α-Klotho regulates mouse embryonic neural stem cell proliferation and differentiation.

A longevity factor α-Klotho has been shown to be neuroprotective and enhance brain function. However, it has not been elucidated whether α-Klotho is involved in the embryonic brain development. To address this, we investigated whether α-Klotho regulates embryonic neural stem cell proliferation and differentiation.

TRAF2 regulates the protein stability of HIPK2.

A nuclear serine/threonine kinase homeodomain-interacting protein kinase 2 (HIPK2) is a critical regulator of development and DNA damage response. HIPK2 can induce apoptosis under cellular stress conditions and thus its protein level is maintained low by constant proteasomal degradation. In the present study, we present evidence that TNF receptor-associated factor 2 (TRAF2) regulates the protein stability of HIPK2.

Antioxidant Responses are Crucial for Defense against Misfolded Human Z-Type α-Antitrypsin.

Background: The Z-type variant of human α-antitrypsin is involved in liver cirrhosis and pulmonary emphysema. Due to its slow folding characteristics, this variant accumulates folding intermediates and forms protein aggregates within hepatocytes. Misfolded proteins may induce oxidative stress and subsequent cell death.

An intrinsically disordered domain in Polaribacter irgensii KOPRI 22228 CspB confers extraordinary freeze-tolerance.

Organisms living in extremely cold environments possess mechanisms to survive low temperatures. Among the known cold-induced genes, cold-shock proteins (Csps) are the most prominent. A csp-homologous gene, cspB, has been cloned from the Arctic bacterium Polaribacter irgensii KOPRI 22228, and overexpression of this gene greatly increased the freezing tolerance of its host.

CspB of an arctic bacterium, Polaribacter irgensii KOPRI 22228, confers extraordinary freeze-tolerance.

Freezing temperatures are a major challenge for life at the poles. Decreased membrane fluidity, uninvited secondary structure formation in nucleic acids, and protein cold-denaturation all occur at cold temperatures. Organisms adapted to polar regions possess distinct mechanisms that enable them to survive in extremely cold environments.

Poly(ADP-ribosyl)ation of p53 contributes to TPEN-induced neuronal apoptosis.

Depletion of intracellular zinc by N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN) induces p53-mediated protein synthesis-dependent apoptosis of mouse cortical neurons. Here, we examined the requirement for poly(ADP-ribose) polymerase (PARP)-1 as an upstream regulator of p53 in zinc depletion-induced neuronal apoptosis. First, we found that chemical inhibition or genetic deletion of PARP-1 markedly attenuated TPEN-induced apoptosis of cultured mouse cortical neurons.

Zinc preconditioning protects against neuronal apoptosis through the mitogen-activated protein kinase-mediated induction of heat shock protein 70.

During brain ischemic preconditioning (PC), mild bursts of ischemia render neurons resistant to subsequent strong ischemic injuries. Previously, we reported that zinc plays a key role in PC-induced neuroprotection in vitro and in vivo. Zinc-triggered p75(NTR) induction transiently activates caspase-3, which cleaves poly(ADP-ribose) polymerase-1 (PARP-1).

Retarded protein folding of the human Z-type α₁-antitrypsin variant is suppressed by Cpr2p.

The human Z-type α1-antitrypsin variant has a strong tendency to accumulate folding intermediates due to extremely slow protein folding within the endoplasmic reticulum (ER) of hepatocytes. Human α1-antitrypsin has 17 peptidyl-prolyl bonds per molecule; thus, the effect of peptidyl-prolyl isomerases on Z-type α1-antitrypsin protein folding was analyzed in this study. The protein level of Cpr2p, a yeast ER peptidyl-prolyl isomerase, increased more than two-fold in Z-type α1-antitrypsin-expressing yeast cells compared to that in wild-type α1-antitrypsin-expressing cells.

Identification of chaperones in freeze tolerance in Saccharomyces cerevisiae.

Exposure to low temperatures reduces protein folding rates and induces the cold denaturation of proteins. Considering the roles played by chaperones in facilitating protein folding and preventing protein aggregation, chaperones must exist that confer tolerance to cold stress. Here, yeast strains lacking individual chaperones were screened for reduced freezing tolerance.

α-Synuclein modulates neurite outgrowth by interacting with SPTBN1.

α-Synuclein is the major component of Lewy bodies and Lewy neurites, the pathological hallmarks of surviving neuronal cells in Parkinson's disease patients. However, the physiological role played by α-synuclein remains unclear. In this study, spectrin beta non-erythrocyte 1 (SPTBN1) interacted with α-synuclein in phage display assays using a normalized human brain cDNA library.

Incidence rates and risk factors for vascular events in patients with essential thrombocythemia: a multicenter study from Korea.

Background: Essential thrombocythemia (ET) is classified as a Philadelphia chromosome-negative classic myeloproliferative neoplasm. ET is a clonal stem cell disorder that is often associated with JAK2 mutations and shares phenotypic and pathogenetic similarities with other myeloproliferative neoplasms. Hemorrhagic complications and arterial and venous thrombosis are common in patients with ET.

Human α-synuclein modulates vesicle trafficking through its interaction with prenylated Rab acceptor protein 1.

α-Synuclein has been implicated in the pathogenesis of Parkinson's disease. Although it is highly conserved, its physiological function has not yet been elucidated in detail. In an effort to define the function of α-synuclein, interacting proteins were screened in phage display assays.

Zinc-triggered induction of tissue plasminogen activator by brain-derived neurotrophic factor and metalloproteinases.

Tissue plasminogen activator (tPA) is necessary for hippocampal long-term potentiation. Synaptically released zinc also contributes to long-term potentiation, especially in the hippocampal CA3 region. Using cortical cultures, we examined whether zinc increased the concentration and/or activity of tPA.

The hexapeptide PGVTAV suppresses neurotoxicity of human α-synuclein aggregates.

In Parkinson's disease patients, α-synuclein is the major component of the intracellular protein aggregates found in dopaminergic neurons. Previously, short synthetic α-synuclein-derived peptides have been shown to not only prevent α-synuclein fibrillation but also dissolve preformed α-synuclein aggregates in vitro. The hexapeptide PGVTAV was the shortest peptide that retained the ability to block α-synuclein fibrillation.

Herpesviridae viral infections following rituximab combined chemotherapy in patients with diffuse large B-cell lymphoma.

Background: Herpesviridae viral infections (HVIs) are particularly common in patients with hematologic malignancies after undergoing hematopoietic stem cell transplantation or receiving chemotherapy. However, there have been few reports on the incidence and risk factors of HVIs in diffuse large B-cell lymphoma (DLBL) patients treated with rituximab combined chemotherapy.

Methods: We analyzed 270 patients who were newly diagnosed with DLBL.

Rescue of a cold-sensitive mutant at low temperatures by cold shock proteins from Polaribacter irgensii KOPRI 22228.

Exposure to low temperatures induces the biosynthesis of specific sets of proteins, including cold shock proteins (Csps). Since many of the specific functions of pychrophilic Csps are unknown, the roles of Csps from an Arctic bacterium, Polaribacter irgensii KOPRI 22228, were examined. The genes encoding CspA and CspC of P.

Overexpression of cold shock protein A of Psychromonas arctica KOPRI 22215 confers cold-resistance.

A polar bacterium was isolated from Arctic sea sediments and identified as Psychromonas artica, based on 16S rDNA sequence. Psychromonas artica KOPRI 22215 has an optimal growth temperature of 10 degrees C and a maximum growth temperature of 25 degrees C, suggesting this bacterium is a psychrophile. Cold shock proteins (Csps) are induced upon temperature downshift by more than 10 degrees C.

beta-Sheet-breaking peptides inhibit the fibrillation of human alpha-synuclein.

alpha-Synuclein is the major components of the intracellular protein-aggregates, found in the dopaminergic neurons of Parkinson's disease patients. Previously, we screened for alpha-synuclein substitution mutants that prevent fibril formation of both wild-type and Parkinson's disease-linked alpha-synuclein variants. In the present study, we show that short synthetic peptides derived from these mutant sequences not only prevented alpha-synuclein fibrillation but also dissolved preformed alpha-synuclein aggregates in vitro.

Aggregation-defective alpha-synuclein mutants inhibit the fibrillation of Parkinson's disease-linked alpha-synuclein variants.

Alpha-synuclein comprises the fibrillar core of Lewy bodies, which is one of the histologically defining lesions of Parkinson's disease. Previously, we screened for alpha-synuclein substitution mutants that do not form fibrils. For preventative or therapeutic uses, it is essential to suppress the oligomerization/fibrillation of the wild-type and PD-linked alpha-synuclein proteins.

Identification and expression of the tig gene coding for trigger factor from psychrophilic bacteria with no information of genome sequence available.

Trigger factor (TF) plays a key role as a molecular chaperone with a peptidyl-prolyl cis-trans isomerase (PPIase) activity by which cells promote folding of newly synthesized proteins coming out of ribosomes. Since psychrophilic bacteria grow at a quite low temperature, between 4 and 15 degrees C, TF from such bacteria was investigated and compared with that of mesophilic bacteria E. coli in order to offer an explanation of cold-adaptation at a molecular level.

Sequence determinants regulating fibrillation of human alpha-synuclein.

alpha-Synuclein is a neural protein that comprises the fibrillar core of Lewy bodies, a histologically defining lesion of Parkinson's disease. To investigate the role of each specific residue of the alpha-synuclein molecule in fibril formation, amino acid substitutions were introduced throughout the molecule. Incorporation of proline, especially in the region spanning residues 37-89, drastically retarded fibril formation.

Expression, purification, and crystallization and preliminary X-ray crystallographic analysis of CnrX from Cupriavidus metallidurans CH34.

The nickel and cobalt resistance of Cupriavidus metallidurans CH34 is mediated by the CnrCBA efflux pump encoded by the cnrYHXCBAT metal resistance determinant. The products of the three genes cnrYXH transcriptionally regulate expression of cnr. CnrY and CnrX are membranebound proteins, probably functioning as anti-sigma factors, whereas CnrH is a cnr-specific extracytoplasmic functions (ECF) sigma factor.

Optimization of expression conditions for soluble protein by using a robotic system of multi-culture vessels.

We have developed a robotic system for an automated parallel cell cultivation process that enables screening of induction parameters for the soluble expression of recombinant protein. The system is designed for parallelized and simultaneous cultivation of up to 24 different types of cells or a single type of cell at 24 different conditions. Twenty-four culture vessels of about 200 ml are arranged in four columns x six rows.

Probing the local conformational change of alpha1-antitrypsin.

The native form of serpins (serine protease inhibitors) is a metastable conformation, which converts into a more stable form upon complex formation with a target protease. It has been suggested that movement of helix-F (hF) and the following loop connecting to strand 3 of beta-sheet A (thFs3A) is critical for such conformational change. Despite many speculations inferred from analysis of the serpin structure itself, direct experimental evidence for the mobilization of hF/thFs3A during the inhibition process is lacking.

Specific interactions of serpins in their native forms attenuate their conformational transitions.

Plasminogen activator inhibitor-1 (PAI-1) belongs to the serine protease inhibitor (serpin) protein superfamily. Serpins are unique in that their native forms are not the most thermodynamically stable conformation; instead, a more stable, latent conformation exists. During the transition to the latent form, the first strand of beta-sheet C (s1C) in the serpin is peeled away from the beta-sheet, and the reactive center loop (RCL) is inserted into beta-sheet A, rendering the serpin inactive.