Ultralocalized Optoelectronic Properties of Nanobubbles in 2D Semiconductors.

The optical properties of transition-metal dichalcogenides have previously been modified at the nanoscale by using mechanical and electrical nanostructuring. However, a clear experimental picture relating the local electronic structure with emission properties in such structures has so far been lacking. Here, we use a combination of scanning tunneling microscopy (STM) and near-field photoluminescence (nano-PL) to probe the electronic and optical properties of single nanobubbles in bilayer heterostructures of WSe on MoSe.

Aberrant protein expression of Appl1, Sortilin and Syndecan-1 during the biological progression of prostate cancer.

Diagnosis and assessment of patients with prostate cancer is dependent on accurate interpretation and grading of histopathology. However, morphology does not necessarily reflect the complex biological changes occurring in prostate cancer disease progression, and current biomarkers have demonstrated limited clinical utility in patient assessment. This study aimed to develop biomarkers that accurately define prostate cancer biology by distinguishing specific pathological features that enable reliable interpretation of pathology for accurate Gleason grading of patients.

Concentration and Composition in Subway Systems in the Northeastern United States.

Objectives: The goals of this study were to assess the air quality in subway systems in the northeastern United States and estimate the health risks for transit workers and commuters.

Methods: We report real-time and gravimetric concentrations and particle composition from area samples collected in the subways of Philadelphia, Pennsylvania; Boston, Massachusetts; New York City, New York/New Jersey (NYC/NJ); and Washington, District of Columbia. A total of 71 stations across 12 transit lines were monitored during morning and evening rush hours.

Single site suppressors of a fission yeast temperature-sensitive mutant in cdc48 identified by whole genome sequencing.

The protein called p97 in mammals and Cdc48 in budding and fission yeast is a homo-hexameric, ring-shaped, ubiquitin-dependent ATPase complex involved in a range of cellular functions, including protein degradation, vesicle fusion, DNA repair, and cell division. The cdc48+ gene is essential for viability in fission yeast, and point mutations in the human orthologue have been linked to disease. To analyze the function of p97/Cdc48 further, we performed a screen for cold-sensitive suppressors of the temperature-sensitive cdc48-353 fission yeast strain.

Nedd8 processing enzymes in Schizosaccharomyces pombe.

Background: Conjugation of the ubiquitin-like modifier Nedd8 to cullins is critical for the function of SCF-type ubiquitin ligases and thus facilitates ubiquitin conjugation and ultimately degradation of SCF substrates, including several cell cycle regulators. Like ubiquitin, Nedd8 is produced as a precursor that must first be processed before it becomes active. In Saccharomyces cerevisiae this is carried out exclusively by the enzyme Yuh1.

Fission yeast 26S proteasome mutants are multi-drug resistant due to stabilization of the Pap1 transcription factor.

Here we report the result of a genetic screen for mutants resistant to the microtubule poison methyl benzimidazol-2-yl carbamate (MBC) that were also temperature sensitive for growth. In total the isolated mutants were distributed in ten complementation groups. Cloning experiments revealed that most of the mutants were in essential genes encoding various 26S proteasome subunits.

The ubiquitin-associated (UBA) 1 domain of Schizosaccharomyces pombe Rhp23 is essential for the recognition of ubiquitin-proteasome system substrates both in vitro and in vivo.

The ubiquitin-proteasome system is essential for maintaining a functional cell. Not only does it remove incorrectly folded proteins, it also regulates protein levels to ensure their appropriate spatial and temporal distribution. Proteins marked for degradation by the addition of Lys(48)-linked ubiquitin (Ub) chains are recognized by shuttle factors and transported to the 26 S proteasome.

Structural and functional characterization of Rpn12 identifies residues required for Rpn10 proteasome incorporation.

The ubiquitin-proteasome system targets selected proteins for degradation by the 26S proteasome. Rpn12 is an essential component of the 19S regulatory particle and plays a role in recruiting the extrinsic ubiquitin receptor Rpn10. In the present paper we report the crystal structure of Rpn12, a proteasomal PCI-domain-containing protein.

Miller (Genee-Wiedemann) syndrome represents a clinically and biochemically distinct subgroup of postaxial acrofacial dysostosis associated with partial deficiency of DHODH.

Biallelic mutations in the gene encoding DHOdehase [dihydroorotate dehydrogenase (DHODH)], an enzyme required for de novo pyrimidine biosynthesis, have been identified as the cause of Miller (Genée-Weidemann or postaxial acrofacial dysostosis) syndrome (MIM 263750). We report compound heterozygous DHODH mutations in four additional families with typical Miller syndrome. Complementation in auxotrophic yeast demonstrated reduced pyrimidine synthesis and in vitro enzymatic analysis confirmed reduced DHOdehase activity in 11 disease-associated missense mutations, with 7 alleles showing discrepant activity between the assays.

Constitutively active Cullin-RING-Ligases fail to rescue loss of NEDD8 conjugation in Schizosaccharomyces pombe.

In fission yeast, the only known essential function of Ned8p is the modification of the cullin, Pcu1p, and subsequent Cullin-RING-Ligase (CRL) activation and substrate ubiquitination. We show here that a functional Pcu1p mutant, deleted for its C-terminal autoinhibitory domain, which negates the requirement of neddylation for ligase activity, is unable to rescue the loss of neddylation. These findings suggest that the neddylation of non-cullin substrate(s) are required for Schizosaccharomyces pombe viability.

Sulphur dioxide evokes a large scale reprogramming of the grape berry transcriptome associated with oxidative signalling and biotic defence responses.

The grape and wine industries are heavily reliant on sulphite preservatives. However, the view that sulphites act directly on bacterial and fungal pathogens may be simplistic. Mechanisms of sulphur-enhanced defences are largely unknown; many sulphur-rich compounds enhance plant defences and sulphite can also have oxidative consequences via production of H(2)O(2) or sulphitolysis.

The essential functions of NEDD8 are mediated via distinct surface regions, and not by polyneddylation in Schizosaccharomyces pombe.

The ubiquitin-like protein NEDD8 is highly conserved in eukaryotes, from man to Schizosaccharomyces pombe. NEDD8 conjugation to cullin proteins is a prerequisite for cullin based E3 ubiquitin ligase activity, and essential for S. pombe viability.

Txl1 and Txc1 are co-factors of the 26S proteasome in fission yeast.

The 26S proteasome is a large proteolytic particle present in the cytosol and nucleus of eukaryotic cells. Most intracellular proteins, including those affected by oxidative damage, are degraded by the proteasome. The human thioredoxin, Txnl1, is known to associate with the 26S proteasome and thereby equips proteasomes with redox capabilities.

Structure of Rpn10 and its interactions with polyubiquitin chains and the proteasome subunit Rpn12.

Schizosaccharomyces pombe Rpn10 (SpRpn10) is a proteasomal ubiquitin (Ub) receptor located within the 19 S regulatory particle where it binds to subunits of both the base and lid subparticles. We have solved the structure of full-length SpRpn10 by determining the crystal structure of the von Willebrand factor type A domain and characterizing the full-length protein by NMR. We demonstrate that the single Ub-interacting motif (UIM) of SpRpn10 forms a 1:1 complex with Lys(48)-linked diUb, which it binds selectively over monoUb and Lys(63)-linked diUb.

Int6 and Moe1 interact with Cdc48 to regulate ERAD and proper chromosome segregation.

Int6/eIF3e is implicated in tumorigenesis, but its molecular functions remain unclear. We have studied its fission yeast homolog Yin6, reporting that it regulates proteolysis by controlling the assembly/localization of proteasomes, and binds directly to another conserved protein, Moe1. In the present study, we isolated Cdc48 as a Moe1-binding protein from a yeast two-hybrid screen, and confirmed biochemically that they form a stable complex in fission yeast.

Quantifying protein-protein interactions in the ubiquitin pathway by surface plasmon resonance.

The commercial availability of instruments, such as Biacore, that are capable of monitoring surface plasmon resonance (SPR) has greatly simplified the quantification of protein-protein interactions. Already, this technique has been used for some studies of the ubiquitin-proteasome system. Here we discuss some of the problems and pitfalls that researchers should be aware of when using SPR analyses for studies of the ubiquitin-proteasome system.

Mechanism of Lys48-linked polyubiquitin chain recognition by the Mud1 UBA domain.

The ubiquitin-pathway associated (UBA) domain is a 40-residue polyubiquitin-binding motif. The Schizosaccharomyces pombe protein Mud1 is an ortholog of the Saccharomyces cerevisiae DNA-damage response protein Ddi1 and binds to K48-linked polyubiquitin through its UBA domain. We have solved the crystal structure of Mud1 UBA at 1.

Ubiquitin and ubiquitin-like proteins as multifunctional signals.

Protein ubiquitylation is a recognized signal for protein degradation. However, it is increasingly realized that ubiquitin conjugation to proteins can be used for many other purposes. Furthermore, there are many ubiquitin-like proteins that control the activities of proteins.

The regulation of proteasome degradation by multi-ubiquitin chain binding proteins.

The 26S proteasome is a large multi-protein complex that functions to degrade proteins tagged with multi-ubiquitin chains. There are several mechanisms employed by the cell to ensure the efficient delivery of multi-ubiquitinated substrate proteins to the 26S proteasome. This is not only important to ensure the degradation of damaged and misfolded proteins, but also the regulated turnover of critical cell regulators.

Uch2/Uch37 is the major deubiquitinating enzyme associated with the 26S proteasome in fission yeast.

Conjugation of proteins to ubiquitin plays a central role for a number of cellular processes including endocytosis, DNA repair and degradation by the 26S proteasome. However, ubiquitination is reversible as a number of deubiquitinating enzymes mediate the disassembly of ubiquitin-protein conjugates. Some deubiquitinating enzymes are associated with the 26S proteasome contributing to and regulating the particle's activity.

Protein degradation: recognition of ubiquitinylated substrates.

A cell-free system has been developed in budding yeast that provides direct evidence that the Dsk2/Dph1, Rad23/Rhp23 and Rpn10/Pus1 multi-ubiquitin-binding proteins, long implicated in substrate recognition and presentation to the 26S proteasome, actually fulfil such a role.