bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of BRAF V600E mutation in odontogenic tumors by high-performance MALDI-TOF analysis
Authors: Togni Lucrezia , Zizzi Antonio , Mazzucchelli Roberta , Santarelli Andrea , Rubini Corrado , Mascitti Marco 
Published: April 2022

AbstractOdontogenic tumors are rare lesions with unknown etiopathogenesis. Most of them are benign, but local aggressiveness, infiltrative potential, and high recurrence rate characterize some entities. The MAP-kinase pathway activation can represent a primary critical event in odontogenic tumorigenesis. Especially, the BRAF V600E mutation has been involved in 80–90% of ameloblastic lesions, offering a biological rationale for developing new targeted therapies. The study aims to evaluate the BRAF V600E mutation in odontogenic lesions, comparing three different detection methods and focusing on the Sequenom MassARRAY System. 81 surgical samples of odontogenic lesions were subjected to immunohistochemical analysis, Sanger Sequencing, and Matrix-Assisted Laser Desorption/Ionization-Time of Flight mass spectrometry (Sequenom). The BRAF V600E mutation was revealed only in ameloblastoma samples. Moreover, the presence of BRAF V600E was significantly associated with the mandibular site (ρ = 0.627; P value <0.001) and the unicystic histotype (ρ = 0.299, P value <0.001). However, any significant difference of 10-years disease-free survival time was not revealed. Finally, Sequenom showed to be a 100% sensitive and 98.1% specific, suggesting its high-performance diagnostic accuracy. These results suggest the MAP-kinase pathway could contribute to ameloblastic tumorigenesis. Moreover, they could indicate the anatomical specificity of the driving mutations of mandibular ameloblastomas, providing a biological rational for developing new targeted therapies. Finally, the high diagnostic accuracy of Sequenom was confirmed.
Recent advances in modulation of cardiovascular diseases by the gut microbiota
Authors: Masenga Sepiso K. , Hamooya Benson , Hangoma Joy , Hayumbu Valerie , Ertuglu Lale A. , Ishimwe Jeanne , Rahman Sharla , Saleem Mohammad , Laffer Cheryl L. , Elijovich Fernando , Kirabo Annet 
Published: April 2022

AbstractThe gut microbiota has recently gained attention due to its association with cardiovascular health, cancers, gastrointestinal disorders, and non-communicable diseases. One critical question is how the composition of the microbiota contributes to cardiovascular diseases (CVDs). Insightful reviews on the gut microbiota, its metabolites and the mechanisms that underlie its contribution to CVD are limited. Hence, the aim of this review was to describe linkages between the composition of the microbiota and CVD, CVD risk factors such as hypertension, diet, ageing, and sex differences. We have also highlighted potential therapies for improving the composition of the gut microbiota, which may result in better cardiovascular health.
Modulation of innate immune response to viruses including SARS-CoV-2 by progesterone
Authors: Su Shan , Hua Duo , Li Jin-Peng , Zhang Xia-Nan , Bai Lei , Cao Li-Bo , Guo Yi , Zhang Ming , Dong Jia-Zhen , Liang Xiao-Wei , Lan Ke , Hu Ming-Ming , Shu Hong-Bing 
Published: April 2022

AbstractWhether and how innate antiviral response is regulated by humoral metabolism remains enigmatic. We show that viral infection induces progesterone via the hypothalamic-pituitary-adrenal axis in mice. Progesterone induces downstream antiviral genes and promotes innate antiviral response in cells and mice, whereas knockout of the progesterone receptor PGR has opposite effects. Mechanistically, stimulation of PGR by progesterone activates the tyrosine kinase SRC, which phosphorylates the transcriptional factor IRF3 at Y107, leading to its activation and induction of antiviral genes. SARS-CoV-2-infected patients have increased progesterone levels, and which are co-related with decreased severity of COVID-19. Our findings reveal how progesterone modulates host innate antiviral response, and point to progesterone as a potential immunomodulatory reagent for infectious and inflammatory diseases.
Antiapoptotic Protein FAIM2 is targeted by miR-3202, and DUX4 via TRIM21, leading to cell death and defective myogenesis
Authors: Soliman Hossam A. N. , Toso Erik A. , Darwish Inas E. , Ali Samia M. , Kyba Michael 
Published: April 2022

AbstractInappropriate expression of DUX4, a transcription factor that induces cell death at high levels of expression and impairs myoblast differentiation at low levels of expression, leads to the development of facioscapulohumeral muscular dystrophy (FSHD), however, the pathological mechanisms downstream of DUX4 responsible for muscle loss are poorly defined. We performed a screen of 1972 miR inhibitors for their ability to interfere with DUX4-induced cell death of human immortalized myoblasts. The most potent hit identified by the screen, miR-3202, is known to target the antiapoptotic protein FAIM2. Inhibition of miR-3202 led to the upregulation of FAIM2, and remarkably, expression of DUX4 led to reduced cellular levels of FAIM2. We show that the E3 ubiquitin ligase and DUX4 target gene, TRIM21, is responsible for FAIM2 degradation downstream of DUX4. Human myoblasts overexpressing FAIM2 showed increased resistance to DUX4-induced cell death, whereas in wild-type cells FAIM2 knockdown resulted in increased apoptosis and failure to differentiate into myotubes. The necessity of FAIM2 for myogenic differentiation of WT cells led us to test the effect of FAIM2 overexpression on the impairment of myogenesis by DUX4. Strikingly, FAIM2 overexpression rescued the myogenic differentiation defect caused by low-level expression of DUX4. These data implicate FAIM2 levels, modulated by DUX4 through TRIM21, as an important factor mediating the pathogenicity of DUX4, both in terms of cell viability and myogenic differentiation, and thereby open a new avenue of investigation towards drug targets in FSHD.
Ageing related thyroid deficiency increases brain-targeted transport of liver-derived ApoE4-laden exosomes leading to cognitive impairment
Authors: Zhang Manman , Gong Wenliang , Zhang Dianjun , Ji Ming , Chen Binjie , Chen Beina , Li Xinyu , Zhou Yuefei , Dong Chengyi , Wen Gehua , Zhan Xiaoni , Wu Xiafang , Cui Lulu , Feng Yuliang , Wang Siman , Yuan Huiya , Xu Enyu , Xia Maosheng , Verkhratsky Alexei , Li Baoman 
Published: April 2022

AbstractAlzheimer’s disease (AD) is the prevalent cause of dementia in the ageing world population. Apolipoprotein E4 (ApoE4) allele is the key genetic risk factor for AD, although the mechanisms linking ApoE4 with neurocognitive impairments and aberrant metabolism remains to be fully characterised. We discovered a significant increase in the ApoE4 content of serum exosomes in old healthy subjects and AD patients carrying ApoE4 allele as compared with healthy adults. Elevated exosomal ApoE4 demonstrated significant inverse correlation with serum level of thyroid hormones and cognitive function. We analysed effects of ApoE4-containing peripheral exosomes on neural cells and neurological outputs in aged or thyroidectomised young mice. Ageing-associated hypothyroidism as well as acute thyroidectomy augmented transport of liver-derived ApoE4 reach exosomes into the brain, where ApoE4 activated nucleotide-binding oligomerisation domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome by increasing cholesterol level in neural cells. This, in turn, affected cognition, locomotion and mood. Our study reveals pathological potential of exosomes-mediated relocation of ApoE4 from the periphery to the brain, this process can represent potential therapeutic target.
LINC00858 promotes colon cancer progression through activation of STAT3/5 signaling by recruiting transcription factor RAD21 to upregulate PCNP
Authors: Xu Ting , Wu Kun , Shi Jin , Ji Lindong , Song Xudong , Tao Guoquan , Zheng Shutao , Zhang Li , Jiang Baofei 
Published: April 2022

AbstractThe purpose of our investigation is to explore the putative molecular mechanisms underpinning LINC00858 involvement in colon cancer. The expression of LINC00858 in TCGA data was identified using the GEPIA website. Colon cancer cancerous tissues were clinically collected. The expression of LINC00858, RAD21, and PCNP in colon tissues or cells was determined using RT-qPCR. The interactions among LINC00858, RAD21, and PCNP promoter region were determined by means of RNA pull down, RIP, and ChIP assays. Cell proliferative, apoptotic, invasive, and migrated capabilities were evaluated. Western blot was conducted to determine RAD21, PCNP, phosphorylated (p)-STAT3, STAT3, p-STAT5 and STAT5 and apoptosis related proteins. A nude mouse model of colon cancer was constructed and tumorigenesis of colon cancer cells was observed. LINC00858 was upregulated in cancerous tissues and cells. LINC00858 recruited the transcription factor RAD21. Overexpression of LINC00858 promoted the binding of RAD21 and PCNP promoter region, which increased the expression of PCNP. Silencing of RAD21 or PCNP reversed the promoting effect of LINC00858 on the disease initiation and development. PCNP silencing inhibited proliferative ability and promoted apoptotic ability of cancerous cells via STAT3/5 inhibition, which was reversed by colivelin-activated STAT3. In vivo experiments further verified that LINC00858 enhanced the tumorigenicity of colon cancer cells in vivo by regulating the RAD21/PCNP/STAT3/5 axis. It indicated the promoting role of LINC00858 in colon cancer progression though activating PCNP-mediated STAT3/5 pathway by recruiting RAD21.
Transcription factors AP-2α and AP-2β regulate distinct segments of the distal nephron in the mammalian kidney
Authors: Lamontagne Joseph O. , Zhang Hui , Zeid Alia M. , Strittmatter Karin , Rocha Alicia D. , Williams Trevor , Zhang Sheryl , Marneros Alexander G. 
Published: April 2022

AbstractTranscription factors AP-2α and AP-2β have been suggested to regulate the differentiation of nephron precursor populations towards distal nephron segments. Here, we show that in the adult mammalian kidney AP-2α is found in medullary collecting ducts, whereas AP-2β is found in distal nephron segments except for medullary collecting ducts. Inactivation of AP-2α in nephron progenitor cells does not affect mammalian nephrogenesis, whereas its inactivation in collecting ducts leads to defects in medullary collecting ducts in the adult. Heterozygosity for AP-2β in nephron progenitor cells leads to progressive distal convoluted tubule abnormalities and β-catenin/mTOR hyperactivation that is associated with renal fibrosis and cysts. Complete loss of AP-2β in nephron progenitor cells caused an absence of distal convoluted tubules, renal cysts, and fibrosis with β-catenin/mTOR hyperactivation, and early postnatal death. Thus, AP-2α and AP-2β have non-redundant distinct spatiotemporal functions in separate segments of the distal nephron in the mammalian kidney.
Shared and unique brain network features predict cognitive, personality, and mental health scores in the ABCD study
Authors: Chen Jianzhong , Tam Angela , Kebets Valeria , Orban Csaba , Ooi Leon Qi Rong , Asplund Christopher L. , Marek Scott , Dosenbach Nico U. F. , Eickhoff Simon B. , Bzdok Danilo , Holmes Avram J. , Yeo B. T. Thomas 
Published: April 2022

AbstractHow individual differences in brain network organization track behavioral variability is a fundamental question in systems neuroscience. Recent work suggests that resting-state and task-state functional connectivity can predict specific traits at the individual level. However, most studies focus on single behavioral traits, thus not capturing broader relationships across behaviors. In a large sample of 1858 typically developing children from the Adolescent Brain Cognitive Development (ABCD) study, we show that predictive network features are distinct across the domains of cognitive performance, personality scores and mental health assessments. On the other hand, traits within each behavioral domain are predicted by similar network features. Predictive network features and models generalize to other behavioral measures within the same behavioral domain. Although tasks are known to modulate the functional connectome, predictive network features are similar between resting and task states. Overall, our findings reveal shared brain network features that account for individual variation within broad domains of behavior in childhood.
Hardware functional obfuscation with ferroelectric active interconnects
Authors: Yu Tongguang , Xu Yixin , Deng Shan , Zhao Zijian , Jao Nicolas , Kim You Sung , Duenkel Stefan , Beyer Sven , Ni Kai , George Sumitha , Narayanan Vijaykrishnan 
Published: April 2022

AbstractExisting circuit camouflaging techniques to prevent reverse engineering increase circuit-complexity with significant area, energy, and delay penalty. In this paper, we propose an efficient hardware encryption technique with minimal complexity and overheads based on ferroelectric field-effect transistor (FeFET) active interconnects. By utilizing the threshold voltage programmability of the FeFETs, run-time reconfigurable inverter-buffer logic, utilizing two FeFETs and an inverter, is enabled. Judicious placement of the proposed logic makes it act as a hardware encryption key and enable encoding and decoding of the functional output without affecting the critical path timing delay. Additionally, a peripheral programming scheme for reconfigurable logic by reusing the existing scan chain logic is proposed, obviating the need for specialized programming logic and circuitry for keybit distribution. Our analysis shows an average encryption probability of 97.43% with an increase of 2.24%/ 3.67% delay for the most critical path/ sum of 100 critical paths delay for ISCAS85 benchmarks.
A dirigent family protein confers variation of Casparian strip thickness and salt tolerance in maize
Authors: Wang Yanyan , Cao Yibo , Liang Xiaoyan , Zhuang Junhong , Wang Xiangfeng , Qin Feng , Jiang Caifu 
Published: April 2022

AbstractPlant salt-stress response involves complex physiological processes. Previous studies have shown that some factors promote salt tolerance only under high transpiring condition, thus mediating transpiration-dependent salt tolerance (TDST). However, the mechanism underlying crop TDST remains largely unknown. Here, we report thatZmSTL1(Salt-Tolerant Locus 1) confers natural variation of TDST in maize.ZmSTL1encodes a dirigent protein (termed ZmESBL) localized to the Casparian strip (CS) domain. Mutants lacking ZmESBL display impaired lignin deposition at endodermal CS domain which leads to a defective CS barrier. Under salt condition, mutation of ZmESBL increases the apoplastic transport of Na+across the endodermis, and then increases the root-to-shoot delivery of Na+via transpiration flow, thereby leading to a transpiration-dependent salt hypersensitivity. Moreover, we show that the ortholog of ZmESBL also mediates CS development and TDST in Arabidopsis. Our study suggests that modification of CS barrier may provide an approach for developing salt-tolerant crops.
Reduced chromatin accessibility correlates with resistance to Notch activation
Authors: van den Ameele Jelle , Krautz Robert , Cheetham Seth W. , Donovan Alex P. A. , Llorà-Batlle Oriol , Yakob Rebecca , Brand Andrea H. 
Published: April 2022

AbstractThe Notch signalling pathway is a master regulator of cell fate transitions in development and disease. In the brain, Notch promotes neural stem cell (NSC) proliferation, regulates neuronal migration and maturation and can act as an oncogene or tumour suppressor. How NOTCH and its transcription factor RBPJ activate distinct gene regulatory networks in closely related cell types in vivo remains to be determined. Here we use Targeted DamID (TaDa), requiring only thousands of cells, to identify NOTCH and RBPJ binding in NSCs and their progeny in the mouse embryonic cerebral cortex in vivo. We find that NOTCH and RBPJ associate with a broad network of NSC genes. Repression of NSC-specific Notch target genes in intermediate progenitors and neurons correlates with decreased chromatin accessibility, suggesting that chromatin compaction may contribute to restricting NOTCH-mediated transactivation.
Analytical solution for nonadiabatic quantum annealing to arbitrary Ising spin Hamiltonian
Authors: Yan Bin , Sinitsyn Nikolai A. 
Published: April 2022

AbstractIsing spin Hamiltonians are often used to encode a computational problem in their ground states. Quantum Annealing (QA) computing searches for such a state by implementing a slow time-dependent evolution from an easy-to-prepare initial state to a low energy state of a target Ising Hamiltonian of quantum spins, HI. Here, we point to the existence of an analytical solution for such a problem for an arbitrary HI beyond the adiabatic limit for QA. This solution provides insights into the accuracy of nonadiabatic computations. Our QA protocol in the pseudo-adiabatic regime leads to a monotonic power-law suppression of nonadiabatic excitations with time T of QA, without any signature of a transition to a glass phase, which is usually characterized by a logarithmic energy relaxation. This behavior suggests that the energy relaxation can differ in classical and quantum spin glasses strongly, when it is assisted by external time-dependent fields. In specific cases of HI, the solution also shows a considerable quantum speedup in computations.
Ratiometric afterglow luminescent nanoplatform enables reliable quantification and molecular imaging
Authors: Liu Yongchao , Teng Lili , Lyu Yifan , Song Guosheng , Zhang Xiao-Bing , Tan Weihong 
Published: April 2022

AbstractAfterglow luminescence is an internal luminescence pathway that occurs after photo-excitation, holds great promise for non-background molecular imaging in vivo, but suffer from poor quantitative ability owing to luminescent attenuation over time. Moreover, the inert structure and insufficient reactive sites of current afterglow materials make it hard to design activatable afterglow probes for specific detection. Here, we report a ratiometric afterglow luminescent nanoplatform to customize various activatable afterglow probes for reliable quantification and molecular imaging of specific analytes, such as NO, ONOO− or pH. Notably, these afterglow probes can not only address the attenuation of afterglow intensity and eliminate the interference of factors (e.g., laser power, irradiation time, and exposure time), but also significantly improve the imaging reliability in vivo and signal-to-background ratios (~1200-fold), both of which enable more reliable quantitative analysis in biological systems. Moreover, as a proof-of-concept, we successfully design an NO-responsive ratiometric afterglow nanoprobe, RAN1. This nanoprobe can monitor the fluctuations of intratumoral NO, as a biomarker of macrophage polarization, making it possible to real-time dynamically evaluate the degree cancer immunotherapy, which provides a reliable parameter to predict the immunotherapeutic effect.
Brillouin Klein bottle from artificial gauge fields
Authors: Chen Z. Y. , Yang Shengyuan A. , Zhao Y. X. 
Published: April 2022

AbstractA Brillouin zone is the unit for the momentum space of a crystal. It is topologically a torus, and distinguishing whether a set of wave functions over the Brillouin torus can be smoothly deformed to another leads to the classification of various topological states of matter. Here, we show that under$${{\mathbb{Z}}}_{2}$$Z2gauge fields, i.e., hopping amplitudes with phases ±1, the fundamental domain of momentum space can assume the topology of a Klein bottle. This drastic change of the Brillouin zone theory is due to the projective symmetry algebra enforced by the gauge field. Remarkably, the non-orientability of the Brillouin Klein bottle corresponds to the topological classification by a$${{\mathbb{Z}}}_{2}$$Z2invariant, in contrast to the Chern number valued in$${\mathbb{Z}}$$Zfor the usual Brillouin torus. The result is a novel Klein bottle insulator featuring topological modes at two edges related by a nonlocal twist, radically distinct from all previous topological insulators. Our prediction can be readily achieved in various artificial crystals, and the discovery opens a new direction to explore topological physics by gauge-field-modified fundamental structures of physics.
TLR4 and SARM1 modulate survival and chemoresistance in an HPV-positive cervical cancer cell line
Authors: Morale Mirian Galliote , Tamura Rodrigo Esaki , Cintra Ricardo , Araújo Natália Meneses , Villa Luisa Lina 
Published: April 2022

AbstractHuman Papillomavirus is responsible for a wide range of mucosal lesions and tumors. The immune system participate in tumorigenesis in different ways. For example, signaling pathways triggered by Toll-like receptors (TLR) play a role in chemotherapy resistance in several tumor types and are candidates for contributing to the development of HPV-induced tumors. Here, we studied the receptor TLR4 and the adaptor molecule SARM1 in HeLa cells, an HPV-positive cervical cancer cell line. Knocking out of these genes individually proved to be important for maintaining cell viability and proliferation. TLR4 knock out cells were more sensitive to cisplatin treatment, which was illustrated by an increased frequency of apoptotic cells. Furthermore, TLR4 and SARM1 modulated ROS production, which was induced by cell death in response to cisplatin. In conclusion, TLR4 and SARM1 are important for therapy resistance and cervical cancer cell viability and may be relevant clinical targets.
The novel adamantane derivatives as potential mediators of inflammation and neural plasticity in diabetes mice with cognitive impairment
Authors: Piątkowska-Chmiel Iwona , Gawrońska-Grzywacz Monika , Popiołek Łukasz , Herbet Mariola , Dudka Jarosław 
Published: April 2022

AbstractDiabetes is a chronic disease leading to memory difficulties and deterioration of learning abilities. The previous studies showed that modulation of inflammatory pathways in the diabetic brain may reduce dysfunction or cell death in brain areas which are important for control of cognitive function. In the present study, we investigated the neuroprotective actions of newly synthesized adamantane derivatives on diabetes-induced cognitive impairment in mice. Our study relied on the fact that both vildagliptin and saxagliptin belong to DPP4 inhibitors and, contain adamantanyl group. Efficacy of tested compounds at reversing diabetes-induced different types of memory impairment was evaluated with the use of selected behavioural tests. The following neuroinflammatory indicators were also analyzed: neuroinflammatory indicators and the expression of genes involved in the inflammatory response of brain (Cav1, Bdnf). Our study demonstrated that new adamantane derivatives, similarly to DPP4 inhibitors, can restrict diabetes-induced cognitive deficits. We demonstrated that the overexpression of GLP-1-glucagon-like peptide as well as Bdnf, Cav1 genes translate into central blockade of pro-inflammatory synthesis of cytokines and significantly improvement on memory performance in diabetes mice. Newly synthesized adamantane derivatives might have important roles in prevention and treatment of cognitive impairment by inflammatory events in patients with diabetes or related diseases.