‘Exceptional sons' from Drosophila melanogaster mothers carrying a balancer X chromosome

This study reports on exceptional males which are obtained by using Drosophila melanogaster mothers carrying the balancers In(l)FM6 or In(l)FM7 as one of their X chromosomes. The phenomenon was first observed in interspecific crosses between D. melanogaster females and males of its closest relatives which normally produce unisexual female hybrid progeny. Whereas hybrid sons from these crosses die as third instar larvae, the presence of the particular X balancers in the mother allows a low percentage of sons to survive. Similar sterile males are also observed among non- hybrid flies. Data are presented which suggest that the males thus generated could be hyperploid for part of their X chromosome as a result of a meiotic event in their mothers or else they could start life as female zygotes and change sex through a mitotic event at an early stag

Versatile Multi-Contact Planning and Control for Legged Loco-Manipulation

Loco-manipulation planning skills are pivotal for expanding the utility of robots in everyday environments. These skills can be assessed based on a system's ability to coordinate complex holistic movements and multiple contact interactions when solving different tasks. However, existing approaches have been merely able to shape such behaviors with hand-crafted state machines, densely engineered rewards, or pre-recorded expert demonstrations. Here, we propose a minimally-guided framework that automatically discovers whole-body trajectories jointly with contact schedules for solving general loco-manipulation tasks in pre-modeled environments. The key insight is that multi-modal problems of this nature can be formulated and treated within the context of integrated Task and Motion Planning (TAMP). An effective bilevel search strategy is achieved by incorporating domain-specific rules and adequately combining the strengths of different planning techniques: trajectory optimization and informed graph search coupled with sampling-based planning. We showcase emergent behaviors for a quadrupedal mobile manipulator exploiting both prehensile and non-prehensile interactions to perform real-world tasks such as opening/closing heavy dishwashers and traversing spring-loaded doors. These behaviors are also deployed on the real system using a two-layer whole-body tracking controller

Selection of patients with germline MLH1 mutated Lynch syndrome by determination of MLH1 methylation and BRAF mutation

Lynch syndrome is one of the most common hereditary colorectal cancer (CRC) syndrome and is caused by germline mutations of MLH1, MSH2 and more rarely MSH6, PMS2, MLH3 genes. Whereas the absence of MSH2 protein is predictive of Lynch syndrome, it is not the case for the absence of MLH1 protein. The purpose of this study was to develop a sensitive and cost effective algorithm to select Lynch syndrome cases among patients with MLH1 immunohistochemical silencing. Eleven sporadic CRC and 16 Lynch syndrome cases with MLH1 protein abnormalities were selected. The BRAF c.1799T>A mutation (p.Val600Glu) was analyzed by direct sequencing after PCR amplification of exon 15. Methylation of MLH1 promoter was determined by Methylation-Sensitive Single-Strand Conformation Analysis. In patients with Lynch syndrome, there was no BRAF mutation and only one case showed MLH1 methylation (6%). In sporadic CRC, all cases were MLH1 methylated (100%) and 8 out of 11 cases carried the above BRAF mutation (73%) whereas only 3 cases were BRAF wild type (27%). We propose the following algorithm: (1) no further molecular analysis should be performed for CRC exhibiting MLH1 methylation and BRAF mutation, and these cases should be considered as sporadic CRC; (2) CRC with unmethylated MLH1 and negative for BRAF mutation should be considered as Lynch syndrome; and (3) only a small fraction of CRC with MLH1 promoter methylation but negative for BRAF mutation should be true Lynch syndrome patients. These potentially Lynch syndrome patients should be offered genetic counselling before searching for MLH1 gene mutation

A mutagenic PCR identifies isolates of Borrelia garinii responsible for Lyme borreliosis

Borrelia garinii is one of the three major Borreliae responsible for Lyme borreliosis in Europe. We have characterized a protein of B. garinii (VS102) and a genomic fragment from the gene encoding this protein was cloned. The DNA sequence of the fragment showed high homology with a known gene of B. burgdorferi sensu stricto. The protein encoded by this gene in B. burgdorferi sensu stricto is a phosphocarrier protein (histidine-containing protein). A mutation T to G polymorphism at codon 57 was found to be specific to B. garinii. A PCR-based approach that allows the rapid detection of this mutation made it possible to specifically discriminate B. garinii from other B. burgdorferi genospecies with high sensitivity and specificit

Evidence for genetic anticipation in hereditary non-polyposis colorectal cancer

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal, dominantly inherited, colorectal cancer (CRC) predisposition syndrome caused by germline mutations in DNA mismatch repair (MMR) genes, predominantly MLH1 and MSH2. Thus far, only limited data exist on the occurrence of genetic anticipation in HNPCC, i.e. the earlier age at diagnosis of CRC in successive generations. Performing nonparametric distribution-free statistical analyses, we investigated 55 parent-child pairs who had been diagnosed with CRC and who came from 21 Swiss HNPCC families with characterised MMR germline mutation (15 in MLH1 and 6 in MSH2). The overall median age at diagnosis was 43years, with an interquartile range (IQR) of 14 and incidence ages ranging from 18 to 62years. Descendants of HNPCC patients (median age at diagnosis 39years, IQR=12) were found to be diagnosed with CRC significantly earlier than their parents (47years, IQR=10), with the median of the paired age difference amounting to 8years (IQR=15; P<0.0001). Birth cohort effects could be excluded, since the same, statistically significant, age difference was also observed in the oldest offspring birth cohort (birth year <1916; P=0.01). Genetic anticipation appeared to be more pronounced when the disease allele was transmitted through the father than through the mother (median age difference 11 vs. 4years, respectively; both P<0.01). If confirmed in larger, ideally prospective studies, these results may have important implications for genetic counselling and clinical management of HNPCC familie

Double frameshift mutations in APC and MSH2 in the same individual

Heterozygous germline DNA mismatch repair gene mutations are typically associated with HNPCC. Here we report the case of a proband whose father was known for familial adenomatous polyposis. The number of polyps (<10) was not typical of polyposis, therefore the diagnosis of HNPCC was entertained. Microsatellite instability analyses were performed on peripheral blood and biopsy of a right-sided dysplastic adenoma. The tumour tissue showed high-grade instability and subsequently immunohistochemistry showed that neither MSH2 nor MSH6 proteins were expressed in tumour cells. Prophylactic colectomy was performed and an adenocarcinoma developing within the adenoma was diagnosed (pT1N0). Genomic DNA analysis revealed a novel mutation in MSH2 as: a frameshift mutation in exon 7 (c.1,191_1,192dupG). Both parents of the proband were analyzed for MSH2 and APC mutations, and in the father a truncating mutation in exon 15 of APC was identified as del3471-3473GAGA. This mutation was found to be present in the proband. His mother was found to bear the MSH2 exon 7 mutation. At follow-up, the proband was diagnosed with fundic, antral and duodenal adenomas (one fundic adenoma showed low-grade dysplasia). Several tubular rectal adenomas with low-grade dysplasia were excised. The patient later developed an intra-abdominal desmoid tumou