Is cytochrome aa3 from thermus thermophilus a single subunit oxidase?

A reliable procedure has been developed for the purification of the cytochrome c1aa3 complex from the plasma membrane of T. thermophilus. The ratios heme C:heme A:Fe:C were found to be 1:2:3:2 confirming previous results, however, the molecular weight was found to be ~92,000 rather than the ~200,000 reported earlier [1]. Polyacrylamide gel electrophoresis under strongly denaturing conditions and high performance reverse phase liquid chromatography showed that cytochrome c1aa3 is composed of only two subunits in 1:1 ratio. Both polypeptides have blocked N-termini. The smaller subunit (~33,000) binds heme c and presumably no other metals. The larger subunit (~55,000) is thus thought to contain the elements of cytochrome aa3 and therefore be considered a single subunit cytochrome oxidase.The bacterial cytochrome c1aa3 has been compared with beef heart cytochrome oxidase with a number of techniques including optical, EPR [1], Raman, MCD, and Mossbauer [2] spectroscopies. These experiments establish that the fundamental chemical properties of the redox centers are substantially similar in these two proteins.Cytochrome c552 (from Thermus), horse heart cytochrome c, and tetramethylphenylenediamine greatly stimulate the ascorbate oxidase activity of cytochrome c1aa3. This enhancement is characterized by a `high affinity' component which results in only a small velocity increase and a `low affinity' component which gives a large velocity increase. Very similar behavior has been previously observed with mammalian cytochrome oxidase [3].Preliminary experiments show that vesicularized c1aa3 is capable of proton pumping.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25363/1/0000811.pd

Observations on the -type cytochromes of the extreme thermophile, HB8: Cytochrome 552 is located in the periplasmic space

We have shown that cytochrome 552 of HB8, isolated previously by Hon-nami and Oshima ([11.] J. Biochem. (Tokyo) , 769-776), resides in the periplasmic space of this gramnegative organism. As much as 90% of this protein was released from cells having the outer membrane disrupted by lysozyme. By contrast less than 1% of the cytoplasmic glucose-6-phosphate dehydrogenase and glutamate dehydrogenase were released by this treatment. It was further observed that the two other -type cytochromes, 549 and 549,555 (split alpha band) are membrane bound proteins. The amount of each of the -cytochromes present in the bacteria was shown to depend strongly on the carbon source in the culture medium.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24420/1/0000691.pd

Phase II study of afatinib plus pembrolizumab in patients with squamous cell carcinoma of the lung following progression during or after first-line chemotherapy (LUX-Lung-IO)

Introduction: Afatinib and pembrolizumab have separately shown survival benefit in patients with squamous cell carcinoma (SqCC) of the lung, and there is biological rationale for concurrent inhibition of the programmed death ligand-1 and epidermal growth factor receptor (EGFR) pathways in this patient population. Materials and Methods: This open-label, single-arm study enrolled patients with SqCC of the lung who had progressed during/after first-line chemotherapy and comprised two parts: a safety run-in to establish the recommended phase II dose (RP2D; afatinib 40 mg or 30 mg once daily with pembrolizumab 200 mg every 3 weeks); and the main part assessing efficacy and safety of the RP2D. The primary endpoint was objective response rate (ORR); secondary endpoints included the RP2D, progression-free survival (PFS) and overall survival (OS). Results: Twenty-four patients were treated in the safety run-in (afatinib 40 mg/30 mg cohorts: n = 12/12). Median age was 63.5 years; 79.2% of patients were male. All patients discontinued afatinib and pembrolizumab, most commonly due to disease progression (58.3% and 75.0%, respectively) or adverse events (AEs; 37.5% and 25.0%, respectively). The study was discontinued early after completion of the safety run-in, and no patients entered the main part. ORR was 12.5%; median PFS and OS were 13.1 and 29.3 weeks, respectively. All patients had > 1 drug-related AE (grade > 3: 45.8%). Conclusion: While there were no new or unexpected safety findings, exploratory analysis of antitumor activity indicated limited efficacy with afatinib plus pembrolizumab in patients with SqCC of the lung who had progressed during/after first-line chemotherapy

National Oceanic and Atmospheric Administration Report 178

This report is based on an observational study on the Hawaiian monk seal, located at French Frigate Shoals in the Hawaiian Islands National Wildlife Refuge. Study took place from April 4th to August 31st 1988 and from March 25th to September 4th 1989. Data was made to conduct atoll-wide beach censuses of monk seals to assess productivity, survival, movements between atolls and islands, and population structure and distribution; furthermore, the study was made to monitor reproduction rates, movement between islands, tagging weaned pups, record injuries and deaths, perform necropsies, and catalogue and destroy debris capable of entangling wildlife

Experience from Asian centers in a named-patient-use program for afatinib in patients with advanced non-small-cell lung cancer who had progressed following prior therapies, including patients with uncommon EGFR mutations

10.1007/s10147-021-01869-0INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY265841-85