Biallelic GINS2 variant p.(Arg114Leu) causes Meier-Gorlin syndrome with craniosynostosis

Contains fulltext : 284813.pdf (Publisher’s version ) (Open Access)INTRODUCTION: Replication of the nuclear genome is an essential step for cell division. Pathogenic variants in genes coding for highly conserved components of the DNA replication machinery cause Meier-Gorlin syndrome (MGORS). OBJECTIVE: Identification of novel genes associated with MGORS. METHODS: Exome sequencing was performed to investigate the genotype of an individual presenting with prenatal and postnatal growth restriction, a craniofacial gestalt of MGORS and coronal craniosynostosis. The analysis of the candidate variants employed bioinformatic tools, in silico structural protein analysis and modelling in budding yeast. RESULTS: A novel homozygous missense variant NM_016095.2:c.341G>T, p.(Arg114Leu), in GINS2 was identified. Both non-consanguineous healthy parents carried this variant. Bioinformatic analysis supports its classification as pathogenic. Functional analyses using yeast showed that this variant increases sensitivity to nicotinamide, a compound that interferes with DNA replication processes. The phylogenetically highly conserved residue p.Arg114 localises at the docking site of CDC45 and MCM5 at GINS2. Moreover, the missense change possibly disrupts the effective interaction between the GINS complex and CDC45, which is necessary for the CMG helicase complex (Cdc45/MCM2-7/GINS) to accurately operate. Interestingly, our patient's phenotype is strikingly similar to the phenotype of patients with CDC45-related MGORS, particularly those with craniosynostosis, mild short stature and patellar hypoplasia. CONCLUSION: GINS2 is a new disease-associated gene, expanding the genetic aetiology of MGORS

Foreword: Control and Conservation of Lampreys Beyond 2020 – Proceedings from the 3rd Sea Lamprey International Symposium (SLIS III)

This special issue summarizes outcomes from the 3rd Sea Lamprey International Symposium (SLIS III; Fig. 1) held 28 July – 2 August 2019 at Wayne State University in Detroit, Michigan, U.S.A. The first two symposia (SLIS I and SLIS II) were held 30 July – 8 August 1979 at Northern Michigan University in Marquette, Michigan and 14–18 August 2000 at Lake Superior State University in Sault Ste. Marie, Michigan, respectively. The published volumes from these symposia in 1980 (Canadian Journal of Fisheries and Aquatic Sciences, Volume 37, Issue 11) and 2003 (Journal of Great Lakes Research Volume 29, Supplement 1) have been invaluable references for the broader scientific community and for management agencies around the Laurentian Great Lakes; cited over 4800 and 3300 times, respectively. SLIS III was attended by over 150 scientists, biologists, resource managers, graduate students, and Commission advisors, including participants from Australia, Canada, China, Japan, New Zealand, Portugal, Spain, the United Kingdom, and the United States (Fig. 2). Similar to SLIS I and SLIS II, the goals of SLIS III were to provide a forum to (i) update and publish information on sea lamprey control and research on lampreys since SLIS II, (ii) exchange knowledge and ideas to bring practitioners to a common plateau of understanding, and (iii) develop innovative initiatives and stimulate new vigor in efforts to control sea lamprey in the Great Lakes and to conserve lampreys in their native ranges. The emphasis on conservation of lampreys is unique to SLIS III and reflects a heightened international recognition that scientific and management advances supporting sea lamprey control in the Great Lakes can benefit the global effort to conserve native lampreys and vice versa

Relative Tolerance of Nine Olve Cultivars to Pseudomonas savastanoi Causing Bacterial Knot Disease

Reactions of nine olive cultivars inoculated with olive or oleander strains of Pseudomonas savastanoi were evaluated under glasshouse conditions. Two quantitative indices of pathogenicity were used: 1. gall size from standardised inoculations, measured after 2 months; 2. rate of change of gall size with increasing inoculum concentration. These two indices were combined in a single plot that appears to give the best resolution of all data. Responses of olive cultivars to olive strains of P. savastanoi suggest that cultivars Carolea, Koroneiki, Leccino and Pendolino are the most tolerant, and that Barnea, Manzanillo, Picholine, Picual and a South Australian selection of Verdale are the least tolerant. Olive and oleander strains of P. savastanoi differed in virulence, and between-plant variability in reaction to inoculation was noted. Hypersensitive reactions do not appear to be part of mechanisms of tolerance. Olive strains of P. savastanoi affected all cultivars more severely than did equivalent inoculations with oleander strains

Quantum regression theorem for non-Markovian Lindblad equations

We find the conditions under which a quantum regression theorem can be assumed valid for non-Markovian master equations consisting in Lindblad superoperators with memory kernels. Our considerations are based on a generalized Born-Markov approximation, which allows us to obtain our results from an underlying Hamiltonian description. We demonstrate that a non-Markovian quantum regression theorem can only be granted in a stationary regime if the dynamics satisfies a quantum detailed balance condition. As an example we study the correlations of a two level system embedded in a complex structured reservoir and driven by an external coherent field.Comment: 14 pages, 5 figures. Extended version. The GBMA is deduced from projector technique. A new appendix is adde

Feeding strategies and energy to protein ratio on tambaqui performance and physiology

The objective of this work was to evaluate the effect of feed deprivation and refeeding with diets containing different energy to protein ratios (E/P) on the performance and physiology of juvenile tambaqui (Colossoma macropomum). A 4x2 factorial arrangement with three replicates was used, with four E/P ratios (11.5, 10.5, 9.5, and 8.5 kcal g-1 digestible energy per protein) and two feeding regimens (with and without deprivation), during 60 days. Fish from the food-deprived group were fasted for 14 days and refed from the fifteenth to the sixtieth day, whereas the remaining fish were fed for 60 days. At the end of the experimental period, weight of fish subjected to food deprivation was lower than that of those continuously fed; however, this condition did not influence the physiological parameters analyzed. Tambaqui fed 11.5 kcal g-1 achieved lower final weight than those fed with the other diets, in both regimens. Among the physiological parameters, only plasma protein presented significant increase in fish fed 8.5 kcal g-1, in both feeding regimens, probably due to the higher dietary protein concentration. These results indicate that fish show a partial compensatory growth, and that 10.5 kcal g-1 can be recommended for the diet of juvenile tambaqui

Wnt signalling and cancer stem cells

[Abstract] Intracellular signalling mediated by secreted Wnt proteins is essential for the establishment of cell fates and proper tissue patterning during embryo development and for the regulation of tissue homeostasis and stem cell function in adult tissues. Aberrant activation of Wnt signalling pathways has been directly linked to the genesis of different tumours. Here, the components and molecular mechanisms implicated in the transduction of Wnt signal, along with important results supporting a central role for this signalling pathway in stem cell function regulation and carcinogenesis will be briefly reviewed.Ministerio de Ciencia e Innovación; SAF2008-0060