant seizure-like activity. Finally, sa10930 homozygotes showed increased dopamine and serotonin levels, decreased gamma-aminobutyric acid (GABA) levels, and unchanged glutamate levels while homozygous sa15296 larvae showed increased levels of serotonin and glutamate, and unaffected levels of GABA and dopamine. Our work provides new insights into the functional role of CACNA1C in behavioural, electrophysiological and biochemical traits linked to psychiatric disorders. We show a functional role for the non-coding mutation (sa15296) in the cacna1c in vivo animal model. Consistent with existing hypotheses, our data suggest that disruption of gene expression, neurotransmission, and cortical excitability are involved in CACNA1C-related mechanisms of psychiatric disorders.
Identification and expression analysis of Shaker K+ channel genes in millet (Setaria italica) under abiotic stresses
Authors: Zhang Ben , Wang Hui , Guo Yue , Wang Xiaoxia , Lv Mengtao , Yang Pu , Zhang Lizhen 
Published: October 2021

AbstractPotassium (K+) is one of the essential nutrients for plant, which is involved in plant growth and development and abiotic stress tolerance. The absorption and transport of K+ depends on Shaker K+ channels. Foxtail millet is a Poaceae crop with strong drought stress-tolerant. In this study, we identified ten Shaker K+ channel genes in foxtail millet. Phylogenetic analysis, prediction of conserved motif, and gene structure analysis classified these genes into five groups. The transcription level of these genes under different abiotic stress treatments (cold, heat, NaCl, PEG) and ABA treatment were analyzed by quantitative real-time PCR. Each gene displayed its own regulation pattern under different treatments, suggests these channels play important role in plant adaptation to different environment conditions.
Experience resetting in reinforcement learning facilitates exploration–exploitation transitions during a behavioral task for primates
Authors: Sakamoto Kazuhiro , Okuzaki Hidetake , Sato Akinori , Mushiake Hajime 
Published: October 2021

AbstractThe exploration–exploitation trade-off is a fundamental problem in re-inforcement learning. To study the neural mechanisms involved in this problem, a target search task in which exploration and exploitation phases appear alternately is useful. Monkeys well trained in this task clearly understand that they have entered the exploratory phase and quickly acquire new experiences by resetting their previous experiences. In this study, we used a simple model to show that experience resetting in the exploratory phase improves performance rather than decreasing the greediness of action selection, and we then present a neural network-type model enabling experience resetting.
Investigation of Dengue Fever Outbreak in a Rural Area of Islamabad, Pakistan: A Case Control Study
Authors: Khan Fawad Khalid , Akram Khurram Shahzad , Chaudhry Ambreen , Bullo Mir Hassan , Hussain Zakir , Baig Mirza Amir , Mehmood Amjad , Baig Zeeshan Iqbal 
Published: October 2021

AbstractBackgroundIn the second week of October 2019, five suspected cases of dengue fever were reported from union council Sohan, Islamabad rural (population 45,747) to the health department, Islamabad Capital Territory (ICT). Outbreak investigation was conducted with the objectives to identify risk factors and recommend control measures.MethodsOutbreak investigation was conducted from 17th October to 25th November 2019. A case was defined as, “fever and two or more of the following signs/symptoms; headache, retro-orbital pain, joint/bone pain, myalgia and petechial rash with NS1 test (Nonstructural Protein 1) positive during 8th October to 25th November 2019 among residents of Sohan”. Age and sex-matched controls were recruited from the same neighborhood. All cases were positive for NS1 antigen. Blood samples from five suspected cases were collected and tested for laboratory confirmation.ResultsA total of 547 households were surveyed and 85 cases were identified. The mean age was 34.4 years + 16.05 (range 3-71 years). The attack rate was 0.19% whereas the most affected age group was the 45-54 years (AR 0.43%). Males were predominantly affected (n=48 56.5%). Among all cases, 32% (n=27)) had stagnant water inside or around their houses (aOR 2.65, CI 1.20-5.83, P=0.005), 33% (n=28) were using mosquito repellent (aOR 0.35, CI 0.17-0.70, P<0.001), 31% (n=26) used indoor residual spray insecticide (aOR 0.48, CI 0.24-0.97, P=0.041), and 73% (n=62) used full protective clothing (aOR 0.17, CI 0.05-0.58, P<0.001). All five blood samples were tested positive for NS-1 antigen.ConclusionThe presence of accumulated rainwater in pools and empty receptacles around houses acted as breeding grounds for Aedes aegypti mosquitos and was the most probable cause of this outbreak. Following our recommendations, the health department-initiated mosquito breeding sites control activities through residual insecticide spray and advocacy on the use of protective measures against mosquito bites.
Humoral cross-reactivity towards SARS-CoV-2 in young children with acute respiratory infection with low-pathogenicity coronaviruses
Authors: Dhochak Nitin , Agrawal Tanvi , Shaman Heena , Khan Naseem Ahmed , Kumar Prawin , Kabra Sushil K , Medigeshi Guruprasad R , Lodha Rakesh 
Published: October 2021

AbstractSARS-CoV-2 infection in children frequently leads to only asymptomatic and mild infections. It has been suggested that frequent infections due to low-pathogenicity coronaviruses in children, imparts immunity against SARS-CoV-2 in this age group. From a prospective birth cohort study prior to the pandemic, we identified children (n=42) with proven low-pathogenicity coronavirus infections. Convalescent sera from these samples had antibodies against the respective seasonal CoVs as demonstrated by immunofluorescence assay. We tested these samples for neutralization of SARS-CoV-2 using virus microneutralization assay. Forty serum samples showed no significant neutralization of SARS-CoV-2, while 2 samples showed inconclusive results. These findings suggest that the antibodies generated in low-pathogenicity coronavirus infections offer no protection from SARS-CoV-2 infection in young children.
Frailty trajectories in the oldest old: Is the level or the rate of change more predictive of mortality?
Authors: Stolz Erwin , Mayerl Hannes , Hoogendijk Emiel O. 
Published: October 2021

AbstractBACKGROUNDIt is unclear whether frailty index (FI) change captures mortality risk better than and independently of the current FI level, i.e. whether a regular FI assessment among older adults provides additional insights for mortality risk stratification or not.METHODSWe used data from the LASA 75-PLUS-study, which monitored health among 508 older adults (75+) between 2016-2019 every 9 months. Joint models for longitudinal and time-to-event data were used to assess the impact of both current FI and within-person FI change during the last year on mortality risk.RESULTS20% of the participants died during 4.5 years of follow-up. Adding within-person FI change to the current FI model improved model fit and it showed that FI increases during the last year were associated with a strong increase in mortality risk. Consequently, the effect of the current FI decreased considerably and became statistically non-significant.CONCLUSIONSThe rate of FI change was more important than the current FI level for short-term mortality prediction among the oldest old, which highlights the benefits of regular frailty assessments.
Presaccadic attention enhances contrast sensitivity, but not at the upper vertical meridian
Authors: Hanning Nina M. , Himmelberg Marc M. , Carrasco Marisa 
Published: October 2021

AbstractHuman visual performance is not only better at the fovea and decreases with eccentricity, but also has striking radial asymmetries around the visual field: At a fixed eccentricity, it is better along (1) the horizontal than vertical meridian and (2) the lower than upper vertical meridian. These asymmetries are not alleviated by covert exogenous or endogenous attention, but have been studied exclusively during eye fixation. However, a major driver of everyday attentional orienting is saccade preparation, during which visual attention automatically shifts to the future eye fixation. This presaccadic shift of attention is considered strong and compulsory, and relies on fundamentally different neural computations and substrates than covert attention. Given these differences, we investigated whether presaccadic attention can compensate for the ubiquitous performance asymmetries observed during eye fixation. Our data replicate polar performance asymmetries during fixation and document the same asymmetries during saccade preparation. Crucially, however, presaccadic attention enhanced contrast sensitivity at the horizontal and lower vertical meridian, but not at the upper vertical meridian. Thus, instead of attenuating polar performance asymmetries, presaccadic attention exacerbates them.
Collagen Pre-strain Discontinuity at the Cartilage - Bone Interface
Authors: Badar Waqas , Ali Husna , Brooker Olivia N , Newham E. , Snow Tim , Terrill Nicholas J , Tozzi Gianluca , Fratzl Peter , Knight Martin M , Gupta Himadri S 
Published: October 2021

AbstractThe bone-cartilage unit (BCU) is a universal feature in diarthrodial joints, which is mechanically-graded and subjected to shear and compressive strains. Changes in the BCU have been linked to osteoarthritis progression. Here we report existence of a physiological internal strain gradient (pre-strain) across the BCU at the ultrastructural scale of the extracellular matrix constituents, specifically the collagen fibril. We use X-ray scattering that probes changes in the axial periodicity of fibril-level D-stagger of tropocollagen molecules in the matrix fibrils, as a measure of microscopic pre-strain. We find that mineralized collagen nanofibrils in the calcified plate are in tensile pre-strain relative to the underlying trabecular bone. This behaviour contrasts with the previously accepted notion that fibrillar pre-strain (or D-stagger) in collagenous tissues always reduces with mineralization, via reduced hydration and associated swelling pressure. Within the calcified part of the BCU, a finer-scale gradient in pre-strain (0.6% increase over ∼50μm) is observed. The increased fibrillar pre-strain is linked to prior research reporting large tissue-level residual strains under compression. The findings may have biomechanical adaptative significance: higher in-built molecular level resilience/damage resistance to physiological compression, and disruption of the molecular-level pre-strains during remodelling of the BCI may be potential factors in osteoarthritis-based degeneration.
Brain stimulation competes with ongoing oscillations for control of spike timing in the primate brain
Authors: Krause Matthew R. , Vieira Pedro G. , Thivierge Jean-Philippe , Pack Christopher C. 
Published: October 2021

AbstractTranscranial alternating current stimulation (tACS) is commonly used to enhance brain rhythms, in the hopes of improving behavioral performance. Unfortunately, these interventions often yield highly variable results. Here, we identify a key source of this variability by recording from single neurons in alert non-human primates. We find that, rather than enhancing rhythmic activity, tACS appears to compete with the brain’s endogenous oscillations for control of spike timing. Specifically, when the strength of stimulation is weak relative to endogenous oscillations, tACS actually decreases the rhythmicity of spiking. However, when stimulation is comparatively stronger, tACS imposes its own rhythm on spiking activity. Thus the effect of tACS depends categorically on the strength of neural entrainment to endogenous oscillations, which varies greatly across behavioral states and brain regions. Without carefully considering these factors, attempts to impose external rhythms on specific brain regions may often yield precisely the opposite of the intended effect.
Topographic connectivity and cellular profiling reveal detailed input pathways and functionally distinct cell types in the subthalamic nucleus
Authors: Jeon Hyungju , Lee Hojin , Kwon Dae-Hyuk , Kim Jiwon , Tanaka-Yamamoto Keiko , Feng Linqing , Park Hyeran , Lim Yong Hoon , Cho Zang-Hee , Paek Sun Ha , Kim Jinhyun 
Published: October 2021

SummaryThe subthalamic nucleus (STN) controls psychomotor activity and is an efficient therapeutic deep brain stimulation target in Parkinson’s disease patients. Despite evidence indicating position-dependent therapeutic effects and distinct functions within the STN, input circuit and cellular profile in the STN remain largely unclear. Using advanced neuroanatomical techniques, we constructed a comprehensive connectivity map of the indirect and hyperdirect pathways in both the mouse and human STN. Our detailed circuit- and cellular-level connectivity revealed a topographically graded organization with three convergent types of indirect and hyperdirect-pathways. Furthermore, we identified two functional types of glutamatergic STN neurons (parvalbumin, PV +/- neurons) segregated with a topographical distribution. Glutamatergic PV+ STN neurons contribute to burst firing. We confirmed synaptic connectivity from indirect and hyperdirect pathways to both PV+ and PV-. These data suggest a complex interplay of information integration within the basal ganglia underlying coordinated movement control and therapeutic effects.
Characterization of Cell-Induced Astigmatism in High-Resolution Imaging
Authors: de Mercado Rick Rodrigues , van Hoorn Hedde , de Valois Martin , Backendorf Claude , Eckert Julia , Schmidt Thomas 
Published: October 2021

AbstractHigh-resolution and super-resolution techniques become more frequently used in thick, inhomogeneous samples. In particular for imaging life cells and tissue in which one wishes to observe a biological process at minimal interference and in the natural environment, sample inhomogeneities are unavoidable. Yet sample-inhomogeneities are paralleled by refractive index variations, for example between the cell organelles and the surrounding medium, that will result in the refraction of light, and therefore lead to sample-induced astigmatism. Astigmatism in turn will result in positional inaccuracies of observations that are at the heart of all super-resolution techniques. Here we introduce a simple model and define a figure-of-merit that allows one to quickly assess the importance of astigmatism for a given experimental setting. We found that astigmatism caused by the cell’s nucleus can easily lead to aberrations up to hundreds of nanometers, well beyond the accuracy of all super-resolution techniques. The astigmatism generated by small objects, like bacteria or vesicles, appear to be small enough to be of any significance in typical super-resolution experimentation.
Encounter networks from collective mitochondrial dynamics support the emergence of effective mtDNA genomes in plant cells
Authors: Giannakis Konstantinos , Chustecki Joanna M. , Johnston Iain G. 
Published: October 2021

AbstractMitochondria in plant cells form strikingly dynamic populations of largely individual organelles. Each mitochondrion contains on average less than a full copy of the mitochondrial DNA (mtDNA) genome. Here, we asked whether mitochondrial dynamics may allow individual mitochondria to ‘collect’ a full copy of the mtDNA genome over time, by facilitating exchange between individuals. Akin to trade on a social network, exchange of mtDNA fragments across organelles may lead to the emergence of full ‘effective’ genomes in individuals over time. We characterise the collective dynamics of mitochondria in Arabidopsis thaliana hypocotyl cells using a recent approach combining single-cell timelapse microscopy, video analysis, and network science. We then use a quantitative model to predict the capacity for the sharing and accumulation of genetic information through the networks of encounters between mitochondria. We find that biological encounter networks are strikingly well predisposed to support the collection of full genomes over time, outperforming a range of other networks generated from theory and simulation. Using results from the coupon collector’s problem, we show that the upper tail of the degree distribution is a key determinant of an encounter network’s performance at this task and discuss how features of mitochondrial dynamics observed in biology facilitate the emergence of full effective genomes.
Host phylogeny and ecological associations best explainWolbachiahost shifts in scale insects
Authors: Sanaei Ehsan , Albery Gregory F , Yeoh Yun Kit , Lin Yen-Po , Cook Lyn G , Engelstädter Jan 
Published: October 2021

AbstractWolbachiaare among the most prevalent and widespread endosymbiotic bacteria on earth.Wolbachia’ s success in infecting an enormous number of arthropod species is attributed to two features: the range of phenotypes they induce in their hosts, and their ability to switch to new host species. Whilst much progress has been made in elucidating the phenotypes induced byWolbachia, our understanding ofWolbachiahost shifting is still very limited: we lack answers to even fundamental questions concerningWolbachia’s routes of transfer and the importance of factors influencing host shifts. Here, we investigate the diversity and host-shift patterns ofWolbachiain scale insects, a group of arthropods with intimate associations with other insects that make them well-suited to studying host shifts. Using Illumina pooled amplicon sequencing ofWolbachia-infected scale insects and their direct associates we determined the identity of allWolbachiastrains, revealing that 32% of samples were multiply infected (with up to five distinct strains per species). We then fitted a Generalised Additive Mixed Model (GAMM) to our data to estimate the influence of factors such as the host phylogeny and the geographic distribution of each species onWolbachiastrain sharing among scale insect species. The model predicts no significant contribution of host geography but strong effects of host phylogeny, with high rates ofWolbachiasharing among closely related species and a sudden drop-off in sharing with increasing phylogenetic distance. We also detected the sameWolbachiastrain in scale insects and several intimately associated species (ants, wasps, beetles, and flies). This indicates putative host shifts and potential routes of transfers via these associates and highlights the importance of ecological connectivity inWolbachiahost-shifting.
Polyamine elevation and nitrogen stress are toxic hallmarks of chronic sleep loss in Drosophila melanogaster
Authors: Bedont Joseph , Kolesnik Anna , Malik Dania , Weljie Aalim , Sehgal Amita 
Published: October 2021

AbstractChronic sleep loss profoundly impacts health in ways coupled to metabolism; however, much existing literature links sleep and metabolism only on acute timescales. To explore the impact of chronically reduced sleep, we conducted unbiased metabolomics on heads from three Drosophila short-sleeping mutants. Common features included elevated ornithine and polyamines; and lipid, acyl-carnitine, and TCA cycle changes suggesting mitochondrial dysfunction. Biochemical studies of overall, circulating, and excreted nitrogen in sleep mutants demonstrate a specific defect in eliminating nitrogen, suggesting that elevated polyamines may function as a nitrogen sink. Both supplementing polyamines and inhibiting their synthesis with RNAi regulated sleep in control flies. Finally, both polyamine-supplemented food and high-protein feeding were highly toxic to sleep mutants, suggesting their altered nitrogen metabolism is maladaptive. Together, our results suggest polyamine accumulation specifically, and nitrogen stress in general, as potential mechanisms linking chronic sleep loss to adverse health outcomes.