Please see http//www.annualreviews.org/page/journal/pubdates for revised estimates.For plant viruses, the ability to load into the vascular phloem and spread systemically within a host is an essential step in establishing a successful infection. However, access to the vascular phloem is highly regulated, representing a significant obstacle to virus loading, movement, and subsequent unloading into distal uninfected tissues. Recent studies indicate that during virus infection, phloem tissues are a source of significant transcriptional and translational alterations, with the number of virus-induced differentially expressed genes being four- to sixfold greater in phloem tissues than in surrounding nonphloem tissues. In addition, viruses target phloem-specific components as a means to promote their own systemic movement and disrupt host defense processes. Combined, these studies provide evidence that the vascular phloem plays a significant role in the mediation and control of host responses during infection and as such is a site of considerable modulation by the infecting virus. This review outlines the phloem responses and directed reprograming mechanisms that viruses employ to promote their movement through the vasculature. Expected final online publication date for the Annual Review of Virology, Volume 7 is September 29, 2020. Please see http//www.annualreviews.org/page/journal/pubdates for revised estimates.In eukaryotic cells, about one-third of the synthesized proteins are translocated into the endoplasmic reticulum; they are membrane or lumen resident proteins and proteins direct to the Golgi apparatus. The co-translational translocation takes place through the heterotrimeric protein-conducting channel Sec61 which is associated with the ribosome and many accessory components, such as the heterotetrameric translocon-associated protein (TRAP) complex. Recently, microscopic techniques, such as cryo-electron microscopy and cryo-electron tomography, have enabled the determination of the translocation machinery structure. However, at present, there is a lack of understanding regarding the roles of some of its components; indeed, the TRAP complex function during co-translational translocation needs to be established. In addition, TRAP may play a role during unfolded protein response, endoplasmic-reticulum-associated protein degradation and congenital disorder of glycosylation (ssr4 CDG). In this article, I describe the current understanding of the TRAP complex in the light of its possible function(s).In this State-of-the-Field article, we explore the main themes from the 62nd Annual Aspen Lung Conference hypoxia, cellular metabolism, inflammatory pathways, aberrant proliferation, and personalized medicine, and highlight challenges and opportunities in the coming decade of pulmonary vascular disease.Pregnancy requires adaptation of maternal insulin sensitivity. In the fed state, a pulse of insulin stimulates glucose uptake and nutrient energy storage via insulin-dependent as well as Hepatic Insulin Sensitizing Substance (HISS)-dependent action. HISS is released by the liver in the fed state in the presence of signals integrated through the liver and a pulse of insulin. HISS promotes glucose storage as glycogen in heart, kidney and skeletal muscle but not gut, liver or adipose tissue. HISS is also responsible for the vasodilatory action previously attributed to insulin. The Rapid Insulin Sensitivity Test (RIST), a dynamic euglycemic clamp, can quantitate both HISS-dependent and insulin-dependent glucose uptake. The RIST was used to characterize postprandial insulin sensitivity in the Sprague Dawley rat and the changes in the partitioning of nutrient energy throughout gestation. Early pregnancy demonstrated increased insulin sensitivity attributable to HISS-dependent glucose uptake with unchanged insulin-dependent glucose uptake, preserved plasma insulin concentration and reduced plasma triglyceride concentration compared to the virgin. Linsitinib nmr In late pregnancy there was reduced HISS-dependent and insulin-dependent glucose uptake accompanied by increased plasma insulin and triglyceride concentration compared to the virgin. These results suggest an important role for HISS in glucose partitioning in pregnancy.Elucidation of the membranes contributing to autophagosomes has been a critical question in the field, and an area of active research. Recently, we showed that key events in autophagosome formation, from PtdIns3P formation/WIPI2 recruitment to LC3-GABARAP membrane conjugation, occur on the RAB11A-positive compartment (recycling endosomes). This observation raised the question of how the LC3-positive autophagosome precursors detach from the recycling endosome. We recently observed that DNM2 (dynamin 2) mediates this step, and described how the DNM2R465W mutation that causes centronuclear myopathy (CNM) leads to the accumulation of autophagic structures on recycling endosomes, thereby stalling macroautophagy/autophagy. This physiologically important step highlights the importance of understanding release of nascent autophagosomes from the recycling endosomes as part of the autophagy itinerary.Low-cost whole-genome assembly has enabled the collection of haplotype-resolved pangenomes for numerous organisms. In turn, this technological change is encouraging the development of methods that can precisely address the sequence and variation described in large collections of related genomes. These approaches often use graphical models of the pangenome to support algorithms for sequence alignment, visualization, functional genomics, and association studies. The additional information provided to these methods by the pangenome allows them to achieve superior performance on a variety of bioinformatic tasks, including read alignment, variant calling, and genotyping. Pangenome graphs stand to become a ubiquitous tool in genomics. Although it is unclear whether they will replace linear reference genomes, their ability to harmoniously relate multiple sequence and coordinate systems will make them useful irrespective of which pangenomic models become most common in the future. Expected final online publication date for the Annual Review of Genomics and Human Genetics, Volume 21 is August 31, 2020.