Highlights d Lung ACE2 levels do not vary by age or sex, but smokers exhibit upregulated ACE2 d ACE2 is expressed in several lung cell types, including the secretory lineage d Chronic smoking triggers the expansion of ACE2 + secretory cells d ACE2 is also upregulated by viral infections and interferon exposure

Females in various species typically avoid males infected with parasites, while parasite-free males advertise their status through conspicuous phenotypic traits. This process selects for heritable resistance and reduces direct exposure of the female to parasites. Coevolving parasites are likely to attempt to circumvent this obstacle. In this paper, we demonstrate a case of parasitic manipulation of host mate choice. We report that Toxoplasma gondii, a sexually transmitted infection of brown rats, enhances sexual attractiveness of infected males. Thus under some evolutionary niches, parasites can indeed manipulate host sexual signaling to their own advantage.

IMPORTANCE Widespread adoption of rapid genomic testing in pediatric critical care requires robust clinical and laboratory pathways that provide equitable and consistent service across health care systems.OBJECTIVE To prospectively evaluate the performance of a multicenter network for ultra-rapid genomic diagnosis in a public health care system. DESIGN, SETTING, AND PARTICIPANTS Descriptive feasibility study of critically ill pediatric patients with suspected monogenic conditions treated at 12 Australian hospitals between March 2018 and February 2019, with data collected to May 2019. A formal implementation strategy emphasizing communication and feedback, standardized processes, coordination, distributed leadership, and collective learning was used to facilitate adoption. EXPOSURES Ultra-rapid exome sequencing. MAIN OUTCOMES AND MEASURESThe primary outcome was time from sample receipt to ultra-rapid exome sequencing report. The secondary outcomes were the molecular diagnostic yield, the change in clinical management after the ultra-rapid exome sequencing report, the time from hospital admission to the laboratory report, and the proportion of laboratory reports returned prior to death or hospital discharge. RESULTSThe study population included 108 patients with a median age of 28 days (range, 0 days to 17 years); 34% were female; and 57% were from neonatal intensive care units, 33% were from pediatric intensive care units, and 9% were from other hospital wards. The mean time from sample receipt to ultra-rapid exome sequencing report was 3.3 days (95% CI, 3.2-3.5 days) and the median time was 3 days (range, 2-7 days). The mean time from hospital admission to ultra-rapid exome sequencing report was 17.5 days (95% CI, 14.6-21.1 days) and 93 reports (86%) were issued prior to death or hospital discharge. A molecular diagnosis was established in 55 patients (51%). Eleven diagnoses (20%) resulted from using the following approaches to augment standard exome sequencing analysis: mitochondrial genome sequencing analysis, exome sequencing-based copy number analysis, use of international databases to identify novel gene-disease associations, and additional phenotyping and RNA analysis. In 42 of 55 patients (76%) with a molecular diagnosis and 6 of 53 patients (11%) without a molecular diagnosis, the ultra-rapid exome sequencing result was considered as having influenced clinical management. Targeted treatments were initiated in 12 patients (11%), treatment was redirected toward palliative care in 14 patients (13%), and surveillance for specific complications was initiated in 19 patients (18%).CONCLUSIONS AND RELEVANCE This study suggests feasibility of ultra-rapid genomic testing in critically ill pediatric patients with suspected monogenic conditions in the Australian public health care system. However, further research is needed to understand the clinical value of such testing, and the generalizability of the findings to other health care settings.

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Cancer cells often harbor chromosomes in abnormal numbers and with aberrant structure. The consequences of these chromosomal aberrations are difficult to study in cancer, and therefore several model systems have been developed in recent years. We show that human cells with extra chromosome engineered via microcell-mediated chromosome transfer often gain massive chromosomal rearrangements. The rearrangements arose by chromosome shattering and rejoining as well as by replication-dependent mechanisms. We show that the isolated micronuclei lack functional lamin B1 and become prone to envelope rupture, which leads to DNA damage and aberrant replication. The presence of functional lamin B1 partly correlates with micronuclei size, suggesting that the proper assembly of nuclear envelope might be sensitive to membrane curvature. The chromosomal rearrangements in trisomic cells provide growth advantage compared to cells without rearrangements. Our model system enables to study mechanisms of massive chromosomal rearrangements of any chromosome and their consequences in human cells.

Highlights d A trisomy increases metastatic behavior in colon cancer cells by inducing a partial EMT d Chromosomal instability activates cGAS/STING signaling but suppresses invasiveness d Whole-chromosome aneuploidies show strong correlations with prognosis across cancers

BackgroundThe Rare and Undiagnosed Diseases Diagnostic Service (RUDDS) refers to a genomic diagnostic platform operating within the Western Australian Government clinical services delivered through Genetic Services of Western Australia (GSWA). GSWA has provided a state-wide service for clinical genetic care for 28 years and it serves a population of 2.5 million people across a geographical area of 2.5milion Km2. Within this context, GSWA has established a clinically integrated genomic diagnostic platform in partnership with other public health system managers and service providers, including but not limited to the Office of Population Health Genomics, Diagnostic Genomics (PathWest Laboratories) and with executive level support from the Department of Health. Herein we describe report presents the components of this service that are most relevant to the heterogeneity of paediatric clinical genetic care.ResultsBriefly the platform : i) offers multiple options including non-genetic testing; monogenic and genomic (targeted in silico filtered and whole exome) analysis; and matchmaking; ii) is delivered in a patient-centric manner that is resonant with the patient journey, it has multiple points for entry, exit and re-entry to allow people access to information they can use, when they want to receive it; iii) is synchronous with precision phenotyping methods; iv) captures new knowledge, including multiple expert review; v) is integrated with current translational genomic research activities and best practice; and vi) is designed for flexibility for interactive generation of, and integration with, clinical research for diagnostics, community engagement, policy and models of care.ConclusionThe RUDDS has been established as part of routine clinical genetic services and is thus sustainable, equitably managed and seeks to translate new knowledge into efficient diagnostics and improved health for the whole community.

Female rats show a distinct attraction for males. This attraction remains consistent without the necessity for the physical presence of the male. However, the identity of the olfactory cues contributing to attraction in rats remains unknown. Rat urine contains copious amounts of major urinary proteins (MUPs). Here, we investigated the hypothesis that MUPs mediate sexual attractiveness in rats. We first demonstrated that a member of a male dyad receiving greater copulatory opportunities in competitive mate choice tests excrete greater amounts of MUPs. Furthermore, the amount of male MUPs positively correlated with both copulatory opportunities received and female exploration of the urine. Using females and a two-choice olfactory attraction test, we demonstrated that urinary fractions containing MUPs were sufficient to induce attraction and that male MUPs activated neurons in the posterodorsal medial amygdala in female rats. Taken together, these results suggest that olfactory cues associated with MUPs act as an attractant to female rats in estrus.