Monocytes of patients with familial hypercholesterolemia show alterations in cholesterol metabolism

<p>Abstract</p> <p>Background</p> <p>Elevated plasma cholesterol promotes the formation of atherosclerotic lesions in which monocyte-derived lipid-laden macrophages are frequently found. To analyze, if circulating monocytes already show increased lipid content and differences in lipoprotein metabolism, we compared monocytes from patients with Familial Hypercholesterolemia (FH) with those from healthy individuals.</p> <p>Methods</p> <p>Cholesterol and oxidized cholesterol metabolite serum levels of FH and of healthy, gender/age matched control subjects were measured by combined gas chromatography – mass spectroscopy. Monocytes from patients with FH and from healthy subjects were isolated by antibody-assisted density centrifugation. Gene expression profiles of isolated monocytes were measured using Affymetrix HG-U 133 Plus 2.0 microarrays. We compared monocyte gene expression profiles from FH patients with healthy controls using a Welch T-test with correction for multiple testing (p < 0.05; Benjamini Hochberg correction, False Discovery Rate = 0.05). The differential expression of FH associated genes was validated at the mRNA level by qRT-PCR and/or at the protein level by Western Blot or flow cytometry. Functional validation of monocyte scavenger receptor activities were done by binding assays and dose/time dependent uptake analysis using native and oxidized LDL.</p> <p>Results</p> <p>Using microarray analysis we found in FH patients a significant up-regulation of 1,617 genes and a down-regulation of 701 genes compared to monocytes from healthy individuals. These include genes of proteins that are involved in the uptake, biosynthesis, disposition, and cellular efflux of cholesterol. In addition, plasma from FH patients contains elevated amounts of sterols and oxysterols. An increased uptake of oxidized as well as of native LDL by FH monocytes combined with a down-regulation of NPC1 and ABCA1 explains the lipid accumulation observed in these cells.</p> <p>Conclusion</p> <p>Our data demonstrate that circulating FH monocytes show differences in cell physiology that may contribute to the early onset of atherosclerosis in this disease.</p

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Parus superciliosus

XIII. Parus superciliosus The position of the White­browed Tit, specially emphasized by Bianchi (1902) with the name “ Poeciloides ”, was also discussed by Kleinschmidt (1911) with no decision regarding the relationships to P. gambeli. To assume conspecificity of these two (Eck 1980) went too far. Knowledge about this group has recently been enhanced by Martens and Gebauer (1993). According to molecular­genetic findings the sympatric species P. gambeli and P. atricapillus are more closely related to one another than either is to P. superciliosus (Gill et al., 2005), a situation reminiscent of a “triangular relationships” (see page 7).Published as part of Eck, Siegfried, 2006, The Palaearctic Titmouse Species (Aves: Paridae: Parus sensu lato) — A current survey *, pp. 7-54 in Zootaxa 1325 on page 41, DOI: 10.5281/zenodo.17404

Parus Eck, 2006, s.l.

2. Parus [m.] minor Opinions about the conspecifity of the major and minor Great Tits have changed according to the evaluation of the situation in the Amur contact region. A very recent analysis (Päckert et al. 2005) makes a species difference seem likely. — This group (P 4) is altogether quite nonuniform: just compare tibetanus with okinawae ! It is not known how different from one another the individual taxa within minor s.l. really are! The paper by Päckert et al. (2005) likewise suggests granting species status to the cinereus group as well, although commixtus has always been regarded as a mixed population comprising representatives of both groups (more precisely, only two neighbouring subspecies). This is concluded from a high cyt­ b distance, but not from observations in a contact region. — P. m. nigriloris Hellmayr (1900) of Ishigaki (also on Iriomote) is about as small and roundwinged as okinawae (cf. Eck 1977: 209), but lacks the lipochrome; Figs. in Kuroda (1925, Plate II, Figs. 5, 6 nigriloris, 7 okinawae). P. minor wladiwostokensis KLEINSCHMIDT, 1913 [Vladivostok]; P. minor minor TEMMINCK & SCHLEGEL, 1848 [Japan, cf. Morioka et al. 2005: 87]; P. minor artatus THAYER & BANGS, 1909 [Yichang, Hubei]; P. minor subtibetanus KLEINSCHMIDT & WEIGOLD, 1922 [Tatsienlu (Kangding)]; P. minor tibetanus HARTERT, 1905 [Chaksam, Tsangpo Valley/Tibet]; P. minor amamiensis KLEINSCHMIDT, 1922 [Amami­Oshima/N Riu­kiu islands]; P. minor okinawae HARTERT, 1905 [Okinawa, C Riu­kiu islands]; P. minor nigriloris HELLMAYR, 1900 [Ishigaki, S Riu­kiu islands]; P. minor dageletensis KURODA & MORI, 1920 [Dagelet island (Ullyngdo)]. The population groups: P 4 wladiwostokensis, minor, artatus, subtibetanus, tibetanus, amamiensis, dageletensis, kagoshimae, okinawae; E and C Asia. – Fig. Quinn: Plate 27: 85 f–j, l, in part. * Variable extent of white on the tail feathers and of the dorsal green. — Relative wing length and relative tail length, P. minor wladiwostokensis has longer wings and a somewhat longer tail than the ssp. minor. In the south of the area wings are longer (tibetanus up to 82 mm). On the islands, small and dark. — Compared to P 3 relatively long­tailed, up to 95 % vs 90 %. P 5 nigriloris; Iriomote, Ishigaki. — Fig. Quinn: Plate 27: 85 k. * No lipochrome, blue back, tail feather R 6 with white spot at tip, small (1 &male; 69 mm [type], 2 ΨΨ 62 and 65 mm wing length).Published as part of Eck, Siegfried, 2006, The Palaearctic Titmouse Species (Aves: Paridae: Parus sensu lato) — A current survey *, pp. 7-54 in Zootaxa 1325 on pages 19-20, DOI: 10.5281/zenodo.17404

Parus venustulus

1. Parus venustulus Parkes (1958: 96) placed the Yellow­bellied Tit P. venustulus with P. amabilis and P. elegans in a superspecies, probably correctly. Löhrl (1987, 1988) examined the ethology of the Yellow­bellied Tit in detail, compared it with other species and found interesting similarities to Coal Tits and Sylviparus modestus. Parus venustulus SWINHOE, 1870 [Yangtze gorges]. The population group: P 14 venustulus; China. — Figs. Berezowski & Bianchi 1891: Plate II: 3; Quinn: Plate 18: 65. * Pronounced sexual dimorphism in plumage coloration; for moult and plumages see Löhrl (1988) and Harrap and Quinn (1996: 311). — Extremely short­tailed, TWI of n= 12: x = 54.6 % ± 1.65, WTI (n= 13): x = 23.7 % ± 1.42. The extremely large P. amabilis, allospecies on Balabac, Calauit and Palawan, is relatively long­tailed (TWI of n= 4: x = 62.2 % ± 2.1; WTI: x = 19.6 % ± 1.76), resembling the other allospecies, the smaller, polytypic P. elegans (for distribution on the Philippines see Dickinson et al., 1991 and Kennedy et al., 2000), with a WTI around 15 %. [Additional taxa of geospecies IV on the Philippines]Published as part of Eck, Siegfried, 2006, The Palaearctic Titmouse Species (Aves: Paridae: Parus sensu lato) — A current survey *, pp. 7-54 in Zootaxa 1325 on page 25, DOI: 10.5281/zenodo.17404

Parus

1. Parus [p.] palustris Opinions about the subspecies of the Marsh Tit on the European continent have always differed; the populations are more or less clinally connected to one another. Acknowledging the western, brownish P. palustris longirostris KLEINSCHMIDT would be somewhat justified if the birds in central Germany are counted as ssp. palustris and the eastern ones as P. palustris stagnatilis C.L. BREHM, 1855 [E Galicia]; see Eck (1980: 142 “n= 7 aus Bolu”); Roselaar (1995: 137); Horvath & Keve (1975). Parus palustris, palustris group P. palustris dresseri STEJNEGER, 1886 [Kent]; P. palustris palustris LINN., 1758 [according to Hartert Sweden; syn. communis CONRAD, 1827, loc. typ. restr. Graubünden; subpalustris C.L. BREHM, Renthendorf, see Hartert 1918: 27; longirostris KLEINSCHMIDT, 1897, La Tour d’Auvergne, Puy de Dôme, France]; P. palustris italicus TSCHUSI & HELLMAYR, 1900 [Siena, Tuscany]; P. palustris stagnatilis C.L. BREHM, 1855 [E Galicia, today W Ukraine, see Hartert 1918: 27]; P. palustris kabardensis (BUTURLIN, 1929) [near Vladikavkas]. Parus palustris, brevirostris group Between the European and Asian Marsh Tits there is not only a broad geographical gap; they also differ remarkably in morphology, although negligibly in their molecular genetics (Gill et al. 2005: 127). The Asian forms have a larger throat spot, smaller feet, more bold bill. I know of no vocal comparisons. For the populations between Altai and Ussuria only subtle differences in colour have been described, but they should not be ignored here. The Sakhalin form is very close to the Japanese one (Eck 1980: 144). — In NE China P. p. jeholicus is adjacent to P. p. crassirostris towards the south; the two presumably interbreed. P. palustris altaicus JOHANSEN, 1952 [Buchtarma River, Katon­Karagai, S Altai]; P. palustris brevirostris (TACZANOWSKI, 1872) [Lake Baikal]; P. palustris crassirostris (TACZANOWSKI, 1885) [Sidemi, S Ussuria]; P. palustris ernsti YAMASHINA, 1933 [Naihoro, S Sakhalin]; P. palustris hensoni STEJNEGER, 1882 [Hakodate, Hokkaido*]; P. palustris jeholicus KLEINSCHMIDT & WEIGOLD, 1922 [30 km north of Balihandién, NE Jehol (Chengde)]; P. palustris hellmayri (BIANCHI, 1902) [Peking]. * The types of hensoni and seebohmi are extremely similar to a bird from the Kuriles in the collection in Washington (No. 96145), according to a letter received from Watson dated 26 December, 1978 (cf. Morioka et al. 2005: 115). The population groups: P 26 dresseri, palustris, stagnatilis, italicus, kabardensis; W Palaearctic. – Figs. Kleinschmidt 1897, J. Ornithol. 45: PlateIII, upper Fig (“ longirostris ”), PlateIV, upper Fig. (palustris); Quinn: Plate 15: 46 a–b (dresseri). * Clinal change from dorsal brown colour in the west to grey in the east, with slight increase in wing length (in England maximally 66 mm, in Slovakia 70 mm). — TWI 84 %, lower in England. P 27 altaicus, brevirostris, crassirostris, ernsti, hensoni; central to E Palaearctic. — Fig. Eck 1980 b: Plate 1 (brevirostris). * In comparison to P 26 thick bill, small feet. Varies in upper­side/flank coloration and bill height (Sakhalin and Japan). — TWI: n= 28 altaicus to crassirostris on average 96.6 % ± 2.26; n= 10 ernsti 89.7 % ± 1.5; n= 24 hensoni 89.5 % ± 2.1. P 28 jeholicus, hellmayri; NE China. — Figs. Eck 1980 b: Plate I (hellmayri); Quinn: Plate 15: 46 d–e (hellmayri). * Dorsal colour consistently brown, differentiated in wing length and relative tail length (13 hellmayri x = 86.2 % ± 1.15; 11 jeholicus x = 92.5 % ± 1.52).Published as part of Eck, Siegfried, 2006, The Palaearctic Titmouse Species (Aves: Paridae: Parus sensu lato) — A current survey *, pp. 7-54 in Zootaxa 1325 on pages 31-32, DOI: 10.5281/zenodo.17404

Sittiparus

Subgenus Sittiparus, type species Parus varius TEMMINCK & SCHLEGEL, 1848 Assigned by PORTENKO and Wolters to Periparus, by Gill et al. (2005) to Poecile (Varied Tits) Between 1830 and 1966 in Japan 6 hybrids between Parus varius and Parus montanus were reported, the last of which was intermediate in plumage but vocally very close to varius (Mishima 1969). Does this support the assignment to Poecile ? What criteria for genus status are applied? At least it must be asserted that P. v a r i u s has become rather isolated within Poecile. The relationship to P. semilarvatus (SALVADORI) on the Philippines, which has a quite different, altogether downwardly bent bill, is unclear.Published as part of Eck, Siegfried, 2006, The Palaearctic Titmouse Species (Aves: Paridae: Parus sensu lato) — A current survey *, pp. 7-54 in Zootaxa 1325 on page 29, DOI: 10.5281/zenodo.17404

Periparus

Subgenus Periparus, type species Parus ater L., 1758 (Coal Tits s.l.) Coal Tits in the broader sense: In Nepal J. Martens discovered a contact zone between P. ater aemodius and P. melanolophus, from which it could be concluded that the two are conspecific (Diesselhorst & Martens 1972; Martens 1975; Martens & Eck 1995). Later studies of birds from this contact region raised the question whether the so­called “cinnamon­breasts” represented a form close to melanolophus that was on the verge of extinction, whereas the extreme western variant of P. ater aemodius was described as P. ater martensi Eck 1998. West of the Thakkhola P. a. martensi becomes mixed with P. a. melanolophus (Löhrl 1994; Martens & Eck 1995: 331–332; Eck 1998). — From NW Africa to NE Iran the Coal Tits are more strongly differentiated, and their relationships require better clarification. — In Nepal Martens (1971, 1975) furthermore discovered that the so­called “Fichtenmeisen” (“spruce tits”) comprise two different species, P. rufonuchalis (monotypic) and P. rubidiventris (markedly polytypic), because they are sympatric in broad areas but have ecological differences. The two species are so closely related that this amounts to one of the rare cases in which a sympatric monotypic species should (?) be included among the “component species” (Clancey 1964, 1966) of the same superspecies, here Parus [rubidiventris], as Martens (1975) had already proposed. However, the vocal differences are considerable (Martens & Eck 1995: 326), so that for the present the question is merely raised; colour Fig. of the main forms l.c., Plate 2.Published as part of Eck, Siegfried, 2006, The Palaearctic Titmouse Species (Aves: Paridae: Parus sensu lato) — A current survey *, pp. 7-54 in Zootaxa 1325 on page 24, DOI: 10.5281/zenodo.17404

Parus

2. Parus [c.] cristatus The distribution was presented by Engel (1952), Mauersberger and Stephan (1967), see also Löhrl (1982). The geographical variation of the Crested Tit proves to be predominantly subtle and clinal; see Vaurie (1957: 16–17), Stugren and Kohl (1964), Kohl (1967), Roselaar (1995). P. cristatus scoticus (PRAZÁK, 1897) [loc. typ. restr. Strathspey, Scotland]; P. cristatus cristatus L., 1759 [Sweden]; P. cristatus baschkirikus (SNIGIREWSKI, 1931) [Miass, S Urals]; P. cristatus weigoldi TRATZ, 1914 [Favaios and Alijo, N Portugal]; P. cristatus abadiei JOUARD, 1929 [Lambézellec, Finistère, Brittany]; P. cristatus mitratus C.L. BREHM, 1831 [conifer forests of Germany]; P. cristatus bureschi V.JORDANS, 1940 [above Bansko, Pirin Mts., Bulgaria]. The population group: P 44 scoticus, abadiei, weigoldi, cristatus, baschkiricus, mitratus, bureschi; Europe. — Fig. Quinn: Plate 20: 68, in part. * Roselaar (1993 in Cramp & Perrins, 7: 206) described the geographical variation in great detail; it consists substantially of clinal coloration shifts from reddish brown to grey. The isolated Scottish population is smaller, and the Crested Tits in SW Europe are probably also. — Wing length from Saxony and Lusatia: 22 &male;&male; 64–68 mm, x = 65.8 mm ± 1.28; 16 ΨΨ 62–65 mm, x = 63.3 mm ± 1.17. Tail length: 22 &male;&male; 50–54 mm, x = 52.0 mm ± 1.12; 16 ΨΨ 49.5–51.5 mm, x = 50.5 mm ± 0.72. — TWI of 22 &male;&male; 75.4–81.5 %, x = 79.1 % ± 1.89, of 16 ΨΨ 76.9–82.4 %, x = 79.9 % ± 1.50.Published as part of Eck, Siegfried, 2006, The Palaearctic Titmouse Species (Aves: Paridae: Parus sensu lato) — A current survey *, pp. 7-54 in Zootaxa 1325 on page 42, DOI: 10.5281/zenodo.17404

Poecile

Subgenus Poecile, type species Parus palustris L., 1758 (Marsh Tits, Willow Tits, chickadees and allies) The Marsh Tits (P. palustris) can be extensively subdivided, in the western as well as the eastern Palaearctic. The Siberian brevirostris group (high bill, small feet, long tail) is clearly distinct from the allopatric palustris (although cyt­ b distance only 0.6 %, see GILL et al., 2005: 127) and the Chinese (parapatric?) hellmayri group. Parus hypermelaenus is here tentatively regarded as a species. Field work in Talish induced Loskot (1977, 1978, 1987) to ascribe species status to Parus lugubris hyrcanus: he observed that its voice deviates from that of other Sombre Tits, and it chisels out its nest holes itself, which would place it closer to the Willow Tits! Stepanjan (1978, 1990) and Harrap and Quinn (1996) shared this view of species independence. Löhrl (1982: 127) demonstrated experimentally that Balkan Sombre Tits (P. lugubris lugubris) also chop up rotten wood in a cavity and carry it out, but probably because of their body size do not prepare their own nest holes; hyrcanus is distinctly smaller. Eck (1980 and earlier) had proposed subdividing the Willow Tits to a greater extent on one hand, while on the other hand considering them closely related to the American chickadees as was formerly customary. Thönen and Fujimaki (1995: 174) and Thönen (1996) point out that Parus atricapillus turneri in Alaska sings “alpine”, like birds of the European montanus group and unlike the remaining Black­capped Chickadees, with which it appears to hybridise (Thönen 1996: 24). Thönen (l.c.) also emphatically declares that it would be erroneous to separate songarus in the Tian Shan from the Willow Tit at species level. Martens and Nazarenko (1993) as well as Martens et al. (1995) analysed the songs of Palaearctic Willow Tits regarding their historic differentiation; cf. also Kvist et al. (2001). The distribution was most recently presented by Quaisser and Eck (2002 /03). It exhibits several obviously parapatric situations (l.c., maps 3, 4!): in Europe between very similar representatives with different song forms, namely the salicarius, montanus and borealis complexes; in Asia between very dissimilar representatives with different but also consistent song forms, namely baicalensis­songarus, weigoldicus­affinis, baicalensisanadyrensis. Parus weigoldicus is evidently parapatric with P. m. affinis, is also separated by a considerable cyt­ b distance, and is here tentatively, and in analogy to P. hypermelaenus and P. teneriffae, considered an (allo)species.Published as part of Eck, Siegfried, 2006, The Palaearctic Titmouse Species (Aves: Paridae: Parus sensu lato) — A current survey *, pp. 7-54 in Zootaxa 1325 on page 30, DOI: 10.5281/zenodo.17404