The response of benthic foraminifer, ostracod and mollusc assemblages to environmental conditions: a case study from the Camalti Saltpan (Izmir-Western Turkey)

The subject of this report is benthic foraminifer populations preserved in the saltpan of Camalti in the Province of Izmir. High salinity in certain habitats of Ammonia tepida Cushman may be the primary cause of the high rate of twins and triplets as well as other morphological abnormalities recorded within this species (50 % as compared to an anomaly rate of 1 % in normal marine waters). Thicker cyst membrane developing in extremely saline environments may encourage twins and other morphological deformities by denying free movement of the offspring. Ecological factors such as heavy metal contamination of ambient waters as well as contamination by other wastes are also not ruled out as leading to such developmental anomalies. Of the 27 collected samples, Number 5 (that is closest to the sea) includes the typical marine foraminifers. Nonion depressulum (Walker & Jacob), Ammonia tepida Cushman and Porosononion subgronosum(Egger) are the dominant species in other samples. A total of 63 abnormal individuals (8 triplets, 24 twins, and 31 morphological anomalies) was found within seven of the 27 samples collected. Ten samples contained freshwater ostracods: Darwinula stevensoni(Brady and Robertson), Leptocythere lacertosa Hirschmann, Cyprideis torasa (Jones), Cyprideis (C.) anatolica Bassiouni, and Loxochoncha elliptica Brady. Among these samples (some of which contained only a few species of ostracods - and those limited in number of offspring), one had an unusually high ratio of healthy foraminifers vs those with anomalies. Worthy of note in another sample was a high abundance of molluscs. Among pelecypods, were found Ostrea edulis Linné, Lucinella divaricata (Linné), Pseudocama gryphina Lamarck,Cerastoderma edule (Linné), and Scrobicularia plana da Costa; and among gastropods were identified Hydrobi (Hydrobia) acuta(Draparnaud), Rissoa labiosa (Montagu), R. parva (da Costa), R. violacea Desmarest, Pirenella conica (Blainville), Bittium desayesi(Cerulli and Irelli), B. lacteum Philippi and B. reticulatum Philippi

MET nucleotide variations and amplification in advanced ovarian cancer: characteristics and outcomes with c-Met inhibitors.

PurposeMET alterations including amplifications and nucleotide variations have been associated with resistance to therapy and aggressive clinical behavior.Experimental designThe medical records of patients presenting to the University of Texas MD Anderson Cancer Center Phase I Clinic with relapsed or metastatic ovarian cancers and known MET nucleotide variation or amplification status were reviewed retrospectively (n=178). Categorical and continuous clinical and molecular characteristics were compared using Fisher's exact and Wilcoxon rank-sum tests, respectively. Univariate and multivariate survival were assessed via Kaplan-Meier and Cox regression analysis, respectively.ResultsMET amplification occurred in 4 (3.5%) of 113 patients, whereas nonsynonomous nucleotide variations were present in 9 (7.4%) of 122 patients. No patients exhibited concomitant amplification and variation. MET variations were observed only in white women with high-grade ovarian tumors, whereas amplifications were observed in both black and white women with high-grade serous ovarian primary tumors. No patients (n=4) exhibiting a MET alteration achieved an objective response when treated on a c-Met inhibitor phase I trial. In addition, ovarian cancer patients treated with a c-Met inhibitor with multikinase activity trended towards a longer time-to-failure compared with those treated with a c-Met-specific inhibitor (median: 1.5 vs. 4.5 months, p=0.07).ConclusionsMET alterations occur in a minority of patients with ovarian cancer. c-Met inhibitors with multikinase activity may exhibit less activity in ovarian cancer than c-Met specific drugs. These findings warrant further investigation

Functional consequence of the MET-T1010I polymorphism in breast cancer.

Major breast cancer predisposition genes, only account for approximately 30% of high-risk breast cancer families and only explain 15% of breast cancer familial relative risk. The HGF growth factor receptor MET is potentially functionally altered due to an uncommon germline single nucleotide polymorphism (SNP), MET-T1010I, in many cancer lineages including breast cancer where the MET-T1010I SNP is present in 2% of patients with metastatic breast cancer. Expression of MET-T1010I in the context of mammary epithelium increases colony formation, cell migration and invasion in-vitro and tumor growth and invasion in-vivo. A selective effect of MET-T1010I as compared to wild type MET on cell invasion both in-vitro and in-vivo suggests that the MET-T1010I SNP may alter tumor pathophysiology and should be considered as a potential biomarker when implementing MET targeted clinical trials

Atlantic overturning: new observations and challenges

This paper provides an introduction to the special issue of the Philosophical Transactions of the Royal Society of London of papers from the 2022 Royal Society meeting on ‘Atlantic overturning: new observations and challenges'. It provides the background and rationale for the meeting, briefly summarizes prior progress on observing the Atlantic overturning circulation and draws out the new challenges that papers presented at the meeting raise, so pointing the way forward for future research. This article is part of a discussion meeting issue 'Atlantic overturning: new observations and challenges'

NCI-MATCH Arms N & P: Phase II study of PI3K beta inhibitor GSK2636771 in patients (pts) with cancers (ca) with PTEN mutation/deletion (mut/del) or PTEN protein loss

Background: The NCI-MATCH trial is the largest national study (1173 sites) for ptswith relapsed/ refractory solid tumors, lymphomas and myeloma, which assigns tar-geted therapies based on individual tumor molecular alterations detected using theadapted Oncomine AmpliSeq panel (143 genes) and immunohistochemistry (IHC).We hypothesized that patients with PTEN-deficient cancers enrolled to Arms N and Pmay benefit from treatment with the PI3K beta-selective inhibitor GSK2636771. Methods: Eligibility: relapsed/refractory ca, good end-organ function, and ECOG PS ≤ 1. Pts were screened for molecular alterations by centralized testing on fresh tumor biopsy and had deleterious PTEN mut/del without loss of expression (Arm N) or complete loss of cytoplasmic and nuclear PTEN staining on IHC (Arm P), and no other aberrations activating the PI3K/MTOR and MAPK pathways (mut in PIK3CA, PIK3R1, BRAF, KRAS, AKT1, TSC1/2, mTOR, RHEB, NF2, NRAS, HRAS). Pts received GSK2636771 400mg/day (28-days cycles). RECIST 1.1 overall response rate (ORR) was the primary endpoint. Results: Of 59 enrolled pts, 56 were eligible and received treatment. Of 22 pts with PTEN mut/del (Arm N: 6 uterine, 2 breast, 2 prostate, 2 head/neck ca, 10 other), all are off treatment as of analysis (14 disease progression, 4 for adverse events [AEs], 4 other). One pt (4.5%) with prostate ca (PTEN deletion, MPRSS2-ERG fusion) attained a partial response (-42%). Of 7 (32%) pts with stable disease (SD), 2 had SD \u3e 6 months (uterine leiomyosarcoma; endometrial carcinoma). Of 34 pts with loss of PTEN protein by IHC (Arm P: 7 prostate, 6 breast, 3 squamous anal ca, 2 cholangiocarcinoma, 16 other), all are off treatment as of analysis (26 disease progression, 4 for AE, 4 other). Of 9 (37.5%) pts with SD, 3 had SD \u3e 6 months (prostate cancer; squamous bladder cancer, squamous anal cancer). Median progression-free survival was 1.8 months for both arms. Gr ≥ 3 treatment-related (tr) reversible toxicities were experienced by 30% (7) and 20% (7) of pts in arms N and P, respectively. No tr Gr 5 toxicities were observed in either arm. Conclusions: Single agent GSK2636771 has very modest activity in ca with PTEN gene mutation/deletion and/or PTEN protein loss

Performance of Monolayer Graphene Nanomechanical Resonators with Electrical Readout

The enormous stiffness and low density of graphene make it an ideal material for nanoelectromechanical (NEMS) applications. We demonstrate fabrication and electrical readout of monolayer graphene resonators, and test their response to changes in mass and temperature. The devices show resonances in the MHz range. The strong dependence of the resonant frequency on applied gate voltage can be fit to a membrane model, which yields the mass density and built-in strain. Upon removal and addition of mass, we observe changes in both the density and the strain, indicating that adsorbates impart tension to the graphene. Upon cooling, the frequency increases; the shift rate can be used to measure the unusual negative thermal expansion coefficient of graphene. The quality factor increases with decreasing temperature, reaching ~10,000 at 5 K. By establishing many of the basic attributes of monolayer graphene resonators, these studies lay the groundwork for applications, including high-sensitivity mass detectors

PI3K Pathway Mutations and PTEN Levels in Primary and Metastatic Breast Cancer

The purpose of this work was to determine whether there are differences in PIK3CA mutation status and PTEN protein expression between primary and matched metastatic breast tumors as this could influence patient management. Fifty-micron paraffin sections were used for DNA extraction and 3-micron slides for immunohistochemistry (IHC) and fluorescent in-situ hybridization (FISH). ER, PR and HER2 IHC were repeated in a central laboratory for both primary and metastasis. PTEN levels were assessed by IHC and PI3K pathway mutations detected by a mass spectroscopy-based approach. Median age was 48 years (range, 30 to 83 years). Tumor subtype included 72% hormone receptor-positive/HER2-negative, 20% HER2-positive, and less than 7.8% triple receptor negative. Tissues were available for PTEN IHC in 46 primary tumors and 52 metastases. PTEN was lost in 14 (30%) primary tumors and 13 (25%) metastases. There were 5 cases of PTEN loss and eight cases of PTEN gain from primary to metastasis (26% discordance). Adequate DNA was obtained on 46 primary tumors and on 50 metastases for PIK3CA analysis. PIK3CA mutations were detected in 19 (40%) of primary tumors and 21 (42%) of metastases. There were five cases of PIK3CA mutation loss, and four cases of mutation gain (18% discordance). There was an increase of the level of PIK3CA mutations in four cases, and decrease in one from primary to metastasis. There is a high level of discordance in PTEN level, PIK3CA mutations, and receptor status between primary and metastatic disease that may influence patient selection and response to PI3K-targeted therapies