Radiation Hybrid Fine Mapping of Two Fertility-Related Genes: Marking the Path to Wheat Hybrids

Over one billion people, more than 1/9th of the global population, are undernourished. Feeding the ever increasing population has to be the most important goal of plant sciences. Since cultivated areas are not likely to increase, I will need to produce more with what is available. This can be summarized in one word: yield. Unfortunately, wheat’s yield is expected to increase only 1.13% by 2019, a prediction that if converted into reality will likely indicate that I failed to cope with the world demographic increase. A new strategy to revolutionize wheat production is required, and some believe that this change might be represented by wheat hybrids. Achieving adequate commercial production of wheat hybrids has the potential to nearly double the yield of one of the world’s most important staple food. The first fundamental step toward this goal is to develop feasible methodologies to sterilize the male part of the complete wheat flowers. Two fertility-related genes are the primary target of this study, namely the species cytoplasm specific on chromosome 1D, and the desynaptic locus on chromosome 3B. This dissertation summarizes the important achievements obtained toward the cloning of the two loci by means of radiation hybrid functional analysis. Radiation hybrid is a technique that employs radiation to create genetic diversity along the targeted chromosome. Chapter 1 explains in details how this methodology can be applied to plants. The use of radiation hybrid mapping permitted creating a comprehensive map of wheat chromosome 3B, as discussed in Chapter 2, and then expanded the mapping information to identify the 2 Mb location of the desynaptic locus desw2, as discussed in Chapter 3. A similar approach on chromosome 1D allowed first to pinpoint the location of the species cytoplasm specific gene to a region of 2 Mb, as discussed in Chapter 4, and then ultimately to find a strong candidate for this locus, as discussed in Chapter 5. Now that the molecular locations of these genes have been unraveled by this study, their sequence can be streamlined into transformation to ultimately produce female wheat plants, and consequently hybrids

Mid-Holocene relative sea-level changes along Atlantic Patagonia: new data from Camarones, Chubut, Argentina

This paper concerns the relative sea-level changes associated with the Atlantic Patagonian coast derived from sea-level index points whose elevation was determined by a differential global position system (DGPS). Bio encrustations from outcrops located near Camarones, Chubut, Argentina, consist of autochthonous deposits characterized by Austromegabalanus psittacus (Molina, 1782), encrusting acer vulinid foraminifera, coralline red algae and bryozoans. The association of the different organisms is interpreted as being associated with an intertidal environment, and they have been used as index points to establish the relative sea-level position. The main conclusion is that the relative sea-level between c. 7000 and 5300 cal. yr BP was in the range ofc. 2?4 m a.s.l., with a mean value of c. 3.5 m a.s.l. Our data seem to support the existence of different rates of relative sea-level fall in different sectors of Atlantic Patagonia during the Holocene and highlight the importance of a more precise and accurate relative sea-level estimation by producing new data and revisiting the indicative meaning of most of the indicators so far used in the area.Facultad de Ciencias Naturales y Muse

Genome-enabled predictions for fruit weight and quality from repeated records in European peach progenies

Background: Highly polygenic traits such as fruit weight, sugar content and acidity strongly influence the agroeconomic value of peach varieties. Genomic Selection (GS) can accelerate peach yield and quality gain if predictions show higher levels of accuracy compared to phenotypic selection. The available IPSC 9K SNP array V1 allows standardized and highly reliable genotyping, preparing the ground for GS in peach. Results: A repeatability model (multiple records per individual plant) for genome-enabled predictions in eleven European peach populations is presented. The analysis included 1147 individuals derived from both commercial and non-commercial peach or peach-related accessions. Considered traits were average fruit weight (FW), sugar content (SC) and titratable acidity (TA). Plants were genotyped with the 9K IPSC array, grown in three countries (France, Italy, Spain) and phenotyped for 3–5 years. An analysis of imputation accuracy of missing genotypic data was conducted using the software Beagle, showing that two of the eleven populations were highly sensitive to increasing levels of missing data. The regression model produced, for each trait and each population, estimates of heritability (FW:0.35, SC:0.48, TA:0.53, on average) and repeatability (FW:0.56, SC:0.63, TA:0.62, on average). Predictive ability was estimated in a five-fold cross validation scheme within population as the correlation of true and predicted henotypes. Results differed by populations and traits, but predictive abilities were in general high (FW:0.60, SC:0.72, TA:0.65, on average). Conclusions: This study assessed the feasibility of Genomic Selection in peach for highly polygenic traits linked to yield and fruit quality. The accuracy of imputing missing genotypes was as high as 96%, and the genomic predictive ability was on average 0.65, but could be as high as 0.84 for fruit weight or 0.83 for titratable acidity. The estimated repeatability may prove very useful in the management of the typical long cycles involved in peach productions. All together, these results are very promising for the application of genomic selection to peach breeding programmes.info:eu-repo/semantics/publishedVersio

Loss of ap4s1 in zebrafish leads to neurodevelopmental defects resembling spastic paraplegia 52.

Autosomal recessive spastic paraplegia 52 is caused by biallelic mutations in AP4S1 which encodes a subunit of the adaptor protein complex 4 (AP-4). Using next-generation sequencing, we identified three novel unrelated SPG52 patients from a cohort of patients with cerebral palsy. The discovered variants in AP4S1 lead to reduced AP-4 complex formation in patient-derived fibroblasts. To further understand the role of AP4S1 in neuronal development and homeostasis, we engineered the first zebrafish model of AP-4 deficiency using morpholino-mediated knockdown of ap4s1. In this model, we discovered several phenotypes mimicking SPG52, including altered CNS development, locomotor deficits, and abnormal neuronal excitability

COVID-19-associated Guillain-Barré syndrome in the early pandemic experience in Lombardia (Italy)

Objective To estimate the incidence and describe clinical characteristics and outcome of GBS in COVID-19 patients (COVID19-GBS) in one of the most hit regions during the frst pandemic wave, Lombardia. Methods Adult patients admitted to 20 Neurological Units between 1/3–30/4/2020 with COVID19-GBS were included as part of a multi-center study organized by the Italian society of Hospital Neuroscience (SNO). Results Thirty-eight COVID19-GBS patients had a mean age of 60.7 years and male frequency of 86.8%. CSF albuminocytological dissociation was detected in 71.4%, and PCR for SARS-CoV-2 was negative in 19 tested patients. Based on neurophysiology, 81.8% of patients had a diagnosis of AIDP, 12.1% of AMSAN, and 6.1% of AMAN. The course was favorable in 76.3% of patients, stable in 10.5%, while 13.2% worsened, of which 3 died. The estimated occurrence rate in Lombardia ranges from 0.5 to 0.05 GBS cases per 1000 COVID-19 infections depending on whether you consider positive cases or estimated seropositive cases. When we compared GBS cases with the pre-pandemic period, we found a reduction of cases from 165 to 135 cases in the 2-month study period in Lombardia. Conclusions We detected an increased incidence of GBS in COVID-19 patients which can refect a higher risk of GBS in COVID-19 patients and a reduction of GBS events during the pandemic period possibly due to a lower spread of more common respiratory infectious diseases determined by an increased use of preventive measures

Clinical-Genetic Features Influencing Disability in Spastic Paraplegia Type 4: A Cross-sectional Study by the Italian DAISY Network

Background and objectives: Hereditary spastic paraplegias (HSPs) are a group of inherited rare neurologic disorders characterized by length-dependent degeneration of the corticospinal tracts and dorsal columns, whose prominent clinical feature is represented by spastic gait. Spastic paraplegia type 4 (SPG4, SPAST-HSP) is the most common form. We present both clinical and molecular findings of a large cohort of patients, with the aim of (1) defining the clinical spectrum of SPAST-HSP in Italy; (2) describing their molecular features; and (3) assessing genotype-phenotype correlations to identify features associated with worse disability. Methods: A cross-sectional retrospective study with molecular and clinical data collected in an anonymized database was performed. Results: A total of 723 Italian patients with SPAST-HSP (58% men) from 316 families, with a median age at onset of 35 years, were included. Penetrance was 97.8%, with men showing higher Spastic Paraplegia Rating Scale (SPRS) scores (19.67 ± 12.58 vs 16.15 ± 12.61, p = 0.009). In 26.6% of patients with SPAST-HSP, we observed a complicated phenotype, mainly including intellectual disability (8%), polyneuropathy (6.7%), and cognitive decline (6.5%). Late-onset cases seemed to progress more rapidly, and patients with a longer disease course displayed a more severe neurologic disability, with higher SPATAX (3.61 ± 1.46 vs 2.71 ± 1.20, p < 0.001) and SPRS scores (22.63 ± 11.81 vs 12.40 ± 8.83, p < 0.001). Overall, 186 different variants in the SPAST gene were recorded, of which 48 were novel. Patients with SPAST-HSP harboring missense variants displayed intellectual disability (14.5% vs 4.4%, p < 0.001) more frequently, whereas patients with truncating variants presented more commonly cognitive decline (9.7% vs 2.6%, p = 0.001), cerebral atrophy (11.2% vs 3.4%, p = 0.003), lower limb spasticity (61.5% vs 44.5%), urinary symptoms (50.0% vs 31.3%, p < 0.001), and sensorimotor polyneuropathy (11.1% vs 1.1%, p < 0.001). Increasing disease duration (DD) and abnormal motor evoked potentials (MEPs) were also associated with increased likelihood of worse disability (SPATAX score>3). Discussion: The SPAST-HSP phenotypic spectrum in Italian patients confirms a predominantly pure form of HSP with mild-to-moderate disability in 75% of cases, and slight prevalence of men, who appeared more severely affected. Early-onset cases with intellectual disability were more frequent among patients carrying missense SPAST variants, whereas patients with truncating variants showed a more complicated disease. Both longer DD and altered MEPs are associated with worse disability

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin

Genome-wide association study of common resistance to rust species in tetraploid wheat

Rusts of the genus Puccinia are wheat pathogens. Stem (black; Sr), leaf (brown; Lr), and stripe (yellow; Yr) rust, caused by Puccinia graminis f. sp. tritici (Pgt), Puccinia triticina (Pt), and Puccinia striiformis f. sp. tritici (Pst), can occur singularly or in mixed infections and pose a threat to wheat production globally in terms of the wide dispersal of their urediniospores. The development of durable resistant cultivars is the most sustainable method for controlling them. Many resistance genes have been identified, characterized, genetically mapped, and cloned; several quantitative trait loci (QTLs) for resistance have also been described. However, few studies have considered resistance to all three rust pathogens in a given germplasm. A genome-wide association study (GWAS) was carried out to identify loci associated with resistance to the three rusts in a collection of 230 inbred lines of tetraploid wheat (128 of which were Triticum turgidum ssp. durum) genotyped with SNPs. The wheat panel was phenotyped in the field and subjected to growth chamber experiments across different countries (USA, Mexico, Morocco, Italy, and Spain); then, a mixed linear model (MLM) GWAS was performed. In total, 9, 34, and 5 QTLs were identified in the A and B genomes for resistance to Pgt, Pt, and Pst, respectively, at both the seedling and adult plant stages. Only one QTL on chromosome 4A was found to be effective against all three rusts at the seedling stage. Six QTLs conferring resistance to two rust species at the adult plant stage were mapped: three on chromosome 1B and one each on 5B, 7A, and 7B. Fifteen QTLs conferring seedling resistance to two rusts were mapped: five on chromosome 2B, three on 7B, two each on 5B and 6A, and one each on 1B, 2A, and 7A. Most of the QTLs identified were specific for a single rust species or race of a species. Candidate genes were identified within the confidence intervals of a QTL conferring resistance against at least two rust species by using the annotations of the durum (cv. ‘Svevo’) and wild emmer wheat (‘Zavitan’) reference genomes. The 22 identified loci conferring resistance to two or three rust species may be useful for breeding new and potentially durable resistant wheat cultivars