bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of the ketogenic diet on glycemic control, insulin resistance, and lipid metabolism in patients with T2DM: a systematic review and meta-analysis
Authors: Yuan Xiaojie , Wang Jiping , Yang Shuo , Gao Mei , Cao Lingxia , Li Xumei , Hong Dongxu , Tian Suyan , Sun Chenglin 
Published: November 2020

Abstract
Background
At present, the beneficial effect of the ketogenic diet (KD) on weight loss in obese patients is generally recognized. However, a systematic research on the role of KD in the improvement of glycemic and lipid metabolism of patients with diabetes is still found scarce.

Methods
This meta-study employed the meta-analysis model of random effects or of fixed effects to analyze the average difference before and after KD and the corresponding 95% CI, thereby evaluating the effect of KD on T2DM.

Results
After KD intervention, in terms of glycemic control, the level of fasting blood glucose decreased by 1.29 mmol/L (95% CI: −1.78 to −0.79) on average, and glycated hemoglobin A1c by 1.07 (95% CI: −1.37 to −0.78). As for lipid metabolism, triglyceride was decreased by 0.72 (95% CI: −1.01 to −0.43) on average, total cholesterol by 0.33 (95% CI: −0.66 to −0.01), and low-density lipoprotein by 0.05 (95% CI: −0.25 to −0.15); yet, high-density lipoprotein increased by 0.14 (95% CI: 0.03−0.25). In addition, patients’ weight decreased by 8.66 (95% CI: −11.40 to −5.92), waist circumference by 9.17 (95% CI: −10.67 to −7.66), and BMI by 3.13 (95% CI: −3.31 to −2.95).

Conclusion
KD not only has a therapeutic effect on glycemic and lipid control among patients with T2DM but also significantly contributes to their weight loss.
Prohibitin, STAT3 and SH2D4A physically and functionally interact in tumor cell mitochondria
Authors: Ploeger Carolin , Huth Thorben , Sugiyanto Raisatun Nisa , Pusch Stefan , Goeppert Benjamin , Singer Stephan , Tabti Redouane , Hausser Ingrid , Schirmacher Peter , Désaubry Laurent , Roessler Stephanie 
Published: November 2020

AbstractChromosome 8p is frequently deleted in various cancer entities and has been shown to correlate with poor patient survival. SH2D4A is located on chromosome 8p and prevents the nuclear translocation of the pro-tumorigenic transcription factor STAT3. Here, we investigated the interaction of SH2D4A and STAT3 to shed light on the non-canonical functions of STAT3 in cooperation with the tumor suppressor SH2D4A. Using an immunoprecipitation-mass spectrometry (IP-MS) approach, we identified the mitochondrial scaffold proteins prohibitin 1 (PHB1) and prohibitin 2 (PHB2) among other proteins to potentially bind to SH2D4A. Co-immunoprecipitation and proximity ligation assays confirmed direct interactions of STAT3, PHB1, and SH2D4A in situ and in vitro. In addition, cell fractionation and immunofluorescence staining revealed co-localization of these proteins with mitochondria. These interactions were selectively interrupted by the small molecule and PHB ligand FL3. Furthermore, FL3 led to a reduction of STAT3 protein levels, STAT3 transcriptional activity, and HIF1α protein stabilization upon dimethyloxalylglycine (DMOG) treatment. Besides, mitochondrial fusion and fission markers, L-OPA1, Mfn1, and FIS1, were dysregulated upon FL3 treatment. This dysregulated morphology was accompanied by significant reduction of mitochondrial respiration, thus, FL3 significantly diminished mitochondrial respirational capacity. In contrast, SH2D4A knockout increased mitochondrial respiration, whereas FL3 reversed the effect of SH2D4A knockout. The here described results indicate that the interaction of SH2D4A and PHB1 is involved in the mitochondrial function and integrity. The demonstrated interaction with STAT3, accompanied by its reduction of transcriptional activity, further suggests that SH2D4A is linking STAT3 to its mitochondrial functions, and inhibition of PHB-interaction may have therapeutic effects in tumor cells with STAT3 activation.
The armed oncolytic adenovirus ZD55-IL-24 eradicates melanoma by turning the tumor cells from the self-state into the nonself-state besides direct killing
Authors: Hu Hai-Jun , Liang Xiu , Li Hai-Lang , Du Chun-Ming , Hao Jia-Li , Wang Huai-Yuan , Gu Jin-Fa , Ni Ai-Min , Sun Lan-Ying , Xiao Jing , Hu Jin-Qing , Yuan Hao , Dai Yan-Song , Jin Xiao-Ting , Zhang Kang-Jian , Liu Xin-Yuan 
Published: November 2020

AbstractZD55-IL-24 is similar but superior to the oncolytic adenovirus ONYX-015, yet the exact mechanism underlying the observed therapeutic effect is still not well understood. Here we sought to elucidate the underlying antitumor mechanism of ZD55-IL-24 in both immunocompetent and immunocompromised mouse model. We find that ZD55-IL-24 eradicates established melanoma in B16-bearing immunocompetent mouse model not through the classic direct killing pathway, but mainly through the indirect pathway of inducing systemic antitumor immunity. Inconsistent with the current prevailing view, our further results suggest that ZD55-IL-24 can induce antitumor immunity in B16-bearing immunocompetent mouse model in fact not due to its ability to lyse tumor cells and release the essential elements, such as tumor-associated antigens (TAAs), but due to its ability to put a “nonself” label in tumor cells and then turn the tumor cells from the “self” state into the “nonself” state without tumor cell death. The observed anti-melanoma efficacy of ZD55-IL-24 in B16-bearing immunocompetent mouse model was practically caused only by the viral vector. In addition, we also notice that ZD55-IL-24 can inhibit tumor growth in B16-bearing immunocompetent mouse model through inhibiting angiogenesis, despite it plays only a minor role. In contrast to B16-bearing immunocompetent mouse model, ZD55-IL-24 eliminates established melanoma in A375-bearing immunocompromised mouse model mainly through the classic direct killing pathway, but not through the antitumor immunity pathway and anti-angiogenesis pathway. These findings let us know ZD55-IL-24 more comprehensive and profound, and provide a sounder theoretical foundation for its future modification and drug development.
Identity-by-descent detection across 487,409 British samples reveals fine scale population structure and ultra-rare variant associations
Authors: Nait Saada Juba , Kalantzis Georgios , Shyr Derek , Cooper Fergus , Robinson Martin , Gusev Alexander , Palamara Pier Francesco 
Published: November 2020

AbstractDetection of Identical-By-Descent (IBD) segments provides a fundamental measure of genetic relatedness and plays a key role in a wide range of analyses. We develop FastSMC, an IBD detection algorithm that combines a fast heuristic search with accurate coalescent-based likelihood calculations. FastSMC enables biobank-scale detection and dating of IBD segments within several thousands of years in the past. We apply FastSMC to 487,409 UK Biobank samples and detect ~214 billion IBD segments transmitted by shared ancestors within the past 1500 years, obtaining a fine-grained picture of genetic relatedness in the UK. Sharing of common ancestors strongly correlates with geographic distance, enabling the use of genomic data to localize a sample’s birth coordinates with a median error of 45 km. We seek evidence of recent positive selection by identifying loci with unusually strong shared ancestry and detect 12 genome-wide significant signals. We devise an IBD-based test for association between phenotype and ultra-rare loss-of-function variation, identifying 29 association signals in 7 blood-related traits.
Quantitative estimates of average geomagnetic axial dipole dominance in deep geological time
Authors: Biggin Andrew J. , Bono Richard K. , Meduri Domenico G. , Sprain Courtney J. , Davies Christopher J. , Holme Richard , Doubrovine Pavel V. 
Published: November 2020

AbstractA defining characteristic of the recent geomagnetic field is its dominant axial dipole which provides its navigational utility and dictates the shape of the magnetosphere. Going back through time, much less is known about the degree of axial dipole dominance. Here we use a substantial and diverse set of 3D numerical dynamo simulations and recent observation-based field models to derive a power law relationship between the angular dispersion of virtual geomagnetic poles at the equator and the median axial dipole dominance measured at Earth’s surface. Applying this relation to published estimates of equatorial angular dispersion implies that geomagnetic axial dipole dominance averaged over 107–109 years has remained moderately high and stable through large parts of geological time. This provides an observational constraint to future studies of the geodynamo and palaeomagnetosphere. It also provides some reassurance as to the reliability of palaeogeographical reconstructions provided by palaeomagnetism.
Perceptually unidentifiable stimuli influence cortical processing and behavioral performance
Authors: Pojoga Sorin A. , Kharas Natasha , Dragoi Valentin 
Published: November 2020

AbstractOur daily behavior is dynamically influenced by conscious and unconscious processes. Although the neural bases of conscious experience have been extensively investigated over the past several decades, how unconscious information impacts neural circuitry and behavior remains unknown. Here, we recorded populations of neurons in macaque primary visual cortex (V1) to find that perceptually unidentifiable stimuli repeatedly presented in the absence of awareness are encoded by neural populations in a way that facilitates their future processing in the context of a behavioral task. Such exposure increases stimulus sensitivity and information encoded in cell populations, even though animals are unaware of stimulus identity. This phenomenon is consistent with a Hebbian mechanism underlying an increase in functional connectivity specifically for the neurons activated by subthreshold stimuli. This form of unsupervised adaptation may constitute a vestigial pre-attention system using the mere frequency of stimulus occurrence to change stimulus representations even when sensory inputs are perceptually invisible.
Light-driven formation of manganese oxide by today’s photosystem II supports evolutionarily ancient manganese-oxidizing photosynthesis
Authors: Chernev Petko , Fischer Sophie , Hoffmann Jutta , Oliver Nicholas , Assunção Ricardo , Yu Boram , Burnap Robert L. , Zaharieva Ivelina , Nürnberg Dennis J. , Haumann Michael , Dau Holger 
Published: November 2020

AbstractWater oxidation and concomitant dioxygen formation by the manganese-calcium cluster of oxygenic photosynthesis has shaped the biosphere, atmosphere, and geosphere. It has been hypothesized that at an early stage of evolution, before photosynthetic water oxidation became prominent, light-driven formation of manganese oxides from dissolved Mn(2+) ions may have played a key role in bioenergetics and possibly facilitated early geological manganese deposits. Here we report the biochemical evidence for the ability of photosystems to form extended manganese oxide particles. The photochemical redox processes in spinach photosystem-II particles devoid of the manganese-calcium cluster are tracked by visible-light and X-ray spectroscopy. Oxidation of dissolved manganese ions results in high-valent Mn(III,IV)-oxide nanoparticles of the birnessite type bound to photosystem II, with 50-100 manganese ions per photosystem. Having shown that even today’s photosystem II can form birnessite-type oxide particles efficiently, we propose an evolutionary scenario, which involves manganese-oxide production by ancestral photosystems, later followed by down-sizing of protein-bound manganese-oxide nanoparticles to finally yield today’s catalyst of photosynthetic water oxidation.
How to speed up ion transport in nanopores
Authors: Breitsprecher Konrad , Janssen Mathijs , Srimuk Pattarachai , Mehdi B. Layla , Presser Volker , Holm Christian , Kondrat Svyatoslav 
Published: November 2020

AbstractElectrolyte-filled subnanometre pores exhibit exciting physics and play an increasingly important role in science and technology. In supercapacitors, for instance, ultranarrow pores provide excellent capacitive characteristics. However, ions experience difficulties in entering and leaving such pores, which slows down charging and discharging processes. In an earlier work we showed for a simple model that a slow voltage sweep charges ultranarrow pores quicker than an abrupt voltage step. A slowly applied voltage avoids ionic clogging and co-ion trapping—a problem known to occur when the applied potential is varied too quickly—causing sluggish dynamics. Herein, we verify this finding experimentally. Guided by theoretical considerations, we also develop a non-linear voltage sweep and demonstrate, with molecular dynamics simulations, that it can charge a nanopore even faster than the corresponding optimized linear sweep. For discharging we find, with simulations and in experiments, that if we reverse the applied potential and then sweep it to zero, the pores lose their charge much quicker than they do for a short-circuited discharge over their internal resistance. Our findings open up opportunities to greatly accelerate charging and discharging of subnanometre pores without compromising the capacitive characteristics, improving their importance for energy storage, capacitive deionization, and electrochemical heat harvesting.
Chronic neuronal activation increases dynamic microtubules to enhance functional axon regeneration after dorsal root crush injury
Authors: Wu Di , Jin Ying , Shapiro Tatiana M. , Hinduja Abhishek , Baas Peter W. , Tom Veronica J. 
Published: November 2020

AbstractAfter a dorsal root crush injury, centrally-projecting sensory axons fail to regenerate across the dorsal root entry zone (DREZ) to extend into the spinal cord. We find that chemogenetic activation of adult dorsal root ganglion (DRG) neurons improves axon growth on an in vitro model of the inhibitory environment after injury. Moreover, repeated bouts of daily chemogenetic activation of adult DRG neurons for 12 weeks post-crush in vivo enhances axon regeneration across a chondroitinase-digested DREZ into spinal gray matter, where the regenerating axons form functional synapses and mediate behavioral recovery in a sensorimotor task. Neuronal activation-mediated axon extension is dependent upon changes in the status of tubulin post-translational modifications indicative of highly dynamic microtubules (as opposed to stable microtubules) within the distal axon, illuminating a novel mechanism underlying stimulation-mediated axon growth. We have identified an effective combinatory strategy to promote functionally-relevant axon regeneration of adult neurons into the CNS after injury.
Spatially expandable fiber-based probes as a multifunctional deep brain interface
Authors: Jiang Shan , Patel Dipan C. , Kim Jongwoon , Yang Shuo , Mills William A. , Zhang Yujing , Wang Kaiwen , Feng Ziang , Vijayan Sujith , Cai Wenjun , Wang Anbo , Guo Yuanyuan , Kimbrough Ian F. , Sontheimer Harald , Jia Xiaoting 
Published: November 2020

AbstractUnderstanding the cytoarchitecture and wiring of the brain requires improved methods to record and stimulate large groups of neurons with cellular specificity. This requires miniaturized neural interfaces that integrate into brain tissue without altering its properties. Existing neural interface technologies have been shown to provide high-resolution electrophysiological recording with high signal-to-noise ratio. However, with single implantation, the physical properties of these devices limit their access to one, small brain region. To overcome this limitation, we developed a platform that provides three-dimensional coverage of brain tissue through multisite multifunctional fiber-based neural probes guided in a helical scaffold. Chronic recordings from the spatially expandable fiber probes demonstrate the ability of these fiber probes capturing brain activities with a single-unit resolution for long observation times. Furthermore, using Thy1-ChR2-YFP mice we demonstrate the application of our probes in simultaneous recording and optical/chemical modulation of brain activities across distant regions. Similarly, varying electrographic brain activities from different brain regions were detected by our customizable probes in a mouse model of epilepsy, suggesting the potential of using these probes for the investigation of brain disorders such as epilepsy. Ultimately, this technique enables three-dimensional manipulation and mapping of brain activities across distant regions in the deep brain with minimal tissue damage, which can bring new insights for deciphering complex brain functions and dynamics in the near future.
Genomic and transcriptomic alterations associated with drug vulnerabilities and prognosis in adenocarcinoma at the gastroesophageal junction
Authors: Lin Yuan , Luo Yingying , Sun Yanxia , Guo Wenjia , Zhao Xuan , Xi Yiyi , Ma Yuling , Shao Mingming , Tan Wen , Gao Ge , Wu Chen , Lin Dongxin 
Published: November 2020

AbstractAdenocarcinoma at the gastroesophageal junction (ACGEJ) has dismal clinical outcomes, and there are currently few specific effective therapies because of limited knowledge on its genomic and transcriptomic alterations. The present study investigates genomic and transcriptomic changes in ACGEJ from Chinese patients and analyzes their drug vulnerabilities and associations with the survival time. Here we show that the major genomic changes of Chinese ACGEJ patients are chromosome instability promoted tumorigenic focal copy-number variations and COSMIC Signature 17-featured single nucleotide variations. We provide a comprehensive profile of genetic changes that are potentially vulnerable to existing therapeutic agents and identify Signature 17-correlated IFN-α response pathway as a prognostic marker that might have practical value for clinical prognosis of ACGEJ. These findings further our understanding on the molecular biology of ACGEJ and may help develop more effective therapeutic strategies.
Bedaquiline reprograms central metabolism to reveal glycolytic vulnerability in Mycobacterium tuberculosis
Authors: Mackenzie Jared S. , Lamprecht Dirk A. , Asmal Rukaya , Adamson John H. , Borah Khushboo , Beste Dany J. V. , Lee Bei Shi , Pethe Kevin , Rousseau Simon , Krieger Inna , Sacchettini James C. , Glasgow Joel N. , Steyn Adrie J. C. 
Published: November 2020

AbstractThe approval of bedaquiline (BDQ) for the treatment of tuberculosis has generated substantial interest in inhibiting energy metabolism as a therapeutic paradigm. However, it is not known precisely how BDQ triggers cell death in Mycobacterium tuberculosis (Mtb). Using 13C isotopomer analysis, we show that BDQ-treated Mtb redirects central carbon metabolism to induce a metabolically vulnerable state susceptible to genetic disruption of glycolysis and gluconeogenesis. Metabolic flux profiles indicate that BDQ-treated Mtb is dependent on glycolysis for ATP production, operates a bifurcated TCA cycle by increasing flux through the glyoxylate shunt, and requires enzymes of the anaplerotic node and methylcitrate cycle. Targeting oxidative phosphorylation (OXPHOS) with BDQ and simultaneously inhibiting substrate level phosphorylation via genetic disruption of glycolysis leads to rapid sterilization. Our findings provide insight into the metabolic mechanism of BDQ-induced cell death and establish a paradigm for the development of combination therapies that target OXPHOS and glycolysis.
Sound generation in zebrafish with Bio-Opto-Acoustics
Authors: Favre-Bulle Itia A. , Taylor Michael A. , Marquez-Legorreta Emmanuel , Vanwalleghem Gilles , Poulsen Rebecca E. , Rubinsztein-Dunlop Halina , Scott Ethan K. 
Published: November 2020

AbstractHearing is a crucial sense in underwater environments for communication, hunting, attracting mates, and detecting predators. However, the tools currently used to study hearing are limited, as they cannot controllably stimulate specific parts of the auditory system. To date, the contributions of hearing organs have been identified through lesion experiments that inactivate an organ, making it difficult to gauge the specific stimuli to which each organ is sensitive, or the ways in which inputs from multiple organs are combined during perception. Here, we introduce Bio-Opto-Acoustic (BOA) stimulation, using optical forces to generate localized vibrations in vivo, and demonstrate stimulation of the auditory system of zebrafish larvae with precise control. We use a rapidly oscillated optical trap to generate vibrations in individual otolith organs that are perceived as sound, while adjacent otoliths are either left unstimulated or similarly stimulated with a second optical laser trap. The resulting brain-wide neural activity is characterized using fluorescent calcium indicators, thus linking each otolith organ to its individual neuronal network in a way that would be impossible using traditional sound delivery methods. The results reveal integration and cooperation of the utricular and saccular otoliths, which were previously described as having separate biological functions, during hearing.
ELISA detection of SARS-CoV-2 antibodies in saliva
Authors: MacMullan Melanie A. , Ibrayeva Albina , Trettner Kylie , Deming Laura , Das Sudipta , Tran Frances , Moreno Jose Ricardo , Casian Joseph G. , Chellamuthu Prithivi , Kraft Jeffrey , Kozak Kenneth , Turner Fred E. , Slepnev Vladimir I. , Le Page Lydia M. 
Published: November 2020

AbstractTo facilitate containment of the COVID-19 pandemic currently active in the United States and across the world, options for easy, non-invasive antibody testing are required. Here we have adapted a commercially available, serum-based enzyme-linked immunosorbent assay (ELISA) for use with saliva samples, achieving 84.2% sensitivity and 100% specificity in a set of 149 clinical samples. This strategy will enable widespread, affordable testing for patients who experienced this disease, whilst minimizing exposure risk for healthcare workers.
Human proximity seeking in family pigs and dogs
Authors: Pérez Fraga Paula , Gerencsér Linda , Andics Attila 
Published: November 2020

Abstract Family dogs (Canis familiaris) seek human contact from an early age, can discriminate and prefer their caregivers over other humans. To investigate if being kept as a family animal is sufficient to induce similar early human proximity-seeking in another domestic mammal, here we directly compared such behaviours in dogs and similarly raised domestic pigs (Sus scrofa domesticus). We used a preference test to measure proximity-seeking behaviours of 4-month-old family pigs and dogs in the presence of their caregiver and either a stranger or a familiar object, in a novel environment. We found that both pigs and dogs preferred their caregivers over the familiar object but not over the stranger. However, when the caregiver and the stranger were present, only dogs showed an overall preference for human proximity, and pigs spent more time away from both humans. These results suggest that both dogs and pigs seek the proximity of their caregiver, but there is a difference in how each species generalizes their experience to other humans. Species-specific predispositions, including that dogs have a longer socialization period and that humans are more salient as a social stimulus for them, may be important for the early development of an overall preference for humans.