The zero exemplar distance problem

Given two genomes with duplicate genes, \textsc{Zero Exemplar Distance} is the problem of deciding whether the two genomes can be reduced to the same genome without duplicate genes by deleting all but one copy of each gene in each genome. Blin, Fertin, Sikora, and Vialette recently proved that \textsc{Zero Exemplar Distance} for monochromosomal genomes is NP-hard even if each gene appears at most two times in each genome, thereby settling an important open question on genome rearrangement in the exemplar model. In this paper, we give a very simple alternative proof of this result. We also study the problem \textsc{Zero Exemplar Distance} for multichromosomal genomes without gene order, and prove the analogous result that it is also NP-hard even if each gene appears at most two times in each genome. For the positive direction, we show that both variants of \textsc{Zero Exemplar Distance} admit polynomial-time algorithms if each gene appears exactly once in one genome and at least once in the other genome. In addition, we present a polynomial-time algorithm for the related problem \textsc{Exemplar Longest Common Subsequence} in the special case that each mandatory symbol appears exactly once in one input sequence and at least once in the other input sequence. This answers an open question of Bonizzoni et al. We also show that \textsc{Zero Exemplar Distance} for multichromosomal genomes without gene order is fixed-parameter tractable if the parameter is the maximum number of chromosomes in each genome.Comment: Strengthened and reorganize

Critical Issues in the Development of Health Information Systems in Supporting Environmental Health: A Case Study of Ciguatera

Emerging environmental pressures resulting from climate change and globalization challenge the capacity of health information systems (HIS) in the Pacific to inform future policy and public health interventions. Ciguatera, a globally common marine food-borne illness, is used here to illustrate specific HIS challenges in the Pacific and how these might be overcome proactively to meet the changing surveillance needs resulting from environmental change.We review and highlight inefficiencies in the reactive nature of existing HIS in the Pacific to collect, collate, and communicate ciguatera fish poisoning data currently used to inform public health intervention. Further, we review the capacity of existing HIS to respond to new data needs associated with shifts in ciguatera disease burden likely to result from coral reef habitat disruption.Improved knowledge on the ecological drivers of ciguatera prevalence at local and regional levels is needed, combined with enhanced surveillance techniques and data management systems, to capture environmental drivers as well as health outcomes data.The capacity of public HIS to detect and prevent future outbreaks is largely dependent on the future development of governance strategies that promote proactive surveillance and health action. Accordingly, we present an innovative framework from which to stimulate scientific debate on how this might be achieved by using existing larger scale data sets and multidisciplinary collaborations

APC/CCdh1-Rock2 pathway controls dendritic integrity and memory

Disruption of neuronal morphology contributes to the pathology of neurodegenerative disorders such as Alzheimer's disease (AD). However, the underlying molecular mechanisms are unknown. Here, we show that postnatal deletion of Cdh1, a cofactor of the anaphasepromoting complex/cyclosome (APC/C) ubiquitin ligase in neurons [Cdh1 conditional knockout (cKO)], disrupts dendrite arborization and causes dendritic spine and synapse loss in the cortex and hippocampus, concomitant with memory impairment and neurodegeneration, in adult mice. We found that the dendrite destabilizer Rho protein kinase 2 (Rock2), which accumulates in the brain of AD patients, is an APC/C substrate in vivo and that Rock2 protein and activity increased in the cortex and hippocampus of Cdh1 cKO mice. In these animals, inhibition of Rock activity, using the clinically approved drug fasudil, prevented dendritic network disorganization, memory loss, and neurodegeneration. Thus, APC/C-mediated degradation of Rock2 maintains the dendritic network, memory formation, and neuronal survival, suggesting that pharmacological inhibition of aberrantly accumulated Rock2 may be a suitable therapeutic strategy against neurodegeneration.This work was funded by Instituto de Salud Carlos III Grants PI15/00473, BAE14/0005, RD12/0014/0007, and RD16/0019/0018 (to A.A.) and RD12/0014/0001 and RD16/0019/0001 (to J.C.); FEDER (European Regional Development Fund); Ministerio de Economía y Competitividad Grant SAF2016-78114-R (to J.P.B.); and European Union’s Horizon 2020 Research and Innovation Programme Grant 686009 (to A.A. and J.C.). V.B.-J. (PI15/00473) and M.D.-E. (CP0014/00010) are supported by the Instituto de Salud Carlos III. I.S.-M. is supported by the Junta de Castilla y León (Spain).Peer Reviewe

Idiopathic pulmonary fibrosis Significance of the usual interstitial pneumonia (UIP) CT-scan patterns defined in new international guidelines

International audienceIntroduction The new 2018 international guidelines for diagnosing usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) by CT scan split the old pattern possible UIP (2011 IPF guidelines) into two new patterns probable UIP and indeterminate for UIP. However, the proportions and prognoses of these new CT-scan patterns are not clear.Methods We used a monocentric retrospective cohort of 322 patients suspected of having IPF (University Hospital of Rennes; Competence Center for Rare Lung Diseases; 1 January 2012-31 December 2017). All patients initially diagnosed by CT scan as possible UIP were included. The chest CT-scans were then reclassified according to the new 2018 international guidelines by 3 observers. These data were then subjected to survival analysis with multivariate Cox regression using a composite endpoint of death, lung transplantation, a decline of ≥ 10% in forced vital capacity (FVC), or hospitalization.Results Of the 89 possible UIP patients included, 74 (83%) were reclassified as probable UIP and 15 (17%) as indeterminate for UIP. Probable UIP patients were more likely to meet the composite endpoint (56/74 [75.7%] vs. 5/15 [33%] patients; HR [IC 95%] = 3.12 [1.24; 7.83], P = 0.015). Multivariate analysis indicated that the probable UIP pattern was associated with significantly increased risk of reaching the composite endpoint (HR [95% CI] = 2.85[1.00; 8.10], P = 0.049).Conclusion The majority of possible UIP diagnoses corresponded to probable UIP, which was associated with a significantly worse prognosis than indeterminate for UIP. This distinction between these two CT patterns emphasizes the relevance of the new international guidelines for the diagnosis of IPF. © 2020 SPLF and Elsevier Masson SA