Role of SNX16 in the Dynamics of Tubulo-Cisternal Membrane Domains of Late Endosomes

In this paper, we report that the PX domain-containing protein SNX16, a member of the sorting nexin family, is associated with late endosome membranes. We find that SNX16 is selectively enriched on tubulo-cisternal elements of this membrane system, whose highly dynamic properties and formation depend on intact microtubules. By contrast, SNX16 was not found on vacuolar elements that typically contain LBPA, and thus presumably correspond to multivesicular endosomes. We conclude that SNX16, together with its partner phosphoinositide, define a highly dynamic subset of late endosomal membranes, supporting the notion that late endosomes are organized in distinct morphological and functional regions. Our data also indicate that SNX16 is involved in tubule formation and cholesterol transport as well as trafficking of the tetraspanin CD81, suggesting that the protein plays a role in the regulation of late endosome membrane dynamics

7th Drug hypersensitivity meeting: part two

No abstract availabl

The term structure of optimal operations

Inventory and capacity planning models generally take the time of sale as something that is exogenously given. For example, the story associated with the well-known newsvendor model is one of stocking for an upcoming selling season that will happen x units of time from now, where x is exogenous. In this paper, we re-visit the capacity planning decision by assuming that demand follows a stochastic process and study what happens when both the time of sale and capacity are decisions. When the selling price is fixed, our baseline case, we find that the optimal time to sell is either now or never. In contrast, when the selling price is stochastic, the optimal time to serve demand is somewhere between now and never. Thus, we link timing preference to two primary sources: uncertainty in demand and uncertainty in the selling price. Our results are useful whenever firms have considerable control over timing, such as in events when firms launch new products or in instances when there is no apparent selling season

Hybridization network for the system of woody plant gene pools in the United States

<div><p></p><p>Hybridization generates similarities among gene pools. This structure can be visualized and analyzed at the systems level using networks. Here we construct a network of the 315 woody plant species native or naturalized in the United States using data compiled by the Forest Service of the US Department of Agriculture (USFS). Each species is represented by a node in the network whose size is proportional to a recent census for live stems in the continental United States. Each of the 416 links between node pairs represents evidence for hybridization compiled from the USFS manual <i>Silvics of North America</i>. The total network resolved into 100 separate connected components or clusters (mean size, 3.15 species), with 44% of species linked to at least one other. <i>Betula</i> had the largest component (18 species) following by the separate <i>Quercus</i> clusters (17 red oaks and 16 white oaks); <i>Q. velutina</i> was the most genetically connected woody plant in the continental US. The number of species held together per component (i.e. size) scaled as a power–law albeit a slightly truncated one. The truncation suggests there are fewer than expected hybridizing species within the large woody genera of plants in the US.</p> </div

Insulin-like growth factor 2 binding protein 3 expression on endoscopic ultrasound guided fine needle aspiration specimens in pancreatic ductal adenocarcinoma

Background: Despite numerous investigations, we still do not have a specific marker for pancreatic ductal adenocarcinoma. Only guideline-recommended biomarker for pancreatic ductal adenocarcinoma is the CA19-9, but it is also present in other gastrointestinal diseases. IMP3 is a new potential biomarker that is over-expressed in some cancers. The aims of our study were (1) to assess IMP3 in benign pancreatic lesions and pancreatic cancer, and (2) to estimate its concentrations in localized and advanced pancreatic cancer. Patients and methods: Seventy-five patients with solid pancreatic lesions who underwent EUS-FNA were included. Patients were divided into three groups: benign lesions, cancer localized only on the pancreas, and patients with advanced pancreatic cancer (locally advanced or with distal metastases). Immunoreactivity of IMP3 was assessed on cytological smears sampled by endoscopic ultrasound. Results: IMP3 was expressed in 89% of the patients with pancreatic cancer and not in benign lesions. Stronger expression of IMP3 protein and stage of the pancreatic cancer was statistically significant. IMP3 was expressed in all localized cancers and in 85% of patients with advanced pancreatic cancer. In the subgroup with locally advanced cancer, IMP3 was expressed in 88%, and in 83% of patients in the subgroup with distal metastasis (P = 0.007). In the present study, sensitivity was 89%, specificity 100%, with positive predictive value of 100% and negative predictive value of 63%. Conclusion: There is a positive correlation between IMP3 expression and TNM stages of the pancreatic cancer. Higher expression of IMP3 on EUS-FNA specimens can suggest poorer prognosis

The role of population pharmacokinetic analysis in rational antibiotic therapy in neonates

status: publishe