The rockefeller university

The vocal behavior of human infants undergoes marked changes across their first year while becoming increasingly speech-like. Conversely, vocal development in nonhuman primates has been assumed to be largely predetermined and completed within the first postnatal months. Contradicting this assumption, we found a dichotomy between the development of call features and vocal sequences in marmoset monkeys, suggestive of a role for experience. While changes in call features were related to physical maturation, sequences of and transitions between calls remained flexible until adulthood. As in humans, marmoset vocal behavior developed in stages correlated with motor and social development stages. These findings are evidence for a prolonged phase of plasticity during marmoset vocal development, a crucial primate evolutionary preadaptation for the emergence of vocal learning and speech.

X-linked severe combined immunodeficiency (X-SCID) is caused by mutations of IL2RG, the gene encoding the interleukin common gamma chain (IL-2R gamma or gamma c) of cytokine receptors for interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Hypomorphic mutations of IL2RG may cause combined immunodeficiencies with atypical clinical and immunological presentations. Here, we report a clinical, immunological, and functional characterization of a missense mutation in exon 1 (c.115G>A; p. Asp39Asn) of IL2RG in a 7-year-old boy. The patient suffered from recurrent sinopulmonary infections and refractory eczema. His total lymphocyte counts have remained normal despite skewed T cell subsets, with a pronounced serum IgE elevation. Surface expression of IL-2R gamma was reduced on his lymphocytes. Signal transducer and activator of transcription (STAT) phosphorylation in response to IL-2, IL-4, and IL-7 showed a partially preserved receptor function. T-cell proliferation in response to mitogens and anti-CD3/anti-CD28 monoclonal antibodies was significantly reduced. Further analysis revealed a decreased percentage of CD4(+) T cells capable of secreting IFN-gamma, but not IL-4 or IL-17. Studies on the functional consequences of IL-2R gamma variants are important to get more insight into the pathogenesis of atypical phenotypes which may lay the ground for novel therapeutic strategies.

Studying how novel phenotypes originate and evolve is fundamental to the field of evolutionary biology as it allows us to understand how organismal diversity is generated and maintained. However, determining the basis of novel phenotypes is challenging as it involves orchestrated changes at multiple biological levels. Here, we aim to overcome this challenge by using a comparative species framework combining behavioral, gene expression, and genomic analyses to understand the evolutionary novel egg-laying substrate-choice behavior of the invasive pest species Drosophila suzukii. First, we used egg-laying behavioral assays to understand the evolution of ripe fruit oviposition preference in D. suzukii compared with closely related species D. subpulchrella and D. biarmipes as well as D. melanogaster. We show that D. subpulchrella and D. biarmipes lay eggs on both ripe and rotten fruits, suggesting that the transition to ripe fruit preference was gradual. Second, using two-choice oviposition assays, we studied how D. suzukii, D. subpulchrella, D. biarmipes, and D. melanogaster differentially process key sensory cues distinguishing ripe from rotten fruit during egg-laying. We found that D. suzukii's preference for ripe fruit is in part mediated through a species-specific preference for stiff substrates. Last, we sequenced and annotated a high-quality genome for D. subpulchrella. Using comparative genomic approaches, we identified candidate genes involved in D. suzukii's ability to seek out and target ripe fruits. Our results provide detail to the stepwise evolution of pest activity in D. suzukii, indicating important cues used by this species when finding a host, and the molecular mechanisms potentially underlying their adaptation to a new ecological niche.

The contribution of bacterial infection to chronic low back pain and its treatment with antibiotics have generated considerable controversy in literature. If efficacious, antibiotics have the potential to transform the treatment of chronic low back pain in a significant subset of patients. Some microbiology studies of disc tissue from patients with CLBP have shown that bacteria are present, most likely due to infection, while others conclude they are absent or if found, it is due to surgical contamination. Clinical studies testing the efficacy of oral antibiotics to treat CLBP have either shown that the treatment is efficacious leading to significantly reduced pain and disability or that their effect is modest and not clinically significant. Critical review of the literature on CLBP, bacterial infection and treatment with antibiotics identified five well-designed and executed microbiology studies characterizing bacteria in disc samples that demonstrate that bacteria do infect herniated disc tissue, but that the bacterial burden is low and may be below the limits of detection in some studies. Two randomized, controlled clinical trials evaluating oral antibiotics in patients with CLBP indicate that for certain subsets of patients, the reduction in pain and disability achieved with antibiotic therapy may be significant. In patients for whom other therapies have failed, and who might otherwise progress to disc replacement or fusion surgery, antibiotic therapy may well be an attractive option to reduce the individual suffering associated with this debilitating condition. Additional clinical research is recommended to refine the selection of patients with CLBP caused or complicated by bacterial infection and most likely to respond to antibiotics, to optimize antibiotic therapy to maximize patient benefit, to minimize and manage side effects, and to address legitimate concerns about antibiotic stewardship. (C) 2021 The Author(s). Published by Elsevier Inc.

Vocal learning is the ability to imitate and modify sounds through auditory experience, a rare trait found in only a few lineages of mammals and birds. It is a critical component of human spoken language, allowing us to verbally transmit speech repertoires and knowledge across generations. In many vocal learning species, the vocal learning trait is sexually dimorphic, where it is either limited to males or present in both sexes to different degrees. In humans, recent findings have revealed subtle sexual dimorphism in vocal learning/spoken language brain regions and some associated disorders. For songbirds, where the neural mechanisms of vocal learning have been well studied, vocal learning appears to have been present in both sexes at the origin of the lineage and was then independently lost in females of some subsequent lineages. This loss is associated with an interplay between sex chromosomes and sex steroid hormones. Even in species with little dimorphism, like humans, sex chromosomes and hormones still have some influence on learned vocalizations. Here we present a brief synthesis of these studies, in the context of sex determination broadly, and identify areas of needed investigation to further understand how sex chromosomes and sex steroid hormones help establish sexually dimorphic neural structures for vocal learning.

Surface epithelia provide a critical barrier to the outside world. Upon a barrier breach, resident epithelial and immune cells coordinate efforts to control infections and heal tissue damage. Inflammation can etch lasting marks within tissues, altering features such as scope and quality of future responses. By remembering inflammatory experiences, tissues are better equipped to quickly and robustly respond to barrier breaches. Alarmingly, in disease states, memory may fuel the inflammatory fire. Here, we review the cellular communication networks in barrier tissues and the integration between tissue-resident and recruited immune cells and tissue stem cells underlying tissue adaptation to environmental stress.

Mendelian susceptibility to mycobacterial disease (MSMD) is a rare group of genetic disorders characterized by infections with weakly virulent environmental mycobacteria (EM) or Mycobacterium bovis bacillus Calmette-Guerin (BCG). Herein, we described the case of a 4.5-year-old boy with protein-losing enteropathy, lymphoproliferation, and candidiasis, who was found to have disseminated Mycobacterium simiae infection. A homozygous mutation in the IL12B gene, c.527_528delCT (p.S176Cfs*12) was identified, responsible for the complete IL-12p40 deficiency. He was resistant to anti-mycobacterial treatment and finally died due to sepsis-related complications.

At the start of the pandemic caused by the novel coronavirus (SARS-CoV-2), the Gaucher disease community anticipated that infection with this emerging viral pathogen would be associated with high morbidity and mortality in individuals with this chronic metabolic disorder. Surprisingly, however, preliminary studies suggest that Gaucher disease does not confer a higher risk of severe, life-threatening effects of SARS-CoV-2 infection, and no severe cases have been reported in large cohorts of patients from the United States, Europe and Israel. It is thought that the accumulation of glucocerebroside in the cells of Gaucher patients may promote immune tolerance rather than inflammation on exposure to SARS-CoV-2. We review here the current concepts of Gaucher disease and SARS-CoV-2 infection, focusing particularly on general prevention and vaccination. We also discuss the susceptibility to COVID-19 of patients with inborn errors of type 1 interferon (IFN alpha and IFN omega) immunity.

Recent advances in human naive pluripotent stem cell culture have demonstrated their ability to generate trophectoderm and descendant trophoblast cell types. Moreover, the same cells when cultured in three-dimensional configurations self-organize to generate blastocyst-like structures called blastoids. These discoveries represent a major step forward in modeling early human embryonic development.