bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toll-like receptor 4 modulation influences human neural stem cell proliferation and differentiation
Authors: Grasselli Chiara , Ferrari Daniela , Zalfa Cristina , Soncini Matias , Mazzoccoli Gianluigi , Facchini Fabio A. , Marongiu Laura , Granucci Francesca , Copetti Massimiliano , Vescovi Angelo Luigi , Peri Francesco , De Filippis Lidia 
Published: February 2018

AbstractToll-like receptor 4 (TLR4) activation is pivotal to innate immunity and has been shown to regulate proliferation and differentiation of human neural stem cells (hNSCs) in vivo. Here we study the role of TLR4 in regulating hNSC derived from the human telencephalic-diencephalic area of the fetal brain and cultured in vitro as neurospheres in compliance with Good Manifacture Procedures (GMP) guidelines. Similar batches have been used in recent clinical trials in ALS patients. We found that TLR2 and 4 are expressed in hNSCs as well as CD14 and MD-2 co-receptors, and TLR4 expression is downregulated upon differentiation. Activation of TLR4 signaling by lipopolysaccharide (LPS) has a positive effect on proliferation and/or survival while the inverse is observed with TLR4 inhibition by a synthetic antagonist. TLR4 activation promotes neuronal and oligodendrocyte differentiation and/or survival while TLR4 inhibition leads to increased apoptosis. Consistently, endogenous expression of TLR4 is retained by hNSC surviving after transplantation in ALS rats or immunocompromised mice, thus irrespectively of the neuroinflammatory environment. The characterization of downstream signaling of TLR4 in hNSCs has suggested some activation of the inflammasome pathway. This study suggests TLR4 signaling as essential for hNSC self-renewal and as a novel target for the study of neurogenetic mechanisms.
G9A promotes gastric cancer metastasis by upregulating ITGB3 in a SET domain-independent manner
Authors: Hu Lei , Zang Ming-de , Wang He-xiao , Zhang Bao-gui , Wang Zhen-qiang , Fan Zhi-yuan , Wu Huo , Li Jian-fang , Su Li-ping , Yan Min , Zhu Zhi-qiang , Yang Qiu-meng , Huang Qiang , Liu Bing-ya , Zhu Zheng-gang 
Published: February 2018

AbstractTumor metastasis is the leading cause of death in patients with advanced gastric cancer (GC). Limited therapeutic regimens are available for this condition, which is associated with a poor prognosis, and the mechanisms underlying tumor metastasis remain unclear. In the present study, increased histone methyltransferase G9A expression in GC tissues correlated with advanced stage and shorter overall survival, and in vitro and in vivo experiments revealed that G9A promoted tumor invasion and metastasis. Moreover, we observed that Reg IV induced G9A via the p-ERK/p-SP1 pathway. SP1 directly binds the G9A promoter and enhances G9A expression, and upregulated G9A then forms a transcriptional activator complex with P300 and GR, thereby promoting ITGB3 expression induced by dexamethasone (DEX) and contributing to GC metastasis. However, the G9A-mediated increase in ITGB3 expression was not dependent on the SET domain and methyltransferase activity of G9A. This study demonstrates that G9A is an independent prognostic marker and promotes metastasis in GC, thus suggesting that it may be a tumor biomarker and potential therapeutic target in GC.
Cinacalcet-mediated activation of the CaMKKβ-LKB1-AMPK pathway attenuates diabetic nephropathy in db/db mice by modulation of apoptosis and autophagy
Authors: Lim Ji Hee , Kim Hyung Wook , Kim Min Young , Kim Tae Woo , Kim Eun Nim , Kim Yaeni , Chung Sungjin , Kim Young Soo , Choi Bum Soon , Kim Yong-Soo , Chang Yoon Sik , Kim Hye Won , Park Cheol Whee 
Published: February 2018

AbstractApoptosis and autophagy are harmoniously regulated biological processes for maintaining tissue homeostasis. AMP-activated protein kinase (AMPK) functions as a metabolic sensor to coordinate cellular survival and function in various organs, including the kidney. We investigated the renoprotective effects of cinacalcet in high-glucose treated human glomerular endothelial cells (HGECs), murine podocytes and C57BLKS/J-db/db mice. In cultured HGECs and podocytes, cinacalcet decreased oxidative stress and apoptosis and increased autophagy that were attributed to the increment of intracellular Ca2+ concentration and the phosphorylation of Ca2+/calmodulin-dependent protein kinase kinaseβ (CaMKKβ)-Liver kinase B1 (LKB1)-AMPK and their downstream signals including the phosphorylation of endothelial nitric oxide synthase (eNOS) and increases in superoxide dismutases and B cell leukemia/lymphoma 2/BCL-2-associated X protein expression. Interestingly, intracellular chelator BAPTA-AM reversed cinacalcet-induced CaMKKβ elevation and LKB1 phosphorylation. Cinacalcet reduced albuminuria without influencing either blood glucose or Ca2+ concentration and ameliorated diabetes-induced renal damage, which were related to the increased expression of calcium-sensing receptor and the phosphorylation of CaMKKβ-LKB1. Subsequent activation of AMPK was followed by the activation of peroxisome proliferator-activated receptor γ coactivator-1α and phospho-Ser1177eNOS-nitric oxide, resulting in a decrease in apoptosis and oxidative stress as well as an increase in autophagy.Our results suggest that cinacalcet increases intracellular Ca2+ followed by an activation of CaMKKβ-LKB1-AMPK signaling in GECs and podocytes in the kidney, which provides a novel therapeutic means for type 2 diabetic nephropathy by modulation of apoptosis and autophagy.
Hemopexin is required for adult neurogenesis in the subventricular zone/olfactory bulb pathway
Authors: Zhu Yanling , Qiu Yang , Chen Mengjia , Zhang Yi , Cao Li , Su Zhida , Yuan Yimin , Huang Aijun , Pu Yinyan , He Cheng 
Published: February 2018

AbstractThe neural stem cells (NSCs) of the subventricular zone (SVZ) reside within a specialized niche critical for neurogenesis. Hemopexin, a plasma glycoprotein, has been extensively studied as a heme scavenger at the systemic level. However, little is known about its function in the central nervous system, especially in neurogenesis. In the present study, we demonstrate that deletion of hemopexin leads to neurogenic abnormalities in the SVZ/olfactory bulb (OB) pathway. The lateral ventricle is enlarged in hemopexin-deficient mice, and more apoptosis was observed in Dcx+ cells. Lineage differentiation of NSCs was also inhibited in the SVZ of hemopexin-deficient mice, with more stem cells stayed in an undifferentiated, GFAP+ radial glia-like cell stage. Moreover, hemopexin deletion resulted in impaired neuroblast migration in the rostral migratory stream. Furthermore, exogenous hemopexin protein inhibited apoptosis and promoted the migration and differentiation of cultured NSCs. Finally, immunohistochemical analysis demonstrated that deletion of hemopexin reduced the number of interneurons in the OB. Together, these results suggest a new molecular mechanism for the NSC niche that regulates adult neurogenesis in the SVZ/OB pathway. Our findings may benefit the understanding for olfactory system development.
Basal condensation of Numb and Pon complex via phase transition during Drosophila neuroblast asymmetric division
Authors: Shan Zelin , Tu Yuting , Yang Ying , Liu Ziheng , Zeng Menglong , Xu Huisha , Long Jiafu , Zhang Mingjie , Cai Yu , Wen Wenyu 
Published: February 2018

AbstractUneven distribution and local concentration of protein complexes on distinct membrane cortices is a fundamental property in numerous biological processes, including Drosophila neuroblast (NB) asymmetric cell divisions and cell polarity in general. In NBs, the cell fate determinant Numb forms a basal crescent together with Pon and is segregated into the basal daughter cell to initiate its differentiation. Here we discover that Numb PTB domain, using two distinct binding surfaces, recognizes repeating motifs within Pon in a previously unrecognized mode. The multivalent Numb-Pon interaction leads to high binding specificity and liquid-liquid phase separation of the complex. Perturbations of the Numb/Pon complex phase transition impair the basal localization of Numb and its subsequent suppression of Notch signaling during NB asymmetric divisions. Such phase-transition-mediated protein condensations on distinct membrane cortices may be a general mechanism for various cell polarity regulatory complexes.
Human Semaphorin-4A drives Th2 responses by binding to receptor ILT-4
Authors: Lu Ning , Li Ying , Zhang Zhiqiang , Xing Junji , Sun Ying , Yao Sheng , Chen Lieping 
Published: February 2018

AbstractSemaphorin-4A (Sema4A) has been implicated in the co-stimulation of T cells and drives Th1 immune responses by binding to the receptor T-cell immunoglobulin and mucin domain protein 2 (Tim-2) in mice. Here we show that human, but not murine, Sema4A is preferentially expressed on antigen-presenting cells, and co-stimulates CD4+T-cell proliferation and drives Th2 responses. By employing two independent cloning strategies, we demonstrate that Immunoglobulin-like transcript 4 (ILT-4) is a receptor for human SEMA4A (hSEMA4A) on activated CD4+T cells. We also find hSEMA4A to be highly expressed in human asthmatic lung tissue, implying its potential function in disease pathogenesis. Our study defines a different biological function of hSEMA4A from its murine homolog through its binding to the receptor of ILT-4 to co-stimulate CD4+T cells and regulate Th2 cells differentiation.
Searching for an exotic spin-dependent interaction with a single electron-spin quantum sensor
Authors: Rong Xing , Wang Mengqi , Geng Jianpei , Qin Xi , Guo Maosen , Jiao Man , Xie Yijin , Wang Pengfei , Huang Pu , Shi Fazhan , Cai Yi-Fu , Zou Chongwen , Du Jiangfeng 
Published: February 2018

AbstractSearching for new particles beyond the standard model is crucial for understanding several fundamental conundrums in physics and astrophysics. Several hypothetical particles can mediate exotic spin-dependent interactions between ordinary fermions, which enable laboratory searches via the detection of the interactions. Most laboratory searches utilize a macroscopic source and detector, thus allowing the detection of interactions with submillimeter force range and above. It remains a challenge to detect the interactions at shorter force ranges. Here we propose and demonstrate that a near-surface nitrogen-vacancy center in diamond can be utilized as a quantum sensor to detect the monopole–dipole interaction between an electron spin and nucleons. Our result sets a constraint for the electron–nucleon coupling, $$g_{{\mathrm{s}}}^{\mathrm{N}}g_{\mathrm{p}}^{\mathrm{e}}$$

g

s

N

g

p

e

, with the force range 0.1–23 μm. The obtained upper bound of the coupling at 20 μm is $$g_{{\mathrm{s}}}^{\mathrm{N}}g_{\mathrm{p}}^{\mathrm{e}}$$

g

s

N

g

p

e

< 6.24 × 10−15.
Microsecond dark-exciton valley polarization memory in two-dimensional heterostructures
Authors: Jiang Chongyun , Xu Weigao , Rasmita Abdullah , Huang Zumeng , Li Ke , Xiong Qihua , Gao Wei-bo 
Published: February 2018

AbstractTransition metal dichalcogenides have valley degree of freedom, which features optical selection rule and spin-valley locking, making them promising for valleytronics devices and quantum computation. For either application, a long valley polarization lifetime is crucial. Previous results showed that it is around picosecond in monolayer excitons, nanosecond for local excitons and tens of nanosecond for interlayer excitons. Here we show that the dark excitons in two-dimensional heterostructures provide a microsecond valley polarization memory thanks to the magnetic field induced suppression of valley mixing. The lifetime of the dark excitons shows magnetic field and temperature dependence. The long lifetime and valley polarization lifetime of the dark exciton in two-dimensional heterostructures make them promising for long-distance exciton transport and macroscopic quantum state generations.
Effector CD4+ T cells recognize intravascular antigen presented by patrolling monocytes
Authors: Westhorpe Clare L. V. , Norman M. Ursula , Hall Pam , Snelgrove Sarah L. , Finsterbusch Michaela , Li Anqi , Lo Camden , Tan Zhe Hao , Li Songhui , Nilsson Susan K. , Kitching A. Richard , Hickey Michael J. 
Published: February 2018

AbstractAlthough effector CD4+ T cells readily respond to antigen outside the vasculature, how they respond to intravascular antigens is unknown. Here we show the process of intravascular antigen recognition using intravital multiphoton microscopy of glomeruli. CD4+ T cells undergo intravascular migration within uninflamed glomeruli. Similarly, while MHCII is not expressed by intrinsic glomerular cells, intravascular MHCII-expressing immune cells patrol glomerular capillaries, interacting with CD4+ T cells. Following intravascular deposition of antigen in glomeruli, effector CD4+ T-cell responses, including NFAT1 nuclear translocation and decreased migration, are consistent with antigen recognition. Of the MHCII+ immune cells adherent in glomerular capillaries, only monocytes are retained for prolonged durations. These cells can also induce T-cell proliferation in vitro. Moreover, monocyte depletion reduces CD4+ T-cell-dependent glomerular inflammation. These findings indicate that MHCII+ monocytes patrolling the glomerular microvasculature can present intravascular antigen to CD4+ T cells within glomerular capillaries, leading to antigen-dependent inflammation.
Long-distance propagation of short-wavelength spin waves
Authors: Liu Chuanpu , Chen Jilei , Liu Tao , Heimbach Florian , Yu Haiming , Xiao Yang , Hu Junfeng , Liu Mengchao , Chang Houchen , Stueckler Tobias , Tu Sa , Zhang Youguang , Zhang Yan , Gao Peng , Liao Zhimin , Yu Dapeng , Xia Ke , Lei Na , Zhao Weisheng , Wu Mingzhong 
Published: February 2018

AbstractRecent years have witnessed a rapidly growing interest in exploring the use of spin waves for information transmission and computation toward establishing a spin-wave-based technology that is not only significantly more energy efficient than the CMOS technology, but may also cause a major departure from the von-Neumann architecture by enabling memory-in-logic and logic-in-memory architectures. A major bottleneck of advancing this technology is the excitation of spin waves with short wavelengths, which is a must because the wavelength dictates device scalability. Here, we report the discovery of an approach for the excitation of nm-wavelength spin waves. The demonstration uses ferromagnetic nanowires grown on a 20-nm-thick Y3Fe5O12 film strip. The propagation of spin waves with a wavelength down to 50 nm over a distance of 60,000 nm is measured. The measurements yield a spin-wave group velocity as high as 2600 m s−1, which is faster than both domain wall and skyrmion motions.
Trace metals from historical mining sites and past metallurgical activity remain bioavailable to wildlife today
Authors: Camizuli Estelle , Scheifler Renaud , Garnier Stéphane , Monna Fabrice , Losno Rémi , Gourault Claude , Hamm Gilles , Lachiche Caroline , Delivet Guillaume , Chateau Carmela , Alibert Paul 
Published: February 2018

AbstractThroughout history, ancient human societies exploited mineral resources all over the world, even in areas that are now protected and considered to be relatively pristine. Here, we show that past mining still has an impact on wildlife in some French protected areas. We measured cadmium, copper, lead, and zinc concentrations in topsoils and wood mouse kidneys from sites located in the Cévennes and the Morvan. The maximum levels of metals in these topsoils are one or two orders of magnitude greater than their commonly reported mean values in European topsoils. The transfer to biota was effective, as the lead concentration (and to a lesser extent, cadmium) in wood mouse kidneys increased with soil concentration, unlike copper and zinc, providing direct evidence that lead emitted in the environment several centuries ago is still bioavailable to free-ranging mammals. The negative correlation between kidney lead concentration and animal body condition suggests that historical mining activity may continue to play a role in the complex relationships between trace metal pollution and body indices. Ancient mining sites could therefore be used to assess the long-term fate of trace metals in soils and the subsequent risks to human health and the environment.
Spatial geometry of stem cell proliferation in the adult hippocampus
Authors: Mineyeva Olga A. , Enikolopov Grigori , Koulakov Alexei A. 
Published: February 2018

AbstractThe modes of stem cell divisions (e.g., symmetric vs. asymmetric) can have a profound impact on the number of progeny and tissue growth, repair, and function. This is particularly relevant for adult neural stem cells, since stem cell-derived neurons affect cognitive and mental states, resistance to stress and disease, and response to therapies. Here we show that although dividing stem cells in the adult hippocampus display a certain bias towards paired distribution (which could imply the prevalence of symmetric divisions), this bias already exists in the distribution of the general population of stem cells and may be responsible for the perceived occurrence of symmetric stem cell divisions. Remarkably, the bias in the distribution of stem cells decreases with age. Our results argue that the preexisting bias in stem cell distribution may affect current assumptions regarding stem cell division and fate as well as conjectures on the prospects of brain repair and rejuvenation.
Distinguishing Human Peripheral Blood NK Cells from CD56dimCD16dimCD69+CD103+ Resident Nasal Mucosal Lavage Fluid Cells
Authors: Rebuli Meghan E. , Pawlak Erica A. , Walsh Dana , Martin Elizabeth M. , Jaspers Ilona 
Published: February 2018

AbstractNatural killer (NK) cells are members of the innate lymphoid cells group 1 (ILC1s), which play a critical role in innate host defense against viruses and malignancies. While many studies have examined the role of circulating peripheral blood (PB) CD56+NK cells, little is known about the resident CD56+cell population. Therefore, matched CD56+cells from nasal lavage fluid (NLF) and PB of smokers and non-smokers were compared phenotypically, via flow cytometry, and functionally, via NK-cell specific gene expression. NLF and PB CD56+cells had similar expression of CD56, but differentially expressed tissue residency (CD69 and CD103) and cytotoxicity (CD16) markers. In addition, NLF CD56dimcells expressed lower levels of cytotoxicity-associated genes, perforin (PRF1) and granzyme B (GZMB), and increased levels of cytokines and cell signaling molecules,TRAIL,IFNGR2, andIL8, as compared to PB CD56dimcells. In smokers,ITGA2was downregulated in NLF CD56dimcells, while markers of cytotoxic function were primarily downregulated in PB CD56dimNK cells. Overall, NLF CD56dimcells are a unique cell population that likely play a role in orchestrating innate immune responses in the nasal cavity, which is distinct from their role as a non-antigen-restricted cytotoxic CD56dimlymphocytes in the PB.
Tunable Mechanical Metamaterials through Hybrid Kirigami Structures
Authors: Hwang Doh-Gyu , Bartlett Michael D. 
Published: February 2018

AbstractInspired by the art of paper cutting, kirigami provides intriguing tools to create materials with unconventional mechanical and morphological responses. This behavior is appealing in multiple applications such as stretchable electronics and soft robotics and presents a tractable platform to study structure-property relationships in material systems. However, mechanical response is typically controlled through a single or fractal cut type patterned across an entire kirigami sheet, limiting deformation modes and tunability. Here we show how hybrid patterns of major and minor cuts creates new opportunities to introduce boundary conditions and non-prismatic beams to enable highly tunable mechanical responses. This hybrid approach reduces stiffness by a factor of ~30 while increasing ultimate strain by a factor of 2 (up to 750% strain) relative to single incision patterns. We present analytical models and generate general design criteria that is in excellent agreement with experimental data from nanoscopic to macroscopic systems. These hybrid kirigami materials create new opportunities for multifunctional materials and structures, which we demonstrate with stretchable kirigami conductors with nearly constant electrical resistance up to >400% strain and magnetoactive actuators with extremely rapid response (>10,000% strain s−1) and high, repeatable elongation (>300% strain).
Culture-free bacterial detection and identification from blood with rapid, phenotypic, antibiotic susceptibility testing
Authors: Shi Xuyang , Kadiyala Usha , VanEpps J. Scott , Yau Siu-Tung 
Published: February 2018

AbstractThe current culture-based approach for the diagnosis of bloodstreams infection is incommensurate with timely treatment and curbing the prevalence of multi-drug resistant organisms (MDROs) due to its long time-to-result. Bloodstream infections typically involve extremely low (e.g., <10 colony-forming unit (CFU)/mL) bacterial concentrations that require a labor-intensive process and as much as 72 hours to yield a diagnosis. Here, we demonstrate a culture-free approach to achieve rapid diagnosis of bloodstream infections. An immuno-detection platform with intrinsic signal current amplification was developed for the ultrasensitive, rapid detection, identification (ID) and antibiotic susceptibility testing (AST) of infections. With its capability of monitoring short-term (1–2 hours) bacterial growth in blood, the platform is able to provide 84-minute simultaneous detection and ID in blood samples below the 10 CFU/mL level and 204-minute AST. The susceptible-intermediate-resistant AST capacity was demonstrated.
The impact of computed high b-value images on the diagnostic accuracy of DWI for prostate cancer: A receiver operating characteristics analysis
Authors: Ning Peigang , Shi Dapeng , Sonn Geoffrey A. , Vasanawala Shreyas S. , Loening Andreas M. , Ghanouni Pejman , Obara Piotr , Shin Lewis K. , Fan Richard E. , Hargreaves Brian A. , Daniel Bruce L. 
Published: February 2018

AbstractTo evaluate the performance of computed high b value diffusion-weighted images (DWI) in prostate cancer detection. 97 consecutive patients who had undergone multiparametric MRI of the prostate followed by biopsy were reviewed. Five radiologists independently scored 138 lesions on native high b-value images (b = 1200 s/mm2), apparent diffusion coefficient (ADC) maps, and computed high b-value images (contrast equivalent to b = 2000 s/mm2) to compare their diagnostic accuracy. Receiver operating characteristic (ROC) analysis and McNemar’s test were performed to assess the relative performance of computed high b value DWI, native high b-value DWI and ADC maps. No significant difference existed in the area under the curve (AUC) for ROCs comparing B1200 (b = 1200 s/mm2) to computed B2000 (c-B2000) in 5 readers. In 4 of 5 readers c-B2000 had significantly increased sensitivity and/or decreased specificity compared to B1200 (McNemar’s p < 0.05), at selected thresholds of interpretation. ADC maps were less accurate than B1200 or c-B2000 for 2 of 5 readers (P < 0.05). This study detected no consistent improvement in overall diagnostic accuracy using c-B2000, compared with B1200 images. Readers detected more cancer with c-B2000 images (increased sensitivity) but also more false positive findings (decreased specificity).