Interactive molecular dynamics in virtual reality from quantum chemistry to drug binding: An open-source multi-person framework

© 2019 Author(s). As molecular scientists have made progress in their ability to engineer nanoscale molecular structure, we face new challenges in our ability to engineer molecular dynamics (MD) and flexibility. Dynamics at the molecular scale differs from the familiar mechanics of everyday objects because it involves a complicated, highly correlated, and three-dimensional many-body dynamical choreography which is often nonintuitive even for highly trained researchers. We recently described how interactive molecular dynamics in virtual reality (iMD-VR) can help to meet this challenge, enabling researchers to manipulate real-time MD simulations of flexible structures in 3D. In this article, we outline various efforts to extend immersive technologies to the molecular sciences, and we introduce "Narupa," a flexible, open-source, multiperson iMD-VR software framework which enables groups of researchers to simultaneously cohabit real-time simulation environments to interactively visualize and manipulate the dynamics of molecular structures with atomic-level precision. We outline several application domains where iMD-VR is facilitating research, communication, and creative approaches within the molecular sciences, including training machines to learn potential energy functions, biomolecular conformational sampling, protein-ligand binding, reaction discovery using "on-the-fly" quantum chemistry, and transport dynamics in materials. We touch on iMD-VR's various cognitive and perceptual affordances and outline how these provide research insight for molecular systems. By synergistically combining human spatial reasoning and design insight with computational automation, technologies such as iMD-VR have the potential to improve our ability to understand, engineer, and communicate microscopic dynamical behavior, offering the potential to usher in a new paradigm for engineering molecules and nano-architectures

Gene expression profiling in pbMEC – in search of molecular biomarkers to predict immunoglobulin production in bovine milk

Abstract Background Optimization of the immunoglobulin (Ig) yield in bovine milk used as therapeutic immune milk or whey for the prevention of Clostridium difficile-associated diarrhea in humans is of great importance to improve the economic efficiency of production. Individual dairy cows have diverse immune responses upon vaccination, resulting in a variable Ig yield in blood and milk. Therefore, it is advisable to pre-select cows with the best ability to produce and secrete high yields of specific Igs. Results The gene expression profile of pbMEC (primary bovine mammary epithelial cells), challenged with the gram-positive, non-mastitis, pathogen Clostridium difficile showed distinct and significant differences in the gene expression of effector molecules of the innate immune system. A number of genes were identified that could possibly serve as molecular biomarkers to differentiate high responder cows from low responder cows. These identified genes play key roles in the promotion of innate immunity. Conclusion Using a gene expression profiling approach, we showed that upon others, especially the gene expression of the pro-inflammatory cytokines was altered between the high and low responder cows. Those genes are indicated as potential molecular biomarkers in the pre-selection of cows that are able to secrete high immunoglobulin yields in milk

Regulation of lipid saturation without sensing membrane fluidity

Cells maintain membrane fluidity by regulating lipid saturation, but the molecular mechanisms of this homeoviscous adaptation remain poorly understood. We have reconstituted the core machinery for regulating lipid saturation in baker’s yeast to study its molecular mechanism. By combining molecular dynamics simulations with experiments, we uncover a remarkable sensitivity of the transcriptional regulator Mga2 to the abundance, position, and configuration of double bonds in lipid acyl chains, and provide insights into the molecular rules of membrane adaptation. Our data challenge the prevailing hypothesis that membrane fluidity serves as the measured variable for regulating lipid saturation. Rather, we show that Mga2 senses the molecular lipid-packing density in a defined region of the membrane. Our findings suggest that membrane property sensors have evolved remarkable sensitivities to highly specific aspects of membrane structure and dynamics, thus paving the way toward the development of genetically encoded reporters for such properties in the future

Regulation of lipid saturation without sensing membrane fluidity

Cells maintain membrane fluidity by regulating lipid saturation, but the molecular mechanisms of this homeoviscous adaptation remain poorly understood. We have reconstituted the core machinery for regulating lipid saturation in baker's yeast to study its molecular mechanism. By combining molecular dynamics simulations with experiments, we uncover a remarkable sensitivity of the transcriptional regulator Mga2 to the abundance, position, and configuration of double bonds in lipid acyl chains, and provide insights into the molecular rules of membrane adaptation. Our data challenge the prevailing hypothesis that membrane fluidity serves as the measured variable for regulating lipid saturation. Rather, we show that Mga2 senses the molecular lipid-packing density in a defined region of the membrane. Our findings suggest that membrane property sensors have evolved remarkable sensitivities to highly specific aspects of membrane structure and dynamics, thus paving the way toward the development of genetically encoded reporters for such properties in the future

Additional file 2: of Gene expression profiling in pbMEC – in search of molecular biomarkers to predict immunoglobulin production in bovine milk

Table S2. Fold changes in gene expression upon C. diff. Treatment - statistical evaluation of the treatment and time-effect with a paired t-test. High responder (n = 5), low responder (n = 4). (DOCX 40 kb

Neural correlates of differential finger gesture imitation deficits in left hemisphere stroke

Behavioural studies in apraxic patients revealed dissociations between the processing of meaningful (MF) and meaningless (ML) gestures. Consequently, the existence of two differential neural mechanisms for the imitation of either gesture type has been postulated. While the indirect (semantic) route exclusively enables the imitation of MF gestures, the direct route can be used for the imitation of any gesture type, irrespective of meaning, and thus especially for ML gestures. Concerning neural correlates, it is debated which of the visuo-motor streams (i.e., the ventral steam, the ventro-dorsal stream, or the dorso-dorsal stream) supports the postulated indirect and direct imitation routes. To probe the hypotheses that regions of the dorso-dorsal stream are involved differentially in the imitation of ML gestures and that regions of the ventro-dorsal stream are involved differentially in the imitation of MF gestures, we analysed behavioural (imitation of MF and ML finger gestures) and lesion data of 293 patients with a left hemisphere (LH) stroke. Confirming previous work, the current sample of LH stroke patients imitated MF finger gestures better than ML finger gestures. The analysis using voxel-based lesion symptom mapping (VLSM) revealed that LH damage to dorso-dorsal stream areas was associated with an impaired imitation of ML finger gestures, whereas damage to ventro-dorsal regions was associated with a deficient imitation of MF finger gestures. Accordingly, the analyses of the imitation of visually uniform and thus highly comparable MF and ML finger gestures support the dual-route model for gesture imitation at the behavioural and lesion level in a substantial patient sample. Furthermore, the data show that the direct route for ML finger gesture imitation depends on the dorso-dorsal visuo-motor stream while the indirect route for MF finger gesture imitation is related to regions of the ventro-dorsal visuo-motor stream

The feminization of the physician assistant profession

Although the physician assistant profession has historically been male-dominated, women now comprise over sixty percent of physician assistants (PAs) in the U.S. This paper explores the reason for the increase of women into the physician assistant profession in recent decades and whether gender differences exist in how PAs are utilized. Twenty-one qualitative interviews with male and female physician assistants and key informants were conducted to assess the reasons for the influx of women. In addition, data from the American Academy of Physician Assistants Census Survey (n = 16,569) were analyzed to assess current gender differences in employment characteristics of PAs. In the interviews, female PAs reported entering the profession because it allowed them to practice within the medical model without having the high expense and demanding schedule of medical school. In fact, they claimed that the profession was quite compatible with family life. Significant gender differences were found in work characteristics, primary employer type, and practice specialty. Although women tend to concentrate in practice areas of women and children's health, evidence suggests that they are moving beyond these traditional roles into areas such as internal medicine and surgery