No abstract

Extensive flooded cave systems are developed in a zone 8-12 km inland of the east coast of the Yucatan Peninsula, Quintana Roo, Mexico. In plan, the systems comprise cross-linked anastomosing networks composed of horizontal elliptical tubes (which are actively developing where associated with the present fresh water/saline water mixing zone) and canyon-shaped passages. Both forms are heavily modified by sediment and speleothem infill, and extensive collapse. The pattern of Quintana Roo caves differs both from the mixing chamber form of flank-margin eogenetic caves, and also the dendritic and rectilinear maze patterns of epigenetic continental (telogenetic) caves. Unlike the latter, Quintana Roo caves are formed by coastal zone fresh water/saline water mixing processes. While mixing dissolution is also responsible for development of flank-margin caves, these may be typical of small islands and arid areas with limited coastal discharge, whereas Quintana Roo-type caves are formed when coastal discharge is greater. In the Quintana Roo caves, multiple phases of cave development are associated with glacio-eustatic changes in sea level. Two critical conditions control cave development following lowstands: (1) if the passage remains occupied by the mixing zone and connected to underlying deep cave systems, and (2) for passages above the mixing zone, if active freshwater flow is maintained by tributaries. In the first case, inflow of saline water drives mixing dissolution, enabling removal of the lowstand carbonate fill and continued passage enlargement. In the second, despite limited dissolution in the fresh water, continued removal of uncemented sediments can maintain the cave void. Where neither of these conditions is met, enlargement will cease, and the cave void will become occluded by collapse and sediment infill.

Understanding how events at the molecular and cellular scales contribute to tissue form and function is key to uncovering the mechanisms driving animal development, physiology and disease. Elucidating these mechanisms has been enhanced through the study of model organisms and the use of sophisticated genetic, biochemical and imaging tools. Here, we present an accessible method for noninvasive imaging of Drosophila melanogaster at high resolution using micro-computed tomography (µ-CT). We show how rapid processing of intact animals, at any developmental stage, provides precise quantitative assessment of tissue size and morphology, and permits analysis of inter-organ relationships. We then use µ-CT imaging to study growth defects in the Drosophila brain through the characterization of abnormal spindle (asp) and WD repeat domain 62 (Wdr62), orthologs of the two most commonly mutated genes in human microcephaly patients. Our work demonstrates the power of combining µ-CT with traditional genetic, cellular and developmental biology tools available in model organisms to address novel biological mechanisms that control animal development and disease.

Highlights d The proximal end of the centriole docks to the spermatid nucleus d Proper centriole docking to the nucleus requires proximal restriction of PCM d Pericentrin-like protein (PLP) restricts PCM to the proximal centriole end d PLP is proximally restricted by eliminating its availability during centriole growth

The relationship between skin cancer and ultraviolet radiation is well established. Behaviors such as seeking shade, avoiding sun exposure during peak hours of radiation, wearing protective clothing, or some combination of these behaviors can provide protection. Sunscreen use alone is not considered an adequate protection against ultraviolet radiation. This report presents the results of systematic reviews of effectiveness, applicability, other harms or benefits, economic evaluations, and barriers to use of selected interventions to prevent skin cancer by reducing exposure to ultraviolet radiation. The Task Force on Community Preventive Services found that education and policy approaches to increasing sun-protective behaviors were effective when implemented in primary schools and in recreational or tourism settings, but found insufficient evidence to determine effectiveness when implemented in other settings, such as child care centers, secondary schools and colleges, and occupational settings. They also found insufficient evidence to determine the effectiveness of interventions oriented to healthcare settings and providers, media campaigns alone, interventions oriented to parents or caregivers of children, and community-wide multicomponent interventions. The report also provides suggestions for areas for future research.

Inhaled diacetyl vapors are associated with flavorings-related lung disease, a potentially fatal airway disease. The reactive a-dicarbonyl group in diacetyl causes protein damage in vitro. Dicarbonyl/ L-xylulose reductase (DCXR) metabolizes diacetyl into acetoin, which lacks this a-dicarbonyl group. To investigate the hypothesis that flavorings-related lung disease is caused by in vivo protein damage, we correlated diacetyl-induced airway damage in mice with immunofluorescence for markers of protein turnover and autophagy. Western immunoblots identified shifts in ubiquitin pools. Diacetyl inhalation caused dose-dependent increases in bronchial epithelial cells with puncta of both total ubiquitin and K63-ubiquitin, central mediators of protein turnover. This response was greater in Dcxr-knockout mice than in wild-type controls inhaling 200 ppm diacetyl, further implicating the a-dicarbonyl group in protein damage. Western immunoblots demonstrated decreased free ubiquitin in airway-enriched fractions. Transmission electron microscopy and colocalization of ubiquitin-positive puncta with lysosomal-associated membrane proteins 1 and 2 and with the multifunctional scaffolding protein sequestosome-1 (SQSTM1/p62) confirmed autophagy. Surprisingly, immunoreactive SQSTM1 also accumulated in the olfactory bulb of the brain. Olfactory bulb SQSTM1 often congregated in activated microglial cells that also contained olfactory marker protein, indicating neuronophagia within the olfactory bulb. This suggests the possibility that SQSTM1 or damaged proteins may be transported from the nose to the brain. Together, these findings strongly implicate widespread protein damage in the etiology of flavorings-related lung disease. (Am J Pathol 2016, 186: 2887e2908; http://dx

Wnt signaling generates patterns in all embryos, from flies to humans, and controls cell fate, proliferation and metabolic homeostasis. Inappropriate Wnt pathway activation results in diseases, including colorectal cancer. The adenomatous polyposis coli (APC) tumor suppressor gene encodes a multifunctional protein that is an essential regulator of Wnt signaling and cytoskeletal organization. Although progress has been made in defining the role of APC in a normal cellular context, there are still significant gaps in our understanding of APC-dependent cellular function and dysfunction. We expanded the APC-associated protein network using a combination of genetics and a proteomic technique called twodimensional difference gel electrophoresis (2D-DIGE). We show that loss of Drosophila Apc2 causes protein isoform changes reflecting misregulation of post-translational modifications (PTMs), which are not dependent on β-catenin transcriptional activity. Mass spectrometry revealed that proteins involved in metabolic and biosynthetic pathways, protein synthesis and degradation, and cell signaling are affected by Apc2 loss. We demonstrate that changes in phosphorylation partially account for the altered PTMs in APC mutants, suggesting that APC mutants affect other types of PTM. Finally, through this approach Aminopeptidase P was identified as a new regulator of β-catenin abundance in Drosophila embryos. This study provides new perspectives on the cellular effects of APC that might lead to a deeper understanding of its role in development.

No abstract