Fleeting: a Novel Ultrasonic Vocalization in Mice That Allows to Define Altered Developmental Milestones in Autism Spectrum Disorder

A major mode of rodent communication occurs through ultrasonic vocalizations (USVs), which are influenced by environmental factors, mouse strain or genetic background and, importantly, by developmental stage. However, few studies have looked into the age-dependent evolution of spectral features of mouse USVs. Here, we report the existence of a novel vocalization, previously unreported, which we named “Fleeting” consisting of two acoustic elements produced with a narrow silent temporal interval between them. Strikingly, this vocalization pattern was extinguished after the second postnatal week, and this temporal pattern was associated with increased emission of Complex vocalizations, by gradual loss of the inter-element interval, suggesting a maturation process occurring at this time point. Importantly, the Fleeting vocalization was analyzed in a mouse model (Tsc2+/-) of Autism Spectrum Disorder (ASD), and showed an abnormal persistence, in particular in females which presented delayed conversion of Fleeting into Complex vocalizations compared with males. The identification of this novel vocalization represents an important insight into the maturation of mouse vocal repertoire and may be used as a developmental milestone in studies on neurodevelopmental disorders with communication impairments.

Exploring Travel Mode Preference of External Trips for Smart City Transportation Planning: Sejong, Korea

In the face of growing concerns about urban problems, smart cities have emerged as a promising solution to address the challenges, for future sustainable societies in cities. Since the early 2000s, 67 local governments in Korea have been participating in smart city projects, as of 2019. The Sejong 5-1 Living Area smart city was selected as one of two pilot national demonstration smart cities. The main objectives of this study are to introduce the Sejong 5-1 Living Area smart city project that is currently in the planning stage, present travel and mode preferences focusing on external trips in a smart city context to be built, and analyze a mode choice model according to the socioeconomic characteristics of individual travelers. One of the distinguishing features of the Sejong smart city is its transportation design concept of designating a sharing car-only district within the city to limit private vehicle ownership to about one-third of residents, while bus rapid transit (BRT) plays a central role in mobility for external trips among four transport modes including private cars, BRT, carsharing, and ridesharing. This study was analyzed using the stated preference survey data under hypothetical conditions by reflecting the unique characteristics of the Sejong smart city transportation policy. Approximately two-thirds of respondents in the survey preferred to spend less than 1.25 USD, traveling less than 35 min on BRT trips. On the basis of the survey data, we developed a mixed logit mode choice model and found the overall model estimates to be statistically significant and reasonable. All people-specific variables examined in this study were associated with mode choices for external commuting trips, including age, income, household size, major mode, driving ability, and presence of preschoolers.

Characterisation of Permanent Deformation Behaviour of Asphalt Mix Based on a Combined Elastic Plastic (CEP) Parameter

Permanent deformation or rutting is a major mode of failure in Hot Mix Asphalt (HMA) pavements. The binder used in the asphalt mixture plays an important role in the rutting resistance performance of the mixture. Currently, the Superpave rutting parameter and a more advanced test called multiple stress creep and recovery (MSCR) are the most widely used tests for rutting characterisation of asphalt binders. However, they both have their own merits and demerits. This study was undertaken to introduce a combined Elastic-Plastic (CEP) parameter as an additional binder rheological rutting parameters. The study also aimed at investigating the applicability and potential of this parameter to supplement the existing binder rheological parameters to characterise the properties of asphalt binder related to HMA rutting performance. Additionally, the correlations of the binder rheological parameters with the asphalt mix rutting parameters generated by the dynamic creep and the dynamic modulus tests were investigated. For the polymer-modified binders, Styrene-Butadiene-Styrene (SBS) was added to the PG 70-16 binder at two concentration levels (4, and 6% by the mass of the binder). A dense-graded HMA AC 14 was tested in the Dynamic Modulus (DM) and Dynamic Creep (DC) tests for evaluating the rutting performance. The CEP parameter was found to be much more reliable than the traditional G*/sin (δ) and the non-recoverable creep compliance (Jnr) parameters for evaluating the rutting behaviour of polymer modified asphalt binders, evident from better correlations of CEP with the asphalt mix performance. Unlike Jnr, the CEP parameter revealed a wider range of values, which is comparable with asphalt mixture test results.

Neurexins in serotonergic neurons regulate serotonin transmission and complex mouse behaviors

Extensive serotonin (5-HT) innervation throughout the brain corroborates 5-HT’s modulatory role in numerous cognitive activities. Volume transmission is the major mode for 5-HT transmission but mechanisms underlying 5-HT signaling are still largely unknown. Abnormal brain 5-HT levels and function have been implicated in autism spectrum disorder (ASD). Neurexin (Nrxn) genes encode presynaptic cell adhesion molecules important for the regulation of synaptic neurotransmitter release, notably glutamatergic and GABAergic transmission. Mutations in Nrxn genes are associated with neurodevelopmental disorders including ASD. However, the role of Nrxn genes in the 5-HT system is poorly understood. Here, we generated a mouse model with all three Nrxn genes disrupted specifically in 5-HT neurons to study how Nrxns affect 5-HT transmission. Loss of Nrxns in 5-HT neurons impaired 5-HT release in the dorsal raphe nucleus and dorsal hippocampus and decreased serotonin transporter distribution in specific brain areas. Furthermore, 5-HT neuron-specific Nrxn knockout reduced sociability and increased depressive-like behavior. Our results highlight functional roles for Nrxns in 5-HT neurotransmission and the execution of complex behaviors.

Unraveling the Contact Network Patterns between Commercial Turkey Operation in North Carolina and the Distribution of Salmonella Species

Salmonellosis originating from poultry poses a significant threat to human health. Surveillance within production is thus needed to minimize risk. The objectives of this work were to investigate the distribution of Salmonella spp. from a commercial turkey operation and describe the animal movement patterns to investigate the association between contact network structure and Salmonella infection status. Four years of routine growout farm samples along with data on facility location, time since barns were built, production style, and bird movement data were utilized. From all of the surveillance samples collected, Salmonella serotyping was performed on positive samples and results showed that the most represented groups were C1 (28.67%), B (24.37%) and C2 (17.13%). The serovar Infantis (26.44%) was the most highly represented, followed by Senftenberg (12.76%) and Albany (10.93%). Results illustrated the seasonality of Salmonella presence with a higher number of positive samples being collected in the second half of each calendar year. We also demonstrated that Salmonella was more likely to occur in samples from older farms compared to farms built more recently. The contact network connectivity was low, although a few highly connected farms were identified. Results of the contact network showed that the farms which tested positive for Salmonella were not clustered within the network, suggesting that even though Salmonella dissemination occurs via transferring infected birds, for this study case it is unlikely the most important route of transmission. In conclusion, this study identified seasonality of Salmonella with significantly more cases in the second half of each year and also uncovered the role of between-farm movement of birds as not a major mode of Salmonella transmission.

From translation zone to sacrifice zone

One of the most extreme challenges facing humanity at present is the climate crisis. Responding appropriately to this crisis requires a fundamental re-examination of received ways of thinking about translation, among other things. Contrasting the eco-minor with the eco-major mode of representing ecological crisis, we argue for the importance of minority perspectives in developing an expanded remit for translation studies in the context of the climate emergency. The concepts of relational and situational minority are advanced to explore how indigenous translation hermeneutics can inform climate debates. In line with environmental debates around the importance of ‘thinking outdoors’, we advocate for a notion of ‘translating outdoors’ and seek to incorporate this line of enquiry into the development of the concept of the city as more-than-human translation zone. In the coming age of extreme climate conditions, no socially responsible understanding of translation can afford to ignore ecological perspectives on the practice.

Review of Social Challenges of Heterosexual Transmission of HIV/AIDS in Uganda

This Chapter reviews and discusses the experiences of Uganda and the lessons learnt during the successful implementation of its HIV/AIDS Control Program. The major mode of transmission was by the heterosexual route. Control measures thus emphasized behavior change and sexual discipline that promoted faithfulness and monogamous sexual relationships. This chapter examines the factors responsible for the positive outcomes in the implementation of the national AIDS control strategy. The review is based on literature, reports and personal experience. The Uganda Program AIDS in the Ministry of Health (MOH) was one of the earliest AIDS Control Programs in the world. A cumulative total of nearly 2 million people have been infected since the onset of the outbreak in 1982. Some one million HIV related deaths also occurred. When the National AIDS Control Program was initially rolled out in the country there was no cure and the disease was like a death sentence. The available evidence then demonstrated heterosexual transmission as the major mode of spread. Interventions based on the promotion of Abstinence, Being faithful, and Condom use (ABC strategy) were the main components of the strategy in the public campaigns. This complex disease also impacted society and the social fabric deeply. The activities were expanded to include the socio and economic dimensions of HIV/AIDS. Later on the combination strategy integrating biomedical and social behavior change strategies offered new and more encompassing opportunities. The introduction of the antiretroviral therapy (ART) and availability of simplified tests for detection of the viral load status improved treatment and restored hope. Social support and programs for reduction of stigma opened up participation by people living with HIV/AIDS. A community based intersectoral and decentralized strategy reached every village and assured community engagement and involvement. Drastic and steady declines in prevalence and incidence followed. Cases have been declining steadily and prevalence and incidence rates continue to drop and reverse the HIV status in the country. Community Engagement strategy to promote monogamous sexual behavior and the introduction of the highly active retroviral treatment significantly consolidated to the successful outcomes.

Characterization of the secretome, transcriptome and proteome of human β cell line EndoC-βH1

ABSTRACTEarly diabetes research is hampered by limited availability, variable quality and instability of human pancreatic islets in culture. Little is known about the human β cell secretome, and recent studies question translatability of rodent β cell secretory profiles. Here, we verify representativeness of EndoC-βH1, one of the most widely used human β cell lines, as a translational human β cell model based on omics and characterize the EndoC-βH1 secretome. We profiled EndoC-βH1 cells using RNA-seq, Data Independent Acquisition (DIA) and Tandem Mass Tag proteomics of cell lysate. Omics profiles of EndoC-βH1 cells were compared to human β cells and insulinomas. Secretome composition was assessed by DIA proteomics. Agreement between EndoC-βH1 cells and primary adult human β cells was ~90% for global omics profiles as well as for β cell markers, transcription factors and enzymes. Discrepancies in expression were due to elevated proliferation rate of EndoC-βH1 cells compared to adult β cells. Consistently, similarity was slightly higher with benign non-metastatic insulinomas. EndoC-βH1 secreted 671 proteins in untreated baseline state and 3,278 proteins when stressed with non-targeting control siRNA, including known β cell hormones INS, IAPP, and IGF2. Further, EndoC-βH1 secreted proteins known to generate bioactive peptides such as granins and enzymes required for production of bioactive peptides. Unexpectedly, exosomes appeared to be a major mode of secretion in EndoC-βH1 cells. We believe that secretion of exosomes and bioactive peptides warrant further investigation with specialized proteomics workflows in future studies.Graphical abstractHighlightsWe validate EndoC-βH1 as a translational human β cell model using omics.We present the first unbiased proteomics composition of human β cell line secretome.The secretome of human β cells is more extensive than previously thought.Untreated cells secreted 671 proteins and stressed cells secreted 3,278 proteins.Secretion of exosomes and bioactive peptides constitute directions of future research.

Emergent Modality

Among Brahms’s solo Lieder that depict a piece-spanning shift between parallel minor and major tonics, “Todessehnen” (op. 86, no. 6), “Schwermut” (op. 58, no. 5), and “Dämmrung senkte sich von oben” (op. 59, no. 1) stand out for setting poetry that portrays a duality between burdensome life and transcendent death, or darkness versus light. This article explores how Brahms’s paradoxical treatment of the life-versus-death theme (associating death with an escape from suffering and the major mode, as noted in related analyses by ".fn_cite($platt_1992)." and ".fn_cite($suurpaa_2003).") correlates with a “tragic-to-transcendent” expressive genre (".fn_cite($hatten_1994).", 69) and enacts a series of poetic “turning points” (".fn_cite($huhn_2005).") that reflect the protagonist’s changing perception of temporality. I argue that the major mode emerges gradually in each song, first as an “implicit” (or “nascent”) tonic, then as a cadentially confirmed (or “realized”) key at the structural cadence. Close Schenkerian analyses of all songs show that their minor-to-major progressions are neither immediate nor direct. Rather, the songs share four tonal features that facilitate the modal change, enact a shift from “tragic” to “transcendent” expression, and actualize “poetic turning points:” 1) the parallel major emerges as a cadentially unconfirmed, nascent tonic; 2) prolongations of ".fn_flat('')."VI or IV delay a cadence in the parallel major key and convey the speaker’s entrance into new temporalities and perceptions; 3) the structural cadence confirms the major key and lays the modal conflict to rest; and 4) the postlude echoes the minor form of ".fn_scaledegree("6").", as if recalling the protagonist’s earlier struggles. The elevated expression of cadential ".fn_figbass("",64)." chords near the structural cadence—treated in the manner of “arrival six-four” chords (".fn_cite($hatten_1994).", 15)—suggests the actualization of a “transcendent” expression and either a future or intensified present temporality that the poem implies but does not realize.

Pericarditis in Covid 19 - An Unusual Presentation

Corona virus disease-19 (COVID-19) infection causing the current pandemic began as a cluster of cases in Wuhan Province of China which has now progressed to the current dangerously exponential rise of billions of cases all over the world.1 COVID19 virus is a single stranded RNA virus having zoonotic origin. It’s ability to cause cross infection is the reason for the current devastating pandemic.2 Adding to that, COVID-19 is also called as novel corona virus as such a strain of virus had never affected mankind before. The spectrum of infection is also quite interesting. Cases range from asymptomatic, mild infections having cold, cough and fever, to life threatening instances of acute respiratory failure requiring ventilator support and intensive care admission.3 With fewer treatment options available, vaccination in the pipeline, the major mode of management is symptomatic treatment. Higher antibiotics, immunity stimulant drugs, oxygen supplementation currently form the mainstay of treatment. The management of Covid-19 still remains us shooting in the dark, exploring for ground-breaking options which prevent mortality and morbidity. Another lesser explored facet of the Covid-19 infection, is its ability to rapidly disseminate in the body and not be restricted just to the respiratory system. This rapid dissemination is the reason for the multi-systemic involvement in extreme cases of Covid-19.4 There have been reported cases of Covid-19 along with neurological and cardiovascular involvement. The cardiovascular involvement can also range from chest pain and palpitations to emergencies like cardiac tamponade and cardiac failure. As the aetiology and complete progression of this disease is yet to be fully understood, such cases with multi-systemic involvement pose imminent challenges in treatment and management.5 Here, we are presenting a case of 29-year-old male Covid positive patient, who presented with chest pain and tachycardia and diagnosed as pericarditis.