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Limited data exist regarding risk factors for aortic stenosis (AS). The plasma proteome is a promising phenotype for discovery of novel biomarkers and potentially causative mechanisms. The aim of this study was to discover novel biomarkers with potentially causal associations with AS. We measured 4,877 plasma proteins (SomaScan aptamer-affinity assay) among ARIC (Atherosclerosis Risk In Communities) study participants in mid-life (visit 3 [V3]; n = 11,430; age 60 ± 6 years) and in late-life (V5; n = 4,899; age 76 ± 5 years). We identified proteins cross-sectionally associated with aortic valve (AV) peak velocity (AVmax) and dimensionless index by echocardiography at V5 and with incident AV-related hospitalization after V3 with the use of multivariable linear and Cox proportional hazard regression. We assessed associations of candidate proteins with changes in AVmax over 6 years and with AV calcification with the use of cardiac computed tomography, replicated analysis in an independent sample, performed Mendelian randomization, and evaluated gene expression in explanted human AV tissue. Fifty-two proteins cross-sectionally were associated with AVmax and dimensionless index at V5 and with risk of incident AV-related hospitalization after V3. Among 3,413 participants in the Cardiovascular Health Study, 6 of those proteins were significantly associated with adjudicated moderate or severe AS, including matrix metalloproteinase 12 (MMP12), complement C1q tumor necrosis factor–related protein 1 (C1QTNF1), and growth differentiation factor-15. MMP12 was also associated with greater increase in AVmax over 6 years, greater degree of AV calcification, and greater expression in calcific compared with normal or fibrotic AV tissue. C1QTNF1 had consistent potential causal effects on both AS and AVmax according to Mendelian randomization analysis. These findings identify MMP12 as a potential novel circulating biomarker of AS risk and C1QTNF1 as a new putative target to prevent AS progression. [Display omitted] [ABSTRACT FROM AUTHOR]

The apicoplast, which is the result of secondary endosymbiosis, is a distinctive subcellular organelle and a crucial therapeutic target for apicomplexan parasites. The majority of apicoplast-resident proteins are encoded by the nuclear genome and target the apicoplast via bipartite targeting signals consisting of a signal peptide and a transit peptide. The properties and functions of these peptides are poorly understood, which hinders the identification of apicoplast proteins and the study for plastid evolution. Here, the targeting signals of the recently discovered apicoplast tRNA thiouridylase Tg MnmA of Toxoplasma gondii were analyzed. Our data using a reporter (the enhanced green fluorescent protein) fused with individual fragments containing various numbers of its N-terminal amino acids unequivocally revealed that the first 28 amino acids of Tg MnmA functioned as a signal peptide for cellular secretion. The N-terminal 150 amino acids were sufficient to direct the fusion protein to the apicoplast, whereas its deletion caused the fusion protein to be localized to the mitochondrion. Our data further demonstrated that the apicoplast, rhoptry, and mitochondrion shared similar targeting signals, indicating that the apicoplast localization peptide was trans-organellar in function. In addition, the apicoplast localization peptide was important for the healthy proliferation of tachyzoites. In conclusion, the targeting signals of the nucleus-encoded apicoplast-targeted protein Tg MnmA have been mapped out and the importance of this localization peptide has been elucidated in the current study. • The first N-terminal 150 AA of Tg MnmA target the EGFP to the apicoplast. • Without the localization peptide, Tg MnmAΔ1−150-EGFP localizes to the mitochondrion. • Mis-localization of Tg MnmA greatly affects the proliferation of T. gondii in vitro. [ABSTRACT FROM AUTHOR]

With the emergence and progress of composite tools in the Middle Stone Age, the adhesive became one of the most widely used materials by early human societies. However, the precise composition identification of adhesive in archaeological remains is a real analytical challenge, because the adhesive mainly consists of organic materials that are susceptible to decay during burial process. Of particular interest is to know which animal/plant species were being exploited for glue manufacturing other than for food. The arid climate of the Xiaohe Cemetery, located in Taklamakan Desert, northwestern China, provides favorable conditions for the preservation of organic residues. A bone sculpture-inlaid wooden artifact was collected from the Xiaohe Cemetery, with some semi-transparent yellowish adhesive exposed due to the detachment of an inlaid bone sculpture. In this paper, micro samples of the adhesive were scraped for FTIR (Fourier Transform Infrared Spectroscopy, primary examination) and subsequent proteomic analysis to determine the proteinous component(s) and precise origin(s). The identified tryptic peptides match most closely to known bovine collagen markers, suggesting that this adhesive was an animal glue made from cattle. These results reveal the diverse utilizations of cattle in the Xiaohe Cemetery, which provided not only meat, milk, hides, sinews and dung, but also leftover parts for manufacturing adhesive. This is the earliest evidence of adhesive identified in China up to our knowledge, which sheds light on adhesive development around 3500 years ago. [ABSTRACT FROM AUTHOR]

Abstract: We report on the geLC–MS/MS proteomics analysis of cereals and cereal food excavated in Subeixi cemetery (500–300BC) in Xinjiang, China. Proteomics provided direct evidence that at the Subexi sourdough bread was made from barley and broomcorn millet by leavening with a renewable starter comprising baker's yeast and lactic acid bacteria. The baking recipe and flour composition indicated that barley and millet bread belonged to the staple food already in the first millennium BC and suggested the role of Turpan basin as a major route for cultural communication between Western and Eastern Eurasia in antiquity. This article is part of a Special Issue entitled: Proteomics of non-model organisms. Biological significance: We demonstrate that organic residues of thousand year old foods unearthed by archeological excavations can be analyzed by geLC–MS/MS proteomics with good representation of protein source organisms and coverage of sequences of identified proteins. In-depth look into the foods proteome identifies the food type and its individual ingredients, reveals ancient food processing technologies, projects their social and economic impact and provides evidence of intercultural communication between ancient populations. Proteomics analysis of ancient organic residues is direct, quantitative and informative and therefore has the potential to develop into a valuable, generally applicable tool in archaeometry. This article is part of a Special Issue entitled: Proteomics of non-model organisms. [Copyright &y& Elsevier]

Abstract: Cheese making has been inferred at several sites in northern Europe as early as the 6th millennium BC and was common in Egypt and Mesopotamia in 3rd millennium BC. However, the remains of ancient cheeses have never been found and recipes of ancient dairy, its production scale, social and economic impact remain poorly understood. Here we present direct proteomics evidence for the production of an earliest known cheese that was found as an organic mass associated with the mummies of Early Bronze Age cemetery of Xiaohe (1980–1450 BC) in Xinjiang, China. Kefir fermentation of ruminant milk by a symbiotic culture of Lactobacillus kefiranofaciens and other lactic acid bacteria and yeasts was the basis of robust, scalable, probiotic, lactose-free dairy and a key technological advance that introduced economic benefits of extensive herding into a semi-pastoral household of the Eastern Eurasia population already in the Early Bronze Age. [Copyright &y& Elsevier]

The spotted hyena (Crocuta crocuta) is the only extant species of the genus Crocuta, which once occupied a much wider range during the Pliocene and Pleistocene. However, its origin and evolutionary history is somewhat contentious due to discordances between morphological, nuclear, and mitochondrial data. Due to the limited molecular data from east Asian Crocuta, also known as cave hyena, and the difficulty of extracting ancient DNA from this area, here we present proteomic analysis of cave hyenas from three locations in northern China. This marks the first proteomic data generated from cave hyenas, adding new molecular data to the east Asian populations. Phylogenetic analysis based on these protein sequences reveals two different groups of cave hyenas in east Asia, one of which could not be distinguished from modern spotted hyenas from northern Africa, tentatively the result of previously suggested gene flow between these lineages. With developments of instrumentation and analytical methods, proteomics holds promising potential for molecular phylogenetic reconstructions of ancient fauna previously thought to be unreachable using ancient DNA. [ABSTRACT FROM AUTHOR]

Characterization of ancient food remains could reflect how people exploited biological resources and interacted with different cultures in antiquity. In this study, Fourier Transform Infrared Spectroscopy (FTIR), starch grain, phytolith, stable isotope analysis and proteomics were adopted to characterize the composition of the food remains including three cereal foodstuffs, some meat strips and a kebab discovered at the Changle Cemetery (202 BCE–220 CE), Ningxia, northwest China, a key area on the Silk Road. The results show that the cereal foods were baked cakes, primarily made from foxtail millet (Setaria italica). One cake was simply made of millet grains, the others were more elaborately comprised of millet flour with the addition of barley flour and meat from cattle (Bos taurus) and chicken (Gallus gallus). These findings indicate that grinding and baking technologies, which were considered as the culinary tradition in western Eurasia, had been adopted at the latest by the inhabitants in Ningxia region at that time. The large-scale migration from central China to Ningxia and the opening up of the Silk Road during the Han Dynasty gave rise to the diet communication and assimilation in this border area. Moreover, the meat strips were identified as dried beef, and the kebab was likely to be made from sheep/goat meat, wherein the latter is the earliest scientific evidence of mutton kebab in ancient China up to our knowledge. The analytical strategy could be widely applied in characterizing ancient visible food remains in order to better understand their preparation methods. [ABSTRACT FROM AUTHOR]

The bronze mou was an important artifact commonly used in the Ba-Shu region (now in Chongqing and Sichuan Province) during the Spring and Autumn Period and the Han Dynasty. Although extensive archaeological study of the bronze mou has been conducted, scientific analysis of the bronze mou has been limited, and no organic residue analysis has been performed on the bronze mou. In this study, four bronze mous dated to the Han dynasty (206 BC–220 AD) with organic residues unearthed in three archaeological sites in Wushan, Chongqing, were selected for analysis by portable X-ray fluorescent spectrometer (P-XRF) and liquid chromatograph-tandem mass spectrometry (LC/MS/MS). The results of the alloy composition indicated that all the samples are copper-tin-lead ternary alloys. The proteomic analysis results confirmed that the bronze mou had been used as cooking utensils or containers. At the Tuchengpo Cemetery, soybeans were found in both bronze mou M32:27 and M38:39, and vigna was discovered in M32:27. No useful protein was discovered in the bronze mou from the Shennvmiao Cemetery. Proteins of ginkgo and chicken were found in M16:12 at the Gaotangguan Cemetery. The discovery indicated that residents in Wushan, Chongqing, had access to a diverse range of food sources around 2000 years ago. Furthermore, this study demonstrates that proteomic analysis is highly effective in studying archaeological organic residues. [ABSTRACT FROM AUTHOR]

Grass woven baskets is a famous feature of Gumugou cemetery (3800 BP), an early Bronze Age necropolis in Tarim basin, northwestern China. They were suggested to be used for storage of liquid foods, for example gruel, ephedra soup or milk, however this notion has not been supported by analytical facts. We applied comprehensive multi-technique analytical approach, including FT-IR, proteomics, GC–MS and starch grains analyses to characterize minute amount of dried organic film preserved on the inner surface of one of the Gumugou grass woven baskets. The analysis revealed the presence of Bovidae milk proteins and traces of lactic acid bacteria. Together with the relative abundance of detected caseins and whey proteins it suggested that the organic deposit in the woven basket was strained sour milk. No ephedra biomarkers or starch grains were found. The protein composition of Gumugou sample differed from solid dairy products recently discovered at the nearby Xiaohe Cemetery. We speculate that the alterations in local dairy technologies might be the result of two processes: climatic changes in the region of Tarim basin and admix of early European settlers with lactose-intolerant Eastern ethnic group. European ancestry of Gumugou inhabitants suggested that the milking practice in the Tarim region was promoted by the eastward migration of European population which was predominantly lactose–persistent. Xiaohe site (3600 BP) was inhabited by a West-East admixed community for whom solid dairy products became a dietary requirement that offered its inhabitants an advantage in better adaptation to the worsening climate. [ABSTRACT FROM AUTHOR]