- A balanced ATP driving force module for enhancing photosynthetic biosynthesis of 3-hydroxybutyrate from CO2. [Journal Article]
- MEMetab Eng 2018 Feb 17
- Using engineered photoautotrophic microorganisms for the direct chemical synthesis from CO2is an attractive direction for both sustainability and CO2mitigation. However, the behaviors of non-native m...
Using engineered photoautotrophic microorganisms for the direct chemical synthesis from CO2is an attractive direction for both sustainability and CO2mitigation. However, the behaviors of non-native metabolic pathways may be difficult to control due to the different intracellular contexts between natural and heterologous hosts. While most metabolic engineering efforts focus on strengthening driving forces in pathway design to favor biochemical production in these organisms, excessive driving force may be detrimental to product biosynthesis due to imbalanced cellular intermediate distribution. In this study, an ATP-hydrolysis based driving force module was engineered into cyanobacterium Synechococcus elongatus PCC 7942 to produce 3-hydroxybutyrate (3HB), a valuable chemical feedstock for the synthesis of biodegradable plastics and antibiotics. However, while the ATP driving force module is effective for increasing product formation, uncontrolled accumulation of intermediate metabolites likely led to metabolic imbalance and thus to cell growth inhibition. Therefore, the ATP driving force module was reengineered by providing a reversible outlet for excessive carbon flux. Upon expression of this balanced ATP driving force module with 3HB biosynthesis, engineered strain produced 3HB with a cumulative titer of 1.2g/L, a significant increase over the initial strain. This result highlighted the importance of pathway reversibility as an effective design strategy for balancing driving force and intermediate accumulation, thereby achieving a self-regulated control for increased net flux towards product biosynthesis.
- Pirouetting pigs: A large non-primate animal model based on unilateral 6-hydroxydopamine lesioning of the nigrostriatal pathway. [Journal Article]
- BRBrain Res Bull 2018 Feb 17
- CONCLUSIONS: Female Göttingen minipigs are susceptible to unilateral dopaminergic degeneration when properly injected unilaterally with sufficient amounts of 6-OHDA in the nigrostriatal pathway. The location of the 6-OHDA injections and thus the accuracy of the employed stereotaxy can be verified in vivo using MRI postoperatively. The injected minipigs display unilateral parkinsonism with a well-defined rotational response to amphetamine that may be ameliated by STN-DBS performed on the lesioned side. The response to apomorphine was, however, not consistent, illustrating that further work on this promising non-primate large animal model is needed, before it is fully similar to the established 6-OHDA models in other species.
- Soluble dietary fiber improves energy homeostasis in obese mice by remodeling the gut microbiota. [Journal Article]
- BBBiochem Biophys Res Commun 2018 Feb 17
- Intervention with dietary fibers is an important strategy to combat the global epidemic of obesity which is a consequence of energy imbalance. However, a possible role of the gut microbiota in effect...
Intervention with dietary fibers is an important strategy to combat the global epidemic of obesity which is a consequence of energy imbalance. However, a possible role of the gut microbiota in effects of dietary fibers on energy homeostasis remains unclear. Here, we treated a high fat diet-induced obese (DIO) mouse model with soluble dietary fiber. Our results showed that soluble dietary fiber reduced body weight gain and the excessive accumulation of white fat tissue in DIO mice. Notably, soluble dietary fiber increased energy expenditure, but not change energy intake in DIO mice. In accordance, 16S rRNA sequencing revealed that the diversity of the gut microbiota was restored by soluble dietary fiber. Moreover, compared with controls, soluble dietary fiber resulted in a decreased ratio of Firmicutes/Bacteroidetes at the phylum level, and an increased relative abundance of the genera Roseburia at the genus level. Taken together, these findings indicate that soluble dietary fiber improves energy homeostasis and prevents obesity by increasing the diversity of the gut microbiota and the colonization of beneficial bacteria.
- A Cross-Talk Between Microbiota-Derived Short-Chain Fatty Acids and the Host Mucosal Immune System Regulates Intestinal Homeostasis and Inflammatory Bowel Disease. [Journal Article]
- IBInflamm Bowel Dis 2018 Feb 15; 24(3):558-572
- Gut microbiota has a fundamental role in the energy homeostasis of the host and is essential for proper "education" of the immune system. Intestinal microbial communities are able to ferment dietary ...
Gut microbiota has a fundamental role in the energy homeostasis of the host and is essential for proper "education" of the immune system. Intestinal microbial communities are able to ferment dietary fiber releasing short-chain fatty acids (SCFAs). The SCFAs, particularly butyrate (BT), regulate innate and adaptive immune cell generation, trafficing, and function. For example, BT has an anti-inflammatory effect by inhibiting the recruitment and proinflammatory activity of neutrophils, macrophages, dendritic cells, and effector T cells and by increasing the number and activity of regulatory T cells. Gut microbial dysbiosis, ie, a microbial community imbalance, has been suggested to play a role in the development of inflammatory bowel disease (IBD). The relationship between dysbiosis and IBD has been difficult to prove, especially in humans, and is probably complex and dynamic, rather than one of a simple cause and effect relationship. However, IBD patients have dysbiosis with reduced numbers of SCFAs-producing bacteria and reduced BT concentration that is linked to a marked increase in the number of proinflammatory immune cells in the gut mucosa of these patients. Thus, microbial dysbiosis and reduced BT concentration may be a factor in the emergence and severity of IBD. Understanding the relationship between microbial dysbiosis and reduced BT concentration to IBD may lead to novel therapeutic interventions.
- The Free-Hand Technique for S2-Alar-Iliac Screw Placement: A Safe and Effective Method for Sacropelvic Fixation in Adult Spinal Deformity. [Journal Article]
- JBJ Bone Joint Surg Am 2018 Feb 21; 100(4):334-342
- CONCLUSIONS: The free-hand technique for S2AI screw placement, when performed in a standardized manner, was demonstrated to be safe and reliable in constructs requiring spinopelvic fixation. The accuracy of screw placement relies on visible and palpable anatomic landmarks that obviate the need for intraoperative fluoroscopy or image guidance, potentially reducing operative time and radiation exposure.
- Heat Shock Protein Reports on Proteome Stress. [Journal Article]
- BJBiotechnol J 2018 Feb 20
- Proper regulation of protein homeostasis (proteostasis) is essential to maintain cellular fitness. Proteome stress causes imbalance of the proteostasis, leading to various diseases represented by neu...
Proper regulation of protein homeostasis (proteostasis) is essential to maintain cellular fitness. Proteome stress causes imbalance of the proteostasis, leading to various diseases represented by neurodegenerative diseases, cancers, and metabolic disorders. The biosensor community recently embarked on the development of proteome stress sensors to report on the integrity of proteostasis in live cells. While most of these sensors are based on metastable mutants of specific client proteins, a recent sensor takes advantage of the specific association of heat shock protein 27 with protein aggregates and exhibits a diffusive to punctate fluorescent change in cells that are subjected to stress conditions. Thus, heat shock proteins can be also used as a family of sensors to monitor proteome stress.
- Endogenous factors and mechanisms of renoprotection and renal repair. [Review]
- EJEur J Clin Invest 2018 Feb 20
- CONCLUSIONS: We have generated a set of renoprotective factors based on literature information, which was functionally annotated and evaluated with respect to tested compounds in kidney disease and diabetes clinical trials. This article is protected by copyright. All rights reserved.
- The Immunologic Paradoxes of IgG4-Related Disease. [Review]
- CRClin Rev Allergy Immunol 2018 Feb 19
- IgG4-related disease (IgG4-RD), which usually occurs in middle-aged and elderly men, is a newly recognized fibroinflammatory condition characterized by swelling and sclerosis of involved organs, incr...
IgG4-related disease (IgG4-RD), which usually occurs in middle-aged and elderly men, is a newly recognized fibroinflammatory condition characterized by swelling and sclerosis of involved organs, increased IgG4-positive plasma cell infiltration in lesions, and elevated IgG4 concentration in serum. Despite growing interest in the research, the pathophysiological mechanism remains elusive. Most IgG4-RD patients respond well to steroid therapy initially, but recurrent and refractory cases are common, especially in advanced fibrotic stage. Recent studies have documented the heterogeneity of the B cell lineages, which suggests their multiple functions in IgG4-RD beyond IgG4 production, such as cytokine secretion, antigen presentation, autoantibody production, and modulation of T and B cell interactions. Thus, a critical balance exists between pathogenic and regulatory B subsets to prevent immunopathology. A prompt response to B cell depletion therapy reported in recent cases strongly suggests the imbalance within B cell lineages in IgG4-RD. A more precise understanding of the pathogenesis of IgG4-RD will open up new perspectives for therapeutic strategy. With a particular emphasis on the novel B cell-targeted therapeutic strategies, this review highlights the immunologic features of IgG4-RD and the possible roles of B cell lineages in the pathogenesis of IgG4-RD.
- Benign and malignant hepatocellular lesions in patients with vascular liver diseases. [Journal Article]
- ARAbdom Radiol (NY) 2018 Feb 19
- A variety of vascular liver disorders can induce hepatocellular tumors. They may be related to portal venous deprivation, venous outflow obstruction, or arterial diseases. Their common feature is an ...
A variety of vascular liver disorders can induce hepatocellular tumors. They may be related to portal venous deprivation, venous outflow obstruction, or arterial diseases. Their common feature is an imbalance between hepatic arterial and portal venous blood flow leading to an increased hepatic arterial inflow. Consequently, hepatocellular tumors may arise, most commonly focal nodular hyperplasia-like lesions but hepatocellular adenomas and hepatocellular carcinoma may be seen as well. This article will review the most common vascular liver diseases associated with hepatocellular nodules (Budd-Chiari syndrome, congenital portosystemic shunt, hereditary hemorrhagic telangiectasia, and portal cavernoma). For each condition, imaging findings will be described as well as the differential diagnosis and the diagnostic clues.
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- Hypothesis: The Vestibular and Cerebellar Basis of the Mal de Debarquement Syndrome. [Journal Article]
- FNFront Neurol 2018; 9:28
- The Mal de Debarquement syndrome (MdDS) generally follows sea voyages, but it can occur after turbulent flights or spontaneously. The primary features are objective or perceived continuous rocking, s...
The Mal de Debarquement syndrome (MdDS) generally follows sea voyages, but it can occur after turbulent flights or spontaneously. The primary features are objective or perceived continuous rocking, swaying, and/or bobbing at 0.2 Hz after sea voyages or 0.3 Hz after flights. The oscillations can continue for months or years and are immensely disturbing. Associated symptoms appear to be secondary to the incessant sensation of movement. We previously suggested that the illness can be attributed to maladaptation of the velocity storage integrator in the vestibular system, but the actual neural mechanisms driving the MdDS are unknown. Here, based on experiments in subhuman primates, we propose a series of postulates through which the MdDS is generated: (1) The MdDS is produced in the velocity storage integrator by activation of vestibular-only (VO) neurons on either side of the brainstem that are oscillating back and forth at 0.2 or 0.3 Hz. (2) The groups of VO neurons are driven by signals that originate in Purkinje cells in the cerebellar nodulus. (3) Prolonged exposure to roll, either on the sea or in the air, conditions the roll-related neurons in the nodulus. (4) The prolonged exposure causes a shift of the pitch orientation vector from its original position aligned with gravity to a position tilted in roll. (5) Successful treatment involves exposure to a full-field optokinetic stimulus rotating around the spatial vertical countering the direction of the vestibular imbalance. This is done while rolling the head at the frequency of the perceived rocking, swaying, or bobbing. We also note experiments that could be used to verify these postulates, as well as considering potential flaws in the logic. Important unanswered questions: (1) Why does the MdDS predominantly affect women? (2) What aspect of roll causes the prolongation of the tilted orientation vector, and why is it so prolonged in some individuals? (3) What produces the increase in symptoms of some patients when returning home after treatment, and how can this be avoided? We also posit that the same mechanisms underlie the less troublesome and shorter duration Mal de Debarquement.