Natural history of nonhuman primates after conjunctival exposure to Ebola virus

Transmission of Ebola virus (EBOV) primarily occurs via contact exposure of mucosal surfaces with infected body fluids. Historically, nonhuman primate (NHP) challenge studies have employed intramuscular or small particle aerosol exposure, which are uniformly lethal routes of infection, but mimic worst-case scenarios such as a needlestick. When exposed by more likely routes of natural infection, limited NHP studies have shown delayed onset of disease and reduced mortality. Here we performed a series of systematic natural history studies in cynomolgus macaques with a range of conjunctival exposure doses. Challenge with 10,000 plaque forming units (PFU) of EBOV was uniformly lethal, whereas 5/6 subjects survived low and moderate dose challenges (100 or 500 PFU). Conjunctival challenge resulted in a protracted time-to death. Asymptomatic disease was observed in survivors with limited detection of EBOV replication. Inconsistent seropositivity in survivors may suggest physical or natural immunological barriers are sufficient to prevent widespread viral dissemination.

Third time’s a charm: reviewing the advertisement call of Gabohyla pauloalvini (Anura: Hylidae: Scinaxinae), an endemic species from Brazil’ Atlantic Forest

The Neotropical tribe Sphaenorhynchini is composed of 15 recognized species commonly named as “lime treefrogs”. Gabohyla pauloalvini occurs in Atlantic Forest lowlands through the states of Bahia and Espírito Santo, Brazil. Based on field observation, literature review, and evaluation of audio files, we conclude that previous bioacoustic descriptions were erroneously assigned to G. pauloalvini. Here, we describe for the first time the advertisement call of G. pauloalvini from two disjunct populations. In addition, we provide new distribution records and an updated map for this species. The advertisement call of G. pauloalvini is composed of 1–5 closely spaced notes, with duration of 0.016–1.976 s, inter-note intervals of 0.340–1.25 s, and an average dominant frequency (= fundamental frequency) of 4966.0 Hz. Harmonics are visible in the spectrogram. Three new populations of G. pauloalvini have been recorded and extended the distribution by 60 km south. Nevertheless, G. pauloalvini is still known only from few localities. We highlight the importance of depositing audio recordings and specimens in scientific collections to promote systematics and natural history studies.

The LORIS MyeliNeuroGene rare disease database for natural history studies and clinical trial readiness

Background Rare diseases are estimated to affect 150–350 million people worldwide. With advances in next generation sequencing, the number of known disease-causing genes has increased significantly, opening the door for therapy development. Rare disease research has therefore pivoted from gene discovery to the exploration of potential therapies. With impending clinical trials on the horizon, researchers are in urgent need of natural history studies to help them identify surrogate markers, validate outcome measures, define historical control patients, and design therapeutic trials. Results We customized a browser-accessible multi-modal (e.g. genetics, imaging, behavioral, patient-determined outcomes) database to increase cohort sizes, identify surrogate markers, and foster international collaborations. Ninety data entry forms were developed including family, perinatal, developmental history, clinical examinations, diagnostic investigations, neurological evaluations (i.e. spasticity, dystonia, ataxia, etc.), disability measures, parental stress, and quality of life. A customizable clinical letter generator was created to assist in continuity of patient care. Conclusions Small cohorts and underpowered studies are a major challenge for rare disease research. This online, rare disease database will be accessible from all over the world, making it easier to share and disseminate data. We have outlined the methodology to become Title 21 Code of Federal Regulations Part 11 Compliant, which is a requirement to use electronic records as historical controls in clinical trials in the United States. Food and Drug Administration compliant databases will be life-changing for patients and families when historical control data is used for emerging clinical trials. Future work will leverage these tools to delineate the natural history of several rare diseases and we are confident that this database will be used on a larger scale to improve care for patients affected with rare diseases.

Natural history notes on worker size, colony size, and nest structure of Azteca muelleri Emery, 1893 (Hymenoptera: Formicidae) in Cecropia glaziovii (Rosales: Urticaceae) from the Atlantic Forest

Mutualistic association between Azteca Forel, 1878 ants and Cecropia Loefl. plants are one of the most studied interactions in Neotropics, however, natural history studies of Azteca species still poorly investigated due to the great effort required to conduct detailed descriptive studies. Here, we describe biological aspects of Azteca muelleri Emery, 1893 nesting in Cecropia glaziovii Snethl. in a fragment of Atlantic Forest, addressing (a) colony size; (b) nest distribution on the tree; and (c) worker and queen morphometrics. We collected two C. glaziovii saplings and counted characteristics of the nests and plants. We randomly selected 140 workers to measure and to determine whether intraspecific polymorphism occurs. Workers, immatures, and mealybugs were present in all hollow internodes of plant, and a queen was found. We found isometric morphological variation in A. muelleri. Our study provides new data to understand the biology of A. muelleri nesting in C. glaziovii, one of the most species-rich genera of arboreal ants known for the neotropics.

Deliberate paradigm shift in research in rare neurodevelopmental disorders

Diagnosis and management of children with rare neurodevelopmental disorders (RNDDs) are complex. The COVID-19 pandemic has forced us to rethink the research activities critical to improve our understanding and treatment of RNDDs, such as creating large international registries and developing natural history studies. In this communication, we reflect on our latest effort in conducting research remotely while providing support, education and feedback to families affected by a specific RNDD. Specifically, we advocate for a deliberate paradigm shift towards virtual family meetings as ecological platforms to enroll and assess individuals with rare disorders. Herein, we demonstrate that such a shift is crucial to substantially increasing geographical and age range coverage, which are essential for capturing the phenotypic variations in RNDDs. Finally, we call on the community to invest in building integrated technological platforms necessary for effective remote research activities, through standardization, collaboration and training.

Molecular systematic investigation of Philippine puddle frogs (Anura: Dicroglossidae: Occidozyga Kuhl and Van Hasselt, 1822) reveals new candidate species and a novel pattern of species dyads

Focusing on the phylogenetic relationships of puddle frog populations spanning the biogeographic interface between Sundaland (Borneo) and the Philippines, we demonstrate, for the first time, a widespread geographic pattern involving the existence of multiple divergent and co-distributed (sympatric) evolutionary lineages, most of which are not each other’s closest relatives, and all of which we interpret as probable distinct species. This pattern of co-occurrence in the form of pairs of ecologically distinct puddle frog forms (dyads), prevails throughout northern Borneo, Palawan, Tawi-Tawi, the Sulu Archipelago, and western Mindanao (Zamboanga). Previously obscured by outdated taxonomy and logistical, legal, and security obstacles to field-based natural history studies, this pattern has remained hidden from biogeographers and amphibian biologists by an uncontested proposal that Philippine Occidozyga laevis is a single, “widespread,” and “highly variable” species. In this paper we use an integrative synthesis of new genetic data, organismal phenotypic data, historical literature reports, and ecological observations to elucidate an interesting and potentially widespread pattern of puddle frog species coexistence at the Sundaland–Philippine biogeographic interface. Calling attention to this pattern opens promising possibilities for future research aimed at understanding the scope of this dyads pattern, and whether it extends to the more northern reaches of the Philippines. On either side of Huxley’s and Wallace’s lines, data suggest that the majority of puddle frog dyads at a given locality are not each other’s closest relatives (are more distantly related, or non-monophyletic) and, thus, assembled ecologically, likely coexisting now as a result of their ecological tendencies toward distinct microhabitats (warmer stagnant pools in open areas, versus cool, flowing streams enclosed in forest). If these pairs of species types are determined to be the geographic norm among the more isolated, central, and northern, Philippine faunas, an obvious question will be whether they have evolved into dual ecological forms, possibly in response to ecological opportunity and/or reduced competition. KEYWORDS: biogeography, taxonomy, microhabitat, cryptic species

Evidence for antibody as a protective correlate for COVID-19 vaccines

Though eleven novel COVID-19 vaccines have demonstrated efficacy, additional affordable, scalable, and deliverable vaccines are needed to meet unprecedented global demand. With placebo-controlled efficacy trials becoming infeasible due to the roll out of licensed vaccines, a correlate of protection is urgently needed to provide a path for regulatory approval of novel vaccines. To assess whether antibody titers may reasonably predict efficacy, we evaluated the relationship between efficacy and in vitro neutralizing and binding antibodies of 7 vaccines for which sufficient data have been generated. Once calibrated to titers of human convalescent sera reported in each study, a robust correlation was seen between neutralizing titer and efficacy (ρ= 0.79) and binding antibody titer and efficacy (ρ = 0.93), despite geographically diverse study populations subject to different forces of infection and circulating variants, and use of different endpoints, assays, convalescent sera panels and manufacturing platforms. This correlation is strengthened by substituting post-hoc analyses for efficacy against the ancestral strain (D614G), where available. Together with an accumulating body of evidence from natural history studies and animal models, these results support the use of post-immunization antibody titers as the basis for establishing a correlate of protection for COVID-19 vaccines.

Spontaneous improvement of carbohydrate-deficient transferrin in PMM2-CDG without mannose observed in CDG natural history study

A recent report on long-term dietary mannose supplementation in phosphomannomutase 2 deficiency (PMM2-CDG) claimed improved glycosylation and called for double-blind randomized study of the dietary supplement in PMM2-CDG patients. A lack of efficacy of short-term mannose supplementation in multiple prior reports challenge this study’s conclusions. Additionally, some CDG types have previously been reported to demonstrate spontaneous improvement in glycosylated biomarkers, including transferrin. We have likewise observed improvements in transferrin glycosylation without mannose supplementation. This observation questions the reliability of transferrin as a therapeutic outcome measure in clinical trials for PMM2-CDG. We are concerned that renewed focus on mannose therapy in PMM2-CDG will detract from clinical trials of more promising therapies. Approaches to increase efficiency of clinical trials and ultimately improve patients’ lives requires prospective natural history studies and identification of reliable biomarkers linked to clinical outcomes in CDG. Collaborations with patients and families are essential to identifying meaningful study outcomes.