Phosphorylation-Mediated Control of Stress Responses Induced by Nanosecond Pulsed Electric Fields

Exposure of living organisms to short electric pulses is widely utilized in the life sciences, for example, for DNA transfection. Recent advances in electrical engineering have enabled the production of extremely short electric pulses in the range of nanoseconds, namely, nanosecond pulsed electric fields (nsPEFs). nsPEFs are increasingly recognized as a novel means for cancer therapy, because of their ability to induce cell death. Recent studies have demonstrated that nsPEFs act as cellular stress and activate two independent signaling pathways that involve phosphorylation of translation initiation factors and lead to suppression of general protein synthesis. eIF2α phosphorylation is one of the key reactions in stress-induced translational suppression and is rapidly induced by nsPEFs. Concomitantly, PERK and GCN2, both of which are stress-responsive protein kinases, are activated in nsPEF-exposed cells. Furthermore, nsPEFs cause a reduction in 4E-BP1 phosphorylation, which is controlled by mTORC1 and constitutes an alternative mechanism for translational suppression, independent of eIF2α phosphorylation. In accordance with elevated eIF2α phosphorylation and decreased 4E-BP1 phosphorylation, general protein synthesis is acutely suppressed after nsPEF exposure. These findings demonstrate that nsPEFs induce two independent signaling pathways for translational suppression, further highlighting a unique feature of nsPEFs as a novel means for life sciences

Measurement of Kinematic Viscosity of Refrigeration Oil and R1234yf Mixture

Refrigerant dissolves in refrigeration oil which is used to lubricate the compressor. Because the viscosity of the oil in which the refrigerant is dissolved is significantly reduced, the rate of the reduction is important information to select a proper oil. However, viscosities have not been sufficiently measured for mixtures of refrigeration oil and new refrigerants which are HFOs and mixtures of HFO and HFC. In order to utilize HFO refrigerants in alternative refrigeration systems, viscosity data of mixtures of refrigeration oil and HFO are essential. In this study, mixture of a refrigeration oil and refrigerant (R410A and R1234yf) viscosity are measured with temperature from 40 to 80 ℃ (313 – 353 K) and the oil mass concentration from 80 to 100 % using the tandem capillary tubes method. In this method, the test fluid flows inside two different length and same diameter capillary tubes connected in series in order to eliminate the pressure drop at the inlet and outlet therefore the measurements have better accuracy than the single capillary tube method

Exercise Therapy for Patients with Heart Failure: Focusing on the Pathophysiology of Skeletal Muscle

In patients with heart failure (HF), it is important to perform exercise therapy with a focus on the pathophysiology of skeletal muscle. Patients with HF have multiple clinical symptoms due to cardiac dysfunction. Recent studies demonstrated the mechanism and treatment strategy for HF, and multiple signaling pathways involved in HF result in reduced exercise capacity and skeletal muscle mass. On the other hand, exercise therapy for HF is known to inhibit the inflammatory cytokines and neurohumoral factors, and increase muscle mass. Therefore, in this chapter, we discuss the importance of exercise therapy for HF, with a focus on the pathophysiology of skeletal muscle

Lehren aus dem regionalen Emissionshandel in Nordamerika

Um die immensen Herausforderungen zu bewältigen, muss das Pariser Klimaabkommenauf allen Regulierungsebenen konkretisiert werden. Lokale und regionale Emissionshandelssysteme bieten gerade in Situationen nationalen Politikversagens Chancen für den Klimaschutz von unten

Autophosphorylation of DNA-PKCS regulates its dynamics at DNA double-strand breaks

The DNA-dependent protein kinase catalytic subunit (DNA-PKCS) plays an important role during the repair of DNA double-strand breaks (DSBs). It is recruited to DNA ends in the early stages of the nonhomologous end-joining (NHEJ) process, which mediates DSB repair. To study DNA-PKCS recruitment in vivo, we used a laser system to introduce DSBs in a specified region of the cell nucleus. We show that DNA-PKCS accumulates at DSB sites in a Ku80-dependent manner, and that neither the kinase activity nor the phosphorylation status of DNA-PKCS influences its initial accumulation. However, impairment of both of these functions results in deficient DSB repair and the maintained presence of DNA-PKCS at unrepaired DSBs. The use of photobleaching techniques allowed us to determine that the kinase activity and phosphorylation status of DNA-PKCS influence the stability of its binding to DNA ends. We suggest a model in which DNA-PKCS phosphorylation/autophosphorylation facilitates NHEJ by destabilizing the interaction of DNA-PKCS with the DNA ends

Extending colonic mucosal microbiome analysis - Assessment of colonic lavage as a proxy for endoscopic colonic biopsies

This study was supported through GI Research funds and MRC Grant Ref: MR/M00533X/1 to GH.Peer reviewedPublisher PD

RETRACTED: DNA-PKcs-PIDDosome: A Nuclear Caspase-2-Activating Complex with Role in G2/M Checkpoint Maintenance

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).This article has been retracted at the request of the Authors.Our paper reported the identification of a nuclear protein complex comprising DNA-PKcs, PIDD, and caspase-2 and characterization of its role in G2/M checkpoint maintenance, thereby providing insight into the functional significance of nuclear caspase-2. We recently identified errors affecting several figure panels where original data were processed inappropriately such that the figure panels do not accurately report the original data. We believe that the most responsible course of action is to retract the paper. We sincerely apologize to the scientific community for any inconvenience this might cause

The ‘microflora hypothesis’ of allergic diseases

Increasingly, epidemiologic and clinical data support the hypothesis that perturbations in the gastrointestinal (GI) microbiota because of antibiotic use and dietary differences in ‘industrialized’ countries have disrupted the normal microbiota-mediated mechanisms of immunological tolerance in the mucosa, leading to an increase in the incidence of allergic airway disease. The data supporting this ‘microflora hypothesis’ includes correlations between allergic airway disease and (1) antibiotic use early in life, (2) altered fecal microbiota and (3) dietary changes over the past two decades. Our laboratory has recently demonstrated that mice can develop allergic airway responses to allergens if their endogenous microbiota is altered at the time of first allergen exposure. These experimental and clinical observations are consistent with other studies demonstrating that the endogenous microbiota plays a significant role in shaping the development of the immune system. Data are beginning to accumulate that a ‘balanced’ microbiota plays a positive role in maintaining mucosal immunologic tolerance long after post-natal development. Other studies have demonstrated that even small volumes delivered to the nasopharynx largely end up in the GI tract, suggesting that airway tolerance and oral tolerance may operate simultaneously. The mechanism of microbiota modulation of host immunity is not known; however, host and microbial oxylipins are one potential set of immunomodulatory molecules that may control mucosal tolerance. The cumulative data are beginning to support the notion that probiotic and prebiotic strategies be considered for patients coming off of antibiotic therapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73451/1/j.1365-2222.2005.02379.x.pd