To what extent can we predict how evolution occurs? Do genetic architectures and developmental processes canalize the evolution of similar outcomes in a predictable manner? Or do historical ...contingencies impose alternative pathways to answer the same challenge? Examples of Müllerian mimicry between distantly related butterfly species provide natural replicates of evolution, allowing us to test whether identical wing patterns followed parallel or novel trajectories. Here, we explore the role that the signaling ligand WntA plays in generating mimetic wing patterns in Heliconius butterflies, a group with extraordinary mimicry-related wing pattern diversity. The radiation is relatively young, and numerous cases of wing pattern mimicry have evolved within the last 2.5–4.5 Ma. WntA is an important target of natural selection and is one of four major effect loci that underlie much of the pattern variation in the group. We used CRISPR/Cas9 targeted mutagenesis to generate WntA-deficient wings in 12 species and a further 10 intraspecific variants, including three co-mimetic pairs. In all tested butterflies, WntA knockouts affect pattern broadly and cause a shift among every possible scale cell type. Interestingly, the co-mimics lacking WntA were very different, suggesting that the gene networks that pattern a wing have diverged considerably among different lineages. Thus, although natural selection channeled phenotypic convergence, divergent developmental contexts between the two major Heliconius lineages opened different developmental routes to evolve resemblance. Consequently, even under very deterministic evolutionary scenarios, our results underscore a surprising unpredictability in the developmental paths underlying convergence in a recent radiation.
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•Mimicry in Heliconius is achieved through divergent developmental networks•WntA is a major patterning gene that is used differently in co-mimics•Regulation of WntA expression and its interaction with other genes shape diversity•WntA modulates wing-scale cell identity
Concha et al. use CRISPR/Cas9 genome editing to knock out a major wing patterning gene, WntA, in mimetic species of Heliconius butterflies and report that WntA is used in divergent gene regulatory networks in co-mimics and that resemblance is achieved through differential expression of WntA and its interaction with the specific genetic background.
OBJECTIVES/GOALS: To assess the impact of FLTCs on CTR on S and F from health professions and basic science academic programs island wide in Puerto Rico. Cycles supported by the Title V Cooperative ...Project at University of Puerto Rico-Medical Sciences Campus (UPRMSC) and Universidad Central del Caribe (UCC)(Title V). METHODS/STUDY POPULATION: After offering FLTCs in CTR to S and F from UPRMSC and UCC, Title V expanded it to S and F from other institutions island wide in PR. These FLTCs were offered the 2
nd
semester of 2018 and consisted of 20 hours of interdisciplinary sessions in: introduction to and definition of CTR; preparation of a CTR-presentation; how to interview/share a presentation of a CT researcher and to prepare a research question in CTR. To assess the knowledge of S and F in the above-mentioned skills and their continuation in the 2
nd
level of CTR training, surveys were administered: pre-test, at the beginning, post-test, sometime during the FLTCs, and satisfaction at the end of the FLTCs. RESULTS/ANTICIPATED RESULTS: Fifty eight (58) S/F from UPRMSC, UCC and 7 other institutions participated. Forty two (42,72%) answered a pre-test and 31/42 (74%) completed the post-test. Results showed that S/F: who correctly defined CTR increased from 7% to 77 %; their ability to identify a CT researcher increased from 10% to 83%. Fifty five percent (55 %) (21/38) S/F that were certified in the FLTCs, answered the satisfaction survey. One hundred percent (100%) indicated that the materials offered contributed in the identification of a CT researcher and a topic in CTR; 100% answered that the FLTCs contributed higher knowledge in and provided new skills in CTR. Moreover, 31/38 (82%) S/F started the 2
nd
level of training. DISCUSSION/SIGNIFICANCE OF IMPACT: The FLTCs were successful in increasing S/F knowledge of CTR and to further engage in 2nd level of trainings. Title V impact extended island wide, increasing the diversity of represented health professions and science fields among participants. The interventions were deemed to be of high quality.
OBJECTIVES/SPECIFIC AIMS: The Title V Cooperative Project of the UPR-MSC and UCC has demonstrated that educational interventions in CTR are very effective in fulfilling the objective of promoting ...awareness, stimulate interest and increase the knowledge, skills and opportunities, to US, GS and F (participants) in CTR. METHODS/STUDY POPULATION: The training sessions (TS) offered through the Title V initiative have become an engine for the involvement in CTR for participants from higher education institutions island-wide. TS consisted of cycles –level 1 and 2–: Research Education Towards Opportunities (RETO,I,II) and Mentorship Offering Training Opportunities for Research (MOTOR,I,II), ending in the formation of the Clinical and Translational Mentoring Teams (CTMT)s, in which participants, paired by their research interests, were mentored by a well-established CT researchers in their research project, to be developed in the Intensive Development and Experiences in Advancement of Research and Increased Opportunities (IDEARIO). RESULTS/ANTICIPATED RESULTS: Up to date, 4 TS-level 1 and 2 TS-level 2 were offered. Eighty (80) participants completed level 1, distributed: 42 (52.5%) US in RETO, 21 (26.25%) GS and 17 (21.25%) F in MOTOR and 17 participants completed level 2, distributed: 4 (23.52%) US in RETO, 6 (25.29%) GS and 7 (41.17%) F in MOTOR. From which, 15, with 8 CT researchers, formed 5 CTMTs in different research areas – cardio, neuro, liver, renal, Zika–. DISCUSSION/SIGNIFICANCE OF IMPACT: US, GS and F were integrated in the active process throughout educational levels for their development in CTR.
Butterflies have become prominent models for studying the evolution and development of phenotypic variation. In Heliconius, extraordinary within species divergence and between species convergence in ...wing color patterns has driven decades of comparative genetic studies. However, connecting genetic patterns of diversification to the molecular mechanisms of adaptation has remained elusive. Recent studies are bridging this gap between genome and function and have driven substantial advances in deciphering the genetic architecture of diversification in Heliconius. While only a handful of large-effect genes were initially identified in the diversification of Heliconius color patterns, recent experiments have begun to unravel the underlying gene regulatory networks and how these have evolved. These results reveal an evolutionary story of many interacting loci and partly independent genetic architectures that underlie convergent evolution.
ABSTRACT IMPACT: This presentation highlights an integrated curriculum in CTR and a scientific entrepreneurship approach to entice and support students and faculty in HP programs into CTR and SE thus ...expanding the pool of new minority CTR researchers. OBJECTIVES/GOALS: To present the TVMSC as a hub for trainings, mentoring programs, courses, entrepreneurship and support activities for health professionals(HP) and HP students :graduate (GS) and UgS and UgF. Responding to the need for CTR minority researchers, in a virtual setting due to COVID-19 crisis. METHODS/STUDY POPULATION: TVMSC will offer an educational program based in the Center for Research,Entrepreneurship and Scientific Collaboration (CRESCO) with on line courses and workshops in CTR and SE, for HP and students and a continued education curriculum for HP and clinician scientists toward a certification in CTR. Two hands-on experiences: a) a Pilot project program(PiP) with teams composed of an F, that previously completed training cycles and a research experience from a previous project in CTR as PI, with a research mentor and students or an established researcher as a PI with UgS and UgF, and b) participation in a SE team which will engage in training and submission of an SE project proposal. RESULTS/ANTICIPATED RESULTS: By the end of the five-year period the project will have had 200 UgS, 200 GS and 200 F that received online assistance in CTR skills, statistics and SE; 48 UgS and 48 GS with the skills in SEFL. In curricular development the project expects to have 6 online tutorials created, one FLSE online course and 18 modules in CTR content areas available for continued education of HP. Certifications in CTR will be completed by 160F/HPs. The expected participation in CTR on-hands experiences is 32 F, 64 students and 32 established researchers. PiP teams will publish at least 8 scientific papers and SEFL teams will submit at least 5 SE project proposals and 100% increase in CRESCO web based resources DISCUSSION/SIGNIFICANCE OF FINDINGS: This Project and its expected results will provide students and faculty members island-wide with the knowledge, skills and experiences in CTR with IE approach to foster the expansion of a cadre of Hispanic minority CTR researchers in direct benefit of the health of the people of Puerto Rico.
OBJECTIVES/GOALS: Research Education Towards Opportunities (RETO) Mentoring Offering Training Opportunities for Research (MOTOR) 1 – 2 and the elective courses (INTD 5998/ MDCL 101) in CTR of Title V ...Coop were designed to provide the participants from higher education institution (HEI) in Puerto Rico (PR), interdisciplinary – interprofesional knowledge in CTR. METHODS/STUDY POPULATION: Since April 2017, Research Education Towards Opportunities (RETO) and Mentoring Offering Training Opportunities for Research (MOTOR) 1 - 2 trainings were offered as part of the Title V Coop. In addition, since January 2020, as part of the institutionalization of the trainings in CTR, two elective courses (INTD 5998 and MDCL 101) were created-offered. The trainings/courses present the main concepts underlying CTR performance through lectures, workshops and presentations, in hybrid modalities, as well as the services-resources of the Center Research Education and Science Commnunication Opportunities (CRESCO). These programs have given students (undergraduate and graduate) and faculty the opportunity to get started in CTR and to integrate in Clinical and Translational Mentoring Teams (CTMT). RESULTS/ANTICIPATED RESULTS: Eight (8) cycles of RETO-MOTOR 1 and seven (7) cycles of RETO-MOTOR 2; two sessions of INTD 5998 and one session of MDCL 101 were offered. The RETO-MOTOR 1 training was completed by 219 participants and RETO-MOTOR 2 by 130 participants. The INTD 5998 course was completed by 22 students and the MDCL 101 course by 18 students. A total of 389 participants have been initiated in the CTR. Of the trainings, 90% indicated that the knowledge acquired in CTR was invaluable, 85% understand that the most significant achievement, as students, was present at a scientific conference, and 100% indicated interest in continuing to do CTR. Of the courses, 100% indicated that they were a good learning experience, helped them increase their knowledge in CTR, met their expectations and would recommend other students to take the course. DISCUSSION/SIGNIFICANCE: The RETO-MOTOR 1, RETO-MOTOR 2 trainings and CTR courses provide a based of research knowledge and valuable interprofessional experience for those who whish to start in the clinical and translational research. The Title V Cooperative Project provides this opportunity to undergraduate and graduate students such as faculty of HEI in PR.
High level of novelty under the hood of convergent evolution Van Belleghem, Steven M; Ruggieri, Angelo A; Concha, Carolina ...
Science (American Association for the Advancement of Science),
03/2023, Letnik:
379, Številka:
6636
Journal Article
Recenzirano
Little is known about the extent to which species use homologous regulatory architectures to achieve phenotypic convergence. By characterizing chromatin accessibility and gene expression in ...developing wing tissues, we compared the regulatory architecture of convergence between a pair of mimetic butterfly species. Although a handful of color pattern genes are known to be involved in their convergence, our data suggest that different mutational paths underlie the integration of these genes into wing pattern development. This is supported by a large fraction of accessible chromatin being exclusive to each species, including the de novo lineage-specific evolution of a modular
enhancer. These findings may be explained by a high level of developmental drift and evolutionary contingency that occurs during the independent evolution of mimicry.
Platelets play a vital role in hemostasis and inflammation. The membrane receptor TREM-like transcript-1 (TLT-1) is involved in platelet aggregation, bleeding, and inflammation, and it is localized ...in the α-granules of platelets. Upon platelet activation, TLT-1 is released from α-granules both in its transmembrane form and as a soluble fragment (sTLT-1). Higher levels of sTLT-1 have been detected in the plasma of patients with acute inflammation or sepsis, suggesting an important role for TLT-1 during inflammation. However, the roles of TLT-1 in hemostasis and inflammation are not well understood. We are developing the mouse model of TLT-1 to mechanistically test clinical associations of TLT-1 in health and disease. To facilitate our studies, monoclonal murine TLT-1 (mTLT-1) antibodies were produced by the immunization of a rabbit using the negatively charged region of the mTLT-1 extracellular domain
PPVPGPREGEEAEDEK
. In the present study, we demonstrate that two selected clones, 4.6 and 4.8, are suitable for the detection of mTLT-1 by western blot, immunoprecipitation, immunofluorescent staining, flow cytometry and inhibit platelet aggregation in aggregometry assays. In addition, we found that the topical administration of clone 4.8 delayed the wound healing process in an experimental burn model. These results suggest that TLT-1 plays an important role in wound healing and because both clones specifically detect mTLT-1, they are suitable to further develop TLT-1 based models of inflammation and hemostasis in vivo.
Vancomycin is the mainstay antibiotic used in hemodialysis group due to high prevalence of methicillin resistant Staphylococcus Aureus. For years regimens of vancomycin in high flux hemodialysis ...(HFHD) patients were designed to achieve a pre-dialysis vancomycin concentration between 5-20 ug/mL. Recent guidelines increased the recommended pre-dialysis level to 15-20 ug/ml for health care associated infections, bacteremia and osteomyelitis. The purpose of this study was to determine if the loading dose (LD) before HFHD and the maintenance dose (MD) of vancomycin achieved a pre-dialysis concentration between 15-20 ug/ml on HFHD in-patients with a suspected infection. The second purpose was to predict an adequate vancomycin dosage to achieve the new recommended levels.
An observational prospective study on hospitalized adult patients on HFHD with evidence of infection treated with 1 gm LD of vancomycin and 500 mg MD. Plasma levels of vancomycin were measured before each HFHD for three consecutive times. Age, gender, weight at admission, blood flow rate, dialyzer flow rate, type of filter and HFHD length were evaluated.
Twenty-one patients met the inclusion criteria. All of them were treated with 1 gm LD of vancomycin and 500 mg MD protocol. The mean pre-dialysis concentration #1 was 10.8 ug/mL. The mean pre-dialysis concentration #2 was 13 ug/mL, and the mean pre-dialysis concentration #3 was 12 ug/mL. Only 36% of HFHD sessions achieved an adequate vancomycin level. A liner regression analysis predicted that a loading dose of 23 mg/kg LD and 8 mg/kg MD achieved the recommended pre-dialysis vancomycin concentration.
Current dose regimen of 1 gm LD and 500 mg MD of Vancomycin are not adequate to achieve recommended pre-dialysis level of 15-20 ug/mL for health care associated infections, bacteremia and osteomyelitis in most patients on HFHD. Based on our statistical analysis, we recommended that 23 mg/kg of LD and 8 mg/kg of MD would achieve an adequate vancomycin level.
Background and purpose
Optic neuritis (ON) is often the initial symptom of neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein‐associated disease (MOGAD). We aimed ...to compare the frequency and pattern of chiasmatic lesions in MOGAD‐related ON (MOGAD‐ON) and NMOSD‐related ON (NMOSD‐ON) using conventional brain imaging (magnetic resonance imaging MRI) in Latin America (LATAM).
Methods
We reviewed the medical records and brain MRI (≤30 days from ON onset) of patients with a first event of MOGAD‐ON and NMOSD‐ON. Patients from Argentina (n = 72), Chile (n = 21), Ecuador (n = 31), Brazil (n = 30), Venezuela (n = 10) and Mexico (n = 82) were included. Antibody status was tested using a cell‐based assay. Demographic, clinical, imaging and prognostic (as measured by the Visual Functional System Score VFSS of the Expanded Disability Status Scale) data were compared.
Results
A total of 246 patients (208 NMOSD and 38 MOGAD) were included. No differences were found in gender and ethnicity between the groups. We observed chiasmatic lesions in 66/208 (31.7%) NMOSD‐ON and in 5/38 (13.1%) MOGAD‐ON patients (p = 0.01). Of these patients with chiasmatic lesions, 54/66 (81.8%) and 4/5 had associated longitudinally extensive optic nerve lesions, 45/66 (68%) and 4/5 had bilateral lesions, and 31/66 (47%) and 4/5 showed gadolinium‐enhancing chiasmatic lesions, respectively. A positive correlation was observed between VFSS and presence of bilateral (r = 0,28, p < 0.0001), chiasmatic (r = 0.27, p = 0.0001) and longitudinally extensive lesions (r = 0,25, p = 0.0009) in the NMOSD‐ON group, but no correlations were observed in the MOGAD‐ON group.
Conclusions
Chiasmatic lesions were significantly more common in NMOSD than in MOGAD during an ON attack in this LATAM cohort. Further studies are needed to assess the generalizability of these results.
We reviewed the medical records and brain magnetic resonance imaging (≤30 days from optic neuritis ON onset) of patients with a first event of myelin oligodendrocyte glycoprotein‐associated disease‐related ON (MOGAD‐ON; n = 38) and neuromyelitis optica spectrum disorder‐related ON (NMOSD‐ON; n = 208) from Latin America. We observed chiasmatic lesions in 66/208 patients (31.7%) with NMOSD‐ON and in 5/38 (13.1%) with MOGAD‐ON (p = 0.01). Of these, 54/66 and 4/5 had associated longitudinally extensive optic nerve lesions, 45/66 and 4/5 had bilateral lesions, and 31/66 and 4/5 had gadolinium‐enhancing chiasmatic lesions, respectively. A positive correlation was observed between Visual Functional System Score and the presence of bilateral (r = 0.28, p < 0.0001), chiasmatic (r = 0.27, p = 0.0001) and longitudinally extensive optic nerve lesions (r = 0.25, p = 0.0009) in the NMOSD‐ON group, but no correlations were observed in the MOGAD‐ON group.
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