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Given the current rate of Arctic warming, the associated ecological changes need to be put into a longer-term context of natural variability. Palaeolimnology offers tools to explore archives stored in the sediments of Arctic lakes and ponds. The interpretation of these archives requires a sound knowledge of the ecology and distribution of the sedimentary proxy organisms used. Here we explored the relationship between diatoms, a widely used proxy group of siliceous algae, and the environmental drivers defining their assemblages and diversity in 115 lakes and ponds in Greenland, a markedly understudied arctic region covering extensive climate and environmental gradients. The main environmental drivers of diatom communities were related to climate and lake ontogeny, including both measured and unmeasured (spatially structured) environmental variables. The lakes and ponds in the northern study regions showed a distinctive dominance of small benthic fragilarioid species, while diatom communities in the South(west) of Greenland were more varied, including many epiphytes, owing to the longer growing season and higher habitat diversity of these lakes and ponds. The newly established lakes in the Ilulissat region host markedly different communities compared to all other sites. Species diversity followed an overall clear latitudinal decline towards the North. Despite the large distances between our study regions, diatom dispersal appeared not to be limited. Based on our results, diatoms are an excellent proxy for climate-mediated lake ecosystem change in the Arctic and thus a valuable tool for climate reconstructions in the region. Particular consideration should be given to often unmeasured climate-related drivers, such as in-lake habitat availability, due to their apparent importance in defining Arctic diatom communities.

Hebrus Valles is an outflow channel system in the plain-forming terrains of southeastern Utopia Planitia, Mars. These terrains may have formed through a combination of liquid water and volcanic processes, yet their nature, subsurface structure, and composition remain unclear. We investigate these terrains by mapping subsurface reflectors across 540 Shallow Radar (SHARAD) profiles and applying two complementary loss tangent inversion techniques. We find moderate loss tangent values across some subregions of Granicus Valles and Hyblaeus Fossae (tan δ = 0.0162 ± 0.0004 and tan δ = 0.019 ± 0.002, respectively), suggesting the presence of basaltic lava flows. We interpret non-detections in the other flows in Granicus Valles to be due to the presence of radar-lossy materials formed through aqueous processes, which supports the hypothesized occurrence of lahars in this region. A small area near Hebrus Valles exhibits subsurface reflectors with low to moderate loss tangents (tan δ = 0.010 ± 0.003), suggesting the presence of pristine lava flows or sedimentary materials capped by lava flows. We also find a widespread occurrence of very low-loss tangent materials near Hyblaeus Dorsa (tan δ = 0.0045 ± 0.0002), which may represent a lobe of the Medusae Fossae Formation or similar high-porosity materials buried underneath a lava flow. Together, these findings suggest that volcanic activity played a central role in the formation of terrains across the broader Hebrus Valles region.

The availability of remote sensing imagery at high spatiotemporal resolutions presents the opportunity to monitor the surface motion of rock glaciers, a key constraint for characterizing the dynamics of their evolution. In this paper, we investigate four North American rock glaciers by automatically measuring their horizontal surface displacement using photogrammetric data acquired with crewed and uncrewed aircraft along with orbital spacecraft over monitoring periods of up to eight years. We estimate vertical surface changes on these rock glaciers with photogrammetrically generated digital elevation models (DEM) and digitized topographic maps. Uncertainty analysis shows that the imagery with the highest resolution and most precise positioning have the best performance when used with the automated change detection algorithm. This investigation produces gridded velocity fields over the entire surface area of each study site, from which we estimate the age of rock glacier formation using along-flow velocity integration. Though the age estimates vary, the ice within the modern extent of these landforms began flowing between 3000 and 7000 years before present, postdating the last glacial maximum. Surface elevation change maps indicate present-day thinning at the lower latitude/higher elevation sites in Wyoming, while the higher latitude/lower elevation sites in Alaska exhibit relatively stable surface elevations.

Abstract Climate change and permafrost thaw are unlocking the vast storage of organic carbon held in northern frozen soils. Here, we evaluated the effects of thawing ice‐rich permafrost on dissolved organic matter (DOM) in freshwaters by optical analysis of 253 ponds across the circumpolar North. For a subset of waters in subarctic Quebec, we also quantified the contribution of terrestrial sources to the DOM pool by stable isotopes. The optical measurements showed a higher proportion of terrestrial carbon and a lower algal contribution to DOM in waters affected by thawing permafrost. DOM composition was largely dominated (mean of 93%) by terrestrial substances at sites influenced by thawing permafrost, while the terrestrial influence was much less in waterbodies located on bedrock (36%) or with tundra soils unaffected by thermokarst processes (42%) in the catchment. Our results demonstrate a strong terrestrial imprint on freshwater ecosystems in degrading ice‐rich permafrost catchments, and the likely shift toward increasing dominance of land‐derived organic carbon in waters with ongoing permafrost thaw.

Disentangling the effects of climate change on nature is one of the main challenges facing ecologists nowadays. Warmer climates forces strong effects on lake biota for fish, leading to a reduction in size, changes in diet, more frequent reproduction, and stronger cascading effects. Space-for-time substitution studies (SFTS) are often used to unravel climate effects on lakes biota; however, results from continental lakes are potentially confounded by biogeographical and evolutionary differences, also leading to an overall higher fish species richness in warm lakes. Such differences may not be found in lakes on remote islands, where natural fish free lakes have been subjected to stocking only during the past few hundred years. We studied 20 species-poor lakes located in two remote island groups with contrasting climates, but similar seasonality: the Faroe Islands (cold; 6.5 ± 2.8 °C annual average (SD) and the Azores Islands (warm; 17.3 ± 2.9 °C)). As for mainland lakes, mean body size of fish in the warmer lakes were smaller overall, and phytoplankton per unit of phosphorus higher. The δ13C carbon range for basal organisms, and for the whole food web, appeared wider in colder lakes. In contrast to previous works in continental fresh waters, Layman metrics of the fish food web were similar between the two climatic regions. Our results from insular systems provide further evidence that ambient temperatures, at least partially, drive the changes in fish size structure and the cascading effects found along latitude gradients in lakes.

An influx of terrestrial dissolved organic carbon (DOC) into freshwater habitats can regulate a range of ecosystem characteristics, from water clarity to productivity. To understand the extent to which DOC can regulate ecosystem functioning, we conducted a survey to determine the source of DOC in low Arctic ponds close to the Arctic Circle (Kangerlussuaq, Greenland), including its role in food web dynamics. We used a multiple element (carbon, nitrogen, and hydrogen) stable isotope approach to examine the proportional contribution of different sources to aquatic consumers in nine arctic ponds that spanned a broad gradient of DOC (6.6–60.1 mgL-1). Our results show that benthic and pelagic primary production decreased along a gradient of increasing DOC content. Additionally, the changes in the organic matter pool with increasing DOC translated into changes in consumer resource use. We found significant differences in resource use between species. All consumers relied on benthic autotrophic material when DOC was low; but when DOC was high some consumers changed their diet. Collectively, our findings demonstrate how the concentration of DOC influences aquatic production and our study can be used as a baseline to predict how the aquatic food web may respond to regionally changing DOC concentrations.

A recent chironomid record of three shallow, high altitude lakes in southern Tibet, as well as a short palaeolimnological history of one lake, are presented. The recent chironomid assemblages consisted of 13 taxa; one of the Orthocladiinae taxa recorded most likely represents a new species. In spite of the low head capsule concentration in the sediment core of Lake Karuugema, probably due to physical disturbance, redistribution and outwash of head capsules, there was a trend from assemblages composed of stenothermal/rheophilic taxa to eurythermal/limnophilic taxa. This shift in assemblage structure suggests that changes in monsoon precipitation and catchment hydrology may have influenced the habitat conditions of the chironomids.

Background: Early discharge and home treatment for pulmonary embolism patients results in fewer hospital complications and may reduce treatment costs. We wished to investigate whether it is as safe and effective as hospital treatment, and if so, how best to select patients for home treatment., Material and Method: We searched the databases Embase, Ovid MEDLINE, In-Process & Other Non-Indexed Citations and the Cochrane Library for clinical trials of acute, objectively verified pulmonary embolism, where outcomes for hospital treatment and home treatment were compared., Results: For a selected group of patients with acute, symptomatic pulmonary embolism, home treatment is as safe and effective as hospital treatment. PESI (Pulmonary Embolism Severity Index) and Hestia criteria have the best documented clinical utility for selection of patients for home treatment., Interpretation: The Hestia criteria represent a pragmatic approach to selection of patients who can be treated at home for pulmonary embolism, and they can be applied without taking other formal criteria into consideration.

Background: Glucose-insulin-potassium (GIK) administration during cardiac surgery inconsistently improves myocardial function, perhaps because hyperglycemia negates the beneficial effects of GIK. The hyperinsulinemic normoglycemic clamp (HNC) technique may better enhance the myocardial benefits of GIK. The authors extended previous GIK investigations by (1) targeting normoglycemia while administering a GIK infusion (HNC); (2) using improved echocardiographic measures of myocardial deformation, specifically myocardial longitudinal strain and strain rate; and (3) assessing the activation of glucose metabolic pathways., Methods: A total of 100 patients having aortic valve replacement for aortic stenosis were randomly assigned to HNC (high-dose insulin with concomitant glucose infusion titrated to normoglycemia) versus standard therapy (insulin treatment if glucose >150 mg/dl). The primary outcomes were left ventricular longitudinal strain and strain rate, assessed using speckle-tracking echocardiography. Right atrial tissue was analyzed for activation of glycolysis/pyruvate oxidation and alternative metabolic pathways., Results: Time-weighted mean glucose concentrations were lower with HNC (127 ± 19 mg/dl) than standard care (177 ± 41 mg/dl; P < 0.001). Echocardiographic data were adequate in 72 patients for strain analysis and 67 patients for strain rate analysis. HNC did not improve myocardial strain, with an HNC minus standard therapy difference of -1.2% (97.5% CI, -2.9 to 0.5%; P = 0.11). Strain rate was significantly better, but by a clinically unimportant amount: -0.16 s (-0.30 to -0.03 s; P = 0.007). There was no evidence of increased glycolytic, pyruvate oxidation, or hexosamine biosynthetic pathway activation in right atrial samples (HNC, n = 20; standard therapy, 22)., Conclusion: Administration of glucose and insulin while targeting normoglycemia during aortic valve replacement did not meaningfully improve myocardial function.

Microorganisms have always been one of the great challenges of humankind, being responsible for both high morbidity and mortality throughout history. In a forensic setting microbiological information will always be difficult to interpret due to lack of antemortem information and changes in flora postmortem. With this study we aim to review the use of microbiological procedures at our forensic institute. In a retrospective study including 42 autopsies performed at our Institute, where microbiological test had been applied, analyses were made with regard to: type of microbiological tests performed, microorganisms found, histological findings, antemortem information, C-reactive protein measurement and cause of death. Fiftyone different microorganisms were found distributed among 37 cases, bacteria being the most abundant. Nineteen of the cases were classified as having a microbiological related cause of death. C-reactive protein levels were raised in 14 cases of the 19 cases, histological findings either supported or were a decisive factor for the classification of microbiologically related cause of death in 14 cases. As a multitude of abundant microorganisms are able to cause infection under the right circumstances, all findings should be compared to anamnestic antemortem information, before conclusions are drawn. A definite list of true pathogens is nearly impossible to compile., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The adenine phosphoribosyltransferase (APRTase) encoded by the open reading frame SSO2342 of Sulfolobus solfataricus P2 was subjected to crystallographic, kinetic, and ligand binding analyses. The enzyme forms dimers in solution and in the crystals, and binds one molecule of the reactants 5-phosphoribosyl-α-1-pyrophosphate (PRPP) and adenine or the product adenosine monophosphate (AMP) or the inhibitor adenosine diphosphate (ADP) in each active site. The individual subunit adopts an overall structure that resembles a 6-oxopurine phosphoribosyltransferase (PRTase) more than known APRTases implying that APRT functionality in Crenarchaeotae has its evolutionary origin in this family of PRTases. Only the N-terminal two-thirds of the polypeptide chain folds as a traditional type I PRTase with a five-stranded β-sheet surrounded by helices. The C-terminal third adopts an unusual three-helix bundle structure that together with the nucleobase-binding loop undergoes a conformational change upon binding of adenine and phosphate resulting in a slight contraction of the active site. The inhibitor ADP binds like the product AMP with both the α- and β-phosphates occupying the 5'-phosphoribosyl binding site. The enzyme shows activity over a wide pH range, and the kinetic and ligand binding properties depend on both pH and the presence/absence of phosphate in the buffers. A slow hydrolysis of PRPP to ribose 5-phosphate and pyrophosphate, catalyzed by the enzyme, may be facilitated by elements in the C-terminal three-helix bundle part of the protein.

Purpose: To investigate in detail the earlier observed combined effect of low dose-rate β-irradiation delivered at a dose-rate of 15 mGy/h and continued intermittent hypoxia that leads to extensive cell death after approximately 3-6 weeks., Material and Methods: Continuous low dose-rate β-irradiation at a dose rate of 15, 1.5 or 0.6 mGy/h was given by incorporation of [(3)H]-labelled valine into cellular protein. The cells were cultivated in an atmosphere with 4% O2 using an INVIVO2 hypoxia glove box. Clonogenic capacity, cell-cycle distribution and cellular respiration were monitored throughout the experiments., Results: After 3-6 weeks most cells died in response to the combined treatment, giving a surviving fraction of only 1-2%. However, on continued cultivation a few cells survived and restarted proliferation as the cellular oxygen supply increased with the reduced cell number. Irradiating the T-47D cells grown in an atmosphere with 4% O2 at dose-rates 10 and 25 times lower than 15 mGy/h did not have a pronounced effect on the clonogenic capacity with surviving fractions of 60-80%., Conclusions: Treatment of T-47D cells with low dose-rate β-irradiation leads to a specific effect on intermittent hypoxic cells, inactivating more than 98% of the cells in the population. Given improved oxygen conditions, the few surviving cells can restart their proliferation.

Hypoxia is an important and common characteristic of many human tumors. It is a challenge clinically due to the correlation with poor prognosis and resistance to radiation and chemotherapy. Understanding the biochemical response to hypoxia would facilitate the development of novel therapeutics for cancer treatment. Here, we investigate alterations in gene expression in response to hypoxia by quantitative proteome analysis using stable isotope labeling with amino acids in cell culture (SILAC) in conjunction with LCMS/MS. Human HeLa cells were kept either in a hypoxic environment or under normoxic conditions. 125 proteins were found to be regulated, with maximum alteration of 18-fold. In particular, three clusters of differentially regulated proteins were identified, showing significant upregulation of glycolysis and downregulation of mitochondrial ribosomal proteins and translocases. This interaction is likely orchestrated by HIF-1. We also investigated the effect of hypoxia on the cell cycle, which shows accumulation in G1 and a prolonged S phase under these conditions. Implications. This work not only improves our understanding of the response to hypoxia, but also reveals proteins important for malignant progression, which may be targeted in future therapies.

Two open reading frames in the genome of Sulfolobus solfataricus (SSO2342 [corrected] and SSO2424) were cloned and expressed in E. coli. The protein products were purified and their enzymatic activity characterized. Although SSO2342 [corrected] was annotated as a gene (gpT-1) encoding a 6-oxopurine phosphoribosyltransferase (PRTase), the protein product turned out to be a PRTase highly specific for adenine and we suggest that the reading frame should be renamed apT. The other reading frame SSO2424 (gpT-2) proved to be a true 6-oxopurine PRTase active with hypoxanthine, xanthine and guanine as substrates, and we suggest that the gene should be renamed gpT. Both enzymes exhibited unusual profiles of activity versus pH. The adenine PRTase showed the highest activity at pH 7.5-8.5, but had a distinct peak of activity also at pH 4.5. The 6-oxo PRTase showed maximal activity with hypoxanthine and guanine around pH 4.5, while maximal activity with xanthine was observed at pH 7.5. We discuss likely reasons why SSO2342 [corrected] in S. solfataricus and similar open reading frames in other Crenarchaeota could not be identified as genes encoding APRTase.

Introduction: Strong evidence demonstrates a genetic susceptibility to suicidal behaviour and a relationship between suicide and mental disorders. The aim of this study was to test for association between suicide and five selected genetic variants, which had shown association with suicide in other populations., Method: We performed a nationwide case-control study on all suicide cases sent for autopsy in Denmark between the years 2000 and 2007. The study comprised 572 cases and 1049 controls and is one of the largest genetic studies in completed suicide to date. The analysed markers were located within the Serotonin Transporter (SLC6A4), Monoamine Oxidase-A (MAOA) and the Tryptophan Hydroxylase I and II (TPH1 and TPH2) genes., Results: None of the genetic markers within SLC6A4, MAOA, TPH1 and TPH2 were significantly associated with completed suicide or suicide method in the basic association tests. Exploratory interaction test showed that the minor allele of rs1800532 in TPH1 has a protective effect for males younger than 35 years and females older than 50 years, whereas for the oldest male subjects, it tended to be a risk factor. We also observed a significant interaction between age-group and the 5-HTTLPR genotype (with and without rs25531) in SLC6A4. The long allele or high expression allele tends to have a protective effect in the middle age-group., Limitation: We only analysed a limited number of genetic variants., Conclusion: None of the analysed variants are strong risk factors. To reveal a better understanding of the genes involved in suicide, we suggest future studies should include both genetic and non-genetic factors., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The adhesion of Plasmodium falciparum-infected erythrocytes to human tissues or endothelium is central to the pathology caused by the parasite during malaria. It contributes to the avoidance of parasite clearance by the spleen and to the specific pathologies of cerebral and placental malaria. The PfEMP1 family of adhesive proteins is responsible for this sequestration by mediating interactions with diverse human ligands. In addition, as the primary targets of acquired, protective immunity, the PfEMP1s are potential vaccine candidates. PfEMP1s contain large extracellular ectodomains made from CIDR (cysteine-rich interdomain regions) and DBL (Duffy-binding-like) domains and show extensive variation in sequence, size, and domain organization. Here we use biophysical methods to characterize the entire ∼300-kDa ectodomain from IT4VAR13, a protein that interacts with the host receptor, intercellular adhesion molecule-1 (ICAM-1). We show through small angle x-ray scattering that IT4VAR13 is rigid, elongated, and monomeric. We also show that it interacts with ICAM-1 through the DBLβ domain alone, forming a 1:1 complex. These studies provide a first low resolution structural view of a PfEMP1 ectodomain in complex with its ligand. They show that it combines a modular domain arrangement consisting of individual ligand binding domains, with a defined higher order architecture that exposes the ICAM-1 binding surface to allow adhesion.

Malaria is a major global health problem. Pregnant women are susceptible to infection regardless of previously acquired immunity. Placental malaria is caused by parasites capable of sequestering in the placenta. This is mediated by VAR2CSA, a parasite antigen that interacts with chondroitin sulfate A (CSA). One vaccine strategy is to block this interaction with VAR2CSA-specific antibodies. It is a priority to define a small VAR2CSA fragment that can be used in an adhesion blocking vaccine. In this, the obvious approach is to define regions of VAR2CSA involved in receptor binding. It has been shown that full-length recombinant VAR2CSA binds specifically to CSA with nanomolar affinity, and that the CSA-binding site lies in the N-terminal part of the protein. In this study we define the minimal binding region by truncating VAR2CSA and analyzing CSA binding using biosensor technology. We show that the core CSA-binding site lies within the DBL2X domain and parts of the flanking interdomain regions. This is in contrast to the idea that single domains do not possess the structural requirements for specific CSA binding. Small-angle x-ray scattering measurements enabled modeling of VAR2CSA and showed that the CSA-binding DBL2X domain is situated in the center of the structure. Mutating classic sulfate-binding sites in VAR2CSA, along with testing dependence of ionic interactions, suggest that the CSA binding is not solely dependent on the sulfated CSA structure. Based on these novel PfEMP1 structure-function studies, we have constructed a small VAR2CSA antigen that has the capacity to induce highly adhesion-blocking antibodies.

Background: Tumour cells are characterized by aerobic glycolysis, which provides biomass for tumour proliferation and leads to extracellular acidification through efflux of lactate via monocarboxylate transporters (MCTs). Deficient and spasm-prone tumour vasculature causes variable hypoxia, which favours tumour cell survival and metastases. Brain metastases frequently occur in patients with advanced breast cancer.Effective treatment strategies are therefore needed against brain metastasis from breast carcinoma., Material and Methods: In order to identify differences in the capacity for lactate exchange, human T-47D breast cancer cells and human glioblastoma T98G cells were grown under 4 % or 20 % oxygen conditions and examined for MCT1, MCT2 and MCT4 expression on plasma membranes by quantitative post embedding immunogold electron microscopy. Whereas previous studies on MCT expression in tumours have recorded mRNA and protein levels in cell extracts, we examined concentrations of the proteins in the microvillous plasma membrane protrusions specialized for transmembrane transport., Results: In normoxia, both tumour cell types highly expressed the low affinity transporter MCT4, which is thought to mainly mediate monocarboxylate efflux, while for high affinity transport the breast tumour cells preferentially expressed MCT1 and the brain tumour cells resembled brain neurons in expressing MCT2, rather than MCT1. The expressions of MCT1 and MCT4 were upregulated in hypoxic conditions in both breast and brain tumour cells. The expression of MCT2 also increased in hypoxic breast cancer cells, but decreased in hypoxic brain tumour cells. Quantitative immunoblots showed similar hypoxia induced changes in the protein levels., Conclusion: The differential expression and regulation of MCTs in the surface membranes of hypoxic and normoxic tumour cells of different types provide a foundation for innovation in tumour therapy through the selective targeting of MCTs. Selective inhibition of various MCTs could be an efficient way to quench an important energy source in both original breast tumour and metastatic cancer tissue in the brain.

In the routine clinical examination of sexual assault victims, apart from documenting physical evidence of abuse, securing evidence, typically DNA from blood, semen, or saliva, is an important part of the process. Often the presence of semen is considered a most interesting piece of evidence. Not only does it often contain enough DNA for DNA profiling, but it also strongly indicates that an actual sexual act has taken place. The examination of smear slides obtained in sexual assault cases is a time-consuming task especially for the less trained and in cases where the smear only contains few sperm cells. In this work the goal was to develop a procedure to rapidly visualize human sperm cells in smear slides with the use of bright-field microscopy. Using SPERM HY-LITER™ by Independent Forensics, human sperm cells are visualized using a fluorescently labeled mouse antibody which significantly decreases the time used to screen smears. By further using an EnVision+ (DAKO) protocol, it was possible to create an immunohistochemical staining method to visualize sperm cells in bright-field microscopy with the same level of certainty as when using SPERM HY-LITER™.

Uridine phosphorylase (UP), a key enzyme in the pyrimidine salvage pathway, catalyzes the reversible phosphorolysis of uridine or 2'-deoxyuridine to uracil and ribose 1-phosphate or 2'-deoxyribose 1-phosphate. This enzyme belongs to the nucleoside phosphorylase I superfamily whose members show diverse specificity for nucleoside substrates. Phylogenetic analysis shows Streptococcus pyogenes uridine phosphorylase (SpUP) is found in a distinct branch of the pyrimidine subfamily of nucleoside phosphorylases. To further characterize SpUP, we determined the crystal structure in complex with the products, ribose 1-phosphate and uracil, at 1.8 Å resolution. Like Escherichia coli UP (EcUP), the biological unit of SpUP is a hexamer with an α/β monomeric fold. A novel feature of the active site is the presence of His169, which structurally aligns with Arg168 of the EcUP structure. A second active site residue, Lys162, is not present in previously determined UP structures and interacts with O2 of uracil. Biochemical studies of wild-type SpUP showed that its substrate specificity is similar to that of EcUP, while EcUP is ∼7-fold more efficient than SpUP. Biochemical studies of SpUP mutants showed that mutations of His169 reduced activity, while mutation of Lys162 abolished all activity, suggesting that the negative charge in the transition state resides mostly on uracil O2. This is in contrast to EcUP for which transition state stabilization occurs mostly at O4.

Four Clostridium perfringens phosphorylases were subcloned, overexpressed and analyzed for their substrate specificity. DeoD(1) and PunA could use a variety of purine substrates, including an antiviral drug 2',3'-dideoxyinosine (ddI). In one-pot synthesis using Clostridium phosphorylases, 2',3'-dideoxyuridine and hypoxanthine were converted to ddI at yield of about 30%.

In patients with cirrhosis of the liver, ascites is a common symptom, some of these patients will also present hydrothorax. Under rare circumstances patients with liver cirrhosis develop hydrothorax without showing any signs of ascites. This study presents one such case and shows autopsy findings consistent with hepatic hydrothorax without ascites. Furthermore, we present CT imaging which shows the possible cause of death in the case of severe hydrothorax.

Uracil phosphoribosyltransferase catalyzes the conversion of 5-phosphoribosyl-alpha-1-diphosphate (PRPP) and uracil to uridine monophosphate (UMP) and diphosphate (PP(i)). The tetrameric enzyme from Sulfolobus solfataricus has a unique type of allosteric regulation by cytidine triphosphate (CTP) and guanosine triphosphate (GTP). Here we report two structures of the activated state in complex with GTP. One structure (refined at 2.8-A resolution) contains PRPP in all active sites, while the other structure (refined at 2.9-A resolution) has PRPP in two sites and the hydrolysis products, ribose-5-phosphate and PP(i), in the other sites. Combined with three existing structures of uracil phosphoribosyltransferase in complex with UMP and the allosteric inhibitor cytidine triphosphate (CTP), these structures provide valuable insight into the mechanism of allosteric transition from inhibited to active enzyme. The regulatory triphosphates bind at a site in the center of the tetramer in a different manner and change the quaternary arrangement. Both effectors contact Pro94 at the beginning of a long beta-strand in the dimer interface, which extends into a flexible loop over the active site. In the GTP-bound state, two flexible loop residues, Tyr123 and Lys125, bind the PP(i) moiety of PRPP in the neighboring subunit and contribute to catalysis, while in the inhibited state, they contribute to the configuration of the active site for UMP rather than PRPP binding. The C-terminal Gly216 participates in a hydrogen-bond network in the dimer interface that stabilizes the inhibited, but not the activated, state. Tagging the C-terminus with additional amino acids generates an endogenously activated enzyme that binds GTP without effects on activity.

Introduction: Computerized tomography (CT) is finding increased use in forensic medicine. In this article we present our experience with CT in medico legal deaths., Materials and Methods: This is a retrospective investigation of 150 deceased individuals who were CT-scanned and autopsied. The CT-scanning was performed and interpreted by a specialist in forensic medicine. The CT-scanning and the autopsy were performed independently by two different physicians., Results: In 9% of the cases, important findings by the CT-scanning were overlooked at the autopsy, and in 51% important findings by the autopsy were not found by the CT-scanning. The cause of death could be established by CT-scanning in 30%, by autopsy in 72% and by toxicology in 21% of the cases. CT-scanning was most useful in cases of traumatic death., Conclusion: CT is rarely a substitute for autopsy, but may contribute with important new information in many cases such as identifications (including mass-disasters), gunshot wounds and traffic accidents. CT provides documentation in digital form that is easily stored and copied, permits review by others and provides pictures that may be more suitable for presentation in court than autopsy photos. CT may be helpful in medico legal external examinations (inquests) in the process of selecting cases for autopsy.

Unlabelled: In a forensic setting, deaths due to seizures, either epileptic or other, present a well-known problem. Cause of death is rarely established on the basis of physical evidence, but on circumstantial evidence such as tongue biting or discharge of urine or faeces. Seizures have several different aetiologies, but in police reports a person known to have seizures is most likely to be reported as suffering from epilepsy. It is a well-known fact that alcoholics have seizures either due to "alcohol-induced epilepsy" or due to withdrawal from drinking. It also seems to be generally accepted that alcoholics may die from these seizures. A literature study was performed of deaths due to alcohol-induced seizures, either during withdrawal or as late-onset seizures where the aetiology was established as long time alcohol abuse and a necropsy had shown no other possible cause of death than a seizure., Results: It was not possible to find any well-documented cases. It is, however, difficult to compare cases in the literature, as there is no generally accepted classification or nomenclature of seizures related to alcohol abuse.

Hydroa vacciniforme is a very rare photodermatosis, commencing in childhood and belonging to the category of idiopathic burns. The inconstancy of the therapeutic results raises the possibility of a clinical syndrome that can have different origins. We present a case that responded very well to carotenoids.