Synergistic Impact of Solvent and Polymer Additives on the Film Formation of Small Molecule Blend Films for Bulk Heterojunction Solar Cells

The addition of polystyrene (PS), a typical insulator, is empirically shown to increase the power conversion efficiencies (PCEs) of a solution‐deposited bulk heterojunction (BHJ) molecular blend film used in solar cell fabrication: p‐DTS(FBTTh₂)₂/PC₇₁BM. The performance is further improved by small quantities of diiodooctane (DIO), an established solvent additive. In this study, how the addition of PS and DIO affects the film formation of this bulk heterojunction blend film are probed via in situ monitoring of absorbance, thickness, and crystallinity. PS and DIO additives are shown to promote donor crystallite formation on different time scales and through different mechanisms. PS‐containing films retain chlorobenzene solvent, extending evaporation time and promoting phase separation earlier in the casting process. This extended time is insufficient to attain the morphology for optimal PCE results before the film sets. Here is where the presence of DIO comes into play: its low vapor pressure further extends the time scale of film evolution and allows for crystalline rearrangement of the donor phase long after casting, ultimately leading to the best BHJ organization.     

Immunostimulatory Effects Triggered by Enterococcus faecalis CECT7121 Probiotic Strain Involve Activation of Dendritic Cells and Interferon-Gamma Production

Probiotics can modulate the immune system, conferring beneficial effects on the host. Understanding how these microorganisms contribute to improve the health status is still a challenge. Previously, we have demonstrated that Enterococcus faecalis CECT7121 implants itself and persists in the murine gastrointestinal tract, and enhances and skews the profile of cytokines towards the Th1 phenotype in several biological models. Given the importance of dendritic cells (DCs) in the orchestration of immunity, the aim of this work was to elucidate the influence of E. faecalis CECT7121 on DCs and the outcome of the immune responses. In this work we show that E. faecalis CECT7121 induces a strong dose-dependent activation of DCs and secretion of high levels of IL-12, IL-6, TNFα, and IL-10. This stimulation is dependent on TLR signaling, and skews the activation of T cells towards the production of IFNγ. The influence of this activation in the establishment of Th responses in vivo shows the accumulation of specific IFNγ-producing cells. Our findings indicate that the activation exerted by E. faecalis CECT7121 on DCs and its consequence on the cellular adaptive immune response may have broad therapeutic implications in immunomodulation.     

Micro-RNAs and macrophage diversity in atherosclerosis: New players,new challenges…new opportunities for therapeutic intervention?

Efforts in experimental therapeutics of atherosclerosis are mostly focused on identifying candidate targets that can be exploited in developing new strategies to reduce plaque progression, induce its regression and/or improve stability of advanced lesions. Plaque macrophages are central players in all these processes, and consequently a significant amount of research is devoted to understanding mechanisms that regulate, for instance, macrophage apoptosis, necrosis or migration. Macrophage diversity is a key feature of the macrophage population in the plaque and can impact many aspects of lesion development. Thus, searching for molecular entities that contribute to atherorelevant functions of a specific macrophage type but not others may lead to identification of targets that can be exploited in phenotype selective modulation of the lesional macrophage. This however, remains an unmet goal. In recent years several studies have revealed critical functions of micro-RNAs (miRs) in mechanisms of macrophage polarization, and a number of miRs have emerged as being specific of distinctive macrophage subsets. Not only can these miRs represent the first step towards recognition of phenotype specific targets, but they may also pave the way to reveal novel atherorelevant pathways within macrophage subsets. This article discusses some of these recent findings, speculates on their potential relevance to atherosclerosis and elaborates on the prospective use of miRs to affect the function of plaque macrophages in a phenotype selective manner.     

Noise-Driven Causal Inference in Biomolecular Networks

Single-cell RNA and protein concentrations dynamically fluctuate because of stochastic ("noisy") regulation. Consequently, biological signaling and genetic networks not only translate stimuli with functional response but also random fluctuations. Intuitively, this feature manifests as the accumulation of fluctuations from the network source to the target. Taking advantage of the fact that noise propagates directionally, we developed a method for causation prediction that does not require time-lagged observations and therefore can be applied to data generated by destructive assays such as immunohistochemistry. Our method for causation prediction, "Inference of Network Directionality Using Covariance Elements (INDUCE)," exploits the theoretical relationship between a change in the strength of a causal interaction and the associated changes in the single cell measured entries of the covariance matrix of protein concentrations. We validated our method for causation prediction in two experimental systems where causation is well established: in an E. coli synthetic gene network, and in MEK to ERK signaling in mammalian cells. We report the first analysis of covariance elements documenting noise propagation from a kinase to a phosphorylated substrate in an endogenous mammalian signaling network.     

Loss of neuronal Miro1 disrupts mitophagy and induces hyperactivation of the integrated stress response

Clearance of mitochondria following damage is critical for neuronal homeostasis. Here, we investigate the role of Miro proteins in mitochondrial turnover by the PINK1/Parkin mitochondrial quality control system in vitro and in vivo. We find that upon mitochondrial damage, Miro is promiscuously ubiquitinated on multiple lysine residues. Genetic deletion of Miro or block of Miro1 ubiquitination and subsequent degradation lead to delayed translocation of the E3 ubiquitin ligase Parkin onto damaged mitochondria and reduced mitochondrial clearance in both fibroblasts and cultured neurons. Disrupted mitophagy in vivo, upon post‐natal knockout of Miro1 in hippocampus and cortex, leads to a dramatic increase in mitofusin levels, the appearance of enlarged and hyperfused mitochondria and hyperactivation of the integrated stress response (ISR). Altogether, our results provide new insights into the central role of Miro1 in the regulation of mitochondrial homeostasis and further implicate Miro1 dysfunction in the pathogenesis of human neurodegenerative disease.     

Enhancing single-molecule fluorescence with nanophotonics

Single-molecule fluorescence spectroscopy has become an important research tool in the life sciences but a number of limitations hinder the widespread use as a standard technique. The limited dynamic concentration range is one of the major hurdles. Recent developments in the nanophotonic field promise to alleviate these restrictions to an extent that even low affinity biomolecular interactions can be studied. After motivating the need for nanophotonics we introduce the basic concepts of nanophotonic devices such as zero mode waveguides and nanoantennas. We highlight current applications and the future potential of nanophotonic approaches when combined with biological systems and single-molecule spectroscopy.     

A new Miocene local fauna from the Sierra Madre Oriental at San Luis Potosí, Central-East Mexico,and its paleontologic significance

Mexico's Late Neogene mammal faunas are largely known from localities in the Trans-Mexican Volcanic Belt; those from other morphotectonic provinces are few and far apart. Thus, the discovery of Late Miocene vertebrates in western Sierra Madre Oriental at San Luis Potosí, the Paso del Águila local fauna, significantly adds to this meager record. The assemblage was collected from the floodplain facies of the San Nicolás Formation, a ∼1100-m thick, dominantly fluviolacustrine and calcilithitic, 15°–20° NE dipping sequence preserved in the Peotillos-Tolentino Graben, between 22°11’–22°19’ N and 100°30’–100°39° W. It includes remains of cf. Trachemys, a small to medium-sized emydid chelonian, a large camelid, a small cervid and a new species of the equini Pliohippus s.s., comparable in size, cranial morphology and odontographic characters to the Clarendonian-Early Hemphillian horses of the Pliohippus clade. Ar-Ar dates from ash-fall tuffs seemingly above and below the fossiliferous strata, bracket the age between 12.33 and 7.41 Ma (i.e., late Middle to Late Miocene), that is, within the Late Clarendonian-Early Hemphillian NALMA interval, making this fauna the first in Mexico from this age. The Paso del Águila local fauna is at least partly correlative with the Hemphillian local faunas from the TMVB and adjacent areas (e.g., Rancho El Ocote, Guanajuato and Tecolotlán, Jalisco), the Central Plateau (e.g., Arroyo Los Fragmentos, Zacatecas), and the Sierra Madre Occidental (e.g., Yepómera). Elsewhere, it is broadly correlative with the Late Clarendonian-Early Hemphillian faunas from the California Coast Ranges (e.g., North Tejon Hills, Ricardo and Dove Springs in the Mohave Desert), and the Gulf Coast Plain, Florida (McGehee Farm and Mixon). The Paso del Águila local fauna was part of a subtropical savannah and pine-oak forest (with a well-developed understory) biome that thrived on a climate regime much more humid than today.