815 research outputs found

    circRAB3IP modulates cell proliferation by reorganizing gene expression and mRNA processing in a paracrine manner

    No full text
    Circular RNAs are an endogenous long-lived and abundant noncoding species. Despite their prevalence, only a few circRNAs have been dissected mechanistically to date. Here, we cataloged nascent RNA-enriched circRNAs from primary human cells and functionally assigned a role to circRAB3IP in sustaining cellular homeostasis. We combined “omics” and functional experiments to show how circRAB3IP depletion deregulates hundreds of genes, suppresses cell cycle progression, and induces senescence-associated gene expression changes. Conversely, excess circRAB3IP delivered to endothelial cells via extracellular vesicles suffices for accelerating their division. We attribute these effects to an interplay between circRAB3IP and the general splicing factor SF3B1, which can affect transcript variant expression levels of cell cycle–related genes. Together, our findings link the maintenance of cell homeostasis to the presence of a single circRNA.</jats:p

    Phosphorylation of Ykt6 SNARE Domain Regulates Its Membrane Recruitment and Activity

    No full text
    Sensitive factor attachment protein receptors (SNARE) proteins are important mediators of protein trafficking that regulate the membrane fusion of specific vesicle populations and their target organelles. The SNARE protein Ykt6 lacks a transmembrane domain and attaches to different organelle membranes. Mechanistically, Ykt6 activity is thought to be regulated by a conformational change from a closed cytosolic form to an open membrane-bound form, yet the mechanism that regulates this transition is unknown. We identified phosphorylation sites in the SNARE domain of Ykt6 that mediate Ykt6 membrane recruitment and are essential for cellular growth. Using proximity-dependent labeling and membrane fractionation, we found that phosphorylation regulates Ykt6 conversion from a closed to an open conformation. This conformational switch recruits Ykt6 to several organelle membranes, where it functionally regulates the trafficking of Wnt proteins and extracellular vesicle secretion in a concentration-dependent manner. We propose that phosphorylation of its SNARE domain leads to a conformational switch from a cytosolic, auto-inhibited Ykt6 to an active SNARE at different membranes

    Khuralgarh Sahib: A Pilgrimage Destination for Adi Dharm Followers

    No full text
    In the 1920s, a protest movement named Ad(i) Dhar(a)m, or Original Religion, emerged in the British province of Punjab with the aim of establishing a religious identity for the untouchable castes and low-caste people, basically from the Sikh community. The Adi Dharmis venerated Sant (Saint) Ravidas, a medieval mystic poet, a Chamar or tanner by origin. The list of their gurus also included Maharishi Valmiki, the legendary first poet — Adi Kavi, or the author of Ramayana, as well as two low-caste Bhakti poets — Kabir and Namdev. The colonial Census of 1931 listed Adi Dharm as a new religion boasting over 420,000 followers; in subsequent censuses, Adi Dharm was listed as a caste. By the mid-1940s, the protest movement subsided, but in the 1970s it came back to life mainly due to the efforts of Punjabi diaspora. Its revival was also linked to the socio-political activities of Dalits (the downtrodden) in India, especially in Punjab where Scheduled Castes account for over 30 percent of the population nowadays. The current phase of the Adi Dharm history is associated with the activities of the All-India Adi Dharm Mission; its main temple is located in at foothills of the Himalayas in the village of Kharali in the district Hoshiarpur, Punjab. This paper presents a brief overview of the Adi Dharm history and highlights the role of the Khuralgarh Sahib pilgrimage site in maintaining and boosting the Adi Dharm religious identity in present-day Punjab and beyond

    ؟adi as a Discourse Marker in Spoken Iraqi Arabic

    No full text
    The linguistic element ؟adi is extensively employed in the variety of Arabic spoken in Iraq to aid in communication and facilitate the cohesion and flow of conversation. ؟adi which roughly means no worries, okay, how dare you?, yeah I hear you, or I've gone through the same thing myself, displays properties typically displayed by discourse markers. For example, it occurs phrase-initially or phrase-finally, it is a grammatically optional lexical item, it is multi-functional and it is an essential feature of spontaneous oral discourse … oral - rather than formal written - discourse among Iraqi speakers of Arabic. The aim of this paper is to investigate the use of ؟adi, its distribution and its varied context-dependent meanings and functions. The description and investigation are based largely on speech samples which the author recorded.  These recordings were then transcribed and analyzed in order to identify the functions associated with ؟adi from a discourse analytical perspective

    PERANCANGAN SISTEM AKUNTANSI PENJUALAN KREDIT PADA CV. SURYA ADI PRATAMA PALEMBANG

    No full text
    THE DESIGN OF ACCOUNTING SYSTEMS CREDIT SALES AT CV. SURYA ADI PRATAMA PALEMBANG. Herlina Septiani, 2015 (xiii + 72 pages) [email protected] Writing the final report is aimed at designing accounting system to credit sales at CV. Surya Adi Pratama Palembang. CV. Surya Adi Pratama Palembang engaged in the invitation printing and the printing of school supplies such as school report and others. Data used by the author in this report are related to the primary data in the form of interviews and the distribution of questionnaires on pimpiman and employees CV. Adi Surya Pratama Palembang and secondary data in the form of a general overview of the company. Based on observations by the author, the accounting system in CV. Adi Surya Pratama Palembang has not been well designed that documents used in connection with the sale of credit is not yet complete, that a number of functions, and the absence of the credit function. Based on observations, the accounting system at CV. Surya Adi Pratama Palembang has not yet well designed. To improve the information generated by the accounting system at CV. Surya Adi Pratama Palembang, the authors designed the accounting system includes the design-related functions, documents, records, network procedures that make up the system, as well as the design flow chart of credit sales accounting system in CV. Adi Surya Pratama Palembang

    The Ceramide-Dependent EV Secretome Differentially Affects Prostate Cancer Cell Migration

    No full text
    Tumor-derived extracellular vesicles (EVs) play an important role in cancer progression. Neutral sphingomyelinases (nSMases) are lipid-modifying enzymes that modulate the secretion of EVs from cells. How nSMase activity and therefore ceramide generation affect the composition and functionality of secreted EVs is not fully understood. Here, we aimed to investigate the expression of nSMases 1 and 2 in prostate cancer (PCa) tissue and their role in EV composition and secretion for prostate cancer cell migration. Reduced nSMase 1 and 2 expression was found in prostate cancer and correlated with the age of the patient. When nSMase 2 was inhibited by GW4869 in PCa cells (PC3 and DU145), the EV secretome was significantly altered, while the number of EVs and the total protein content of released EVs were not significantly changed. Using proteomic analysis, we found that extracellular matrix proteins, such as SDC4 (Syndecan-4) and SRPX-2, were differentially secreted on EVs from GW4869-treated PC3 cells. In scratch wound migration assays, GW4869 significantly increased migration compared to control PC3 cells but not DU145 cells, while SDC4 knockdown significantly reduced the migration of PC3 cells. These and other nSMase-2-dependent secreted proteins are interesting candidates for understanding the role of stress-induced EVs in the progression of prostate cancer

    Perancangan Sistem Informasi Akuntansi Persediaan Pada CV Adi Putra Utama Menggunakan Microsoft Access

    No full text
    The purpose of this paper is to develop an inventory accounting information system at CV Adi Putra Utama using Microsoft Access. Warehouse computerization is very important for CV Adi Putra Utama to optimize inventory recording. The focus of the analysis in this final report is on the incoming and outgoing office supplies at CV Adi Putra Utama. System comparison is done by comparing the manual system currently used with the accounting information system analyzed by the author. Based on the available data, the author identified several problems, including frequent loss of inventory data because the company still uses manual methods in folio bookkeeping. The output of this design is in the form of warehouse cards, warehouse receipt and warehouse expenditure reports, and inventory reports that support CV Adi Putra Utama's business activities
    corecore