bluuebunny/crossref_metadata_2025 huggingface dataset:
Responses of neurons in the caudal medullary lateral tegmental field to visceral inputs and vestibular stimulation in vertical planes
Authors: Yates Bill J , Moy Jennifer D , Miller Daniel J , Catanzaro Michael F , Boyle Bret D , Ogburn Sarah W , Cotter Lucy A , McCall Andrew A
Published: June 2021

The dorsolateral reticular formation of the caudal medulla, or lateral tegmental field (LTF), has been classified as the brain's “vomiting center” as well as an important region in regulating blood pressure. We examined in cats the responses of LTF neurons to rotations of the body that activate vertical semicircular canals and otolith organs, as well as to stimulation of baroreceptors and gastrointestinal receptors (through the intragastric administration of the emetic compound copper sulfate). Half of the LTF neurons exhibited graviceptive responses to vestibular stimulation, similar to primary afferents innervating otolith organs. The other half of the neurons had complex responses, suggesting that they received convergent inputs from a variety of vestibular receptors, as expected for neurons that contribute to the generation of motion sickness. The administration of copper sulfate often modulated the gain of responses of LTF neurons to vestibular stimulation, particularly for units whose spontaneous firing rate was altered by infusion of drug (median of 459%). The present results thus raise the prospect that emetic signals from the gastrointestinal tract modify the processing of vestibular inputs by LTF neurons, thereby affecting the probability that vomiting will occur as a consequence of motion sickness.
Characterizing the expression of voltage gated calcium channels in rat superior cervical ganglia
Authors: Scott Mallory , Kammermeier Paul
Published: June 2021

Voltage gated calcium channels (Cav) are comprised of several different subunits necessary to achieve proper function. Some of the subunits (β, α2‐γ) contribute to not only channel properties, but to trafficking. In heterologous expression systems that lack endogenous Cav channels, pore‐forming subunits must be co‐expressed with accessory subunits for channel localization to the plasma membrane and for proper function. In some neurons expression of an exogenous pore, without co‐expression of its respective subunits, can result in a functional channel. We investigate the channel expression in the cell body of rat superior cervical ganglion neurons (SCG) using whole cell patch clamping. SCG neurons express mainly type 2 Cav channels. Interestingly, when the cDNA encoding Cav pore‐forming subunits are injected intranuclearly into SCG neurons, large increases in current density corresponding to recombinant Cav channel expression are observed in a subunit specific manner. These data suggest that pre‐formed, sub‐unit specific “slots” exist in SCG neurons to allow for the expression, trafficking and function of certain Cav channel subunits, but not others. Using this approach, we observe significant increases in calcium current density following the expression of Cav 2.1, mCav2.3, Cav 1.3 subunits, but no increase in current density when Cav 2.2 or Cav 1.2 are injected. RO1 GM101023
Expressions of epithelial Na+ channel subunits in the supraoptic nucleus of the hypothalamus in the male rat in response to dietary NaCl intake
Authors: Haque Masudul , Wilson Lori L , Teruyama Ryoichi
Published: June 2021

All three epithelial Na+ channel (ENaC) subunits (α, β, and γ) were demonstrated in vasopressin (VP) synthesizing magnocellular neurons (MNCs) in the hypothalamic supraoptic (SON) and paraventricular nuclei. Our recent findings showed that ENaC mediates a Na+ leak current that changes the frequency of action potentials in MNCs. In the present study, we assessed the effect of dietary NaCl intake on ENaC subunits in the SON. Male rats were fed either a 8% NaCl diet, a NaCl deficient, or a control diet for two weeks. Then, relative changes in the subunit mRNAs in the SON and kidney were measured by real‐time RT‐PCR. The 8% NaCl diet caused significant increase in β‐ and γ‐ENaC mRNAs in the SON, while expression of α‐ENaC did not change. In contrast, the 8% NaCl diet did not cause any marked changes in expressions of the subunits in the kidney, while a deficiency in dietary NaCl caused a significant rise in α‐ENaC mRNA. Change in the subcellular distribution of α‐ENaC immunoreactivety in MNCs was also observed using confocal microscopy. The labeling in the MNCs from the 8% NaCl diet group was distinctively concentrated towards the plasma membrane in all 5 rats tested, while those from the NaCl deficient and control groups were mainly dispersed in the cytoplasm with no distinct labeling at the plasma membrane. These findings imply that dietary NaCl affects ENaC activity in VP MNCs, which, in turn, affects VP secretion.

NIH grant: R21 HL093728
Stress‐induced changes in gene expression of urocortin 2 and other corticotrophin‐releasing hormone family members in rat adrenal medulla
Authors: Sabban Esther Louise , Tillinger Andrej , Nostramo Regina , Kvetnansky Richard , Serova Lidia
Published: June 2021

The endocrine stress response is influenced by the corticotrophin‐releasing hormone (CRH) family of peptides, with Urocortin 2 (Ucn2) implicated in the regulation of adrenomedullary catecholamine synthesis and release. Here, we examined the effect of immobilization stress (IMO) on gene expression of CRH family members in rat adrenal medulla. Basal Ucn2 mRNA levels were several orders of magnitude higher than CRH, Ucn1 and CRH receptors, and Ucn3 mRNA was undetectable. IMO increased Ucn2 gene expression >;30 fold and also raised CRH mRNA levels, albeit to a lesser extent (6 fold). Involvement of glucocorticoids was studied. Treatment of PC12 cells with dexamethasone greatly increased Ucn2 mRNA levels in a dose‐dependent manner, a response abolished by pretreatment with transcription inhibitor, actinomycin D. Modest changes in CRH receptor type 1 (CRHR1) and type 2 (CRHR2) were also observed. Moreover, IMO did not induce Ucn2 mRNA in CRH knockout mice. The results suggest that the stress‐triggered rise in glucocorticoids stimulates a large induction of Ucn2 mRNA levels which may allow Ucn2 to act in an autocrine/paracrine fashion to modulate adrenomedullary function, or act as an endocrine hormone. Supported by American Heart Association grant 10GRNT4420001 and Slovak grants APVV‐0088–10 and VEGA 2/0036/11.
Development of the lateral line system in the rostrum of the paddlefish
Authors: Caldwell Joshua S. , Robertson John
Published: June 2021

The rostrum of the paddlefish (Polyodon spathula) develops over a short period soon after hatching. The mechanosensory lateral line system includes two canals that run the length of the rostrum and feature numerous neuromasts. The rostrum canals connect with the external environment via a series of accessory canals that open to the rostrum's ventral surface. Thus, these fish are an interesting model for sensory development and integration. The goal of this study was to further the understanding of the development and function of the rostrum. We compared the number of, and the distance between, accessory canals in the rostrum of paddlefish at four developmental stages. After bleaching of 10% NBF‐preserved fish, external application of India ink was used to fill the rostrum lateral line system. Each filled rostrum was imaged and accessory canal numbers and inter‐accessory canal distances were assessed using image analysis programs (ImageJ and GIMP 2). Data indicate that the number of accessory canals and the inter‐accessory canal distances both increased as development proceeded. These results suggest that the two main lateral line canals elongate with rostrum growth via distal extension and elongation of inter‐accessory canal segments. This work indicates that neuromast proliferation in the rostrum lateral line canals would be an interesting subject for further study.
Mechanism of ammonia excretion by ionocytes in medaka (Oryzias latipes) acclimated to seawater
Authors: Liu SianTai
Published: June 2021

The acid‐trapping mechanism is critical for fish to excrete ammonia in fresh water. However, is it also a critical mechanism for seawater fish remains to be examined. Using a scanning ion‐selective electrode technique (SIET) to measure H+ gradients, an acidic boundary layer was detected at the skin surface of SW‐acclimated medaka larvae. Adding tricine buffer or EIPA (a Na+/H+ exchanger inhibitor) in seawater abolished the acid layer and decreased ammonia excretion of larvae. In situ hybridization and immunochemistry showed that slc9a2 (NHE2) and slc9a3 (NHE3) were expressed in skin ionocytes. Real‐time PCR analysis showed that slc9a3 and rhcg1 expression was induced by high ammonia acclimation. This study suggests that ionocytes play a critical role in ammonia excretion, Na+/H+ exchanger (slc9a2 and slc9a3) and Rh glycoprotein (Rhcg1) are involved in the acid‐trapping ammonia excretion of ionocytes in seawater.
Frog skin function revisited; physiology of cutaneous surface fluid of Rana esculenta
Authors: Larsen Erik Hviid , Ramlov Hans
Published: June 2021

Amphibians are adapted to living on dry land where body fluid turnover is governed by evaporative water loss. We aimed at testing the hypothesis [EH Larsen (2011) Acta Physiologica 202: 435–464] that water is evaporating from the cutaneous surface fluid (CSF) secreted by subepidermal glands. Samples of CSF contained, [Na] = 64.5±5.1 and [K] = 14.9±1.6 mM (mean±s.e.m., n = 16) with osmotic pressures of CSF and hemolymph, 168±4 (n = 22) and 238±1.7 (n = 25) mOsm/Kg. The relatively high [K] of CSF and an inwardly directed driving force for transepithelial water flux confirm that gland secretions characterized by high [K] constitute the source of water evaporating from the body surface. Thus, on land CSF is maintained by a balance between fluid secretion by subepidermal glands, water evaporation into the atmosphere, and reabsorption of water and Na by principal cells and Cl by mitochondria‐rich cells of the epidermis. These mechanisms have evolved pari passu with life alternating between aquatic and terrestrial habitats associated with permeabilities of the skin controlled by external ion‐ and osmotic concentrations (loc. cit.). This allows for fast switching of the cutaneous uptake of chloride between active and passive transport associated with dynamic electrical coupling of active sodium uptake by principal cells and passive chloride uptake by mitochondria‐rich cells. Supported by the Carlsberg Foundation.
Role of Endothelin‐1 in altered carotid body function by chronic intermittent hypoxia
Authors: Peng Ying‐Jie , Nanduri Jayasri , Raghuraman Gayatri , Wang Ning , Kumar Ganesh K , Prabhakar Nanduri R
Published: June 2021

Previous studies suggest that endothelin 1 (ET‐1) mediates the chronic intermittent hypoxia (CIH)‐evoked augmented carotid body sensitivity to hypoxia. In addition to affecting the hypoxic sensitivity, CIH induces sensory long‐term facilitation (sLTF) of the carotid body. In the present study, we examined whether ET‐1 contributes to CIH‐induced sLTF. Experiments were performed on adult male rats exposed to 10 days of normoxia or CIH (15s 5%O2 separated by 5 min 21%O2, 8hrs/d). CIH increased ET‐1 content, ET‐1‐like immonustaining and ETA mRNA expression and facilitated hypoxia‐evoked ET‐1 release from the carotid body. ETA receptor antagonist BQ‐610 blocked the augmented hypoxic sensitivity but not the sLTF in CIH exposed rats. Repetitive application of ET‐1 ( 50nM) stimulated the carotid body activity but did not elicit sLTF. These results demonstrate that CIH up regulates ET‐1 in the carotid body and it contributes to CIH‐evoked augmented hypoxic sensitivity but not to sLTF. Supported by NIH‐HL‐76537, and HL‐90554.
PI3‐kinase is involved in plasticity of adult myofibers acting as a nodal step that originates divergent pathways for gene expression
Authors: Jorquera Gonzalo , Altamirano Francisco , Buvinic Sonja , Contreras‐Ferrat Ariel , Jaimovich Enrique , Casas Mariana
Published: June 2021

In skeletal myofibers, transcription of a specific group of genes is regulated by different stimulation frequencies, process known as muscle plasticity. We described IP3‐dependent calcium signals after slow frequency stimulation which were dependent on Cav1.1 and ATP release through pannexin channels. Phosphatidyl inositol 3 kinase (PI3K) is one of the downstream proteins involved in activation of this signaling pathway. Here we present a central role for PI3K in muscle plasticity. We studied expression of sarcomeric (slow and fast troponin I) and metabolic (citrate synthase and enolase) genes, ATP release and IP3 production in adult myofibers from murine FDB muscle. We found a biphasic ATP release and intracellular IP3 increments after 20 Hz stimulation, as well as an increase in TnI‐slow and a decrease in TnI‐fast mRNA levels. In metabolic genes, we observed an increase in citrate synthase and a decrease in enolase mRNA levels. These events were dependent on Cav1.1, pannexin and PI3K. Cav1.1 and Pannexin co‐localize at the T‐tubule membrane. Nevertheless, when fibers were treated with an IP3R blocker (5 μM xestospongin B), we observed an inhibition of TnI gene expression but not of metabolic genes. At 90 Hz, gene expression appears to be independent of IP3‐driven calcium movements. These results show PI3K as a nodal step for plasticity‐related gene expression where signals originated by low frequency stimulation diverge to different routes that control the expression of some sarcomeric genes on one hand and of some metabolic genes on the other.

FONDECYT‐1110467/ACT‐1111, AT‐24110054
The diaphragm rapidly increases expression of muscle atrophy genes following acute cervical spinal cord injury (cSCI)
Authors: Gill Luther , Hamilton‐Ross Heather , Gonzalez‐Rothi Elisa J. , Smuder Ashley J. , Judge Andrew R. , Fuller David D.
Published: June 2021

High cSCI typically leads to diaphragm dysfunction. The purpose of the current work was to explore changes in gene expression in the diaphragm following acute cSCI. Our primary hypothesis was that following unilateral cSCI induced by hemisection of the cervical (C2) spinal cord (C2Hx), the ipsilateral hemidiaphragm would show an increase in the mRNA level of specific proteolytic biomarkers. Diaphragm tissue was harvested from uninjured adult male Sprague‐Dawley rats or rats at 1 or 7 days following C2Hx. Tissue samples were obtained from the medial costal diaphragm ipsilateral to C2Hx. In pilot studies, an 84 well gene array was used to screen for mRNA changes in genes associated with muscle plasticity. Results were subsequently validated using qRT‐PCR. At 1 day post‐C2Hx, the following atrophy biomarkers showed substantial relative increases: MAFbx/atrogin‐1 (5‐fold); MuRF1 (42‐fold); Caspase‐3 (3‐fold); FoxO3 (2‐fold). Genes associated with myogenesis also showed increased expression at both 1 (myogenin, 22‐fold; Myf6, 4‐fold) and 7 days post injury (MyoD, 11‐fold). These data indicate that following C2Hx, the ipsilateral hemidiaphragm undergoes rapid plasticity with increased expression of genes related to muscle atrophy and plasticity.
Mechanical ventilation impairs sarcomeric protein function in rat diaphragm single fibers
Authors: Ahn Bumsoo S. , Sollanek Kurt J. , Smuder Ashley J. , Wiggs Michael P. , Powers Scott K. , Ferreira Leonardo F.
Published: June 2021

Mechanical ventilation (MV) is a widely used clinical intervention for patients unable to maintain alveolar ventilation. Although a life‐saving measure for patients suffering from respiratory failure, MV promotes diaphragm atrophy and contractile dysfunction. The cellular basis of contractile dysfunction remains unclear. The mechanisms of contractile dysfunction are important to understand because MV‐induced diaphragm weakness can delay the weaning process. We studied triton‐permeabilized diaphragm single fibers from rats after 12 hrs of spontaneous breathing (SB) and MV (n = 4/group). Key parameters of isometric contractile properties were maximal specific tetanic force (sPo), rate constant of tension redevelopment (ktr), and calcium sensitivity (pCa50). In type I diaphragm fibers, sPo did not differ between groups. MV slowed ktr by ~6% and decreased the pCa50 such that calcium concentration eliciting 50% sPo increased by ~20%. In type II diaphragm fibers, MV diminished sPo by ~32% and slowed ktr by ~22%. However, pCa50 did not differ between groups. Together, our data suggest that MV impairs diaphragm sarcomeric protein function as evidenced by diminished specific force and calcium sensitivity, and slowing of cross bridge cycling kinetics in membrane‐permeabilized single fibers.

Funding support: NIH R00‐HL098453 (LFF) and HL087839 (SKP)
Muscle disuse atrophy is greater in young compared with elderly individuals
Authors: Dirks Marlou , Wall Benjamin , Snijders Tim , Verdijk Lex , van Loon Luc
Published: June 2021

It is currently unclear whether elderly individuals are more or less susceptible to muscle disuse atrophy compared with young. Here, we compared the magnitude of muscle disuse atrophy between young and elderly subjects. Twelve healthy young (age 23±2 y) and 11 healthy elderly (age 69±3 y) men were subjected to a 5 day period of one‐legged knee immobilization by means of a full leg cast.

Three days prior to and immediately after the immobilization period, single slice CT scans and DXA scans were performed to determine quadriceps cross sectional area (CSA) and leg lean mass, respectively. In addition, muscle biopsies were collected to assess myocellular characteristics (analyses ongoing) and 1RM tests were performed to determine muscle strength. Quadriceps CSA decreased with immobilization in both groups (P<0.001 over time), but to a greater extent in the young (−3.5±0.5 % in young vs −1.1±0.6 % in old, P<0.05 between groups). Leg lean mass declined by 1.4±0.7 % with immobilization in young subjects (P=0.07) while no change was detected in the elderly. Strength was reduced to the same extent in young and old after 5 days (−9.0±2.2 % and −7.6±3.7 % respectively; both P<0.01). We conclude that 5 days of muscle disuse leads to significant muscle atrophy and a substantial decline in muscle strength in both young and old individuals. However, the disuse‐induced loss of muscle mass is greater in young compared with elderly individuals.
Continuous resistance training alters exercise‐induced MMPs activation and expression of ECM components
Authors: Ogasawara Riki , Nakazato Koichi , Sato Koji , Boppart Marni , Fujita Satoshi
Published: June 2021

Recent studies indicate that matrix metalloproteinases (MMPs) and skeletal muscle extracellular matrix (ECM), especially basal lamina, components play a role in muscle mass regulation, although the effects of resistance training (RT) on those proteins are unclear. Thus, the purpose of the study was to investigate the effects of RT on activities and protein expression of MMPs and ECM. Ten male SD rats were divided into 1‐exercise bout (1B) or 18‐exercise bouts (18B) group. This study was conducted in conformance with the FASEB Statement of Principles for the use of animals in research and education. The right gastrocnemius muscle was isometrically trained via percutaneous electrical stimulation (maximum contraction for 5 sec × 5, 5 sets) every other day, whereas the left leg served as a control. MMP‐2 and MMP‐9 activities (via gelatin zymography) were increased 10 min after acute exercise with no change in expression of tissue inhibitors of metalloproteinases in 1B group. However, repeated bouts attenuated exercise‐induced MMPs activation in 18B group. MMPs expressions were significantly higher in trained muscles. RT increased β1‐integrin expression but not the other ECM proteins. Our results suggest that resistance exercise activates MMPs during initial phase of RT but this response is attenuated with continuation of RT.

This study was supported by grant from Meiji Yasuda Life Foundation of Health and Welfare.
Preventive effect of diurnal endogenous melatonin combined with exercise on the cartilage destruction in collagenase‐induced arthritic rats
Authors: Hong Yunkyung , Jo Youngjin , Lee Seunghoon , Hong Yonggeun
Published: June 2021

Osteoarthritis (OA) is characterized by articular cartilage destruction, subsequent joint space narrowing, and pain. The purpose of the study is to determine effects of endogenous melatonin with exercise on the cartilage break‐down in OA rats. Rats, which were injected with type VII collagenase, were divided into two groups: OA + vehicle (Veh), and OA + exercise (Ex). Treadmill exercise (30min/day, 5 days/week) was initiated at 07:00 (Ex[7AM]), 14:00 (Ex[2PM]), and 22:00 (Ex[10PM]), depending on diurnal melatonin rhythm. Compared with the Veh, reduction was shown in the not joint thickness but width of Ex[2PM] as well as Ex[10PM] rats at 4 weeks (P<0.05). MMP13 mRNA was significantly increased at 1 week (P<0.05). MMP13 mRNA was the highest in the Ex[7AM] at 4 weeks, whereas its expression was the lowest in Ex[10PM] (P<0.05). COL2A1 mRNA was increased in the Ex[10PM], whereas it was decreased in the Ex[7AM] as well as Ex[2PM] rats at 1 week (P<0.05). Compared to unaffected side, the bone volume density of affected joint was increased in the Veh at 4 weeks (P<0.05). Trabecular thickness was increased in the Veh (P<0.05). However, there was no significance for both parameters in the intervention groups. These findings suggest that treadmill exercise has a prophylactic effect on articular cartilage destruction, and it is dependent on diurnal rhythm.
Intestine mucosal IL‐22 is reduced following oral probiotic administration: implications on epithelial barrier repair
Authors: Rigby Rachael Jane , Thagia Imtiyaz , Pattisson Charlotte , Ng Siew , Kamm Michael , Knight Stella C
Published: June 2021

Interleukin‐22 (IL‐22) is known to play a key regulatory role at mucosal surfaces including the gut. IL‐22 receptor is predominantly expressed on intestinal epithelial cells (IEC) and evidence suggests that IL‐22 can promote intestinal inflammation and mucosal healing. This study demonstrates a role of probiotics in reducing mucosal IL‐22 and investigates the functional role of IL‐22 on IEC in vitro.

Rectal biopsies were obtained from active ulcerative colitis patients immediately prior to probiotic (VSL#3) oral administration and approx. 2 months post‐exposure. Biopsies were cultured in complete medium overnight, supernatant collected and spontaneous IL‐22 secretion measured using ELISA. Effects of varying IL‐22 concentration (100ngml−1–1ngml−1) were tested in vitro using both cancer (SW480) and non‐transformed IEC lines. Stimulation was carried out for 48h (proliferation) or 2h (mRNA). A significant reduction in IL‐22 secreted from mucosal biopsies was detected following probiotic treatment (n=9; p<0.03). In our system, addition of IL‐22 to in vitro IEC cultures did not significantly change proliferation rates (n=12, per concentration). IL‐22 induced moderate increases in SOCS3 and TNFα mRNA at the 50ng and 10ng/ml doses.

The long‐term effects of IL‐22 on IEC and the predominant source of IL‐22 in the intestinal mucosa will now be investigated.
Hypoxia‐Inducible Factor‐2α Promotes Intestinal Inflammation Through Induction of Epithelial TNF‐α
Authors: Xue Xiang , Shah Yatrik M
Published: June 2021

Background & Aims

Hypoxia can induce a robust inflammatory process termed “hypoxic inflammation”, which is a notable feature in inflammatory bowel disease (IBD). Hypoxic response is mediated by transcription factors hypoxia‐inducible factor (HIF)‐1α and HIF‐2α, both of which are highly induced in IBD. HIF‐1α is a protective factor that limits intestinal barrier dysfunction during inflammation. However, the role of HIF‐2α has not been assessed in hypoxic inflammation and IBD. We hypothesize that HIF‐2α promotes hypoxic inflammation during the progression of IBD.

Methods

The role of HIF‐2α in colitis was assessed in dextran sulfate sodium and citrobacter‐induced colitis mouse models with intestine‐specific gain‐ and loss‐of‐function of HIF‐2α.

Results

Activation of HIF‐2α potentiated colonic inflammation, whereas disruption of HIF‐2α attenuated inflammation in these mouse models of colitis. Further mechanistic analysis showed that HIF‐2α is a master regulator of epithelial derived pro‐inflammatory meditators and directly regulates epithelial tumor necrosis factor (TNF)‐α. In silico analysis predicted and luciferase reporter assay verified that the transcription factor MAZ could bind to TNF‐α promoter and potentiate HIF‐2α mediated TNF‐α induction.

Conclusions

These data demonstrate that HIF‐2α is a critical transcription factor essential in intestinal inflammatory response.

Funding:

National Institutes of Health (grant CA148828 to Y.M.S.); The University of Michigan Gastrointestinal Peptide Center; Jeffrey A.Colby Colon Cancer Research and the Tom Liu Memorial Funds of the University of Michigan Comprehensive Cancer Center.
Alpha melanocortin stimulating hormone actions at the ventromedial hypothalamus increase renal sympathetic nerve activity in fat fed rabbits
Authors: Barzel Benjamin , Burke Sandra L , Armitage James A , Head Geoffrey A
Published: June 2021

The hormone leptin plays a key role in energy homeostasis by a neuronal signalling pathway that starts at the arcuate nucleus. The ventromedial hypothalamus (VMH) receives direct input from the arcuate in the form of downstream alpha‐Melanocortin Stimulating Hormone (α‐MSH) signalling which have been implicated in the development of obesity related hypertension. We aimed to determine the role of α‐MSH signalling in regulating cardiovascular and renal sympathetic nerve activity (RSNA) responses in obesity related hypertension. Rabbits were instrumented with brain guide cannulae allowing drug delivery into the lateral ventricle (ICV; 1, 3, 10 nmol) or VMH (0.3, 1 nmol) and fed a high fat diet (HFD;13.5% fat, n=13) or normal fat diet (NFD, n=13) for 3 weeks. HFD rabbits had higher BP, HR, RSNA and plasma leptin levels (P<0.05 for all) compared with controls. ICV α‐MSH increased RSNA and HR (P<0.01) in HFD but not NFD rabbits. Microinjections into the VMH increased HR in both dietary groups (P<0.01) whilst RSNA increased only in the HFD group (P<0.05). These findings suggest that sensitivity to α‐MSH induced sympatho‐excitation is increased on a HFD at the level of the VMH. Thus, chronic activation of melanocortin receptors in this region may contribute to the development of obesity related hypertension. The project was funded by the National Health and Medicine Research Council Australia.
The effect of training on individuals’ interactions with visual data
Authors: Pfaff Lee A , Colliard Kitzia , Zumwalt Ann
Published: June 2021

Traditionally, students demonstrate their learning via testing and demonstrations but little is known about how learners’ interaction with information changes during and after training. Our lab's goal is to explore this question using gaze tracking and quantitative measures. Subjects in the experimental group are trained to use salient features to identify images of cells, which have been assigned a number 1–6. In a post‐training “quiz,” subjects are then asked to identify the cells by number. We tested the hypotheses that, after training: (1) the experimental group will take less time to first fixate on an educationally salient, and (2) the number of subjects who fixate on educationally salient features will increase compared to baseline in the experimental group but not in the controls. Our preliminary results indicate no difference in time to first fixation on an educationally salient feature between experimental [1502.673 +/− 1485.077 ms] and control groups [3046 +/− 2558.974 ms]. The number of subjects in the experimental group that fixate on salient features remains constant after training (means: 6.4 view baseline; 6.2 view after training), whereas the control group viewed them less (7.4 baseline; 4.8 after training). While our second hypothesis was not upheld, these results do indicate an effect of training on gaze patterns, indicating that gaze tracking may be a useful tool to quantify learning.

Grant Funding Source: Boston University (Internally funded)
Top‐Down Influences on Visuospatial Human Anatomy Comprehension
Authors: Glena Katlyn , Johnson Marjorie , Nguyen Ngan
Published: June 2021

The purpose of this study is to examine how learners’ spatial ability and prior domain knowledge contribute to the comprehension of visuospatial anatomical information from instructional animation. Spatial ability refers to one's capacity to construct, maintain, and manipulate mental representations. Prior domain knowledge refers to one's previously acquired knowledge of human anatomy. Visuospatial anatomy refers to the spatial properties of anatomical structures such as their 3D shape, form, position in the body, and relative location to surrounding structures. In cognitive science there is growing evidence suggesting that the educational value of instructional materials depends on how well their design reflects human cognitive architecture. Educational value depends on whether learners have enough cognitive resources to store and process the information presented. This study will provide objective evidence as to how learner's spatial ability and prior anatomy knowledge influence visuospatial anatomy comprehension. It will also help to determine who will benefit the most from instruction with animation. The results can be used to improve the design and implementation of instructional resources that will augment learning of visuospatial anatomical information for all learners, regardless of their innate spatial ability or prior knowledge of anatomy.

Grant Funding Source: University of Western Ontario
The Intermingled History of Occupational Therapy and Anatomical Education – A Retrospective Exploration
Authors: Carroll Melissa A , Lawson Katherine A
Published: June 2021

The 18th Century brought about a revolutionary movement that transformed traditional methods of treatment. The 20th Century gave structure and importance to occupations as a therapy. First mentioned in WWI, “Reconstruction Aides” relied on a combination of behavioral and anatomical knowledge to rehabilitate soldiers with injuries that were incompatible with normal function. These ventures contributed to the development of AOTA and a standardized curriculum. Since October, 1923, minimum standards of practice have included a strong foundation in biological sciences that specifically address human structure, function and motion. New standards and minimums have been identified through the progression and expansion of the OT field. The need to understand human development, congenital disorders and the life span are now critical to the treatment of children and adults with disabilities. The goal has always been to provide skills for daily living; for this reason, anatomical education has remained a benchmark of the field.

Grant Funding Source: N/A
Codebook Analysis of Metacognitive Blogs in an Anatomy Learning Skills Course
Authors: Schutte Audra
Published: June 2021

At Indiana University MSCI M100: Improving Learning Skills in Anatomy was developed to help students to recognize and implement study methods which will help them to be successful in Anat A215: Basic Human Anatomy. One of the course assignments is a weekly blog in which students reflect on various aspects of the learning process, such as assessing the effectiveness of their study methods or managing their time. The goal of this assignment was to help increase metacognitive awareness in students.

Thematic analysis was conducted to assess the blogs submitted by MSCI M100 students from three different semesters. This analysis involved the development of a codebook in which various categories, themes and subthemes were generated from the data itself. After multiple codebook iterations the blogs were coded, and code frequencies were produced to identify trends in the topics discussed within students’ blogs. Similar trends were found across all three semesters. As each semester progressed students spent a greater percentage of their discussion sharing which methods and tools were helping them to be successful and suggesting changes to their methods. Their time management plans became more detailed in nature, and self‐efficacy regarding anatomy exams improved.

Grant Funding Source: Lippincott Williams Wilkins/AAA Education Research Scholarship
Specialized anatomy electives for fourth year medical students in preparation for residency specialties: Plastic Surgery, Orthopaedics, and Obstetrics & Gynecology
Authors: Viscomi Natalie S , Suprenant‐Kotal Stephanie , Jones Braden K. , Combs Ryan A. , Clough Rich W.
Published: June 2021

Gross anatomy is taught during the first year at our medical school when students are often unsure what specialty they plan to pursue. Based on residency type, students may take an individualized 4th‐year anatomy elective to strengthen their knowledge and technique as it relates to the field they have chosen. Using surgical textbooks or current primary literature to learn the procedures, students independently perform mock surgical or exposure techniques on cadavers to better learn anatomical relationships as they relate to surgery. Having studied and reviewed the surgical technique, the students perform dissection often dictating their approach, precautions, procedures and findings. Many of the procedures are videotaped for later review by the students and attending physicians. This allows students the ability to visualize important anatomical landmarks, review anatomical structures at risk during the particular surgical processes, and regain a sense of three‐dimensional anatomy. This elective has been well received by our residency directors and has proven successful for students to develop an applied use of anatomy as it relates to surgical approaches and techniques before starting residency. Supported by SIU School of Medicine.

Grant Funding Source: None
The role of clinical imaging tutorials in anatomy education
Authors: Smith Lindsay , Hoover Alison , Brian Pamela , Lazarus Michelle
Published: June 2021

Radiology imaging aids anatomy learning, and computer modules offer flexibility; however, few studies evaluate the impact of radiology tutorials on anatomy knowledge. We evaluated the impact of imaging tutorials on medical student anatomy learning through objective repeated measures. Axial and appendicular regions were used to determine if radiologic tutorials impact student learning and if learning depends on structural region. Various radiologic image types, structural labeling, and clinical correlations were included within each tutorial. The control group (n=18) received basic anatomy education, while the intervention groups (n=16) received, additionally, the thoracic or lower limb tutorial. The mean differences in assessment scores were calculated between intervention and control groups. Tutorial access positively impacted overall anatomy knowledge (+11.92% thorax; +7.26% lower limb). The most significant impact of these tutorials on learning was in structure identification of radiologic images (+32.95% thorax; +20.42% lower limb). Tutorial users improved their knowledge in novel anatomy concepts within the thoracic region (+9.82% change), but not in the lower limb, suggesting a greater positive impact of these tutorials in axial anatomy education. This study provides evidence that clinical imaging tutorials are a viable adjunct in enhancing anatomy education.

Grant Funding Source: None
Taking a SecondLook™ at teaching histology – Development of a self‐evaluation iPad application
Authors: Hortsch Michael
Published: June 2021

As today's generation of students gravitates more and more to electronic teaching resources that are interactive and provide efficient feedback, I developed an iPad app that allows students studying histology to test their knowledge before participating in quizzes and exams. This iPad app called “Michigan eHistology – A SecondLook™ Series” is based on 28 PowerPoint files that cover all aspects of human histology. In two surveys to which 289 Michigan M1 students, who used the SecondLook™ PowerPoint files, responded, 95.8% named this resource as one of the three most valuable learning resources available to them. The second most valued histology learning resource was attending the lectures in person, which was named by 34.9% of all respondents. Both SecondLook™ formats allow students to efficiently gauge their level of histology knowledge in a free question–answer format, with the iPad app version offering some additional performance enhancing features, like a progress indicator and slide randomizer (see http://www.med.umich.edu/lrc/secondlook/).

Supported by a Teaching with Technology Institute award from the University of Michigan Center of Research on Learning and Teaching (CRLT)
Dual‐Lecturer‐Mode in Teaching Advanced Medical Histology
Authors: Chen Jian , Daley William , Cui Dongmei
Published: June 2021

Basic medical science education in medical school is more clinically oriented in both the preparation of medical board examination and following clinical rotation. We are introducing a new lecture mode, which involves dual lecturers in advanced medical histology class as compared to traditional one lecturer mode. Audiences are senior medical students who have already completed medical histology and medical pathology. During the lecture, lecturers teach the same topics but from different perspectives. A histologist presents histological terms and interprets normal microscopic structures, while a pathologist integrates clinical cases, presents and interprets pathological changes and findings at the same time. Students are encouraged to ask and discuss questions during and after each topic. Both lecturers are involved in leading the discussion and answering questions from different angles and expertises. Compared to traditional teaching given by one lecturer, dual‐lecturer‐mode is more effective in delivering contents and more appreciated by senior students. With availability of multi‐media and other teaching technologies, this teaching mode may be implemented in first year histology course. However, the success of this dual‐lecturer‐mode requires cooperation of both the basic and clinical departments.

Grant Funding Source: University of Mississippi Medical Center
Evaluation of gross anatomy teaching styles at the University of Auckland
Authors: Reilly Keryn , Wearn Andy , Riordan Peter
Published: June 2021

Traditional methods of teaching gross anatomy include cadaveric dissection. Our medical programme at the University of Auckland includes an integrated clinical anatomy programme involving whole body dissection. Due to unforeseen circumstances in 2011 we were forced to teach without the use of cadavers or the dissecting room, and instead used structured workshops with plastinated and prosected materials and models. We surveyed the students to gauge their opinions on the different approaches to teaching. We had two cohorts, one had a semester of dissection prior to structured workshops (Year 3 students), the other had the reverse experience (Year 2 students).

The survey was offered online and consisted of ratings, open questions and demographics. 74% students responded. The cohorts had different results regarding which style better helped them learn anatomy, both preferring their first experience. However when asked which they would choose if they could experience only one style, 51% of Year 2 students and 79% of Year 3 students chose dissection.

Students identified inherent value in both styles of teaching. This presentation will explore the results and their implications for anatomy learning.
Development of a Resource for Training Anatomy Lab Dissection Techniques
Authors: Bladon John H , Zumwalt Ann
Published: June 2021

Human cadaver dissection is a well‐established tool for teaching medical gross anatomy. Often students formally learn the subject matter, but learn the technique of dissection and tissue manipulation informally during their first labs. Previous classes have indicated the desire for more formal training in dissection techniques to reduce their uncertainty and nervousness. In response, we developed a formal curriculum and resources to help students more quickly become comfortable with dissection tools and techniques. The curriculum involved training Teaching Assistants (TAs) about a range of dissection techniques and uses for the tools. The TAs then taught lessons in tool use to the medical students during the first 3 labs of our course. Both TAs and students valued the techniques incorporated into this curriculum. We are also developing a website that will highlight the same lessons, which will be made freely available. Feedback indicates that using a formal framework to teach dissection techniques helped students become more comfortable with dissection and ultimately dissect more efficiently. Both students and teachers benefitted from the module and recommend it for future classes.

Grant Funding Source: Boston University
The Development and Assessment of a Medical Education Resource that uses Surface Anatomy to create a link between gross anatomy and clinical skills
Authors: Szymus Julianna
Published: June 2021

As physicians use living anatomy in clinical practice, it is essential for medical students to gain similar experiences by studying surface anatomy. Using observation and palpation to identify surface landmarks for structures beneath the skin, there was an opportunity to refine skills required for clinical examination. A Surface Anatomy Resource was created to link foundational knowledge learned in gross anatomy with clinical skills. An in‐class workshop was developed to teach medical students techniques for identifying surface landmarks of anatomical structures, followed by an interactive, online module with questions that enhanced their skills. Diagnostic Quizzes were completed at the beginning and end of the study, and were used to assess the resource's effectiveness. Evidence that the Surface Anatomy resource improved Post Quiz scores was highly significant (p value = .0049), suggesting that the resource provided students with an opportunity to augment clinical examination skills. The greatest improvements in post quiz scores were found for students in years 2 and 3 of undergraduate medicine, suggesting that this resource served as a valuable review for upper‐year medical students in particular. This resource allowed participants to review and apply gross anatomy in their clinical skill development; quiz scores and positive feedback reflected its effectiveness.
Introducing Anatomical Concepts to Junior High School Students: Early Engagement
Authors: Franz‐Odendaal Tamara
Published: June 2021

Anatomical concepts can be challenging for undergraduate students to grasp. Often fundamental concepts (body axes, relationships between cells and tissues, the importance of understanding structure and function) are either assumed knowledge or are taught very quickly in the first week of classes. Students are then expected to fully understand these terms as they get loaded with a large quantity of very specific terminology in Anatomy, Cell Biology and Developmental Biology courses. By introducing some of these concepts during junior high school in a fun hands‐on way, students will develop a stronger foundation in these key concepts, will be exposed to and possibly develop a desire to pursue these subjects later on, and can also get introduced to problem‐based learning. An early introduction to anatomical concepts in a fun way will ensure that students are excited about this subject and will remember these fundamental concepts as they continue with their courses.

Grant Funding Source: NSERC Canada
Emphasis placed on active learning in remodeling the Histology course in the Prematriculation Summer Program for entering medical and dental students
Authors: Stefan Ancuta M.
Published: June 2021

The Prematriculation Summer Program at Georgia Regents University is designed to prepare students for the academic, social and environmental adjustments they will face upon entering the medical or dental schools. Histology is one of the mandatory courses for all participants. In 2012 this course was remodeled by the author (new course director) to place the emphasis on active learning. All sessions followed an interactive format with continuity between them. The instructional strategies included independent study, discussions with the entire class and in groups, drawing from personal observation of slides (virtual microscopy and microscopes), and role playing. A key factor was represented by taking time to navigate on slides, look at multiple examples and analyze them instead of memorizing images. Powerpoint presentations were used in moderation, alternating them with drawings on the board while explaining concepts. The students were encouraged at all times not only to identify but describe morphological features, compare and contrast them, explain their significance, relate them with functions and interpret some of the changes they noticed. Selected pathological examples and applications augmented the discussions. Thanks to the Office of Diversity Affairs for its support and for providing the students with individual copies of the required book as well as colored pencils and sketching pads.
Zinc supplementation prevents diabetes‐induced heart malformation in mouse model
Authors: Srinivasan Dinesh Kumar , Murugaiyan Vijaya , Tay Samuel Sam Wah
Published: June 2021

Cardiac malformations are frequently observed in infants born of diabetic mothers in the clinics. Metallothionein (MT) is a cysteine‐rich protein that binds metals such as zinc (Zn) and acts as an antioxidant that is very efficient in scavenging various free radicals or reactive oxygen species (ROS). We analyzed the preventive role of Zn in diabetic cardiac embryopathy. In vivo study revealed a significant decrease in lipid peroxidation, superoxide ions, oxidized glutathione and an increase in reduced glutathione, nitric oxide and superoxide dismutase in the developing heart at E13.5 and E15.5 in Zn supplemented diabetic group when compared to diabetic group. In addition, significantly down‐regulated protein and mRNA expression of MT in the developing heart of embryos from the diabetic group was rescued by Zn supplementation. Further, nuclear microscopy results showed that trace elements such as Phosphorus, Calcium and Zn levels were significantly increased (p<0.001), whereas the iron level was significantly decreased (p<0.05) in the developing heart of embryos from the Zn supplemented diabetic group. In vitro study showed a significant increase in cellular apoptosis and the generation of ROS in H9c2 cells exposed to high glucose concentrations. Supplementation with Zn significantly decreased apoptosis and reduced the levels of ROS. In summary, maternal diabetes could play a role in the development and progression of cardiac embryopathy, and Zn supplementation could be a potential therapy for diabetic cardiac embryopathy.

Grant Funding Source: Academic Research Fund Singapore & Start‐Up Grant, LKCMedicine
A novel series of antitumor ruthenium beta‐diketonato compounds
Authors: Matthews Julian , Caruso Francesco , Pettinari Claudio , Marchetti Fabio , Pettinari Riccardo , Cariboldi Marzia , Rossi Miriam
Published: June 2021

Metal complexes are important chemotherapeutic agents against diseases; cisplatin is a widely used antitumor agent. Other metal centers are promising and ruthenium complexes are already in pre‐clinical trials. Recently, we described the excellent antitumor activity on colon‐rectal tumor cell line of a ruthenium‐curcumin complex and we described the interaction of this complex with the metal binding to guanine N7 of a DNA moiety (Caruso F, Rossi M, Benson A, Opazo C, Freedman D, Monti E, Gariboldi MB, Shaulky J, Marchetti F, Pettinari R, Pettinari C. J Med Chem. 2012 55, 1072). We present here a novel series of Ru compounds where curcumin is replaced with several beta‐diketone ligands. One has particularly strong antitumor activity in vitro; in observing the structure‐activity relationship, we hypothesize a potential intercalation of the ligand naphthalene moiety in between the bases of DNA. We describe a theoretical docking procedure for this species and also include antitumor activity and X‐ray diffraction studies. Supported by HHMI52006322.