Recovering wetland biogeomorphic feedbacks to restore the world's biotic carbon hotspots

Biogeomorphic wetlands cover 1% of Earth's surface but store 20% of ecosystem organic carbon. This disproportional share is fueled by high carbon sequestration rates and effective storage in peatlands, mangroves, salt marshes, and seagrass meadows, which greatly exceed those of oceanic and forest ecosystems. Here, we review how feedbacks between geomorphology and landscape-building vegetation underlie these qualities and how feedback disruption can switch wetlands from carbon sinks into sources. Currently, human activities are driving rapid declines in the area of major carbon-storing wetlands (1% annually). Our findings highlight the urgency to stop through conservation ongoing losses and to reestablish landscape-forming feedbacks through restoration innovations that recover the role of biogeomorphic wetlands as the world's biotic carbon hotspots

Cytokine Gene Polymorphisms and the Outcome of Invasive Candidiasis: A Prospective Cohort Study

Background. Candida bloodstream infections cause significant morbidity and mortality among hospitalized patients. Although clinical and microbiological factors affecting prognosis have been identified, the impact of genetic variation in the innate immune responses mediated by cytokines on outcomes of infection remains to be studied. Methods. A cohort of 338 candidemia patients and 351 noninfected controls were genotyped for singlenucleotide polymorphisms (SNPs) in 6 cytokine genes (IFNG, IL10, IL12B, IL18, IL1b, IL8) and 1 cytokine receptor gene (IL12RB1). The association of SNPs with both candidemia susceptibility and outcome were assessed. Concentrations of pro-and antiinflammatory cytokines were measured in in vitro peripheral blood mononuclear cell stimulation assays and in serum from infected patients. Results. None of the cytokine SNPs studied were associated with susceptibility to candidemia. Persistent fungemia occurred in 13% of cases. In the multivariable model, persistent candidemia was significantly associated with (odds ratio [95% confidence interval]): total parenteral nutrition (2.79 [1. 26-6.17 .0]). In vitro production capacity of interleukin-10 and interferon-c was influenced by these polymorphisms, and significantly lower proinflammatory cytokine concentrations were measured in serum from patients with persistent fungemia. Conclusions. Polymorphisms in IL10 and IL12B that result in low production of proinflammatory cytokines are associated with persistent fungemia in candidemia patients. This provides insights for future targeted management strategies for patients with Candida bloodstream infections

Biomaterial bridges enable regeneration and re-entry of corticospinal tract axons into the caudal spinal cord after SCI: Association with recovery of forelimb function

Severed axon tracts fail to exhibit robust or spontaneous regeneration after spinal cord injury (SCI). Regeneration failure reflects a combination of factors, including the growth state of neuronal cell bodies and the regeneration-inhibitory environment of the central nervous system. However, while spared circuitry can be retrained, target reinnervation depends on longitudinally directed regeneration of transected axons. This study describes a biodegradable implant using poly(lactideco-glycolide) (PLG) bridges as a carrier scaffold to support regeneration after injury. In order to detect regeneration of descending neuronal tracts into the bridge, and beyond into intact caudal parenchyma, we developed a mouse cervical implantation model and employed Crym:GFP transgenic mice. Characterization of Crym:GFP mice revealed that descending tracts, including the corticospinal tract, were labeled by green fluorescent protein (GFP), while ascending sensory neurons and fibers were not. Robust co-localization between GFP and neurofilament-200 (NF-200) as well as GFP and GAP-43 was observed at both the rostral and caudal bridge/tissue interface. No evidence of similar regeneration was observed in mice that received gelfoam at the lesion site as controls. Minimal co-localization between GFP reporter labeling and macrophage markers was observed. Taken together, these data suggest that axons originating from descending fiber tracts regenerated, entered into the PLG bridge at the rostral margin, continued through the bridge site, and exited to re-enter host tissue at the caudal edge of the intact bridge. Finally, regeneration through implanted bridges was associated with a reduction in ipsilateral forelimb errors on a horizontal ladder task

Detection of Tuberculosis in HIV-Infected and -Uninfected African Adults Using Whole Blood RNA Expression Signatures: A Case-Control Study

BACKGROUND: A major impediment to tuberculosis control in Africa is the difficulty in diagnosing active tuberculosis (TB), particularly in the context of HIV infection. We hypothesized that a unique host blood RNA transcriptional signature would distinguish TB from other diseases (OD) in HIV-infected and -uninfected patients, and that this could be the basis of a simple diagnostic test. METHODS AND FINDINGS: Adult case-control cohorts were established in South Africa and Malawi of HIV-infected or -uninfected individuals consisting of 584 patients with either TB (confirmed by culture of Mycobacterium tuberculosis [M.TB] from sputum or tissue sample in a patient under investigation for TB), OD (i.e., TB was considered in the differential diagnosis but then excluded), or healthy individuals with latent TB infection (LTBI). Individuals were randomized into training (80%) and test (20%) cohorts. Blood transcriptional profiles were assessed and minimal sets of significantly differentially expressed transcripts distinguishing TB from LTBI and OD were identified in the training cohort. A 27 transcript signature distinguished TB from LTBI and a 44 transcript signature distinguished TB from OD. To evaluate our signatures, we used a novel computational method to calculate a disease risk score (DRS) for each patient. The classification based on this score was first evaluated in the test cohort, and then validated in an independent publically available dataset (GSE19491). In our test cohort, the DRS classified TB from LTBI (sensitivity 95%, 95% CI [87-100]; specificity 90%, 95% CI [80-97]) and TB from OD (sensitivity 93%, 95% CI [83-100]; specificity 88%, 95% CI [74-97]). In the independent validation cohort, TB patients were distinguished both from LTBI individuals (sensitivity 95%, 95% CI [85-100]; specificity 94%, 95% CI [84-100]) and OD patients (sensitivity 100%, 95% CI [100-100]; specificity 96%, 95% CI [93-100]). Limitations of our study include the use of only culture confirmed TB patients, and the potential that TB may have been misdiagnosed in a small proportion of OD patients despite the extensive clinical investigation used to assign each patient to their diagnostic group. CONCLUSIONS: In our study, blood transcriptional signatures distinguished TB from other conditions prevalent in HIV-infected and -uninfected African adults. Our DRS, based on these signatures, could be developed as a test for TB suitable for use in HIV endemic countries. Further evaluation of the performance of the signatures and DRS in prospective populations of patients with symptoms consistent with TB will be needed to define their clinical value under operational conditions. Please see later in the article for the Editors' Summary

Recovering wetland biogeomorphic feedbacks to restore the world’s biotic carbon hotspots

Biogeomorphic wetlands cover 1% of Earth’s surface but store 20% of ecosystem organic carbon. This disproportional share is fueled by high carbon sequestration rates and effective storage in peatlands, mangroves, salt marshes, and seagrass meadows, which greatly exceed those of oceanic and forest ecosystems. Here, we review how feedbacks between geomorphology and landscape-building vegetation underlie these qualities and how feedback disruption can switch wetlands from carbon sinks into sources. Currently, human activities are driving rapid declines in the area of major carbon-storing wetlands (1% annually). Our findings highlight the urgency to stop through conservation ongoing losses and to reestablish landscape-forming feedbacks through restoration innovations that recover the role of biogeomorphic wetlands as the world’s biotic carbon hotspots

Recovering wetland biogeomorphic feedbacks to restore the world’s biotic carbon hotspots

Biogeomorphic wetlands cover 1% of Earth’s surface but store 20% of ecosystem organic carbon. This disproportional share is fueled by high carbon sequestration rates and effective storage in peatlands, mangroves, salt marshes, and seagrass meadows, which greatly exceed those of oceanic and forest ecosystems. Here, we review how feedbacks between geomorphology and landscape-building vegetation underlie these qualities and how feedback disruption can switch wetlands from carbon sinks into sources. Currently, human activities are driving rapid declines in the area of major carbon-storing wetlands (1% annually). Our findings highlight the urgency to stop through conservation ongoing losses and to reestablish landscape-forming feedbacks through restoration innovations that recover the role of biogeomorphic wetlands as the world’s biotic carbon hotspots

Pathways of IL-1β secretion by macrophages infected with clinical Mycobacterium tuberculosis strains.

The pro-inflammatory cytokine IL-1β is a key mediator of inflammation and plays an important role in the host resistance to Mycobacterium tuberculosis infections. To date, most studies have examined the mechanisms of IL-1β secretion using laboratory strains of M. tuberculosis and the findings may not be widely applicable to contemporary clinical strains. Here, we investigated the primary pathways of IL-1β secretion in macrophages infected with a panel of 17 clinical M. tuberculosis isolates, representing Euro-American, Indo-Oceanic and East-Asian/Beijing lineages. Our aim was to dissect the pathways involved in M. tuberculosis induced IL-1β secretion and to determine whether they are common to all clinical isolates. We found that the isolates were capable of eliciting variable concentrations of IL-1β from infected murine macrophages, but this phenomenon could not be attributed to differential IL-1β mRNA transcription or pro-IL-1β accumulation. We demonstrate that viable bacteria are required to induce IL-1β secretion from macrophages, but IL-1β secretion was only partially abrogated by caspase-1 inhibition. Almost complete IL-1β secretion inhibition was produced with combined caspase-1 and some serine protease inhibitors. Taken together, these findings demonstrate that clinical strains of M. tuberculosis employ a unique caspase-1 independent pathway to stimulate IL-1β secretion from macrophages