Pyridine nucleotide cycle: studies in Escherichia coli and the human cell line D98/AH2

Journal ArticleDifferent metabolic steps comprise the pyridine nucleotide cycles in Escherichia coli and in the human cell line HeLa D98/AH2. An analysis of the "P-labeling patterns in vivo reveals that in E. coli, pyrophosphate bond cleavage of intracellular NAD predominates, while in the human cell line, cleavage of the nicotinamide ribose bond predominates

The Effect of Two Sock Fabrics on Physiological Parameters Associated with Blister Incidence: A Laboratory Study

The goal of the present study was to investigate physiological effects, mainly at the level of the foot, of two sock fabrics with distinct moisture properties. Twelve participants wore two different socks, one on each foot. The following two sock types were used: PP: 99.6% polypropylene and 0.4% elastane and BLEND: 50% Merino wool, 33% polypropylene, and 17% polyamide. The participants walked three times on a treadmill at 5 km h−1, with no gradient for the first and third phase and a 10% upward inclination for the second walking phase. The microclimate temperature between the boot and foot was measured during walking. Preceding and following the walking phases, additional measurements were carried out at the level of the foot, i.e. skin temperature and skin hydration on three locations and skin friction between the posterior surface of the calcaneus and a glass plate. In addition, the moisture absorption of boots and socks was determined. Differences between the sock fabrics were found for weight gain and microclimate temperature: (i) PP tended to hold less water compared to BLEND, (ii) the boot's microclimate temperature resulted in larger values for BLEND measured at the dorsal surface at the level of the third metatarsal, and (iii) warmer microclimates of the boot were measured for PP compared to BLEND at the distal anterior end of the tibia. The established differences in moisture behavior of both socks did not result in detectable differences in parameters measured on the skin of the foo

A novel germline mutation of PDGFR-β might be associated with clinical response of colorectal cancer to regorafenib

This is the first description of a germline mutation of the PDGFR-β gene, that correlates with response to regorafenib in a patient with metastatic colorectal cance

North to south: ecosystem features determine seagrass community response to sea otter foraging

We compared sea otter recovery in California (CA) and British Columbia (BC) to determine how key ecosystem properties shape top-down effects in seagrass communities. Potential ecosystem drivers of sea otter foraging in CA and BC seagrass beds that we examined include the role of coastline complexity and environmental stress on sea otter effects. In BC, we found greater species richness across seagrass trophic assemblages. Furthermore, Cancer spp. crabs, an important link in the seagrass trophic cascade observed in CA, was less common. Additionally, the more recent reintroduction of sea otters, more complex coastline, and reduced environmental stress in BC seagrass habitats supported the hypothesis that sea otter foraging pressure is currently reduced in more northern latitudes. In order to manage the ecosystem features that lead to regional differences in top predator effects in seagrass communities, we review our findings, their spatial and temporal constraints, and present a social-ecological framework for future re- search

Improving the turnaround time of molecular profiling for advanced non-small cell lung cancer: Outcome of a new algorithm integrating multiple approaches

BACKGROUND Molecular tumor profiling to identify oncogenic drivers and actionable mutations has a profound impact on how lung cancer is treated. Especially in the subgroup of non-small cell lung cancer (NSCLC), molecular testing for certain mutations is crucial in daily clinical practice and is recommended by international guidelines. To date, a standardized approach to identify druggable genetic alterations are lacking. We have developed and implemented a new diagnostic algorithm to harmonize the molecular testing of NSCLC. PATIENTS AND METHODS In this retrospective analysis, we reviewed 119 patients diagnosed with NSCLC at the University Hospital Zurich. Tumor samples were analyzed using our standardized diagnostic algorithm: After the histological diagnosis was made, tissue samples were further analyzed by immunohistochemical stainings as well as the real-time PCR test Idylla™. Extracted DNA was further utilized for comprehensive genomic profiling (FoundationOne®CDx, F1CDx). RESULTS Out of the 119 patients were included in this study, 100 patients were diagnosed with non-squamous NSCLC (nsqNSCLC) and 19 with squamous NSCLC (sqNSCLC). The samples from the nsqNSCLC patients underwent testing by Idylla™ and were evaluated by immunohistochemistry (IHC). F1CDx analysis was run on 67 samples and 46 potentially actionable genomic alterations were detected. Ten patients received the indicated targeted treatment. The median time to test results was 4 days for the Idylla test, 5 days for IHC and 13 days for the F1CDx. CONCLUSION In patients with NSCLC, the implementation of a standardized molecular testing algorithm provided information on predictive markers for NSCLC within a few working days. The implementation of broader genomic profiling led to the identification of actionable targets, which would otherwise not have been discovered

ROS1 genomic rearrangements are rare actionable drivers in microsatellite stable colorectal cancer

c-Ros oncogene 1, receptor tyrosine kinase (ROS1) genomic rearrangements have been reported previously in rare cases of colorectal cancer (CRC), yet little is known about the frequency, molecular characteristics, and therapeutic vulnerabilities of ROS1-driven CRC. We analyzed a clinical dataset of 40 589 patients with CRC for ROS1 genomic rearrangements and their associated genomic characteristics (Foundation Medicine, Inc [FMI]). We moreover report the disease course and treatment response of an index patient with ROS1-rearranged metastatic CRC. ROS1 genomic rearrangements were identified in 34 (0.08%) CRC samples. GOPC-ROS1 was the most common ROS1 fusion identified (11 samples), followed by TTC28-ROS1 (3 samples). Four novel 5' gene partners of ROS1 were identified (MCM9, SRPK1, EPHA6, P4HA1). Contrary to previous reports on fusion-positive CRC, ROS1-rearrangements were found exclusively in microsatellite stable (MSS) CRCs. KRAS mutations were significantly less abundant in ROS1-rearranged vs ROS1 wild type cases. The index patient presented with chemotherapy-refractory metastatic right-sided colon cancer harboring GOPC-ROS1. Molecularly targeted treatment with crizotinib induced a rapid and sustained partial response. After 15 months on crizotinib disseminated tumor progression occurred and KRAS Q61H emerged in tissue and liquid biopsies. ROS1 rearrangements define a small, yet therapeutically actionable molecular subgroup of MSS CRC. In summary, the high prevalence of GOPC-ROS1 and noncanonical ROS1 fusions pose diagnostic challenges. We advocate NGS-based comprehensive molecular profiling of MSS CRCs that are wild type for RAS and BRAF and patient enrollment in precision trials. Keywords: ROS1 rearrangement; acquired resistance; colorectal cancer; crizotinib; molecular subgroups; precision treatmen

ROS1 genomic rearrangements are rare actionable drivers in microsatellite stable colorectal cancer.

c-Ros oncogene 1, receptor tyrosine kinase (ROS1) genomic rearrangements have been reported previously in rare cases of colorectal cancer (CRC), yet little is known about the frequency, molecular characteristics, and therapeutic vulnerabilities of ROS1-driven CRC. We analyzed a clinical dataset of 40 589 patients with CRC for ROS1 genomic rearrangements and their associated genomic characteristics (Foundation Medicine, Inc [FMI]). We moreover report the disease course and treatment response of an index patient with ROS1-rearranged metastatic CRC. ROS1 genomic rearrangements were identified in 34 (0.08%) CRC samples. GOPC-ROS1 was the most common ROS1 fusion identified (11 samples), followed by TTC28-ROS1 (3 samples). Four novel 5' gene partners of ROS1 were identified (MCM9, SRPK1, EPHA6, P4HA1). Contrary to previous reports on fusion-positive CRC, ROS1-rearrangements were found exclusively in microsatellite stable (MSS) CRCs. KRAS mutations were significantly less abundant in ROS1-rearranged vs ROS1 wild type cases. The index patient presented with chemotherapy-refractory metastatic right-sided colon cancer harboring GOPC-ROS1. Molecularly targeted treatment with crizotinib induced a rapid and sustained partial response. After 15 months on crizotinib disseminated tumor progression occurred and KRAS Q61H emerged in tissue and liquid biopsies. ROS1 rearrangements define a small, yet therapeutically actionable molecular subgroup of MSS CRC. In summary, the high prevalence of GOPC-ROS1 and noncanonical ROS1 fusions pose diagnostic challenges. We advocate NGS-based comprehensive molecular profiling of MSS CRCs that are wild type for RAS and BRAF and patient enrollment in precision trials