Long-Term Increase in Aboveground Carbon Stocks Following Exclusion of Grazers and Forest Establishment in an Alpine Ecosystem

Ecosystem stores of carbon are a key component in the global carbon cycle. Many studies have examined the impact of climate change on ecosystem carbon storage, but few have investigated the impact of land-use change and herbivory. However, land-use change is a major aspect of environmental change, and livestock grazing is the most extensive land use globally. In this study, we combine a grazing exclosure experiment and a natural experiment to test the impact of grazer exclusion on vegetation dynamics and ecosystem carbon stores in the short term (12-year exclosures), and the long term (islands inaccessible to livestock), in a heavily grazed mountain region in Norway. Following long-term absence of sheep, birch forest was present. The grazing-resistant grass Nardus stricta, dominated under long-term grazing, whilst the selected grass Deschampsia flexuosa and herb species dominated the vegetation layer in the long-term absence of sheep. The established birch forest led to vegetation carbon stocks being higher on the islands (0.56 kg C m^?2 on the islands compared to 0.18 kg C m^?2 where grazed) and no difference in soil carbon stocks. In the short-term exclusion of sheep, there were minor differences in carbon stocks reflecting the longer term changes. These results show that aboveground carbon stocks are higher in the long-term absence of sheep than in the continual presence of high sheep densities, associated with a vegetation state change between tundra and forest. The reduction of herbivore populations can facilitate forest establishment and increase aboveground carbon stocks, however, the sequestration rate is low.     

Antibiotic Treatment Regimes as a Driver of the Global Population Dynamics of a Major Gonorrhea Lineage

The Neisseria gonorrhoeae multilocus sequence type (ST) 1901 is among the lineages most commonly associated with treatment failure. Here, we analyze a global collection of ST-1901 genomes to shed light on the emergence and spread of alleles associated with reduced susceptibility to extended-spectrum cephalosporins (ESCs).The genetic diversity of ST-1901 falls into a minor and a major clade, both of which were inferred to have originated in East Asia. The dispersal of the major clade from Asia happened in two separate waves expanding from ∼1987 and 1996, respectively. Both waves first reached North America, and from there spread to Europe and Oceania, with multiple secondary reintroductions to Asia.The ancestor of the second wave acquired the penA 34.001 allele, which significantly reduces susceptibility to ESCs. Our results suggest that the acquisition of this allele granted the second wave a fitness advantage at a time when ESCs became the key drug class used to treat gonorrhea. Following its establishment globally, the lineage has served as a reservoir for the repeated emergence of clones fully resistant to the ESC ceftriaxone, an essential drug for effective treatment of gonorrhea.We infer that the effective population sizes of both clades went into decline as treatment schemes shifted from fluoroquinolones via ESC monotherapy to dual therapy with ceftriaxone and azithromycin in Europe and the United States. Despite the inferred recent population size decline, the short evolutionary path from the penA 34.001 allele to alleles providing full ceftriaxone resistance is a cause of concern.     

Pneumococcal CbpD is a murein hydrolase that requires a dual cell envelope binding specificity to kill target cells during fratricide

Pneumococci that are competent for natural genetic transformation express a number of proteins involved in binding, uptake, translocation and recombination of DNA. In addition, they attack and lyse non‐competent sister cells present in the same environment. This phenomenon has been termed fratricide. The key effector of pneumococcal fratricide is CbpD, a secreted protein encompassing an N‐terminal CHAP domain, two SH3b domains and a C‐terminal choline‐binding domain (CBD). CbpD is believed to degrade the cell wall of target cells, but experimental evidence supporting this hypothesis has been lacking. Here, we show that CbpD indeed has muralytic activity, and that this activity requires functional CBD and SH3b domains. To better understand the critical role played by the non‐catalytic C‐terminal region of CbpD, various translational fusions were constructed between the CBD and SH3b domains and green fluorescent protein (GFP). The results showed that the SH3b domains specifically recognize and bind peptidoglycan, while the CBD domain functions as a localization signal that directs CbpD to the septal region of the pneumococcal cell. Intriguingly, transmission electron microscopy analysis revealed that target cells attacked by CbpD ruptures at the septal region, in accordance with the binding specificity displayed by the CBD domain.     

Semi mature blood dendritic cells exist in patients with ductal pancreatic adenocarcinoma owing to inflammatory factors released from the tumor

Background

Much evidence exists regarding the fact that blood DCs, both myeloid DCs (MDCs) and plasmacytoid DCs (PDCs), are negatively affected in different types of cancer, with both reduced numbers and impaired functionality. Functional impairment of DCs in patients with pancreatic ductal adenocarcinoma (PDAC), may contribute to the poor clinical outcome. The aim of this study was to examine the effects PDAC had on blood DCs and elucidate the underlying mechanism responsible for the DC impairment.

Methodology/Principal Findings

We examined the systemic influence PDAC exerted on blood DCs by ex vivo measuring numerous activation and maturation markers expressed on these cells. Furthermore, the effect patient plasma and the inflammatory factors CXCL8 and PGE₂ had on purified MDCs and PDCs from healthy donors was assessed and compared to the DCs existing in PDAC patients. We found a partial maturation of the blood MDCs and PDCs in PDAC patients with significantly enhanced expression of CD83, CD40, B7H3, PDL-1, CCR6, and CCR7 and decreased expression of ICOSL, and DCIR. These changes lead to impairment in their immunostimulatory function. Furthermore, chronic pancreatitis gave rise to DCs with similar semi-mature phenotype as seen in PDAC. Low expression of ICOSL was associated with poor prognosis. We found that the mechanism underlying this semi-maturation of DCs was inflammatory factors existing in the PDAC patients'' plasma. Of note, PGE₂, which is elevated PDAC patient plasma, was one contributing factor to the changes seen in MDCs and PDCs phenotype.

Conclusion/Significance

Our findings point to a role for the systemic inflammation in transforming blood MDCs and PDCs into semi-mature cells in PDAC patients and we show a correlation between maturation status and clinical outcome. Thus, means to preserve a functional blood DC compartment in PDAC patients by diminishing the inflammation could facilitate their ability to control the disease and improve survival.     

A first insight into the genetic diversity of Mycobacterium tuberculosis in Dar es Salaam, Tanzania, assessed by spoligotyping

Background  

Tanzania has a high tuberculosis incidence, and genotyping studies of Mycobacterium tuberculosis in the country are necessary in order to improve our understanding of the epidemic. Spoligotyping is a potentially powerful genotyping method due to fast generation of genotyping results, high reproducibility and low operation costs. The recently constructed SpolDB4 database and the model-based program 'spotclust' can be used to assign isolates to families, subfamilies and variants. The results of a study can thus be analyzed in a global context.     

Effects of triple treatment with octreotide, galanin and serotonin on a human pancreas cancer cell line in xenografts

Human pancreas cancer cells were implanted s.c. in nude mice. After 11 days, the mice were divided into two groups of 13. The first group received sterile saline solution and the second received triple therapy containing octreotide, galanin and serotonin, 40 microg/kg/day as a continuous i.p. infusion via an implanted osmotic pump for 14 days. Triple therapy prolonged the survival rate of the mice bearing human pancreatic carcinoma. Both the volume and weight of tumours in mice given triple therapy were less than in controls (not statistically significant). The proliferation index and the labelling index for epidermal growth factor (EGF) increased significantly in mice given triple therapy vis-a-vis controls. There was no statistically significant difference between control and treated tumours as regards, apoptotic index, necrosis, or number of tumour blood vessels. The increased survival rate was attributed to the reduced tumour load, since both weight and volume were reduced. It is most probable that octreotide was the responsible agent. Further investigation with single and double combinations of octreotide, galanin and serotonin are needed to identify the cause of increased cell proliferation in tumours subjected to these bioactive substances. Identifying the agent(s) inducing pancreatic cancer cell proliferation may be useful in combining a new treatment, as antagonists to these bioactive substances are available.     

Maintenance of Chronic Fatigue Syndrome (CFS) in Young CFS Patients Is Associated with the 5-HTTLPR and SNP rs25531 A > G Genotype

Earlier studies have shown that genetic variability in the SLC6A4 gene encoding the serotonin transporter (5-HTT) may be important for the re-uptake of serotonin (5-HT) in the central nervous system. In the present study we investigated how the 5-HTT genotype i.e. the short (S) versus long (L) 5-HTTLPR allele and the SNP rs25531 A > G affect the physical and psychosocial functioning in patients with chronic fatigue syndrome (CFS). All 120 patients were recruited from The Department of Paediatrics at Oslo University Hospital, Norway, a national referral center for young CFS patients (12–18 years). Main outcomes were number of steps per day obtained by an accelerometer and disability scored by the Functional Disability Inventory (FDI). Patients with the 5-HTT SS or SL_G genotype had a significantly lower number of steps per day than patients with the 5-HTT L_AL_G, SL_A or L_AL_A genotype. Patients with the 5-HTT SS or SL_G genotype also had a significantly higher FDI score than patients with the 5-HTT L_AL_G, SL_A or L_AL_A genotype. Thus, CFS patients with the 5-HTT SS or SL_G genotype had worse 30 weeks outcome than CFS patients with the 5-HTT L_AL_G, SL_A or L_AL_A genotype. The present study suggests that the 5-HTT genotype may be a factor that contributes to maintenance of CFS.     

Complement opsonization of HIV-1 enhances the uptake by dendritic cells and involves the endocytic lectin and integrin receptor families

Interaction with the complement system is an underappreciated aspect of HIV-1 infection; even in primary infection, complement fragments are found on virions with potential to affect the interplay between the virus and dendritic cells (DC). Since opsonization may affect the efficiency of uptake and the type of receptors utilized, we compared the interactions of DC with free HIV-1 (F-HIV) and complement opsonized HIV-1 (C-HIV). We demonstrate that C-HIV significantly enhanced the uptake by immature DC (IDC) and mature DC (MDC) and that the internalization rate was dependent on both opsonization of the virus and DC maturation state. Increased DC uptake of C-HIV was not due to opsonization related increased binding of virus to the surface of DC but rather increased internalization of C-HIV despite utilizing a similar repertoire of receptors as F-HIV. Both F-HIV and C-HIV interacted with C-type lectins, integrins, and CD4 and blocking these receptor families prevented HIV-1 from binding to DC at 4°C. Blocking integrins significantly reduced the binding and uptake of F-HIV and C-HIV implicating the involvement of several integrins such as β1-integrin, CR3, LFA-1, and α4β7. Distinctive for C-HIV was usage of β1-integrin and for F-HIV, usage of β7-integrin, whereas both F-HIV and C-HIV utilized both integrin chains of CR3. We have in this study identified the receptor types used by both F-HIV and C-HIV to bind to DC. Noteworthy, C-HIV was internalized more efficiently by DC than F-HIV, probably via receptor mediated endocytosis, which may entail different intracellular processing of the virus leading to both elevated infection and altered activation of HIV specific immune responses.