In Vivo Microbial Coevolution Favors Host Protection and Plastic Downregulation of Immunity

Microbiota can protect their hosts from infection. The short timescales in which microbes can evolve presents the possibility that “protective microbes” can take-over from the immune system of longer-lived hosts in the coevolutionary race against pathogens. Here, we found that coevolution between a protective bacterium (Enterococcus faecalis) and a virulent pathogen (Staphylococcus aureus) within an animal population (Caenorhabditis elegans) resulted in more disease suppression than when the protective bacterium adapted to uninfected hosts. At the same time, more protective E. faecalis populations became costlier to harbor and altered the expression of 134 host genes. Many of these genes appear to be related to the mechanism of protection, reactive oxygen species production. Crucially, more protective E. faecalis populations downregulated a key immune gene, , known to be effective against S. aureus infection. These results suggest that a microbial line of defense is favored by microbial coevolution and may cause hosts to plastically divest of their own immunity.     

NOTES ON GEOGRAPHICAL VARIATION AND THE ANNUAL CYCLE IN PATAGONIAN POPULATIONS OF THE RUFOUS-COLLARED SPARROW ZONOTRICHIA CAPENSIS

Zonotrichia capensis australis inhabits Argentina from the northernmost limits of the Patagonian steppe south through Tierra del Fuego, and extends westward to the Pacific slope in southern Chile. At least part of the population has a north-south migration along the Andean foothills of Argentina as far north as southwestern Bolivia. The breeding range of australis is bounded on the north and northwest by subspecies of Z. capensis (chilensis, choraules , and possibly hypoleuca ) having conspicuous black lateral crown-stripes. Topotypical australis (Tierra del Fuego) have plain grey crowns, but the frequency of black nuchal markings and faint lateral crown-lines increases northward in the coastal populations. In inland populations (Andean piedmont) the frequency of black crown markings is apparently reversed, increasing southward. The size (wing-length, tarsus, bill, and probably body-weight) of australis decreases northward in both coastal and inland samples.
The nesting season of australis begins in late November and early December and extends to mid January and early February. Postnuptial moult begins from mid December to early January. Moult proceeds while the testes are apparently still functional. Postnuptial moult terminates from late January through mid March. There is no evidence in the current data of geographical trends in the chronology of nesting and postnuptial moult. The calendars appear to be about the same throughout the range of australis .
Postjuvenal moult begins about 4–5 weeks later than the onset of postnuptial moult and terminates in the latest birds in about mid March. Northward migration begins at about this time.     

Ecological succession among iron-oxidizing bacteria

Despite over 125 years of study, the factors that dictate species dominance in neutrophilic iron-oxidizing bacterial (FeOB) communities remain unknown. In a freshwater wetland, we documented a clear ecological succession coupled with niche separation between the helical stalk-forming Gallionellales (for example, Gallionella ferruginea) and tubular sheath-forming Leptothrix ochracea. Changes in the iron-seep community were documented using microscopy and cultivation-independent methods. Quantification of Fe-oxyhydroxide morphotypes by light microscopy was coupled with species-specific fluorescent in situ hybridization (FISH) probes using a protocol that minimized background fluorescence caused by the Fe-oxyhydroxides. Together with scanning electron microscopy, these techniques all indicated that Gallionellales dominated during early spring, with L. ochracea becoming more abundant for the remainder of the year. Analysis of tagged pyrosequencing reads of the small subunit ribosomal RNA gene (SSU rRNA) collected during seasonal progression supported a clear Gallionellales to L. ochracea transition, and community structure grouped according to observed dominant FeOB forms. Axis of redundancy analysis of physicochemical parameters collected from iron mats during the season, plotted with FeOB abundance, corroborated several field and microscopy-based observations and uncovered several unanticipated relationships. On the basis of these relationships, we conclude that the ecological niche of the stalk-forming Gallionellales is in waters with low organic carbon and steep redoxclines, and the sheath-forming L. ochracea is abundant in waters that contain high concentrations of complex organic carbon, high Fe and Mn content and gentle redoxclines. Finally, these findings identify a largely unexplored relationship between FeOB and organic carbon.     

Clinal variation at aspartate aminotransferase-2 in spotted seatrout,Cynoscion nebulosus (Cuvier), inhabiting the north-western Gulf of Mexico

Clinal variation was observed at the aspartate aminotransferase-2 (AAT-2) locus in the marine fish Cynoscion nebulosus (Cuvier) inhabiting the bays and estuaries of the Texas and northern Mexico Gulf coasts. Frequency of the AAT-2(80) allele increased from 0.9% at Sabine Lake, Texas to 17.1% at Rio Soto La Marina, Mexico. A statistically significant correlation existed in the frequency of this allele with degrees north latitude and west longitude. This information, if properly incorporated into a comprehensive enhancement programme, could facilitate supplemental stocking success.     

Inhibition of Janus Kinase 1 synergizes docetaxel sensitivity in prostate cancer cells

Prostate cancer (PCa) is the second most common malignancy and is the fifth leading cause of cancer mortality among men globally. Docetaxel-based therapy remains the first-line treatment for metastatic castration-resistant prostate cancer. However, dose-limiting toxicity including neutropenia, myelosuppression and neurotoxicity is the major reason for docetaxel dose reductions and fewer cycles administered, despite a recent study showing a clear survival benefit with increased total number of docetaxel cycles in PCa patients. Although previous studies have attempted to improve the efficacy and reduce docetaxel toxicity through drug combination, no drug has yet demonstrated improved overall survival in clinical trial, highlighting the challenges of improving the activity of docetaxel monotherapy in PCa. Herein, we identified 15 lethality hits for which inhibition could enhance docetaxel sensitivity in PCa cells via a high-throughput kinome-wide loss-of-function screen. Further drug-gene interactions analyses identified Janus kinase 1 (JAK1) as a viable druggable target with existing experimental inhibitors and FDA-approved drugs. We demonstrated that depletion of endogenous JAK1 enhanced docetaxel-induced apoptosis in PCa cells. Furthermore, inhibition of JAK1/2 by baricitinib and ruxolitinib synergizes docetaxel sensitivity in both androgen receptor (AR)–negative DU145 and PC3 cells, but not in the AR-positive LNCaP cells. In contrast, no synergistic effects were observed in cells treated with JAK2-specific inhibitor, fedratinib, suggesting that the synergistic effects are mainly mediated through JAK1 inhibition. In conclusion, the combination therapy with JAK1 inhibitors and docetaxel could be a useful therapeutic strategy in the treatment of prostate cancers.