bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new method for objective assessment of organ position during human development (540.6)
Authors: de Bakker Bernadette , Besselink Clara , Hagoort Jaco , Moorman Antoon 
Published: June 2021

It is generally accepted that throughout development organs change position to one another within the body. Nonetheless, clear‐cut reports are lacking. Therefore, we aimed to unambiguously determine the position of organs compared to spinal ganglia and vertebrae.Sections of human embryos from the Carnegie collection (CS14‐23 or 31‐60 days) were digitized. All organs were manually segmented and 3D‐reconstructions were made. To determine the position of organs, the intersection of the developing vertebrae with the notochord was used to generate planes perpendicular to the notochord, which were used to assess the position of an organ relative to the vertebrae or spinal ganglia.For the first time a method is presented to unambiguously determine the position of an organ, relative to the vertebrae or spinal ganglia during development. We illustrate the value of the method by an example of the supposed changing position of the kidney, which, in contrast to descriptions in current textbooks, does not change significantly from stage CS17 to CS23. This implies that the proposed relationship of the development of a horseshoe kidney and the inferior mesenteric artery is questionable, because the kidney remains in place, whereas the inferior mesenteric artery descents owing to significant growth of the aorta.
CR405884, a hypothetical uncharacterized coding sequence, exhibits a peculiar expression pattern and FGF responsiveness during limb development (541.4)
Authors: Lujan Gabrielle 
Published: June 2021

CR405884, a hypothetical uncharacterized coding sequence, exhibits a peculiar expression pattern and FGF responsiveness during limb development.Gabrielle N Lujan, Christopher Armstrong, Charmaine U. Pira, Kerby C. Oberg: Division of Human Anatomy, Loma Linda University, Loma Linda, CA During limb development, the apical ectodermal ridge (AER) secretes fibroblast growth factors (FGFs) which maintain limb outgrowth, in part, by regulating Sonic Hedgehog (SHH) expression. SHH from the zone of polarizing activity (ZPA) in the distal posterior aspect of the limb bud is responsible for posterior limb growth and patterning. The molecules and pathways used by FGF to regulate SHH expression are not known. Application of ectopic FGF in the posterior limb mesoderm can induce SHH expression. Using this capacity, we performed microarray analysis on the tissue surrounding an FGF soaked bead, 24 hrs after application. Interestingly, CR405884, an uncharacterized hypothetical coding sequence, exhibited an 11‐fold increased expression in response to FGF and thus, was analyzed further.We isolated CR405884 from chick cDNA by PCR and generated mRNA probes for whole mount in situ hybridization. We then determined the expression profile of CR405884 during limb development in stage 17‐27 embryos. To verify the microarray data, we implanted FGF‐soaked beads into stage 23 embryo limb buds, harvested the tissue after 24 hours, and evaluated CR405884 expression.Expression of CR405884 was first evident in stage 21 limb buds as a focal, 100 um diameter region just anterior to the SHH expression domain. Over the next several stages examined, the expression expanded anteriorly and distally. Furthermore, CR405884 expression increased in response to FGF.The focal expression of CR405884 anterior to and coincident with the expression of SHH may indicate a role for CR405884 in localizing SHH’s expression domain. This concept is further supported by its responsiveness to FGF, a known regulator of SHH expression.
Cardiac myocyte growth response to IGF1 and increased systolic load in lambs (542.2)
Authors: Wilburn Adrienne , Giraud George , Louey Samantha , Jonker Sonnet 
Published: June 2021

The plasticity of the fetal heart allows a proliferative response to growth signals such as increased systolic arterial load (Load) and insulin‐like growth factor 1 (IGF1). The neonatal responses to these stimuli are unknown. OBJECTIVE To determine the in vivo growth response of neonatal cardiomyocytes to IGF1 and to Load compared to controls. METHODS Lambs were instrumented 7 days after birth with inflatable descending thoracic aortic occluders and vascular catheters. On 11‐18 days of age, lambs were given IGF1 (149 μg/kg/day, i.v.), vehicle (i.v.; control), or the occluder was inflated (final day: +35mmHg mean arterial pressure). Hearts were then enzymatically dissociated and myocyte size, maturation (nucleation), and cell cycle activity (an index of proliferation) were measured. RESULTS Hearts were heavier in Load (9.1±0.9 g/kg) and IGF1 (7.2±0.8 g/kg) groups compared to controls (6.6±0.4 g/kg). Cell cycle activity was not different between groups. In IGF1 lambs, mono and quadrinucleated right ventricular myocytes were significantly wider than controls (by 10% and 17%, respectively). In Load lambs, left ventricular mononucleated myocytes were significantly longer (by 14%), and there were 5% fewer binucleated myocytes compared to controls. CONCLUSIONS In the second week after birth, neonatal lamb cardiomyocytes respond to IGF1 and Load with cellular hypertrophy rather than proliferation.Grant Funding Source: Supported by R01HD071068.
Morphological variant of the posterior cerebral artery's origin and trajectory: a case report (543.13)
Authors: Daescu Ecaterina , Enache Alexandra , Baderca Flavia , Sztika Dorina , Zahoi Delia 
Published: June 2021

The complexities of cerebral pathology have led to the necessity of detailed knowledge of arterial blood flow in the region. An important part of this is represented by the cerebral arterial circle.During a routine dissection within the Department of Anatomy and Embryology’s laboratory, an atypical cerebral arterial circle was observed on the cadaver of a 58‐year‐old male. The subject’s cause of death had been unrelated.From their origins, both posterior cerebral arteries cross the optic tracts and descend along the medial portion of the homolateral cerebral peduncle’s anterior side, down to the pontopeduncular sulcus. At this level, the left artery anastomoses with the superior cerebellar artery at its’ origin, changes direction by almost 90 degrees, crosses the optic tract yet again and continues towards the lateral side of the peduncle. The right artery also joins the superior cerebellar artery before taking an S‐shaped path. It takes a first sharp turn, crosses the anterior side of the cerebral peduncle obliquely up to the optic tract, before taking a second, wider turn and descending parallel to the lateral side of the peduncle.The existence and variety of such morphological anomalies need to be taken into account by practitioners, both in investigations such as angiographies as well as during surgical interventions.
Anomalous drainage of the right testicular vein: a case report (543.4)
Authors: Zahoi Delia , Enache Alexandra , Sztika Dorina , Baderca Flavia , Daescu Ecaterina 
Published: June 2021

Typically, the right testicular vein drains blood into the inferior vena cava, while the left testicular veins drains into the left renal vein. However, variations in the paths of the testicular veins do occur. Such variations can influence testicular drainage and even lead to varicocele, one of the causes of male infertility.During a routine dissection conducted within the Department of Anatomy and Embryology’s laboratory, an anomalous path of the right testicular vein was observed on the cadaver of a 60‐year old. The person’s death had been the result of an unrelated cause. The anomaly discovered was that both the left and right testicular veins drained into the left renal vein. The right testicular vein ascended diagonally, crossed in front of the inferior vena cava and joined the lower side of the left renal vein, at an almost 90 degree angle and at a distance of 0.3cm from the inferior vena cava. The left testicular vein joined the left renal vein on the same side, but 4cm further away from the vena cava.Such anatomical variants are clinically and surgically significant, given their influence on venous drainage at a testicular level, as well as the potential haemorrhagic complications during retroperitoneal surgery.
Endothelial insulin‐like growth factor‐1 induced proliferation of vascular smooth muscle cells in response to low shear stress (544.4)
Authors: Qiu Yingxin , Wang Luis , Han Yue , Jiang Zonglai 
Published: June 2021

Objective: Endothelial cells (ECs) are directly exposed to shear stress and modulate the function of vascular smooth muscle cells (VSMCs). Our previous proteomic research revealed insulin‐like growth factors (IGFs) might participate in low shear stress (LowSS) induced vascular remodeling.Methods and Results: Using EC/VSMC co‐cultured parallel‐plate flow chamber system, our results showed, compared with normal shear stress (NSS, 15 dyn/cm2), LowSS (5 dyn/cm2) induced IGF‐1 mRNA expression in ECs, while increased phosphorylation of IGF‐1 receptor (IGF‐1R) and Akt, and expression of Sirt2 in co‐cultured VSMCs. Decreasing expression of IGF‐1 in ECs by RNA interference (RNAi) reversed the effects of LowSS on co‐cultured VSMCs. In separated VSMCs, IGF‐1 increased phosphorylation of IGF‐1R and Akt, expression of Sirt2, and cellular proliferation. PI3K/Akt specific inhibitor decreased expression of Sirt2 and VSMC proliferation, but had no effect on IGF‐1R. Whereas Sirt2 RNAi decreased VSMC proliferation, but had no effect on IGF‐1R and Akt.Conclusion: The present results indicated that LowSS might induce the production of IGF‐1 from ECs, which subsequently paracrine controlled the phosphorylation of IGF‐1R and Akt in VSMCs, and then induced the expression of Sirt2, which finally modulated the proliferation of VSMCs. (Supported by National Natural Science Foundation of China, Nos. 11002091 and 11222223)Grant Funding Source: Supported by National Natural Science Foundation of China, Nos. 11002091 and 11222223
Effects of smoking on heart rate variability in students (545.6)
Authors: Saperova Elena , Dimitriev Dmitry 
Published: June 2021

The purpose of the present study was to investigate cardiac autonomic function in smokers and nonsmoker controls.Methods: Thirty nine light smokers (smoking less than 10 cigarettes a day) and thirty nine nonsmoking students with a mean age of 20.61±0.39 years take part in the study. Subjects were matched by sex, age, menstrual cycle phase and the level of anxiety. They were studied in the morning hours under standardized conditions, in a quiet room at a comfortable temperature. Time domain (SDNN, RMSSD, pNN50) and frequency domain (HF, LF and LF/HF ratio) parameters of HRV were obtained from all participants for 10 minutes while subjects were resting in a supine position. Statistical analysis was performed using Mann‐Whitney test.Results: In this study heart rate was found to be higher in smokers than in nonsmokers (74.08±1.31 vs 64.98±1.12 beat/min, p=0.000007). Time domain parameters were found to be lower in smokers than in nonsmokers (SDNN: 52.54±3.47 vs 72.74±5.35, р=0.0009; RMSSD: 47.68±4.37 vs 71.22±7.72 ms, p=0.009 and pNN50: 26.01±3.21 vs 39.49±3.85, p=0.01). Frequency domain measures were also significantly lower in smokers than non‐smokers (TP: 3498.94±487.42 vs 6527.34±986.47, p=0.005; VLF: 787.28±82.31 vs 1934.20±214.45, p=0.0003; LF: 1147.14±257.82 vs 1895.41±346.76, p=0.007 and HF: 1184.21±245.04 vs 2274.53±487.37, p=0.026). The other HRV parameters including LF/HF ratio, pLF and pHF were not significantly different.Conclusions: These results suggest that smoking has been associated with increased activity of the sympathetic nervous system and decrease in vagal cardiac control.This work was supported by the Ministry of Education and Science of the Russian Federation (grant 4.4904.2011, grant 14.B37.21.0215).
Phosphatidylcholine‐specific PLC plays a central role in the development of myogenic tone in murine resistance arteries (546.4)
Authors: Mauban Joseph , Zacharia Joseph , Fairfax Seth , Wier W 
Published: June 2021

The Bayliss mechanism posits that an increase in transmural pressure causes an artery to contract in response to distending pressure. Previous studies have established that PLC is critical for the myogenic response. However, the functional type/s of phospholipase C (PI‐PLC or PC‐PLC) involved and actions of PLC second messenger products (IP3, DAG) have not been clarified. This study of myogenic tone was therefore carried out to 1) identify the functional type/s of PLC involved and 2) investigate the role of IP3 and IP3‐induced Ca2+ release, in the maintenance of myogenic constriction. Pressurized mesenteric arteries showed that inhibition of phosphoinositide‐specific PLC with Edelfosine, surprisingly,increases myogenic tone at physiological pressures. In contrast, inhibition of phosphatidylcholine‐specific PLC with D609 abolishes myogenic tone. The Bayliss mechanism therefore involves a hitherto unrecognized role for the cleavage of phosphatidylcholine and formation of DAG. Ca2+ waves are virtually absent in myogenically active arteries. In addition, 1) SR Ca2+ release via IP3 and ryanodine receptors, and 2) Ca2+ store emptying, all do not eliminate myogenic constriction. In summary, the Bayliss mechanism signaling cascade in murine mesenteric resistance arteries does not require 1) sustained IP3 formation, 2) or Ca2+ release from SR stores via ryanodine and IP3 receptors. Instead, the signaling cascade critically requires PLC cleavage of phosphatidylcholine.Grant Funding Source: Supported by NHLBI RO1091969 and NIH T32HL072751
Acute BH4 depletion leads to a loss of myocardial protection conferred by cardiac‐specific overexpression of inducible nitric oxide synthase in mice (547.11)
Authors: Boslett James , Barga Elizabeth , Kotwal Ameya , Choppara Bhavana , Zweier Jay 
Published: June 2021

Many studies have shown that cardiac overexpression of NOS enzymes can lead to myocardial protection against ischemia/reperfusion (I/R) injury. However, none of these studies experiment with modulating BH4 levels. Because adequate BH4 levels lead iNOS to produce nitric oxide and inadequate BH4 levels lead iNOS to produce damaging superoxide, we hypothesized that depletion of BH4 in a model of constitutive iNOS expression would lead to a loss of iNOS function and diminished recovery of post‐ischemic myocardial contractility. The study involved two groups of iNOS TG mice: untreated mice and treated mice. Treated mice received 21 days of BH4 depletion diet using food with GTP cyclohydrolase inhibitor 2,4‐舃Diamino‐舃6‐舃hydroxypyrimidine (DAHP). The 21 day DAHP treatment led to a roughly 65% myocardial depletion of BH4 as measured by HPLC. Hearts from these two groups were used in isolated heart experiments and were subjected to 30’ of ischemia and 60’ of reperfusion. Compared to untreated mice, DAHP‐treated mice had significantly less recovery of rate pressure product, left ventricular developed pressure, and significantly more elevated end diastolic pressure at 30 and 60’ of reperfusion. This work shows the importance of adequate BH4 levels in protection against myocardial I/R, especially in the context of NOS overexpression.Grant Funding Source: 00000784
Luteolinidin, a naturally occurring flavonoid, decreases ischemia/reperfusion injury through inhibition of CD38 and preservation of NADPH and BH4 (547.14)
Authors: Boslett James , De Pascali Francesco , Hemann Craig , Zweier Jay 
Published: June 2021

CD38, a consumer of NAD+ and NADP+, is activated in I/R, leading to depletion of myocardial NADP(H) and consequently, lower eNOS function due to low levels of cofactor NADPH. Isolated hearts were subjected to two treatments: pre‐ischemic luteolinidin (25μM) infusion or vehicle control infusion (empty liposomes). In vehicle‐treated hearts at 30’ ischemia and 30’ reperfusion, NADPH and BH4 were depleted by 67% and 64% respectively. With 3’ of luteolinidin infusion (25μM), these numbers changed to 23% and 32% for NADPH and BH4, respectively, representing an impressive 44% salvage of NADPH, and a 32% salvage of BH4 compared to vehicle‐treated hearts. This NADPH and BH4 salvage was manifested physiologically as an increased loss of coronary flow (CF) in response to eNOS inhibitor L‐NAME (1mM) at 30’ reperfusion. Moreover, we found in luteolinidin‐treated hearts more post‐ischemic recovery of rate pressure product, left ventricular developed pressure and CF, and, a less elevated end diastolic pressure. This work suggests that inhibition of CD38 with luteolinidin is beneficial in I/R as measured by parameters of post‐ischemic endothelial and contractile function. The work also suggests that that post‐ischemic NADPH and BH4 levels are related, possibly through modulation of dihydrofolate reductase activity by NADPH levels.Grant Funding Source: Supported by 00000784
Chronic exposure to low doses of HgCl2 avoids the impaired on calcium handling in the right ventricle after myocardial infarction in rat (547.3)
Authors: Stefanon Ivanita , Faria Thais , Costa Gustavo , Almenara Camila , Angeli Jhuli , Padilha Alessandra , Vassallo Dalton , Vassallo Paula 
Published: June 2021

The aim of this study was to investigate if chronic exposure to low doses of mercury chloride (HgCl2) causes functional alterations in right ventricle (RV) strips after myocardial infarction (MI). Male Wistar rats were divided into four groups: Control (vehicle); HgCl2 (exposure during 4 weeks‐ 1st dose 4.6 μg/kg, subsequent dose 0.07 μg/kg/day, i.m to cover daily loss); MI surgery induced and HgCl2‐MI group. One week after MI RV strips, superfused with Krebs solution, were studied using an isometric tension system. Contractile function of HgCl2 group did not change compared to Control. On basal conditions, despite similar maximum isometric force at L‐max, relaxation time was reduced in the MI group but preserved in the HgCl2‐MI compared to Control group. The MI group presented a depression in the tetanic peak and plateau of developed force. Additionally, impaired sarcoplasmic reticulum (SR) function and a reduced sarcolemmal calcium influx were observed only in MI animals. The SERCA2a protein expression was reduced in both MI groups while PLB protein expression was increased only in MI group. These results suggest that chronic exposure to low doses of HgCl2 avoids the impaired SR function and the reduced sarcolemmal calcium influx observed in MI probably acting on PLB and SERCA2a protein expression.Grant Funding Source: Supported by: PRONEX ‐ FAPES, CNPq, CAPES
Mitochondrial DNA damage and mitochondrial function during acute oxidative stress induced by H2O2 in Saccharomyces cereviseae (550.4)
Authors: Arroyo Yaria , Acevedo‐Torres Karina , Ayala‐Peña Sylvette , Torres‐Ramos Carlos 
Published: June 2021

Base excision repair (BER) is the main repair mechanism responsible for the removal of mitochondrial DNA (mtDNA) damage, however, the relationship between mtDNA damage and mitochondrial function is not fully understood. We seek to determine the effect of mtDNA damage and mitochondrial function in yeast strains harboring mutations in BER genes after acute oxidative stress induced by H2O2. We observed that compared to a wild type (Wt) strain, mtDNA lesions after H2O2 treatment increased 4.3 fold in an ogg1∆ strain, 4.1 fold in an apn1∆ strain and 21.2 fold in a double mutant ogg1∆ apn1∆ strain. Similarly, mtDNA mutation rate increased in cells treated with H2O2 in the following manner: Wt strain, 7.7 fold; ogg1∆ strain, 11.9 fold; apn1∆ strain, 19.9 fold, and ogg1∆ apn1∆ strain, 30.6 fold. H2O2 treatment disrupted mitochondrial function as determined by mitochondrial membrane potential measurements: 15%, 15%, 10% and 24% decreased in Wt, ogg1∆, apn1∆, and ogg1∆ apn1∆, respectively. Finally, increased superoxide anion generation was observed after H2O2 treatment, particularly in the BER double mutant strain. We can conclude that an interaction between the OGG1 and APN1 genes is required for the maintenance of mitochondrial DNA integrity and function after an acute oxidative stress insult.Grant Funding Source: Supported by 5SC3GM08475902, R25GM068138 and G12RR03051
Translocation of catalase and SODs protects from doxorubicin‐induced nuclear damage in cultured human ovarian cancer cells (554.2)
Authors: Best Charles 
Published: June 2021

Doxorubicin is applied clinically to treat ovarian cancer, and yet the molecular mode of actions of doxorubicin is far from clear. Our most recent study has shown that antioxidant N‐acetylcysteine (NAC) potentiates doxorubicin‐induced activation of p53 and ATM, suggesting that endogenous antioxidant enzymes may play important roles in the response of ovarian cancer cells to doxorubicin treatment. In this study, we investigated the expression of catalase and SOD1, 2 and 3 in cultured ovarian cancer cells (CaOV3). Western blot data showed that CaOV3 cells express catalase and SOD1, 2, and 3. Serum starvation reduces expression of those enzymes, while EGF treatment induces EGFR and mTOR activation and the expression of those enzymes. mTOR inhibitor, Rapamycin, PI3K/AKT inhibitor LY294002, and MEK/ERK inhibitor U0126 inhibit expression. Interestingly, doxorubicin treatment induces translocation of those enzymes from cytoplasm to nucleus in a dose and time dependent manner, however, chemo drug paclitaxel has no such effect. Our data suggest that to avoid widespread oxidative stress and nuclear damage, ovarian cancer cells protect themselves via translocation of the antioxidant enzymes in response to doxorubicin treatment. Thus, inhibition of such translocation may enhance the efficacy of doxorubicin in vivo. Collectively, our data support the notion that combo treatment with inhibitors of mTOR and MEK/ERK pathways and doxorubicin may yield better clinical outcome.Grant Funding Source: Rhode Island INBRE
Analysis of the transcriptional activation and post‐transcriptional regulation of transient receptor potential mucolipin‐2 gene (561.5)
Authors: Valadez Jessica , Cuajungco Math 
Published: June 2021

Mucolipidosis type IV (MLIV) is a neurodegenerative disease caused by loss or dysfunction of the human transient receptor potential mucolipin 1 (TRPML1) protein. TRPML1 is a non‐selective cation channel related to two other proteins, TRPML2 and TRPML3. The high degree of sequence and functional similarities between TRPML1 and TRPML2 make TRPML2 an excellent candidate to potentially substitute for the loss of TRPML1 function in MLIV. In order to consider this possibility, we first needed to study the mechanisms that control the expression of TRPML2 gene. We cloned DNA regions of varying size upstream of the TRPML2 gene transcriptional start site (TSS) into a dual luciferase reporter assay. We identified a putative core promoter region between ‐320 and ‐287 of the TSS containing a consensus sequence for six transcription factors. Heterologous expression of the candidate TFs conferred an effect on the expression of endogenous TRPML2 transcripts compared to control. Meanwhile, we found that a specific micro‐RNA was responsible for post‐transcriptional regulation of endogenous TRPML2 transcripts as evidenced by real‐time quantitative PCR (qPCR) technique. We then screened a drug library and confirmed by real‐time qPCR that each drug candidate significantly increased the expression of endogenous TRPML2 transcripts. These results show that we could induce the expression of the TRPML2 gene through exogenous manipulation of transcriptional activators or post‐transcriptional regulators. Understanding the mechanism of TRPML2 expression is a step closer to our goal of using TRPML2 protein to substitute for the loss of TRPML1 protein function in MLIV.Grant Funding Source: Supported by NIH R15‐NS070774 and CSUF Intramural Grants