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The devastation caused by fetal obstructive uropathy is now well known. At the most severe end of the spectrum of obstructive uropathy not only is the developing kidney damaged but the resultant oligohydra-mnios prevents pulmonary development and causes skeletal defects. The most significant changes are noted in patients with posterior urethral values (PUV). The obvious solution to the problem is to either correct or by pass the obstruction prior to the development of permanent changes. Unfortunately, this simple concept is not easy to apply since it raises numerous ethical, legal, economic and technical problems. [ABSTRACT FROM AUTHOR]

Abstract Background Inability to control autoimmunity is the primary barrier to developing a cure for type 1 diabetes (T1D). Evidence that human cord blood-derived multipotent stem cells (CB-SCs) can control autoimmune responses by altering regulatory T cells (Tregs) and human islet β cell-specific T cell clones offers promise for a new approach to overcome the autoimmunity underlying T1D. Methods We developed a procedure for Stem Cell Educator therapy in which a patient's blood is circulated through a closed-loop system that separates lymphocytes from the whole blood and briefly co-cultures them with adherent CB-SCs before returning them to the patient's circulation. In an open-label, phase1/phase 2 study, patients (n = 15) with T1D received one treatment with the Stem Cell Educator. Median age was 29 years (range: 15 to 41), and median diabetic history was 8 years (range: 1 to 21). Results Stem Cell Educator therapy was well tolerated in all participants with minimal pain from two venipunctures and no adverse events. Stem Cell Educator therapy can markedly improve C-peptide levels, reduce the median glycated hemoglobin A1C (HbA1C) values, and decrease the median daily dose of insulin in patients with some residual β cell function (n = 6) and patients with no residual pancreatic islet β cell function (n = 6). Treatment also produced an increase in basal and glucose-stimulated C-peptide levels through 40 weeks. However, participants in the Control Group (n = 3) did not exhibit significant change at any follow-up. Individuals who received Stem Cell Educator therapy exhibited increased expression of co-stimulating molecules (specifically, CD28 and ICOS), increases in the number of CD4+CD25+Foxp3+ Tregs, and restoration of Th1/Th2/Th3 cytokine balance. Conclusions Stem Cell Educator therapy is safe, and in individuals with moderate or severe T1D, a single treatment produces lasting improvement in metabolic control. Initial results indicate Stem Cell Educator therapy reverses autoimmunity and promotes regeneration of islet β cells. Successful immune modulation by CB-SCs and the resulting clinical improvement in patient status may have important implications for other autoimmune and inflammation-related diseases without the safety and ethical concerns associated with conventional stem cell-based approaches. Trial registration ClinicalTrials.gov number, NCT01350219.

Potato cyst nematodes (PCNs), an umbrella term used for two species, Globodera pallida and G. rostochiensis, belong worldwide to the most harmful pathogens of potato. Pathotype-specific host plant resistances are essential for PCN control. However, the poor delineation of G. pallida pathotypes has hampered the efficient use of available host plant resistances. Long-read sequencing technology allowed us to generate a new reference genome of G. pallida population D383 and, as compared to the current reference, the new genome assembly is 42 times less fragmented. For comparison of diversification patterns of six effector families between G. pallida and G. rostochiensis, an additional reference genome was generated for an outgroup, the beet cyst nematode Heterodera schachtii (IRS population). Large evolutionary contrasts in effector family topologies were observed. While VAPs (venom allergen-like proteins) diversified before the split between the three cyst nematode species, the families GLAND5 and GLAND13 only expanded in PCNs after their separation from the genus Heterodera. Although DNA motifs in the promoter regions thought to be involved in the orchestration of effector expression ("DOG boxes") were present in all three cyst nematode species, their presence is not a necessity for dorsal gland-produced effectors. Notably, DOG box dosage was only loosely correlated with the expression level of individual effector variants. Comparison of the G. pallida genome with those of two other cyst nematodes underlined the fundamental differences in evolutionary history between effector families. Resequencing of PCN populations with different virulence characteristics will allow for the linking of these characteristics to the composition of the effector repertoire as well as for the mapping of PCN diversification patterns resulting from extreme anthropogenic range expansion., (© 2022 The Authors. Molecular Ecology published by John Wiley & Sons Ltd.)

Plant-parasitic nematodes are a major threat to crop production in all agricultural systems. The scarcity of classical resistance genes highlights a pressing need to find new ways to develop nematode-resistant germplasm. Here, we sequence and assemble a high-quality phased genome of the model cyst nematode Heterodera schachtii to provide a platform for the first system-wide dual analysis of host and parasite gene expression over time, covering all major parasitism stages. Analysis of the hologenome of the plant-nematode infection site identified metabolic pathways that were incomplete in the parasite but complemented by the host. Using a combination of bioinformatic, genetic, and biochemical approaches, we show that a highly atypical completion of vitamin B5 biosynthesis by the parasitic animal, putatively enabled by a horizontal gene transfer from a bacterium, is required for full pathogenicity. Knockout of either plant-encoded or now nematode-encoded steps in the pathway significantly reduces parasitic success. Our experiments establish a reference for cyst nematodes, further our understanding of the evolution of plant-parasitism by nematodes, and show that congruent differential expression of metabolic pathways in the infection hologenome represents a new way to find nematode susceptibility genes. The approach identifies genome-editing-amenable targets for future development of nematode-resistant crops., (© 2022. The Author(s).)

To investigate relationships within the subfamily Telotylenchinae, more than 500 soil samples were collected from various natural and agricultural habitats in several localities of Iran. Individuals of seven known species, including Bitylenchus dubius, B. parvus, B. serranus, Sauertylenchus maximus, Tylenchorhynchus clarus, T. microconus and Trophurus ussuriensis, were recovered and characterized based on morphological and morphometric characters. Furthermore, phylogenetic relationships within representatives of the subfamily Telotylenchinae were explored using 13 sequences from the D2-D3 expansion regions of 28S ribosomal (r) DNA and 13 sequences for the partial 18S rDNA genes obtained in the present study. Analyses based on the relatively conserved 18S rDNA gene underlined the polyphyletic status of Tylenchorhynchus sensu lato, as three clusters representing Tylenchorhynchus, Bitylenchus and Sauertylenchus were well separated, and interspersed by, e.g., representatives of the Macrotrophurinae. Analysis of the more variable D2-D3 28S rDNA sequences suggested at least four clades within the subfamily Telotylenchinae: two clades dominated by Tylenchorhynchus species; a third clade harbouring representatives of Sauertylenchus, Bitylenchus, and Paratrophurus in distinct but unresolved branches;and a fourth clade dominated by Trophurus species. Although no molecular information was available from a number of genera that were originally gathered under Tylenchorhynchus sensu lato, we concluded that both Bitylenchus and Sauertylenchus should be seen as valid Telotylenchinae genera related to, but distinct from Tylenchorhynchus.

Neonatal and pediatric surgical emergencies in Low and Low Middle Income countries remain a significant challenge in combatting the burden and inequities of global health. IPSAC-Vietnam is a small Non-Governmental Organization that has been engaged in a 12-year multi-pronged partnership with several children's hospitals in Vietnam VN to enhance pediatric surgery capacity. We describe the health care, medical training and emergency system in VN as the background for IPSAC activities and development of Pediatric Acute Surgical Support (PASS) course. The course goal is to prepare health care personnel in the immediate management of neonatal/pediatric life-threatening surgical conditions and road injuries at their first point of entry into Vietnam hospitals. PASS is a horizontal outreach initiative that adopts an interprofessional, multidisciplinary, team-training, train-the-trainers, and outcome-based training approach. PASS can be used as a tool for sustainable horizontal capacity-building by champion leaders at the teaching children's hospitals and medical universities in developing countries, to strengthen training for pediatric surgical emergencies, to integrate pediatric and pediatric surgical care and to advocate for a comprehensive approach to emergency care of the critically ill child., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nguyen, Holterman, Holterman and Dinh.)

Potato cyst nematodes (PCNs), the umbrella term for Globodera rostochiensis and G. pallida , coevolved with their Solanaceous hosts in the Andean Mountain region. From there, PCN proliferated worldwide to virtually all potato production areas. PCN is a major factor limiting the potato production in Indonesia. In our survey, only G . rostochiensis was found. Fourteen field populations were collected on Java and Sumatra, and unique variants were called by mapping resequencing data on a G . rostochiensis reference genome. A phylogenetic tree based on 1.4 million unique variants showed a genotypic separation between the outgroup, a Scottish Ro1 population, and all Indonesian populations. This separation was comparable in size with the genotypic distinction between the Javanese and the Sumatran PCN populations. Next, variants within PCN effector gene families SPRYSEC, 1106, 4D06, and venom allergen-like protein (VAL) that all interfere with the host innate immune system were compared. Distinct selective pressures acted on these effector families; while SPRYSECs (4,341 single-nucleotide polymorphisms [SNPs]/insertions or deletions of bases [indels]) behaved like neutral genes, the phylogenetic trees of 1106, 4D06, and VAL proteins (235, 790, and 150 SNPs/indels, respectively) showed deviating topologies. Our data suggest that PCN was introduced on Java not too long after the introduction of potato in the middle of the eighteenth century. Soon thereafter, the pathogen established on Sumatra and started to diversify independently. This scenario was corroborated by diversification patterns of the effector families 1106, 4D06, and VAL. Our data demonstrate how genome resequencing data from a nonindigenous pathogen can be used to reconstruct the introduction and diversification process.

Background: Potato cyst nematodes belong to the most harmful pathogens in potato, and durable management of these parasites largely depends on host-plant resistances. These resistances are pathotype specific. The current Globodera rostochiensis pathotype scheme that defines five pathotypes (Ro1 - Ro5) is both fundamentally and practically of limited value. Hence, resistant potato varieties are used worldwide in a poorly informed manner., Results: We generated two novel reference genomes of G. rostochiensis inbred lines derived from a Ro1 and a Ro5 population. These genome sequences comprise 173 and 189 scaffolds respectively, marking a ≈ 24-fold reduction in fragmentation as compared to the current reference genome. We provide copy number variations for 19 effector families. Four dorsal gland effector families were investigated in more detail. SPRYSECs, known to be implicated in plant defence suppression, constitute by far the most diversified family studied herein with 60 and 99 variants in Ro1 and Ro5 distributed over 18 and 26 scaffolds. In contrast, CLEs, effectors involved in feeding site induction, show strong physical clustering. The 10 and 16 variants cluster on respectively 2 and 1 scaffolds. Given that pathotypes are defined by their effectoromes, we pinpoint the disparate nature of the contributing effector families in terms of sequence diversification and loss and gain of variants., Conclusions: Two novel reference genomes allow for nearly complete inventories of effector diversification and physical organisation within and between pathotypes. Combined with insights we provide on effector family-specific diversification patterns, this constitutes a basis for an effectorome-based virulence scheme for this notorious pathogen., (© 2021. The Author(s).)

Plant-parasitic nematodes secrete effectors that manipulate plant cell morphology and physiology to achieve host invasion and establish permanent feeding sites. Effectors from the highly expanded SPRYSEC (SPRY domain with a signal peptide for secretion) family in potato cyst nematodes have been implicated in activation and suppression of plant immunity, but the mechanisms underlying these activities remain largely unexplored. To study the host mechanisms used by SPRYSEC effectors, we identified plant targets of GpRbp-1 from the potato cyst nematode Globodera pallida. Here, we show that GpRbp-1 interacts in yeast and in planta with a functional potato homologue of the Homology to E6-AP C-Terminus (HECT)-type ubiquitin E3 ligase UPL3, which is located in the nucleus. Potato lines lacking StUPL3 are not available, but the Arabidopsis mutant upl3-5 displaying a reduced UPL3 expression showed a consistently small but not significant decrease in susceptibility to cyst nematodes. We observed a major impact on the root transcriptome by the lower levels of AtUPL3 in the upl3-5 mutant, but surprisingly only in association with infections by cyst nematodes. To our knowledge, this is the first example that a HECT-type ubiquitin E3 ligase is targeted by a pathogen effector and that a member of this class of proteins specifically regulates gene expression under biotic stress conditions. Together, our data suggest that GpRbp-1 targets a specific component of the plant ubiquitination machinery to manipulate the stress response in host cells., (© 2019 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.)

Anthropogenic modification of soil systems has diverse impacts on food web interactions and ecosystem functioning. To understand the positive, neutral or adverse effects of agricultural practices on the associations of community members of soil microbes and microfaunal biomes, we characterized the effects of different fertilization types (organic, inorganic and a combination of organic and inorganic) on the food web active communities in the bulk soil and rhizosphere compartments in field conditions. We examined the influence of fertilization on (i) individual groups (bacteria, protozoa and fungi as microbe representatives and metazoans as microfauna representatives) and (ii) inter-kingdom interactions (focusing on the interactions between bacteria and eukaryotic groups) both neglecting and considering environmental factors in our analysis in combination with the microbial compositional data. Our results revealed different patterns of biota communities under organic versus inorganic fertilization, which shaped food web associations in both the bulk and rhizosphere compartments. Overall, organic fertilization increased the complexity of microbial-microfaunal ecological associations with inter- and intra- connections among categories of primary decomposers (bacteria and fungi) and predators (protozoa and microfauna) and differences in potential function in the soil food web in both the bulk and rhizosphere compartments. Furthermore, the inter-connections between primary decomposers and predators in bulk soil were more pronounced when environmental factors were considered. We suggest that organic fertilization selects bacterial orders with different potential ecological functions and interactions as survival, predation and cooperation due to more complex environment than those of inorganic or combined fertilization. Our findings support the importance of a comprehensive understanding of trophic food web patterns for soil management systems., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Free-living nematodes, an ancient animal phylum of unsegmented microscopic roundworms, have successfully adapted to nearly every ecosystem on Earth: from marine and freshwater to land, from the polar regions to the tropics, and from the mountains to the ocean depths. They are globally the most abundant animals in sediments and soils. In the present article, we identify the factors that collectively explain the successful ecological proliferation of free-living nematodes and demonstrate the impact they have on vital sediment and soil processes. The ecological success of nematodes is strongly linked to their ability to feed on various food sources that are present in both sediments and soils, and to proliferate rapidly and survive in contrasting environmental conditions. The adaptations, roles, and behaviors of free-living nematodes have important implications for the resilience of sediments and soils, and for emergent animal communities responding to human alterations to ecosystems worldwide., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Institute of Biological Sciences.)

Conventional agricultural production systems, typified by large inputs of mineral fertilizers and pesticides, reduce soil biodiversity and may negatively affect ecosystem services such as carbon fixation, nutrient cycling and disease suppressiveness. Organic soil management is thought to contribute to a more diverse and stable soil food web, but data detailing this effect are sparse and fragmented. We set out to map both the resident (rDNA) and the active (rRNA) fractions of bacterial, fungal, protozoan and metazoan communities under various soil management regimes in two distinct soil types with barley as the main crop. Contrasts between resident and active communities explained 22%, 14%, 21% and 25% of the variance within the bacterial, fungal, protozoan, and metazoan communities. As the active fractions of organismal groups define the actual ecological functioning of soils, our findings underline the relevance of characterizing both resident and active pools. All four major organismal groups were affected by soil management (p < 0.01), and most taxa showed both an increased presence and an enlarged activity under the organic regime. Hence, a prolonged organic soil management not only impacts the primary decomposers, bacteria and fungi, but also major representatives of the next trophic level, protists and metazoa.

We have recently demonstrated that treatment of NOD mice with the epigenetic drug Trichostatin A (TSA) ameliorated myelin peptide induced progressive experimental autoimmune encephalomyelitis (P-EAE). Protection was accompanied by induction of antigen-specific T-cell tolerance in the periphery and reduced influx of T cells into the spinal cord. In this investigation, we examined whether the epigenetic drug could impact the innate immune system as well. Whereas the mature (MHC class II + ) CD11b + Ly-6G + neutrophils expanded substantially in the peripheral lymphoid compartment during the preclinical phase, the MHC class II + , CD11b + Ly-6C + mature monocytes increased modestly throughout the disease course. Amelioration of the clinical disease by TSA treatment was accompanied by diminished abundance of CD11b + Ly-6G dim activated neutrophils in secondary lymphoid organs and their influx into the spinal cord without affecting monocytes. Interestingly, the co-inhibitory ligand CD274 + (PD-L1 + ) but not CD275 + (ICOS-L + ), CD39 + or CD11c + dendritic cells were decreased in the peripheral lymphoid compartment of drug treated mice. Thus, in addition to myelin-specific T cell tolerance induction observed previously, selective repression of mature neutrophils and PD-L1 + cells is critically involved in the epigenetic regulation of P-EAE., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Multiple sclerosis is a T cell mediated chronic demyelinating disease of the central nervous system. Although currently available therapies reduce relapses, they do not facilitate tolerization of myelin antigen-specific T lymphocytes to ensure prolonged protection against multiple sclerosis. Here, we show that treatment of NOD mice with the histone deacetylase inhibitor, Trichostatin A affords robust protection against myelin peptide induced experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. Protection was accompanied by histone hyperacetylation, and reduced inflammation and axonal damage in the spinal cord. Drug treatment diminished the generation of CD4 + memory T cells and induced tolerance in CD4 + T cells recognizing the immunizing myelin peptide. During the early immunization period, CD4 + T cells producing GM-CSF+IFN-γ, GM-CSF+IL-17A, as well as those expressing both IL-17A+IFN-γ (double-producers) were detected in the secondary lymphoid organs followed by the appearance of cells producing IFN-γ and GM-CSF. On the other hand, IFN-γ producing Th1 cells appear first in the spinal cord followed by cells producing IL-17A and GM-CSF. Treatment with Trichostatin A substantially reduced the frequencies of all T cells secreting various lymphokines both in the periphery and in the spinal cord. These data indicate that epigenetic modifications induced by histone hyperacetylation facilitates T cell tolerance induction in the periphery leading to reduced migration of T cells to the spinal cord and mitigation of neuronal damage and improved clinical outcome. These results suggest that epigenetic modulation of the genome may similarly offer benefits to multiple sclerosis patients via abrogating the function of encephalitogenic T lymphocytes without exerting severe side effects associated with currently used disease-modifying therapies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Plant parasitism has arisen time and again in multiple phyla, including bacteria, fungi, insects and nematodes. In most of these organismal groups, the overwhelming diversity hampers a robust reconstruction of the origins and diversification patterns of this trophic lifestyle. Being a moderately diversified phylum with ≈ 4,100 plant parasites (15% of total biodiversity) subdivided over four independent lineages, nematodes constitute a major organismal group for which the genesis of plant parasitism could be mapped. Since substantial crop losses worldwide have been attributed to less than 1% of these plant parasites, research efforts are severely biased towards this minority. With the first molecular characterisation of numerous basal and supposedly harmless plant parasites as well as their non-parasitic relatives, we were able to generate a comprehensive molecular framework that allows for the reconstruction of trophic diversification for a complete phylum. In each lineage plant parasites reside in a single taxonomic grouping (family or order), and by taking the coverage of the next lower taxonomic level as a measure for representation, 50, 67, 100 and 85% of the known diversity was included. We revealed distinct gain and loss patterns with regard to plant parasitism per se as well as host exploitation strategies between these lineages. Our map of parasitic nematode biodiversity also revealed an unanticipated time reversal in which the two most ancient lineages showed the lowest level of ecological diversification and vice versa.