bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 and Digitalization: Its Influence in the Dutch Real Estate Market Process
Authors: Veuger Jan
Published: May 2024

COVID-19, disruption in society and real estate - which clearly bear characteristics of this era - and the user will have an impact on real estate. Disruptive real estate organizations clearly respond to the agility and modularity of the built environment and therefore determine the right of existence of real estate organizations. This also influences the current and future financial and functional valuation of real estate. The added value of the possible applications of digitalization of real estate processes is expressed in agility, modularity, more effective and efficient transactions, increasing transparency and a better basis for investments. This will increase confidence in fundamental parts of the real estate economy. In recent months, COVID-19 has held sway over the Netherlands and almost everywhere else in the world. Although COVID-19 began making its way through Asia in January, the Netherlands and Europe were surprised by it. The intelligent lockdown, announced in the third week of 2020 and later lifted, has now become a partial lockdown again in October 2020. This has a major impact on people's daily lives: how people live, how they work, how they shop and get groceries. Things like 'place' and 'connection' suddenly take on a whole new meaning. This has meant quite a lot for real estate. Considering the fact that COVID-19 will be present in many ways as long as no vaccination or effective medicine is available, COVID-19, as well as digitalization, will have considerable consequences for real estate, urban development and building production. The methodology is based on literature review of papers from the recently written collection of essays RICS Research & Innovation (Kok et al., 2020) in which the experts, based on current knowledge, research and insights, present a picture of what COVID-19 means for our real estate and urban development. In the following sections, we present a number of important insights and conclusions as well as a number of current research developments. These insights and conclusions are: (1) the Unique Object Identifier (UOI) respects existing identifiers and connects them, (2) COVID-19 can also stimulate the integration of technology in real estate, and (3) urban strategy foresees a future of networked regions.
Predicting Future of Senior Housing Markets amid COVID-19 Pandemic in India Using Dependency Models
Authors: Pandya Jigar V.
Published: May 2024

The COVID-19 pandemic has contributed to a very high percentage of senior deaths in India. Senior citizens constitute about 10% of total population while 73% of deaths during COVID-19 pandemic in India have been of people with co-morbidities such as diabetes, hypertension, heart and respiratory diseases. Amidst this pandemic, the senior housing market is poised for exponential growth despite a low market share as well as slow sales. To inquire as to which factors influence the seniors for not buying into exclusive senior housing communities and whether the decision varies among ages as well as genders; a questionnaire survey was conducted pre-COVID-19 using sales leads of 143 senior respondents from five cities; Delhi, Lavasa, Chennai, Pune and Ahmedabad. These data were tested using binary probit regression models for age and gender. The survey required the respondents to rate decision factors which included; amenities, location, social isolation, wealth, family, urban connect, new relationships, inheritance and moral values - on Likert scale of 1 to 9. The tested model for gender shows that males are dependent on factors of location of the project and fear isolation as compared to females. Males also rated new acquaintances as a discouraging factor as compared to females. The age model shows that older seniors (aged 66-75) do not wish to move to an exclusive senior citizen homes due to factors of distance, fear of social isolation and attachment to urban elements as compared to younger seniors (aged 55-65). An attempt is made to use the results arising from these models to predict the future of senior housing market post-COVID-19 pandemic in India. By integrating new factors such as social distancing, personal hygiene and recreational activities, the existing models can be used to forecast post-COVID-19 senior housing markets in India.
Uncoupling of Damped Linear Potential Multi-Degrees-of-Freedom Structural and Mechanical Systems
Authors: Udwadia Firdaus E. , Bulatovic Ranislav M.
Published: May 2024

This paper provides the necessary and sufficient conditions for a multi-degrees-of-freedom linear potential system with an arbitrary damping matrix to be uncoupled into independent subsystems of at most two degrees-of-freedom using a real orthogonal transformation. The incorporation of additional information about the matrices, which many structural and mechanical systems commonly possess, shows a reduction in the number of these conditions to three. Several new results are obtained and are illustrated through examples. A useful general form for the damping matrix is developed that guarantees the uncoupling of such systems when they satisfy just two conditions. The results provided herein lead to new physical insights into the dynamical behavior of potential systems with general damping matrices and robust computational procedures. It is shown that the dynamics of a damped potential system in which the damping matrix may be arbitrary is identical to that of a damped gyroscopic potential system with a symmetric damping matrix. This brings, for the first time, these two systems, which are seen today as belonging to different categories of dynamical systems, under a unified framework.
The Autoregulation Rest-Redistribution Training Method Mitigates Sex Differences in Neuromuscular and Perceived Fatigue During Resistance Training
Authors: Dello Iacono Antonio , Watson Kevin , Jukic Ivan
Published: May 2024

Purpose: To examine the sex differences in performance and perceived fatigue during resistance training prescribed using traditional (TRA) and autoregulation rest-redistribution training (ARRT) approaches. Methods: Twelve resistance-trained men and 12 women completed 2 sessions including the bench-press exercise matched for load (75% of 1-repetition maximum), volume (24 repetitions), and total rest (240 s). Sessions were performed in a counterbalanced randomized design with TRA consisting of 3 sets of 8 repetitions with 120-second interset rest and ARRT employing a personalized combination of clusters, repetitions per cluster, and between-clusters rest regulated with a 20% velocity-loss threshold. The effects of TRA and ARRT on velocity loss, unilateral isometric peak force, and rating of fatigue (ROF) were compared between sexes. Results: The velocity loss was generally lower during ARRT compared with TRA (−0.47% [0.11%]), with velocity loss being mitigated by ARRT to a greater extent among males compared with females (−0.37% [0.15%]). A smaller unilateral isometric peak force decline was observed after ARRT than TRA among males compared with females (−38.4 [8.4] N). Lower ROF after ARRT than TRA was found among males compared to females (−1.97 [0.55] AU). Additionally, males reported greater ROF than females across both conditions (1.92 [0.53] AU), and ARRT resulted in lower ROF than TRA overall (−0.83 [0.39] AU). Conclusions: The ARRT approach resulted in decreased velocity loss, peak force impairment, and ROF compared with TRA in both sexes. However, male subjects exhibited more pronounced acute within-session benefits from the ARRT method.
Bacterial cell differentiation enables population level survival strategies
Authors: Chong Trisha N. , Shapiro Lucy
Published: May 2024

Clonal reproduction of unicellular organisms ensures the stable inheritance of genetic information. However, this means of reproduction lacks an intrinsic basis for genetic variation, other than spontaneous mutation and horizontal gene transfer. To make up for this lack of genetic variation, many unicellular organisms undergo the process of cell differentiation to achieve phenotypic heterogeneity within isogenic populations. Cell differentiation is either an inducible or obligate program. Induced cell differentiation can occur as a response to a stimulus, such as starvation or host cell invasion, or it can be a stochastic process. In contrast, obligate cell differentiation is hardwired into the organism’s life cycle. Whether induced or obligate, bacterial cell differentiation requires the activation of a signal transduction pathway that initiates a global change in gene expression and ultimately results in a morphological change. While cell differentiation is considered a hallmark in the development of multicellular organisms, many unicellular bacteria utilize this process to implement survival strategies. In this review, we describe well-characterized cell differentiation programs to highlight three main survival strategies used by bacteria capable of differentiation: (i) environmental adaptation, (ii) division of labor, and (iii) bet-hedging.
Identification of a novel first-generation HIV-1 circulating recombinant form (CRF152_DG) among people living with HIV in Karachi, Pakistan
Authors: Rashid Abdur , Kang Li , Yi Feng , Getaneh Yimam , Chu Qingfei , Shah Sharaf Ali , Abidi Syed Hani , Shao Yiming
Published: May 2024

The objective of this study was to characterize a novel circulating recombinant form of human immunodeficiency virus type 1 (HIV-1) among people living with HIV in Karachi, Pakistan. We conducted near-full-length genome (NFLG) sequencing on eight samples exhibiting D/G recombination signals in the
pol
gene region. We successfully obtained NFLG sequences (790–9,614; with reference to the HXB2 genome) from four of the eight samples and then conducted phylogenetic and recombination analyses on them. The four NFLG sequences from our study and one DG unique recombinant form previously identified in the United Kingdom (GenBank accession:
MF109700
) formed a distinct monophyletic cluster with an Shimodaira-Hasegawa approximate likelihood ratio test node support value of 100%. Bootscan analyses of the five NFLG sequences of DG recombinants showed that all five NFLGs shared the same unique mosaic pattern of recombination breakpoints between D and G clades, with two D fragments in the
pol
and
vif
regions inserted into a G backbone. Subregion phylogenetic analyses confirmed these sequences to be a novel circulating recombinant form (CRF) composed of subtypes D and G. The DG recombinant sequences were eventually designated as CRF152_DG by the Los Alamos HIV Sequence Database staff.

IMPORTANCE

In Pakistan, the genetic diversity of human immunodeficiency virus type 1 (HIV-1) is becoming increasingly complex, compared to the early years of the epidemic that started after the detection of the first cases of HIV-1 in 1987 in Karachi. Based on the available molecular studies, two dominant HIV-1 clades, sub-subtype A1 and CRF02_AG, have been found to co-circulate with other clades, namely B, C, D, G, CRF01_AE, CRF35_A1D, and CRF56_cpx, in various urban areas of Pakistan. Several novel recombinant forms have also been detected. This first report of CRF152_DG highlights the complex nature of the HIV epidemic in Pakistan and emphasizes the importance of continual molecular surveillance (ideally based on whole-genome sequences) of HIV.
Innervated vastus lateralis muscle: complementing and completing the anterolateral thigh flap for abdominal wall reconstruction
Authors: Dixit Pawan Kumar , Karmakar Shilpi , Singla Priyanka
Published: May 2024

Reconstruction of composite abdominal wall defects is challenging. An anterolateral thigh (ALT) flap has established itself in the algorithm for abdominal wall reconstruction. Augmenting innervated vastus lateralis (iVL) muscle to ALT has added advantages. We describe previously unreported advantage of ALT with iVL.

A woman in her 30s, suffering from Mullerian adenocarcinoma with metastasis to the right anterior abdominal wall and right inguinal lymph node, was taken for wide local excision and reconstruction. After excision, there was a 15×12 cm defect of the anterior abdominal wall. We reconstructed the defect with prosthetic mesh and pedicled composite ALT and iVL. There was venous congestion in the ALT flap and it could not be salvaged. We debrided the ALT flap and applied split skin graft over iVL. The grafted and donor sites healed well. The patient was able to do moderate strenuous activities. The presence of iVL allowed us to get away with minor procedure and averted the need for another flap.
Acute bilateral sensorineural hearing loss as presentation of leptomeningeal metastases
Authors: Agarwal Ayush , Garg Divyani , Priya Shikha , Bylappa Punith Saroja , Garg Ajay , Shamim Shamim Ahmed , Elhence Anshuman , Radhakrishnan Divya M , Pandit Awadh Kishor , Srivastava Achal K
Published: May 2024

We describe a rare occurrence of bilateral acute severe sensorineural hearing loss in a middle-aged man that heralded the diagnosis of metastatic gastric cancer.
Numerical modeling of reaction–diffusion e-epidemic dynamics
Authors: Yasin Muhammad Waqas , Ashfaq Syed Muhammad Hamza , Ahmed Nauman , Raza Ali , Rafiq Muhammad , Akgül Ali
Published: May 2024

The objective of this paper is to understand the dynamics of virus spread in a computer network by e-epidemic reaction–diffusion model and applying an implicit finite difference (FD) scheme for a numerical solution. The SIR models are used in studies of epidemiology to predict the behavior of the propagation of biological viruses within the population. We divide the population of computer nodes into three parts i.e. susceptible (may catch the virus), infected 1 (infected but not completely), and infected 2 (completely infected). By using Taylor’s series expansion the consistency of the implicit scheme is proved. The unconditional stability of the implicit FD model is proved by using the Von Numan stability analysis. The qualitative analysis of the underlying model is also analyzed such as positivity and boundedness of the model. The numerical stability and bifurcation of is also analyzed. Likewise, identical modeling techniques are adopted to analyze the spread of the virus in digital networks. Because the computer virus behaves in the identical way as the biological virus behaves, this paper emphasizes the significance of diffusion in decreasing the gap between reality and theory, offering a more precise depiction of the spread of the virus within the digital network.
Design and analysis of a planar and multilayer metamaterial with the dual-functions of an ultra-broadband and high absorptivity absorber and a multi-wavelength resonator
Authors: Du Yong , Wang Chih-Hsuang , Ke Pei-Xiu , Yang Cheng-Fu , Lin Jing-Jenn
Published: May 2024

This absorber exhibits a hierarchical structure, featuring layers of ZnO, Zr, yttria-stabilized zirconia (YSZ), Zr, YSZ, Al, YSZ and Al from top to bottom. Simulation analyses were conducted using COMSOL Multiphysics® simulation software (version 6.1). The primary innovation of this multilayer metamaterial lies in its entirely planar configuration, enabling switchable functionality: one ultra-broadband with high absorptivity (facilitated by the ZnO layer) and three narrowband absorption peaks (achieved through the Al layer). The simulation results clearly demonstrate that when light was incident from the ZnO direction onto this designed structure, the investigated planar and multi-functional absorber exhibited excellent absorber characteristics. Over an ultra-wide broadband range from 395 to 2070[Formula: see text]nm, the average absorptivity reached an impressive 95.03%. When light was incident from the Al direction onto the investigated planar and dual-functional absorber, three narrowband absorption peaks were observed at wavelengths 355, 550 and 1200[Formula: see text]nm. The second innovation highlights the effectiveness of ZnO as an anti-reflection layer, elevating the absorptivity of the ultra-broadband absorber. The third innovation establishes that Al is the optimal metal choice. It is worth noting that while using no Al layer or substituting Al with other metals did not diminish the absorptivity of the ultra-broadband absorber, alternative metals might adversely affect the absorptivity of the multi-wavelength absorber.
A Combined simulation and experimental investigation on tool radius influence on enhancing the formability SPIF process for Al1050 sheet material
Authors: Luyen The-Thanh , Hoang Trung-Kien , Nguyen Duc-Toan
Published: May 2024

This research presents a comprehensive investigation into the pioneering domain of single point incremental forming (SPIF), focusing on elucidating the nuanced interplay between tool radius and formability. By employing a combination of rigorous simulation and experimental methodologies, the study sheds light on the pivotal influence of tool radius on forming performance. Various tool radius values spanning from 2 to 7 are systematically tested in conjunction with corresponding forming angles, revealing crucial insights into their synergistic effects. A critical threshold radius (Rt) is discerned, representing the point at which optimal formability is attained. Below this threshold, a decline in formability is observed, attributed to excessive surface cutting and metal pressing phenomena evident in tests utilizing pointed tools. Finite element (FE) analysis corroborates these findings, demonstrating that compression beneath the tool center induces unstable strain, consequently diminishing forming height as tool radius decreases. Conversely, beyond the Rt, an increase in tearing is noted due to reduced compression. This underscores the delicate balance required in selecting an appropriate tool radius to maximize shaping capacity in SPIF processes. Importantly, the research highlights the significance of achieving high compression capacity alongside an optimal tool radius, emphasizing the intricate yet essential factors influencing SPIF’s formability and shaping capabilities. Furthermore, this study contributes to the advancement of SPIF technology by uncovering novel insights into the dynamic relationship between tool geometry and formability, thereby paving the way for enhanced process optimization and design in various manufacturing applications. This research delves into the innovative realm of SPIF by exploring the intricate relationship between tool radius and formability. Through meticulous simulation and experimentation, the study unveils the pivotal role of tool radius in forming performance. The different values of tool radius, ranging from 2 to 7, are coupled with appropriate forming angles. A critical Rt is identified, where optimal formability is achieved. Conversely, below this threshold, formability declines due to excessive surface cutting and metal pressing, observed in tests employing pointed tools. FE analysis substantiates that compression below the tool center triggers unstable strain, diminishing forming height with decreasing tool radius. Notably, above the Rt, an increase in tearing is observed due to decreased compression. In this context, attaining high compression capacity alongside an appropriate tool radius emerges as the key to maximizing shaping capacity in SPIF.
Thermal analysis of nanofluid magnetic flow on a rotating disk in the presence of radiation considering response surface method
Authors: Jalili Payam , Asadi Zohreh , Shateri Amirali , Jalili Bahram , Ahmad Hijaz , Albalwi M. Daher , Ganji Davood Domiri
Published: May 2024

This study examines Titania nanofluids that conduct electricity and are combined with various base fluids, focusing on various aspects. A magnetic field analyzes a continuous flow of nanofluid over a rotating disk that is positioned at an angle with a three-dimensional geometry assumption. The continuity, momentum, and energy balance equations are established, transformed using similarity variables, and solved through Akbari–Ganji Method (AGM) and Homotopy Perturbation Method (HPM) semi-analytical methods. The effects of several parameters, such as Magnetic parameter (M), Hall parameter (m), Porosity parameter ([Formula: see text]), Radiation parameter (Rd), and Thickness of liquid ([Formula: see text]), are examined through a graphical representation of state variables, including skin friction and Nusselt number. Additionally, the Response Surface Method (RSM) method has been utilized to simultaneously display the effects of porosity parameters and various factors across the disk. The findings showed that the magnetic, porosity, Hall, and thickness parameters had a significant impact on the behavior of the nanofluid. Specifically, the magnetic field had a strong influence on the velocity and temperature distribution of the fluid as it flowed over the rotating disk, while changes in porosity, Hall, and thickness parameters also affected these state variables.
Thermoelastic Damping of Micromechanical Resonators Based on Quintanilla Theory
Authors: Kumar Pravin , Kumar Roushan , Prasad Rajesh
Published: May 2024

This paper addresses the exploration of thermoelastic damping (TED) in a microbeam resonator, utilizing the Quintanilla generalized thermoelasticity theory. The study emphasized analyzing the influence of beam height on the microbeam resonators TED and also conducted a thorough assessment of the frequency shift and normalized attenuation in microbeam resonators. These outcomes are then compared with different materials, like silicon (Si) and lead (Pb). The current undertaking demonstrates its utility in tackling challenges associated with science and engineering.
KCC theory for a type of nonlinear damped SD oscillators
Authors: Li Runhong , Liu Yongjian , Wang Minan
Published: May 2024

Smooth and discontinuous (SD) oscillators are the nonlinear models that will exhibit SD dynamics due to continuous variation of the smooth parameter. Kosambi–Cartan–Chern (KCC) theory is a differential geometric theory that describes the deviations from the entire trajectory of the variational equation to the nearby trajectory. This paper presents a completely new dynamical analysis of a type of SD oscillators with nonlinear damping based on the KCC theory. First, the paper gives five KCC geometrical invariants of SD oscillators in the smooth and non-smooth cases, respectively. The results show that the geometric quantities in the non-smooth case cannot be derived directly from the geometric quantities in the smooth case. Second, from these geometric quantities, KCC stability of SD oscillators trajectory at any point except [Formula: see text] is analyzed. Lastly, numerical results show that in some regions that deviate from the equilibrium point of system, the system will exhibit complex and variable dynamical behavior due to small changes in parameters. This paper shows that the KCC theory is also a useful tool in the dynamical analysis of non-smooth systems.
Experimental Study on Cold Start Strategies of Fuel Cell Stack: Sensitivity Analysis, Optimization, and Boundaries
Authors: Wang Zhina , Hu Zunyan , Xu Liangfei , Li Jianqiu , Ouyang Minggao
Published: May 2024

The adaptability of fuel cell vehicles in low-temperature environments remains challenging for their commercialization owing to the propensity of water within the fuel cell to freeze during a cold start, which impedes gas transmission and subsequent reactions. Consequently, the initial water content before cold start and the heat and water generated during this process are crucial for achieving a successful cold start. In this study, current- and voltage-controlled starting strategies are analyzed using a stack comprising 20 cells with an area of 285 cm2. Furthermore, key parameters related to shut down purging and cold start are optimized using starting time and reverse polarity cell count as optimization objectives. The optimal conditions for cold start include a current density of 0.5 A cm−2, voltage of 0.45 V, purging time of 180 s, and stack temperature (during purging) of 60 °C. Furthermore, the ambient temperature boundary is determined as −25 °C–−30 °C for a successful cold start without auxiliary heating in the stack.
Impact of neonatal noninvasive resuscitation strategies on lung mechanics, tracheal pressure, and tidal volume in preterm lambs
Authors: Bizzotto Davide , Dahl Mar Janna , Veneroni Chiara , Lavizzari Anna , Rebentisch Andrew , Dawson Elaine , Bowen Sydney , Zuspan Kaitlin , Yoder Bradley A. , Albertine Kurt H. , Dellacà Raffaele L.
Published: May 2024

We compared invasive and noninvasive resuscitation on lambs at birth, including or not sustained inflation (SI). Lung volume recruitment was faster in those receiving SI. During noninvasive resuscitation, larynx modulation reduced tracheal pressure from that applied to the mask in lambs receiving SI, while it led to increased auto-positive end-expiratory pressure and very large tidal volumes in lambs not receiving SI. Our results highlight the need for individualizing pressures and monitoring tidal volumes during resuscitation at birth.
Upregulation of the Urotensin II System in Diabetic Kidney Disease Includes Urotensin II-Related Peptide
Authors: Michael Olugbenga , Kanthakumar Praghalathan , Soni Hitesh , Lenin Raji , Jha Kumar Abhiram , Gangaraju Rajashekhar , Adebiyi Adebowale
Published: May 2024

The urotensin II (UII) system consists of endogenous ligands UII and its paralog urotensin II-related peptide (URP) and their receptor, UT. Originally isolated from the rat brain, URP is conserved across all vertebrates and shares the same cyclic hexapeptide core sequence with UII. However, UII and URP exhibit different N-terminal amino acid sequences. Beyond the central nervous system, UII and URP are functionally expressed in peripheral tissues. Alterations in tissue expression levels of UII and UT and blood or urinary UII concentrations have been associated with cardiovascular, pulmonary, and kidney dysfunctions, including hypertension, chronic heart failure, pulmonary hypertension, glomerulonephritis, and diabetes, making the UII system a potential therapeutic target for cardiovascular and kidney disease. The skeletal muscle and plasma levels of UII are increased in diabetic mice. Increased kidney tissue expression levels of UII and UT have also been demonstrated in humans and animals with diabetic kidney disease (DKD). Our recent work showed that UT is functionally expressed in cultured mouse glomerular mesangial cells (GMCs). Activation of UT by UII contributes to Ca2+-dependent GMC proliferation and extracellular matrix protein accumulation under high glucose conditions. We have also shown that DKD is attenuated in UT knockout mice. Despite the structural homology between UII and URP, studies have shown that the peptides may exhibit differential central and peripheral expression and pathophysiological function. However, whether URP is dysregulated in DKD remains unclear. Here, we examined whether URP production and kidney expression levels are altered in a hyperglycemic milieu and associated with DKD. Using a streptozotocin (STZ)-induced diabetes model, we examined the kidney tissue, plasma, and urinary levels of UII peptides. We also tested the hypothesis that, like UII, URP stimulates GMC proliferation and matrix protein synthesis. Our data show that protein and mRNA expression levels of both UII and URP were increased in the kidneys of hyperglycemic mice that developed albuminuria. Urinary and plasma UII and URP concentrations were also elevated in the mice. Although both UII and URP stimulated proliferation and type IV collagen production in cultured mouse GMCs by activating UT, the effect of UII was greater. Our data suggests that changes in the UII system in DKD are not limited to UII and UT but include the less-studied URP. GMC proliferation and extracellular matrix accumulation driven by UII and URP may contribute to DKD.

NHLBI: R01 HL151735.

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Urotensin II system contributes to ischemic acute kidney injury in neonatal pigs
Authors: De La Cruz Julia E , Michael Olugbenga , Kanthakumar Praghalathan , Falayi Olufunke , Iwhiwhu Samson , Afolabi Jeremiah , Kumar Ravi
Published: May 2024

Urotensin II (UII) and UII-related peptide (URP) and their receptor, UT, comprise the UII system. Although UII is conserved across all vertebrates and shares a cyclic hexapeptide core-sequence motif of CFWKYC, there are differences in N-terminal amino acid sequences between species. The kidney is a significant source of UII, the level of which is amplified in infants with chronic kidney disease. We have previously shown that human UII increases renal vascular resistance (RVR) and reduces renal blood flow in neonatal pigs. However, the effect of pig UII (pUII) on renal microcirculation remains unclear. Since the mechanisms of renal ischemia-reperfusion (IR) injury include kidney hypoperfusion, increased activity of the UII system may contribute to ischemic acute kidney injury (AKI). Here, we demonstrate that kidney tissue UII, URP, and UT and renal vascular UT expression levels are higher in neonatal pigs than in adults. Intrarenal artery infusion of pUII reduced kidney perfusion and increased RVR, which was reversed by urantide, a peptide UT inhibitor. One hour of renal ischemia, followed by 8 hours of reperfusion, did not alter kidney tissue UT but upregulated kidney tissue UII and URP and renal vascular UT expression levels. Urantide mitigated renal IR-induced increase in AKI biomarkers. Urantide also attenuated renal IR-induced increases in serum interleukin-1beta, interleukin-10, interferon-α, and morphological kidney injury. The enzyme that converts prepro UII to active UII has been proposed to be serine protease furin. Kidney tissue expression of furin is higher in neonatal pigs compared with adults. Renal IR also upregulated furin expression in neonatal pig kidneys. Exposure of primary neonatal pig renal epithelial cells to the cellular model of IR (cIR) increased furin levels. cIR also increased UII production in the cells, an effect attenuated by furin inhibitor SS3. These findings suggest that in pigs, 1) the UII system is upregulated in immature kidneys, 2) renal IR upregulates furin, UII, and URP in kidney tissues and UT in renal blood vessels of neonates, 3) ischemic activation of furin promotes UII biosynthesis by renal epithelial cells, and 4) pharmacological inhibition of UT mitigates renal IR-induced AKI. We conclude that the UII systems may contribute to IR-induced neonatal renal insuffciency.

NIH R01DK120595 R01DK127625.

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Cold-water foot immersion and physiological strain of adults with coronary artery disease during hot and humid heat exposure
Authors: Mornas Adèle , Bettremieux Léa , Sardar Soha , Iglesies-Grau Josep , Capon Tony , Crandall Craig G. , Fiataronesingh Maria
Published: May 2024

Introduction: Heat extremes are associated with a greater risk of adverse cardiovascular outcomes, especially among adults with coronary artery disease. While air-conditioning provides exceptional protection during heat extremes, it is neither sustainable nor widely accessible. Cold-water foot immersion reduces physiological heat strain in healthy young adults but its effect in more vulnerable populations remains unknown. Objective and hypotheses: This study aims to identify the effect of cold-water foot immersion on markers of physiological heat strain in adults with coronary artery disease. We hypothesized that cold-water foot immersion would reduce physiological heat strain when used on its own and that this effect would be greater when combined with an electric fan. Methods: 17 adults living with stable coronary artery disease (2 females/15 males; 67±8 years) were exposed to a 38°C, 60% relative humidity environment for 3 hours on three separate, randomized occasions: i) no cooling (control; CON); ii) cold-water foot immersion (20 min of immersion each 30 min, ~30 cm in water kept at ~18°C; FI); iii) cold-water foot immersion and fan use (FI+FAN). Rectal and skin temperatures, heart rate (5-lead ECG), and whole-body sweat loss (change in nude weight) were measured. Results: The increase in rectal temperature did not differ between conditions (CON: 0.40±0.24°C, FI: 0.41±0.29°C, and FI+FAN: 0.36±0.22°C; p≥0.49). The increase in skin temperature was reduced with FI and FI+FAN compared to CON (CON: 4.9±0.8°C, FI: 4.1±1.2°C, and FI+FAN: 4.3±0.8°C; p≤0.01), with no difference between FI and FI+FAN (p=0.15). Similarly, the increase in heart rate was reduced with FI and FI+FAN compared to CON (CON: 8±6 bpm, FI: 4±6 bpm, and FI+FAN: 3±6 bpm; p≤0.01), with no difference between FI and FI+FAN (p=0.45). Sweat loss was also reduced by FI and FI+FAN compared with CON (CON: 823±114 g, FI: 544±174 g, and FI+FAN: 671±255 g; p≤0.03), with sweat loss during FI sweat loss being lower than during FI+FAN (p=0.03). Conclusion: The results show that cold-water foot immersion, used alone or in combination with an electric fan, reduces the increase in heart rate and whole-body sweat loss of adults living with coronary artery disease exposed to a hot and humid environment for 3 hours. This could be linked to the lower increase in skin temperature with foot immersion.

National Health and Medical Research Council of Australia (APP1147789).

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Depressing Ubiquitin-Dependent Proteolysis in a Hibernator Whose Body Temperature Is Normally Variable: The Common Tenrec
Authors: Aviles Hector , van Breukelen Frank
Published: May 2024

In a canonical mammalian hibernator like a ground squirrel, the cold body temperatures (Tb) of the torpid squirrel depresses protein degradation at the level of the 26S proteasome. Ubiquitylation per se is less temperature sensitive as ubiquitylation rates of colder temperatures continue at 30% to 60% of the maximal rates of warmer temperatures. This leads to an accumulation of ubiquitin-conjugated proteins of 2-3 fold in torpid squirrels as compared to active squirrels. The common tenrec is a bizarre Afrotherian placental mammal with many plesiomorphic traits such as a cloaca, internal testes, indeterminate growth, and the smallest brain of all extant mammals with very little neocortex. Interestingly, these tenrecs may be fully active with a Tb of 12°C or hibernating at a Tb of 28°C. Moreover, oxygen consumption rates may vary 25 fold in active tenrecs. We found expected decreases of 26S proteolytic activity at low temperatures. Capacitance for proteolysis varied by state and there was no evidence that torpor per se would arrest protein degradation. Indeed, in sharp contrast to the squirrel, ubiquitylation rates were essentially unaffected by temperature and ranged at colder temperatures from 80% to 90% of the maximal ubiquitylation rates. In other words, the only in vitro evidence for the control of ubiquitin-dependent proteolysis that we found would only be available to very cold tenrecs independent of if they were active or torpid. However, ubiquitin-conjugate concentrations appear low but unaffected by state. All in all, we hypothesize a ‘Life in the Slow Lane’ model for tenrecs wherein an inability to effectively regulate proteolysis led to a modest rate of degradation that is not as affected by changes incurred by torpor state or changes in Tb.

NSF and Department of Education (GAANN).

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Distribution and Metabolism of Dietary Nitrate in Porcine Ocular Tissues
Authors: Park Ji Won , Piknova Barbora , Tunau-Spencer Khalid J , Cai Hongyi , Walter Peter J , Jenkins Audrey , Hellinga David G
Published: May 2024

Extensive recent studies have provided evidence of the important role of dietary nitrates in improving cardiovascular health and enhancing exercise performance. This is generally attributed to the conversion of these nitrate ions (NO3−) obtained from dietary sources into nitrite (NO2−) and subsequently into nitric oxide (NO) within the body. In a prior study, we demonstrated that porcine ocular tissues contain significant amounts of nitrate and nitrite, comparable to those found in the blood. Notably, cornea and sclera exhibited the capability to reduce nitrate to nitrite. In our current study, we sought to gain a deeper understanding of ocular nitrate metabolism. To achieve this, we administered two groups of pigs either NaCl or Na15NO3 orally and evaluated the levels of both total and 15N-labeled nitrate and nitrite in various ocular tissues three hours after Na15NO3 ingestion. We observed a substantial increase in both 15NO3− and 15NO2− in all parts of the eye measured by LC-MS/MS. Particularly, the aqueous and vitreous humor displayed a remarkably high 15NO3− enrichment similar to that of plasma and even higher 15NO2− enrichment than that of plasma. Cornea, sclera, retina and lens also showed notable increases in 15NO3−. The 15NO2− analysis revealed that most eye parts, except aqueous and vitreous humor, had levels similar to those observed in plasma. Furthermore, the total amounts of NO3− and NO2− measured by chemiluminescence in these tissues exhibited patterns consistent with those observed in the 15N analysis. These findings provide valuable insights into the distribution and metabolism of dietary nitrates within ocular tissues, shedding light on their potential roles in ocular health and function.

This work was supported by intramural NIDDK/NIH grant ZIA DK 025104-15 to Alan N. Schechter.

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Single-Nuclei RNA-Sequencing Uncovers Alterations in the Transcriptional Profile of Skeletal Muscle in Peripheral Artery Disease
Authors: Pass Caroline , Palzkill Victoria , Tan Jianna , Kim Kyoungrae , Thome Trace , Yang Qingping , Fazzone Brian
Published: May 2024

BACKGROUND: Lower extremity peripheral artery disease (PAD) is caused by atherosclerotic occlusion of lower limb blood vessels, impacting >200 million people worldwide. PAD causes life-altering symptomatology such as claudication, ischemic rest pain, and gangrene, with limited effective treatment options. Herein, we performed single-nuclei RNA-sequencing (snRNAseq) to facilitate a better understanding of the complex pathobiological environment within the PAD limb and intercellular communication. METHODS: Gastrocnemius muscle specimens were collected from 20 patients with PAD and 12 non-PAD controls. Patients with PAD were classified as Rutherford category 3 (severe claudication). Non-PAD participants were of similar age, body mass index and medication usage as patients with PAD. Nuclei were isolated and snRNAseq was performed. Bioinformatic analysis was conducted to determine differences in gene expression between PAD and non-PAD nuclei, as well as analysis of intercellular signaling networks. Histological analysis of muscle specimens assessed the following: myosin heavy chain fiber distributions, myofiber cross-sectional area and myofiber denervation. RESULTS: 57,364 high-quality nuclei were captured (21,417 PAD; 35,947 non-PAD) and unsupervised clustering revealed 12 distinct nuclei populations based on their transcriptional profile. Quantification of the relative abundance of nuclei populations identified several differences, including PAD muscles having a lower percentage of type I myonuclei, muscle stem cells, and endothelial cells but a higher proportion of type II and regenerating myonuclei. Differentially expressed gene analysis of myonuclei populations uncovered upregulation of genes involved in stress response, autophagy, and atrophy in patients with PAD. Ligand-receptor interactions were used to determine how PAD alters the communication between identified nuclei populations. The inferred strength of interactions was greater in non-PAD compared to PAD patients. Further, intercellular communication network analysis revealed fibro-adipogenic progenitors as a primary signaling hub in PAD muscle. CONCLUSION: snRNAseq uncovered novel transcriptional differences and intercellular communication pathways unique to PAD muscle.

This study was supported by National Institutes of Health (NIH) grant R01-HL149704 (T. Ryan). K. Kim supported by the American Heart Association grant POST903198. T. Thome supported by NIH grant F31-DK128920.

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Sex-dependent benefit of B vitamins on cardiac function and lipid metabolism in a murine model of heart failure with reduced ejection fraction
Authors: David Chloé , Deschênes Sonia , Daneault Caroline , Robillard Frayne Isabelle , Shi Yan Fen , Higgins Marie-Ève , Tardif Jean-Claude
Published: May 2024

Background: Heart failure (HF) is a global health problem requiring more effective therapeutic alternatives. While HF involves disturbances in cardiac metabolism associated with lipidomic remodeling, there is a lack of approaches to specifically target cardiac metabolism. Recently, it has been shown in murine models of HF, that the use of nicotinamide riboside (vitamin B3) alone or the combination of B9 and B12 vitamins, before the development of HF, improved cardiac metabolism and function. Our hypothesis is that the combination of B3, B9 and B12 vitamins, used when HF is declared, will improve lipid metabolism, cardiac function and survival. The aim of this study is to evaluate the curative benefit of a synthetic diet enriched with the combination of these three vitamins (VitB) in a murine model of HF with reduced ejection fraction (EF). Method: Pressure overload was induced by constriction of the transverse aorta (TAC) in male and female mice. After 4 weeks, TAC mice reaching a pressure gradient of 60 mmHg, an increased left ventricle mass >30% and a reduced EF >10%, were randomized to a VitB-enriched diet or not. Results: In females, VitB improved survival and cardiac hypertrophy (-24%, p<0.05) as well as EF (+22%, p<0.01). We also observed a reduction of cardiac fibrosis emphasized by a significant decrease expression of collagen 1a and 3 (-30% and -19% respectively) and hydroxyproline concentration (-32%, p<0.01). No benefit was observed in males in terms of survival, cardiac function and fibrosis. Untargeted mass spectrometry (MS)-based lipidomics on plasmas at 8 weeks of treatment showed a decrease in several individual triglycerides (TG from 43 to 48 %; p<0.05) in TAC females that were normalized by VitB. In contrast, in TAC males, most of the annotated TGs were increased (from ̴35 to 210%; p<0.05), a profile exacerbated upon VitB treatment. MSMS identification of TG side chains revealed a differential profile in terms of fatty acid composition according to sex and treatment. In VitB females, longer and polyunsaturated TGs (53 to 60C; 5 to 12 double bonds) were significantly increased (1.6- to 2.1-fold) while, in VitB males, the increased TGs (1.2- to 5.2-fold) were shorter (24C to 48C) and saturated (no double bonds). Conclusion: Our study pointed out a sexual dimorphism in the response to VitB treatment in HF in favor of females and implying a lipidomic remodeling promoting cardioprotective polyunsaturated TGs.

European Research Area Network on Cardiovascular Diseases, Canadian Institutes of Health Research, Fonds de recherche du Québec - Santé.

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Effect of dosage duration on oropharyngeal and locomotor in a toxicological rat model of Parkinson’s disease
Authors: Patel Shivam , Wojtas Ireneusz , Gould Francois
Published: May 2024

Parkinson’s Disease (PD) is a prevalent and devastating neurodegenerative disorder that causes progressively worsening motor symptoms affecting locomotor and oropharyngeal function. There is limited research in animal models on swallowing dysfunction in PD. To examine how neurodegeneration in PD produces progressive impairment in the oropharyngeal and locomotor processes, rotenone, a type II mitochondrial inhibitor, was injected into Lewis rat models to reproduce a parkinsonian phenotype. We hypothesized that the animal models injected with the rotenone will exhibit both oropharyngeal dysfunction and locomotor deficiency with an increased deficit that correlates with prolonged treatment. We utilized 18 rats receiving either 2.75 mg/kg of rotenone or vehicle intraperitoneal injections. Animals received daily injections for 17 or 8 days. At the end of the injections in each group brains were perfused and immunostained for striatal tyrosine hydroxylase (TH). High speed (200 fps) videofluoroscopic recording was taken of these rats and average chew cycle length, chewing rate, and total chewing time data were collected from days 0, 1, 4, 7 and 16 of those recordings. The number of rears by a rat in a glass cylinder over 4 minutes was counted on the same days to assess locomotor behavior. We used mixed model ANOVA, controlling for the effect of individual variation, to test the impact of rotenone treatment on feeding and locomotor variables. We used a Kruskall-Wallis non parametric test to test the effect of rotenone treatment on striatal TH levels. Total chewing time, and average chew cycle duration increased in rotenone treated rats from day 0 to day 4, but the difference disappeared from day 7 onwards. However, rearing behavior was consistently reduced in rotenone treated rats for all 16 days. TH staining intensity in the striatum decreased consistently over the course of the injections. These results suggest that rotenone treated rats have temporary/short term deficiency in chewing function, despite sustained reduction in spontaneous locomotor activity. The restoration of function after day 4 may indicate a learned behavior to compensate for this dysfunction in chewing, or point to a different neurological impairment than that seen in locomotor behavior. Further research needs to be undertaken to understand this phenomenon.

Internal Rowan funding to F. Gould supported this work.

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.