Forest diseases caused by invasive fungal pathogens are becoming more common, sometimes with dramatic consequences to forest ecosystems. The development of early detection systems is necessary for ...efficient surveillance and to mitigate the impact of invasive pathogens. Windborne spores are an important pathway for introduction of fungal pathogens into new areas; the design of spore trapping devices adapted to forests, capable of collecting different types of spores, and aligned with development of efficient molecular methods for detection of the pathogen, should help forest managers anticipate new disease outbreaks. Two types of Rotorod samplers were evaluated for the collection of airborne inoculum of forest fungal pathogens with a range of spore sizes in five forest types. Detection was by specific quantitative PCR (qPCR) and by high-throughput sequencing (HTS) of amplified internal transcribed spacer sequences using a new bioinformatic pipeline, FungiSearch, developed for diagnostic purposes. Validation of the pipeline was conducted on mock communities of 10 fungal species belonging to different taxa. Although the sensitivity of the new HTS pipeline was lower than the specific qPCR, it was able to detect a wide variety of fungal pathogens. FungiSearch is easy to use, and the reference database is updatable, making the tool suitable for rapid identification of new pathogens. This new approach combining spore trapping and HTS detection is promising as a diagnostic tool for invasive fungal pathogens.
Abstract
The CGIAR genebank International
Musa
Germplasm Transit Centre (ITC) currently holds 1617 banana accessions from 38 countries as an in vitro collection, backed-up by a cryopreserved ...collection to safeguard global
Musa
diversity in perpetuity. The ITC also serves as a vital safety backup and transit centre for national banana genebanks and ensures that germplasm is clean of pests and diseases and freely available under the International Treaty on Plant Genetic Resources for Food and Agriculture. In more than 35 years of activity, the ITC has distributed over 18,000 banana accession samples to researchers and farmers in 113 countries. Ex situ conservation of vegetatively-propagated crops such as banana poses very particular challenges. Maintaining the ITC genebank is labor intense and costly. Efficiencies are sought through research and development of techniques on detecting viruses, the genetic integrity of accessions, and on innovative means of safeguarding banana diversity, such as conserving populations of wild species by seed banking. Although the conservation of global banana diversity is the main objective of the ITC, significant value comes from its holistic approach to better understand and promote its germplasm through numerous research activities and resources. Techniques for morphological and molecular characterization serve to identify and describe the collection, while also determining what gaps should be filled by collecting missions with national partners. The evaluation of desirable agronomic traits inherent in
Musa
spp. are investigated by a high-throughput phenotyping platform, which helps breeding programs to select cultivars resistant or tolerant to biotic and abiotic stresses. Genomic and bioinformatic studies of several banana wild relatives greatly enhance our understanding of
Musa
genetic diversity, links to important phenotypic traits and bring new methods for management of the collection. Collectively, these research activities produce enormous amounts of data that require curation and dissemination to the public. The two information systems at the ITC,
Musa
Genebank Management System and the
Musa
Germplasm Information System, serve to manage the genebank activities and to make public germplasm-related data for over 30 banana collections worldwide, respectively. By implementing the 10-year workplan set out in the Global Strategy for the Conservation and Use of
Musa
Genetic Resources, the network MusaNet supports
Musa
researchers and stakeholders, including the ITC, and most importantly, links to the world’s banana-producing countries via three regional banana networks.
Congenital hydrocephalus is a potentially devastating, highly heterogeneous condition whose genetic subset remains incompletely known. We here report a consanguineous family where three fetuses ...presented with brain ventriculomegaly and limb contractures and shared a very rare homozygous variant of KIDINS220, consisting of an in-frame deletion of three amino acids adjacent to the fourth transmembrane domain. Fetal brain imaging and autopsy showed major ventriculomegaly, reduced brain mass, and with no histomorphologic abnormalities. We demonstrate that the binding of KIDINS220 to TrkA is diminished by the deletion mutation. This family is the second that associates a KIDINS220 genetic variant with human ventriculomegaly and limb contractures, validating causality of the gene and indicating TrkA as a likely mediator of the phenotype.
Congenital hydrocephalus is characterized by ventriculomegaly, defined as a dilatation of cerebral ventricles, and thought to be due to impaired cerebrospinal fluid (CSF) homeostasis. Primary ...congenital hydrocephalus is a subset of cases with prenatal onset and absence of another primary cause, e.g., brain hemorrhage. Published series report a Mendelian cause in only a minority of cases. In this study, we analyzed exome data of PCH patients in search of novel causal genes and addressed the possibility of an underlying oligogenic mode of inheritance for PCH.
We sequenced the exome in 28 unrelated probands with PCH, 12 of whom from families with at least two affected siblings and 9 of whom consanguineous, thereby increasing the contribution of genetic causes. Patient exome data were first analyzed for rare (MAF < 0.005) transmitted or de novo variants. Population stratification of unrelated PCH patients and controls was determined by principle component analysis, and outliers identified using Mahalanobis distance 5% as cutoff. Patient and control exome data for genes biologically related to cilia (SYScilia database) were analyzed by mutation burden test.
In 18% of probands, we identify a causal (pathogenic or likely pathogenic) variant of a known hydrocephalus gene, including genes for postnatal, syndromic hydrocephalus, not previously reported in isolated PCH. In a further 11%, we identify mutations in novel candidate genes. Through mutation burden tests, we demonstrate a significant burden of genetic variants in genes coding for proteins of the primary cilium in PCH patients compared to controls.
Our study confirms the low contribution of Mendelian mutations in PCH and reports PCH as a phenotypic presentation of some known genes known for syndromic, postnatal hydrocephalus. Furthermore, this study identifies novel Mendelian candidate genes, and provides evidence for oligogenic inheritance implicating primary cilia in PCH.
The prevalence of chemotherapy associated liver injuries (CALI), especially SOS (sinusoidal obstruction syndrome) and NRH (nodular regenerative hyperplasia) might be reduced since the introduction of ...routine use of biological agents with chemotherapy in colorectal liver metastases (CRLM).
One hundred patients with CRLM having undergone at least one liver segment resection were prospectively included, and chemotherapy data recorded. Specimens were reviewed by a single pathologist and CALI were described. Prevalence of CALI was compared to our previous experience published in 2013. NRH diagnosis was performed on reticulin special stain, by contrast to our previous study. Postoperative outcome was analysed.
Bevacizumab was more frequently administrated in patients of the present study: 53/100 (53%) compared to 20/151 (13%), p < 0.0001. Overall, in the present series, SOS was only observed in 28/100 (28%) patients compared to 116/151 (77%) in 2013 (p < 0.001). When looking specifically to patients receiving Bevacizumab with Folfox, we observed a reduced SOS prevalence compared to Folfox alone (p = 0.008). A higher prevalence of NRH was found in the present study, related to increased detection accuracy, but in patients receiving Bevacizumab in association with Folfox, this prevalence was also reduced compared to Folfox alone (p = 0.03). Both SOS and NRH were associated with severe complications (p = 0.008 and p = 0.005, respectively) and postoperative liver insufficiency (p < 0.001 and p < 0.01, respectively).
The routine use of Bevacizumab in association with Folfox significantly reduced CALI prevalence, in turn linked to severe postoperative complications.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract
Background and Aims
Renal operational tolerance is a rare and beneficial state of prolonged renal allograft function in the absence of immunosuppression. The underlying mechanisms are ...unknown. We hypothesized that tolerance might be driven by inherited protein coding genetic variants with large effect, at least in some patients.
Method
We set up a European survey of over 218,000 renal transplant recipients and collected DNAs from 40 recipients of an allogeneic kidney transplant who maintained good graft function (serum creatinine <1.7 mg/dL and proteinuria ≤1g/day or /g creatinine) in the absence of immunosuppression for at least one year. We performed an exome-wide association study comparing the distribution of moderate to high impact variants in 36 tolerant patients, selected for genetic homogeneity using principal component analysis, and 192 controls, using an optimal sequence-kernel association test adjusted for small samples.
Results
We identified rare variants (allele frequency < 1%) of HOMER2 (3/36, FDR 0.0387), IQCH (5/36, FDR 0.0362), and LCN2 (3/36, FDR 0.102) in 10 tolerant patients vs 0 controls. One patient carried a variant in both HOMER2 and LCN2. Furthermore, the three genes showed an identical variant in two patients each. The three genes are expressed at the primary cilium (p0= 0.01), a key structure in immune responses. Both LCN2 variants were located 9 base pairs apart, in the 20 amino-acid long signal peptide of the encoded NGAL protein, suggesting the possibility of a shared functional effect
Conclusion
Rare protein coding variants in a small set of primary cilium genes are associated with operational tolerance in a sizable portion of patients. Our findings have important implications for a better understanding of immune tolerance in transplantation and other fields of medicine.
ClinicalTrials.gov Identifier NCT05124444.
Primary microcephaly (PM) is characterized by a small head since birth and is vastly heterogeneous both genetically and phenotypically. While most cases are monogenic, genetic interactions between ...Aspm and Wdr62 have recently been described in a mouse model of PM. Here, we used two complementary, holistic in vivo approaches: high throughput DNA sequencing of multiple PM genes in human patients with PM, and genome‐edited zebrafish modeling for the digenic inheritance of PM. Exomes of patients with PM showed a significant burden of variants in 75 PM genes, that persisted after removing monogenic causes of PM (e.g., biallelic pathogenic variants in CEP152). This observation was replicated in an independent cohort of patients with PM, where a PM gene panel showed in addition that the burden was carried by six centrosomal genes. Allelic frequencies were consistent with digenic inheritance. In zebrafish, non‐centrosomal gene casc5 −/− produced a severe PM phenotype, that was not modified by centrosomal genes aspm or wdr62 invalidation. A digenic, quadriallelic PM phenotype was produced by aspm and wdr62. Our observations provide strong evidence for digenic inheritance of human PM, involving centrosomal genes. Absence of genetic interaction between casc5 and aspm or wdr62 further delineates centrosomal and non‐centrosomal pathways in PM.
In a cohort of patients with primary microcephaly (PM), exome sequencing showed a significant burden of variants in PM genes, that persisted after removing monogenic causes of PM. The finding was confirmed in a replication cohort (not shown), and candidate centrosomal gene pairs were identified. Zebrafish genome editing produced a severe PM phenotype in casc5 −/− and no phenotype in aspm −/− or wdr62 −/− fishes. Zebrafish crosses displayed digenic interactions between centrosomal genes aspm and wdr62, and no interactions between non‐centrosomal gene casc5 and either aspm or wdr62, delineating centrosomal and non‐centrosomal pathways in PM. *p = .028.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
In the original publication (Houwe et al. 2020) affiliations 1 and 2 were accidentally swapped, the error affected the affiliations of Van den Houwe, Chase, Sardos, Ruas, Guignon, Carpentier, Panis, ...Rouard and Roux. This correction article shows the correct and incorrect information. Incorrect: 1Bioversity International, Parc Scientifique Agropolis II, 34397 Montpellier, France. 2Bioversity International, Willem De Croylaan 42, 3001 Leuven, Belgium. 1Bioversity International, Parc Scientifique Agropolis II, 34397 Montpellier, France. 2Bioversity International, Willem De Croylaan 42, 3001 Leuven, Belgium. Correct: 1Bioversity International, Willem De Croylaan 42, 3001 Leuven, Belgium. 2Bioversity International, Parc Scientifique Agropolis II, 34397 Montpellier, France. 1Bioversity International, Willem De Croylaan 42, 3001 Leuven, Belgium. 2Bioversity International, Parc Scientifique Agropolis II, 34397 Montpellier, France. The original publication has been updated to reflect the correct affiliations.
Candidemia is a high-risk complication among intensive care unit (ICU) patients. While selective digestive decontamination (SDD) has been shown to be effective in preventing ICU-acquired bacterial ...secondary infection, its effects on ICU-acquired candidemia (ICAC) remain poorly explored. Therefore, we sought to assess the effects of SDD on ICAC.
Using the REA-REZO network, we included adult patients receiving mechanical ventilation for at least 48 h from January 2017 to January 2023. Non-parsimonious propensity score matching with a 1:1 ratio was performed to investigate the association between SDD and the rate of ICAC.
A total of 94 437 patients receiving at least 48 h of mechanical ventilation were included throughout the study period. Of those, 3 001 were treated with SDD and 651 patients developed ICAC. The propensity score matching included 2 931 patients in the SDD group and in the standard care group. In the matched cohort analysis as well as in the overall population, the rate of ICAC was lower in patients receiving SDD (0.8% versus 0.3%; p = 0.012 and 0.7% versus 0.3%; p = 0.006, respectively). Patients with ICAC had higher mortality rate (48.4% versus 29.8%; p < 0.001). Finally, mortality rates as well as ICU length of stay in the matched populations did not differ according to SDD (31.0% versus 31.1%; p = 0.910 and 9 days 5-18 versus 9 days 5-17; p = 0.513, respectively).
In this study with a low prevalence of ICAC, SDD was associated with a lower rate of ICAC that did not translate to higher survival.
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