SWI/SNF senses carbon starvation with a pH-sensitive low complexity sequence [preprint]

It is increasingly appreciated that intracellular pH changes are important biological signals. This motivates the elucidation of molecular mechanisms of pH-sensing. We determined that a nucleocytoplasmic pH oscillation was required for the transcriptional response to carbon starvation in S. cerevisiae. The SWI/SNF chromatin remodeling complex is a key mediator of this transcriptional response. We found that a glutamine-rich low complexity sequence (QLC) in the SNF5 subunit of this complex, and histidines within this sequence, were required for efficient transcriptional reprogramming during carbon starvation. Furthermore, the SNF5 QLC mediated pH-dependent recruitment of SWI/SNF to a model promoter in vitro. Simulations showed that protonation of histidines within the SNF5 QLC lead to conformational expansion, providing a potential biophysical mechanism for regulation of these interactions. Together, our results indicate that that pH changes are a second messenger for transcriptional reprogramming during carbon starvation, and that the SNF5 QLC acts as a pH-sensor

mTORC1 Controls Phase Separation and the Biophysical Properties of the Cytoplasm by Tuning Crowding

International audienceMacromolecular crowding has a profound impact on reaction rates and the physical properties of the cell interior, but the mechanisms that regulate crowding are poorly understood. We developed genetically encoded multimeric nanoparticles (GEMs) to dissect these mechanisms. GEMs are homomultimeric scaffolds fused to a fluorescent protein that self-assemble into bright, stable particles of defined size and shape. By combining tracking of GEMs with genetic and pharmacological approaches, we discovered that the mTORC1 pathway can modulate the effective diffusion coefficient of particles ≥20 nm in diameter more than 2-fold by tuning ribosome concentration, without any discernable effect on the motion of molecules ≤5 nm. This change in ribosome concentration affected phase separation both in vitro and in vivo. Together, these results establish a role for mTORC1 in controlling both the mesoscale biophysical properties of the cytoplasm and biomolecular condensation

Barozh 12: formation processes of a late Middle Paleolithic open-air site in western Armenia

© 2020 Elsevier Ltd Barozh 12 is a Middle Paleolithic (MP) open-air site located near the Mt Arteni volcanic complex at the margins of the Ararat Depression, an intermontane basin that contains the Araxes River. Sedimentology, micromorphology, geochronology, biomarker evidence, together with an assessment of artifact taphonomy permits the modelling of site formation processes and paleoenvironment at a level of detail not previously achieved in this area. Obsidian MP artifacts were recovered in high densities at Barozh 12 from four stratigraphic units deposited during marine oxygen isotope stage 3 (MIS 3) (60.2 ± 5.7–31.3 ± 3 ka). The MIS 3 sequence commences with low energy alluvial deposits that have been altered by incipient soil formation, while artifact assemblages in these strata were only minimally reworked. After a depositional hiatus, further low energy alluvial sedimentation and weak soil formation occurred, followed by higher energy colluvial (re)deposition and then deflation. Artifacts in these last stratigraphic units were more significantly reworked than those below. Analysis of plant leaf wax (n-alkane) biomarkers shows fluctuating humidity throughout the sequence. Collectively the evidence suggests that hunter-gatherers equipped with MP lithic technology repeatedly occupied this site during variable aridity regimes, demonstrating their successful adaptation to the changing environments of MIS 3

Superluminal X-shaped beams propagating without distortion along a coaxial guide

In a previous paper [Phys. Rev. E64 (2001) 066603; e-print physics/0001039], we showed that localized Superluminal solutions to the Maxwell equations exist, which propagate down (non-evanescence) regions of a metallic cylindrical waveguide. In this paper we construct analogous non-dispersive waves propagating along coaxial cables. Such new solutions, in general, consist in trains of (undistorted) Superluminal "X-shaped" pulses. Particular attention is paid to the construction of finite total energy solutions. Any results of this kind may find application in the other fields in which an essential role is played by a wave-equation (like acoustics, geophysics, etc.). [PACS nos.: 03.50.De; 41.20;Jb; 83.50.Vr; 62.30.+d; 43.60.+d; 91.30.Fn; 04.30.Nk; 42.25.Bs; 46.40.Cd; 52.35.Lv. Keywords: Wave equations; Wave propagation; Localized beams; Superluminal waves; Coaxial cables; Bidirectional decomposition; Bessel beams; X-shaped waves; Maxwell equations; Microwaves; Optics; Special relativity; Coaxial metallic waveguides; Acoustics; Seismology; Mechanical waves; Elastic waves; Guided gravitational waves.]Comment: plain LaTeX file (22 pages), plus 15 figures; in press in Phys. Rev.

Foraging on human-derived foods by urban bird species

Capsule: Providing peanuts on bird feeders was shown to attract more individuals and more species than providing cheese or bread. Aims: To investigate how the provision of different human-derived foods affected visit rates of urban birds at bird feeders. Methods: A fully replicated study design was set up in parkland, offering a binary choice from three food types (peanuts, bread and cheese) on bird tables. Birds were observed by using a scan-sample method. Results: Peanuts attracted more visits, and a greater diversity of bird species, than cheese or bread. This preference was strongest for Blue Tits Cyanistes caeruleus and Great Tits Parus major, whereas European Robins Erithacus rubecula visited all food types equally, and Blackbirds Turdus merula preferred cheese. Bread was the most consumed food type when measured by mass, but this could be linked to varying bite sizes. Conclusion: Our results indicate that birds preferred to visit feeding stations with the most protein- and energy-rich foods, but that some birds still chose the carbohydrate-rich bread. The findings indicate that peanuts, rather than household scraps like bread and cheese, attract the highest number of species and individuals to bird tables. The findings will be of interest to the public and to organizations providing information on bird feeding for recreational purposes

Leishmania-Induced Inactivation of the Macrophage Transcription Factor AP-1 Is Mediated by the Parasite Metalloprotease GP63

Leishmania parasites have evolved sophisticated mechanisms to subvert macrophage immune responses by altering the host cell signal transduction machinery, including inhibition of JAK/STAT signalling and other transcription factors such as AP-1, CREB and NF-κB. AP-1 regulates pro-inflammatory cytokines, chemokines and nitric oxide production. Herein we show that upon Leishmania infection, AP-1 activity within host cells is abolished and correlates with lower expression of 5 of the 7 AP-1 subunits. Of interest, c-Jun, the central component of AP-1, is cleaved by Leishmania. Furthermore, the cleavage of c-Jun is dependent on the expression and activity of the major Leishmania surface protease GP63. Immunoprecipitation of c-Jun from nuclear extracts showed that GP63 interacts, and cleaves c-Jun at the perinuclear area shortly after infection. Phagocytosis inhibition by cytochalasin D did not block c-Jun down-regulation, suggesting that internalization of the parasite might not be necessary to deliver GP63 molecules inside the host cell. This observation was corroborated by the maintenance of c-Jun cleavage upon incubation with L. mexicana culture supernatant, suggesting that secreted, soluble GP63 could use a phagocytosis-independent mechanism to enter the host cell. In support of this, disruption of macrophage lipid raft microdomains by Methyl β-Cyclodextrin (MβCD) partially inhibits the degradation of full length c-Jun. Together our results indicate a novel role of the surface protease GP63 in the Leishmania-mediated subversion of host AP-1 activity

Excessive Cell Growth Causes Cytoplasm Dilution And Contributes to Senescence

Cell size varies greatly between cell types, yet within a specific cell type and growth condition, cell size is narrowly distributed. Why maintenance of a cell-type specific cell size is important remains poorly understood. Here we show that growing budding yeast and primary mammalian cells beyond a certain size impairs gene induction, cell-cycle progression, and cell signaling. These defects are due to the inability of large cells to scale nucleic acid and protein biosynthesis in accordance with cell volume increase, which effectively leads to cytoplasm dilution. We further show that loss of scaling beyond a certain critical size is due to DNA becoming limiting. Based on the observation that senescent cells are large and exhibit many of the phenotypes of large cells, we propose that the range of DNA:cytoplasm ratio that supports optimal cell function is limited and that ratios outside these bounds contribute to aging

Stage-Specific Pathways of Leishmania infantum chagasi Entry and Phagosome Maturation in Macrophages

The life stages of Leishmania spp. include the infectious promastigote and the replicative intracellular amastigote. Each stage is phagocytosed by macrophages during the parasite life cycle. We previously showed that caveolae, a subset of cholesterol-rich membrane lipid rafts, facilitate uptake and intracellular survival of virulent promastigotes by macrophages, at least in part, by delaying parasitophorous vacuole (PV)-lysosome fusion. We hypothesized that amastigotes and promastigotes would differ in their route of macrophage entry and mechanism of PV maturation. Indeed, transient disruption of macrophage lipid rafts decreased the entry of promastigotes, but not amastigotes, into macrophages (P<0.001). Promastigote-containing PVs were positive for caveolin-1, and co-localized transiently with EEA-1 and Rab5 at 5 minutes. Amastigote-generated PVs lacked caveolin-1 but retained Rab5 and EEA-1 for at least 30 minutes or 2 hours, respectively. Coinciding with their conversion into amastigotes, the number of promastigote PVs positive for LAMP-1 increased from 20% at 1 hour, to 46% by 24 hours, (P<0.001, Chi square). In contrast, more than 80% of amastigote-initiated PVs were LAMP-1+ at both 1 and 24 hours. Furthermore, lipid raft disruption increased LAMP-1 recruitment to promastigote, but not to amastigote-containing compartments. Overall, our data showed that promastigotes enter macrophages through cholesterol-rich domains like caveolae to delay fusion with lysosomes. In contrast, amastigotes enter through a non-caveolae pathway, and their PVs rapidly fuse with late endosomes but prolong their association with early endosome markers. These results suggest a model in which promastigotes and amastigotes use different mechanisms to enter macrophages, modulate the kinetics of phagosome maturation, and facilitate their intracellular survival

Addressing the needs of children with disabilities experiencing disaster or terrorism

Purpose of review: This paper reviews the empirical literature on psychosocial factors relating to children with disabilities in the context of disaster or terrorism. Recent findings: Research indicates individuals with disabilities experience increased exposure to hazards due to existing social disparities and barriers associated with disability status. However, studies on the psychological effects of disaster/terrorism on children with preexisting disabilities are exceedingly few and empirical evidence of the effectiveness of trauma-focused therapies for this population is limited. Secondary adversities, including social stigma and health concerns, also compromise the recovery of these children post-disaster/terrorism. Schools and teachers appear to be particularly important in the recovery of children with disabilities to disaster. Disasters, terrorism, and war all contribute to the incidence of disability, as well as disproportionately affect children with preexisting disabilities. Summary: Disaster preparedness interventions and societal changes are needed to decrease the disproportionate environmental and social vulnerability of children with disabilities to disaster and terrorism