bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structures and specificity of the human kallikrein-related peptidases KLK 4, 5, 6, and 7
Authors: Debela Mekdes , Beaufort Nathalie , Magdolen Viktor , Schechter Norman M. , Craik Charles S. , Schmitt Manfred , Bode Wolfram , Goettig Peter 
Published: July 2008

Abstract
Human kallikrein-related peptidases (KLKs) are (chymo)-trypsin-like serine proteinases that are expressed in a variety of tissues such as prostate, ovary, breast, testis, brain, and skin. Although their physiological functions have been only partly elucidated, many of the KLKs appear to be useful prognostic cancer markers, showing distinct correlations between their expression levels and different stages of cancer. Recent advances in the purification of ‘new type’ recombinant KLKs allowed solution of the crystal structures of KLK4, KLK5, KLK6, and KLK7. Along with these data, enzyme kinetic studies and extended substrate specificity profiling have led to an understanding of the non-prime-side substrate preferences of KLK4, 5, 6, and 7. The shape and polarity of the specificity pockets S1–S4 explain well their substrate preferences. KLK4, 5, and 6 exhibit trypsin-like specificity, with a strong preference for Arg at the P1 position of substrates. In contrast, KLK7 displays a unique chymotrypsin-like specificity for Tyr, which is also preferred at P2. All four KLKs show little specificity for P3 residues and have a tendency to accept hydrophobic residues at P4. Interestingly, for KLK4, 5, and 7 extended charged surface regions were observed that most likely serve as exosites for physiological substrates.
Human tissue kallikreins as promiscuous modulators of homeostatic skin barrier functions
Authors: Eissa Azza , Diamandis Eleftherios P. 
Published: July 2008

AbstractHuman tissue kallikreins (KLKs) are the largest family of secreted serine protease endopeptidases encoded by 15 genes clustered on chromosome 19q13.4. Multiple KLK enzymes are co-localized in the upper stratum granulosum and stratum corneum of human epidermis, and in associated appendages such as hair follicle epithelia and sweat glands. Until recently, kallikrein proteolytic activity in the skin was exclusively attributed to KLK5 and KLK7. However, wider cutaneous roles of kallikreins became evident in recent years as the proposal of KLK proteolytic activation cascades emerged. We postulate that these proteolytic enzymes may serve as promiscuous mediators of different skin barrier functions, since they are capable of proteolysing different substrates that govern skin desquamation, antimicrobial defense, and lipid permeability. Growing evidence now attests to potential kallikrein involvement in skin inflammation, pigmentation, and tumor suppression via their ability to target proteinase-activated receptor signaling pathways. Current knowledge on kallikrein roles in skin physiology and pathobiology is described in this review.
Genetic deficiency in tissue kallikrein activity in mouse and man: effect on arteries, heart and kidney
Authors: Pizard Anne , Richer Christine , Bouby Nadine , Picard Nicolas , Meneton Pierre , Azizi Michel , Alhenc-Gelas François 
Published: July 2008

AbstractTissue kallikrein (KLK1) is a kinin-forming serine protease synthesized in many organs including arteries and kidney. Study of the physiological role of KLK1 has benefited from the availability of mouse and human genetic models of KLK1 deficiency, through engineering ofKLK1mouse mutants and discovery of a major polymorphism in the humanKLK1gene that induces a loss of enzyme activity. Studies in KLK1-deficient mice and human subjects partially deficient in KLK1 have documented its critical role in arterial function in both species. KLK1 is also involved in the control of ionic transport in the renal tubule, an action that may not be kinin-mediated. Studies of experimental diseases in KLK1-deficient mice have revealed cardio- and nephro-protective effects of KLK1 and kinins in acute cardiac ischemia, post-ischemic heart failure, and diabetes. Potential clinical and therapeutic developments are discussed.
Development of diabetic cardiomyopathy and the kallikrein-kinin system – new insights from B1 and B2 receptor signaling
Authors: Tschöpe Carsten , Westermann Dirk 
Published: July 2008

Abstract
Diabetic cardiomyopathy is a specific cardiomyopathy which develops in patients with diabetes mellitus in the absence of coronary atherosclerosis and hypertension. Despite the potential importance of this disease entity, the underlying mechanisms are only incompletely understood. Changes in calcium handling, disruption of the extracellular matrix regulation with accumulation of cardiac collagen, and furthermore cardiac inflammation may be an important mediator of this disease. This brief review focuses on the current aspects of the kallikrein-kinin system and its influence on the development of diabetic cardiomyopathy with particular regard to the kinin receptors B1 and B2, as their role in the development of this disease is still under discussion. Whether the role of the B1 receptor is similar to the well-described beneficial role of the B2 receptor or whether its function is opposed to the B2 receptor is controversial. Some recent findings suggest that the B1 receptor mediates cardiac inflammation and therefore may be detrimental for cardiac function in the setting of diabetic cardiomyopathy.
Immunofluorometric activity-based probe analysis of active KLK6 in biological fluids
Authors: Oikonomopoulou Katerina , Hansen Kristina K. , Baruch Amos , Hollenberg Morley D. , Diamandis Eleftherios P. 
Published: July 2008

Abstract
Immunoassay measurements of human kallikrein-related peptidases (KLKs) such as prostate-specific antigen (KLK3) are of great value as diagnostic indices of cancer. Despite extensive knowledge of the abundance of immunoreactive KLKs in normal and cancer-related settings, there is little information available about the proportion of immunoreactive KLK that represents active enzyme in such samples. Using KLK6 as a prototype enzyme, we have developed an assay using a serine proteinase-targeted activity-based probe coupled to antibody capture. By employing activity-based labeling, we were able to quantify the proportion of enzymatically active relative to total immunoreactive KLK6 in crude cerebrospinal fluid from routine analyses and ascites fluid from ovarian cancer patients, as well as in supernatants from cancer cell lines. Our approach allowed monitoring of pro-KLK6 conversion to its active enzyme species and demonstrated that up to 5% of immunoreactive KLK6 detected in clinical samples represents active enzyme. We suggest that this new activity-based probe assay will prove of value as a complement to routine KLK immunoassay measurements for validating KLKs as cancer biomarkers.
Kallikrein 6 is a mediator of K-RAS-dependent migration of colon carcinoma cells
Authors: Henkhaus Rebecca S. , Gerner Eugene W. , Ignatenko Natalia A. 
Published: July 2008

AbstractKallikrein 6 (KLK6) is a trypsin-like serine peptidase whose relevance in various types of cancers is currently being explored. Previous studies have shown that KLK6 mRNA is upregulated in colon and gastric cancers; however, the regulatory mechanisms and phenotypic consequences of this upregulation are largely unknown. ActivatingK-RASmutations are common in colon cancer, occurring in approximately 50% of cases. We have recently reported the upregulation of KLK6 mRNA in Caco2 human colon cancer cells stably transfected with a mutantK-RASallele (K-RASG12V). In this study we examined the pattern of K-RAS-dependent KLK6 expression and secretion in colon cancer cells. Using pharmacological inhibitors of pathways downstream of K-RAS, we could show that the PI3K and p42/44 MAPK pathways play an important role in the induction of KLK6 in mutant K-RAS-expressing colon cancer cells. Increased KLK6 expression enhanced colon cancer cell migration through laminin and Matrigel. Inhibition of KLK6 using small interference RNA treatment or a specific KLK6 antibody in Caco2 cells stably expressing the mutant K-RAS and in SW480 cells carrying a mutation in theK-RASoncogene resulted in a reduction in invasiveness through cell culture inserts. These data support the oncogenic role of KLK6 in colorectal cancer.
Gene expression changes associated with the anti-angiogenic activity of kallikrein-related peptidase 3 (KLK3) on human umbilical vein endothelial cells
Authors: Mattsson Johanna M. , Laakkonen Pirjo , Kilpinen Sami , Stenman Ulf-Håkan , Koistinen Hannu 
Published: July 2008

Abstract
Kallikrein-related peptidase 3 (KLK3, also known as prostate-specific antigen, PSA) is a chymotrypsin-like kallikrein that has anti-angiogenic properties. We have previously shown in a human umbilical vein endothelial cell (HUVEC) model that the anti-angiogenic effect of KLK3 is related to its enzyme activity. However, the mechanism of this effect remains to be clarified. To this end, we used a DNA microarray to study KLK3-induced changes in gene expression associated with reduction of HUVEC tube formation. Among the 41 000 genes studied, 311 were differentially expressed between control and KLK3-treated cells. These changes were enriched in several pathways, including those associated with proteasome, ubiquitin-mediated proteolysis, focal adhesion and regulation of the actin cytoskeleton. Furthermore, the changes were opposite to those previously described to occur during tubulogenesis. In conclusion, our results show that KLK3 induces gene expression changes in HUVECs. Although these changes might be relevant for the mechanism by which KLK3 exerts its anti-angiogenic activity, it cannot be judged from the present results whether they reflect the primary mechanism mediating the effect of KLK3 or are secondary to morphogenic differentiation.
Comparative studies on the dissolution of ceramic UO2 pellets in nitric acid by microwave and conventional heating
Authors: Zhao Yunfeng , Chen Jing 
Published: July 2008

Summary
The dissolution data of UO2 are important to develop the new process of uranium ore leaching and new head-end reprocessing of spent nuclear fuel. The dissolution experiments of UO2 pellets in 8 M nitric acid by microwave heating and conventional heating were carried out respectively in the present work. Compared with the conventional heating, the microwave heating can remarkably promote the dissolution process of UO2 pellets with a dissolution ratio increase of 26%–46%. The kinetics results show that the dissolution processes by microwave heating and conventional heating match well with the diffusion control model and the surface reaction control model, respectively.
Selenide retention onto pyrite under reducing conditions
Authors: Liu Xiaolan , Fattahi Massoud , Montavon Gilles , Grambow Bernd 
Published: July 2008

Summary
Pyrite (FeS2) is a mineral phase often present as inclusions in temperate soils. Moreover, it turns out to be a sorption sink for certain radionuclides in deep geological disposals. The present study was thus initiated to determine the capacity of pyrite to immobilize selenide (Se(-II)). Due to the fact that pyrite surface oxidizes readily, potentials were applied in order to minimise its surface evolution, and ensure the reducing conditions necessary for stabilizing Se(-II). The sorption experiments were carried out in NaCl electrolyte and were amperometrically controlled. After only several minutes of reaction, at least 97% of Se(-II) initially present in solution was disappeared. The K
d values vary from 7–65 L/g and the isotherm curve shows site saturation at higher initial selenide concentrations and no pH-dependence. By means of several spectroscopic techniques, the reaction mechanism was investigated. The XRD and in situ XANES results indicate the presence of Se(0) on pyrite surface, which explain the rapid disappearance of Se observed in the sorption experiments. Moreover, XPS results obtained from Se-reacted pyrite particles reveal cleavage of S–S bonding which resulted in formation of S2− on pyrite surface. Thus, we conclude that Se(-II) can be immobilized by pyrite via surface redox reaction:
≡FeS2 + HSe− ⇔ ≡FeS + Se(0) + HS−.
Cross sections of proton induced nuclear reactions on natural cadmium leading to the formation of radionuclides of indium
Authors: Al-Saleh F. S. 
Published: July 2008

SummaryCross sections of proton induced nuclear reactions onnatCd, leading to the formation of110gIn,111In,113mIn, and116m1In for energies up to 14.7 MeV were measured using the stacked-foil irradiation technique and high resolution gamma-ray spectroscopy. Our experimental data were analyzed and the excitation functions for the studied radionuclides were compared with the previously reported data. Model codes ALICE-IPPE and EMPIRE-II were used for calculating the excitation functions theoretically. Integral yields of the radionuclides110gIn,111In,113mIn and116m1In were also calculated.
Elective single embryo transfer
Authors: Kosmas Ioannis , Van der Elst Jossiane , Devroey Paul , Tournaye Herman 
Published: July 2008

Elective single embryo transfer has been implemented in Belgium and Scandinavian countries to decrease the incidence of twin pregnancy and the associated complications.
The extra cost associated with achieving an equal number of pregnancies through elective single embryo transfer needs to be considered in the context of any additional neonatal care expenses associated with double embryo transfer.
Acceptable ongoing pregnancy and delivery rates have been obtained when comparing single with double embryo transfer.
Maternal age, previous attempts, day of embryo transfer and cost should be taken into account.

Learning objectives:

To understand the issues raised when helping a couple choose single or double embryo transfer.

Ethical issues:

Where does patient autonomy over treatment end and national regulation begin?
The management of obstetric complications and the long‐term sequelae of premature birth should be factored in when considering treatment costs.

Please cite this article as: Kosmas I, Van der Elst J, Devroey P, Tournaye H. Elective single embryo transfer. The Obstetrician & Gynaecologist 2008;10:163–169.
Assessing the risks of persistent organic pollutants to top predators: A review of approaches
Authors: Leonards Pim EG , van Hattum Bert , Leslie Heather 
Published: July 2008

Abstract
Accurate risk assessment of secondary poisoning by persistent organic pollutants (POPs) in top predators is possible but requires multidisciplinary input from wildlife ecology, ecotoxicology, and analytical chemistry. Because of the transfer of POPs up the food chain, traditional approaches to exposure assessment based on POPs in abiotic compartments or organisms low in the food chain can make the assessment of risk to top predators complicated. For more direct, accurate, and site-specific methods of assessing the risks of secondary poisoning of top predator by POPs, we classify 2 main approaches: diet based and tissue based. Exposure assessment via the diet-based approach requires samples of the predator's diet and measured concentrations in the prey items, realistic estimates of dietary composition, and ingestion rates. The even more direct, tissue-based approach uses measured POP concentrations in tissues of top predators to determine internal exposure coupled with tissue-based effect concentrations (or biological responses measured via biomarkers) to determine risk. The advantage of these methods is that uncertain estimates of POPs transfer to top predators from lower trophic levels are avoided. In practice, the availability of dose-response data and internal exposure-response relationships for POPs in top predators is limited, so these may have to be extrapolated from surrogate species. In this paper we illustrate and evaluate the potential of diet-based and tissue-based risk assessment approaches with case studies and demonstrate that appropriate methodologies significantly reduce the uncertainty in risk assessments of POPs.
Mental Health in Sumatra After the Tsunami
Authors: Frankenberg Elizabeth , Friedman Jed , Gillespie Thomas , Ingwersen Nicholas , Pynoos Robert , Rifai Iip Umar , Sikoki Bondan , Steinberg Alan , Sumantri Cecep , Suriastini Wayan , Thomas Duncan 
Published: July 2008

Objectives. We assessed the levels and correlates of posttraumatic stress reactivity (PTSR) of more than 20000 adult tsunami survivors by analyzing survey data from coastal Aceh and North Sumatra, Indonesia. Methods. A population-representative sample of individuals interviewed before the tsunami was traced in 2005 to 2006. We constructed 2 scales measuring PTSR by using 7 symptom items from the Post Traumatic Stress Disorder (PTSD) Checklist–Civilian Version. One scale measured PTSR at the time of interview, and the other measured PTSR at the point of maximum intensity since the disaster. Results. PTSR scores were highest for respondents from heavily damaged areas. In all areas, scores declined over time. Gender and age were significant predictors of PTSR; markers of socioeconomic status before the tsunami were not. Exposure to traumatic events, loss of kin, and property damage were significantly associated with higher PTSR scores. Conclusions. The tsunami produced posttraumatic stress reactions across a wide region of Aceh and North Sumatra. Public health will be enhanced by the provision of counseling services that reach not only people directly affected by the tsunami but also those living beyond the area of immediate impact.
Process Is the Point
Authors: Gruskin Sofia , Daniels Norman 
Published: July 2008

Most people responsible for setting priorities in health have considerable expertise relevant to deciding how to use resources effectively and the kinds of improvements that should be emphasized. Most are also concerned with distributing improvements equitably. Accordingly, they often invoke human rights or principles of distributive justice to legitimize choices that create winners and losers. We propose an approach that draws on the strengths of both perspectives as a way to add legitimacy to efforts to set priorities in health. Our proposal provides a process for setting priorities but is not a formula or an algorithm for generating particular priorities. We propose an approach that would do away with the process through which priorities are set and decisions made, and suggest the value of a focus on the process of legitimizing these decisions.
Legal and Public Health Considerations Affecting the Success, Reach, and Impact of Menu-Labeling Laws
Authors: Pomeranz Jennifer L. , Brownell Kelly D. 
Published: July 2008

Because the rate of consumption of away-from-home meals has increased dramatically, the distinction between requiring nutrition information for packaged but not restaurant products is no longer reasonable. Public health necessitates that nutrition labels must be included with restaurant menus as a strategy to educate consumers and address the escalation of obesity. Menu-labeling laws are being considered at the local, state, and federal levels, but the restaurant industry opposes such action. We discuss the public health rationale and set forth the government’s legal authority for the enactment of menu-labeling laws. We further aim to educate the public health community of the potential legal challenges to such laws, and we set forth methods for governments to survive these challenges by drafting laws according to current legal standards.
Building and Sustaining a Multiuniversity and Multicampus Program or School of Public Health
Authors: Greenberg Michael R. , Gotsch Audrey , Rhoads George , Schneider Dona 
Published: July 2008

Drawing from New Jersey’s successful efforts and from other less successful efforts, we offer lessons learned for those who will consider a multiuniversity and multi-campus program or school of public health. These lessons include building a faculty collaboration, senior administrative support, and external constituencies and developing a set of documents that institutionalize processes, logistics, and other operations. In our experience, building and sustaining faculty support is the greatest challenge, followed by protecting existing resources and securing additional resources when administrators in the host universities change.
Time Series Analysis of Spontaneous Upper-Extremity Movements of Premature Infants With Brain Injuries
Authors: Ohgi Shohei , Morita Satoru , Loo Kek Khee , Mizuike Chihiro 
Published: July 2008

Background and Purpose
Comparisons of spontaneous movements of premature infants with brain injuries and those without brain injuries can provide insights into normal and abnormal processes in the ontogeny of motor development. In this study, the characteristics of spontaneous upper-extremity movements of premature infants with brain injuries and those without brain injuries were examined with time series analysis.

Subjects
Participants were 7 premature infants with brain injuries and 7 matched, low-risk, premature infants at the age of 1 month after term.

Methods
A triaxial accelerometer was used to measure upper-extremity limb acceleration in 3-dimensional space. Acceleration signals were recorded from the right wrist when the infant was in an active, alert state and lying in the supine position. The recording time was 200 seconds. The acceleration signal was sampled at a rate of 200 Hz. The acceleration time series data were analyzed by nonlinear analysis as well as linear analysis.

Results
The nonlinear time series analysis indicated that spontaneous movements of premature infants have nonlinear, chaotic, dynamic characteristics. The movements of the infants with brain injuries were characterized by larger dimensionality, and they were more unstable and unpredictable than those of infants without brain injuries.

Discussion and Conclusion
As determined by nonlinear analysis, the spontaneous movements of the premature infants with brain injuries had the characteristics of increased disorganization compared with those of the infants without brain injuries. Infants with brain injuries may manifest problems with self-organization as a function of the coordination of subsystems. Physical therapists should be able to support interactions among the subsystems and promote self-organization of motor learning through the individualized provision of various sensorimotor experiences for infants.
Activating *CO by Strengthening Fe–CO π‐Backbonding to Enhance Two‐Carbon Products Formation toward CO2 Electroreduction on Fe–N4 Sites
Authors: Zhu Weiwei , Liu Suqin , Zhao Kuangmin , Su Yuke , Yang Yuliang , Huang Kui , He Zhen 
Published: April 2024

AbstractMany non‐precious metal‐nitrogen (M–Nx)‐containing catalysts are highly efficient for electrochemical reduction of CO2 to CO and yet encounter challenges in further converting CO to more valuable two‐carbon products (C2), such as ethanol and acetic acid. The ambiguous structure‐activity relationship of the M–Nx moieties toward CO2 reduction reaction (CO2RR) results in difficulties in regulating the CO2RR product selectivity on the M–Nx‐containing catalysts. Herein, by using fluorinated iron phthalocyanines with axial‐coordinated ligands (L–FePc–F) as an M–N4‐based model electrocatalyst for CO2RR, a correlation between the electronic structure and C2 selectivity of Fe–N4 is revealed and a comprehensive descriptor based on the Fe–CO π‐backbonding is proposed for guiding the regulation of M–N4 toward higher C2 selectivity. Based on the regulation principle, the Br‐axial‐coordinated FePc–F (Br–FePc–F) remarkably increases the Faradic efficiency (FE) of C2 products from 0% (i.e., the FEC2 of FePc–F) to 34% due to the strengthened Fe–CO π‐backbonding stemming from the elevated 3dxz/dyz orbital energy and enhanced electron‐donating ability of the Fe centers of Fe–N4. This work provides a strategy and mechanism insights on the regulation of the C2 selectivity of CO2RR on the Fe–N4 moieties, which may be inspiring for precise construction and regulation of the M–Nx‐containing catalysts for specific CO2RR products.