Human protein secretory pathway genes are expressed in a tissue-specific pattern to match processing demands of the secretome.
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ABSTRACT:
SUBMITTER: Feizi A
PROVIDER: S-EPMC5562915 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The compound eye of insects imposes a tradeoff between resolution and sensitivity, which should exacerbate with diminishing eye size. Tiny lenses are thought to deliver poor acuity because of diffraction; nevertheless, miniature insects have visual systems that allow a myriad of lifestyles. Here, we investigate whether size constraints result in an archetypal eye design shared between miniature dipterans by comparing the visual performance of the fruit fly Drosophila and the killer fly Coenosia. These closely related species have neural superposition eyes and similar body lengths (3 to 4 mm), but Coenosia is a diurnal aerial predator, whereas slow-flying Drosophila is most active at dawn and dusk. Using in vivo intracellular recordings and EM, we report unique adaptations in the form and function of their photoreceptors that are reflective of their distinct lifestyles. We find that although these species have similar lenses and optical properties, Coenosia photoreceptors have three- to fourfold higher spatial resolution and rate of information transfer than Drosophila. The higher performance in Coenosia mostly results from dramatically diminished light sensors, or rhabdomeres, which reduce pixel size and optical cross-talk between photoreceptors and incorporate accelerated phototransduction reactions. Furthermore, we identify local specializations in the Coenosia eye, consistent with an acute zone and its predatory lifestyle. These results demonstrate how the flexible architecture of miniature compound eyes can evolve to match information processing with ecological demands.
| S-EPMC3054003 | biostudies-literature
Project description:Research describing the match and specific positional demands during match play in women's collegiate soccer is limited. The purpose of the study was to quantify the match demands of National Collegiate Athletic Association (NCAA) Division III soccer and assess position differences in movement kinematics, heart rate (HR), and energy expenditure. Twenty-five Division III women soccer players (height: 1.61 ± 0.3 m; body mass: 66.7 ± 7.5 kg; fat-free mass: 50.3 ± 6.5 kg; body fat%: 25.6 ± 5.1%) were equipped with a wearable global positioning system to assess the demands of 22 matches throughout a season. Players were categorized by position (goal keepers (GK), center defenders (CB), flank players (FP), forwards (F), and center midfielders (CM)). Players covered 9807 ± 2588 m and 1019 ± 552 m at high speeds (>249.6 m·m-1), with an overall average speed of 62.85 ± 14.7 m·m-1. This resulted in a mean HR of 74.2 ± 6% HR max and energy expenditure of 1259 ± 309 kcal. Significant and meaningful differences in movement kinematics were observed across position groups. CM covered the most distance resulting in the highest training load. FP covered the most distance at high speeds and mean HR values were highest in CM, CB, and FP positions.
| S-EPMC7353669 | biostudies-literature
Project description:BackgroundEukaryotes use distinct networks of biogenesis factors to synthesize, fold, monitor, traffic, and secrete proteins. During heterologous expression, saturation of any of these networks may bottleneck titer and yield. To understand the flux through various routes into the early secretory pathway, we quantified the global and membrane-associated translatomes of Komagataella phaffii.ResultsBy coupling Ribo-seq with long-read mRNA sequencing, we generated a new annotation of protein-encoding genes. By using Ribo-seq with subcellular fractionation, we quantified demands on co- and posttranslational translocation pathways. During exponential growth in rich media, protein components of the cell-wall represent the greatest number of nascent chains entering the ER. Transcripts encoding the transmembrane protein PMA1 sequester more ribosomes at the ER membrane than any others. Comparison to Saccharomyces cerevisiae reveals conservation in the resources allocated by gene ontology, but variation in the diversity of gene products entering the secretory pathway.ConclusionA subset of host proteins, particularly cell-wall components, impose the greatest biosynthetic demands in the early secretory pathway. These proteins are potential targets in strain engineering aimed at alleviating bottlenecks during heterologous protein production.
| S-EPMC7816318 | biostudies-literature
Project description:Antibodies raised against plasma prothrombin and the prothrombin propeptide were used to identify prothrombin precursors in rough and smooth microsomes and in the Golgi apparatus. The data demonstrate that the propeptide is part of the prothrombin molecule when undergoing a variety of modifications in the Golgi apparatus. It is shown that these modifications result in an increase in the apparent molecular mass of the prothrombin precursor from 78 kDa in early processing to 83 kDa in late processing. The 83 kDa prothrombin precursor was not recognized by the anti-propeptide antiserum and most likely represents the final product of the precursor in the secretory pathway. Evidence is presented that the propeptide is released from the parent molecule in the Golgi apparatus by a membrane-bound Ca(2+)-dependent serine proteinase(s) with characteristics similar to those of the proalbumin-to-albumin-converting enzyme. Vitamin K-dependent carboxylase activity was measured in membrane fragments obtained from the Golgi apparatus preparation. Sucrose-density-gradient centrifugation and the use of marker enzymes showed that carboxylase activity was highest in fractions enriched in cis-Golgi cisternae. Two different synthetic peptides were used as substrates for the carboxylase. These peptides were from the N-terminal and the C-terminal part of the gamma-carboxyglutamic acid (Gla) region of prothrombin. It is shown that the N-terminal and the C-terminal peptides were preferred as substrates for the carboxylase in the microsomal and the Golgi apparatus preparations respectively. It is also shown that the prothrombin precursor acquires negative charges in the Golgi apparatus that do not result from addition of sugars in late processing. These negative charges could be eliminated by thermal decarboxylation, suggesting that Gla residues may also be synthesized in late processing.
| S-EPMC1151191 | biostudies-other
Project description:Mutations in the Golgi SNARE (SNAP [soluble NSF attachment protein] receptor) protein Membrin (encoded by the GOSR2 gene) cause progressive myoclonus epilepsy (PME). Membrin is a ubiquitous and essential protein mediating ER-to-Golgi membrane fusion. Thus, it is unclear how mutations in Membrin result in a disorder restricted to the nervous system. Here, we use a multi-layered strategy to elucidate the consequences of Membrin mutations from protein to neuron. We show that the pathogenic mutations cause partial reductions in SNARE-mediated membrane fusion. Importantly, these alterations were sufficient to profoundly impair dendritic growth in Drosophila models of GOSR2-PME. Furthermore, we show that Membrin mutations cause fragmentation of the presynaptic cytoskeleton coupled with transsynaptic instability and hyperactive neurotransmission. Our study highlights how dendritic growth is vulnerable even to subtle secretory pathway deficits, uncovers a role for Membrin in synaptic function, and provides a comprehensive explanatory basis for genotype-phenotype relationships in GOSR2-PME.
| S-EPMC5640804 | biostudies-literature
Project description:BACKGROUND: Helminths are important socio-economic organisms, responsible for causing major parasitic infections in humans, other animals and plants. These infections impose a significant public health and economic burden globally. Exceptionally, some helminth organisms like Caenorhabditis elegans are free-living in nature and serve as model organisms for studying parasitic infections. Excretory/secretory proteins play an important role in parasitic helminth infections which make these proteins attractive targets for therapeutic use. In the case of helminths, large volume of expressed sequence tags (ESTs) has been generated to understand parasitism at molecular level and for predicting excretory/secretory proteins for developing novel strategies to tackle parasitic infections. However, mostly predicted ES proteins are not available for further analysis and there is no repository available for such predicted ES proteins. Furthermore, predictions have, in the main, focussed on classical secretory pathways while it is well established that helminth parasites also utilise non-classical secretory pathways. RESULTS: We developed a free Helminth Secretome Database (HSD), which serves as a repository for ES proteins predicted using classical and non-classical secretory pathways, from EST data for 78 helminth species (64 nematodes, 7 trematodes and 7 cestodes) ranging from parasitic to free-living organisms. Approximately 0.9 million ESTs compiled from the largest EST database, dbEST were cleaned, assembled and analysed by different computational tools in our bioinformatics pipeline and predicted ES proteins were submitted to HSD. CONCLUSION: We report the large-scale prediction and analysis of classically and non-classically secreted ES proteins from diverse helminth organisms. All the Unigenes (contigs and singletons) and excretory/secretory protein datasets generated from this analysis are freely available. A BLAST server is available at http://estexplorer.biolinfo.org/hsd, for checking the sequence similarity of new protein sequences against predicted helminth ES proteins.
| S-EPMC3546426 | biostudies-literature
Project description:BackgroundIt has been previously reported that most mammalian genes display a circadian oscillation in their baseline expression. Consequently, the phase and amplitude of each component of a signal transduction cascade has downstream consequences.ResultsHere, we report our analysis of alternative transcripts in the leptin signaling pathway which is responsible for the systemic regulation of macronutrient storage and energy balance. We focused on the circadian expression pattern of a critical component of the leptin signaling system, suppressor of cytokine signaling 3 (SOCS3). On an Affymetrix GeneChip 430A2 microarray, this gene is represented by three probe sets targeting different regions within the 3' end of the last exon. We demonstrate that in murine brown adipose tissue two downstream 3' probe sets experience circadian baseline oscillation in counter-phase to the upstream probe set. Such differences in expression patterns are a telltale sign of alternative splicing within the last exon of SOCS3. In contrast, all three probe sets oscillated in a common phase in murine liver and white adipose tissue. This suggests that the regulation of SOCS3 expression in brown fat is tissue specific. Another component of the signaling pathway, Janus kinase (JAK), is directly regulated by SOCS and has alternative transcript probe sets oscillating in counter-phase in a white adipose tissue specific manner.ConclusionWe hypothesize that differential oscillation of alternative transcripts may provide a mechanism to maintain steady levels of expression in spite of circadian baseline variation.
| S-EPMC2099483 | biostudies-literature
Project description:BACKGROUND:The aim of this study is to describe the peak match demands and compare them with average demands in basketball players, from an external load point of view, using different time windows. Another objective is to determine whether there are differences between positions and to provide an approach for practical applications. METHODS:During this observational study, each player wore a micro technology device. We collected data from 12 male basketball players (mean ± SD: age 17.56 ± 0.67 years, height 196.17 ± 6.71 cm, body mass 90.83 ± 11.16 kg) during eight games. We analyzed intervals for different time windows using rolling averages (ROLL) to determine the peak match demands for Player Load. A separate one-way analysis of variance (ANOVA) was used to identify statistically significant differences between playing positions across different intense periods. RESULTS:Separate one-way ANOVAs revealed statistically significant differences between 1 min, 5 min, 10 min, and full game periods for Player Load, F (3,168) = 231.80, ?p2 = 0.76, large, p < 0.001. It is worth noting that guards produced a statistically significantly higher Player Load in 5 min (p < 0.01, ?p2 = -0.69, moderate), 10 min (p < 0.001, ?p2 = -0.90, moderate), and full game (p < 0.001, ?p2 = -0.96, moderate) periods than forwards. CONCLUSIONS:The main finding is that there are significant differences between the most intense moments of a game and the average demands. This means that understanding game demands using averages drastically underestimates the peak demands of the game. This approach helps coaches and fitness coaches to prepare athletes for the most demanding periods of the game and present potential practical applications that could be implemented during training and rehabilitation sessions.
| S-EPMC7177956 | biostudies-literature
Project description:Progressing digitalization and technological changes triggered by COVID-19 lockdowns means for organizations that new technologies need to be implemented in shorter time periods. The implementation of new technologies in the workplace poses various change demands on employees. Organizations try to counteract these effects by providing change support in the form of for example training or participation options. However, to date, it is unclear how change demands develop a detrimental effect and whether change support can buffer this relation due to which working mechanisms, and whether the effectiveness of support measures can be increased by matching them to specific change demands. Based on the integrative framework of social support theory, which draws on the job demands-resources model and self-determination theory, we hypothesize that change demands can be most effectively addressed through matching change support. In three consecutive experimental vignette studies (N 1 = 89, N 2 = 134, N 3 = 138) of dependently employed samples, we analyzed the interaction of change demands and change support on attitude to change, satisfaction with the change process, and behavioral intention to use by manipulating the degree of demand (high vs. low) and provided support (high vs. low) and by conducting moderated mediation analyses, and integrated the results meta-analytically. The results show that change demands have a detrimental effect on technology implementation outcomes. In one of the three studies we confirmed a moderating effect of change support. The relation was mediated by perceived frustration, but the mediating effect of psychological need satisfaction was inconclusive. Based on our results, we discuss that the research on matching support requires the evaluation of the personal relevance of the support receiver to increase the chance of achieving a match.
| S-EPMC9261962 | biostudies-literature
Project description:Object categorization and exemplar identification place conflicting demands on the visual system, yet humans easily perform these fundamentally contradictory tasks. Previous studies suggest the existence of dissociable visual processing subsystems to accomplish the two abilities-an abstract category (AC) subsystem that operates effectively in the left hemisphere and a specific exemplar (SE) subsystem that operates effectively in the right hemisphere. This multiple subsystems theory explains a range of visual abilities, but previous studies have not explored what mechanisms exist for coordinating the function of multiple subsystems and/or resolving the conflicts that would arise between them. We collected functional MRI data while participants performed two variants of a cue-probe working memory task that required AC or SE processing. During the maintenance phase of the task, the bilateral intraparietal sulcus (IPS) exhibited hemispheric asymmetries in functional connectivity consistent with exerting proactive control over the two visual subsystems: greater connectivity to the left hemisphere during the AC task, and greater connectivity to the right hemisphere during the SE task. Moreover, probe-evoked activation revealed activity in a broad frontoparietal network (containing IPS) associated with reactive control when the two visual subsystems were in conflict, and variations in this conflict signal across trials was related to the visual similarity of the cue-probe stimulus pairs. Although many studies have confirmed the existence of multiple visual processing subsystems, this study is the first to identify the mechanisms responsible for coordinating their operations.
| S-EPMC4870143 | biostudies-literature