Integrating isotopes and documentary evidence : dietary patterns in a late medieval and early modern mining community, Sweden

We would like to thank the Archaeological Research Laboratory, Stockholm University, Sweden and the Tandem Laboratory (Ångström Laboratory), Uppsala University, Sweden, for undertaking the analyses of stable nitrogen and carbon isotopes in both human and animal collagen samples. Also, thanks to Elin Ahlin Sundman for providing the δ13C and δ15N values for animal references from Västerås. This research (Bäckström’s PhD employment at Lund University, Sweden) was supported by the Berit Wallenberg Foundation (BWS 2010.0176) and Jakob and Johan Söderberg’s foundation. The ‘Sala project’ (excavations and analyses) has been funded by Riksens Clenodium, Jernkontoret, Birgit and Gad Rausing’s Foundation, SAU’s Research Foundation, the Royal Physiographic Society of Lund, Berit Wallenbergs Foundation, Åke Wibergs Foundation, Lars Hiertas Memory, Helge Ax:son Johnson’s Foundation and The Royal Swedish Academy of Sciences.Peer reviewedPublisher PD

Activation of Latent HIV Using Drug-Loaded Nanoparticles

Antiretroviral therapy is currently only capable of controlling HIV replication rather than completely eradicating virus from patients. This is due in part to the establishment of a latent virus reservoir in resting CD4+ T cells, which persists even in the presence of HAART. It is thought that forced activation of latently infected cells could induce virus production, allowing targeting of the cell by the immune response. A variety of molecules are able to stimulate HIV from latency. However no tested purging strategy has proven capable of eliminating the infection completely or preventing viral rebound if therapy is stopped. Hence novel latency activation approaches are required. Nanoparticles can offer several advantages over more traditional drug delivery methods, including improved drug solubility, stability, and the ability to simultaneously target multiple different molecules to particular cell or tissue types. Here we describe the development of a novel lipid nanoparticle with the protein kinase C activator bryostatin-2 incorporated (LNP-Bry). These particles can target and activate primary human CD4+ T-cells and stimulate latent virus production from human T-cell lines in vitro and from latently infected cells in a humanized mouse model ex vivo. This activation was synergistically enhanced by the HDAC inhibitor sodium butyrate. Furthermore, LNP-Bry can also be loaded with the protease inhibitor nelfinavir (LNP-Bry-Nel), producing a particle capable of both activating latent virus and inhibiting viral spread. Taken together these data demonstrate the ability of nanotechnological approaches to provide improved methods for activating latent HIV and provide key proof-of-principle experiments showing how novel delivery systems may enhance future HIV therapy

De novo activating mutations drive clonal evolution and enhance clonal fitness in KMT2A-rearranged leukemia

Activating signaling mutations are common in acute leukemia with KMT2A (previously MLL) rearrangements (KMT2A-R). These mutations are often subclonal and their biological impact remains unclear. Using a retroviral acute myeloid mouse leukemia model, we demonstrate that FLT3 ITD, FLT3 N676K, and NRAS G12D accelerate KMT2A-MLLT3 leukemia onset. Further, also subclonal FLT3 N676K mutations accelerate disease, possibly by providing stimulatory factors. Herein, we show that one such factor, MIF, promotes survival of mouse KMT2A-MLLT3 leukemia initiating cells. We identify acquired de novo mutations in Braf, Cbl, Kras, and Ptpn11 in KMT2A-MLLT3 leukemia cells that favored clonal expansion. During clonal evolution, we observe serial genetic changes at the Kras G12D locus, consistent with a strong selective advantage of additional Kras G12D . KMT2A-MLLT3 leukemias with signaling mutations enforce Myc and Myb transcriptional modules. Our results provide new insight into the biology of KMT2A-R leukemia with subclonal signaling mutations and highlight the importance of activated signaling as a contributing driver

Decrease in prevalence of Helicobacter pylori infection during a 10-year period in Brazilian children Diminuição na prevalência da infecção por Helicobacter pylori em crianças brasileiras num período de 10 anos

BACKGROUND: Decreasing prevalence of H pylori infection has been reported in some countries. AIM: To evaluate the prevalence of Helicobacter pylori infection in a 10-year period in children submitted to upper digestive endoscopy. METHODS: It was a retrospective observational study. The records of 1,165 endoscopies performed during a 10-year period in a public hospital of the City of São Paulo, SP, Brazil, in patients up to 18-year-old. Only the first endoscopy was considered. Helicobacter pylori infection was defined by the rapid urease test, performed with one fragment of antral mucosa. Chi-square for trend has been estimated to compare Helicobacter pylori prevalence across the period. RESULTS: The main indication for endoscopy was epigastric pain (47.4%). There were 392 patients with H pylori infection (33.6%), 12.8% being infants, 19.4% toddlers, 28.8% schoolchildren and 46.3% adolescents. Prevalence was 60.47% in the first year of the study and 30.43% in the last. Among the less than 6-year-old patients there was a decrease in infection prevalence from 25% for the 1993-6 period to 14.3% in the 2000-02 period, while among the over 12-year-old patients the decrease was from 55.5% in the first period to 39.6% in the latter. The decrease in H pylori infection prevalence was more intense within patients with epigastric pain, in which prevalence has decreased from 48.2% (92/191) in 1993-6, to 41.9% (65/155) in 1997-9 and 27.7% (57/206) in 2000-02. CONCLUSION: The study suggests a significant decrease in the prevalence of H pylori infection regarding the studied patients. The trend was mainly observed in the younger age group and in patients with epigastric pain.<br>RACIONAL: Redução da prevalência de infecção por Helicobacter pylori tem sido relatada em alguns países. OBJETIVO: Avaliar, em crianças, a prevalência de infecção por H pylori em um período de 10 anos, realizando endoscopia digestiva alta. MÉTODOS: Estudo retrospectivo observacional. Os relatórios de 1.165 endoscopias digestivas altas realizadas em 10 anos em um hospital público da cidade de São Paulo, SP, foram revisados, sendo incluídas as primeiras endoscopias de pacientes com idade inferior a 18 anos. A infecção por H pylori foi definida pelo teste rápido da urease, com um fragmento de mucosa antral. RESULTADOS: A principal indicação de endoscopia foi dor epigástrica (47,4%). A prevalência de infecção foi 33,6% (12,8% em lactentes, 19,4% em pré-escolares, 28,8% em escolares e 46,3% em adolescentes). No primeiro ano de estudo foi 60,47%, e 30,43% no último. Entre os pacientes menores de 6 anos, houve diminuição na prevalência de 25% (1993-6) para 14.3% (2000-02), enquanto entre os pacientes maiores de 12 anos a diminuição foi de 55,5% (1993-6) para 39,6% (2000-02). A diminuição da prevalência foi significativa nos pacientes com dor epigástrica, nos quais passou de 48,2% (92/191) em 1993-6, para 41,9% (65/155) em 1997-9 e 27,7% (57/206) em 2000-02. CONCLUSÃO: O estudo sugere que houve diminuição significativa na prevalência da infecção por H pylori nos pacientes estudados. A tendência foi principalmente observada no grupo etário mais jovem e nos pacientes com dor epigástrica

Thermal stability and structural changes in bacterial toxins responsible for food poisoning.

The staphylococcal enterotoxins (SEs) are secreted by the bacteria Staphylococcus aureus and are the most common causative agent in staphylococcal food poisoning. The staphylococcal enterotoxin A (SEA) has been associated with large staphylococcal food poisoning outbreaks, but newer identified SEs, like staphylococcal enterotoxin H (SEH) has recently been shown to be present at similar levels as SEA in food poisoning outbreaks. Thus, we set out to investigate the thermo-stability of the three-dimensional structures of SEA, SEH and staphylococcal enterotoxin E (SEE), since heat inactivation is a common method to inactivate toxins during food processing. Interestingly, the investigated toxins behaved distinctly different upon heating. SEA and SEE were more stable at slightly acidic pH values, while SEH adopted an extremely stable structure at neutral pH, with almost no effects on secondary structural elements upon heating to 95°C, and with reversible formation of tertiary structure upon subsequent cooling to room temperature. Taken together, the data suggests that the family of staphylococcal enterotoxins have different ability to withstand heat, and thus the exact profile of heat inactivation for all SEs causing food poisoning needs to be considered to improve food safety

Ambiguous pots:Everyday practice, migration and materiality.The case of medieval Baltic ware on the island of Bornholm (Denmark)

Archaeologists routinely deal with the remains of everyday life. Yet the significance and dimensions of daily practices are rarely reflected upon. Merging Bourdieu’s theory of practice, recent theories of everyday life and the materiality approach in archaeology, this study addresses the potential importance of daily practices and mundane objects in dealing with a rupture caused by migration. As a case study I use an example of medieval (eleventh century) Western Slavic migration to the island of Bornholm (Denmark) and production and daily handling of ceramic pots, the so-called Baltic ware. I explore the possible background to the introduction of the new pottery style, its significance for the local population of the island and above all the meanings these types of ceramics could have had for the immigrant Slavs