A β-Catenin-Dependent Wnt Pathway Mediates Anteroposterior Axon Guidance in C. elegans Motor Neurons

Wnts are secreted glycoproteins that regulate diverse aspects of development, including cell proliferation, cell fate specification and differentiation. More recently, Wnts have been shown to direct axon guidance in vertebrates, flies and worms. However, little is known about the intracellular signaling pathways downstream of Wnts in axon guidance.Here we show that the posterior C. elegans Wnt protein LIN-44 repels the axons of the adjacent D-type motor neurons by activating its receptor LIN-17/Frizzled on the neurons. Moreover, mutations in mig-5/Disheveled, gsk-3, pry-1/Axin, bar-1/beta-catenin and pop-1/TCF, also cause disrupted D-type axon pathfinding. Reduced BAR-1/beta-catenin activity in D-type axons leads to undergrowth of axons, while stabilization of BAR-1/beta-catenin in a lin-23/SCF(beta-TrCP) mutant results in an overextension phenotype.Together, our data provide evidence that Wnt-mediated axon guidance can be transduced through a beta-catenin-dependent pathway

The Lung Image Database Consortium (LIDC): An Evaluation of Radiologist Variability in the Identification of Lung Nodules on CT Scans

RATIONALE AND OBJECTIVES: The purpose of this study was to analyze the variability of experienced thoracic radiologists in the identification of lung nodules on CT scans and thereby to investigate variability in the establishment of the “truth” against which nodule-based studies are measured. MATERIALS AND METHODS: Thirty CT scans were reviewed twice by four thoracic radiologists through a two-phase image annotation process. During the initial “blinded read” phase, radiologists independently marked lesions they identified as “nodule ≥ 3mm (diameter),” “nodule < 3mm,” or “non-nodule ≥ 3mm.” During the subsequent “unblinded read” phase, the blinded read results of all radiologists were revealed to each of the four radiologists, who then independently reviewed their marks along with the anonymous marks of their colleagues; a radiologist’s own marks then could be deleted, added, or left unchanged. This approach was developed to identify, as completely as possible, all nodules in a scan without requiring forced consensus. RESULTS: After the initial blinded read phase, a total of 71 lesions received “nodule ≥ 3mm” marks from at least one radiologist; however, all four radiologists assigned such marks to only 24 (33.8%) of these lesions. Following the unblinded reads, a total of 59 lesions were marked as “nodule ≥ 3 mm” by at least one radiologist. 27 (45.8%) of these lesions received such marks from all four radiologists, 3 (5.1%) were identified as such by three radiologists, 12 (20.3%) were identified by two radiologists, and 17 (28.8%) were identified by only a single radiologist. CONCLUSION: The two-phase image annotation process yields improved agreement among radiologists in the interpretation of nodules ≥ 3mm. Nevertheless, substantial variabilty remains across radiologists in the task of lung nodule identification

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2

Experimental manipulation of a signal trait reveals complex phenotype-behaviour coordination

Abstract Animals use morphological signals such as ornamental traits or weaponry to mediate social interactions, and the extent of signal trait elaboration is often positively associated with reproductive success. By demonstrating relationships between signal traits and fitness, researchers often make inferences about how behaviour operates to shape those outcomes. However, detailed information about fine-scale individual behaviour, and its physiological basis, can be difficult to obtain. Here we show that experimental manipulations to exaggerate a signal trait (plumage colour) and concomitant changes in testosterone and stress-induced corticosterone levels altered social interactivity between manipulated males and their social mates. On average, darkened males did not have higher levels of interactivity than unmanipulated males; however, males who experienced a greater shift in colour (pale to dark), a larger, positive change in testosterone levels, and a dampened stress-induced corticosterone response had a larger increase in the number of interactions with their social mate post-manipulation compared to pre-manipulation. This work provides new insights into the integration and real-time flexibility of multivariate phenotypes and direct evidence for the role of social interactions in pair bond maintenance

Differences in Patient Outcomes of Prevalence, Interval, and Screen-Detected Lung Cancers in the CT Arm of the National Lung Screening Trial

Lung cancer screening identifies cancers with heterogeneous behaviors. Some lung cancers will be identified among patients who had prior negative CT screens and upon follow-up scans develop a de novo nodule that was determined to be cancerous. Other lung cancers will be identified among patients who had one or more prior stable positive scans that were not determined to be lung cancer (indeterminate pulmonary nodules), but in follow-up scans was diagnosed with an incidence lung cancer. Using data from the CT arm of the National Lung Screening Trial, this analysis investigated differences in patient characteristics and survival endpoints between prevalence-, interval-, and screen-detected lung cancers, characterized based on sequence of screening results. Lung cancers immediately following a positive baseline (T0), and prior to the T1 screen, formed the prevalence cohort. Interval cancers were diagnosed following a negative screen at any time point prior to the next screening round. Two cohorts of screen-detected lung cancers (SDLC) were identified that had a baseline positive screen that was that was not determined to be lung cancer (i.e., an indeterminate pulmonary nodule), but in follow-up scans was diagnosed with an incidence lung cancer 12 (SDLC1) or 24 (SDLC2) months later. Two other incidence cohorts had screen-detected lung cancers that had baseline negative screen and upon follow-up scans developed a de novo nodule determined to be cancerous at 12 (SDLC3) or 24 (SDLC4) months later. Differences in patient characteristics, progression-free survival (PFS), and overall survival (OS) were assessed. The lung cancer-specific death rate was higher for SDLC3/SDLC4 compared to SDLC1/SDLC2 lung cancers (136.6/1,000 person-years vs. 71.3/1,000 person-years, P \u3c 0.001). Moreover, PFS and OS were significantly lower for SDLC3/SDLC4 compared to SDLC1/SDLC2 (P \u3c 0.004; P \u3c 0.002, respectively). The findings were consistent when stratified by stage and histology. Multivariable Cox proportional models revealed that the SDLC3/SDLC4 case groups were associated with significantly poorer PFS (HR = 1.89; 95% CI 1.31–2.74) and OS (HR = 1.80; 95% CI 1.21–2.67) compared to SDLC1/SDLC2 lung cancers (HR = 1.00). Lung cancer patients who develop a de novo nodule that determined to be cancerous (i.e., at least one negative CT screen prior to cancer diagnosis) had poorer survival outcomes compared to patients who had at least one positive screen prior to cancer diagnosis. As such, the observation that de novo screen-detected are associated with poorer survival could be attributed to faster growing, more aggressive cancers that arose from a lung environment previously lacking focal abnormalities

Multivariable Cox Proportional Hazards Models for Progression Free and Overall Survival for the Screen-Detected Cohorts.

<p>Multivariable Cox Proportional Hazards Models for Progression Free and Overall Survival for the Screen-Detected Cohorts.</p

Clinical Characteristics and Outcomes of the Grouped Screen-Detected, Prevalence, and Interval Cancer Cohorts.

<p>Clinical Characteristics and Outcomes of the Grouped Screen-Detected, Prevalence, and Interval Cancer Cohorts.</p

Baseline Demographic of the Grouped Screen-Detected, Prevalence, and Interval Cancer Cohorts.

<p>Baseline Demographic of the Grouped Screen-Detected, Prevalence, and Interval Cancer Cohorts.</p