The cross-talk of LDL-cholesterol with cell migration: Insights from the Niemann Pick Type C1 mutation

Cholesterol is considered indispensible for the recruitment and functioning of integrins in focal adhesions for cell migration. However, the physiological cholesterol pools that control integrin trafficking and focal adhesion assembly remain unclear. Using Niemann Pick Type C1 (NPC) mutant cells, which accumulate Low Density lipoprotein (LDL)-derived cholesterol in late endosomes (LE), several recent studies indicate that LDL-cholesterol has multiple roles in regulating focal adhesion dynamics. Firstly, targeting of endocytosed LDL-cholesterol from LE to focal adhesions controls their formation at the leading edge of migrating cells. Other newly emerging literature suggests that this may be coupled to vesicular transport of integrins, Src kinase and metalloproteases from the LE compartment to focal adhesions. Secondly, our recent work identified LDL-cholesterol as a key factor that determines the distribution and ability of several Soluble NSF Attachment Protein (SNAP) Receptor (SNARE) proteins, key players in vesicle transport, to control integrin trafficking to the cell surface and extracellular matrix (ECM) secretion. Collectively, dietary, genetic and pathological changes in cholesterol metabolism may link with efficiency and speed of integrin and ECM cell surface delivery in metastatic cancer cells. This commentary will summarize how direct and indirect pathways enable LDL-cholesterol to modulate cell motility.

Tracking the migration of the Indian continent using the carbonate clumped isotope technique on Phanerozoic soil carbonates

Approximately 140 million years ago, the Indian plate separated from Gondwana and migrated by almost 90 degrees latitude to its current location, forming the Himalayan-Tibetan system. Large discrepancies exist in the rate of migration of Indian plate during Phanerozoic. Here we describe a new approach to paleo-latitudinal reconstruction based on simultaneous determination of carbonate formation temperature and delta O-18 of soil carbonates, constrained by the abundances of C-13-O-18 bonds in palaeosol carbonates. Assuming that the palaeosol carbonates have a strong relationship with the composition of the meteoric water, delta O-18 carbonate of palaeosol can constrain paleo-latitudinal position. Weighted mean annual rainfall delta O-18 water values measured at several stations across the southern latitudes are used to derive a polynomial equation: delta(18)Ow = -0.006 x (LAT)(2) - 0.294 x (LAT) - 5.29 which is used for latitudinal reconstruction. We use this approach to show the northward migration of the Indian plate from 46.8 +/- 5.8 degrees S during the Permian (269 M. y.) to 30 +/- 11 degrees S during the Triassic (248 M. y.), 14.7 +/- 8.7 degrees S during the early Cretaceous (135 M. y.), and 28 +/- 8.8 degrees S during the late Cretaceous ( 68 M. y.). Soil carbonate delta O-18 provides an alternative method for tracing the latitudinal position of Indian plate in the past and the estimates are consistent with the paleo-magnetic records which document the position of Indian plate prior to 135 +/- 3 M. y.

Prediction and confirmation of seasonal migration of Pacific sardine (Sardinops sagax) in the California Current Ecosystem

During the last century, the population of Pacific sardine (Sardinops sagax) in the California Current Ecosystem has exhibited large fluctuations in abundance and migration behavior. From approximately 1900 to 1940, the abundance of sardine reached 3.6 million metric tons and the “northern stock” migrated from offshore of California in the spring to the coastal areas near Oregon, Washington, and Vancouver Island in the summer. In the 1940s, the sardine stock collapsed and the few remaining sardine schools concentrated in the coastal region off southern California, year-round, for the next 50 years. The stock gradually recovered in the late 1980s and resumed its seasonal migration between regions off southern California and Canada. Recently, a model was developed which predicts the potential habitat for the northern stock of Pacific sardine and its seasonal dynamics. The habitat predictions were successfully validated using data from sardine surveys using the daily egg production method; scientific trawl surveys off the Columbia River mouth; and commercial sardine landings off Oregon, Washington, and Vancouver Island. Here, the predictions of the potential habitat and seasonal migration of the northern stock of sardine are validated using data from “acoustic–trawl” surveys of the entire west coast of the United States during the spring and summer of 2008. The estimates of sardine biomass and lengths from the two surveys are not significantly different between spring and summer, indicating that they are representative of the entire stock. The results also confirm that the model of potential sardine habitat can be used to optimally apply survey effort and thus minimize random and systematic sampling error in the biomass estimates. Furthermore, the acoustic–trawl survey data are useful to estimate concurrently the distributions and abundances of other pelagic fishes.

Y chromosome haplotypes reveal prehistorical migrations to the Himalayas

By using 19 Y chromosome biallelic markers and 3 Y chromosome microsatellite markers, we analyzed the genetic structure of 31 indigenous Sino-Tibetan speaking populations (607 individuals) currently residing in East, Southeast, and South Asia. Our results showed that a T to C mutation at locus M122 is highly prevalent in almost all of the Sino-Tibetan populations, implying a strong genetic affinity among populations in the same language family. Furthermore, the extremely high frequency of H8, a haplotype derived from M122C, in the Sino-Tibetan speaking populations in the Himalayas including Tibet and northeast India indicated a strong bottleneck effect that occurred during a westward and then southward migration of the founding population of Tibeto-Burmans. We, therefore, postulate that the ancient people, who lived in the upper-middle Yellow River basin about 10,000 years ago and developed one of the earliest Neolithic cultures in East Asia, were the ancestors of modem Sino-Tibetan populations.

Y-chromosome evidence of southern origin of the East Asian - Specific haplogroup O3-M122

The prehistoric peopling of East Asia by modern humans remains controversial with respect to early population migrations. Here, we present a systematic sampling and genetic screening of an East Asian-specific Y-chromosome haplogroup (O3-M122) in 2,332 individuals from diverse East Asian populations. Our results indicate that the O3-M122 lineage is dominant in East Asian populations, with an average frequency of 44.3%. The microsatellite data show that the O3-M122 haplotypes in southern East Asia are more diverse than those in northern East Asia, suggesting a southern origin of the O3-M122 mutation. It was estimated that the early northward migration of the O3-M122 lineages in East Asia occurred similar to 25,000-30,000 years ago, consistent with the fossil records of modern humans in East Asia.

Comparative ontogenetic behavior and migration of kaluga, Huso dauricus, and Amur sturgeon, Acipenser schrenckii, from the Amur River

We conducted laboratory experiments with kaluga, Huso dauricus, and Amur sturgeon, Acipenser schrenckii, to develop a conceptual model of early behavior. We daily observed embryos (first life phase after hatching) and larvae (period initiating exogenous feeding) to day-30 (late larvae) for preference of bright habitat and cover, swimming distance above the bottom, up- and downstream movement, and diel activity. Day-0 embryos of both species strongly preferred bright, open habitat and initiated a strong, downstream migration that lasted 4 days (3 day peak) for kaluga and 3 days (2 day peak) for Amur sturgeon. Kaluga migrants swam far above the bottom (150 cm) on only 1 day and moved day and night; Amur sturgeon migrants swam far above the bottom (median 130 cm) during 3 days and were more nocturnal than kaluga. Post-migrant embryos of both species moved day and night, but Amur sturgeon used dark, cover habitat and swam closer to the bottom than kaluga. The larva period of both species began on day 7 (cumulative temperature degree-days, 192.0 for kaluga and 171.5 for Amur sturgeon). Larvae of both species preferred open habitat. Kaluga larvae strongly preferred bright habitat, initially swam far above the bottom (median 50-105 cm), and migrated downstream at night during days 10-16 (7-day migration). Amur sturgeon larvae strongly avoided illumination, had a mixed response to white substrate, swam 20-30 cm above the bottom during most days, and during days 12-34 (most of the larva period) moved downstream mostly at night (23-day migration). The embryo-larva migration style of the two species likely shows convergence of non-related species for a common style in response to environmental selection in the Amur River. The embryo-larva migration style of Amur sturgeon is unique among Acipenser yet studied.

PHYLOGEOGRAPHIC PATTERNS INDICATE TRANSATLANTIC MIGRATION FROM EUROPE TO NORTH AMERICA IN THE RED SEAWEED CHONDRUS CRISPUS (GIGARTINALES, RHODOPHYTA)1

Inferring how the Pleistocene climate oscillations have repopulated the extant population structure of Chondrus crispus Stackh. in the North Atlantic Ocean is important both for our understanding of the glacial episode promoting diversification and for the conservation and development of marine organisms. C. crispus is an ecologically and commercially important red seaweed with broad distributions in the North Atlantic. Here, we employed both partial mtDNA Cox1 and nrDNA internal transcribed spacer region 2 (ITS2) sequences to explore the genetic structure of 17 C. crispus populations from this area. Twenty-eight and 30 haplotypes were inferred from these two markers, respectively. Analysis of molecular variance (AMOVA) and of the population statistic Theta(ST) not only revealed significant genetic structure within C. crispus populations but also detected significant levels of genetic subdivision among and within populations in the North Atlantic. On the basis of high haplotype diversity and the presence of endemic haplotypes, we postulate that C. crispus had survived in Pleistocene glacial refugia in the northeast Atlantic, such as the English Channel and the northwestern Iberian Peninsula. We also hypothesize that C. crispus from the English Channel refugium repopulated most of northeastern Europe and recolonized northeastern North America in the Late Pleistocene. The observed phylogeographic pattern of C. crispus populations is in agreement with a scenario in which severe Quaternary glaciations influenced the genetic structure of North Atlantic marine organisms with contiguous population expansion and locally restricted gene flow coupled with a transatlantic dispersal in the Late Pleistocene.

Features of Late Cenozoic Deepwater Sedimentation in Southern Qiongdongnan Basin, Northwestern South China Sea

Based on high resolution 2D and 3D seismic data acquired in recent years, using sequence stratigraphy analysis and geophysical methods, we discuss the features of Late Cenozoic deepwater sedimentation in the southern Qiongdongnan (sic) basin. The study area entered a bathyal slope environment in the Miocene. The channel developed in the Sanya (sic) Formation was controlled by a fault break, and its shingled seismic characteristics represent multiple erosion and fill, which may indicate that turbidite current developed in the slope environment. The polygon faults found in mudstone of the Meishan (sic) Formation represent the deepwater hungry sedimentary environment. The large-scale channels developed on the top of Huangliu (sic) Formation could be the result of a big sea level drop and an increase of sediment supply. The fantastic turbidite channel developed in Late Quaternary in the slope environment has "fan-like" body and long frontal tiny avulsion channel. The analysis of these features suggests that the sediment supply of the study area in the post-rifting period was dominant from the Vietnam uplift in the southwest. These deepwater sedimentary features could be potential reservoirs or migration pathways for deepwater petroleum systems.

Sequence variation in the CHAT locus shows no association with late-onset Alzheimer's disease

There is substantial evidence for a susceptibility gene for late-onset Alzheimer's disease (AD) on chromosome 10. One of the characteristic features of AD is the degeneration and dysfunction of the cholinergic system. The genes encoding choline acetyltransferase (ChAT) and its vesicular transporter (VAChT), CHAT and SLC18A3 respectively, map to the linked region of chromosome 10 and are therefore both positional and obvious functional candidate genes for late-onset AD. We have screened both genes for sequence variants and investigated each for association with late-onset AD in up to 500 late-onset AD cases and 500 control DNAs collected in the UK. We detected a total of 17 sequence variants. Of these, 14 were in CHAT, comprising three non-synonymous variants (D7N in the S exon, A120T in exon 5 and L243F in exon 8), one synonymous change (H547H), nine single-nucleotide polymorphisms in intronic, untranslated or promoter regions, and a variable number of tandem repeats in intron 7. Three non-coding SNPs were detected in SLC18A3. None demonstrated any reproducible association with late-onset AD in our samples. Levels of linkage disequilibrium were generally low across the CHAT locus but two of the coding variants, D7N and A120T, proved to be in complete linkage disequilibrium.

An anthropometric history of the World, 1810-1980: did migration and globalization influence country trends?

We find that regional height levels around the world were fairly uniform throughout most of the 19th century, with two exceptions: above-average levels in Anglo-Saxon settlement regions and below-average levels in Southeast Asia. After 1880, substantial diver- gences began to differentiate other regions -- making the world population taller, but more unequal. During the late 19th century and 20th century, heights between world regions devi- ated significantly, when incomes also became very unequal. Interestingly, during the “breaking point period” between the two regimes, heights declined significantly in the cattle-rich New World countries, whereas they started to increase in Old Europe. We discuss in this study whether immigration was a core factor to influence the height decline in the “Anthropometric Decline of the Cowboy and Gaucho Empires”.

"...and they won land among the Picts by friendly treaty or the sword": How a re-examination of early historical sources and an analysis of early medieval settlement in north Co. Antrim confirms the validity of traditional accounts of Dál Riatic migration to Scotland from Ulster

Much recent scholarship has been critical of the concept of a Dál Riatic migration to, or colonisation of, Argyll. Scepticism of the accuracy of the early medieval accounts of this population movement, arguing that these are late amendments to early sources, coupled with an apparent lack of archaeological evidence for such a migration have led to its rejection. It is argued here, however, that this rejection has been based on too narrow a reading of historical sources and that there are several early accounts which, while differing in detail, agree on one point of substance, that the origin of Scottish Dál Riata lies in Ireland. Also, the use of archaeological evidence to suggest no migration to Argyll by the Dál Riata is flawed, misunderstanding the nature of early migrations and how they might be archaeologically identified, and it's proposed that there is actually quite a lot of evidence for migration to Argyll by the Dál Riata, in the form of settlement and artefactural evidence, but that it is to be found in Ireland through the mechanism of counterstream migration, rather than in Scotland.

Neolithic and Bronze age migration to Ireland and establishment of the insular Atlantic genome

The Neolithic and Bronze Age transitions were profound cultural shifts catalyzed in parts of Europe by migrations, first of early farmers from the Near East and then Bronze Age herders from the Pontic Steppe. However, a decades-long, unresolved controversy is whether population change or cultural adoption occurred at the Atlantic edge, within the British Isles. We address this issue by using the first whole genome data from prehistoric Irish individuals. A Neolithic woman (3343–3020 cal BC) from a megalithic burial (10.3× coverage) possessed a genome of predominantly Near Eastern origin. She had some hunter–gatherer ancestry but belonged to a population of large effective size, suggesting a substantial influx of early farmers to the island. Three Bronze Age individuals from Rathlin Island (2026–1534 cal BC), including one high coverage (10.5×) genome, showed substantial Steppe genetic heritage indicating that the European population upheavals of the third millennium manifested all of the way from southern Siberia to the western ocean. This turnover invites the possibility of accompanying introduction of Indo-European, perhaps early Celtic, language. Irish Bronze Age haplotypic similarity is strongest within modern Irish, Scottish, and Welsh populations, and several important genetic variants that today show maximal or very high frequencies in Ireland appear at this horizon. These include those coding for lactase persistence, blue eye color, Y chromosome R1b haplotypes, and the hemochromatosis C282Y allele; to our knowledge, the first detection of a known Mendelian disease variant in prehistory. These findings together suggest the establishment of central attributes of the Irish genome 4,000 y ago.

Critical reappraisal of Late Mesozoic-Cenozoic Central and North Atlantic, Caribbean and Mediterranean evolution

(l) The Pacific basin (Pacific area) may be regarded as moving eastwards like a double zip fastener relative to the continents and their respective plates (Pangaea area): opening in the East and closing in the West. This movement is tracked by a continuous mountain belt, the collision ages of which increase westwards. (2) The relative movements between the Pacific area and the Pangaea area in the W-E/E-W direction are generated by tidal forces (principle of hypocycloid gearing), whereby the lower mantle and the Pacific basin or area (Pacific crust = roof of the lower mantle?) rotate somewhat faster eastwards around the Earth's spin axis relative to the upper mantle/crust system with the continents and their respective plates (Pangaea area) (differential rotation). (3) These relative West to East/East to West displacements produce a perpetually existing sequence of distinct styles of opening and closing ocean basins, exemplified by the present East to West arrangement of ocean basins around the globe (Oceanic or Wilson Cycle: Rift/Red Sea style; Atlantic style; Mediterranean/Caribbean style as eastwards propagating tongue of the Pacific basin; Pacific style; Collision/Himalayas style). This sequence of ocean styles, of which the Pacific ocean is a part, moves eastwards with the lower mantle relative to the continents and the upper-mantle/crust of the Pangaea area. (4) Similarly, the collisional mountain belt extending westwards from the equator to the West of the Pacific and representing a chronological sequence of collision zones (sequential collisions) in the wake of the passing of the Pacific basin double zip fastener, may also be described as recording the history of oceans and their continental margins in the form of successive Wilson Cycles. (5) Every 200 to 250 m.y. the Pacific basin double zip fastener, the sequence of ocean styles of the Wilson Cycle and the eastwards growing collisional mountain belt in their wake complete one lap around the Earth. Two East drift lappings of 400 to 500 m.y. produce a two-lap collisional mountain belt spiral around a supercontinent in one hemisphere (North or South Pangaea). The Earth's history is subdivided into alternating North Pangaea growth/South Pangaea breakup eras and South Pangaea growth/North Pangaea breakup eras. Older North and South Pangaeas and their collisional mountain belt spirals may be reconstructed by rotating back the continents and orogenic fragments of a broken spiral (e.g. South Pangaea, Gondwana) to their previous Pangaea growth era orientations. In the resulting collisional mountain belt spiral, pieced together from orogenic segments and fragments, the collision ages have to increase successively towards the West. (6) With its current western margin orientated in a West-East direction North America must have collided during the Late Cretaceous Laramide orogeny with the northern margin of South America (Caribbean Andes) at the equator to the West of the Late Mesozoic Pacific. During post-Laramide times it must have rotated clockwise into its present orientation. The eastern margin of North America has never been attached to the western margin of North Africa but only to the western margin of Europe. (7) Due to migration eastwards of the sequence of ocean styles of the Wilson Cycle, relative to a distinct plate tectonic setting of an ocean, a continent or continental margin, a future or later evolutionary style at the Earth's surface is always depicted in a setting simultaneously developed further to the West and a past or earlier style in a setting simultaneously occurring further to the East. In consequence, ahigh probability exists that up to the Early Tertiary, Greenland (the ArabiaofSouth America?) occupied a plate tectonic setting which is comparable to the current setting of Arabia (the Greenland of Africa?). The Late Cretaceous/Early Tertiary Eureka collision zone (Eureka orogeny) at the northern margin of the Greenland Plate and on some of the Canadian Arctic Islands is comparable with the Middle to Late Tertiary Taurus-Bitlis-Zagros collision zone at the northern margin of the Arabian Plate.

Interregional migration 'wage premia': the case of creative and science and technology graduates in the UK

We analyze the migration behavior of graduates from UK universities with a focus on the salary benefits they receive from the migration process. We focus on sequential interregional migration and specifically examine the case of Science, Technology, Engineering and Mathematics (STEM) and Creative subject graduates. Our analysis differs from previous studies in that it accounts explicitly for migrant selectivity through propensity score matching, and it also classifies graduates into different migration behavior categories. Graduates were classified according to their sequential migration behavior first from their pre-university domicile to university and then from university to first job post-graduation. Our results show that ‘repeat migration’, as expected, is associated with the highest wage premium (around 15%). Other migration behaviors are also advantageous although this varies across different types of graduates. Creative graduates, for instance, do not benefit much from migration behaviors other than repeat migration. STEM graduates, on the contrary, benefit from both late migration and staying in the university area to work.

Mid- to late Holocene Indian Ocean monsoon variability recorded in four speleothems from Socotra Island, Yemen

Four stalagmites covering the last 7.0 ka were sampled on Socotra, an island in the northern Indian Ocean to investigate the evolution of the northeast Indian Ocean Monsoon (IOM) since the mid Holocene. On Socotra, rain is delivered at the start of the southwest IOM in May–June and at the start of the northeast IOM from September to December. The Haggeher Mountains act as a barrier forcing precipitation brought by the northeast winds to fall preferentially on the eastern side of the island, where the studied caves are located. δ18O and δ13C and Mg/Ca and Sr/Ca signals in the stalagmites reflect precipitation amounts brought by the northeast winds. For stalagmite STM6, this amount effect is amplified by kinetic effects during calcite deposition. Combined interpretation of the stalagmites' signals suggest a weakening of the northeast precipitation between 6.0 and 3.8 ka. After 3.8 ka precipitation intensities remain constant with two superimposed drier periods, between 0 and 0.6 ka and from 2.2 to 3.8 ka. No link can be established with Greenland ice cores and with the summer IOM variability. In contrast to the stable northeast rainy season suggested by the records in this study, speleothem records from western Socotra indicate a wettening of the southwest rainy season on Socotra after 4.4 ka. The local wettening of western Socotra could relate to a more southerly path (more over the Indian Ocean) taken by the southwest winds. Stalagmite STM5, sampled at the fringe between both rain areas displays intermediate δ18O values. After 6.2 ka, similar precipitation changes are seen between eastern Socotra and northern Oman indicating that both regions are affected similarly by the monsoon. Different palaeoclimatologic records from the Arabian Peninsula currently located outside the ITCZ migration pathway display an abrupt drying around 6 ka due to their disconnection from the southwest rain influence. Records that are nowadays still receiving rain by the southwest winds, suggest a more gradual drying reflecting the weakening of the southwest monsoon.