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3.
J Clin Med ; 13(8)2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38673588

ABSTRACT

Background: The anatomical reconstruction of the wrist is the aim when treating distal radius fractures. Current literature on the importance of preoperative reduction in fractures that are treated operatively is limited. Methods: This study investigated the effect of the preoperative closed reduction of distal radius fractures on the day of trauma and the time to surgery on postoperative palmar inclination. A total of eighty patients (48 females and 32 males, mean age 55.6 years) were studied retrospectively. All patients were treated with an open reduction and internal fixation. The palmar inclination angle was measured using X-rays by two investigators, and the interobservers and pre- and post-reduction parameters were compared. Results: When the surgical management of closed distal radius fractures is required, neither initial repositioning nor a delay of up to 14 days to the surgical treatment influences postoperative palmar inclination. Conclusions: The significance of preoperative reduction of distal radius fractures without neurovascular or extensive soft tissue damage is limited and is not leading to improved outcomes. When surgery is about to be performed, surgeons should carefully consider if reduction is really vital preoperatively. Level of evidence: III.

4.
Technol Health Care ; 32(2): 585-593, 2024.
Article in English | MEDLINE | ID: mdl-37781822

ABSTRACT

BACKGROUND: C-reactive protein (CRP)- and leukocyte levels are common parameters to evaluate the inflammatory response after orthopaedic surgery and rule out infectious complications. Nevertheless, both parameters are vulnerable to disturbing biases and therefore leave room for interpretation. OBJECTIVE: Since blood groups are repeatedly discussed to influence inflammatory response, our aim was to observe their impact on CRP and leukocyte levels after total hip and knee arthroplasty (THA/TKA). METHODS: Short term postoperative CRP and leukocyte levels of 987 patients, who received either primary TKH (n= 479) or THA (n= 508), were retrospectively correlated with their blood group. ABO, Rhesus and a combination of both blood groups were differentiated. RESULTS: CRP levels after TKA were significantly higher in blood type AB than in type A and O on day 2-4 and also than in type A on day 6-8. Leukocyte levels after THA were significantly higher in blood group type O than in type A on day 6-8 while still remaining in an apathological range. We observed no significant differences between Rhesus types and Rhesus types and CRP or leukocyte levels. CONCLUSION: We observed significantly increased CRP levels after TKA in patients with blood group AB. Since the elevated CRP levels do not account for early periprosthetic infection, surgeons should include this variation in their postoperative evaluation.


Subject(s)
Arthroplasty, Replacement, Hip , Arthroplasty, Replacement, Knee , Blood Group Antigens , Humans , C-Reactive Protein/analysis , Retrospective Studies
5.
Technol Health Care ; 32(1): 459-466, 2024.
Article in English | MEDLINE | ID: mdl-37694326

ABSTRACT

BACKGROUND: The cup inclination in total hip arthroplasty is key to minimising complications. Stereometric effects (parallax) in two-dimensional projections can alter angle measurements. Even for different approaches, fluoroscopy causes different results in the measurement of inclination. A previous study has introduced a corrective factor for intraoperative radiographic cup inclination measurements compared to the postoperative standing radiographs. OBJECTIVE: The aim of this study was to find out whether, first, the correction factor is reproducible and second, whether the correction factor is independent of the surgical approach and C-arm model used. METHODS: A series of 377 cases of primary total hip arthroplasty was reviewed. We compared the cup inclination angle in the intraoperative and postoperative radiographic images. Based on this, it was possible to specify a standard of correction factor in defined ranges. RESULTS: The mean cup inclination in intraoperative images was 37.47∘ and the mean angle in postoperative images was 41.42, resulting in a mean difference of 3.95∘ with a strong correlation (r= 0.706). CONCLUSION: An added correction factor of 4∘ should be respected in intraoperative inclination measurements to adapt for parallax. An increased correction factor of 6∘ in particularly low-positioned cups (< 31∘) and a decreased correction factor of 2∘ in particularly steeply positioned cups (> 43∘) is recommended.


Subject(s)
Arthroplasty, Replacement, Hip , Hip Prosthesis , Humans , Arthroplasty, Replacement, Hip/methods , Acetabulum/surgery , Radiography , Fibrinogen
6.
Nat Commun ; 13(1): 7844, 2022 12 21.
Article in English | MEDLINE | ID: mdl-36543773

ABSTRACT

Channelrhodopsins are light-gated ion channels used to control excitability of designated cells in large networks with high spatiotemporal resolution. While ChRs selective for H+, Na+, K+ and anions have been discovered or engineered, Ca2+-selective ChRs have not been reported to date. Here, we analyse ChRs and mutant derivatives with regard to their Ca2+ permeability and improve their Ca2+ affinity by targeted mutagenesis at the central selectivity filter. The engineered channels, termed CapChR1 and CapChR2 for calcium-permeable channelrhodopsins, exhibit reduced sodium and proton conductance in connection with strongly improved Ca2+ permeation at negative voltage and low extracellular Ca2+ concentrations. In cultured cells and neurons, CapChR2 reliably increases intracellular Ca2+ concentrations. Moreover, CapChR2 can robustly trigger Ca2+ signalling in hippocampal neurons. When expressed together with genetically encoded Ca2+ indicators in Drosophila melanogaster mushroom body output neurons, CapChRs mediate light-evoked Ca2+ entry in brain explants.


Subject(s)
Calcium , Drosophila melanogaster , Animals , Calcium/metabolism , Channelrhodopsins/genetics , Drosophila melanogaster/genetics , Drosophila melanogaster/metabolism , Ion Channels/physiology , Neurons/metabolism
7.
Nat Commun ; 13(1): 7253, 2022 11 25.
Article in English | MEDLINE | ID: mdl-36433995

ABSTRACT

The green unicellular alga Chlamydomonas reinhardtii with two photoreceptors called channelrhodopsins is a model organism that gave birth to a new scientific field of biomedical studies, optogenetics. Although channelrhodopsins are helping to decipher the activity of the human brain, their functionality has never been extensively studied in the organism of origin, mainly due to the difficulties connected to reverse genetic interventions. In this study, we present a CRISPR-Cas9-based technique that enables a precise in vivo exchange of single amino acids in a selected gene. To shed light on the function of channelrhodopsins ChR1 (C1) and ChR2 (C2) in vivo, we deleted both channelrhodopsins independently in the wild-type strain and introduced point mutations in the remaining channel, causing modified photocycle kinetics and ion selectivity. The mutated strains, ΔC1C2-E123T, ΔC1C2-E90R and ΔC1C2-E90Q, showed about 100-fold decrease in photosensitivity, a reduced photophobic response and faster light adaptation rates due to accelerated photocycle kinetics and reduced Ca2+ conductance. Moreover, the ΔC1C2-E90Q with an additionally reduced H+ permeability produced an electrical response only in the presence of Na+ ions, highlighting a contribution and importance of H+ conductance to photocurrents in the wild-type algae. Finally, in the ΔC1C2-E90R strain with the channelrhodopsin selectivity converted to anions, no photo-responses were detected. We conclude that the precise photocycle kinetics and the particular ion selectivity of channelrhodopsins are the key parameters for efficient phototaxis in low light conditions.


Subject(s)
Chlamydomonas reinhardtii , Chlamydomonas , Humans , Channelrhodopsins/genetics , Channelrhodopsins/metabolism , Chlamydomonas/genetics , Chlamydomonas/metabolism , Point Mutation , Chlamydomonas reinhardtii/metabolism , Ions/metabolism
8.
Z Orthop Unfall ; 2022 Oct 04.
Article in English, German | MEDLINE | ID: mdl-36195112

ABSTRACT

BACKGROUND: Preoperative templating is the gold standard in planning elective total knee arthroplasty. This retrospective study analyses preoperative templating by using two different calibration devices. METHODS: Preoperative radiographic templating with TraumaCad using two different calibration devices was performed in 231 patients. RESULTS: Overall, 60.6% (n = 140) did not match and 39.4% (n = 91) matched for tibial as well as femoral size. Group I showed significantly more combined matches as well as for just the size of the femoral component. CONCLUSIONS: In this study, the KingMark calibration should be preferred to standardised ball markers.

9.
Pathol Res Pract ; 237: 154036, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35907280

ABSTRACT

The anterior cruciate ligament (ACL) plays a significant role in knee stability, protects the joint under multiple loading conditions and shows complex biomechanics. Beside mechanical stability, the ACL seems to play a crucial role in proprioception, and it is well known, that ACL injuries can cause functional deficits due to decreased proprioception. However, the mechanism of proprioception is not completely understood yet. In this context, primary cilia (PC), which play a significant role in the signaling between the intra- and extracellular space, could be of interest. However, until today, primary cilia are not yet described in human ACL. In total, seven human ACL's underwent transmission electron microscopical examination. Three cadaveric ACL's and four freshly injured ACL's were examined. Single cells of each ACL were examined regarding the presence of axonemes or basal bodies, which represent components of a PC. In total, 276 cells of the cadaveric ACL's and 180 cells of the injured ACL's were examined. Basal bodies could be detected in three of the four specimens of the injured ACL's as well as in one of the three cadaveric ACL's, resulting in a mean positivity of 2.54% in the cadaveric group and 2.78% in the injured group. In case of PC-presence, only one PC per cell could be detected. No statistically significant difference regarding the frequency could be detected between both groups. In this pilot-study, we present for the first time an ultrastructural study of human ACLs with respect to the occurrence of PC and any structural and morphological features of these complex and dynamic cell organelles. PCs are present in almost all non-hematopoietic tissues of the human body. However, there are different reports on the number, incidence, orientation, and morphology of these cell organelles in the respective tissues. Compared to other tissues and ligaments of other species, we found a significantly lower rate of PC positive cells. This observation might represent a tissue-specific characteristic of ACL tissue. However, our observations need to be explored in more detail in further studies.


Subject(s)
Anterior Cruciate Ligament Injuries , Anterior Cruciate Ligament , Humans , Anterior Cruciate Ligament/anatomy & histology , Anterior Cruciate Ligament/physiology , Pilot Projects , Cilia , Knee Joint , Cadaver
10.
Technol Health Care ; 30(3): 725-733, 2022.
Article in English | MEDLINE | ID: mdl-34397439

ABSTRACT

BACKGROUND: Lesions of articular cartilage represent a crucial risk factor for the early development of osteoarthritis. Autologous chondrocyte implantation (ACI) is a well-established procedure in therapy of those lesions in the knee. The aim of the presented study is to detect differences in short-term radiological outcome depending on defect localization (femoral condyle vs. retropatellar) after spheroid-based ACI. OBJECTIVE: This study aimed to demonstrate that radiological outcome after spheroid-based ACI in the knee is independent of defect localization. METHODS: MRI-scans after retropatellar ACI and ACI of the medial/lateral femoral condyle, with a preoperative Outerbridge grade of III or IV were evaluated regarding MOCART 2.0. RESULTS: The mean defect-size was 5.0 ± 1.8 cm2, with a minimum size of 2 cm2 and a maximum size of 9 cm2. Scans were performed 7.7 months (± 3.1 months) postoperatively. The mean MOCART 2.0 score was 78.5 ± 15.6. No statistically significant influence neither of the localization (p= 0.159), the gender (p= 0.124) nor defect size (< 5 cm2 vs. ⩾ 5 cm2; p= 0.201) could be observed. CONCLUSIONS: The presented data demonstrate good to excellent radiological short-term results after spheroid-based ACI. Data indicates, that at least radiological results are independent of gender, defect-size and defect-localization.


Subject(s)
Cartilage, Articular , Orthopedic Procedures , Cartilage, Articular/diagnostic imaging , Cartilage, Articular/surgery , Chondrocytes , Humans , Knee Joint/diagnostic imaging , Knee Joint/surgery , Orthopedic Procedures/methods , Transplantation, Autologous/methods , Treatment Outcome
11.
Acta Orthop Traumatol Turc ; 55(4): 349-354, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34464312

ABSTRACT

OBJECTIVE: The aim of the study was to investigate the effect of different arm positions (hand pronation/supination and elbow flexion/extension) on fragment rotation in extra-articular distal radius fractures in a cadaveric model. METHODS: In this study, ten fresh-frozen cadaveric upper extremities from five donors with a mean age of 69 ± 12 years were used. Two cortical pins were inserted in the radius and the ulna. In a custom-made device, different forearm (30°, 60°, and 90° of pronation and supination) and elbow positions (full extension) were tested, using a fluoroscopic analysis. The degree of malrotation between the two pins was measured in these positions. At the last test sequence, the tendon of the brachioradialis muscle was released. RESULTS: A significant difference was found in concerns of the rotational angle between the distal fragment and the radial shaft at different degrees of pronation and supination if the elbow joint was in an extended and flexed position. The release of the brachioradialis tendon did not show any effect. CONCLUSION: The results of this study supported that rotational malpositions in distal radius fractures can be decreased if the forearm is in a neutral position. Accordingly, the forearm should be in a neutral position while initially immobilization in a plaster splint is performed.


Subject(s)
Forearm , Radius Fractures , Aged , Aged, 80 and over , Cadaver , Humans , Middle Aged , Pronation , Radius/diagnostic imaging , Rotation , Supination
12.
Int J Mol Sci ; 22(6)2021 Mar 17.
Article in English | MEDLINE | ID: mdl-33802838

ABSTRACT

Osteoarthritis (OA) is a multifactorial disease which is characterized by a change in the homeostasis of the extracellular matrix (ECM). The ECM is essential for the function of the articular cartilage and plays an important role in cartilage mechanotransduction. To provide a better understanding of the interaction between the ECM and the actin cytoskeleton, we investigated the localization and expression of the Ca2+-dependent proteins cartilage oligomeric matrix protein (COMP), thrombospondin-1 (TSP-1), plastin 3 (PLS3) and stromal interaction molecule 1 (STIM1). We investigated 16 patients who suffered from varus knee OA and performed a topographical analysis of the cartilage from the medial and lateral compartment of the proximal tibial plateau. In a varus knee, OA is more pronounced in the medial compared to the lateral compartment as a result of an overloading due to the malalignment. We detected a location-dependent staining of PLS3 and STIM1 in the articular cartilage tissue. The staining intensity for both proteins correlated with the degree of cartilage degeneration. The staining intensity of TSP-1 was clearly reduced in the cartilage of the more affected medial compartment, an observation that was confirmed in cartilage extracts by immunoblotting. The total amount of COMP was unchanged; however, slight changes were detected in the localization of the protein. Our results provide novel information on alterations in OA cartilage suggesting that Ca2+-dependent mechanotransduction between the ECM and the actin cytoskeleton might play an essential role in the pathomechanism of OA.


Subject(s)
Cartilage, Articular/metabolism , Knee Joint/metabolism , Membrane Glycoproteins/metabolism , Microfilament Proteins/metabolism , Osteoarthritis, Knee/metabolism , Stromal Interaction Molecule 1/metabolism , Thrombospondins/metabolism , Aged , Aged, 80 and over , Cartilage Oligomeric Matrix Protein/metabolism , Chondrocytes/metabolism , Female , Humans , Knee Joint/pathology , Male , Middle Aged , Osteoarthritis, Knee/pathology , Protein Transport
13.
Arch Bone Jt Surg ; 8(6): 675-681, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33313347

ABSTRACT

BACKGROUND: Osteoporosis represents the most common bone disease and has to be respected in planning total hip replacement, especially against the background of increasing uncemented total hip replacement. In this context, the radiographic geometry of the proximal femur got into focus and is controversially discussed.The aim of the presented study was to find any difference regarding known indices for proximal femur bone geometry between patients with high-grade osteoarthritis and patients suffering from a femoral neck fracture caused by low impact trauma. METHODS: Retrospective matched-paired analysis of 100 plane pelvic radiographs from 50 patients who suffered from high-grade hip osteoarthritis and 50 patients who suffered from femoral neck fracture was performed. Measurement of Canal-Bone Ratio (CBR), Canal-Calcar Ratio (CCR), Mineral Cortical Index (MCI) and Canal Flare Index (CFI) were performed. RESULTS: CBR was significantly higher in the fracture-group (0.45 +/- 0.06 vs. 0.41 +/- 0.08) (P-value= 0.008). Moreover, the femoral thickness 10 cm below the trochanter minor [F] was significantly higher in the osteoarthritis-group (34.68 +/- 4.14 vs 32.11 +/- 3.43) (P-value 0.001). CONCLUSION: In conclusion, patients with a femoral neck fracture demonstrated a higher CBR, which indicates a poorer bone quality. In case of planning a THA, the CBR is an index which can easily be measured and can be seen as one decision criterion in THA regarding fixation technique.

14.
Oper Orthop Traumatol ; 32(6): 477-485, 2020 Dec.
Article in German | MEDLINE | ID: mdl-33185698

ABSTRACT

OBJECTIVE: Reliable wound coverage of the fingertip and palmar aspect of the middle finger with a sensate flap in order to restore early function. INDICATIONS: Palmar, oblique pulp defects or amputations at the distal finger phalange with uncovered bone, tendons, and/or neurovascular structures. CONTRAINDICATIONS: Peripheral perfusion deficiency, size of defect exceeding flap capacity, obliteration of the flap artery, i.e. contralateral finger artery. SURGICAL TECHNIQUE: Harvesting of adipocutane, midlateral triangle based on proper digital vessel flap; distal flap transposition and primary closure of the harvesting defect, flap dimension 4-5 mm larger than defect. POSTOPERATIVE MANAGEMENT: Finger splint for 2 weeks, followed by exercises with flap conditioning. RESULTS: Very reliable defect coverage with 9% minor and temporary complications, all of which healed without consequences.


Subject(s)
Amputation, Traumatic , Finger Injuries , Plastic Surgery Procedures , Amputation, Traumatic/surgery , Finger Injuries/surgery , Fingers/surgery , Humans , Surgical Flaps , Treatment Outcome
15.
Curr Biol ; 30(24): 4910-4920.e5, 2020 12 21.
Article in English | MEDLINE | ID: mdl-33065010

ABSTRACT

Channelrhodopsins (ChRs) are light-gated ion channels widely used as optogenetic tools for manipulating neuronal activity. The currently characterized ChR families include green algal and cryptophyte cation-conducting ChRs (CCRs) and cryptophyte, haptophyte, and stramenopile anion-conducting ChRs (ACRs). Here, we report the discovery of a new family of phylogenetically distinct ChRs encoded by marine giant viruses and acquired from their unicellular green algal hosts. These previously unknown viral and green algal ChRs act as ACRs when expressed in cultured neuroblastoma-derived cells and are likely involved in behavioral responses to light.


Subject(s)
Channelrhodopsins/genetics , Chlorophyta/genetics , Gene Transfer, Horizontal , Genes, Viral , Giant Viruses/genetics , Animals , Anions/metabolism , Cell Line , Channelrhodopsins/metabolism , Chlorophyta/metabolism , Chlorophyta/radiation effects , Chlorophyta/virology , Giant Viruses/metabolism , Hybrid Cells , Light , Metagenomics , Mice , Optogenetics , Phylogeny , Rats
16.
Arch Orthop Trauma Surg ; 140(5): 639-650, 2020 May.
Article in English | MEDLINE | ID: mdl-32193678

ABSTRACT

Distal radioulnar joint (DRUJ) instability is often an underestimated or missed lesion which may entail fatal consequences. The triangular fibrocartilage complex is a biomechanically very important stabilizer of the DRUJ and guarantees unrestricted range of motion of the forearm. To detect DRUJ instability a systematic examination is of uppermost importance. The contralateral healthy arm will be used for comparison during clinical examination. X-rays are required to exclude osseous lesions or deformities. Computed tomography of both wrists in neutral forearm rotation, supination, and pronation may be necessary to verify DRUJ instability in ambiguous situations. Following a systematic clinical examination wrist and DRUJ arthroscopy detects lesions definitely. Tears of the distal radioulnar ligaments which entail DRUJ instability should be repaired preferably anatomically. Ulnar-sided ligament ruptures which cause instability are detected more often than radial-sided ones. Osseous ligament avulsions are mostly refixated osteosynthetically. Ligamentous tears of the distal radioulnar ligaments may be reconstructed using anchor suture or transosseous refixation. Secondary procedures such as tendon transplants are necessary for anatomical reconstruction in cases of unrepairable ligament tears.


Subject(s)
Arthroscopy/methods , Fracture Fixation, Internal/methods , Joint Instability/surgery , Range of Motion, Articular/physiology , Supination/physiology , Wrist Joint/surgery , Humans , Joint Instability/etiology , Joint Instability/physiopathology , Male , Radiography , Wrist Joint/diagnostic imaging , Wrist Joint/physiopathology
17.
J Orthop Res ; 38(4): 747-758, 2020 04.
Article in English | MEDLINE | ID: mdl-31696983

ABSTRACT

Knee osteoarthritis (OA) involves several structures and molecules in the joint, which interact in a pathophysiological process. One of these molecules is the cartilage oligomeric matrix protein (COMP). Elevated COMP levels in the synovial fluid as well as in the serum have been described in OA patients. However, this has not been described in the infrapatellar fat pad (IPFP) tissue before. In this prospective trial, we collected 14 IPFPs from patients with high-grade OA (mean age 63.8 ± 17.6 years) who underwent total knee replacement (OA group) and from 11 healthy patients (mean age 33.7 ± 14.8 years) who underwent anterior cruciate ligament reconstruction (control group). The presence of macrophages (CD68 and CD206) and proinflammatory cytokines (interleukin 1ß [IL-1ß] and IL-6) was analyzed. Histological and immunohistological examinations as well as immunoblotting analysis for COMP, leptin, and matrix-metalloproteinase-3 were performed. The IPFPs of both the OA and control group consisted of adipose tissue and fibrous tissue, and the fibrous tissue showed higher score values than the adipose tissue for COMP staining (intensity as well as stained area) in both groups. Although COMP could be detected in most samples, leptin expression was found only in single specimens. COMP could be detected mostly in the fibrous tissue portion of the IPFP. We speculate that it is involved in a remodeling process taking place in the IPFP during OA. Presence of leptin was irregular in immunohistology, and the control group showed higher scores in case of presence. Interestingly, immunoblotting could detect leptin in all analyzed samples. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society J Orthop Res 38:747-758, 2020.


Subject(s)
Adipose Tissue/metabolism , Cartilage Oligomeric Matrix Protein/metabolism , Osteoarthritis, Knee/metabolism , Adipose Tissue/pathology , Age Factors , Aged , Aged, 80 and over , Antigens, CD/analysis , Antigens, Differentiation, Myelomonocytic/analysis , Case-Control Studies , Extracellular Matrix/metabolism , Female , Humans , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Lectins, C-Type/analysis , Leptin/metabolism , Male , Mannose Receptor , Mannose-Binding Lectins/analysis , Matrix Metalloproteinases/metabolism , Middle Aged , Osteoarthritis, Knee/pathology , Patella , Receptors, Cell Surface/analysis
18.
Oper Orthop Traumatol ; 31(5): 422-432, 2019 Oct.
Article in German | MEDLINE | ID: mdl-31486853

ABSTRACT

OBJECTIVE: Anatomic reduction and stabile fixation for immediate mobilisation and restoration of unrestricted function. INDICATIONS: Instabile metacarpal fractures with or without malrotation, dislocated metacarpal fractures with malrotation or finger extension deficit, longitudinally shortened metacarpal fractures with finger extension deficit. CONTRAINDICATIONS: Persistent infections (empyema, osteomyelitis, phlegmon) SURGICAL TECHNIQUE: Longitudinal intermetacarpal incision along the fracture zone, debridement of the fracture zone with retainment of periost, anatomic reduction and retention of spiral fractures with at least two lag screws or retention of comminuted or transverse fractures with locking plate osteosynthesis while retaining periost. POSTOPERATIVE MANAGEMENT: Buddy splinting of the corresponding finger to enable immediate mobilisation without weight bearing for 6 weeks. RESULTS: Locking plate osteosynthesis and compression screw osteosynthesis after anatomic reduction of metacarpal fractures proved to be very reliable with a low complication rate and a good functional outcome (modified Mayo Wrist Score [MMWS]: mean 88 (20-100); Disabilities of Arm, Shoulder, and Hand (DASH) questionnaire: mean 41(24-86)).


Subject(s)
Fractures, Bone , Metacarpal Bones , Bone Plates , Bone Screws , Fracture Fixation, Internal , Fractures, Bone/surgery , Humans , Metacarpal Bones/injuries , Metacarpal Bones/surgery , Open Fracture Reduction , Treatment Outcome
19.
Nat Commun ; 10(1): 3315, 2019 07 25.
Article in English | MEDLINE | ID: mdl-31346176

ABSTRACT

Channelrhodopsins (ChRs) are algal light-gated ion channels widely used as optogenetic tools for manipulating neuronal activity. ChRs desensitize under continuous bright-light illumination, resulting in a significant decline of photocurrents. Here we describe a metagenomically identified family of phylogenetically distinct anion-conducting ChRs (designated MerMAIDs). MerMAIDs almost completely desensitize during continuous illumination due to accumulation of a late non-conducting photointermediate that disrupts the ion permeation pathway. MerMAID desensitization can be fully explained by a single photocycle in which a long-lived desensitized state follows the short-lived conducting state. A conserved cysteine is the critical factor in desensitization, as its mutation results in recovery of large stationary photocurrents. The rapid desensitization of MerMAIDs enables their use as optogenetic silencers for transient suppression of individual action potentials without affecting subsequent spiking during continuous illumination. Our results could facilitate the development of optogenetic tools from metagenomic databases and enhance general understanding of ChR function.


Subject(s)
Anions/metabolism , Bacteria/genetics , Channelrhodopsins/genetics , Multigene Family , Viruses/genetics , Animals , Bacteria/classification , Bacteria/isolation & purification , Bacteria/metabolism , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Channelrhodopsins/chemistry , Channelrhodopsins/metabolism , Humans , Kinetics , Light , Metagenome , Neurons/metabolism , Optogenetics , Phylogeny , Seawater/microbiology , Seawater/virology , Viral Proteins/genetics , Viral Proteins/metabolism , Viruses/classification , Viruses/isolation & purification , Viruses/metabolism
20.
Article in English | MEDLINE | ID: mdl-29605862

ABSTRACT

Unfortunately, the following reference was not included in the original publication of the article.

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