Biology subjects

Klein, L. K.

Publications and source records attributed to Klein, L. K..

9 recordsLinked to original sources

bioRxiv2024

Comparative Characterization of Bronchial and Nasal Mucus Reveals Key Determinants of Influenza A Virus Inhibition

Differentiated primary human respiratory epithelial cells grown at air-liquid interface have become a widely used cell culture model of the human conducting airways. These cultures contain secretory cells such as goblet and club cells, which produce and secrete mucus. Here, we characterize the composition of mucus harvested from airway cultures of nasal and bronchial origin. We find that despite inter-donor variability, the salt, sugar, lipid, and protein content and composition are very similar between nasal and bronchial mucus. However, subtle differences in the abundance of individual components in nasal versus bronchial mucus can influence its antimicrobial properties: The ability of mucus to neutralize influenza A virus varies with the anatomical origin of the airway cultures and correlates with the abundance of triglycerides and sialylated glycoproteins and glycolipids. ImportanceRespiratory mucus plays an important role during the transmission and infection process of microbes in the human respiratory tract. In case of influenza A virus, mucus stabilizes virions in infectious respiratory particles and droplets but hampers virus particles before they reach the respiratory epithelium through its physicochemical properties and the presence of sialylated decoy receptors. However, it is thus far not well understood which components of mucus mediate protection and inhibition. Our study now provides a comprehensive analysis of bronchial and nasal mucus from primary human airway cultures that can be used as a resource for future experimental designs and interpretations.

microbiology↗

bioRxiv2024

Impact of Organic Compounds on the Stability of Influenza A Virus in deposited 1-ul droplets

The composition of respiratory fluids influences the stability of viruses in exhaled aerosol particles and droplets, though the role of respiratory organics in modulating virus stability remains poorly understood. This study investigates the effect of organic compounds on the stability of influenza A virus (IAV) in deposited droplets. We compare the infectivity loss of IAV at different relative humidities (RH) over the course of one hour in 1-l droplets consisting of phosphate-buffered saline (without organics), synthetic lung fluid, or nasal mucus (both containing organics). We show that IAV stability increases with increasing organic:salt ratios. Among the various organic species, proteins are identified as the most protective component, with smaller proteins stabilizing IAV more efficiently at the same mass concentration. Organics act by both increasing the efflorescence RH and shortening the drying period until efflorescence at a given RH. This research advances our mechanistic understanding of how organics stabilize exhaled viruses and thus influence their inactivation in respiratory droplets.

microbiology↗

bioRxiv2024

Stability of influenza A virus in droplets and aerosols is heightened by the presence of commensal respiratory bacteria.

Aerosol transmission remains a major challenge for the control of respiratory viruses, particularly for those that cause recurrent epidemics, like influenza A virus (IAV). These viruses are rarely expelled alone, but instead are embedded in a consortium of microorganisms that populate the respiratory tract. The impact of microbial communities and inter-pathogen interactions upon the stability of transmitted viruses is well-characterised for pathogens of the gut, but is particularly under-studied in the respiratory niche. Here, we assessed whether the presence of 5 different species of common commensal respiratory bacteria could influence the stability of IAV within droplets deposited on surfaces and within airborne aerosol particles at typical indoor air humidity. It was found that bacterial presence within stationary droplets, either a mixed community or individual strains, resulted in 10- to 100-fold more infectious IAV remaining after 1 hour. Bacterial viability was not required for this viral stabilisation, though maintained bacterial morphology seemed to be essential. Additionally, non-respiratory bacteria tested here had little stabilising effect, indicating this phenomenon was respiratory-specific. The protective bacteria stabilised IAV in droplets via induction of early efflorescence due to flattened droplet morphology during drying. Even when no efflorescence occurred at high humidity or the bacteria-induced changes in droplet morphology were abolished by aerosolization instead of deposition on a well-plate, the bacteria remained protective. This indicates an additional stabilisation mechanism that is currently unknown. Notably, respiratory bacteria at equivalent density offered varying degrees of protection in droplets, with the Gram-positive species Staphylococcus aureus and Streptococcus pneumoniae being the most robustly stabilising. This suggests that the composition of an individuals respiratory microbiota could be a previously un-considered host-specific factor influencing the efficacy of expelled viral spread. Identifying novel host-specific factors such as the commensal microbiota that can influence viral stability in the environment will further increase our understanding of individual transmission risks, and will provide novel opportunities to limit the spread of respiratory infections within our populations. SynopsisOur findings have significant environmental and health relevance, as they identify the host respiratory microbiota as a novel factor potentially contributing to environmental viral stability within indoor environments.

microbiology↗

bioRxiv2023

Salt-mediated inactivation of influenza A virus in 1-ul droplets exhibits exponential dependence on NaCl molality

Influenza A virus (IAV) spreads through exhaled aerosol particles and larger droplets. Estimating the stability of IAV is challenging and depends on factors such as the respiratory matrix and drying kinetics. Here, we combine kinetic experiments on millimeter-sized saline droplets with a biophysical aerosol model to quantify the impact of NaCl on IAV stability. We show that IAV inactivation is determined by NaCl concentration, which increases during water evaporation and then decreases again when efflorescence occurs. When drying in air with relative humidity RH = 30%, inactivation follows an inverted sigmoidal curve, with inactivation occurring most rapidly when the NaCl concentration exceeds 20 molal immediately prior to efflorescence. Efflorescence reduces the NaCl molality to saturated conditions, resulting in a significantly reduced inactivation rate. We demonstrate that the inactivation rate k depends exponentially on NaCl molality, and after the solution reaches equilibrium, the inactivation proceeds at a first-order rate. Introducing sucrose, an organic co-solute, attenuates IAV inactivation via two mechanisms, firstly by decreasing the NaCl molality during the drying phase, and secondly by a protective effect against the NaCl-induced inactivation. For both pure saline and sucrose-containing droplets, our biophysical model ResAM accurately simulates the inactivation when NaCl molality is used as the only inactivating factor. This study highlights the role of NaCl molality in IAV inactivation and provides a mechanistic basis for the observed inactivation rates. SYNOPSIS: This work quantifies the dependence of influenza A virus stability on salt molality in drying droplets and furthers the understanding of airborne virus transmission.SYNOPSIS: This work quantifies the dependence of influenza A virus stability on salt molality in drying droplets and furthers the understanding of airborne virus transmission.

microbiology↗

bioRxiv2023

Distinct neural components of visually guided grasping during planning and execution

Selecting suitable grasps on three-dimensional objects is a challenging visuomotor computation, which involves combining information about an object (e.g., its shape, size, and mass) with information about the actors body (e.g., the optimal grasp aperture and hand posture for comfortable manipulation). Here we used functional magnetic resonance imaging to investigate brain networks associated with these distinct aspects during grasp planning and execution. Human participants viewed and then executed preselected grasps on L-shaped objects made of wood and/or brass. By leveraging a computational approach that accurately predicts human grasp locations, we selected grasp points that disentangled the role of multiple grasp-relevant factors: grasp axis, grasp size, and object mass. Representational Similarity Analysis revealed that grasp axis was encoded along dorsal-stream regions during grasp planning. Grasp size was first encoded in ventral-stream areas during grasp planning, then in premotor regions during grasp execution. Object mass was encoded in ventral-stream and (pre)motor regions only during grasp execution. Premotor regions further encoded visual predictions of grasp comfort, whereas the ventral stream encoded grasp comfort during execution, suggesting its involvement in haptic evaluation. These shifts in neural representations thus capture the sensorimotor transformations that allow humans to grasp objects. Significance StatementGrasping requires integrating object properties with constraints on hand and arm postures. Using a computational approach that accurately predicts human grasp locations by combining such constraints, we selected grasps on objects that disentangled the relative contributions of object mass, grasp size, and grasp axis during grasp planning and execution in a neuroimaging study. Our findings reveal a greater role of dorsal-stream visuomotor areas during grasp planning, and surprisingly, increasing ventral stream engagement during execution. We propose that during planning, visuomotor representations initially encode grasp axis and size. Perceptual representations of object material properties become more relevant instead as the hand approaches the object and motor programs are refined with estimates of the grip forces required to successfully lift the object.

neuroscience↗

bioRxiv2021

Friction is preferred over grasp configuration in precision grip grasping

How humans visually select where to grasp an object depends on many factors, including grasp stability and preferred grasp configuration. We examined how endpoints are selected when these two factors are brought into conflict: Do people favor stable grasps or do they prefer their natural grasp configurations? Participants reached to grasp one of three cuboids oriented so that its two corners were either aligned with, or rotated away from, each individuals natural grasp axis (NGA). All objects were made of brass (mass: 420 g) but the surfaces of their sides were manipulated to alter friction: 1) all-brass, 2) two opposing sides covered with wood, while the other two remained of brass, or 3) two opposing sides covered with sandpaper, and the two remaining brass sides smeared with vaseline. Grasps were evaluated as either clockwise (thumb to the left of finger in frontal plane) or counterclockwise of the NGA. Grasp endpoints depended on both object orientation and surface material. For the all-brass object, grasps were bimodally distributed in the NGA-aligned condition but predominantly clockwise in the NGA-unaligned condition. These data reflected participants natural grasp configuration independently of surface material. When grasping objects with different surface materials, endpoint selection changed: Participants sacrificed their usual grasp configuration to choose the more stable object sides. A model in which surface material shifts participants preferred grip angle proportionally to the perceived friction of the surfaces accounts for our results. Our findings demonstrate that a stable grasp is more important than a biomechanically comfortable grasp configuration. NEW & NOTEWORTHYWhen grasping an object, humans can place their fingers at several positions on its surface. The selection of these endpoints depends on many factors, with two of the most important being grasp stability and grasp configuration. We put these two factors in conflict and examine which is considered more important. Our results highlight that humans are not reluctant to adopt unusual grasp configurations in order to satisfy grasp stability.

neuroscience↗

bioRxiv2020

Humans can visually judge grasp quality and refine their judgments through visual and haptic feedback

How humans visually select where to grasp objects is determined by the physical object properties (e.g., size, shape, weight), the degrees of freedom of the arm and hand, as well as the task to be performed. We recently demonstrated that human grasps are near-optimal with respect to a weighted combination of different cost functions that make grasps uncomfortable, unstable or impossible e.g., due to unnatural grasp apertures or large torques. Here, we ask whether humans can consciously access these rules. We test if humans can explicitly judge grasp quality derived from rules regarding grasp size, orientation, torque, and visibility. More specifically, we test if grasp quality can be inferred (i) by using motor imagery alone, (ii) from watching grasps executed by others, and (iii) through performing grasps, i.e. receiving visual, proprioceptive and haptic feedback. Stimuli were novel objects made of 10 cubes of brass and wood (side length 2.5 cm) in various configurations. On each object, one near-optimal and one sub-optimal grasp were selected based on one cost function (e.g. torque), while the other constraints (grasp size, orientation, and visibility) were kept approximately constant or counterbalanced. Participants were visually cued to the location of the selected grasps on each object and verbally reported which of the two grasps was best. Across three experiments, participants could either (i) passively view the static objects, (ii) passively view videos of other participants grasping the objects, or (iii) actively grasp the objects themselves. Our results show that participants could already judge grasp optimality from simply viewing the objects, but were significantly better in the video and grasping session. These findings suggest that humans can determine grasp quality even without performing the grasp--perhaps through motor imagery--and can further refine their understanding of how to correctly grasp an object through sensorimotor feedback but also by passively viewing others grasp objects.

neuroscience↗

bioRxiv2018

Object visibility, not energy expenditure, accounts for spatial biases in human grasp selection

Humans exhibit spatial biases when grasping objects. These biases may be due to actors attempting to shorten their reaching movements and therefore minimize energy expenditures. An alternative explanation could be that they arise from actors attempting to minimize the portion of a grasped object occluded from view by the hand. We re-analyze data from a recent study, in which a key condition decouples these two competing hypotheses. The analysis reveals that object visibility, not energy expenditure, most likely accounts for spatial biases observed in human grasping.

neuroscience↗

bioRxiv2018

How humans grasp three-dimensional objects

We rarely experience difficulty picking up objects, yet of all potential contact points on the surface, only a small proportion yield effective grasps. Here, we present extensive behavioral data alongside a normative model that correctly predicts human precision grasping of unfamiliar 3D objects. We tracked participants forefinger and thumb as they picked up objects of 10 wood and brass cubes configured to tease apart effects of shape, weight, orientation, and mass distribution. Grasps were highly systematic and consistent across repetitions and participants. We employed these data to construct a model which combines five cost functions related to force closure, torque, natural grasp axis, grasp aperture, and visibility. Even without free parameters, the model predicts individual grasps almost as well as different individuals predict one anothers, but fitting weights reveals the relative importance of the different constraints. The model also accurately predicts human grasps on novel 3D-printed objects with more naturalistic geometries and is robust to perturbations in its key parameters. Together, the findings provide a unified account of how we successfully grasp objects of different 3D shape, orientation, mass, and mass distribution. Author SummaryA model based on extensive behavioral data unifies the varied and fragmented literature on human grasp selection by correctly predicting human grasps across a wide variety of conditions.

neuroscience↗