bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developmental modeling of hepatogenesis using obese iPSCs-hepatocyte differentiation uncovers pathological features
Authors: Varghese Divya Saro , Alawathugoda Thilina T. , Sheikh Muhammad Abid , Challagandla Anil Kumar , Emerald Bright Starling , Ansari Suraiya A. 
Published: August 2022

AbstractObesity is a multigene disorder. However, in addition to genetic factors, environmental determinants also participate in developing obesity and related pathologies. Thus, obesity could be best described as a combination of genetic and environmental perturbations often having its origin during the early developmental period. Environmental factors such as energy-dense food and sedentary lifestyle are known to be associated with obesogenicity. However, the combinatorial effects of gene-environment interactions are not well understood. Understanding the role of multiple genetic variations leading to subtle gene expression changes is not practically possible in monogenic or high-fat-fed animal models of obesity. In contrast, human induced pluripotent stem cells (hiPSCs) from individuals with familial obesity or an obesogenic genotype could serve as a good model system. Herein, we have used hiPSCs generated from normal and genetically obese subjects and differentiated them into hepatocytes in cell culture. We show that hepatocytes from obese iPSCs store more lipids and show increased cell death than normal iPSCs. Whole transcriptome analyses in both normal and obese iPSCs treated with palmitate compared to control revealed LXR-RXR and hepatic fibrosis pathways were enriched among other pathways in obese iPSCs compared to normal iPSCs. Among other genes, increased CD36 and CAV1 expression and decreased expression of CES1 in obese iPSCs could have been responsible for excess lipid accumulation, resulting in differential expression of genes associated with hepatic fibrosis, a key feature of non-alcoholic fatty liver disease (NAFLD). Our results demonstrate that iPSCs derived from genetically obese subjects could serve as an excellent model to understand the effects of this multigene disorder on organ development and may uncover pathologies of NAFLD, which is highly associated with obesity.
Breast cancer cell-derived extracellular vesicles promote CD8+ T cell exhaustion via TGF-β type II receptor signaling
Authors: Xie Feng , Zhou Xiaoxue , Su Peng , Li Heyu , Tu Yifei , Du Jinjin , Pan Chen , Wei Xiang , Zheng Min , Jin Ke , Miao Liyan , Wang Chao , Meng Xuli , van Dam Hans , ten Dijke Peter , Zhang Long , Zhou Fangfang 
Published: August 2022

AbstractCancer immunotherapies have shown clinical success in various types of tumors but the patient response rate is low, particularly in breast cancer. Here we report that malignant breast cancer cells can transfer active TGF-β type II receptor (TβRII) via tumor-derived extracellular vesicles (TEV) and thereby stimulate TGF-β signaling in recipient cells. Up-take of extracellular vesicle-TβRII (EV-TβRII) in low-grade tumor cells initiates epithelial-to-mesenchymal transition (EMT), thus reinforcing cancer stemness and increasing metastasis in intracardial xenograft and orthotopic transplantation models. EV-TβRII delivered as cargo to CD8+ T cells induces the activation of SMAD3 which we demonstrated to associate and cooperate with TCF1 transcription factor to impose CD8+ T cell exhaustion, resulting in failure of immunotherapy. The levels of TβRII+ circulating extracellular vesicles (crEV) appears to correlate with tumor burden, metastasis and patient survival, thereby serve as a non-invasive screening tool to detect malignant breast tumor stages. Thus, our findings not only identify a possible mechanism by which breast cancer cells can promote T cell exhaustion and dampen host anti-tumor immunity, but may also identify a target for immune therapy against the most devastating breast tumors.
Germanium silicon oxide achieves multi-coloured ultra-long phosphorescence and delayed fluorescence at high temperature
Authors: Chen Huai , Wei Mingyang , He Yantao , Abed Jehad , Teale Sam , Sargent Edward H. , Yang Zhenyu 
Published: August 2022

AbstractColour-tuned phosphors are promising for advanced security applications such as multi-modal anti-counterfeiting and data encryption. The practical adoption of colour-tuned phosphors requires these materials to be responsive to multiple stimuli (e.g., excitation wavelength, excitation waveform, and temperature) and exhibit excellent materials stability simultaneously. Here we report germanium silicon oxide (GSO) – a heavy-metal-free inorganic phosphor – that exhibits colour-tuned ultra-long phosphorescence and delayed fluorescence across a broad temperature range (300 – 500 K) in air. We developed a sol-gel processing strategy to prepare amorphous oxides containing homogeneously dispersed Si and Ge atoms. The co-existence of Ge and Si luminescent centres (LC) leads to an excitation-dependent luminescence change across the UV-to-visible region. GSO exhibits Si LC-related ultra-long phosphorescence at room-temperature and thermally activated delayed fluorescence at temperatures as high as 573 K. This long-lived PL is sensitized via the energy transfer from Ge defects to Si LCs, which provides PL lifetime tunability for GSO phosphors. The oxide scaffold of GSO offers 500-day materials stability in air; and 1-week stability in strong acidic and basic solutions. Using GSO/polymer hybrids, we demonstrated colour-tuned security tags whose emission wavelength and lifetime can be controlled via the excitation wavelength, and temperature, indicating promise in security applications.
A conflict between spatial selection and evidence accumulation in area LIP
Authors: Seideman Joshua A. , Stanford Terrence R. , Salinas Emilio 
Published: August 2022

AbstractThe lateral intraparietal area (LIP) contains spatially selective neurons that help guide eye movements and, according to numerous studies, do so by accumulating sensory evidence in favor of one choice (e.g., look left) or another (look right). To examine this functional link, we trained two monkeys on an urgent motion discrimination task, a task with which the evolution of both the recorded neuronal activity and the subject’s choice can be tracked millisecond by millisecond. We found that while choice accuracy increased steeply with increasing sensory evidence, at the same time, the LIP selection signal became progressively weaker, as if it hindered performance. This effect was consistent with the transient deployment of spatial attention to disparate locations away from the relevant sensory cue. The results demonstrate that spatial selection in LIP is dissociable from, and may even conflict with, evidence accumulation during informed saccadic choices.
Grafted hPSC-derived GABA-ergic interneurons regulate seizures and specific cognitive function in temporal lobe epilepsy
Authors: Upadhya Dinesh , Attaluri Sahithi , Liu Yan , Hattiangady Bharathi , Castro Olagide W. , Shuai Bing , Dong Yi , Zhang Su-Chun , Shetty Ashok K. 
Published: August 2022

AbstractInterneuron loss/dysfunction contributes to spontaneous recurrent seizures (SRS) in chronic temporal lobe epilepsy (TLE), and interneuron grafting into the epileptic hippocampus reduces SRS and improves cognitive function. This study investigated whether graft-derived gamma-aminobutyric acid positive (GABA-ergic) interneurons directly regulate SRS and cognitive function in a rat model of chronic TLE. Human pluripotent stem cell-derived medial ganglionic eminence-like GABA-ergic progenitors, engineered to express hM4D(Gi), a designer receptor exclusively activated by designer drugs (DREADDs) through CRISPR/Cas9 technology, were grafted into hippocampi of chronically epileptic rats to facilitate the subsequent silencing of graft-derived interneurons. Such grafting substantially reduced SRS and improved hippocampus-dependent cognitive function. Remarkably, silencing of graft-derived interneurons with a designer drug increased SRS and induced location memory impairment but did not affect pattern separation function. Deactivation of DREADDs restored both SRS control and object location memory function. Thus, transplanted GABA-ergic interneurons could directly regulate SRS and specific cognitive functions in TLE.
DNA barcode reference library for the West Sahara-Sahel reptiles
Authors: Velo-Antón Guillermo , Henrique Margarida , Liz André Vicente , Martínez-Freiría Fernando , Pleguezuelos Juan Manuel , Geniez Philippe , Crochet Pierre-André , Brito José Carlos 
Published: August 2022

AbstractDNA barcode reference libraries are now continuously produced for the tree of life, which are essential pillars for the study of biological diversity. Yet, our knowledge about global diversity is largely limited in undersampled regions such as the largest warm desert, the Sahara-Sahel. This dataset provides a DNA barcode reference library for the reptiles of the Western Sahara-Sahel (WSS) and neighbouring countries across this region. It includes 760 barcodes from 133 reptile taxa, distributed in 23 families, and covering the intraspecific diversity of some species. A total of 84 species were collected in the WSS (83% of the total reptile species richness) over 18 overland field expeditions conducted since 2003. DNA barcodes resulted in a high success rate (95%) of species identification and barcoding gap analysis highlighted the effectiveness of the COI fragment as a barcode marker for the WSS reptiles. This dataset represents a comprehensive and reliable DNA reference library for the WSS, filling an important biodiversity gap across a remote and hard-to-sample region.
Development of microsatellites markers for the deep coral Madracis myriaster (Pocilloporidae: Anthozoa)
Authors: Ballesteros-Contreras Diana C. , Barrios Lina M. , Preziosi Richard 
Published: August 2022

AbstractIn 2013 Colombia made an important step towards the construction and management of Marine Protected Areas (MPAs) by establishing the first Deep Corals National Park (PNNCP). Inside this MPA, the coral Madracis myriaster (Cnidaria: Pocilloporidae) was found as the main reef builder, offering habitat for many species of fish and invertebrates. In order to improve the study of deep-sea coral habitats, their connectivity and prospective management, nine new genetic markers (microsatellites) were developed for M. myriaster and tested in samples from PNNCP. We present the assessment of these markers, with a specificity for the deep coral, and its prospective use in future analysis for the PNNCP and other areas in the Caribbean and the Atlantic, where M. myriaster is reported. We also include an additional taxonomic analysis performed on samples of M. myriaster using scanning electron microscopy.
COVID-19 forecasts via stock market indicators
Authors: Liang Yi , Unwin James 
Published: August 2022

AbstractWe propose that technical analysis tools developed to give buy/sell signals in asset trading can be applied to analyze time series datasets in the natural sciences, and we show this explicitly for a study of WHO COVID-19 data. Notably, reliable short term forecasting can provide potentially lifesaving insights into logistical planning, and in particular, into the optimal allocation of resources such as hospital staff and equipment. By reinterpreting COVID-19 daily cases in terms of candlesticks, we are able to apply some of the most popular stock market technical indicators to obtain predictive power over the course of the pandemics. By providing a quantitative assessment of MACD, RSI, and candlestick analyses, we show their statistical significance in making predictions for both stock market data and WHO COVID-19 data. In particular, we show the utility of this novel approach by considering the identification of the beginnings of subsequent waves of the pandemic. Finally, our new methods are used to assess whether current health policies are impacting the growth in new COVID-19 cases.
Induction of potassium channel regulator KCNE4 in a submandibular lymph node metastasis model
Authors: Mano Ryosuke , Tanaka Tomoko , Hashiguchi Shiho , Takahashi Hiroyuki , Sakata Naoaki , Kondo Seiji , Kodama Shohta 
Published: August 2022

AbstractCancer cells often metastasize to the lymph nodes (LNs) before disseminating throughout the body. Clinically, LN metastasis correlates with poor prognosis and influences treatment options. Many studies have shown that cancer cells communicate with immune and stromal cells to prepare a suitable niche for metastasis. In this study, mice were injected with B16–F10 murine melanoma cells to generate a tongue submandibular lymph node (SLN) metastasis model in which genes of interest could be investigated. Microarray analyses were performed on SLNs, identifying 162 upregulated genes, some of which are known metastasis genes. Among these upregulated genes, Kcne4, Slc7a11, Fscn1, and Gadd45b were not associated with metastasis, and increased expression of Kcne4 and Slc7a11 was confirmed by real-time PCR and immunohistochemistry. The roles of KCNE4 in chemokine production and cell adhesion were examined using primary lymphatic endothelial cells, and demonstrated that Ccl17 and Ccl19, which are involved in melanoma metastasis, were upregulated by KCNE4, as well as Mmp3 matrix metalloproteinase. Expression of KCNE4 was detected in human LNs with metastatic melanoma. In conclusion, we found that LN metastatic melanoma induces KCNE4 expression in the endothelium of LNs.
On non-Kolmogorov turbulence in blood flow and its possible role in mechanobiological stimulation
Authors: Saqr Khalid M. , Zidane Iham F. 
Published: August 2022

AbstractThe study of turbulence in physiologic blood flow is important due to its strong relevance to endothelial mechanobiology and vascular disease. Recently, Saqr et al. (Sci Rep 10, 15,492, 2020) discovered non-Kolmogorov turbulence in physiologic blood flow in vivo, traced its origins to the Navier–Stokes equation and demonstrated some of its properties using chaos and hydrodynamic-stability theories. The present work extends these findings and investigates some inherent characteristics of non-Kolmogorov turbulence in monoharmonic and multiharmonic pulsatile flow under ideal physiologic conditions. The purpose of this work is to propose a conjecture for the origins for picoNewton forces that are known to regulate endothelial cells’ functions. The new conjecture relates these forces to physiologic momentum-viscous interactions in the near-wall region of the flow. Here, we used high-resolution large eddy simulation (HRLES) to study pulsatile incompressible flow in a straight pipe of $$L/D=20$$

L
/
D
=
20

. The simulations presented Newtonian and Carreau–Yasuda fluid flows, at $$R{e}_{m}\approx 250$$

R

e
m

≈
250

, each represented by one, two and three boundary harmonics. Comparison was established based on maintaining constant time-averaged mass flow rate in all simulations. First, we report the effect of primary harmonics on the global power budget using primitive variables in phase space. Second, we describe the non-Kolmogorov turbulence in frequency domain. Third, we investigate the near-wall coherent structures in time and space domains. Finally, we propose a new conjecture for the role of turbulence in endothelial cells’ mechanobiology. The proposed conjecture correlates near-wall turbulence to a force field of picoNewton scale, suggesting possible relevance to endothelial cells mechanobiology.
On the survival of the quantum depletion of a condensate after release from a magnetic trap
Authors: Ross J. A. , Deuar P. , Shin D. K. , Thomas K. F. , Henson B. M. , Hodgman S. S. , Truscott A. G. 
Published: August 2022

AbstractWe present observations of the high momentum tail in expanding Bose–Einstein condensates of metastable Helium atoms released from a harmonic trap. The far-field density profile exhibits features that support identification of the tails of the momentum distribution as originating in the in-situ quantum depletion prior to release. Thus, we corroborate recent observations of slowly-decaying tails in the far-field beyond the thermal component. This observation is in conflict with the hydrodynamic theory, which predicts that the in-situ depletion does not survive when atoms are released from a trap. Indeed, the depleted tails even appear stronger in the far-field than expected before release, and we discuss the challenges of interpreting this in terms of the Tan contact in the trapped gas. In complement to these observations, full quantum simulations of the experiment show that, under the right conditions, the depletion can persist into the far field after expansion. Moreover, the simulations provide mechanisms for survival and for the the large-momentum tails to appear stronger after expansion due to an acceleration of the depleted atoms by the mean-field potential. However, while in qualitative agreement, the final depletion observed in the experiment is much larger than in the simulation.
Efficient tactile encoding of object slippage
Authors: Willemet Laurence , Huloux Nicolas , Wiertlewski Michaël 
Published: August 2022

AbstractWhen grasping objects, we rely on our sense of touch to adjust our grip and react against external perturbations. Less than 200 ms after an unexpected event, the sensorimotor system is able to process tactile information to deduce the frictional strength of the contact and to react accordingly. Given that roughly 1,300 afferents innervate the fingertips, it is unclear how the nervous system can process such a large influx of data in a sufficiently short time span. In this study, we measured the deformation of the skin during the initial stages of incipient sliding for a wide range of frictional conditions. We show that the dominant patterns of deformation are sufficient to estimate the distance between the frictional force and the frictional strength of the contact. From these stereotypical patterns, a classifier can predict if an object is about to slide during the initial stages of incipient slip. The prediction is robust to the actual value of the interfacial friction, showing sensory invariance. These results suggest the existence of a possible compact set of bases that we callEigenstrains. These Eigenstrains are a potential mechanism to rapidly decode the margin from full slip from the tactile information contained in the deformation of the skin. Our findings suggest that only 6 of these Eigenstrains are necessary to classify whether the object is firmly stuck to the fingers or is close to slipping away. These findings give clues about the tactile regulation of grasp and the insights are directly applicable to the design of robotic grippers and prosthetics that rapidly react to external perturbations.
Ortholog genes from cactophilic Drosophila provide insight into human adaptation to hallucinogenic cacti
Authors: Padró Julian , De Panis Diego N. , Luisi Pierre , Dopazo Hernan , Szajnman Sergio , Hasson Esteban , Soto Ignacio M. 
Published: August 2022

AbstractCultural transformations of lifestyles and dietary practices have been key drivers of human evolution. However, while most of the evidence of genomic adaptations is related to the hunter-gatherer transition to agricultural societies, little is known on the influence of other major cultural manifestations. Shamanism is considered the oldest religion that predominated throughout most of human prehistory and still prevails in many indigenous populations. Several lines of evidence from ethno-archeological studies have demonstrated the continuity and importance of psychoactive plants in South American cultures. However, despite the well-known importance of secondary metabolites in human health, little is known about its role in the evolution of ethnic differences. Herein, we identified candidate genes of adaptation to hallucinogenic cactus in Native Andean populations with a long history of shamanic practices. We used genome-wide expression data from the cactophilic flyDrosophila buzzatiiexposed to a hallucinogenic columnar cactus,also consumed by humans, to identify ortholog genes exhibiting adaptive footprints of alkaloid tolerance. Genomic analyses in human populations revealed a suite of ortholog genes evolving under recent positive selection in indigenous populations of the Central Andes. Our results provide evidence of selection in genetic variants related to alkaloids toxicity, xenobiotic metabolism, and neuronal plasticity in Aymara and Quechua populations, suggesting a possible process of gene-culture coevolution driven by religious practices.
Plasmid-mediated gene transfer of Cas9 induces vector-related but not SpCas9-related immune responses in human retinal pigment epithelial cells
Authors: Pfromm Julia K. , Bonillo Mario , Dauletbekov Daniyar , Bucher Kirsten , Fischer M. Dominik 
Published: August 2022

AbstractThe clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9) system represents a powerful gene-editing tool and could enable treatment of blinding diseases of the retina. As a peptide of bacterial origin, we investigated the immunogenic potential of Cas9 in models of retinal immunocompetent cells: human microglia (IMhu) and ARPE-19 cells. Transfection with Streptococcus pyogenes-Cas9 expression plasmids (SpCas9 plasmid) induced Cas9 protein expression in both cell lines. However, only ARPE-19 cells, not IMhu cells, responded with pro-inflammatory immune responses as evidenced by the upregulation of IL-8, IL-6, and the cellular activation markers HLA-ABC and CD54 (ICAM). These pro-inflammatory responses were also induced through transfection with equally sized non-coding control plasmids. Moreover, viability rates of ARPE-19 cells were reduced after transfection with both the SpCas9 plasmids and the control plasmids. Although these results demonstrate cell type-specific responses to the DNA plasmid vector, they show no evidence of an immunogenic effect due to the presence of Cas9 in models of human retinal pigment epithelial and microglia cells. These findings add another layer of confidence in the immunological safety of potential future Cas9-mediated retinal gene therapies.
The spatial profile of skin indentation shapes tactile perception across stimulus frequencies
Authors: Grigorii Roman V. , Colgate J. Edward , Klatzky Roberta 
Published: August 2022

AbstractMultiple human sensory systems exhibit sensitivity to spatial and temporal variations of physical stimuli. Vision has evolved to offer high spatial acuity with limited temporal sensitivity, while audition has developed complementary characteristics. Neural coding in touch has been believed to transition from a spatial to a temporal domain in relation to surface scale, such that coarse features (e.g., a braille cell or corduroy texture) are coded as spatially distributed signals, while fine textures (e.g., fine-grit sandpaper) are encoded by temporal variation. However, the interplay between the two domains is not well understood. We studied tactile encoding with a custom-designed pin array apparatus capable of deforming the fingerpad at 5 to 80 Hz in each of 14 individual locations spaced 2.5 mm apart. Spatial variation of skin indentation was controlled by moving each of the pins at the same frequency and amplitude, but with phase delays distributed across the array. Results indicate that such stimuli enable rendering of shape features at actuation frequencies up to 20 Hz. Even at frequencies > 20 Hz, however, spatial variation of skin indentation continues to play a vital role. In particular, perceived roughness is affected by spatial variation within the fingerpad even at 80 Hz. We provide evidence that perceived roughness is encoded via a summary measure of skin displacement. Relative displacements in neighboring pins of less than 10 µm generate skin stretch, which regulates the roughness percept.