Multinucleated Giant Cells’ Incidence, Immune Markers, and Significance: A Study of 172 Cases of Papillary Thyroid Carcinoma

Multinucleated giant cells (MGCs) are often detected in cases of papillary thyroid carcinoma (PTC). Their origin and significance, however, has not been established. One possibility is that they form in response to injury induced by fine needle aspiration biopsy (FNAB). Other hypotheses are that the chemically-altered colloid produced by PTC induces MGCs to act as colloidophages, or else MGCs are a non-specific immune response ingesting neoplastic follicle cells. We assigned 172 cases of PTC a semi-quantitative score for MGCs. Cases with “many” MGCs were immunohistochemically stained for AEI/AEIII, CD68, and CD163 to assess for epithelial vs histiocytic differentiation, and for thyroglobulin and TTF-1 to assess for MGC ingestion of colloid or thyroid follicle cells respectively. Overall, we identified MGCs in 100/172 (58.1%) PTC specimens; in 45 (26.2%), “many” MGCs were found, while in 55 (31.9%) MGCs were “few.” The mean sizes of PTC in cases with many as opposed to rare/no MGCs was 2.50 cm vs 1.8 [P = 0.003]. The cases of PTC with many MGCs had higher multifocality (26/45 vs 51/127 [P = 0.06]), extrathyroidal extension (21/45 vs 36/127 [P = 0.03]), and recurrence (8/45 vs 9/127 [P = 0.08]), than did cases with rare or no MGCs. The majority of patients both with and without numerous MGCs had previous histories of FNA or hemilobectomy: 40/45 and 99/127 respectively (P = 0.062). The majority of MGCs were positive for CD68 (45/45), CD163 (44/45), thyroglobulin (34/45) and negative for AEI/AEIII (44/45) and TTF-1 (44/45). These results indicate that MGCs in PTC are of histiocytic origin. Cases of PTC with many MGCs have a significantly greater likelihood of extrathyroidal extension and greater tumor size than cases with few/no MGCs. MGCs appear to be functioning largely as colloidophages

Small Interfering RNA against Transcription Factor STAT6 Leads to Increased Cholesterol Synthesis in Lung Cancer Cell Lines

STAT6 transcription factor has become a potential molecule for therapeutic intervention because it regulates broad range of cellular processes in a large variety of cell types. Although some target genes and interacting partners of STAT6 have been identified, its exact mechanism of action needs to be elucidated. In this study, we sought to further characterize the molecular interactions, networks, and functions of STAT6 by profiling the mRNA expression of STAT6 silenced human lung cells (NCI-H460) using microarrays. Our analysis revealed 273 differentially expressed genes after STAT6 silencing. Analysis of the gene expression data with Ingenuity Pathway Analysis (IPA) software revealed Gene expression, Cell death, Lipid metabolism as the functions associated with highest rated network. Cholesterol biosynthesis was among the most enriched pathways in IPA as well as in PANTHER analysis. These results have been validated by real-time PCR and cholesterol assay using scrambled siRNA as a negative control. Similar findings were also observed with human type II pulmonary alveolar epithelial cells, A549. In the present study we have, for the first time, shown the inverse relationship of STAT6 with the cholesterol biosynthesis in lung cancer cells. The present findings are potentially significant to advance the understanding and design of therapeutics for the pathological conditions where both STAT6 and cholesterol biosynthesis are implicated viz. asthma, atherosclerosis etc

New Insight into the Colonization Processes of Common Voles: Inferences from Molecular and Fossil Evidence

Elucidating the colonization processes associated with Quaternary climatic cycles is important in order to understand the distribution of biodiversity and the evolutionary potential of temperate plant and animal species. In Europe, general evolutionary scenarios have been defined from genetic evidence. Recently, these scenarios have been challenged with genetic as well as fossil data. The origins of the modern distributions of most temperate plant and animal species could predate the Last Glacial Maximum. The glacial survival of such populations may have occurred in either southern (Mediterranean regions) and/or northern (Carpathians) refugia. Here, a phylogeographic analysis of a widespread European small mammal (Microtus arvalis) is conducted with a multidisciplinary approach. Genetic, fossil and ecological traits are used to assess the evolutionary history of this vole. Regardless of whether the European distribution of the five previously identified evolutionary lineages is corroborated, this combined analysis brings to light several colonization processes of M. arvalis. The species' dispersal was relatively gradual with glacial survival in small favourable habitats in Western Europe (from Germany to Spain) while in the rest of Europe, because of periglacial conditions, dispersal was less regular with bottleneck events followed by postglacial expansions. Our study demonstrates that the evolutionary history of European temperate small mammals is indeed much more complex than previously suggested. Species can experience heterogeneous evolutionary histories over their geographic range. Multidisciplinary approaches should therefore be preferentially chosen in prospective studies, the better to understand the impact of climatic change on past and present biodiversity

Longitudinal and seasonal variations in plasmaspheric electron density: Implications for electron precipitation

The tilt and offset of the Earth's magnetic field can significantly affect the longitudinal and seasonal distribution of electron density in the plasmasphere. Here we show that for the solar maximum conditions of 1990–1991, the largest annual variation determined from CRRES measurements of plasmaspheric equatorial electron density in the range L = 2.5–5.0 occurs at American longitudes (−60°E), while no annual variation occurs at Asian longitudes (+100°E). Plasmaspheric electron density is larger in December than in June at most longitudes, from −180°E eastward to +20°E. At all other longitudes the density ratio from December to June is very close to 1.0. The largest December/June density ratio is at L = 3.0 at American longitudes (−60°E). At L = 4.5 and above, the annual variation disappears. The lowest electron density values for a given L-shell occur at American longitudes, in June. Ion densities also show significant annual variations, with similar longitudinal and seasonal characteristics in the case of IMAGE EUV He+ measurements. Atomic mass density measurements calculated using the magnetometer cross-phase technique show significant seasonal variations but also imply composition changes with longitude. Using the quasilinear PADIE code we calculate the bounce-averaged diffusion rate of electrons by plasmaspheric hiss with a fixed wave intensity. December to June variations in plasmaspheric density, particularly at American longitudes, drive changes in the wave-particle interactions, increasing diffusion into the loss cone by a factor of ∼3 at 1 MeV at L = 3.0, thus hardening the electron precipitation spectrum during the southern hemisphere winter (in June)

Vegetation history and lake-level changes from the Younger Dryas to the present in Eastern Pyrenees (France): pollen, plant macrofossils and lithostratigraphy from Lake Racou (2000 m a.s.l.)

A multi-proxy palaeoecological investigation including pollen, plant macrofossil, radiocarbon and sedimentological analyses, was performed on a small mountain lake in the Eastern Pyrenees. This has allowed the reconstruction of: ( 1) the vegetation history of the area based on five pollen diagrams and eight AMS(14)C dates and ( 2) the past lake-level changes, based on plant macrofossil, lithological and pollen analysis of two stratigraphical transects correlated by pollen analysis. The palaeolake may have appeared before the Younger Dryas; the lake-level was low and the vegetation dominated by cold steppic grasslands. The lake-level rose to its highest level during the Holocene in the Middle Atlantic ( at ca. 5060+/-45 b. p.). Postglacial forests ( Quercetum mixtum and Abieto-Fagetum) developed progressively in the lower part of the valley, while dense Pinus uncinata forests rapidly invaded the surroundings of the mire and remained the dominant local vegetation until present. The observed lowering of the lake levels during the Late Atlantic and the Subboreal ( from 5060 +/- B. P. to 3590+/-40 b. p.) was related to the overgrowth of the mire. The first obvious indications of anthropogenic disturbances of the vegetation are recorded at the Atlantic/Subboreal boundary as a reduction in the forest component, which has accelerated during the last two millennia

Apport des longues s\ue9quences lacustres \ue0 la connaissance des variations des climats et des paysages pl\ue9istoc\ue8nes

The already well-known pollen sequence from Velay illustrates the great complexity of the climate oscillations during the last 450 000 years (four climatic cycles). This sequence is compared with two records from northern Italy, Leffe (Lower Pleistocene till ca \u20131 Ma) and Pi\ue0nico S\ue8llere (starting at ca \u2013800 ka). It confirms that the glacial/interglacial cycles dramatically changed between 1 Ma and 800 ka. Lower Pleistocene cycles are shorter and warmer, with poorly marked glacial intervals; the climatic amplitude of Middle Pleistocene cycles is greater, from cold and dry glacial to interglacial optimums similar to the present. This change corresponds to the setting of the 100 000-year cycles associated with a major extinction phase for forest trees unable to survive during glacial intervals

Multiproxy analyses of Lake Allos reveal synchronicity and divergence in geosystem dynamics during the Lateglacial/Holocene in the Alps

Palaeoenvironmental reconstructions of ecosystem responses to external forcing are generally limited by the difficulty of understanding the geosystem as a whole, because of the complex interactions between ecological compartments. Therefore, identifying which geosystem compartments or proxies co-vary is a prerequisite in unravelling the propagation of disturbances (e.g. climatic or anthropogenic) from one compartment to another. A multiproxy study of a continuous 13,500-year sedimentary profile cored in Lake Allos (European Alps, 2200 m a.s.l) was carried out on the basis of high-resolution sedimentological, geochemical, and botanical analyses, as well as determination of aquatic biotic proxies (diatoms, ostracods). These multiproxy datasets are rare at these high altitudes. Major changes occurred in the course of the palaeoenvironmental history of this alpine watershed at 12,000, 8600, 7200 and 3000 cal. BP. During the Holocene, two main transitions were recorded in all the ecological compartments (8600 and 3000 cal. BP), but the period 4500-3000 cal. BP stands out because of major changes that concerned only the lacustrine ecosystem. The frequent switches in lake level might correspond to the 4.2 ka climatic event. Proximity of this alpine lake to climatically-sensitive thresholds (ice-cover, thermal stratification, hydrological balance) may have amplified climatic signals in the lake ecosystem. This study illustrates the difficulties inherent to the use of common intra-Holocene stratigraphical limits, given that ecological compartments are likely to have different responses to forcing factors depending on the characteristics of the watershed and its capacity to accommodate disturbances

LATE GLACIAL AND HOLOCENE BIOCLIMATIC RECONSTRUCTION IN SOUTHERN ITALY: THE TRIFOGLIETTI LAKE

The pollen record from Trifoglietti lake (Calabria region) provides new information about the paleoenvironmental and palaeoclimatic changes occurred during the LateGlacial and Holocene period. The LateGlacial part of the record, for which only preliminary data is available, is a new and original sequence from southern Italy. The Holocene sequence, with 11 AMS radiocarbon dates shows a stable Fagus forest for the entire period. Apart from sporadic pastoralism activities and the selective exploitation of Abies, only a weak human impact is recognized in the pollen records. Lake level oscillations have been reconstructed and annual precipitations quantified using the Modern Analogue Technique. The reconstruction was effectuated both at millennial and centennial scale: the first shows an increasing of moisture from 11000 to 9400 cal BP and a maximum of humidity from 9400 to 6200 cal BP. Moreover, several climatic oscillations punctuated the Holocene and therefore superimposed the millennial trend

A historical ecology of the Ecrins (Southern French Alps): Archaeology and palaeoecology of the Mesolithic to the Medieval period

International audienceThis paper elucidates the nature of human–environment interactions in a mountainous landscape (the southern zone of the Ecrins, French Alps) from the Mesolithic through to the Post-Medieval Period. We present an integrated programme of palynology, pedo- and archaeo-anthracology, and archaeology. These data permit the development of a historical ecology that allows us to differentiate between climatic and anthropogenic influences on vegetation, and the development of anthropogenic landscapes in an Alpine region. This study is of profound relevance for the broader understanding of human–environment interactions in ecologically sensitive environments both within the Alpine arc, but also beyond this region.We identify and explain evidence for possible human landscape management practices in a high altitude landscape. Palynology defines the broad floral context and evolution of the environment through the Holocene. Palynology also permits an assessment of human activities and practices (arable agriculture, pastoralism and haymaking). The combination of these data with anthracological and archaeological evidence permits a nuanced assessment of human interaction with the landscape. We consider phases of anthropological–ecological succession across the range of altitudes, from valley-bottom to the alpine zones in the Ecrins National Park.Four important stages of landscape use and change have been inferred from our evidence: the Mesolithic, the Chalcolithic/Bronze Age, Iron Age and Roman, and (Post)Medieval. During the Mesolithic (c. 8000–4500 BC), a major event is the expansion of fir in the montane stage. At higher altitudes, people exploit the ecotone, defined by the forest edge (or tree-line): an ideal zone for hunting. The Neolithic sees low-altitude clearances, but a continuation of hunting and low levels of human impact on high-altitude vegetation. The Chalcolithic/Bronze Age (2400–1000 BC) sees complex interplay of climatic changes, and the appearance of direct human intervention in the high altitude landscape as part of a new transhumant system. Although the Roman Period is characterised by phases of climatic amelioration after the deterioration of the Iron Age, the increase in human activity that is usually seen in low-lying areas is not reflected in the sub-alpine and alpine altitudes. The Medieval Period, including the Little Ice Age, witnesses a steady increase in human use of these landscapes, with forest manipulation and clearance becoming the defining characteristics of these areas. Despite the supposed inclement nature of the Little Ice Age, human activity achieves its zenith, and the combination people and climate produces the most open and managed landscape of the Holocene

1400 years of extreme precipitation patterns over the Mediterranean French Alps and possible forcing mechanisms

International audienceInvestigation of Lake Allos sediments revealed ~ 160 graded layers, interpreted as flood deposits, over the last 1400 yr. Comparisons with records of historic floods support the interpretation of flood deposits and suggest that most recorded flood events are the result of intense meso-scale precipitation events. As there is no evidence for any major changes in erosion processes in the catchment since the Medieval Warm Period (MWP), we interpret the Allos record in terms of repeated intense precipitation events over the last millennium, with a low flood frequency during the MWP and more frequent and more intense events during the Little Ice Age. This interpretation is consistent with the pattern of increasingly humid conditions in the northwestern Mediterranean region. This long-term trend is superimposed on high frequency oscillations that correlate with solar activity and autumnal North Atlantic Oscillation (NAO). Finally, a comparison of flood records across the northwestern Mediterranean region showed that intense precipitation events in Allos (east of the Rhône Valley) were out of phase with events in the Cévennes (west of the Rhône) but in phase with events in eastern Spain. Supported by meteorological analyses, this suggests an oscillation in atmospheric circulation patterns over the northwestern Mediterranean