PLCε1 suppresses tumor growth by regulating murine T cell mobilization

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154282/1/cei13409.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154282/2/cei13409_am.pd

Structure-Function Analysis of Nucleolin and ErbB Receptors Interactions

The ErbB receptor tyrosine kinases and nucleolin are major contributors to malignant transformation. Recently we have found that cell-surface ErbB receptors interact with nucleolin via their cytoplasmic tail. Overexpression of ErbB1 and nucleolin leads to receptor phosphorylation, dimerization and anchorage independent growth.In the present study we explored the regions of nucleolin and ErbB responsible for their interaction. Using mutational analyses, we addressed the structure–function relationship of the interaction between ErbB1 and nucleolin. We identified the ErbB1 nuclear localization domain as nucleolin interacting region. This region is important for nucleolin-associated receptor activation. Notably, though the tyrosine kinase domain is important for nucleolin-associated receptor activation, it is not involved in nucleolin/ErbB interactions. In addition, we demonstrated that the 212 c-terminal portion of nucleolin is imperative for the interaction with ErbB1 and ErbB4. This region of nucleolin is sufficient to induce ErbB1 dimerization, phosphorylation and growth in soft agar.The oncogenic potential of ErbB depends on receptor levels and activation. Nucleolin affects ErbB dimerization and activation leading to enhanced cell growth. The C-terminal region of nucleolin and the ErbB1 NLS-domain mediate this interaction. Moreover, when the C-terminal 212 amino acids region of nucleolin is expressed with ErbB1, it can enhance anchorage independent cell growth. Taken together these results offer new insight into the role of ErbB1 and nucleolin interaction in malignant cells

Progress on Gust Load Alleviation Wind Tunnel Experiment and Aeroservoelastic Model Validation for a Flexible Wing with Variable Camber Continuous Trailing Edge Flap System

This paper discusses a wind tunnel experiment of active gust load alleviation of a flexible wing which took place at University of Washington (UW) in 2019. The experiment performed under a NASA SBIR contract with Scientific Systems Company, Inc (SSCI). The objective of the experiment is to demonstrate active controls of the Variable Camber Continuous Trailing Edge Flap (VCCTEF) system for gust load alleviation and real-time drag optimization. The wind tunnel model is a 8.2% sub-scale Common Research Model (CRM) wing. The wing structure is designed to provide a substantial degree of flexibility to represent that of a modern high-aspect ratio wing. Eight active control surfaces are employed in the VCCTEF. A new gust generator system was designed and installed by UW under a sub-contract with SSCI. The first test entry started in July 2019 and ended in September 2019. During this test entry, many significant issues were found with the hardware and software. The significant issues with the servos prevented the test objective from being completed. A follow-up second test entry in 2020 is being planned. The wing system is being repaired by SSCI. This paper reports on the progress of this experimental effort and the aeroservoelastic (ASE) model validation which was conducted during the test entry

Rap1-interacting adapter molecule (RIAM) associates with the plasma membrane via a proximity detector

Adaptive immunity depends on lymphocyte adhesion that is mediated by the integrin lymphocyte functional antigen 1 (LFA-1). The small guanosine triphosphatase Rap1 regulates LFA-1 adhesiveness through one of its effectors, Rap1-interacting adapter molecule (RIAM). We show that RIAM was recruited to the lymphocyte plasma membrane (PM) through its Ras association (RA) and pleckstrin homology (PH) domains, both of which were required for lymphocyte adhesion. The N terminus of RIAM inhibited membrane translocation. In vitro, the RA domain bound both Rap1 and H-Ras with equal but relatively low affinity, whereas in vivo only Rap1 was required for PM association. The PH domain bound phosphoinositol 4,5-bisphosphate (PI(4,5)P2) and was responsible for the spatial distribution of RIAM only at the PM of activated T cells. We determined the crystal structure of the RA and PH domains and found that, despite an intervening linker of 50 aa, the two domains were integrated into a single structural unit, which was critical for proper localization to the PM. Thus, the RA-PH domains of RIAM function as a proximity detector for activated Rap1 and PI(4,5)P2

Borg : the next generation

This paper analyzes a newly-published trace that covers 8 different Borg [35] clusters for the month of May 2019. The trace enables researchers to explore how scheduling works in large-scale production compute clusters. We highlight how Borg has evolved and perform a longitudinal comparison of the newly-published 2019 trace against the 2011 trace, which has been highly cited within the research community. Our findings show that Borg features such as alloc sets are used for resource-heavy workloads; automatic vertical scaling is effective; job-dependencies account for much of the high failure rates reported by prior studies; the workload arrival rate has increased, as has the use of resource over-commitment; the workload mix has changed, jobs have migrated from the free tier into the best-effort batch tier; the workload exhibits an extremely heavy-tailed distribution where the top 1% of jobs consume over 99% of resources; and there is a great deal of variation between different clusters.Publisher PD

Hubungan bentuk lutut terhadap risiko cedera patellofemoral pain syndrome pada pemain futsal putri

Latar Belakang : Futsal putri di Indonesia telah berkembang dan memiliki banyak peminat. Olahraga futsal ini memiliki gerakan yang komplit dan menuntut mobilitas yang tinggi, maka dalam olahraga ini sering sekali terjadi cedera maka tingkat resiko cedera pada olahraga futsal sering terjadi pada atlet futsal dimana terdapat banyak gerakan yang sering menyebabkan cedera olahraga seperti patellofemoral pain syndrome. Patellofemoral pain syndrome dipengaruhi oleh beberapa faktor, salah satunya adalah bentuk lutut Tujuan : Untuk mengetahui hubungan bentuk lutut terhadap risiko cedera patellofemoral pain syndrome pada pemain futsal putri. Metode : Penelitian ini adalah penelitian observasional dengan pendekatan cross sectional. Populasi dalam penelitian ini sebanyak 34 pemain futsal putri dan menggunakan teknik total sampling. Variabel penelitian terdiri dari variabel independen yaitu bentuk lutut dengan menggunakan pengukuran apecs posture analysis, dan variabel dependen yaitu resiko cedera patellofemoral pain syndrome dengan menggunakan pengukuran pattelar apprehension test. Teknik analisis data yang digunakan adalah uji korelasi rank spearman menggunakan bantuan softwere SPSS for windows versi 26. Hasil : Ada hubungan yang signifikan antara bentuk lutut terhadap resiko cedera patellofemoral pain syndrome dengan nilai p= 0,000 (p<0,05). Kesimpulan : Ada hubungan yang signifikan antara bentuk lutut terhadap resiko cedera patellofemoral pain syndrome pada pemain futsal putri. Saran : Peneliti berikutnya diasarnkan untuk melakukan penelitian dengan jumlah sampel yang lebih banyak dan jangka waktu yang panjang, selain itu tentang faktor lain yang dapat mempengaruhi terjadinya patellofemoral pain syndrome

PKC Regulates a Farnesyl-Electrostatic Switch on K-Ras that Promotes its Association with Bcl-Xl on Mitochondria and Induces Apoptosis

K-Ras associates with the plasma membrane (PM) through farnesylation that functions in conjunction with an adjacent polybasic sequence. We show that phosphorylation by protein kinase C (PKC) of S181 within the polybasic region promotes rapid dissociation of K-Ras from the PM and association with intracellular membranes, including the outer membrane of mitochondria where phospho-K-Ras interacts with Bcl-Xl. PKC agonists promote apoptosis of cells transformed with oncogenic K-Ras in a S181-dependent manner. K-Ras with a phosphomimetic residue at position 181 induces apoptosis via a pathway that requires Bcl-Xl. The PKC agonist bryostatin-1 inhibited the growth in vitro and in vivo of cells transformed with oncogenic K-Ras in a S181-dependent fashion. These data demonstrate that the location and function of K-Ras are regulated directly by PKC and suggest an approach to therapy of K-Ras-dependent tumors with agents that stimulate phosphorylation of S18

The Chloroplast Envelope Protease FTSH11 – Interaction With CPN60 and Identification of Potential Substrates

FTSH proteases are membrane-bound, ATP-dependent metalloproteases found in bacteria, mitochondria and chloroplasts. The product of one of the 12 genes encoding FTSH proteases in Arabidopsis, FTSH11, has been previously shown to be essential for acquired thermotolerance. However, the substrates of this protease, as well as the mechanism linking it to thermotolerance are largely unknown. To get insight into these, the FTSH11 knockout mutant was complemented with proteolytically active or inactive variants of this protease, tagged with HA-tag, under the control of the native promoter. Using these plants in thermotolerance assay demonstrated that the proteolytic activity, and not only the ATPase one, is essential for conferring thermotolerance. Immunoblot analyses of leaf extracts, isolated organelles and sub-fractionated chloroplast membranes localized FTSH11 mostly to chloroplast envelopes. Affinity purification followed by mass spectrometry analysis revealed interaction between FTSH11 and different components of the CPN60 chaperonin. In affinity enrichment assays, CPN60s as well as a number of envelope, stroma and thylakoid proteins were found associated with proteolytically inactive FTSH11. Comparative proteomic analysis of WT and knockout plants, grown at 20°C or exposed to 30°C for 6 h, revealed a plethora of upregulated chloroplast proteins in the knockout, some of them might be candidate substrates. Among these stood out TIC40, which was stabilized in the knockout line after recovery from heat stress, and three proteins that were found trapped in the affinity enrichment assay: the nucleotide antiporter PAPST2, the fatty acid binding protein FAP1 and the chaperone HSP70. The consistent behavior of these four proteins in different assays suggest that they are potential FTSH11 substrates