Nervous system development in the fairy shrimp Branchinella sp. (Crustacea: Branchiopoda: Anostraca): Insights into the development and evolution of the branchiopod brain and its sensory organs

Using immunohistochemical labeling against acetylated a‐tubulin and serotonin in combination with confocal laser scanning microscopy and 3D‐reconstruction, we investigated the temporary freshwater pond inhabitant Branchinella sp. (Crustacea: Branchiopoda: Anostraca) for the first time to provide detailed data on the development of the anostracan nervous system. Protocerebral sense organs such as the nauplius eye and frontal filament organs are present as early as the hatching stage L0. In the postnaupliar region, two terminal pioneer neurons grow from posterior to anterior to connect the mandibular neuromeres. The first protocerebral neuropil to emerge is not part of the central complex but represents the median neuropil, and begins to develop from L0+ onwards. In stage L3, the first evidence of developing compound eyes is visible. This is followed by the formation of the visual neuropils and the neuropils of the central complex in the protocerebrum. From the deutocerebral lobes, the projecting neuron tract proceeds to both sides of the lateral protocerebrum, forming a chiasma just behind the central body. In the postnaupliar region, the peripheral nervous system, commissures and connectives develop along an anterior–posterior gradient after the fasciculation of the terminal pioneer neurons with the mandibular neuromere. The peripheral nervous system in the thoracic segments consists of two longitudinal neurite bundles on each side which connect the intersegmental nerves, together with the ventral nervous system forming an orthogon‐like network. Here, we discuss, among other things, the evidence of a fourth nauplius eye nerve and decussating projecting neuron tract found in Branchinella sp., and provide arguments to support our view that the crustacean frontal filament (organ) and onychophoran primary antenna are homologous. J. Morphol. 277:1423–1446, 2016. © 2016 Wiley Periodicals, Inc.     

Intrinsic vs. extrinsic influences on life history expression: metabolism and parentally induced temperature influences on embryo development rate

Intrinsic processes are assumed to underlie life history expression and trade‐offs, but extrinsic inputs are theorised to shift trait expression and mask trade‐offs within species. Here, we explore application of this theory across species. We do this based on parentally induced embryo temperature as an extrinsic input, and mass‐specific embryo metabolism as an intrinsic process, underlying embryonic development rate. We found that embryonic metabolism followed intrinsic allometry rules among 49 songbird species from temperate and tropical sites. Extrinsic inputs via parentally induced temperatures explained the majority of variation in development rates and masked a relationship with metabolism; metabolism explained a minor proportion of the variation in development rates among species, and only after accounting for temperature effects. We discuss evidence that temperature further obscures the expected interspecific trade‐off between development rate and offspring quality. These results demonstrate the importance of considering extrinsic inputs to trait expression and trade‐offs across species.     

Effectiveness of Losartan-Loaded Hyaluronic Acid (HA) Micelles for the Reduction of Advanced Hepatic Fibrosis in C3H/HeN Mice Model

Advanced hepatic fibrosis therapy using drug-delivering nanoparticles is a relatively unexplored area. Angiotensin type 1 (AT1) receptor blockers such as losartan can be delivered to hepatic stellate cells (HSC), blocking their activation and thereby reducing fibrosis progression in the liver. In our study, we analyzed the possibility of utilizing drug-loaded vehicles such as hyaluronic acid (HA) micelles carrying losartan to attenuate HSC activation. Losartan, which exhibits inherent lipophilicity, was loaded into the hydrophobic core of HA micelles with a 19.5% drug loading efficiency. An advanced liver fibrosis model was developed using C3H/HeN mice subjected to 20 weeks of prolonged TAA/ethanol weight-adapted treatment. The cytocompatibility and cell uptake profile of losartan-HA micelles were studied in murine fibroblast cells (NIH3T3), human hepatic stellate cells (hHSC) and FL83B cells (hepatocyte cell line). The ability of these nanoparticles to attenuate HSC activation was studied in activated HSC cells based on alpha smooth muscle actin (α-sma) expression. Mice treated with oral losartan or losartan-HA micelles were analyzed for serum enzyme levels (ALT/AST, CK and LDH) and collagen deposition (hydroxyproline levels) in the liver. The accumulation of HA micelles was observed in fibrotic livers, which suggests increased delivery of losartan compared to normal livers and specific uptake by HSC. Active reduction of α-sma was observed in hHSC and the liver sections of losartan-HA micelle-treated mice. The serum enzyme levels and collagen deposition of losartan-HA micelle-treated mice was reduced significantly compared to the oral losartan group. Losartan-HA micelles demonstrated significant attenuation of hepatic fibrosis via an HSC-targeting mechanism in our in vitro and in vivo studies. These nanoparticles can be considered as an alternative therapy for liver fibrosis.     

COVID-19 and “natural” experiments arising from physical distancing: a hypothetical case study from chronobiology

ABSTRACT

With countless “natural” experiments triggered by the COVID-19-associated physical distancing, one key question comes from chronobiology: “When confined to homes, how does the reduced exposure to natural daylight arising from the interruption of usual outdoor activities plus lost temporal organization ordinarily provided from workplaces and schools affect the circadian timing system (the internal 24 h clock) and, consequently, health of children and adults of all ages?” Herein, we discuss some ethical and scientific facets of exploring such natural experiments by offering a hypothetical case study of circadian biology.     

c-Myc Regulates Proliferation and Fgf10 Expression in Airway Smooth Muscle after Airway Epithelial Injury in Mouse

During lung development, Fibroblast growth factor 10 (Fgf10), which is expressed in the distal mesenchyme and regulated by Wnt signaling, acts on the distal epithelial progenitors to maintain them and prevent them from differentiating into proximal (airway) epithelial cells. Fgf10-expressing cells in the distal mesenchyme are progenitors for parabronchial smooth muscle cells (PSMCs). After naphthalene, ozone or bleomycin-induced airway epithelial injury, surviving epithelial cells secrete Wnt7b which then activates the PSMC niche to induce Fgf10 expression. This Fgf10 secreted by the niche then acts on a subset of Clara stem cells to break quiescence, induce proliferation and initiate epithelial repair. Here we show that conditional deletion of the Wnt target gene c-Myc from the lung mesenchyme during development does not affect proper epithelial or mesenchymal differentiation. However, in the adult lung we show that after naphthalene-mediated airway epithelial injury c-Myc is important for the activation of the PSMC niche and as such induces proliferation and Fgf10 expression in PSMCs. Our data indicate that conditional deletion of c-Myc from PSMCs inhibits airway epithelial repair, whereas c-Myc ablation from Clara cells has no effect on airway epithelial regeneration. These findings may have important implications for understanding the misregulation of lung repair in asthma and COPD.     

Spinal Loads during Cycling on an Ergometer

Cycling on an ergometer is an effective exercise for improving fitness. However, people with back problems or previous spinal surgery are often not aware of whether cycling could be harmful for them. To date, little information exists about spinal loads during cycling. A telemeterized vertebral body replacement allows in vivo measurement of implant loads during the activities of daily living. Five patients with a severe compression fracture of a lumbar vertebral body received these implants. During one measurement session, four of the participants exercised on a bicycle ergometer at various power levels. As the power level increased, the maximum resultant force and the difference between the maximum and minimum force (force range) during each pedal revolution increased. The average maximum-force increases between the two power levels 25 and 85 W were 73, 84, 225 and 75 N for the four patients. The corresponding increases in the force range during a pedal revolution were 84, 98, 166 and 101 N. There were large variations in the measured forces between the patients and also within the same patient, especially for high power levels. In two patients, the maximum forces during high-power cycling were higher than the forces during walking measured on the same day. Therefore, the authors conclude that patients with back problems should not cycle at high power levels shortly after surgery as a precaution.     

Induction of SerpinB2 and Th1/Th2 Modulation by SerpinB2 during Lentiviral Infections In Vivo

SerpinB2, also known as plasminogen activator inhibitor type 2, is a major product of activated monocytes/macrophages and is often strongly induced during infection and inflammation; however, its physiological function remains somewhat elusive. Herein we show that SerpinB2 is induced in peripheral blood mononuclear cells following infection of pigtail macaques with CCR5-utilizing (macrophage-tropic) SIV_mac239, but not the rapidly pathogenic CXCR4-utilizing (T cell-tropic) SHIV_mn229. To investigate the role of SerpinB2 in lentiviral infections, SerpinB2^−/− mice were infected with EcoHIV, a chimeric HIV in which HIV gp120 has been replaced with gp80 from ecotropic murine leukemia virus. EcoHIV infected SerpinB2^−/− mice produced significantly lower anti-gag IgG1 antibody titres than infected SerpinB2^+/+ mice, and showed slightly delayed clearance of EcoHIV. Analyses of published microarray studies showed significantly higher levels of SerpinB2 mRNA in monocytes from HIV-1 infected patients when compared with uninfected controls, as well as a significant negative correlation between SerpinB2 and T-bet mRNA levels in peripheral blood mononuclear cells. These data illustrate that SerpinB2 can be induced by lentiviral infection in vivo and support the emerging notion that a physiological role of SerpinB2 is modulation of Th1/Th2 responses.