ATG13: Just a companion,or an executor of the autophagic program?

During the past 20 years, autophagy signaling has entered the main stage of the cell biological theater. Autophagy represents an intracellular degradation process that is involved in both the bulk recycling of cytoplasmic components and the selective removal of organelles, protein aggregates, or intracellular pathogens. The understanding of autophagy has been greatly facilitated by the characterization of the molecular machinery governing this process. In yeast, initiation of autophagy is controlled by the Atg1 kinase complex, which is composed of the Ser/Thr kinase Atg1, the adaptor protein Atg13, and the ternary complex of Atg17-Atg31-Atg29. In vertebrates, the orthologous ULK1 kinase complex contains the Ser/Thr kinase ULK1 and the accessory proteins ATG13, RB1CC1, and ATG101. Among these components, Atg1/ULK1 have gained major attention in the past, i.e., for the identification of upstream regulatory kinases, the characterization of downstream substrates controlling the autophagic flux, or as a druggable target for the modulation of autophagy. However, accumulating data indicate that the function of Atg13/ATG13 has been likely underestimated so far. In addition to ensuring proper Atg1/ULK1 recruitment and activity, this adaptor molecule has been implicated in ULK1-independent autophagy processes. Furthermore, recent data have identified additional binding partners of Atg13/ATG13 besides the components of the Atg1/ULK1 complex, e.g., Atg8 family proteins or acidic phospholipids. Therefore, in this review we will center the spotlight on Atg13/ATG13 and summarize the role that Atg13/ATG13 assumes in the autophagy stage play.     

Biomarker research with prospective study designs for the early detection of cancer

This article describes the principles of marker research with prospective studies along with examples for diagnostic tumor markers. A plethora of biomarkers have been claimed as useful for the early detection of cancer. However, disappointingly few biomarkers were approved for the detection of unrecognized disease, and even approved markers may lack a sound validation phase. Prospective studies aimed at the early detection of cancer are costly and long-lasting and therefore the bottleneck in marker research. They enroll a large number of clinically asymptomatic subjects and follow-up on incident cases. As invasive procedures cannot be applied to collect tissue samples from the target organ, biomarkers can only be determined in easily accessible body fluids. Marker levels increase during cancer development, with samples collected closer to the occurrence of symptoms or a clinical diagnosis being more informative than earlier samples. Only prospective designs allow the serial collection of pre-diagnostic samples. Their storage in a biobank upgrades cohort studies to serve for both, marker discovery and validation. Population-based cohort studies, which may collect a wealth of data, are commonly conducted with just one baseline investigation lacking serial samples. However, they can provide valuable information about factors that influence the marker level. Screening programs can be employed to archive serial samples but require significant efforts to collect samples and auxiliary data for marker research. Randomized controlled trials have the highest level of evidence in assessing a biomarker's benefit against usual care and present the most stringent design for the validation of promising markers as well as for the discovery of new markers. In summary, all kinds of prospective studies can benefit from a biobank as they can serve as a platform for biomarker research. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge.     

Scanning electron microscopic surface analysis of cryoconserved skull bone after decompressive craniectomy

Bone flaps removed during decompressive craniectomy are commonly frozen at ?80 °C and stored until cranioplasty. Histological integrity and regenerative capacity have been shown for cryoconserved bone. The effects of cryoconservation on the surface structure are unknown, although these might cause mechanical instability or facilitate bacterial adhesion. This study evaluates the surface structure of cryoconserved bone by scanning electron microscopy. Five patients were identified who could not receive their autologous bone flaps after decompressive craniectomy. These redundant bone specimens were obtained after cryoconservation for 6–8 months and the outer surface was analyzed by scanning electron microscopy. We found varying surface structures which did not correlate with any variables, such as patient age, gender or duration of freezing, and probably reflect physiological interindividual variation. Pathological findings, such as microscopic crack formation, were not observed. Cryoconservation for up to 8 months does not appear to alter the surface structure of skull bone on scanning electronic microscopy.     

Tissue-Specific Fatty Acids Response to Different Diets in Common Carp (Cyprinus carpio L.)

Fish depend on dietary fatty acids (FA) to support their physiological condition and health. Exploring the FA distribution in common carp (Cyprinus carpio), one of the world''s most consumed freshwater fish, is important to understand how and where FA of different sources are allocated. We investigated diet effects on the composition of polar and neutral lipid fatty acids (PLFA and NLFA, respectively) in eight different tissues (dorsal and ventral muscle, heart, kidney, intestine, eyes, liver and adipose tissue) of common carp. Two-year old carp were exposed to three diet sources (i.e., zooplankton, zooplankton plus supplementary feeds containing vegetable, VO, or fish oil, FO) with different FA composition. The PLFA and NLFA response was clearly tissue-specific after 210 days of feeding on different diets. PLFA were generally rich in omega-3 polyunsaturated FA and only marginally influenced by dietary FA, whereas the NLFA composition strongly reflected dietary FA profiles. However, the NLFA composition in carp tissues varied considerably at low NLFA mass ratios, suggesting that carp is able to regulate the NLFA composition and thus FA quality in its tissues when NLFA contents are low. Finally, this study shows that FO were 3X more retained than VO as NLFA particularly in muscle tissues, indicating that higher nutritional quality feeds are selectively allocated into tissues and thus available for human consumption.     

Long-Term Single Cell Analysis of S. pombe on a Microfluidic Microchemostat Array

Although Schyzosaccharomyces pombe is one of the principal model organisms for studying the cell cycle, surprisingly few methods have characterized S. pombe growth on the single cell level, and no methods exist capable of analyzing thousands of cells and tens of thousands of cell division events. We developed an automated microfluidic platform permitting S. pombe to be grown on-chip for several days under defined and changeable conditions. We developed an image processing pipeline to extract and quantitate several physiological parameters including cell length, time to division, and elongation rate without requiring synchronization of the culture. Over a period of 50 hours our platform analyzed over 100000 cell division events and reconstructed single cell lineages up to 10 generations in length. We characterized cell lengths and division times in a temperature shift experiment in which cells were initially grown at 30°C and transitioned to 25°C. Although cell length was identical at both temperatures at steady-state, we observed transient changes in cell length if the temperature shift took place during a critical phase of the cell cycle. We further show that cells born with normal length do divide over a wide range of cell lengths and that cell length appears to be controlled in the second generation, were large newly born cells have a tendency to divide more rapidly and thus at a normalized cell size. The platform is thus applicable to measure fine-details in cell cycle dynamics, should be a useful tool to decipher the molecular mechanism underlying size homeostasis, and will be generally applicable to study processes on the single cell level that require large numbers of precision measurements and single cell lineages.     

Hell Is Other People? Gender and Interactions with Strangers in the Workplace Influence a Person’s Risk of Depression

We suggest that interactions with strangers at work influence the likelihood of depressive disorders, as they serve as an environmental stressor, which are a necessary condition for the onset of depression according to diathesis-stress models of depression. We examined a large dataset (N = 76,563 in K = 196 occupations) from the German pension insurance program and the Occupational Information Network dataset on occupational characteristics. We used a multilevel framework with individuals and occupations as levels of analysis. We found that occupational environments influence employees’ risks of depression. In line with the quotation that ‘hell is other people’ frequent conflictual contacts were related to greater likelihoods of depression in both males and females (OR = 1.14, p<.05). However, interactions with the public were related to greater likelihoods of depression for males but lower likelihoods of depression for females (OR_intercation = 1.21, p<.01). We theorize that some occupations may involve interpersonal experiences with negative emotional tones that make functional coping difficult and increase the risk of depression. In other occupations, these experiences have neutral tones and allow for functional coping strategies. Functional strategies are more often found in women than in men.