Dedicated chaperones coordinate co-translational regulation of ribosomal protein production with ribosome assembly to preserve proteostasis.

The biogenesis of eukaryotic ribosomes involves the ordered assembly of around 80 ribosomal proteins. Supplying equimolar amounts of assembly-competent ribosomal proteins is complicated by their aggregation propensity and the spatial separation of their location of synthesis and pre-ribosome incorporation. Recent evidence has highlighted that dedicated chaperones protect individual, unassembled ribosomal proteins on their path to the pre-ribosomal assembly site.

An ATP-dependent partner switch links flagellar C-ring assembly with gene expression.

Bacterial flagella differ in their number and spatial arrangement. In many species, the MinD-type ATPase FlhG (also YlxH/FleN) is central to the numerical control of bacterial flagella, and its deletion in polarly flagellated bacteria typically leads to hyperflagellation. The molecular mechanism underlying this numerical control, however, remains enigmatic.

Conformational proofreading of distant 40S ribosomal subunit maturation events by a long-range communication mechanism.

Eukaryotic ribosomes are synthesized in a hierarchical process driven by a plethora of assembly factors, but how maturation events at physically distant sites on pre-ribosomes are coordinated is poorly understood. Using functional analyses and cryo-EM, we show that ribosomal protein Rps20 orchestrates communication between two multi-step maturation events across the pre-40S subunit. Our study reveals that during pre-40S maturation, formation of essential contacts between Rps20 and Rps3 permits assembly factor Ltv1 to recruit the Hrr25 kinase, thereby promoting Ltv1 phosphorylation.

Tsr4 and Nap1, two novel members of the ribosomal protein chaperOME.

Dedicated chaperones protect newly synthesized ribosomal proteins (r-proteins) from aggregation and accompany them on their way to assembly into nascent ribosomes. Currently, only nine of the ∼80 eukaryotic r-proteins are known to be guarded by such chaperones. In search of new dedicated r-protein chaperones, we performed a tandem-affinity purification based screen and looked for factors co-enriched with individual small subunit r-proteins.

Nuclear import of dimerized ribosomal protein Rps3 in complex with its chaperone Yar1.

After their cytoplasmic synthesis, ribosomal proteins need to be transported into the nucleus, where they assemble with ribosomal RNA into pre-ribosomal particles. Due to their physicochemical properties, they need protection from aggregation on this path. Newly synthesized ribosomal protein Rps3 forms a dimer that is associated with one molecule of its specific chaperone Yar1.

The eukaryote-specific N-terminal extension of ribosomal protein S31 contributes to the assembly and function of 40S ribosomal subunits.

The archaea-/eukaryote-specific 40S-ribosomal-subunit protein S31 is expressed as an ubiquitin fusion protein in eukaryotes and consists of a conserved body and a eukaryote-specific N-terminal extension. In yeast, S31 is a practically essential protein, which is required for cytoplasmic 20S pre-rRNA maturation. Here, we have studied the role of the N-terminal extension of the yeast S31 protein.

Sequential domain assembly of ribosomal protein S3 drives 40S subunit maturation.

Eukaryotic ribosomes assemble by association of ribosomal RNA with ribosomal proteins into nuclear precursor particles, which undergo a complex maturation pathway coordinated by non-ribosomal assembly factors. Here, we provide functional insights into how successive structural re-arrangements in ribosomal protein S3 promote maturation of the 40S ribosomal subunit. We show that S3 dimerizes and is imported into the nucleus with its N-domain in a rotated conformation and associated with the chaperone Yar1.

Co-translational capturing of nascent ribosomal proteins by their dedicated chaperones.

Exponentially growing yeast cells produce every minute >160,000 ribosomal proteins. Owing to their difficult physicochemical properties, the synthesis of assembly-competent ribosomal proteins represents a major challenge. Recent evidence highlights that dedicated chaperone proteins recognize the N-terminal regions of ribosomal proteins and promote their soluble expression and delivery to the assembly site.

The prognostic value of plasma galectin-3 in chronic heart failure patients is maintained when treated with mineralocorticoid receptor antagonists.

Objective: Galectin-3 (Gal-3) is considered as a myocardial fibrosis biomarker with prognostic value in heart failure (HF). Since aldosterone is a neurohormone with established fibrotic properties, we aimed to investigate if mineralocorticoid receptor antagonists (MRAs) would modulate the prognostic value of Gal-3.

Methods: The IBLOMAVED cohort comprised 427 eligible chronic HF patients (CHF) with echocardiography and heart failure biomarkers assessments (BNP).

Asymptomatic anomalous origin of left anterior descending artery from the pulmonary artery and multiple atherosclerotic stenoses revealed by silent ischaemia.

Anomalous origin of the left coronary artery from the pulmonary artery is a rare congenital disease responsible for a high mortality rate in childhood. Here, we report for the first time the case of an asymptomatic 61-year old patient showing a combination of anomalous origin of the left anterior descending artery from pulmonary artery and atherosclerotic stenosis in both the right coronary artery and the left circumflex artery without anomalous origin.

Clinical significance of serum tenascin-c levels in epithelial ovarian cancer.

Tenascin-C (TNC) is an extracellular matrix protein that is expressed at low levels in normal adult tissue but is highly expressed around many tumors including ovarian tumors. The objective of this study was to determine the clinical significance of the serum levels of TNC in epithelial ovarian cancer (EOC) patients. A total of 50 patients with a pathologically confirmed diagnosis of EOC were included in this study.

Mak5 and Ebp2 act together on early pre-60S particles and their reduced functionality bypasses the requirement for the essential pre-60S factor Nsa1.

Ribosomes are the molecular machines that translate mRNAs into proteins. The synthesis of ribosomes is therefore a fundamental cellular process and consists in the ordered assembly of 79 ribosomal proteins (r-proteins) and four ribosomal RNAs (rRNAs) into a small 40S and a large 60S ribosomal subunit that form the translating 80S ribosomes. Most of our knowledge concerning this dynamic multi-step process comes from studies with the yeast Saccharomyces cerevisiae, which have shown that assembly and maturation of pre-ribosomal particles, as they travel from the nucleolus to the cytoplasm, relies on a multitude (>200) of biogenesis factors.

New twist to nuclear import: When two travel together.

Ribosomes are the nanomachines that synthesize all cellular proteins from mRNA templates. In eukaryotes, ribosomes, which are composed of ribosomal proteins and rRNA, are mainly assembled in the nucleus. Thus, ribosomal proteins require a nuclear transport step from their place of synthesis in the cytoplasm to their site of assembly in the nucleus.

Yar1 protects the ribosomal protein Rps3 from aggregation.

2000 ribosomes have to be synthesized in yeast every minute. Therefore the fast production of ribosomal proteins, their efficient delivery to the nucleus and correct incorporation into ribosomal subunits are prerequisites for optimal growth rates. Here, we report that the ankyrin repeat protein Yar1 directly interacts with the small ribosomal subunit protein Rps3 and accompanies newly synthesized Rps3 from the cytoplasm into the nucleus where Rps3 is assembled into pre-ribosomal subunits.

Treatment of patients with coronary artery disease with biodegradable polymer based paclitaxel-eluting Infinnium coronary stent system: results of 1-year clinical follow-up a single center experience.

Objectives: Evaluating the efficacy of the Infinnium paclitaxel-eluting coronary stent system with the biodegradable polymer in the treatment of symptomatic coronary artery disease.

Methods And Results: Total 153 patients were treated with native coronary artery lesion treated with Infinnium paclitaxel-eluting coronary stent system. This study was a single centre, non-randomized, retrospective study.

High-yield electrofusion of biological cells based on field tailoring by microfabricated structures.

The authors present the use of electric-field constriction created by a microfabricated structure to realise high-yield electrofusion of biological cells. The method uses an orifice on an electrically insulating wall (orifice plate) whose diameter is as small as that of the cells. Owing to the field constriction created by the orifice, we can induce the controlled magnitude of membrane voltage selectively around the contact point, regardless of the cell size.

Possible therapeutic role of vitamin D3 in aggressive fibromatosis.

Desmoids, also known as aggressive fibromatoses, are locally invasive tumors that are intermediate in their biological behavior that lies between benign fibrous proliferations and low-grade fibrosarcomas. In this report, we present a case of a young female patient with a huge tumoral mass located in the right shoulder region that recurred after total resection and was resistant to radio-chemo-hormonal therapy. Eventually, she responded to 1,25-(OH)(2)-vitamin D(3) treatment.