Biology subjects

Stark, B.

Publications and source records attributed to Stark, B..

4 recordsLinked to original sources

bioRxiv2025

IcmX Plug Ejection in L. pneumophila's Type IV Secretion System: Is It Possible?

1Legionella pneumophila is a gram-negative bacterial pathogen that is the causative agent of several infectious diseases, notably the severe form of pneumonia known as Legionnaires Disease. L. pneumophila targets amoebas and, in humans, alveolar macrophages. L. pneumophila infects its host by envelopment into the host cell through phagocytosis followed by the activation of the Type IV Secretion System (T4SS). The T4SS secretes effector proteins into the host cell which deactivate cell defenses and reprogram cell function to support L. pneumophila reproduction. After reproduction, L. pneumophila lyses the host cell and the cycle repeats, causing swelling and destroying a primary cell in the hosts immune system--infections caused by L. pneumophila are notoriously hard to treat. The stages of the infection process are known but the physical mechanisms are poorly understood. The structure of the T4SS includes a 13 member polymer, DotG which protrudes from the outer leaflet of the bacterial outer membrane. Given this exposure and the necessity of T4SS for infection, DotG is a promising drug target. However, designing an effective drug requires understanding the physical mechanisms. Via MD simulations we have tested hypotheses regarding its function. Specifically, we show the feasibility that an applied force on IcmX, a plug-like penta-mer that initially blocks transport through the T4SS channel, can cause a structural change in DotG and allow for protein release. Further, this applied force could reasonably come from a build up of pressure in the channel from other effector proteins. We conclude that the process of secretion is dependent on the induced structural change in DotG. Inhibiting this change provides a possible drug development direction.

biophysics↗

bioRxiv2025

Host genetic background and social environment have different effects on the establishment and structure of the adult worker honey bee gut microbiota

Many studies have highlighted the importance of gut microbiomes to many aspects of host physiology. Therefore, understanding how factors, such host genetics and social environment, impact the establishment and composition of the gut microbiota can provide insight into host biological functioning. Here, we controlled the microbial inoculation of honey bees across distinct social groups, each composed of a mixture of bees from three distinct genetic backgrounds, to determine the relative effects of host genetic background and social environment on the establishment and composition of the gut microbiota. Using 16S rRNA gene sequencing, we found that host genetic background and social environment had effects on gut microbiota structure, with each influencing gut microbiota beta diversity. In addition, host genetic background and social environment each affected the abundance of different individual gut microbes. Together, these results suggest that host genetic background and social environment may play distinct roles in shaping the establishment and structure of host gut microbiota.

ecology↗

bioRxiv2020

Neuroanatomical dissociations of syntax and semantics revealed by lesion-symptom mapping

Theories of language organization in the brain commonly posit that different regions underlie distinct linguistic mechanisms. However, such theories have been criticized on the grounds that many neuroimaging studies of language processing find similar effects across regions. Moreover, condition by region interaction effects, which provide the strongest evidence of functional differentiation between regions, have rarely been offered in support of these theories. Here we address this by using lesion-symptom mapping in three large, partially-overlapping groups of aphasia patients with left hemisphere brain damage due to stroke (N=121, N=92, N= 218). We identified multiple measure by region interaction effects, associating damage to the posterior middle temporal gyrus with syntactic comprehension deficits, damage to posterior inferior frontal gyrus with expressive agrammatism, and damage to inferior angular gyrus with semantic category word fluency deficits. Our results are inconsistent with recent hypotheses that regions of the language network are undifferentiated with respect to high-level linguistic processing.

neuroscience↗

bioRxiv2020

Agrammatism and paragrammatism: a cortical double dissociation revealed by lesion-symptom mapping

The fundamental distinction of grammatical deficits in aphasia, agrammatism and paragrammatism, was made over a century ago. However, the extent to which the agrammatism/paragrammatism distinction exists independently of differences in speech fluency has not clearly been investigated. Despite much research on agrammatism, the lesion correlates of paragrammatism are essentially unknown. Lesion-symptom mapping was used to investigate the degree to which the lesion correlates of agrammatism and paragrammatism overlap or dissociate. Four expert raters assessed videos of 53 right-handed patients with aphasia following chronic left hemisphere stroke retelling the Cinderella story. Consensus discussion determined each subjects classification with respect to grammatical deficits as Agrammatic, Paragrammatic, Both, or No Grammatical Deficit. Each subjects lesion was manually drawn on a high-resolution MRI and warped to standard space for group analyses. Lesion-symptom mapping analyses were performed in NiiStat including lesion volume as a covariate. Secondary analyses included speech rate (words per minute) as an additional covariate. Region of interest analyses identified a double dissociation between these syndromes: damage to Brocas area was significantly associated with agrammatism, p = 0.001 (but not paragrammatism, p = 0.930), while damage to the left posterior superior and middle temporal gyri was significantly associated with paragrammatism, p < 0.001 (but not agrammatism, p = 0.873). The same results obtained when regressing out the effect of speech rate, and non-overlapping lesion distributions between the syndromes were confirmed by uncorrected whole brain analyses. Our results support a fundamental distinction between agrammatism and paragrammatism.

neuroscience↗