Unique Connections Research Articles

Convergent Evolution of Coenzyme Metabolism in Methanosarcina mazei: Insights Into Primitive Life and Metabolic Adaptations.

The convergent evolution of coenzyme metabolism in methanogens provides critical insights into primitive life and metabolic adaptations. This study investigated the molecular evolution and functional dynamics of eight coenzymes and cofactors in Methanosarcina mazei, a model methanogen essential for methane production and energy conservation in anaerobic environments. Phylogenetic and genetic diversity analyses of the 706 protein sequences revealed conserved evolutionary trajectories interspersed with lineage-specific adaptations driven by gene duplication, horizontal gene transfer, and selective pressures. Key findings included the purifying selection of methanofuran (Tajima's D = -2.9589) and coenzyme A (Tajima's D = -2.8555), indicating the conservation of critical metabolic functions. The coenzyme B biosynthesis pathway showed balanced selection (Tajima's D = 2.38602), reflecting its evolutionary plasticity. Phylogenetic analyses linked coenzyme F420 biosynthetic enzymes closely to Methanosarcina horonobensis, while coenzyme F430 enzymes highlighted prokaryotic specialization distinct from their eukaryotes. Coenzyme M biosynthetic genes have demonstrated unique evolutionary connections with species across domains, such as Methanothermobacter thermautotrophicus and Gekko japonicus, emphasizing their broad adaptive significance. These evolutionary trajectories reveal how M. mazei optimized its metabolic pathways to thrive in extreme anaerobic environments, bridging ancient metabolic systems from the Last Universal Common Ancestor with contemporary ecological adaptations.

Structural and functional alterations in hypothalamic subregions in male patients with alcohol use disorder.

Structural and functional alterations in hypothalamic subregions in male patients with alcohol use disorder.

Heterogeneous Graph Neural Network with Adaptive Relation Reconstruction.

Heterogeneous Graph Neural Network with Adaptive Relation Reconstruction.

Comparative analysis of waterlogging and drought stress regulatory networks in barley (Hordeum vulgare).

We applied a systems biology approach to gain a deep insight into the regulatory mechanisms of barley (Hordeum vulgare ) under drought and waterlogging stress conditions. To identify informative models related to stress conditions, we constructed meta-analysis and two distinct weighted gene co-expression networks. We then performed module trait association analyses. Additionally, we conducted functional enrichment analysis of significant modules to shed light on the biological performance of underlying genes in the two contrasting stresses. In the next step, we inferred the gene regulatory networks between top hub genes of significant modules, kinases, and transcription factors (TFs) using a machine learning algorithm. Our results showed that at power=10, the scale-free topology fitting index (R2) was higher than 0.8 and the connectivity mean became stable. We identified 31 co-expressed gene modules in barley, with 13 and 14 modules demonstrating significant associations with drought and waterlogging stress, respectively. Functional enrichment analysis indicated that these stress-responsive modules are involved in critical processes, including ADP-rybosylation factors (ARF) protein signal transduction, ethylene-induced autophagy, and phosphoric ester hydrolase activity. Specific TFs and kinases, such as C2C2-GATA, HB-BELL, and MADS-MIKC, were identified as key regulators under these stress conditions. Furthermore, certain TFs and kinases established unique connections with hub genes in response to waterlogging and drought conditions. These findings enhance our understanding of the molecular networks that modulate barley's response to drought and waterlogging stresses, offering insights into the regulatory mechanisms essential for stress adaptation.

Early menarche and childbirth accelerate aging-related outcomes and age-related diseases: Evidence for antagonistic pleiotropy in humans.

Aging can be understood as a consequence of the declining force of natural selection with age. Consistent with this, the antagonistic pleiotropy theory of aging proposes that aging arises from trade-offs that favor early growth and reproduction. However, evidence supporting antagonistic pleiotropy in humans remains limited. Using Mendelian Randomization (MR), we demonstrated that later ages of menarche or first childbirth were genetically associated with longer parental lifespan, decreased frailty index, slower epigenetic aging, later menopause, and reduced facial aging. Moreover, later menarche or first childbirth were also genetically associated with a lower risk of several age-related diseases, including late-onset Alzheimer's disease (LOAD), type 2 diabetes, heart disease, essential hypertension, and chronic obstructive pulmonary disease (COPD). We validated the associations between the age of menarche, childbirth, and the number of childbirths with several age-related outcomes in the UK Biobank by conducting regression analysis of nearly 200,000 subjects. Our results demonstrated that menarche before the age 11 and childbirth before 21 significantly accelerated the risk of several diseases, and almost doubled the risk for diabetes, heart failure, and quadrupled the risk of obesity, supporting the antagonistic pleiotropy theory. We identified 126 significant single nucleotide polymorphisms (SNPs) that influenced age-related outcomes, some of which were involved in known longevity pathways, including IGF1, growth hormone, AMPK, and mTOR signaling. Our study also identified higher BMI as a mediating factor in causing the increased risk of certain diseases, such as type 2 diabetes and heart failure, in women with early menarche or early pregnancy, emphasizing the importance of the thrifty gene hypothesis in explaining in part the mechanisms behind antagonistic pleiotropy. Our study highlights the complex relationship between genetic legacies and modern diseases, emphasizing the need for gender-sensitive healthcare strategies that consider the unique connections between female reproductive health and aging.

A network analysis of postpartum depression and mother-to-infant bonding shows common and unique symptom-level connections across three postpartum periods

Postpartum depression and mother-to-infant bonding difficulties (MIBD), two issues crucial to maternal and infant mental health, often coexist and affect each other. Our study aims to dissect their complex relationship through a graphical LASSO network analysis of individual symptoms in 5594 Japanese postpartum women, whose geographical distribution was nationally representative. We identified ‘fear’, ‘enjoyment’, ‘overwhelm’, and ‘insomnia’ as common bridge symptoms linking postpartum depression and MIBD across three distinct postpartum periods. Moreover, ‘self-harm’ emerged as a bridge symptom in the first 6 months and the 7–12 month period, while ‘laugh’ was a bridge symptom in the first 6 months and the 13–24 month period. Notably, ‘self-blame’ was identified as a unique bridge symptom specific to the 13–24 month period. Our analysis highlights the complexities of symptom connectivity across postpartum stages and underscores the critical need for interventions that address both common and stage-specific bridge symptoms to effectively support maternal mental health and strengthen mother-to-infant bonding.

An Intelligent Fuzzy-Based Routing Protocol for Vehicular Opportunistic Networks

Opportunistic networks are characterized by intermittent connectivity and dynamic topologies, which pose significant challenges for efficient message delivery, resource management, and routing decision-making. This paper introduces the Fuzzy Control Routing Protocol, a novel approach designed to address these challenges by leveraging fuzzy logic to enhance routing decisions and improve overall network performance. The protocol considers buffer occupancy, angle to destination, and the number of unique connections of the target nodes to make context-aware routing decisions. It was implemented and evaluated using the FuzzyC framework for simulations and the opportunistic network environment simulator for realistic network scenarios. Simulation results demonstrate that the Fuzzy Control Routing Protocol achieves competitive delivery probability, efficient resource utilization, and low overhead compared to the Epidemic and MaxProp protocols. Notably, it consistently outperformed the Epidemic protocol across all metrics and exhibited comparable delivery probability to MaxProp while maintaining significantly lower overhead, particularly in low-density scenarios. The results demonstrate the protocol’s ability to adapt to varying network conditions, effectively balance forwarding and resource management, and maintain robust performance in dynamic vehicular environments.

DDEL-03. INTRANASAL DELIVERY OF PDGFRA-TARGETED NANOTHERAPEUTICS FOR THE TREATMENT OF PEDIATRIC HIGH-GRADE GLIOMA

Abstract Pediatric high-grade glioma (pHGG) is the most common cause of cancer-related death in children, of which the most malignant and devastating tumors include diffuse midline glioma (DMG). Its anatomical location in the brainstem, infiltrative nature, and blood-brain barrier (BBB) limit surgical resection and the distribution of systemically administered drugs. Intranasal delivery (IND) is a noninvasive method that bypasses the BBB, by leveraging the unique anatomic connections of the olfactory and trigeminal nerve pathways with the nasal cavity. We previously demonstrated the efficacy of IND of nanoliposomal (LS) formulation of the active metabolite of the DNA topoisomerase I inhibitor, irinotecan, LS-SN-38, in orthotopic human brainstem xenograft models. The specificity of liposomes can be enhanced by using immunoliposome (iLS) formulation, which are coated with antibodies specific to the tumor cells leading to targeted drug delivery and reduced toxicity to normal cells. Platelet-derived growth factor receptor alpha (PDGFRA) plays a role in DMG oncogenesis and is expressed in as much as 70% of DMG by immunohistochemistry. In this study, we evaluated the effect of anti-PDGFRA monoclonal antibody-conjugated immunoliposome encapsulated SN-38 (PDGFRA-iLS-SN-38) in pHGG cell lines. PDGFRA signals were assessed in pHGG cells using western blotting. Cells were treated with rhodamine (Rho)-labeled PDGFRA-iLS and cellular uptake was confirmed with a fluorescent microscope. PDGFRA-iLS-SN38 had the additive effect on the LS-SN-38 in DIPG007 cells (PDGFRA positive), but not in SF8628 cells (PDGFRA negative) in vitro. We treated mice bearing human DMG xenografts with IND of PDGFRA-iLS-SN38. Tumor growth and response to therapy are quantitatively measured by bioluminescence imaging, and efficacy is assessed by survival analysis. Results of survival analysis will be reported at the meeting. PDGFRA-targeted nanotherapeutics represented a specific effect on glioma cells expressing PDGFRA, providing a promising therapeutic approach for targeting pHGG.

Exploring the Decision-Making Process of International Students: Factors Influencing their Choice of US Colleges

The United States is the top destination for international students seeking higher education. These students encounter various factors that shape their decisions throughout the college application journey. This research aims to pinpoint the main variables that influence international students’ choices to study in the US. Important factors include the reputation and rankings of universities, tuition costs, geographic location, personal recommendations, unique connections, and the complexity of the admissions process. Despite facing challenges like strict immigration policies and lengthy visa application procedures, US universities continue to attract students due to their global prestige and the numerous opportunities they provide for personal and professional development. The study sheds light on the preferences and considerations of international students when choosing colleges in the US. By doing so, it offers valuable insights for higher education institutions to improve their support services and refine recruitment strategies, ultimately enhancing the experiences and outcomes for international students.

The effects of music mood and binaural beats on academic advertising

The effects of music mood and binaural beats on academic advertising

Disruptions in segregation mechanisms in fMRI-based brain functional network predict the major depressive disorder condition

Disruptions in segregation mechanisms in fMRI-based brain functional network predict the major depressive disorder condition

Review of Opportunities and Challenges for Additive Manufacturing of Steels in the Construction Industry

Abstract Additive manufacturing (AM), or 3-D printing, encompasses a range of technologies that “print” material layer by layer to create the final part. Though there is significant interest in the AM of concrete in the construction sector, opportunities for the AM of steel still need to be explored. This review focuses on the AM of low-alloy steels, stainless steels, duplex stainless steels (DSSs), precipitation-hardened (PH) stainless steels, and tool steels, highlighting the challenges and opportunities of employing AM technology for construction applications. Fusion-based AM technologies, such as wire arc additive manufacturing (WAAM), laser powder bed fusion (LPBF), and laser-directed energy deposition (LDED), are the core technologies that have been tested in the industry so far. WAAM has seen the most exploration for construction applications because of its higher deposition rate, larger build volume, and lower cost than other AM technologies. The mechanical performance of low-alloy steel, stainless steel, and tool steel shows increased tensile strengths after AM processing compared with wrought counterparts. Although AM is not economical for geometrically simple metal components or geometries, there is potential for AM to fabricate unique structural connections or joints, optimized load-bearing columns, and even entire bridges, as highlighted in this paper. AM’s digital nature (i.e., using computer-aided design (CAD) to create G-code paths for printing) can increase structural efficiency if coupled with topology optimization methods and high-strength alloys. Currently, however, general applications of AM in the industry are limited because of barriers with structural codes and standards not incorporating AM parts and AM technology barriers (i.e., limited build volumes).

Interplay between music and mathematics in the eyes of the beholder: focusing on differing types of expertise

This study explored the unique connections between music and mathematics as perceived by four groups of experts: professional mathematicians and musicians, as well as teacher educators in these two fields. Using 2 × 2 study design, we studied four groups of participants, comprising theorists and educators from various Israeli universities. During semi-structured interviews, the study participants were asked about their views on the connections between mathematics and music. This study proposes a model of experts’ conceptions of the connection between mathematics and music, which is of descriptive and explanatory power. that reveals differences between the four groups of experts. Theoreticians in both disciplines highlighted Mathematics as a key tool for music analysis and creation. Musical educators emphasized the role of music as a tool for learning mathematics. All the study participants, independently of the field of their expertise, value structure, beauty, sense of wonder, freedom and creative thinking as characteristics of both fields. Additionally, all the experts hold conceptions of the importance of integrating music and mathematics into various discipline. This study opened new doors for future research wherein utilization of experts’ insights to craft integrated study modules of music and mathematics can be explored, a pursuit that carries substantial significance.

FSDC: Flow Samples and Dimensions Compression for Efficient Detection of DNS-over-HTTPS Tunnels

This paper proposes an innovative approach capitalized on the distinctive characteristics of command and control (C&C) beacons, namely, time intervals and frequency between consecutive unique connections, to compress the network flow dataset. While previous studies on the same matter used single technique, we propose a multi-technique approach for efficient detection of DoH tunnels. We use a baseline public dataset, CIRA-CIC-DoHBrw-2020, containing over a million network flow properties and statistical features of DoH, tunnels, benign DoH and normal browsing (HTTPS) traffic. Each sample is represented by 33 features with a timestamp. Our methodology combines star graph and bar plot visualizations with supervised and unsupervised learning techniques. The approach underscores the importance of C&C beacon characteristic features in compressing a dataset and reducing a flow dimension while enabling efficient detection of DoH tunnels. Through compression, the original dataset size and dimensions are reduced by approximately 95% and 94% respectively. For supervised learning, RF emerges as the top-performing algorithm, attaining precision and recall scores of 100% each, with speed increase of ≈6796 times faster in training and ≈55 in testing. For anomaly detection models, OCSVM emerges as the most suitable choice for this purpose, with precision (88.89) and recall (100). Star graph and bar graph models also show a clear difference between normal traffic and DoH tunnels. The reduction in flow sample size and dimension, while maintaining accuracy, holds promise for edge networks with constrained resources and aids security analysts in interpreting complex ML models to identify Indicators of Compromise (IoC).

HGG-51. INTRANASAL DELIVERY OF PDGFRA-IMMUNOLIPOSOMAL SN-38 FOR THE TREATMENT OF PEDIATRIC HIGH-GRADE GLIOMAS

Abstract INTRODUCTION pHGGs are the most common cause of cancer-related death in children, of which the most malignant and devastating tumors include diffuse midline glioma (DMG). Its anatomical location in the braistem, infiltrative nature, and blood-brain barrier (BBB) limit surgical resection and the distribution of systemically administered drugs. Intranasal delivery (IND) is a noninvasive method that bypasses the BBB, by leveraging the unique anatomic connections of the olfactory and trigeminal nerve pathways with the nasal cavity. We previously demonstrated the efficacy of IND of liposomal (LS) formulation of the active metabolite of the DNA topoisomerase I inhibitor, irinotecan, LS-SN-38, in orthotopic human brainstem xenograft models. The specificity of liposomes can be enhanced by using immunoliposome (iLS) formulation, which are coated with antibodies specific to the tumor cells leading to targeted drug delivery and reduced toxicity to normal cells. Platelet-derived growth factor receptor alpha (PDGFRA) plays a role in DMG oncogenesis and is expressed in as much as 70% of DMG by immunohistochemistry. In this study, we evaluated the specificity of anti-PDGFRA monoclonal antibody conjugated immunoliposome (PDGFRA-iLS) in pHGG cell lines. METHODS PDGFRA signals were assessed in pHGG cells using western blotting. Cells with high and low expression of PDGFRA were treated with rhodamine (Rho) labeled PDGFRA-iLS and imaged with fluorescent microscope. RESULTS DIPG007, SF7761 and KNS42 expressed high levels of PDGFRA, while SF8628 and DIPG36 cells showed low expression. Fluorescence microscopy revealed high PDGFRA-rhodamine (Rho)-iLS expression in DIPG007 cells (PDGFRA high), relative to SF8628 and DIPG36 cells (PDGFRA low). CONCLUSION PDGFRA-Rho-iLS shows increase cellular uptake in DIPG cells. Work is underway to determine the biodistribution, host toxicity, and anti-tumor activity of IND of PDGFRA-iLS-SN- 38 alone and in combination with radiation therapy in pHGG xenograft models.

Mentoring Networks in Academic Medicine: A Longitudinal Exploration.

The importance of ethnic and gender representation in academic medicine is of paramount importance. While mentoring effectively attracts and retains underrepresented individuals, scientists from underrepresented groups face barriers to high-quality mentorship. The developmental network model by Higgins and Kram suggests that a variety of people with unique knowledge, connections, and resources can help propel an individual's career and personal growth. This study experimentally tested the outcomes of a workshop series and mentorship program to assist early-career biomedical investigators from predominantly minority institutions establish and maintain developmental networks. This study provides preliminary insights into the characteristics of these developmental networks for investigators with different funding goals and how these networks evolve, potentially impacting career trajectories.

Moving Beyond Official Cultural Diplomacy: Unleashing the Potential of Moroccan Students as Unofficial Cultural Ambassadors

Cultural diplomacy plays a pivotal role in international relations, enabling states to project their soft power and shape their global image. This paper explores the current state of Moroccan cultural diplomacy, highlighting the need to go beyond official approaches and embrace unofficial cultural diplomacy. While extensive research exists on official cultural diplomacy, little attention has been given to the contribution of Moroccan study-abroad students in bolstering their country's cultural diplomacy and soft power. More specifically, this paper argues that Morocco's cultural diplomacy is primarily politically oriented and institutionally based, relying heavily on the monarchy and the Ministry of Foreign Affairs. The strategic utilization of Morocco's cultural and religious heritage and diaspora politics showcases the government's efforts to secure its regional and global influence. However, these initiatives are largely driven by official institutions and lack the involvement of ordinary citizens. By examining the limitations of official cultural diplomacy, this paper argues for the inclusion of Moroccan study-abroad students as unofficial ambassadors in the service of their country’s cultural diplomacy. Drawing inspiration from successful examples of unofficial diplomacy, this paper advocates for the active participation of Moroccan study-abroad students as unofficial cultural ambassadors. Their unique perspectives, connections, and grassroots status can offer valuable contributions that official diplomats may not possess. This research paper contends that Moroccan study-abroad students have many resources of power that qualify them to leverage their country’s cultural diplomacy. These resources are informality and grassroots engagement, volunteering and community service, and the power of the virtual sphere. By utilizing these power resources, these students have the potential to foster cross-cultural understanding, build relationships, and enhance Morocco's soft power. In conclusion, this paper highlights the need for a paradigm shift in Morocco's cultural diplomacy, advocating for a combination of both official and unofficial cultural diplomacies.

Autistic Traits Modulate Social Synchronizations Between School-Aged Children: Insights From Three fNIRS Hyperscanning Experiments

The current study investigated how autistic traits modulate peer interactions using functional near-infrared spectroscopy (fNIRS) hyperscanning. Across three experiments, we tested the effect of copresence, joint activity, and a tangible goal during cooperative interactions on interbrain coherence (IBC) in school-aged children between 9 and 11 years old. Twenty-three dyads of children watched a video alone or together in Experiment 1, engaged in joint or self-paced book reading in Experiment 2, and pretended to play a Jenga game or played for real in Experiment 3. We found that all three formats of social interactions increased IBC in the frontotemporoparietal networks, which have been reported to support social interaction. Further, our results revealed the shared and unique interbrain connections that were predictive of the lower and higher parent-reported autism-spectrum quotient scores, which indicated child autistic traits. Results from a convergence of three experiments provide the first evidence to date that IBC is modulated by child autistic traits.

Digital disparities beyond the stably housed: Researching global homelessness and mobile media

As the study of mobile media and communication matures, an important expansion in focus is to explore the experiences of people and communities living on the peripheries of social and economic power. In this special issue, we ask what happens when the stability of the “home” is pulled out from under our assumptions of mobile media and communication, as well as what happens when we shift our attention to the Global South. Additionally, mobility has a special relation to homelessness and, in turn, to media that is mobile. It enters both as a resource and a liability for the unstably housed in contexts around the globe. Tackling this combination of mobility, media, and homelessness, this special issue asks: What kind of opportunity is a mobile device for those who lack stable shelter? How do different experiences and drivers of homelessness interact with the possibilities of mobile media? What are communities and institutions doing to provide assistance to those at risk of, or experiencing, homelessness through mobile technologies? The articles gathered in this issue draw attention to homelessness as a set of diverse experiences with significant consequences for well-being and unique connections to mobile media. The authors challenge the taken-for-granted focus on the stably housed by studying those without access to the same basic need. We take an international perspective on contemporary homelessness to foreground its global existence and diverse expressions across a range of national contexts, and to challenge the predominant focus on North America and Western Europe in existing literature.

Recreational vessel networks reveal potential hot spots for marine pest introduction and spread

Abstract Recreational vessels are an important pathway for spreading marine non‐indigenous species (NIS) around coastal environments globally. However, most vessels are not tracked, limiting our ability to map their movements and identify locations at greater risk of NIS introductions. Using New Zealand as a case study, we quantified spread and risk patterns of recreational vessel movements, using a web‐based survey allowing the more than 1,800 respondents to map significant trips with over 12,000 visits. These vessel routes were used to build a network model representing nationwide recreational vessel movements. Two proxies were used to quantify the risk of introduction of marine NIS: (i) incoming hull length and (ii) cumulative residency periods at sites. There was significant variation in the distances travelled, the destinations they visited and the duration of their stays. New Zealand's recreational boating network contained 317 destinations with over 4,000 unique connections, concentrated within two distinct areas of the country. Network‐based metrics and risk proxies quantified the relative importance of domestic locations as incursion or spreading hubs for NIS. This approach highlighted several areas that pose high relative biosecurity risk within the national network, but are underrepresented within current surveillance programmes. Synthesis and applications. Our study demonstrates how the movement dynamics of recreational vessels can be quantified at a regional scale to inform proactive management. The identification of spreading hubs and locations at particular risk of NIS introductions, enables managers to design risk‐based and effective surveillance and monitoring programmes. Our network‐based approach to determine the biosecurity implications posed by recreational vessels is transferable to other parts of the world. It enables managers to understand the distribution of risk within an area of interest (e.g. a jurisdiction) and develop optimised approaches for mitigating impact.