bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for the Regulation of Prostatic Oxytocin by Gonadal Steroids in the Rat
Authors: JENKIN LOUISA , NICHOLSON HELEN D.
Published: October 2023

ABSTRACT: Oxytocin and its receptor are present in the mammalian prostate, and the peptide has been shown to increase prostatic growth, 5α‐reductase activity, and contractility. This study was performed to investigate whether local concentrations of the peptide were regulated by gonadal steroids in order to establish whether oxytocin has a physiological role in the prostate. Both intact and castrated adult Wistar rats were treated daily for 7 days with either testosterone propionate or the antiandrogen cyproterone acetate. Animals were then killed, and plasma hormone and prostatic oxytocin concentrations were measured. A separate group of rats was treated with the 5α‐reductase inhibitor finasteride to investigate whether testosterone or dihydrotestosterone (DHT) was involved in regulating oxytocin concentrations. In a further series of experiments, rats were treated with diethylstilbestrol (DES) or the antiestrogen tamoxifen. Treatment with testosterone significantly decreased prostatic oxytocin, whereas reduction of androgens by castration or by administration of cyproterone acetate increased prostatic peptide concentrations without altering circulating levels of the peptide. Treatment with finasteride increased plasma testosterone but decreased DHT concentrations. Prostatic oxytocin concentrations were higher in finasteride‐treated animals than in control animals with comparable testosterone levels. The data suggest that both testosterone and DHT are capable of decreasing prostatic oxytocin concentrations. Treatment with DES did not significantly alter prostatic oxytocin, but administration of tamoxifen decreased concentrations of the peptide, suggesting that low levels of estrogen may be necessary for oxytocin production. These data provide evidence that oxytocin is regulated by androgens, and we hypothesize that this regulatory mechanism may be involved in controlling prostatic growth.
Inhibin B Levels in Plasma of the Male Rat from Birth to Adulthood: Effect of Experimental Manipulation of Sertoli Cell Number
Authors: SHARPE R.M. , TURNER K.J. , McKINNELL C. , GROOME N.P. , ATANASSOVA N. , MILLAR M.R. , BUCHANAN D.L. , COOKE AND P.S.
Published: October 2023

ABSTRACT: Sertoli cells undergo important changes in their number and function at different ages in the rat and may be the primary source of circulating inhibin B. The aims of this study were 1) to establish the profile of inhibin B levels from birth to adulthood in normal rats and 2) to identify whether experimental manipulation of Sertoli cell numbers was able to alter this profile. Levels of inhibin B, measured by a specific two‐site assay, increased fivefold in normal Wistar rats between day 3 and days 10–15, plateaued, and then declined in ate puberty to reach adult levels which were ∽60% of those observed on days 10–15. The increase in inhibin B levels in the neonatal period coincided with the period of Sertoli cell multiplication as indicated by incorporation of bromodeoxyuridine. Neonatal treatment of rats with a GnRH antagonist (GnRHa) reduced Sertoli cell number and adult testis weight by 48% and significantly reduced plasma levels of inhibin B at all ages through to adulthood. Induction of neonatal hypothyroidism in Sprague‐Dawley rats by administration of propylthiouracil (PTU) up to day 25 of age increased final testis weight by 41% (indicative of increased Sertoli cell numbers) and resulted in elevation of plasma levels of inhibin B at all ages beyond 7 days of age. The degree of change in inhibin B levels in adult rats in the two experimental treatment groups was approximately proportional to the change in final testis weight. Plasma follicle‐stimulating hormone (FSH) showed changes opposite to inhibin B, with levels being lowered in PTU‐treated rats and elevated (beyond day 25) in GnRHa‐treated animals. The present results suggest that final Sertoli cell number per testis exerts an important effect on the circulating level of inhibin B (and FSH) in the rat. These findings are compared to the emerging data for the human male.
Testosterone‐Dependent Restoration of Spermatogenesis in Adult Rats Is Impaired by a 5α‐Reductase Inhibitor
Authors: O'DONNELL LIZA , PRATIS KYRIAKOS , STANTON PETER G. , ROBERTSON DAVID M. , McLACHLAN ROBERT I.
Published: October 2023

ABSTRACT: Germ cell development (spermlogenesis In particular) in the adult rat is known to be testosterone dependent. Recently we proposed a role for the 5α reduction of testosterone to dihydrotestosterone (DHT) in the short‐term restoration of round spermatid maturation when testicular testosterone levels are experimentally lowered. The current study aimed to further characterize the involvement of 5α‐reductase in the restoration of spermatogenesis by investigating the short‐ and long‐term restoration of specific germ cell populations by testosterone in the presence or absence of a 5α‐reductase inhibitor (L.685,273). Spermatogenesis in adult rats was suppressed for 8 weeks using 3‐cm testosterone and 0.4‐cm estradiol silastic implants (testosteroneestra‐diol [TE] treatment); spermatogenesis was then restored by administration of increasing doses of testosterone with or without a competitive 5α‐reductase inhibitor or with the androgen receptor antagonist flutamide. Animals were then killed after either 4 days or 6 weeks of treatment so that we could study the short‐ and long‐term restorations of spermatogenesis. Stereological analysis showed that germ cell development between late pachytene spermatocytes to round spermatids in stage VII during either short‐ or long‐term restoration was not affected by 5α‐reductase inhibition, but it was affected by flutamide. The conversion of round spermatids between stages VII and VIII was restored by testosterone treatment, but this restoration was prevented by flutamide. Both the short‐ and long‐term restorations of this midspermiogenic event were significantly decreased when 5α‐reductase was inhibited. After long‐term restoration of spermatogenesis, elongated spermatids were restored to 42% of control but were significantly suppressed to 20% of control by coadministration of the 5α‐reductase inhibitor because of a reduction in the number of round spermatids progressing between stages VII and VIII. The results demonstrate that the 5α‐reduction of testosterone is particularly important for progression through midspermiogenesis, because this phase of germ cell development is more sensitive to withdrawal of androgens. We suggest that testicular 5α‐reductase activity is important for the restoration or maintenance of low levels of sperm production in a hormonally based contraceptive setting.
Modulation of Insulin‐like Growth Factor‐1 in the Seminal Plasma of Infertile Men
Authors: COLOMBO JAMES B. , NAZ RAJESH K.
Published: October 2023

ABSTRACT: It has been suggested that insulin‐like growth factor (IGF)‐1 plays an important role in the regulation of spermatogenesis in the testes. In the present study, concentrations of total IGF‐1 were determined in the seminal plasma of fertile (n = 44), malefactor infertile (n = 34), and immunoinfertile (n = 10) men in order to investigate the role of IGF‐1 in male infertility. Levels of IGF‐1 were expressed both as nanograms per milliliter and as nanograms per milligram of protein. IGF‐1 was detected in the seminal plasma of both fertile and infertile men. IGF‐1 levels differed significantly between fertile and immunoinfertile groups (P < 0.035 to P < 0.0001), whether expressed as nanograms per milliliter or as nanograms per milligram of protein. The immunoinfertile group showed a 31.3–37.9% increase in the mean IGF‐1 concentration over the fertile group. There was no statistical difference in the mean or median levels of IGF‐1 between the fertile and male‐factor infertile groups, whether expressed as nanograms per milliliter or as nanograms per milligram of protein. However, when the male‐factor infertile subjects were divided into four subgroups based on which seminal parameter was defective, the subgroup having a low sperm count had IGF‐1 levels that were significantly different from the fertile group, the immunoinfertile subgroup, and the other malefactor infertile subgroups. The low‐sperm‐count subgroup had the lowest mean and median IGF‐1 levels of all the groups and subgroups tested. IGF‐1 levels linearly correlated (r = 0.30‐0.499) significantly (P = 0.023‐0.027) with the total sperm count in the semen, whether analyzed with all groups together or in subgroups by condition. These findings suggest that IGF‐1 has a role in fertility and that its derangement may be involved in male infertility, especially when mediated through low sperm count and immunologic factors.
Some Vasovasostomized Men Are Characterized by Low Levels of P34H, An Epididymal Sperm Protein
Authors: GUILLEMETTE CHRISTINE , THABET MICHEL , DOMPEERRE LUCE , SULLIVAN ROBERT
Published: October 2023

ABSTRACT: During epididymal transit, sperm surface proteins involved in the fertilization process can be added or modified. P34H, a human epididymal‐sperm protein, is proposed to be involved in the interactions between spermatozoa and the zona pellucida. We have previously demonstrated that P34H is present in men of proven fertility and is absent in 50% of men presenting with idiopathic infertility. Spermatozoa with a low amount of P34H exhibit a dramatic reduction in their ability to interact with zona pellucida. Even if the surgical success of vasectomy reversal is high, fertility is not always reestablished, possibly due to epididymal damage caused by vasectomy. In this study, western blot analyses were performed to determine the level of P34H present on spermatozoa of men who underwent vasectomy reversal. Spermatozoa obtained from different semen samples from a given individual had similar P34H levels; however, samples from different men were highly variable. When quantified by densitometric scanning, P34H levels from vasovasostomized men varied between 1.5% and 149% compared with that from a fertile donor who represented 100%. Eighteen of 25 vasovasostomized men had a P34H level lower than 30% of the normal value, while the remaining 7 males were in the normal range. Furthermore, the population of vasovasostomized men with P34H levels lower than 30% was significantly different from the control group of 19 fertile men. The high variation of P34H levels observed in vasovasostomized men did not correlate with the spermiogram values (P < 0.05). An important factor in determining sperm P34H level appears to be the period of time elapsed between the vasectomy and vasovasostomy. In summary, our results show that the P34H level varied from one man to another and that low levels of the epididymal sperm protein is associated with vasectomy reversal.
Kininogenase Activity of Prostate‐Derived Human Glandular Kallikrein (hK2) Purified From Seminal Fluid
Authors: CHARLESWORTH M. CRISTINE , YOUNG CHARLES Y. E. , MILLER VIRGINIA M. , TINDALL DONALD J.
Published: October 2023

ABSTRACT: Prostate‐specific human glandular kallikrein (hK2) is an active enzyme in human seminal fluid. It is one of three serine proteases in the human kallikrein gene family, which includes hK1 (tissue kallikrein) and hK3 (prostate‐specific antigen [PSA]). In order to examine kininogenase activity (i.e., production of kinin by these enzymes), we tested for bradykinin and/or Lys‐bradykinin release upon incubation of hK2 and for other kallikreins with high‐molecular weight kininogen (HMWK), which contains the nonapeptide bradykinin. Kinins are important regulatory peptides (especially for vascular permeability), and they may have a role in enhancing sperm motility. High‐molecular weight kininogen is the substrate for plasma kallikrein (PK— a potent kinin‐generating enzyme circulating in blood, not of the same gene family) and for hK1. Glandular kallikrein and protein‐C inhibitor (PCI)‐hK2 complex, a serpin protease inhibitor that binds hK2, were purified to homogeneity by affinity and size‐exclusion chromatography. About one‐half of the hK2 is found in complex with PCI. The kallikrein enzymes were incubated with HMWK, and the resulting cleavage products were analyzed for kinin activity using enzyme immunoassay, high‐performance liquid chromatography and mass spectrometry, and in vitro bioassay. Our results show that hK2 cleaves HMWK to produce bradykinin, not Lys‐bradykinin (like hK1), and the resultant heavy (56‐kDa) and light (42‐kDa) chains of HMWK show similar electrophoretic mobility to those cleaved by PK. Prostate‐specific antigen (hK3) had no kinin‐generating activity. We also identified three other internal cleavage sites for hK2 in HMWK (Arg427, Arg427, and Arg457) that yielded two peptides, one of which is identical to a PK‐cleaved peptide. Glandular kallikrein is about 500‐fold less active than is PK or tissue kallikrein, but it may play a physiologically important role in bradykinin release in seminal fluid.
Reproductive Tract Secretions and Bull Spermatozoa Contain Different Clusterin Isoforms That Cluster Cells and Inhibit Complement‐induced Cytolysis
Authors: IBRAHIM NASRELDIN M. , TROEDSSON MATS H. T. , FOSTER DOUGLAS N. , LOSETH KATHRYN J. , FARRIS JAMES A. , BLASCHUK OREST , CRABO BO G.
Published: October 2023

ABSTRACT: Clusterin from bull rete testis fluid (RTF), cauda epididymal fluid (CEF), and octyl‐β‐D‐glucopyranoside extract of Cauda epididymal sperm (CES) was identified and characterized using monoclonal and polyclonal antibodies (Abs) developed against ram clusterin and a β‐subunit‐specific oligopeptide of porcine clusterin. One‐dimensional sodium dodecyl sulphate‐polyacrylamide gel electrophoresis and western blotting showed that bovine RTF clusterin had dimeric and monomelic molecular weights (Mrs) of ≅94 kDa and of 42 and 43 kDa, respectively. Clusterin in CEF and CES had similar dimeric Mrs (74 kDa). Reduced CEF clusterin appeared as three monomers (Mr = 40, 39, and 38 kDa), whereas reduced CES clusterin appeared only at Mr 40 kDa. Enzymatic deglycosylation resulted in similar Mrs of clusterin from RTF, CEF, and CES. The Mr of RTF clusterin decreased from 94 kDa to 51 kDa, indicating a carbohydrate content of 45%. After deglycosylation, the Mr of the CEF clusterin decreased from 74 kDa to two distinct bands at 51 and 50 kDa (with carbohydrate contents of 31 and 32%, respectively), suggesting that two isoforms of the heterodimeric protein are present because of the two isoforms of the a‐subunit. Under nonreduced conditions, a β‐subunit‐specific Ab reacted with Mr of 36–38 kDa, indicating the existence of free clusterin α‐subunits in CES. RTF, CEF, and CES extracts all caused mouse fibroblastic L‐cell aggregation. CEF cell aggregation was inhibited by Hyb‐17 Ab but not by other Abs. Both RTF and CEF caused a dose‐dependent inhibition of complement‐induced cytolysis, although RTF clusterin was more potent than CEF clusterin. We conclude that several isoforms of clusterin occur in the bull reproductive tract and that the variation in carbohydrate content among these isoforms may affect the biological or functional activity of the protein.
A Pilot Study Demonstrating Clinical Benefit From Intralesional Interferon Alpha 2B in the Treatment of Peyronie's Disease
Authors: AHUJA SUNIL , BIVALACQUA TRINITY J. , CASE JOHN , VINCENT MARK , SJXKA SURESH C. , HELLSTROM WAYNE J. G.
Published: October 2023

ABSTRACT: Intralesional therapy is a less invasive method for the treatment of Peyronie's disease. The objective of this study was to evaluate intralesional injections of interferon alpha 2B (IFN‐α‐2B) as an effective alternative to the surgical treatment of Peyronie's disease. Twenty‐one patients with Peyronie's disease were evaluated by use of penile duplex Doppler ultrasonography for cavernosal blood flows, degree of penile curvature, and plaque size. A questionnaire was given to all patients to assess sexual function. Each patient then received biweekly intralesional injections of 1 × 106 units of IFN‐α‐2B in 10 ml of normal saline over a period of 6 months. There was no placebo control group in this study. At the conclusion of the study, penile duplex Doppler imaging was repeated. A questionnaire was completed by all patients to assess changes in sexufunction after treatment. Twenty patients completed the study, with all men reporting subjective softening of their plaques. Nine of 10 patients initially reporting penile pain with erection (90%) had resolution of their phallalgia while on study protocol. Thirteen patients (65%) had significant improvement in curvature, ranging from 20 to 90%. Seventeen patients (85%) demonstrated an objective 10 to 80% decrease in plaque size. Biweekly intralesional injections of Peyronie's plaques with IFN‐α‐2B resulted in a significant improvement in penile curvature, diminished pain, and reduced plaque size, and resulted in a subjective improvement in sexual function.
Prostatic Growth Rate Determined from MRI Data: Age‐Related Longitudinal Changes
Authors: WILLIAMS ADRIANNE M. , SIMON INPAKALA , LANDIS PATRICIA K. , MOSER CHERYL , CHRISTENS‐BARRY WILLIAM , CARTER H. BALLENTINE , METTER E. JEFFREY , PARTIN ALAN W.
Published: October 2023

ABSTRACT: Men with prostatic enlargement are at highest risk of developing symptomatic lower urinary tract symptoms (LUTS) and related outcomes, such as acute urinary retention. The study of prostatic growth rate can identify the age range at which prostate growth peaks. Evaluation of the natural course of prostate growth requires repeated intraindividual volume measurements at time intervals sufficient to document growth. Our objective was to examine age‐stratified prostate growth rates from men taking part in a longitudinal study of aging using magnetic resonance imaging (MRI) of the prostate. Sixty‐four men (ages 30–71 years) enrolled in the Baltimore Longitudinal Study of Aging (BLSA) who had T2 pelvic MRIs taken approximately every 2 years were studied. Men were age stratified into four groups: <45, 45–55, 56–65, and <65 years old. Whole prostate and central gland (anatomically referred to as the transition zone) volumes were determined from the MRI images by a semi‐automated image analysis program. Peripheral gland volumes were calculated as the difference between whole prostate and central gland volumes. Growth rates (cc per year) were calculated as change in volume divided by the time interval. On the basis of measurements from the T2 images (n = 128), we observed a linear trend between prostate volume and age. The overall prostate growth rate was 2.36 ± 3.52 cc per year. Age‐stratified growth rates revealed that prostate growth increased with age, peaked at 4.15 ± 4.98 cc/year for the 56–65‐year‐old age group and then declined rapidly for the older‐aged men. The central gland growth rates followed a trend similar to total prostate volume. These data suggest that there is an age‐related increase in prostate growth rate that peaks in men ages 56–65 and then declines. Identification of this trend in prostate growth may aid physicians in targeting men for early diagnosis of LUTS and for possible early intervention. Future studies with a larger sample size are necessary to substantiate these findings.
Reproductive Aging in the Brown Norway Rat Is Characterized by Accelerated Germ Cell Apoptosis and Is Not Altered by Luteinizing Hormone Replacement
Authors: WANG CHRISTINA , HIKIM AMIYA P. SINHA , LUE YAN‐HE , LEUNG ANDREW , BARAVARIAN SIMA , SWERDLOFF RONALD S.
Published: October 2023

ABSTRACT: Reproductive aging in the male Brown Norway (BN) rat is characterized by decreased Leydig cell steroidogenesis associated with seminiferous tubule dysfunction. This could be a result of a combination of a primary testicular defect and a secondary hypothalamic pituitary dysfunction. In the present study, we determined in the BN rat whether germ cell loss occurred via apoptosis. We then defined the age of onset of Leydig cell dysfunction and germ cell loss and examined whether chronic luteinizing hormone (LH) replacement would delay or prevent reproductive aging. Plasma hormone levels, testicular sperm concentrations, and germ cell apoptosis were studied in 6, 9, 12, 15, 18, and 21‐month‐old BN rats. Beginning at 15 months, testicular weight, sperm concentration, total sperm counts, plasma testosterone, LH, and inhibin decreased, whereas the proportion of regressed testes and plasma follicle‐stimulating hormone (FSH) levels increased with aging. Accelerated germ cell apoptosis involving spermatogonia, preleptotene and pachytene spermatocytes, and spermatids was evident in some tubules of the relatively normal testes from 21‐month‐old rats. In the regressed testes, complete cessation of spermatogenesis occurred. The apoptotic index was higher in the testes of old (21‐month‐old) rats in particular at stages XII‐XIV when compared with younger animals. Chronic LH replacement (0.5 μg IP twice per day) administered to 15‐month‐old BN rats for 6 months did not alter plasma hormone levels, testes weight, sperm concentration or content, or the germ cell apoptotic index. In the control group, 3 out of 10 testes were regressed, whereas in the LH‐replaced group, only 1 out of 12 testes was regressed. We show in this study that early reproductive aging in the BN rat began at around 15 months. Germ cell loss associated with aging occurs via apoptosis. Replacement therapy with LH for 6 months does not decrease or delay the testicular dysfunction associated with aging. It is unlikely that hypothalamic‐pituitary dysregulation is the major cause of testicular aging.
Production of Endothelin by Canine Prostatic Epithelial Cells and Its Stimulatory Effects on Their Growth
Authors: ISHIZAKA KAZUHIRO , AZUMA HIROSHI , MATSUBARA OSAMU , KTTAHARA SATOSHI , OSHIMA HIROYUKI
Published: October 2023

ABSTRACT: The current study has been designed to explore expressions of endothelin (ET) receptors and ETS in the canine prostate and the effect of ETs on canine prostatic epithelial cells. ET receptors were characterized by biotinylated ET‐1 binding in frozen sections of the prostate. Canine prostatic epithelial cells in primary culture were used for demonstration of ET‐1 expression by reversephase HPLC coupled with radloimmunoassay and Northern blotting and were subjected to growth assay. Biotinylated ET‐1 binding was localized in the epithelial component, and the binding was also blocked with an antagonist specific for ETB subtype receptors. ET‐1 and ET‐3 stimulated canine prostatic epithelial cell growth in vitro. The effect was also reversed in the presence of an antagonist specific for ETB subtype receptors. Elution profile of epithelial cell culture medium revealed two peaks, corresponding to ET‐1 and big ET‐1. Epithelial cells in culture expressed pre‐pro‐ET‐1 mRNA. Canine prostatic epithelial cells expressed ETB receptors and ET‐1. It appears most likely that the expressed ET‐1 acts as an autocrine/paracrine proliferative factor on canine prostatic epithelial cells via ETB receptors.
Spermatic Granulomata Are Experimentally Induced in Epididymides of Mice Receiving High‐Dose Testosterone Implants. I. A Light–Microscopical Study
Authors: ITOH MASAHIRO , MIYAMOTO KENSAKU , SATRIOTOMO IRAWAN , TAKEUCHI YOSHIKI
Published: October 2023

ABSTRACT: It is known that a spermatic granuloma is induced by the inflammatory reaction following leakage of spermatozoa outside the germ cell ducts and is the main clinical complication of vasectomy. In the present study, we found that spermatic granulomata were experimentally induced in the epididymides of mice treated with high‐dose testosterone. Testosterone powder (0.02,0.2, or 2 mg per gram body weight) was implanted into ICR male mice, which were then killed from 7 to 63 days after the treatment for histological examination at the light–microscopic level. The results showed that the testis exhibited little or no degenerative change; however, the epididymides were frequently affected by spermatic granulomata after day 35 in mice implanted with high‐dose testosterone (2 but not 0.2 or 0.02 mg per gram body weight). Observation of the early histological changes revealed that the ductal epithelium of the epididymides became vacuolated around day 25. Thereafter, the basement membrane of the epididymal ducts was ruptured after day 30, followed by leakage of spermatozoa into the adjacent interstitial tissue. The extravasated spermatozoa were then surrounded by macrophages (= epithelioid cells) and lymphocytes, resulting in the formation of a spermatic granuloma. In contrast, other mice treated with the same dose of deoxycorticosterone or estradiol did not show the induction of spermatic granulomata. Therefore, this study demonstrated that a spermatic granuloma is specifically formed in the epididymis by testosterone and that the lesion is started by vacuolation of the epididymal duct epithelium.
Evaluation of Oxidative DNA Damage in Human Sperm and Its Association with Male Infertility
Authors: SHEN HAN‐MING , CHIA SIN‐ENG , ONG CHOON‐NAM
Published: October 2023

ABSTRACT: Recently, there is increasing evidence suggesting that oxidative sperm DNA damage is closely associated with impaired sperm function and male infertility. 8‐Hydroxydeoxyguanosine (8‐OHdG) is considered to be a precise and sensitive biomarker of oxidative DNA damage. The present study was thus designed to evaluate the extent of oxidative DNA damage in sperm and its association with male infertility by assaying the 8‐OHdG levels in human sperm samples. A total of 114 subjects (60 infertile patients and 54 age‐matched healthy workers) participated in this study. The level of 8‐OHdG in sperm DNA was determined by high‐performance liquid chromatography with electrochemical detection, and the conventional seminal parameters were also measured according to World Health Organization guidelines. It was found that the level of sperm 8‐OHdG in infertile patients was significantly higher than that in healthy subjects (10.03 vs. 4.79 8‐OHdG/105 dG; geometric mean, P < 0.001). The correlation between sperm 8‐OHdG levels and conventional seminal parameters were also analyzed. There is a significant positive correlation between 8‐OHdG and sperm head defects (r = 0.38, P < 0.001), whereas significant inverse correlations were noted for 8‐OHdG with sperm density (r = −0.42, P < 0.001), total sperm number (r = −0.42, P < 0.001), sperm motility (r = −0.24, P < 0.01), and normal sperm morphology (r = −0.39, P < 0.001). Data from this study thus indicate that oxidative damage to sperm DNA may be important in the etiology of male infertility and that the assay of sperm 8‐OHdG may have potential diagnostic value in the evaluation of sperm function and male fertility.
Relationship Between Rapid Eye Movement Sleep and Testosterone Secretion in Normal Men
Authors: LUBOSHITZKY RAFAEL , HERER PAULA , LEVI MICHAL , SHEN‐ORR ZILA , LAVIE PERETZ
Published: October 2023

ABSTRACT: The relation between the pituitary‐gonadal hormones' rhythm and sleep physiology in men is not fully elucidated. To examine whether the reproductive hormones are correlated with sleep architecture, we determined the nocturnal serum levels of testosterone, luteinizing hormone (LH), and follicle‐stimulating hormone (FSH) in six healthy young men. Serum hormone levels were obtained every 15 minutes from 1900 to 0700 hours with simultaneous polysomnography sleep recordings. Hourly testosterone levels were lowest when subjects were awake (1900–2200 hours) than during sleep (2300‐0700 hours). Testosterone nocturnal rise antedated the first REM by about 90 minutes. The rise in testosterone levels was slower when REM latency was longer. Mean nocturnal testosterone levels did not correlate with the number of rapid eye movment (REM) episodes. Also, pre‐non‐REM (NREM) testosterone levels were higher as compared with the pre‐REM periods and lower during the first NREM period as compared with other nocturnal NREM periods. Serum LH levels disclosed a nocturnal rise that proceeded a similar rise in testosterone by about an hour. We conclude that in young adult men, testosterone levels begin to rise on falling asleep, peak at about the time of first REM, and remain at the same levels until awakening.
Round Spermatids Show Normal Testis‐Specific Hit but Reduced cAMP‐Responsive Element Modulator and Transition Protein 1 Expression in Men With Round‐Spermatid Maturation Arrest
Authors: STEGER KLAUS , KLONISCH THOMAS , GAVENIS KARSTEN , BEHR RÜDIGER , SCHALLER VOLKER , DRABENT BIRGIT , DOENECKE DETLEF , NIESCHLAG EBERHARD , BERGMANN MARTIN , WEINBAUER GERHARD F.
Published: October 2023

ABSTRACT: During spermiogenesis, histones are replaced by transition proteins, which in turn are replaced by protamines. The TNP1 gene‐encoding TP1 (transition protein 1) protein contains a cAMP‐responsive element (CRE) that serves as binding site for the CRE modulator (CREM). To gain further insight into the complex regulation of nucleoprotein exchanges in haploid spermatids and its potential role for spermatogenic impairment, we studied the gene expression of testis‐specific histone H1t, CREM, and TNP1 in testicular biopsies from men with normal spermatogenesis (n = 20) and with round spermatid maturation arrest (n = 16). During normal spermatogenesis, H1t messenger RNA (mRNA) was present in 86.2% ± 8.7% of pachytene spermatocytes (stages III‐V), whereas Hit protein was synthesized in 83.5% ± 13.0% of pachytene spermatocytes (stages III‐V) and persisted in 95.2% ± 3.1% of spermatids (steps 1–5). CREM mRNA was detectable in 74.2% ± 9.4% of pachytene spermatocytes (stages IV‐V) and in 78.7% ± 10.0% of spermatids (steps 1–3). CREM protein was synthesized in 81.2% ± 14.2% of spermatids (steps 1–3). TNP1 mRNA was present in 80.0% ± 13.5% of spermatids (steps 2–4), whereas TP1 protein was synthesized in 89.7% ± 5.3% of spermatids (steps 3–4). In men with round spermatid maturation arrest, spermatids only develop to step 3 of differentiation. These spermatids were devoid of both CREM and TP1 but did contain H1t. These results indicate that TP1 is likely to be an important parameter in the histone‐to‐protamine exchange and in the initiation of spermatid elongation. CREM is involved in the regulation of TNP1 gene expression and consequently plays a vital role in the correct differentiation step from round spermatids to mature spermatozoa.
Secular Sperm Trends in Stallions Between 1981 and 1996
Authors: MULTIGNER LUC , MAGISTRINI MICHÈLE , DUCOT BÉATRICE , SPIRA ALFRED
Published: October 2023

ABSTRACT: Several reports have suggested that human semen quality has declined throughout the world over the last few decades. Chemicals in the environment acting as endocrine disrupters have been implicated as a possible cause. If this is indeed the case, then similar effects may be observed in animals. We analyzed 1489 ejaculates collected from 390 Breton draught stallions between 1981 and 1996. Semen was collected from all the stallions at a single center, according to standardized semen collection protocols and laboratory methods. Semen volume decreased slightly but significantly and there was an increase in sperm concentration over the study period. However, total sperm production was unchanged. Seminal fluid volume is controlled by accessory sex glands, which are regulated by androgens. Chemicals with antiandrogenic properties have been detected in the environment. By affecting the development or function of accessory sex glands, these chemicals may be at least partly responsible for the observed decrease in semen volume.
Talk It Up! Oral Communication for the Real World
Authors: Roemer Ann E.
Published: October 2023

Joann Rishel Kozyrev. Boston: Houghton Mifflin, 1998.
About Language: Tasks for Teachers of English
Authors: Bartels Nat
Published: October 2023

Scott Thornbury. Cambridge: Cambridge University Press, 1997
The impact of IFRS 9 on the cyclicality of loan loss provisions
Authors: Hansen Smilla , Charifzadeh Michel , Herberger Tim A.
Published: October 2023

Through their procyclical behavior, loan loss provisions have been determined as one of the factors that contribute to financial instability during a crisis. IFRS 9 was introduced in 2018 with an expected credit loss model replacing the incurred loss model of IAS 39 to mitigate the effect in the future. Our study aims to analyze loan loss provisions of major banks in the Eurozone to determine for the first time if the implementation of IFRS 9, as intended by regulators, has a dampening effect on procyclicality, especially during the stressed situation under COVID‐19. We analyze 51 banks from 12 countries of the European Monetary Union using 2856 firm‐year observations. While no robust evidence of less procyclicality can be found after the implementation of IFRS 9 until the pandemic, we find evidence that loan loss provisions moved countercyclical during 2020, indicating an alleviating effect at the beginning of the exogenous shock.
Diagnostic certainty during in‐person and telehealth autism evaluations
Authors: Ludwig Natasha N. , Holingue Calliope , Hong Ji Su , Kalb Luther G. , Pfeiffer Danika , Reetzke Rachel , Menon Deepa , Landa Rebecca
Published: October 2023

Background

Many diagnostic evaluations abruptly shifted to telehealth during the COVID‐19 pandemic; however, little is known about the impact on diagnosis patterns for children evaluated for autism spectrum disorder (ASD). The purpose of this clinical research study was to examine (1) the frequency of diagnoses evaluated beyond ASD; (2) the frequency of diagnoses made, including ASD; and (3) clinician diagnostic certainty for all diagnoses evaluated for children who received an evaluation due to primary concerns about ASD via telehealth during the pandemic compared to those evaluated in person before the pandemic at an ASD specialty clinic.

Methods

The sample included 2192 children, 1–17 years (M = 6.5 years; SD = 3.9), evaluated by a physician/psychologist at an ASD specialty center. A total of 649 children were evaluated in‐person September 1, 2019–March 13, 2020 (pre‐pandemic) and 1543 were evaluated via telehealth March 14, 2020–July 26, 2021 (during pandemic). Upon completion of each evaluation, clinicians provided a final diagnostic determination (i.e., “Yes,” “No,” “Possible,” or “Not Assessed”) for the following DSM‐5 conditions: ASD, attention‐deficit/hyperactivity disorder (ADHD), intellectual developmental disorder (IDD), anxiety (ANX), depression (DEP), and behavioral disorder (BD). “Possible” indicated lower certainty and the diagnosis was not provided. “Not Assessed” indicated the disorder was not evaluated.

Results

Diagnostic certainty for ASD and ADHD was lower and clinicians evaluated for and made diagnoses of IDD less often during evaluations that occurred via telehealth during the pandemic versus in person before the pandemic. DEP and BD were diagnosed more frequently, diagnostic certainty of DEP was lower, and no differences in the frequency of ANX diagnoses emerged during evaluations conducted via telehealth during the pandemic compared to those conducted in person before the pandemic.

Conclusions

Differences emerged in the frequency of diagnoses evaluated and made and diagnostic certainty for evaluations conducted via telehealth during the pandemic compared to in person before the pandemic, which likely impacted patients and reflect real‐word challenges. Future work should examine whether these patterns are generalizable and the mechanisms that contribute to these differences.
Investigating the prognostic role of lncRNAs associated with disulfidptosis‐related genes in clear cell renal cell carcinoma
Authors: Sun Zhou , Wang Jie , Fan Zheqi , Yang Yongjin , Meng Xiangdi , Ma Zhaosen , Niu Jiqiang , Guo Rui , Tran Lisa Jia , Zhang Jing , Jiang Tianxiao , Liu Yunfei , Yang Qiwei , Ma Baoluo
Published: October 2023

Introduction

Renal cell carcinoma (RCC) is a grave malignancy that poses a significant global health burden with over 400,000 new cases annually. Disulfidptosis, a newly discovered programmed cell death process, is linked to the actin cytoskeleton, which plays a vital role in maintaining cell shape and survival. The role of disulfidptosis is poorly depicted in the clear cell histologic variant of RCC (ccRCC).

Methods

Three sets of ccRCC cohorts, ICGC_RECA‐EU (n = 91), GSE76207 (n = 32) and TCGA‐KIRC (n = 607), were included in our study, the batch effect of which was removed using the “combat” function. Correlation was calculated using the “rcorr” function of the “Hmisc” package for Pearson analysis, which was visualized using the “pheatmap” package. Principal component analysis was performed by the “vegan” package, visualized using the “scatterplot3d” package. Long non‐coding RNAs (lncRNAs) associated with disulfidptosis were screened out using least absolute shrinkage and selection operator (LASSO) and COX analysis. Tumor mutation, immune landscaping and immunotherapy prediction were performed for further characterization of two risk groups.

Results

A total of 1822 disulfidptosis‐related lncRNAs was selected, among which 308 lncRNAs were found to be significantly associated with the clinical outcome of ccRCC patients. We retained 11 disulfidptosis‐related lncRNAs, namely, AP000439.3, RP11‐417E7.1, RP11‐119D9.1, LINC01510, SNHG3, AC156455.1, RP11‐291B21.2, EMX2OS, AC093850.2, HAGLR and RP11‐389C8.2, through LASSO and COX analysis for prognosis model construction, which displayed satisfactory accuracy (area under the curve, AUC, values all above 0.6 in multiple cohorts) in stratification of ccRCC prognosis. A nomogram model was constructed by integrating clinical factors with risk score, which further enhanced the prediction efficacy (AUC values all above 0.7 in multiple cohorts). We found that patients of male gender, higher clinical stages and advanced pathological T stage were inclined to have higher risk score values. Dactinomycin_1911, Vinblastine_1004, Daporinad_1248 and Vinorelbine_2048 were identified as promising candidate drugs for treating ccRCC patients of higher risk score value. Moreover, patients of higher risk value were prone to be resistant to immunotherapy.

Conclusion

We developed a prognosis predicting model based on 11 selected disulfidptosis‐related lncRNAs, the efficacy of which was verified in different cohorts. Furthermore, we delineated an intricate portrait of tumor mutation, immune topography and pharmacosensitivity evaluations within disparate risk stratifications.
A non‐canonical role of endothelin converting enzyme 1 (ECE1) in promoting lung cancer development via directly targeting protein kinase B (AKT)
Authors: Chen Li , Lu Yikai , Zhao Mengmeng , Xu Junfang , Wang Yan , Xu Qinghua , Cao Yajuan , Liu Haipeng
Published: October 2023

Background

Lung cancer is the second most common malignancy in the world, and lung adenocarcinoma (LUAD) in particular is the leading cause of cancer death worldwide. Endothelin converting enzyme 1 (ECE1) is a membrane‐bound metalloprotease involved in endothelin‐1 (ET‐1) processing and regulates vasoconstriction. However, very few studies have reported the involvement of ECE1 in regulating tumor cell proliferation, and the mechanism remains poorly understood. Therefore, we aimed to determine the role of ECE1 in lung cancer development.

Methods

The Cancer Genome Atlas database and Kaplan–Meier plotter were used to assess the association between ECE1 and lung cancer. The expression of ECE1 was detected using immunohistochemistry staining and western blotting. A variety of in vitro assays were performed to evaluate the effects of ECE1 on the colony formation, proliferation, migration and invasion using ECE1 knockdown lung cancer cells. The gene expression profiles regulated by ECE1 were investigated by RNA sequencing. An immunoprecipitation assay and immunofluorescence assay were used to evaluate the mechanism underlying the regulatory effect of ECE1 on protein kinase B (AKT). The effect of ECE1 on tumor development was assessed by xenografted lung cancer cells in either C57BL/6 mice or nude mice.

Results

ECE1 was upregulated in LUAD and correlated with the poor prognosis of patients with LUAD. Functional studies showed that knockdown of ECE1 retarded the progression of tumors formed by lung cancer cells at least partly by inhibiting tumor cell proliferation. Moreover, ECE1 accelerated tumor cell proliferation through promoting AKT activation dispensable of its canonical target ET‐1. Mechanically, ECE1 interacted with the pleckstrin homology (PH) domain of AKT and facilitated its translocation to the plasma membrane for activation. Furthermore, the inhibition of AKT activity counteracted the lung cancer cell growth inhibition observed both in vitro and in xenografts caused by ECE1 suppression.

Conclusions

The present study reveals a non‐canonical function of ECE1 in regulating AKT activation and cell proliferation, which provides the basis for the development of a novel strategy for the intervention of cancer including LUAD by abrogating ECE1‐AKT signaling.
Hardware Implementation of Ultra‐Fast Obstacle Avoidance Based on a Single Photonic Spiking Neuron
Authors: Gao Shuang , Xiang Shuiying , Song Ziwei , Han Yanan , Zhang Yuna , Guo Xingxing , Zhang Yahui , Hao Yue
Published: October 2023

Visual obstacle avoidance is widely applied to unmanned aerial vehicles (UAVs) and mobile robot fields. A simple system architecture, low power consumption, optimized processing, and real‐time performance are extremely needed due to the limited payload of some mini UAVs. To address these issues, an obstacle avoidance system harnessing the rate encoding features of a photonic spiking neuron based on a Fabry–Pérot (FP) laser is proposed, which simulates the monocular vision. Here, time to collision is used to describe the distance of obstacles. The experimental results show that the FP laser excites ultra‐fast spike responses in real time for the following cases, facilitating the generation of control commands by motor neurons to realize accurate decision‐making. Four cases of mobile obstacle avoidance scenarios, including “Constant velocity approach”, “Approach and retreat”, “The motion state involving stays”, and “Approach with different velocities”, and obstacle avoidance problems with multiple stationary obstacles appearing simultaneously are experimentally analyzed. The system exhibits a spike response rate of up to 5 GHz. This work proves the feasibility of applying the ultra‐fast photonic obstacle avoidance system to UAVs and other fields in the future and highlights the potential of photonic neuromorphic processor platforms.
Asymptotic expected T$T$‐functionals of random polytopes with applications to Lp$L_p$ surface areas
Authors: Hoehner Steven , Li Ben , Roysdon Michael , Thäle Christoph
Published: October 2023

An asymptotic formula is proved for the expected ‐functional of the convex hull of independent and identically distributed random points sampled from the Euclidean unit sphere in according to an arbitrary positive continuous density. As an application, the approximation of the sphere by random polytopes in terms of surface area differences is discussed.
A prospect theory extension of data envelopment analysis model for wave‐wind energy site selection in New Zealand
Authors: Wang Chia‐Nan , Nguyen Hoang‐Kha , Nhieu Nhat‐Luong , Hsu Hsien‐Pin
Published: October 2023

Renewable energy sources have been utilized by countries worldwide, but offshore energy exploitation projects remain highly promising for both the world and New Zealand specifically. The selection of equipment installation locations can be challenging and requires significant investment, prompting the need for optimization in offshore energy exploitation. Wind and wave location (WWL) integrated sites offer a highly potential solution for reducing installation costs and enhancing efficiency in renewable energy exploitation. However, the decision‐making process for selecting equipment locations is crucial and directly affects the outcome. This study aims to evaluate and consider sustainable and effective equipment installation sites based on both quantitative indicators and behavioral psychology of decision making. To achieve this goal, the study utilizes the prospect theory Data Envelopment Analysis (PT‐DEA) model, which builds on PT to analyze and evaluate the effectiveness of offshore installation site selection with consideration for human psychology. By combining the results of quantitative indicators and decision‐making behavior, the study identifies sustainable and effective offshore installation sites, recommending appropriate equipment installation locations WWL. The study is also compared and referenced with relevant plans, projects, and development policies in New Zealand for confirmation.
White paper touts gaming as tool to combat youth MH crisis
Authors: Canady Valerie A.
Published: October 2023

In an effort to help the public better understand the mental health implications of gaming, an international foundation and a public health nonprofit this month released a white paper, calling it a first‐of‐its‐kind report, that analyzes the potential role of gaming as an innovative solution to the increasing mental health crisis in this country.
BD research hub to offer new treatments, clinical options
Authors: Canady Valerie A.
Published: October 2023

A national research grant totaling more than $6 million to fund this country's first bipolar disorder (BD) patient and research hub will address the limited treatment options for some of the millions of Americans living with the condition and will make it easier for patients to find new treatments and clinical trials, research officials said.