Distinct TORC1 signalling branches regulate Adc17 proteasome assembly chaperone expression.

When stressed, cells need to adapt their proteome to maintain protein homeostasis. This requires increased proteasome assembly. Increased proteasome assembly is dependent on increased production of proteasome assembly chaperones.

Translation regulation in response to stress.

Cell stresses occur in a wide variety of settings: in disease, during industrial processes, and as part of normal day-to-day rhythms. Adaptation to these stresses requires cells to alter their proteome. Cells modify the proteins they synthesize to aid proteome adaptation.

Proteasome assembly chaperone translation upon stress requires Ede1 phase separation at the plasma membrane.

Proteome adaptation is key to cells surviving stresses. Increased translation of proteasome assembly chaperones (PACs) is critical for increasing proteasome assembly and cell degradative capacity. The endocytic protein Ede1 recruits PAC mRNA to cortical actin patches in for translation upon stress.

The ribosome-associated chaperone Zuo1 controls translation upon TORC1 inhibition.

Protein requirements of eukaryotic cells are ensured by proteostasis, which is mediated by tight control of TORC1 activity. Upon TORC1 inhibition, protein degradation is increased and protein synthesis is reduced through inhibition of translation initiation to maintain cell viability. Here, we show that the ribosome-associated complex (RAC)/Ssb chaperone system, composed of the HSP70 chaperone Ssb and its HSP40 co-chaperone Zuo1, is required to maintain proteostasis and cell viability under TORC1 inhibition in Saccharomyces cerevisiae.

Actin dynamics in protein homeostasis.

Cell homeostasis is maintained in all organisms by the constant adjustment of cell constituents and organisation to account for environmental context. Fine-tuning of the optimal balance of proteins for the conditions, or protein homeostasis, is critical to maintaining cell homeostasis. Actin, a major constituent of the cytoskeleton, forms many different structures which are acutely sensitive to the cell environment.

Actin remodelling controls proteasome homeostasis upon stress.

When cells are stressed, bulk translation is often downregulated to reduce energy demands while stress-response proteins are simultaneously upregulated. To promote proteasome assembly and activity and maintain cell viability upon TORC1 inhibition, 19S regulatory-particle assembly chaperones (RPACs) are selectively translated. However, the molecular mechanism for such selective translational upregulation is unclear.

Living on soup: macropinocytic feeding in amoebae.

Macropinocytosis is used by a variety of amoebae for feeding on liquid medium. The amoebae project cups and ruffles from their plasma membrane, driven by actin polymerization, and eventually fuse these back to the membrane, entrapping droplets of medium into internal vesicles. These vesicles are of up to several microns in diameter and are processed through the lysosomal digestive system to extract nutrients.

Adding proactive and reactive case detection into the integrated community case management system to optimise diagnosis and treatment of malaria in a high transmission setting of Cameroon: an observational quality improvement study.

Objective: Integrated community case management (iCCM) of childhood illness is a powerful intervention to reduce mortality. Yet, only 29% and 59% of children with fever in sub-Saharan Africa had access to malaria testing and treatment between 2015 and 2017. We report how iCCM+ based on incorporating active case detection of malaria into iCCM could help improve testing and treatment.

Function of small GTPases in Dictyostelium macropinocytosis.

Macropinocytosis-the large-scale, non-specific uptake of fluid by cells-is used by Dictyostelium discoideum amoebae to obtain nutrients. These cells form circular ruffles around regions of membrane defined by a patch of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) and the activated forms of the small G-proteins Ras and Rac. When this ruffle closes, a vesicle of the medium is delivered to the cell interior for further processing.

Genetic Engineering of Dictyostelium discoideum Cells Based on Selection and Growth on Bacteria.

Dictyostelium discoideum is an intriguing model organism for the study of cell differentiation processes during development, cell signaling, and other important cellular biology questions. The technologies available to genetically manipulate Dictyostelium cells are well-developed. Transfections can be performed using different selectable markers and marker re-cycling, including homologous recombination and insertional mutagenesis.

Akt and SGK protein kinases are required for efficient feeding by macropinocytosis.

Macropinocytosis is an actin-driven process of large-scale and non-specific fluid uptake used for feeding by some cancer cells and the macropinocytosis model organism In , macropinocytic cups are organized by 'macropinocytic patches' in the plasma membrane. These contain activated Ras, Rac and phospholipid PIP3, and direct actin polymerization to their periphery. We show that a Akt (PkbA) and an SGK (PkbR1) protein kinase act downstream of PIP3 and, together, are nearly essential for fluid uptake.

The Atypical MAP Kinase ErkB Transmits Distinct Chemotactic Signals through a Core Signaling Module.

Signaling from chemoattractant receptors activates the cytoskeleton of crawling cells for chemotaxis. We show using phosphoproteomics that different chemoattractants cause phosphorylation of the same core set of around 80 proteins in Dictyostelium cells. Strikingly, the majority of these are phosphorylated at an [S/T]PR motif by the atypical MAP kinase ErkB.

Feasibility of integrating HIV testing into local youth development p rogrammes in Cameroon.

Many young people do not know their HIV status in sub-Saharan Africa where it is estimated that only 10% of young men and 15% of young women know their HIV status. In a rural community in Cameroon, we present a collaborative project that has successfully nested HIV testing for youths into a youth life skills development programme run by youths themselves with support from various local government services and private organisations. We tested 2024 clients, including 1623 (80%) aged ≤35 years, of whom 839 (51.

Rapid and efficient genetic engineering of both wild type and axenic strains of Dictyostelium discoideum.

Dictyostelium has a mature technology for molecular-genetic manipulation based around transfection using several different selectable markers, marker re-cycling, homologous recombination and insertional mutagenesis, all supported by a well-annotated genome. However this technology is optimized for mutant, axenic cells that, unlike non-axenic wild type, can grow in liquid medium. There is a pressing need for methods to manipulate wild type cells and ones with defects in macropinocytosis, neither of which can grow in liquid media.

Amplification of PIP3 signalling by macropinocytic cups.

In a role distinct from and perhaps more ancient than that in signal transduction, PIP3 and Ras help to spatially organize the actin cytoskeleton into macropinocytic cups. These large endocytic structures are extended by actin polymerization from the cell surface and have at their core an intense patch of active Ras and PIP3, around which actin polymerizes, creating cup-shaped projections. We hypothesize that active Ras and PIP3 self-amplify within macropinocytic cups, in a way that depends on the structural integrity of the cup.

The physiological regulation of macropinocytosis during growth and development.

Macropinocytosis is a conserved endocytic process used by amoebae for feeding on liquid medium. To further as a model for macropinocytosis, we developed a high-throughput flow cytometry assay to measure macropinocytosis, and used it to identify inhibitors and investigate the physiological regulation of macropinocytosis. has two feeding states: phagocytic and macropinocytic.

A plasma membrane template for macropinocytic cups.

Macropinocytosis is a fundamental mechanism that allows cells to take up extracellular liquid into large vesicles. It critically depends on the formation of a ring of protrusive actin beneath the plasma membrane, which develops into the macropinocytic cup. We show that macropinocytic cups in are organised around coincident intense patches of PIP, active Ras and active Rac.

Electronic tagging and population structure of Atlantic bluefin tuna.

Electronic tags that archive or transmit stored data to satellites have advanced the mapping of habitats used by highly migratory fish in pelagic ecosystems. Here we report on the electronic tagging of 772 Atlantic bluefin tuna in the western Atlantic Ocean in an effort to identify population structure. Reporting electronic tags provided accurate location data that show the extensive migrations of individual fish (n = 330).

Intramuscular anesthesia of bonito and Pacific mackerel with ketamine and medetomidine and reversal of anesthesia with atipamezole.

Objective: To determine anesthetic effects of ketamine and medetomidine in bonitos and mackerels and whether anesthesia could be reversed with atipamezole.

Design: Clinical trial.

Animals: 43 bonitos (Sarda chiliensis) and 47 Pacific mackerels (Scomber japonica).

In situ cardiac performance of Pacific bluefin tuna hearts in response to acute temperature change.

This study reports the cardiovascular physiology of the Pacific bluefin tuna (Thunnus orientalis) in an in situ heart preparation. The performance of the Pacific bluefin tuna heart was examined at temperatures from 30 degrees C down to 2 degrees C. Heart rates ranged from 156 beats min(-1) at 30 degrees C to 13 beats min(-1) at 2 degrees C.

HIPAA...one size does not necessarily fit all.

HIPPA is an important piece of legislation that will affect agency operations, clinical practice, regulatory compliance, and patient care. This article gives you the foundation needed to understand how HIPPA will affect you!

Influence of age, sex, capture technique, and restraint on hematologic measurements and serum chemistries of wild California sea otters.

Hematologic and/or serum chemical analyses were done on a total of 27 non-tranquilized adult and juvenile wild sea otters, 66 tranquilized adult and juvenile wild sea otters, and 26 wild sea otter pups. The median and inner 90 percentile range were determined for the adult, juvenile, and pup groups and for the following subgroups: adult male versus adult female, juvenile male versus juvenile female, pup male versus pup female, captured with dip net versus captured with Wilson trap, and tranquilized adults and juveniles versus non-tranquilized adults and juveniles. When values for adults were compared to values for juveniles and pups, hematocrits, red blood cell counts, and hemoglobin levels were significantly lower in pups.