05 Our findings offer a potential therapeutic strategy for significantly promoting the viability of surgical pedicle flaps by ischemic preconditioning with HIF-1α DNA plasmidPAX6 is considered the master regulator of eye development, the majority of variants affecting this gene cause the pan-ocular developmental eye disorder aniridia Although no genotype-phenotype correlations are clearly established, missense variants affecting the DNA-binding paired domain of PAX6 are usually associated with non-aniridia phenotypes like microphthalmia, coloboma or isolated foveal hypoplasia In this study, we report two missense heterozygous variants in the paired domain of PAX6 resulting in isolated foveal hypoplasia with nystagmus in two independent families c112 C gt; G; pArg38Gly and c214 G gt; C; pGly72Arg in exons 5 and 6, respectively Furthermore, we provide evidence that paternal postzygotic mosaicism is the cause of inheritance, with clinically unaffected fathers and reduced affected allele fraction This work contributes to increase the phenotypic spectrum caused by PAX6 variants, and to our knowledge, is the first report to describe the presence of postzygotic parental mosaicism causing isolated foveal hypoplasia with nystagmus These results support the growing evidence that suggest an overestimation of sporadic cases with PAX6 variants, which has strong implications for both genetic counselling and family planningViruses are extremely diverse and modulate important biological and ecological processes globally However, much of viral diversity remains uncultured and yet to be discovered Several powerful culture-independent tools, in particular metagenomics, have substantially advanced virus discovery Among those tools is single-virus genomics, which yields sequenced reference genomes from individual sorted virus particles without the need for cultivation This new method complements virus culturing and metagenomic approaches and its advantages include targeted investigation of specific virus groups and investigation of genomic microdiversity within viral populations In this Review, we provide a brief history of single-virus genomics, outline how this emergent method has facilitated advances in virus ecology and discuss its current limitations and future potential Finally, we address how this method may synergistically intersect with other single-virus and single-cell approachesDuring the past 85 years of antibiotic use, we have learned a great deal about how these 'miracle' drugs work We know the molecular structures and interactions of these drugs and their targets and the effects on the structure, physiology and replication of bacteria Collectively, we know a great deal about these proximate mechanisms of action for virtually all antibiotics in current use What we do not know is the ultimate mechanism of action; that is, how these drugs irreversibly terminate the 'individuality' of bacterial cells by removing barriers to the external world cell envelopes or by destroying their genetic identity DNA Antibiotics have many different 'mechanisms of action' that converge to irreversible lethal effects In this Perspective, we consider what our knowledge of the proximate mechanisms of action of antibiotics and the pharmacodynamics of their interaction with bacteria tell us about the ultimate mechanisms by which these antibiotics kill bacteriaTraditionally, the viral replication cycle is envisioned as a single, well-defined loop with four major steps attachment and entry into a target cell, replication of the viral genome, maturation of viral proteins and genome packaging into infectious progeny, and egress and dissemination to the next target cell However, for many viruses, a growing body of evidence points towards extreme heterogeneity in each of these steps In this Review, we reassess the major steps of the viral replication cycle by highlighting recent advances that show considerable variability during viral infection First, we discuss heterogeneity in entry receptors, followed by a discussion on error-prone and low-fidelity polymerases and their impact on viral diversity Next, we cover the implications of heterogeneity in genome packaging and assembly on virion morphology Last, we explore alternative egress mechanisms, including tunnelling nanotubes and host microvesicles In summary, we discuss the implications of viral phenotypic, morphological and genetic heterogeneity on pathogenesis and medicine This Review highlights common themes and unique features that give nuance to the viral replication cycleSevere acute respiratory syndrome coronavirus 2 SARS-CoV-2 is a highly transmissible and pathogenic coronavirus that emerged in late 2019 and has caused a pandemic of acute respiratory disease, named 'coronavirus disease 2019' COVID-19, which threatens human health and public safety In this Review, we describe the basic virology of SARS-CoV-2, including genomic characteristics and receptor use, highlighting its key difference from previously known coronaviruses We summarize current knowledge of clinical, epidemiological and pathological features of COVID-19, as well as recent progress in animal models and antiviral treatment approaches for SARS-CoV-2 infection We also discuss the potential wildlife hosts and zoonotic origin of this emerging virus in detailInvasive mucinous adenocarcinoma IMA of the lung is a unique variant of lung adenocarcinoma Aberrant mucin expression is associated with cancer development and metastasis However, the clinicopathological significance of mucin expression in IMA is not fully understood Herein, we evaluated the clinicopathological, immunohistochemical, and molecular characteristics of 70 IMA tumors EGFR, KRAS, GNAS, and TP53 mutations were assessed by PCR-based sequencing Next-generation sequencing was used to assess cases without EGFR/KRAS mutations https//wwwselleckchemcom/products/Eloxatinhtml A NanoString-based screening for fusions was performed in all IMAs without mitogenic driver mutations Expression of mucins MUC1, MUC2, MUC4, MUC5AC, and MUC6 was evaluated by immunohistochemistry and categorized as follows negative less then 10 of tumor cells, patchy expression less then 90 of tumor cells, or diffuse expression ≥90 of tumor cells Immunohistochemical testing for transcription factors TTF-1, CDX2, HNF1β, HNF3α, HNF3β, and HNF4α was also performed