Ontogenetic and sexual differences in the venom of Bothrops moojeni: insights from a litter and its mother.

Variability in snake venom composition is well-documented and crucial for understanding snake ecology and predicting snakebites. In this study, we characterize the venom composition and biological activities of newborn female and male Bothrops moojeni and their mother. Our results reveal significant differences between the venom of newborn females and males, demonstrating a broad and diverse range of proteins. The venoms of newborn females showed higher serine protease effects, increased hemorrhagic activity, and greater lethality compared to the venom of newborn males. However, no differences were observed in phospholipase A2 and coagulant activity. The differences in protein composition and toxic activities between maternal and neonatal venom, as well as between the venoms of newborn females and males, contribute to understanding the diverse outcomes of snakebites. These results underscore the importance of considering sex and ontogeny in understanding venom composition in snakes.

Risk of orofacial clefts in relation to maternal body mass index, diabetes and hypertension.

BACKGROUND: To investigate if maternal body mass index, diabetes and hypertension are associated with orofacial clefts. METHODS: Case-control study. Information from 53,188 live births with and without orofacial cleft registered at USA Vital Statistics Natality Birth Data between 2017 and 2021. Case group consisted of all affected live births diagnosed with orofacial clefts (13,297 cases). Comparison group consisted of 39,891 live births without clefts or any other congenital malformation. Information about orofacial cleft cases were compared with the comparison group. The unadjusted and adjusted Odds Ratios were estimated to evaluate the strength of association between mother's pre-pregnancy body mass index, maternal diabetes and hypertension and orofacial cleft occurrence, assuming a p value < 0.05 and 95% confidence intervals (95% C.I.) for statistically significant differences. RESULTS: Mother's pre-pregnancy body mass index, maternal diabetes and maternal hypertension are conditions associated with an increased risk of orofacial cleft development in the child (OR = 1.08, p = 0.004, 95% C.I. = 1.024-1.149; OR = 1.32, 95%, p = 0.000, 95% C.I. = 1.202-1.444; and OR = 1.35, p = 0.000, 95% C.I. = 1.239-1.484; respectively). Maternal ethnicity, sex of infant, and cigarette smoking pregnancy remained as covariates after adjustments in all logistic regression models. CONCLUSION: Due to the increased prevalence of obesity, diabetes, and hypertension, and also to their association with congenital malformations, such as clefts, it is recommended that mothers planning to become pregnant to follow healthy habits, maintain healthy weight, and be screened for possible diabetes or hypertension prior to conception and early in pregnancy.

Care Technologies to Improve Treatment Adherence in Patients Undergoing Organ Transplant: A Scoping Review.

BACKGROUND: The objective of this study was to map care technologies being developed to improve treatment adherence in patients undergoing organ transplant. METHODS: A scoping review was developed according to the Joanna Briggs Institute manual. The research question was developed according to the population, concept, and context strategy. Searches were conducted independently in 6 databases between June and August 2021. The data were evaluated and organized together. The review protocol was published. RESULTS: Fifteen articles were part of the study, mostly published in the United States (33.3%) and in 2016 (33.3%). The main research method identified was clinical studies (80%). Most of the care technologies identified are in relation to medication adherence in the post-transplant setting. Another intervention identified was health education action with the support of mobile apps, electronic monitoring systems, and a card game. CONCLUSIONS: The results present technologies directed at the importance of post-transplant drug adherence; however, it is important to adapt the technologies to the reality experienced by the patient, as well as to train patients so that they can introduce these technologies in their daily lives. Furthermore, it is important that technologies are developed that include other aspects of adherence to post-transplant treatment.

Brachio-cervical inflammatory myopathy associated with systemic sclerosis. Case series and review of literature.

This study was aimed at describing a case series of brachio-cervical inflammatory myopathy (BCIM) associated with systemic sclerosis (SSc), due to its rarity and limited coverage in published data. Another aim was to provide a literature review. We reported four cases of BCIM-SSc from our tertiary center. In addition, we researched the literature and found six articles featuring 17 patients who fit this phenotype. We pooled all cases and reported their features. Most patients were female and had limited SSc, and the median time of BCIM presentation was three years after SSc diagnosis. Asymmetric muscle involvement, scapular winging, dropped head, axial weakness, camptocormia, dysphagia, and dermatomyositis stigmas were common features. All patients had esophageal involvement. Most had positive antinuclear antibody results, a scleroderma pattern in their capillaroscopy images, elevated serum creatine phosphokinase, myopathic electrophysiology, and muscle involvement in magnetic resonance imaging. Muscle histopathological findings varied widely, but in general all showed the presence of lymphoid infiltrates, muscle atrophy, increased MHC-I expression, MAC deposits, vasculopathy, and muscle fiber necrosis. The response to immunosuppressive therapy was highly irregular. BCIM-SSc is a rare disorder that shares many similar phenotypes among the described cases, but has a highly heterogeneous response to treatment. At present, more data on the physiopathology, clinical features, and treatment is still needed.

Differential coagulotoxicity of metalloprotease isoforms from Bothrops neuwiedi snake venom and consequent variations in antivenom efficacy.

Bothrops (lance-head pit vipers) venoms are rich in weaponised metalloprotease enzymes (SVMP). These toxic enzymes are structurally diverse and functionally versatile. Potent coagulotoxicity is particularly important for prey capture (via stroke-induction) and relevant to human clinical cases (due to consumption of clotting factors including the critical depletion of fibrinogen). In this study, three distinct isoforms of P-III class SVMPs (IC, IIB and IIC), isolated from Bothrops neuwiedi venom, were evaluated for their differential capacities to affect hemostasis of prey and human plasma. Furthermore, we tested the relative antivenom neutralisation of effects upon human plasma. The toxic enzymes displayed differential procoagulant potency between plasma types, and clinically relevant antivenom efficacy variations were observed. Of particular importance was the confirmation the antivenom performed better against prothrombin activating toxins than Factor X activating toxins, which is likely due to the greater prevalence of the former in the immunising venoms used for antivenom production. This is clinically relevant as the enzymes displayed differential potency in this regard, with one (IC) in particular being extremely potent in activating Factor X and thus was correspondingly poorly neutralised. This study broadens the current understanding about the adaptive role of the SVMPs, as well as highlights how the functional diversity of SVMP isoforms can influence clinical outcomes. Key Contribution: Our findings shed light upon the hemorrhagic and coagulotoxic effects of three SVMPs of the P-III class, as well as the coagulotoxic effects of SVMPs on human, avian and amphibian plasmas. Antivenom neutralised prothrombin-activating isoforms better than Factor X activating isoforms.

Where do we aspire to publish? A position paper on scientific communication in biochemistry and molecular biology.

The scientific publication landscape is changing quickly, with an enormous increase in options and models. Articles can be published in a complex variety of journals that differ in their presentation format (online-only or in-print), editorial organizations that maintain them (commercial and/or society-based), editorial handling (academic or professional editors), editorial board composition (academic or professional), payment options to cover editorial costs (open access or pay-to-read), indexation, visibility, branding, and other aspects. Additionally, online submissions of non-revised versions of manuscripts prior to seeking publication in a peer-reviewed journal (a practice known as pre-printing) are a growing trend in biological sciences. In this changing landscape, researchers in biochemistry and molecular biology must re-think their priorities in terms of scientific output dissemination. The evaluation processes and institutional funding for scientific publications should also be revised accordingly. This article presents the results of discussions within the Department of Biochemistry, University of São Paulo, on this subject.

Comparison of the effects of 1MHz and 3MHz therapeutic ultrasound on endothelium-dependent vasodilation of humans: a randomised clinical trial.

OBJECTIVE: To compare the effects of different waveforms of 1MHz and 3MHz therapeutic ultrasound on endothelial function in healthy subjects. DESIGN: Randomised placebo-controlled, crossover study with concealed allocation and assessor blinding. SETTING: Imaging Centre of the University Hospital. PARTICIPANTS: Thirty volunteers aged between 18 and 35 years were divided into two homogeneous groups (1MHz and 3MHz). INTERVENTIONS: Continuous (CUT; 0.4W/cm2SATA), pulsed (PUT; 20% duty cycle, 0.08W/cm2SATA) and placebo waveforms (equipment off) of ultrasound (1MHz and 3MHz) were randomized and applied over the brachial artery for 5minutes. MAIN OUTCOME MEASURES: Endothelial function was evaluated using the flow-mediated dilation (FMD) technique. RESULTS: Both 1MHz [CUT: mean difference 4%, 95% confidence interval (CI) 2 to 6%, P<0.001; PUT: mean difference 4%, 95% CI 2 to 6%, P<0.001] and 3MHz (CUT: mean difference 4%, 95% CI 2 to 6%, P<0.001; PUT: mean difference 4%, 95% CI 2 to 6%, P<0.001) of therapeutic ultrasound increased %FMD by approximately 4% compared with the placebo waveforms. The endothelium-dependent vasodilator responses were the same for both types of waves and frequencies. No differences in baseline diameter, hyperaemic flow, and nitroglycerin-mediated diameter and vasodilation were observed between groups. CONCLUSION: Both CUT and PUT ultrasound waveforms improved endothelial function. The 1MHz and 3MHz frequencies of therapeutic ultrasound led to similar improvement in endothelial function in healthy volunteers. Clinical trial registration number RBR-4z5z3t.

Where do we aspire to publish? A position paper on scientific communication in biochemistry and molecular biology

The scientific publication landscape is changing quickly, with an enormous increase in options and models. Articles can be published in a complex variety of journals that differ in their presentation format (online-only or in-print), editorial organizations that maintain them (commercial and/or society-based), editorial handling (academic or professional editors), editorial board composition (academic or professional), payment options to cover editorial costs (open access or pay-to-read), indexation, visibility, branding, and other aspects. Additionally, online submissions of non-revised versions of manuscripts prior to seeking publication in a peer-reviewed journal (a practice known as pre-printing) are a growing trend in biological sciences. In this changing landscape, researchers in biochemistry and molecular biology must re-think their priorities in terms of scientific output dissemination. The evaluation processes and institutional funding for scientific publications should also be revised accordingly. This article presents the results of discussions within the Department of Biochemistry, University of São Paulo, on this subject.

Model for End-Stage Liver Disease Score Before Hepatic Transplantation and Root Mean Square of the Diaphragmatic Domes Affect Postoperative Extubation Time.

INTRODUCTION: The liver transplantation procedure, in addition to its prolonged surgical time, also predisposes to complications such as changes in respiratory mechanics, lung volumes, and gas exchange. OBJECTIVE: This study aims to verify if clinical factors related to the recipient, namely immediate pretransplant Model for End-Stage Liver Disease (MELD) score, surgical time, and root square metric (RMS) of the diaphragmatic domes, affect the extubation time after liver transplantation. METHOD: A prospective study, with a sample collected for convenience, gathered age (years), sex (male or female), MELD score immediately prior to transplantation (without the addition of special situation scores), and surgical time and time for extubation (in minutes). The latter were obtained from the physiotherapy team records, and surface electromyography was performed within 30 minutes after elective extubation, by a single researcher, with supplemental oxygen support, maintaining SpO2 ≥ 95% and following protocol of positioning and acquisition of electromyographic signals based on the study of Oliveira et al (2012). RESULTS: For the 21 patients studied, the RMS of the left dome showed a moderate-intensity correlation (-0.56) with the time of extubation, and linear multiple regression model the left dome (P = .013) and preoperative MELD score (P = .048) showed significant correlation with extubation time. CONCLUSION: The preoperative MELD score and the RMS values of the left dome significantly correlate with the time for patient extubation after liver transplantation, showing the effect of previously acquired muscle weakness and preoperative MELD score on postoperative outcome.

Observations of the Interaction and Transport of Fine Mode Aerosols with Cloud and/or Fog in Northeast Asia from Aerosol Robotic Network (AERONET) and Satellite Remote Sensing.

Analysis of sun photometer measured and satellite retrieved aerosol optical depth (AOD) data has shown that major aerosol pollution events with very high fine mode AOD (>1.0 in mid-visible) in the China/Korea/Japan region are often observed to be associated with significant cloud cover. This makes remote sensing of these events difficult even for high temporal resolution sun photometer measurements. Possible physical mechanisms for these events that have high AOD include a combination of aerosol humidification, cloud processing, and meteorological co-variation with atmospheric stability and convergence. The new development of Aerosol Robotic network (AERONET) Version 3 Level 2 AOD with improved cloud screening algorithms now allow for unprecedented ability to monitor these extreme fine mode pollution events. Further, the Spectral Deconvolution Algorithm (SDA) applied to Level 1 data (L1; no cloud screening) provides an even more comprehensive assessment of fine mode AOD than L2 in current and previous data versions. Studying the 2012 winter-summer period, comparisons of AERONET L1 SDA daily average fine mode AOD data showed that Moderate Resolution Imaging Spectroradiometer (MODIS) satellite remote sensing of AOD often did not retrieve and/or identify some of the highest fine mode AOD events in this region. Also, compared to models that include data assimilation of satellite retrieved AOD, the L1 SDA fine mode AOD was significantly higher in magnitude, particularly for the highest AOD events that were often associated with significant cloudiness.

Lung Ultrasound and Pulmonary Function Test in Cirrhotic Patients.

Lung ultrasound (LU) is useful in the diagnosis of pulmonary interstitial-alveolar syndrome (IAS) when B-lines are detected. Its prevalence and effect in lung function is not well studied in cirrhotic patients. The objective of this study was to detect the prevalence of interstitial-alveolar involvement with LU and correlate with pulmonary function test to distinguish the effect of ascites and B-lines in pulmonary function. This was an observational single-center study with 49 patients listed for liver transplantation submitted for LU and pulmonary function tests. Patients were divided into 4 groups: no ascites and no B-lines (n = 19), B-lines only (n = 19), ascites only (n = 6), and ascites and B-lines (n = 5). There was a worse forced vital capacity (FVC) in patients with B-lines only (76.1% ± 9.2; P = .0058) and ascites only (66.8% ± 10.2; P = .0010). 1-second forced expiratory volume (FEV1) also was lower in patients with B-lines only (78.5% ± 10.3; P = .0001), ascites only (71.3% ± 13.2; P = .0004), and B-lines and ascites (74.2% ± 7.6; P = .0035). Model for End-Stage Liver Disease score was worse in the group with ascites and B-lines (22.4 ± 10.1; P = .0229). B-Lines reduced FVC and FEV1 in our study and may be an independent factor in worsening pulmonary function in these patients.

Diaphragm Muscle Surface Electromyography in Patients Submitted to Liver Transplant and Eligible for Extubation.

INTRODUCTION: Liver disease induces many organic and metabolic changes, leading to malnutrition and weight and muscular function loss. Surface electromyography is an easily applicable, noninvasive study, through which the magnitudes of the peaks on the charts depict voluntary muscle activity. AIM: To evaluate the diaphragmatic surface electromyography of postoperative liver transplantation subjects. METHODS: Subjects were patients who underwent liver transplantation and extubation in the Clinical Hospital of State University of Campinas. Electromyography data were collected with support pressure of ≤10 cm H2O, Glasgow Coma Scale = 11, and minimum dosages of vasoactive drugs, and data were collected again 30 minutes after extubation. Signal collection was performed with sEMG System Brazil SAS1000V3 electromyograph and electrode stickers. Statistical analysis was performed using R software. RESULTS: The average time of surgery was 345.36 ± 125.62 minutes. Time from spontaneous mode until extubation was 417.14 ± 362.97 minutes. The RMS (root mean square) values of the right and left domes in spontaneous mode with minimal ventilation parameters were 26.68 ± 10.92 and 26.55 ± 10.53, respectively, and the RMS values after extubation were 31.93 ± 18.69 to 34.62 ± 13.55, for right and left domes. The last calculated pretransplant Model for End-stage Liver Disease score averaged 19.64 ± 8.41. CONCLUSION: There were significant differences between the RMS of the diaphragm domes under mechanical ventilation and after extubation, showing lower effectiveness of the diaphragm muscle against resistance, without the aid of positive pressure and the existing overload of the left dome.

The MERRA-2 Aerosol Reanalysis, 1980 Onward. Part II: Evaluation and Case Studies.

The Modern-Era Retrospective Analysis for Research and Applications, version 2 (MERRA-2), is NASA's latest reanalysis for the satellite era (1980 onward) using the Goddard Earth Observing System, version 5 (GEOS-5), Earth system model. MERRA-2 provides several improvements over its predecessor (MERRA-1), including aerosol assimilation for the entire period. MERRA-2 assimilates bias-corrected aerosol optical depth (AOD) from the Moderate Resolution Imaging Spectroradiometer and the Advanced Very High Resolution Radiometer instruments. Additionally, MERRA-2 assimilates (non bias corrected) AOD from the Multiangle Imaging SpectroRadiometer over bright surfaces and AOD from Aerosol Robotic Network sunphotometer stations. This paper, the second of a pair, summarizes the efforts to assess the quality of the MERRA-2 aerosol products. First, MERRA-2 aerosols are evaluated using independent observations. It is shown that the MERRA-2 absorption aerosol optical depth (AAOD) and ultraviolet aerosol index (AI) compare well with Ozone Monitoring Instrument observations. Next, aerosol vertical structure and surface fine particulate matter (PM2.5) are evaluated using available satellite, aircraft, and ground-based observations. While MERRA-2 generally compares well to these observations, the assimilation cannot correct for all deficiencies in the model (e.g., missing emissions). Such deficiencies can explain many of the biases with observations. Finally, a focus is placed on several major aerosol events to illustrate successes and weaknesses of the AOD assimilation: the Mount Pinatubo eruption, a Saharan dust transport episode, the California Rim Fire, and an extreme pollution event over China. The article concludes with a summary that points to best practices for using the MERRA-2 aerosol reanalysis in future studies.

The MERRA-2 Aerosol Reanalysis, 1980 - onward, Part I: System Description and Data Assimilation Evaluation.

The Modern-Era Retrospective Analysis for Research and Applications, Version 2 (MERRA-2) updates NASA's previous satellite era (1980 - onward) reanalysis system to include additional observations and improvements to the Goddard Earth Observing System, Version 5 (GEOS-5) Earth system model. As a major step towards a full Integrated Earth Systems Analysis (IESA), in addition to meteorological observations, MERRA-2 now includes assimilation of aerosol optical depth (AOD) from various ground- and space-based remote sensing platforms. Here, in the first of a pair of studies, we document the MERRA-2 aerosol assimilation, including a description of the prognostic model (GEOS-5 coupled to the GOCART aerosol module), aerosol emissions, and the quality control of ingested observations. We provide initial validation and evaluation of the analyzed AOD fields using independent observations from ground, aircraft, and shipborne instruments. We demonstrate the positive impact of the AOD assimilation on simulated aerosols by comparing MERRA-2 aerosol fields to an identical control simulation that does not include AOD assimilation. Having shown the AOD evaluation, we take a first look at aerosol-climate interactions by examining the shortwave, clear-sky aerosol direct radiative effect. In our companion paper, we evaluate and validate available MERRA-2 aerosol properties not directly impacted by the AOD assimilation (e.g. aerosol vertical distribution and absorption). Importantly, while highlighting the skill of the MERRA-2 aerosol assimilation products, both studies point out caveats that must be considered when using this new reanalysis product for future studies of aerosols and their interactions with weather and climate.

Respiratory Profile in Patients After Liver Transplantation.

BACKGROUND: Patients in the immediate post-operative liver transplantation (LxT) period can develop respiratory and functional complications. In the postoperative months, these functions tend to improve. Nevertheless, there are few studies that evaluate precisely and specifically respiratory function in post-LxT long-term after surgery. The objective of the study was to describe the respiratory profile of patients 1 to 6 months after LxT, accompanied by LxT outpatients. METHODS: We included patients between 25 and 60 years old. We excluded patients with chronic renal or cerebrovascular impairment, severe heart disease, and history of lung surgery or liver re-transplantation. Evaluations were carried out on 3 occasions: 1 month, 3 months, and 6 months after LxT. The following evaluations were submitted: respiratory muscle strength (manuvacuometer), value flows and lung volumes (spirometer), and surface electromyography analyzing root mean square in the right (RMS-R) and left (RMS-L) diaphragm. We analyzed MELD (Model for End-Stage Liver Disease). After normality tests, we used the Friedman test (non-parametric values) and ANOVA (parametric values), P ≥ .5 with the use of SPSS 21.0. RESULTS: Patients (n = 15) had a mean age of 53.0 ± 7.5 years and 25.9 ± 4.6 MELD score. The statistically significant value obtained at the 3 occasions of evaluation was RMS-R, with a decline during periods of evaluation. This can be caused by removal of the liver, resulting in a denervation and reduction in compliance of this portion of the muscle. CONCLUSIONS: Patients between 1 and 6 months after transplantation have a specific respiratory profile, close to normal values. However, there are few studies on this subject, and we suggest that more research be done.

THE EARTH SYSTEM PREDICTION SUITE: Toward a Coordinated U.S. Modeling Capability.

The Earth System Prediction Suite (ESPS) is a collection of flagship U.S. weather and climate models and model components that are being instrumented to conform to interoperability conventions, documented to follow metadata standards, and made available either under open source terms or to credentialed users. The ESPS represents a culmination of efforts to create a common Earth system model architecture, and the advent of increasingly coordinated model development activities in the U.S. ESPS component interfaces are based on the Earth System Modeling Framework (ESMF), community-developed software for building and coupling models, and the National Unified Operational Prediction Capability (NUOPC) Layer, a set of ESMF-based component templates and interoperability conventions. This shared infrastructure simplifies the process of model coupling by guaranteeing that components conform to a set of technical and semantic behaviors. The ESPS encourages distributed, multi-agency development of coupled modeling systems, controlled experimentation and testing, and exploration of novel model configurations, such as those motivated by research involving managed and interactive ensembles. ESPS codes include the Navy Global Environmental Model (NavGEM), HYbrid Coordinate Ocean Model (HYCOM), and Coupled Ocean Atmosphere Mesoscale Prediction System (COAMPS®); the NOAA Environmental Modeling System (NEMS) and the Modular Ocean Model (MOM); the Community Earth System Model (CESM); and the NASA ModelE climate model and GEOS-5 atmospheric general circulation model.

Jararhagin disruption of endothelial cell anchorage is enhanced in collagen enriched matrices.

Hemorrhage is one of the most striking effects of bites by viper snakes resulting in fast bleeding and ischemia in affected tissues. Snake venom metalloproteinases (SVMPs) are responsible for hemorrhagic activity, but the mechanisms involved in SVMP-induced hemorrhage are not entirely understood and the study of such mechanisms greatly depends on in vivo experiments. In vivo, hemorrhagic SVMPs accumulate on basement membrane (BM) of venules and capillary vessels allowing the hydrolysis of collagen IV with consequent weakness and rupture of capillary walls. These effects are not reproducible in vitro with conventional endothelial cell cultures. In this study we used two-dimension (2D) or three-dimension (3D) cultures of HUVECs on matrigel and observed the same characteristics as in ex vivo experiments: only the hemorrhagic toxin was able to localize on surfaces or internalize endothelial cells in 2D cultures or in the surface of tubules formed on 3D cultures. The contribution of matrigel, fibronectin and collagen matrices in jararhagin-induced endothelial cell damage was then analyzed. Collagen and matrigel substrates enhanced the endothelial cell damage induced by jararhagin allowing toxin binding to focal adhesions, disruption of stress fibers, detachment and apoptosis. The higher affinity of jararhagin to collagen than to fibronectin explains the localization of the toxin within BM. Moreover, once located in BM, interactions of jararhagin with α2ß1 integrin would favor its localization on focal adhesions, as observed in our study. The accumulation of toxin in focal adhesions, observed only in cells grown in collagen matrices, would explain the enhancement of cell damage in these matrices and reflects the actual interaction among toxin, endothelial cells and BM components that occurs in vivo and results in the hemorrhagic lesions induced by viper venoms.

Characterization of Neuwiedin, a new disintegrin from Bothrops neuwiedi venom gland with distinct cysteine pattern.

Disintegrins are cysteine-rich toxins containing the RGD motif exposed in a loop that binds integrins such as αIIbß3, α5ß1 and αvß3. The flexibility of the RGD loop, controlled by the profile of the cysteine pairs and the residues flanking the RGD sequence, are key structural features for the functional activity of these molecules. Recently, our group reported a transcript in the venom gland of Bothrops neuwiedi corresponding to a new P-II SVMP precursor, BnMPIIx, in which the RGD-binding loop includes many substituted residues and unique cysteine residues at the C-terminal. In this paper, we obtained the recombinant disintegrin domain of BnMPIIx, Neuwiedin, which inhibited ADP-induced platelet aggregation, endothelial cell adhesion to fibrinogen and tube formation in Matrigel with no particular selectivity to αIIbß3 or endothelial cell integrins. This value was also comparable to the inhibition observed with other recombinant disintegrins with conserved cysteine positions and residues in RGD loop. In this regard, Neuwiedin is an important component to understand the functional relevance of the diversity generated by accelerated evolution of venom toxins as well as to find out eventual new disintegrin-dependent targets that may be approached with disintegrins.