Multiplex genome editing eliminates lactate production without impacting growth rate in mammalian cells.

The Warburg effect, which describes the fermentation of glucose to lactate even in the presence of oxygen, is ubiquitous in proliferative mammalian cells, including cancer cells, but poses challenges for biopharmaceutical production as lactate accumulation inhibits cell growth and protein production. Previous efforts to eliminate lactate production in cells for bioprocessing have failed as lactate dehydrogenase is essential for cell growth. Here, we effectively eliminate lactate production in Chinese hamster ovary and in the human embryonic kidney cell line HEK293 by simultaneous knockout of lactate dehydrogenases and pyruvate dehydrogenase kinases, thereby removing a negative feedback loop that typically inhibits pyruvate conversion to acetyl-CoA.

Importance of an N-terminal structural switch in the distinction between small RNA-bound and free ARGONAUTE.

ARGONAUTE (AGO) proteins bind to small non-coding RNAs to form RNA-induced silencing complexes. In the RNA-bound state, AGO is stable while RNA-free AGO turns over rapidly. Molecular features unique to RNA-free AGO that allow its specific recognition and degradation remain unknown.

Immediate effect of alone and combined virtual reality, gait-like muscle vibration and transcranial direct current stimulation on neuropathic pain after spinal cord injury: a pilot study.

Study Design: Quasi-experimental pilot study.

Objectives: Evaluate the immediate effect of virtual reality (VR), gait-like muscle vibration (MV) and transcranial direct current stimulation (tDCS) combined or alone on neuropathic pain in individuals with spinal cord injury (SCI).

Setting: Inpatient rehabilitation centre.

Multiplex genome editing eliminates the Warburg Effect without impacting growth rate in mammalian cells.

The Warburg effect is ubiquitous in proliferative mammalian cells, including cancer cells, but poses challenges for biopharmaceutical production, as lactate accumulation inhibits cell growth and protein production. Previous efforts to eliminate lactate production via knockout have failed in mammalian bioprocessing since lactate dehydrogenase has proven essential. However, here we eliminated the Warburg effect in Chinese hamster ovary (CHO) and HEK293 cells by simultaneously knocking out lactate dehydrogenase and regulators involved in a negative feedback loop that typically inhibits pyruvate conversion to acetyl-CoA.

Inferring secretory and metabolic pathway activity from omic data with secCellFie.

Understanding protein secretion has considerable importance in biotechnology and important implications in a broad range of normal and pathological conditions including development, immunology, and tissue function. While great progress has been made in studying individual proteins in the secretory pathway, measuring and quantifying mechanistic changes in the pathway's activity remains challenging due to the complexity of the biomolecular systems involved. Systems biology has begun to address this issue with the development of algorithmic tools for analyzing biological pathways; however most of these tools remain accessible only to experts in systems biology with extensive computational experience.

Ribosomal RNA 2'-O-methylation dynamics impact cell fate decisions.

Translational regulation impacts both pluripotency maintenance and cell differentiation. To what degree the ribosome exerts control over this process remains unanswered. Accumulating evidence has demonstrated heterogeneity in ribosome composition in various organisms.

Changing the channel: a qualitative analysis of an innovative video intervention to explore resident attitudes towards interprofessional collaboration on a Geriatric Medicine Unit.

Background: Medical learners develop a more positive attitude toward Interprofessional Collaboration (IPC) following Interprofessional Education (IPE) programs. However, IPE is not standardized, and the most effective teaching tool is unclear. The purpose of our study was to develop an IPE teaching tool for medical residents during an inpatient geriatric medicine rotation at an academic hospital, evaluate and explore the impact of the program on resident attitudes towards teamwork, and identify barriers and facilitators to interprofessional collaboration.

Inferring secretory and metabolic pathway activity from omic data with secCellFie.

Understanding protein secretion has considerable importance in the biotechnology industry and important implications in a broad range of normal and pathological conditions including development, immunology, and tissue function. While great progress has been made in studying individual proteins in the secretory pathway, measuring and quantifying mechanistic changes in the pathway's activity remains challenging due to the complexity of the biomolecular systems involved. Systems biology has begun to address this issue with the development of algorithmic tools for analyzing biological pathways; however most of these tools remain accessible only to experts in systems biology with extensive computational experience.

Transferability of Published Population Pharmacokinetic Models for Apixaban and Rivaroxaban to Subjects with Obesity Treated for Venous Thromboembolism: A Systematic Review and External Evaluations.

Apixaban and rivaroxaban have first-line use for many patients needing anticoagulation for venous thromboembolism (VTE). The pharmacokinetics of these drugs in non-obese subjects have been extensively studied, and, while changes in pharmacokinetics have been documented in obese patients, data remain scarce for these anticoagulants. The aim of this study was to perform an external validation of published population pharmacokinetic (PPK) models of apixaban and rivaroxaban in a cohort of obese patients with VTE.

Regulation of translation by site-specific ribosomal RNA methylation.

Ribosomes are complex ribozymes that interpret genetic information by translating messenger RNA (mRNA) into proteins. Natural variation in ribosome composition has been documented in several organisms and can arise from several different sources. A key question is whether specific control over ribosome heterogeneity represents a mechanism by which translation can be regulated.

Increased mAb production in amplified CHO cell lines is associated with increased interaction of CREB1 with transgene promoter.

Most therapeutic monoclonal antibodies in biopharmaceutical processes are produced in Chinese hamster ovary (CHO) cells. Technological advances have rendered the selection procedure for higher producers a robust protocol. However, information on molecular mechanisms that impart the property of hyper-productivity in the final selected clones is currently lacking.

Unmanned aerial image dataset: Ready for 3D reconstruction.

Unmanned aerial vehicles (UAVs) have become popular platforms for collecting various types of geospatial data for various mapping, monitoring and modelling applications. With the advancement of imaging and computing technologies, a vast variety of photogrammetric, computer-vision and, nowadays, end-to-end learning workflows are introduced to produce three-dimensional (3D) information in form of digital surface and terrain models, textured meshes, rectified mosaics, CAD models, etc. These 3D products might be used in applications where accuracy and precision play a vital role, e.

Development and Evaluation of a UAV-Photogrammetry System for Precise 3D Environmental Modeling.

The specific requirements of UAV-photogrammetry necessitate particular solutions for system development, which have mostly been ignored or not assessed adequately in recent studies. Accordingly, this paper presents the methodological and experimental aspects of correctly implementing a UAV-photogrammetry system. The hardware of the system consists of an electric-powered helicopter, a high-resolution digital camera and an inertial navigation system.

Ventilator associated pneumonia and endotracheal tube repositioning: an underrated risk factor.

Aspiration of secretions toward lower airways potentially occurs during endotracheal tube (ETT) repositioning in mechanically ventilated patients in the intensive care unit and may be a risk factor for developing ventilator-associated pneumonia (VAP). This case-control study confirms that repositioning of the ETT is an independent risk factor for VAP.

Selecting an interprofessional education model for a tertiary health care setting.

The World Health Organization describes interprofessional education (IPE) and collaboration as necessary components of all health professionals' education - in curriculum and in practice. However, no standard framework exists to guide healthcare settings in developing or selecting an IPE model that meets the learning needs of licensed practitioners in practice and that suits the unique needs of their setting. Initially, a broad review of the grey literature (organizational websites, government documents and published books) and healthcare databases was undertaken for existing IPE models.

Tousled-like kinases phosphorylate Asf1 to promote histone supply during DNA replication.

During DNA replication, nucleosomes are rapidly assembled on newly synthesized DNA to restore chromatin organization. Asf1, a key histone H3-H4 chaperone required for this process, is phosphorylated by Tousled-like kinases (TLKs). Here, we identify TLK phosphorylation sites by mass spectrometry and dissect how phosphorylation has an impact on human Asf1 function.

Evaluation of nurses' perceptions on providing patient decision support with cardiopulmonary resuscitation.

The decision whether to receive cardiopulmonary resuscitation (CPR) is a decision in which the personal values of the patient must be considered along with information about the risks and benefits of the treatment. A decision aid can be used to provide patient decision support to a patient who is seriously ill and needs to consider CPR options. The goal of this project was to identify the barriers and facilitators to using a CPR decision aid, through evaluating nursing perceptions on providing patient decision support.

Codanin-1, mutated in the anaemic disease CDAI, regulates Asf1 function in S-phase histone supply.

Efficient supply of new histones during DNA replication is critical to restore chromatin organization and maintain genome function. The histone chaperone anti-silencing function 1 (Asf1) serves a key function in providing H3.1-H4 to CAF-1 for replication-coupled nucleosome assembly.

[Ameloblastoma of the jaws. A retrospective analysis from 1994 to 2007].

Introduction: Ameloblastomas and keratocysts are the most frequent epithelial odontogenic tumors of the jaws. They have a high recurrence rate. This retrospective study reviews the features of ameloblastomas operated on in our unit from 1994 to 2007.

The chromatin-remodeling factor CHD4 coordinates signaling and repair after DNA damage.

In response to ionizing radiation (IR), cells delay cell cycle progression and activate DNA repair. Both processes are vital for genome integrity, but the mechanisms involved in their coordination are not fully understood. In a mass spectrometry screen, we identified the adenosine triphosphate-dependent chromatin-remodeling protein CHD4 (chromodomain helicase DNA-binding protein 4) as a factor that becomes transiently immobilized on chromatin after IR.

Shoot differentiation from protocorm callus cultures of Vanilla planifolia (Orchidaceae): proteomic and metabolic responses at early stage.

Background: Vanilla planifolia is an important Orchid commercially cultivated for the production of natural vanilla flavour. Vanilla plants are conventionally propagated by stem cuttings and thus causing injury to the mother plants. Regeneration and in vitro mass multiplication are proposed as an alternative to minimize damage to mother plants.

Evaluation of a natural health product decision aid: a tool for middle aged women considering menopausal symptom relief.

Objective: To evaluate the effectiveness of a self-administered decision aid for menopausal women facing decisions about natural health products.

Study Design: This pre-/post-test study included peri- or post-menopausal women, aged 45-64 considering the use of a natural health product for management of menopausal symptoms. They were recruited from a Women's Health Center.

A treatment algorithm for adult ameloblastomas according to the Pitié-Salpêtrière Hospital experience.

During a 13-year period (from 1994 to 2007), in the Oral and Maxillofacial Surgery Department of the Pitié-Salpêtrière Hospital, 116 new cases of adult ameloblastomas, were analyzed for treatment composed against radiographic presentation, size, histological type. Follow-up and recurrence were also analyzed. Treatment was surgical consisting of enucleations (82%), segmental mandibulectomy (8.