In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.

Input: Consider Input: Autophagy is a key innate immune response to intracellular parasites that promotes their delivery to degradative lysosomes following detection in the cytosol or within damaged vacuoles. Like Listeria and Shigella, which use specific mechanisms to avoid autophagic detection and capture, the bacterial pathogen Francisella tularensis proliferates within the cytosol of macrophages without demonstrable control by autophagy. To examine how Francisella evades autophagy, we screened a library of F. tularensis subsp. tularensis Schu S4 HimarFT transposon mutants in GFP-LC3-expressing murine macrophages by microscopy for clones localised within autophagic vacuoles after phagosomal escape. Eleven clones showed autophagic capture at six hours postinfection, whose HimarFT insertions clustered to four genetic loci involved in lipopolysaccharidic and capsular O-antigen biosynthesis. Consistent with the HimarFT mutants, in-frame deletion mutants of two representative loci, FTT1236 and FTT1448c (manC), lacking both LPS and capsular O-antigen, underwent phagosomal escape but were cleared from the host cytosol. Unlike wild type Francisella, the O-antigen deletion mutants were ubiquitinated, and recruited the autophagy adaptor p62/SQSTM1 and LC3 prior to cytosolic clearance. Autophagy-deficient macrophages partially supported replication of both mutants, indicating that O-antigen-lacking Francisella are controlled by autophagy. These data demonstrate the intracellular protective role of this bacterial surface polysaccharide against autophagy.

Output: The Francisella O-antigen mediates survival in the macrophage cytosol via autophagy avoidance NIH Public Access


Input: Consider Input: Muscle wasting is one of the main features of cancer cachexia, a multifactorial syndrome frequently occurring in oncologic patients. The onset of cachexia is associated with reduced tolerance and response to antineoplastic treatments, eventually leading to clinical conditions that are not compatible with survival. Among the mechanisms underlying cachexia, protein and energy dysmetabolism play a major role. In this regard, several potential treatments have been proposed, mainly on the basis of promising results obtained in preclinical models. However, at present, no treatment yet reached validation to be used in the clinical practice, although several drugs are currently tested in clinical trials for their ability to improve muscle metabolism in cancer patients. Along this line, the results obtained in both experimental and clinical studies clearly show that cachexia can be effectively approached by a multidirectional strategy targeting nutrition, inflammation, catabolism, and inactivity at the same time. In the present study, approaches aimed to modulate muscle metabolism in cachexia will be reviewed.

Output: Modulating Metabolism to Improve Cancer-Induced Muscle Wasting


Input: Consider Input: Porcine deltacoronavirus (δ-CoV) is the object of extensive research in several countries including the United States. In contrast, the epidemiology of δ-CoVs in wild birds in the US is largely unknown. Our aim was to comparatively assess the prevalence of δand γ-CoVs in wild migratory terrestrial and aquatic birds in Arkansas, Illinois, Indiana, Maryland, Mississippi, Missouri, Ohio, Tennessee and Wisconsin. A total of 1236 cloacal/fecal swabs collected during the period 2015-2018 were tested for γand δ-CoVs using genus-specific reverse transcription-PCR assays. A total of 61 (4.99%) samples were γ-CoV positive, with up to 29 positive samples per state. In contrast, only 14 samples were positive for δ-CoV (1.14%) with only 1-4 originating from the same state. Thus, unlike previous reports from Asia, γ-CoVs are more prevalent than δ-CoVs in the US, suggesting that δ-CoVs may spread in birds with lower efficiency. This may indicate δ-CoV emerging status and incomplete adaptation to new host species limiting its spread. Phylogenetic analysis of the partial N gene revealed that the newly identified δ-CoV strains were most closely related to the HKU20 (wigeon) strain. Further studies are necessary to investigate the role of aquatic bird δ-CoVs in the epidemiology of δ-CoVs in swine and terrestrial birds. Viruses 2019, 11, 897 2 of 11 and mammals including pigs [4] . Porcine deltacoronavirus (PDCoV) emerged in the US in 2014 as a new enteropathogenic CoV causing diarrhea, vomiting, and mortality in neonatal piglets, resulting in economic losses to the swine industry [4, 5] . Its origin is unknown, but it is hypothesized that it may have spilled over from an avian host. δ-CoV and γ-CoV are co-circulating in wild avian species, but their epidemiology (prevalence and diversity) differ [6] [7] [8] [9] [10] [11] [12] [13] . In a screening study of 918 wild Australian birds, 141 of them tested positive for CoVs. After sequencing, δ-CoV was detected in pacific black ducks, curlew sandpiper, red-necked stints, ruddy turnstones, and pied herons [6] . However, γ-CoV (80% of sequenced samples) was identified more frequently than δ-CoV (20% of sequenced samples) [6] . γ-CoV was also detected in quails and pheasants in Italy [7] . RNA-dependent RNA polymerase (RdRp) analyses found that quail were also infected with δ-CoV [7]. Wild birds harbor genetically diverse δ-CoV with some of them potentially transmittable to pigs [8] . A previous report from Brazil showed that δ-CoVs were detected in two species of wild terrestrial birds, purple-breasted-parrot and plain parakeet. These avian CoVs were monophyletically related to CoVs from Sparrow (SPaCoV HKU19) and swine (PorCoV HKU15), which were also found to be δ-CoV. This information supports the hypothesis that δ-CoV can cross inter-species barriers, with the potential to transmit from birds to swine [8] . Previous studies of CoVs in Hong Kong reported three novel CoVs in bulbuls (BuCoV HKU11), thrushes (ThCoV HKU12) and munias (MuCoV HKU13), which were hypothesized to belong to the novel genus δ-CoV [9]. These three novel δ-CoVs clustered with a δ-CoV detected in Asian leopard cats [10]; however, further studies are necessary to understand interspecies transmission from birds [9]. In a surveillance study in Hong Kong and Cambodia, δ-CoVs were found in different wild aquatic birds: gray herons, pond herons, great cormorants, black-faced spoonbills, and several duck species [11] . δ-CoVs do not cause severe illness in birds, leading to their endemic nature in the avian population [11] . In a screening study for δ-CoVs in China, none were found in Asian leopard cats, bats, domestic cats, cattle, chickens, dogs, humans, monkeys, and rodents [12] . The investigators discovered seven novel δ-CoVs in pigs and wild birds (white-eye, sparrow, magpie robin, night heron, wigeon, and common moorhen) [12] . Genome sequencing and comparative genome analysis showed that avian and swine δ-CoVs had similar genome characteristics and structures [12] . Similarly, a recent study in the US described a novel sparrow δ-CoV that clustered together with PDCoV [13] and other terrestrial, but aquatic bird δ-CoVs. In Brazil, screening revealed the presence of CoVs in vinaceous-breasted amazon and plain parakeet, that were closely related to δ-CoVs from birds (SpaCoV HKU17) and swine (PorCoV). This emphasizes the increased risk for direct interspecies transmission and that in contrast to waterfowl, terrestrial birds may act as intermediate hosts and are commonly found in the sites of bird-swine co-mingling [8]. In Finland, two different avian δ-CoV strains from lesser black-backed gull and black-headed gull were detected which shared 83% and 85% nucleotide identity with avian and mammalian δ-CoVs, respectively [14] . In summary, recently identified δ-CoVs are emerging globally that possess high genetic and antigenic plasticity. Porcine δ-CoV is being studied extensively in the US and elsewhere [4, 5] . In contrast, the diversity and epidemiology of δ-CoVs in wild birds in the US are largely unknown. The association of porcine δ-CoV with enteric disease in pigs and its continuous spread underscore an urgent need to further investigate the mechanisms of its persistence and spread. Extensive epidemiological studies are needed to evaluate δ-CoV prevalence in avian species, swine farms, pig-bird comingling sites and high pig-traffic sites such as abattoirs, assembly yards and truck washes. In this study, we investigated the prevalence of δand γ-CoVs in wild migratory terrestrial and aquatic birds in Arkansas, Illinois, Indiana, Maryland, Mississippi, Missouri, Ohio, Tennessee, and Wisconsin. Author Contributions: Conceptualization, A.N.V.; methodology, F.C.P., L.M., B.J.F. and D.M.; software, F.C.P., A.N.V., L.M and D.M.; validation, A.N.V. and F.C.P.; formal analysis, A.N.V.; F.C.P.; investigation, F.C.P. and A.N.V.; resources, A.S.B. and A.N.V.; data curation, F.C.P. and A.N.V.; writing-original draft preparation, F.C.P.; writing-review and editing, F.C.P., A.N.V., L.J.S., A.S.B. and B.J.F.; visualization, A.N.V and F.C.P.; supervision, A.N.V. and L.J.S.; project administration, A.N.V. and L.J.S.; funding acquisition, A.N.V. and L.J.S.


Output: Epidemiology of Deltacoronaviruses (δ-CoV) and Gammacoronaviruses (γ-CoV) in Wild Birds in the United States