POLθ processes ssDNA gaps and promotes replication fork progression in BRCA1-deficient cells.

Polymerase theta (POLθ) is an error-prone DNA polymerase whose loss is synthetically lethal in cancer cells bearing breast cancer susceptibility proteins 1 and 2 (BRCA1/2) mutations. To investigate the basis of this genetic interaction, we utilized a small-molecule inhibitor targeting the POLθ polymerase domain. We found that POLθ processes single-stranded DNA (ssDNA) gaps that emerge in the absence of BRCA1, thus promoting unperturbed replication fork progression and survival of BRCA1 mutant cells.

POLθ prevents MRE11-NBS1-CtIP-dependent fork breakage in the absence of BRCA2/RAD51 by filling lagging-strand gaps.

POLθ promotes repair of DNA double-strand breaks (DSBs) resulting from collapsed forks in homologous recombination (HR) defective tumors. Inactivation of POLθ results in synthetic lethality with the loss of HR genes BRCA1/2, which induces under-replicated DNA accumulation. However, it is unclear whether POLθ-dependent DNA replication prevents HR-deficiency-associated lethality.

Smart Artificial Soft Tissue - Application to a Hybrid Simulator for Training of Laryngeal Pacemaker Implantation.

Surgical simulators are safe and evolving educational tools for developing surgical skills. In particular, virtual and hybrid simulators are preferred due to their detailedness, customization and evaluation capabilities. To accelerate the revolution of a novel class of hybrid simulators, a Smart Artificial Soft Tissue is presented here, that determines the relative position of conductive surgical instruments in artificial soft tissue by inverse resistance mappings without the need for a fixed reference point.

miR-1 sustains muscle physiology by controlling V-ATPase complex assembly.

Muscle function requires unique structural and metabolic adaptations that can render muscle cells selectively vulnerable, with mutations in some ubiquitously expressed genes causing myopathies but sparing other tissues. We uncovered a muscle cell vulnerability by studying miR-1, a deeply conserved, muscle-specific microRNA whose ablation causes various muscle defects. Using , we found that miR-1 represses multiple subunits of the ubiquitous vacuolar adenosine triphosphatase (V-ATPase) complex, which is essential for internal compartment acidification and metabolic signaling.

Thickness accuracy of virtually designed patient-specific implants for large neurocranial defects.

The combination of computer-aided design (CAD) techniques based on computed tomography (CT) data to generate patient-specific implants is in use for decades. However, persisting disadvantages are complicated design procedures and rigid reconstruction protocols, for example, for tailored implants mimicking the patient-specific thickness distribution of missing cranial bone. In this study we used two different approaches, CAD- versus thin-plate spline (TPS)-based implants, to reconstruct extensive unilateral and bilateral cranial defects in three clinical cases.

Worker ants promote outbreeding by transporting young queens to alien nests.

Choosing the right mating partner is one of the most critical decisions in the life of a sexually reproducing organism and is the basis of sexual selection. This choice is usually assumed to be made by one or both of the sexual partners. Here, we describe a system in which a third party - the siblings - promote outbreeding by their sisters: workers of the tiny ant Cardiocondyla elegans carry female sexuals from their natal nest over several meters and drop them in the nest of another, unrelated colony to promote outbreeding with wingless, stationary males.

Targeting the DNA Repair Enzyme Polymerase θ in Cancer Therapy.

Targeted cancer therapies represent a milestone towards personalized treatment as they function via inhibition of cancer-specific alterations. Polymerase θ (POLQ), an error-prone translesion polymerase, also involved in DNA double-strand break (DSB) repair, is often upregulated in cancer. POLQ is synthetic lethal with various DNA repair genes, including known cancer drivers such as BRCA1/2, making it essential in homologous recombination-deficient cancers.

Characterization of tissue properties in epidural needle insertion on human specimen and synthetic materials.

The force experienced while inserting an 18-gauge Tuohy needle into the epidural space or dura is one of only two feedback components perceived by an anaesthesiologist to deduce the needle tip position in a patient's spine. To the best of the authors knowledge, no x-ray validated measurements of these forces are currently available to the public. A needle insertion force recording during an automated insertion of an 18-gauge Tuohy needle into human vertebral segments of four female donors was conducted.

Publisher Correction: Human DEF6 deficiency underlies an immunodeficiency syndrome with systemic autoimmunity and aberrant CTLA-4 homeostasis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Development of open-cell polyurethane-based bone surrogates for biomechanical testing of pedicle screws.

Artificial bones made of polyurethane are frequently used as an alternative to human bone for biomechanical testing. However, the biomechanical characteristics of these materials are often not validated against those of human bones. Thus, synthetic bone surrogates reflecting procedure-specific biomechanical properties of human bones are necessary for reliable implant design and testing.

Methuselah's daughters: Paternal age has little effect on offspring number and quality in ants.

Male age may directly or indirectly affect the fitness of their female mating partners and their joint progeny. While in some taxa of insects, old males make better mates and fathers, young males excel in others. Males of most social Hymenoptera are relatively short lived and because of testis degeneration have only a limited sperm supply.

Bone surrogates provide authentic onlay graft fixation torques.

Onlay graft bone augmentation is a standard practice to restore the loss of height of the alveolar ridge following loss of a tooth. Cranial grafts, lifted from the parietal bone, are sandwiched and used to bridge the bony defect in the jaw by means of small screws. During the elevation of the covering gum and subsequent screw placement, care has to be taken in order to preserve underlying nerves.

Characterization of polyurethane-based synthetic vertebrae for spinal cement augmentation training.

Vertebral augmentation techniques are used to stabilize impacted vertebrae. To minimize intraoperative risks, a solid education of surgeons is desirable. Thus, to improve education of surgeons as well as patient safety, the development of a high-fidelity simulator for the surgical training of cement augmentation techniques was initiated.

Characterization of an artificial skull cap for cranio-maxillofacial surgery training.

Cranial grafts are favored to reconstruct skeletal defects because of their reduced resorption and their histocompatibility. Training possibilities for novice surgeons include the "learning by doing" on the patient, specimens or simulators. Although the acceptance of simulators is growing, the major drawback is the lack of validated bone models.

Procedure-Specific Validation of Artificial Vertebrae.

Objective: The development of a novel hybrid patient simulator was initiated to provide a safe training possibility for novice surgeons. Integrated artificial vertebrae should be able to realistically mimic the haptics of transpedicular vertebroplasty instrument insertion and pedicle screw placement. Therefore, new open-celled material compositions were developed, tested, and validated with reference to elderly human vertebrae.

Validation of a simulator for cranial graft lift training: Face, content, and construct validity.

Purpose: Surgical skills can be improved through practical exercise. The use of specimens, human as well as animal, or live animals for surgical training is limited due to ethical concerns. Drawbacks of simulators are costs, fidelity and creditibility.

Individual- and ejaculate-specific sperm traits in ant males.

Sperm cells are the most morphologically diverse cells across animal taxa. Within species, sperm and ejaculate traits have been suggested to vary with the male's competitive environment, e.g.

Effect of alternating postures on cognitive performance for healthy people performing sedentary work.

Prolonged sitting is a risk factor for several diseases and the prevalence of worksite-based interventions such as sit-to-stand workstations is increasing. Although their impact on sedentary behaviour has been regularly investigated, the effect of working in alternating body postures on cognitive performance is unclear. To address this uncertainty, 45 students participated in a two-arm, randomised controlled cross-over trial under laboratory conditions.

Novel synthetic vertebrae provide realistic haptics for pedicle screw placement.

During vertebral surgery, misplaced pedicle screws can harm vital neural and vascular structures. Haptic distinction between cortical and cancellous bone structures is therefore essential for correct screw placement. This tactile experience during pedicle screw placement can be obtained by training on human or animal specimens even if expensive or ethically questionable.

A hybrid, low-cost tissue-like epidural needle insertion simulator.

Epidural and spinal anesthesia are mostly performed "blind" without any medical imaging. Currently, training of these procedures is performed on human specimens, virtual reality systems, manikins and mostly in clinical practice supervised by a professional. In this study a novel hybrid, low-cost patient simulator for the training of needle insertion into the epidural space was designed.

Interaction of 2A proteinase of human rhinovirus genetic group A with eIF4E is required for eIF4G cleavage during infection.

In enteroviruses, the inhibition of protein synthesis from capped host cell mRNA is catalyzed by the virally encoded 2A proteinase (2A), which cleaves eukaryotic initiation factors (eIF) 4GI and 4GII. Despite much investigation, the exact mechanism of 2A cleavage remains however unclear. Here, we identify the domains responsible for the eIF4E/HRV2 2A interaction using molecular modelling and describe mutations that impair this interaction and delay in vitro cleavage of eIF4G isoforms.

Ant queens increase their reproductive efforts after pathogen infection.

Infections with potentially lethal pathogens may negatively affect an individual's lifespan and decrease its reproductive value. The terminal investment hypothesis predicts that individuals faced with a reduced survival should invest more into reproduction instead of maintenance and growth. Several studies suggest that individuals are indeed able to estimate their body condition and to increase their reproductive effort with approaching death, while other studies gave ambiguous results.