Molecular recognition of an RNA trafficking element by heterogeneous nuclear ribonucleoprotein A2

Heterogeneous nuclear ribonucleoprotein (hnRNP) A2 is a multitasking protein involved in RNA packaging, alternative splicing of pre-mRNA. telomere maintenance, cytoplasmic RNA trafficking, and translation. It binds short segments of single-stranded nucleic acids, including the A2RE11 RNA element that is necessary and sufficient for cytoplasmic transport of a subset of rnRNAs in oligodendrocytes and neurons. We have explored the structures of hnRNP A2, its RNA recognition motifs (RRMs) and Gly-rich module, and the RRM complexes with A2RE11. Circular dichroism spectroscopy showed that the secondary structure of the first 189 residues of hnRNP A2 parallels that of the tandem beta alpha beta beta alpha beta RRMs of its paralogue, hnRNP A1, previously deduced from X-ray diffraction studies. The unusual GRD was shown to have substantial beta-sheet and beta-turn structure. Sedimentation equilibrium and circular dichroism results were consistent with the tandem RRM region being monomeric and supported earlier evidence for the binding of two A2RE11 oligoribonucleotides to this domain, in contrast to the protein dimer formed by the complex of hnRNP A1 with the telomeric ssDNA repeat. A three-dimensional structure for the N-terminal, two-RRM-containing segment of hnRNP A2 was derived by homology modeling. This structure was used to derive a model for the complex with A2RE11 using the previously described interaction of pairs of stacked nucleotides with aromatic residues on the RRM beta-sheet platforms, conserved in other RRM-RNA complexes, together with biochemical data and molecular dynamics-based observations of inter-RRM mobility.

“Samira Doesn’t Live Here Any More” : Somali-Swedes’ mobility as transnational practice

This article explores transnational experiences within a group of Somali- Swedes, particularly how parents’ transnational practices are transferred to their children and how a transnational social space, built on close relationships on a global scale, is constructed. The readiness to relocate between countries and the implications for the children is illuminated. The onward migration to Egypt is highlighted as an example. According to research on Somalis in diaspora, they explain their propensity to move by claiming to be nomads, but this article indicates that it is also about their desire for better opportunities in combination with the cultural and economic marginalisation experienced in the West.

An application of strategic group theory to the UK pharmaceuticals industry

Conducts a strategic group mapping exercise by analysing R&D investment, sales/marketing cost and leadership information pertaining to the pharmaceuticals industry. Explains that strategic group mapping assists companies in identifying their principal competitors, and hence supports strategic decision-making, and shows that, in the pharmaceutical industry, R&D spending, the cost of sales and marketing, i.e. detailing, and technological leadership are mobility barriers to companies moving between sectors. Illustrates, in bubble-chart format, strategic groups in the pharmaceutical industry, plotting detailing-costs against the scale of activity in therapeutic areas. Places companies into 12 groups, and profiles the strategy and market-position similarities of the companies in each group. Concludes with three questions for companies to ask when evaluating their own, and their competitors, strategies and returns, and suggests that strategy mapping can be carried out in other industries, provided mobility barriers are identified.

The 'Healthy Passport' intervention with older people in an English urban environment:effects of incentives and peer-group organisers in promoting healthy living

This paper reports the evaluation of the effectiveness of incentives (viz. points and prizes) and of peer-group organisers ('older people's champions') in the outcomes of a health-improvement programme for people aged 50 + years in a multi-ethnic district of the West Midlands, England. Health promotion activities Were provided, and adherence, outcome variables and barriers to adherence were assessed over six months, using a `passport' format. Those aged in the fifties and of Asian origin Were under represented, but people of Afro-Caribbean origin were well represented and proportionately most likely to stay in the project. Those of greater age and With more illness were most likely to drop out. There were significant improvements in exercise, diet and the uptake of influenza vaccines and eyesight tests, but slighter improvements in wellbeing. Positive outcomes related to the incentives and to liking the format. The number of reported barriers was associated with lower involvement and lack of change, as was finding activities too difficult, the level of understanding, and transport and mobility problems, but when these were controlled, age did not predict involvement. Enjoying the scheme was related to positive changes, and this was associated with support from the older people's champions.

Molecular Characterization of Three Novel Phospholipase A2 Proteins from the Venom of Atheris chlorechis, Atheris nitschei and Atheris squamigera

Secretory phospholipase A2 (sPLA2) is known as a major component of snake venoms and displays higher-order catalytic hydrolysis functions as well as a wide range of pathological effects. Atheris is not a notoriously dangerous genus of snakes although there are some reports of fatal cases after envenomation due to the effects of coagulation disturbances and hemorrhaging. Molecular characterization of Atheris venom enzymes is incomplete and there are only a few reports in the literature. Here, we report, for the first time, the cloning and characterization of three novel cDNAs encoding phospholipase A2 precursors (one each) from the venoms of the Western bush viper (Atheris chlorechis), the Great Lakes bush viper (Atheris nitschei) and the Variable bush viper (Atheris squamigera), using a “shotgun cloning” strategy. Open-reading frames of respective cloned cDNAs contained putative 16 residue signal peptides and mature proteins composed of 121 to 123 amino acid residues. Alignment of mature protein sequences revealed high degrees of structural conservation and identity with Group II venom PLA2 proteins from other taxa within the Viperidae. Reverse-phase High Performance Liquid Chromatography (HPLC) profiles of these three snake venoms were obtained separately and chromatographic fractions were assessed for phospholipase activity using an egg yolk suspension assay. The molecular masses of mature proteins were all identified as approximately 14 kDa. Mass spectrometric analyses of the fractionated oligopeptides arising from tryptic digestion of intact venom proteins, was performed for further structural characterization.

On the Economics and Politics of Mobility

Exit, Voice and Political Change: Evidence from Swedish Mass Migration to the United States. During the Age of Mass Migration, 30 million Europeans immigrated to the United States. We study the long-term political effects of this large-scale migration episode on origin communities using detailed historical data from Sweden. To instrument for emigration, we exploit severe local frost shocks that sparked an initial wave of emigration, interacted with within-country travel costs. Because Swedish emigration was highly path dependent, the initial shocks strongly predict total emigration over 50 years. Our estimates show that emigration substantially increased membership in local labor organizations, the strongest political opposition groups at the time. Furthermore, emigration caused greater strike participation, and mobilized voter turnout and support for left-wing parties in national elections. Emigration also had formal political effects, as measured by welfare expenditures and adoption of inclusive political institutions. Together, our findings indicate that large-scale emigration can achieve long-lasting effects on the political equilibrium in origin communities. Mass Migration and Technological Innovation at the Origin. This essay studies the effects of migration on technological innovations in origin communities. Using historical data from Sweden, we find that large-scale emigration caused a long-run increase in patent innovations in origin municipalities. Our IV estimate shows that a ten percent increase in emigration entails a 7 percent increase in a muncipality’s number of patents. Weighting patents by a measure of their economic value, the positive effects are further increased. Discussing possible mechanisms, we suggest that low skilled labor scarcity may be an explanation for these results.  Richer (and Holier) Than Thou? The Impact of Relative Income Improvements on Demand for Redistribution. We use a tailor-made survey on a Swedish sample to investigate how individuals' relative income affects their demand for redistribution. We first document that a majority misperceive their position in the income distribution and believe that they are poorer, relative to others, than they actually are. We then inform a subsample about their true relative income, and find that individuals who are richer than they initially thought demand less redistribution. This result is driven by individuals with prior right-of-center political preferences who view taxes as distortive and believe that effort, rather than luck, drives individual economic success. Wealth, home ownership and mobility. Rent controls on housing have long been thought to reduce labor mobility and allocative efficiency. We study a policy that allowed renters to purchase their rent-controlled apartments at below market prices, and examine the effects of home ownership and wealth on mobility. Treated individuals have a substantially higher likelihood of moving to a new home in a given year. The effect corresponds to a 30 percent increase from the control group mean. The size of the wealth shock predicts lower mobility, while the positive average effect can be explained by tenants switching from the previous rent-controlled system to market-priced condominiums. By contrast, we do not find that the increase in residential mobility leads to a greater probability of moving to a new place of work.

Virtual Mobility and Learning for PhD students of six European Countries: students’ programme evaluation

In this paper, the authors, as teachers of the Virtual Mobility and Learning ERASMUS Intensive Programme (VML–IP), put forward an analysis of the student’s final evaluation of the Programme as to the most important competences they have developed. In terms of methodology, this study has an exploratory and descriptive nature; hence, being based on empiric evidence. Thus, in the last face-to-face session, students were asked by the Programme’s coordination to present an overall evaluation of their experience in the VML–IP. Data were collected in loco, i.e. through the posters created by each group, as well as the video of the students’ oral presentations. They were later analysed using content analysis as data analysis technique. The results unveil that, although the main goal was fulfilled – i.e. to be able to design and implement a course on a ‘Virtual Mobility and Learning’ topic underpinned by solid theoretical background in the area –, the fact is that every group also pointed out several soft competences as a very important part of their experiences, and crucial for their development as students and future professionals.

Beyond hope: Rhetorics of mobility, possibility, and literacy

When writing teachers enter the classroom, they often bring with them a deep faith in the power of literacy to rectify social inequalities and improve their students’ social and economic standing. It is this faith—this hope for change—that draws some writing teachers to locations of social and economic hardship. I am interested in how teachers and theorists construct their own narratives of social mobility, possibility, and literacy. My dissertation analyzes the production and expression of beliefs about literacy in the narratives of a diverse group of writing teachers and theorists, from those beginning their careers to those who are published and widely read. The central questions guiding this study are: How do teachers’ and theorists’ narratives of becoming literate intersect with literacy theories? and How do such literacy narratives intersect with beliefs in the power of literacy to improve individuals’ lives socially, economically, and personally? I contend that the professional literature needs to address more fully how teachers’ and theorists’ personal histories with literacy shape what they see as possible (and desirable) for students, especially those from marginalized communities. A central focus of the dissertation is on how teachers and theorists attempt to resolve a paradox they are likely to encounter in narratives about literacy. On one hand, they are immersed in a popular culture that cherishes narrative links between literacy and economic advancement (and, further, between such advancement and a “good life”). On the other hand, in professional discourse and in teacher preparation courses, they are likely to encounter narratives that complicate an assumed causal relationship between literacy and economic progress. Understanding, through literacy narratives, how teachers and theorists chart a practical path through or around this paradox can be beneficial to literacy education in three ways. First, it can offer direction in professional development and teacher education, addressing how teachers negotiate the boundaries between personal experience, theory, and pedagogy. Second, it can help teachers create spaces wherein students can explore the impact of paradoxical views about the role of literacy on their own lives. Finally, it can offer direction in public policy discourse, extending awareness of what we want—and need—from English language arts education in the twenty-first century. To explore these issues, I draw on case studies and ethnographic observation as well as narrative inquiry into teachers’ and theorists’ published literacy narratives. I situate my findings within three interrelated frames: 1) the narratives of new teachers, 2) the published works of literacy educators and theorists, and 3) my own literacy narrative. My first chapter, “Beyond Hope,” explores the tenuous connections between hope and critique in literacy studies and provides a methodological overview of the study. I argue that scholarship must move beyond a singular focus on either hope or critique in order to identify the transformative potential of literacy in particular circumstances. Analyzing literacy narratives provides a way of locating a critically informed sense of possibility. My second chapter, “Making Teachers, Making Literacy,” explores the intersection between teachers’ lives and the theories they study, based on qualitative analysis of a preservice course for secondary education English teachers. I examine how these preservice English teachers understood literacy, how their narratives of becoming literate and teaching English connected—and did not connect—with theoretical and pedagogical positions, and how these stories might inform their future work as practitioners. Centering primarily on preservice teachers who resisted Nancie Atwell’s pedagogy of possibility because they found it too good to be true, this research concentrates on moments of disjuncture, as expressed in class discussion and in one-on-one interviews, when literacy theories failed to align with aspiring teachers’ understandings of their own experiences and also with what they imagined as possible in disadvantaged educational settings. In my third and fourth chapters, I analyze the narratives of celebrated teachers and theorists who put forth an agenda that emphasizes possibilities through literacy, examining how they negotiate the relationship between their own literacy stories and literacy theories. Specifically, I investigate the narratives of three proponents of critical literacy: Mike Rose, Paulo Freire, and Myles Horton, all highly respected literacy teachers whose working-class backgrounds influenced their commitment to teaching in disenfranchised communities. In chapter 3, “Reading Lives on the Boundary,” I demonstrate how Mike Rose’s 1989 autobiographical text, Lives on the Boundary, juxtaposes rhetorics of mobility with critiques of such possibility. Through an analysis of work published in professional journals, I offer a reception history of Rose’s narrative, focusing specifically on how teachers have negotiated the tension between hope and critique. I follow this analysis with three case studies, drawn from a larger sampling, that inquire into the personal connections that writing teachers make with Lives on the Boundary. The teachers in this study, who provided written responses and participated in audio-recorded follow-up interviews, were asked to compare Rose’s story to their own stories, considering how their personal literacy histories influenced their teaching. My findings illustrate how a group of teachers and theorists have projected their own assessments of what literacy and higher education can and cannot accomplish onto this influential text. In my fourth chapter, “Horton and Freire’s Road as Literacy Narrative,” I concentrate on Myles Horton and Paulo Freire’s 1990 collaborative spoken book, We Make the Road by Walking. Central to my analysis are the educators’ stories about their formative years, including their own primary and secondary education experiences. I argue that We Make the Road by Walking demonstrates how theories of literacy cannot be divorced from personal histories. I begin by examining the spoken book as a literacy narrative that fuses personal and theoretical knowledge, focusing specifically on its authors’ ideas on theory. Drawing on Bakhtin’s notion of the chronotope—the intersection of time and space within narrative—I then explore the literacy narratives emerging from the production process of the book, in a video production about Horton and Freire’s meeting, and ultimately in the two men’s reflections on their childhood years (Dialogic). Interspersed with these accounts is archival material on the book’s editorial production that illustrates the value of increased dialogue between personal history and theories of literacy. My fifth chapter is both a reflective analysis and a qualitative study of my work at a men’s medium-high security prison in Illinois, where I conducted research and served as the instructor of an upper-level writing course, “Writing for a Change,” in the spring of 2009. Entitled “Doing Time with Literacy Narratives,” this chapter explores the complex ways in which literacy and incarceration are configured in students’ narratives as well as my own. With and against students’ stories, I juxtapose my own experiences with literacy, particularly in relation to being the son of an imprisoned father. In exploring the intersections between such stories, I demonstrate how literacy narratives can function as a heuristic for exploring beliefs about literacy between teachers and students both inside and outside of the prison-industrial complex. My conclusion pulls together the various themes that emerged in the three frames, from the making of new teachers to the published literacy narratives of teachers and theorists to my own literacy narrative. Writing teachers encounter considerable pressure to align their curricula with one or another theory of literacy, which has the effect of negating the authority of knowledge about literacy gleaned from experience as readers and writers. My dissertation contends that there is much to be gained by finding ways of articulating theories of literacy that encompass teachers’ knowledge of reading and writing as expressed in personal narratives of literacy. While powerful cultural rhetorics of upward social mobility often neutralize the critical potential of teachers’ own narratives of literacy—potential that has been documented by scholars in writing studies and allied disciplines—this is not always the case. The chapters in this dissertation offer evidence that hopeful and critical positions on the transformational possibilities of literacy are not mutually exclusive.

An Asp49 Phospholipase A2 From Snake Venom Induces Cyclooxygenase-2 Expression And Prostaglandin E2 Production Via Activation Of Nf-κb, P38mapk, And Pkc In Macrophages.

Phospholipases A2 (PLA2) are key enzymes for production of lipid mediators. We previously demonstrated that a snake venom sPLA2 named MT-III leads to prostaglandin (PG)E2 biosynthesis in macrophages by inducing the expression of cyclooxygenase-2 (COX-2). Herein, we explored the molecular mechanisms and signaling pathways leading to these MT-III-induced effects. Results demonstrated that MT-III induced activation of the transcription factor NF-κB in isolated macrophages. By using NF-κB selective inhibitors, the involvement of this factor in MT-III-induced COX-2 expression and PGE2 production was demonstrated. Moreover, MT-III-induced COX-2 protein expression and PGE2 release were attenuated by pretreatment of macrophages with SB202190, and Ly294002, and H-7-dihydro compounds, indicating the involvement of p38MAPK, PI3K, and PKC pathways, respectively. Consistent with this, MT-III triggered early phosphorylation of p38MAPK, PI3K, and PKC. Furthermore, SB202190, H-7-dihydro, but not Ly294002 treatment, abrogated activation of NF-κB induced by MT-III. Altogether, these results show for the first time that the induction of COX-2 protein expression and PGE2 release, which occur via NF-κB activation induced by the sPLA2-MT-III in macrophages, are modulated by p38MAPK and PKC, but not by PI3K signaling proteins.

Otorhinolaryngological Findings In A Group Of Patients With Rheumatic Diseases.

Otorhinolaryngological manifestations of rheumatologic diseases represent a great challenge not only to the generalistphysician but also to the ENT doctor andrheumatologist. They often represent early manifestations of an autoimmune disorder which requires prompt and aggressive immunosuppressive treatment. Auditory, nasal, laryngeal and eye symptoms can be the first manifestation of rheumatic diseases and their proper assessment helps the doctor to identify signs of disease activity. The objective of this study is to identify the ENT manifestations in patients with rheumatic diseases in a high complexity hospital, regarding facilitating an early diagnosis and treatment. We performed clinical and complete otorhinolaryngological evaluations in patients selected from the outpatient rheumatology in a standardized manner by the use of a standardized form filling during the secondhalf of 2010. In the study group, systemic lupus erythematosus (SLE) patients had predominantly laryngeal manifestations, while patients with Sjögren's syndrome showed a higher prevalence of otologic manifestations. Changes in audiometric tests were found in 53% of Wegener's granulomatosis (WG) patients, 80% of relapsing polychondritis (RP), 33% of systemic lupus erythematosus (SLE) and 50% of Churg-Strauss syndrome (SCS). Regarding nasal alterations, these were found so prevalent in all conditions, especially Churg-Strauss syndrome. This study demonstrated that most patients treated in our hospital has the ENT signs and symptoms commonly associated in previous studies on rheumatic diseases, but further studies with a larger number of patients must be made to establish such relations.

Molecular And Morphological Evidence Reveals A New Species In The Phyllomedusa Hypochondrialis Group (hylidae, Phyllomedusinae) From The Atlantic Forest Of The Highlands Of Southern Brazil.

The taxonomic status of a disjunctive population of Phyllomedusa from southern Brazil was diagnosed using molecular, chromosomal, and morphological approaches, which resulted in the recognition of a new species of the P. hypochondrialis group. Here, we describe P. rustica sp. n. from the Atlantic Forest biome, found in natural highland grassland formations on a plateau in the south of Brazil. Phylogenetic inferences placed P. rustica sp. n. in a subclade that includes P. rhodei + all the highland species of the clade. Chromosomal morphology is conservative, supporting the inference of homologies among the karyotypes of the species of this genus. Phyllomedusa rustica is apparently restricted to its type-locality, and we discuss the potential impact on the strategies applied to the conservation of the natural grassland formations found within the Brazilian Atlantic Forest biome in southern Brazil. We suggest that conservation strategies should be modified to guarantee the preservation of this species.

Rh, Kell, Duffy, Kidd And Diego Blood Group System Polymorphism In Brazilian Japanese Descendants.

Polymorphisms of Rh, Kell, Duffy, Kidd and Diego blood group systems were studied in 209 unrelated Brazilian Japanese descendants from South of Brazil. The methods used were multiplex-PCR, AS-PCR and RFLP-PCR. The differences in frequencies among the populations were evaluated using chi-square test. The frequencies for Rh, Kell, Kidd and Diego system were similar to those of the Japanese. RHCE(*)CC, RHCE(*)EE genotypes and FY(*)01 allele were lower and FY(*)01N.01 was higher than Japanese. These differences in the frequencies between Brazilian Japanese descendants and Japanese could indicate a gene flow in Brazilian population and reinforce the importance of this knowledge to achieve safe red blood cells.

National Institutes Of Health Consensus Development Project On Criteria For Clinical Trials In Chronic Graft-versus-host Disease: I. The 2014 Diagnosis And Staging Working Group Report.

The 2005 National Institutes of Health (NIH) Consensus Conference proposed new criteria for diagnosing and scoring the severity of chronic graft-versus-host disease (GVHD). The 2014 NIH consensus maintains the framework of the prior consensus with further refinement based on new evidence. Revisions have been made to address areas of controversy or confusion, such as the overlap chronic GVHD subcategory and the distinction between active disease and past tissue damage. Diagnostic criteria for involvement of mouth, eyes, genitalia, and lungs have been revised. Categories of chronic GVHD should be defined in ways that indicate prognosis, guide treatment, and define eligibility for clinical trials. Revisions have been made to focus attention on the causes of organ-specific abnormalities. Attribution of organ-specific abnormalities to chronic GVHD has been addressed. This paradigm shift provides greater specificity and more accurately measures the global burden of disease attributed to GVHD, and it will facilitate biomarker association studies.

The Neuromuscular Activity Of Bothriopsis Bilineata Smaragdina (forest Viper) Venom And Its Toxin Bbil-tx (asp49 Phospholipase A2) On Isolated Mouse Nerve-muscle Preparations.

The presynaptic action of Bothriopsis bilineata smaragdina (forest viper) venom and Bbil-TX, an Asp49 PLA2 from this venom, was examined in detail in mouse phrenic nerve-muscle (PND) preparations in vitro and in a neuroblastoma cell line (SK-N-SH) in order to gain a better insight into the mechanism of action of the venom and associated Asp49 PLA2. In low Ca(2+) solution, venom (3μg/ml) caused a quadriphasic response in PND twitch height whilst at 10μg/ml the venom additionally induced an abrupt and marked initial contracture followed by neuromuscular facilitation, rhythmic oscillations of nerve-evoked twitches, alterations in baseline and progressive blockade. The venom slowed the relaxation phase of muscle twitches. In low Ca(2+), Bbil-TX [210nM (3μg/ml)] caused a progressive increase in PND twitch amplitude but no change in the decay time constant. Venom (10μg/ml) and Bbil-TX (210nM) caused minor changes in the compound action potential (CAP) amplitude recorded from sciatic nerve preparations, with no significant effect on rise time and latency; tetrodotoxin (3.1nM) blocked the CAP at the end of the experiments. In mouse triangularis sterni nerve-muscle (TSn-m) preparations, venom (10μg/ml) and Bbil-TX (210nM) significantly reduced the perineural waveform associated with the outward K(+) current while the amplitude of the inward Na(+) current was not significantly affected. Bbil-TX (210nM) caused a progressive increase in the quantal content of TSn-m preparations maintained in low Ca(2+) solution. Venom (3μg/ml) and toxin (210nM) increased the calcium fluorescence in SK-N-SH neuroblastoma cells loaded with Fluo3 AM and maintained in low or normal Ca(2+) solution. In normal Ca(2+), the increase in fluorescence amplitude was accompanied by irregular and frequent calcium transients. In TSn-m preparations loaded with Fluo4 AM, venom (10μg/ml) caused an immediate increase in intracellular Ca(2+) followed by oscillations in fluorescence and muscle contracture; Bbil-TX did not change the calcium fluorescence in TSn-m preparations. Immunohistochemical analysis of toxin-treated PND preparations revealed labeling of junctional ACh receptors but a loss of the presynaptic proteins synaptophysin and SNAP25. Together, these data confirm the presynaptic action of Bbil-TX and show that it involves modulation of K(+) channel activity and presynaptic protein expression.

Digestive Peptidase Evolution In Holometabolous Insects Led To A Divergent Group Of Enzymes In Lepidoptera.

Trypsins and chymotrypsins are well-studied serine peptidases that cleave peptide bonds at the carboxyl side of basic and hydrophobic l-amino acids, respectively. These enzymes are largely responsible for the digestion of proteins. Three primary processes regulate the activity of these peptidases: secretion, precursor (zymogen) activation and substrate-binding site recognition. Here, we present a detailed phylogenetic analysis of trypsins and chymotrypsins in three orders of holometabolous insects and reveal divergent characteristics of Lepidoptera enzymes in comparison with those of Coleoptera and Diptera. In particular, trypsin subsite S1 was more hydrophilic in Lepidoptera than in Coleoptera and Diptera, whereas subsites S2-S4 were more hydrophobic, suggesting different substrate preferences. Furthermore, Lepidoptera displayed a lineage-specific trypsin group belonging only to the Noctuidae family. Evidence for facilitated trypsin auto-activation events were also observed in all the insect orders studied, with the characteristic zymogen activation motif complementary to the trypsin active site. In contrast, insect chymotrypsins did not seem to have a peculiar evolutionary history with respect to their mammal counterparts. Overall, our findings suggest that the need for fast digestion allowed holometabolous insects to evolve divergent groups of peptidases with high auto-activation rates, and highlight that the evolution of trypsins led to a most diverse group of enzymes in Lepidoptera.