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Biomedical subjects

Y Sun

Publications and source records attributed to Y Sun.

At least 271 records · Page 15Linked to original sources

Selenoprotein W accumulates primarily in primate skeletal muscle, heart, brain and tongue.

The human selenoprotein W coding region with the selenocysteine codon (TGA) changed to a cysteine codon (TGT) was fused to six histidine codons (at its 3' end), cloned into a prokaryotic expression vector (pTrc99a), and the corresponding mutated selenoprotein W was expressed in bacteria. The protein was purified by Ni-NTA agarose column and reverse phase HPLC. Polyclonal antibodies raised against this protein were used in Western blots to determine tissue distribution of selenoprotein W from rhesus monkeys fed a commercial chow. Selenoprotein W was found in several tissues with highest amounts in skeletal muscle and heart (muscle 6 fold greater than liver) and lowest levels in liver, but selenium concentrations were highest in kidneys (10 fold greater than muscle) and lowest in skeletal muscle. Northern blots using a human selenoprotein W cDNA probe indicated that mRNA levels were highest in monkey skeletal muscle and heart (2-2.5 fold greater than in liver), which is similar to the pattern found with a human multiple tissue Northern blot. However, as in the monkey, selenium concentrations were highest in human kidney and lowest in skeletal muscle and heart. Thus, selenoprotein W protein levels correlated with selenoprotein W mRNA levels but not with tissue selenium concentrations.

Animals↗

Effects of high-potassium-induced depolarization on amino acid chemistry of the dorsal cochlear nucleus in rat brain slices.

High K+ was used to depolarize glia and neurons in order to study the effects on amino acid release from and concentrations within the dorsal cochlear nucleus (DCN) of brain slices. The release of glutamate, gamma-aminobutyrate (GABA) and glycine increased significantly during exposure to 50 mM K+, while glutamine and serine release decreased significantly during and/or after exposure, respectively. After 10 min of exposure to 50 mM K+, glutamine concentrations increased in all three layers of DCN slices, to more than 5 times the values in unexposed slices. In the presence of a glutamate uptake blocker, L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC), glutamine concentrations in all layers did not increase as much during 50 mM K+. Similar but smaller changes occurred for serine. Mean ATP concentrations were lower in 50 mM K(+)-exposed slices compared to control. The results suggest that depolarization, such as during increased neural activity, can greatly affect amino acid metabolism in the cochlear nucleus.

Adenosine Triphosphate↗

Knocking the NT4 gene into the BDNF locus rescues BDNF deficient mice and reveals distinct NT4 and BDNF activities.

To directly compare biological activities of the neurotrophins NT4 and BDNF in vivo, we replaced the BDNF coding sequence with the NT4 sequence in mice (Bdnfnt4-ki). Mice expressing NT4 in place of BDNF were viable, in contrast with BDNF null mutants, which die shortly after birth. Although the Bdnfnt4-ki/nt4-ki and wild-type Bdnf+/+ alleles yielded similar levels of NT4 and BDNF proteins, NT4 supported more sensory neurons than BDNF and promoted functional synapse formation in cultured hippocampal neurons. Homozygous Bdnfnt4-ki/nt4-ki mice showed reduced body weight, infertility and skin lesions, suggesting unique biological activities of NT4 in vivo. The distinct activities of NT4 and BDNF may result partly from differential activation of the TrkB receptor and its down-stream signals.

Animals↗

Increased non-major histocompatibility complex-restricted lytic activity in melanoma patients vaccinated with cytokine gene-transfected autologous tumor cells.

Genetically modified antitumoral vaccines focus on eliciting or increasing the T-cell-mediated antitumoral response. Little is known about non-major histocompatibility complex-restricted responses. In two phase I studies, we have immunized advanced melanoma patients with either interleukin-7 (IL-7) gene-transfected or IL-12 gene-transfected, autologous, irradiated melanoma cells. To monitor the immune response, peripheral blood mononuclear cells were collected before the first vaccination and 2 weeks after the third vaccination. Spontaneous lytic activity and lymphokine-activated killer (LAK) activity after a 5-day culture in the presence of 1000 U/mL IL-2 against autologous and against allogeneic melanoma cells were measured. In parallel, a precursor cytotoxic T-cell frequency analysis was performed using a 25-day limiting dilution analysis assay. A total of 10 of 14 immunologically evaluable patients demonstrated a marked increase in LAK activity, and 7 of 14 showed increased spontaneous lytic activities against autologous melanoma cells after three vaccinations. Remarkably, two patients with a good clinical performance status (Karnofsky index of >70; Multitest Merieux of >13.4 mm/3) and -the highest cytotoxic T-lymphocyte (CTL)-response after vaccination showed the only clear decrease in LAK and spontaneous lytic activity. Otherwise, three patients with no detectable CTL response after vaccination demonstrated an increase in LAK activity and the strongest increase in the autologous spontaneous lytic activity. This group of patients was associated with a poor clinical performance status (Karnofsky index of <70; Multitest Merieux of <4 mm/1) and with no clinical response. In conclusion, in accordance with other studies, a good clinical and immunological performance status appears to be the prerequisite for a successful CTL response. However, even strong non-major histocompatibility complex-restricted responses could be generated in patients with reduced clinical performance in vaccination therapies with gene-transfected autologous tumor cells.

Adult↗

In vivo gene transfer of CD40 ligand into colon cancer cells induces local production of cytokines and chemokines, tumor eradication and protective antitumor immunity.

The interaction between CD40 ligand (CD40L, CD154) and its receptor CD40 on antigen-presenting cells, is essential for the initiation of cell-mediated and humoral immune responses. In this study, we investigated the antitumor effect of in vivo gene transfer of CD40L to tumor cells using an adenoviral vector (AdCMVmCD40L) in a murine CT-26 colon cancer model. We found that injection of AdCMVmCD40L caused tumor regression in a dose-dependent manner. A complete regression of tumor was observed in 81% of mice treated with 10(9) p.f.u. of AdCMVmCD40L. The antitumor effect induced by CD40L was mediated by CD8+ T cells and was associated with the generation of tumor-specific cytolytic T lymphocytes (CTL). Animals that eradicated the tumor were protected against tumor cell rechallenge, and both CD4+ and CD8+ T cells were involved in specific protective immunity. Treatment with AdCMVmCD40L in one tumor nodule also caused complete regression of established tumors at distant sites. The antitumor effect elicited by AdCMVmCD40L was associated with the intratumoral production of IL-12 and IFN-gamma and with an increased intratumoral expression of chemokines such as MIP- 1alpha, MIP-1beta, MIP-2, RANTES, and eotaxin. These data demonstrate that intratumoral injection of AdCMVmCD40L induces a powerful cascade of chemokines and cytokines in the tumor mass and stimulates an efficient antitumor immunity leading to regression of established colon cancer and protection against tumor cell rechallenge.

Adenoviridae↗

Apolipoprotein E is a genetic risk factor for fetal iodine deficiency disorder in China.

Fetal iodine deficiency disorder (FIDD) is the principal form of endemic cretinism, and the most common cause of preventable mental deficiency in the world. However not everyone at risk develops FIDD and familial aggregation is common. This suggests that genetic factors may also be involved. The Apolipoprotein E (APOE) gene encodes for a lipoprotein that possesses a thyroid hormone binding domain, and APOE genotype may affect the efficiency with which thyroid hormone influences neuronal cell growth during the first and second trimesters of fetal development. We have compared ApoE genotypes in 91 FIDD cases with 154 local control subjects, recruited from three iodine deficiency areas in central China. We have also genotyped 42 FIDD family cases and 158 normal individuals from the families of local controls, and 375 population controls from Shanghai. APOE epsilon4 genotypes were significantly enriched in FIDD probands from each of the three iodine deficiency areas; the epsilon4 allele frequency was 16% vs 6% in controls. The same effect was also observed when we compared FIDD family cases with controls and control families. Our data suggest that in iodine-deficient areas, the APOE epsilon4 allele is a genetic risk factor for FIDD. The phenomenon may affect population selection and contribute to the low frequency of the epsilon4 allele in Chinese compared to Caucasian populations.

Adolescent↗

Determination of trace selenium in human plasma and hair with ternary inclusion compound-fluorescent spectrophotometry.

A method for determination of selenium in plasma and hair with ternary inclusion compound-fluorescent spectrophotometry has been developed. The determination of selenium in plasma and hair can be performed directly in aqueous solution. Blood and hair samples were destroyed by oxygen flask combustion. The linear range was 10-500 ng mL-1 for plasma and 10-100 ng mL-1 for hair. Within-day and day-to-day precisions for plasma ranged from 5.4% to 9.3% (n = 7) and from 3.5% to 14.5% (n = 7), respectively. Within-day precisions for hair ranged from 0.6% to 6.2% (n = 7). Recoveries ranged from 91.0% to 97.8% for plasma and from 95.0% to 102.0% for hair. The blood samples from 15 Hans and 20 Uygurs in Xinjiang Uygur automatic region and 23 Hans in Liaoning province were collected and determined. It was indicated that no statistically significant difference in plasma selenium concentration of the Hans between Xinjiang and Liaoning was found (F = 1.36, P > 0.05). However, there were statistically significant differences between the Hans and the Uygurs in Xinjiang (F = 1.01, P < 0.01) and between males and females in the two areas (P < 0.01). There was a low correlation between plasma selenium concentration and hair selenium concentration. The ratio of hair selenium concentration to plasma selenium concentration was 2.17, with a range of 1.63-2.88.

Hair↗

A kinetic study of the synthesis of ascorbate fatty acid esters catalysed by immobilized lipase in organic media.

The kinetics of the synthesis of L-ascorbyl laurate and L-ascorbyl palmitate catalysed by immobilized lipase from L-ascorbic acid and an acyl donor (lauric acid, palmic acid and their methyl and ethyl esters) in 2-methylbutan-2-ol have been investigated. The factors affecting the reaction rate (shaking speed, temperature, water activity, enzyme concentration as well as substrate concentration) are discussed. The reaction conditions have been optimized as follows: shaking speed 200 rev./min, temperature 55 degrees C, enzyme 17-20% (w/w of substrate) for these substrates. The most suitable substrate concentration for all of these substrates was 300 mmol/l. The reactions were modelled. For lauric acid, methyl laurate and ethyl laurate: K(m)=74.3, 48.97 and 55.8 mmol/l, respectively; and V(max)=0.010764, 0.0114, 0.01116 mmol.min(-1).g(-1), respectively. The most suitable substrate was methyl laurate. For palmic acid, methyl palmitate and ethyl palmitate: K(m)=102, 94.9 and 104 mmol/l, respectively; and V(max)=0.0417, 0.0424 and 0.0435 mmol.min(-1).g(-1), respectively. The most suitable substrate was methyl palmitate.

Ascorbic Acid↗

Cardiac remodeling by fibrous tissue after infarction in rats.

After transmural myocardial infarction (MI), extensive myocardial remodeling by fibrous tissue appears in both infarcted and noninfarcted myocardium, which contributes to ventricular diastolic dysfunction. In the present study we sought to assess the time course of collagen remodeling in the infarcted rat hearts by detecting spatial and time-dependent cellular events related to collagen synthesis and degradation 2 to 28 days after left coronary artery ligation. In infarcted hearts, and compared with findings in sham-operated and unoperated rat hearts, we found the following: (1) macrophages infiltrated into sites of MI and visceral pericardium on day 2 and gradually disappeared after day 14; (2) myofibroblasts (MyoFb) first appeared at these sites of repair on day 3 and remained abundant thereafter at all time points examined; (3) transforming growth factor-beta1 (TGF-beta1) mRNA was enhanced in infarcted and noninfarcted myocardium on day 2 and remained throughout 28 days; (4) type I and III collagen mRNAs began to increase at and remote to MI on day 3 and remained elevated thereafter; (5) matrix metalloproteinase-1 mRNA was significantly increased at and remote to MI on day 3, declined to the control level on day 7, and remained low thereafter; (6) tissue inhibitor of matrix metalloproteinase (TIMP)-I, -II, and -III mRNAs were markedly elevated at sites of repair on day 3 and sustained throughout 28 days; (7) fibrillar collagen accumulation that was evident at and remote to MI on day 7 continued to accumulate thereafter at each site over 4 weeks. When compared with findings in unoperated rat heart, pericardial fibrosis was evident in both infarcted and noninfarcted heart, and the temporal response of collagen generation/ degradation in pericardium was similar to that in infarcted myocardium. Thus collagen synthesis is activated in both infarcted and noninfarcted rat myocardium after transmural anterior infarction and is persistent throughout the 28-day period of study, whereas early collagen degradation is short lived and inactivated in the fibrogenic phase. Activated TGF-beta1 mRNA expression is accompanied by the appearance of MyoFb and the expression of fibrillar collagens and TIMPs, suggesting that this fibrogenic cytokine may contribute to collagen remodeling in the rat heart after MI.

Actins↗

Effects of neural blocking agents on motor activity and secretion in the proximal and distal rat colon: evidence of marked segmental differences in nicotinic receptor activity.

BACKGROUND: Neuromodulation may be a new therapeutic approach in inflammatory bowel disease, but very little is known about neural control of colonic secretion in vivo. We therefore determined the effects of neural blockade on colonic motor activity and mucosal secretion in anaesthetized rats. METHODS: A proximal and a distal colonic segment were isolated in four groups of chloralose-anaesthetized rats (n = 8 in each group), and we measured luminal pressure and transmural potential difference (PD) as a marker of electrogenic chloride secretion. Recordings were made from proximal and distal segments simultaneously, which made it possible to directly compare response patterns. RESULTS: Under control conditions luminal pressure waves were associated with phasic, lumen-negative increases in PD which had a significantly greater magnitude and longer duration in the distal colon. Atropine blocked both pressure waves and PD waves in the proximal colon, but some PD waves, although of lower magnitude, remained in the distal colon. Hexamethonium abolished pressure waves in both segments and induced a marked reduction in PD in the distal but not in the proximal colon. Lidocaine also reduced PD, more so in the distal colon, and dissociated the pressure-PD linkage. CONCLUSION: In the distal but not in the proximal colon, there is a strong nicotinic, neurogenic 'tone' that maintains a high basal secretory activity. The results encourage the search for neuromodulatory agents in the treatment of colonic secretory disease.

Anesthetics, Local↗

Serum uric acid and patterns of radiographic osteoarthritis--the Ulm Osteoarthritis Study.

OBJECTIVE: To assess the association between uric acid and patterns of osteoarthritis (OA). METHODS: OA patterns were studied in 809 patients with arthroplasty due to hip or knee OA. Patients with OA were categorized as having bilateral or generalized OA according to the presence of radiographic OA in the contralateral or different finger joints. Odds ratios (OR) and 95% confidence intervals (CI) for thirds of serum uric acid and OA patterns were estimated with multivariable logistic regression. RESULTS: Eighty-five percent of the participants had bilateral OA and 26% generalized OA. A positive association between serum uric acid and generalized OA was observed in patients with hip OA (highest versus lowest tertile OR=3.5; 95% CI: 1.3-9.1), but not among patients with knee OA (corresponding OR = 1.1). Serum uric acid was not associated with bilateral OA. CONCLUSION: Our results suggest a possible role of elevated serum uric acid in the multifactorial etiology of generalized OA.

Aged↗

Quantitative determination of surface concentration of human apolipoprotein H with capillary electrophoresis.

The phospholipid monolayer at an air/water interface is widely used to mimic the biological membrane. The dynamic process of the protein or peptide interacting with lipid molecules can be reflected in the change in surface pressure of the monolayer. But the conventional method used to measure the surface pressure change gives results that cannot easily be correlated with the contribution of a single protein molecule. Previously, measuring the surface concentration of the protein molecules at the air/water interface has required the protein to be labeled with radioactivity or fluorescence. Here, a new method using capillary electrophoresis is introduced to measure the surface concentration of the protein. The results show at least two advantages of the new method: The numerical results of protein concentration can be obtained in a more precise and rapid way; and there is no need to label the protein sample or to build a special monolayer setup.

Cell Membrane↗

Solid-phase microextraction and headspace solid-phase microextraction for the determination of high molecular-weight polycyclic aromatic hydrocarbons in water and soil samples.

The feasibility of direct-immersion (DI) solid-phase microextraction (SPME) and headspace (HS) SPME for the determination of high-ring polycyclic aromatic hydrocarbons (PAHs) (4- to 6-ring PAHs) in water and soil samples is studied. Three SPME fibers--100- and 30-microm polydimethylsiloxane (PDMS) and 85-microm polyacrylate (PA) fibers-are compared for the effective extraction of PAHs. Parameters affecting the sorption of PAHs into the fiber such as sampling time, sampling volume, and temperature are also evaluated. The extracted amounts of high-ring PAHs decrease with the decreasing of film thickness, and the 100-microm PDMS has the highest extraction efficiency than 85-microm PA and 30-microm PDMS fibers. Also, the extraction efficiency decreases with the increasing molecular weights of PAHs. Of the 10 high-ring PAHs, only fluoranthene and pyrene can reach equilibrium within 120 min at 25 degrees C for DI-SPME in a water sample. Increasing the temperature to 60 degrees C can increase the sensitivity of PAHs and shorten the equilibrium time. A 0.7- to 25-fold increase in peak area is obtained for DI-SPME when the working temperature is increased to 60 degrees C. For HS-SPME, the extraction efficiency of PAHs decrease when the headspace volume of the sampling system increases. All high-ring PAHs can be detected in a water sample by increasing the temperature to 80 degrees C. However, only 4- and 5-ring PAHs can be quantitated in a CRM soil sample when HS-SPME is used. The addition of a surfactant with high hydrophilic property can effectively enhance the sensitivity of high-ring PAHs. HS-SPME as well as DI-SPME with 100-microm PDMS or 85-microm PA fibers are shown to be suitable methods for analyzing high-ring PAHs in a water sample; however, this technique can only apply in a soil sample for PAHs having up to 5 rings.

Chromatography, Gas↗

PRELI, the human homologue of the avian px19, is expressed by germinal center B lymphocytes.

We report the identification of a human cDNA encoding a 25 kDa protein of relevant evolutionary and lymphoid interest (PRELI). PRELI was cloned by screening a B lymphocyte-specific cDNA library with a probe generated by mRNA differential display. PRELI amino acid sequence is 85% similar to the avian px19 protein, expressed within the blood islands and in the liver during avian embryo development. PRELI and px19 contain tandem repeats (A/TAEKAK) of the late embryogenesis abundant (LEA) motif, characteristic of a group of survival molecules and originally thought to be present only in plant proteins. Interestingly, PRELI expression is high in the fetal liver, a major site for B cell lymphopoiesis, while the mRNA levels in other fetal tissues such as the brain, lung, and kidney are comparatively low. At the adult stage, PRELI expression is drastically reduced in the liver but exhibits high mRNA levels in the spleen, brain, lung and kidney tissues, suggesting that PRELI expression may be important for the development of vital and immunocompetent organs. Moreover, PRELI is also highly expressed in the adult lymph nodes and peripheral blood leukocytes, further stressing that at the adult stage, PRELI expression may be important during secondary immune responses. Consistent with this hypothesis, the expression of PRELI is predominant within germinal centers (GC), a stage in which B lymphocytes are under a stressful selection pressure. Taken together these data: (i) strongly support the notion that the conserved LEA motif represents a phylogenetic link between plants and animals, (ii) reveal a novel molecule whose expression may play a role in the maturation of distinct human tissues, and (iii) suggest that PRELI expression may be important for GC B lymphocytes.

Adult↗

Integrin-like proteins in the pollen tube: detection, localization and function.

The distribution of integrin-like proteins in the pollen tube was examined by immunofluorescent labeling and western blotting techniques using antibodies against human placenta integrin vitronectin receptor (VnR), and alpha(v), beta3 and beta1 integrin subunits. Pseudocolor-coded confocal images showed intense immunostaining within 10 and 5 microm of the tip of the pollen tube in Lilium davidii and Nicotiana tabacum respectively. In both segments the site near the plasma membrane was labeled. Western blotting analyses revealed cross-reaction of anti-beta3, anti-alpha(v) and anti-VnR with the proteins in the plasma membrane preparation of L. davidii and Hemerocallis citrina pollen tube. These studies provide evidence for the first time that the integrin-like protein is present in pollen tubes, and it may be mainly composed of alpha(v) and beta3 subunits in lily pollen tubes. In a functional assay, neither anti-VnR antibody nor the Arg-Gly-Asp-Ser tetrapeptide inhibited pollen tube growth of N. tabacum in vitro, but both of them depressed tube growth on the stigma and in style under quasi in vivo culture conditions. The integrin-like proteins localized in the tip and periphery of the pollen tube appeared to play roles in growth of the pollen tube tip and interaction with the extracellular matrix of the style.

Antibodies, Monoclonal↗

Selective requirement for Cdc25C protein synthesis during meiotic progression in porcine oocytes.

Fundamental differences between meiosis and mitosis suggest that the shared central cell cycle machinery may be regulated differently during the two division cycles. This paper focuses on unique features of Cdc25C protein function during meiotic progression. We report on the existence of oocyte-specific CDC25C transcripts that differ from their somatic counterparts in the 3' untranslated region. While CDC25C mRNA levels remain constant in fully-grown oocytes, corresponding protein levels increase progressively during maturation to a maximum at metaphase II. Elevation of Cdc25C protein levels in G2-oocytes by mRNA injection failed to increase MPF-kinase levels or to induce premature entry into M-phase. Likewise, antisense-induced arrest of translation (translational arrest) had no effect on chromosome condensation, nucleolar disassembly, or nuclear membrane contraction. By contrast, translational arrest inhibited subsequent events including membrane disassembly and spindle formation. Neither up- nor down-regulation of Cdc25C synthesis after metaphase I plate formation influenced progression to metaphase II. However, translational arrest during metaphase resulted in incomplete chromosome decondensation and abnormal pronuclear membrane assembly after activation. We conclude that Cdc25 protein, translated from unique transcripts, is preferentially located in the oocyte nucleus and is essential for progress through late diakinesis. Subsequently, new synthesis of Cdc25C protein is required for the orderly transition from meiotic to mitotic cell division.

Animals↗

A stand-alone windows applications for computing exact person-years, standardized mortality ratios and confidence intervals in epidemiological studies.

We introduce a stand-alone and user-friendly person-years and mortality computation program (PAMCOMP) for calculating exact person-years and standardized mortality and incidence ratios running under Windows 95/98 and NT. The calculation of person-years allows flexible stratification by self-defined and unrestricted categories of age and calendar years. Furthermore, it is possible to lag person-years to account for latency periods. The standardized mortality ratio computation includes calculation of 90%, 95%, and 99% confidence intervals. Import and export filters for standard personal computer file formats are available. The software is free of charge and can be downloaded from: http://medweb.uni-muenster.de/institute/epi/ pamcomp/pamcomp.html

Cohort Studies↗

Mapping of quantitative trait loci (QTL) of differential stress gene expression in rat recombinant inbred strains.

OBJECTIVE: Stress has been shown to be a major environmental contributor to cardiovascular diseases through its effects on blood pressure variability and cardiac function. The cellular stress response is characterized by the expression of specific heat stress genes (hsps), under the transcriptional control of heat shock transcription factors (HSTFs). The levels of hsp mRNA depend on the severity of the stress, with hstf1 acting as a stress sensor. The aim of this work was to evaluate the genetic contribution of the variability in hsp expression, and to identify its putative quantitative trait loci (QTL). METHODS: Twenty recombinant inbred rat strains (RIS) were studied. The animals underwent a standardized, identical 1 h immobilization stress in restraint cages, followed by 1 h of rest before sacrifice. Total RNA was extracted from the heart kidneys and adrenals, and the mRNA levels of hsp27, hsp70, hsp84, hsp86 and hsp105 were measured. The strain distribution pattern (SDP) of hsp expression was correlated with that of 475 polymorphic markers distributed throughout the RIS genome. A polymorphism of rat hstf1 in RIS was used for its mapping in RIS. RESULTS: Despite an identical stress being applied to all strains, hsp expression showed up to a 1 2-fold gradient with little intra-strain variability, indicative of a strong genetic contribution to the trait Heritability ranged from 50 to 77% for most hsp genes in the three target organs. The continuous SDP of stress gene expression indicated the polygenic nature of the trait A common locus on chromosome 7 (at D7Cebrp187s3 marker) was consistently associated with all hsp expression in most of the organs [with a likelihood of odds (LOD) score of 3.0 for hsp27 expression]. We have mapped rat hstf1 on chromosome 7 at the same locus. Finally, the D4Mit19 marker was significantly associated with hsp84 expression in the heart (LOD score of 3.1). CONCLUSION: Two loci were linked with the differential expression of HSPs in response to immobilization stress in target organs of RIS. The chromosome 7 locus unveiled for all HSPs could explain up to 42% of the observed inter-strain variability of hsp levels in response to stress. We propose hstf1 as a positional candidate at this locus.

Adrenal Glands↗