23 research outputs found

    Natural and Induced Mitochondrial Phosphate Carrier Loss: DIFFERENTIAL DEPENDENCE OF MITOCHONDRIAL METABOLISM AND DYNAMICS AND CELL SURVIVAL ON THE EXTENT OF DEPLETION.

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    The relevance of mitochondrial phosphate carrier (PiC), encoded by SLC25A3, in bioenergetics is well accepted. However, little is known about the mechanisms mediating the cellular impairments induced by pathological SLC25A3 variants. To this end, we investigated the pathogenicity of a novel compound heterozygous mutation in SLC25A3 First, each variant was modeled in yeast, revealing that substituting GSSAS for QIP within the fifth matrix loop is incompatible with survival on non-fermentable substrate, whereas the L200W variant is functionally neutral. Next, using skin fibroblasts from an individual expressing these variants and HeLa cells with varying degrees of PiC depletion, PiC loss of ∼60% was still compatible with uncompromised maximal oxidative phosphorylation (oxphos), whereas lower maximal oxphos was evident at ∼85% PiC depletion. Furthermore, intact mutant fibroblasts displayed suppressed mitochondrial bioenergetics consistent with a lower substrate availability rather than phosphate limitation. This was accompanied by slowed proliferation in glucose-replete medium; however, proliferation ceased when only mitochondrial substrate was provided. Both mutant fibroblasts and HeLa cells with 60% PiC loss showed a less interconnected mitochondrial network and a mitochondrial fusion defect that is not explained by altered abundance of OPA1 or MFN1/2 or relative amount of different OPA1 forms. Altogether these results indicate that PiC depletion may need to be profound (\u3e85%) to substantially affect maximal oxphos and that pathogenesis associated with PiC depletion or loss of function may be independent of phosphate limitation when ATP requirements are not high

    Natural and induced mitochondrial phosphate carrier loss: differential dependence of mitochondrial metabolism and dynamics, and cell survival, on the extent of depletion

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    The relevance of PiC, encoded by SLC25A3, in bioenergetics is well accepted. However, little is known about the mechanisms mediating the cellular impairments induced by pathological SLC25A3 variants. To this end, we investigated the pathogenicity of a novel compound heterozygous mutation in SLC25A3. First, each variant was modeled in yeast, revealing that substituting GSSAS for QIP within the 5th matrix loop is incompatible with survival on non-fermentable substrate whereas the L200W variant is functionally neutral. Next, using skin fibroblasts from an individual expressing these variants, and HeLa cells with varying degrees of PiC depletion, PiC loss of ~60% was still compatible with uncompromised maximal oxidative phosphorylation (oxphos) whereas lower maximal oxphos was evident at ~85% PiC depletion. Furthermore, intact mutant fibroblasts displayed suppressed mitochondrial bioenergetics consistent with a lower substrate availability rather than phosphate limitation. This was accompanied by slowed proliferation in glucose-replete media, however proliferation ceased when only mitochondrial substrate was provided. Both mutant fibroblasts and HeLa cells with 60% PiC loss showed a less interconnected mitochondrial network and a mitochondrial fusion defect that is not explained by altered abundance of OPA1, MFN1/2 or relative amount of different OPA1 forms. Altogether these results indicate that PiC depletion may need to be profound (>85%) to substantially affect maximal oxphos and that pathogenesis associated with PiC depletion or loss-of-function may be independent of phosphate limitation when ATP requirements are not high

    MaNmrA, a Negative Transcription Regulator in Nitrogen Catabolite Repression Pathway, Contributes to Nutrient Utilization, Stress Resistance, and Virulence in Entomopathogenic Fungus Metarhizium acridum

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    The NCR pathway plays an important regulatory role in the nitrogen metabolism of filamentous fungi. NmrA, a central negative regulatory protein in the NCR pathway and a key factor in sensing to the carbon metabolism, plays important roles in pathogenic fungal nutrition metabolism. In this study, we characterized the functions of MaNmrA in the insect pathogenic fungus M. acridum. Multiple sequence alignments found that the conserved domain (NAD/NADP binding domain) of MaNmrA was highly conservative with its homologues proteins. Deletion of MaNmrA improved the utilization of multiple carbon sources (such as glucose, mannose, sucrose, and trehalose) and non-preferred nitrogen sources (such as NaNO3 and urea), significantly delayed the conidial germination rate and reduced the conidial yield. The MaNmrA-disruption strain (ΔMaNmrA) significantly decreased tolerances to UV-B and heat-shock, and it also increased the sensitivity to the hypertonic substance sorbitol, oxygen stress substance H2O2, and cell wall destroyer calcofluor white, indicating that loss of MaNmrA affected cell wall integrity, tolerances to hypertonic and oxidative stress. Bioassays demonstrated that disruption of MaNmrA decreased the virulence in both topical inoculation and intrahemocoel injection tests. Further studies revealed that the appressorium formation, turgor pressure, and colonization in hemolymph were significantly reduced in the absence of MaNmrA. Our work will deepen the functional cognition of MaNmrA and make a contribution to the study of its homologous proteins

    Prog. Chem.

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    Co-production of pulp and organic fertilizer is an effective method to realize clean utilization of stalk. In this paper, the evolution of stalk utilization and clean pulp technique are reviewed in detail. The content of this cycle economic mode and the prospect in future are introduced. The mode applies the melt hydrolyzation technology to prepare KOH and phosphorus fertilizer in order to reduce the material cost, and uses KOH to cook the straw to produce pulp. The black liquor rich with potassium can be used to produce the liquid fertilizer, solid organic fertilizer and irrigation water, and the liquor can be entirely used to achieve resource utilization, therefore no wastes would be released out of the whole system. The straw comes from the crops, and the fertilizer made from the straw return to serve the farming. At the same time the pulp for paper industry is prepared. So the technique system of clean production by the co-production of pulp and fertilizer is the way to realize the clean and effective utilization of straw resource.Co-production of pulp and organic fertilizer is an effective method to realize clean utilization of stalk. In this paper, the evolution of stalk utilization and clean pulp technique are reviewed in detail. The content of this cycle economic mode and the prospect in future are introduced. The mode applies the melt hydrolyzation technology to prepare KOH and phosphorus fertilizer in order to reduce the material cost, and uses KOH to cook the straw to produce pulp. The black liquor rich with potassium can be used to produce the liquid fertilizer, solid organic fertilizer and irrigation water, and the liquor can be entirely used to achieve resource utilization, therefore no wastes would be released out of the whole system. The straw comes from the crops, and the fertilizer made from the straw return to serve the farming. At the same time the pulp for paper industry is prepared. So the technique system of clean production by the co-production of pulp and fertilizer is the way to realize the clean and effective utilization of straw resource

    Dynamic Characteristic Analysis of Centrifugal Pump Impeller Based on Fluid-Solid Coupling

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    Purpose: Centrifugal pumps are prone to vibration problems during operation due to poor dynamic characteristics of its impellers that serve as the only running parts of such devices; the dynamic characteristics of the impeller during operation are the main reasons for the vibration of the centrifugal pump. Therefore, it is important to study the internal fluid flow and its influence on the dynamic characteristics of the pump impeller and to explore the causes of vibration during the transient start-up process. The understanding of such phenomena may lead to better design of such impellers. Methods: The geometry of the flow channel inside the centrifugal pump is established using Creo 4.0 software (American PTC company). The internal fluid flow computer simulation is carried out using Flomaster V9 software (UK Flowmaster company) to obtain the variation law of speed and flow during the start-up of the centrifugal pump, which is loaded into the simulation calculation of the centrifugal pump. The variation of speed and flow during the start-up process was further processed using the fluid-structure coupling method, and the structural vibration characteristics of the impeller under transient radial force are obtained by harmonic response analysis. Results: During the starting process of the centrifugal pump, the speed and flow first increased sharply and then decreased until reaching a stable process. During this period, the impeller vibration changed sharply; the overall vibration amplitude increased and fluctuated stably at the amplitude of 0.01 mm. In the unsteady numerical simulation of the centrifugal pump, the radial force on the impeller changes periodically. The time domain signal is transformed into a frequency domain signal, and the fundamental frequency of the impeller and the passing frequency of the blade are 101.67 Hz and 610 Hz, respectively. Conclusions: The radial force is the main cause of impeller vibration, and the transient radial force has the least dynamic impact on the impeller structure under the design condition and has a relatively large impact under the off-design condition. In order to ensure the stable operation of the centrifugal pump, it is necessary to avoid the centrifugal pump working under the non-standard flow condition, especially the small flow condition

    Environment-Aware Worker Trajectory Prediction Using Surveillance Camera in Modular Construction Facilities

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    The safety of workers in modular construction remains a concern due to the dynamic hazardous work environments and unawareness of the potential proximity of equipment. To avoid potential contact collisions and to provide a safe workplace, workers’ trajectory prediction is required. With recent technology advancements, the study in the area of trajectory prediction has benefited from various data-driven approaches. However, existing data-driven approaches are mostly limited to considering only the movement information of workers in the workplace, resulting in poor estimation accuracy. In this study, we propose an environment-aware worker trajectory prediction framework based on long short-term memory (LSTM) network to not only take the individual movement into account but also the surrounding information to fully exploit the context in the modular construction facilities. By incorporating worker-to-worker interactions as well as environment-to-worker interactions into our prediction model, a sequence of the worker’s future positions can be predicted. Extensive numerical tests on synthetic as well as modular construction datasets show the improved prediction performance of the proposed approach in comparison to several state-of-the-art alternatives. This study offers a systematic and flexible framework to incorporate rich contextual information into the prediction model in modular construction. The observation of how to integrate construction data analytics into a single framework could be inspiring for further future research to support robust construction safety practices

    Where are we? Towards an understanding of the selective accumulation of microplastics in mussels

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    Mussels are suggested as bioindicators of marine microplastic pollution. However, they are selective in regards to accumulation of microplastics. To make studies more targeted and comparable, ultimately helping to determine the suitability of the mussel as a bioindicator species for microplastic exposure, we review the published literature that has directly or indirectly demonstrated particle selection in mussels. The reported difference between microplastic levels in mussel tissues and environmental matrices provides evidence for their selective uptake characteristics. Both the organ-specific fate characteristics of microplastics, and the different movement patterns of microplastics in the same organ, show that selective translocation processes take place. The selective elimination is reflected in multiple aspects which include (1) the different characteristics of microplastics in excretion and mussel body; (2) the different retention time of various microplastics in mussels; and (3) the tissue-specific change in the numbers of microplastics during the depuration process. This selectivity is affected by the characteristics of the microplastics, the environmental, or laboratory exposure concentrations, feeding status, and other factors. There are still many research gaps and contradictory viewpoints in this field due to this complexity. The current methodology needs improvement and a breakthrough in standardization

    Management of Acute Achilles Tendon Rupture Using the Krackow and Tendon-Bundle Techniques

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    ABSTRACT: Background: Acute Achilles tendon rupture is a severe injury of the lower extremities; however, optimal treatment options are not yet available. This study aimed to investigate the surgical method and clinical effect of the Krackow and tendon-bundle techniques for managing acute Achilles tendon rupture. Methods: This retrospective case series study analyzed 17 cases of acute Achilles tendon rupture at the Beijing Jishuitan Hospital from December 2012 to January 2020. There were 16 men and one woman, aged 27–45 years, with an average of 39.6 years. Thirteen patients were injured while playing basketball or badminton, and 4 patients were injured while participating in a football match or other sports. All injuries were repaired using the Krackow and tendon-bundle techniques. Postoperative evaluation indicators included active range of motion during ankle plantar flexion and dorsiflexion, height of single foot heel lifting, Amer-Lindholm Achilles tendon function score, and American Orthopedic Foot and Ankle Society (AOFAS) score. Results: The patients were followed-up for 6–45 months (average, 18.9 months). There was no re-rupture of the Achilles tendon, wound infection, or sural nerve injury. At the final follow-up, the affected and contralateral sides exhibited plantar flexion of 42.1 ± 4.4 ° and 43.8 ± 2.8 °, dorsiflexion of 15.8 ± 2.9 ° and 16.6 ± 2.9 °, respectively, and one foot exhibited a heel lifting height of 7.2 ± 1.0 cm and 7.5 ± 0.9 cm, respectively. There was no significant difference between the affected and contralateral sides (P>0.05). At the final follow-up, the Amer-Lindholm Achilles tendon function score was excellent in 94.1% (16/17) of the patients and good in 5.9% (1/17) of the patients. The AOFAS scores ranged from 90 to 100, with an average of 96.4 ± 3.7. Conclusion: Krackow and tendon-bundle techniques can improve the strength of the suture used for the Achilles tendon repair and ensure good matching for broken ends, and thus it is an effective repair method for closed Achilles tendon injury

    Oceanitalea nanhaiensis gen nov, sp nov, an actinobacterium isolated from seawater

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    NSFC [91028001, 41076063]; SOA [201105021]A Gram-positive, motile, short-rod-shaped bacterium, designated strain JLT1488(T), was isolated from the South China Sea and investigated in a taxonomic study using a polyphasic approach. The peptidoglycan type determined for strain JLT1488(T) was A4 alpha with lysine as the diagnostic cell-wall diamino acid and an interpeptide bridge of L-Lys L-Glu. The polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannosides, an unknown glycolipid and an unknown phospholipid. The only detected menaquinone was MK-8(H-4), and the major fatty acids were summed feature 8 (C-18:1 omega 7c/C-18:1 omega 6C) C-16:0 and summed feature 3 (C-16:1 omega 7c/C-16:1 omega 6c); significant amounts of C-12:0 3-OH, C-10:0 and C-19:0 cyclo omega 8c were also present. The G + C content of the genomic DNA was 62.3 mol%. Comparison of the 16S rRNA gene sequence of strain JLT1488(T) with those of related type strains demonstrated that it represented a novel lineage within the family Bogoriellaceae, suborder Micrococcineae, being closely related to species of the genera Georgenia, Bogoriella and Cellulomonas (94.6-96.8% sequence similarity). These results demonstrate that strain JLT1488T is a member of a new genus, for which the name Oceanitalea nanhaiensis gen. nov., sp. nov. is proposed. The type strain of the type species is JLT1488(T) (=JCM 17755(T)=CGMCC 1.10826(T))
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