In silico identification of genetically attenuated vaccine candidate genes for Plasmodium liver stage.

Genetically attenuated parasites (GAPs) that lack genes essential for the liver stage of the malaria parasite, and therefore cause developmental arrest, have been developed as live vaccines in rodent malaria models and recently been tested in humans. The genes targeted for deletion were often identified by trial and error. Here we present a systematic gene - protein and transcript - expression analyses of several Plasmodium species with the aim to identify candidate genes for the generation of novel GAPs.

Radiosensitivity of Patient-Derived Glioma Stem Cell 3-Dimensional Cultures to Photon, Proton, and Carbon Irradiation.

Purpose: To investigate the radiosensitivity of primary glioma stem cell (GSC) cultures with different CD133 status in a 3-dimensional (3D) model after photon versus proton versus carbon irradiation.

Methods And Materials: Human primary GSC spheroid cultures were established from tumor specimens of six consented glioblastoma patients. Human U87MG was used as a classical glioblastoma radioresistant cell line.

Plasmodium falciparum coronin organizes arrays of parallel actin filaments potentially guiding directional motility in invasive malaria parasites.

Background: Gliding motility in Plasmodium parasites, the aetiological agents of malaria disease, is mediated by an actomyosin motor anchored in the outer pellicle of the motile cell. Effective motility is dependent on a parasite myosin motor and turnover of dynamic parasite actin filaments. To date, however, the basis for directional motility is not known.

CD8+ tumour-infiltrating lymphocytes in relation to HPV status and clinical outcome in patients with head and neck cancer after postoperative chemoradiotherapy: A multicentre study of the German cancer consortium radiation oncology group (DKTK-ROG).

We examined the prognostic value of tumour-infiltrating lymphocytes (TILs) in patients with squamous cell carcinoma of the head and neck (SCCHN) after surgery and postoperative cisplatin-based chemoradiotherapy. FFPE-tissue originating from the surgery of 161 patients treated in 8 DKTK partner sites was immunohistochemically stained for CD3 and CD8. Their expression was correlated with clinicopathological characteristics as well as overall survival (OS), local progression-free survival (LPFS) and distant metastases free-survival (DMFS), also in the context of the HPV16-DNA/p16 status.

Active migration and passive transport of malaria parasites.

Malaria parasites undergo a complex life cycle between their hosts and vectors. During this cycle the parasites invade different types of cells, migrate across barriers, and transfer from one host to another. Recent literature hints at a misunderstanding of the difference between active, parasite-driven migration and passive, circulation-driven movement of the parasite or parasite-infected cells in the various bodily fluids of mosquito and mammalian hosts.

Nanoscopic Localization of Surface-Exposed Antigens of Borrelia burgdorferi.

Borrelia burgdorferi sensu lato, the causative agent of Lyme disease, is transmitted to humans through the bite of infected Ixodes spp. ticks. Successful infection of vertebrate hosts necessitates sophisticated means of the pathogen to escape the vertebrates' immune system.

The combinatorial complexity of cancer precision medicine.

Precision medicine approaches have recently been developed that offer therapies targeting mainly single genetic alterations in malignant tumors. However, next generation sequencing studies have shown that tumors normally harbor multiple genetic alterations, which could explain the so far limited successes of personalized medicine, despite considerable benefits in certain cases. Combination therapies may contribute to a solution, but will pose a major challenge for clinical trials evaluating those therapies.

Synergistic effects of crizotinib and radiotherapy in experimental EML4-ALK fusion positive lung cancer.

Background And Purpose: Non-small cell lung cancer (NSCLC) patients with chromosomal rearrangements of the anaplastic lymphoma kinase gene (ALK) are sensitive to the tyrosine kinase inhibitor crizotinib. We aimed to investigate the effects of combined radiotherapy and crizotinib in ALK-positive vs. wild type NSCLC models.

Host cell phosphatidylcholine is a key mediator of malaria parasite survival during liver stage infection.

During invasion, Plasmodium, the causative agent of malaria, wraps itself in a parasitophorous vacuole membrane (PVM), which constitutes a critical interface between the parasite and its host cell. Within hepatocytes, each Plasmodium sporozoite generates thousands of new parasites, creating high demand for lipids to support this replication and enlarge the PVM. Here, a global analysis of the total lipid repertoire of Plasmodium-infected hepatocytes reveals an enrichment of neutral lipids and the major membrane phospholipid, phosphatidylcholine (PC).

HPV16 DNA status is a strong prognosticator of loco-regional control after postoperative radiochemotherapy of locally advanced oropharyngeal carcinoma: results from a multicentre explorative study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG).

Objective: To investigate the impact of HPV status in patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who received surgery and cisplatin-based postoperative radiochemotherapy.

Materials And Methods: For 221 patients with locally advanced squamous cell carcinoma of the hypopharynx, oropharynx or oral cavity treated at the 8 partner sites of the German Cancer Consortium, the impact of HPV DNA, p16 overexpression and p53 expression on outcome were retrospectively analysed. The primary endpoint was loco-regional tumour control; secondary endpoints were distant metastases and overall survival.

3 T MRI-based measurements for the integrity of the female pelvic floor in 25 healthy nulliparous women.

Aims: Measurements indicating a loss of integrity of the levator ani muscle, which is an integral part of the pelvic floor, have been subject of recent studies using translabial ultrasound and 3D-MRI-models. We transferred these measurements into 2D-3 T-MR-images for clinical routine, as it is objective and does not need exhaustive post-processing.

Methods: The trial was accepted by the local ethics committee.

Compression of human primary cementoblasts leads to apoptosis: A possible cause of dental root resorption?

Objectives: One of the most common side effects of orthodontic treatment is root resorption on the pressure side of tooth movement. This is usually repaired by cementoblasts, but 1-5 % of patients eventually experiences a marked reduction in root length because no repair has occurred. The reason why cementoblasts should lose their repair function in such cases is not well understood.

Intersectoral action: local governments promoting health.

Many local governments around the world promote health through intersectoral action, but to date there has been little systematic evidence of these experiences. To bridge this gap, the World Health Organization Centre for Health Development conducted a study in 2011-2013 on intersectoral action for health (ISA) at local government level. A total of 25 cases were included in the final review.

A cysteine protease inhibitor of plasmodium berghei is essential for exo-erythrocytic development.

Plasmodium parasites express a potent inhibitor of cysteine proteases (ICP) throughout their life cycle. To analyze the role of ICP in different life cycle stages, we generated a stage-specific knockout of the Plasmodium berghei ICP (PbICP). Excision of the pbicb gene occurred in infective sporozoites and resulted in impaired sporozoite invasion of hepatocytes, despite residual PbICP protein being detectable in sporozoites.

Vascularized treatment options for reconstruction of the ascending mandible with introduction of the femoral medial epicondyle free flap.

Reconstruction of the ascending portion of the mandible, including the angle, ramus, and condyle, can be a challenging surgical problem. Many treatment options are available, but no single procedure has been able to restore long-term form and function in every case. Currently, autologous nonvascularized bone grafts are the most common treatment, with the costochondral graft as the historic leader.

Size and synchronization of auditory cortex promotes musical, literacy, and attentional skills in children.

Playing a musical instrument is associated with numerous neural processes that continuously modify the human brain and may facilitate characteristic auditory skills. In a longitudinal study, we investigated the auditory and neural plasticity of musical learning in 111 young children (aged 7-9 y) as a function of the intensity of instrumental practice and musical aptitude. Because of the frequent co-occurrence of central auditory processing disorders and attentional deficits, we also tested 21 children with attention deficit (hyperactivity) disorder [AD(H)D].

Intramitochondrial recruitment of endolysosomes mediates Smac degradation and constitutes a novel intrinsic apoptosis antagonizing function of XIAP E3 ligase.

Intrinsic apoptosis involves BH3-only protein activation of Bax/Bak-mediated mitochondrial outer membrane permeabilization (MOMP). Consequently, cytochrome c is released from the mitochondria to activate caspases, and Smac (second mitochondria-derived activator of caspases) to inhibit XIAP-mediated caspase suppression. Dysfunctional mitochondria can be targeted for lysosomal degradation via autophagy (mitophagy), or directly through mitochondria-derived vesicle transport.

For the next trick: new discoveries in radiobiology applied to glioblastoma.

Glioblastoma (GBM) is the most common malignant brain tumor. Radiotherapy post surgical resection remained the mainstay of the management of GBM for decades until the addition of temozolomide was shown to prolong the median overall survival (OS) by 2.5 months to 14.

Magnetic resonance imaging of cervical carcinoma using an endorectal surface coil.

Introduction: The objective of this trial is to investigate the diagnostic value of magnetic resonance imaging (MRI) with an endorectal surface coil for precise local staging of patients with histologically proven cervical cancer by comparing the radiological, clinical, and histological results.

Materials And Methods: Women with cervical cancer were recruited for this trial between February 2007, and September 2010. All the patients were clinically staged according to the FIGO classification and underwent radiological staging by MRI that employed an endorectal surface coil.

Structural differences explain diverse functions of Plasmodium actins.

Actins are highly conserved proteins and key players in central processes in all eukaryotic cells. The two actins of the malaria parasite are among the most divergent eukaryotic actins and also differ from each other more than isoforms in any other species. Microfilaments have not been directly observed in Plasmodium and are presumed to be short and highly dynamic.

Management of subcondylar mandible fractures in the adult patient.

The treatment of subcondylar mandible fractures is a topic of debate and can be variable even though these fractures are commonly seen. Historically, the treatment algorithm was between open reduction and closed treatment. Now, recent technical advances regarding the use of the endoscope in the field of craniofacial surgery provide additional treatment options.

MRI findings before and after prolapse surgery.

Background: Therapeutical outcome after prolapse surgery is evaluated using a standardized grading system based on maximum prolapse extent, which might not provide the full picture of the patient's subjective outcome. We therefore applied an evaluation method, which is detached from a grading system.

Purpose: To evaluate the impact of pelvic organ mobility in dynamic magnetic resonance imaging (MRI) before and after mesh-repair surgery in patients with symptomatic pelvic organ prolapse.

Tunable substrates unveil chemical complementation of a genetic cell migration defect.

Cell migration is dependent on a number of physical and chemical parameters of the substrate that influence cellular signaling events as cell surface receptors interact with the substrate. These events can strengthen or loosen the contact of the cell with its environment and need to be orchestrated for efficient motility. A set of tunable substrates was used in combination with quantitative imaging to probe for potentially subtle differences in genetically modified and chemically treated rapidly migrating cells.

Cryo-electron tomography reveals four-membrane architecture of the Plasmodium apicoplast.

Background: The apicoplast is a plastid organelle derived from a secondary endosymbiosis, containing biosynthetic pathways essential for the survival of apicomplexan parasites. The Toxoplasma apicoplast clearly possesses four membranes but in related Plasmodium spp. the apicoplast has variably been reported to have either three or four membranes.