Beyond Critical Period Learning: Striatal FoxP2 Affects the Active Maintenance of Learned Vocalizations in Adulthood.

In humans, mutations in the transcription factor forkhead box P2 (FOXP2) result in language disorders associated with altered striatal structure. Like speech, birdsong is learned through social interactions during maturational critical periods, and it relies on auditory feedback during initial learning and on-going maintenance. Hearing loss causes learned vocalizations to deteriorate in adult humans and songbirds. In the adult songbird brain, most FoxP2-enriched regions (e.g., cortex, thalamus) show a static expression level, but in the striatal song control nucleus, area X, FoxP2 is regulated by singing and social context: when juveniles and adults sing alone, its levels drop, and songs are more variable. When males sing to females, FoxP2 levels remain high, and songs are relatively stable: this "on-line" regulation implicates FoxP2 in ongoing vocal processes, but its role in the auditory-based maintenance of learned vocalization has not been examined. To test this, we overexpressed FoxP2 in both hearing and deafened adult zebra finches and assessed effects on song sung alone versus songs directed to females. In intact birds singing alone, no changes were detected between songs of males expressing FoxP2 or a GFP construct in area X, consistent with the marked stability of mature song in this species. In contrast, songs of males overexpressing FoxP2 became more variable and were less preferable to females, unlike responses to songs of GFP-expressing control males. In deafened birds, song deteriorated more rapidly following FoxP2 overexpression relative to GFP controls. Together, these experiments suggest that behavior-driven FoxP2 expression and auditory feedback interact to precisely maintain learned vocalizations

Which Classes of Structures Are Both Pseudo-elementary and Definable by an Infinitary Sentence?

When classes of structures are not first-order definable, we might still try to find a nice description. There are two common ways for doing this. One is to expand the language, leading to notions of pseudo-elementary classes, and the other is to allow infinite conjuncts and disjuncts. In this paper we examine the intersection. Namely, we address the question: Which classes of structures are both pseudo-elementary and $\mathcal{L}_{\omega_1 \omega}$-elementary? We find that these are exactly the classes that can be defined by an infinitary formula that has no infinitary disjunctions

FoxP2 isoforms delineate spatiotemporal transcriptional networks for vocal learning in the zebra finch.

Human speech is one of the few examples of vocal learning among mammals yet ~half of avian species exhibit this ability. Its neurogenetic basis is largely unknown beyond a shared requirement for FoxP2 in both humans and zebra finches. We manipulated FoxP2 isoforms in Area X, a song-specific region of the avian striatopallidum analogous to human anterior striatum, during a critical period for song development. We delineate, for the first time, unique contributions of each isoform to vocal learning. Weighted gene coexpression network analysis of RNA-seq data revealed gene modules correlated to singing, learning, or vocal variability. Coexpression related to singing was found in juvenile and adult Area X whereas coexpression correlated to learning was unique to juveniles. The confluence of learning and singing coexpression in juvenile Area X may underscore molecular processes that drive vocal learning in young zebra finches and, by analogy, humans

Which classes of structures are both pseudo-elementary and definable by an infinitary sentence?

When classes of structures are not first-order definable, we might still try to find a nice description. There are two common ways for doing this. One is to expand the language, leading to notions of pseudo-elementary classes, and the other is to allow infinite conjuncts and disjuncts. In this paper we examine the intersection. Namely, we address the question: Which classes of structures are both pseudo-elementary and Lω1,ω-elementary? We find that these are exactly the classes that can be defined by an infinitary formula that has no infinitary disjunctions.Natural Sciences and Engineering Research Council Discovery Grant 312501 || Natural Sciences and Engineering Research Council Banting Fellowshi

Which Classes of Structures are Both Pseudo-Elementary and Definable by an Infinitary Sentence

© The Author(s), 2023. Published by Cambridge University Press on behalf of The Association for Symbolic Logic.When classes of structures are not first-order definable, we might still try to find a nice description. There are two common ways for doing this. One is to expand the language, leading to notions of pseudo-elementary classes, and the other is to allow infinite conjuncts and disjuncts. In this paper we examine the intersection. Namely, we address the question: Which classes of structures are both pseudo elementary and Lω1,ω-elementary? We find that these are exactly the classes that can be defined by an infinitary formula that has no infinitary disjunctions

Research Staff COVID-19 Pandemic Survey-Results from the Prevention and Early Treatment of Acute Lung Injury (PETAL) Network

Objectives: There is a lack of knowledge about the challenges of researchers who continued in-person research during the early phases of the COVID-19 pandemic. Design: Electronic survey assessing work-related exposure to COVID-19, logistical challenges, and procedural changes during the first year of the COVID-19 pandemic on clinical research. Setting: National Heart, Lung, and Blood Institute-sponsored Prevention and Early Treatment of Acute Lung Injury Clinical Trial Network Centers. Subjects: Research staff at research Network Sites. Measurements and Main Results: The 37-question survey was completed by 277 individuals from 24 states between 29 September 2020, and 12 December 2020, yielding a response rate of 37.7%. Most respondents (91.5%) indicated that non-COVID-19 research was affected by COVID-19 research studies. In response to the COVID-19 pandemic, 20% of respondents were reassigned to different roles at their institution. Many survey takers were exposed to COVID-19 (56%), with more than 50% of researchers requiring a COVID-19 test and 8% testing positive. The fear of infection was 2.7-times higher compared to pre-COVID-19 times. Shortages of personal protective equipment were encountered by 34% of respondents, primarily due to lack of access to N95 masks, followed by gowns and protective eyewear. Personal protective equipment reallocation from research to clinical use was reported by 31% of respondents. Most of the respondents (88.5%), despite these logistical challenges, indicated their willingness to enroll COVID-19 patients. Conclusions: During the first year of the COVID-19 pandemic, members of the research network were engaged in COVID-19 research despite logistical challenges, limited access to personal protective equipment, and fear of exposure. The research network’s survey experience can inform ongoing policy discussions to create research enterprises that can dexterously refocus research to address the knowledge gaps associated with novel public health emergencies while mitigating the effect of pandemics on existing research projects and research personnel

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes