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1.	Wallin, Cecilia, et al. (författare) Characterization of Mn(II) ion binding to the amyloid-beta peptide in Alzheimer's disease 2016 Ingår i: Journal of Trace Elements in Medicine and Biology. - : Elsevier BV. - 0946-672X .- 1878-3252. ; 38, s. 183-193 Tidskriftsartikel (refereegranskat)abstract Growing evidence links neurodegenerative diseases to metal exposure. Aberrant metal ion concentrations have been noted in Alzheimer's disease (AD) brains, yet the role of metals in AD pathogenesis remains unresolved. A major factor in AD pathogenesis is considered to be aggregation of and amyloid formation by amyloid-beta (A beta) peptides. Previous studies have shown that A beta displays specific binding to Cu(II) and Zn(II) ions, and such binding has been shown to modulate A beta aggregation. Here, we use nuclear magnetic resonance (NMR) spectroscopy to show that Mn(II) ions also bind to the N-terminal part of the A beta(1-40) peptide, with a weak binding affinity in the milli- to micromolar range. Circular dichroism (CD) spectroscopy, solid state atomic force microscopy (AFM), fluorescence spectroscopy, and molecular modeling suggest that the weak binding of Mn(II) to A beta may not have a large effect on the peptide's aggregation into amyloid fibrils. However, identification of an additional metal ion displaying A beta binding reveals more complex AD metal chemistry than has been previously considered in the literature.
2.	Österlund, Nicklas, et al. (författare) Amyloid-beta Peptide Interactions with Amphiphilic Surfactants : Electrostatic and Hydrophobic Effects 2018 Ingår i: ACS Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 9:7, s. 1680-1692 Tidskriftsartikel (refereegranskat)abstract The amphiphilic nature of the amyloid-beta (A beta) peptide associated with Alzheimer's disease facilitates various interactions with biomolecules such as lipids and proteins, with effects on both structure and toxicity of the peptide. Here, we investigate these peptide-amphiphile interactions by experimental and computational studies of A beta(1-40) in the presence of surfactants with varying physicochemical properties. Our findings indicate that electrostatic peptide-surfactant interactions are required for coclustering and structure induction in the peptide and that the strength of the interaction depends on the surfactant net charge. Both aggregation-prone peptide-rich coclusters and stable surfactant-rich coclusters can form. Only A beta(1-40) monomers, but not oligomers, are inserted into surfactant micelles in this surfactant-rich state. Surfactant headgroup charge is suggested to be important as electrostatic peptide-surfactant interactions on the micellar surface seems to be an initiating step toward insertion. Thus, no peptide insertion or change in peptide secondary structure is observed using a nonionic surfactant. The hydrophobic peptide-surfactant interactions instead stabilize the A beta monomer, possibly by preventing self-interaction between the peptide core and C terminus, thereby effectively inhibiting the peptide aggregation process. These findings give increased understanding regarding the molecular driving forces for A beta aggregation and the peptide interaction with amphiphilic biomolecules.
3.	Bartelink, Eric J., et al. (författare) A Case of Contested Cremains Analyzed Through Metric and Chemical Comparison 2015 Ingår i: Journal of Forensic Sciences. - : Wiley. - 0022-1198 .- 1556-4029. ; 60:4, s. 1068-1073 Tidskriftsartikel (refereegranskat)abstract Since the 1980s, cremation has become the fastest growing area of the U.S. funeral industry. At the same time, the number of litigations against funeral homes and cremation facilities has increased. Forensic anthropologists are often asked to determine whether the contents of an urn are actually cremated bone, and to address questions regarding the identity of the remains. This study uses both metric and chemical analyses for resolving a case of contested cremains. A cremains weight of 2021.8 g was predicted based on the decedent's reported stature and weight. However, the urn contents weighed 4173.5 g. The urn contents also contained material inconsistent with cremains (e.g., moist sediment, stones, ferrous metal). Analysis using XRD and SEM demonstrated that the urn contained thermally altered bone as well as inorganic material consistent with glass fiber cement. Although forensically challenging, cremains cases such as this one can be resolved using a multidisciplinary approach.
4.	Bulut, Ozgur, et al. (författare) Sexual dimorphism in frontal bone roundness quantified by a novel 3D-based and landmark-free method 2016 Ingår i: Forensic Science International. - : Elsevier BV. - 0379-0738 .- 1872-6283. ; 261, s. 162.e1-162.e5 Tidskriftsartikel (refereegranskat)abstract In this study we present a novel and landmark-free method for quantifying shape differences between male and female frontal bones. CT scans were recorded for 80 male and 80 female Turkish hospital patients, age 25-40. The frontal bones were first isolated from the 3D models by digital cutting along the bordering sutures, and then aligned to a CAD-based sphere. This allowed us to quantify the amount of frontal bone overlapping with the sphere (on average 43.2 +/- 6.5% for males and 33.9 +/- 6.6% for females, the difference is significant at p < 0.0001), and to identify areas of shape difference and deviation from the sphere surface in male and female bones. The larger proportion of spherical frontal bone surface in males challenges the common description of the female forehead as rounder''. Based on the overlap data, we developed discriminant functions able to correctly classify 77.5% of the frontal bone models as male/female. This demonstrates that 3D-based and landmark-free approaches to statistical shape analysis may become a viable alternative to the currently dominating landmark-based approaches for shape investigation.
5.	Chemerovski-Glikman, Marina, et al. (författare) Self-Assembled Cyclic D,L-alpha-Peptides as Generic Conformational Inhibitors of the alpha-Synuclein Aggregation and Toxicity : In Vitro and Mechanistic Studies 2016 Ingår i: Chemistry - A European Journal. - : Wiley. - 0947-6539 .- 1521-3765. ; 22:40, s. 14236-14246 Tidskriftsartikel (refereegranskat)abstract Many peptides and proteins with large sequences and structural differences self-assemble into disease-causing amyloids that share very similar biochemical and biophysical characteristics, which may contribute to their cross-interaction. Here, we demonstrate how the self-assembled, cyclic D,L-alpha-peptide CP-2, which has similar structural and functional properties to those of amyloids, acts as a generic inhibitor of the Parkinson's disease associated alpha-synuclein (alpha-syn) aggregation to toxic oligomers by an, off-pathway mechanism. We show that CP-2 interacts with the N-terminal and the non-amyloid-beta component region of alpha-syn, which are responsible for alpha-syn's membrane intercalation and self-assembly, thus changing the overall conformation of alpha-syn. CP-2 also remodels alpha-syn fibrils to nontoxic amorphous species and permeates cells through endosomes/lysosomes to reduce the accumulation and toxicity of intracellular alpha-syn in neuronal cells overexpressing alpha-syn. Our studies suggest that targeting the common structural conformation of amyloids may be a promising approach for developing new therapeutics for amyloidogenic diseases.
6.	Dong, Xiaolin, et al. (författare) Copper ions induce dityrosine-linked dimers in human but not in murine islet amyloid polypeptide (IAPP/amylin) 2019 Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 510:4, s. 520-524 Tidskriftsartikel (refereegranskat)abstract Dysregulation and aggregation of the peptide hormone IAPP (islet amyloid polypeptide, a.k.a. amylin) into soluble oligomers that appear to be cell-toxic is a known aspect of diabetes mellitus (DM) Type 2 pathology. IAPP aggregation is influenced by several factors including interactions with metal ions such as Cu(II). Because Cu(II) ions are redox-active they may contribute to metal-catalyzed formation of oxidative tyrosyl radicals, which can generate dityrosine cross-links. Here, we show that such a process, which involves Cu(II) ions bound to the IAPP peptide together with H2O2, can induce formation of large amounts of IAPP dimers connected by covalent dityrosine cross-links. This cross-linking is less pronounced at low pH and for murine IAPP, likely due to less efficient Cu(II) binding. Whether IAPP can carry out its hormonal function as a cross-linked dimer is unknown. As dityrosine concentrations are higher in blood plasma of DM Type 2 patients - arguably due to disease-related oxidative stress - and as dimer formation is the first step in protein aggregation, generation of dityrosine-linked dimers may be an important factor in IAPP aggregation and thus relevant for DM Type 2 progression.
7.	Frković, Vedran, et al. (författare) Finger width as a measure of femoral block puncture site : an ultrasonographic anatomical-anthropometric study 2015 Ingår i: Journal of clinical anesthesia. - : Elsevier BV. - 0952-8180 .- 1873-4529. ; 27:7, s. 553-557 Tidskriftsartikel (refereegranskat)abstract Study objective: Femoral nerve blockade is a regional anesthetic procedure that may be used in prehospital and emergency settings in cases of femoral trauma. Its speed and performance depend on how well the puncture site can be accurately located, something that usually is achieved via visible landmarks and/or by combining various universal preestablished measurements. Most of these methods have been derived from cadaver studies, which often suffer limitations in clinical settings. To facilitate a quick and easy determination of the puncture site, we here attempt to find an in vivo anthropometric measure that closely corresponds to the distance between the femoral artery and femoral nerve.Design: This is a prospective observational study.Patients: The study includes 67 patients presenting for elective surgery.Measurements: The distance from the femoral nerve to the femoral artery, projected to the skin, was measured by a 13-MHz ultrasonographic linear probe. Anthropometric measurements of the width of the hand fingers were carried out at the distal interphalangeal joints.Results: The distance from the femoral artery to the femoral nerve projected to the skin was found to closely correspond to the width of the fifth finger of the dominant hand measured at the distal interphalangeal joint.Conclusion: Because it relies on individual anthropometric information, this finding offers an individualized approach to determining the puncture site in a given patient. We believe that such an approach can improve and simplify femoral nerve blockade procedures in prehospital and emergency settings.
8.	Horvath, Istvan, et al. (författare) Co-aggregation of pro-inflammatory S100A9 with alpha-synuclein in Parkinson's disease : ex vivo and in vitro studies 2018 Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 15 Tidskriftsartikel (refereegranskat)abstract Background: Chronic neuroinflammation is a hallmark of Parkinson's disease (PD) pathophysiology, associated with increased levels of pro-inflammatory factors in PD brain tissues. The pro-inflammatory mediator and highly amyloidogenic protein S100A9 is involved in the amyloid-neuroinflammatory cascade in Alzheimer's disease. This is the first report on the co-aggregation of alpha-synuclein (alpha-syn) and S100A9 both in vitro and ex vivo in PD brain. Methods: Single and sequential immunohistochemistry, immunofluorescence, scanning electron and atomic force (AFM) microscopies were used to analyze the ex vivo PD brain tissues for S100A9 and alpha-syn location and aggregation. In vitro studies revealing S100A9 and alpha-syn interaction and co-aggregation were conducted by NMR, circular dichroism, Thioflavin-T fluorescence, AFM, and surface plasmon resonance methods. Results: Co-localized and co-aggregated S100A9 and alpha-syn were found in 20% Lewy bodies and 77% neuronal cells in the substantia nigra; both proteins were also observed in Lewy bodies in PD frontal lobe (Braak stages 4-6). Lewy bodies were characterized by ca. 10-23 mu m outer diameter, with S100A9 and alpha-syn being co-localized in the same lamellar structures. S100A9 was also detected in neurons and blood vessels of the aged patients without PD, but in much lesser extent. In vitro S100A9 and alpha-syn were shown to interact with each other via the alpha-syn C-terminus with an apparent dissociation constant of ca. 5 mu M. Their co-aggregation occurred significantly faster and led to formation of larger amyloid aggregates than the self-assembly of individual proteins. S100A9 amyloid oligomers were more toxic than those of alpha-syn, while co-aggregation of both proteins mitigated the cytotoxicity of S100A9 oligomers. Conclusions: We suggest that sustained neuroinflammation promoting the spread of amyloidogenic S100A9 in the brain tissues may trigger the amyloid cascade involving alpha-syn and S100A9 and leading to PD, similar to the effect of S100A9 and A beta co-aggregation in Alzheimer's disease. The finding of S100A9 involvement in PD may open a new avenue for therapeutic interventions targeting S100A9 and preventing its amyloid self-assembly in affected brain tissues.
9.	Leshem, Guy, et al. (författare) Photoactive chlorin e6 is a multifunctional modulator of amyloid-β aggregation and toxicity via specific interactions with its histidine residues 2019 Ingår i: Chemical Science. - : Royal Society of Chemistry (RSC). - 2041-6520 .- 2041-6539. ; 10:1, s. 208-217 Tidskriftsartikel (refereegranskat)abstract The self-assembly of A to -sheet-rich neurotoxic oligomers is a main pathological event leading to Alzheimer's disease (AD). Selective targeting of A oligomers without affecting other functional proteins is therefore an attractive approach to prevent the disease and its progression. In this study, we report that photodynamic treatment of A in the presence of catalytic amounts of chlorin e6 can selectively damage A and inhibit its aggregation and toxicity. Chlorin e6 also reversed the amyloid aggregation process in the dark by binding its soluble and low molecular weight oligomers, as shown by thioflavin T (ThT) fluorescence and photoinduced cross-linking of unmodified protein (PICUP) methods. Using HSQC NMR spectroscopy, ThT assays, amino acid analysis, SDS/PAGE, and EPR spectroscopy, we show that catalytic amounts of photoexcited chlorin e6 selectively damage the A histidine residues H6, H13, and H14, and induce A cross-linking by generating singlet oxygen. In contrast, photoexcited chlorin e6 was unable to cross-link ubiquitin and -synuclein, demonstrating its high selectivity for A. By binding to the A histidine residues, catalytic amounts of chlorin e6 can also inhibit the Cu2+-induced aggregation and toxicity in darkness, while at stoichiometric amounts it acts as a chelator to reduce the amount of free Cu2+. This study demonstrates the great potential of chlorin e6 as a multifunctional agent for treatment of AD, and shows that the three N-terminal A histidine residues are a suitable target for A-specific drugs.
10.	Luo, Jinghui, et al. (författare) Cross-interactions between the Alzheimer Disease Amyloid-beta Peptide and Other Amyloid Proteins : A Further Aspect of the Amyloid Cascade Hypothesis 2016 Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 291:32, s. 16485-16493 Forskningsöversikt (refereegranskat)abstract Many protein folding diseases are intimately associated with accumulation of amyloid aggregates. The amyloid materials formed by different proteins/peptides share many structural similarities, despite sometimes large amino acid sequence differences. Some amyloid diseases constitute risk factors for others, and the progression of one amyloid disease may affect the progression of another. These connections are arguably related to amyloid aggregates of one protein being able to directly nucleate amyloid formation of another, different protein: the amyloid cross-interaction. Here, we discuss such cross-interactions between the Alzheimer disease amyloid-beta (A beta) peptide and other amyloid proteins in the context of what is known from in vitro and in vivo experiments, and of what might be learned from clinical studies. The aim is to clarify potential molecular associations between different amyloid diseases. We argue that the amyloid cascade hypothesis in Alzheimer disease should be expanded to include cross-interactions between A beta and other amyloid proteins.
11.	Luo, Jinghui, et al. (författare) Reciprocal Molecular Interactions between the A beta Peptide Linked to Alzheimer's Disease and Insulin Linked to Diabetes Mellitus Type II 2016 Ingår i: ACS Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 7:3, s. 269-274 Tidskriftsartikel (refereegranskat)abstract Clinical studies indicate diabetes mellitus type II (DM) doubles the risk that a patient will also develop Alzheimer's disease (AD). DM is caused by insulin resistance and a relative lack of active insulin. AD is characterized by the deposition of amyloid beta (A beta) peptide fibrils. Prior to fibrillating, A beta forms intermediate, prefibrillar oligomers, which are more cytotoxic than the mature A beta fibrils. Insulin can also form amyloid fibrils. In vivo studies have revealed that insulin promotes the production of A beta, and that soluble A beta competes with insulin for the insulin receptor. Here, we report that monomeric insulin interacted with soluble A beta and that both molecules reciprocally slowed down the aggregation kinetics of the other. Prefibrillar oligomers of A beta that eventually formed in the presence of insulin were less cytotoxic than A beta oligomers formed in the absence of insulin. Mature A beta fibrils induced fibrillation of soluble insulin, but insulin aggregates did not promote A beta fibrillation. Our study indicates that direct molecular interactions between insulin and A beta may contribute to the strong link between DM and AD.
12.	Neiß (Neiss), Michael, 1977-, et al. (författare) New applications of 3D modeling in artefact analysis : three case studies in Viking Age brooches 2016 Ingår i: Archaeological and Anthropological Sciences. - Springer : Berlin. - 1866-9557 .- 1866-9565. ; 8:4, s. 651-662 Tidskriftsartikel (refereegranskat)abstract Three-dimensional (3D) laser scanning is a nondestructive and versatile technique that provides archaeologists with 3D models of archaeological and ethnographic objects. We have previously shown that 3D models facilitate shape analysis of archaeological bones and stone tools, due to the high measurement accuracy inherent in the latest generation of 3D laser scanners. Here, we explore the utility of 3D modeling as a tool for analyzing Viking Age metal artefacts with complex morphologies. Four highly ornate Viking Age brooches from Scandinavia and Russia were digitized with a portable laser scanner, and the resulting 3D models were used in three case studies of (a) artefact reconstruction, (b) tool mark analysis, and (c) motif documentation. The results revealed both strengths and limitations of the employed techniques. 3D modeling proved to be very well suited for artefact reconstruction and was helpful also in the stylistic and motif analysis. The tool mark analysis was only partially successful, due to the resolution limits of the laser scanner used. 3D-based motif analysis of a grandiose Scandinavian-style brooch from Yelets, Russia, identified an anthropomorphic figure with a bird-like body that previously has been overlooked. This figure may be a Rurikid coat of arms, possibly linking the object to a princely household and providing further evidence for a connection between Scandinavia and the Rurikids. As 3D technology keeps improving, we expect that additional applications for 3D modeling in archaeology will be developed, likely leading to many new findings when old objects are re-analyzed with modern techniques. However, our results indicate that 3D modeling cannot completely replace traditional artefact analysis—instead, we argue that the two approaches are best used in combination.
13.	Owen, Michael C., et al. (författare) Effects of in vivo conditions on amyloid aggregation 2019 Ingår i: Chemical Society Reviews. - : Royal Society of Chemistry (RSC). - 0306-0012 .- 1460-4744. ; 48:14, s. 3946-3996 Forskningsöversikt (refereegranskat)abstract One of the grand challenges of biophysical chemistry is to understand the principles that govern protein misfolding and aggregation, which is a highly complex process that is sensitive to initial conditions, operates on a huge range of length- and timescales, and has products that range from protein dimers to macroscopic amyloid fibrils. Aberrant aggregation is associated with more than 25 diseases, which include Alzheimer's, Parkinson's, Huntington's, and type II diabetes. Amyloid aggregation has been extensively studied in the test tube, therefore under conditions that are far from physiological relevance. Hence, there is dire need to extend these investigations to in vivo conditions where amyloid formation is affected by a myriad of biochemical interactions. As a hallmark of neurodegenerative diseases, these interactions need to be understood in detail to develop novel therapeutic interventions, as millions of people globally suffer from neurodegenerative disorders and type II diabetes. The aim of this review is to document the progress in the research on amyloid formation from a physicochemical perspective with a special focus on the physiological factors influencing the aggregation of the amyloid-beta peptide, the islet amyloid polypeptide, alpha-synuclein, and the hungingtin protein.
14.	Pansieri, Jonathan, et al. (författare) Pro-Inflammatory S100A9 Protein Aggregation Promoted by NCAM1 Peptide Constructs 2019 Ingår i: ACS Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 14:7, s. 1410-1417 Tidskriftsartikel (refereegranskat)abstract Amyloid cascade and neuroinflammation are hallmarks of neurodegenerative diseases, and pro-inflammatory S100A9 protein is central to both of them. Here, we have shown that NCAM1 peptide constructs carrying polycationic sequences derived from A beta peptide (KKLVFF) and PrP protein (KKRPKP) significantly promote the S100A9 amyloid self-assembly in a concentration-dependent manner by making transient interactions with individual S100A9 molecules, perturbing its native structure and acting as catalysts. Since the individual molecule misfolding is a rate-limiting step in S100A9 amyloid aggregation, the effects of the NCAM1 construct on the native S100A9 are so critical for its amyloid self-assembly. S100A9 rapid self assembly into large aggregated clumps may prevent its amyloid tissue propagation, and by modulating S100A9 aggregation as a part of the amyloid cascade, the whole process may be effectively tuned.
15.	Petaros, Anja, et al. (författare) Evaluating sexual dimorphism in the human mastoid process : A viewpoint on the methodology 2015 Ingår i: Clinical anatomy (New York, N.Y. Print). - : Wiley. - 0897-3806 .- 1098-2353. ; 28:5, s. 593-601 Tidskriftsartikel (refereegranskat)abstract The mastoid process is one of the most sexually dimorphic features in the human skull, and is therefore often used to identify the sex of skeletons. Numerous techniques for assessing variation in the size and shape of the mastoid process have been proposed and implemented in osteological research, but its complex form still presents difficulties for consistent and effective analysis. In this article, we compare the different techniques and variables that have been used to define, measure, and visually score sexual dimorphism in the mastoid process. We argue that the current protocols fail to capture the full morphological range of this bony projection, and suggest ways of improving and standardizing them, regarding both traditional and 3D-based approaches. Clin. Anat. 28:593-601, 2015.
16.	Petaros, Anja, et al. (författare) Sexual dimorphism and regional variation in human frontal bone inclination measured via digital 3D models 2017 Ingår i: Legal Medicine. - : Elsevier BV. - 1344-6223 .- 1873-4162. ; 29, s. 53-61 Tidskriftsartikel (refereegranskat)abstract The frontal bone is one of the most sexually dimorphic elements of the human skull, due to features such as the glabella, frontal eminences, and frontal inclination. While glabella is frequently evaluated in procedures to estimate sex in unknown human skeletal remains, frontal inclination has received less attention. In this study we present a straightforward, quick, and reproducible method for measuring frontal inclination angles from glabella and supraglabella. Using a sample of 413 human crania from four different populations (U.S. Whites, U.S. Blacks, Portuguese, and Chinese), we test the usefulness of the inclination angles for sex estimation and compare their performance to traditional methods of frontal inclination assessment. Accuracy rates in the range 75-81% were achieved for the U.S. White, U.S. Black, and Portuguese groups. For Chinese the overall accuracy was lower, i.e. 66%. Although some regional variation was observed, a cut-off value of 78.2 for glabellar inclination angles separates female and male crania from all studied populations with good accuracy. As inclination angles measured from glabella captures two sexually dimorphic features (i.e. glabellar prominence and frontal inclination) in a single measure, the observed clear male/female difference is not unexpected. Being continuous variables, inclination angles are suitable for use in statistical methods for sex estimations.
17.	Saage, Ragnar, et al. (författare) Metal residues in 5th c. BCE-13th c. CE Estonian tools for non-ferrous metal casting 2018 Ingår i: Journal of Archaeological Science. - : Elsevier BV. - 2352-409X .- 2352-4103. ; 19, s. 35-51 Tidskriftsartikel (refereegranskat)abstract This paper investigates Estonian tools for non-ferrous metal casting in the form of crucibles, moulds, and casting ladles dating to the Estonian Iron Age (500 BCE-1227 CE), adding elemental analysis and 3D modelling to the traditional typological comparison. In contrast to the neighbouring countries of Russia, Latvia, and Sweden, no comprehensive study has previously been published on this subject for Estonian material. The typological analysis sets Iron Age Estonia in the same metalworking tradition as that of other eastern Baltic countries and Northwestern Russia. However, some classes of casting tools present in Scandinavian and Slavonic areas have so far not been encountered in the Estonian archaeological record. The elemental analysis included qualitative pXRF analysis of 175 artefacts and detailed residue analysis using SEM-EDS of thirteen selected artefacts. This analysis identified for the first time Estonian Iron Age casting tools - crucibles - used for casting gold and silver. Most of the investigated crucibles were used for casting various copper alloys, while the casting ladles and most of the stone moulds were used for casting pewter. Casting of pewter and precious metals only occurred in regional centres such as hill forts and strongholds, while copper alloys were cast in all parts of Estonia. In addition to clarifying fundamental questions about Estonian Iron Age metal casting, this study also lays a foundation for using modern analytical techniques in future investigations of Estonian metalworking traditions.
18.	Sholts, Sabrina B., et al. (författare) Tracing social interactions in Pleistocene North America via 3D model analysis of stone tool asymmetry 2017 Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:7 Tidskriftsartikel (refereegranskat)abstract Stone tools, often the sole remnant of prehistoric hunter-gatherer behavior, are frequently used as evidence of ancient human mobility, resource use, and environmental adaptation. In North America, studies of morphological variation in projectile points have provided important insights into migration and interactions of human groups as early as 12-13 kya. Using new approaches to 3D imaging and morphometric analysis, we here quantify bifacial asymmetry among early North American projectile point styles to better understand changes in knapping technique and cultural transmission. Using a sample of 100 fluted bifaces of Clovis and post-Clovis styles in the eastern United States ca. 13,100-9,000 cal BP (i.e., Clovis, Debert-Vail, Bull Brook, Michaud-Neponset/Barnes, and Crowfield), we employed two different approaches for statistical shape analysis: our previously presented method for analysis of 2D flake scar contours, and a new approach for 3D surface analysis using spherical harmonics (SPHARM). Whereas bifacial asymmetry in point shape does not vary significantly across this stylistic sequence, our measure of asymmetric flake scar patterning shows temporal variation that may signify the beginning of regionalization among early New World colonists.
19.	Smith, Kevin N., et al. (författare) Residue analysis links sandstone abraders to on San Nicolas Island, California shell fishhook production 2015 Ingår i: Journal of Archaeological Science. - : Elsevier BV. - 0305-4403 .- 1095-9238. ; 54, s. 287-293 Tidskriftsartikel (refereegranskat)abstract Excavations at the upper component of the Tule Creek site (CA-SNI-25), dating between approximately 600-350 cal BP, yielded numerous well-preserved sandstone abraders referred to as saws. Many of these tools show heavy use-wear and abundant white residue still adhering to the surface. We used X-ray diffraction (XRD) analysis to characterize the residue from two of the abraders, which identified the mineral phases calcite and aragonite (both CaCO3), albite (NaAlSi3O8), and quartz (SiO2). A scanning electron microscope (SEM) equipped for Energy Dispersive X-Ray (EDS) analysis identified the elements C, Ca, S, Na, and Al in the samples, confirming the XRD results. Albite, quartz, and calcite in the scrapings are consistent with the mineralogy of sandstone, though the presence of calcium carbonate in the form of calcite and aragonite suggests marine shell is also present in the residue samples. XRD and SEM analysis of a modern red abalone (Haliotis rufescens) shell indicates that the inner-layer (nacre) consists mostly of aragonite phase calcium carbonate, whereas the outer layer (epidermis) is made up mostly of calcite phase. SEM images revealed that calcite and aragonite from the archaeological residues display similar morphologies as the material from a modern abalone sample, and a greater presence of aragonite over calcite suggests the abraders were primarily used to work the inner layer of the abalone shell. These results provide a functional linkage between sandstone saws and shell fishhook production at CA-SNI-25.
20.	Smith, Kevin N., et al. (författare) Residue analysis, use-wear patterns, and replicative studies indicate that sandstone tools were used as reamers when producing shell fishhooks on San Nicolas Island, California 2018 Ingår i: Journal of Archaeological Science. - : Elsevier BV. - 2352-409X .- 2352-4103. ; 20, s. 502-505 Tidskriftsartikel (refereegranskat)abstract Elucidating the tools and production steps involved in manufacturing the characteristic circular shell fishhooks found on the California Channel Islands has been a long-standing problem in California archaeology. A prehistoric production site for shell fishhooks excavated on the most remote island, San Nicolas Island, has provided a rare opportunity to examine manufacturing sequences. We have previously employed a multidisciplinary research approach to demonstrate that fishhook production at this site involved using sandstone slabs as abraders, or saws. Here, we use chemical residue analysis, replicative experiments, and microwear patterns to show that fishhook production also involved the use of small pointed pieces of sandstone as reamers. These results bring us one step closer to understanding the complete prehistoric toolkit used for production of circular shell fishhooks.
21.	Teixeira, Pedro F., et al. (författare) Mechanism of Peptide Binding and Cleavage by the Human Mitochondrial Peptidase Neurolysin 2018 Ingår i: Journal of Molecular Biology. - : Academic Press. - 0022-2836 .- 1089-8638. ; 430:3, s. 348-362 Tidskriftsartikel (refereegranskat)abstract Proteolysis plays an important role in mitochondrial biogenesis, from the processing of newly imported precursor proteins to the degradation of mitochondrial targeting peptides. Disruption of peptide degradation activity in yeast, plant and mammalian mitochondria is known to have deleterious consequences for organism physiology, highlighting the important role of mitochondrial peptidases. In the present work, we show that the human mitochondrial peptidase neurolysin (hNLN) can degrade mitochondrial presequence peptides as well as other fragments up to 19 amino acids long. The crystal structure of hNLNE475Q in complex with the products of neurotensin cleavage at 2.7 Å revealed a closed conformation with an internal cavity that restricts substrate length and highlighted the mechanism of enzyme opening/closing that is necessary for substrate binding and catalytic activity. Analysis of peptide degradation in vitro showed that hNLN cooperates with presequence protease (PreP or PITRM1) in the degradation of long targeting peptides and amyloid-β peptide, Aβ1–40, associated with Alzheimer disease, particularly cleaving the hydrophobic fragment Aβ35–40. These findings suggest that a network of proteases may be required for complete degradation of peptides localized in mitochondria.
22.	Tiiman, Ann, et al. (författare) Specific Binding of Cu(II) Ions to Amyloid-Beta Peptides Bound to Aggregation-Inhibiting Molecules or SDS Micelles Creates Complexes that Generate Radical Oxygen Species 2016 Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 54:3, s. 971-982 Tidskriftsartikel (refereegranskat)abstract Aggregation of the amyloid-beta (A beta) peptide into insoluble plaques is a major factor in Alzheimer's disease (AD) pathology. Another major factor in AD is arguably metal ions, as metal dyshomeostasis is observed in AD patients, metal ions modulate A beta aggregation, and AD plaques contain numerous metals including redox-active Cu and Fe ions. In vivo, A beta is found in various cellular locations including membranes. So far, Cu(II)/A beta interactions and ROS generation have not been investigated in a membrane environment. Here, we study Cu(II) and Zn(II) interactions with A beta bound to SDS micelles or to engineered aggregation-inhibiting molecules (the cyclic peptide CP-2 and the Z(A beta 3)(12-58) Y18L Affibody molecule). In all studied systems the A beta N-terminal segment was found to be unbound, unstructured, and free to bind metal ions. In SDS micelles, A beta was found to bind Cu(II) and Zn(II) with the same ligands and the same K-D as in aqueous solution. ROS was generated in all Cu(II)/A beta complexes. These results indicate that binding of A beta to membranes, drugs, and other entities that do not interact with the A beta N-terminal part, appears not to compromise the N-terminal segment's ability to bind metal ions, nor impede the capacity of N-terminally bound Cu(II) to generate ROS.
23.	Wallin, Cecilia, et al. (författare) Alzheimer's disease and cigarette smoke components : effects of nicotine, PAHs, and Cd(II), Cr(III), Pb(II), Pb(IV) ions on amyloid-beta peptide aggregation 2017 Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7 Tidskriftsartikel (refereegranskat)abstract Cigarette smoking is a significant risk factor for Alzheimer’s disease (AD), which is associated with extracellular brain deposits of amyloid plaques containing aggregated amyloid-β (Aβ) peptides. Aβ aggregation occurs via multiple pathways that can be influenced by various compounds. Here, we used AFM imaging and NMR, fluorescence, and mass spectrometry to monitor in vitro how Aβ aggregation is affected by the cigarette-related compounds nicotine, polycyclic aromatic hydrocarbons (PAHs) with one to five aromatic rings, and the metal ions Cd(II), Cr(III), Pb(II), and Pb(IV). All PAHs and metal ions modulated the Aβ aggregation process. Cd(II), Cr(III), and Pb(II) ions displayed general electrostatic interactions with Aβ, whereas Pb(IV) ions showed specific transient binding coordination to the N-terminal Aβ segment. Thus, Pb(IV) ions are especially prone to interact with Aβ and affect its aggregation. While Pb(IV) ions affected mainly Aβ dimer and trimer formation, hydrophobic toluene mainly affected formation of larger aggregates such as tetramers. The uncharged and hydrophilic nicotine molecule showed no direct interactions with Aβ, nor did it affect Aβ aggregation. Our Aβ interaction results suggest a molecular rationale for the higher AD prevalence among smokers, and indicate that certain forms of lead in particular may constitute an environmental risk factor for AD.
24.	Wallin, Cecilia, et al. (författare) The Amyloid-beta Peptide in Amyloid Formation Processes : Interactions with Blood Proteins and Naturally Occurring Metal Ions 2017 Ingår i: Israel Journal of Chemistry. - : Wiley. - 0021-2148. ; 57:7-8, s. 674-685 Forskningsöversikt (refereegranskat)abstract This review describes interactions between the amyloid- peptide (A) involved in Alzheimer's disease (AD) and endogenous metal ions and proteins, with an emphasis on future potential drug therapies and targets. AD is characterised by loss of neurons, memory, and cognitive functions, and by formation of cerebral senile plaque deposits. These plaques consist mainly of aggregated A peptides. AD pathology includes a) on the molecular level imbalanced concentrations of A peptides and metal ions, and formation of amyloid structures, and b) on the physiological level a combination of inflammatory responses and oxidative stress effects causing neuronal death. Interestingly, certain blood proteins and metal ions can affect the A amyloid aggregation process. These interactions are the topics of the present review. A deeper understanding of these interactions could facilitate new therapeutic strategies against AD. Previous therapeutic approaches and trials are also briefly described.
25.	Wallin, Cecilia, et al. (författare) The Neuronal Tau Protein Blocks in Vitro Fibrillation of the Amyloid-beta (A beta) Peptide at the Oligomeric Stage 2018 Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 140:26, s. 8138-8146 Tidskriftsartikel (refereegranskat)abstract In Alzheimer's disease, amyloid-beta (A beta) plaques and tau neurofibrillary tangles are the two pathological hallmarks. The co-occurrence and combined reciprocal pathological effects of A beta and tau protein aggregation have been observed in animal models of the disease. However, the molecular mechanism of their interaction remain unknown. Using a variety of biophysical measurements, we here show that the native full-length tau protein solubilizes the A beta(40) peptide and prevents its fibrillation. The tau protein delays the amyloid fibrillation of the A beta(40) peptide at substoichiometric ratios, showing different binding affinities toward the different stages of the aggregated A beta(40) peptides. The A beta monomer structure remains random coil in the presence of tau, as observed by nuclear magnetic resonance (NMR), circular dichroism (CD) spectroscopy and photoinduced cross-linking methods. We propose a potential interaction mechanism for the influence of tau on A beta fibrillation.
26.	Wärmländer, Sebastian K. T. S., et al. (författare) Analysis and Interpretation of a Unique Arabic Finger Ring from the Viking Age Town of Birka, Sweden 2015 Ingår i: Scanning. - : Wiley. - 0161-0457 .- 1932-8745. ; 37:2, s. 131-137 Tidskriftsartikel (refereegranskat)abstract In this work we used non-destructive SEM imaging and EDS analysis to characterize the material composition of an Arabic finger ring, which was found in a 9(th) c. woman's grave at the Viking Age (A.D. 793-1066) trading center of Birka, Sweden. The ring is set with a violet stone inscribed with Arabic Kufic writing, here interpreted as reading il-la-lah, i.e. For/to Allah. The stone was previously thought to be an amethyst, but the current results show it to be coloured glass. The ring has been cast in a high-grade silver alloy (94.5/5.5 Ag/Cu) and retains the post-casting marks from the filing done to remove flash and mold lines. Thus, the ring has rarely been worn, and likely passed from the silversmith to the woman buried at Birka with few owners in between. The ring may therefore constitute material evidence for direct interactions between Viking Age Scandinavia and the Islamic world. Being the only ring with an Arabic inscription found at a Scandinavian archaeological site, it is a unique object among Swedish Viking Age material. The technical analysis presented here provides a better understanding of the properties and background of this intriguing piece of jewelry.
27.	Wärmländer, Sebastian K. T. S., et al. (författare) Estimating the Temperature of Heat-exposed Bone via Machine Learning Analysis of SCI Color Values : A Pilot Study 2019 Ingår i: Journal of Forensic Sciences. - : Wiley. - 0022-1198 .- 1556-4029. ; 64:1, s. 190-195 Tidskriftsartikel (refereegranskat)abstract Determining maximum heating temperatures of burnt bones is a long-standing problem in forensic science and archaeology. In this pilot study, controlled experiments were used to heat 14 fleshed and defleshed pig vertebrae (wet bones) and archaeological human vertebrae (dry bones) to temperatures of 400, 600, 800, and 1000 degrees C. Specular component included (SCI) color values were recorded from the bone surfaces with a Konica-Minolta cm-2600d spectrophotometer. These color values were regressed onto heating temperature, using both a traditional linear model and the k-nearest neighbor (k-NN) machine-learning algorithm. Mean absolute errors (MAE) were computed for 1000 rounds of temperature prediction. With the k-NN approach, the median MAE prediction errors were 41.6 degrees C for the entire sample, and 20.9 degrees C for the subsample of wet bones. These results indicate that spectrophotometric color measurements combined with machine learning methods can be a viable tool for estimating bone heating temperature.
28.	Wärmländer, Sebastian K. T. S., et al. (författare) Hollow comb rivets made from strip-drawn copper wire and two possible antler draw plates from 11th-12th c. Sigtuna, Sweden 2019 Ingår i: Fornvännen. - 0015-7813 .- 1404-9430. ; 114:2, s. 88-99 Tidskriftsartikel (refereegranskat)abstract Modern metal wire is produced by drawing solid metal rods through a draw-plate. Scandinavian smiths used this technique already during the Viking Age, but little is known about earlier Scandinavian methods for making metal wire. It has previously been suggested that the metal rivets in composite bone and antler combs may have been hollow and produced by strip-drawing, but no metallurgical studies have so far been carried out to investigate this possibility. Here, we used scanning electron microscopy (SEM) to investigate copper-alloy rivets in 11th - 12th c. composite combs from Sigtuna, the administrative centre for middle Sweden's first Christian kings during the early Medieval period. Our SEM images showed that while some rivets were made from solid circular wire, other rivets are hollow and probably manufactured from strip-drawn wire. We also examined two perforated antler plates, likely dated to the 12th c. and excavated from a bronzesmith's workshop in the block Trekanten in central Sigtuna. The copper and lead particles detected by SEM analysis around the plates' holes indicate that the plates were used in metalworking activities. Because the holes are cylindrical and not conical, however, the plates would not be viable tools for drawing solid metal wire. In the strip-drawing technique, on the other hand, cylindrical holes might have been used to produce hollow metal wire. The holes in the studied antler plates have the same diameter - 2.0 mm - as many comb rivet holes, possibly suggesting a standardization for large-scale production. The bronzesmith's location next to a combmakers' workshop provides further support for a production connection between the two crafts. Taken together, our results indicate that the two perforated plates may have been tools for strip-drawing copper wire, used to make comb rivets.
29.	Wärmländer, Sebastian K. T. S., et al. (författare) Landmark Typology in Applied Morphometrics Studies : What's the Point? 2019 Ingår i: Anatomical Record Advances in Integrative Anatomy and Evolutionary Biology. - : Wiley. - 1932-8486. ; 302:7, s. 1144-1153 Tidskriftsartikel (refereegranskat)abstract Landmarks are the hallmark of biological shape analysis as discrete anatomical points of correspondence. Various systems have been developed for their classification. In the most widely used system, developed by Bookstein in the 1990s, landmarks are divided into three distinct types based on their anatomical locations and biological significance. As Bookstein and others have argued that different landmark types possess different qualities, e.g., that Type 3 landmarks contain deficient information about shape variation and are less reliably measured, researchers began using landmark types as justification for selecting or avoiding particular landmarks for measurement or analysis. Here, we demonstrate considerable variation in landmark classifications among 17 studies using geometric morphometrics (GM), due to disagreement in the application of both Bookstein's landmark typology and individual landmark definitions. A review of the literature furthermore shows little correlation between landmark type and measurement reproducibility, especially when factors such as differences in measurement tools (calipers, digitizer, or computer software) and data sources (dry crania, 3D models, or 2D images) are considered. Although landmark typology is valuable when teaching biological shape analysis, we find that employing it in research design introduces confusion without providing useful information. Instead, researchers should choose landmark configurations based on their ability to test specific research hypotheses, and research papers should include justifications of landmark choices along with landmark definitions, details on landmark collection methods, and appropriate interobserver and intraobserver analyses. Hence, while the landmarks themselves are crucial for GM, we argue that their typology is of little use in applied studies. Anat Rec, 302:1144-1153, 2019.
30.	Wärmländer, Sebastian K. T. S., et al. (författare) Metal binding to the amyloid-beta peptides in the presence of biomembranes : potential mechanisms of cell toxicity 2019 Ingår i: Journal of Biological Inorganic Chemistry. - : Springer Science and Business Media LLC. - 0949-8257 .- 1432-1327. ; 24:8, s. 1189-1196 Forskningsöversikt (refereegranskat)abstract The amyloid-beta (A beta) peptides are key molecules in Alzheimer's disease (AD) pathology. They interact with cellular membranes, and can bind metal ions outside the membrane. Certain oligomeric A beta aggregates are known to induce membrane perturbations and the structure of these oligomers-and their membrane-perturbing effects-can be modulated by metal ion binding. If the bound metal ions are redox active, as e.g., Cu and Fe ions are, they will generate harmful reactive oxygen species (ROS) just outside the membrane surface. Thus, the membrane damage incurred by toxic A beta oligomers is likely aggravated when redox-active metal ions are present. The combined interactions between A beta oligomers, metal ions, and biomembranes may be responsible for at least some of the neuronal death in AD patients.
31.	Zarina, Gunita, et al. (författare) Cribra orbitalia as a potential indicator of childhood stress : Evidence from paleopathology, stable C, N, and O isotopes, and trace element concentrations in children from a 17th-18th century cemetery in Jekabpils, Latvia 2016 Ingår i: Journal of Trace Elements in Medicine and Biology. - : Elsevier BV. - 0946-672X .- 1878-3252. ; 38, s. 131-137 Tidskriftsartikel (refereegranskat)abstract Cribra orbitalia (CO), or porotic hyperostosis (PH) of the orbital roof, is one of the most common pathological conditions found in archaeological subadult skeletal remains. Reaching frequencies higher than 50% in many prehistoric samples, CO has been generally attributed to a variety of factors including malnutrition (e.g., megaloblastic anemia) and parasitism. In this study, we tested the relationship between CO, trace element concentrations, and stable isotope values (delta C-13, delta N-15, delta O-18) in subadult skeletons from a 17th to 18th century cemetery in the historic town of Jekabpils, Latvia. A total of 28 subadults were examined, seven of which (25%) showed evidence of CO. Bioarchaeological evidence indicated high mortality for children in this cemetery: half of the burials were subadults under the age of 14, while a third were under the age of four. Life expectancy at birth was estimated to have been only 21.6 years. Trace element concentrations measured by Inductively Coupled Plasma - Mass Spectrometry (ICP-MS) showed no relationship between presence or absence of CO and levels of manganese, zinc, strontium, barium, copper, cadmium, or lead in the bones (p>0.05). However, a significant correlation (p<0.05) was found between the presence of CO and decreased levels of iron. The correlations between CO and decreased levels of copper and lead approached significance (p=0.056 for both elements). Individuals with CO furthermore displayed significantly lower delta N-15 isotope values, suggesting greater consumption of lower trophic level food resources than those unaffected by CO; delta C-13 and delta O-18 values, in contrast, showed no significant differences. These results suggest that the prevalence of CO may be related to dietary deficiencies. In this case, low iron levels may also signify a diet low in other key vitamins (e.g., B-g and B-12), which are known to cause megaloblastic anemia.
32.	Österlund, Nicklas, et al. (författare) Membrane-mimetic systems for biophysical studies of the amyloid-beta peptide 2019 Ingår i: Biochimica et Biophysica Acta - Proteins and Proteomics. - : Elsevier BV. - 1570-9639 .- 1878-1454. ; 1867:5, s. 492-501 Tidskriftsartikel (refereegranskat)abstract The interplay between the amyloid-beta (A beta) peptide and cellular membranes have been proposed as an important mechanism for toxicity in Alzheimer's disease (AD). Membrane environments appear to influence A beta aggregation and may stabilize intermediate A beta oligomeric states that are considered to be neurotoxic. One important role for molecular biophysics within the field of A beta studies is to characterize the structure and dynamics of the A beta peptide in various states, as well as the kinetics of transfer between these states. Because biological cell membranes are very complex, simplified membrane models are needed to facilitate studies of A beta and other amyloid proteins in lipid environments. In this review, we examine different membrane-mimetic systems available for molecular studies of A beta. An introduction to each system is given, and examples of important findings are presented for each system. The benefits and drawbacks of each system are discussed from methodical and biological perspectives.

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