Miracle-dz/UniFAR-FTUs huggingface dataset:
Flow-induced Reorganization of Laminin-integrin Networks Within the Endothelial Basement Membrane Uncovered by Proteomics

Hemodynamics is crucial for the function of vascular endothelial cells, and its disturbance has been linked to vascular diseases. Here, we combined quantitative mass spectrometry and immunofluorescence studies to dissect the endothelial response to flow-exposure. Our data uncover extensive flow-induced remodeling of the laminin network and unveil the relocation of laminin-associated integrins on the basal endothelial surface. These data highlight the importance of the endothelial basement membrane in vascular homeostasis and emphasize its plasticity. Graphical Abstract Highlights Proteomics uncovers the flow-induced remodeling of the endothelial basement membrane. Flow alters the composition and localization of the laminin-integrin network. Flow induces proteolytic processing of LAMA4, resulting in shedding of LG4–5 region. TNFα- and flow-exposure induce a distinct proteomic signature with limited interplay. The vessel wall is continuously exposed to hemodynamic forces generated by blood flow. Endothelial mechanosensors perceive and translate mechanical signals via cellular signaling pathways into biological processes that control endothelial development, phenotype and function. To assess the hemodynamic effects on the endothelium on a system-wide level, we applied a quantitative mass spectrometry approach combined with cell surface chemical footprinting. SILAC-labeled endothelial cells were subjected to flow-induced shear stress for 0, 24 or 48 h, followed by chemical labeling of surface proteins using a non-membrane permeable biotin label, and analysis of the whole proteome and the cell surface proteome by LC-MS/MS analysis. These studies revealed that of the >5000 quantified proteins 104 were altered, which were highly enriched for extracellular matrix proteins and proteins involved in cell-matrix adhesion. Cell surface proteomics indicated that LAMA4 was proteolytically processed upon flow-exposure, which corresponded to the decreased LAMA4 mass observed on immunoblot. Immunofluorescence microscopy studies highlighted that the endothelial basement membrane was drastically remodeled upon flow exposure. We observed a network-like pattern of LAMA4 and LAMA5, which corresponded to the localization of laminin-adhesion molecules ITGA6 and ITGB4. Furthermore, the adaptation to flow-exposure did not affect the inflammatory response to tumor necrosis factor α, indicating that inflammation and flow trigger fundamentally distinct endothelial signaling pathways with limited reciprocity and synergy. Taken together, this study uncovers the blood flow-induced remodeling of the basement membrane and stresses the importance of the subendothelial basement membrane in vascular homeostasis.
Central α-Klotho Suppresses NPY/AgRP Neuron Activity and Regulates Metabolism in Mice

α-Klotho is a circulating factor with well-documented antiaging properties. However, the central role of α-klotho in metabolism remains largely unexplored. The current study investigated the potential role of central α-klotho to modulate neuropeptide Y/agouti-related peptide (NPY/AgRP)-expressing neurons, energy balance, and glucose homeostasis. Intracerebroventricular administration of α-klotho suppressed food intake, improved glucose profiles, and reduced body weight in mouse models of type 1 and 2 diabetes. Furthermore, central α-klotho inhibition via an anti–α-klotho antibody impaired glucose tolerance. Ex vivo patch clamp electrophysiology and immunohistochemical analysis revealed that α-klotho suppresses NPY/AgRP neuron activity, at least in part, by enhancing miniature inhibitory postsynaptic currents. Experiments in hypothalamic GT1-7 cells observed that α-klotho induces phosphorylation of AKTser473, ERKthr202/tyr204, and FOXO1ser256 as well as blunts AgRP gene transcription. Mechanistically, fibroblast growth factor receptor 1 (FGFR1) inhibition abolished the downstream signaling of α-klotho, negated its ability to modulate NPY/AgRP neurons, and blunted its therapeutic effects. Phosphatidylinositol 3 kinase (PI3K) inhibition also abolished α-klotho’s ability to suppress food intake and improve glucose clearance. These results indicate a prominent role of hypothalamic α-klotho/FGFR1/PI3K signaling in the modulation of NPY/AgRP neuron activity and maintenance of energy homeostasis, thus providing new insight into the pathophysiology of metabolic disease.
Bacterial Pathogens Associated With Urinary Tract Infections among Rural Women in Doma, Nasarawa State

Urinary tract infection (UTI) is frequently occurring infection in women when compared with men, though in men the symptoms are more severe and protracted (Abdulhadi et al., 2008). Urinary tract includes kidneys, ureter, bladder, and urethra. Compromise of the organs could lead to kidney infections, urethritis, cystitis, and pyelonephritis (Farajnia, 2009). It is common for women to report an episode of urinary tract infection at one time or another, while about 25% of them have recurrences (Fihn, 2003; Foxman, 2000). Infections of the urinary tract are caused by pathogens which colonize the genital tract and express virulence that allow attachment to the mucosa of the urethra. Ahmed (2008) and Davis (2003) reported that while poor hygiene, low socio-economic status, and malnutrition affect people in rural setting; the infections (UTIs) are common in both community and hospital settings UTI increases disease burden on community thus, an important source of morbidity in community (Frank 2013). International Journal of Current Microbiology and Applied Sciences ISSN: 2319-7706 Volume 7 Number 08 (2018) Journal homepage: http://www.ijcmas. com
Glycolaldehyde is an endogenous source of lysine N-pyrrolation

Lysine N-pyrrolation converts lysine residues to Nϵ-pyrrole-l-lysine (pyrK) in a covalent modification reaction that significantly affects the chemical properties of proteins, causing them to mimic DNA. pyrK in proteins has been detected in vivo, indicating that pyrrolation occurs as an endogenous reaction. However, the source of pyrK remains unknown. In this study, on the basis of our observation in vitro that pyrK is present in oxidized low-density lipoprotein and in modified proteins with oxidized polyunsaturated fatty acids, we used LC–electrospray ionization–MS/MS coupled with a stable isotope dilution method to perform activity-guided separation of active molecules in oxidized lipids and identified glycolaldehyde (GA) as a pyrK source. The results from mechanistic experiments to study GA-mediated lysine N-pyrrolation suggested that the reactions might include GA oxidation, generating the dialdehyde glyoxal, followed by condensation reactions of lysine amino groups with GA and glyoxal. We also studied the functional significance of GA-mediated lysine N-pyrrolation in proteins and found that GA-modified proteins are recognized by apolipoprotein E, a binding target of pyrrolated proteins. Moreover, GA-modified proteins triggered an immune response to pyrrolated proteins, and monoclonal antibodies generated from mice immunized with GA-modified proteins specifically recognized pyrrolated proteins. These findings reveal that GA is an endogenous source of DNA-mimicking pyrrolated proteins and may provide mechanistic insights relevant for innate and autoimmune responses associated with glucose metabolism and oxidative stress.
Convolutional neural network-based surgical instrument detection

BACKGROUND: Minimally invasive surgery (MIS), unlike open surgery in which surgeons can perform surgery directly, is performed using miniaturized instruments with indirect but careful observation of the surgical site. OBJECTIVE: Instrument detection is a crucial requirement in conventional and robot-assisted MIS, which can also be very useful during surgical training. In this paper, we propose a novel framework of using two three-layer convolutional neural networks (CNNs) in a series to detect surgical instrument in in-vivo video frames. METHODS: The two convolutional neural networks proposed in this paper have different tasks. (i) The former CNN is trained to detect the edges points of the instrument shaft directly from images patches. (ii) The latter is trained to locate the instrument tip also from images patches after the former detection finishes. RESULTS: We validated our method on the publicly available EndoVisSub dataset and a standard dataset, and it detected tools with an accuracy of 91.2% and 75% respectively. CONCLUSION: Our two-step detection method achieves better performance than other existing approaches in terms of detection accuracy.
Compensating for climate change-induced cue-environment mismatches: evidence for contemporary evolution of a photoperiodic reaction norm in Colias butterflies.

Anthropogenic climate change alters seasonal conditions without altering photoperiod and can thus create a cue-environment mismatch for organisms that use photoperiod as a cue for seasonal plasticity. We investigated whether evolution of the photoperiodic reaction norm has compensated for this mismatch in Colias eurytheme. This butterfly's wing melanization has a thermoregulatory function and changes seasonally. In 1971, Hoffmann quantified how larval photoperiod determines adult wing melanization. We recreated his experiment 47 years later using a contemporary population. Comparing our results to his, we found decreased melanization at short photoperiods but no change in melanization at long photoperiods, which is consistent with the greater increase in spring than summer temperatures recorded for this region. Our study shows that evolution can help correct cue-environment mismatches but not in the same way under all conditions. Studies of contemporary evolution may miss important changes if they focus on only a limited range of conditions.
TRIC-A shapes oscillatory Ca2+ signals by interaction with STIM1/Orai1 complexes

Trimeric intracellular cation (TRIC) channels have been proposed to modulate Ca2+ release from the endoplasmic reticulum (ER) and determine oscillatory Ca2+ signals. Here, we report that TRIC-A–mediated amplitude and frequency modulation of ryanodine receptor 2 (RyR2)-mediated Ca2+ oscillations and inositol 1,4,5-triphosphate receptor (IP3R)-induced cytosolic signals is based on attenuating store-operated Ca2+ entry (SOCE). Further, TRIC-A–dependent delay in ER Ca2+ store refilling contributes to shaping the pattern of Ca2+ oscillations. Upon ER Ca2+ depletion, TRIC-A clusters with stromal interaction molecule 1 (STIM1) and Ca2+-release–activated Ca2+ channel 1 (Orai1) within ER–plasma membrane (PM) junctions and impairs assembly of the STIM1/Orai1 complex, causing a decrease in Orai1-mediated Ca2+ current and SOCE. Together, our findings demonstrate that TRIC-A is a negative regulator of STIM1/Orai1 function. Thus, aberrant SOCE could contribute to muscle disorders associated with loss of TRIC-A.
Dysregulation of CO2-Driven Heart-Rate Chemoreflex Is Related Closely to Impaired CO2 Dynamic Vasomotor Reactivity in Mild Cognitive Impairment Patients

Background: Significant reduction of dynamic vasomotor reactivity (DVR) was recently reported in patients with amnestic mild cognitive impairment (MCI) relative to age-matched controls. These results were obtained via a novel approach that utilizes data-based predictive dynamic models to quantify DVR. Objective: Using the same methodological approach, we seek to quantify the dynamic effects of the CO2-driven chemoreflex and baroreflex upon heart-rate in order to examine their possible correlation with the observed DVR impairment in each MCI patient. Methods: The employed approach utilizes time-series data to obtain subject-specific predictive input-output models of the dynamic effects of changes in arterial blood pressure and end-tidal CO2 (putative “inputs”) upon cerebral blood flow velocity in large cerebral arteries, cortical tissue oxygenation, and heart-rate (putative “outputs”). Results: There was significant dysregulation of CO2-driven heart-rate chemoreflex (p = 0.0031), but not of baroreflex (p = 0.5061), in MCI patients relative to age-matched controls. The model-based index of CO2-driven heart-rate chemoreflex gain (CRG) correlated significantly with the DVR index in large cerebral arteries (p = 0.0146), but not with the DVR index in small/micro-cortical vessels (p = 0.1066). This suggests that DVR impairment in small/micro-cortical vessels is not mainly due to CO2-driven heart-rate chemoreflex dysregulation, but to other factors (possibly dysfunction of neurovascular coupling). Conclusion: Improved delineation between MCI patients and controls is achieved by combining the DVR index for small/micro-cortical vessels with the CRG index (p = 2×10–5). There is significant correlation (p < 0.01) between neuropsychological test scores and model-based DVR indices. Combining neuropsychological scores with DVR indices reduces the composite diagnostic index p-value (p∼10–10).
Docosahexaenoic Acid Improves Diabetic Wound Healing in a Rat Model by Restoring Impaired Plasticity of Macrophage Progenitor Cells

Background: Chronic inflammation associated with delayed diabetic wound healing is induced by disturbed polarization of macrophages derived mainly from predisposed progenitor cells in bone marrow. Docosahexaenoic acid plays a critical role in regulating the function of macrophage progenitor cells. The authors evaluated whether docosahexaenoic acid accelerates diabetic wound healing in rats. Methods: Streptozotocin-induced diabetic rats divided into control and docosahexaenoic acid–treated groups (n = 10) were subjected to paired dorsal skin wounds. Docosahexaenoic acid (100 mg/kg per day) was orally supplemented 2 weeks before wounding until termination. The wound healing process was recorded 0, 7, and 14 days after wounding. At day 7, blood perfusion was measured by laser Doppler perfusion imaging; angiogenesis was compared using immunofluorescent CD31 and α-smooth muscle actin staining; macrophage polarization was detected using immunofluorescence for CD68, CD206, and inducible nitric oxide synthase. Hematoxylin and eosin staining was used to examine wound healing at day 14. Activation status of macrophages derived from bone marrow cells in normal, diabetic, and docosahexaenoic acid–treated diabetic rats was determined in vitro using Western blotting and enzyme-linked immunosorbent assay. Results: Docosahexaenoic acid significantly accelerated wound healing 7 and 14 days (p < 0.01) after wounding. Increased vessel densities (1.96-fold; p < 0.001) and blood perfusion (2.56-fold; p < 0.001) were observed in docosahexaenoic acid–treated wounds. Immunofluorescence revealed more CD206+ and fewer inducible nitric oxide synthase–positive macrophages (p < 0.001) in treated wounds. Furthermore, macrophages derived from diabetic rats expressed higher levels of inducible nitric oxide synthase and tumor necrosis factor-α and lower arginase-1 and interleukin-10 (p < 0.05). Conclusion: Docosahexaenoic acid accelerates diabetic wound healing at least in part by restoring impaired plasticity of macrophage progenitor cells.
Darolutamide antagonizes androgen signaling by blocking enhancer and super‐enhancer activation

Prostate cancer (PCa) is one of the most frequent tumor types in the male Western population. Early‐stage PCa and late‐stage PCa are dependent on androgen signaling, and inhibitors of the androgen receptor (AR) axis represent the standard therapy. Here, we studied in detail the global impact of darolutamide, a newly approved AR antagonist, on the transcriptome and AR‐bound cistrome in two PCa cell models. Darolutamide strongly depleted the AR from gene regulatory regions and abolished AR‐driven transcriptional signaling. Enhancer activation was blocked at the chromatin level as evaluated by H3K27 acetylation (H3K27ac), H3K4 monomethylation (H3K4me1), and FOXA1, MED1, and BRD4 binding. We identified genomic regions with high affinities for the AR in androgen‐stimulated, but also in androgen‐depleted conditions. A similar AR affinity pattern was observed in healthy and PCa tissue samples. High FOXA1, BRD4, H3K27ac, and H3K4me1 levels were found to mark regions showing AR binding in the hormone‐depleted setting. Conversely, low FOXA1, BRD4, and H3K27ac levels were observed at regulatory sites that responded strongly to androgen stimulation, and AR interactions at these sites were blocked by darolutamide. Beside marked loss of AR occupancy, FOXA1 recruitment to chromatin was also clearly reduced after darolutamide treatment. We furthermore identified numerous androgen‐regulated super‐enhancers (SEs) that were associated with hallmark androgen and cell proliferation‐associated gene sets. Importantly, these SEs are also active in PCa tissues and sensitive to darolutamide treatment in our models. Our findings demonstrate that darolutamide is a potent AR antagonist blocking genome‐wide AR enhancer and SE activation, and downstream transcription. We also show the existence of a dynamic AR cistrome that depends on the androgen levels and on high AR affinity regions present in PCa cell lines and also in tissue samples.
Meta-analysis of the association between dietary inflammatory index (DII) and upper aerodigestive tract cancer risk

Abstract Background: Epidemiological studies have reported an inconsistent relationship between dietary inflammatory index (DII) and upper aerodigestive tract (UADT) cancer risk. However, no systematic review or meta-analysis has been reported up to now. To quantify the association between DII and UADT cancer risk, we performed this meta-analysis. Methods: The PubMed, EMBASE, Web of Science and Cochrane Library database were searched for relevant studies from inception December 2018. All case-control studies investigating the association between DII and UADT cancer risk were selected. Results: A total of 9 case-control studies were identified, involving 13,714 participants. The adjusted pooled OR of UADT cancer for the highest (the most pro-inflammatory diet) vs lowest (the most anti-inflammatory diet) DII categories were 2.27 (95% CI: 1.89–2.73). Subgroup analysis showed that individuals with the highest category of DII score were independently associated with esophagus cancer (OR = 2.53, 95% CI: 1.74–3.68), oral cavity cancer (OR = 2.23, 95% CI: 1.73–2.86), pharyngeal cancer (OR = 2.02, 95% CI: 1.54–2.64), and laryngeal cancer (OR = 2.05, 95% CI: 0.85–4.93). Conclusion: This meta-analysis suggested that the most pro-inflammatory diets (the highest DII scores) are associated with increased UADT cancer risk. However, the association between DII and laryngeal cancer risk need to be further investigated.
ACD: An Adaptable Approach for RFID Cloning Attack Detection

With the rapid development of the internet of things, radio frequency identification (RFID) technology plays an important role in various fields. However, RFID systems are vulnerable to cloning attacks. This is the fabrication of one or more replicas of a genuine tag, which behave exactly as a genuine tag and fool the reader to gain legal authorization, leading to potential financial loss or reputation damage. Many advanced solutions have been proposed to combat cloning attacks, but they require extra hardware resources, or they cannot detect a clone tag in time. In this article, we make a fresh attempt to counterattack tag cloning based on spatiotemporal collisions. We propose adaptable clone detection (ACD), which can intuitively and accurately display the positions of abnormal tags in real time. It uses commercial off-the-shelf (COTS) RFID devices without extra hardware resources. We evaluate its performance in practice, and the results confirm its success at detecting cloning attacks. The average accuracy can reach 98.7%, and the recall rate can reach 96%. Extensive experiments show that it can adapt to a variety of RFID application scenarios.
Review of Research into the Determination of Acrylamide in Foods

Acrylamide (AA) is produced by high-temperature processing of high carbohydrate foods, such as frying and baking, and has been proved to be carcinogenic. Because of its potential carcinogenicity, it is very important to detect the content of AA in foods. In this paper, the conventional instrumental analysis methods of AA in food and the new rapid immunoassay and sensor detection are reviewed, and the advantages and disadvantages of various analysis technologies are compared, in order to provide new ideas for the development of more efficient and practical analysis methods and detection equipment.
Oven-Controlled MEMS Oscillator with Integrated Micro-Evaporation Trimming

This study reports an oven-controlled microelectromechanical systems oscillator with integrated micro-evaporation trimming that achieves frequency stability over the industrial temperature range and permanent frequency trimming after vacuum packaging. The length-extensional-mode resonator is micro-oven controlled and doped degenerately with phosphorous to achieve a frequency instability of ±2.6 parts per million (ppm) in a temperature range of −40 to 85 °C. The micro-evaporators are bonded to the resonator, integrated face-to-face, and encapsulated in vacuum. During trimming, the micro-evaporators are heated electrically, and the aluminum layers on their surfaces are evaporated and deposited on the surface of the resonator that trims the resonant frequency of the resonator permanently. The impact of the frequency trimming on the temperature stability is very small. The temperature drift increases from ±2.6 ppm within the industrial temperature range before trimming to ±3.3 ppm after a permanent trimming of −426 ppm based on the local evaporation of Al. The trimming rate can be controlled by electric power. A resonator is coarse-trimmed by approximately −807 ppm with an evaporation power of 960 mW for 0.5 h, and fine-trimmed by approximately −815 ppm with an evaporation power of 456 mW for 1 h. Though the Q-factor decreases after trimming, a Q-factor of 304,240 is achieved after the trimming of −1442 ppm.
Diagnostic and prognostic roles of circulating miRNA-223-3p in hepatitis B virus–related hepatocellular carcinoma

Background Circulating microRNAs (miRNAs) have been shown to dysregulate in many cancer types including hepatocellular carcinoma (HCC). The purpose of this study was to examine the potential diagnostic or prognostic roles of circulating miRNAs in patients with hepatitis B virus (HBV)-related HCC. Methods Paired cancerous and adjacent non-cancerous liver tissue specimens of patients with HBV-related HCC were used as a discovery set for screening 800 miRNAs by a Nanostring quantitative assay. Differentially expressed miRNAs were then examined by SYBR green quantitative RT-PCR in a validation cohort of serum samples obtained from 70 patients with HBV-related HCC, 70 HBV patients without HCC and 50 healthy controls. Results The discovery set identified miR-223-3p, miR-199a-5p and miR-451a significantly lower expressed in cancerous tissues compared with non-cancerous tissues. In the validated cohort, circulating miR-223-3p levels were significantly lower in the HCC group compared with the other groups. The combined use of serum alpha-fetoprotein and miR-223-3p displayed high sensitivity for detecting early HCC (85%) and intermediate/advanced stage HCC (100%). Additionally, serum miR-223-3p had a negative correlation with tumor size and BCLC stage. On multivariate analysis, serum miR-223-3p was identified as an independent prognostic factor of overall survival in patients with HCC. In contrast, circulating miRNA-199a-5p and miR-451a did not show any clinical benefit for the diagnosis and prognostic prediction of HCC. Conclusions Our results demonstrated that miR-223-3p was differentially expressed in cancerous compared with paired adjacent non-cancerous tissues. In addition, circulating miRNA-223-3p could represent a novel diagnostic and prognostic marker for patients with HBV-related HCC.