Protein profiling in hepatocellular carcinoma by label-free quantitative proteomics in two west african populations.

Background Hepatocellular Carcinoma is the third most common cause of cancer related death worldwide, often diagnosed by measuring serum AFP; a poor performance stand-alone biomarker. With the aim of improving on this, our study focuses on plasma proteins identified by Mass Spectrometry in order to investigate and validate differences seen in the respective proteomes of controls and subjects with LC and HCC. Methods Mass Spectrometry analysis using liquid chromatography electro spray ionization quadrupole time-of-flight was conducted on 339 subjects using a pooled expression profiling approach. ELISA assays were performed on four significantly differentially expressed proteins to validate their expression profiles in subjects from the Gambia and a pilot group from Nigeria. Results from this were collated for statistical multiplexing using logistic regression analysis. Results Twenty-six proteins were identified as differentially expressed between the three subject groups. Direct measurements of four; hemopexin, alpha-1-antitrypsin, apolipoprotein A1 and complement component 3 confirmed their change in abundance in LC and HCC versus control patients. These trends were independently replicated in the pilot validation subjects from Nigeria. The statistical multiplexing of these proteins demonstrated performance comparable to or greater than ALT in identifying liver cirrhosis or carcinogenesis. This exercise also proposed preliminary cut offs with achievable sensitivity, specificity and AUC statistics greater than reported AFP averages. Conclusions The validated changes of expression in these proteins have the potential for development into high-performance tests usable in the diagnosis and or monitoring of HCC and LC patients. The identification of sustained expression trends strengthens the suggestion of these four proteins as worthy candidates for further investigation in the context of liver disease. The statistical combinations also provide a novel inroad of analyses able to propose definitive cut-offs and combinations for evaluation of performance

Incongruent patterns of genetic connectivity among four ophiuroid species with differing coral host specificity on North Atlantic seamounts

Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of John Wiley & Sons for personal use, not for redistribution. The definitive version was published in Marine Ecology 31 (2010): 121-143, doi:10.1111/j.1439-0485.2010.00395.x.Seamounts are considered to play a defining role in the evolution and diversity of marine fauna, acting as “stepping-stones” for dispersal, regional centers of genetic isolation and speciation, and refugia for deep-sea populations. This study focused on the patterns of dispersal and genetic connectivity of four seamount ophiuroid species (Asteroschema clavigera, Ophiocreas oedipus, Ophioplinthaca abyssalis and Ophioplinthaca chelys) displaying differing levels of associative (epifaunal) specificity to cold-water coral hosts inhabiting the New England and Corner Rise Seamount chains, and Muir Seamount in the Northwestern Atlantic. Analyses of mt16S and mtCOI revealed evidence for recent population expansion and high gene flow for all four species. However, species-specific genetic differentiation was significant based on seamount region and depth. Significant differences were found among regional seamount groups for A. clavigera, within seamount regions and seamounts for O. chelys, among 250 m depth intervals for A. clavigera, among 100 m depth intervals for O. oedipus, and there were indications of isolation by distance for A. clavigera and O. oedipus. In addition, A. clavigera and O. oedipus, broadcast spawners with high fidelity to specific coral hosts, displayed predominantly westward historical migration, while the ophioplinthacids, with lower host-specificity, displayed predominantly eastward migration. No congruent patterns of historical migration were evident among species and seamounts, yet these patterns can be correlated with species-specific host specificity, specific depth strata, and dispersal strategies. Conservation efforts to protect seamount ecosystems should promote multi-species approaches to genetic connectivity, and consider the impact of the “dependence” of biodiversity on host fauna in these vulnerable marine ecosystems.We are grateful for the support provided by the Office of Ocean Exploration, National Oceanic and Atmospheric Administration (NA05OAR4601054) the National Science Foundation (OCE- 0624627; OCE-0451983; OCE-0647612), the Deep Ocean Exploration Institute (Fellowship support to TMS), the Ocean Life Institute and Academic Programs Office of the Woods Hole Oceanographic Institution, and the Census of Marine Life field program CenSeam (a global census of marine life on seamounts) (Grant #12301)

How to Minimize the Attack Rate during Multiple Influenza Outbreaks in a Heterogeneous Population

<div><h3>Background</h3><p>If repeated interventions against multiple outbreaks are not feasible, there is an optimal level of control during the first outbreak. Any control measures above that optimal level will lead to an outcome that may be as sub-optimal as that achieved by an intervention that is too weak. We studied this scenario in more detail.</p> <h3>Method</h3><p>An age-stratified ordinary-differential-equation model was constructed to study infectious disease outbreaks and control in a population made up of two groups, adults and children. The model was parameterized using influenza as an example. This model was used to simulate two consecutive outbreaks of the same infectious disease, with an intervention applied only during the first outbreak, and to study how cumulative attack rates were influenced by population composition, strength of inter-group transmission, and different ways of triggering and implementing the interventions. We assumed that recovered individuals are fully immune and the intervention does not confer immunity.</p> <h3>Results/Conclusion</h3><p>The optimal intervention depended on coupling between the two population sub-groups, the length, strength and timing of the intervention, and the population composition. Population heterogeneity affected intervention strategies only for very low cross-transmission between groups. At more realistic values, coupling between the groups led to synchronization of outbreaks and therefore intervention strategies that were optimal in reducing the attack rates for each subgroup and the population overall coincided. For a sustained intervention of low efficacy, early intervention was found to be best, while at high efficacies, a delayed start was better. For short interventions, a delayed start was always advantageous, independent of the intervention efficacy. For most scenarios, starting the intervention after a certain cumulative proportion of children were infected seemed more robust in achieving close to optimal outcomes compared to a strategy that used a specified duration after an outbreak’s beginning as the trigger.</p> </div

Functional Complexity of the Axonal Growth Cone: A Proteomic Analysis

The growth cone, the tip of the emerging neurite, plays a crucial role in establishing the wiring of the developing nervous system. We performed an extensive proteomic analysis of axonal growth cones isolated from the brains of fetal Sprague-Dawley rats. Approximately 2000 proteins were identified at ≥99% confidence level. Using informatics, including functional annotation cluster and KEGG pathway analysis, we found great diversity of proteins involved in axonal pathfinding, cytoskeletal remodeling, vesicular traffic and carbohydrate metabolism, as expected. We also found a large and complex array of proteins involved in translation, protein folding, posttranslational processing, and proteasome/ubiquitination-dependent degradation. Immunofluorescence studies performed on hippocampal neurons in culture confirmed the presence in the axonal growth cone of proteins representative of these processes. These analyses also provide evidence for rough endoplasmic reticulum and reveal a reticular structure equipped with Golgi-like functions in the axonal growth cone. Furthermore, Western blot revealed the growth cone enrichment, relative to fetal brain homogenate, of some of the proteins involved in protein synthesis, folding and catabolism. Our study provides a resource for further research and amplifies the relatively recently developed concept that the axonal growth cone is equipped with proteins capable of performing a highly diverse range of functions

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

Isolated celiac artery avulsion from blunt abdominal trauma

Introduction: Trauma-related celiac artery injuries are a rare and life-threatening pathology that often requires urgent multidisciplinary care. Rarer still are cases of celiac artery avulsion in the setting of blunt trauma. There is little literature describing such injury patterns. The farthest-reaching is a case series by Kronich et al. 2017, which compiles eleven cases. The majority of these injuries were incomplete intimal injuries only appreciated on admission imaging. A further literature review reveals five cases of full avulsions in the setting of blunt trauma. Management varied dramatically among these cases. The multidisciplinary nature of vascular trauma, in combination with new vascular repair techniques provides a paradox of choice regarding acute management in unusual presentations. With intuitional review board approval, we report a case of blunt trauma with complete celiac trunk avulsion in a patient with aberrant visceral vascular anatomy, managed with open exploration and ligation