Actin Polymerization Controls the Organization of WASH Domains at the Surface of Endosomes

Sorting of cargoes in endosomes occurs through their selective enrichment into sorting platforms, where transport intermediates are generated. The WASH complex, which directly binds to lipids, activates the Arp2/3 complex and hence actin polymerization onto such sorting platforms. Here, we analyzed the role of actin polymerization in the physiology of endosomal domains containing WASH using quantitative image analysis. Actin depolymerization is known to enlarge endosomes. Using a novel colocalization method that is insensitive to the heterogeneity of size and shape of endosomes, we further show that preventing the generation of branched actin networks induces endosomal accumulation of the WASH complex. Moreover, we found that actin depolymerization induces a dramatic decrease in the recovery of endosomal WASH after photobleaching. This result suggests a built-in turnover, where the actin network, i.e. the product of the WASH complex, contributes to the dynamic exchange of the WASH complex by promoting its detachment from endosomes. Our experiments also provide evidence for a role of actin polymerization in the lateral compartmentalization of endosomes: several WASH domains exist at the surface of enlarged endosomes, however, the WASH domains coalesce upon actin depolymerization or Arp2/3 depletion. Branched actin networks are thus involved in the regulation of the size of WASH domains. The potential role of this regulation in membrane scission are discussed

Effects of barefoot and shod running on lower extremity joint loading, a musculoskeletal simulation study

PURPOSE: The aim of the current investigation was to utilize a musculoskeletal simulation based approach, to examine the effects of barefoot and shod running on lower extremity joint loading during the stance phase. METHODS: Twelve male runners, ran over an embedded force plate at 4.0 m/s, in both barefoot and shod conditions. Kinematics of the lower extremities were collected using an eight camera motion capture system. Lower extremity joint loading was also explored using a musculoskeletal simulation and mathematical modelling approach, and differences between footwear conditions were examined using paired samples t-tests. RESULTS: Peak Achilles tendon force was significantly larger (P=0.039) when running barefoot (6.85 BW) compared to shod (6.07 BW). In addition, both medial (P=0.013) and lateral (P=0.007) tibiofemoral instantaneous load rates were significantly larger in the barefoot (medial = 289.17 BW/s & lateral = 179.59 BW/s) in relation to the shod (medial = 167.57 BW/s & lateral = 116.40 BW/s) condition. Finally, the barefoot condition (9.70 BW) was associated with a significantly larger (P=0.037) peak hip force compared to running shod (8.51 BW). CONCLUSIONS: The current investigation indicates that running barefoot may place runners at increased risk from the biomechanical factors linked to the aetiology of chronic lower extremity pathologies. However, future analyses using habitual barefoot runners, are required before more definitive affirmations regarding injury predisposition can be made

Microcrack‐associated bone remodeling is rarely observed in biopsies from athletes with medial tibial stress syndrome

The pathology of medial tibial stress syndrome (MTSS) is unknown. Studies suggest that MTSS is a bony overload injury, but histological evidence is sparse. The presence of microdamage, and its potential association with targeted remodeling, could provide evidence for the pathogenesis of MTSS. Understanding the pathology underlying MTSS could contribute to effective preventative and therapeutic interventions for MTSS. Our aim was to retrospectively evaluate biopsies, previously taken from the painful area in athletes with MTSS, for the presence of linear microcracks, diffuse microdamage and remodeling. Biopsies, previously taken from athletes with MTSS, were evaluated at the Department of Anatomy and Cell Biology at the Indiana University. After preparing the specimens by en bloc staining, one investigator evaluated the presence of linear microcracks, diffuse microdamage and remodeling in the specimens. A total of six biopsies were evaluated for the presence of microdamage and remodeling. Linear microcracks were found in 4 out of 6 biopsies. Cracking in one of these specimens was artefactual due to the biopsy procedure. No diffuse microdamage was seen in any of the specimens, and only one potential remodeling front in association with the microcracks. We found only linear microcracks in vivo in biopsies taken from the painful area in 50% of the athletes with MTSS, consistent with the relationship between linear cracks and fatigue-associated overloading of bone. The nearly universal absence of a repair reaction was notable. This suggests that unrepaired microdamage accumulation may underlie the pathophysiological basis for MTSS in athletes

Os histiócitos e as histiocitoses não Langerhans em dermatologia Histiocytes and non-Langerhans cell histiocytoses in dermatology

Atualmente, os histiócitos não são mais compreendidos como células únicas, mas como um grupo heterogêneo de células com o mesmo aspecto histológico, mas com características e funções distintas entre si. Várias doenças proliferativas de histiócitos, conhecidas como histiocitoses, são descritas. Tais doenças são raras, e seu estudo costuma ser difícil. Este artigo objetiva simplificar o entendimento desse grupo de doenças, adequando-o a esse novo paradigma da heterogeneidade dos histiócitos.<br>Histiocytes are no longer recognized as singular cells. The term ‘histiocyte’ now refers to a heterogeneous group of cells with unique histologic morphology, but with singular functions and characteristics. Histiocytoses are a group of different diseases caused by proliferative histiocytes. Such diseases are rare and their study usually tends to be difficult. The objective of this paper is to simplify the study of these diseases under the novel paradigm of histiocyte heterogeneity