Analysis of the expression of cytokines and chemokines, platelet-leukocyte aggregates, sCD40L and sCD62P in cutaneous melanoma.

BACKGROUND: Cutaneous melanoma (CM) is a malignancy with a variable incidence worldwide and a poor advanced-stage prognosis. Melanoma growth is closely associated with the immune system. METHODS: A cross-sectional study was performed on CM patients admitted at the Hospital de Cancer de Pernambuco (HCP) between 2015 and 2018. Fifty-one CM patients were included, and 30 healthy individuals. The study aimed to evaluate the association of platelet activation mechanisms and inflammatory response in patients with cutaneous melanoma. RESULTS: Elevated serum IL10 and low serum TNF levels in CM patients compared to controls (p < 0.05). High IL6 levels in patients with negative lymph nodes LN (-) compared to positive lymph nodes group (LN +, p = 0.0005). Low RANTES levels in patients compared to controls (p < 0.05). Elevated levels of platelet-lymphocyte (PLA), platelet-monocytes (PMA), and platelet-neutrophils (PNA) aggregates were observed in patients compared to controls (p < 0.05). CM patients with stage II had lower PMA levels than stages I and III (p < 0.05). High PMA levels were observed in patients with LN (+) compared to the LN (-) group (p < 0.0001). Patients with SSM had high levels of sCD40L and sCD62P compared to controls (p < 0.05)). High sCD40L levels in stage II compared to the stage III group, and sCD62P in stages I and II compared to the stage III group (p < 0.05). High sCD62P levels in patients with LN (-) compared to the group LN (+) (p < 0.05). CONCLUSION: It was observed the immunosuppressive profile in CM may favor tumor progression. High levels of platelet-leukocyte aggregates, sCD40L, and sCD62P may be associated with the worst prognosis.

Soluble levels of 4-1BB (CD137) and OX40 (CD134) are associated with cancer progression in gastric adenocarcinoma.

BACKGROUND AND OBJECTIVES: Previous studies have demonstrated that soluble forms of T-cell costimulatory molecules 4-1BB (s4-1BB) and OX40 (sOX40) interact with immune cells and may constitute a mechanism of immune evasion by tumors in various cancers. The role of the soluble forms of 4-1BB and OX40 in GC remains unclear. We aimed to examine the association between serum levels of s4-1BB and sOX40 and tumor progression in patients with GC. METHODS: Between 2017 and 2018, a cross-sectional study was performed with serum samples of 83 GC patients and 20 healthy controls. RESULTS: Patients with stage IV metastatic gastric cancer had significantly higher levels of soluble OX40 in comparison with stage III patients with lymph nodes metastasis (p = 0.0003) and stages I and II patients (p = 0.005), whereas the opposite was found for soluble 4-1BB levels, with lower levels being found in advanced stage III (p = 0.003) compared with initial stages I/II. CONCLUSIONS: The sOX40 and s4-1BB-mediated T cell interactions may be involved in antitumor immune responses in GC, possibly favoring tumor escape and progression. Serum levels of sOX40 and s4-1BB are associated with staging in GC and may constitute biomarkers for prognosis, as well as potential targets for immunotherapy.

Evaluation of soluble co-inhibitors and co-stimulators levels of the immune response in gastric cancer.

BACKGROUND: Co-inhibitor and co-stimulator mediators trigger actions that result in immunological homeostasis and are being evaluated as potential therapeutic targets in gastric cancer (GC). OBJECTIVE: To evaluate the soluble levels of sPD-1, sPD-L1, sPD-L2, sTIM-3, sGal9, sGITR, and sGITRL in GC patients. METHODS: The cross-sectional study was carried out at the Hospital de Cancer de Pernambuco, Brazil between 2017 and 2018. A total of 74 GC patients and 30 healthy controls were included. RESULTS: Low levels of sPD1 (p = 0.0179), sPDL2 (p = 0.0003), and sGal9 (p < 0.0001), and higher levels of sPDL1 (p = 0.004), sTIM-3 (p = 0.0072), sGITR (p = 0.0179), and sGITRL (p = 0.0055) compared to the control group. High sPD-1, sTIM-3, and sGal9 levels in stage IV compared I/II and III (p < 0.05). High sPDL1, sGal9, and sGITRL levels in esophagogastric junction compared to body and Pylorus/Antrum groups (p < 0.05). No significant differences were observed in sPD1, sPDL1, sPDL2, sTIM3, sGal9, sGITR, and sGITRL levels between the intestinal, diffuse, and mixed GC groups. Low sGITR levels in GC patients who died within the first 24 months compared to the who survived (p = 0.0332). CONCLUSIONS: There is an association of sPD1, sTIM-3, and sGal9 with disease progression and sGITR with death, these mediators may be potential prognostic biomarkers in GC.

Effect of treatment of transverse maxillary deficiency using rapid palatal expansion on oral health-related quality of life in children: complementary results for a controlled clinical trial.

OBJECTIVE: To evaluate the effect of rapid palatal expansion (RPE) using Haas-type expanders on children's oral health-related quality of life (OHRQOL) and compare said effect with that previously reported for the use of Hyrax-type expanders. MATERIALS AND METHODS: Forty participants aged 8-10 years with transverse maxillary deficiency were treated using Haas appliances. OHRQOL was measured using the CPQ8 - 10 before RPE, during RPE (T1), at the end of RPE (T2), and 1 month after appliance removal (T3). Generalized mixed models were fitted to assess the effect of the Haas-type expander compared to previously collected data (a nontreated and a Hyrax-type expander-treated group). RESULTS: RPE with Haas-type appliances had a negative impact on overall OHRQOL at T1 and T2 (P = 0.001), and a positive impact at T3 (P = 0.001). The Haas-type expander had a significantly greater negative impact on OHRQOL than the Hyrax-type appliance during RPE. At T1, overall scores using the Haas-type expander were 1.08 times the scores using the Hyrax-type expander (i.e., 8% increase; 95% CI, 1.01-1.17; P = 0.033). Patients using the Haas appliance had 1.24 times the scores of those using Hyrax-type devices for the oral symptoms domain at T1 (i.e., 24% increase; 95% CI, 1.06-1.46; P = 0.009). CONCLUSIONS: Correction of the transverse maxillary deficiency by RPE using the Haas appliance in children 8-10 years improves OHRQOL. The Haas- and Hyrax-type devices temporarily worsen OHRQOL during treatment, however, the negative impact is less with the Hyrax-type expander than with the Haas-type expander, because it causes fewer negative oral symptoms. CLINICAL RELEVANCE: From a patient-centered perspective, the use of the Hyrax over the Haas appliance may be suggested as it causes less negative oral symptoms during use.

Studying actin-induced cell shape changes using Giant Unilamellar Vesicles and reconstituted actin networks.

Cell shape changes that are fuelled by the dynamics of the actomyosin cytoskeleton control cellular processes such as motility and division. However, the mechanisms of interplay between cell membranes and actomyosin are complicated to decipher in the complex environment of the cytoplasm. Using biomimetic systems offers an alternative approach to studying cell shape changes in assays with controlled biochemical composition. Biomimetic systems allow quantitative experiments that can help to build physical models describing the processes of cell shape changes. This article reviews works in which actin networks are reconstructed inside or outside cell-sized Giant Unilamellar Vesicles (GUVs), which are models of cell membranes. We show how various actin networks affect the shape and mechanics of GUVs and how some cell shape changes can be reproduced in vitro using these minimal systems.

High soluble OX40 levels correlate with metastatic gastric cancer.

BACKGROUND AND OBJECTIVES: Previous studies demonstrated an association between OX40+T cell expression with poor prognosis in gastric cancer (GC). The soluble form of OX40 (sOX40) could block the interactions between OX40 on the effector T cell, and it is a ligand (OX40L) in dendritic cells. However, the role of sOX40 as a pretreating biomarker and prognostic predictor remains unclear. This study aimed to evaluate the association of levels of sOX40 and sOX40L with disease progression in GC. METHODS: Between 2017 and 2018, a cross-sectional study was performed on 83 GC patients and 20 healthy controls. RESULTS: Among 83 GC patients (median of 63 years), 32.4% of patients with I/II stages, 42.3% III, and 25.3% in IV stages. Metastatic GC patients had significantly higher levels of soluble OX40 compared with stage III (p = 0.0003) and early stages I and II patients (p = 0.005). There was no significant differences in the sOX40 and sOX40L levels between Lauren's histological subtype (intestinal, diffuse, and mixed). CONCLUSIONS: This study showed that soluble OX40 levels have an essential role in GC progression. OX40 molecules may constitute a predictor for poor prognosis and a potential target for immunotherapy in GC.

Unbalanced expression of sICOS and sPD-1 correlates with tumor progression in gastric cancer.

BACKGROUND AND OBJECTIVES: T cells are central in antitumor immunity in gastric cancer (GC). The inducible costimulatory molecule (ICOS) is a T cell receptor that primarily transmits positive signals for T cell activation and is associated with poor prognosis in GC. In contrast, the costimulatory molecule programmed death 1 (PD-1) is an inhibitory receptor related to tumor immune escape. This study aimed to analyze soluble sites and sPD-1 levels in GC. METHODS: This study enrolled 83 GC patients and 20 healthy controls. RESULTS: The median survival time was 23.22 months in the GC patients. Low levels of sPD-1 and sICOS in GC patients compared to the control group (p = 0.003; p < 0.0001, respectively). High sPD-1 levels in stage IV patients compared to I/II and III stages groups (p = 0.008 and p = 0.0004, respectively). GC patients with stages I and II had higher levels of sICOS compared to III and IV stages (p = 0.0005 and p = 0.02, respectively). There were no significant differences in sPD-1 and sICOS levels between Lauren subtypes. CONCLUSION: These results suggest a predominance of inhibitory costimulatory signals in advanced stages of GC, facilitating tumor immune escape, as the opposite occurs in early stages, resulting in an effective antitumor T-cell-mediated immune response.

Evaluation of platelet activation marker expression and its correlation with tumorigenesis and tumor progression in patients with gastric cancer.

BACKGROUND AND OBJECTIVES: Gastric cancer (GC) remains responsible for over one million new cases in 2020. Activated platelets express the CD40 ligand (CD40L) and CD62P in the cytoplasmic membrane, and interaction with the vascular endothelium can induce the production of tumor growth factors and metastases. We aimed to characterize the soluble levels of sCD40L and sCD62P in GC patients. METHODS: A cross-sectional study was performed on 83 GC patients and 20 healthy controls. RESULTS: High levels of sCD40L were obtained in GC patients compared to healthy controls (p = 0.003) and in the I/II compared with III and IV stages (p < 0.0001 and p = 0.007, respectively). Low levels of sCD62P in the GC patients compared to healthy controls (p = 0.009). High soluble levels of sCD62P in I/II compared with III and IV stages (p = 0.002 and p = 0.01, respectively). There are no significant differences in the levels of sCD40L and sCD62P were observed between intestinal, diffuse, and mixed types. CONCLUSIONS: We concluded that sCD40L and sCD62P molecules may be predictive biomarkers since the increase in plasma levels was associated with disease progression and metastasis in GC. In addition, the serum sCD40L and sCD62P can potentially be used as an indicator of response to anticancer therapy.

Remodelling of membrane tubules by the actin cytoskeleton.

Inside living cells, the remodelling of membrane tubules by actomyosin networks is crucial for processes such as intracellular trafficking or organelle reshaping. In this review, we first present various in vivo situations in which actin affects membrane tubule remodelling, then we recall some results on force production by actin dynamics and on membrane tubules physics. Finally, we show that our knowledge of the underlying mechanisms by which actomyosin dynamics affect tubule morphology has recently been moved forward. This is thanks to in vitro experiments that mimic cellular membranes and actin dynamics and allow deciphering the physics of tubule remodelling in biochemically controlled conditions, and shed new light on tubule shape regulation.

Magnitude of visceral leishmaniasis and HIV coinfection and association with social determinants of health in the Northeast region of Brazil: a retrospective, spatiotemporal model (2010-2018).

The Northeast region of Brazil (NRB) includes the states with the highest prevalence of visceral leishmaniasis (VL), as well as those with significant increases in HIV cases. This study aims to analyze the spatiotemporal patterns of VL-HIV coinfection and its association with the social determinants of health (SDH) in the NRB. Time trend analysis and Bayesian spatial statistical inferences, Moran's autocorrelation, and retrospective space-time scanning were performed. Spatial regression modelling was used to build an explanatory model for the occurrence of VL-HIV coinfection within NRB. A total of 1550 cases of VL-HIV coinfection were confirmed. We observed a higher prevalence among males (1232; 83%), individuals aged from 20 to 59 years (850; 54.8%), non-white skin color (1,422; 91.7%), and with low education (550; 35.48%). NRB showed an increasing and significant trend in the detection rate of coinfection (APC, 5.3; 95% CI, 1.4 to 9.4). The states of Maranhão and Piauí comprised the high-risk cluster. The SDH that most correlated with the occurrence of coinfection were poor housing, low income, and low education. VL-HIV is dispersed in the NRB but chiefly affects states with greater social vulnerability. Taken together, these findings reinforce the necessity to implement surveillance strategies that will contribute to the reduction of cases in these populations.

Discrete-event models for the simulation of computed tomography sectors according to hospital structural/organizational changes and expected patient arrival rates.

OBJECTIVE: To analyze the types of computed tomography (CT) scanners most suitable for different hospital sizes and 'scenarios' (exam rates and structural/organizational changes), using discrete-event simulation models. MATERIALS AND METHODS: CT exams were divided into stages, measured during on-site surveys at CT services in small and average size private hospitals. Ten devices in nine health units, five cities and two states of Brazil were studied to this end, and the following data were collected: Time spent in each stage for each type of exam; average monthly number of exams performed and general characteristics of exams. Three arrival rates were defined (103, 154 and 206 patients/day), representing expected demand for the studied units. From these parameters, six scenarios were simulated, consisting of changes in personnel and hospital structure (e.g., 'adding a changing room') in a base scenario (one CT, one changing room, no nursing assistance, arrival rate 1). RESULTS: It was possible to identify a scenario most useful for very large demands, such as large emergency hospitals in big cities, (a CT, nursing assistance and three changing rooms added to the base scenario). Another identified scenario was more adequate for small demands (adding a changing room to the base scenario). CONCLUSION: Administrative/organizational measures are a very important factor in defining productivity in a hospital imaging sector. The focus of these measures should be on detecting bottlenecks and improving processes, regardless of the type of equipment used.

Distribution of anxiety and depression among different subtypes of temporomandibular disorder: A systematic review and meta-analysis.

BACKGROUND: The evidence on the relationship between anxiety and depression and patients with distinct subtypes of temporomandibular disorder (TMD) is uncertain, so a thorough review study on the topic is still missing. OBJECTIVES: This systematic review investigated the distribution and severity of anxiety and depression in patients diagnosed with different subtypes of TMD. METHODS: The study is registered in PROSPERO (CRD42020150562) and it followed the PRISMA 2020 Statement. We searched in PubMed, Web of Science, Scopus and SciELO databases (last search: 12 March 2021) and the reference list from the included studies. Study eligibility criteria consisted of: (i) patients diagnosed with TMD using the Research Diagnostic Criteria (RDC/TMD) or Diagnostic Criteria (DC/TMD) instruments; (ii) assessment of anxiety and/or depression with validated psychological instruments and (iii) allocation of patients into a minimum of two distinct TMD subtypes with at least one group having myofascial pain (comparison group). Analyses were carried out using RevMan 5.3.5 statistical package and random- or fixed-effects models (α = 0.05). The quality of evidence was assessed based on review authors' judgment derived from a 10-item appraisal tool for prevalence studies and with the Newcastle-Ottawa scale. RESULTS: Of the 4086 records identified in total, 24 were eligible for inclusion; meta-analyses were conducted with 20 studies. In total, 3678 subjects were included in the review. Most of the studies found that patients with myofascial pain showed similar occurrence and severity of anxiety/depression as compared to other subtypes of TMD, although the average prevalence seemed to be higher among the diagnoses consisting of myofascial pain (muscular TMD). Despite the moderate-to-high heterogeneity, anxiety and depression were more frequently distributed within patients with myofascial pain (p = .001). TMD patients without myofascial pain presented less severe levels of anxiety and depression than patients with only myofascial pain (p ≤ .01). The type of psychological instrument seems to affect the assessment of both anxiety and depression emotional states. CONCLUSION: The findings of this review suggest that patients with myofascial pain are more anxious and more depressed than patients with other subtypes of TMD. IMPLICATIONS: Considering that anxiety and depression are differently distributed within the TMD population, a proper assessment of the psychological state of patients seems essential to offer an adequate treatment and management of each specific subtype of TMD.

Effect of treatment of transverse maxillary deficiency using rapid palatal expansion on oral health-related quality of life in children: A randomized controlled trial.

INTRODUCTION: This trial aimed to longitudinally evaluate the effect of the treatment of transverse maxillary deficiency using rapid palatal expansion (RPE) on self-perceived oral health-related quality of life (OHRQOL) in children. METHODS: Eighty participants aged 8-10 years with transverse maxillary deficiency and bilateral posterior crossbite were randomly assigned to 2 groups (n = 40 each): a group treated with RPE using hyrax-type appliances and a nontreated control group. OHRQOL was assessed by using the Child Perceptions Questionnaire for 8-10-year-olds at 4 times: before RPE, during RPE (T1), at the end of RPE (T2), and 1 month after the appliance removal (T3). Generalized mixed models were used for data analysis (α = 0.05). RESULTS: Both groups exhibited similar demographic characteristics and OHRQOL scores at baseline. All participants completed the study. RPE had a time-dependent effect on OHRQOL. At T1 and T2, this therapy is expected to increase the overall OHRQOL scores by 1.17 times (ie, ∼17% increase; T1 95% confidence interval [CI], 1.08-1.26; T2 95% CI, 1.09-1.27; P = 0.001). In contrast, the overall OHRQOL scores at T3 are expected to be 0.28 times the baseline scores (ie, ∼72% reduction; T3 95% CI, 0.26-0.31; P = 0.001). All individual domains of the OHRQOL evidenced a positive impact of treatment at T3 (P = 0.001). Only the oral symptoms and social well-being domains showed a significantly negative impact of the treatment at T1 and T2. CONCLUSIONS: Correction of the transverse maxillary deficiency by RPE in children aged 8-10 years improves OHRQOL. There is a temporary worsening of OHRQOL during the treatment of this condition using RPE. REGISTRATION: This trial was not registered. PROTOCOL: The protocol was not published before trial commencement. FUNDING: This study was financed by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brazil, Financing Code 001.

The role of anthropogenic habitats in freshwater mussel conservation.

Anthropogenic freshwater habitats may provide undervalued prospects for long-term conservation as part of species conservation planning. This fundamental, but overlooked, issue requires attention considering the pace that humans have been altering natural freshwater ecosystems and the accelerated levels of biodiversity decline in recent decades. We compiled 709 records of freshwater mussels (Bivalvia, Unionida) inhabiting a broad variety of anthropogenic habitat types (from small ponds to large reservoirs and canals) and reviewed their importance as refuges for this faunal group. Most records came from Europe and North America, with a clear dominance of canals and reservoirs. The dataset covered 228 species, including 34 threatened species on the IUCN Red List. We discuss the conservation importance and provide guidance on how these anthropogenic habitats could be managed to provide optimal conservation value to freshwater mussels. This review also shows that some of these habitats may function as ecological traps owing to conflicting management practices or because they act as a sink for some populations. Therefore, anthropogenic habitats should not be seen as a panacea to resolve conservation problems. More information is necessary to better understand the trade-offs between human use and the conservation of freshwater mussels (and other biota) within anthropogenic habitats, given the low number of quantitative studies and the strong biogeographic knowledge bias that persists.

Innovation in the teaching of human physiology at university and school: pedagogical process based on interdisciplinarity and learning station rotation.

This paper presents the description and analysis of a didactic experience involving the participation of a university and a community school, developed as part of the National Science and Technology Week, at a public university in northeastern Brazil. For this purpose, the use of learning station rotation enabled innovation in the teaching of physiology integrated with biochemistry and health education contents. The didactic approach consisted of creating a learning circuit comprising seven stations. The central theme of the stations emphasized physiology, with specific foci on biochemistry and cardiorespiratory and endocrine health. Each station provided unique activities related to the central theme, including a station concerning digital technology in physiology. The school students were divided into small groups (6 or 7 people) that rotated through the stations, with a total of 81 students visiting each station. A qualitative assessment was performed using a Likert-scale questionnaire to measure the level of satisfaction of the students. It was found that this didactic approach increased the receptivity of the students to the contents, facilitated student-teacher dialogue, and provided an excellent tool for establishing an interface between the university and the community school. Overall, 76.5% of the students rated the activity as excellent.

Impact of oral-health-related quality of life and self-esteem on patients with missing maxillary lateral incisor after orthodontic space closure: a single-blinded, randomized, controlled trial.

BACKGROUND: The maxillary lateral incisor is one of the teeth most likely to suffer agenesis, resulting in spacing between the central incisor and the canine. OBJECTIVE: To compare maxillary lateral incisor agenesis with space closure treatment versus non-treatment based on measurements of the self-perceived oral-health-related quality of life (OHRQoL) and self-esteem of the participants. SUBJECTS AND METHODS: A total of 44 people, aged 17-49 years, with missing lateral incisors were randomly assigned to two groups (n = 22 in each)-a treated group in which the space was orthodontically closed (TG) and a control group that remained untreated (CG). Randomization was performed by a researcher who was not involved in the clinical part of the study. The outcomes were assessed using the Oral Health Impact Profile and Rosenberg's Self-Esteem Scale, which were applied before (phase 1) and after (phase 2) the orthodontic treatment in the TG, and at baseline (phase 1) and 12 months after (phase 2) in the CG. All the data were blindly evaluated, supporting the single-blinded design of the study. RESULTS: All participants finished the randomized controlled trial, and the demographic characteristics were similar between the groups. In phase 1, the levels of self-esteem and OHRQoL at baseline were similar (P = 0.079, P = 0.693, respectively). In phase 2, the self-esteem scores of the CG decreased and the OHRQoL increased (P = 0.005, P < 0.001, respectively), while self-esteem increased in the TG and the OHRQoL decreased (P < 0.001). The CG had lower scores than the TG for self-esteem, but the opposite was observed for OHRQoL (P < 0.001). LIMITATIONS: Information bias may have occurred. Since the questionnaires could not have been applied at the same time in both groups, the time difference between the two assessments may have led to random and systematic error. CONCLUSIONS: The spacing resulting from missing maxillary lateral incisors had a negative impact on the OHRQoL and self-esteem of the participants, while orthodontically closing those spaces had a positive impact on those aspects. CLINICAL TRIAL REGISTRATION: This study was not registered. PROTOCOL: The protocol was not published before trial commencement.

In vivo biocompatibility of silicon dioxide nanofilm used as antimicrobial agent on acrylic surface.

the focus ofthis study was to testthe hypothesisthatthere would be no difference betweenthe biocompatibility of silicon dioxide nanofilms used as antimicrobial agents. Sixty male Wistar rats were divided into 4 groups (n=15): Group C (Control,Polyethylene), Group AR (Acrylic Resin), Group NP (Acrylic Resin coated with NP-Liquid), Group BG (Acrylic Resin coated with Bacterlon).the animals were sacrificed with 7,15 and 30 days and tissues analyzed as regardsthe events of inflammatory infiltrate, edema, necrosis, granulation tissue, mutinucleated giant cells, fibroblasts and collagen. Kruskal-Wallis and Dunn tests was used (P<0.05). Intense inflammatory infiltrate was shown mainly in Groups BG and AR, with significant difference from Control Group inthe time interval of 7days (P=0.004). Necrosis demonstrated significant difference between Group BG and Control Group (P<0.05) inthe time intervals of 7 days. For collagen fibers,there was significant difference betweenthe Control Group and Groups AR and BG inthe time interval of 7 days (P=0.006), and between BG and Control Groups inthe time intervals of 15 days (P=0.010).the hypothesis was rejected. Bacterlon demonstratedthe lowest level, and NP-Liquid Glassthe highest level of tissue compatibility, and best cell repair.the coating with NP-Liquid Glass was demonstrated to be highly promising for clinical use.

Actin shells control buckling and wrinkling of biomembranes.

Global changes of cell shape under mechanical or osmotic external stresses are mostly controlled by the mechanics of the cortical actin cytoskeleton underlying the cell membrane. Some aspects of this process can be recapitulated in vitro on reconstituted actin-and-membrane systems. In this paper, we investigate how the mechanical properties of a branched actin network shell, polymerized at the surface of a liposome, control membrane shape when the volume is reduced. We observe a variety of membrane shapes depending on the actin thickness. Thin shells undergo buckling, characterized by a cup-shape deformation of the membrane that coincides with the one of the actin network. Thick shells produce membrane wrinkles, but do not deform their outer layer. For intermediate micrometer-thick shells, wrinkling of the membrane is observed, and the actin layer is slightly deformed. Confronting our experimental results with a theoretical description, we determine the transition between buckling and wrinkling, which depends on the thickness of the actin shell and the size of the liposome. We thus unveil the generic mechanism by which biomembranes are able to accommodate their shape against mechanical compression, through thickness adaptation of their cortical cytoskeleton.

Host Plants Indirectly Influence Plant Virus Transmission by Altering Gut Cysteine Protease Activity of Aphid Vectors.

The green peach aphid, Myzus persicae, is a vector of the Potato leafroll virus (PLRV, Luteoviridae), transmitted exclusively by aphids in a circulative manner. PLRV transmission efficiency was significantly reduced when a clonal lineage of M. persicae was reared on turnip as compared with the weed physalis, and this was a transient effect caused by a host-switch response. A trend of higher PLRV titer in physalis-reared aphids as compared with turnip-reared aphids was observed at 24 h and 72 h after virus acquisition. The major difference in the proteomes of these aphids was the up-regulation of predicted lysosomal enzymes, in particular the cysteine protease cathepsin B (cathB), in aphids reared on turnip. The aphid midgut is the site of PLRV acquisition, and cathB and PLRV localization were starkly different in midguts of the aphids reared on the two host plants. In viruliferous aphids that were reared on turnip, there was near complete colocalization of cathB and PLRV at the cell membranes, which was not observed in physalis-reared aphids. Chemical inhibition of cathB restored the ability of aphids reared on turnip to transmit PLRV in a dose-dependent manner, showing that the increased activity of cathB and other cysteine proteases at the cell membrane indirectly decreased virus transmission by aphids. Understanding how the host plant influences virus transmission by aphids is critical for growers to manage the spread of virus among field crops.

Could OX40 agonist antibody promote activation of the anti-tumor immune response in gastric cancer?

BACKGROUND AND OBJECTIVES: OX40, a membrane-bound molecule of the tumor-necrosis-factor-receptor superfamily, is a critical costimulatory receptor during the immune response, especially to T cells, but studies described their presence of OX-40 on neutrophils and monocytes, suggesting a potential role in the activation of immune response. Our aim was to characterize costimulatory receptors OX40 expression on circulating leukocytes in gastric cancer to identify novel targets for immunotherapy. METHODS: Peripheral blood mononuclear cells were isolated from 24 gastric cancer patients and 34 healthy controls and the expression of costimulatory (OX40) receptors were analyzed on T cells, neutrophil and monocyte using monoclonal antibodies by flow cytometry. RESULTS: We found that the higher levels of OX40 + T cells, monocytes/OX40+ and neutrophils/OX40+ from gastric cancer patients when compared to controls (P < 0.0001), and also higher levels of OX40+ T cells when compared to stages III and IV (P = 0.02). Percentage levels of total T cells were similar between patients and controls. CONCLUSIONS: OX40 as a therapeutic agent has been investigated in many preclinical tumor models. Our findings suggest that of levels of costimulatory in T cells in GC will direct future studies on the role that costimulatory receptors play in the failure of T cell-mediated immunity.