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Introduction/Objective. Epidemiology of melanoma including the number of new cases and mortality have been established in most developed countries, but data on pathohistological features are mostly missing. The objective of the study was to investigate epidemiological, clinical, and pathohistological features of melanoma patients and compare the results with trends in other countries. Methods. Our sample comprised patients surgically treated for skin melanoma at the Hospital for Burns, Plastic and Reconstructive Surgery during the 2015?2017 period. Pathohistological, clinical, and demographic features of melanoma were studied. Results. The retrospective study comprised 201 patients (109 men and 92 women) aged 25?87 years. Melanoma was more common in men than in women (54.2% vs. 45.8%). Melanoma in male population most commonly presented on the trunk, while in females presentation on the trunk and lower extremities was almost equal. Superficial spreading melanoma was the most common type of melanoma (68.7%), without correlation to the sex. No correlation was observed in relation to the stage of the disease and the patient?s sex (p = 0.294). A statistical difference was observed in relation to the type of melanoma and the Breslow classification (p < 0.001). Breslow?s thickness correlated with neither age nor sex. In relation to tumor invasiveness, 12.4% of the lesions were classified as in situ lesions, while 87.6% of the lesions were invasive. The majority of patients were identified as stage pT1a. Conclusion. This study can help to identify patients at high risk for melanoma and contribute to optimize screening efforts in a defined target population.

In this work, we designed and developed a method to detect S1 spike protein of SARS-CoV-2. The portable Localized Surface Plasmon Resonance instrument equipped with a two-channel system was combined with the biotin-streptavidin platform on a nanogold surface to immobilize biotinylated aptamers. The proposed assay does not utilize antibodies or enzyme-based reagents, further simplifying the detection method. Using aptamer-protein bioaffinity interactions, the aptasensor selectively and specifically detected in real-time S1 spike protein, rather than S2 spike protein, RBD spike protein, or bovine serum albumin. The dynamic range and limit of detection of the aptasensor was determined to be 1 nM-100 nM and 0.26 nM, respectively. Notably, aptasensor detected preferentially S1 protein of SARS-CoV-2 compared to SARS-CoV and detected S1 protein with >95% recovery in artificial saliva, and serum albumin, excellent repeatability and shelf-life stability. The method may provide a low-cost, rapid, and real-time detection and monitoring of viruses in the general public.

Introduction Silicone implants have been used ever since the second half of the 20th century. Over that period several generations of implants have been developed that differed in thickness of the shell and viscosity of the silicone gel. Development of these generations of implants was accompanied with different complication rates. The first-generation implants had the lowest tendency to rupture, but were more prone to capsular contracture and calcification formation. Case outline An 81-year-old female patient had her silicone implants placed in 1983. After a chest injury in 2015. on the lateral aspect of the left breast a tumefaction becomes palpable and she complains of pain. She denies any subjective problems before the injury. After pertinent diagnostic procedures and clinical examination, silicone implant rupture was suspected. Surgical findings confirmed ruptures of both implants so that they were extracted, capsulectomy was performed and the surrounding tissue imbibed with silicone removed. Samples were sent for histopathological examination. Conclusion Implant rupture is one of late complications of breast augmentation. The incidence of ruptures has changed with development of newer generations of silicone implants. We believe that our patient had the first-generation silicone implants, knowing the time from their placement to the occurrence of symptoms and macroscopic appearance of the shell after extraction. The fact is that these implants have proved to be very durable, but regardless of the lack of symptoms, current guidelines recommend regular screening for rupture, while possible preventive extraction, particularly in case of so old implants should be considered.

Introduction/Objective. The development of safer cosmetic medical procedures has lead to an increase in the number of minimally invasive esthetic procedures. The main aim of the current paper is to examine the connection of the number/location of esthetic procedures with the overall body image dissatisfaction, affective temperament traits, and the index of self-esteem in persons who have undergone several minimally invasive cosmetic procedures for esthetic reasons. The subsidiary aim is to compare the predominance of the abovementioned traits in the sample with the results in the general population. Methods. The study included 228 participants, aged from 21 to 73 years, who had multiple minimally invasive cosmetic procedures, purely for esthetic reasons. Data were collected using a socio-demographic questionnaire, medical documentation, the Body Image Assessment Scale-Body Dimensions, TEMPS-A temperament scale, and Rosenberg Self-Esteem Scale. Results. Overall body image dissatisfaction was moderate in our patients (11.56 ? 11.877). With an increase of dissatisfaction, the number of procedures did not grow (r = 0.075, p = 0.263); however, the number of body parts on which the procedures had been performed did. The patients who had their body parts altered most were found to have deeper dissatisfaction with their overall body image (F(2,225) = 4.963, p = 0.008, ?2 = 0.04), and the most prominent temperament was wound to be hyperthymic (F(2,225) = 3.408, p = 0.035, ?2 = 0.03), similar to the Serbian general population. Conclusion. Through establishing potential relations between physical, social, and psychological variables, like body image dissatisfaction, temperament, and self-esteem, we could provide a better insight into a mental state of individuals who frequently undergo minimally invasive cosmetic procedures.

Introduction/Objective. Frostbite is a cold-induced injury of the tissue caused by the freezing of intraand extracellular water, and characterized by thrombosis and ischemic necrosis. Although individual, socioeconomic, and environmental factors are all considered fundamental determinants of human health in general, their role in the occurrence of frostbite remains largely unknown. The aim of this study was to examine the associations among these factors and frostbite for patients in Belgrade, Serbia. Methods. We investigated a total of 24 patients that were hospitalized and treated for frostbites at the Clinic for Burns, Plastic, and Reconstructive surgery, Clinical Center of Serbia, 2008?2017. Results. The majority (88%) of the patients were male, 58% were long-term alcohol consumers, 46% were long-term smokers, and one patient was drug addict. Of the patients, 14 (58%) had no income and depended on government support, 10 (42%) were employed in physical labor or work on the field, and three (13%) of the patients were homeless. Of the 24 frostbite patients identified, deep frostbite accounted for 18 (75%), of whom 17 (70.8%) had an operative outcome. A majority of patients (42%) sustained frostbite when the temperature was in the range of -5?0?C on the date of occurrence. Conclusion. The results of our study showed that individual, social, and environmental factors were important determinants of frostbite. Our results will contribute to existing evidence for risk factors related to frostbite and will allow for comparisons across countries where these factors have been examined.

The Breast Size Satisfaction Survey (BSSS) was established to assess women's breast size dissatisfaction and breasted experiences from a cross-national perspective. A total of 18,541 women were recruited from 61 research sites across 40 nations and completed measures of current-ideal breast size discrepancy, as well as measures of theorised antecedents (personality, Western and local media exposure, and proxies of socioeconomic status) and outcomes (weight and appearance dissatisfaction, breast awareness, and psychological well-being). in the total dataset, 47.5 % of women wanted larger breasts than they currently had, 23.2 % wanted smaller breasts, and 29.3 % were satisfied with their current breast size. There were significant cross-national differences in mean ideal breast size and absolute breast size dissatisfaction, but effect sizes were small (eta(2) = .02-.03). the results of multilevel modelling showed that greater Neuroticism, lower Conscientiousness, lower Western media exposure, greater local media exposure, lower financial security, and younger age were associated with greater breast size dissatisfaction across nations. in addition, greater absolute breast size dissatisfaction was associated with greater weight and appearance dissatisfaction, poorer breast awareness, and poorer psychological well-being across nations. These results indicate that breast size dissatisfaction is a global public health concern linked to women's psychological and physical well-being. (C) 2020 Elsevier Ltd. All rights reserved., Hungarian Scientific Research Fund (OTKA)Orszagos Tudomanyos Kutatasi Alapprogramok (OTKA) [K125437], Data collection in Hungary was supported by a Hungarian Scientific Research Fund (OTKA) awarded to the sixty-third author (K125437).

The Body Appreciation Scale-2 (BAS-2; Tylka & Wood-Barcalow, 2015a, 2015b) is a widely used measure of positive body image within many cultures and countries; yet, cross-cultural examinations are few. The present study aimed to investigate the measurement invariance of the BAS-2 across adults from five countries: Iran, Japan, Poland, Serbia, and the U.S. The sample included 2944 participants ranging in age from 18 to 82 years. The findings provided evidence that the BAS-2's one-dimensional structure is the same in these countries. Partial metric invariance (when some but not all items contribute to a latent construct equally for groups) indicated that nine out of 10 items contributed to the latent body appreciation construct to a similar degree across the countries. When a Multiple Indicators Multiple Causes (MIMIC) model was applied with participants' age and gender as covariates, evidence of differential item functioning was found. Results suggest that both age and gender influenced body appreciation, indicating that the body appreciation factor means are different at different levels of the covariates. In conclusion, cross-culturally body appreciation may be shaped by country, language, age, and gender correlates to different degrees. In future research, measurement invariance analyses should be conducted prior to cultural group comparisons on the BAS-2.

Melanoma is malignant disease and the incidence of melanoma has been increasing worldwide, resulting in an important socio-economic problem especially in not well development countries. At the time when the incidence of many tumors is decreasing, melanoma incidence continues to increase. Incidence in Southern Europe is ranging from 1,9/100.00 in Albania across 3,3/100.000 in Bulgaria to 14,5/100.000 in Slovenia and in Serbia 8,5/100.000 for male and 5,9/100.000for female (ASR-W, 2012). In Serbia, during 2007 to 2012, according to Cancer Registry of Central Serbia, there are about 622 new melanoma diagnoses, 320 male and 302 female. During 2012, in Republic of Serbia melanoma was the 10th most common diagnosed cancer and 12th most common cancer caused death, in both, females and males. The aim of this study was to analyzed clinical and epidemiological characteristic of melanoma. Retrospective study, data analysis, all patients referred and treated in two year period in Clinic for Burns, plastic and reconstructive surgery, Clinical Center of Serbia, Belgrade. All data are collected in hospital based registry The analyzed characteristics of interest: sex, age, subtype of melanoma, primary location of melanoma, Breslow thickness and Clark level of invasion, number of mitosis, ulceration, TNM stadium, the presents of microsatellites, metastases, level of Protein S and LDH and decision of future treatment . Decision about future treatment are made according AJCC (re-excision and SLNB – Sentinel Lymph Node Biopsy ) and follow-up of patients after SLNB is still lasting. In two year period, 201 patients were treated in our hospital, all patients in this study were with pathohistologically verified diagnoses of melanoma. The average age of patients was 61, 47 ( 25 - 87). The most common primary location of melanoma was trunk with some differences between sexes. The most common subtype of melanoma was superficial subtype in 69% of patients. Ulceration were present in 22% of all primary melanomas and mitosis in 47, 5% and microsatellites in 3, 5%. Protein S and LDH level were elevated in patients with higher Breslow thickness. According to the AJCC protocol we made a decision about future treatment, re-excision and SLNB. The follow-up after SLNB is still lasting and we are still collecting data. The study showed the correlation between subtype of melanoma, higher Breslow thickness and the level of invasion by Clark, as well as elevated level of protein S and LDH and the presents of ulcerations and mitosis with decision about future treatment according to AJCC protocol.

Graphical Abstract ga1, Nanoparticles provide new opportunities in merging therapeutics and new materials, with current research efforts just beginning to scratch the surface of their diverse benefits and potential applications. One such application, the use of inorganic nanoparticles in antiseptic coatings to prevent pathogen transmission and infection, has seen promising developments. Notably, the high reactive surface area to volume ratio and unique chemical properties of metal-based nanoparticles enables their potent inactivation of viruses. Nanoparticles exert their virucidal action through mechanisms including inhibition of virus-cell receptor binding, reactive oxygen species oxidation and destructive displacement bonding with key viral structures. The prevention of viral outbreaks is one of the foremost challenges to medical science today, emphasizing the importance of research efforts to develop nanoparticles for preventative antiviral applications. In this review, the use of nanoparticles to inactivate other viruses, such as influenza, HIV-1, or norovirus, among others, will be discussed to extrapolate broad-spectrum antiviral mechanisms that could also inhibit SARS-CoV-2 pathogenesis. This review analyzes the published literature to highlight the current state of knowledge regarding the efficacy of metal-based nanoparticles and other antiviral materials for biomedical, sterile polymer, and surface coating applications.

The minor phospholipid, phosphatidylinositol 4-phosphate (PI4P), is emerging as a key regulator of lipid transfer in ER-membrane contact sites. Four different phosphatidylinositol 4-kinase (PI4K) enzymes generate PI4P in different membrane compartments supporting distinct cellular processes, many of which are crucial for the maintenance of cellular integrity but also hijacked by intracellular pathogens. While type III PI4Ks have been targeted by small molecular inhibitors, thus helping decipher their importance in cellular physiology, no inhibitors are available for the type II PI4Ks, which hinders investigations into their cellular functions. Here, we describe the identification of small molecular inhibitors of PI4K type II alpha (PI4K2A) by implementing a large scale small molecule high-throughput screening. A novel assay was developed that allows testing of selected inhibitors against PI4K2A in intact cells using a bioluminescence resonance energy transfer approach adapted to plate readers. The compounds disclosed here will pave the way to the optimization of PI4K2A inhibitors that can be used in cellular and animal studies to better understand the role of this enzyme in both normal and pathological states.

Phosphoinositides are a class of phospholipids generated by the action of phosphoinositide kinases with key regulatory functions in eukaryotic cells. Here, we present the atomic structure of phosphatidylinositol 4-kinase type IIα (PI4K IIα), in complex with ATP solved by X-ray crystallography at 2.8 Å resolution. The structure revealed a non-typical kinase fold that could be divided into N- and C-lobes with the ATP binding groove located in between. Surprisingly, a second ATP was found in a lateral hydrophobic pocket of the C-lobe. Molecular simulations and mutagenesis analysis revealed the membrane binding mode and the putative function of the hydrophobic pocket. Taken together, our results suggest a mechanism of PI4K IIα recruitment, regulation, and function at the membrane.

Trafficking of glucocerebrosidase (GBA) enzyme from the endoplasmic reticulum to the lysosome requires lysosomal integral membrane protein type 2 (LIMP-2), which is a receptor for GBA. This study shows that phosphatidylinositol 4-kinase (PI4K) type IIIβ controls the exit of LIMP-2/GBA complex from the Golgi, while PI4KIIα is required for the post-Golgi trafficking of the complex via the late endosomes., Gaucher disease is a lysosomal storage disorder caused by a defect in the degradation of glucosylceramide catalyzed by the lysosomal enzyme β-glucocerebrosidase (GBA). GBA reaches lysosomes via association with its receptor, lysosomal integral membrane protein type 2 (LIMP-2). We found that distinct phosphatidylinositol 4-kinases (PI4Ks) play important roles at multiple steps in the trafficking pathway of the LIMP-2/GBA complex. Acute depletion of phosphatidylinositol 4-phosphate in the Golgi caused accumulation of LIMP-2 in this compartment, and PI4KIIIβ was found to be responsible for controlling the exit of LIMP-2 from the Golgi. In contrast, depletion of PI4KIIα blocked trafficking at a post-Golgi compartment, leading to accumulation of LIMP-2 in enlarged endosomal vesicles. PI4KIIα depletion also caused secretion of missorted GBA into the medium, which was attenuated by limiting LIMP-2/GBA exit from the Golgi by PI4KIIIβ inhibitors. These studies identified PI4KIIIβ and PI4KIIα as important regulators of lysosomal delivery of GBA, revealing a new element of control to sphingolipid homeostasis by phosphoinositides.

Epidermal growth factor receptor tyrosine kinase substrate 15 (Eps15) homology (EH)-domain proteins can be divided into two classes: those with an N-terminal EH-domain(s), and the C-terminal Eps15 homology domain-containing proteins (EHDs). Whereas many N-terminal EH-domain proteins regulate internalization events, the best characterized C-terminal EHD, EHD1, regulates endocytic recycling. Because EH-domains interact with the tripeptide Asn-Pro-Phe (NPF), it is of critical importance to elucidate the molecular mechanisms that allow EHD1 and its paralogs to interact selectively with a subset of the hundreds of NPF-containing proteins expressed in mammalian cells. Here, we capitalize on our findings that C-terminal EH-domains possess highly positively charged interaction surfaces and that many NPF-containing proteins that interact with C-terminal (but not N-terminal) EH-domains are followed by acidic residues. Using the recently identified EHD1 interaction partner molecule interacting with CasL (MICAL)-Like 1 (MICAL-L1) as a model, we have demonstrated that only the first of its two NPF motifs is required for EHD1 binding. Because only this first NPF is followed by acidic residues, we have utilized glutathione S-transferase pulldowns, two-hybrid analysis, and NMR to demonstrate that the flanking acidic residues "fine tune" the binding affinity to EHD1. Indeed, our NMR solution structure of the EHD1 EH-domain in complex with the MICAL-L1 NPFEEEEED peptide indicates that the first two flanking Glu residues lie in a position favorable to form salt bridges with Lys residues within the EH-domain. Our data provide a novel explanation for the selective interaction of C-terminal EH-domains with specific NPF-containing proteins and allow for the prediction of new interaction partners with C-terminal EHDs.

Eps15 homology (EH)-domain containing proteins are regulators of endocytic membrane trafficking. EH-domain binding to proteins containing the tripeptide NPF has been well characterized, but recent studies have shown that EH-domains are also able to interact with ligands containing DPF or GPF motifs. We demonstrate that the three motifs interact in a similar way with the EH-domain of EHD1, with the NPF motif having the highest affinity due to the presence of an intermolecular hydrogen bond. The weaker affinity for the DPF and GPF motifs suggests that if complex formation occurs in vivo, they may require high ligand concentrations, the presence of successive motifs and/or specific flanking residues.

The C-terminal Eps15 homology domain (EHD) 1/receptor-mediated endocytosis-1 protein regulates recycling of proteins and lipids from the recycling compartment to the plasma membrane. Recent studies have provided insight into the mode by which EHD1-associated tubular membranes are generated and the mechanisms by which EHD1 functions. Despite these advances, the physiological function of these striking EHD1-associated tubular membranes remains unknown. Nuclear magnetic resonance spectroscopy demonstrated that the Eps15 homology (EH) domain of EHD1 binds to phosphoinositides, including phosphatidylinositol-4-phosphate. Herein, we identify phosphatidylinositol-4-phosphate as an essential component of EHD1-associated tubules in vivo. Indeed, an EHD1 EH domain mutant (K483E) that associates exclusively with punctate membranes displayed decreased binding to phosphatidylinositol-4-phosphate and other phosphoinositides. Moreover, we provide evidence that although the tubular membranes to which EHD1 associates may be stabilized and/or enhanced by EHD1 expression, these membranes are, at least in part, pre-existing structures. Finally, to underscore the function of EHD1-containing tubules in vivo, we used a small interfering RNA (siRNA)/rescue assay. On transfection, wild-type, tubule-associated, siRNA-resistant EHD1 rescued transferrin and β1 integrin recycling defects observed in EHD1-depleted cells, whereas expression of the EHD1 K483E mutant did not. We propose that phosphatidylinositol-4-phosphate is an essential component of EHD1-associated tubules that also contain phosphatidylinositol-(4,5)-bisphosphate and that these structures are required for efficient recycling to the plasma membrane.

This report describes a molecular biotechnology-based laboratory curriculum developed to accompany an undergraduate genetics course. During the course of a semester, students researched the pathogen, developed a research question, designed experiments, and performed transcriptional analysis of a set of genes that confer virulence to the food-borne pathogen, Listeria monocytogenes. Gene fragments were amplified via PCR and utilized in "mini-arrays," a dot-blot-based format suitable for the simultaneous transcriptional analysis of multiple genes. The project provides exposure to a wide range of molecular techniques and can be easily modified for variations in class size. Data are generated at various steps of the process, allowing for student interpretation, troubleshooting, and assessment opportunities.

Eps15 homology domain (EHD) 1 enables membrane recycling by controlling the exit of internalized molecules from the endocytic recycling compartment (ERC) en route to the plasma membrane, similar to the role described for Rab11. However, no physical or functional connection between Rab11 and EHD-family proteins has been demonstrated yet, and the mode by which they coordinate their regulatory activity remains unknown. Here, we demonstrate that EHD1 and EHD3 (the closest EHD1 paralog), bind to the Rab11-effector Rab11-FIP2 via EH–NPF interactions. The EHD/Rab11-FIP2 associations are affected by the ability of the EHD proteins to bind nucleotides, and Rab11-FIP2 is recruited to EHD-containing membranes. These results are consistent with a coordinated role for EHD1 and Rab11-FIP2 in regulating exit from the ERC. However, because no function has been attributed to EHD3, the significance of its interaction with Rab11-FIP2 remained unclear. Surprisingly, loss of EHD3 expression prevented the delivery of internalized transferrin and early endosomal proteins to the ERC, an effect differing from that described upon EHD1 knockdown. Moreover, the subcellular localization of Rab11-FIP2 and endogenous Rab11 were altered upon EHD3 knockdown, with both proteins absent from the ERC and retained in the cell periphery. The results presented herein promote a coordinated role for EHD proteins and Rab11-FIP2 in mediating endocytic recycling and provide evidence for the function of EHD3 in early endosome to ERC transport.

Specificity of membrane fusion in vesicular trafficking is dependent on proper subcellular distribution of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). Although SNARE complexes are fairly promiscuous in vitro, substantial specificity is achieved in cells owing to the spatial segregation and shielding of SNARE motifs prior to association with cognate Q-SNAREs. In this study, we identified phosphatidylinositol 4-kinase IIα (PI4K2A) as a binding partner of vesicle-associated membrane protein 3 (VAMP3), a small R-SNARE involved in recycling and retrograde transport, and found that the two proteins co-reside on tubulo-vesicular endosomes. PI4K2A knockdown inhibited VAMP3 trafficking to perinuclear membranes and impaired the rate of VAMP3-mediated recycling of the transferrin receptor. Moreover, depletion of PI4K2A significantly decreased association of VAMP3 with its cognate Q-SNARE Vti1a. Although binding of VAMP3 to PI4K2A did not require kinase activity, acute depletion of phosphatidylinositol 4-phosphate (PtdIns4P) on endosomes significantly delayed VAMP3 trafficking. Modulation of SNARE function by phospholipids had previously been proposed based on in vitro studies, and our study provides mechanistic evidence in support of these claims by identifying PI4K2A and PtdIns4P as regulators of an R-SNARE in intact cells.

Glycosphingolipid (GSL) trafficking and metabolism are closely linked with cell fate determination, balancing signaling cascades controlling proliferation, apoptosis and autophagy. Altered cellular...

The C-terminal Eps15 homology domain-containing protein, EHD1, is an important regulator of receptor recycling back to the plasma membrane. In addition to its vesicular localization, EHD1 also localizes to a unique array of tubular membrane structures that emanate from the endocytic recycling compartment. While these structures have been described over seven years ago, addressing their lipid composition and physiological function has been challenging. Moreover, it was not known whether EHD1 itself induces tubule formation, or whether it localizes to pre-existing tubular membrane structures. We have demonstrated that in vivo, EHD1 localizes to pre-existing tubular membranes that contain both phosphatidylinositol-4-phosphate and phosphatidylinositol-(4,5)-bisphosphate. Moreover, we have determined that ‘non-tubular’ EHD1 mutants with a single residue substitution do not efficiently facilitate receptor recycling. Our data suggest that EHD1-associated tubules are required for efficient recycling and we propose models that describe the potential mechanisms by which EHD1 functions.

The BAR (Bin/Amphiphysin/Rvs) domain proteins arfaptin1 and arfaptin2 are localized to the trans-Golgi network (TGN) and, by virtue of their ability to sense and/or generate membrane curvature, could play an important role in the biogenesis of transport carriers. We report that arfaptins contain an amphipathic helix (AH) preceding the BAR domain, which is essential for their binding to phosphatidylinositol 4-phosphate (PI(4)P)-containing liposomes and the TGN of mammalian cells. The binding of arfaptin1, but not arfaptin2, to PI(4)P is regulated by protein kinase D (PKD) mediated phosphorylation at Ser100 within the AH. We also found that only arfaptin1 is required for the PKD-dependent trafficking of chromogranin A by the regulated secretory pathway. Altogether, these findings reveal the importance of PI(4)P and PKD in the recruitment of arfaptins at the TGN and their requirement in the events leading to the biogenesis of secretory storage granules.

A spectrin-based cytoskeleton is associated with endomembranes, including the Golgi complex and cytoplasmic vesicles, but its role remains poorly understood. Using new generated antibodies to specific peptide sequences of the human βIII spectrin, we here show its distribution in the Golgi complex, where it is enriched in the trans-Golgi and trans-Golgi network. The use of a drug-inducible enzymatic assay that depletes the Golgi-associated pool of PI4P as well as the expression of PH domains of Golgi proteins that specifically recognize this phosphoinositide both displaced βIII spectrin from the Golgi. However, the interference with actin dynamics using actin toxins did not affect the localization of βIII spectrin to Golgi membranes. Depletion of βIII spectrin using siRNA technology and the microinjection of anti-βIII spectrin antibodies into the cytoplasm lead to the fragmentation of the Golgi. At ultrastructural level, Golgi fragments showed swollen distal Golgi cisternae and vesicular structures. Using a variety of protein transport assays, we show that the endoplasmic reticulum-to-Golgi and post-Golgi protein transports were impaired in βIII spectrin-depleted cells. However, the internalization of the Shiga toxin subunit B to the endoplasmic reticulum was unaffected. We state that βIII spectrin constitutes a major skeletal component of distal Golgi compartments, where it is necessary to maintain its structural integrity and secretory activity, and unlike actin, PI4P appears to be highly relevant for the association of βIII spectrin the Golgi complex.

Endocytosis marks the entry of internalized receptors into the complex network of endocytic trafficking pathways. Endocytic vesicles are rapidly targeted to a distinct membrane-bound endocytic organelle referred to as the early endosome. Despite the existence of numerous internalization routes, early endosomes (EE) serve as a focal point of the endocytic pathway. Sorting events initiated at this compartment determine the subsequent fate of internalized proteins and lipids, destining them either for recycling to the plasma membrane, degradation in lysosomes or delivery to the trans-Golgi network. Sorting of endocytic cargo to the latter compartments is accomplished through the formation of distinct microdomains within early endosomes, through the coordinate recruitment and assembly of the sorting machinery. An elaborate network of interactions between endocytic regulatory proteins ensures synchronized sorting of cargo to microdomains followed by morphological changes at the early endosomal membranes. Consequently, the cargo targeted either for recycling back to the plasma membrane, or for retrograde transport to the trans-Golgi network, localizes to newly-formed tubular membranes. With a high ratio of membrane surface to lumenal volume, these tubules effectively concentrate the recycling cargo, ensuring efficient transport out of the EE. Conversely, receptors sorted for degradation cluster at the flat clathrin lattices involved in invaginations of the limiting membrane, associating with newly formed intralumenal vesicles. In this review we will discuss the characteristics of early endosomes, their role in the regulation of endocytic transport, and their aberrant function in a variety of diseases.

The main goals of this work is to gain understanding of antenna coupling in real propagation environments and to assess the possibility to separately model the antenna and the propagation channel. It is shown that ideal antenna coupling modeling is accurate also for real dipole antennas. Further it is indeed validated that antenna and propagation channel modeling may be separated without degrading the modeling accuracy. The most important observed effect of antenna coupling is efficiency loss. Moreover, the coupling results in antenna decorrelation which may partly compensate the efficiency loss depending on the specific transmission scheme used.

EHD1 is a member of the mammalian C-terminal Eps15 homology domain (EH) containing protein family, and regulates the recycling of various receptors from the endocytic recycling compartment to the plasma membrane. The EH domain of EHD1 binds to proteins containing either an Asn-Pro-Phe or Asp-Pro-Phe motif, and plays an important role in the subcellular localization and function of EHD1. Thus far, the structures of five N-terminal EH domains from other proteins have been solved, but to date, the structure of the EH domains from the four C-terminal EHD family paralogs remains unknown. In this study, we have assigned the 133 C-terminal residues of EHD1, which includes the EH domain, and solved its solution structure. While the overall structure resembles that of the second of the three N-terminal Eps15 EH domains, potentially significant differences in surface charge and the structure of the tripeptide-binding pocket are discussed.

beta1 integrins bind to the extracellular matrix and stimulate signaling pathways leading to crucial cellular functions, including proliferation, apoptosis, cell spreading and migration. Consequently, control of beta1 integrin function depends upon its subcellular localization, and recent studies have begun to unravel the complex regulatory mechanisms involved in integrin trafficking. We report that the C-terminal Eps15-homology (EH) domain-containing protein EHD1 plays an important role in regulating beta1 integrin transport. Initially, we demonstrated that RNAi-knockdown of Ehd1 results in impaired recycling of beta1 integrins and their accumulation in a transferrin-containing endocytic recycling compartment. Mouse embryonic fibroblast (MEF) cells derived from EHD1-knockout mice (Ehd1(-/-) MEF) exhibited lower overall levels of beta1 integrins on the plasma membrane, but higher cell-surface-expressed activated beta1 integrins, and larger, more prominent focal adhesions resulting from slower kinetics of focal adhesion disassembly. In addition, both migration and cell spreading on fibronectin were impaired in Ehd1(-/-) MEF cells, and these defects could be similarly induced by EHD1-RNAi treatment of normal Ehd1(+/+) MEF cells. They could also be rescued by transfection of wild-type EHD1 into Ehd1(-/-) MEF cells. Our data support a role for EHD1 in beta1 integrin recycling, and demonstrate a requirement for EHD1 in integrin-mediated downstream functions.

We examined the validity of the Serbian version of the Acceptance of Cosmetic Surgery Scale (ACSS; Henderson-King and Henderson-King 2005). A total of 622 Serbian adults completed the ACSS, along with Serbian translations of measures for the discrepancy between actual body weight and ideal body weight, body appreciation, sociocultural attitudes toward appearance, and demographics. Confirmatory factor analyses were conducted to compare how different ACSS models fitted the collected data. A three-factor model provided the best fit to the data relative to two- and one-factor models. The three-factor model had good internal consistency, convergent and discriminant validity, and nomological validity. The ACSS seems to be a valid instrument for use in Serbian populations. Our study will contribute towards better understanding of the acceptance of cosmetic surgery from a cross-cultural perspective.

As with any new technology with a potentially wide impact, securing that the benefits are fully utilized and the take-up is facilitated requires effort from several disciplines. However, the skills for interdisciplinary cooperation and communication are often times lacking. This paper summarizes the findings of a trial course, which was created as an attempt to alleviate this issue. The course is focused around the use of Wireless Sensor Networks, a relative recent technology, in a set of medical applications, as well as an accompanying business models to make such products commercially viable. The course was designed to be given to students from three groups of majors: computer engineering, medicine, and business. The results show that after the proposed collaborative multidisciplinary course, the results of joint team efforts of the students increased, as well the individual level knowledge.

Endocytosis marks the entry of internalized receptors into the complex network of endocytic trafficking pathways. Endocytic vesicles are rapidly targeted to a distinct membrane-bound endocytic organelle referred to as the early endosome. Despite the existence of numerous internalization routes, early endosomes (EE) serve as a focal point of the endocytic pathway. Sorting events initiated at this compartment determine the subsequent fate of internalized proteins and lipids, destining them either for recycling to the plasma membrane, degradation in lysosomes or delivery to the trans-Golgi network. Sorting of endocytic cargo to the latter compartments is accomplished through the formation of distinct microdomains within early endosomes, through the coordinate recruitment and assembly of the sorting machinery. An elaborate network of interactions between endocytic regulatory proteins ensures synchronized sorting of cargo to microdomains followed by morphological changes at the early endosomal membranes. Consequently, the cargo targeted either for recycling back to the plasma membrane, or for retrograde transport to the trans-Golgi network, localizes to newly-formed tubular membranes. With a high ratio of membrane surface to lumenal volume, these tubules effectively concentrate the recycling cargo, ensuring efficient transport out of the EE. Conversely, receptors sorted for degradation cluster at the flat clathrin lattices involved in invaginations of the limiting membrane, associating with newly formed intralumenal vesicles. In this review we will discuss the characteristics of early endosomes, their role in the regulation of endocytic transport, and their aberrant function in a variety of diseases.