1.Proteomic changes in mammalian spermatozoa during epididymal maturation.
R John AITKEN ; Brett NIXON ; Minjie LIN ; Adam J KOPPERS ; Yun H LEE ; Mark A BAKER
Asian Journal of Andrology 2007;9(4):554-564
Epididymal maturation is associated with the activation of a cAMP-induced tyrosine phosphorylation cascade, which is ultimately associated with the expression of capacitation-dependent sperm functions, such as hyperactivated movement and acrosomal exocytosis. As spermatozoa progress through the epididymis they first acquire the capacity to phosphorylate tyrosine on targets on the principal piece, followed by the midpiece. By the time these cells have reached the cauda epididymidis they can phosphorylate the entire tail from neck to endpiece. This particular pattern of phosphorylation is associated with the ontogeny of fully functional spermatozoa that are capable of fertilizing the oocyte. Proteomic analyses indicate that this change is associated with the phosphorylation of several mitochondrial proteins, creation of a mitochondrial membrane potential and activation of mitochondrial free radical generation. At least in rodent species, activation of sperm mitochondria appears to be a particularly important part of epididymal maturation.
Acrosome Reaction
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Aging
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Animals
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Epididymis
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growth & development
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physiology
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Humans
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Male
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Mammals
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Mice
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Proteome
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Sperm Capacitation
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physiology
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Spermatozoa
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physiology
2.17β-Estradiol Changes The Human Cerebral Endothelial Cell Proteome Upon Exposure To Cyclic Stretch
Nurul Farhana JUFRI ; Abidali MOHAMEDALI ; Seong Beom AHN ; Alberto AVOLIO ; Mark BAKER
Malaysian Journal of Health Sciences 2018;16(Special Issue (Article)):55-65
Hypertension and estrogen deficiency in women have been identified as significant risk factors for cerebrovasculardiseases. Hypertension causes excessive vascular stretch and contributes to the initiation of cellular injury in bloodvessels while estrogen has been demonstrated to exert beneficial protective effects on the vascular system. Although thespecific biological outcomes exerted by either excessive stretch or estrogen exposure are well established, the combinedbiochemical effects of both stimuli remain unclear. Therefore, this study was conducted for quantitative proteomics studyon human cerebral microvascular endothelial cells (HCMECs) subjected to 20% “pathological” cyclic stretch for aperiod of 18 hour in the presence or absence of 17β-estradiol by isobaric Taqs for Relative and Absolute Quantification.The results showed that only some proteins responded to 17β-estradiol (e.g., thioredoxin reductase-1), stretch (e.g., 14-3-3 protein epsilon or acidic leucine-rich nuclear phosphoprotein 32 family member B) and interestingly, some proteinsreturned to control pre-treatment levels when exposed to both (e.g., d-dopachrome decarboxylase, thrombospondin-1). Inaddition, HCMECs that exposed only to estrogen had a very similar proteomic profile (i.e., up-regulation of structural,cellular adhesion and proliferation proteins) as to those exposed to estrogen with 20% stretching for 18 hour, suggestingthat estrogen ablated the detrimental effects by the stretch alone. These findings sheds light on the molecular mechanismsby which the cerebrovascular protective actions of estrogen on HCMEC exposed to pathological levels of cyclic stretchwhich could provide a platform for future research in therapeutic approach.
3.Propagation Characteristics of Fasting Duodeno-Jejunal Contractions in Healthy Controls Measured by Clustered Closely-spaced Manometric Sensors
Jason R BAKER ; Joseph R DICKENS ; Mark KOENIGSKNECHT ; Ann FRANCES ; Allen A LEE ; Kerby A SHEDDEN ; James G BRASSEUR ; Gordon L AMIDON ; Duxin SUN ; William L HASLER
Journal of Neurogastroenterology and Motility 2019;25(1):100-112
BACKGROUND/AIMS: High-resolution methods have advanced esophageal and anorectal manometry interpretation but are incompletely established for intestinal manometry. We characterized normal fasting duodeno-jejunal manometry parameters not measurable by standard techniques using clustered closely-spaced recordings. METHODS: Ten fasting recordings were performed in 8 healthy controls using catheters with 3–4 gastrointestinal manometry clusters with 1–2 cm channel spacing. Migrating motor complex phase III characteristics were quantified. Spatial-temporal contour plots measured propagation direction and velocity of individual contractions. Coupling was defined by pressure peak continuity within clusters. RESULTS: Twenty-three phase III complexes (11 antral, 12 intestinal origin) with 157 (95% CI, 104–211) minute periodicities, 6.99 (6.25–7.74) minute durations, 10.92 (10.68–11.16) cycle/minute frequencies, 73.6 (67.7–79.5) mmHg maximal amplitudes, and 4.20 (3.18–5.22) cm/minute propagation velocities were recorded. Coupling of individual contractions was 39.1% (32.1–46.1); 63.0% (54.4–71.6) of contractions were antegrade and 32.8% (24.1–41.5) were retrograde. Individual phase III contractions propagated > 35 fold faster (2.48 cm/sec; 95% CI, 2.25–2.71) than complexes themselves. Phase III complexes beyond the proximal jejunum were longer in duration (P = 0.025) and had poorer contractile coupling (P = 0.025) than proximal complexes. Coupling was greater with 1 cm channel spacing vs 2 cm (P < 0.001). CONCLUSIONS: Intestinal manometry using clustered closely-spaced pressure ports characterizes novel antegrade and retrograde propagation and coupling properties which degrade in more distal jejunal segments. Coupling is greater with more closely-spaced recordings. Applying similar methods to dysmotility syndromes will define the relevance of these methods.
Catheters
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Fasting
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Intestines
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Jejunum
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Manometry
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Muscle Contraction
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Myoelectric Complex, Migrating
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Periodicity
4.Implementing hospital-based surveillance for severe acute respiratory infections caused by influenza and other respiratory pathogens in New Zealand
Q Sue Huang ; Michael Baker ; Colin McArthur ; Sally Roberts ; Deborah Williamson ; Cameron Grant ; Adrian Trenholme ; Conroy Wong ; Susan Taylor ; Lyndsay LeComte ; Graham Mackereth ; Don Bandaranayake ; Tim Wood ; Ange Bissielo ; Ruth Se ; Nikki Turner ; Nevil Pierse ; Paul Thomas ; Richard Webby ; Diane Gross ; Jazmin Duque ; Mark Thompson ; Marc-Alain Widdowson
Western Pacific Surveillance and Response 2014;5(2):23-30
Recent experience with pandemic influenza A(H1N1)pdm09 highlighted the importance of global surveillance for severe respiratory disease to support pandemic preparedness and seasonal influenza control. Improved surveillance in the southern hemisphere is needed to provide critical data on influenza epidemiology, disease burden, circulating strains and effectiveness of influenza prevention and control measures. Hospital-based surveillance for severe acute respiratory infection (SARI) cases was established in New Zealand on 30 April 2012. The aims were to measure incidence, prevalence, risk factors, clinical spectrum and outcomes for SARI and associated influenza and other respiratory pathogen cases as well as to understand influenza contribution to patients not meeting SARI case definition.All inpatients with suspected respiratory infections who were admitted overnight to the study hospitals were screened daily. If a patient met the World Health Organization’s SARI case definition, a respiratory specimen was tested for influenza and other respiratory pathogens. A case report form captured demographics, history of presenting illness, co-morbidities, disease course and outcome and risk factors. These data were supplemented from electronic clinical records and other linked data sources.Hospital-based SARI surveillance has been implemented and is fully functioning in New Zealand. Active, prospective, continuous, hospital-based SARI surveillance is useful in supporting pandemic preparedness for emerging influenza A(H7N9) virus infections and seasonal influenza prevention and control.
5.Validating lactate dehydrogenase (LDH) as a component of the PLASMIC predictive tool (PLASMIC-LDH)
Christopher Chin KEONG LIAM ; Jim Yu-Hsiang TIAO ; Yee Yee YAP ; Yi Lin LEE ; Jameela SATHAR ; Simon MCRAE ; Amanda DAVIS ; Jennifer CURNOW ; Robert BIRD ; Philip CHOI ; Pantep ANGCHAISUKSIRI ; Sim Leng TIEN ; Joyce Ching MEI LAM ; Doyeun OH ; Jin Seok KIM ; Sung-Soo YOON ; Raymond Siu-Ming WONG ; Carolyn LAUREN ; Eileen Grace MERRIMAN ; Anoop ENJETI ; Mark SMITH ; Ross Ian BAKER
Blood Research 2023;58(1):36-41
Background:
The PLASMIC score is a convenient tool for predicting ADAMTS13 activity of <10%.Lactate dehydrogenase (LDH) is widely used as a marker of haemolysis in thrombotic thrombocytopenic purpura (TTP) monitoring, and could be used as a replacement marker for lysis. We aimed to validate the PLASMIC score in a multi-centre Asia Pacific region, and to explore whether LDH could be used as a replacement marker for lysis.
Methods:
Records of patients with thrombotic microangiopathy (TMA) were reviewed. Patients’ ADAMTS13 activity levels were obtained, along with clinical/laboratory findings relevant to the PLASMIC score. Both PLASMIC scores and PLASMIC-LDH scores, in which LDH replaced traditional lysis markers, were calculated. We generated a receiver operator characteristics (ROC) curve and compared the area under the curve values (AUC) to determine the predictive ability of each score.
Results:
46 patients fulfilled the inclusion criteria, of which 34 had ADAMTS13 activity levels of <10%. When the patients were divided into intermediate-to-high risk (scores 5‒7) and low risk (scores 0‒4), the PLASMIC score showed a sensitivity of 97.1% and specificity of 58.3%, with a positive predictive value (PPV) of 86.8% and negative predictive value (NPV) of 87.5%. The PLASMIC-LDH score had a sensitivity of 97.1% and specificity of 33.3%, with a PPV of 80.5% and NPV of 80.0%.
Conclusion
Our study validated the utility of the PLASMIC score, and demonstrated PLASMIC-LDH as a reasonable alternative in the absence of traditional lysis markers, to help identify high-risk patients for treatment via plasma exchange.