bluuebunny/crossref_metadata_2025_split huggingface dataset:
There is a greater ratio of Phox2B positive neurons to total neurons in the Nucleus of the Solitary Tract (NTS) than in the Dorsal Motor Nucleus of the Vagus (DMV)
Authors: Smith Madison , Martino Paul F. , Miller Justiin , Neumueller Suzanne , Hodges Matthew R. , Forster Hubert V. 
Published: November 2023

BackgroundCongenital Central Hypoventilation Syndrome (CCHS) is characterized by severe apnea during sleep and dysfunctional chemosensitivity while awake. These patients exhibit a mutation in the 4p13 gene which codes for the Phox2b transcription factor. It has been established that the chemosensitive Retrotrapezoid Nucleus (RTN) is defined by Phox2b positive neurons on the ventral surface of the medulla which underlies the ventilator deficits for this syndrome. However, some patients also exhibit gastrointestinal and auditory complications, which are not related to the RTN. These neurons have yet to be defined in other areas of the brainstem for their specific functionality such as in the Nucleus of the Solitary Tract (NTS) and Dorsal nucleus of the vagus nerve (DMV). Discovering the functions of Phox2b+ neurons in other nuclei will help explain the other complications that can be expressed by the 4p13 gene mutation other than hypoventilation.MethodTo begin this process we defined whether there are Phox2b+ neurons in the NTS and DMV of goat subjects as well as the ratio of Phox2b+ neurons to total number of neurons in the NTS both caudal and rostral to obex. This was done through counting neurons in both a nissl and a Phox2b stain under a standard microscope.ResultThus far, we have found a significant number of Phox2b+ neurons from −1 to 3 mm in NTS and DMV. However, there is a lower ratio of Phox2b+ to total neurons within 1 millimeter both caudal and rostral from obex in the NTS, and from obex to 2 millimeters rostral in the DMV. The caudal portion of NTS has been known to be a site of central chemosensitivity, while the DMV is known to have gastrointestinal and respiratory functions.ConclusionNow that we have characterized the expression of Phox2b in the NTS and DMV, future studies will be aimed at determining their contribution to physiologic functions characterized in the NTS.Support or Funding InformationSupport: NIH HL25739 & Veterans Administration
The inwardly‐rectifying potassium channel subunit Kir5.1 contributes to acute and chronic pH homeostasis in rats
Authors: Hodges Matthew Robert , Puissant Madeleine Marie , Geurts Aron M. 
Published: November 2023

The brain contains pH/CO2‐sensitive cells that may contribute to the acute regulation of pH through the ventilatory CO2 chemoreflex, including serotonergic neurons. However, molecular mechanisms by which these cells “sense” pH and or CO2 are not clear. We previously showed that inwardly‐rectifying potassium (Kir) subunit genes, Kcnj10 and Kcnj16 and their respective proteins (Kir4.1 and Kir5.1, respectively) increased in expression across development in serotonin (5‐HT) neuron‐enriched cell pools collected via flow cytometry. These Kir channel subunits combine with each other and other subunits to form pH sensitive K+ channels, and knockout of Kir5.1 in mice eliminates neuronal pH responses. Thus, we tested the hypotheses that in rats: 1) Kir5.1 channels were expressed in mature 5‐HT neurons, 2) that mutation of Kir5.1 channels would disrupt pH homeostasis and blunt the relationship between ventilation and pH/CO2. Kir4.1 and Kir5.1 immunoreactive (‐ir) cells were found throughout the brainstem, where all Kir4.1‐ir was co‐localized to glial cells (GFAP+). In contrast, Kir5.1‐ir cells were both glial and neuronal (NeuN+), where many 5‐HT (TPH+) neurons co‐localized with Kir5.1. We then measured breathing and blood gases in Kcnj16 mutant rats, in which a 18 base pair deletion was created in exon 1 of the Kcnj16 gene in Dahl S (SS) rats (SS‐Kcnj16em1Mcwi rats). SS‐Kcnj16em1Mcwi rats were smaller in size (~40%) but did not show increased mortality after weaning. SS‐Kcnj16em1Mcwi rats had Kir5.1‐ir cells throughout the CNS, indicating the mutation was not a null mutation. SS‐Kcnj16em1Mcwi rats were in chronic metabolic acidosis (pH ~7.32) at rest breathing room air, which was partially compensated as ventilation was increased (via increased tidal volume) and arterial PCO2 was decreased compared to naïve SS rats (P<0.05). Paradoxically, SS‐Kcnj16em1Mcwi rats showed a blunted relationship between ventilation and arterial PCO2 and pH when environmental CO2 was increased to 3, 5, 7 or 9% CO2. In control SS rats, ventilation increased 528.5 ± 58.4 ml/min for every decrease of 0.1 of pH units, compared to 300.8 ± 51.2 ml/min/0.1 pH unit in SS‐Kcnj16em1Mcwi rats. Similarly, ventilation increased 40.4 ml/min/mmHg and 25.8 ± 2.9 ml/min/mmHg in control and SS‐Kcnj16em1Mcwi rats, respectively. These data suggest that pH sensitive Kir5.1‐containing channels may contribute to glial and (5‐HT) neuronal pH sensitivity in rats, and that Kir5.1 channels contribute to acute and chronic regulation of pH homeostasis.Support or Funding InformationNIH HL122358 and HL112996
Activation of Bitter Taste Receptors in Rat Pulmonary Sensory Neurons Augments Capsaicin‐Evoked TRPV1 Responses
Authors: Gu Qihai , Joe Deanna , Gilbert Carolyn , Gabriel Sabry 
Published: November 2023

Bitter taste receptors (T2Rs), a G‐protein‐coupled receptor family capable of detecting hundreds of bitter‐tasting compounds, have recently been shown to be expressed and play diverse roles in various extraoral tissues. Here we report the functional expression of T2Rs in rat pulmonary sensory neurons. In anesthetized spontaneously breathing rats, intratracheal instillation of T2Rs agonist chloroquine (10 mM, 0.1 ml) significantly augmented the chemoreflex responses evoked by right‐atrial injection of capsaicin, a specific activator for transient receptor potential vanilloid receptor 1 (TRPV1); whereas intravenous infusion of chloroquine failed to significantly affect capsaicin‐evoked reflexes. In patch‐clamp recordings with isolated rat vagal pulmonary sensory neurons, pretreatment with chloroquine (1–1000 μM, 90 s) concentration‐dependently potentiated capsaicin‐induced inward currents. This sensitizing effect of chloroquine was effectively blocked by phospholipase C inhibitor U73122 (0.75 μM), or by protein kinase C inhibitor chelerythrine (5 μM). In summary, our study showed that activation of T2Rs augments capsaicin‐evoked TRPV1 responses in rat pulmonary sensory neurons, through phospholipase C and protein kinase C signaling pathway.Support or Funding InformationSupported by funds from MEDCEN and MUSM.
Blocking Volume Regulated Anion Channels (VRAC) with DCPIB Depresses Avian Intrapulmonary Chemoreceptor (IPC) Discharge more in Tonic than Phasic Units
Authors: Molloy Rhett Gordon , Bassett Peter Ross , Lonjaret Jean‐Guillaume , Burchinal Krystal L , Hempleman Steven Curtis 
Published: November 2023

Intrapulmonary chemoreceptors (IPC) are respiratory vagal afferents that sense PCO2 changes and are responsible for controlling breathing in birds. Volume regulated anion channels (VRAC) are responsible for volume regulation in a large variety of cell types. Small doses of DCPIB (1 to 8 μmol/kg), a specific blocker of VRAC, were used to test for VRAC presence in IPC of pentobarbital‐anesthetized ducks (Anas platyrhyncos, n=11). Cycle triggered stimulus histograms of IPC action potential discharge to 0%–7% inspired CO2 steps were recorded and separated into 2 groups according to their spike frequency adaptation: phasic (n=4), tonic (n=7). The IPC discharge for phasic units remained unchanged from the control for the 1 to 4 μmol/kg doses, while the 8 μmol/kg dose reduced the peak phasic adaptation (ANOVA, p<0.01). Tonic units progressively reduced discharge for all doses (ANOVA, p<0.01). Since DCPIB more strongly affects IPC discharge in tonic units compared to phasic units the results suggest that: 1. Tonic and phasic units may have different mechanisms for VRAC activation, or 2. Tonic units express more VRAC than phasic units.Support or Funding InformationSupport: NIH R15 HL087269‐02.
The Testing Effect Varies with Spaced Versus Massed Learning of Skeletal Muscle Information
Authors: Dobson John , Perez Jose 
Published: November 2023

Learners who engage in testing or effortful retrieval throughout learning tend to retain more following a delay compared to those who read and reread to‐be‐learned materials. Additionally, studying sessions that are spaced apart by one or more days tend to promote more recall than do those that are massed together at the same time. Although both the testing and spacing effects are well‐established in the cognitive psychology literature, no studies have examined their additive effect with anatomy and physiology information. The purpose of this study was to determine if the benefits of a testing‐based strategy vary with massed versus spaced learning sessions. Participants used the following strategies to learn sets of human skeletal muscle information: 1. reading‐rereading on three different days (RRRRx3), 2. reading‐testing on three different days (RTRTx3), 3. reading‐rereading on two different days (RRRRRRx2), 4. reading‐testing on two different days (RTRTRTx2) and 5. reading‐testing on a single day (RT6x1). The five strategies were standardized so that participants used each for a total of exactly twenty four minutes. The retention of muscle information was assessed via free recall. One week after learning, the assessment scores were 24.10 ± 3.08, 33.74 ± 3.43, 15.47 ± 2.44, 20.56 ± 2.89 and 12.76 ± 2.02 for the RRRRx3, RTRTx3, RRRRRRx2, RTRTRTx2 and RT6x1 strategies, respectively. In conclusion, the more spaced strategies produced better recall than the less spaced strategies, the testing‐based strategies produced better recall than reading‐only strategies, and the combination of spacing and testing generated the greatest recall of muscle information.Support or Funding InformationNone
How do we train our future faculty to teach? Results from a multidisciplinary comparison of pedagogy courses offered at a large midwestern university
Authors: O'Loughlin Valerie Dean , Kearns Katherine D , Robinson Jennifer Meta , Sherwood‐Laughlin Catherine 
Published: November 2023

Much effort is devoted to training graduate students (a.k.a. future faculty) to perform research; less attention is paid to their development as teachers. Previous research has demonstrated that pedagogy courses help support the developmental progression of graduate students. These courses allow the student to develop and reflect on teaching experience, and progress from excellent teachers to teacher‐scholars (individuals who practice scholarly teaching). This previous research typically has focused on single pedagogy courses, where findings may be context‐specific and sample sizes (i.e., student enrollment) typically is small.Our research is the result of a metacollaboration among individuals with prior experience in studying the effects of individual pedagogy courses. Here, we focus on examining multiple (over 30) discipline‐specific and interdisciplinary graduate pedagogy courses offered at Indiana University, a large midwestern research‐intensive university. By comparing and pooling data from multiple courses, we have been able to substantially increase sample sizes and generalize our research findings about teacher‐scholar development. Faculty who teach pedagogy courses were invited to complete an online survey and provide the researchers with the syllabi from their courses for analysis of how these courses help graduate students a) develop into teacher‐scholars and b) express their teaching identity through a teaching statement.Survey results indicated that multiple disciplines across the university offer graduate pedagogy courses. These courses typically are 3‐credit hour semester courses, although some courses are offered as intensive summer sessions or as 8 week courses. Enrollment means range from 8–15 students for most courses. Over 3/4 of these courses introduce students to the concept of a teaching statement, and the majority of these courses require students to complete a teaching statement as part of the course. Additional data and comparisons will be presented at the meetings, and the implications for graduate student teacher‐scholar development will be discussed.Support or Funding InformationThis research was funded, in part, by a 2015 Indiana University SoTL (Scholarship of Teaching and Learning) grant
Measurement Theory and the P‐matrix: Ramifications of Variable Choice
Authors: Savell Kristen R. R. , Auerbach Benjamin M. 
Published: November 2023

Choosing which measurements to include in an analysis is often as much a matter of tradition and training as critical evaluation. Variable choice, however, may have unintended consequences on conclusions, especially in studies that assume these variables reflect evolutionary and developmental processes. Such studies include quantitative genetic analyses that use phenotypic variance‐covariance matrices (P‐matrices) as an estimation of genotypic variance‐covariance. P‐matrices are assumed to be proportional to G‐matrices within a population, and therefore serve as proxies for interpreting evolutionary change. However, since the multivariate space of a P‐matrix will change with the addition or subtraction of variables, P‐matrices may be limited by the biases associated with variable choice. For example, what is the range of possible variation observed in the P‐matrices of a single skeletal element within the same taxa, and how can this variance inform our understanding of P‐matrix construction?To study the ramifications of variable choice in the construction of P‐matrices, linear measurements (representing a range of genetic, developmental, and activity‐based morphologies) were taken from the tibiae of 60 tamarins (Saguinus). These dimensions were mean‐scaled to remove the effects of trait size magnitude. Individuals from three subspecies (S. oedipus, S.f. illigeri, S. f. nigrifrons) were pooled, as random skewer analysis indicated no significant differences between their sub‐specific P‐matrices. This pooled P‐matrix was created of all six measurements then subjected to randomly‐generated selection gradients to allow for comparison between responses (following Lande). The influence of matrix construction was evaluated by calculating cosine‐similarities between the response vectors of the complete P‐matrix and P‐matrices that had either one measurement or a pair of related measurements (lengths, diaphyseal diameters, or epiphyseal widths) removed. Results indicate that, regardless of selection gradient, tibial length provides nearly all of information included in the complete P‐matrix response. Similarly, the removal of other measurements did not substantially alter the response vector. In fact, the role of non‐length measurements was so low and the correlation between the two length measurements so high, the same amount of explanatory information was contained within a single variable of length as in the complete variance‐covariance matrix.Though this relationship may be unsurprising on a biological level, it demonstrates the importance of variable choice in the creation of a P‐matrix. Ultimately, quantitative genetic analyses of this variety rely on understanding the structure and apportionment of variance, and so traits that explain most of the variance will swamp the explanatory power of other traits that may be evolutionarily informative. Care must therefore be taken in selecting traits to include in evolutionary studies using P‐matrices.
Surgery to Relieve Thoracic Outlet Syndrome Complaints Should Have Preoperative Imaging:MRI/MRA/MRV
Authors: Collins James Douglas , Saxton Ernestina Howell , Gelabert Hugh Anthony , Carnes Alfred 
Published: November 2023

INTRODUCTIONThoracic Outlet Syndrome (TOS) patients are normally managed conservatively with physical therapy (PT) and may undergo scalenectomy and first rib resection without imaging. Bilateral multiplanar magnetic resonance imaging and 2D time of flight magnetic resonance angiography and venography (MRA/MRV) of the brachial plexus display costoclavicular compression of the draining veins within the neck, supraclavicular fossae, and neurovascular bundles as the diagnostic cause of thoracic outlet syndrome.METHODSBilateral MRI/MRA/MRV displays sites of obstruction of the draining veins of the neck and the subclavian and axillary arteries with binding nerve roots. Monitored multiplanar images are acquired on a 1.5 Tesla GE Signa LX unit, 44 cm field of view, 512 × 256 matrix with saline water bags to enhance signal to noise ratio.SUMMARYThe case selected for this presentation was diagnosed with left TOS and left pectoralis minor syndrome. Her surgeon convinced her that there was no need for imaging. However, she developed postoperative complaints and sought evaluation by a neurologist. Thereafter, bilateral imaging of the brachial plexus was requested displaying the surgical alteration of landmark anatomy, costoclavicular compression of binding nerves to the subclavian and axillary arteries, obstruction to venous drainage, scarring and fibrosis from the resected lymphatics marginating veins within the pectoralis minor muscle adhering the pectoralis major muscle to the anterior chest wall.CONCLUSIONNerves, arteries, veins and lymphatics are within the fascial planes marginating muscles. Health professionals should be aware that resection of the pectoralis minor muscle tendon (tenotomy) at the coracoid process disrupts lymph drainage precipitating fibrosis and scarring of those structures within. Baseline plain radiographs and MRI of the brachial plexus should be obtained prior to all surgical intervention.
The Use of “Structured Lab Review” to Augment Student Learning and Its’ Impact on Cadaveric Practical Examination Performance
Authors: Vasan Cheryl , Gentile Mathew , Vasan Nagaswami 
Published: November 2023

In an integrated organ systems‐based preclinical curriculum time for cadaveric dissection and learning from it is becoming a challenge due to reduced curricular hours for delivery of anatomy content. This poses a challenge in which judicial planning is essential in determining how to maximize the available time to benefit student learning. At Cooper Medical School of Rowan University, we faced such a challenge in our Skin and Musculoskeletal (SMS) course during the 2013/2014 academic year that resulted in poorer student exam performance. While students performed satisfactorily on anatomy specific content in the written exam, their performance in the cadaver based practical exam suffered. The cadaver oriented exam required students to identify a tagged structure and answer a primary, secondary, or tertiary question related to the tagged structure. We realized that students were able to identify structures on their cadaver, but not on their fellow classmate's cadavers as they spent very little time in reviewing cadavers other than their own. This resulted in a lack of familiarity, on the part of the students, with regards to structures on the other cadavers. This presented a challenge as to how to improve student recognition of structures across cadavers, as well as it created an opportunity to institute Structured Lab Review sessions within the 2015 SMS course. The Structured Lab Review required students to rotate as a dissection team through all the cadavers, identify several structures from a list provided at each cadaver, answer secondary and tertiary questions about the structures, as well as engage in peer‐to‐peer teaching when group members required help in answering a question(s). We found that students performed significantly better in the 2015 SMS practical exams when compared to the 2014 exams. In addition, students were very satisfied with the Structured Lab Review sessions. This poster will provide the details of planning and executing a Structured Lab Review session as well as provide examples of questions used. Analysis of student performance will be presented. Furthermore, we have since instituted “Structured Lab Review” sessions in the other system‐based modules for academic year 2015/2016.Support or Funding InformationThis study was supported by the Department of Biomedical Sciences.
Proteomic analysis of a meiotic recombination hotspot
Authors: Storey Aaron J , Protacio Reine U , Tackett Alan J , Davidson Mari K , Wahls Wayne P 
Published: November 2023

Meiotic recombination promotes genetic diversity within species and is essential for accurate segregation of homologous chromosomes in meiosis I. Hotspots regulate the frequency and distribution of recombination in the genome. DNA binding proteins and post‐translational modifications (PTMs) of histones help to regulate hotspots by recruiting the basal recombination machinery (e.g., Spo11/Rec12), but few of the ~400 known histone PTMs have even been interrogated for a potential role in recombination. Here, we developed a mass spectrometry‐based approach for the unbiased, systematic discovery of hotspot‐specific (potentially regulatory) proteins and histone PTMs using the well‐characterized, DNA sequence‐dependent hotspot ade6‐M26 of fission yeast. We constructed small (4.2 kbp) minichromosomes (MiniCs) harboring hotspot and negative control alleles. Chromatin immunoprecipitation (ChIP) of recombination‐initiating dsDNA breaks revealed that the hotspot is active in MiniCs. MiniCs were purified from meiotic cultures using the high‐affinity interaction between LacO DNA sites in the MiniCs and a prA‐LacI fusion protein conjugated to beads. Enrichment levels of 20,000‐fold (relative to single copy loci) were routinely observed by gel electrophoresis and quantitative PCR. Mass spectrometry of the MiniCs identified 1023 proteins, 71 of which were enriched specifically in the hotspot sample. Fifteen different histone PTMs were identified, along with 7 histone modifying enzymes and 37 recombination‐related proteins. The DNA repair proteins Dmc1 and Rad50 were highly enriched in the hotspot sample, further validating the sensitivity and accuracy of this approach. We are currently implementing isobaric mass tag strategies using the latest generation of mass spectrometry instruments for more powerful quantitation of resulting proteomic datasets, and we are validating the biological functions of newly discovered hotspot factors.Support or Funding InformationNational Institute of General Medical Sciences (R01 GM081766)
Complex Roles of ADAM Cell Surface Metalloproteases During Cranial Neural Crest Cell Migration
Authors: Alfandari Dominique , Abbruzzese Genevieve , Mathavan Ketan , Cousin Helene 
Published: November 2023

Objective/BackgroundADAMs are cell surface metalloproteases that shed a variety of substrate from the plasma membrane and contribute to multiple signaling cascades. Our objective was to determine the role of this protease during cranial neural crest cell migration.MethodsWe have used replacement of the endogenous ADAM proteins with proteins encoding truncated and mutated forms to test their ability to promote neural crest cell migration. Migration was assessed by following fluorescently labeled cells in vivo and in vitro.ResultsWe found that meltrins (ADAM9, 13 and 19) play a complex role to promote cranial neural crest cell migration. ADAM9 and 13 cleave Cadherin‐11 to release an extracellular fragment that promotes cell migration by signaling via receptor tyrosine kinases. In addition ADAM13 cleaves multiple protocadherins and extracellular matrix proteins that may contribute to its activity during CNC migration. Finally, the cytoplasmic domain of ADAM13 undergoes multiple phosphorylation and cleavage that result in its translocation into the nucleus where it regulates the expression of multiple genes including cytoplasmic (calpain8) and extracellular proteases (MMP13).ConclusionsWhile the proteolytic activity of ADAM is certainly critical as confirmed by our study, our result also uncovered an independent role for the cytoplasmic domains that has been conserved during evolution.Support or Funding InformationNIH RO1‐DE016289, NIH F31‐DE023275