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Mechanism of sperm capacitation and the acrosome reaction： role of protein kinases

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Asian Journal of Andrology 2012年第6期14卷 816-821页

作者： debby Ickowicz Maya Finkelstein Haim Breitbart The Mina & Everard Faculty of Life Sciences Bar-Ilan University Ramat-Gan 52100 Israel

Mammalian sperm must undergo a series of biochemical and physiological modifications, collectively called capacitation, in the female reproductive tract prior to the acrosome reaction （AR）. The mechanisms of these modifications are not well characterized though protein kinases were shown to be involved in the regulation of intracellular Ca2＋ during both capacitation and the AR. In the present review, we summarize some of the signaling events that are involved in capacitation. During the capacitation process, phosphatidyl-inositol-3-kinase （PI3K） is phosphorylated/activated via a protein kinase A （PKA）-dependent cascade, and downregulated by protein kinase C a （PKCa）. PKCa is active at the beginning of capacitation, resulting in PI3K inactivation. During capacitation, PKCa as well as PP172 is degraded by a PKA-dependent mechanism, allowing the activation of PI3K. The activation of PKA during capacitation depends mainly on cyclic adenosine monophosphate （cAMP） produced by the bicarbonate-dependent soluble adenylyl cyclase. This activation of PKA leads to an increase in actin polymerization, an essential process for the development of hyperactivated motility, which is necessary for successful fertilization. Actin polymerization is mediated by PIP2 in two ways： first, PIP2 acts as a cofactor for phospholipase D （PLD） activation, and second, as a molecule that binds and inhibits actin-severing proteins such as gelsolin. Tyrosine phosphorylation of gelsolin during capacitation by Src family kinase （SFK） is also important for its inactivation. Prior to the AR, gelsolin is released from PIP2 and undergoes dephosphorylation/activation, resulting in fast F-actin depolymerization, leading to the AR.

关键词： sperm capacitation acrosome reaction AR PKCα PI3K PKA gelsolin PIP2

SMARCB1/INI1-deficient pancreatic undifferentiated rhabdoid carcinoma mimicking solid pseudopapillary neoplasm: A case report and review of the literature

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World Journal of Gastroenterology 2020年第36期26卷 5520-5526页

作者： Yinan Hua Piyush Soni Douglas Larsen Riyam Zreik Bing Leng debby Rampisela Department of Pathology Baylor Scott&White HealthTexas A&M University College of MedicineTempleTX 76508United States

BACKGROUND SMARCB1/INI1-deficient pancreatic undifferentiated rhabdoid carcinoma is a very aggressive tumor that is rarely reported in the literature.The tumor has a predominant rhabdoid cell component and different patterns of growth have been reported.CASE SUMMARY A 59-year-old woman presented with diffuse abdominal pain,increasing in severity and accompanied by weight loss,nausea,and vomiting.Imaging showed a pancreatic head mass.Fine needle aspiration demonstrated atypical epithelioid cells with a pseudopapillary growth pattern suggestive of solid pseudopapillary neoplasm.The excised neoplasm showed monotonous epithelioid and focally spindle cells with pseudopapillary structures,rhabdoid features,and loss of SMARCB1 protein expression with wild-type KRAS,consistent with a SMARCB1/INI1-deficient undifferentiated rhabdoid carcinoma.The patient’s condition deteriorated rapidly following surgery and she expired 3 mo post operation.CONCLUSION In this article,we report the first case of SMARCB1/INI1-deficient undifferentiated pancreatic rhabdoid carcinoma mimicking solid pseudopapillary neoplasm.

关键词： Pancreatic undifferentiated rhabdoid carcinoma Solid pseudopapillary neoplasm SMARCB1/INI1 KRAS Case report

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英伟达芯片重塑AI大脑

商业周刊（中文版） 2023年第11期 60-67页

作者： debby Wu 许诺(译) 不详

黄仁勋(Jensen Huang)第一次试用ChatGPT时,让它给他的公司英伟达的霍珀100处理器写首诗。十多年前黄仁勋就押下赌注,认为英伟达的电脑芯片可以成为人工智能的大脑。ChatGPT给出的结果让他很满意——它写道:“英伟达应对了挑战。/凭借... 详细信息

黄仁勋(Jensen Huang)第一次试用ChatGPT时,让它给他的公司英伟达的霍珀100处理器写首诗。十多年前黄仁勋就押下赌注,认为英伟达的电脑芯片可以成为人工智能的大脑。ChatGPT给出的结果让他很满意——它写道:“英伟达应对了挑战。/凭借强大的GPU和AI,/他们将前沿技术的边界向前推进。”以他的文学水平来看,机器人作的这首诗表明,他之前那个赌打赢了。

关键词：电脑芯片人工智能机器人 GPU AI Chat GPT 黄仁

Pharmacomicrobiomics： a novel route towards personalized medicine？

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Protein & Cell 2018年第5期9卷 432-445页

作者： Marwah Doestzada Arnau Vich Vila Alexandra Zhernakova debby P.Y. Koonen Rinse K. Weersma Daan J. TOUW Folkert Kuipers Cisca Wijmenga Jingyuan Fu Departments of Genetics University Medical Center Groningen PO Box 30001 9700 RB Groningen The Netherlands Departments of Paediatrics University Medical Center Groningen PO Box 30001 9700 RB Groningen The Netherlands Departments of Gastroenterology & Hepatology University Medical Center Groningen PO Box 30001 9700 RB Groningen The Netherlands Departments of Clinical Pharmacy & Pharmacology University Medical Center Groningen PO Box 30001 9700 RB Groningen The Netherlands Departments of Laboratory Medicine University Medical Center Groningen PO Box 30001 9700 RB Groningen The Netherlands K.G. Jebsen Coeliac Disease Research Centre Department of Immunology University of Oslo P.O. Box 1072 Blindern 0316 Oslo Norway

Inter-individual heterogeneity in drug response is a serious problem that affects the patient＇s wellbeing and poses enormous clinical and financial burdens on a societal level. Pharmacogenomics has been at the forefront of research into the impact of individual genetic background on drug response variability or drug toxicity, and recently the gut microbiome, which has also been called the second genome, has been recog- nized as an important player in this respect. Moreover, the microbiome is a very attractive target for improving drug efficacy and safety due to the opportunities to manipulate its composition. Pharmacomicrobiomics is an emerging field that investigates the interplay of microbiome variation and drugs response and disposi- tion （absorption, distribution, metabolism and excretion）. In this review, we provide a historical overview and examine current state-of-the-art knowledge on the complex interactions between gut microbiome, host and drugs. We argue that combining pharmacogenomics and pharmacomicrobiomics will provide an important foundation for making major advances in personalized medicine.

关键词： gut microbiome drug metabolism personalized medicine

Diagnostic accuracy of tests for Helicobacter pylori in an Alaska Native population

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World Journal of Gastroenterology 2011年第42期17卷 4682-4688页

作者： Dana L Bruden Michael G Bruce Karen M Miernyk Julie Morris debby Hurlburt Thomas W Hennessy Helen Peters Frank Sacco Alan J Parkinson Brian J McMahon Arctic Investigations Program Division of Preparedness and Emerging InfectionsNational Center for Emerging Zoonoses and Infectious DiseasesCenters for Disease Control and Prevention Alaska Native Tribal Health Consortium Anchorage

AIM:To evaluate the accuracy of two non-invasivetests in a population of Alaska Native persons. Highrates of Helico bacter pylori(H. pylori) infection,H. pylori treatment failure,and gastric cancer in this population necessitate documentation of infection status atmultiple time points over a patient's life.METHODS:In 280 patients undergoing endoscopy,H. pylori was diagnosed by culture,histology,rapidurease test,13C urea breath test(UBT) ,and immuno-globulin G antibodies to H. pylori in serum. The performances of 13C-UBT and antibody test were compared to a gold standard defined by a positive H. pylori testby culture or,in case of a negative culture result,bypositive histology and a positive rapid urease test.RESULTS:The sensitivity and specificity of the 13C-UBT were 93% and 88%,respectively,relative to thegold standard. The antibody test had an equivalents ensitivity of 93% with a reduced specificity of 68%.The false positive results for the antibody test were as-sociated with previous treatment for an H. pylori infection [relative risk(RR) = 2.8]. High levels of antibodiesto H. pylori were associated with chronic gastritis and male gender,while high scores in the 13C-UBT testwere associated with older age and with the H. pyloribacteria load on histological examination(RR = 4.4) .CONCLUSION:The 13C-UBT out performed the anti-body test for H. pylori and could be used when a non-invasive test is clinically necessary to document treatment out come or when monitoring for reinfection.

关键词：阿拉斯加幽门螺杆菌测试人口幽门螺旋杆菌准确率原住民抗体检测

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英伟达市值破万亿美元黄仁勋的高光时刻

商业周刊（中文版） 2023年第9期 50-51页

作者： debby Wu Vlad Savov 陈佳靖(译) 不详

芯片行业巨擘英伟达的首席执行官黄仁勋出访台北期间,获得了明星般的礼遇。现年60岁的黄仁:勋日前参加台北国际电脑展览会(Computex),期间频频被粉丝和媒体围堵,他在当地夜市觅食时,拥趸也跟随左右。5月30日,数十人包围在他身旁,想要与... 详细信息

芯片行业巨擘英伟达的首席执行官黄仁勋出访台北期间,获得了明星般的礼遇。现年60岁的黄仁:勋日前参加台北国际电脑展览会(Computex),期间频频被粉丝和媒体围堵,他在当地夜市觅食时,拥趸也跟随左右。5月30日,数十人包围在他身旁,想要与他自拍合影。

关键词：首席执行官黄仁夜市台北国际电脑展市值

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富士康离实现电动汽车梦想颇为遥远

商业周刊（中文版） 2023年第5期 55-56页

作者： Sean O'Kane debby Wu David Welch 汪泽(译) 不详

这家iPhone生产商的电动汽车梦想遭遇现实--召回事件以及菜鸟合作方过去10年里,富士康科技集团(Foxconn Technology Group)遵循苹果公司(Apple Inc.)越来越复杂的计划,将硅、玻璃、塑料、铜以及其他原材料变成数以亿计的iPhone。苹果公... 详细信息

这家iPhone生产商的电动汽车梦想遭遇现实--召回事件以及菜鸟合作方过去10年里,富士康科技集团(Foxconn Technology Group)遵循苹果公司(Apple Inc.)越来越复杂的计划,将硅、玻璃、塑料、铜以及其他原材料变成数以亿计的iPhone。苹果公司只是这家台湾公司几十家重头客户之一:谷歌(Google)、微软(Microsoft)、索尼(Sony)等众多公司都曾委托富士康生产手机、计算机、平板电脑、游戏机、服务器等产品。因此如果认为富士康在汽车方面也会做同样的事情,这或许与事实不会相去太远。

关键词：召回事件富士康苹果公司电动汽车平板电脑 iPhone

Spatial Disparity in Availability of Tuberculosis Diagnostic Services Based on Sector and Level of Care in Nigeria

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Journal of Tuberculosis Research 2023年第1期11卷 12-22页

作者： Bethrand Odume Sani Useni Egwuma Efo Degu Dare Elias Aniwada Nkiru Nwokoye Ogoamaka Chukwuogo Chidubem Ogbudebe Michael Sheshi Aminu Babayi Emperor Ubochioma Obioma Chijioke-Akaniro Chukwumah Anyaike Rupert Eneogu debby Nongo KNCV Nigeria Abuja Nigeria KNCV Netherlands The Hague Netherlands Department of Community Medicine University of Nigeria Nsukka Nigeria NTBLCP FMOH Abuja Nigeria USAID Abuja Nigeria

Background: Delay in Tuberculosis (TB) diagnosis can contribute to late presentation, severe disease, and continued transmission. KNCV TB Foundation Nigeria through the United States Agency for International Development (USAID) funded the TB Local Organization Network (LON) 1 and 2 projects that explored the availability of Tuberculosis services based on sector and levels of care. Methods: TB Patient Pathway Analysis was carried out in 14 states comprising 92 facilities. It involved primary, secondary, and tertiary levels of health care in both the public and private sectors. This was a cross-sectional study under program implementation. Proforma was used to collect data on the available TB diagnostic services. Results: In public health facilities, GeneXpert was available at 100% in tertiary facilities in 8 (57%) states;up to 82% in 4 (33%) states, 50% available at secondary facilities in 2 states, and There is none at the primary facilities. Smear microscopy was available at 100% in tertiary facilities in 9 (64%) states and 3 (25%) states have 50% to 82%;secondary -10 (71%) states have > 70% at facilities;primary 1 (7%) state has it in 61% of facilities. Loop-mediated isothermal amplification (TB-LAMP) in tertiary 2 (17%) states have 20% and 100% respectively;secondary 4 (<30%) states have in 1 or 2 facilities;none for primary facilities. In private health facilities, 79% of states have Smear microscopy at both primary and secondary facilities, and only 2 states (14%) at tertiary facilities. Only 1 (7%) state has GeneXpert in all tertiary facilities, 2 (14%) states have secondary facilities, and 4 states in about 1% of facilities. TB LAMP was not available in any tertiary facility, one (7%) state at secondary with coverage of 1%, and 2 (14%) states at primary both with 4% overall facility coverage. Conclusions: There is an inequitable distribution of TB diagnostic services in both sectors and levels of care in Nigeria. TB care and control will improve with enhanced equitable distribution of TB diagnostic service

关键词： Tuberculosis Diagnostic Services Disparity Sector Level Nigeria

Patient Health Seeking Behavior and Choice of Place of Care among Tuberculosis Clients in Selected States in Nigeria

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Journal of Tuberculosis Research 2023年第4期11卷 149-161页

作者： Bethrand Odume Aminu Babayi Ogoamaka Chukwuogo Chidubem Ogbudebe Elias Aniwada Egwuma Efo Degu Dare Useni Sani Nkiru Nwokoye Emperor Ubochioma Obioma-Chijioke Akaniro debby Nongo Rupert Eneogu Temitayo Lagundoye-Odusote Chukwuma Anyaike Technical and Programs Department KNCV Nigeria Abuja Nigeria Department of Community Medicine Faculty of Medical Sciences University of Nigeria Enugu Campus Enugu Nigeria Technical Department KNCV Tuberculosis Fund The Hague Netherlands The Programs and Coordination Department National Tuberculosis Leprosy & Buruli Control Program Abuja Nigeria Program Management Department HIV/AIDS & TB Office USAID/Nigeria Abuja Nigeria

Background: Tuberculosis (TB) remains a major global public health problem. Early detection and initiation of treatment shortens infectious period and is key to TB control. A considerable proportion of TB patients presenting with advanced symptoms suggests delay in seeking care. As TB control programs rely on passive case finding, TB care-seeking behavior is critical as un-diagnosed cases act as reservoirs for transmission. This study assessed patient health seeking behavior and choice of place of care among TB patients in Nigeria. Methods: This was a pro-gramme implementation, facility-based cross-sectional study in 14 states, 92 facilities across three levels of care. Interviewer-administered semi-structured questionnaires were used. Information on personal characteristics and health seeking behavior was collected from June 2020 to December 2021. The analysis was based on the various healthcare providers where the respondents first sought care. Data analysis was done using IBM SPSS and summarized using frequency and percentages. Chi square test was used for associations of characteristics of patients and choice of place of care at p Results: In all 14 states, distribution of overall first place of seeking care for TB symptoms was: 7208 (75.8%) health facilities (range 57% to 88%), while 2294 (24.2%) visited other places including community pharmacist, patent medicine vendor, traditional/home, un-specified/none. For Health facilities, the majority were at public facilities 6563 (69.1%) and private 641 (6.7%). Moreover, 6 states had >20% of respondents who first sought care at PMVs, while 3 states (Delta, Imo, and Rivers) had 10% of respondents who first sought care at Community Pharmacist. Conclusions: Nearly a quarter of people with TB first sought care outside health facilities, suggesting the need to align availability of services with their needs.

关键词： Patient Pathway Analysis TB Patients TB Treatment Healthcare Facility