Life and Death of an Influential Passenger: Wolbachia and the Evolution of CI-Modifiers by Their Hosts

Wolbachia are intracellular bacteria widely distributed among arthropods and nematodes. In many insect species these bacteria induce a cytoplasmic incompatibility (CI) between sperm of infected males and eggs of uninfected females. From an evolutionary point of view, CI is puzzling: In order to induce this modification-rescue system, Wolbachia affect sperm of infected males even though Wolbachia are only transmitted maternally. Phylogenetic studies of Wolbachia and hosts show that the bacteria rarely cospeciate with their hosts, indicating that infections are lost in host species. However, the mechanisms leading to Wolbachia loss are not well understood.Using a population genetic model, we investigate the spread of host mutants that enhance or repress Wolbachia action by affecting either bacterial transmission or the level of CI. We show that host mutants that decrease CI-levels in males (e.g. by reducing Wolbachia-density during spermatogenesis) spread, even at cost to mutant males. Increase of these mutants can lead to loss of Wolbachia infections, either as a direct consequence of their increase or in a step-wise manner, and we derive analytically a threshold penetrance above which a mutation's spread leads to extinction of Wolbachia. Selection on host modifiers is sexually antagonistic in that, conversely, host mutants that enhance Wolbachia in females are favoured whereas suppressors are not.Our results indicate that Wolbachia is likely to be lost from host populations on long evolutionary time scales due to reduction of CI levels in males. This can occur either by evolution of single host modifiers with large effects or through accumulation of several modifier alleles with small effects on Wolbachia action, even at cost to mutant males and even if infected hosts do not incur fecundity costs. This possibility is consistent with recent findings and may help to explain the apparent short evolutionary persistence times of Wolbachia in many host systems

Existence, regularity and boundary behaviour of bounded variation solutions of a one-dimensional capillarity equation

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A New Model and Method for Understanding Wolbachia-Induced Cytoplasmic Incompatibility

Wolbachia are intracellular bacteria transmitted almost exclusively vertically through eggs. In response to this mode of transmission, Wolbachia strategically manipulate their insect hosts' reproduction. In the most common manipulation type, cytoplasmic incompatibility, infected males can only mate with infected females, but infected females can mate with all males. The mechanism of cytoplasmic incompatibility is unknown; theoretical and empirical findings need to converge to broaden our understanding of this phenomenon. For this purpose, two prominent models have been proposed: the mistiming-model and the lock-key-model. The former states that Wolbachia manipulate sperm of infected males to induce a fatal delay of the male pronucleus during the first embryonic division, but that the bacteria can compensate the delay by slowing down mitosis in fertilized eggs. The latter states that Wolbachia deposit damaging “locks” on sperm DNA of infected males, but can also provide matching “keys” in infected eggs to undo the damage. The lock-key-model, however, needs to assume a large number of locks and keys to explain all existing incompatibility patterns. The mistiming-model requires fewer assumptions but has been contradicted by empirical results. We therefore expand the mistiming-model by one quantitative dimension to create the new, so-called goalkeeper-model. Using a method based on formal logic, we show that both lock-key- and goalkeeper-model are consistent with existing data. Compared to the lock-key-model, however, the goalkeeper-model assumes only two factors and provides an idea of the evolutionary emergence of cytoplasmic incompatibility. Available cytological evidence suggests that the hypothesized second factor of the goalkeeper-model may indeed exist. Finally, we suggest empirical tests that would allow to distinguish between the models. Generalizing our results might prove interesting for the study of the mechanism and evolution of other host-parasite interactions

A Helminth Immunomodulator Exploits Host Signaling Events to Regulate Cytokine Production in Macrophages

Parasitic worms alter their host's immune system to diminish the inflammatory responses directed against them, using very efficient immunomodulating molecules. We have previously shown that the helminth immunomodulator cystatin (AvCystatin) profoundly reduces the progression of inflammatory diseases via modulation of macrophages. Here we elucidate the signaling events in macrophages triggered by AvCystatin. Labeled AvCystatin was predominantly taken up by macrophages and subsequently induced the phosphorylation of the mitogen-activated protein kinases (MAPK) ERK1/2 and p38. IL-10 expression induced by AvCystatin in macrophages was tyrosine kinase sensitive and dependent on activation of both MAP kinases, in clear contrast to expression of IL-12/23p40. In addition, phosphorylation of the transcription factors CREB and STAT3 was induced by AvCystatin and regulated by phospho-ERK. Chemical inhibition of phosphoinositide 3-kinase (PI3K) reduced AvCystatin-induced cytokine release; however, AKT, the downstream target of PI3K, was not activated following AvCystatin exposure. To characterize signaling elements involved in alteration of the macrophage phenotype we applied mathematical modeling. Experimental testing of the in silico generated hypotheses identified dual specificity phosphatase (DUSP) 1 and 2, as regulators in AvCystatin triggered macrophages in vitro and in vivo. In particular, DUSP1 was subsequently found to be responsible for regulation of ERK- and p38-phosphorylation and controlled the IL-10 expression in macrophages by AvCystatin. Thus, we show that AvCystatin exploits activation and deactivation pathways of MAP kinases to induce regulatory macrophages. This study provides insights into molecular mechanisms of macrophage manipulation by parasites and highlights the utility of mathematical modeling for the elucidation of regulatory circuits of immune cells

Tidal Disruption Event Demographics with the Zwicky Transient Facility: Volumetric Rates, Luminosity Function, and Implications for the Local Black Hole Mass Function

We conduct a systematic tidal disruption event (TDE) demographics analysis using the largest sample of optically selected TDEs. A flux-limited, spectroscopically complete sample of 33 TDEs is constructed using the Zwicky Transient Facility over 3 yr (from 2018 October to 2021 September). We infer the black hole (BH) mass (M BH) with host galaxy scaling relations, showing that the sample M BH ranges from 105.1 M ⊙ to 108.2 M ⊙. We developed a survey efficiency corrected maximum volume method to infer the rates. The rest-frame g-band luminosity function can be well described by a broken power law of ϕ ( L g ) ∝ L g / L bk 0.3 + L g / L bk 2.6 − 1 , with L bk = 1043.1 erg s−1. In the BH mass regime of 105.3 ≲ (M BH/M ⊙) ≲ 107.3, the TDE mass function follows ϕ ( M BH ) ∝ M BH − 0.25 , which favors a flat local BH mass function ( dn BH / d log M BH ≈ constant ). We confirm the significant rate suppression at the high-mass end (M BH ≳ 107.5 M ⊙), which is consistent with theoretical predictions considering direct capture of hydrogen-burning stars by the event horizon. At a host galaxy mass of M gal ∼ 1010 M ⊙, the average optical TDE rate is ≈3.2 × 10−5 galaxy−1 yr−1. We constrain the optical TDE rate to be [3.7, 7.4, and 1.6] × 10−5 galaxy−1 yr−1 in galaxies with red, green, and blue colors

Characterizing the Ordinary Broad-line Type Ic SN 2023pel from the Energetic GRB 230812B

We report observations of the optical counterpart of the long gamma-ray burst (GRB) GRB 230812B and its associated supernova (SN) SN 2023pel. The proximity (z = 0.36) and high energy (E γ,iso ∼ 1053 erg) make it an important event to study as a probe of the connection between massive star core collapse and relativistic jet formation. With a phenomenological power-law model for the optical afterglow, we find a late-time flattening consistent with the presence of an associated SN. SN 2023pel has an absolute peak r-band magnitude of M r = −19.46 ± 0.18 mag (about as bright as SN 1998bw) and evolves on quicker timescales. Using a radioactive heating model, we derive a nickel mass powering the SN of M Ni = 0.38 ± 0.01 M ⊙ and a peak bolometric luminosity of L bol ∼ 1.3 × 1043 erg s−1. We confirm SN 2023pel’s classification as a broad-line Type Ic SN with a spectrum taken 15.5 days after its peak in the r band and derive a photospheric expansion velocity of v ph = 11,300 ± 1600 km s−1 at that phase. Extrapolating this velocity to the time of maximum light, we derive the ejecta mass M ej = 1.0 ± 0.6 M ⊙ and kinetic energy E KE = 1.3 − 1.2 + 3.3 × 10 51 erg . We find that GRB 230812B/SN 2023pel has SN properties that are mostly consistent with the overall GRB-SN population. The lack of correlations found in the GRB-SN population between SN brightness and E γ,iso for their associated GRBs across a broad range of 7 orders of magnitude provides further evidence that the central engine powering the relativistic ejecta is not coupled to the SN powering mechanism in GRB-SN systems

A Combined Adsorption-Gel Filtration Technique for the Determination of the Cortisol-Binding Capacity of Transcortin

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