bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of Pnn in neurons regulates protein expression of genes involved in frontotemporal dementia and alters locomotor activities in mice
Authors: Leu Steve 
Published: May 2024

The regulation of pre-mRNA alternative splicing in neurons is considered to be associated with neurodegeneration disease. In the present study, we applied an inducible neuron-specific gene depletion mouse model to determine whether the expression of Pnn, a mRNA splicing regulator, is involved in the induction of neurodegeneration. Six-weeks old male mice carrying CaMKII-CreERT2 gene cassette and Pnnflox/flox allele were injected with tamoxifen to induce the disruption of Pnn gene structure. In addition to histopathological and biochemical examination, brain MRI analysis and the observation on behavior alteration were also performed on mice with neuronal Pnn depletion. Locomotor activity measurement showed that the travel distance, ratio of moving/resting, central time, and central distance in neuronal Pnn-depleted mice were all higher than that in wild type mice since three months after induction of Pnn gene disruption. Moreover, the decrease in gripping force was observed in mice with neuronal Pnn depletion. MRI analysis further demonstrated that loss of Pnn in neurons leads to cerebral ventricular dilatation and hippocampal atrophy in 10-month-old mice. Mass spectrometry-based immuno-precipitation proteomics indicated the interaction between Pnn and frontotemporal dementia (FTD)-associated proteins, including TDP-43, FUS, and hnRNPA1. It is worth noting that both immunofluorescent stainings and Western blottings demonstrated the up-regulation of FTD-associated proteins in hippocampus and cerebral cortex of mice with neuronal Pnn depletion. However, the transcriptional level of genes involved in FTD were not altered by Pnn depletion. In conclusion, loss of Pnn in neurons leads to behavioral alteration in mice with regulating protein expression of genes involved in FTD, implying the involvement of Pnn deficiency in neurodegeneration. This research was supported by Chang Gung Medical Research Program Grant (Grant number: CMRPG 8N0341-2). 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.
Associations between Illicit ADHD Medication Use and Aspects of Mental Distress Among College Students
Authors: Bonventre Samantha , Taufman Kayla , Polis Jenna , Lin Julia , Patrissy Cara , Begdache Lina 
Published: May 2024

The illicit use of Attention-Deficit Hyperactivity Disorder (ADHD) medication has become a prevalent issue on college campuses. Illicit ADHD medications are used without a medical prescription. The concern is that these medications are psychostimulants that may alter brain chemistry and affect the quality of brain maturity in individuals who do not need them medically, which potentially can affect mental health. An alarmingly high percent of reported illicit ADHD medication users are college aged students between the age of 18 and 22 years. Little is known about the effect of illicit ADHD medication use on mental well-being among college students. Thus, the purpose of the study was to assess the impact of illicit ADHD medication use on different aspects of mental distress among college students. The study collected 702 responses from undergraduate students at several US colleges and included self-reported data on illicit Adderall use, age and symptoms of mental distress. The anonymous survey was created in Google Forms. Mental distress was evaluated through The Kessler Psychological Distress Scale (K10). The data were analyzed in SPSS, Version 28.0, using Pearson’s Correlation Coeffcient. Of the 72.5% of the participants who reported using ADHD medication without a prescription, 71.4% reported academic reasons as their motivation for use. There is a positive correlation between feelings of worthlessness and illicit ADHD medication use (p<0.05). Age was negatively correlated with feelings nervous (p<0.01) and restless or fidgety (p<0.01). Additionally, a negative correlation was found between age and being able to do only half or less of what you would normally have been able to do (p<0.01). On the other hand, illicit ADHD medication use was negatively correlated with feeling that everything was an effort (p<0.05), as well feeling unable to work or carry out normal activities (p<0.01). Our results suggest that students who use ADHD medication illicitly are more likely to experience symptoms of mental distress. Interestingly, our findings propose that the younger the age of use, the higher the risk of mental distress. We received no support or financial grants. 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.
Lack of Pkd1 enhances intestinal integrity and motility prior to accelerated kidney cyst growth
Authors: Sedaka Randee , Lovelady Caleb , Shinde Sejal , Hallit Emily , Yamaguchi Shinobu , Lee Goo , Maynard Craig 
Published: May 2024

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder, primarily caused by PKD1 germline mutations. Polycystin-1, PKD1’s encoded protein, is essential to maintain kidney epithelial cell integrity, but its role in the gut has yet to be determined. Considering macrophage infiltration precedes accelerated cyst growth in Pkd1 knockout ( Pkd1KO) mice, and the gut is the body’s largest reservoir of inflammatory cells, we hypothesized that loss of Pkd1 would weaken the intestinal epithelial cell barrier and mount an inflammatory response, potentially preceding kidney damage. Plasma, urine, kidney, and intestines were collected from 11-12 week old male and female conditional Pkd1KO (CAGG-creER; tamoxifen-induced at 5-6 weeks) and flox (control) mice. Plasma was used to measure intestinal permeability as well as monocyte chemoattractant protein-1 (MCP-1) and lipocalin-2 (LCN-2) concentration. Urine was utilized to assess kidney injury, while tissues were used for RT-PCR and histology. Pkd1KO mice had significantly elevated kidney-to-body weight ratio, cyst ratio, and expression of tubular injury markers kidney injury molecule 1 (Kim1) and Lcn2 compared to flox mice. Despite this cellular injury, kidney inflammatory gene expression and urine osmolality did not differ between genotypes. No overt morphological changes were observed in the ileum or colon, nor were there differences in expression of proinflammatory chemokines or cytokines in either tissue. Plasma abundance of MCP-1 and LCN-2 was similar between genotypes. Epithelial permeability in the small and large intestines was significantly decreased in Pkd1KO versus flox mice. Moreover, Pkd1KO mice had a significantly reduced whole gut transit time compared to flox mice. This corresponded with increases in colonic expression of epithelial integrity marker occludin and water channels aquaporin 4 and aquaporin 8 in Pkd1KO mice. Together, these data insinuate that loss of Pkd1 in the intestines leads to a tighter intestinal barrier accompanied by increased water channel expression and gut motility. These findings appear unrelated to inflammatory involvement in early PKD. These studies were supported by NIH T32 DK007545 to RS, R01 DK132028 to TS, and R03 DK119717 to TS. 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.
Spinal TNF-α receptor expression in a rodent model of respiratory motor neuron death
Authors: Lewis Ryan , Smith Catherine , Nichols Nicole 
Published: May 2024

Intrapleural injection of cholera toxin B fragment conjugated to saporin (CTB-SAP) selectively kills respiratory motor neurons, and mimics aspects of neurodegenerative diseases including breathing deficits. In this model, phrenic long-term facilitation (pLTF) induced by acute intermittent hypoxia is enhanced following 7 days (d) of CTB-SAP vs. control rats, whereas pLTF in 28d CTB-SAP treated rats is comparable to pLTF in controls suggesting that the underlying mechanisms of plasticity at both time points differ. Inflammation is a hallmark of neurodegenerative diseases and is known to prevent pLTF. Furthermore, ketoprofen (NSAID) delivery attenuates pLTF in 7d CTB-SAP-treated rats, but enhances it in 28d CTB-SAP-treated rats; this suggests that inflammation contributes to pLTF in 7d CTB-SAP-treated rats, but undermines pLTF in 28d CTB-SAP-treated rats. In addition, cervical spinal inflammatory marker gene expression ( e.g., TNF-a) is increased in CTB-SAP rats, and pilot data suggest that soluble TNF receptor 1 (sTNFR1) inhibition differentially affects pLTF (Nichols and Smith , ibid). Thus, the goal of the current study is to investigate TNFR1 as a pharmacological target that can modulate inflammation to maximize pLTF and breathing in CTB-SAP rats. We hypothesized that C4 TNFR1 expression would be increased on phrenic motor neurons and glial cells of CTB-SAP rats vs. controls. To address this, we studied TNFR1 expression on phrenic motor neurons and glial cells using immunohistochemistry, confocal microscopy, and ImageJ analysis in male Sprague Dawley rats 7 and 28 days after intrapleural injection of: CTB-SAP or un-conjugated CTB and SAP (control); n=8/group. Our preliminary data (n=4/group) suggest that phrenic TNFR1 expression is increased in 7d CTB-SAP rats vs. controls (p<0.05), but is unaffected in 28d CTB-SAP rats vs. controls (p>0.05). Further data analysis is underway for phrenic as well as glial TNFR1 expression in CTB-SAP rats vs. controls. If C4 TNFR1 expression is increased, this would suggest that TNFR1 is a viable target for therapeutic intervention in CTB-SAP rats, and potentially in patients with breathing deficits due to respiratory motor neuron death. NSF Computational Neuroscience grant, MU CVM COR grant, and Spinal Cord Injury & Disease Research Program grant. 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.
Shared and Distinct Cellular and Molecular Landscapes of Cardiac Left Ventricle Injury in Three Models of Hypertension: Insights from Single-nucleus RNA Sequencing
Authors: Qiu Qiongzi , Liu Yong , Xue Hong , Liu Jing , Therani Bhavika , Usa Kristie , Huang Jing 
Published: May 2024

High blood pressure is the leading risk factor of heart diseases, affecting millions of patients who remain hypertensive despite taking three or more anti-hypertensive medications. Understanding the cellular and molecular basis of heart damage at cell type-specific level in different types of hypertension is crucial for developing targeted therapies. In this study, we applied 10x Genomics' single-nucleus RNA sequencing (snRNA-seq) technology to cardiac left ventricle samples from three well-established hypertension models: C57BL/6 mice treated with Ang II, the Dahl salt-sensitive rat, and the spontaneous hypertensive rat, along with their respective controls. Our dataset included 166,489 nuclei from 18 samples across 9 experimental conditions. Our analysis revealed a shared set of cellular and molecular changes across these hypertensive models. For instance, we observed extracellular matrix remodeling in fibroblasts in salt-sensitive and spontaneous hypertension, as indicated by increased collagen production. Endothelial cells showed an increased proportion in all three models, and showed higher levels of injury based on expression patterns of increased proliferation and migration. Both AngII-induced and spontaneous hypertension showed cardiomyocyte dysfunction, affecting cardiac muscle contraction and ATP metabolic process. Notably, impaired ATP generation was a common response in AngII-induced hypertension, involving not only cardiomyocytes but also endothelial cells and fibroblasts. During the progression of salt-sensitive hypertension, a notable increase in inflammation occurred, marked by steadily increasing immune cell infiltration, eventually reaching a 1.5-fold increase in immune cells. T cells were particularly elevated during the high-salt diet and actively engaged in the CD45 signaling network in the late stage of spontaneous hypertension, where an elevated interaction between cardiomyocyte and endothelial cells through vascular endothelial growth factor was observed. In conclusion, the utilization of snRNA-seq identified shared and distinct cellular and molecular changes associated with left ventricular injury in various models of hypertension. NIH grant HL149620. 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.
Use and Perception of Peer Recommendations to Improve Study Skills in Undergraduate Anatomy and Physiology Courses
Authors: Brundage Cord 
Published: May 2024

Student success data from students enrolled in an undergraduate anatomy and Physiology (A&P) course at the University of Wisconsin-La Crosse indicated that student performance closely correlated with the number of prior completed university semesters. Based on this data we hypothesized that some students may have gained (or use) study skills that may have contributed to their success. Students at the end of the term were asked to provide recommendations to future A &P students on how to be successful in the course. A total of 408 recommendations from 68 students were received and underwent inductive and then deductive coding. More than 50% of respondents encouraged group studying and frequent engagement with material. The ranked and coded list of recommendations was then provided to the entering student at the start of the new term. Entering students were subsequently polled to gauge perceptions/reactions to this information. 91% of entering A&P students (n = 73) responded that they valued receiving study recommendations at the start of the term 59% of which said they preferred having that information come from former students rather than the faculty. Following the 1st lecture examination these students completed an Ink Shedding activity in which they shared exam studying strategies with their peers. Of the 62 participants 80% both found the activity helpful and recommended it be incorporated into future semesters. Collectively this data supports the perceived value of offering study skill resources to upper division A&P students and a positive reaction to peer guidance. Student performance improved on embedded course assessments. This information has been used to further develop peer mentoring programs and resource collaboration within the A&P lecture and laboratory curriculum. This research was supported by a UWL FY2023 Course Improvement Grant and a University of Wisconsin System IDEAS Alliance Curriculum Reform Grant. 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.
Advanced Metrics and Early Predictors of Cardiogenic Shock
Authors: Shah Nisarg 
Published: May 2024

Cardiogenic shock (CS) can be defined as a range of illnesses that describes a state where cardiac output, which is the blood volume ejected from the left ventricle every minute that leads to tissue perfusion of nutrients, is insuffcient in providing adequate oxygenation to the systemic circulation. The incidence of CS on admission has increased in recent years, with the six- and 12-month mortality rates remaining unchanged. The purpose of this literature review is to bring forth several parameters that have been utilized in the past 10 years to predict CS mortality. Further studies to implement these parameters in management algorithms, along with early screenings and advanced treatment options such as mechanical cardiac assist devices, can improve the mortality associated with CS. This literature-based review was conducted by evaluating current research focusing on the clinical presentation of CS and predictors of CS. PubMed served as the primary database for article retrieval due to access. Two searches were conducted: One for clinical presentations and advanced metrics for CS and another for early predictors for CS. Thirteen articles regarding clinical presentation and seven articles regarding early predictors were selected. Three tools/scores and five laboratory tests were identified that allowed clinicians to prognosticate outcomes in patients suffering from CS based on clinical and laboratory presentations. Examining these predictors will allow earlier intervention in the development of CS and potentially help lower the mortality rate of CS. The eventual creation of a scoring system that incorporates multiple metrics discussed in this review can provide the most accurate prognosis of CS, which can lead to more targeted interventions. 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.
Studies on Membrane Potential and Ca2+ Oscillations in Rat Carotid Body Type I Cells
Authors: Kim Donghee , White Carl 
Published: May 2024

Carotid body (CB) glomus cells sense changes in arterial O2 pressure (PO2) and pH, and adjust the secretory and carotid sinus nerve activity and ventilation to help maintain normal levels of blood PO2 and pH. Our recent studies showed that isolated CB cell clusters perfused with physiological buffer solution generate spontaneous Ca2+ oscillations at low frequency in normoxia. Mild and moderate levels of hypoxia (2-5%O2) and acidosis (pHo7.2-7.3) increased the frequency and amplitude of Ca2+ oscillations. Inhibitors of voltage-dependent Ca2+ channels and removal of external Ca2+ abolished Ca2+ oscillations, indicating that Ca2+ influx was critical for generating Ca2+ oscillations. To better understand the phenomenon of Ca2+oscillations in glomus cells, we examined the potential role of oscillations in cell membrane potential (Em) in CB cells in triggering Ca2+ influx and Ca2+ oscillations. Using the cell-attached patch configuration, we assessed cell Em by recording TASK single channels, because a linear relationship exists between TASK amplitude and cell Em. Recording of TASK in CB cells in normoxia showed that many CB cells exhibit oscillations in TASK amplitude, indicating the presence of spontaneous oscillations in cell Em. The oscillation frequency of cell Em was similar to that of Ca2+ oscillations. Oscillations in TASK single channel amplitude were blocked by nifedipine (Ca2+ channel antagonist), by removal of extracellular Ca2+, and by 2-APB (an inhibitor of ER Ca2+ channel and store-operated Ca2+ entry). Mild hypoxia increased the frequency of oscillations of TASK amplitude, indicating that mild hypoxia increased the frequency of cell Em oscillations. These findings suggest that cell Em oscillations (that open voltage-dependent Ca2+ channels and increase Ca2+ influx) are an integral component of the cellular signaling mechanism by which Ca2+ oscillations are produced in CB cells. This work was funded by National Institutes of Health (NIH) grants to D.K. (HL111497) and C.W. (HL142906), and an award from Rosalind Franklin University of Medicine and Science. 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.
Caloric Restriction Improves Hepatic Thyroid Hormone Signaling During Metabolic Syndrome
Authors: Jardines Eira , Cornejo Manuel , Nakano Daisuke , Nishiyama Akira , Ortiz Rudy 
Published: May 2024

Thyroid hormone dysregulation has been associated with metabolic syndrome (MetS) risk factors: hypertension, atherogenic dyslipidemia, obesity, and glucose intolerance. Several pathways are regulated by thyroid hormones such as the insulin signaling pathway, lipid metabolism, and antioxidant production among others. Impairment of thyroid hormone production causes dysregulation of these pathways. Caloric restriction (CR) is a form of non-pharmaceutical approach that has been shown to ameliorate MetS cluster factor conditions. However, caloric restriction's effects on thyroid hormone signaling during MetS remains unclear. A cohort of 11-week-old Otsuka Long Evan Tokushima Fatty (OLETF) and lean-strain control Long Tokushima Evans Otsuka (LETO) rats were fed chow ad libitium for 4 weeks. At 15 weeks, the animals were fed a 50% CR diet (compared to their control) for 10 days and assigned to four groups: (1) LETO (n=14), (2) LETO CR (n=14), (3) OLETF (n=14), and (4) OLETF CR (n=14). After the CR period, 7 animals from each group were then refed at pre-CR levels for 7 days and assigned to four groups: (1) LETO (n=7), (2) LETO post-recovery (LETO PR; n=7), (3) OLETF (n=7), and (4) OLETF PR (n=7). Mean body mass decreased 12% and 14% in LETO and OLETF, respectively, during the CR period compared to their ad lib controls. Hepatic deiodinase 1 (Dio1) protein expression was reduced by 41% in the OLETF compared to LETO. Dio1 protein expression was increased by 150% during CR and 88% by PR in OLETF. Deiodinase 2 (Dio2) showed a decreasing trend in OLETF rats compared to LETO and an increasing trend in the OLETF CR group compared to its ad lib control. Both free (fT4) and total T4 (tT4) had increasing trends in OLETF compared to LETO. CR induced a decreasing trend in fT4 and tT4 in OLETF compared to ad lib OLETF controls. These findings demonstrate that caloric restriction induces changes in hepatic thyroid hormone signaling that can improve impaired metabolism induced by MetS. Doctoral fellowship UC MEXUS-CONACYT 440553 National Institute on Minority Health and Health Disparities grant 9T37-MD001480 American Heart Association 23DIVSUP1066372. 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.