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2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Nabamita Boruah ◽  
Chongtham Sovachandra Singh ◽  
Pooja Swargiary ◽  
Hughbert Dkhar ◽  
Anupam Chatterjee

Abstract Background Raw areca nut (RAN) consumption induces oral, esophageal and gastric cancers, which are significantly associated with the overexpression of pituitary tumor transforming gene 1/securin and chromosomal instability (CIN). An association of Securin/PTTG1 upregulation and gastric cancer in human was also demonstrated earlier. Since the molecular mechanism underlying securin upregulation remains unclear, this study intended to investigate the association of securin upregulation with the Rb-E2F1 circuit and epigenetic histone (H3) modification patterns both globally and in the promoter region of the securin gene. Methods Six groups of mice were used, and in the treated group, each mouse consumed 1 mg of RAN extract with lime per day ad libitum in the drinking water for 60 days, after which the dose was increased by 1 mg every 60 days. Histopathological evaluation of stomach tissues was performed and securin expression was analysed by immunoblotting as well as by immunohistochemistry. ChIP-qPCR assays were performed to evaluate the recruitment of different histone modifications in the core promoter region of securin gene as well as its upstream and downstream regions. Results All mice developed gastric cancer with securin overexpression after 300 days of feeding. Immunohistochemistry data revealed hyperphosphorylation of Rb and upregulation of E2F1 in the RAN-treated samples. Increased trimethylation of H3 lysine 4 and acetylation of H3 lysine 9 and 18 both globally and in the promoter region of the securin gene were observed by increasing the levels of lysine-N-methyltransferase 2A, lysine-acetyltransferase, EP-300 and PCAF after RAN treatment. ChIP-qPCR data revealed that the quantity of DNA fragments retrieved from the immunoprecipitated samples was maximum in the -83 to -192 region than further upstream and the downstream of the promoter for H3K4Me3, H3K9ac, H3K18ac and H3K9me3. Conclusions RAN-mediated pRb-inactivation induced securin upregulation, a putative E2F1 target, by inducing misregulation in chromatin remodeling in its promoter region, which led to transcriptional activation and subsequent development of chromosomal instability. Therefore, present results have led to the hypothesis that RAN-induced changes in the epigenetic landscape, securin overexpression and subsequent elevation of chromosomal instability is probably byproducts of inactivation of the pRb pathway.


2022 ◽  

The island of Manhattan is one of five boroughs that comprises modern-day New York City. Joining the neighboring boroughs of Brooklyn, Queens, the Bronx, and Staten Island, the City of New York was consolidated as such in 1898. While part of a larger whole, “New York City architecture” typically refers to the built environment of Manhattan. Indeed, the iconic image of contemporary New York City is the Manhattan skyline. Its tall buildings have historically been concentrated in the Financial District on the southern tip of the island, and in Midtown, although recent developments have seen these traditional boundaries expand northward and to the outer boroughs. By the early 1700s, the Native Lenape population had largely been displaced by colonists—first the Dutch, who named their community on the southern tip of Manhattan New Amsterdam, and later the British, who again rechristened this area New York. As a result of the near-continuous cycle of demolition and construction that has characterized so much of New York’s history, little evidence of the earliest structures—both Native and European—survives. Yet the Dutch and British settlements laid the ground work for future expansion. With a population concentrated at the southern tip of the island, subsequent development continuously pushed northward. Infrastructure projects like the Brooklyn Bridge, completed in 1883, physically connected Manhattan to then-neighboring city of Brooklyn, and subsequent bridges and tunnels further linked the island to its surroundings, creating a regional metropolis. Because of New York’s significance to national history—for a short time, it was the capital of the early Republic, and in the 20th and 21st centuries it is a capital of finance, media, and visual culture—literature on the city’s built environment is vast. This bibliography thus proceeds from general resources to a chronology that begins in the late 18th century, and continues up to recent developments in the architecture and urban planning that shape the city in the early 21st century.


Cobot ◽  
2022 ◽  
Vol 1 ◽  
pp. 4
Author(s):  
Rui Xu ◽  
Lu Qian ◽  
Xingwei Zhao

Background: With the increasing demand of mobile robots in warehousing, logistics and service fields, simple planar motion is difficult to meet the task requirements of complex environment. The combination of mobile robot and cooperative robot is helpful to improve the dexterity of robot movement and expand the application of robots. Methods: Aiming at the application requirements of dual-arm robots and mobile robots in practical applications, this paper designed the hardware of a platform, built a simulation platform based on ROS (Robot Operating System), and designed the actual software control framework. Finally, the feasibility of the platform design was verified by the coupling motion experiment of the two robots. Results:  We have established a simulation of the dual-arm mobile platform in ROS, designed the actual software control framework, and verified the feasibility of the platform design through experiments. Conclusions:  The mobile platform can meet a variety of application requirements and lay the foundation for subsequent development.


2022 ◽  
Vol 12 ◽  
Author(s):  
Mei Ying Xuan ◽  
Shang Guo Piao ◽  
Jun Ding ◽  
Qi Yan Nan ◽  
Mei Hua Piao ◽  
...  

Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, offers renoprotection in diabetes. However, potential for use in nondiabetic kidney disease remains unknown. Herein, we assessed whether dapagliflozin alleviates renal fibrosis by interfering with necroinflammation in a rat model of unilateral ureteral obstruction (UUO) and in vitro. After induction of UUO, rats were administered dapagliflozin daily for seven consecutive days. UUO induced significant renal tubular necrosis and overexpression of RIP1-RIP3-MLKL axis proteins; these coincided with NLRP3 inflammasome activation, and subsequent development of renal fibrosis. Oxidative stress caused by UUO is tightly associated with endoplasmic reticulum stress and mitochondrial dysfunction, leading to apoptotic cell death through Wnt3α/β-catenin/GSK-3β signaling; all of which were abolished by both dapagliflozin and specific RIP inhibitors (necrostatin-1 and GSK872). In H2O2-treated HK-2 cells, dapagliflozin and RIP inhibitors suppressed overexpression of RIP1-RIP3-MLKL proteins and pyroptosis-related cytokines, decreased intracellular reactive oxygen species production and apoptotic cell death, whereas cell viability was improved. Moreover, activated Wnt3α/β-catenin/GSK-3β signaling was inhibited by dapagliflozin and Wnt/β-catenin inhibitor ICG-001. Our findings suggest that dapagliflozin ameliorates renal fibrosis by inhibiting RIP1-RIP3-MLKL-mediated necroinflammation via Wnt3α/β-catenin/GSK-3β signaling in UUO.


Healthcare ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 102
Author(s):  
Sun-Hee Lee ◽  
Ickpyo Hong ◽  
Hae Yean Park

Play has been used as an intervention or evaluation tool for children. Developing a social play evaluation tool can provide clinical criteria for intervening in social play. We aimed to develop a social play evaluation tool for preschool children based on Parten’s stages of development. We tested the construct validity of the scale using confirmatory factor analysis and Rasch analysis, and the known-groups validity by examining the Rasch-calibrated mean score differences across age groups. A total of 40 preliminary items—17 items for associative play and 23 items for cooperative play—were examined. There were significant differences in the scores for associative play between ages 3 and 6 (F = 2.65, p = 0.049), and for cooperative play between ages 3 and 5, 3 and 6, and 4 and 6 (F = 10.44, p < 0.0001). The findings could contribute to subsequent development and validation of occupational therapy programs on play.


2022 ◽  
Author(s):  
Xiaomin Zhang ◽  
Chuanzhen Zheng ◽  
Kaixuan Wang ◽  
Kailei Guo ◽  
Qingqin Tao ◽  
...  

Abstract IntroductionThe aim of this study was to report the clinical profile and outcomes of retinal pigment epithelial detachment (PED) in Vogt-Koyanagi-Harada (VKH) disease, and to evaluate the correlation between PED and the subsequent development of central serous chorioretinopathy (CSC) throughout the whole corticosteroid treatment course.materials and methodsA total of 470 eyes with VKH were reviewed, and 12 eyes with VKH and PED were recruited. Patients were divided into two groups according to the CSC onset or not throughout the whole course (CSC group and non-CSC group). Best-corrected visual acuity (BCVA) improvement, and PED angle (PEDA, the angle between the two lines of the vertex of the lifted retinal pigment epithelium to the two edge points of the Bruch membrane) were compared between the two groups.ResultsThe prevalence of PED and CSC in VKH was 2.55% (12/470) and 1.06% (5/470), respectively. BCVA improvement in the non-CSC group was greater than that in the CSC group, but without a statistical difference (P=0.25). PEDA was significantly smaller in the CSC group than in the non-CSC group (P=0.03).DiscussionPEDA is an ideal parameter to reflect hydrostatic pressure and stretches for RPE. As PED predisposes to the development of CSC in selected VKH eyes, PEDA may be a valuable predictive factor for the development of CSC in VKH patients.


2022 ◽  
Vol 1 ◽  
Author(s):  
Yusuke Higuchi ◽  
Jun-ichirou Yasunaga ◽  
Masao Matsuoka

Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia-lymphoma (ATL) and inflammatory diseases including HTLV-1-associated myelopathy (HAM). A remarkable feature of HTLV-1 is that this virus transmits primarily through cell-to-cell contact. HTLV-1 increases the number of infected cells in vivo to ensure its survival and transmission. Therefore, survival of HTLV-1-infected cells in vivo is very critical for transmission under the host immune surveillance. HTLV-1 possesses multiple strategies to evade host immune responses. Among viral genes, Tax and HTLV-1 bZIP factor (HBZ) play crucial roles in the proliferation of infected cells and the subsequent development of ATL. Although Tax strongly activates the NF-kB pathway, the immunogenicity of Tax is very high; it is a major target of cytotoxic T lymphocytes. Therefore, the virus minimizes Tax production, expressing it only intermittently in vivo. On the other hand, the immunogenicity of HBZ is low, and its expression is maintained in all ATL cases. HBZ transforms the immunophenotype of infected cells into regulatory T cell-like (CD4+ CD25+ CCR4+ TIGIT+ Foxp3+), and promotes the production of immunosuppressive cytokines. Furthermore, HBZ mRNA not only encodes the protein but also functions itself like long non-coding RNA. As a result, Tax and HBZ enable long-term escape from host immunity, persistent infection, and proliferation of infected cells. Here, we review the viral strategies to counteract to host immune surveillance system.


2022 ◽  
pp. 91-118
Author(s):  
Paulo Botelho Pires ◽  
António Correia Barros

This case traces the life of a new endeavor, starting with a small patisserie and coffeehouse and the subsequent development of the business, considering three alternatives, namely optimizing the concept, expanding through a franchise network, and building a network of company-owned stores. The story of Rui and Joana raises a wide range of issues that managers need to address. After reading and working through the case, students will be able to evaluate the product portfolio, based on actual sales data, and to evaluate and propose strategic options using classical models.


2022 ◽  
Author(s):  
Michael D Kessler ◽  
Amy Damask ◽  
Sean O'Keeffe ◽  
Michael Michael Van Meter ◽  
Nilanjana Banerjee ◽  
...  

Clonal hematopoiesis (CH) refers to the expansion of certain blood cell lineages and has been associated with aging and adverse health outcomes. Here, we use exome sequence data on 628,388 individuals to identify 40,208 carriers of clonal hematopoiesis of indeterminate potential (CHIP). Using genome-wide and exome-wide association analyses, we identify 27 loci (24 novel) where germline genetic variation influences CH/CHIP predisposition, including missense variants in the DNA-repair gene PARP1 and the lymphocytic antigen coding gene LY75 that are associated with reduced incidence of CH/CHIP. Analysis of 5,194 health traits from the UK Biobank (UKB) found relationships between CHIP and severe COVID outcomes, cardiovascular disease, hematologic traits, malignancy, smoking, obesity, infection, and all-cause mortality. Longitudinal analyses revealed that one of the CHIP subtypes, DNMT3A-CHIP, is associated with the subsequent development of myeloid but not lymphoid leukemias, and with solid cancers including prostate and lung. Additionally, contrary to previous findings from the initial 50,000 UKB exomes, our results in the full sample do not support a role for IL-6 inhibition in reducing the risk of cardiovascular disease among CHIP carriers. Our findings demonstrate that CHIP represents a complex set of heterogenous phenotypes with shared and unique germline genetic causes and varied clinical implications.


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