Novel regulation of Ras proteins by direct tyrosine phosphorylation and dephosphorylation

Somatic mutations in the RAS genes are frequent in human tumors, especially in pancreatic, colorectal, and non-small-cell lung cancers. Such mutations generally decrease the ability of Ras to hydrolyze GTP, maintaining the protein in a constitutively active GTP-bound form that drives uncontrolled cell proliferation. Efforts to develop drugs that target Ras oncoproteins have been unsuccessful. Recent emerging data suggest that Ras regulation is more complex than the scientific community has believed for decades. In this review, we summarize advances in the "textbook" view of Ras activation. We also discuss a novel type of Ras regulation that involves direct phosphorylation and dephosphorylation of Ras tyrosine residues. The discovery that pharmacological inhibition of the tyrosine phosphoprotein phosphatase SHP2 maintains mutant Ras in an inactive state suggests that SHP2 could be a novel drug target for the treatment of Ras-driven human cancers

Pengaruh Hidrolisis Menggunakan Asam Sulfat pada Karakteristik Micro-fibrillated Cellulose (MFC) dari Serat Tandan Kosong Kelapa Sawit (TKKS) sebagai Agen Nukleasi

Micro-fibrillated cellulose (MFC) dapat diproduksi dari ekstraksi serat Tandan Kosong Kelapa Sawit (TKKS) melalui proses alkalinisasi, oksidasi H2O2, dan hidrolisis asam. Tujuan dari penelitian ini adalah untuk mengetahui pengaruh waktu reaksi terhadap proses hidrolisis H2SO4. MFC dibuat dengan proses alkalinisasi menggunakan natrium hidroksida (NaOH) 4% pada suhu 90 °C selama 2 jam, oksidasi H2O2 20% pada suhu kamar selama 2 jam, dan hidrolisis H2SO4 pada suhu kamar. Hidrolisis asam dilakukan menggunakan H2SO4 20% dengan variasi waktu reaksi 1 jam, 2 jam, dan 3 jam. MFC dianalisis menggunakan Fourier Transform Infrared Spectroscopy (FTIR), X-Ray Difraction (XRD), dan Thermal Gravimetric Analysis (TGA). Analisis FTIR menunjukkan bahwa terjadi penurunan konsentrasi lignin dan selulosa, analisis TGA menunjukkan stabilitas termal pada waktu reaksi 3 jam lebih tinggi dibandingkan waktu reaksi lainnya, dan analisis XRD menunjukkan bahwa semakin lama waktu hidrolisis H2SO4 terjadi kecenderungan persentase kristalisasi meningkat. Dari hasil yang diperoleh, MFC dari serat TKKS memiliki potensi untuk digunakan sebagai agen nukleasi dalam polimer

Processor Design for Portable Systems

: Processors used in portable systems must provide highly energy-efficient operation, due to the importance of battery weight and size, without compromising high performance when the user requires it. The user-dependent modes of operation of a processor in portable systems are described and separate metrics for energy efficiency for each of them are found to be required. A variety of well known low-power techniques are re-evaluated against these metrics and in some cases are not found to be appropriate leading to a set of energy-efficient design principles. Also, the importance of idle energy reduction and the joint optimization of hardware and software will be examined for achieving the ultimate in lowenergy, high-performance design. 1. Introduction The recent explosive growth in portable electronics requires energy conscious design, without sacrificing performance. Simply increasing the battery capacity is not sufficient because the battery has become a significant fraction of the t..

From sovereignty in Australia to Australian sovereignty

The article argues that sovereignty in Australia is as yet incomplete, but that full sovereignty could be achieved through engagement with the indigenous Aboriginal 'first nations'. First, the inter-constitution of the concepts of sovereignty and politics is outlined. Then the unfinished character of sovereignty since white settlement is examined, indicating the default nature of the sovereignty settlement. The challenge arising from complex indigenous claims to sovereignty is then explored through two elements of a differend, or power differential, which has excluded indigenous peoples from meaningful recognition as political actors. The meaning of sovereignty in the broad field of indigenous claims is then analysed. Finally, a proposal for constitutional amendment is outlined, building both upon Aboriginal self-understandings as belonging to specific nations and groups and upon the logic of the history of white settlement. Constitutional revision which takes account of these histories provides an opportunity to extend the scope of the parties who are federated. Such a process could stimulate debate that generates a meaningful Australian sovereignty settlement identity for both indigenous and non-indigenous communities

A UVB-responsive common variant at chromosome band 7p21.1 confers tanning response and melanoma risk via regulation of the aryl hydrocarbon receptor, AHR

Genome-wide association studies (GWASs) have identified a melanoma-associated locus on chromosome band 7p21.1 with rs117132860 as the lead SNP and a secondary independent signal marked by rs73069846. rs117132860 is also associated with tanning ability and cutaneous squamous cell carcinoma (cSCC). Because ultraviolet radiation (UVR) is a key environmental exposure for all three traits, we investigated the mechanisms by which this locus contributes to melanoma risk, focusing on cellular response to UVR. Fine-mapping of melanoma GWASs identified four independent sets of candidate causal variants. A GWAS region-focused Capture-C study of primary melanocytes identified physical interactions between two causal sets and the promoter of the aryl hydrocarbon receptor (AHR). Subsequent chromatin state annotation, eQTL, and luciferase assays identified rs117132860 as a functional variant and reinforced AHR as a likely causal gene. Because AHR plays critical roles in cellular response to dioxin and UVR, we explored links between this SNP and AHR expression after both 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and ultraviolet B (UVB) exposure. Allele-specific AHR binding to rs117132860-G was enhanced following both, consistent with predicted weakened AHR binding to the risk/poor-tanning rs117132860-A allele, and allele-preferential AHR expression driven from the protective rs117132860-G allele was observed following UVB exposure. Small deletions surrounding rs117132860 introduced via CRISPR abrogates AHR binding, reduces melanocyte cell growth, and prolongs growth arrest following UVB exposure. These data suggest AHR is a melanoma susceptibility gene at the 7p21.1 risk locus and rs117132860 is a functional variant within a UVB-responsive element, leading to allelic AHR expression and altering melanocyte growth phenotypes upon exposure

Being Ourselves, Naming Ourselves, Writing Ourselves: Indigenous Australian Women Disrupting What It Is to Be Academic Within the Academy

This chapter shares the experience of a group of Indigenous women with academic writing. In our stories, we discuss the professional and personal challenges we face as Indigenous people, as women and as academics, and most specifically as academic writers. Paramount is the difficulty of being in institutions that do not value our cultural knowledges, our ways of being, and our specific expertise. In its institutional form, the university remains largely assimilationist that denies other ways of thinking, being and writing. For us, our writing is about being resistant to that assimilation, and provides an avenue to have our voices heard, while staying strong and true to our Indigenous cultures and heritage