bluuebunny/crossref_metadata_2025 huggingface dataset:
Biochemical composition of the functional amiloride‐sensitive, hetero‐multimeric, 4ps ENaC
Authors: Malik Bela , Yue Qiang , Liu Lian , Al‐Khalili Otor , Alli Abdel , Eaton Douglas C
Published: June 2021

Epithelial sodium channels (ENaC) consist of α, β, and γ subunits. As ENaC subunit proteins are synthesized in the rough endoplasmic reticulum, they are core glycosylated and co‐assembled into a hero‐multimeric channel. As they traffic through the Golgi to the apical membrane, some subunits are further glycosylated in the Golgi because the sugars become resistant to endo‐H glycosidase digestion, a hallmark of Golgi glycosylation. Since the protease, furin is active in the trans‐Golgi and at the plasma membrane, but prostasins are active only at the plasma membrane, the ENaC α and γ subunits must be cleaved either in the trans‐Golgi or at the apical membrane or both. Apical membranes of renal A6 cells contain subunits from each maturation step, endo‐H‐resistant, endo‐H‐sensitive, cleaved, and un‐cleaved as determined by isolation of biotinylated apical subunits. Because A6 cells contain only one type of functional channel, functional channel must be formed only from a subset of these modified subunits corresponding to the different bands. Therefore, we analyzed which modified subunits make‐up functional channels using co‐immunoprecipitation and other techniques. This research is supported by DK‐037963.
Role of cytoskeletal elements in the trafficking of KCa3.1
Authors: Lee Shih‐Liang , Devor Daniel C , Hamilton Kirk L
Published: June 2021

Previously, we have reported a di‐leucine (L18/L19) motif within the N‐terminus of the intermediate‐conductance Ca2+‐activated K+ channel (KCa3.1) that prevented trafficking of the channel to the membrane of HEK cells (Jones et al., J. Biol. Chem. 279:15531–15540, 2004). Additionally, we reported that the mutated KCa3.1‐L18A, KCa3.1‐L19A, and KCa3.1‐L18A/L19A channels were trafficked to the proteasome (Jones et al., 2004; McKenzie and Hamilton, FASEB J. 24:608.1, 2010). The aim of the study was to examine the role of cytoskeletal elements in the trafficking of KCa3.1, KCa3.1‐L18A, KCa3.1‐L19A and KCa3.1‐L18A/19A using western blotting. WT‐KCa3.1 and all channel constructs were HA‐tagged and stably expressed in HEK cells. Our experiments explored the effects of inhibitors of microtubule (colchicine, n=4), actin (cytochalasin D, n=3), myosin light chain kinase (ML‐7, n=4) and non‐muscle myosin II (blebbistatin, n=2) on the trafficking of these channels. Colchicine (10 μM, 5 hr) increased WT‐KCa3.1 and the mutated channel constructs in the whole cell lysates compared with controls. However, cytochalasin D (10 μM, 8 hr) only increased the mutated channel constructs but not WT‐KCa3.1. ML‐7 (10 μM, 5 hr) increased the whole cell expression of all channels. Lastly, blebbastatin (10–50 μM, 5 hr) increased expression of all channels at 50 μM. These data suggest that microtubule, actin and myosin light chain kinase assist trafficking of the mutated channel constructs to the proteasome for degradation. This work was funded by Lotteries Health and Department of Physiology (KLH) and NIH (DCD).
Endoplasmic reticulum signaling in neuron adaptation to hypoxia: role of unfolded protein response genes
Authors: Bickler Philip , Michels William , Gabatto Pablo , Birch Alexandra
Published: June 2021

The endoplasmic reticulum (ER) plays a key role in neuron response to hypoxia by coupling cytosolic NADH changes to ER Ca2+ release, survival kinase phosphorylation and gene expression. We propose that the ER also senses and responds to mild hypoxia via a subset of unfolded protein response (UPR) genes, which normally senses misfolded proteins. In rat hippocampal slice cultures (postnatal days 6–9), the UPR translation regulator eif2alpha is downregulated by phosphorylation after just 15 min of hypoxia, before unfolded proteins accumulate. Bcl‐2 protein, a pro‐survival factor associated with the ER and the UPR, is increased within 30 min of hypoxia. We used quantitative PCR to examine the expression of genes associated with the UPR: Slice cultures were exposed to 30 min hypoxia and total mRNA was collected 1 and 6 hrs later. Relative to control (GAPDH), we found no significant changes in Eifak3/PERK, Ern1(IRE1), Ddit3 (Gadd153), Xbp1, Hsp1a (BiP), Hsp90b1, or Hsp1a mRNA. However our previous gene profiling studies found significant up‐regulation of several Hsp's at 24 hr post‐hypoxia. To further clarify the role of the ER in hypoxia response, we are assaying for cytoplasmic splicing of the Xbp1 mRNA and using whole genome microarray studies. This experimental approach will confirm whether ER stress adaptation is important in neuronal adaptation to hypoxia. Support NIH GM52212.
The effects of maternal hypoxia on the heart development in fetal and neonatal rats
Authors: Tong Wenni , Xue Qin , Zhang Lubo
Published: June 2021

Fetal hypoxia leads to progressive cardiac remodeling in the rat offspring. Our objective is to determine the effects of hypoxia on heart remodeling in fetus and neonates. Pregnant rats were treated with normoxia or hypoxia (10.5% O2) from day 15 to 21 of gestation. Hearts were isolated from 21‐day fetuses (E21) and 7‐day‐old pups (PD7). The fibrillar collagen was examined by scanning electron microscopy (SEM). The expression of matrix metalloproteinases (MMP) 1, 2, 9 & 13, tissue inhibitors of metalloproteinases (TIMP) 1, 2, 3 and collagen 1 & 3 in the heart was measured by Western blots. Maternal hypoxia caused a significant decrease in the body weight of the pups at both E21 and PD7. The heart weight was decreased at PD7, but not in E21. SEM indicated less amount of fibrillar collagen at E21 but greater amount of collagen at PD7 in the heart of hypoxic pups, as compared with those of control animals. Myocardium wall thickness was decreased by hypoxia in both E21 and PD7. Hypoxia also reduced collagen‐1 and MMP‐1 in fetuses, while increased collagen‐1 and MMP‐1 in neonates. MMP‐13 was enhanced in fetuses but reduced in neonates, while TIMP‐3 level was increased in both developmental stages. There was no change in MMP‐2 & 9, TIMP‐1 & 2 and collagen‐3. Maternal hypoxia results in differential remodeling of fibrillar collagen in fetal and neonatal hearts, which may be mediated by the altered expression patterns of MMPs and TIMPs.
Exposure to cyclic intermittent hypoxia increases expression of the AMPA receptor subunit GluR1 in the carotid body
Authors: Liu Yuzhen , Li Xianghong , Weiss J. Woodrow
Published: June 2021

We previously reported that: 1) N‐methyl‐D‐aspartate (NMDA) receptor subunits NR1 and NR2A/2B are expressed in rat carotid body; 2) exposure of rats to cyclic intermittent hypoxia (CIH) enhances carotid body NR1 levels, and 3) administration of the NR1 blocker, MK801, reduces endothelin‐1 induced carotid sinus nerve activity in CIH‐exposed rats. To further explore glutamatergic signaling in the modulation of chemosensitivity after CIH exposure we assessed carotid bodies from Sprague‐Dawley (SD) rats for non‐NMDA glutamate receptors, including α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors and Kainate receptors using RT‐PCR, immunohistochemistry, immunofluorescence and western blot analysis. mRNA of the AMPA receptor subunit GluR1 is strongly expressed in the carotid body while there is weak expression of mRNA from GluR2, GluR3, GluR6 and KA2. Furthermore, the intense GluR1 immunoreactivity in the carotid body co‐localizes with tyrosine hydroxylase in glomus cells. To examine the effect of CIH on the GluR1 level in the carotid body, we next exposed male SD rats to CIH or to room air sham for 8 h/day for 3 weeks. CIH significantly enhanced the expression of both GluR1 mRNA (206.50 ± 13.35% of sham) and GluR1 protein (174.27 ± 9.12% of sham). These findings further suggest glutamatergic signaling may contribute to changes in carotid chemoreflex sensitivity induced by CIH exposure.
Myocardial ischemia and hypoxia exert opposite effects on the expression of amiloride binding protein 1 (Abp1)
Authors: Kirschner Karin Michaela , Braun Julian F W , Scholz Holger
Published: June 2021

The polyamine putrescine is required for normal cell growth and division. Putrescine formation is enhanced during myocardial ischemia presumably due to increased ornithine decarboxylase activity. The goal of this study was to assess the role of the diamine oxidase Abp1 in regulating putrescine degradation in the ischemic rat heart. At 24 h, 3 and 6 weeks after myocardial infarction Abp1 mRNA was significantly reduced compared to sham‐operation. Inhibition of Abp1 by amiloride prevented the in vitro differentiation of C2C12 myoblasts. Exposure of mice at 8% O2 (6 h) increased Abp1 mRNA in the hearts 11‐fold (P<0.02, n=5). Abp1 mRNA was also increased in several cell lines at 1% O2 (24 h). Reporter gene assays revealed an approx. 3,5‐fold stimulation of the Abp1 promoter in transfected C2C12 myoblasts at 1% O2. Promoter activity was also significantly enhanced by the Wilms' tumor transcription factor (Wt1), which is activated in hypoxia and controls myocardial blood vessel formation. Abp1 transcripts were reduced 60% in the hearts of Wt1‐deficient vs. wild‐type murine embryos (P<0.05, n=6). Silencing of Wt1 by RNAi reduced the Abp1 mRNA in M15 cells by more than 60%. In conclusion, myocardial ischemia and hypoxia exert opposite effects on Abp1 expression. A cooperative regulation of the Abp1 promoter by Wt1 and hypoxia may contribute to adequate putrescine levels in the developing and ischemic heart.
Responses to exercise training are genetically determined in inbred mouse strains
Authors: Avila Joshua James , Kim Seung Kyum , Massett Michael P
Published: June 2021

Exercise capacity is a complex trait influenced by environmental and genetic factors. Little is known regarding the role of genetics in the changes in exercise capacity with training. The aim of this study was to characterize the response to exercise training in inbred mice and determine the genetic contribution to adaptational responses to exercise. Six male mice from 14 inbred strains completed a graded exercise performance test before and after 4 weeks of treadmill running. Changes in time and work (post minus pre) were used to determine training responses. Changes in time and work varied significantly across inbred strains. 129S1 mice showed the greatest increase in time (9.6 ± 1.0 min), which was ~10 fold greater than NZW (−0.7 ± 1.0 min). The difference between these strains for the change in work was approximately 110‐fold (129S1 = 2.01 ± 0.23 kg·m; NZW = 0.02 ± 0.23 kg·m). Two broad sense heritability estimates were calculated for each measure of exercise capacity. The intraclass correlation (rI) for change in run time was 0.57 and the coefficient of genetic determination (g2) was 0.40. Heritability estimates were similar for the change in work: rI = 0.60 and g2 = 0.43. These data demonstrate that there are large strain‐dependent differences in training responses among inbred mouse strains that could be the basis for future genetic analyses of adaptations to exercise training. Supported by NIH grant HL085918 to MPM
Genetic determinants of lung architecture are linked to mouse chromosomes 12 and 18
Authors: Tankersley Clarke G , Broman Karl W
Published: June 2021

Genetic determinants regulate a complexity of lung architectural and mechanical traits. We sought to identify major genes that regulate variation in alveolar structure. To this end, F2 mice (n = 238) were derived using C3H/HeJ and C57Bl/6J inbred mice and their recombinant inbred offspring. Lung function was characterized in each F2 progeny and alveolar dimensions were assessed by quantifying mean chord length (MCL) from histological sections. Genome‐wide screens for single nucleotide polymorphisms were detailed for F2 mice using Illumina linkage panels, and quantitative trait loci (QTL) analyses were performed to construct linkage associations. Three significant QTL (LOD > 3.5) were shown to modulate variation in MCL in the F2 progeny; two peaks on mouse chromosome (mChr) 12 and one on mChr 18. Another suggestive QTL (LOD > 2.8) was seen on mChr 6. Variation in total lung capacity among F2 mice was significantly linked to mChr 12 and 13, but not mChr 18 or 6. These data implicate major genes that regulate variable alveolar structure and ultimately whole lung function.
Angiotensin Converting Enzyme Exerts System Control Over Fuel Handling In Skeletal Muscle
Authors: Flueck Martin , Vaughan David , Allwood William , Hoppeler Hans , Huber‐Abel Felicitas , Rittweger Joern , Dunn Warwick , O'Hagen Steven , Goodacre Royston
Published: June 2021

Using a genetical metabolomics approach we assessed whether altered energy supply in locomoter muscle underlies the elevated aerobic performance of human genotypes containing a silencer region (I‐allele) of the major regulatory enzyme of vasoconstriction, angiotensin converting enzyme (ACE).

Extensor muscle, m. vastus lateralis, of ACE‐II/ID genotypes holding the I‐allele demonstrated a trend for elevated capillarity compared to ACE‐DD counterparts lacking the I‐allele (311.0 vs. 279.7 mm‐2, n=20, p=0.10). In untrained subjects, maximal oxygen uptake during bicycle exercise was lower in ACE‐DD genotypes (44.9 vs. 47.8 ml O2/min/kg). Exhaustive aerobic exercise selectively reduced low density lipoproteins in serum of ACE‐II/ID genotypes (−14%) but was spared in ACE‐DD (+6%, p=0.25). By contrast, non‐polar metabolites in exercised muscle, comprising tentatively identified LDL‐derived glycerophosphocholine species, were depleted in ACE‐DD genotypes (q=2.8%; statistical analysis of microarrays). The interaction effect of exercise and genotype on lipidic muscle metabolites was maintained in trained subjects (p=0.03, ANOVA). The observations indicate that elevated import of serum lipids into exercised muscle underlies the enhanced aerobic exercise performance of I‐allelic genotypes for this major checkpoint of vascular perfusion.
Proteomic analysis of mitochondrial protein expression in the medullary thick ascending limb of Henle (mTAL) of the Dahl salt‐sensitive (SS) compared to salt‐insensitive SS.13BN consomic rat
Authors: Zheleznova Nadezhda N , Ryan Robert P , Yang Chun , Liang Mingyu , Cowley Allen W
Published: June 2021

The renal medullary thick ascending limb (mTAL) of the Dahl salt‐sensitive rat (SS) is the site of enhanced NaCl reabsorption and excess superoxide production. The present studies were designed to advance the conventional paradigm of focusing exclusively upon whole tissue homogenates to the physiological responses of a single subcellular organelle from a single cell type within the kidney known to be of importance in salt‐sensitive hypertension. We have isolated mitochondria from mTAL of SS and salt‐resistant SS.13BN rats on 0.4% and 8% salt diet and performed a proteomic analysis using LC/MS spectral analysis techniques. mTAL mitochondrial proteins were injected (~30 ug from extracts of 4 kidneys; 4 SS and 4 SS.13BN) to identify proteins that might be involved in salt‐sensitive hypertension. We identified ~120 mitochondrial proteins (probability >0.85; scan count >2), three of which were differentially expressed on 0.4% salt and 21 were significantly up‐ or down‐regulated following 8% salt diet for 7 days. The analysis indicated several potentially important pathways to include the tricarboxylic acid (TCA) cycle and mitochondrial apoptotic pathways. The results support a significant role for mTAL mitochondria in salt‐sensitive hypertension (HL‐82798; HL‐29587)
Automating modular model construction using JSim
Authors: Raymond Gary M. , Bassingthwaighte James B.
Published: June 2021

Modular modeling of physiological processes over orders of magnitude of spatial and time scales requires the merging of semantic content with the syntactic content of mathematical formulas. Using JSim's Mathematical Modeling Language (MML), we have designed simple processes which allow us to extract the mathematics from existing models, relabel the parameters and variables with names reflecting semantic content, and combine algebraic, ordinary differential and partial differential equations in an automated fashion to generate more powerful, biologically realistic models. An example is constructing a model for three regions (plasma, interstitial fluid region, and parenchymal cell) using partial differential equations. It includes two metabolites competing for a transporter on the cellular membrane with enzyme conversion of the first metabolite to a second metabolite in the cell. The method uses basic models for diffusion in one region, flow in one region, exchange between two regions, two state conformational change, and an enzyme on‐off model. The method supports taking archived models (CellML, SBML, JSim) and combining them in aggregated or hierarchical forms. Grant support NIH T15HL88516 EB08407.
Allergen and BDNF‐induced TRP Channel Expression in Nodose Cough‐fiber Neurons
Authors: Lieu TinaMarie , Undem Bradley J
Published: June 2021

We evaluated the effect of allergic inflammation on TRPV1 and TRPA1 expression in vagal nodose afferent Aδ “cough fibers” innervating the guinea pig trachea. Actively sensitized guinea pigs were exposed to ovalbumin, (OVA) via aerosol for three days. The nodose neurons innervating the trachea were identified via a standard retrograde trace dye injected into the tracheal wall 3 weeks earlier. Gene expression in indentified neurons was evaluated using single cell RT‐PCR methods. Relatively few trachea Aδ cough receptor neurons express TRPV1 mRNA (5–20% in a given ganglion). One day following the last OVA exposure, greater than 65% of the neurons expressed TRPV1 (P<0.01, χ2). Likewise, allergen exposure nearly doubled the % of cough receptor neurons expressing TRPA1 mRNA (P<0.01). We next characterized the neurotrophin receptor expression in these nodose “cough receptor” neurons. Over 80% of them expressed TRKB, but few expressed either TRKA or TRKC. We therefore went on to test whether BDNF (an agonist for TRKB) could mimic the neuroplasticity noted with allergen challenge. Local application of BDNF (200ng/ml) mimicked the effect of allergen challenge, in that over 65% of the nodose tracheal neurons were induced to express TRPV1 (P<0.01). BDNF did not increase the % of neurons expressing TRPA1. Allergen‐induced TRPA1 and TRPV1 in vagal A‐fiber neurons may contribute to the heightened sensory sensitivity of individuals to various sensory irritants. Supported by NIH HL062296 & HL07534, Bethesda, MD
IL‐13 mediates PDGF‐induced bronchial smooth muscle cell proliferation: Involvement of oxidant signaling
Authors: Bansal Geetanjali , Suzuki Yuichiro J
Published: June 2021

Smooth muscle cell (SMC) hyperplasia contributes to airway hyperresponsiveness and remodeling in asthma. IL‐13, a Th2 cytokine, is a critical mediator of asthma pathogenesis through its inflammatory and growth promoting functions. The present study investigated the role of IL‐13 in PDGF‐induced human bronchial SMC (HBSMC) growth. Cultured HBSMCs showed basal level of IL‐13 mRNA as observed by nested PCR that was upregulated by PDGF. Further, PDGF‐induced HBSMC growth was significantly inhibited by pretreatment with IL‐13 neutralizing antibody, implicating IL‐13 in PDGF‐induced HBSMC growth. Since oxidant signaling plays an important part in PDGF‐induced cell growth, we tested the involvement of metal‐catalyzed oxidation (MCO). Inhibitors of MCO, deferoxamine and HBED, inhibited PDGF‐induced increase in IL‐13 mRNA levels as well as PDGF‐induced HBSMC growth, suggesting a role for MCO in PDGF‐mediated effects on HBSMCs. Our data shows that PDGF, a potent growth factor involved in airway remodeling, causes human bronchial SMC proliferation by upregulating IL‐13 levels through oxidant signaling.

This work was supported by NIH.
Left branch of the hepatic portal vein. Study on corrosion casts
Authors: MATUSZ Petru L.
Published: June 2021

Left branch (LBr) of the hepatic portal vein (HPV) gives rise by the forking of the HPV together with the right branch. Accordingly to Terminologia Anatomica (1998), from the transverse part of LBr originate the caudate branches, and from the omblical portion – the lateral and medial branches. On a studied material represented by 150 hepatic corrosion casts one analyzed the variability of origin and the branches which originate from LBr. The corrosion casts were realized by injection of the hepatic vasculo‐ductal systems with plastic mass, followed by the corrosion of the hepatic parenchyma. I revealed 4 modalities of origin of LBr, the modal type beeing pointed out in 96% of the cases. In 90.67% of the cases I revealed 2 lateral branches, and in 9.33% of the cases ‐ 3 lateral branches. In 84.67% of the cases the medial branches are multiple and with reduced sizes. In 10% of the cases I observed 2 medial multiple branches, and in 5% ‐ 3 medial distinctive branches were pointed out. From the transverse part of the LBr originated 75.39% from the caudate branches of HPV. The number of caudate branches of HPV with the origin in LBr varied between 1 and 3 and were destinated to the papillary process and to the paracaval portion of the caudate lobe. These morphological data are very useful when performing reglated hepatic resections. (Supported by Grant CNMP 41092/2007).
Population Differences of Nasofrontal Angle Expression: A Coordinate‐Based Study
Authors: Masters Alina , Yuan Derek Y. , Pagano Anthony S. , Marquez Samuel
Published: June 2021

The nasofrontal angle has long been studied within the context of rhinoplasty and aesthetic surgery. However, few have observed the distribution of this trait over clinal zones ranging from temperate to tropical latitudes. This study tests the relationship between climate and nasofrontal angle on a sample (n=130) of dry crania from geographically diverse human populations. The nasofrontal angle was calculated from coordinate data collected among the landmarks glabella, nasion, and rhinion. Specimens of both sexes were used so that the maximum range of variation could be expressed in each population, thus allowing for a more stringent analysis. It was found that northern and southern Europeans are not significantly (p<0.05) different from each other or from North Africans and South East Asians. However, they possessed significantly (p<0.05) smaller (i.e., more acute) angles than the Inuit, Chinese, and East and West African samples, which did not exhibit any significant differences among each other or from the North Africans and South East Asians. Nasofrontal angle may share a closer relationship with nasal projection than climate as leptorrhine Europeans possess the most acute angles. However, the results may indicate separate population histories of Europeans and Inuit who, despite both inhabiting relatively northerly latitudes, developed separate adaptations to cold climate.

Grant Funding Source: SUNY Downstate College of Medicine
Experimentally induced thermal aseasonality reveals a potential source of variation in Alligator cranial evolution
Authors: Sadleir Rudyard W
Published: June 2021

In the 80 million year evolution, declines in crocodylian diversity correlated with drops in global temperature suggest global temperature is a generative mechanism in crocodylian morphological diversity. Environmentally induced change during development can strongly influence an organism's phenotype. Changes in phenotype in response environment can be broadly referred to as phenotypic plasticity. Alligator mississippiensis ranching provides a unique test of whether seasonality during ontogeny induces cranial shape variability, and if the environmentally induced plasticity corresponds with fossil Alligator evolution. I use 3D geometric morphometrics to analyze extant and fossil Alligator cranial shape. I compare ontogenetic shape change and statistically test for shared ontogenetic shape trajectories; I evaluate patterns of phenotypic evolution, and test for phylogenetic signals in a distribution of shape data. I also present a new software application to visualize 3D morphometric data. Results show the removal of seasonality in Alligator significantly alters cranial shape and shape ontogeny from the wild population. The A. mississippiensis plasticity, climate record, and fossil Alligator cranial shape evolution suggests of a causal link between climate change, ontogeny, and Alligator cranial evolution and insight on rates of evolution of traits in the fossil record.
A Unique Nervous Trunk in the Cervical Region. Vagal‐Hypoglossal Trunk with Unususal Organization Pattern of the Ansa Cervicalis
Authors: Veras Wilson Rafael
Published: June 2021

During dissection of the cervical region in the anatomy laboratory a unique nervous trunk was found bilaterally just inferior to the base of the cranium. The length of this trunk is about 25 mm. The nervous trunk is placed lateral to the internal carotid artery and medial to the internal jugular vein, later the single trunk runs posterior to the internal carotid artery. At the level of the occipital artery both trunks divide into two branches. One branch loops around this artery and goes below the tendon of the digastric muscle. This branch correspond to the hypoglossal nerve. Another branch arising from this unique nervous trunk runs posterior to the internal carotid artery and then posterior to the common carotid artery and then descends toward the thorax. This branch corresponds to the vagus nerve.

On the right side, the hypoglossal nerve gives rise a single branch that then divides into two branches one for the geniohyoid and another for the thyrohyoid muscles. The descending hypoglossal branch was absent. Thirteen millimeters from its origin the vagus nerve gives rise a long branch that anastomoses with a long branch arising from the accessory nerve forming a nerve loop, vagal‐accessory ansa cervicalis. From this loop the arise the branches to the stenohyoid, omohyoid and sternothyroid muscles.

On the left side the unique trunk receive comunicating branches from C2, then C2 gives a long descendig branch that anastomoses with a long branch from the vagus nerve. This cervico‐vagal ansa cervicalis gives a branch to the omohyoid muscle. The vagus nerve gives a branch to the sternohyoid and sternothyroid muscles. The thyrohyoid muscle receives innervation directly from the hypoglossal nerve. Awareness of this unique anatomical variation in the cervical region is important to the surgeon during a reinnervation of the paralyzed larynx.
A new saber‐tooth morphotype: The cookie‐cutter cat
Authors: Naples Virginia L.
Published: June 2021

Until recently, three cat‐like carnivore morphotypes based on canine features and postcranial skeletal proportions were known. Xenosmilus hodsonae (Early Pleistocene of Florida) a new saber‐tooth genus and species, combining bear‐like postcrania with comparatively short, coarsely serrated upper canines, a semicircle of enlarged serrated incisors and plantigrade hind feet was recently described. In this cat incisors and canines together removed a semicircular bolus of flesh; this bite rather than stabbing constituted the killing system. These short‐legged animals are now termed cookie‐cutter cats, in contrast with the previously well‐known scimitar‐tooth, dirk‐tooth and conical‐tooth forms. Other cranial features correlating only with the cookie‐cutter killing system include an overhanging occiput and an anteroposteriorly elongated temporal fossa for a relatively larger M. temporalis with a more horizontal line of action than in other saber‐tooths. Together with a reoriented M. masseter, X. hodsonae could exert more consistent pressures at all gapes than other saber‐tooths with maximized initial closing pressures. X. hodsonae must have been an ambush predator, and occurring in a tall grass savannah, has been restored with stripes. Two skeletons originally found in a possible limestone cave “den” were associated with many peccary skeletons and a few gomphotherine mastodont bones as preferred prey.
Functional morphology of the cranio‐cervical integument and constrictor musculature in Alligator mississippiensis
Authors: Hopkins Brooke Andriane , Homberger Dominique G
Published: June 2021

The skin, superficial fascia, and constrictor muscles of alligators form a tri‐layered envelope of the neck. These structurally correlated layers determine the stretchability of the intermandibular, gular and cervical regions. The skin stretches only at the interscale skin, whose width is related to the size of the scales. The stretchability of the superficial fascia is determined by the organization of its fibers. In the stretchable intermandibular region, wide, longitudinal folds of interscale skin separate small scales laterally, and narrow interscale skin separates mid‐sized scales medially; the superficial fascia fibers are loosely organized. In the less stretchable gular region, wide interscale skin separates mid‐sized scales laterally, and narrow interscale skin separates larger scales medially; the superficial fascia splits into three laminae with crosswise oblique fibers. In the least stretchable cervical region, wide interscale skin separates mid‐sized scales laterally, and narrow interscale skin separates large scales medially; the superficial fascia fibers are mostly circumferential. During inertial feeding, food is propelled into the pharynx and stretches the intermandibular region, while the less stretchable skin and fascia of the rest of the neck assist the tri‐layered constrictor muscles in pushing the prey caudally and in repositioning the stretched tissues.

Grant Funding Source: LSU Foundation
Structural computational modelling of the tracheo‐bronchial tree of the bottlenose dolphin
Authors: Cozzi Bruno , Bagnoli Paola , Acocella Fabio , Tamplenizza Paolo , Costantino Maria Laura
Published: June 2021

The trachea of marine mammals is composed by irregular semi‐continuous branching cartilaginous rings, lacks muscular tissue in the dorsal region, and possesses a huge network of venous lacunae in the submucosal layer. Several questions remain open concerning how the tracheal dead space may stand the pressure during prolonged and very deep dives. We investigated the structure of the trachea‐bronchial tree of both the bottlenose dolphin (Tursiops truncatus) and the goat (used for comparison with man), and developed a computational model to simulate the structural deformation of the organ during diving. Biomechanical tests provided reliable data on the stress‐strain relationships for cartilage and connective tissue to be implemented in a computational FE model. Our data showed that in the goat the smooth muscle collapses when external water pressure increases. Contrarily to that, the tracheo‐bronchial tree of the bottlenose dolphin better resists to external pressure due to the stiffer mechanical properties of the cartilage and the peculiar conformation of the cartilaginous rings. Furthermore, the absence of a tracheal muscle increases the robustness of the structure, and the air trapped within contributes to hinder the airways collapse phenomenon.
Production of a new transgenic mouse (Jtmt) that specifically overexpresses the antioxidant metallothionein in endothelial cells
Authors: Teiken Jennifer Mary , Grove Bryon D. , Epstein Paul N. , Carlson Edward C.
Published: June 2021

Diabetes mellitus increases the risk for cardiovascular disease due, in part, to hyperglycemia‐induced oxidative stress. To investigate the potential for antioxidant protection of the vasculature, a transgenic mouse (Jtmt) that overexpresses the antioxidant metallothionein (MT) specifically in endothelial cells (EC) was produced. A 16kb transgene consisting of the murine Tie2 promoter and enhancer ligated to the human MTII gene was microinjected into FVB mouse embryos. Five Jtmt(1–5) founder mice were identified by PCR using human MTII primers. Two of these founder mice, Jtmt1 and Jtmt4, have generated numerous transgenic progeny. Further characterization of the Jtmt1 line showed that at 60 days of age heart, kidney and body weights as well as blood glucose, HbA1c, and urine albumin excretion levels were normal. Importantly, MT overexpression in EC in the micro‐ and macrovasculature of kidney, heart, and tail tissues was confirmed by immunohistochemical studies. Ongoing studies are assessing the amount of MT overexpression in renal, hepatic and myocardial tissues by competitive ELISA and Western blot analyses as well as the effect of MT overexpression on EC cytological features by TEM. Future studies include crossing Jtmt1 and OVE26 transgenic diabetic mice in an effort to determine the potential benefits of endothelial‐specific antioxidant protection of the diabetic vasculature.

Grant Funding Source: North Dakota Lions Foundation
TEM stereometric analyses of glomeruli in aging OVE26 transgenic diabetic mice
Authors: Teiken Jennifer Mary , Laturnus Donna I. , Epstein Paul N. , Carlson Edward C.
Published: June 2021

Glomerular lesions in diabetic nephropathy (DN) have been studied in numerous murine diabetic models, but the critical feature of aging is often absent. Since DN lesions may just begin to develop at about five months of age, we utilized the long‐lived OVE26 transgenic diabetic model for stereometric analyses of DN glomerulopathic aging. Albuminuria was determined by ELISA and TEM stereometry was utilized exclusively to demonstrate morphometric alterations in the glomerular filtration barrier (GFB) in OVE26 mice at 60, 150 and 450 days of age. Relative to age‐matched controls, albuminuria in diabetic mice is significant at 60 days and profound at 120 days. At 150 days, glomerular volume, mesangial, endothelial, and total cell number are significantly increased, while podocyte, endothelial, and total cell density are significantly decreased. Dystrophic changes in the GFB include podocyte effacement, glomerular basement membrane thickening, and increased non‐fenestrated areas of glomerular capillary endothelium. At 450 days most stereometric alterations are exacerbated. Our data indicate that in OVE26 mice, intense albuminuria precedes morphological lesions and could be due to early‐onset hyperglycemia. Most morphological changes occur relatively late in life and appear unrelated to early renal decompensation. It is possible that they may result from prolonged hyperglycemia‐induced oxidative stress.

Grant Funding Source: Supported in part by grants R01DK072032, COBRE P20 RR024489, Juvenile Diabetes Research Foundation Grant 1‐200‐88 and the North Dakota Lions Foundation
Electroneuromyographic Investigation of the Sciatic Nerve in Spontaneously Hypertensive Rats: Comparison Between Age and Gender
Authors: Fontanesi Lucas Baptista , Schiavoni Maria Cristina Lopes , Junior Wilson Marques , Fazan Valeria Paula Sassoli
Published: June 2021

Previous results from our laboratory have shown morphological alterations on the sural nerves of female spontaneously hypertensive rats (SHR), mainly on the small myelinated fibers but there are no investigations on the functional significance of these alterations. Also, there are no reports on nerve functional differences between genders and age, particularly on the SHR. The present study investigated the alterations on the electrophysiological parameters of the sciatic nerves of male and female SHR with 5 and 8 weeks of age, compared to their normotensive controls WKY. After direct measurements of arterial pressure (cuff tail method), rats were anesthetized and electroneuromyographic studies were performed with the aid of a Keypoint® 4, Dantec‐Medtronic® equipment. Body weight and sensory and motor conduction velocities were significantly higher in older animals, for both genders and strains. Nevertheless, blood pressure values were similar between genders and strains, indicating that the SHR animals have not became hypertensive in the ages studied. The increase in the conduction velocity values reflects the nerve fibers growth that follows the animals aging.
Hindbrain neurovascular architecture in zebrafish and goldfish
Authors: Rahmat Sulman , Gilland Edwin
Published: June 2021

Vascular dye injections and confocal microscopy, combined with transgenic or retrograde neuronal labeling, were used to document the hindbrain neurovascular architecture in larval and adult cyprinid fish (zebrafish & goldfish). The data provide initial assessments of the neurovascular territories of central arterial stems and the specific blood supplies to particular hindbrain nuclei. The hindbrain central arteries arose from the basilar artery as a segmental series of 8 to 11 unpaired vessels that penetrated the pial midline of each rhombomere (r). The arteries branched into vascular trees within the hindbrain neuroepithelium near the ventricular surface, continued branching towards the pial surface and ended as small, unbranched channels that traversed nuclei and fiber tracts. These capillaries then joined to form tributary vessels of a large pial venous plexus. Notably, the neurovascular territories supplied by central arterial stems in r3 and r8 were by far the largest. The r3 stem served trigeminal motor nuclei in r2–3, as well as migrated facial motoneurons in r6–7 via long descending branches. A single large stem in r8 served most of the vagal lobe, with stems in r4–7 and caudal r8 supplying smaller zones. The data showed that hindbrain vascular and CNS elements are patterned in relation to the early rhombomeric segmental framework, with aspects of the segmental plan being maintained in adult brains.

Grant Funding Source: None
Variation in the Branching Pattern and Gross Appearance of Coronary Artery Branches
Authors: Im Jiye , Yee Alyssa , Lazar Jason , Pagano Anthony , Marquez Samuel
Published: June 2021

Research on coronary arterial branching patterns is of great clinical importance as coronary artery disease is a leading cause of death in developed nations. This study examined 16 hearts excised from donor bodies whose coronary arterial systems have experienced 64 or more years of continuous function. Gross appearance in two branches of right (sinoatrial nodal artery and posterior interventricular artery) and left (anterior interventricular and posterior circumflex arteries) coronary arteries were graded as: extremely small (ES), moderately small (MS), normal (N), moderately hypertrophied (MH), extremely hypertrophied (EH), and absent. Dominance was also recorded. Results showed that most (12/16) hearts were right‐dominated with 3 exhibiting a dual origin of the posterior interventricular artery and one case of left‐dominance. This artery, graded MH, was found enlarged in 69% of specimens. The anterior interventricular artery was graded MH in 2 cases while one graded EH. Conversely, the posterior circumflex artery was graded MS in 6 specimens, ES in 2, and absent in 4 individuals. All 16 individuals graded N in sinoatrial nodal artery appearance. Results indicate that posterior and anterior interventricular arteries are the most frequently hypertrophied, which is confirmed from our coronary angiogram data, identifying them as the most common sites for blockage.

Grant Funding Source: American Association of Anatomists
Aneurysm of the left anterior descending coronary artery revealed by CT angiography
Authors: MICLAUS Gratian D. , PLES Horia , MATUSZ Petru L.
Published: June 2021

Nonatherosclerotic coronary artery aneurysms are exceptionally rare. We examined a 31 years old male patient, who was sent to undergo CT angiography, in order to detect the possible existence of a cardiac malformation at the level of the right ventricle. One performed an ECG synchronized CT angiography, using a SOMATOM Sensation 64 computer‐tomograph, after administration of 110 ml iodine‐based contrast agent, with a flow rate of 5 ml/s. Images were reconstructed with 0.75 mm wall thickness, and the post‐processing was realized on a multimodality station, using software Syngo In Space and Syngo 3D. The analysis of the images highlights an aneurysm of the left anterior descending coronary artery, with the sizes of 5.91/3.84/3.79 cm, located at 12.68 cm from the left coronary artery ostium, fistulizated at the level of the right ventricle appendix, area where it presents a pseudoaneurysm, which communicates in the superior part with the right ventricle's cavity. The knowledge of the anatomy of the coronary arteries, concerning normal imagistics, but also the pathology, are mandatory requirements in order to establish complete and correct diagnostic accuracy. CT coronary angiography represents the elective method for precise anatomical coronary detail and is very useful to identify the pathology of coronary artery disease.
Variation in the branching pattern of the four major caudal vessels emerging from the external carotid artery
Authors: Heltzel Sara , Jaynes David
Published: June 2021

The branching pattern of vessels emerging from the external carotid artery (ECA) displays considerable variation. Knowledge of these variations is of particular interest to clinicians. Surprisingly, there are few reports in the literature assessing these differences with regard to gender and sidedness (i.e., branching patterns of the right vs. left neck). The objective of the current study was to assess the origin of the four primary caudal branches of the external carotid artery: the superior thyroid (STA), lingual (LA), facial (FA), and occipital (OA) arteries with regard to gender and side. Seventy‐three cadavers (35 male, 38 female) were studied (65 right necks, 62 left necks). We observed that the STA on the right side emerged from the ECA more frequently than it did from the common carotid artery (CCA) (28 and 20, respectively), however, on the left side, the STA emerged more frequently from the CCA than the ECA (34 and 19, respectively). We observed the LA and FA to arise individually more frequently than from a common trunk (right 72%, left 81%). We observed that the OA emerged below the origin of the FA more frequently than above (right 55%, left 64%). With regard to gender, branching pattern variation was similar for the vessels studied. We conclude that variation in the branching pattern is substantial regarding sidedness but not so regarding gender. This study was supported by the JMU Department of Biology.
An anatomical study of variations in the brachial‐axillary artery
Authors: Khmara Kseniya , Zyloney Carolyn , Pagano Anthony , Marquez Samuel
Published: June 2021

Previous studies have reported on variations in branching pattern of the brachial‐axillary artery. These include unusual branching of the thoracodorso‐subscapular trunk and duplication and early bifurcation of the brachial artery. This study observed the branching patterns and symmetry of the brachial‐axillary artery. A sample of 24 donor bodies was examined following dissection. The results show that 30 of the specimens (62.5%) had at least one variation identified in the brachial‐axillary artery and its branches. A total of 12 distinct patterns were observed with 5 of these (42%) expressed bilaterally. The most common variations included: (1) branch to deltoid or superficial back muscles coming from the axillary artery, (18.8%), (2) branch to serratus anterior muscle coming from the subscapular artery (16.7%), (3) circumflex humeral arteries branching off the subscapular artery (12.5%), and (4) branch to teres major muscle arising from the subscapular arteries (12.5%). The results indicate that variations in the arteries of the axilla and brachium are common. The observed patterns of variation in the brachial‐axillary artery are of particular importance in cases of ischemia as routes of collateral blood flow. Knowledge of these branching patterns may also help to avoid potential surgical complication.

Grant Funding Source: n/a
Morphometric analysis of murine ischemic hindlimb revascularization after stem cell therapy
Authors: Jiao Chunhua , Sheriff Don D , Leymaster Nick , Thedens Daniel , Cheera Sudheer , Dunnwald Martine , Tomanek Robert , Schatteman Gina C
Published: June 2021

The mouse ischemic hindlimb model is commonly used to study revascularization after stem cell (SC) treatment, but the nature of these vessels is poorly described, especially in the context of diabetes. Ischemic limbs of obese diabetic (db/db) mice were treated with saline or bone marrow‐derived SCs (BMSCs) on day 0. Since BMSCs from db/db and monocyte chemoattractant protein‐1 knockout mice inhibit or only weakly stimulate vascular growth, we studied the impact of these cells and cells from healthy young mice on revascularization. We performed whole limb microCT at day 5 and 11 and morphometric analysis of serial sections from perfused anti‐α‐smooth muscle actin labeled calf muscle at day 2 and day 5. Day 5 MicroCTs showed that two large vessels supply blood to the calf and a large branched vessel arising from the iliac artery supplies the thigh in all mice. However, the density and patterning of other vessels in the limbs vary among groups. In some animals large vessels appeared to arise from the skin and large tortuous vessels were observed in animals in all groups at both time points. Arteriolar analysis showed that vessel diameter, numerical density, and total vascular volume are similar among all groups at day 2, but differ depending on treatment at day 5. Thus, characteristics of vessels in the revascularized limbs differ depending on treatment and the origin of blood flow may come from unexpected sources.
Vascular anatomy of canine hepatic venous system
Authors: fabio acocella , Matteo Lodi , Lorenzo Mari
Published: June 2021

Canine liver vascular anatomy is still unclear. The aim of our study is to provide a comprehensive and detailed description of canine hepatic venous system. Nine livers were perfused with 10% formalin solution. After mechanical removal of the parenchyma portal and hepatic vein system casts were obtained and data collected. The liver could be divided in two separate sections: right and left. The right one is perfused by the right portal branch and drained in the caudal vena cava by two separate vessels. The left section is perfused by the left portal branch and drained by a single main hepatic vein collecting blood from a central and a left veins, except for two solitary veins that drain individually in the caudal vena cava. Basing on our results hepatic parenchyma can be divided in two main segments by the portal venous system and this not match the traditional anatomical subdivision based on the liver scissures. Though anatomical scissures allow to divide the gland in four lobes: left, right, quadrate and caudate, we suggest a new nomenclature and division of liver parenchyma on the basis of portal venous perfusion as in the man.
Distinctive patterns of Hsp60 levels and localization in human colon mucosa
Authors: Cappello Francesco , David Sabrina , Rappa Francesca , Campanella Claudia , Pitruzzella Alessandro , de Macario Everly Conway , Macario Alberto JL , Zummo Giovanni
Published: June 2021

Hsp60 is a Group I chaperonin highly conserved during evolution that in normal human cells is localized mainly in the mitochondrial matrix but stress causes changes in its levels and localization. We studied with a battery of techniques human mucosa from: a) normal colon (NM); b) hyperplastic polyps (HP); c) tubular adenomas with dysplasia (TAD); d) Crohn's disease (CD); e) ulcerative colitis (UC); and f) adenocarcinomas (AC). We observed patterns of Hsp60 levels and subcellular localization which depended on the pathology. Hsp60 levels in TAD, CD and UC (all pre‐tumoral conditions) were higher than in NM and HP but lower than in AC that showed the highest levels. Hsp60 was localized mainly in epithelial cells and, sparsely also in lamina propria. In epithelial cells of all the conditions examined (except NM and HP) Hsp60 was abundantly present not only in mitochondria but also in the cytosol, the latter being a pre‐requisite for its secretion. In conclusion, Hsp60 levels and localization patterns distinctively reflect the health status of these tissues and help to distinguish pathologic conditions.

Grant Funding Source: University of Palermo