Molecular and cellular mechanisms of transformation of C3H/10T1/2 Cl 8 and diploid human fibroblasts by unique carcinogenic,nonmutagenic metal compounds

Work from our laboratory showed that carcinogenic metal salts of arsenic, nickel, and chromium induced morphological transformation of cultured C3H/10T^1/2 Cl 8 (10T^1/2) mouse embryo cells, and that many of the transformants grow in soft agarose and form tumors in nude mice. Concentrations of arsenic, nickel, and chromium compounds that induced morphological transformation did not induce mutation to ouabain resistance in 10T^1/2 cells. This indicated that the mechanism of metal induced morphological transformation was likely not caused by induction of base substitution mutations, and in the case of lead chromate, likely not caused by frameshift or deletion mutations. In addition, we showed that carcinogenic arsenic, nickel, and chromium compounds, and MNNG, induced anchorage independence in diploid human fibroblasts. Anchorage-independent cell strains derived from anchorage-independent colonies were stable but did not form foci and eventually senesced, therefore, arsenic and nickel compounds and lead chromate induced stable anchorage independence as an isolated phenotype. Nickel compounds and lead chromate induced anchorage independence but not mutation to ouabain resistance or to 6-thioguanine resistance. Hence, the mechanism of induction of anchorage independence by these metal salts in human fibroblasts was likely not via induction of base substitution, frameshift, or deletion mutations that would be measured in these mutation assays. MNNG, on the other hand, induced mutation to 6-thioguanine resistance and to ouabain resistance over the same concentration ranges that induced anchorage independence was induced, indicating that MNNG might induce anchorage independence by inducing base substitution, frameshift, or deletion mutations. It is likely, therefore that the mechanisms of metal salt induced morphological and anchorage independent transformation in murine and human base substitution mutations. We hypothesize that rearrangements or amplification of proto-oncogenes, or, possibly, inactivation of suppressoro oncogenes, might play a role in the mechanism of metal salt induced morphological or anchorage independent transformation of 10T^1/2 and diploid human fibroblasts, respectively. *** DIRECT SUPPORT *** A03GS019 00027     

Factors Predisposing to Maxillary Anchorage Loss: A Retrospective Study of 1403 Cases

Anchorage loss is very disturbing for orthodontists and patients during orthodontic treatment, which usually results in bad treatment effects. Despite the same treatment strategy, different patients show different tendencies toward anchorage loss, which influences the treatment results and should preferably be predicted before the treatment is begun. However, relatively little research has been conducted on which patients are more likely to lose anchorage. The mesial tipping of the first molar marks the onset of anchorage loss, and changes in the angulation of the first molar are closely related to anchorage loss. This cross-sectional study aimed to determine how the mesiodistal angulation of the upper first molars changes during general orthodontic treatment and to identify the individual physiologic factors leading to these changes in a large sample of 1403 patients with malocclusion. The data indicate that the upper first molars tend to be tipped mesially during orthodontic treatment, and this constitutes a type of anchorage loss that orthodontists should consider carefully. Compared to treatment-related factors, patients'' physiologic characteristics have a greater influence on changes in the angulation of the upper first molars during orthodontic treatment. The more distally tipped the upper first molars are before treatment, the more they will tip mesially during treatment. Mesial tipping of the upper first molars, and therefore, anchorage loss, is more likely to occur in adolescents, males, patients with class II malocclusion and patients who have undergone maxillary premolar extraction. This finding is of clinical significance to orthodontists who wish to prevent iatrogenic anchorage loss by tipping originally distally tipped upper molars forward, and provides a new perspective on anchorage during orthodontic treatment planning.     

Spatial Organization of DNA in the Nucleus May Determine Positions of Recombination Hot Spots

A hypothesis has been proposed that the regions of DNA loop anchorage to the nuclear matrix are the preferential sites (hot spots) of illegitimate recombination mediated or triggered by topoisomerase II of the nuclear matrix. Recombination between the regions of DNA loop anchorage to the nuclear matrix may result in deletion or repositioning of DNA loops or their groups. The proposed hypothesis is confirmed by the results of original experiments and published data obtained by other researchers.__________Translated from Molekulyarnaya Biologiya, Vol. 39, No. 4, 2005, pp. 633–638.Original Russian Text Copyright © 2005 by Razin, Iarovaia.     

Breast MRI in nonpalpable breast lesions: a randomized trial with diagnostic and therapeutic outcome – MONET – study

Background

In orthodontic treatment, anchorage control is a fundamental aspect. Usually conventional mechanism for orthodontic anchorage control can be either extraoral or intraoral that is headgear or intermaxillary elastics. Their use are combined with various side effects such as tipping of occlusal plane or undesirable movements of teeth. Especially in cases, where key-teeth are missing, conventional anchorage defined as tooth-borne anchorage will meet limitations. Therefore, the use of endosseous implants for anchorage purposes are increasingly used to achieve positional stability and maximum anchorage.

Methods/Design

The intended study is designed as a prospective, multicenter randomized controlled trial (RCT), comparing and contrasting the effect of early loading of palatal implant therapy versus implant loading after 12 weeks post implantation using the new ortho-implant type II anchor system device (Orthosystem Straumann, Basel, Switzerland). 124 participants, mainly adult males or females, whose diagnoses require temporary stationary implant-based anchorage treatment will be randomized 1:1 to one of two treatment groups: group 1 will receive a loading of implant standard therapy after a healing period of 12 week (gold standard), whereas group 2 will receive an early loading of orthodontic implants within 1 week after implant insertion. Participants will be at least followed for 12 months after implant placement. The primary endpoint is to investigate the behavior of early loaded palatal implants in order to find out if shorter healing periods might be justified to accelerate active orthodontic treatment. Secondary outcomes will focus e.g. on achievement of orthodontic treatment goals and quantity of direct implant-bone interface of removed bone specimens. As tertiary objective, a histologic and microtomography evaluation of all retrieved implants will be performed to obtain data on the performance of the SLA surface in human bone evaluation of all retrieved implants. Additionally, resonance frequency analysis (RFA, Osstell? mentor) will be used at different times for clinically monitoring the implant stability and for histological comparison in order to measure the reliability of the resonance frequency measuring device.

Trial registration

Current Controlled Trials ISRCTN97142521.     

Spontaneous cell shedding by tumor cells in monolayer culture

Summary Sarcoma 180 monolayers spontaneously shed single cells and small multicellular aggregates into the surrounding medium to produce a dual population of floating and substratum-attached cells. Shedding was a motility-associated event that occurred when cells attempted to migrate over one another. It resulted from a combination of cell shape change and active motility, which increased sensitivity to fluid shear dislodgement by reducing a cell's surface area of adhesive contact and increasing strain tension at its adhesive contact points. Shedding occurred at all phases of the cell cycle. Extracellular matrix but not conditioned medium enhanced the floating subpopulation by slowing the kinetics of rattachment to plastic and cellular substrata. Although sarcoma 180 cells are anchorage independent in the sense that they grow readily in single cell suspension, they nevertheless exhibited anchorage modulation of their cell cycle. Short periods in suspension produced a mild G₁ accumulation, whereas longer periods of anchorage deprivation led to a mild G₂ accumulation which appeared to result from an interference with cytokinesis. This work was supported by grants from the Medical Research Council of Canada, The National Cancer Institute of Canada, the Alberta Heritage Savings and Trust Fund for Applied Cancer Research, and the Alberta Heritage Fund for Medical Research.     

Epigenetic reprogramming as a key contributor to melanocyte malignant transformation

Melanoma progression requires deregulation of gene expression by currently uncharacterized epigenetic mechanisms. A mouse model based on changes in cell microenvironment was developed by our group to study melanocyte malignant transformation. Melanoma cell lines (4C11- and 4C11+) were obtained as result of 5 sequential anchorage blockades of non-tumorigenic melan-a melanocytes. Melan-a cells submitted to 4 de-adhesion cycles were also established (4C), are non-tumorigenic and represent an intermediary phase of tumor progression. The aim of this work was to identify factors contributing to epigenetic modifications in early and later phases of malignant transformation induced by anchorage impediment. Epigenetic alterations occur early in tumorigenesis; 4C cell line shows changes in global and gene-specific DNA methylation and histone marks. Many histone modifications differ between melan-a, 4C, 4C11- (non-metastatic melanoma cell line) and 4C11+ (metastatic melanoma cell line) which could be associated with changes in gene and microRNA expression. These epigenetic alterations seem to play a key role in malignant transformation since melanocytes treated with 5-Aza-2'-deoxycytidine before each anchorage blockade do not transform. Some epigenetic changes seem to be also responsible for the maintenance of malignant phenotype, since melanoma cell lines (4C11- and 4C11+) treated in vitro with 5-Aza-2'-deoxycytidine or Trichostatin A showed reduction of tumor growth in vivo. Changes in gene expression reflecting cell adaptation to new environment were also observed. We propose a model in which sustained microenvironmental stress in melanocytes results in epigenetic reprogramming. Thus, after adaptation, cells may acquire epigenetic marks that could contribute to the establishment of a malignant phenotype.     

Mechanotransduction and anoikis: Death and the homeless cell

Developed organs display strict spatial organization of differentiated cells which is required for proper organ function. One important device that prevents tissue disorganization is the death of cells that lose anchorage to their native matrix, a signal that indicates potential loss of proper tissue context. Termed anoikis (Greek for Homelessness), this form of cell death is a specialized form of apoptosis. Interestingly, at certain stages of development and tissue repair, cells are required to migrate in an unanchored state, suggesting that anoikis must be strictly regulated at some level. Likewise, cellular transformation is often accompanied by an inappropriate loss of anoikis and subsequent acquisition of a metastatic phenotype. Despite its importance, the molecular pathways involved in the regulation of anoikis and the proximal signals reporting loss of anchorage are poorly understood. Recent studies suggest that attachment may be reported by a mechanosensory testing of the cell's physical environment.     

The extracellular matrix is instructive

The extracellular matrix does more than just blanket cells; it also provides informational cues which affect a variety of developmental and cellular maintenance activities. The constituents of the matrix provide the fabric for cell motility and cell shape as well as anchorage sites for bioactive factors which directly affect the cell's developmental pattern or mitotic activity. The influence of the extracellular matrix is controlled by the cell's responsiveness to these complex signals. The same matrix component, for example hyaluronic acid, can have completely different effects depending on the cell's lineage and developmental history. The functional interaction between the extracellular matrix and specific cell surface receptors provides cues which affect the control of development and the maintenance and aging events that affect specific cells and tissues.     

The Mechanics of Anchorage in Wheat Triticum aestivum L.: II. ANCHORAGE OF MATURE WHEAT AGAINST LODGING

The root system of mature wheat Triticum aestivum Marts Doveis dominated by the 7 to 15 adventitious roots which emergefrom the perimeter of the stem base, pointing radially outwardsand downwards. The basal, coronal region of these roots is thickand unbranched, attached to a rhizosheath of earth by a densecovering of root hairs and stiffened in bending by lignificationof outer layers of the cortex. Root lodging of plants involves bending of the coronal rootsat their base and axial movement of leeward and windward rootsthrough the soil; their resistance to these motions providemoments resisting lodging. A model of anchorage was producedby summing the resistance of each root to both forms of motionto give two anchorage components. The model was tested in aseries of mechanical experiments in which simulated lodgingwas followed by loading of individual roots; results supportedthe anchorage model and suggested that in the experimental conditionsthe two components of anchorage were approximately equal inmagnitude. The stem was about 30% stronger than the anchoragesystem. The coronal anchorage roots made up 4.4% of total dry mass;it is suggested that anchorage could be improved either by increasinginvestment in this region or by altering root orientation. Sequentialdevelopment of seminal and adventitious root systems is relatedto the changes in anchorage requirement with age.     

Mechanical Differences Between Free-standing and Supported Wheat Plants, Triticum aestivum L.

The effect of wind sway on the mechanical characteristics ofthe anchorage roots and the stem was investigated in maturewinter wheat (Triticum aestivumL., cv. Hereward). Wheat plantswere field-grown, either supported by a frame, which preventedwind sway, or unsupported (free-standing) and the morphologyand mechanical properties of the stems and the anchorage, ‘coronal’, roots were measured. Wind sway had little influence on either the stem height orear weight of the plants but did affect the mechanical propertiesof the stem. Stems of supported plants were weaker and moreflexible than the stems of free-standing plants. There werealso differences in the anchorage systems between the treatments:supported plants had just under half as many ‘coronal’ anchorage roots as the free-standing plants. This reducedthe anchorage strength of supported plants by a third. These differences in mechanical structure meant that the free-standingplants were more resistant to stem buckling and more resistantto anchorage failure. However, considering the difference inthe need for mechanical strength in plants from the two regimes,these differences were small. This suggests that wheat has inherentmechanical integrity and, as a monocotyledon with no secondarythickening, it differs little structurally between environments. Triticum aestivumL.; thigmomorphogenesis; anchorage; safety factor; mechanical stimulation     

Habitat selection of nesting and fledgling salt marsh songbirds in northeast Florida

Understanding habitat selection by breeding birds and their newly fledged young can be an essential aspect of the conservation of vulnerable species. During 2015–2017, we examined nest site selection of Worthington's marsh wren (Cistothorus palustris griseus) and MacGillivray's seaside sparrow (Ammospiza maritima macgillivraii), and fledgling habitat use by Worthington's marsh wren, 2 imperiled species in northeast Florida, USA. We compared vegetation at unused points to vegetation at nests of both subspecies and at locations used by radio-tagged marsh wren fledglings. Vegetation was taller and stem counts were greater at nest sites compared to unused points. Worthington's marsh wrens also used nest sites with a greater proportion of tall-form smooth cordgrass (Spartina alterniflora) than was observed at unused points. Worthington's marsh wren fledglings also used locations with taller, denser vegetation, but vegetation use changed with fledgling age and tidal stage; older fledglings more frequently used areas with short-form smooth cordgrass and bare ground (and more so during low tides). In contrast, so few nests and nestlings were in black needlerush (Juncus roemerianus) that we could not consider it in our analysis despite its prevalence within our study sites. Our results indicate that tall, dense cordgrass is an important habitat component for these subspecies during the nesting and fledgling life stages in southeastern Atlantic salt marshes.     

Design and testing of a novel measuring system for use in dental biomechanics--principles and examples of measurements with the hexapod measuring system]

A novel measuring set-up based on a hexapod system for use in dental biomechanics is described. It was specially developed to measure force/deflection characteristics of different dental materials and devices. The functionability and suitability of the system for use in experimental biomechanics were investigated in two different studies. In a first study the micro mobility of prosthetic telescopic crowns prior to and after simulated wear was determined to investigate the influence of wear processes on the stability of the anchorage elements and thus of prostheses. This study investigated the ability of the setup to load a specimen with high forces or torques of up to 100 Newton. The second study looked at the force/deflection characteristics of orthodontic anchorage pins used in orthodontics to additionally stabilize the anchorage unit, for example during molar movement. In this study specimens were loaded with small forces of less than 10 Newton, as are typically used in orthodontics. Using the setup, the deflection behaviour of these devices under high and low loading was measured at a resolution of approximately one micrometer or one angular second.     

OSMOTIC RELATIONSHIPS IN THE HEN'S EGG

Data have been given to illustrate the difficulty of obtaining consistent freezing point data with a viscous fluid such as the yolk of the hen''s egg and a technique has been described for obtaining reproducible and accurate results consistently. Further freezing point data have been given which were obtained with both fertile and unfertile hen''s eggs by the use of a freezing point method previously described by the writer. These data show that there is a pronounced difference between the freezing points of the yolk and the white in contrast to data obtained by the use of the same method by Howard who found the freezing points of the yolk and the white to be the same. It was shown by freezing point determinations that even in a mixture of yolk and white osmotic equilibrium is slowly arrived at. This again emphasizes the fact established by Smith and Shepherd that since osmotic equilibrium between yolk and white is slowly arrived at, the postulation of a vital activity at the yolk membrane is unnecessary, since the steady state previously postulated need not be assumed to exist.     

Ecological Footprint: Informative and evolving – A response to van den Bergh and Grazi (2014)

Ecological Footprint accounting is used to track human demand on the Earth's biological resource flows, and compares that demand with the Earth's capacity to generate these flows. It is an evolving tool which has undergone many improvements alongside advancements in science and in response to critical review. Here we respond to van den Bergh and Grazi's recent points of criticism toward Ecological Footprint accounting. While the authors suggest that new criticism is accumulating, the main issues appear to be the same. We suggest that the majority of the criticism is derived from the misconception that the Ecological Footprint measures land “use,” which cannot exceed land availability. In response to these criticisms, we aim here to summarize and further clarify the major points of debate and confusion and allow readers to determine the relevance of these issues. We conclude that much of the prior discussion and many of the points repeated here reflect a divergence in general philosophical or semantic perspectives.     

The point of no return: Up to what point should we be allowed to withdraw consent to the storage and use of embryos and gametes?

This article discusses when it is ethically acceptable to withdraw consent for the storage and use of embryos and gametes. Currently, the law in the UK states that consent to use of a gamete or embryo can be withdrawn up to the point of the embryo's transfer to the recipient's uterus or when the gamete is used in providing treatment services; that is, the ‘point of no return’. In this article, we will consider other points of no return and argue that having a single point of no return, a one size fits all form of consent can, in some cases, lead to restrictions on individuals’ autonomy and cause particular types of harm. Therefore, having different points of no return that fit different circumstances could extend autonomy and allow people to enter into agreements that are tailored more to their own particular needs and circumstances.     

ADP-ribosylation intensifies cleavage of DNA loops in the nuclear matrix

Pulsed-field electrophoresis of DNA was used to demonstrate that ADP-ribosylation stimulates the cleavage of DNA loops at the sites of their anchorage to the nuclear matrix in nucleoids of human mononuclear leukocytes and rat brain neurons. ADP-ribosylation was assumed to play a role in regulating the activity of topoisomerase II in the nuclear matrix of eukaryotic cells.__________Translated from Molekulyarnaya Biologiya, Vol. 39, No. 2, 2005, pp. 317–320.Original Russian Text Copyright © 2005 by G. Zaalishvili, Tsetskladze, Margiani, Gabriadze, T. Zaalishvili.     

On the Rotation of Canonical Solutions

Some points of CLIFF /KRUS 's important rotation procedure are criticized. This result in the definition of simple structure of canonical solutions, the use of STEWART /LOVE 's redundancy index as a measure of common variance, and two new rotation procedures (HAKSTIAN 's modified varimax rotation, separate rotation of both sets). The objects of rotation should be the (intraset) loadings.