INVESTIGATING THE ROLE OF VASOPRESSIN RECEPTOR 1A EXPRESSING NEURONS IN MOUSE DORSAL RAPHE

Human social interactions heavily impact our physical and mental wellbeing. Arginine-vasopressin (Avp) and serotonin have both been implicated in modulation of social behaviors ranging from affiliation to aggression. In male mice, Avp neurons in the bed nucleus of stria terminalis (BNST) show increased activity during prosocial behavior. BNST sends Avp afferents to the dorsal raphe (DR) in the midbrain, a home to a large portion of serotonin neurons in the mouse brain. Previous data suggests that DR is activated during male prosocial behavior with a female stimulus, and Avp indirectly excites serotonin neurons. We hypothesized that DR contains a population of vasopressin receptor 1a-expressing (Avpr1a) cells that may be involved in the regulation of social behavior. Our Fos expression data revealed that DR Avpr1a cells are active during an exposure to a female stimulus, suggesting that DR Avpr1a neurons may influence prosocial behavior. Using a novel Avrp1a-Cre mouse, we characterized the neuroanatomy of DR Avpr1a neurons. Then, hM4Di-mediated inhibition of DR Avpr1a neurons showed reduced social behavior, but unaltered nonsocial behavior, during interactions with a female stimulus in both male and female subjects. Interestingly, inhibition of DR Avpr1a neurons increased aspects of social behavior selectively in males exposed to a male stimulus. Overall, our studies provide insights into the role of DR Avpr1a cells during social behavior and establish a novel mouse model that is poised to accelerate research on the mouse Avp system

Life of Tau: Oligomerization, CNS Extracellular Clearance and Role as Plasma Biomarker

The microtubule associated protein tau (MAPT, commonly referred to as tau) is an intrinsically disordered, highly soluble protein predominantly expressed in axons where it binds and stabilizes microtubules. Under normal physiological conditions, soluble monomeric tau is released in the extracellular space in the interstitial fluid (ISF) by neurons. Additionally it undergoes reversible phosphorylation and other extensive modifications inside the cell under the action of a host of enzymes. However in the disease process tau loses this solubility, detaches from microtubules and ultimately migrates to the somatodendritic compartment of the neuron, where it ultimately forms insoluble fibrillar aggregates known as tau tangles. The nature, timeframe, and inciting factors of this transformation are active areas of research and as such, remain only partially understood. In addition to its role in AD, tau is also implicated in several other neurodegenerative conditions collectively referred to as tauopathies, all of which feature insoluble tau tangles. This list, which is still evolving, includes conditions such as frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), chronic traumatic encephalopathy (CTE), and argyrophilic grain disease (AGD). The prevailing hypothesis about the pathogenesis of tauopathies is that following an initiating event, intracellular tau aggregates and eventually spreads to other parts of the brain where it seeds previously normal tau, in a prion-like manner. These seeding and spreading phenomena have been observed in numerous mouse models. The nature of tau species involved in this spread, as well as the exact mechanism of trans-synaptic spread are not well understood. Tauճ involvement in neurodegeneration has made it an attractive therapeutic target. Passive immunotherapy with monoclonal antibodies has shown promise and is being tested in clinical trials in humans. Vaccination trials are also underway. In addition, other approaches such as antisense oligonucleotides (ASOs) and small molecule inhibitors have been tested in animal models. Here we have mainly focused on three distinct but related aspects in the Ҭife of tau:Ӽ/p\u3e1. Developing methods to measure tau oligomers2. Determining clearance kinetics of extracellular tau from the CNS to the periphery3. Evaluating plasma tau as a potential biomarker for CNS tau pathologyTau oligomers are thought to be an important intermediate step en route to the eventual fibrillization of soluble monomeric tau. We developed a high-sensitivity assay on a single molecule detection platform to detect tau oligomers. Our work characterizing extracellular tau clearance is the first comprehensive work of its type and strongly suggests that dural lymphatic system plays a key role in this process. Mice lacking these lymph vessels retain more tau in the brain as well as show slowed clearance. Lastly we asked whether plasma tau could serve as a reliable biomarker for soluble CNS tau and give us an accurate snapshot of tau pathology. Administration of an anti-tau antibody resulted in dose dependent increase in plasma tau in both humans and mice, most likely because of its role in extending the half-life of plasma tau from 8 minutes to 3 hours. Furthermore plasma tau levels correlated with soluble CNS tau levels (and therefore, inversely with tau pathology), making this a potentially good strategy to monitor tau pathology load in mouse model of tauopathy and potentially in humans. The work done here represents an important step in characterizing the role of tau in normal physiology and disease and will help guide future therapy as well as diagnostic approaches

A systematic literature review on Security of Unmanned Aerial Vehicle Systems

Unmanned aerial vehicles (UAVs) are becoming more common, and their operational range is expanding tremendously, making the security aspect of the inquiry essential. This study does a thorough assessment of the literature to determine the most common cyberattacks and the effects they have on UAV assaults on civilian targets. The STRIDE assault paradigm, the challenge they present, and the proper tools for the attack are used to categorize the cyber dangers discussed in this paper. Spoofing and denial of service assaults are the most prevalent types of UAV cyberattacks and have the best results. No attack style demands the employment of a hard-to-reach gadget, indicating that the security environment currently necessitates improvements to UAV use in civilian applications.Comment: 10 Pages, 4 Figure

Study of outcomes of metaphyseal plate fixation in extra articular lower tibia fractures in adults

Background: The purpose of the present study was to see results of metaphyseal plate fixation in fractures of distal tibia in adults.Methods: This is a retrospective study of 45 patients with 45 open fractures of tibia operated primarily by either Solid Titanium or Stainless steel tibia interlocking nail within 24 hours of injury.Results: In Our Study we had studied 30 lower tibial fractures treated by precontoured metaphyseal anatomical plate. 24 (80%) patients were male. 19 patients were 20-45 years age group. Mean age was 34 years. 24(80%) fractures were due to Road traffic accidents. We had 26 (86%) patients with closed fracture and 4(14%) patients with open fracture. Average time of surgery in our series was 52 minutes. 6(20%) patients had infection. And 2(6.67%) patients had nonunion and both were due to infection and required implant removal and conversion to external fixation. Average time for fracture union was 18 months. In our study of 30 patients 23(76.67%) patients had good to excellent results as assessed by AOFAS score. Conclusions: From this study we can conclude that when properly indicated the use of anatomically precontoured medial tibial metaphyseal plate in treatment of distal tibia fractures gives good union and good functional result

Comparison study of compound fractures of tibial shaft treated by titanium and stainless steel interlocking nails

Background: The purpose of the present study was to compare the outcomes of compound fractures of tibia shaft managed by Solid Titanium and Stainless Steel interlocking intramedullary nailing.Methods: This is a retrospective study of 45 patients with 45 open fractures of tibia shaft operated primarily by either Solid Titanium or Stainless steel tibia interlocking nail.Results: In Our Study we had 45 patients with 45 open tibial fractures. All were male. 35 patients were from 20-50 years age group. Mean age was 36.4 years. In this study of 45 open tibial fractures following strict protocol of thorough debridement, primary wound closure and Solid Titanium or stainless steel interlocking nailing; it was observed at final follow up that patients operated by titanium nail compared to stainless steel had 6.45% vs. 14.29% infection rate, 12.9% vs. 21.89% rate of non-union and 3.22% vs. 7.14% screw breakage rate. According to modified ketenjian’s criteria in our study out of 31 patients operated by Titanium interlocking nail 17 (54.84%) excellent, 10 (32.26%) Good, 3(9.68%) fair and 1(3.22%) poor functional results while out of 14 patients managed by stainless steel nail 8 (57.14%) excellent, 3 (21.43%) good, 1 (7.14%) fair and 2 (14.28%) poor functional results. Conclusions: In open tibial fractures titanium interlocking implants offer lower complication rate as compared to stainless steel implants and better overall patient outcome

Affiliative Social Interactions Activate Vasopressin-Responsive Neurons in the Mouse Dorsal Raphe

Social behavior is inextricably linked to human health, shaping both our susceptibility and resilience to disease and stress. Positive interactions as simple as maternal contact or friendships among children and adults can protect against emotional distress and improve treatment outcomes, whereas negative interactions such as abuse, social isolation, or bullying can increase aggression and precipitate mood disorders. Discovering the structure and function of neural circuits underlying social behavior is critical to understanding the link between social interaction and health. The neuropeptide vasopressin has been implicated in the regulation of multiple social interactions including social memory, aggression, mating, pair-bonding, and parental care. Vasopressin producing neurons in the bed nucleus of the stria terminalis (BNST) and medial amygdala (MeA), in particular, are predicted to be involved in social behavior. While the innervation targets of BNST and MeA vasopressin neurons and patterns of vasopressin receptor binding have been well-documented in multiple species, the identity and functional characteristics of neurons targeted by vasopressin innervation are less well understood

Integrated Image and Location Analysis for Wound Classification: A Deep Learning Approach

The global burden of acute and chronic wounds presents a compelling case for enhancing wound classification methods, a vital step in diagnosing and determining optimal treatments. Recognizing this need, we introduce an innovative multi-modal network based on a deep convolutional neural network for categorizing wounds into four categories: diabetic, pressure, surgical, and venous ulcers. Our multi-modal network uses wound images and their corresponding body locations for more precise classification. A unique aspect of our methodology is incorporating a body map system that facilitates accurate wound location tagging, improving upon traditional wound image classification techniques. A distinctive feature of our approach is the integration of models such as VGG16, ResNet152, and EfficientNet within a novel architecture. This architecture includes elements like spatial and channel-wise Squeeze-and-Excitation modules, Axial Attention, and an Adaptive Gated Multi-Layer Perceptron, providing a robust foundation for classification. Our multi-modal network was trained and evaluated on two distinct datasets comprising relevant images and corresponding location information. Notably, our proposed network outperformed traditional methods, reaching an accuracy range of 74.79% to 100% for Region of Interest (ROI) without location classifications, 73.98% to 100% for ROI with location classifications, and 78.10% to 100% for whole image classifications. This marks a significant enhancement over previously reported performance metrics in the literature. Our results indicate the potential of our multi-modal network as an effective decision-support tool for wound image classification, paving the way for its application in various clinical contexts

Can NLP Models 'Identify', 'Distinguish', and 'Justify' Questions that Don't have a Definitive Answer?

Though state-of-the-art (SOTA) NLP systems have achieved remarkable performance on a variety of language understanding tasks, they primarily focus on questions that have a correct and a definitive answer. However, in real-world applications, users often ask questions that don't have a definitive answer. Incorrectly answering such questions certainly hampers a system's reliability and trustworthiness. Can SOTA models accurately identify such questions and provide a reasonable response? To investigate the above question, we introduce QnotA, a dataset consisting of five different categories of questions that don't have definitive answers. Furthermore, for each QnotA instance, we also provide a corresponding QA instance i.e. an alternate question that ''can be'' answered. With this data, we formulate three evaluation tasks that test a system's ability to 'identify', 'distinguish', and 'justify' QnotA questions. Through comprehensive experiments, we show that even SOTA models including GPT-3 and Flan T5 do not fare well on these tasks and lack considerably behind the human performance baseline. We conduct a thorough analysis which further leads to several interesting findings. Overall, we believe our work and findings will encourage and facilitate further research in this important area and help develop more robust models.Comment: TrustNLP Workshop at ACL 202

Analysis of in vivo turnover of tau in a mouse model of tauopathy

BACKGROUND: Intracellular accumulation of tau as neurofibrillary tangles (NFTs) is the hallmark of Alzheimer’s disease (AD) as well as in other tauopathies. Tau is present not only in the cytoplasm but also in the extracellular space such as cerebrospinal fluid (CSF) and brain interstitial fluid (ISF). Although clearance is one critical parameter leading to such intracellular/extracellular tau accumulation, in vivo turnover of tau has not been well characterized. The current study has attempted to precisely determine in vivo turnover rates of tau utilizing tet-off regulatable mice. In particular, we assessed intracellular tau and extracellular tau, soluble tau, insoluble tau and phosphorylated tau at certain sites utilizing a combination of in vivo microdialysis, biochemical analysis and specific ELISAs recognizing each species. To examine the effect of a tauopathy-associated mutation on tau clearance, half-lives of various tau species were compared between the mice with a FTDP-17 mutation that induces β-sheet formation, ΔK280 mutation (pro-aggregant mice) and control mice with additional β-sheet breaking mutations (anti-aggregant mice). RESULTS: Here we report that tau is metabolized at much slower turnover rates in vivo than in cell culture. We found that insoluble tau in pro-aggregant mice had a significantly slower half-life (t(1/2) = ~34.2 days) than soluble tau (t(1/2) = ~9.7 days). In contrast, soluble tau phosphorylated in the proline rich region was cleared faster than total soluble tau. When comparing pro-aggregant mice to anti-agregant mice, turnover rates of soluble tau species were not significantly different. CONCLUSIONS: The current study provides a comprehensive description of in vivo turnover of various tau species present in mice that express human tau. The turnover rate of soluble tau was not significantly altered between pro-aggregant mice and anti-aggregant mice. This suggests that altered conformation by ΔK280 does not have a major impact on clearance pathways for soluble tau. In contrast, different tau species displayed different half-lives. Turnover was significantly delayed for insoluble tau whereas it was accelerated for soluble tau phosphorylated in the proline rich region. These differences in susceptibilities to clearance suggest that aggregation and phosphorylation influences tau clearance which may be important in tau pathogenesis