bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Lipidomic Approach to Understand Human Diabetic Heart Disease
Authors: Pinz Ilka , Robich Michael P. , Ryzhov Sergey , Sawyer Douglas B. , Vary Calvin
Published: November 2023

Diabetes mellitus is an important risk factor for acute myocardial infarction and chronic ischemic heart disease. We have demonstrated in an animal model that high fat feeding causes lipotoxic changes in the heart that includes the accumulation of sphingolipids, lipids that are enriched in specialized membrane microdomains called caveolae. Accumulation of sphingolipids causes the loss of caveolin proteins (CAV) from the plasma membrane, as well as the loss of receptor tyrosine kinase signaling, such as insulin and other growth and survival signaling. We have now expanded our work from animal models to informed and consented human diabetic patients who are scheduled to undergo coronary artery bypass grafting (CABG) surgery at Maine Medical Center. The protocol and use of human tissue samples for this study has been approved by the Institutional Review Board of Maine Medical Center. We tested whether disrupted membrane lipid homeostasis is associated with the loss of survival signaling in the diabetic heart, and thus may contribute to the increased risk of cardiovascular complications in diabetics. To test this idea, we used an unbiased mass spectrometric lipidomics approach to determine the lipid profiles in right atrial appendix (RAA) tissue and blood plasma, and determined the expression of CAV1, CAV3, IRS‐1, and ERBB2, 3 and 4 receptors in RAA by Western blotting. We found different lipidomic signatures in human diabetic vs. non‐diabetic blood plasma and right atrial appendage tissue demonstrated by different principle components in the global lipid comparison. A more detailed analysis showed that diabetic subjects have increased plasma and tissue levels of sphingolipids, which dependent on the specific sphingolipid species, are between 2 and 15 times higher compared to non‐diabetics (n = 5 in both groups). The expression of caveolin proteins and total ERBB receptors varied throughout our patient population (n = 8), however increased lipid levels correlated with lower RTK expression and lower caveolin protein expression. Flow cytometric analysis of isolated atrial endothelial cells showed reduced cell surface ERBB2 expression in diabetics compared with non‐diabetics.

These data support the hypothesis that dysregulated lipid homeostasis in cardiac cell membranes of diabetic patients may be contributing to disrupted RTK signaling. To our knowledge this is the first study to characterize these changes in this patient population.
ob/ob Mice Fail to Lose Weight on an Alternate‐Day Fasting Diet, Yet Improve Glucose Control
Authors: Bingaman Mark Jake , Hult Elissa M , Swoap Steven John
Published: November 2023

Alternate day fasting (ADF) has proven effective for weight loss in humans and rodents on a high‐fat diet. Mice with a homozygous mutation in the ob gene are obese, diabetic, and exhibit reduced body temperature (Tb) with variable torpor bouts in the fed state. We tested the hypotheses that an ADF protocol in genetically obese mice would result in (i) body weight (BW) loss, (ii) improved glucose control, and (iii) induction of torpor on fasted days. We evaluated the physiological effects of ADF in control and ob/ob mice for caloric intake, BW, Tb, and circulating glucose and insulin. Adult female ob/ob mice were implanted with temperature telemeters and randomly assigned to either 1) ad lib food availability (n=6) or 2) an ADF protocol, where the mice were fasted every other day, with ad lib feeding between fasts (n=11). Over 18 days of ADF, ob/ob mice consumed 258±11 kcal, approximately two‐thirds of that consumed by ob/ob mice on an ad lib diet (410±21 kcal). Despite this, ob/ob mice on the ADF diet lost only 0.7±0.2g of BW compared to the 3.9 ± 1.3g weight gain by ad lib ob/ob mice. ADF caused long and deep bouts of torpor in ob/ob mice such that the average and minimum 48‐hour Tb was 34.0±0.2 and 26.1±0.2°C, respectively, as compared to ad lib ob/ob mice (35.2±0.3; 31.1±0.9°C, respectively). Circulating glucose fell in the ADF mice, but only on fasting days (ad lib 307±57, ADF‐Fed 271±8, ADF‐Fast 132±17 mg/dl). The HOMA index, which evaluates insulin sensitivity using circulating glucose and insulin, improved significantly in the ob/ob ADF mice, but only on fasting days (ad lib 913±349, ADF‐Fed 1256±393, ADF‐Fast 288±146). These data demonstrate that weight loss is diminished, likely due to the deep bouts of torpor on fasted days, even though ADF significantly reduces food intake in ob/ob mice. Further, circulating glucose and the HOMA index fell in the ob/ob ADF mice on fasting days, suggesting improved glucose control in the face of minimal weight loss.

Support or Funding Information

Supported by 1R15HL120072‐01A1 to SJS
Effects of Sleep Duration on Insulin Resistance – A Longitudinal Study in Healthy, Lean, College‐Age, Males
Authors: McGregor Kathryn , Cialkowski Kathryn , Townsend Dana K
Published: November 2023

Introduction

There are sparse interventional, within subject, clinical sleep studies. College‐age adults can experience substantial changes in sleep duration but have received little attention relative to potential concomitant changes in in fasting and dynamic measures of glucose metabolism.

Purpose

To test the hypothesis that in healthy, lean males in a college‐age group (18–26 yrs.), that sleep attenuation measured in the home environment for 1 week, at a level approximate to average college‐age sleep deprivation (1.5 hrs. < 7–7.5 hrs./night), will significantly increase insulin resistance while augmentation for 1 week, to recommended average levels for this age group (8 hrs.), will significantly decrease insulin resistance.

Methods

17 healthy, lean, male subjects (age 21.1 ± 2.0 yr., BMI 22.4 ± 2.2) slept according to their normal schedule in the home environment (7hrs 22min ± 33min) for one week, slept 1.5 hours below their baseline (6hrs 7min ± 35min) per night on week two, and with sleep duration augmented to optimal sleep (7hrs 56min ± 28min), on week three. Sleep was measured by wrist actigraphy augmented with individual sleep logs. Following each week, fasted subjects underwent a two‐hour oral glucose tolerance test. HOMA‐IR, a measure of hepatic insulin resistance, and the Matsuda Index, a measure of whole body insulin sensitivity, were calculated each week. The average differences in values of the HOMA and Matsuda between baseline, short sleep, and augmented sleep were analyzed using one way repeated measures ANOVA.

Results

There was no statistically significant effect of sleep augmentation or deprivation between baseline, short sleep, and long sleep on HOMA‐IR (p‐value=.06) and Matsuda Index (p‐value=.30) values.

Conclusion

This study shows sleep reduction and augmentation, at moderate levels that approximate normal college‐age sleep, may not have significant short‐term impacts on insulin sensitivity in lean males.

Support or Funding Information

2015, 2016 Aldeen Award‐‐Wheaton College, office of the Provost 2015, 2016 Summer Science Research Student in Residence support‐‐Wheaton College, Alumni Association
Gα12 is required for renal cystogenesis through ADAM10 dependent junction dysfunction pathway
Authors: Xu Frank , Ho Li‐Lun , Kong Tianqing , Lu Tzongshi
Published: November 2023

Background

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common life‐threatening genetic diseases and is characterized by early formation and gradual enlargement of multiple kidney cysts, which eventually results in end‐stage renal disease (ESRD). At ADPKD, cell‐cell junctions and polarity between epithelial cells are disrupted. Cadherins constitute a major protein family in polycystin‐1 (PC1) complexes in renal epithelial cells. And, E‐cadherin plays an important role to maintain the integrity of cell‐cell contacts and polarity. Our previous data showed that PC1‐regulated protein, Gα12, deletion protected kidneys from development of kidney cysts induced by Pkd1 inactivation, and activation of Gα12 increased the shedding of E‐cadherin. The signaling pathways of PC1 in ADPKD are not fully understood.

Aim and Methods

To understand how the interaction of PC1 and Gα12 affect the shedding of junction proteins, we used MDCK cells, Pkd1 deletion renal cells and Pkd1 knockout mice kidney tissue. Generation of inducible Pkd1 knockout mice (Mx1Cre+Pkd1flox/flox) were made by exons 2 through 6 flanked by two LoxP sites. Double knockout of Pkd1 and Gα12 mice were obtained by crossing Mx1Cre+Pkd1flox/flox mice with Gα12−/− mice. Madin‐Darby canine kidney (MDCK) Tet‐off inducible Gα12 and Gα12QL cell lines were characterized for three‐dimensional cell culture.

Results

Our results provided genetic evidence that Gα12 was essential for the development of kidney cysts induced by Pkd1 knockout, and Pkd1 deletion caused accumulation of cleaved E‐cadherin fragment in renal cystic fluid. There was no phenotype in mice with deletion of Gα12 (Gα12−/−). Conditional deletion of Pkd1 (Pkd1−/−) in one week old mice resulted in multiple kidney cysts by 9 weeks, but the mice with double knockout of Pkd1 and Gα12 (Pkd1−/−Gα12−/−) had no structural and functional abnormalities in the kidneys. In addition, Gα12 increased the active form of ADAM10 and knockdown of ADAM10 blocked the Gα12 mediated E‐cadherin shedding. Our data indicate that ADAM10 is the major sheddase for cleavage of E‐cadherin caused by Gα12 activation. Furthermore, deletion of Pkd1 increased the activation of Gα12, which subsequently decreased cell‐matrix and cell‐cell adhesion by affecting the function of focal adhesion, and E‐cadherin, respectively.

Conclusions

Our results demonstrate that Gα12 activation increases ADAM10 activity and promotes the ectodomain shedding of E‐cadherin, which plays the key role in on the development of kidney cysts in Pkd1 deletion induced ADPKD.
Quantitative Proteomic Analysis of Endothelial Cells in G‐protein Coupled Estrogen Receptor (Gper1) Knockout Rats
Authors: Galla Sarah , Waghulde Harshal , Cheng Xi , Chakraborty Saroj , Mell Blair , Basrur Venkatesha , Joe Bina
Published: November 2023

G‐protein coupled estrogen receptor (Gper1), a previously identified orphan receptor, now known to be a receptor for estrogen and aldosterone, has been localized to blood vessels, heart, and the central nervous system. Gper1 knockout models have been developed in mice and rats and have shown increased blood pressure as compared to controls. In addition, a Gper1 agonist, G1, caused decreased blood pressure when injected into mice. Women with a GPERP16L amino acid substitution in their GPER1 protein have increased BP. In order to study the effects of this receptor further, we created a novel CRISPR/Cas9 gene deletion model of the Gper1 gene on a Dahl Salt‐Sensitive (S) rat background. Hemodynamic and vascular phenotypic studies demonstrated that the Gper1 knockout rats had lower blood pressure and improved vascular function compared to the S rat. Microbiotal and metabolomics studies showed that Gper1 knockout rats had a significantly altered microbiotal composition and an increased circulating level of the short chain fatty acid, acetate. Since the improved vascular function was observed to be occurring in an endothelial dependent manner, we hypothesize that deletion of Gper1 in endothelial cells causes quantitative alterations in proteins that are directly impacted by the function of Gper1. To test this hypothesis and explore mechanisms behind the observed BP lowering effect in Gper1 knockout rats, a quantitative proteomic analysis was conducted on endothelial cells isolated and cultured from the thoracic aorta of Gper1 knockout rats and wildtype S rats. Endothelial cell cultures were digested and quantitatively analyzed by Mass Spectrometry. A total of 101 statistically significant differentially expressed proteins were identified, of which 97 proteins were with higher expression in the Gper1 knockout rats. Data prioritizing three of the most significantly upregulated proteins, Fibrillin‐1, Ephrin B1, and Cd99, as potential mechanistic links downstream of the functionality of Gper1 in endothelial cells will be presented.

Support or Funding Information

Funding for this work to BJ from the NHLBI/NIH (HL020176) is gratefully acknowledged.
Inhibition of Estrogen Sulfotransferase and Adipocyte Differentiation by Hydroxylated Metabolites of Lower Chlorinated Polychlorinated Biphenyls
Authors: Parker Victoria Shayla , Squirewell Edwin , Lehmler Hans‐Joachim , Robertson Larry , Klingelhutz Aloysius , Duffel Michael
Published: November 2023

Polychlorinated biphenyls (PCBs) are persistent molecules that are associated with the risk of developing diabetes, metabolic syndrome, cancer, thyroid abnormalities, and other diseases. PCBs are commonly found in air, food, water, paint pigments, and various materials from older buildings. The PCBs with four or fewer chlorine atoms (lower chlorinated PCBs) are readily metabolized to hydroxylated congeners (OH‐PCBs) in reactions catalyzed by cytochrome P450s. Our primary interest is in the OH‐PCBs that are derived from the lower‐chlorinated PCBs that are present in indoor and outdoor air. OH‐PCBs interact with cytosolic sulfotransferases (SULTs) as either substrates or inhibitors. Endocrine function may be altered by inhibiting the estrogen sulfotransferase (SULT1E1) that converts estradiol (active at estrogen receptors) to estradiol sulfate (inactive form), thus increasing cellular estradiol concentrations. Several of these lower‐chlorinated OH‐PCBs are potent inhibitors of SULT1E1. SULT1E1 has been previously shown to be a critical enzyme in adipogenesis, and its inhibition may alter the differentiation of pre‐adipocytes to mature adipocytes. We hypothesized that lower chlorinated congeners of OH‐PCBs that are potent inhibitors of the human SULT1E1 will also inhibit cellular differentiation in an immortalized human adipocyte cell line. Our initial studies have examined 4‐OH‐PCB 3, 4‐OH‐PCB 8, 4‐OH‐PCB 11, 4‐OH‐PCB 25, and 4‐OH PCB 52. Non‐differentiated pre‐adipocytes were treated for 4 days with either 1 μM or 10 μM of each of the OH‐PCBs, and these concentrations of OH‐PCBs did not alter overall cell viability (as judged by MTT assay). Adipogenesis studies were then conducted by incubating pre‐adipocytes in pre‐adipocyte growth media containing either 1 μM or 10 μM concentrations of each of these OH‐PCBs for 3 days. The media containing the OH‐PCB was then removed, and the cells were grown for 11 days in adipocyte differentiation media. Adipored staining was used to quantify the amount of lipid accumulation as an indicator of adipocyte differentiation. All but one of the OH‐PCBs (i.e., 4‐OH‐PCB 3) significantly inhibited adipocyte differentiation. The results were consistent both with our findings on these OH‐PCBs as inhibitors of purified recombinant human SULT1E1 and with the hypothesis that SULT1E1‐inhibition by lower‐chlorinated OH‐PCBs may inhibit adipocyte differentiation. Future work will determine cellular levels of estradiol and estradiol‐sulfate in both the pre‐adipocytes and the differentiated adipocytes under these conditions as well as changes in mRNA and protein expression for SULT1E1 and key cellular markers of differentiation.

Support or Funding Information

Supported by NIH P42 ES013661 and R25 GM058939
THE ROLE OF LIGHT AND PHOTO‐OXIDATIVE STRESS IN CORAL BLEACHING
Authors: Parrin Austin , Blackstone Neil
Published: November 2023

Octocorals remain one of the understudied groups of cnidarians. Nevertheless, energy‐converting symbionts and organelles may be central to the cnidarian stress response. Stress may slow photochemistry in Symbiodinium spp., leaving photosystems I and II relatively reduced and increasing reactive oxygen species (ROS). Alternatively, ROS may emanate from mitochondria. These sources of ROS can be distinguished by using microscopy to examine the effects of light on stressed cnidarians incubated in the dark with a fluorescent, ROS‐detecting probe (H2DCFDA). Experiments were carried out with three species of alcyonacean octocoral, Phenganax parrini, Sarcothelia sp., and Sympodium sp. After incubating colonies for 1 h at elevated temperature, imaging and illumination (ex. 450 – 490, em. 515 – 565 nm) were begun simultaneously. ROS formation largely corresponded to the onset of illumination. On the other hand, chlorophyll fluorescence (ex. 530 – 580, em. 620 – 690 nm) did not conform to this pattern. This difference is consistent with the expected rates of reaction. Remarkably, treatment with the inhibitor 3‐(3,4‐dichorophenyl)‐1,1‐dimethylurea (DCMU) resulted in dramatically higher levels of light‐induced ROS. Chlorophyll fluorescence exhibited higher levels in DCMU treatment but not significantly so. By controlling for variation between individual symbionts, however, DCMU produced significantly greater levels of chlorophyll fluorescence, indicating the expected greater reduction of photosystem II. A brief exposure to light and thermal stress produced a similar effect in all three species. In addition to ROS being initiated by light, these results indicate: (i) a brief period of stress shifts photosystem redox state toward reduction, (ii) photosystem II can donate electrons to oxygen when blocked with DCMU, (iii) chlorophyll fluorescence is highly variable between individual Symbiodinium. Imaging of individual symbionts in hospite thus provides a powerful method for understanding the initial steps of the cnidarian stress response.
Multi‐Tissue Chromatin Modulation During Hibernation
Authors: Dhillon Rashpal S , Krautkramer Kimberly A , Denu John M , Carey Hannah V
Published: November 2023

Hibernation is characterized by a dramatic reduction in energy demand that profoundly alters metabolic state. Changes in metabolic rate during torpor‐arousal cycles affect levels of circulating metabolites, which in turn have the potential to induce dynamic alterations in histone acetylation and methylation status. Eukaryotic histone‐modifying enzymes are known to be sensitive to levels of small molecule metabolites. The fundamental unit of chromatin is the nucleosome, which is comprised of a core of histone proteins that is wrapped ~2.5 times by genomic DNA. Histones are small, globular proteins with highly flexible N‐terminal tails that are subject to a multitude of covalent post‐translational modifications which dictate how accessible genomic DNA is to processes such as transcription and replication. In this study, we investigate how different metabolic and nutritional phases across the annual hibernation cycle affects histone modifications in multiple tissues of thirteen‐lined ground squirrels. Liver, brain, and brown adipose tissue were analyzed in squirrels sampled in summer, winter torpor, winter interbout arousal (IBA) and spring phases. Using an in‐house LC‐MS/MS workflow, we identified > 50 distinct chromatin signatures that segregate by tissues and metabolic/nutritional state. Hierarchical clustering shows that histone post translational modification (PTM) states of brain and brown adipose are more similar to one another than either are to liver. Histone acetylation, which has a significantly shorter half‐life than histone methylation, generally associates with more rapid switches in metabolic state (i.e., torpor vs. IBA). In contrast, switches between torpor and either of the two fed states (spring, summer) associate with changes in histone methylation. Collectively, our results suggest that the robust metabolic and nutritional shifts associated with hibernation drive changes in chromatin state.
The neurokinin‐2 receptor antagonist GR 159897 protects against neuroinflammation in the mouse enteric nervous system during colitis
Authors: Delvalle Ninotchska M , Gulbransen Brian
Published: November 2023

Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal (GI) disorder that affects 20% of Americans. The motility changes in IBS are driven by changes in the enteric nervous system (ENS). IBS has no cure, but recently, a neurokinin‐2 receptor (NK2R) antagonist has been shown to improve overall symptoms in a phase II study of diarrhea‐predominant IBS. However, the effects of NK2R antagonists on the ENS are not understood. We hypothesize that the beneficial effects of this antagonist on IBS are, in part, due to effects on the ENS. We tested our hypothesis by treating mice with the NK2R antagonist GR 159897 in a dinitrobenzene sulfonic acid (DNBS) model of colitis. To assess changes in the ENS, we used immunohistochemistry to quantify neuronal survival and performed a glial morphology analysis to assess reactive gliosis in the ENS. Calcium imaging recordings were performed in tissue preparations from mice expressing the genetically‐encoded calcium indicator GCaMP5g expressed under the control of the SOX10 promoter (SOX10::creERT2/+; PC::G5‐TdT+/−) or by loading cells with the calcium indicator dye Fluo4‐AM. Our results show that treatment with GR 159897 prevents increases in glial fibrillary acid protein (GFAP) immunoreactivity (n= 3–4 mice; p= 0.0141), increases in glial process length (n= 9–12 glia; p= 0.013) and neurodegeneration (n = 3–4; p= 0.0028). Immunohistochemical and calcium imaging data show that enteric glia express NK2Rs that are activated by neurokinin‐A (NKA). Glial responses to NKA were decreased in the presence of GR 159897 (n= 101–113 glia; p= 0.0001) or tetrodotoxin and were significantly reduced in samples from mice lacking glial connexin‐43 hemichannels (SOX10::creERT2/+; Cx43f/f mice; n= 50–113 glia; p= 0.0001). Glial responses to NKA were completely abolished in tissue samples from SOX10::creERT2/+; Cx43f/f mice in the presence of GR 159897 (n= 34–113; p= 0.0001). In conclusion, our data demonstrate that GR 159897 provides neuroprotection during colitis through mechanisms that involve decreasing glial activity driven by NKA. We speculate that these mechanisms could explain some of the clinical benefits of current NK2R antagonists in IBS.

Support or Funding Information

RO1DK103723‐02S1
Regulation of Pancreatic Beta Cell Function by Ankyrin‐B
Authors: Lorenzo Damaris N , Hostettler Janell , Bennett Vann
Published: November 2023

Functional variants of the cytoskeletal protein ankyrin‐B (AnkB) have been implicated in human hereditary cardiac arrhythmia and type 2 diabetes (T2D).1–3 We recently showed that knock‐in mice expressing human AnkB variants p.R1788W (present in 0.2% Caucasians and associated with T2D) or p.L1622I (present in 7.5% of African Americans), exhibit a metabolic syndrome that combines deficits in insulin secretion with age‐ and diet‐dependent adiposity, and insulin resistance.3 Here, we demonstrate that beta cell‐specific depletion of AnkB is sufficient to promote alterations in pancreatic islet morphology, reduction in insulin secretion, abnormal glucose tolerance, and the onset of diabetes in mice. We found that AnkB, through multiple structural and signaling functions, is a critical player in pancreatic islet biology. Biochemical and proximity ligation assays show that AnkB interacts with the inositol‐1,4,5‐triphosphate receptor (InsP3R) and with the Kir6.2 subunit of the ATP‐sensitive potassium channel. Expression of T2D‐associated AnkB mutations or loss of AnkB altered the level and localization of the InsP3R and Kir6.2 in beta cells, which, in turn, resulted in decreased insulin secretion in response to glucose and carbachol stimulation in vivo and in isolated islets, and hyperglycemia in mice. Immunohistochemistry of the pancreas revealed reduction in beta‐cell area, along with increase in apoptosis and endoplasmic reticulum stress markers. These morphological and metabolic deficits are exacerbated with age or following a high‐fat diet. These results show that Ank‐B is a critical regulator of pancreatic beta cell function in a cell‐autonomous fashion, and its deficits might cause diabetes.

Support or Funding Information

Howard Hughes Medical Institute
Dietary High and Low Copper‐Fructose Interactions Induce Hepatic Steatosis Associated with Distinct Alterations of Gut Microbial Activity in Male Rats
Authors: Song Ming , Zhang Xiang , Vos Miriam , Prough Russell , Cave Matthew , McClain Craig
Published: November 2023

Objective

Dietary copper‐fructose interactions play critical roles in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). The aim of this study was to determine the effect of different dietary doses of copper and their interactions with high fructose on gut microbial activity and the development of steatosis.

Methods

Male weanling Sprague‐Dawley rats were fed diets with adequate copper (6 ppm, CuA), marginal copper (1.5 ppm, CuM) (low‐copper) or copper supplementation (20 ppm, CuS) (high‐copper) for 4 weeks. Deionized water or deionized water containing 30% fructose (w/v) was given ad lib. Copper status, liver enzymes, histology, gut barrier function and gut microbial activity were evaluated.

Results

Copper levels were significantly lower in rats fed with a marginal copper diet than in those fed with an adequate copper diet. However, high‐copper diet did not lead to excessive copper accumulation in the liver, likely due to the downregulation of copper transporter‐1(Ctr‐1) mRNA. Both low‐ and high‐copper diets led to liver injury and fat accumulation in high fructose fed rats, and this accumulation was associated with gut barrier dysfunction. The increased abundance of the gut Gram‐negative bacteria, Enterobacteriaceae, did not parallel plasma endotoxin levels, with low copper‐fructose induced steatosis being characterized with endotoxemia, whereas high copper‐fructose induced steatosis was not, despite the fact that both of these regimens resulted in increased gut permeability. Fecal metabolomics study and 16S rRNA gene expression analysis revealed distinct gut microbial metabolic characteristics in response to dietary low‐ and high‐copper high‐fructose feeding.

Conclusion

Our data demonstrated that dietary copper‐fructose interaction regulates gut microbial metabolic activity, which might contribute to the development of hepatic steatosis. The distinct alterations of gut microbial activity which were associated with the different dietary doses of copper and fructose imply that separate mechanism(s) may be involved.

Support or Funding Information

This study was supported in part by NIH Grants U01AA021901, U01AA022489, R01AA023681, an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20GM113226 and by the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health under Award Number P50AA024337. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health (C.J.M.); K23AA018399, R01ES021375 (M.C.); the Veterans Administration (C.J.M.); and the U of L Clinical and Translational Pilot Program (C.J.M.).
Anatomical Variations of Renal Artery Branching in Cadavers
Authors: Nasr Kristie , Hurley Mary , Olivieri Marion P. , Gervasi Megan
Published: November 2023

The main blood supply of the kidney comes from the renal artery. The renal artery branches off of the abdominal aorta at the L2 region and enters the renal hilum where the renal artery branches into segmental arteries. The renal blood flow displays variations within accessory and aberrant arteries. Right and left kidneys differ with these variations. Understanding the anatomical renal differences will be beneficial for clinicians in various procedures such as partial nephrectomies. Although this is a minimally invasive technique, there have been numerous issues. Main renal artery clamping increases the chance for ischemia, but this can be reduced through selective clamping of only pertinent segmental arteries. Through a better understanding of the variations of accessory and aberrant renal arteries, clinicians will develop more efficient surgical techniques. In this study, more variations are examined, specifically to see the number of renal arteries branching from the aorta, and the number of segmental arteries that branch proximal to renal parenchyma. The number of arteries ranged from one to two on both the right and left sides, and segmental arteries ranged from zero to four. Further studies will trace the branching patterns within kidney parenchyma.

Support or Funding Information

Supported and Funded by the Department of Biology and Mathematics of D'Youville College, Buffalo NY
Asymmetric Supernumeric Renal Arteries: A Case Study
Authors: Dunnwald Martine , Pizzimenti Marc A
Published: November 2023

Blood supply to each kidney is typically provided by renal arteries that arise from the aorta. However, bilateral variation in this vascular pattern occurs in approximately 15% of cases, ranging from the presence of multiple‐branched renal arteries, supernumeric renal arteries, and vessels of various origin along the aortic axis. Here, we report a case of kidneys with asymmetric and supernumeric renal arteries identified in a donor following cadaveric dissection. Both kidneys were retroperitoneal and measured 12.3 cm (L) and 12.7 cm (R) in length, respectively. Hilar structures were not projected medially, where the renal pelvis, veins, and most of the arteries contributed to an anteriorly faced hilum. The blood supply to the left kidney consisted of three renal arteries with various origins. The superior left renal artery originated from the abdominal aorta and supplied the superior pole. The middle left renal artery originated from the iliac junction, just anterior to the median sacral artery, and supplied the middle portion of the kidney. The inferior left renal artery originated from the common illiac artery, and coursed posteriorly to the kidney before entering the hilum anteriorly (from the lateral aspect of the organ), to supply the inferior pole. On the contralateral side, the vasculature to the right kidney consisted of only two renal arteries, both originating from the abdominal aorta. The superior renal artery branched laterally from the aorta (at the same level as the left superior renal) and supplied the superior pole. Arterial supply to the inferior pole originated inferior to the inferior mesenteric artery. Together, these observations describe asymmetric supernumeric renal arteries and reflects, to some extent, the chronology for ascent of the kidney during embryological development.

Support or Funding Information

no funding disclosures
Accessory Brachial Artery ‐ A Unique Variant
Authors: Ziemann Sarika , Esterson Aryeh , Velavan Sumathilatha Sakthi , Rich Sushama
Published: November 2023

The anatomical variations of arterial patterns of the upper limb are associated with embryological and clinical significance. A unique variant of the brachial artery was observed and is reported due to its rarity. This was a case study that examined the vasculature of the right upper limb during routine dissection of a 57 year old female Caucasian cadaver. Two arteries were observed in the anterior aspect of the arm. The first artery (accessory brachial artery) was larger, continued from axillary artery, coursed superficial to the median nerve and terminated as ulnar and radial arteries. The second artery (brachial artery) arose at the level of the third part of the axillary artery, was enclosed by the two roots of the median nerve and coursed deep to the median nerve. The posterior and anterior circumflex humeral, two profunda brachii, and superior and inferior ulnar collateral arteries emerged as branches of the second artery. Anastomosis was noted between the two arteries in the cubital fossa. Accessory brachial artery served as the main feeding artery of forearm and hand in this case while the brachial artery terminated after supplying the brachium. Failure of regression of the superficial brachial artery during stage five of embryological development explains this uncommon variant. The knowledge of such a variation is valuable to consider in routine evaluation of angiographic images, and for surgical intervention.

Support or Funding Information

Touro College of Osteopathic Medicine Department of Anatomy provided our source of support.
Histopathologic changes in gastric mucosa after experimental gastric restriction
Authors: Filho Guilherme Mota , Itezerote Ana Maria , Saleh Samir , Hojaij Flávio , Andrade Mauro , Martinez Carlos Augusto Real , Akamatsu Flávia Emi , Jacomo Alfredo Luiz
Published: November 2023

Bariatric procedures play an important role to control metabolic disorders secondary to morbid obesity. Our group developed a technique to simulate gastric restriction in rats in order to establish the physiological effects of these procedures.

In this study, we aimed to analyze the histological features of gastric restriction. We used 30 Adult, male Wistar rats (Rattus norvegicus albicans) weighing between 250–350 grams. To produce gastric restriction, The rats were submitted to laparotomy and gastrostomy to insert a cylindrical sleeve Luffa (loofah) (1.5cm in diameter) made of cylindrical luffa, producing experimental phytobezoar.

The animals of Sham group (S) were exposed to the same surgical procedure described above, except for the implant of phytobezoar. From the first day after surgery, the animals were divided into three groups of 10 animals each. The group of 10 days until euthanasia was subjected to the stomach reduction surgery (R10) with their controls sham (S10) and normal controls (C10) 10 days. Each animal was weighed every other day until the day of euthanasia. Gastric mucosa in all groups were studied with hematoxylin and eosine and we performed morphometric analyzes of crypts, mucous cells and inflammatory cells.

The data were submitted to the Kolmogorov‐Smirnov test and ANOVA followed by Bonferroni or Dunnet T3 multiple comparisons (p<0.05).

The experimental group showed deeper crypts and increased counts in either neutrophils and mucous cells as compared to the sham and control groups. The histopathological changes produced by experimental gastric restriction may be related to acute inflammatory reaction caused by the operative procedure and also increased gastric cell secretion of mucus as a compensatory or secondary effect of phytobezoar.
Evaluation of Toxicological Effect of Pausinystalia yohimbe Extract on Histology of Kidney of Adult Male Wistar Rat
Authors: Ugochukwu Chioma , Ihentuge Churchill , Okechukwu Hope
Published: November 2023

Pausinystalia yohimbine has been used for the treatment of sexual side effects caused by some antidepressants, as a blood pressure boosting agent, for dry mouth, and for nervous system dysfunction. Twenty adult male wistar rats weighing between 150g to 200g were used in this research to determine the effects of Pausinystalia yohimbe on the histology of kidney. They were divided into five groups; A, B, C, D and E of four rat each. Group A served as control and was fed with feed and water only. Groups B, C, D and E were administered with extract of Pausinystalia yohimbe at a daily dose of 3mg/kgbw, 5mg/kgbw, 7mg/kgbw and 9mg/kgbw respectively for 21 days. At the end of the experiment, the animals were sacrificed by cervical dislocation after anaesthetized with chloroform. The organ of study (kidney) was harvested and sections cut for histological preparation using H and E staining method. Results showed poor perfusion of renal tissue with moderately to severe damage of renal architecture indicating severe fatty change, tubular necrosis, depletion of glomeruli, moderate clumping and distortion of renal architecture and intra renal hemorrhage in all the experimental groups. The severity was more in groups D and E indicating that Pausinystalia yohimbe is capable of causing renal damage in a dose dependent manner
Desmosomal cadherin association with a dynein‐cortactin complex promotes actin rearrangements required for epidermal morphogenesis
Authors: Green Kathleen J , Nekrasova Oxana Y.
Published: November 2023

The epidermis is a multi‐layered, renewing epithelium that serves as an essential barrier against water loss and environmental insults in vertebrates. Its morphogenesis occurs through a tightly regulated program of biochemical and architectural changes in which epidermal keratinocytes in the basal layer commit to differentiate, and move towards the skin's surface in a process called stratification. During this process, tissue integrity is ensured by intercellular junctions called desmosomes, which anchor the intermediate filament cytoskeleton to sites of desmosomal cadherin‐mediated adhesion. In contrast to the adherens junction protein, E‐cadherin, which is expressed in all epidermal layers, seven desmosomal cadherins are expressed in a highly patterned differentiation‐dependent manner in epidermis. This genomic complexity and spatial patterning of desmosome components in stratified tissues suggests that they do more than perform textbook functions in mediating cell‐cell adhesion. Here, we reveal an unexpected role for the cadherin desmoglein 1 (Dsg1) in remodeling the actin cytoskeleton to promote the transit of basal cells into suprabasal layers through a process of delamination/extrusion. This function requires a newly recognized association between Dsg1 and the dynein light chain, Tctex‐1, and actin scaffolding protein, cortactin. We demonstrate that Tctex‐1, as a part of the dynein complex, controls the proper biochemical compartmentalization and segregation of Dsg1‐containing desmosomes from adherens junctions. Moreover, uncoupling the Dsg1‐Tctex‐1 complex from dynein or abrogation of Dsg1‐Tctex‐1 interactions interfered with the proper positioning of cortactin, which in turn is required to recruit the Arp2/3 complex and promote F‐actin network reorganization. Assembly of this molecular complex at the onset of Dsg1 expression during differentiation in cells already containing E‐cadherin results in decreased tension at adherens junctions, as measured through an E‐cadherin FRET sensor and accumulation of the mechanosensitive molecule vinculin. The proper coordination of this chain of events is required for the efficient delamination of basal cells in an organotypic model of tissue development. Thus, Dsg1 serves as a scaffold that exerts spatial control over mechanical changes necessary to promote early stages of epidermal morphogenesis.

Support or Funding Information

Supported by NIH R01AR041836, R37AR043380, R01CA122151, the Dermatology Foundation and J.L. Mayberry Endowment.
Prostaglandins regulate mechanotransduction to the nucleus
Authors: Tootle Tina , Toombs Emily , Lamb Maureen
Published: November 2023

Prostaglandins (PGs) are lipid signals that play critical roles in physiology, including regulating pain and inflammation, reproduction, and cancer. However, the cellular mechanisms of PG action remain poorly understood. PGs are synthesized downstream of cyclooxygenase (COX) enzymes. In Drosophila, there is one COX‐like enzyme Pxt. Loss of PG synthesis in both mammals and flies results in female sterility. Specifically, in flies the loss of Pxt causes numerous defects in oogenesis, i.e. follicle development. One mechanism whereby PGs mediate follicle development is by regulating actin cytoskeletal remodeling necessary for both cell migration, and cellular and follicular morphogenesis. Here we focus on the role of PGs in regulating the invasive and collective migration of somatic cells termed border cells. The border cells delaminate from the epithelium surrounding the follicle, invade between the germline‐derived nurse or support cells, and migrate to the dorsal anterior of the oocyte. Loss of PGs results in both delayed migration, and cluster elongation and disruption. Invasive migration is highly dependent on the ability of the cells to respond to mechanical force. Substrate stiffness is sensed by cell surface receptors, these receptors transmit the mechanical information to the cytoskeleton, and the cytoskeleton interacts with the Linker of the Nucleoskeleton and Cytoskeleton (LINC) Complex on the nuclear envelope to convey that information to the nucleus. The nucleus then responds by altering its shape and/or stiffness. Our findings support that model that PGs regulate border cell migration by controlling the actin binding protein Fascin, and that Fascin, in turn, regulates the activity of the LINC Complex to mediate the changes in nuclear position and shape needed for invasive cell migration. The model is supported by the following findings. First, PGs regulate Fascin later in oogenesis to control actin remodeling necessary for follicle morphogenesis. Second, Fascin is highly expressed in the border cells and regulates invasive cell migration in other systems. Third, Fascin localizes to the nuclear periphery, and this localization requires both PG signaling and a functional LINC Complex. Finally, loss of either Fascin or the LINC Complex results in pxt‐like border cell migration defects. These studies are expected to establish the molecular mechanisms whereby PG signaling regulates mechanical signaling to the nucleus to control nuclear position and shape changes necessary for invasive migration. Such findings are applicable to other 3D cell migrations, including those occurring during development and in the context of cancer.

Support or Funding Information

NIH/NIGMS R01GM116885
Supernumerary rectus capitis posterior muscle in Hylobates agilis
Authors: Grider‐Potter Neysa
Published: November 2023

The neck is the junction between the head and thorax, and one of its primary functions is to maintain a balanced head. In animals that practice ricochetal brachiation, such as gibbons, head stability may be especially important because this energetic form of arboreal locomotion requires the rapid assessment of the location and stability of the superstrate. The gibbon cervical musculoskeletal system should be adapted to providing head stability. The suboccipital region was of particular interest as these muscles are significant contributors to head extension and rotation, both important aspects of primate head stabilization during locomotion. Brachiation in particular, involves much larger ranges of rotation than other forms of primate locomotion. Furthermore, this region has not been previously described in gibbons.

The posterior neck and back of a single Hylobates agilis and one Symphalangus syndactylus were dissected. The H. agilis individual presented a supernumerary rectus capitis posterior muscle. The muscle originates from the spinous process of the second cervical vertebra and inserts on the inferior nuchal line of the occiput, similar to rectus capitis posterior major. The supernumerary muscle, however, is lateral and deep to rectus capitis posterior major and deep to obliquus capitis superior. The supernumerary muscle is similar in location to the rectus capitis posterior medius muscle described in cats. Supernumerary suboccipital muscles have also been described in humans. This muscle has not, however, been identified in any described nonhuman primate taxa including: macaques, baboons, and great apes nor was not present in the siamang. Thus, it is unclear if this aberration is an individual or species‐specific variation. The supernumerary muscle inserts more laterally than rectus capitis posterior major and this placement potentially offers greater mechanical advantage in head rotation when activated unilaterally. Such an advantage might offer greater or more efficient head stability during brachiation.
The Relationship Between the McGregor Ligament, the Masseteric Ligaments and the Deep Fascia of the Infraorbital Region
Authors: Amodeo Chiara Andretto , Chevallier Jean‐Marc , Delmas Vincent , Keller Gregory
Published: November 2023

The facial ligaments are very important structures that not only anchor the soft tissues to the deep structures but they also represent reference points to identify other anatomical elements such as nerves and vessels and define anatomical areas. In the midface the Mc Gregor and the massateric ligaments are important anatomical landmarks to identify the path of the facial nerve just anterior to the parotid gland toward the zygomaticus major muscle. The aim of this study is to evaluate the relationship between these two ligaments and the deep fascia of the infraorbital region.

Materials and Methods

20 hemifaces have been dissected at the Centre du Don des Corps de l'Université Paris DesCartes in Paris to study the relationship between the Mc Gregor and the massateric ligaments and the deep fascia that continues from the temporal region and covers the mimetic muscles of the infraorbital area.

Results

The Mc Gregor ligament was identified as a osteocutaneous strong thick band posterior to the zygomaticus major muscle, more caudally a fasciocutaneous cluster of ligaments was observed, the lattest appeared as a fusion between the parotid fascia of the infraorbital area and the deep fascia of the infraorbital area running toward the dermis and corresponded to the massateric ligaments.

The Mc Gregor ligament took relationship with the superficial layer of the deep temporal fascia in the portion where the fascial layer reaches the zygomatic bone.

The path of the zygomatic branch of the facial nerve was always identified just caudal to these ligaments and protected by the deep fascia coming from the temporal region.

Conclusions

In all the specimens the Mc Gregor ligament and the massateric ligaments were in relationship with the superficial layer of the deep temporal fascia and a fusion between the superficial layer of the deep temporal fascia and the upper third of the parotid fascia was identified, corresponding to the masseteric ligaments. These deep fascial connections are landmarks to identify the zygomatic branch of the facial nerve toward the zygomaticus muscle.
The incidence of the fifth head of Quadriceps Femoris, the Tensor Vanstus Intermedius, and its Relationship to the Tensor Fasciae Latae
Authors: Alimohammadi Majid
Published: November 2023

For many years anatomist have extensively studied the quadriceps femoris muscle and some believed that it consisted of only four heads where as some others believed in the existence of an additional fifth head. The most recent studies (Grob et al. 2016), in the second group, introduced a new head, named tensor of the vastus intermedius (TVI). However, according to the latest publications on the topic, it is still unclear whether TVI is a separate muscle or part of vastus lateralis (VL type) or vastus intermedius (VI type). The aim of this study was to carefully examine the quadriceps femoris muscle group of cadaver bodies and explore the incidence of TVI and to show whether there is a relationship between the presence of TVI and the size of tensor fasciae latae (TFL). This relationship between TVI and TFL was suspected due to similar lines of pull caused by the similar orientation of these two muscles. Eighty‐eight lower limbs of forty‐four cadavers were dissected with special attention to the innervation and blood supply to the TVI. Each and every muscle bellies that resembled the TVI were carefully traced from origin to insertion to determine their affiliation. TVI was found in 51% (45 out of 88) of limbs. Three morphological types were identified: independent type (44.4%), VL‐type (11.1%) and VI‐type (44.4%). This study confirmed the latest published findings in regards to the architecture of the quadriceps femoris muscle group. However, there was no apparent association between the size or presence of TVI and the size of the TFL. Nor were there significant differences of the findings between right and left sides or between female or male cadavers.

Support or Funding Information

University of British Columbia (Canada)