The emerging importance of group II PAKs

2010 ◽  
Vol 425 (3) ◽  
pp. 465-473 ◽  
Author(s):  
Claire M. Wells ◽  
Gareth E. Jones

The Rho-family GTPases Rho Rac and Cdc42 regulate many intracellular processes through their interaction with downstream effector proteins. The PAKs (p21-activated kinases) are a family of effector proteins for Rac and Cdc42. PAKs are important regulators of actin cytoskeletal dynamics, neurite outgrowth, cell survival, hormone signalling and gene transcription. There are six mammalian PAKs that can be divided into two groups: group I PAKs (PAK1–3) and group II PAKs (PAK4–6). Although the two PAK groups are architecturally similar, there are differences in their mode of regulation, suggesting that their cellular functions are likely to be different. Whereas much is known about group I PAKs, less is known about the more recently discovered PAK4, PAK5 and PAK6. This review will focus on the latest structural and functional results relating to the group II PAKs and discuss the emerging importance of group II PAKs in disease progression.

Author(s):  
Maksim V Sinitsyn ◽  
Nadezhda A Pozdeyeva ◽  
Nikolai P Pashtayev

ABSTRACT Purpose To comparatively analyze the intrastromal MyoRing implantation with femtosecond laser (FL) using the standard and optimized technologies in the experiment and based on the long-term clinical-functional results of the patients with keratoconus (KC) at stages II and III. Materials and methods The experimental work was performed on 24 eyes of rabbits. All eyes were divided into six groups according to the method of operation. In the clinical part of the research, the surgical treatment of 70 patients (76 eyes) with KC at stages II and III was done. Depending on the technology of the operation, all patients were divided into two groups. Group I consisted of 29 patients (32 eyes) with KC, in which MyoRing implantation was performed according to the standard, group II consisted of 31 patients (32 eyes) with KC, in which MyoRing implantation was performed according to the optimized technology. Results Higher voltage was required for stretching samples of the second group in comparison with the third and the sixth group in comparison with the fifth group. In group I, during the period of 6 to 36 months the surgery reverses keratometry, corneal thickness above the MyoRing, and posterior corneal elevation. In group II, 12 months after surgery the clinical and functional parameters remained stable throughout the period of observation. Conclusion Greater reduction in corneal biomechanical stability was observed after formation of the intrastromal pocket in comparison with an intrastromal tunnel; a more pronounced increase in the strength characteristics of the cornea was observed after implantation of the ring in intrastromal pocket, compared with implantation intracorneal segments in intrastromal tunnel, and with increasing depth of intrastromal ring implantation. Application of optimized MyoRing implantation technology compared with standard allows more biomechanical parameters of the cornea to improve and reduce the risk of the ring protrusion. How to cite this article Sinitsyn MV, Pozdeyeva NA, Pashtayev NP. Comparative Analysis of the Intrastromal MyoRing Implantation performed with the Femtosecond Laser. Int J Kerat Ect Cor Dis 2017;6(2):49-57.


2012 ◽  
Vol 40 (6) ◽  
pp. 1378-1382 ◽  
Author(s):  
Alan Hall

Rho GTPases comprise a family of molecular switches that control signal transduction pathways in eukaryotic cells. A conformational change induced upon binding GTP promotes an interaction with target (effector) proteins to generate a cellular response. A highly conserved function of Rho GTPases from yeast to humans is to control the actin cytoskeleton, although, in addition, they promote a wide range of other cellular activities. Changes in the actin cytoskeleton drive many dynamic aspects of cell behaviour, including morphogenesis, migration, phagocytosis and cytokinesis, and the dysregulation of Rho GTPases is associated with numerous human diseases and disorders.


2017 ◽  
Vol 107 (11) ◽  
pp. 1305-1311 ◽  
Author(s):  
Lichun Yan ◽  
Baishi Hu ◽  
Gong Chen ◽  
Mei Zhao ◽  
Ron R. Walcott

Bacterial fruit blotch, caused by the gram-negative bacterium Acidovorax citrulli, is a serious economic threat to cucurbit crop production worldwide. A. citrulli strains can be divided into two genetically distinct groups, with group I strains infecting a range of cucurbit species and group II strains being predominantly associated with watermelon. Group I and II A. citrulli strains differ in their arsenal of type III secreted (T3S) effector proteins and we hypothesize that these effectors are critical for cucurbit host preference. However, the pathogenicity or virulence assays used for A. citrulli, including infiltration of seedling cotyledons and mature fruit rind tissues with cell suspensions and spray inoculation of seedlings, lack the sensitivity to consistently distinguish strains of the two groups. Here, we describe an immature, detached melon fruit assay based on ‘Joaquin Gold’ melon (Syngenta, Rogers Brand) that clearly indicates differences in host specificity between group I and II A. citrulli strains. Using this assay, four group I strains (M6, AAC213-52, AAC213-55, and XJL12) induced typical water-soaked lesions in melon fruit rind tissue 7 to 10 days after pinprick inoculation. In contrast, four group II strains (AAC00-1, AAC213-44, AAC213-47, and AAC213-48) did not induce water-soaked lesions on detached melon fruit rinds during the same period. These data suggest that group I A. citrulli strains have a specific capacity to infect immature Joaquin Gold melon fruit, whereas group II strains do not. Interestingly, this differential pathogenicity phenotype was not observed on foliar seedling tissues of the same melon cultivar, suggesting that host preference of A. citrulli strains is specific to immature fruit tissues. Using the immature melon fruit inoculation assay, a T3S system mutant of the group I A. citrulli strain, M6 (M6ΔhrcV), failed to induce water soaking. This indicates that T3S effectors are involved in A. citrulli cucurbit host preference, and that this assay is suitable for future studies of unique T3S effectors that distinguish group I and II strains.


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Chung-Ting Liu ◽  
Ten-Fang Yang

Abstract Background Acromioclavicular (AC) separation can be treated with the use of a hook plate. Some studies have reported that coracoclavicular (CC) ligament augmentation is necessary to reduce the complications of hook plate fixation, whereas others recommend hook plate fixation alone without augmentation. The aim of this study was to compare the results and complications between these two groups. Methods This was an observational case-control study. Patients with acute (less than 2 weeks) Rockwood type V AC separation were treated with a hook plate at our hospital. A total of 105 cases received hook plate fixation with CC ligament augmentation (group I), and 112 cases received hook plate fixation without augmentation (group II). Constant-Murley scores were used to evaluate the function before and after implant removal, and radiographs were taken to evaluate the complications. The results and complications were compared between groups. Results Before removal, the Constant-Murley score was significantly higher in group I (mean, 50.1) than in group II (mean, 42.6) (p = 0.004); however, there was no significant difference between groups at 3 and 6 months after removal. The incidence of significant acromion osteolysis was higher in group II (65/112) than in group I (25/105). Before removal, the patients with significant acromion osteolysis had worse Constant-Murley scores than those of the patients without osteolysis in both groups. The incidence of peri-implant fracture of the hook plate was higher in group II (8/112) than in group I (1/105). Conclusion The patients without CC ligament augmentation had worse functional results before hook plate removal, a higher incidence of radiographic acromion osteolysis, and a higher incidence of peri-implant fractures than those patients with CC ligament augmentation. Therefore, CC ligament augmentation is highly recommended to improve short-term outcomes and decrease complications for Rockwood type V AC separation treated by hook plate.


Author(s):  
N. Setaro ◽  
M. Rotini ◽  
P. Luciani ◽  
G. Facco ◽  
A. Gigante

Abstract Background Proximal humeral fractures (PHFs) are fairly common injuries, and their treatment is a challenge. The aim of this study is to compare clinical and functional outcomes of different osteosynthesis techniques. Materials and methods We retrospectively reviewed patients’ files and the hospital’s digital database between March 2002 and April 2018. We treated surgically 148 patients with 2- and 3-part PHFs: 64 with plate and screws, 53 with intramedullary nailing and 31 with retrograde K-wires. We constituted three groups according to the type of treatment and two subgroups for each according to the number of fragments (Neer II or Neer III). Disabilities of the Arm, Shoulder and Hand (DASH) and Short Form-12 (SF-12) scores were recorded. Results Mean DASH and SF-12 scores both from the group treated with plate (Group I) and the one subjected to intramedullary nailing (Group II) were statistically superior to results from the patients treated by retrograde K-wires (Group III), while nails showed better functional results than the locking plates. In the first two groups, no difference was found between Neer II and III subgroups, while in Group III the DASH scores were significantly better in Neer II subgroup than those in Neer III subgroup. Avascular necrosis was the most frequent cause of revision surgery in Group I (4 cases) where we had 8 cases of reintervention (12.5%). In Group II, the subacromial impingement was the only cause for revision surgery with 3 cases (5.6%). Conclusions Intramedullary nails showed better functional results and a lower complication rate than the locking plates. Both techniques showed superior results compared to those available with retrograde K-wires. So the nail seems to be a more reliable and adequate method for treating 2- and 3-part proximal humeral fractures.


2003 ◽  
Vol 31 (3) ◽  
pp. 681-685 ◽  
Author(s):  
P.A. Lund ◽  
A.T. Large ◽  
G. Kapatai

Heat-shock protein (Hsp) 60 chaperones are almost ubiquitous and almost always essential. They can be divided on the basis of sequence homology into two broad types: group I (found in bacteria, mitochondria and chloroplasts) and group II (found in Archaea and the eukaryotic cytosol). Of the two, the group I chaperones are the better understood. Data on their structure, mechanism of action and cellular role will be briefly presented. The group II chaperones are less well studied. In eukaryotes they form large complexes with 8-fold symmetry containing eight different subunits, all of which are essential. They appear to have a major role in the folding of actin and tubulin, although they may also act on other substrates. No crystal structures are available for these complexes. The situation in the Archaea is simpler, with organisms containing between one and three genes for these chaperones. A 2.6 Å structure exists for one archaeal group II chaperone complex. Some progress has been made in defining the reaction cycle of the archaeal group II chaperones and this has shown that they have some properties distinct from the group I chaperones. To date, the in vivo role and importance of the archaeal group II Hsp60 chaperones has not been determined. We have now shown that in the halophilic archaeon Haloferax volcanii not all the genes for these proteins are essential. Further analysis of these proteins in the Archaea should be very productive in yielding more information about these important chaperones and their cellular functions.


2015 ◽  
Vol 8 (1) ◽  
pp. 5-11
Author(s):  
Tat'yana Andreevna Avanesova

Background: Optical coherence tomography (OCT) findings are helpful in assessing the cause of reduced visual acuity (VA) after successful rhegmatogenous retinal detachment (RRD) surgery. Objective: To study anatomical and functional results after successful RRD surgery with gas-air mixture or silicone oil (SO) tamponade using OCT. Materials and methods. 70 patients were divided into 2 groups: group I (n = 34) - gas-air mixture tamponade; group II (n = 36) - SO tamponade. At baseline, were no significant differences by gender, age and VA between the groups. Follow-up was 12 months after the surgery. OCT was performed with the Cirrus HD-OCT 4000, CARL ZEISS MEDITEC, USA. Results: VA increased significantly in both groups. Regression analysis showed lower VA in group II and statistically significant association between VA and IS/OS and ELM defects. Сonclusions. There is a strong association of disruption of the IS/OS and ELM with reduced vision after successful retinal detachment surgery. Gas-air mixture tamponade showed some benefits in comparison with SO tamponade.


2006 ◽  
Vol 174 (5) ◽  
pp. 701-713 ◽  
Author(s):  
Abhinav Seth ◽  
Chinatsu Otomo ◽  
Michael K. Rosen

Diaphanous-related formins (DRFs) are key regulators of actin cytoskeletal dynamics whose in vitro actin assembly activities are thought to be regulated by autoinhibition. However, the in vivo consequences of autoinhibition and the involvement of DRFs in specific biological processes are not well understood. In this study, we show that in the DRFs FRLα (formin-related gene in leukocytes α) and mouse diaphanous 1, autoinhibition regulates a novel membrane localization activity in vivo as well as actin assembly activity in vitro. In FRLα, the Rho family guanosine triphosphatase Cdc42 relieves the autoinhibition of both membrane localization and biochemical actin assembly activities. FRLα is required for efficient Fc-γ receptor–mediated phagocytosis and is recruited to the phagocytic cup by Cdc42. These results suggest that mutual autoinhibition of biochemical activity and cellular localization may be a general regulatory principle for DRFs and demonstrate a novel role for formins in immune function.


2020 ◽  
Author(s):  
Nikolaus Balthasar Dietz ◽  
Markus Huber ◽  
Isabel Sorg ◽  
Arnaud Goepfert ◽  
Alexander Harms ◽  
...  

SummaryRas-homology (Rho) family GTPases are conserved molecular switches controlling fundamental cellular activities in eukaryotic cells. As such, they are targeted by numerous bacterial toxins and effector proteins, which have been intensively investigated regarding their biochemical activities and discrete target spectra; however, molecular mechanisms of target selectivity have remained elusive. Here, we report a bacterial effector protein that targets all four Rac subfamily members of Rho family GTPases, but none of the closely related Cdc42 or RhoA subfamilies. This exquisite target selectivity of the FIC domain AMP-transferase Bep1 from Bartonella rochalimae is based on electrostatic interactions with a subfamily-specific pair of residues in the nucleotide-binding motif and the Rho insert helix. Residue substitutions at the identified positions in Cdc42 facilitate modification by Bep1, while corresponding Cdc42-like substitutions in Rac1 greatly diminish modification. Our study establishes a structural paradigm for target selectivity towards Rac subfamily GTPases and provides a highly selective tool for their functional analysis.


Author(s):  
Sreekanth Kashayi-Chowdoji rao ◽  
Lalith Mohan Chodavarapu ◽  
Bharath Reddy Buchupalli ◽  
Chandrasekhar Patnala ◽  
Vijaya Krishna Chilakamarri

<p class="abstract"><strong>Background:</strong> Ipsilateral femoral shaft and hip fractures are commonly encountered following high energy trauma. Despite many treatment methods, controversy exists regarding the optimal management of these fractures. This study was planned to compare reconstruction-type intramedullary nailing and various plate combinations on the fracture healing and functional outcome in patients with these fractures.</p><p class="abstract"><strong>Methods:</strong> 25 patients with ipsilateral femoral shaft and hip fractures were operated by one of the  two modalities - cancellous lag screws or dynamic hip screw for fracture hip and compression plate fixation for fracture shaft of the femur (Group I, 13 patients) and Reconstruction-type intramedullary nailing  alone (Group II, 12 patients) -  depending on surgeon's preference. The functional results of the patients were assessed with the system used by Friedman and Wyman. Radiological and functional assessment was done by an independent evaluator blinded to the surgical procedure.<strong></strong></p><p class="abstract"><strong>Results:</strong> The mean age was 33.6±4.03 in group I and 35.3±4.04 years in group II (p=0.70). The average follow up was 15 months. The average union time for femoral neck fracture was 15.75±0.89 and 16.48±1.40 (p=0.36) weeks and for fracture shaft was 19.27±1.18 and 20.06±1.16 (p=0.15) in group I and group II respectively. 10 patients (76.9%) in group I and 9 (75%) in group II showed good functional results. Two patients needed re-operation in group I and one patient in group II.</p><strong>Conclusions:</strong> Ipsilateral femoral shaft and hip fractures can be treated satisfactorily either with nailing alone or various plate combinations with similar outcome.


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