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.
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Question: Several clinical scoring systems for diagnosis of bovine respiratory disease (BRD) in calves have been proposed. However, such systems were based on subjective judgment, rather than statistical methods, to weight scores. Data from a pair-matched case-control study on a California calf raising facility was used to develop three novel scoring systems to diagnose BRD in preweaned dairy calves. Disease status was assigned using both clinical signs and diagnostic test results for BRD-associated pathogens. Regression coefficients were used to weight score values. The systems presented use nasal and ocular discharge, rectal temperature, ear and head carriage, coughing, and respiratory quality as predictors. The systems developed in this research utilize fewer severity categories of clinical signs, require less calf handling, and had excellent agreement (Kappa > 0.8) when compared to an earlier scoring system. The first scoring system dichotomized all clinical predictors but required inducing a cough. The second scoring system removed induced cough as a clinical abnormality but required distinguishing between three levels of nasal discharge severity. The third system removed induced cough and forced a dichotomized variable for nasal discharge. The first system presented in this study used the following predictors and assigned values: coughing (induced or spontaneous coughing, 2 points), nasal discharge (any discharge, 3 points), ocular discharge (any discharge, 2 points), ear and head carriage (ear droop or head tilt, 5 points), fever (≥39.2 • C or 102.5 • F, 2 points), and respiratory quality (abnormal respiration, 2 points). Calves were categorized "BRD positive" if their total score was ≥4. This system correctly classified 95.4% cases and 88.6% controls. The second presented system categorized the predictors and assigned weights as follows: coughing (spontaneous only, 2 points), mild nasal discharge (unilateral, serous, or watery discharge, 3 points), moderate to severe nasal discharge (bilateral, cloudy, mucoid, mucopurlent, or copious discharge, 5 points), ocular discharge (any discharge, 1 point), ear and head carriage (ear droop or head tilt, 5 points), fever (≥39.2 • C, 2 points), and respiratory quality (abnormal How to cite this article Love et al. (2014), Development of a novel clinical scoring system for on-farm diagnosis of bovine respiratory disease in pre-weaned dairy calves. PeerJ 2:e238; DOI 10.7717/peerj.238 respiration, 2 points). Calves were categorized "BRD positive" if their total score was ≥4. This system correctly classified 89.3% cases and 92.8% controls. The third presented system used the following predictors and scores: coughing (spontaneous only, 2 points), nasal discharge (any, 4 points), ocular discharge (any, 2 points), ear and head carriage (ear droop or head tilt, 5 points), fever (≥39.2 • C, 2 points), and respiratory quality (abnormal respiration, 2 points). Calves were categorized "BRD positive" if their total score was ≥5. This system correctly classified 89.4% cases and 90.8% controls. Each of the proposed systems offer few levels of clinical signs and data-based weights for on-farm diagnosis of BRD in dairy calves.

Answer: OPEN ACCESS


Question: Basic and translational research on lung biology has discovered multiple progenitor cell types, specialized or facultative, responsible for turnover, renewal, and repair. Isolation of populations of resident lung progenitor cells (LPCs) has been described by multiple protocols, and some have been successfully applied to healthy human lung tissue. We aimed at understanding how different cell culture conditions may affect, in vitro, the phenotype of LPCs to create an ideal niche-like microenvironment. The influence of different substrates (i.e., fibronectin, gelatin, laminin) and the impact of a three-dimensional/two-dimensional (3D/2D) culture switch on the biology of LPCs isolated as lung spheroids (LSs) from normal adult human lung biopsy specimens were investigated. We applied a spheroid culture system as the selective/inductive step for progenitor cell culture, as described in many biological systems. The data showed a niche-like proepithelial microenvironment inside the LS, highly sensitive to the 3D culture system and significantly affecting the phenotype of adult LPCs more than culture substrate. LSs favor epithelial phenotypes and LPC maintenance and contain cells more responsive to specific commitment stimuli than 2D monolayer cultures, while secreting a distinctive set of paracrine factors. We have shown for the first time, to our knowledge, how culture as 3D LSs can affect LPC epithelial phenotype and produce strong paracrine signals with a distinctive secretomic profile compared with 2D monolayer conditions. These findings suggest novel approaches to maintain ex vivo LPCs for basic and translational studies. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:1-11 SIGNIFICANCE A lung niche-like microenvironment was created ex vivo inside the pneumosphere. Pneumospheres have a distinctive secretomic profile compared with two-dimensional culture. Three-dimensional culture switch significantly affects lung progenitor phenotype. Lung progenitors in pneumospheres were more committed toward epithelial lineages.

Answer: Tissue-Specific Progenitor and Stem Cells Human Lung Spheroids as In Vitro Niches of Lung Progenitor Cells With Distinctive Paracrine and Plasticity Properties


Question: Macroautophagy (autophagy) involves the formation of a double-membrane organelle called the autophagosome, which sequesters cytoplasmic components that are degraded upon its fusion with the lysosome (Stolz et al., 2014; Kaur and Debnath, 2015) . Studies in yeast have identified >30 autophagy-related (ATG) proteins, many of which have identified mammalian orthologues. The canonical process of autophagy begins with initiation at the phagophore assembly site, mediated by the UNC51-like kinase (ULK) complex, which is composed of the ATG proteins ULK1/2, ATG13, FIP200, and ATG101. The ULK complex supports the activation of a class III phosphatidylinositol 3-kinase complex consisting of Beclin 1 (ATG6), ATG14, and VPS34 to produce phosphatidylinositol triphosphate, which serves as the initial membrane mark recognized by early autophagic effector proteins. Phagophore membrane expansion is mediated by the two ubiquitin-like conjugation systems involving multiple ATG proteins that ultimately lead to the lipidation of microtubule-associated protein 1 light chain 3 (LC3), the mammalian orthologue of ATG8. LC3 is recognized by autophagy cargo receptors that promote the selective capture and engulfment of proteins, organelles, or microbes. The closed autophagosome is then trafficked to and fuses with the lysosome to degrade its cargo (Stolz et al., 2014; Kaur and Debnath, 2015) . ATG proteins traditionally have been studied for their roles in autophagosome formation and maturation, but we have recently begun to appreciate that they may have pleiotropic roles beyond autophagy (Bestebroer et al., 2013) . In this issue, through a comprehensive functional screen for ATG proteins in the control of viral replication, Mauthe et al. highlight the importance of the nontraditional functions of ATG proteins in the host viral response. In a tour-de-force study examining multiple models of viral infection, Mauthe et al. (2016) interrogated the individual roles of ATG proteins in the replication of herpes simplex virus type 1, mouse hepatitis virus (MHV), vaccinia virus (VaV), semliki forest virus, encephalomyocarditis virus, and influenza A virus. The authors generated a curated siRNA library to target all ATG proteins individually as well as functionally redundant groups concurrently to evaluate how they promote the replication of these six viruses in two model cell lines (HeLa and U2OS). Indeed, their screen reveals that unconventional functions of ATG proteins are widespread; overall, 16 out of the 44 tested ATG proteins (36%) appear to have unconventional functions. Rarely does knockdown of individual ATG genes result in concordant effects on viral replication, arguing against a general role for autophagy. Moreover, the authors fail to identify any single ATG protein that regulates viral replication in all of the tested viruses; rather, specific ATG genes influenced the replication of each virus. Remarkably, most of the ATG proteins show a beneficial role for VaV replication in U2OS cells yet negatively impact VaV replication in HeLa cells. Overall, the effect of ATG loss of function on viral replication is exquisitely ATG specific, virus specific, and cell line specific. To demonstrate functions of ATG proteins independent of autophagy, the authors scrutinized ATG13 and FIP200, two ULK complex proteins that initiate formation of the autophagosome, and found that these proteins exert effects on viral replication distinct from the effects of other ULK complex components. Mauthe et al. (2016) demonstrate that depletion of ATG13 and FIP200 reduces the replication of two picornaviruses, encephalomyocarditis virus and coxsackievirus (CV) B3, whereas the other ULK complex components promote their replication. Furthermore, a principal upstream regulator of ULK complex activity, mammalian target of rapamycin complex 1, showed no changes in activity during infection or knockdown of the ULK complex components. Altogether, this evidence indicates that ATG13 and FIP200 act independently of the ULK complex to modify picornaviral replication outside the context of autophagy. Although the precise mechanism of this unconventional function of ATG13 and FIP200 remains to be elucidated, Mauthe et al. (2016) uncovered that these proteins control viral replication as opposed to viral entry or viral translation. However, ATG13 and FIP200 do not interact with any CV proteins or affect the morphology of CV replication structures, suggesting Autophagy-related (ATG) proteins have increasingly demonstrated functions other than cellular self-eating. In this issue, Mauthe et al. (2016. J. Cell Biol. http ://dx .doi .org /10 .1083 /jcb .201602046) conduct an unbiased RNA interference screen of the ATG proteome to reveal numerous noncanonical roles for ATG proteins during viral infection.

Answer:
At the crossroads of autophagy and infection: Noncanonical roles for ATG proteins in viral replication