Lymphangioleiomyomatosis Biomarkers Linked to Lung Metastatic Potential and Cell Stemness

Lymphangioleiomyomatosis (LAM) is a rare lung-metastasizing neoplasm caused by the proliferation of smooth muscle-like cells that commonly carry loss-of-function mutations in either the tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) genes. While allosteric inhibition of the mechanistic target of rapamycin (mTOR) has shown substantial clinical benefit, complementary therapies are required to improve response and/or to treat specific patients. However, there is a lack of LAM biomarkers that could potentially be used to monitor the disease and to develop other targeted therapies. We hypothesized that the mediators of cancer metastasis to lung, particularly in breast cancer, also play a relevant role in LAM. Analyses across independent breast cancer datasets revealed associations between low TSC1/2 expression, altered mTOR complex 1 (mTORC1) pathway signaling, and metastasis to lung. Subsequently, immunohistochemical analyses of 23 LAM lesions revealed positivity in all cases for the lung metastasis mediators fascin 1 (FSCN1) and inhibitor of DNA binding 1 (ID1). Moreover, assessment of breast cancer stem or luminal progenitor cell biomarkers showed positivity in most LAM tissue for the aldehyde dehydrogenase 1 (ALDH1), integrin-beta 3 (ITGB3/CD61), and/or the sex-determining region Y-box 9 (SOX9) proteins. The immunohistochemical analyses also provided evidence of heterogeneity between and within LAM cases. The analysis of Tsc2-deficient cells revealed relative over-expression of FSCN1 and ID1; however, Tsc2-deficient cells did not show higher sensitivity to ID1-based cancer inhibitors. Collectively, the results of this study reveal novel LAM biomarkers linked to breast cancer metastasis to lung and to cell stemness, which in turn might guide the assessment of additional or complementary therapeutic opportunities for LAM.

Diel movements of fishes linked to benthic seascape structure in a Caribbean coral reef ecosystem

Many common fishes associated with Caribbean coral reef ecosystems use resources from more than 1 patch type during routine daily foraging activities. Few studies have provided direct evidence of connectivity across seascapes, and the importance of benthic seascape structure on movement behavior is poorly known. To address this knowledge gap, we coupled hydro-acoustic technology to track fish with seafloor mapping and pattern analysis techniques from landscape ecology to quantify seascape structure. Bluestriped grunts Haemulon sciurus and schoolmaster snapper Lutjanus apodus were tracked over 24 h periods using boat-based acoustic telemetry. Movement pathways, and day and night activity spaces were mapped using geographical information system (GIS) tools, and seafloor structure within activity spaces was mapped from high-resolution aerial photography and quantified using spatial pattern metrics. For both fish species, night activity spaces were significantly larger than day activity spaces. Fish exhibited a daytime preference for seascapes with aggregate coral reef and colonized bedrock, then shifted to night activity spaces with lower complexity soft sediment including sand, seagrass, and scattered coral/rock. Movement path complexity was negatively correlated with seascape complexity. This demonstrates direct connectivity across multiple patch types and represents the first study to apply quantitative landscape ecology techniques to examine the movement ecology of marine fish. The spatially explicit approach facilitates understanding to the linkages between biological processes and the heterogeneity of the landscape. Such studies are essential for identifying ecologically relevant spatial scales, delineating essential fish habitat and designing marine protected areas.

Southern California's megaflood event of ca. 1605 AD linked to large-scale atmospheric forcing

A distinct, 1- to 2-cm-thick flood deposit found in Santa Barbara Basin with a varve-date of 1605 AD ± 5 years testifies to an intensity of precipitation that remains unmatched for later periods when historical or instrumental records can be compared against the varve record. The 1605 AD ± 5 event correlates well with Enzel's (1992) finding of a Silver Lake playa perennial lake at the terminus of the Mojave River (carbon-14-dated 1560 AD ± 90 years), in relative proximity to the rainfall catchment area draining into Santa Barbara Basin. According to Enzel, such a persistent flooding of the Silver Lake playa occurred only once during the last 3,500 years and required a sequence of floods, each comparable in magnitude to the largest floods in the modern record. To gain confidence in dating of the 1605 AD ± 5 event, we compare Southern California's sedimentary evidence against historical reports and multi-proxy time-series that indicate unusual climatic events or are sensitive to changes in large-scale atmospheric circulation patterns. The emerging pattern supports previous suggestions that the first decade of the 17th century was marked by a rapid cooling of the Northern Hemisphere, with some indications for global coverage. A burst of volcanism and the occurrence of El Nino seem to have contributed to the severity of the events. The synopsis of the 1605 AD ± 5 years flood deposit in Santa Barbara Basin, the substantial freshwater body at Silver Lake playa, and much additional paleoclimatic, global evidence testifies for an equatorward shift of global wind patterns as the world experienced an interval of rapid, intense, and widespread cooling.

Development, validation, and utilization of a competitive enzyme-linked immunosorbent assay for the detection of antibodies against Brucella species in marine mammals

A competitive enzyme-linked immunosorbent assay (cELISA) was developed by using a whole-cell antigen from a marine Brucella sp. isolated from a harbor seal (Phoca vitulina). The assay was designed to screen sera from multiple marine mammal species for the presence of antibodies against marine-origin Brucella. Based on comparisons with culture-confirmed cases, specificity and sensitivity for cetacean samples tested were 73% and 100%, respectively. For pinniped samples, specificity and sensitivity values were 77% and 67%, respectively. Hawaiian monk seal (Monachus schauinslandi; n = 28) and bottlenose dolphin (Tursiops truncatus; n = 48) serum samples were tested, and the results were compared with several other assays designed to detect Brucella abortus antibodies. The comparison testing revealed the marine-origin cELISA to be more sensitive than the B. abortus tests by the detection of additional positive serum samples. The newly developed cELISA is an effective serologic method for detection of the presence of antibodies against marine-origin Brucella sp. in marine mammals.

The association of the Arabidopsis actin-related protein (ARP) 2/3 complex with cell membranes is linked to its assembly status but not its activation

国科图

Rapid evolution of an X-linked microRNA cluster in primates

MicroRNAs (miRNAs) are a growing class of small RNAs ( about 22 nt) that play crucial regulatory roles in the genome by targeting mRNAs for cleavage or translational repression. Most of the identified miRNAs are highly conserved among species, indicating

Winter Temperature and UV Are Tightly Linked to Genetic Changes in the p53 Tumor Suppressor Pathway in Eastern Asia

The tumor suppressor p53 is a master sensor of stress. Two human-specific polymorphisms, p53 codon 72 and MDM2 SNP309, influence the activities of p53. There is a tight association between cold winter temperature and p53 Arg72 and between low UV intensity

Rapid evolution of mammalian X-linked testis microRNAs

Background: MicroRNAs (miRNAs), which are small, non-coding RNAs approximately 21-nucleotides in length, have become a major focus of research in molecular biology. Mammalian miRNAs are proposed to regulate approximately 30% of all protein-coding genes. P

Antimicrobial peptides from skin secretions of Chinese red belly toad Bombina maxima

Two groups of antimicrobial peptides have been isolated from skin secretions of Bombina maxima. Peptides in the first group, named maximins 1, 2, 3, 4 and 5, are structurally related to bombinin-like peptides (BLPs). Unlike BLPs, sequence variations in maximins occurred all through the molecules. In addition to the potent antimicrobial activity, cytotoxicity against tumor cells and spermicidal action of maximins, maximin 3 possessed a significant anti-HIV activity. Maximins 1 and 3 were toxic to mice with LD50 values of 8.2 and 4.3 mg/kg, respectively. Peptides in the second group, termed maximins H1, H2, H3 and H4, are homologous with bombinin H peptides. cDNA sequences revealed that one maximin peptide plus one maximin H peptide derived from a common larger protein. (C) 2002 Elsevier Science Inc. All rights reserved.

Two families of antimicrobial peptides with multiple functions from skin of rufous-spotted torrent frog, Amolops loloensis

There are around 27 species of Amolops amphibian distributed in South-east of Asia. Seven antimicrobial peptides (AMPs) belonging to two different families were purified from skin of rufous-spotted torrent frog, Amolops loloensis, and designated brevinins

Two antimicrobial peptides from skin secretions of Rana grahami

Two antimicrobial peptides manifested a broad spectrum of anti microbial activity against various microorganisms have been isolated from skin secretions of Rana grahami. These antimicrobial peptides were named grahamin 1 and grahamin 2. Their primary Stru