Variants in CHEK2 other than 1100delC do not make a major contribution to breast cancer susceptibility

We recently reported that a sequence variant in the cell-cycle-checkpoint kinase CHEK2 (CHEK2 1100delC) is a low-penetrance breast cancer-susceptibility allele in noncarriers of BRCA1 or BRCA2 mutations. To investigate whether other CHEK2 variants confer susceptibility to breast cancer, we screened the full CHEK2 coding sequence in BRCA1/2-negative breast cancer cases from 89 pedigrees with three or more cases of breast cancer. We identified one novel germline variant, R117G, in two separate families. To evaluate the possible association of R117G and two germline variants repo

System for deployment of groups of unmanned micro aerial vehicles in GPS-denied environments using onboard visual relative localization

A complex system for control of swarms of micro aerial vehicles (MAV), in literature also called as unmanned aerial vehicles (UAV) or unmanned aerial systems (UAS), stabilized via an onboard visual relative localization is described in this paper. The main purpose of this work is to verify the possibility of self-stabilization of multi-MAV groups without an external global positioning system. This approach enables the deployment of MAV swarms outside laboratory conditions, and it may be considered an enabling technique for utilizing fleets of MAVs in real-world scenarios. The proposed visual-based stabilization approach has been designed for numerous different multi-UAV robotic applications (leader-follower UAV formation stabilization, UAV swarm stabilization and deployment in surveillance scenarios, cooperative UAV sensory measurement) in this paper. Deployment of the system in real-world scenarios truthfully verifies its operational constraints, given by limited onboard sensing suites and processing capabilities. The performance of the presented approach (MAV control, motion planning, MAV stabilization, and trajectory planning) in multi-MAV applications has been validated by experimental results in indoor as well as in challenging outdoor environments (e.g., in windy conditions and in a former pit mine)

Marketing of unproven stem cell-based interventions:A call to action

Commercial promotion of unsupported therapeutic uses of stem cells is a global problem that has proven resistant to regulatory efforts. Here, we suggest a coordinated approach at the national and international levels focused on engagement, harmonization, and enforcement to reduce the risks associated with direct-to-consumer marketing of unproven stem cell treatments

Regenerative medicine in society : interdisciplinary perspectives (Part 1)

This Digital Gateway brings together 29 short contributions of leading inter-disciplinary scholars on regenerative medicine. These contributions are written for patients, practitioners, and the wider public

Regenerative medicine in society: Introduction to the digital resource

This digital resource accompanies the publication of the double special issue ‘Regenerative Medicine in Society – Interdisciplinary Perspectives’ in the journal Regenerative Medicine (Part 1 and Part 2 ). It contains free-to-access summaries (and downloadable PDFs) of each of the articles written by leading international academics. Our aspiration is that this material will be read, discussed and ultimately used by policymakers, regulators, funders, healthcare leaders, people affected by conditions, professionals and the wider public to inform their decisions regarding the future of Regenerative Medicine

Foreword to special focus issue on regenerative medicine in society : interdisciplinary perspectives (Part I)

During the last two decades, funding bodies in many countries have financed a growing number of interdisciplinary research projects that have examined the social, ethical, regulatory, legal, economic and healthcare aspects of the regenerative medicine field. This emerging body of research has contributed to the shaping and evaluation of regulations and policies, the facilitation of public debate and engagement, and the critical reflection of the practices, limits and values through which new therapeutic strategies are translated from the lab bench to patients, healthcare systems and the market. It has also played a vital role in identifying and discussing the challenges and opportunities that result from the globalization of regenerative medicine research and the existence of regulatory, cultural and socio-economic differences between countries

A protein encoded by a group I intron in Aspergillus nidulans directly assists RNA splicing and is a DNA endonuclease

Some group I introns self-splice in vitro, but almost all are thought to be assisted by proteins in vivo. Mutational analysis has shown that the splicing of certain group I introns depends upon a maturase protein encoded by the intron itself. However the effect of a protein on splicing can be indirect. We now provide evidence that a mitochondrial intron-encoded protein from Aspergillus nidulans directly facilitates splicing in vitro. This demonstrates that a maturase is an RNA splicing protein. The protein-assisted reaction is as fast as that of any other known group I intron. Interestingly the protein is also a DNA endonuclease, an activity required for intron mobilization. Mobile elements frequently encode proteins that promote their propagation. Intron-encoded proteins that also assist RNA splicing would facilitate both the transposition and horizontal transmission of introns

A multicenter study of cancer incidence in CHEK2 1100delC mutation carriers

The CHEK2 1100delC protein-truncating mutation has a carrier frequency of approximately 0.7% in Northern and Western European populations and confers an approximately 2-fold increased risk of breast cancer. It has also been suggested to increase risks of colorectal and prostate cancer, but its involvement with these or other types of cancer has not been confirmed. The incidence of cancer other than breast cancer in 11,116 individuals from 734 non-BRCA1/2 breast cancer families from the United Kingdom, Germany, Netherlands, and the United States was compared with that predicted by population rates. Relative risks (RR) to carriers and noncarriers were estimated by maximum likelihood, via the expectation-maximization algorithm to allow for unknown genotypes. Sixty-seven families contained at least one tested CHEK2 1100delC mutation carrier. There was evidence of underreporting of cancers in male relatives (422 cancers observed, 860 expected) but not in females (322 observed, 335 expected); hence, we focused on cancer risks in female carriers. The risk of cancers other than breast cancer in female carriers was not significantly elevated, although a modest increase in risk could not be excluded (RR, 1.18; 95% confidence interval, 0.64-2.17). The carrier risk was not significantly raised for any individual cancer site, including colorectal cancer (RR, 1.60; 95% confidence interval, 0.54-4.71). However, between ages 20 to 50 years, the risks of colorectal and lung cancer were both higher in female carriers than noncarriers (P = 0.041 and 0.0001, respectively). There was no evidence of a higher prostate cancer risk in carriers than noncarriers (P = 0.26), although underreporting of male cancers limited our power to detect such a difference. Our results suggest that the risk of cancer associated with CHEK2 1100delC mutations is restricted to breast cancer, although we cannot rule out a small increase in overall cancer ris