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Polymorphisms of the mannose-binding lectin gene (MBL2) affect the concentration and functional efficiency of the protein. We recently used haplotype-specific sequencing to identify 23 MBL2 haplotypes, associated with enhanced susceptibility to several diseases.
In this work, we applied the same method in 288 and 470 chromosomes from Gabonese and European adults, respectively, and found three new haplotypes in the last group. We propose a phylogenetic nomenclature to standardize MBL2 studies and found two major phylogenetic branches due to six strongly linked polymorphisms associated with high MBL production. They presented high Fst values and were imbedded in regions with high nucleotide diversity and significant Tajima's D values. Compared to others using small sample sizes and unphased genotypic data, we found differences in haplotyping, frequency estimation, Fu and Li's D* and Fst results.
Using extensive testing for selective neutrality, we confirmed that stochastic evolutionary factors have had a major role in shaping this polymorphic gene worldwide.
MBL (mannose-binding lectin) is an important component of innate immunity and a central recognition molecule of the lectin pathway of complement, which probably represents the most ancient pathway of complement activation [1]. It binds to an array of carbohydrates such as D-mannose and N-acetyl-D-glucosamine on the surface of pathogens and directly opsonizes the microorganism for phagocytosis or activates the complement system via interaction with MBL-associated serine proteases (MASP-1, -2, -3 and Map19). Complement activation kills the pathogen by the membrane-attack complex or by complement-mediated phagocytosis through increased deposition of opsonic C3 fragments. MBL is also able to recognize altered self structures present on apoptotic cells, promoting their clearance, and to modulate the release of various pro-inflammatory cytokines [2,3].
The MBL2 genetic polymorphism is responsible for the very common and widespread variation of circulating levels of MBL oligomers and of functional activity of the protein in the human species. This variation is mainly caused by three single nucleotide polymorphisms (SNPs) in the first exon of the gene: MBL2*D (Arg52Cys), *B (Gly54Asp) and *C (Gly57Glu). These mutations have a profound effect on the assembly and stability of the protein, which leads to an increase of low-molecular-mass MBL that has reduced capacity of activating complement and of ligand binding [4,5]. The D, B and C SNPs have been collectively labeled O, whereas the major alleles at these loci have been called A. The concentration of the protein in serum is further modulated by at least three SNPs in the promoter region: MBL2*H,L (located 550 bp before the transcription start site), X, Y (located 221 bp before the transcription start site) and P, Q (non coding SNP located 4 bp after the transcription start site) [6,7]. The combination of structural and promoter polymorphisms results in a dramatic variation in the concentration of high-order MBL oligomers in apparently healthy individuals of up to 1,000-fold (European: range <20-10,000 ng/ml) [8]. Linkage disequilibrium between the SNPs is responsible for only eight haplotypes (as opposed to the 64 theoretically possible) associated with increasingly lower MBL serum concentration: MBL2*HYPA = LYQA = LYPA > LXPA ≫ HYPD = LYPB = LYQC = LYPD [7,9-13]. Using a haplotyping strategy developed by one of us, we recently defined 14 additional allelic haplotypes, most of them similar to LYQA or LYPA [2]. Genotypes carrying two copies of either HYPD, LYPB, LYQC or LYPD or one of them and LXPA are particularly associated with the susceptibility and severity of many diseases, as well as with protection against intracellular infections such as tuberculosis, leprosy and leishmaniasis [14-16].
In this work, we aimed to improve our former analysis by sequencing and haplotyping larger samples of European- and African-derived populations. In order to standardize and simplify comparisons between future association studies, we propose a nomenclature based on the evolutionary convergence of the identified MBL2 haplotypes [17]. We tested our samples for the hypothesis of selective neutrality and suggest that stochastic evolutionary factors have had a major role in shaping this polymorphism worldwide.
To uncover the selective role diseases could have exerted on the MBL2 polymorphism, we evaluated the MBL2 promoter and exon 1 region from 856 chromosomes of Gabonese adults (this work) and children [2], as well as from 470 chromosomes belonging to individuals of European descent, and compared it with previously published data. Genotype frequencies were at Hardy and Weinberg equilibrium.
MBL2 haplotypes identified in this study are listed in Table 1. They were named according to their evolutionary divergence [17] from a hypothetical ancient sequence probably related to LYQA and LYPA [11,18]. According to the nomenclature system we adopted, the first clades to diverge are numbered with Arabic numerals. The 26 identified haplotypes are divided into two major phylogenetic branches by six polymorphisms (P1, Q1 or g.396A > C; P2, Q2 or g.474A > G; P3, Q3 or g.487A > G; P4, Q4 or g.495_500del6; P5, Q5 or g.753C > T, all in strong linkage disequilibrium with the commonly investigated P6, Q6 polymorphism or g.826C > T) (Figure 1). Clade *1 is represented by LYPA and other haplotypes with P variants. Clade *4 is represented by LYQA and other haplotypes with Q variants. Other clades are represented by the intermediate rare haplotypes previously found by our group in Gabon (2 and 3) [2]. Sublineages of each clade are subsequently designated with capital letters (e.g. LYQA-derived haplotypes = *4A and LYQC-derived haplotypes = *4F), and individual present-day haplotypes are given Arabic numerals (e.g. LYQA = *4A1), following the schema numerals/letters/numerals, if they diverge further (e.g. the LYQC-derived haplotype with the g.797C > A SNP, associated with severe malaria = *4F2A). This system is flexible enough for the accommodation of new haplotypes. For example, we added the LYPA-similar haplotypes H16 and H19 found by others exclusively in Pygmy populations [19] as *1K1 and *1L1, and added the HYPG haplotype described by us in another study [16], as 1B4. It is however not suited for recombinant haplotypes. In this case, we chose to call them by the names of the parental haplotypes, separated by a dot. LYPD for example is most probably the product of a recent intragenic recombination event between HYPD (*1B2) and LYPA (*1A1) or LYPB (*1F1) [20]. Since the recombination between HYPD and LYPB would have generated HYPB, which has not been found, we arbitrarily chose to call this haplotype *1A1.1B2 (equivalent to LYPA × HYPD). We also wished to incorporate reported associations of haplotypes with MBL concentration. In order to do this, we added a dash followed by small capitalized "h" or "l" letters, referring to "high" or "low" MBL levels in serum, respectively (e.g. LYQA = *4A1-h).
Table 1. Nucleotide changes and haploypes of MBL2.
Figure 1. Maximum parsimony tree with suggested phylogenetic nomenclature (see text). The recombinant haplotype *1A1.1B2-l (LYPD) was excluded. Bootstrap values are given at nodes of the tree.
We identified in this and in other studies 14 haplotypes belonging to clade *1 and 9 haplotypes belonging to clade *4 and added data from others for comparison (Table 2). Eight of the first 14 and 6 of the last 9 haplotypes were polymorph in at least one population. Among the rare haplotypes, we found three previously unknown in the European population: *1B3, a rare HYPA-similar haplotype; *1C2, the only LXPA-similar haplotype; and *4C1-h, a LYQA-similar haplotype with a g.456G > T SNP found in three heterozygotes (the first two haplotypes were singletons). The g.456G > T SNP was assigned by others to an otherwise HYPA haplotype reconstructed from unphased genotypic data of one Sardinian heterozygote [19]. Maximum likelihood phasing of our own data with the EM and ELB algorithms generated 1-2% erroneously assembled haplotypes in the Gabonese and European samples. Only in the Gabonese, seven spurious "new" haplotypes were generated with the EM and eleven with the ELB algorithm (Table 3). To verify the effect of sample size in frequency estimates, we compared the haplotype distribution between some populations investigated by us and by others [19]. Although there were no significant differences with the exact population differentiation test, differences between individual haplotype frequencies were significant, even between samples with similar ancestry (Table 2).
Table 2. MBL2 haplotype frequencies (%) in diverse populations.
Table 3. Performance of haplotyping algorithms.
With the exception of LYQA (*4A1-h), *4 haplotypes are well represented only in the African population. In contrast, HYPA (*1B1-h) and LYPB (*1F1-l) are among the *1 haplotypes that reach high frequencies in the European, Asian and Native American, but not in the African population (Figure 2). The uneven haplotype distribution around the world is reflected by the average Fst value among all segregating sites (0.1831, P < 0.00001), which indicate great genetic differentiation between the analysed populations. One of the lowest individual significant Fst values corresponded to the X/Y SNP, whereas the highest values corresponded to the H, L and P, Q segregating sites (Figure 3). The time to the most recent common ancestor of the MBL2 alleles was inferred at 73,251 years ago [95% CI 5,220 - 214,440]. The mean coalescence time implies that the ancestor of groups *1 and *4 alleles were separated before the modern human dispersal from Africa [21]. The TMRCA of groups *1 and *4 was estimated to be ca. 55,000 years ago, which also indicates that the presence of alleles of African populations in both clades is a result of an ancient ancestry.
Figure 2. Mutational network of MBL2 haplotypes. The size of each node is proportional to the haplotype frequency in the pooled sample (this work and [18,28]). Variant nucleotide positions are indicated in red. In black: African; red: European; orange: North Chinese; blue: Guarani; green: Kaingang.
*1B-derived haplotypes, even those found using maximum-likelihood phasing by others [19], seem to be restricted to Euroasiatic populations. Beyond those described in this work, we recently identified *1B4 in the Euro-Brazilian population. This haplotype is similar to HYPA but with a synonymous substitution in codon 44 (also called HYPG) [16]. To our knowledge, LXPA (*1C1-l) has only one rare similar haplotype (*1C2), identified in one European individual. We also found only one LYPB-similar haplotype (*1F2), but others cite another four [19]. Each occur with frequencies around 2% in Asian/Amerindian groups (Ashkenazi Jewish, Japanese, Chinese and Kaingang), but three were defined by SNPs upstream to the region analysed in this study. The *1H1-h haplotype has a similar global distribution as the commonly investigated haplotypes and is well represented in African, Asian and Amerindian(-derived) populations, being less frequent in European groups. We found a similar haplotype (*1H2-h) once in a Gabonese and once in a Euro-Brazilian individual. All other clade *1 haplotypes are concentrated in African groups. *1E1-h has a rare coding mutation found only once in the Gabonese, as *1G1-h [2]. The *1D1-h haplotype, which we found with 3% frequency in this population, was found by others with comparable frequencies (1.6 - 4.2%) in the Mbuti Pygmy, Nigerian Yoruba and Somali populations [19]. *1J1-h was also found with 1.6% and 0.8% frequencies in Tanzanian Chagga and in the Somali groups, respectively. *2A1-h and *3A1-h are intermediate between P and Q containing haplotypes and most probably reminiscent of the ancient original MBL2 haplotype [2]. The LYQA-similar *4B1-l haplotype carries a coding mutation and was found only once in the Gabonese, as the LYQC-similar haplotype *4F2B-l. In addition to the Gabonese, *4D1-h was found by others with 1.6% frequencies in the Tanzanian Chagga [19]. *4E1-h has a SNP within a glucocorticoid responsive element and seems to be well distributed in Africa, except in the Mbuti and Baka Pygmies [19]. 4F2A-l was formerly found associated with severe malaria [2] and has a similar distribution, except for the fact that it is also present in South-West Asian and European(-derived) groups with 11.9% (Ashkenazi Jewish [19]) to 0.5% (Germans, this work) frequencies. *4F3-l was also found in the Biaka Pygmy (2.1%), Nigerian Yoruba (1.6%) and Tanzanian Chagga (4.7%) groups [19], as well as in Afro-Americans [18] and in one individual of the Kaingang Amerindian population, known to be of mixed ancestry [22].
Tajima's D was significant in those regions containing five of the six P, Q segregating sites in the Gabonese population (Figure 4A). Yet Fu and Li's D* was significant in regions with rare SNPs: the LXPA-derived *1C2 haplotype in Europeans and the LYPA-derived *1E1-h haplotype in the Gabonese (also called LYPF due to a non-synonymous SNP in the exon 1 region) (Figure 4B). Highest nucleotide diversity was registered in the same windows with Tajima's D peaks (Figure 4C). None of the neutrality tests employed for the whole sequence or parts of it yielded significant results (Table 4).
Table 4. MBL2 sequence diversity parameters of several populations.
Figure 4. Sliding window plot of (A) Tajima's D values, (B) Fu and Li's D* values and (C) nucleotide diversity for the entire sequenced region. Statistics were calculated for overlapping windows of 60 bp, placed at 15 bp intervals along the sequence. * P < 0.05.
Both circulating levels of MBL oligomers and functional activity have been correlated with common MBL2 genetic variants. There are at least 28 segregating sites in the MBL2 promoter and exon 1 sequence [23], and 26 allelic haplotypes were physically defined in this study. Nucleotide diversity in Afro-derived populations reached 5 × the average value of chromosome 10 (8.25 × 10-4) [24], where the MBL2 gene resides (10q11.2→q21). This is still 2 × less than the lowest values found for polymorphic MHC regions (1%) [25], indicating that the MBL2 promoter-exon1 nucleotide diversity is intermediate among immune protein coding genes.
Several of the newly identified haplotypes are polymorph and of interest for disease association studies. Nevertheless beside the A/B/C/D system adopted for exon 1 alleles since 1991 [26] and of the H, L, X, Y and P, Q names for promoter SNPs since 1998, no other nomenclature was suggested. We adopted a phylogenetic approach that easily accommodates new haplotypes following a logical order, and suggested a way to call eventual recombinant haplotypes, incorporating knowledge about MBL serum levels.
Nevertheless haplotypes generated with EM and ELB haplotyping algorithms should be included with caution, especially when containing singletons. In our comparison, EM and ELB algorithms allowed for 1-2% errors in populations with high nucleotide diversity (π). The pseudo-Bayesian ELB performed worse in groups with very high π values, as Africans, generating more spurious "new" haplotypes. We did not find six of the haplotypes reconstructed by others using the Bayesian method implemented in PHASE software [19]. Two were recombinant (LYQB and HXPA), one presented a SNP that we haplotyped to LYQA and three were LYPA-similar haplotypes that seemed to be restricted to Pygmy populations, with SNPs presenting high Fst values. To avoid the inclusion of false haplotypes in the nomenclature system, we followed the approach of a group which only analysed haplotypes having a minimal frequency of 10% [27]. Two of the Pygmy haplotypes fulfilled this requirement, but all other haplotypes should ideally be phased by a physical haplotyping technique before inclusion.
Others used sample sizes at least four times smaller than ours [18,19]. This caused discrepant frequency results especially for the most common haplotypes. Since rare variants are not easily detected in small population samples, we also found considerable differences between our Fu and Li's D* and F* and other's results [18]. Indeed, two singletons caused significant D* values in regions with very low nucleotide diversity levels specifically in our European and Gabonese samples.
We added data from other studies [2,18,19,22,28] to calculate the Fst statistic. This approach resulted in much higher Fst values for the whole gene (0.18), than those found previously by others (0.06 [18]) and by us using only the Amerindian and Chinese samples (0.12, [22]). The same was true for the H/L and P/Q SNPs (Fst values around 0.2-0.25, compared to published 0.1-0.15, [18]), which indicate that they are good markers for population differentiation. As opposed to these high Fst values, the X/Y SNP presented values lower than 0.05 in this and in another study [18], compatible with global balancing selection.
We previously discussed the origin and distribution of the LYPA (*1A1-h), HYPA (*1B1-h), HYPD (*1B2-l), LXPA (*1C1-l), LYPB (*1F1-l), LYPD (*1A1.1B2-l), LYQA (*4A1-h) and LYQC (*4F1-l) haplotypes [22]. In general, the most frequent clade *1 haplotypes are globally distributed, whereas clade *4 haplotypes are more restricted to the African continent. Four of the five most ancient haplotypes also belong to clade *1: *1A1-h, *1B1-h, *1C1-l and *1H1-h. Among them, only *1C1-l (with the X variant) is associated with low (although complement-activating) MBL production. This and the *4A1-h haplotype do not naturally occur in native Aboriginal, Greenlandic and Amerindian populations [11,22,29,30], having probably been lost through bottleneck effects along the migration routes. The other eight polymorph haplotypes (with a frequency higher than 1%) have probably had a more recent origin, being geographically more restricted. Among them, only two are associated with high MBL levels: *1D1-h and *4E1-h. All others generate low MBL levels that, in addition, are greatly restricted in complement activation due to the B, C and D mutations, which occur in critical residues of the collagen-like region (*1B2-l, *1F1-l, *4F1-l, *4F2A-l, *4F3-l and *1F2) (Figure 5). Interestingly, the MBL1P1 pseudogene has been selectively turned off during evolution through the same molecular mechanisms causing the non-functional recent MBL2 haplotypes in man [31]. A more restricted distribution is obviously the case of all haplotypes containing singletons, as well as of *1J1-h, *4D1-h and *4F3-l in Africa, *1A1.1B2-l, *1B2-l and *4C1-h in Europe. They are therefore characteristic of different ethnic groups.
Figure 5. Distribution and origins of the MBL2 alleles in the world. Arrows denote the mutational steps between haplotypes (six between *1 and *4) and when dotted, the ancient migratory routes with their approximate ages [51]. The haplotypes which could have been lost by natural selection and/or genetic drift were denoted by '?'. In bold: haplotypes generated before human out-of-Africa migration. Squared: more recent haplotypes, with geographically restricted distribution. KYA thousand years ago.
The clades *1 and *4 are separated by six mutational steps (P, Q variants), which probably occurred before the human out-of-Africa migration (Figure 5). Of these six segregating sites, probably the most ancient is the g.487G > A variant and the most recent, the g.396A > C variant [2]. Q variants are less widely distributed than P variants, justifying their high Fst values. They are functionally associated with higher promoter activity [6,32] and five of them presented positive, significant Tajima's D values in the Gabonese population. A significant positive value for Tajima's D test indicates an excess of intermediate-frequency variants, as compared with expected frequencies under neutrality, and constitutes evidence of balancing selection (mutations leading to higher MBL levels could have been selectively retained in the ancient human population) or population subdivision. Nevertheless the emergence of several recent mutations as well as genetic drift erased the selective signature at the long haplotype scale, leading to non-significant, although positive, Tajima's D values for the whole haplotype in this and in other studies (eg. Table 4), one of which included 1,166 chromosomes from 24 worldwide populations [18,19,22]. The patterns of MBL2 variation at the large temporal scale would thus have been shaped by stochastic evolutionary factors and therefore be compatible with neutral evolution.
In this work, we evaluated the MBL2 promoter-exon 1 region using haplotype-specific sequencing in more than 700 chromosomes and found three new European haplotypes. We propose a phylogenetic nomenclature to standardize MBL2 studies and found two major phylogenetic branches due to six strongly linked polymorphisms associated with high MBL production. They present high Fst values and are imbedded in regions with high nucleotide diversity and significant Tajima's D values. Compared to others using small sample sizes and unphased genotypic data, we found differences in haplotyping, frequency estimation, Fu and Li's D* and Fst results. Using extensive testing for selective neutrality, we confirmed that stochastic evolutionary factors have had a major role in shaping this polymorphic gene worldwide.
Subjects and samples
We investigated 104 German Europeans, 131 Euro-Brazilians and 144 Gabonese adults. The German Europeans were healthy unrelated students and employees of the University of Tübingen, enrolled as controls in a genetic association study with type 2 diabetes, approved by the Ethics Committee of the University of Tübingen in Germany [33]. The Euro-Brazilians were healthy blood donors with mixed, however predominantly European ancestry, resident in Paraná state, South Brazil, sampled for different association studies, all approved by the Ethics Committee of Research in Humans of the Clinical Hospital, Federal University of Paraná, Brazil [16,34,35]. The Gabonese individuals took part in a large epidemiologic survey to detect the prevalence of asymptomatic Plasmodium falciparum infection in the villages around Lambaréné, Gabon, a study approved by the ethics committee of the International Foundation Albert Schweitzer Hospital [36]. All individuals signed an informed consent form prior to their inclusion in these studies.
MBL2 typing
DNA was collected with anticoagulant ethylenediaminetetraacetic acid and extracted from peripheral blood mononuclear cells through standard salting-out and phenol/chloroform/isoamyl alcohol methods. A fragment of 1059 nucleotides was amplified using the forward primers MBLfor (5'-ATGGGGCTAGGCTGCTGAG-3') and the reverse primer MBLrev (5'-CCAACACGTACCTGGTTCCC-3'). Sequence specific (SSP) PCR products were generated using the same reverse primer, combined to forward primers specific for variant H (Hf: 5'-GCTTACCCAGGCAAGCCTGTG-3') or for the variant L (Lf: 5'-GCTTACCCAGGCAAGCCTGTC-3'); for the variant X (Xf: 5'-CCATTTGTTCTCACTGCCACC-3') or for the variant Y (Yf: 5'-CCATTTGTTCTCACTGCCACG-3'). The PCR products with the primers Hf or Lf with MBLrev and Xf or Yf with MBLrev were 837 and 508 nucleotides in length, respectively. Hf and Lf were also combined to specific reverse primers for the variant P (Pr: 5'-CTCAGTTAATGAACACATATTTACCG-3') or for the variant Q (Qr: 5'-CTCAGTTAATGAACACATATTTACCA-3'), generating a product of 599 nucleotides. All fragments were sequenced with the amplification primers or with an internal exon 1 sequencing primer, MBLint (5'-GAGGCCAGGGATGGGTCATC-3'), using Big dye terminator version 1.1 chemistry (Applied Biosystems, Foster City, CA). Amplification conditions are described in detail elsewhere [20]. The reactions were purified with the Performa DTR V3 system (Edge BioSystems, Gaithersburg, MD) and analyzed on an automated sequencer (ABI Prism 3100 Genetic Analyzer, Applied Biosystems, Foster City, CA). New variants (singletons) were verified by reamplification and resequencing.
Statistical analyses
Genotype and haplotype frequencies were obtained by direct counting. We tested for deviations from Hardy-Weinberg proportions with the exact test of Guo and Thompson [37]. The haplotype frequency distributions of the populations examined by our group and by others were compared by applying the exact test of population differentiation of Raymond and Rousset [38]. Genetic differentiation among populations was estimated from haplotype frequencies using the Fst statistic, based on the analysis of molecular variance [39]. To verify the effect of other methods to infer haplotypes compared to physical haplotyping of SNPs, we simulated our own data using the (maximum-likelihood) EM algorithm or the (pseudo-Bayesian) ELB algorithm, with the settings recommended by the authors [40,41]. These statistical analyses were done using the software package ARLEQUIN version 3.1 [42]. Fisher's exact tests were performed for differences between individual haplotype frequencies, using SISA software package http://home.clara.net/sisa webcite.
We calculated the following summary statistics of genetic diversity: the number of polymorphic sites (S), the nucleotide diversity over loci (π) and Watterson's θ, defined as 4Neμ, where Ne is the effective population size and μ, the estimated mutation rate. We examined deviation from neutrality-equilibrium conditions using Tajima's D statistic [43], Fu and Li's D and Fu and Li's F without an outgroup (also known as D* and F*) [44] and Fay and Wu's H [45] tests. Significance was assessed by comparing the observed values to 104 coalescent simulations, conditional on the observed sample size and on the value of S or on the value of θ, assuming a standard neutral model with no recombination. Deletions were excluded from all analyses. To see if deviation from selective neutrality can be found in specific regions of the gene, we also tested the 5' upstream regulatory region (which includes the non-coding P, Q SNP) and the exon 1 coding region separately. The heterogeneity in π values and Tajima's D statistic across the sequenced region was also examined by use of the sliding window feature of the DnaSP program. Statistics were calculated for overlapping windows of 60 bp, placed at 15 bp intervals along the sequence. Neutrality tests and sequence diversity parameters were calculated using the DnaSP version 4.10.1 software [46].
The Network 18.104.22.168 package http://www.fluxus-technology.com/sharenet.htm webcite was used to construct the minimum-mutation network, which reflects the mutational relationships among the MBL2 haplotypes by means of the Median Joining (MJ) algorithm [47]. The MEGA 3.1 program was used to construct the phylogenetic maximum parsimony tree with bootstrap test http://www.megasoftware.net/ webcite. The time to the most recent common ancestor (TMRCA) of MBL2 was estimated using a relaxed molecular clock approach [48]. Evolutionary rate was modeled by the uncorrelated lognormal distribution and a coalescent prior (Bayesian skyline) was assigned to the tree. The average rate of molecular evolution of the MBL2 gene (1 × 10-7) was obtained using a theta per site value of 0.0039 calculated for human sequences in DnaSP [46] and the estimate of human effective population size of 10,000 [49]. A normal prior with mean 1 × 10-7 and standard deviation of 1 × 10-7 was used for the rate of evolution. Divergence time inference was conducted in BEAST 1.4.8 [50]. In order to obtain the posterior distribution of divergence times, the Markov chain was sampled 50,000 times and 10% of the states were discarded as burn-in.
Authors' contributions
ABWB carried out the molecular biological studies and wrote the manuscript. IJM-R participated in the molecular work and conducted the recruitment of subjects. ABWB, DM, CGS, MLP-E and KD participated in statistical analyses. FL, BL, and PGK conducted the recruitment of individuals for the study. JFJK supervised the molecular work and finalised the manuscript.
All authors read and approved the final manuscript.
The subjects of this investigation were informed about the aims of the study and their consent to participate is gratefully acknowledged. We thank Andrea Weierich and Silvelia Grummes for excellent technical assistance. Financial support was provided by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).
Fujita T, Matsushita M, Endo Y: The lectin-complement pathway - its role in innate immunity and evolution.
Immunol Rev 2004, 198:185-202. PubMed Abstract | Publisher Full Text
Boldt AB, Luty A, Grobusch MP, Dietz K, Dzeing A, Kombila M, et al.: Association of a new mannose-binding lectin variant with severe malaria in Gabonese children.
Genes Immun 2006, 7:393-400. PubMed Abstract | Publisher Full Text
Gadjeva M, Takahashi K, Thiel S: Mannan-binding lectin--a soluble pattern recognition molecule.
Mol Immunol 2004, 41:113-121. PubMed Abstract | Publisher Full Text
Garred P, Larsen F, Madsen HO, Koch C: Mannose-binding lectin deficiency--revisited.
Mol Immunol 2003, 40:73-84. PubMed Abstract | Publisher Full Text
Larsen F, Madsen HO, Sim RB, Koch C, Garred P: Disease-associated mutations in human mannose-binding lectin compromise oligomerization and activity of the final protein.
J Biol Chem 2004, 279:21302-21311. PubMed Abstract | Publisher Full Text
Juliger S, Luckner D, Mordmuller B, May J, Weierich A, Lell B, et al.: Promoter variants of the human mannose-binding lectin gene show different binding.
Biochem Biophys Res Commun 2000, 275:617-622. PubMed Abstract | Publisher Full Text
Madsen HO, Garred P, Thiel S, Kurtzhals JA, Lamm LU, Ryder LP, et al.: Interplay between promoter and structural gene variants control basal serum level of mannan-binding protein.
J Immunol 1995, 155:3013-3020. PubMed Abstract | Publisher Full Text
Dommett RM, Klein N, Turner MW: Mannose-binding lectin in innate immunity: past, present and future.
Tissue Antigens 2006, 68:193-209. PubMed Abstract | Publisher Full Text
Ip WK, To YF, Cheng SK, Lau YL: Serum mannose-binding lectin levels and mbl2 gene polymorphisms in different age and gender groups of southern Chinese adults.
Scand J Immunol 2004, 59:310-314. PubMed Abstract | Publisher Full Text
Lee SG, Yum JS, Moon HM, Kim HJ, Yang YJ, Kim HL, et al.: Analysis of mannose-binding lectin 2 (MBL2) genotype and the serum protein levels in the Korean population.
Mol Immunol 2005, 42:969-977. PubMed Abstract | Publisher Full Text
Madsen HO, Satz ML, Hogh B, Svejgaard A, Garred P: Different molecular events result in low protein levels of mannan-binding lectin in populations from southeast Africa and South America.
J Immunol 1998, 161:3169-3175. PubMed Abstract | Publisher Full Text
Minchinton RM, Dean MM, Clark TR, Heatley S, Mullighan CG: Analysis of the relationship between mannose-binding lectin (MBL) genotype, MBL levels and function in an Australian blood donor population.
Scand J Immunol 2002, 56:630-641. PubMed Abstract | Publisher Full Text
Steffensen R, Thiel S, Varming K, Jersild C, Jensenius JC: Detection of structural gene mutations and promoter polymorphisms in the mannan-binding lectin (MBL) gene by polymerase chain reaction with sequence-specific primers.
J Immunol Methods 2000, 241:33-42. PubMed Abstract | Publisher Full Text
Alonso DP, Ferreira AF, Ribolla PE, de MSI, do Socorro Pires e Cruz, Aecio dC, et al.: Genotypes of the mannan-binding lectin gene and susceptibility to visceral leishmaniasis and clinical complications.
J Infect Dis 2007, 195:1212-1217. PubMed Abstract | Publisher Full Text
Garred P, Harboe M, Oettinger T, Koch C, Svejgaard A: Dual role of mannan-binding protein in infections: another case of heterosis?
Eur J Immunogenet 1994, 21:125-131. PubMed Abstract | Publisher Full Text
Messias-Reason IJ, Boldt AB, Moraes AC, Rosen SE, Dornelles L, Pereira-Ferrari L, et al.: The association between mannan-binding lectin gene polymorphism and clinical leprosy: new insight into an old paradigm.
J Infect Dis 2007, 196:1379-1385. PubMed Abstract | Publisher Full Text
Nebert DW: Proposal for an allele nomenclature system based on the evolutionary divergence of haplotypes.
Hum Mutat 2002, 20:463-472. PubMed Abstract | Publisher Full Text
Bernig T, Taylor JG, Foster CB, Staats B, Yeager M, Chanock SJ: Sequence analysis of the mannose-binding lectin (MBL2) gene reveals a high degree of heterozygosity with evidence of selection.
Genes Immun 2004, 5:461-476. PubMed Abstract | Publisher Full Text
Verdu P, Barreiro LB, Patin E, Gessain A, Cassar O, Kidd JR, et al.: Evolutionary insights into the high worldwide prevalence of MBL2 deficiency alleles.
Hum Mol Genet 2006, 15:2650-2658. PubMed Abstract | Publisher Full Text
Boldt AB, Petzl-Erler ML: A new strategy for mannose-binding lectin gene haplotyping.
Hum Mutat 2002, 19:296-306. PubMed Abstract | Publisher Full Text
Cavalli-Sforza LL, Piazza A, Menozzi P, Mountain J: Reconstruction of human evolution: bringing together genetic, archaeological, and linguistic data.
Proc Natl Acad Sci USA 1988, 85:6002-6006. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Boldt AB, Culpi L, Tsuneto LT, de Souza IR, Kun JF, Petzl-Erler ML: Diversity of the MBL2 gene in various Brazilian populations and the case of selection at the mannose-binding lectin locus.
Hum Immunol 2006, 67:722-734. PubMed Abstract | Publisher Full Text
Messias-Reason I, Boldt AB: Mannose-Binding Lectin, A Multifunctional Molecule of the Innate Immune System: Biology, Genetics and Disease Association. In Genetic Predisposition to Disease. 1st edition. Edited by Torres SL, Marin MS. New York: Nova Science; 2008.
Sachidanandam R, Weissman D, Schmidt SC, Kakol JM, Stein LD, Marth G, et al.: A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms.
Nature 2001, 409:928-933. PubMed Abstract | Publisher Full Text
Gaudieri S, Dawkins RL, Habara K, Kulski JK, Gojobori T: SNP profile within the human major histocompatibility complex reveals an extreme and interrupted level of nucleotide diversity.
Genome Res 2000, 10:1579-1586. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Sumiya M, Super M, Tabona P, Levinsky RJ, Arai T, Turner MW, et al.: Molecular basis of opsonic defect in immunodeficient children.
Lancet 1991, 337:1569-1570. PubMed Abstract | Publisher Full Text
Hummelshoj T, Munthe-Fog L, Madsen HO, Garred P: Functional SNPs in the human ficolin (FCN) genes reveal distinct geographical patterns.
Mol Immunol 2008, 45:2508-2520. PubMed Abstract | Publisher Full Text
Zhang H, Zhou G, Zhi L, Yang H, Zhai Y, Dong X, et al.: Association between mannose-binding lectin gene polymorphisms and susceptibility to severe acute respiratory syndrome coronavirus infection.
J Infect Dis 2005, 192:1355-1361. PubMed Abstract | Publisher Full Text
Turner MW, Dinan L, Heatley S, Jack DL, Boettcher B, Lester S, et al.: Restricted polymorphism of the mannose-binding lectin gene of indigenous Australians.
Hum Mol Genet 2000, 9:1481-1486. PubMed Abstract | Publisher Full Text
Juliger S, Kremsner PG, Alpers MP, Reeder JC, Kun JF: Restricted polymorphisms of the mannose-binding lectin gene in a population of Papua New Guinea.
Mutat Res 2002, 505:87-91. PubMed Abstract | Publisher Full Text
Seyfarth J, Garred P, Madsen HO: The 'involution' of mannose-binding lectin.
Hum Mol Genet 2005, 14:2859-2869. PubMed Abstract | Publisher Full Text
Naito H, Ikeda A, Hasegawa K, Oka S, Uemura K, Kawasaki N, et al.: Characterization of human serum mannan-binding protein promoter.
Schwab M, Lupescu A, Mota M, Mota E, Frey A, Simon P, et al.: Association of SGK1 gene polymorphisms with type 2 diabetes.
Cell Physiol Biochem 2008, 21:151-160. PubMed Abstract | Publisher Full Text
Alves ML, Boldt AB, Pereira-Ferrari L, Steffensen R, Strauss E, Jensenius JC, et al.: Mannan-binding lectin MBL2 gene polymorphism in chronic hepatitis C: association with the severity of liver fibrosis and response to interferon therapy.
Clin Exp Immunol 2008, 152:258-264. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Messias RI, Schafranski MD, Jensenius JC, Steffensen R: The association between mannose-binding lectin gene polymorphism and rheumatic heart disease.
Hum Immunol 2006, 67:991-998. PubMed Abstract | Publisher Full Text
Dal-Bianco MP, Koster KB, Kombila UD, Kun JF, Grobusch MP, Ngoma GM, et al.: High prevalence of asymptomatic Plasmodium falciparum infection in Gabonese adults.
Am J Trop Med Hyg 2007, 77:939-942. PubMed Abstract | Publisher Full Text
Guo SW, Thompson EA: Performing the exact test of Hardy-Weinberg proportion for multiple alleles.
Biometrics 1992, 48:361-372. PubMed Abstract | Publisher Full Text
Raymond M, Rousset F: An exact test for population differentiation.
Evolution 1995, 49:1280-1283. Publisher Full Text
Excoffier L, Smouse PE, Quattro JM: Analysis of molecular variance inferred from metric distances among DNA haplotypes: application to human mitochondrial DNA restriction data.
Genetics 1992, 131:479-491. PubMed Abstract | PubMed Central Full Text
Excoffier L, Slatkin M: Maximum-likelihood estimation of molecular haplotype frequencies in a diploid population.
Mol Biol Evol 1995, 12:921-927. PubMed Abstract | Publisher Full Text
Excoffier L, Laval G, Balding D: Gametic phase estimation over large genomic regions using an adaptive window approach.
Hum Genomics 2003, 1:7-19. PubMed Abstract | Publisher Full Text
Excoffier L, Laval G, Schneider S: Arlequin (version 3.0): An integrated software package for population genetics data analysis.
Evol Bioinform Online 2005, 1:47-50. PubMed Abstract | PubMed Central Full Text
Tajima F: Statistical method for testing the neutral mutation hypothesis by DNA polymorphism.
Genetics 1989, 123:585-595. PubMed Abstract | PubMed Central Full Text
Fu YX, Li WH: Statistical tests of neutrality of mutations.
Genetics 1993, 133:693-709. PubMed Abstract | PubMed Central Full Text
Fay JC, Wu CI: Hitchhiking under positive Darwinian selection.
Genetics 2000, 155:1405-1413. PubMed Abstract | PubMed Central Full Text
Rozas J, Sanchez-DelBarrio JC, Messeguer X, Rozas R: DnaSP, DNA polymorphism analyses by the coalescent and other methods.
Bioinformatics 2003, 19:2496-2497. PubMed Abstract | Publisher Full Text
Bandelt HJ, Forster P, Rohl A: Median-joining networks for inferring intraspecific phylogenies.
Mol Biol Evol 1999, 16:37-48. PubMed Abstract | Publisher Full Text
Drummond AJ, Ho SY, Phillips MJ, Rambaut A: Relaxed phylogenetics and dating with confidence.
PLoS Biol 2006, 4:e88. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Takahata N: Relaxed natural selection in human populations during the Pleistocene.
Jpn J Genet 1993, 68:539-547. PubMed Abstract | Publisher Full Text
Drummond AJ, Rambaut A: BEAST: Bayesian evolutionary analysis by sampling trees.
BMC Evol Biol 2007, 7:214. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text
Stanyon R, Sazzini M, Luiselli D: Timing the first human migration into eastern Asia.
J Biol 2009, 8:18. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text


text:
Moishele 8 Months Later
Thank you Shturem.
Dream it . . . Believe it . . . Plan it . . . Achieve it . . .
Netanyahu has said on a number of occasions that he agrees that no new settlements would be built, but that he cannot tell families in the existing ones "not to have children."
Excerpts from Letters of The Rebbe
The Rebbe

subset: commoncrawl


text:
I intended to continue blogging while away, but I didn't even take pictures, despite my self-professed cuteness. We had a very productive weekend in terms of wedding stuff, and did get to visit 3 dozen friends and family (a family gathering on Sunday did take care of most of that).
I'm not sure I'm doing the capsule wardrobe. I haven't heard anything on it, nor do I have the energy to plan much, as I not only start writing my first chapter of my thesis this week, but I also defend my thesis proposal this week (yes, a couple days after I start writing - bureaucratic processes take too long for my liking).
Anyway, I hope to be back to blogging soon, and I promise, I've been wearing my pink!


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Karup's Hometown Amateurs
Current Member
over 1 year
(at the time of review).
Great site!
*Tons of models
*more added all the time
*Beautiful girls
*Theyve been using the hitachi (something I think every model should at least try on camera).
*Some models really get down on their solo.
*More than one scenario per model.
*Fully downloadable and streaming available.
* Video work (although done with good equipment) is shaky, Too much movement, Trying to be too fuckin artsy.
* search engine
Bottom Line:
Overall its an awesome site.
I ONLY watch videos and ONLY the solo videos so thats all Im commenting on.
VERY, VERY annoying video work. It could be worse...but could be a lot better.
They constantly do the wrong thing at the wrong time. Mainly when the model is about ready to orgasm. They move away, get a closeup of their face, get a shot of everything except their snatch and puter (2 items that should be in the shot, but not necessarily a closeup). All the artsy shit should be done at the beginning of the shoot. Afterwords, concentrate on the model, what shes doing and her orgasm. Location is another thing. Quit following the other places. Bedroom, Living-room and bathroom should be the primary masturbation locations. Not on a little fucking foot stool, table, stove...WTF?
Most sites need to fix their fucking search engine. This one is no exception. A good portion of your content is solo models...so why not make it possible to search for specific things? orgasm, hitachi, magic wand, pocket rocket, vibrator, contractions.
I currently have a subscription for:
The female orgasm
ATK petites
ATK movies
ATK exotics
This site has the best possibility of over taking the rest....just a few flaws to workout. overall, love the place and cant wait until the next update. But get real bummed when the wait was to watch some BS the camera man was throwing in.
Karup's PC
Beware of Karups
As it was said in my review, I had very bad experience with Karups. First of all I believe that it is cheating on billing. Second, the quality is poor. Even recent photos look like they were made 15 years ago. The most of the vdeos are unfocused and filmed with terrbly overused close-up. So do not pay for nothing
Karup's PC
Current Member
over 6 months
(at the time of review).
According the site rules I am supposed to say something good about the site that I am reviewing. Well... I don't now. My experiance at Karups was not good. I can't say anything positive. Sorry. If you read my comment in full you will realize why.
I joined it in August, didn't like the content a tiny bit, canceled same very day. It was nothing but blurry photos and unfocused videos. Macro close up was unprofessionally over used in ALL movies. The models were filmed on the distance of 1-2 feet from their bodies. Because of this fact the video gets unfocused permanently and you don't realize what part of the model's body you are looking at. So I canceled it and forgot.
However Karups reminded me about itself by billing my card next month. I tried to contact the customer service but looked like all people in Karups died. Nobody responded. I was billed next 3 months until I closed my card.
Bottom Line:
Do I recommend this site to others? No I don't. In fact I recommend to every one to stay away from Karups. Try alternative adult sites.
Karup's Hometown Amateurs
Addition to my review
I did a review last summer, and for the most part, I stand by my score and everything I said about the site. I recently joined again, mainly because I recently became a fan of picture sets. I commented on it last time, but after getting into the picture sets more, I have a few things to add...
+There are alot of cute girls that are softcore only, so the picture sets are often the only way to see some of these girls. I guess you could put this as a con aa well, but its a nice surprise.
+The vast majority of the girls, unlike on Karups Older Women, are at least moderated attractive, and most Id say are very attractive. There are approximately 1500 girls on the site, and Id say 1400 are pretty hot. Beauty is in the eye of the beholder, so that may vary both ways depending what you like.
-This site suffers from alot of the same downfalls as KarupsOW. Some of the photoshoots...even newer ones, are poorly shot. Whether its poor lighting, poor focus, or just poor direction, there are many sets than werent up to par. The biggest problem with these, like with Older Women, is the fact that they often focus way too much on vaginal shots. Like I said, I like pussy as much as any heterosexual male on this planet, but they show too many of the same shot and dont focus nearly enough on the rest of the girls body. There were several sets where they girl had a beautiful ass or just body in general, and they either focused way too much on cooter shots, or they kept the girl clothed. Some girls were completely ruined altogether because of horrible direction.
-The site has no consistency whatsoever in terms of the picture sets. Some of them arent labeled properly, so you have to create a seperate folder to download them too to keep track. Not a huge deal, but I dont what is so hard about being consistent and labeling the sets in the same format. And its not as if this just applies to older sets. Alot of newers sets arent labeled properly either.
-For some reason, some current picture sets arent in high def. I get older ones, but I was just looking at a few girls that were shot in late 2012 that didnt have high def photos. WTF? There are sets from 2010 and 2011 that are high def....but now, every fucking set should be shot in high def.
In conclusion...its still a quality site thats worth a look, but so many little things drag it down. These are all things that are correctable, but seeing as how they just repeat the mistakes over and over, Im not confident they will ever change.
Karup's Hometown Amateurs
Former Members, Keep An Eye on E-mail
I received quite a nice 1-month offer, which I took advantage of. If, like me, you're a former member, keep an eye on your e-mail - you might like what you see.
Some of their recent updates are REALLY nice!
Karup's PC
Current Member
less than 1 month
(at the time of review).
Huge number of attractive models going back over a decade! I think its well over 2000 girls.
Updates include 3 photo sets a day (6 days a week), and 1 or 2 videos a day
Content appears to be exclusive (except for the feeds)
Photos and videos have just the right amount of explicitness for me (meaning pussy close ups and spreads, but nothing extreme like gaping or speculums). No pussy shy girls here!
Photo sets have a good variety of poses-front view, rear view, laying down, doggy
Flash player for videos works well-I can scan through a video very quickly to see if I want to download it.
Zip files for photo sets have unique names--no need to type in a name when downloading.
My biggest gripe is the with the site layout and navigation. There doesn't seem to be a way to list ALL photo sets by date, or all models by date of first appearance. This makes it a little bit of work to view all the new material posted since my last membership there (you have to go through 5 different photo categories to do this).
The solo girl videos (which usually involve a quick strip and masturbation) are kind of hit or miss. Some girls give good performances, others seem a bit apprehensive. I would prefer for the stripping to be slower and more seductive. I don't see a lot of real girl cum here, again suggesting maybe the girls aren't really relaxed.
The camera guys shooting the videos tilt their cameras way too much!
The boy/girl hardcore vids have improved since the last time I was there, but I still rarely find any worth downloading.
The photo/video sets have too many chairs and sofas, and not enough beds. The furniture could be more upscale too.
Bottom Line:
is primarily a solo girl photo/video site. Each model typically shoots 5 photo sets and 3 videos. The more popular girls have more than this. Some of the models do hardcore B/G videos (most do solo vids only), but recently these have averaged only about 1 a week. For example, in the last 3 months of 2012, there were 117 solo girl videos, 13 B/G hardcore videos, and 2 G/G lesbian videos. The hardcore videos have decreased in number from a couple of years ago (possibly due to the syphillis outbreak and new Russian porn law).
The models are generally attractive, although there are more "7s" and "8s" here than at some other sites like Met-Art and
. They do have their share of beautiful girls, and it seems like all of the most popular Euro girls have some material here.
The photo sets have zips and come in 3 resolutions: 1024p, 1500p, and 3000p (long dimension pixels). Older sets have only 1024 and 1500. I am not certain, but it appears that some (maybe all) of the photo sets are vid caps from the videos. There are never any flashes going off in the videos, and the photo set that corresponds to the videos doesn't seem to be noticeably different. Again, I am not sure about this. Having said that, the photo sets are well lit and in focus, and generally well done.
I noted above that there are very few if any "pussy shy" girls here. Just the right amount of explicitness for me. Also, some other things that you DON'T find here: pissing, speculums, huge dildos, public nudity, and I don't remember any anal action either (certainly not with dildos). I only found 1 video with "squirting". All of this is fine with me, as I am not into any of the above.
The 50 most recent photo sets and 33 most recent videos are on the home page. The homepage also has 2 buttons for the videos (Hardcore and Softcore). The photosets have 7 buttons/categories, and I really don't know why, as they are so similar. Those categories are Amateurs, Exotics, Girls with Toys, Hardcore, Models, Older Women, and Teens. I wish they would put them all on one main page organized by date, and then have the buttons. The search feature is OK, but needs more categories. It's a little work to get through all their content (of course they have a lot of content!).
The sets for the photos and videos are pretty basic, and as I mentioned above, they have too many chairs and sofas. Sometimes the models just don't look comfortable. They used to have some horrible painted sets with loud colors and painted bricks, but it appears that those are history. A little more variety would be nice. And more beds too.
The videos come in 3 resolutions: mobile, "medium", and HD. The HD is 720p (I don't remember any 1080p), but it still looks very good when full-screened on my 17" laptop monitor (my monitor is 1080p). I'm not sure what resolution the medium vids are, as I only download the HD. The videos come in MP4 and WMV formats. The flash player works very well, and is a big improvement from the last time I was there. The older videos (5 years or so old) are usually in 2 to 4 parts--I remember having to download and join those (ughhh). It would be nice if they could join the older ones for us.
The hardcore B/G videos are not a main feature of this site (at least, the ones done with their models). Apparently some of the members have requested more hardcore, so in response to this, they have several different "feeds". The main hardcore feed has a huge amount of material, but to me it is B and C grade stuff with B and C grade models. It also is not shot in the same style as their hardcore, so I really don't know why they bother. They also have video and photo feeds from
Viv Thomas
, but the videos are not HD (pity because many of those are good), and the photo sets don't have zips. They also have a webcam feed (which I didn't bother with) and several others including Sex TV, Paradise Feeds, and Whore Hunter. None of the feeds really interested me, and it would be nice if there was an option to join the site without these, as I am sure everyone is paying for them.
The Karups hardcore B/G videos were nothing special for me. In particular, the girls just don't look like they are really enjoying themselves. Another pet peeve, every freaking one that I've seen ends with a facial cumshot. Please Karups, add a little variety here! There has been some change in the videos--most are longer than I remember and less repetitive, but I still don't find many worth downloading. The rare girl/girl videos are better, with some on par with the better lesbian vid sites.
Bottom line: Despite all my nit picking,
is a solid solo girl photo/video site. I have been a member there 5 times now in as many years, and always find a lot of good material to download when I go back. A first time member should do the 3 month membership, as 1 month is no way enough time to work through all of their content.
Karup's Hometown Amateurs
Current Member
less than 1 month
(at the time of review).
-TONS of content for both hardcore and softcore fans
-Lots of hardcore videos featuring well known teen/early 20s pornstars and some hot amatuers as well.
-Updates ALOT
-Action is pretty damn hot.
-Newer video content has streaming options.
-Newer videos are in "HD" (see negatives)
-You can search for models alphabetically or in certain categories (athletic, ethnic, a few others...)
-Pictures look great. Newer sets are in High Res, and even med res and low res arent bad on older sets.
-Advanced Search option helps you find what you are looking for.
-Male talent deliver some good cumshots in HC scenes
-Site is organized. Not hard to navigate and find what you want.
-No DRM
-No download limit
-Lone site...meaning not part of a network, despite having several other sites that could be part of one (KarupsOW and PC)
-Expensive for what it offers compared to other sites and what they offer.
-No model info...at all.
-Scene offered in HD arent TRULY HD. Doesnt bother me much but may bother some.
-Nearly 2/3rds of the videos on the site have no full download option...meaning you have to download them in parts.
-Content is extremely straight forward. No frills at all really.
-Site Navigation is easy, but is also very tedious due to limited options and large amount of content.
-Site design is very bland.
-Some Download Managers dont work with site.
-Setting is pretty much always the same for hardcore stuff (bed on generic set or in generic room)
Bottom Line:
There honestly isnt alot to say that TBP didnt cover in their review...Im just not quite as generous with my score for several reasons.
There is alot to like about KarupsHA. I joined because there were some cute faces I never seen before and I wasnt disppointed with the girls or the amount of content. There is enough content here to keep teen porn lovers fat an giggly for awhile.
But being that I am not that big into pictures, videos are my focus. I do give them credit for the pictures though. They deliver on that for those who are into it. And yes, I did factor it into my score, despite it not being my thing.
The videos offered are good all around. Not GREAT, but good. The quality of video for newer scenes is solid, but the HD scenes are not true HD. Im not big into the 2 GB file sizes so I rarely download true HD vids anyway. What annoys me here is that their "HD" videos are still pushing 1 GB in alot of cases, and they dont look much better than DVD qualtiy scenes on other sites, which are about half the size of these files.
The biggest issue I think I had was the lack of full video downloads before mid-2008. I mean come on...MID 2008? They werent fucking offering full downloads as of that point? I can understand the stuff from the early 2000s and even 2005 maybe...but 2000 fucking 8? Gimme a break. And even if that is the case....by now, they shouldve started converting them to full videos like
Reality Kings
and other sites have done. But NO...they are content offering a huge amount of their video content in parts, and there are ALOT of good videos in that form....so you have to go through each one individually and save them in parts.
That fact alone dropped this site 10 points in my book. Thats unacceptable, especially considering how recent it is and that they dont even seem to care about converting those into full videos.
Im not going to rant on forever, because my review and TBPs review say most of what needs to be said.
Bottom line...I do recommend this site if you are into the type of content it offers. There is alot of keep you happy, and even more if you like softcore stuff and pictures.
Personally, I wont be staying past my 1 month. Not so much because its not a good site or worth more months, but because there are many better porn offerings that offer better stuff, more of it and for the same price or cheaper.
Thats another issue I had....is the fact that they have this site, and then KarupsOW and
. Why not offer that as a packaged network? Then I could see staying more time. As it is, you have to join each site separately at 30 bones a month, which is way WAY too much.
So its definitely a quality site worth a looksee, but for me, its one and done. If you like pictures and softcore, you may want to (and have to) spend a few months there to see everything they have to offer.
Karup's PC
Current Member
less than 1 month
(at the time of review).
The site appears geared more toward photos - which is what I personally enjoy.
- This site has a huge concentration of the sexiest woman in porn that I have seen.
- There are about 3 photo updates 6 days per week.
- There's about 2 video updates 5 days per week.
- Plenty of HighRes photos. The high resolution photos are 1000x1500
- It seems like half of the site is in their higher resolution format.
- The newer photo sets have well over a hundred pics each enough to get the shots that you want.
***Best upper body boob shots I've seen on any website.***
***My number #1 Standout is that the photo shoots has almost the perfect model poses and it seems standard in almost every photo shoot at least with the newer shoots. I haven't found this anywhere else.***
- Site layout is great and very clean without any confusion.
- I think the overall site navigation was great with good search categories.
- The high resolution photos are 1000x1500 are pretty small for those with a larger monitors.
- The quality of the photos can be a little better.
- The older photos lower resolution photos are so small that they are useless should bump off site.
- Way too much make-up need more natural.
- Some bad lighting either too dark or too bright degrading detail.
- Unnatural skin colors
- Not enough butt shots for those who like that.
- The solo masturbations vids are boring, rushed, no moans, not much looking into camera, no words.
- The hard core videos are pretty boring a little realistic clean roughness sometimes.
Bottom Line:
Potential Score: 95-100
I know there's quite a bit of personal negatives that's because I am a critical person however, this site is actually the most satisfying site that I have visited to date.
During my month of membership, I never got bored that was a first. There's so much content and good content to look through that it'll keep you busy.
My biggest issue is the small photo sizes but I hear they will be increasing the sizes very soon
When the larger photos come in, the site score should go through the roof.
For those who have smaller monitors this site is great, but if you're like me and have a larger monitor you may be a little discouraged in the beginning. After a bit, I actually got a little use to it but I'm looking forward to the larger images. My monitor size 26
Boob shots: The closer-up portrait photos of the models from the belly up are perfect boob shots and they look absolutely amazing on my monitor.
The photos can use a little boost in quality especially for the landscape photos but the quality is as good as any site.
I highly recommend this site you won't be disappointed.
The customer service is great and they actually work with you and answer your concerns.
Karup's PC
I sent three emails to support and they still have not responded. Does anyone know how long karups take to respond to emails? It is very frustrating.
Karup's PC
Pic Sizes and quality?
Does anyone know if the pic sizes are larger now with good detail. I looked at the review on here and it says "1500X1000". That's pretty small for today. I have a pretty decent sized monitor.
Karup's PC
Exclusive or Not ?
Are You sure that the content is exclusive ?
I see in some previews some
model and a recent scene that is clearly taken from that Company.
So, I ask to the current/previous member: is the review correct when it says "exclusive content" ?
Karup's Older Women
Disappointed on last subscription.
Whilst there are still regular updates, there hasn't been as many new models added in the last year as I would have expected.
What with that & the dated site layout, I get the impression that this one is a bit on the back burner.
A shame really.
Cap'n. :0/
Karup's Older Women
Current Member
less than 1 month
(at the time of review).
-Over 500 models.
-Over 280 hardcore videos.
-Over 1000 softcore videos.
-Nearly 2300 photosets.
-They have a good search system that allows searches by age, body type, fetish and so forth.
-They update with new content daily and all of it is dated.
-This may only be me but I find that many of the models don't fall under my understanding of the term older. I guess they are older than models on their other site but not by that many years.
-This is primarily a photoset site with most of that content being softcore.
-Only about half of the movies are in one file.
Bottom Line:
-This is another site that has disapointed me because it doesn't really have what I'm looking for in older content. I was hoping for a lot more hardcore videos but that doesn't seem to be karups way. It has the same qualities found on karups PC but not anywhere near the same amount of content. I guess that's normal since porn is often a young girls job.
-I'm not really sure who will really enjoy most of the content found on this site. I guess if you like women over the age of 30 and prefer softcore photosets than you should get your moneys worth. It probably isn't worth staying a long term member.
-It should be avoided by anyone wanting hardcore videos with older women. You're likely to be disatisified with this site.
-My score is based on what the site offers and not what I found to my liking. I in fact did not find one video that I want to keep.
Karup's PC
Current Member
less than 1 month
(at the time of review).
-Over 900 hardcore videos.
-Over 2800 softcore videos.
-Over 11,000 photosets to choose from and more than 1900 of these are hardcore shoots.
-Over 2000 models to choose from
-They have a search system that helps members find a specic type of video or photoset.
-They update daily and all their content is dated
-This is primarily a softcore photoset site.
-A little more than half of the hardcore videos are B/G. 1/3 are G/G only and the rest are solo stuff.
-About half of the hardcore videos are in parts only. It's much worse for the softcoire videos.
Bottom Line:
-This is a hard site for me to review beause I can see how amazing it must be for people that like photosets. There is such a large amount to be found here that a month may not be enough to find all that you would want. I'm primarily a video guy so this site leaves me a disapointed because there is just not enough to satisfy my needs. You then add the fact that many models have hardcore photosets but no accompanying video and that just increases my frustration.
-I was able to find about 5 rare videos that I don't believb can be found anywhere else and they are of models that have only done hardcore for this site.
-People that prefer photosets should find more than enough to satisfy their desires.
-This might also satisfy some video fnas but this depends on the type of hardcore you prefer.
-My score is based on what the site offers and not what I was able to download.
Karup's Hometown Amateurs
Beware, if you sign for a monthly...
membership and cancel a few days later, then, exactly two days later, you are not allowed anymore in the site. I signed on February the 24TH and cancelled the 25th, well, soon enough, on February the 27th i can't access the site.
This is what they write to you when you join the site: "Your transaction has been processed by EENT, Inc. through RSBilling. You can cancel at any time and your membership will continue for the remainder of your subscription. After the initial period (30 days) you will be billed 29.90 every 30 days."
It seems that they do not fulfill their promises.
And be sure that i have typed endless times my username, password and the verification code.
On february the 27th i received this e-mail: "Dear KarupsHA Member,
You are receiving this e-mail because your membership is expiring today. We thank you for being a member and hope to see you again sometime in the future. We have recently created Facebook and Twitter pages for our fans & members, where you can get sneak peeks of new models that continue to be added regularly."
So i was member for a total of four days, some deal i made.
Karup's Older Women
Sloppy Bookkeeping!
Just got a notice that my membership had expired despite the fact that I still have almost 3 weeks to go. They weren't slow in cutting me off either! That's why I appreciate Billing Companies like Epoch and CCBill who have never made a mistake like that in connection with a cancellation. I sent KarupsOW an email and we'll see how promptly they re-instate me, if at all.
Update: I finally got a response after three emails and apparently there's a glitch with their Billing Company that affects users who signed up around Jan. 15 and later. They are working to resolve it and will add additional days to the subscription as a compensation. Review being restored to its original score.
Karup's Older Women
I Like This Site .. A Lot!
My review may not reflect this but anything that has been offered to their subscribers during the (approx) last 2 years by this site has been outstanding, technically and esthetically, and I've had a good time downloading all kinds of photo sets and videos because of their high quality.
I still have a problem with all the enhanced breasts but there's such a wealth of material that I can leave those to the BB enthusiasts and still get enough to satisfy me, even within my narrow niche of sexy lingerie. (Thanks otoh and Cap'n for giving me that little push to sign on!) Definitely a thumbs up for the modern version of Karups! I would say for the old Karups as well but I do prefer HD and 1500px pictures.
Karup's Older Women
Current Member
less than 1 month
(at the time of review).
A huge archive of mature, attractive models.
Picture sets: Older sets display at 1024x680 px, not bad if they are all like the sample set, dated 2005, that I test-downloaded. Newer sets are at 1500x1001px.
Latest videos are in HD at 1280x720, total bitrate close to 4000 kbps. Nice! I could not quite determine when either pictures or videos changed to a higher resolution but it cannot have been too long ago because even early 2010 videos are in 640x480 at 2000 kbps. However it must be stressed that they, as well, are of good quality and quite crisp if one does not insist on watching them full screen.
Excellent search engine.
Excellent basic home page lay out, even though it looks a bit dated, but it makes it very easy to find one's way around.
Bonus pictures and feeds: Bonus picture sets are from
. It would be nice if they could be downloaded zipped and in their best resolution. Many of us simply don't feel like downloading a set, one picture at a time.
The bonus "feeds" are even more disappointing because they consist of 1 minute clips of various DVDs only, and are further ruined by a logo running across the picture. Karups would do better not to offer bonuses that aren't really bonuses.
However, in all fairness, one of the bonuses,
Content, is a nice little gift because the picture sets are zipped and the quality itself is fine even though they date back to 2005.
Search engine, as much as I like it, should have the additional function of filtering HD content and High Res Picture sets. Many users are no longer content with less than HD quality and don't like to sift through all the updates and models to find what they want.
Too many enhanced breasts.
Cons continued below:
Bottom Line:
The term older does not really fit because most models would be called MILFS or Cougars or Mature in other places. There is only a handful of models over 50 and only one over 60.
Bottom Line:
A nice, solid, quality site for lovers of mature women. So far it does not live up to my personal expectations because my preferred niche is erotic lingerie, while most models that are found under "Lingerie" or "Panties" in their advanced search appear to wear daily ho-hum "underwear" that is practical rather than arousing.
Experience has taught me that my taste is not necessarily the generally accepted one so I won't hold this against the site.
I have also found a few videos and picture sets that do come a bit closer to what I want in the short time I have been with this site, so who knows, maybe between the updates and the site's vast store of material I'll be able to dig out a few more erotic nuggets during my month of membership.
Edited Jan. 28, 2011
I received a notice yesterday informing me that my subscription had expired despite the fact that I have still three weeks to go. Access was cut off immediately and two emails to support to correct the situation brought no response. It is impossible to get in touch with their Billing Company because the only link provided is that of KarupsOW support. Because support, when needed, plays such an important part I have downgraded my review by five points.
Edit: Score restored to its original because I got a response to my 3rd email informing me of a glitch in their system and their efforts to correct it. Additional days have been promised for every day lost now.
Karup's Older Women
Current Member
less than 1 month
(at the time of review).
- A lot of material
- Daily movie and gallery updates
- Reasonably good navigation options
- Most models in 30s & early 40s, which works for me
- Good movie quality; streaming, download options and screen caps
- Some good/protracted strips from casual and business attire
- Would prefer a camerawoman rather than man for the interview/chat movies
- Age of models (some under 30) may stretch 'OW' for some
- Slightly retro design (although front end has been updated; am sure member area will follow)
- Very typical lighting/sets/premise for all scenes
- Many models a little too enhanced for my taste, and relatively few unshaved
- Very little girl-girl content
- Could use a few more navigation options
- Older movies are lower quality and split into parts.
- Some daft fake uniforms and hackneyed outfits (newer sets are redressing this, thankfully)
Bottom Line:
Looking for girls up to around my own age (40), it was a choice between this,
and All over 30. They all look similar and suspect they offer similar content; the quality of samples I found on TGPs just tipped the scales in favour of Karups OW. (Interestingly, they include bonus content from, and link some models to, the other two sites.)
There is a lot of material here, it's a bit daunting at first! On top of that, they add a new movie AND a new photo set 6 days a week, so it is growing at a good rate. Navigation is fine; 4 categories of pictures and two of movies - although with the amount of material, we could use more, and/or the ability to sort each list by model name or date added.
Most of the material is soft, with maybe a quarter hardcore; the latter isn't really my thing, but actually the scenes are relatively well-positioned and I enjoyed them. Of the softcore, it's probably about 50/50 between toys and fingers; and there are some good strips and teases before getting to that point. Only a handful of girl-girl shoots and movies; I'd like to see more.
Movies are good quality, sharp and well-lit (even if slightly saturated) - 720p and each page shows a few download options and screen caps of the action, which is useful. This format goes back about a year and a half (a bit less for the screen caps); before that, the movies are mostly SD and many are only available in parts. Image quality is OK; available in 1024px and 1500px which is just about acceptable; I'd prefer 2000px.
I was quite disappointed that so many of the models have fake:
- boobs (I'm no expert but could spot these a mile away)
- tans (and the lighting makes them look even more orange)
- smiles (only the minority of models show their personality and a range of expressions)
Natural is always better in my book, but it seems this is endemic in the milf genre. Similarly, I like a mixture of pubic hair arrangements; shaved, trimmed or natural - although I do prefer the latter and there are very few unshaved girls here. Am hoping it tells them something that the hairiest girl I found is their 4th top model! (Am planning to join
We Are Hairy
at some point to redress the balance.) OTOH, it's a little churlish to complain, given the quantity of material here.
Overall, nothing groundbreaking here but a good site nonetheless. Although I'm only staying one month, I've definitely got my $30 worth; I will likely join again sometime, but will probably try the other two sites beforehand.
Karup's PC
Doing a Few Nice "Comeback" Reposts
Remember Avery Adams? She was at quite a few sites back around 2003-2004, KarupsPC included. This year, they've reposted some of her sets there (now at 1500 pixels). There's one of her in a sudsy bathtub that is especially hot. (And I don't usually go for the sudsy tub scenes.)
Another is "Simona" (aka "Kitty" at LSG). She's like the naughty girl you knew before you knew what a retirement plan was.
It would be great to see them reissue their Evelyn Lory sets, btw. I'm pretty sure that KarupsPC was the first site I saw her at. There's some nice exclusive stuff.
Karup's PC
Key-logger (in a jpeg image?)
Just received this...
"It sounds like a possible case of a false positive. If you would like to send us the zip file in question, we would be happy to scan it and confirm a false positive. You can send the zip file to us at..."
My apology to Karups! Sorry for impugning your reputation! The zip file in question caused a "false positive" for some reason.
Karups is and has been a safe and reliable source for adult content. Thank you for your understanding in working to clear this up!
Karup's PC
Current Member
less than 1 month
(at the time of review).
+ An exorbitant amount of material
+ You can go on for days/weeks/months in your search
+ You'll find a lot of exclusive/licensed material here, that's hard to find anywhere else.
+ Even with the use of licensed material (too!), you'll find stuff here that might take you a lot of time to locate anywhere else (and save you some money)
+ Easy navigation - it's generally fun to browse all this content.
+ A lot of exclusive vids and photosets - even if they generally got external providers.
+ Fine updates - every day. (Except weekends)
+ Much better vid-quality - lately.
+ DM allowed and zip for pix
+ Almost ALL vids in WMV
Not so damn much in the cons. - but:
- The new/newer vids quality could still be a bit better!!
- In spite of the enormous amount of material, quite a lot - or at least some of the models are VERY average.
- I like old stuff, by all means - but too much of this are in low quality.
- Most of the vids here are in average quality - only the very new are in HD - wish they would update some of the old vids.
- The navigation is generally fine - but the design is an 'old timer' - they need to renew that - with a touch, though.
- A lot of model-name confusion.
AND - Cons bottomline: Why not get together a Karups network, too!
Bottom Line:
Karup's PC
- man, I've been here a LOT of times over the years - it's porn - no: PORN - from when things where a little bit greener/younger.
This site - and the
Karup's Hometown Amateurs
- and the later
Karup's Older Women
kind of reminds me of the old days - not so much bullshit - just a lot of fine material in vids and pix-sets - and hours and hours of browsing - and enjoying.
Like the deal where you can find models with pix and vids from long time back:
MAN, dig this - I even found the greatest vids and sets of an hungarian model - Chanel - who's now a 'working girl' (escort-service) here in Denmark/Europe - always wanted to fuck her - and now she has very fine vids and sets here - funny!
You can go on at this
Karup's PC
- and locate girls/models that you have not seen in a long time - and wow, suddenly, you'll find material - sometimes a little older stuff than you'll find at 21. Sextury or DDF or elsewhere. BUT the same model.... I like that!
Generally the pix/photosets of just a little older material seems/are better than the older vids.
The quality of newer vids - from late 2009 and 2010 has increased a lot. Most now in HD - whatever that means - because even if they're ok in viewing quality - none of the vids - even the latest are in the same league as what you can watch from 21. Sextury/DDF/and alike - and very far from
In The Crack
- if
Karup's PC
would ever get there, I'd put another 5 on the score...
But bottomline
Karup's PC
is a very decent site with a hell of a lot of fine material for the serious pornbrowser - but bare in mind 2/3 of the vids/sets are softcore - only 1/3 hc (aproxx.) - the same goes for the pixsets.
(BTW: That my score is the same as the DUKE's (TBP), says more about the DUKE than this user, but we agree here... LOL)
Karup's PC
Back to "The Roots"
Just got back as a member again after some years away...
Man, what a paysite!!! - in these days and compared to a lot others.
Not that the pix are so fantastic in resolution, nor the vids.
But a lot better than some years ago.
But foremost: Going through that massive content of well known - and especially not so well known models for just a couple of hours - I'm amazed...vids and sets of girls I've never seen before - and that's the amazing part for this user..thought I knew them all (most). And even if Karups still got a serious problem with modelnames /alias.
Some flaws, of course..........but Karups is a good old site to rely on, it seems...... be back with a review...
Karup's PC
Was a member approx.
2 months
prior to this review.
Great customer feel and good reputation. No dirty tricks. You do not find yourself signing up unknowingly for some other site or promotion. Advertising and promotion is mimimal, and they have no download limits or drm.
The proverbial wealth of material is here, going back years, so great value for money.
The girls look for the most part like genuine amateurs rather than porn stars. I would say some have that girl next door look, except she looks and sounds like a rottweiler.
Refreshingly few tattoos, piercings, and fake breasts.
The focus is on the girls. The males are not irritating and do not get in the way. There is no back to front baseball cap, trying to act black, while waving their arms at the camera and yelling "yo" or slapping the girls ass while shouting "whore." Here kid, just hold this pin for a few seconds will you? Oh yeah and the grenade too.
Material is exclusive.
Quality zipped pics.
No choking and spitting, girls treated with respect.
Bonus material from H.A.
Biggest negative for me is the real scarcity of hardcore.
Beautiful girls but a disappointing small number of girls outside the white slim category. There are only a few latin, black, or asian girls, and not that many full figure girls.
The look of the site is imo really boring and dreary. The index and home sections just look, well...uninspiring and as exciting as a phone directory. Okay, just my opinion and it is a small negative.
I personally found the navigation hard. It's been mentioned before but it is sometimes difficult to distinguish between the girls, because of the small photos in the uninispiring index, the way they are named, and my cross referencing problems. Others think the navigation is fine, so maybe it's me.
For girls who do both hard and soft, instead of mixing the softcore shoots together with the hardcore ones they are separate, which is a shame because you cannot get a slow strip to naked, softcore poses, then hardcore.
No build up in hardcore videos.
Bottom Line:
Pics are 1001x1500 or 684x1024. Top spec downloadable wmv videos are 960x540 then 640x480.
MP4 streaming.
Regarding navigation, from the index you can choose from categories like "teens, "exotics" "hardcore" or just an A-Z of all the girls in chronological order. You can look up a girl and find the categories they comes under like "teen " or "hardcore" and find all their shoots and videos. I found it really hard to navigate and cross reference, for instance - teen amateur hardcore video.
There are tons of pages but the navigation is a mess with all the material they have.
The naming system and the index are not great and add to the fog of trying to find out what there is, where it is, and who it is. There is a wealth of material but it was a real chore, not a pleasure looking through the site.
The videos and pics have a samey look about them, but are professionally done, with good camerawork and lighting which makes the best of the models.
The videos do not take long to get down to action. There is no real build up, stripping or teasing. Oral is followed by mainly straight sex. Not a lot of anal. The videos show the whole girl as well as the close ups. I hate too many close ups but thankfully the cameraman allows you to see the whole girl while having sex, not just a groin.
The whole style of the photos and the videos is a little old fashioned. I don't mean that in a bad way. It is like it used to be before they started slapping the girl's ass, pulling her face, choking her, and generally doing stuff that made the girl and the porn shoot less attractive. I personally could have done with more anal and more hardcore videos. There is a great shortage of hardcore on the site. Despite that I consider my money well spent. I will probably join Hometown Amateurs at some stage when I can bring myself to brave the navigation problems.
Their videos and pics although not top high res, are still good quality.
The older pics and videos situation is similar to other older sites. They are not up to the quality of the new material and the videos are split into smaller segments. If they had removed all that it would not be noticed as a negative, and some sites do remove it. It cannot be considered a negative because they have so much to see plus you get the old material as bonus. They also update fairly regularly.
For me, the main negative is the scarcity of hardcore material. I have seen other reviews so knew what to expect, but was still a little disappointed. You will notice a lot of my pros are negative negatives along the lines of no download limits and no irritating males, which you would hope most sites wouldn't have anyway. But in the real world a lot of sites get it wrong whereas mostly this site gets it right.
I hope this review stays as the latest review for a while and gets em some customers and isn't replaced by some 3 line newbie review consisting of great videos, great pics, great girls, what more can you ask, 100.
Karup's Hometown Amateurs
Question Regarding Karups
I am a bit confused about the two sites, Karup's Private Collection and this site, Karup's Hometown Amateurs. Basically, what is the difference between the two sites? Anyone that can help me with this distinction would be greatly appreciated. Thanks for your time.
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Stay at the Best of Easton, PA Hotels The Holiday Inn Express® Easton is nestled in the heart of the beautiful Lehigh Valley.Our hotel's location is just off Routes 22 and 33 and I-78. You'll find it easy to get to meetings and local attractions. Business travelers to the area are pleased by our hotel's location in Easton, PA, our friendly staff and great services. They appreciate being near Lafayette College, Crayola LLC, Georgia-Pacific, Dixie and Lehigh University. In addition, our Business Center provides copying and faxing services, while our 8,000-sq-ft meeting space can accommodate your event or meeting in Easton, PA. Our hotel's also perfect for families, as the fabulous Crayola Factory, where you and your kids can release your creative genius, is less than three miles away in downtown Easton. The National Canal Museum, the Sands Casino, the Lost River Caverns and the State Theater in Lehigh Valley are nearby, so our hotel's guests can easily enjoy a variety of activities. Other hotels in Easton, PA, just can't compete with the hospitality and amenities that we offer. From the free wireless Internet access to the indoor, heated pool and to the comfortable rooms, we have what you want. Don't forget there's a free, hot Express Start Breakfast Bar to start your day, and fresh-baked cookies, fruit, coffee and juice for a quick snack. Make your reservations today to enjoy the best of the Lehigh Valley as our hotel's guest.InterContinental
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Complimentary breakfast
Express check out
Fitness center
Indoor pool
Laundry facilities
Laundry service
Meeting/Banquet facilities
Pets not allowed
No smoking
Free parking
Wheelchair accessible
Storage available
Free Wi-Fi
Get Rates
Get Flight + Hotel


text:
Nemis Clothing
Aztec Tee Green
$19.00 $39.00
The Nemis Aztec Tee Green is printed in a geometric take on classical native aztec patterns.
The tshirt is made out of light and extremely comfortable jersey cotton.
Size Guide:
S: Chest 36-38in (91-96CM)
M: Chest 38-40in (96-101CM)
L: Chest 40-42in (101-106CM)
XL: Chest 42-44in (106-111CM)


text:
New OGR Maps
Posted 26 January 2011 - 10:52 PM
08-14-2010 - Nachos_Rule http://www.thegamerp...ead.php?t=19788
08-31-2010 - Lets_Party http://www.thegamerp...ead.php?t=19795
09-12-2010 - Bring_It and Bring_it_Spawn http://www.thegamerp...ead.php?t=19799
09-26-2010 - Kiss_the_Ground_Day http://www.thegamerp...ead.php?t=19814
10-22-2010 - Major_Smackage and Total_Smackage http://www.thegamerp...ead.php?t=19825
10-31-2010 - Staring_at_Goats http://www.thegamerp...ead.php?t=19830
12-12-2010 - Epic_Failure http://www.thegamerp...ead.php?t=19859
12-25-2010 - Toy_Store http://www.thegamerp...ead.php?t=19869
12-26-2010 - The_Dude_Abides http://www.thegamerp...ead.php?t=19872
12-30-2010 - Prison_Break_2 http://www.thegamerp...ead.php?t=19874
01-01-2011 - Pucker_Factor http://www.thegamerp...ead.php?t=19876
01-09-2011 - Cowboy_Style http://www.thegamerp...ead.php?t=19881
01-23-2011 - Die_Tryin and Respawners_Joy http://www.thegamerp...ead.php?t=19888
Posted 26 January 2011 - 11:23 PM
You have been busy, I'll get these added to the downloads in the next day or two.
Posted 27 January 2011 - 01:51 PM
Posted 21 March 2011 - 04:53 AM
Edited by =TS=Crosshair2, 21 March 2011 - 04:54 AM.
Posted 21 March 2011 - 09:52 AM
Posting about this in the forums is not the best way to resolve this problem, ask him why he has done this then we may be able to help you but you need to have proof of what he has done.
Posted 23 March 2011 - 04:06 PM
I changed his map completely and I clearly credited him for the base landscape. The best I could do not having a clue who to contact. Who would know that he has two virtual names.
Seems like he's happier to have his work limited to the respawners (did he even notice that I made a respawn version of the map - in the same zip - as well, only for his crowd ?). But fine with me. It is amazing how protective folks get once they invest a lot of time into making things, even if there's absolutely no gain in it beyond actually being able to play on the terrain. If somebody felt like reusing one of my terrains, I'd be happy to see another map on it. The more the merrier. Heck, just last month I posted 3+ hours of tutorial videos to help others make more maps, which ultimately is what this is all about. But pride wins this time, so now there are a few million variations less that his terrain can be experienced in. Loss for the community, nothing else happening here.
Why I did it? To create more maps to play on. Why not? He came out of the woodworks and claimed his terrain back - fine. Responed. Map is gone and will resurface in a new version, with 100% non-Hitman-crosshair content, so that it will replace the maps already in circulation. give me a few weeks, as I am heading for some backcountry skiing in the coming weeks and will be completely offline.
And full disclosure - you can pin this on any map making thread: my maps are available for anyone to take apart and use, terrains, scripting, etc - I don't care one bit - they are out there, and trying to control copyright on something like that is futile and pointless, and in fact counterproductive to making the game better and attracting more players. It is the custom maps that attract people to this game, the fact that you can play so many different scenarios, and many of them on the same terrain. It takes 50 hours to make a decent terrain, while it takes 5-10 hours to create a completely new complex random mission on existing terrain. That's the simple reason behind reusing maps. Go grab some of mine - there should be enough for any map maker to come up with something new and save days of terrain work - invest the time into a better mission instead.
Posted 31 May 2011 - 07:07 PM
02-06-2011 - fight_club http://www.thegamerp...ead.php?t=19892
04-17-2011 - die_tryin http://www.thegamerp...ead.php?t=19933 (totally fresh, 100% original, and obviously better)
04-23-2011 - hello_kitty http://www.thegamerp...ead.php?t=19936
05-02-2011 - ruin_their_day http://www.thegamerp...ead.php?t=19940
05-07-2011 - rampage http://www.thegamerp...ead.php?t=19946
05-21-2011 - rapture http://www.thegamerp...ead.php?t=19956
05-29-2011 - abbottabad http://www.thegamerp...ead.php?t=19959
05-30-2011 - hotel_california http://www.thegamerp...ead.php?t=19960
Edited by fishmonger, 31 May 2011 - 07:09 PM.
Posted 31 May 2011 - 11:25 PM
Posted 01 June 2011 - 10:26 AM
Posted 03 January 2012 - 10:23 PM
06-25-2011 - Explosive Diarrhea http://www.thegamerp...ead.php?t=19981
07-04-2011 - Kinetic Operation http://www.thegamerp...ead.php?t=19987
07-23-2011 - We are Sparta http://www.thegamerp...ead.php?t=20000
09-05-2011 - Sucker Punch http://www.thegamerp...ead.php?t=20022
09-10-2011 - Fruit Punch http://www.thegamerp...ead.php?t=20029
09-10-2011 - Shock and Awe http://www.thegamerp...ead.php?t=19993
09-25-2011 - Calle Reloaded http://www.thegamerp...ead.php?t=20039
10-02-2011 - Hearts and Minds http://www.thegamerp...ead.php?t=20042
10-16-2011 - Extra Cheese http://www.thegamerp...ead.php?t=20051
10-22-2011 - Blistering Fury http://www.thegamerp...ead.php?t=20052
11-05-2011 - Careful Eugene http://www.thegamerp...ead.php?t=20058
11-19-2011 - Texas Speedbump http://www.thegamerp...ead.php?t=20067 (really map by Razamataz1234, I just fixed bad spawns for him)
11-28-2011 - Stool Sample http://www.thegamerp...ead.php?t=20073
12-18-2011 - Seething with Rage http://www.thegamerp...ead.php?t=20083
12-31-2011 - Tastes like Chicken http://www.thegamerp...ead.php?t=20086
01-01-2012 - Come to Papa http://www.thegamerp...ead.php?t=20087
01-02-2012 - Fish Taco http://www.thegamerp...ead.php?t=20088
Posted 03 January 2012 - 10:28 PM
Posted 04 January 2012 - 02:01 PM
@ Riley, let's not dredge up a 9 month old debate.
Posted 04 January 2012 - 04:13 PM
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text:
Jester Jacques Art is an Online Art Publication and Hosts Events in Shoreditch, East London.
The Publication highlights street artists and visual artists from around the world. It includes exhibition coverage and artist interviews, trends in design and fashion, as well as local Shoreditch art and exhibitions.
Co owner Karen Shidlo has written for and been featured on Flux Magazine, Made in Shoreditch, Advertising Week Social Club, Let's Be Brief, Fat Cap and De Dominicis Agency . She has also been interviewed by Art Pro Motivate, London Art Net, Trebuchet Magazine and Artsy Shark and featured on Investors Mag.
Jester Jacques began as a gallery, exhibiting in London throughout 2013, with a Pop Up at Box Park, Shoreditch, a booth at the Other Art Fair in London and a successful inaugural exhibition in East London.
Click for Past Pop Ups, Workshops, Art Fairs.
Click for Fine Art Collection 2013.
Click for Full Press List.


text:
Grey's Anatomy: Wish You Were Here
(S05E11) "Sexed-up stalkers." - Sloan
I thought Grey's Anatomy had gone far enough with the Izzie/Denny mess - until this episode. Why you ask? Because they introduced a doctor who gets around on Heelys!! Do you have any idea how much I hate Heelys? Nine-year-olds come whipping by on those damn things when you're walking around the mall, and as much as you hate to wish bad things upon a 9-year-old, I'm just waiting for the headline "Local Sixth Grader Wearing Heelys Cracks Skull Open in Front of Orange Julius." Oh and that doctor (Dr. Arizona Robbins) that got introduced tonight? She's a pediatric surgeon. Great message to send to the youth of America.At this point, I've decided to take Webber's approach and not get attached to any new doctors that come through the front doors of Seattle Grace Hospital. No one stays - they all quit! That being said, Dr. Robbins seems like she has a pretty good attitude about things, and I loved how she didn't take any crap from Bailey.
And speaking of Bailey, her whole "Nazi" schtick is starting to get old, and I'm glad it got worked into the story when Webber brought it up with her. Has she ever liked any of her fellow doctors? She trash-talks and insults colleagues with the best of 'em, and it's about time someone came after her for it. She gets too attached to patients - way too attached - and all it ends up doing is clouding her judgment. At it's core, it's really not that different than Izzie and the LVAD wire mess, and remember how much Bailey chastised her for that? Bailey might not be physically cutting any wires, but her stubbornness and inaction will have the same effect.
OK, moving on. Sloan and Callie? I say go for it when it comes to Lexie and Sadie. I've resigned myself to accepting a simple truth about Grey's Anatomy - by the end of this series everyone will have slept with everyone else, so why try and fight it? Drink, operate, have sex. Take your pick - every doctor on this show is only ever doing one of those three things.
A few more thoughts...
OK, so Izzie told Alex everything about Denny, and he didn't seem to care or think it was a big deal. WTF? Is this just Shonda Rhimes reacting to all the negative feedback and trying to tone down the sheer ridiculousness of this plot by making the characters on the show not care? Not working. It's still bonkers. Izzie has deeper conversations with Denny than she does with living people.
Alex used one of my personal favorite insults: hosebag. Very underrated and quite fun to say.
It's a Grey's storytelling staple, but I hate when the cases mirror the doctor's lives. While Eric Stoltz was great as Dunn (the serial killer), it feels like he was brought in simply to add to the Yang/Meredith tension. It felt forced and that killed it (no pun intended) for me.
It's been mentioned two, maybe three times now - what happened between Sadie and Meredith in Amsterdam?
Frankly, I don't see how Yang and Meredith never speaking again is a bad thing.
For the duration of this series, we're going to have to endure Sloan saying "I'm going to Denver" whenever he's chasing tail. Super.
While much of this episode annoyed me (could ya tell?), I especially liked the ending when we found out about Derek's father being shot by thieves who stole his watch. To me, Shepherd is one of the few remaining interesting character on this show, and with this little bit of info, I'm really looking forward to the introduction of his mother (Tyne Daly) next week.
Grey's Anatomy' Photos
Joe Corrigan/WireImage.com
Joe Corrigan/WireImage.com
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Getty Images
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Dan MacMedan/WireImage.com
Dan MacMedan/WireImage.com


text:
President Mukherjee hosts 'At-home' reception for freedom fighters
President Pranab Mukherjee hosted the 'At-home' reception at Rashtrapati Bhawan for Freedom Fighters on the occasion of 72nd anniversary of Quit India Movement today.
Prime Minister Narendra Modi, and former prime minister Manmohan Singh were also present on the occasion.
Freedom fighters from across the country have been invited to attend a reception to be honoured and felicitated by the President in the presence of various dignitaries of the country.
Freedom fighters from following States/Union Territories across the country have been invited for the reception i.e. Andhra Pradesh, Assam, Bihar, Chhattisgarh, Goa, Gujarat, Haryana, Himachal Pradesh, Jammu and Kashmir, Jharkhand, Karnataka, Kerala, Madhya Pradesh, Maharashtra, Manipur, Odisha, Punjab, Rajasthan, Uttar Pradesh, Uttarakhand, West Bengal, Daman and Diu and the National Capital Territory of Delhi.
Since 2003, the President of India has been hosting an 'At Home' function in the Rashtrapati Bhavan to mark the anniversary of the Quit India Movement on 9th August of every year in honour of freedom fighters.
The Quit India Movement was launched on August 9, 1942. On August 8, 1942, the All India Congress Committee (A.I.C.C.) formally adopted in Bombay a resolution calling on the British to 'Quit India'. The next day national leaders including Gandhiji were arrested by the British. From that very day i.e. August 9, a spontaneous civil disobedience movement in response to Gandhiji's call for immediate independence spread all over the country.
(Posted on 09-08-2014)
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