Anatomical and functional dissection of fruitless positive courtship circuit in Drosophila melanogaster

Angeborene Verhaltensweisen beruhen auf genetisch determinierten Verschaltungen im Nervensystem. Das bemerkenswerteste angeborene Verhaltensmuster von Drosophila melanogaster ist das Balzverhalten. Während der Balz verarbeiten männliche Fliegen vielfache sensorische Reize von weiblichen Fliegen. Wie kann das stereotyp verschaltete Nervensystem diese Reize wahrnehmen und prozessieren um darauf beruhend Entscheidungen über das Balzverhalten zu treffen? Laut einem gängigen Modell bilden Neurone, die fruitless exprimieren (fru+ Neurone) einen spezifischen Schaltkreis für das Balzverhalten, dass für dieses unabkömmlich ist. Das Ziel der vorliegenden Arbeit ist es, die Bestandteile dieses neuronalen Schaltkreises anatomisch und funktional zu charakterisieren. Um ausgewählte fru+ Neurone zu manipulieren, wurde ein FLP-in System und eine neuartige Bibliothek von GAL4 Linien (VT Linien) verwendet und ein anatomischer Screen durchgeführt. Im Vergleich zu Enhancer Trap GAL4 Linien exprimieren VT Linien in kleineren Teilmengen der fru+ Neurone, was es möglich machte, verschiedene Klassen von fru+ Neuronen zu beschreiben und sie in den Schaltplan für das Balzverhalten einzufügen. Für eine funktionelle Charakterisierung der fru+ Neurone wurden neuronale Aktivierungsscreens durchgeführt. Auf diese Weise wurden vier verschiedene Klassen von fru+ Neuronen identifiziert, die bei Aktivierung Balzgesang evozieren (P1, pIP10, dPR1 und vPR6) sowie die neuronale Klasse vMS11, die bei thermischer Aktivierung einseitige Flügelbewegung hervorruft. Die Inaktivierung dieser Neurone vermindert die Produktion von Balzgesang. Des Weiteren wurden sechs neuronale Klassen gefunden, die bei Aktivierung eine Krümmung des Abdomen induzieren (dAB4, dAB5, dAB8, dMT3, vAB2 und dAB7). Die Inaktivierung von dAB4 oder dAB5 hat keinen Einfluss auf die Intensität des Balzverhaltens, verhindert aber die Kopulation. Das weist darauf hin, dass dAB4 und dAB5 spezifisch für das Kopulationsverhalten benötigt werden. Um fru+ Neurone ausfindig zu machen, die die Balzmotivation steuern, wurde ein thermischer Aktivierungsscreen in der Anwesenheit einer zweiten, als Balzobjekt dienenden männlichen Fliege durchgeführt. In diesem Screen wurden die neuronalen Klassen P1 und LAN1 gefunden, von denen bereits zuvor bekannt war, dass ihre Aktivierung an ein Männchen gerichtetes Balzverhalten hervorrufen kann. Zusätzlich wurden zwei Unterklassen von P1 (pMP4 und pMP4_1) und 4 andere Klassen von fru+ Neuronen (aSP2, pIP6, aSP21, aSP4) identifiziert, die an ein Männchen gerichtetes Balzverhalten auslösen, wenn sie aktiviert werden. Die Inaktivierung von P1 und aSP2 vermindern das Balzverhalten dramatisch, wohingegen die Inaktivierung der anderen neuronalen Klassen nur einen geringen oder keinen messbaren Einfluss auf das Balzverhalten hat. P1 und aSP2 sind Kandidaten für Sensorische Integration, die für das Balzverhalten benötigt werden. Die großen Überlappungsbereiche der Arborisierungen dieser Neurone im Hirn legt es nahe, dass sie miteinander verbunden sind und deutet darauf hin, dass sie möglicherweise sensorische Reize verarbeiten und integrieren. In der vorliegenden Arbeit wurde ein verfeinerter und detaillierter anatomischer Schaltplan der fru+ Neuronen erstellt und Neurone identifiziert, die eine funktionelle Rolle für den Balzgesang, das Kopulationsverhalten und die Balzmotivation spielen.Drosophila melanogaster male display a complex innate behaviors, the courtship ritual. Male flies initiates the following based on the sensory cues from females. During the courtship, males extend their wing unilaterally and vibrate it to create the courtship song. In the end, males attempt the copulation by bending his abdomen and succeed in copulation. What is the neuronal basis for courtship? Neurons that express the gene fruitless (fru+ neurons) are essential for courtship and have been proposed to form courtship circuit. The aim of this study was to identify the components of the courtship circuit anatomically and functionally. We used FLP-in system and a new GAL4 library (Vienna Tile lines; VT lines) generated in the lab to target specific subsets of fru+ neurons. We performed an anatomical screen with VT lines. We found that VT lines label smaller subsets of fru+ neurons compared to enhancer trap GAL4 lines. The sparse labeling with VT lines enabled us to indentify and characterize previously uninvestigated fru+ neurons and extend the courtship circuit diagram. In order to elucidate how the fru+ neurons are functionally involved in courtship, we performed neuronal activation screens with isolated males. We identified four types of fru+ neurons (P1, pIP10, dPR1 and vPR6) that triggered courtship song and one type of fru+ neurons (vMS11) that triggered unilateral wing extension upon thermal activation. Neuronal silencing of these neurons reduces the courtship song during courtship. Additionally, we identified six types of fru+ neuron (dAB4, dAB5, dAB8, dMT3, vAB2, and dAB7) that trigger edabdominal bending on activation. Neuronal silencing of dAB4 or dAB5 did not affect the vigorousness of courtship but abolished copulation, suggesting their specific necessity for copulation. We thus identified two groups of neurons involved in different steps of courtship ritual, song production and copulation. To identify the fru+ neurons that drive the courtship behavior, we performed a thermal activation screen in the presence of a target male. We found P1 and LAN1 from this screen which are known to trigger courtship toward target males on activation. In addition, we found two subtypes of P1 (pMP4 and pMP4_1) and four other types of fru+ neurons (aSP2, pIP6, aSP21, aSP4) that trigger courtship towards target males on activation. Silencing of P1 or aSP2 reduced courtship dramatically, while the silencing of other identified neurons had either minor impact or no impact on courtship. This suggests that P1 and aSP2 are necessary for courtship and may play a role in integrating multiple sensory signals which are required for courtship. The extensive overlap of these neurons in the brain suggests potential connections and involvement in mediating and integrating sensory inputs. Thus, in this study, we developed new tools providing restricted genetic access to individual fru+ neurons and obtained a more detailed anatomical map of fru+ neurons. Moreover, we identified fru+ neurons involved in specific courtship steps such as courtship song and copulation. Another different approach allowed isolation of different types of fru+ neurons that promote the courtship behavior

Reasons for Sharing With Separate Social Media Audiences During Life Transitions

During life transitions, people sometimes turn to social media audiences separate from their typical online networks. By qualitatively analyzing open-ended data from a U.S.-based survey (N = 775), we examined why and how people discuss life transitions with these separate audiences. Survey questions asked about life events experienced, separate networks and the interactions that occurred there, and participants’ reasoning behind these online behaviors. We found that people use separate networks, especially online support groups, to interact with others anonymously, receive informational and emotional support, and have direct and focused discussions with people with similar experiences.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162570/1/LiuReasonsForSharing.pdfSEL

Retrieval-Enhanced Visual Prompt Learning for Few-shot Classification

Prompt learning has become a popular approach for adapting large vision-language models, such as CLIP, to downstream tasks. Typically, prompt learning relies on a fixed prompt token or an input-conditional token to fit a small amount of data under full supervision. While this paradigm can generalize to a certain range of unseen classes, it may struggle when domain gap increases, such as in fine-grained classification and satellite image segmentation. To address this limitation, we propose Retrieval-enhanced Prompt learning (RePrompt), which introduces retrieval mechanisms to cache the knowledge representations from downstream tasks. we first construct a retrieval database from training examples, or from external examples when available. We then integrate this retrieval-enhanced mechanism into various stages of a simple prompt learning baseline. By referencing similar samples in the training set, the enhanced model is better able to adapt to new tasks with few samples. Our extensive experiments over 15 vision datasets, including 11 downstream tasks with few-shot setting and 4 domain generalization benchmarks, demonstrate that RePrompt achieves considerably improved performance. Our proposed approach provides a promising solution to the challenges faced by prompt learning when domain gap increases. The code and models will be available

Evaluation of genetic susceptibility of common variants in CACNA1D with schizophrenia in Han Chinese

The heritability of schizophrenia (SCZ) has been estimated to be as high as 80%, suggesting that genetic factors may play an important role in the etiology of SCZ. Cav1.2 encoded by CACNA1C and Cav1.3 encoded by CACNA1D are dominant calcium channel-forming subunits of L-type Voltage-dependent Ca(2+) channels, expressed in many types of neurons. The CACNA1C has been consistently found to be a risk gene for SCZ, but it is unknown for CACNA1D. To investigate the association of CACNA1D with SCZ, we designed a two-stage case-control study, including a testing set with 1117 cases and 1815 controls and a validation set with 1430 cases and 4295 controls in Han Chinese. A total of selected 97 tag single nucleotide polymorphisms (SNPs) in CACNA1D were genotyped, and single-SNP association, imputation analysis and gender-specific association analyses were performed in the two independent datasets. None was found to associate with SCZ. Further genotype and haplotype association analyses indicated a similar pattern in the two-stage study. Our findings suggested CACNA1D might not be a risk gene for SCZ in Han Chinese population, which add to the current state of knowledge regarding the susceptibility of CACNA1D to SCZ

Evaluation of voltage-dependent calcium channel gamma gene families identified several novel potential susceptible genes to schizophrenia

Voltage-gated L-type calcium channels (VLCC) are distributed widely throughout the brain. Among the genes involved in schizophrenia (SCZ), genes encoding VLCC subunits have attracted widespread attention. Among the four subunits comprising the VLCC (α − 1, α −2/δ, β, and γ), the γ subunit that comprises an eight-member protein family is the least well understood. In our study, to further investigate the risk susceptibility by the γ subunit gene family to SCZ, we conducted a large-scale association study in Han Chinese individuals. The SNP rs17645023 located in the intergenic region of CACNG4 and CACNG5 was identified to be significantly associated with SCZ (OR = 0.856, P = 5.43 × 10(−5)). Similar results were obtained in the meta-analysis with the current SCZ PGC data (OR = 0.8853). We also identified a two-SNP haplotype (rs10420331-rs11084307, P = 1.4 × 10(−6)) covering the intronic region of CACNG8 to be significantly associated with SCZ. Epistasis analyses were conducted, and significant statistical interaction (OR = 0.622, P = 2.93 × 10(−6), P(perm) < 0.001) was observed between rs192808 (CACNG6) and rs2048137 (CACNG5). Our results indicate that CACNG4, CACNG5, CACNG6 and CACNG8 may contribute to the risk of SCZ. The statistical epistasis identified between CACNG5 and CACNG6 suggests that there may be an underlying biological interaction between the two genes

Two-stage association study to identify the genetic susceptibility of a novel common variant of rs2075290 in ZPR1 to type 2 diabetes

The SNP of rs964184 in ZPR1 has recently been associated with type 2 diabetes mellitus (T2DM) in Japanese individuals. To comprehensively investigate the association of common variants in ZPR1 with T2DM in Han Chinese individuals, we designed a two-stage case-control study of 3,505 T2DM patients and 6,911 unrelated healthy Han Chinese individuals. A total of 24 single nucleotide polymorphisms (SNPs) were genotyped, and single-SNP association, imputation and gender-specific association analyses were performed. To increase the coverage of genetic markers, we implemented imputation techniques to extend the number of tested makers to 280. A novel SNP, rs2075290, and the previously reported SNP, rs964184, were significantly associated with T2DM in the two independent datasets, and individuals harboring the CC genotype of rs2075290 and GG genotype of rs964184 exhibited higher levels of fasting plasma glucose (FPG) and blood hemoglobin A1c (HbA1c) than individuals of other genotypes. Additionally, haplotype analyses indicated that two haplotype blocks containing rs2075290 or rs964184 were also significantly associated with T2DM. In summary, these results suggest that ZPR1 plays an important role in the etiology of T2DM, and this gene might be involved in abnormal glucose metabolism

The Online Authenticity Paradox: What Being “Authentic” on Social Media Means, and Barriers to Achieving It

People often strive to present themselves authentically on social media, but this may not be possible for everyone. To understand how people view online authenticity, how it relates to social media sharing behaviors, and whether it is achievable, we interviewed 28 social media users who had recently experienced major life transitions. We found that to many participants, online authenticity required presenting a consistent, positive, and “true” self across online and offline contexts. Though most stated that they considered online authenticity achievable, their social media self-disclosure behaviors around life transitions revealed what we call the online authenticity paradox: people strive to achieve online authenticity, yet because doing so requires sharing negative experiences on social media, online authenticity is often unreachable, or is possible only at great personal cost – especially for those with marginalized identities and difficult life experiences.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/169586/1/V5cscw423-haimsonA.pdfDescription of V5cscw423-haimsonA.pdf : Main articleSEL

Effect of acupuncture inclusion in the enhanced recovery after surgery protocol on tumor patient gastrointestinal function: a systematic review and meta-analysis of randomized controlled studies

IntroductionAcupuncture has been shown to be effective in restoring gastrointestinal function in tumor patients receiving the enhanced recovery after surgery (ERAS) protocol. The present systematic review and meta-analysis aimed to evaluate the rationality and efficacy of integrating acupuncture in the ERAS strategy to recuperate gastrointestinal function.MethodsWe searched eleven databases for relevant randomized clinical trials (RCTs) of acupuncture for the treatment of gastrointestinal dysfunction in tumor patients treated with the ERAS protocol. The quality of each article was assessed using the Cochrane Collaboration risk of bias criteria and the modified Jadad Scale. As individual symptoms, the primary outcomes were time to postoperative oral food intake, time to first flatus, time to first distension and peristaltic sound recovery time (PSRT). Pain control, adverse events, and acupoint names reported in the included studies were also investigated.ResultsOf the 211 reviewed abstracts, 9 studies (702 patients) met eligibility criteria and were included in the present systematic review and meta‑analysis. Compared to control groups, acupuncture groups showed a significant reduction in time to postoperative oral food intake [standardized mean difference (SMD) = -0.77, 95% confidence interval (CI) -1.18 to -0.35], time to first flatus (SMD=-0.81, 95% CI -1.13 to -0.48), time to first defecation (SMD=-0.91, 95% CI -1.41 to -0.41, PSRT (SMD=-0.92, 95% CI -1.93 to 0.08), and pain intensity (SMD=-0.60, 95% CI -0.83 to -0.37).The Zusanli (ST36) and Shangjuxu (ST37) acupoints were used in eight of the nine included studies. Adverse events related to acupuncture were observed in two studies, and only one case of bruising was reported. DiscussionThe present systematic review and meta‑analysis suggested that acupuncture significantly improves recovery of gastrointestinal function and pain control in tumor patients receiving the ERAS protocol compared to the control group. Moreover, ST36 and ST37 were the most frequently used acupoints. Although the safety of acupuncture was poorly described in the included studies, the available data suggested that acupuncture is a safe treatment with only mild side effects. These findings provide evidence-based recommendations for the inclusion of acupuncture in the ERAS protocol for tumor patients.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/ PROSPERO, identifier CRD42023430211