bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reconstruct high-resolution 3D genome structures for diverse cell-types using FLAMINGO
Authors: Wang Hao , Yang Jiaxin , Zhang Yu , Qian Jianliang , Wang Jianrong 
Published: May 2022

AbstractHigh-resolution reconstruction of spatial chromosome organizations from chromatin contact maps is highly demanded, but is hindered by extensive pairwise constraints, substantial missing data, and limited resolution and cell-type availabilities. Here, we present FLAMINGO, a computational method that addresses these challenges by compressing inter-dependent Hi-C interactions to delineate the underlying low-rank structures in 3D space, based on the low-rank matrix completion technique. FLAMINGO successfully generates 5 kb- and 1 kb-resolution spatial conformations for all chromosomes in the human genome across multiple cell-types, the largest resources to date. Compared to other methods using various experimental metrics, FLAMINGO consistently demonstrates superior accuracy in recapitulating observed structures with raises in scalability by orders of magnitude. The reconstructed 3D structures efficiently facilitate discoveries of higher-order multi-way interactions, imply biological interpretations of long-range QTLs, reveal geometrical properties of chromatin, and provide high-resolution references to understand structural variabilities. Importantly, FLAMINGO achieves robust predictions against high rates of missing data and significantly boosts 3D structure resolutions. Moreover, FLAMINGO shows vigorous cross cell-type structure predictions that capture cell-type specific spatial configurations via integration of 1D epigenomic signals. FLAMINGO can be widely applied to large-scale chromatin contact maps and expand high-resolution spatial genome conformations for diverse cell-types.
Molecular basis for inhibiting human glucose transporters by exofacial inhibitors
Authors: Wang Nan , Zhang Shuo , Yuan Yafei , Xu Hanwen , Defossa Elisabeth , Matter Hans , Besenius Melissa , Derdau Volker , Dreyer Matthias , Halland Nis , He Kaihui Hu , Petry Stefan , Podeschwa Michael , Tennagels Norbert , Jiang Xin , Yan Nieng 
Published: May 2022

AbstractHuman glucose transporters (GLUTs) are responsible for cellular uptake of hexoses. Elevated expression of GLUTs, particularly GLUT1 and GLUT3, is required to fuel the hyperproliferation of cancer cells, making GLUT inhibitors potential anticancer therapeutics. Meanwhile, GLUT inhibitor-conjugated insulin is being explored to mitigate the hypoglycemia side effect of insulin therapy in type 1 diabetes. Reasoning that exofacial inhibitors of GLUT1/3 may be favored for therapeutic applications, we report here the engineering of a GLUT3 variant, designated GLUT3exo, that can be probed for screening and validating exofacial inhibitors. We identify an exofacial GLUT3 inhibitor SA47 and elucidate its mode of action by a 2.3 Å resolution crystal structure of SA47-bound GLUT3. Our studies serve as a framework for the discovery of GLUTs exofacial inhibitors for therapeutic development.
Genomic diversity across the Rickettsia and ‘Candidatus Megaira’ genera and proposal of genus status for the Torix group
Authors: Davison Helen R. , Pilgrim Jack , Wybouw Nicky , Parker Joseph , Pirro Stacy , Hunter-Barnett Simon , Campbell Paul M. , Blow Frances , Darby Alistair C. , Hurst Gregory D. D. , Siozios Stefanos 
Published: May 2022

AbstractMembers of the bacterial genusRickettsiawere originally identified as causative agents of vector-borne diseases in mammals. However, manyRickettsiaspecies are arthropod symbionts and close relatives of ‘CandidatusMegaira’, which are symbiotic associates of microeukaryotes. Here, we clarify the evolutionary relationships between these organisms by assembling 26 genomes ofRickettsiaspecies from understudied groups, including the Torix group, and two genomes of ‘Ca. Megaira’ from various insects and microeukaryotes. Our analyses of the new genomes, in comparison with previously described ones, indicate that the accessory genome diversity and broad host range of TorixRickettsiaare comparable to those of all otherRickettsiacombined. Therefore, the Torix clade may play unrecognized roles in invertebrate biology and physiology. We argue this clade should be given its own genus status, for which we propose the name ‘CandidatusTisiphia’.
Epicardium-derived cells organize through tight junctions to replenish cardiac muscle in salamanders
Authors: Eroglu Elif , Yen Christopher Y. T. , Tsoi Yat-Long , Witman Nevin , Elewa Ahmed , Joven Araus Alberto , Wang Heng , Szattler Tamara , Umeano Chimezie H. , Sohlmér Jesper , Goedel Alexander , Simon András , Chien Kenneth R. 
Published: May 2022

AbstractThe contribution of the epicardium, the outermost layer of the heart, to cardiac regeneration has remained controversial due to a lack of suitable analytical tools. By combining genetic marker-independent lineage-tracing strategies with transcriptional profiling and loss-of-function methods, we report here that the epicardium of the highly regenerative salamander species Pleurodeles waltl has an intrinsic capacity to differentiate into cardiomyocytes. Following cryoinjury, CLDN6+ epicardium-derived cells appear at the lesion site, organize into honeycomb-like structures connected via focal tight junctions and undergo transcriptional reprogramming that results in concomitant differentiation into de novo cardiomyocytes. Ablation of CLDN6+ differentiation intermediates as well as disruption of their tight junctions impairs cardiac regeneration. Salamanders constitute the evolutionarily closest species to mammals with an extensive ability to regenerate heart muscle and our results highlight the epicardium and tight junctions as key targets in efforts to promote cardiac regeneration.
Dorzagliatin add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 3 trial
Authors: Yang Wenying , Zhu Dalong , Gan Shenglian , Dong Xiaolin , Su Junping , Li Wenhui , Jiang Hongwei , Zhao Wenjuan , Yao Minxiu , Song Weihong , Lu Yibing , Zhang Xiuzhen , Li Huifang , Wang Guixia , Qiu Wei , Yuan Guoyue , Ma Jianhua , Li Wei , Li Ziling , Wang Xiaoyue , Zeng Jiao’e , Yang Zhou , Liu Jingdong , Liang Yongqian , Lu Song , Zhang Huili , Liu Hui , Liu Ping , Fan Kuanlu , Jiang Xiaozhen , Li Yufeng , Su Qing , Ning Tao , Tan Huiwen , An Zhenmei , Jiang Zhaoshun , Liu Lijun , Zhou Zunhai , Zhang Qiu , Li Xuefeng , Shan Zhongyan , Xue Yaoming , Mao Hong , Shi Lixin , Ye Shandong , Zhang Xiaomei , Sun Jiao , Li Ping , Yang Tao , Li Feng , Lin Jingna , Zhang Zhinong , Zhao Ying , Li Ruonan , Guo Xiaohui , Yao Qi , Lu Weiping , Qu Shen , Li Hongmei , Tan Liling , Wang Wenbo , Yao Yongli , Chen Daoxiong , Li Yulan , Gao Jialin , Hu Wen , Fei Xiaoqiang , Wu Tianfeng , Dong Song , Jin Wenlong , Li Chenzhong , Zhao Dong , Feng Bo , Zhao Yu , Zhang Yi , Li Xiaoying , Chen Li 
Published: May 2022

AbstractMetformin, the first-line therapy for type 2 diabetes (T2D), decreases hepatic glucose production and reduces fasting plasma glucose levels. Dorzagliatin, a dual-acting orally bioavailable glucokinase activator targeting both the pancreas and liver glucokinase, decreases postprandial glucose in patients with T2D. In this randomized, double-blind, placebo-controlled phase 3 trial, the efficacy and safety of dorzagliatin as an add-on therapy to metformin were assessed in patients with T2D who had inadequate glycemic control using metformin alone. Eligible patients with T2D (n = 767) were randomly assigned to receive dorzagliatin or placebo (1:1 ratio) as an add-on to metformin (1,500 mg per day) for 24 weeks of double-blind treatment, followed by 28 weeks of open-label treatment with dorzagliatin for all patients. The primary efficacy endpoint was the change in glycated hemoglobin (HbA1c) levels from baseline to week 24, and safety was assessed throughout the trial. At week 24, the least-squares mean change from baseline in HbA1c (95% confidence interval (CI)) was −1.02% (−1.11, −0.93) in the dorzagliatin group and −0.36% (−0.45, −0.26) in the placebo group (estimated treatment difference, −0.66%; 95% CI: −0.79, −0.53; P < 0.0001). The incidence of adverse events was similar between groups. There were no severe hypoglycemia events or drug-related serious adverse events in the dorzagliatin and metformin combined therapy group. In patients with T2D who experienced inadequate glycemic control with metformin alone, dorzagliatin resulted in effective glycemic control with good tolerability and safety profile (NCT03141073).
Excitatory deep brain stimulation quenches beta oscillations arising in a computational model of the subthalamo-pallidal loop
Authors: Alavi Seyed Mojtaba , Mirzaei Amin , Valizadeh Alireza , Ebrahimpour Reza 
Published: May 2022

AbstractParkinson’s disease (PD) is associated with abnormal $$\beta$$
β
band oscillations (13–30 Hz) in the cortico-basal ganglia circuits. Abnormally increased striato-pallidal inhibition and strengthening the synaptic coupling between subthalamic nucleus (STN) and globus pallidus externa (GPe), due to the loss of dopamine, are considered as the potential sources of $$\beta$$
β
oscillations in the basal ganglia. Deep brain stimulation (DBS) of the basal ganglia subregions is known as a way to reduce the pathological $$\beta$$
β
oscillations and motor deficits related to PD. Despite the success of the DBS, its underlying mechanism is poorly understood and, there is controversy about the inhibitory or excitatory role of the DBS in the literature. Here, we utilized a computational network model of basal ganglia which consists of STN, GPe, globus pallidus interna, and thalamic neuronal population. This model can reproduce healthy and pathological $$\beta$$
β
oscillations similar to what has been observed in experimental studies. Using this model, we investigated the effect of DBS to understand whether its effect is excitatory or inhibitory. Our results show that the excitatory DBS is able to quench the pathological synchrony and $$\beta$$
β
oscillations, while, applying inhibitory DBS failed to quench the PD signs. In light of simulation results, we conclude that the effect of the DBS on its target is excitatory.
The impact of pitolisant, an H3 receptor antagonist/inverse agonist, on perirhinal cortex activity in individual neuron and neuronal population levels
Authors: Hirano Kyosuke , Morishita Yoshikazu , Minami Masabumi , Nomura Hiroshi 
Published: May 2022

AbstractHistamine is a neurotransmitter that modulates neuronal activity and regulates various brain functions. Histamine H3 receptor (H3R) antagonists/inverse agonists enhance its release in most brain regions, including the cerebral cortex, which improves learning and memory and exerts an antiepileptic effect. However, the mechanism underlying the effect of H3R antagonists/inverse agonists on cortical neuronal activity in vivo remains unclear. Here, we show the mechanism by which pitolisant, an H3R antagonist/inverse agonist, influenced perirhinal cortex (PRh) activity in individual neuron and neuronal population levels. We monitored neuronal activity in the PRh of freely moving mice using in vivo Ca2+ imaging through a miniaturized one-photon microscope. Pitolisant increased the activity of some PRh neurons while decreasing the activity of others without affecting the mean neuronal activity across neurons. Moreover, it increases neuron pairs with synchronous activity in excitatory-responsive neuronal populations. Furthermore, machine learning analysis revealed that pitolisant altered the neuronal population activity. The changes in the population activity were dependent on the neurons that were excited and inhibited by pitolisant treatment. These findings indicate that pitolisant influences the activity of a subset of PRh neurons by increasing the synchronous activity and modifying the population activity.
Electric field induced pure spin-photo current in zigzag stanene and germanene nanoribbons
Authors: Rahimi F. , Phirouznia A. 
Published: May 2022

AbstractThe spin-photo current in single layer stanene and germanene under a linearly polarized light is theoretically investigated based on the tight-binding Hamiltonian combined with the nonequilibrium Green’s function at room temperature. The results show that by considering the simultaneous effect of the linear illumination and a vertical external electric field without any magnetic exchange element, pure spin-photo current without charge current is generated in two-dimensional lattices with a large intrinsic spin–orbit coupling. The necessity of enhanced spin life-time for detection of spin polarization can be explained by spin-valley locking concept. Spin-valley locking arises in buckled two-dimensional materials as a result of the large spin–orbit coupling and electric-field reversible valley spin polarization. Equal absorption of the linearly illumination at both valleys with different spin polarization, leads to pure spin-photo current injection. In addition, an acceptable photoresponsivity has been reported in a broad range of photon energy. The numerical results indicate high quantum efficiency with a maximum of nearly 83% and 50% for stanene and germanene, respectively. This work may pave theoretical reference toward design of new spin-optoelectronic devices based on satanene and germanene junctions with high performance.
A biodegradable film based on cellulose and thiazolidine bearing UV shielding property
Authors: Baseer Rasha A. , Dacrory Sawsan , El Gendy Mohamed A. M. , Ewies Ewies F. , Kamel Samir 
Published: May 2022

AbstractThe current rationale is exploring new eco-friendly UV- shielding films based on cellulose and thiazolidine. Cellulose was oxidized to dialdehyde cellulose (DAC) and tricarboxy cellulose (TCC) by periodate and TEMPO/periodate/hypochlorite, respectively. While E-3-amino-5-(phenyldiazenyl)-2-thioxothiazolidin-4-one (TH) was synthesized by coupling diazonium salt with the 5-methylene of 2-thioxo-4-thiazolidinone. DAC was then coupled with TH via Schiff base reaction and incorporated onto TCC with different ratios to get UV-shielding films. 1HNMR, infrared spectroscopy (FTIR), and thermal gravimetric analysis (TGA) were used to investigate the chemical structure of the synthesized materials. In addition, the films' morphology, thermal, mechanical, and UV-shielding properties were investigated. The UV-shielding studies revealed that the film with 10% DAC-TH has 99.88, 99.99, and 96.19% UV-blocking (UVB), UV-absorbance (UVA), and Ultra-violet protection (UPF), respectively. Moreover, the prepared films demonstrated promising antimicrobial activity against Escherichia coli, S. aureus, P. aeruginosa, and Candida albicans. Finally, the prepared films showed no cytotoxic effects on normal human skin fibroblast's HFB-4 cell line.
Age-based spatial distribution of workers is resilient to worker loss in a subterranean termite
Authors: Lee Sang-Bin , Chouvenc Thomas , Mizumoto Nobuaki , Mullins Aaron , Su Nan-Yao 
Published: May 2022

AbstractElaborate task allocation is key to the ecological success of eusocial insects. Termite colonies are known for exhibiting age polyethism, with older instars more likely to depart the reproductive center to access food. However, it remains unknown how termites retain this spatial structure against external disturbances. Here we show that a subterranean termiteCoptotermes formosanusShiraki combines age polyethism and behavioral flexibility to maintain a constant worker proportion at the food area. Since this termite inhabits multiple wood pieces by connecting them through underground tunnels, disastrous colony splitting events can result in the loss of colony members. We simulated this via weekly removal of all individuals at the food area. Our results showed that termites maintained a worker proportion of ~ 20% at the food area regardless of changes in total colony size and demographic composition, where younger workers replaced food acquisition functions to maintain a constant worker proportion at the food area. Food consumption analysis revealed that the per-capita food consumption rate decreased with younger workers, but the colony did not compensate for the deficiency by increasing the proportion of workers at the feeding site. These results suggest that termite colonies prioritize risk management of colony fragmentation while maintaining suitable food acquisition efficiency with the next available workers in the colony, highlighting the importance of task allocation for colony resiliency under fluctuating environments.
Efficient deformation mechanisms enable invasive cancer cells to migrate faster in 3D collagen networks
Authors: Laforgue Laure , Fertin Arnold , Usson Yves , Verdier Claude , Laurent Valérie M. 
Published: May 2022

AbstractCancer cell migration is a widely studied topic but has been very often limited to two dimensional motion on various substrates. Indeed, less is known about cancer cell migration in 3D fibrous-extracellular matrix (ECM) including variations of the microenvironment. Here we used 3D time lapse imaging on a confocal microscope and a phase correlation method to follow fiber deformations, as well as cell morphology and live actin distribution during the migration of cancer cells. Different collagen concentrations together with three bladder cancer cell lines were used to investigate the role of the metastatic potential on 3D cell migration characteristics. We found that grade-3 cells (T24 and J82) are characterized by a great diversity of shapes in comparison with grade-2 cells (RT112). Moreover, grade-3 cells with the highest metastatic potential (J82) showed the highest values of migration speeds and diffusivities at low collagen concentration and the greatest sensitivity to collagen concentration. Our results also suggested that the small shape fluctuations of J82 cells are the signature of larger migration velocities. Moreover, the displacement fields generated by J82 cells showed significantly higher fiber displacements as compared to T24 and RT112 cells, regardless of collagen concentration. The analysis of cell movements enhanced the fact that bladder cancer cells were able to exhibit different phenotypes (mesenchymal, amoeboid). Furthermore, the analysis of spatio-temporal migration mechanisms showed that cancer cells are able to push or pull on collagen fibers, therefore producing efficient local collagen deformations in the vicinity of cells. Our results also revealed that dense actin regions are correlated with the largest displacement fields, and this correlation is enhanced for the most invasive J82 cancer cells. Therefore this work opens up new routes to understand cancer cell migration in soft biological networks.
Functional in-vitro evaluation of the non-specific effects of BCG vaccination in a randomised controlled clinical study
Authors: Wilkie Morven , Tanner Rachel , Wright Daniel , Lopez Ramon Raquel , Beglov Julia , Riste Michael , Marshall Julia L. , Harris Stephanie A. , Bettencourt Paulo J. G. , Hamidi Ali , van Diemen Pauline M. , Moss Paul , Satti Iman , Wyllie David , McShane Helen 
Published: May 2022

AbstractBacille Calmette-Guérin (BCG), the only currently licenced tuberculosis vaccine, may exert beneficial non-specific effects (NSE) in reducing infant mortality. We conducted a randomised controlled clinical study in healthy UK adults to evaluate potential NSE using functional in-vitro growth inhibition assays (GIAs) as a surrogate of protection from four bacteria implicated in infant mortality. Volunteers were randomised to receive BCG intradermally (n = 27) or to be unvaccinated (n = 8) and were followed up for 84 days; laboratory staff were blinded until completion of the final visit. Using GIAs based on peripheral blood mononuclear cells, we observed a significant reduction in the growth of the Gram-negative bacteria Escherichia coli and Klebsiella pneumonia following BCG vaccination, but no effect for the Gram-positive bacteria Staphylococcus aureus and Streptococcus agalactiae. There was a modest association between S. aureus nasal carriage and growth of S. aureus in the GIA. Our findings support a causal link between BCG vaccination and improved ability to control growth of heterologous bacteria. Unbiased assays such as GIAs are potentially useful tools for the assessment of non-specific as well as specific effects of TB vaccines. This study was funded by the Bill and Melinda Gates Foundation and registered with ClinicalTrials.gov (NCT02380508, 05/03/2015; completed).
Partially-covered fractal induced turbulence on fins thermal dissipation
Authors: Chew Soon Hong , Hoi Su Min , Tran Manh-Vu , Foo Ji Jinn 
Published: May 2022

AbstractThe impacts of partially-covered fractal grids induced turbulence on the forced convective heat transfer across plate-fin heat sink at Reynolds number ReDh = 22.0 × 103 were numerically and experimentally investigated. Results showed that partially covered grids rendered a higher thermal dissipation performance, with partially-covered square fractal grid (PCSFG) registering an outstanding increase of 43% in Nusselt number relative to the no grid configuration. The analyzation via an in-house developed single particle tracking velocimetry (SPTV) system displayed the findings of unique “Turbulence Annulus” formation, which provided a small degree of predictivity in the periodic annulus oscillations. Further assessments on PCSFG revealed the preferred inter-fin flow dynamics of (i) high flow velocity, (ii) strong turbulence intensity, (iii) vigorous flow fluctuations, (iv) small turbulence length scale, and (v) heightened decelerated flow events. These features stemmed from the coupling effects of multilength-scale fractal bar thicknesses in generating a veracity of eddy sizes, and a vertical segmentation producing heightened mass flow rate while inducing favourable wake-flow structures to penetrate inter-fin regions. Teeming effects of such energetic eddies within plate-fin array unveiled a powerful vortex shedding effect, with PCSFG achieving fluctuation frequency f = 18.5 Hz close to an optimal magnitude. The coaction of such traits limits the growth of fin boundary layers, providing superior thermal transfer capabilities which benefits the community in developing for higher efficiency heat transfer systems.
Characterization of Castellani nineteenth-century gold jewellery by in situ micro-XRF spectroscopy
Authors: Manca Rosarosa , Scrivano Simona , Manfriani Chiara , Ager Vàzquez Francisco J. , Ortega-Feliu Inés , Ferretti Marco , Respaldiza Miguel Angel , Benvenuti Marco 
Published: May 2022

AbstractThe material characterization of nineteenth-century artifacts is of great interest, due both to the breakthrough technological advances and to the unprecedented spread of forgeries of antiquities which took place in that period. However, this type of artifacts has been largely overlooked in the past. In this paper we present the compositional analysis of gold jewels by the Castellani, one of the most important families of goldsmiths in nineteenth-century Europe. The use of a portable micro-XRF spectrometer, specifically developed for jewellery analysis at the Centro Nacional de Aceleradores (Seville), allowed us to analyse, in a completely non-invasive way, the alloys, joining techniques and surface treatments of the jewels of the Castellani collection at the National Etruscan Museum of Villa Giulia in Rome. The addition to the spectrometer of a second X-rays detector with a zinc filter allowed us to check the possible presence of low amounts of cadmium, a metal added to gold soldering only from the nineteenth century and often used in authenticity studies. Moreover, the relative intensities of the Au X-ray lines were studied in order to check non-invasively the presence of surface enrichments in gold.