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The hamster egg penetration test may decrease intracytoplasmic sperm injection utilization while maintaining high conventional fertilization rates

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Asian Journal of Andrology 2021年第1期23卷 11-15页

作者： Yetunde Ibrahim Brett Einerson Douglas T Carrell benjamin r emery Erica Johnstone Division of reproductive Endocrinology and Infertility Department of Obstetrics and GynecologyUniversity of UtahSchool of MedicineSalt Lake CityUT 84132USA Division of Maternal-Fetal Medicine Department of Obstetrics and GynecologyUniversity of UtahSchool of MedicineSalt Lake CityUT 84132USA Division of Urology Department of SurgeryUniversity of UtahSchool of MedicineSalt Lake CityUT 84132USA Department of Human Genetics University of UtahSchool of MedicineSalt Lake CityUT 84132USA

This was a cohort study of in vitro fertilization(IVF)subjects at the University of Utah,Salt Lake City(UT,USA)utilizing partner *** where both the hamster egg penetration test(HEPT)and semen analysis were performed within 2 years prior to IVF cycles were stratified into four groups based on a normal or an abnormal HEPT and *** mean conventional and intracytoplasmic sperm injection(ICSI)fertilization rates were calculated in each *** performed a univariate analysis on the primary outcome comparing clinically interesting *** performed a cost-effectiveness analysis of a policy of HEPT versus universal ICSI in couples with an abnormal *** patients with a normal HEPT,there was no difference in the mean conventional fertilization rates between those with a normal and an abnormal *** was no difference in the mean conventional fertilization rates between subjects with a normal morphology without a hamster test and those with a normal HEPT without a morphology *** 1000 simulated cycles with an abnormal morphology,a policy of HEPT was cost saving compared to universal ICSI,yet produced similar fertilization *** HEPT is similar to the World Health Organization edition 5(WHO-5)morphology in predicting successful conventional fertilization while allowing decreased utilization of ICSI.A policy of HEPT for males with abnormal morphology saves cost in selecting couples for a fertilization method.

关键词： conventional fertilization hamster egg penetration test intracytoplasmic sperm injection semen analysis sperm penetration assay

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The effect of epigenetic sperm abnormalities on early embryogenesis

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Asian Journal of Andrology 2006年第2期8卷 131-142页

作者： benjamin r. emery Douglas T.Carrel Andrology & IVF Laboratories Department of Physiology Department of Obstetrics and Gynecology School of Medicine University of UtahSalt Lake CityUtah 84108USA

Sperm are a highly specialized cell type derived to deliver the paternal haploid genome to the oocyte. The epigenetic, or gene regulatory, properties and mechanisms of the sperm assist in preparation of the paternal genome to contribute to embryogenesis and the genome of the zygote. Many recent studies have addressed the issue of altered epigenetic processes in the sperm. This review evaluates the current understanding of DNA damage, chromosome aneuploidy, reduced telomere length, malformations of the centrosome, genomic imprinting errors, altered mrNA profiles, and abnormal nuclear packaging in the sperm prior to fertilization and the observed effects on embryogenesis. Attention has also been given to understanding the underlying etiology of sperm with altered epigenetic mechanisms in humans. （Asian J Androl 2006 Mar; 8： 131-142）

关键词： embryogenesis DNA damage imprinting aneuploidy telomere centrosome nuclear packaging male infertility

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Proton-pump inhibitor use does not affect semen luality in subfertile men

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Asian Journal of Andrology 2018年第3期20卷 290-293页

作者： Sorena Keihani James r Craig Chong Zhang Angela P Presson Jeremy B Myers William O Brant Kenneth I Aston benjamin r emery Timothy G Jenkins Douglas T Carrell James M Hotaling Division of Urology Department of Surgery University of Utah Salt Lake City Utah 84132 USA Division of Epidemiology Department of Internal Medicine University of Utah Salt Lake City Utah 84132 USA Andrology and IVF Laboratory Department of Surgery (Urology) University of Utah Salt Lake City Utah 84108 USA

Proton-pump inhibitors （PPIs） are among the most widely used drugs worldwide. PPI use has recently been linked to adverse changes in semen quality in healthy men; however, the effects of PPI use on semen parameters remain largely unknown specifically in cases with male factor infertility. We examined whether PPI use was associated with detrimental effects on semen parameters in a large population of subfertile men. We retrospectively reviewed data from 12 257 subfertile men who had visited our fertility clinic from 2003 to 2013. Patients who reported using any PPIs for 〉3 months before semen sample collection were included; 7698 subfertile men taking no medication served as controls. Data were gathered on patient age, medication use, and conventional semen parameters; patients taking any known spermatotoxic medication were excluded. Linear mixed-effect regression models were used to test the effect of PPI use on semen parameters adjusting for age. A total of 248 patients （258 samples） used PPIs for at least 3 months before semen collection. In regression models, PPI use （either as the only medication or when used in combination with other nonspermatotoxic medications） was not associated with statistically significant changes in semen parameters. To our knowledge, this is the largest study to compare PPI use with semen parameters in subfertile men. Using PPIs was not associated with detrimental effects on semen quality in this retrospective study.

关键词： infertility proton-pump inhibitors semen analysis sperm quality spermatozoa

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Novel UBE2B-associated polymorphisms in an azoospermic / oligozoospermic population

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Asian Journal of Andrology 2008年第3期10卷 461-466页

作者： Ivan Huang benjamin r. emery Greg L. Christensen Jeanine Griffin C. Matthew Peterson Douglas T. Carrell Division of reproductive Endocrinology University of Utah Health Sciences Salt LakeCity Utah 84106 USA Andrology and IVF Laboratories University of Utah Health Sciences Salt LakeCity Utah 84106 USA

Aim： To assess whether abnormalities exist in the UBE2B gene in a population of infertile human males, and to establish biologic plausibility of any discovered mutations. Methods： We carried out polymerase chain reaction （PCr） amplification and sequence analysis of the 5＇-untranslated region and six exons of the UBE2B gene, including flanking intronic regions, in a group of fertile and infertile men. Following the identification of a putative promoter region that contained single or dual triplet deletions within a 10-CGG repeat island, we evaluated the binding affinity of these identified polymorphisms as compared to the wild-type sequence to transcription factor SP1 using a DNA-protein gel shift assay. results： There was a novel exonic single nucleotide polymorphism （SNP） noted in exon 4 in 5% of infertile men. In silico 3D modeling of the altered protein showed an innocuous isoleucine for valine substitution. There were no mutations noted within any of the other exons. Three novel intronic SNPs were identified within the fertile group, and seven novel intronic SNPs identified in the infertile group. The DNA-protein gel shift assay noted that both single CGG deletion and double CGG deletion bands had approximately twice the binding affinity compared to the wild-type for SP1. The negative control confirmed no non-specific protein binding. Conclusion- By themselves, a single or double CGG deletion is unlikely to pose biologic significance. However, such deletions in this suspected promoter region are associated with increased binding affinity for SP1, and might represent one of several factors required for alteration of UBE2B gene expression.

关键词： UBE2B SP1 spermatogenesis male infertility single nucleotide polymorphism

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特发性少精子症和无精子症与Pygo2基因蛋白编码区SNPs的相关性

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遗传 2013年第5期35卷 616-622页

作者：葛少钦 Jeanine Grifin 刘丽华 Kenneth I.Aston Luke Simon Timothy G.Jenkins benjamin r.emery Douglas T.Carrell Andrology and IVF Laboratories Division of UrologyDepartment of SurgeryUniversity of Utah School of MedicineSalt Lake City UT 84108USA 河北大学医学部 Department of Obstetrics and Gynecology University of Utah School of MedicineSalt Lake City UT 84108USA Department of Physiology University of Utah School of MedicineSalt Lake City UT 84108USA

男性不育常伴随精子数量减少。Pygo2基因在染色质重塑的伸长精细胞中表达,其功能受损会导致精子形成阻滞和精子生成减少而引发不育。文章旨在检测引起人特发性少精子症和无精子症的Pygo2基因突变。从77例正常生育力男性和195例特发性少... 详细信息

男性不育常伴随精子数量减少。Pygo2基因在染色质重塑的伸长精细胞中表达,其功能受损会导致精子形成阻滞和精子生成减少而引发不育。文章旨在检测引起人特发性少精子症和无精子症的Pygo2基因突变。从77例正常生育力男性和195例特发性少精子症和无精子症患者静脉血提取DNA,采用聚合酶链式反应-测序方法对Pygo2基因3个蛋白质编码区进行测序对比,非同义单核苷酸多态性(Single nucleotide polymorphisms,SNPs)位点分别用SIFT、Polyphen-2和Mutation Taster软件进行诱发蛋白质结构和表型改变的检测和分析。结果表明,195例患者中,178例(30例轻度或中度少精子症,57例重度少精子症和91例无精子症)基因序列分析报告完好,无精子症中3例患者分别在2个位点(rs61758740,rs141722381)发生了非同义突变SNPs,重度少精子症中1例患者在位点rs61758741发生了非同义突变,3个突变位点在SNPs基因数据库都已有报道,轻度或中度少精子症患者以及正常生育力男性中不存在SNPs。rs61758740可使PYGO2蛋白第141位蛋氨酸(M)变为异亮氨酸(I),rs61758741使PYGO2蛋白第261位碱性赖氨酸(K)变为酸性谷氨酸(E),rs141722381使PYGO2蛋白第240位亲水侧链天冬酰胺(N)变为疏水侧链异亮氨酸(I)。软件分析表明,在所发现的3个SNP非同义突变位点中,rs141722381引起的单个氨基酸改变会导致PYGO2蛋白空间结构破坏和诱发相关疾病。因此,Pygo2基因蛋白质编码序列区SNPs可能是特发性少精子症和无精子症的诱发因素之一,导致男性不育。

关键词：特发性少精子症特发性无精子症 Pygo2基因 SNPs

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Spastin and alsin protein interactome analyses begin to reveal key canonical pathways and suggest novel druggable targets

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Neural regeneration research 2025年第3期20卷 725-739页

作者： benjamin r.Helmold Angela Ahrens Zachary Fitzgerald P.Hande Ozdinler Department of Neurology Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Center for Molecular Innovation and Drug Discovery Center for Developmental TherapeuticsChemistry of Life Processes InstituteNorthwestern UniversityEvanstonILUSA Mesulam Center for Cognitive Neurology and Alzheimer’s Disease Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Feinberg School of Medicine Les Turner ALS Center at Northwestern UniversityChicagoILUSA

Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. Protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.

关键词： ALS2 alsin amyotrophic lateral sclerosis hereditary spastic paraplegia neurodegenerative diseases personalized medicine precision medicine protein interactome protein-protein interactions SPAST spastin

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Matrilinear hierarchy in the American black bear (Ursus americanus)

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Integrative Zoology 2022年第1期17卷 139-155页

作者： benjamin KILHAM James r.SPOTILA Kilham Bear Center LymeNew HampshireUSA Department of Biodiversity Earth and Environmental ScienceDrexel UniversityPhiladelphiaPennsylvaniaUSA

The American black bear(Ursus americanus)was long thought to be solitary and its social organization has not been well ***,we present new data on black bear social *** objectives of the study were to make detailed observations of the behavior of wild black bears to determine their social interactions and *** tested whether black bears interacted socially beyond mating and competing for resources,if black bears tracked relationships and interacted regularly even when resources were not limited,and whether the social structure of a population of black bears was based on a matrilinear *** collected data by direct observation of bears from 1993 to *** of 1210 social interactions at a provisioning site indicated that females compete and form matrilinear *** bears established a hierarchy for food,control of space,and control of younger *** interaction scent marking took place,which suggested that dominant females were conditioning subordinates to their scent *** behavior occurred between related and unrelated bears and helped to establish the social structure of the bear *** on our data,human–bear conflicts can be reduced by behavioral modifications by humans when they encounter *** of bear behavior and the matrilinear hierarchy provide a basis for non-lethal management of bears that find themselves in a bear–human conflict situation.

关键词： bear matrilinear hierarchy New Hampshire rank social behavior Ursus

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Are we Athens or Florence? COVID-19 in historical context

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Family Medicine and Community Health 2021年第1期9卷 43-45页

作者： benjamin r Doolittle Internal Medicine&Pediatrics Yale UniversityNew HavenConnecticutUSA

We have been here *** 430 BCE,a plague struck Athens,killing as much as 25%of the *** 1347 CE,the bubonic plague afflicted western Europe for 4 years,killing as much as 50%of the *** plague of Athens led to a collapse of their religion,cultural norms and *** contrast,the bubonic plague led eventually to the renaissance,a growth of art,science and *** we contend with the COVID-19 global pandemic,will we become Athens or Florence?

关键词： population. eventually renaissance

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Giant duodenal ulcers

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World Journal of Gastroenterology 2008年第32期14卷 4995-4999页

作者： Eric benjamin Newton Mark r Versland Thomas E Sepe Department of Medicine Division of Gastroenterology-Hepatology University of Connecticut Health Center Warren Alpert School of Medicine Brown University Providence

Giant duodenal ulcers （GDUs） are a subset of duodenal ulcers that have historically resulted in greater morbidity than usual duodenal ulcers. Until recently, few cases had been successfully treated with medical therapy. However, the widespread use of endoscopy, the introduction of H-2 receptor blockers and proton p^Jmp inhibitors, and the improvement in surgical techniques all have revolutionized the diagnosis, treatment and outcome of this condition. Nevertheless, GDUs are still associated with high rates of morbidity, mortality and complications. Thus, surgical evaluation of a patient with a GDU should remain an integral part of patient care. These giant variants, while usually benign, can frequently harbor malignancy. A careful review of the literature highlights the important differences when comparing GDUs to classical peptic ulcers and why they must be thought of differently than their more common counterpart.

关键词： Giant duodenal ulcer Hel/cobacter py/ori Nonsteroidal anti-inflammatory drugs Malignancy Endoscopy

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Histone/protein deacetylase 3 dictates critical aspects of regulatory T cell development and function

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Cellular & Molecular Immunology 2016年第4期13卷 415-417页

作者： benjamin D. Singer Franco r. D'Alessio Johns Hopkins University Division of Pulmonary and Critical Care Medicine Baltimore MD USA

regulatory T cells （Tregs） comprise a subset of CD4＋ T lymphocytes that holds promise as immunotherapy for inflammat- ory disease states including autoimmune disorders, solid organ allograft rejection, graft-versus-host disease, and acute inflam- matory conditions. However, limited availability of Treg numbers restricts their usefulness in cell transfer applications, particularly as patients may need multiple infusions for chronic diseases.

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