A trail of dark-matter-free galaxies from a bullet-dwarf collision.

The ultra-diffuse galaxies DF2 and DF4 in the NGC 1052 group share several unusual properties: they both have large sizes1, rich populations of overluminous and large globular clusters2-6, and very low velocity dispersions that indicate little or no dark matter7-10. It has been suggested that these galaxies were formed in the aftermath of high-velocity collisions of gas-rich galaxies11-13, events that resemble the collision that created the bullet cluster14 but on much smaller scales. The gas separates from the dark matter in the collision and subsequent star formation leads to the formation of one or more dark-matter-free galaxies12. Here we show that the present-day line-of-sight distances and radial velocities of DF2 and DF4 are consistent with their joint formation in the aftermath of a single bullet-dwarf collision, around eight billion years ago. Moreover, we find that DF2 and DF4 are part of an apparent linear substructure of seven to eleven large, low-luminosity objects. We propose that these all originated in the same event, forming a trail of dark-matter-free galaxies that is roughly more than two megaparsecs long and angled 7° ± 2° from the line of sight. We also tentatively identify the highly dark-matter-dominated remnants of the two progenitor galaxies that are expected11 at the leading edges of the trail.

Multiplexable and Scalable Aqueous Synthesis Platform for Oleate-Based, Bilayer-Coated Gold Nanoparticles.

Despite gold-based nanomaterials having a unique role in nanomedicine, among other fields, synthesis limitations relating to reaction scale-up and control result in prohibitively high gold nanoparticle costs. In this work, a new preparation procedure for lipid bilayer-coated gold nanoparticles in water is presented, using sodium oleate as reductant and capping agent. The seed-free synthesis not only allows for size precision (8-30 nm) but also remarkable particle concentration (10 mm Au). These reaction efficiencies allow for multiplexing and reaction standardization in 96-well plates using conventional thermocyclers, in addition to simple particle purification via microcentrifugation. Such a multiplexing approach also enables detailed spectroscopic investigation of the nonlinear growth process and dynamic sodium oleate/oleic acid self-assembly. In addition to scalability (at gram-level), resulting gold nanoparticles are stable at physiological pH, in common cell culture media, and are autoclavable. To demonstrate the versatility and applicability of the reported method, a robust ligand exchange with thiolated polyethylene glycol analogues is also presented.

Variations on the Bergman Cyclization Theme: Electrocyclizations of Ionic Penta-, Hepta-, and Octadiynes.

The Bergman cyclization of (Z)-hexa-3-ene-1,5-diyne to form the aromatic diradical p-benzyne has garnered attention as a potential antitumor agent due to its relatively low cyclization barrier and the stability of the resulting diradical. Here, we present a theoretical investigation of several ionic extensions of the fundamental Bergman cyclization: electrocyclizations of the penta-1,4-diyne anion, hepta-1,6-diyne cation, and octa-1,7-diyne dication, leveraging the spin-flip formulation of the equation-of-motion coupled cluster theory with single and double substitutions (EOM-SF-CCSD). Though the penta-1,4-diyne anion exhibits a large cyclization barrier of +66 kcal mol-1, cyclization of both the hepta-1,6-diyne cation and octa-1,7-diyne dication along a previously unreported triplet pathway requires relatively low energy. We also identified the presence of significant aromaticity in the triplet diradical products of these two cationic cyclizations.

Endoplasmic reticulum chaperones stabilize ligand-receptive MR1 molecules for efficient presentation of metabolite antigens.

The antigen-presenting molecule MR1 (MHC class I-related protein 1) presents metabolite antigens derived from microbial vitamin B2 synthesis to activate mucosal-associated invariant T (MAIT) cells. Key aspects of this evolutionarily conserved pathway remain uncharacterized, including where MR1 acquires ligands and what accessory proteins assist ligand binding. We answer these questions by using a fluorophore-labeled stable MR1 antigen analog, a conformation-specific MR1 mAb, proteomic analysis, and a genome-wide CRISPR/Cas9 library screen. We show that the endoplasmic reticulum (ER) contains a pool of two unliganded MR1 conformers stabilized via interactions with chaperones tapasin and tapasin-related protein. This pool is the primary source of MR1 molecules for the presentation of exogenous metabolite antigens to MAIT cells. Deletion of these chaperones reduces the ER-resident MR1 pool and hampers antigen presentation and MAIT cell activation. The MR1 antigen-presentation pathway thus co-opts ER chaperones to fulfill its unique ability to present exogenous metabolite antigens captured within the ER.

First evidence of regional migration of the copper shark Carcharhinus brachyurus (Günther, 1870) in the Southwest Atlantic.

Regional migration of the copper shark Carcharhinus brachyurus was recorded for the first time in the Southwest Atlantic (SWA) from Argentina (latitude: -38.1037, longitude: -57.5371) to Brazil (latitude: -20.6833, longitude: -40.2846) as a result of a citizen science tagging project. The recaptured specimen was a female (103 kg weight), with 18 developing embryos within the uterus. The total distance was at least 2566 km, and it is the longest ever recorded for the species. Furthermore, it extends its northern distribution in the SWA.

Flight tone characterisation of the South American malaria vector Anopheles darlingi (Diptera: Culicidae).

BACKGROUND: Flight tones play important roles in mosquito reproduction. Several mosquito species utilise flight tones for mate localisation and attraction. Typically, the female wingbeat frequency (WBF) is lower than males, and stereotypic acoustic behaviors are instrumental for successful copulation. Mosquito WBFs are usually an important species characteristic, with female flight tones used as male attractants in surveillance traps for species identification. Anopheles darlingi is an important Latin American malaria vector, but we know little about its mating behaviors. OBJECTIVES: We characterised An. darlingi WBFs and examined male acoustic responses to immobilised females. METHODS: Tethered and free flying male and female An. darlingi were recorded individually to determine their WBF distributions. Male-female acoustic interactions were analysed using tethered females and free flying males. FINDINGS: Contrary to most mosquito species, An. darlingi females are smaller than males. However, the male's WBF is ~1.5 times higher than the females, a common ratio in species with larger females. When in proximity to a female, males displayed rapid frequency modulations that decreased upon genitalia engagement. Tethered females also modulated their frequency upon male approach, being distinct if the interaction ended in copulation or only contact. MAIN CONCLUSIONS: This is the first report of An. darlingi flight acoustics, showing that its precopulatory acoustics are similar to other mosquitoes despite the uncommon male:female size ratio, suggesting that WBF ratios are common communication strategies rather than a physical constraint imposed by size.

A filamentous bacteriophage targeted to carcinoembryonic antigen induces tumor regression in mouse models of colorectal cancer.

Colorectal cancer is a deadly disease, which is frequently diagnosed at advanced stages, where conventional treatments are no longer effective. Cancer immunotherapy has emerged as a new form to treat different malignancies by turning-on the immune system against tumors. However, tumors are able to evade antitumor immune responses by promoting an immunosuppressive microenvironment. Single-stranded DNA containing M13 bacteriophages are highly immunogenic and can be specifically targeted to the surface of tumor cells to trigger inflammation and infiltration of activated innate immune cells, overcoming tumor-associated immunosuppression and promoting antitumor immunity. Carcinoembryonic antigen (CEA) is highly expressed in colorectal cancers and has been shown to promote several malignant features of colorectal cancer cells. In this work, we targeted M13 bacteriophage to CEA, a tumor-associated antigen over-expressed in a high proportion of colorectal cancers but largely absent in normal cells. The CEA-targeted M13 bacteriophage was shown to specifically bind to purified CEA and CEA-expressing tumor cells in vitro. Both intratumoral and systemic administration of CEA-specific bacteriophages significantly reduced tumor growth of mouse models of colorectal cancer, as compared to PBS and control bacteriophage administration. CEA-specific bacteriophages promoted tumor infiltration of neutrophils and macrophages, as well as maturation dendritic cells in tumor-draining lymph nodes, suggesting that antitumor T-cell responses were elicited. Finally, we demonstrated that tumor protection provided by CEA-specific bacteriophage particles is mediated by CD8+ T cells, as depletion of circulating CD8+ T cells completely abrogated antitumor protection. In summary, we demonstrated that CEA-specific M13 bacteriophages represent a potential immunotherapy against colorectal cancer.

Recombinant monovalent llama-derived antibody fragments (VHH) to rotavirus VP6 protect neonatal gnotobiotic piglets against human rotavirus-induced diarrhea.

Group A Rotavirus (RVA) is the leading cause of severe diarrhea in children. The aims of the present study were to determine the neutralizing activity of VP6-specific llama-derived single domain nanoantibodies (VHH nanoAbs) against different RVA strains in vitro and to evaluate the ability of G6P[1] VP6-specific llama-derived single domain nanoantibodies (VHH) to protect against human rotavirus in gnotobiotic (Gn) piglets experimentally inoculated with virulent Wa G1P[8] rotavirus. Supplementation of the daily milk diet with 3B2 VHH clone produced using a baculovirus vector expression system (final ELISA antibody -Ab- titer of 4096; virus neutralization -VN- titer of 256) for 9 days conferred full protection against rotavirus associated diarrhea and significantly reduced virus shedding. The administration of comparable levels of porcine IgG Abs only protected 4 out of 6 of the animals from human RVA diarrhea but significantly reduced virus shedding. In contrast, G6P[1]-VP6 rotavirus-specific IgY Abs purified from eggs of hyperimmunized hens failed to protect piglets against human RVA-induced diarrhea or virus shedding when administering similar quantities of Abs. The oral administration of VHH nanoAb neither interfered with the host's isotype profiles of the Ab secreting cell responses to rotavirus, nor induced detectable host Ab responses to the treatment in serum or intestinal contents. This study shows that the oral administration of rotavirus VP6-VHH nanoAb is a broadly reactive and effective treatment against rotavirus-induced diarrhea in neonatal pigs. Our findings highlight the potential value of a broad neutralizing VP6-specific VHH nanoAb as a treatment that can complement or be used as an alternative to the current strain-specific RVA vaccines. Nanobodies could also be scaled-up to develop pediatric medication or functional food like infant milk formulas that might help treat RVA diarrhea.

Expression and characterization of the gD protein of HSV-2 fused to the tetramerization domain of the transcription factor p53.

The highly immunogenic glycoprotein D (gD) of herpes simplex virus type 2 (HSV-2) is a very important element for entry of this virus into host cells. These characteristics have made this protein a very interesting HSV-2 subunit vaccine candidate. Despite efforts to prevent genital herpes using gD-based subunit vaccines, to date, clinical trials using this antigen have failed. Therefore, using a small animal model, we sought to determine if a tetramerized truncated form of gD subunit vaccine, produced by recombinant baculovirus infected insect larvae, would elicit better protection against genital herpes than a monomeric gD-2 subunit vaccine. Three out of 5 mice immunized with the tetramerized antigen produced in a baculovirus expression vector system, survived a lethal challenge with a wild type HSV-2 strain (for more than 3 weeks after challenge). In contrast, all the mice (5) immunized with the truncated protein, produced by the same methodology, died within 2 weeks after challenge. These results suggest that multimerization (increasing the structural complexity) of the truncated gD antigen might be more likely protective than the monomer form. Also the use of an alternative cost-efficient eukaryotic expression system is described.

Standard Quality Characteristics and Efficacy of a New Third-Generation Antivenom Developed in Colombia Covering Micrurus spp. Venoms.

In Colombia, Micrurus snakebites are classified as severe according to the national clinical care guidelines and must be treated with specific antivenoms. Unfortunately, these types of antivenoms are scarce in certain areas of the country and are currently reported as an unavailable vital medicine. To address this issue, La Universidad de Antioquia, through its spin-off Tech Life Saving, is leading a project to develop third-generation polyvalent freeze-dried antivenom. The goal is to ensure access to this therapy, especially in rural and dispersed areas. This project aims to evaluate the physicochemical and preclinical parameters (standard quality characteristics) of a lab-scale anti-elapid antivenom batch. The antivenom is challenged against the venoms of several Micrurus species, including M. mipartitus, M. dumerilii, M. ancoralis, M. dissoleucus, M. lemniscatus, M. medemi, M. spixii, M. surinamensis, and M. isozonus, following the standard quality characteristics set by the World Health Organization (WHO). The antivenom demonstrates an appearance consistent with standards, 100% solubility within 4 min and 25 s, an extractable volume of 10.39 mL, a pH of 6.04, an albumin concentration of 0.377 mg/mL (equivalent to 1.22% of total protein), and a protein concentration of 30.97 mg/mL. Importantly, it maintains full integrity of its F(ab')2 fragments and exhibits purity over 98.5%. Furthermore, in mice toxicity evaluations, doses up to 15 mg/mouse show no toxic effects. The antivenom also demonstrates a significant recognition pattern against Micrurus venoms rich in phospholipase A2 (PLA2) content, as observed in M. dumerilii, M. dissoleucus, and M. isozonus. The effective dose 50 (ED50) indicates that a single vial (10 mL) can neutralize 2.33 mg of M. mipartitus venom and 3.99 mg of M. dumerilii venom. This new anti-elapid third-generation polyvalent and freeze-dried antivenom meets the physicochemical parameters set by the WHO and the regulators in Colombia. It demonstrates significant efficacy in neutralizing the venom of the most epidemiologically important Micrurus species in Colombia. Additionally, it recognizes seven other species of Micrurus venom with a higher affinity for venoms exhibiting PLA2 toxins. Fulfilling these parameters represents the first step toward proposing a new pharmacological alternative for treating snakebites in Colombia, particularly in dispersed rural areas, given that this antivenom is formulated as a freeze-dried product.

Effect of dietary garlic (Allium sativum) on the zootechnical performance and health indicators of aquatic animals: A mini-review.

Considerable efforts have been made by modern aquaculture to mitigate the environmental damages caused by its practices while also attempting to improve the quality of the aquatic organisms by promoting alternatives, such as the use of natural products, like garlic (Allium sativum), and instead of chemical agents. Garlic has multiple properties, including antifungal, antibacterial, antiviral, antitoxic, and anticancer effects. In fish, the antiparasitic activity of garlic is one of the most reported effects in the literature, mainly using immersion baths for aquatic organisms. Using garlic also has an antimicrobial effect on the culture of aquatic organisms. Therefore, this review focuses on the impact of garlic on the health and production of aquatic organisms.

In Vitro-Based Production of Virus-Tested Babaco (Vasconcellea x heilbornii, syn. Carica pentagona) in Ecuador: An Integrated Approach to an Endangered Crop.

Babaco (Vasconcellea x heilbornii), a fruit-bearing vegetatively propagated crop native to Ecuador, is appreciated for its distinctive flavor and nutritional properties. The aim of this research was to determine a functional protocol for tissue culture propagation of virus-free babaco plants including in vitro establishment, multiplication, rooting, and acclimation. First, symptomless babaco plants from a single commercial nursery were analyzed for virus detection and cared for using different disinfection treatments in the greenhouse to reduce contamination during the in vitro establishing step, and three cytokinins, 6-(γ,γ-Dimethylallylamino) purine (2IP), 6-Benzylaminopurine (BAP), and Thidiazuron (TDZ), were used to determine the best hormone for multiplication. The best treatment for plant disinfection was the weekly application of copper sulfate at the greenhouse and a laboratory disinfection using ethanol (EtOH) (70%), Clorox (2%), and a solution of povidone iodine (2.5%), with an 80% survival during in vitro plant establishment. TDZ showed a better multiplication rate when compared with other hormones, and 70% of the rooted plants were successfully acclimated at the greenhouse. Generated plants were virus-free when tested against babaco mosaic virus (BabMV) and papaya ringspot virus (PRSV), two of the most important viruses that can affect babaco. An efficient protocol to produce virus-free babaco plants was elaborated with an integrated use of viral diagnostic tools to ensure the production of healthy start material to farmers.

Rotavirus A-specific single-domain antibodies produced in baculovirus-infected insect larvae are protective in vivo.

BACKGROUND: Single-domain antibodies (sdAbs), also known as nanobodies or VHHs, are characterized by high stability and solubility, thus maintaining the affinity and therapeutic value provided by conventional antibodies. Given these properties, VHHs offer a novel alternative to classical antibody approaches. To date, VHHs have been produced mainly in E. coli, yeast, plants and mammalian cells. To apply the single-domain antibodies as a preventive or therapeutic strategy to control rotavirus infections in developing countries (444,000 deaths in children under 5 years of age) has to be minimized their production costs. RESULTS: Here we describe the highly efficient expression of functional VHHs by the Improved Baculovirus Expression System (IBES® technology), which uses a baculovirus expression vector in combination with Trichoplusia ni larvae as living biofactories. Two VHHs, named 3B2 and 2KD1, specific for the inner capsid protein VP6 of Group A rotavirus, were expressed in insect larvae. The IBES® technology achieved very high expression of 3B2 and 2KD1, reaching 2.62% and 3.63% of the total soluble protein obtained from larvae, respectively. These expression levels represent up to 257 mg/L of protein extract after insect processing (1 L extract represents about 125 g of insect biomass or about 375 insect larvae). Larva-derived antibodies were fully functional when tested in vitro and in vivo, neutralizing Group A rotaviruses and protecting offspring mice against rotavirus-induced diarrhea. CONCLUSIONS: Our results open up the possibility of using insects as living biofactories (IBES® technology) for the cost-efficient production of these and other fully functional VHHs to be used for diagnostic or therapeutic purposes, thereby eliminating concerns regarding the use of bacterial or mammalian cells. To the best of our knowledge, this is the first time that insects have been used as living biofactories to produce a VHH molecule.

Acquired Vitelliform-Like Lesion in Uveitis: A case-series.

PURPOSE: To study acquired vitelliform-like lesions (AVLL) and their diagnostic and prognostic values in uveitis. PATIENTS AND METHODS: This was a retrospective case series. The clinical course, diagnostic value, and prognostic significance of AVLL were compared between uveitic patients with AVLL and uveitic patients without AVLL. RESULTS: Twelve patients (21 eyes) with both uveitis and AVLL (study group) and thirteen patients (24 eyes) without AVLL (control group) were included in the study. Macular leakage (p = .005), the presence of vasculitis (p = .01), the presence of active choroiditis (p = .01), and the presence of CME on OCT (p = .008) were significantly higher in the AVLL group compared to the control group. Best-corrected visual acuity was significantly lower at presentation (p < .001) and the last follow-up visit (p = .014) in the AVLL group. CONCLUSION: The presence of acquired vitelliform-like lesion can have both a diagnostic (uveitis as a differential diagnosis) and prognostic value in patients with different types of uveitis.

Epidemiology of Snake Bites Linked with the Antivenoms Production in Colombia 2008-2020: Produced Vials Do Not Meet the Needs.

Introduction: Snakebite envenomation is a public health event of mandatory reporting in Colombia. It is considered a medical emergency in which the government must guarantee antivenom availability. We describe snakebite epidemiological figures in Colombia between 2008 and 2020 and correlate them with antivenom manufacturing figures to determine rate coverage and the need for antivenom. Methods: We performed an ecological study based on secondary official figures from the National Health Institute, the National Institute for Surveillance of Medicines and Foods, the National Administrative Department of Statistics and the Ministry of Health and Social Protection. Absolute and relative frequencies were calculated with 95% confidence intervals, position measurements, dispersion and central tendency. Results: Through our research, we revealed that in the last 13 years (2008-2020), there were an average of 4467 annual snakebite envenomation cases affecting all the departments in Colombia. Antioquia reported the highest number of snakebites with 647 (95% CI 588-706) cases per year. The population incidence per 100,000 inhabitants was 9.5; the highest rates were found in Vaupés at 116.1 and Guaviare at 79.24. During the last seven years (2014-2020) Colombia produced an average of 21,104 antivenom vials per year, while the annual demand for antivenom is estimated at 54,440 units needed to guarantee access. Discussion: Colombia does not produce sufficient vials to cover their needs, and this is why only 74.4% of accidents (out of the 92% not classified as dry bites) were treated, and even 9.7% of the severe accidents did not receive the specific treatment (8% of the victims were classified as dry bites). Figures support the regular antivenom shortages declared by the Ministry of Health and Social Protection in the last 13 years (11 health emergency declarations). New efforts are needed to: 1) boost the production of GMP-based high-quality antivenom, that covers the national needs and is made availability, 2) a better estimation method to calculate the need for antivenom in Colombia, and 3) implementation of production-distribution chains guaranteeing access in remote communities.

Linking toxicity and predation in a venomous arthropod: the case of Tityus fuhrmanni (Scorpiones: Buthidae), a generalist predator scorpion.

BACKGROUND: Scorpions are arachnids that have a generalist diet, which use venom to subdue their prey. The study of their trophic ecology and capture behavior is still limited compared to other organisms, and aspects such as trophic specialization in this group have been little explored. METHODS: In order to determine the relationship between feeding behavior and venom toxicity in the scorpion species Tityus fuhrmanni, 33 specimens were offered prey with different morphologies and defense mechanisms: spiders, cockroaches and crickets. In each of the experiments we recorded the following aspects: acceptance rate, immobilization time and the number of capture attempts. The median lethal dose of T. fuhrmanni venom against the three different types of prey was also evaluated. RESULTS: We found that this species does not have a marked difference in acceptance for any of the evaluated prey, but the number of capture attempts of spiders is higher when compared to the other types of prey. The immobilization time is shorter in spiders compared to other prey and the LD50 was higher for cockroaches. CONCLUSIONS: These results indicate that T. fuhrmanni is a scorpion with a generalist diet, has a venom with a different potency among prey and is capable of discriminating between prey types and employing distinct strategies to subdue them.

Characterization of a Lab-Scale Process to Produce Whole IgG Antivenom Covering Scorpion Stings by Genus Tityus and Centruroides of Colombia.

Scorpion stings are a public health event in Colombia lacking official epidemiological data, and are considered a medical emergency. Despite the two local producers of antivenoms, neither of them is currently manufacturing scorpion antivenoms. We present the characterization of a lab-scale process to produce the first specific scorpion antivenom for Colombia, formulated to cover scorpion stings produced by Tityus pachyurus, Tityus asthenes, Tityus fuhrmanii, Centruroides spp. To do so, rabbits were immunized by subcutaneous injection with each venom using an immunization program of 3 months. After each rabbit reached the required IgG concentration, rabbits were bled, and plasma was separated by decantation under refrigeration. Immunoglobulins were purified from each hyperimmune plasma using a methodology including precipitation with ammonium sulfate, thermocoagulation, and purification through an ultrafiltration process using a ready-to-use and reusable laboratory crossflow tangential cassette with a polyethersulfone membrane. Each hyperimmune plasma was processed by being separated and freeze-dried at the end of the process. Rabbits were able to produce specific IgG antibodies recognizing the respective immunization venom; even an in vitro interspecies cross-recognition was detected. The separation and purification processes allowed us to obtain IgG products without considerable contaminants (except for albumin). The process was characterized, and critical stages were identified.

Diagnostic and Prognostic Roles of Serum Interleukin-6 Levels in Patients with Uveitis.

PURPOSE: To examine the diagnostic and prognostic roles of serum interleukin-6 levels in patients with uveitis. METHODS: This was a retrospective observational case series. Demographic and clinical characteristics were compared between Group One (sixty patients) with normal serum IL-6 levels and Group Two (twenty patients) with high serum interleukin-6 levels. RESULTS: Mean IL-6 level was 1.77 ± 0.97 pg/ml and 10.2 ± 9.7 pg/ml in Group One and Group Two respectively. Age, presence of systemic disease, and mean number of flare-ups were statistically significant (p = .015, p = .000, p = .03, respectively). Multivariate analysis was performed on variables that were statistically significant in univariate analysis and showed that three variables had significant correlation with IL-6 levels in both groups: systemic disease (OR = 10.83, p < .001), Age (OR = 0.95, p = .03) and number of flare-ups (OR = 2.9, p = .02). CONCLUSION: Serum IL-6 levels can provide diagnostic and prognostic information in regard to the course of disease and its treatment.

Improving the Annotation of the Venom Gland Transcriptome of Pamphobeteus verdolaga, Prospecting Novel Bioactive Peptides.

Spider venoms constitute a trove of novel peptides with biotechnological interest. Paucity of next-generation-sequencing (NGS) data generation has led to a description of less than 1% of these peptides. Increasing evidence supports the underestimation of the assembled genes a single transcriptome assembler can predict. Here, the transcriptome of the venom gland of the spider Pamphobeteus verdolaga was re-assembled, using three free access algorithms, Trinity, SOAPdenovo-Trans, and SPAdes, to obtain a more complete annotation. Assembler's performance was evaluated by contig number, N50, read representation on the assembly, and BUSCO's terms retrieval against the arthropod dataset. Out of all the assembled sequences with all software, 39.26% were common between the three assemblers, and 27.88% were uniquely assembled by Trinity, while 27.65% were uniquely assembled by SPAdes. The non-redundant merging of all three assemblies' output permitted the annotation of 9232 sequences, which was 23% more when compared to each software and 28% more when compared to the previous P. verdolaga annotation; moreover, the description of 65 novel theraphotoxins was possible. In the generation of data for non-model organisms, as well as in the search for novel peptides with biotechnological interest, it is highly recommended to employ at least two different transcriptome assemblers.

A specialized tyrosine-based endocytosis signal in MR1 controls antigen presentation to MAIT cells.

MR1 is a highly conserved microbial immune-detection system in mammals. It captures vitamin B-related metabolite antigens from diverse microbes and presents them at the cell surface to stimulate MR1-restricted lymphocytes including mucosal-associated invariant T (MAIT) cells. MR1 presentation and MAIT cell recognition mediate homeostasis through host defense and tissue repair. The cellular mechanisms regulating MR1 cell surface expression are critical to its function and MAIT cell recognition, yet they are poorly defined. Here, we report that human MR1 is equipped with a tyrosine-based motif in its cytoplasmic domain that mediates low affinity binding with the endocytic adaptor protein 2 (AP2) complex. This interaction controls the kinetics of MR1 internalization from the cell surface and minimizes recycling. We propose MR1 uses AP2 endocytosis to define the duration of antigen presentation to MAIT cells and the detection of a microbial metabolic signature by the immune system.