Parasitic nematodes exert antimicrobial activity and benefit from microbiota-driven support for host immune regulation

Intestinal parasitic nematodes live in intimate contact with the host microbiota. Changes in the microbiome composition during nematode infection affect immune control of the parasites and shifts in the abundance of bacterial groups have been linked to the immunoregulatory potential of nematodes. Here we asked if the small intestinal parasite Heligmosomoides polygyrus produces factors with antimicrobial activity, senses its microbial environment and if the anti-nematode immune and regulatory responses are altered in mice devoid of gut microbes. We found that H. polygyrus excretory/secretory products exhibited antimicrobial activity against gram(+/-) bacteria. Parasites from germ-free mice displayed alterations in gene expression, comprising factors with putative antimicrobial functions such as chitinase and lysozyme. Infected germ-free mice developed increased small intestinal Th2 responses coinciding with a reduction in local Foxp3(+)RORγt(+) regulatory T cells and decreased parasite fecundity. Our data suggest that nematodes sense their microbial surrounding and have evolved factors that limit the outgrowth of certain microbes. Moreover, the parasites benefit from microbiota-driven immune regulatory circuits, as an increased ratio of intestinal Th2 effector to regulatory T cells coincides with reduced parasite fitness in germ-free mice

Simplified methodology for large scale isolation of homozygous transgenic lines of lettuce

Background: Lettuce is a globally important leafy vegetable and a model plant for biotechnology due to its adaptability to tissue culture and stable genetic transformation. Lettuce is also crucial for functional genomics research in the Asteraceae which includes species of great agronomical importance. The development of transgenic events implies the production of a large number of shoots that must be differentiated between transgenic and non-transgenic through the activity of the selective agent, being kanamycin the most popular. Results: In this work we adjusted the selection conditions of transgenic seedlings to avoid any escapes, finding that threshold concentration of kanamycin was 75 mg/L. To monitor the selection system, we studied the morphological response of transgenic and non-transgenic seedlings in presence of kanamycin to look for a visual morphological marker. Several traits like shoot length, primary root length, number of leaves, fresh weight, and appearance of the aerial part and development of lateral roots were affected in non-transgenic seedlings after 30 d of culture in selective media. However, only lateral root development showed an early, qualitative and reliable association with nptII presence, as corroborated by PCR detection. Applied in successive transgenic progenies, this method of selection combined with morphological follow-up allowed selecting the homozygous presence of nptII gene in 100% of the analyzed plants from T2 to T5. Conclusions: This protocol allows a simplified scaling-up of the production of multiple homozygous transgenic progeny lines in the early generations avoiding expensive and time-consuming molecular assays

RNA isolation for transcriptomics of human and mouse small skin biopsies

<p>Abstract</p> <p>Background</p> <p>Isolation of RNA from skin biopsies presents a challenge, due to the tough nature of skin tissue and a high presence of RNases. As we lacked the dedicated equipment, i.e. homogenizer or bead-beater, needed for the available RNA from skin isolation methods, we adapted and tested our zebrafish single-embryo RNA-isolation protocol for RNA isolation from skin punch biopsies.</p> <p>Findings</p> <p>We tested our new RNA-isolation protocol in two experiments: a large-scale study with 97 human skin samples, and a small study with 16 mouse skin samples. Human skin was sampled with 4.0 mm biopsy punches and for the mouse skin different punch diameter sizes were tested; 1.0, 1.5, 2.0, and 2.5 mm. The average RNA yield in human samples was 1.5 μg with an average RNA quality RIN value of 8.1. For the mouse biopsies, the average RNA yield was 2.4 μg with an average RIN value of 7.5. For 96% of the human biopsies and 100% of the mouse biopsies we obtained enough high-quality RNA. The RNA samples were successfully tested in a transcriptomics analysis using the Affymetrix and Roche NimbleGen platforms.</p> <p>Conclusions</p> <p>Using our new RNA-isolation protocol, we were able to consistently isolate high-quality RNA, which is apt for further transcriptomics analysis. Furthermore, this method is already useable on biopsy material obtained with a punch diameter as small as 1.5 mm.</p

Exposing the myths of household water insecurity in the global north: A critical review

Safe and secure water is a cornerstone of modern life in the global North. This article critically examines a set of prevalent myths about household water in high-income countries, with a focus on Canada and the United States. Taking a relational approach, we argue that household water insecurity is a product of institutionalized structures and power, manifests unevenly through space and time, and is reproduced in places we tend to assume are the most water-secure in the world. We first briefly introduce “modern water” and the modern infrastructural ideal, a highly influential set of ideas that have shaped household water provision and infrastructure development over the past two centuries. Against this backdrop, we consolidate evidence to disrupt a set of narratives about water in high-income countries: the notion that water access is universal, clean, affordable, trustworthy, and uniformly or equitably governed. We identify five thematic areas of future research to delineate an agenda for advancing scholarship and action—including challenges of legal and regulatory regimes, the housing-water nexus, water affordability, and water quality and contamination. Data gaps underpin the experiences of household water insecurity. Taken together, our review of water security for households in high-income countries provides a conceptual map to direct critical research in this area for the coming years

The revised role of TGF-β in aortic aneurysms in Marfan syndrome

BACKGROUND\nRecently, we demonstrated that losartan reduced the aortic root dilatation rate (AoDR) in adults with Marfan syndrome (MFS); however, responsiveness was diverse. The aim was to determine the role of transforming growth factor-β (TGF-β) as therapeutic biomarker for effectiveness of losartan on AoDR.\nMETHODS\nBaseline plasma TGF-β levels of 22 healthy controls and 99 MFS patients, and TGF-β levels after 1 month of losartan treatment in 42 MFS patients were measured. AoDR was assessed by magnetic resonance imaging at baseline and after 3 years of follow-up.\nRESULTS\nPatients with MFS had higher TGF-β levels compared with healthy controls (121 pg/ml versus 54 pg/mL, p = 0.006). After 1 month of therapy, losartan normalised the TGF-β level in 15 patients (36%); the other 27 patients (64%) showed a significant increase of TGF-β. After 3 years of losartan therapy, patients with a decrease in TGF-β had significantly higher AoDR compared with patients with increased TGF-β (1.5 mm/3 years versus 0.5 mm/3 years, p = 0.04). Patients showing a decrease in TGF-β after losartan therapy had significantly elevated baseline TGF-β levels compared with patients with increased TGF-β (189 pg/ml versus 94 pg/ml, p = 0.05).\nCONCLUSION\nPatients responding to losartan therapy with a reduction of the plasma TGF-β level had higher baseline TGF-β levels and a higher AoDR. Most likely, TGF-β levels may be considered to be a readout of the disease state of the aorta. We propose that increased angiotensin II is the initiator of aorta dilatation and is responsible for increased TGF-β levels in MFS. The concept of TGF-β as initiator of aortic dilatation in MFS patients should be nuanced.Medical Biochemistr

Why dig looted tombs? Two examples and some answers from Keushu (Ancash highlands, Peru)

Looted tombs at Andean archaeological sites are largely the result of a long tradition of trade in archaeological artefacts coupled with the 17th century policy of eradicating ancestor veneration and destroying mortuary evidence in a bid to “extirpate idolatry”. On the surface, looted funerary contexts often present abundant disarticulated and displaced human remains as well as an apparent absence of mortuary accoutrements. What kind of information can archaeologists and biological anthropologists hope to gather from such contexts? In order to gauge the methodological possibilities and interpretative limitations of targeting looted tombs, we fully excavated two collective funerary contexts at the archaeological site of Keushu (district and province of Yungay, Ancash, Peru; c. 2000 B.C.-A.D. 1600), which includes several dozen tombs, many built under large boulders or rock shelters, all of which appear disturbed by looting. The first is located in the ceremonial sector and excavation yielded information on four individuals; the second, in the funerary and residential sector, held the remains of seventy individuals - adults and juveniles. Here, we present and discuss the recovered data and suggest that careful, joint excavations by archaeologists and biological anthropologists can retrieve evidence of past mortuary practices, aid the biological characterisation of mortuary populations and help distinguish between a broad range of looting practices and post-depositional processes

Offspring of parents with Balkan Endemic Nephropathy have higher C-reactive protein levels suggestive of inflammatory processes: a longitudinal study

<p>Abstract</p> <p>Background</p> <p>Despite the characteristic extensive tubulointerstitial fibrosis, Balkan Endemic Nephropathy (BEN) is usually considered a non-inflammatory disease.</p> <p>Methods</p> <p>We examined a marker of inflammation, C-reactive protein (CRP), in the offspring of patients with BEN, a population at risk for BEN, prior to development of established disease to determine if an inflammatory process could be identified in the early stages of the disease. In 2003/04, 102 adult offspring whose parents had BEN and a control group of 99 adult offspring of non-BEN patients were enrolled in this prospective study. This cohort was re-examined yearly for four consecutive years. Levels of serum CRP were measured in years 3 and 4 and compared between groups. The data were analyzed with mixed models.</p> <p>Results</p> <p>Compared to controls, offspring of BEN parents had statistically higher CRP levels in two consecutive years, suggestive of early inflammatory reactivity. Whenever the mother was affected by BEN (both parents, or mother only), serum CRP was significantly increased, but not if only the father had BEN. CRP was inversely related to kidney cortex width but not to markers or renal function.</p> <p>Conclusion</p> <p>Early stages of BEN may involve inflammatory processes. The observation of a maternal involvement supports the concept of fetal programming, which has been implicated in the pathogenesis of other chronic kidney diseases.</p

Exposing the myths of household water insecurity in the global north: A critical review

Safe and secure water is a cornerstone of modern life in the global North. This article critically examines a set of prevalent myths about household water in high-income countries, with a focus on Canada and the United States. Taking a relational approach, we argue that household water insecurity is a product of institutionalized structures and power, manifests unevenly through space and time, and is reproduced in places we tend to assume are the most water-secure in the world. We first briefly introduce “modern water” and the modern infrastructural ideal, a highly influential set of ideas that have shaped household water provision and infrastructure development over the past two centuries. Against this backdrop, we consolidate evidence to disrupt a set of narratives about water in high-income countries: the notion that water access is universal, clean, affordable, trustworthy, and uniformly or equitably governed. We identify five thematic areas of future research to delineate an agenda for advancing scholarship and action—including challenges of legal and regulatory regimes, the housing-water nexus, water affordability, and water quality and contamination. Data gaps underpin the experiences of household water insecurity. Taken together, our review of water security for households in high-income countries provides a conceptual map to direct critical research in this area for the coming years. This article is categorized under: Human Water \u3e Human Water