Generic phase diagram of active polar films

We study theoretically the phase diagram of compressible active polar gels such as the actin network of eukaryotic cells. Using generalized hydrodynamics equations, we perform a linear stability analysis of the uniform states in the case of an infinite bidimensional active gel to obtain the dynamic phase diagram of active polar films. We predict in particular modulated flowing phases, and a macroscopic phase separation at high activity. This qualitatively accounts for experimental observations of various active systems, such as acto-myosin gels, microtubules and kinesins in vitro solutions, or swimming bacterial colonies.Comment: 4 pages, 1 figur

Spontaneous flow transition in active polar gels

We study theoretically the effects of confinement on active polar gels such as the actin network of eukaryotic cells. Using generalized hydrodynamics equations derived for active gels, we predict, in the case of quasi one-dimensional geometry, a spontaneous flow transition from a homogeneously polarized immobile state for small thicknesses, to a perturbed flowing state for larger thicknesses. The transition is not driven by an external field but by the activity of the system. We suggest several possible experimental realizations.Comment: 7 pages, 3 figures. To appear in Europhys. Let

Mitophagy coordination with retrograde transport ensures the integrity of synaptic mitochondria

Mitochondria sustain various essential functions at synaptic terminals. Synaptic mitochondria deficits have been implicated in early Alzheimer disease (AD) pathophysiology. Mitophagy, a selective autophagy for removal of damaged mitochondria, plays a key role in mitochondrial quality control in neurons. However, fundamental questions remain unanswered as to whether mitophagy regulates synaptic mitochondrial integrity and whether AD-associated early deficits in synaptic mitochondria are attributed to mitophagy failure. We have recently revealed that the integrity of synaptic mitochondria is maintained by a coordination of RHEB-mediated mitophagy with dynein- and SNAPIN-driven retrograde transport. We demonstrate that increased mitophagy initiation, coupled with defective retrograde transport, triggers mitophagy stress at AD synapses. Excitingly, SNAPIN-enhanced retrograde transport reduces synaptic mitophagy stress and ameliorates mitochondrial deficits, thereby counteracting synaptic damage in AD mouse brains. Therefore, our study provides new mechanistic insights into how mitophagy facilitates synaptic mitochondrial maintenance and how mitophagy failure exacerbates AD-linked mitochondrial defects and synaptic degeneration. Abbreviation: AD: Alzheimer disease; Aβ: amyloid-β; APP: amyloid beta precursor protein; CCCP: carbonyl cyanide m-chlorophenylhydrazone; LE: late endosome; Δψm, mitochondrial membrane potential; RHEB: Ras homolog enriched in brain; RNAi: RNA interference; shRNA: small hairpin RNA; Tg: transgenic

Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases

Protein kinases are essential for signal transduction and control of most cellular processes, including metabolism, membrane transport, motility, and cell cycle. Despite the critical role of kinases in cells and their strong association with diseases, good coverage of their interactions is available for only a fraction of the 535 human kinases. Here, we present a comprehensive mass-spectrometry-based analysis of a human kinase interaction network covering more than 300 kinases. The interaction dataset is a high-quality resource with more than 5,000 previously unreported interactions. We extensively characterized the obtained network and were able to identify previously described, as well as predict new, kinase functional associations, including those of the less well-studied kinases PIM3 and protein O-mannose kinase (POMK). Importantly, the presented interaction map is a valuable resource for assisting biomedical studies. We uncover dozens of kinase-disease associations spanning from genetic disorders to complex diseases, including cancer.Peer reviewe

Faculty Members Promoted, Granted Tenure

Seven members of the Lawrence University faculty have been promoted to the rank of associate professor and eight faculty have been granted tenure appointments by the college’s Board of Trustees. Garth Bond, Dominica Chang, Scott Corry, Stefan Debbert, Adam Galambos, Doug Martin and Peter Thomas all have been granted tenure and promoted to associate professor. David Gerard, associate professor of economics, also has been granted tenure

Prebiotic Oligosaccharides Potentiate Host Protective Responses against L. Monocytogenes Infection.

Prebiotic oligosaccharides are used to modulate enteric pathogens and reduce pathogen shedding. The interactions with prebiotics that alter Listeria monocytogenes infection are not yet clearly delineated. L. monocytogenes cellular invasion requires a concerted manipulation of host epithelial cell membrane receptors to initiate internalization and infection often via receptor glycosylation. Bacterial interactions with host glycans are intimately involved in modulating cellular responses through signaling cascades at the membrane and in intracellular compartments. Characterizing the mechanisms underpinning these modulations is essential for predictive use of dietary prebiotics to diminish pathogen association. We demonstrated that human milk oligosaccharide (HMO) pretreatment of colonic epithelial cells (Caco-2) led to a 50% decrease in Listeria association, while Biomos pretreatment increased host association by 150%. L. monocytogenes-induced gene expression changes due to oligosaccharide pretreatment revealed global alterations in host signaling pathways that resulted in differential subcellular localization of L. monocytogenes during early infection. Ultimately, HMO pretreatment led to bacterial clearance in Caco-2 cells via induction of the unfolded protein response and eIF2 signaling, while Biomos pretreatment resulted in the induction of host autophagy and L. monocytogenes vacuolar escape earlier in the infection progression. This study demonstrates the capacity of prebiotic oligosaccharides to minimize infection through induction of host-intrinsic protective responses

What happens next? Exploring women's transport motility through the story completion method

This paper explores the three elements of motility (access, competence, appropriation) through women's perceptions of travel using the metro rail in Delhi, India. Studies on metro rails are a recent phenomenon in developing countries where this is a relatively new transport mode. The concept of motility to explore gendered use of metro is useful in context of this South Asian city where women's movements (potential and actual) are contingent upon their ability to travel safely. Data was collected using story completion methods. Participants were asked to complete an online semi-structured form that presented five fictional story stems/openings. Data in this paper is based on stories finished by 84 female participants across Delhi with varying demographic profiles. This paper advances qualitative research on women's mobility and transport use by highlighting situation-specific metro access; necessary skills to optimize access; and how women actually use the metro system. Feelings of un/safety related to fear of sexual harassment, getting lost, and risk of contracting diseases in unhygienic conditions results in specific access of the metro to feel safe. Diverse skills to manage the access include: coping (e.g., adapting to delay in services), performative (e.g., mannerisms to feel safe from threat of violence), spatial (e.g., location of coach), cultural (e.g., awareness of norms), and sanitary skills (e.g., bodily modifications to feel safe from unhygienic conditions). Based on travel priorities and past mobility experiences (personal/shared), the skills and access shape how women travel and what they decide to do to travel safely. This paper advocates for gender inclusive guidelines and collecting disaggregate data in transport, especially for newer metro systems being planned or constructed. It presents an opportunity to consider the barriers to women's potential mobility; how/where transport systems can play a part; and the use of qualitative research methods to appreciate the diversity of women's travel experiences across different segments of their journeys