Primary Microcephaly Gene MCPH1 Shows Signatures of Tumor Suppressors and Is Regulated by miR-27a in Oral Squamous Cell Carcinoma

Mutations in the MCPH1 (microcephalin 1) gene, located at chromosome 8p23.1, result in two autosomal recessive disorders: primary microcephaly and premature chromosome condensation syndrome. MCPH1 has also been shown to be downregulated in breast, prostate and ovarian cancers, and mutated in 1/10 breast and 5/41 endometrial tumors, suggesting that it could also function as a tumor suppressor (TS) gene. To test the possibility of MCPH1 as a TS gene, we first performed LOH study in a panel of 81 matched normal oral tissues and oral squamous cell carcinoma (OSCC) samples, and observed that 14/71 (19.72%) informative samples showed LOH, a hallmark of TS genes. Three protein truncating mutations were identified in 1/15 OSCC samples and 2/5 cancer cell lines. MCPH1 was downregulated at both the transcript and protein levels in 21/41 (51.22%) and 19/25 (76%) OSCC samples respectively. A low level of MCPH1 promoter methylation was also observed in 4/40 (10%) tumor samples. We further observed that overexpression of MCPH1 decreased cellular proliferation, anchorage-independent growth in soft agar, cell invasion and tumor size in nude mice, indicating its tumor suppressive function. Using bioinformatic approaches and luciferase assay, we showed that the 3'-UTR of MCPH1 harbors two non-overlapping functional seed regions for miR-27a which negatively regulated its level. The expression level of miR-27a negatively correlated with the MCPH1 protein level in OSCC. Our study indicates for the first time that, in addition to its role in brain development, MCPH1 also functions as a tumor suppressor gene and is regulated by miR-27a.

Design and implementation of spectrum sensing for cognitive radios with a frequency-hopping primary system

In this work, spectrum sensing for cognitive radios is considered in the presence of multiple Primary Users (PU) using frequency-hopping communication over a set of frequency bands. The detection performance of the Fast Fourier Transform (FFT) Average Ratio (FAR) algorithm is obtained in closed-form, for a given FFT size and number of PUs. The effective throughput of the Secondary Users (SU) is formulated as an optimization problem with a constraint on the maximum allowable interference on the primary network. Given the hopping period of the PUs, the sensing duration that maximizes the SU throughput is derived. The results are validated using Monte Carlo simulations. Further, an implementation of the FAR algorithm on the Lyrtech (now, Nutaq) small form factor software defined radio development platform is presented, and the performance recorded through the hardware is observed to corroborate well with that obtained through simulations, allowing for implementation losses. (C) 2015 Elsevier B.V. All rights reserved.

Influence of shelf-break fronts on shellfish and fish stocks off Argentina [Contribution to ICES Annual Science Conference, Reykjavik, Iceland, 27 Sep- 04 Oct 1996]

The general circulation pattern in the western boundary of the SW Atlantic is dominated by the opposite flows of Malvinas (-Falkland)and Brazil Current. In the Confluence region both currents separate from the continental slope and flow offshore creating an area of strong contracts and complex dynamics. The shelf-break fronts off Argentina mark the transition between shelf waters of mixed origin and nutrient rich Malvinas waters. Two areas deserve special attention due to the steep gradients introduced by the outflow of important sources of continental waters: the Rio de la Plata and the Magellan Strait to the north and south of the study area. Characteristics of the front is the high primary and secondary production, and the presence of important invertebrate and fish stocks that concentrate along the front to feed or spawn. The area comprises nearly 30 o/o (333 million U$S in 1995)of all Argentine catches of fish and squid. Resources in the area, beyond the EEZ limits, support international fisheries mainly of Russia, Poland and Spain. (Document contains 15 pages & figs)

The mechanism of PEO process on Al–Si alloys with the bulk primary silicon

This study focuses on mechanism of ceramic coating on Al-Si alloys with bulk primary Si using plasma electrolytic oxidation (PEO) technology. Al-Si alloys with 27-32% Si in weight were used as substrates. The morphologies, composition and microstructure of PEO coatings were investigated by scanning electron microscopy (SEM) with energy dispersive X-ray system (EDX). Results showed that the PEO process had four different stages. The effect of bulk Si is greatly on the morphology and composition of coatings at first three stages. Anodic oxide films formed on Al and Si phases, respectively. When the voltage exceeded 40 V, glow appeared and concentrated on the localized zone of interface of Al and Si phase. Al-Si-O compounds formed and covered on the dendrite Si phase surface, and the coating on bulk Si, which was silicon oxide, was rougher than that on other phase. If the treatment time was long enough, the coatings with uniform surface morphologies and elements distribution will be obtained but the microstructure of inner layer is looser due to the bulk Si.

Challenges in using science-based shoreline setbacks: Examples from South Carolina

Beachfront jurisdictional lines were established by the South Carolina Beachfront Management Act (SC Code §48- 39-250 et seq.) in 1988 to regulate the new construction, repair, or reconstruction of buildings and erosion control structures along the state’s ocean shorelines. Building within the state’s beachfront “setback area” is allowed, but is subject to special regulations. For “standard beaches” (those not influenced by tidal inlets or associated shoals), a baseline is established at the crest of the primary oceanfront sand dune; for “unstabilized inlet zones,” the baseline is drawn at the most landward point of erosion during the past forty years. The parallel setback line is then established landward of the baseline a distance of forty times the long-term average annual erosion rate (not less than twenty feet from the baseline in stable or accreting areas). The positions of the baseline and setback line are updated every 8-10 years using the best available scientific and historical data, including aerial imagery, LiDAR, historical shorelines, beach profiles, and long-term erosion rates. One advantage of science-based setbacks is that, by using actual historical and current shoreline positions and beach profile data, they reflect the general erosion threat to beachfront structures. However, recent experiences with revising the baseline and setback line indicate that significant challenges and management implications also exist. (PDF contains 3 pages)

Information science and the scientist. A look at information requirements and the technologies available to scientists in the pursuit of information

A review article looking at the type of information requirements commonly shared by scientists and their use of traditional information services. Areas covered include primary requirements of IFE (Institute of Freshwater Ecology) staff, pure versus applied research, informal and personal sources of information, and traditional library and information services. It goes on to describe how research into information systems and technology may improve the wider accessibility and use of information to the scientific community. Technologies covered include online databases, telecommunications, gateways, expert systems, optical technology and applications of CDROM.

Age determination manual of the Alaska Fisheries Science Center Age and Growth Program

The Age and Growth Program at the Alaska Fisheries Science Center is tasked with providing age data in order to improve the basic understanding of the ecology and fisheries dynamics of Alaskan fish species. The primary focus of the Age and Growth Program is to estimate ages from otoliths and other calcified structures for age-structured modeling of commercially exploited stocks; however, the program has recently expanded its interests to include numerous studies on topics ranging from age estimate validation to the growth and life history of non-target species. Because so many applications rely upon age data and particularly upon assurances as to their accuracy and precision, the Age and Growth Program has developed this practical guide to document the age determination of key groundfish species from Alaskan waters. The main objective of this manual is to describe techniques specific to the age determination of commercially and ecologically important species studied by the Age and Growth Program. The manual also provides general background information on otolith morphology, dissection, and preparation, as well as descriptions of methods used to measure precision and accuracy of age estimates. This manual is intended not only as a reference for age readers at the AFSC and other laboratories, but also to give insight into the quality of age estimates to scientists who routinely use such data.

A novel short neurotoxin, cobrotoxin c, from monocellate cobra (Naja kaouthia) venom: isolation and purification, primary and secondary structure determination, and tertiary structure modeling

A novel short neurotoxin, cobrotoxin c (CBT C) was isolated from the venom of monocellate cobra (Naja kaouthia) using a combination of ion-exchange chromatography and FPLC. Its primary structure was determined by Edman degradation. CBT C is composed of 61 amino acid residues. It differs from cobrotoxin b (CBT B) by only two amino acid substitutions, Thr/Ala11 and Arg/Thr56, which are not located on the functionally important regions by sequence similarity. However, the LD50 is 0.08 mg/g to mice, i.e. approximately five-fold higher than for CBT B. Strikingly, a structure-function relationship analysis suggests the existence of a functionally important domain on the outside of Loop III of CBT C. The functionally important basic residues on the outside of Loop III might have a pairwise interaction with alpha subunit, instead of gamma or delta subunits of the nicotinic acetylcholine receptor (nAChR). (C) 2002 Elsevier Science Inc. All rights reserved.

Strikingly different penetrance of LHON in two Chinese families with primary mutation G11778A is independent of mtDNA haplogroup background and secondary mutation G13708A

The penetrance of Leber's hereditary optic neuropathy (LHON) in families with primary mitochondrial DNA (mtDNA) mutations is very complex. Matrilineal and nuclear genetic background, as well as environmental factors, have been reported to be involved in d

Assessment of pelagic primary and secondary production in Sefidrud River estuary

Sefid-Rood River Estuary (SRE) is the most important riverine ecosystem in the south Caspian Sea along the Iranian coast lines. The aim of this study was to examine spatial and temporal variability in Phytoplankton and Zooplankton abundance and diversity in SRE. Variability of Chlorophyll a and inorganic nutrient concentration were determined during a year (November 2004– October 2005) in five sampling stations. Primary and secondry production were determined during a year. Total chlorophyll a concentration during the investigation ranged between zero to 22.8 μgl-1 and the highest levels were consistently recorded during summer and the lowest during winter with a annual mean concentration 4.48 μgl-1. Nutrient concentration was seasonally related to river flow with annual mean concentration: NO2 0.05±0.2 mgl-1, NO3 1.13±0.57 mgl-1, NH4 0.51±0.66 mgl-1, total phosphate 0.13±0.1mgl-1 and SiO2 5.68±1.91 mgl-1. Bacillariophytes, Cyanophytes, Chlorophytes, Pyrophytes and Euglenophytes were the dominant phytoplankton groups in this shallow and turbid estuary. The diversity and abundance of phytoplankton had a seasonal pattern while Diatomas and Chrysophytes were dominant throughout the year but Cyanophytes observed only during the summer. Zooplankton community structure was dominated by copepods which 68% of the total zooplankton. In the winter and summer seasons two increased in the number of zooplankton community and usually toward the sea had occurred. Zooplankton also showed a significant spatial and temporal variation. The high turbidity and temperature prime characteristics of SRE seem to be determining factors acting directly on phytoplankton and zooplankton temporal variability and nutrient fluctuations. Everywhere in this estuary nutrients appeared to be in excess of algal requirement and did not influence a phytoplankton and zooplankton composition. Also there was a positive correlation between chlorophyll a and temperature and a negative one with DIN and TP. Primary production determined in this estuary by dark and light butter method and G.P.P. 38.27±34.12 mgcm-2h-1 and N,PP 201.6±289.9 mgcm-2d-1. secondry production determined 15/128 mgc/m3/year. Everywhere in this estuary nutrients appeared to be in excess to algal requirement and did not influence in Chl. a and primary production. The most important factor influence on Chl. a was water temperature.

A Structured Model of Video Reproduces Primary Visual Cortical Organisation

The visual system must learn to infer the presence of objects and features in the world from the images it encounters, and as such it must, either implicitly or explicitly, model the way these elements interact to create the image. Do the response properties of cells in the mammalian visual system reflect this constraint? To address this question, we constructed a probabilistic model in which the identity and attributes of simple visual elements were represented explicitly and learnt the parameters of this model from unparsed, natural video sequences. After learning, the behaviour and grouping of variables in the probabilistic model corresponded closely to functional and anatomical properties of simple and complex cells in the primary visual cortex (V1). In particular, feature identity variables were activated in a way that resembled the activity of complex cells, while feature attribute variables responded much like simple cells. Furthermore, the grouping of the attributes within the model closely parallelled the reported anatomical grouping of simple cells in cat V1. Thus, this generative model makes explicit an interpretation of complex and simple cells as elements in the segmentation of a visual scene into basic independent features, along with a parametrisation of their moment-by-moment appearances. We speculate that such a segmentation may form the initial stage of a hierarchical system that progressively separates the identity and appearance of more articulated visual elements, culminating in view-invariant object recognition.

Combined effects of polyfluorinated and perfluorinated compounds on primary cultured hepatocytes from rare minnow (Gobiocypris rarus) using toxicogenomic analysis

Polyfluorinated and perfluorinated compounds (PFCs) are used in numerous commercial products and have been ubiquitously detected in the environment as well as in the blood of humans and wildlife. To assess the combined effects caused by PFCs in mixtures, gene expression profiles were generated using a custom cDNA microarray to detect changes in primary cultured hepatocytes of rare minnows exposed to six individual PFCs (perfluorooctanoic acid, perfluorononanoic acid, perfluorodecanoic acid, perfluorododecanoic acid, perfluorooctane sulfonate, and 8:2 fluorotelomer alcohol) and four formulations of the PFCs mixtures. Mixtures as well as individual compounds consistently regulated a particular gene set, which suggests that these conserved genes may play a central role in the toxicity mediated by PFCs. Specifically, a number of genes regulated by the mixtures were identified in this study, which were not affected by exposure to any single component. These genes are implicated in multiple biological functions and processes, including fatty acid metabolism and transport, xenobiotic metabolism, immune responses, and oxidative stress. More than 80% of the altered genes in the PFOA- and PFOS-dominant mixture groups were of the same gene set, while the gene expression profiles from single PFOA and PFOS exposures were not as similar. This work contributes to the development of toxicogenomic approaches in combined toxicity assessment and allows for comprehensive insights into the combined action of PFCs mixtures in multiple environmental matrices. (C) 2009 Elsevier B.V. All rights reserved.

Effects of 2,3,7,8-TCDD and benzo[a]pyrene on modulating vitellogenin expression in primary culture of crucian carp (Carassius auratus) hepatocytes

Vitellogenin (Vtg) is the precursor of yolk protein. Its expression and secretion are estrogen-regulated and are crucial for oocyte maturation. An in vitro xenoestrogen screening model was established by measuring Vtg induction in cultured primary hepatocytes from crucian carp. Vtg production was detected by biotin-avidin sandwich ELISA method while Vtg and cytochrome P4501A1 (CYP1A1) mRNA induction were measured by semi- quantitative PCR-primer dropping technique. Vtg and Vtg mRNA were dose-dependently induced by diethylstilbestrol (DES, 0.2-200 ng/mL) in hepatocytes of crucian carp. Co-treatment of the DES-induced hepatocytes with either 2,3,7,8-TCDD (TCDD, 0.1-4 pg/mL) or benzo[a]pyrene (B[a]P, 5-1000 ng/mL) resulted in a reduction of Vtg production and an increment of CYP1A1 mRNA expression both in a dose dependent manner, indicating the anti-estrogenic effects of the compounds. However, at lower tested concentrations, TCDD (0.1, 0.2 pg/mL), B[a]P (5 ng/mL) seemed to have a potentiating effect on Vtg expression and secretion, although by their own these compounds had no observable estrogenic effect on Vtg induction. Tamoxifen (a selective estrogen receptor modulators, 1 nmol/L-1 mumol/L), and P-naphtho-flavone (beta-NF, an aryl hydrocarbon receptor inducing compounds, 2.5-1000 ng/mL) also were employed to study the possible interactions in DES-induced Vtg expression. In co-treatment of the DES-induced hepatocytes with beta-NF or tamoxifen, the decrease in Vtg production did parallel induction of CYP1A1 for beta-NF, but tamoxifen inhibited Vtg induction did not parallel induced CYP1A1 expression in all test concentrations. On the contrary, it was found that in co-treatment of the TCDD-induced hepatocytes with DES, TCDD induced CYP1A1 mRNA production was inhibited by DES also. These results implicated a possible cross talk between estrogen receptor- and aryl hydrocarbon receptor-mediated pathways in the hepatocytes.

STUDY ON THE MODE OF PRIMARY CONTROL IN THE EGG OF GYNOGENETIC CRUCIAN CARP FOR INHIBITING THE DEVELOPMENT OF 2 TYPES OF SPERM NUCLEI

By comparing the different developmental characteristics of two types of sperm nuclei which were from gynogenetic fish (crucian carp) and amphimictic fishes (red carp, red goldfish and sex-reversal red carp) respectively in the eggs of gynogenetic crucian carp, it was preliminarily revealed that there existed selective inhibiting actions of the primary control in the eggs of crucian carp for inhibiting the development of the two types of sperm nuclei. To homologous sperms, the primary control showed weak effect, thus leading to the decondensation of homologous sperm nuclei at different degrees in the eggs of crucian carp. But to heterologous sperms, the primary control showed strong effects, resulting in the total inhibition of the development of heterologous sperm nuclei. Moreover, our experimental results also showed that the different developmental behavior of the two types of sperm nuclei might have a great relationship to the changes of the sex ratio in the population of gynogenetic crucian carp. The infiltration of "the genetic materials in sperm nuclei" into the female nucleus at random might play an important role in male emergence in the naturally gynogenetic population of crucian carp.