Evolution of Enzyme Superfamilies: Comprehensive Exploration of Sequence-Function Relationships.

The sequence and functional diversity of enzyme superfamilies have expanded through billions of years of evolution from a common ancestor. Understanding how protein sequence and functional "space" have expanded, at both the evolutionary and molecular level, is central to biochemistry, molecular biology, and evolutionary biology. Integrative approaches that examine protein sequence, structure, and function have begun to provide comprehensive views of the functional diversity and evolutionary relationships within enzyme superfamilies. In this review, we outline the recent advances in our understanding of enzyme evolution and superfamily functional diversity. We describe the tools that have been used to comprehensively analyze sequence relationships and to characterize sequence and function relationships. We also highlight recent large-scale experimental approaches that systematically determine the activity profiles across enzyme superfamilies. We identify several intriguing insights from this recent body of work. First, promiscuous activities are prevalent among extant enzymes. Second, many divergent proteins retain "function connectivity" via enzyme promiscuity, which can be used to probe the evolutionary potential and history of enzyme superfamilies. Finally, we discuss open questions regarding the intricacies of enzyme divergence, as well as potential research directions that will deepen our understanding of enzyme superfamily evolution.

Detection of seed DNA in regurgitates of granivorous carabid beetles.

Granivory can play a pivotal role in influencing regeneration, colonization as well as abundance and distribution of plants. Due to their high abundance, nutrient content and longevity, seeds are an important food source for many animals. Among insects, carabid beetles consume substantial numbers of seeds and are thought to be responsible for a significant amount of seed loss. However, the processes that govern which seeds are eaten and are therefore prevented from entering the seedbank are poorly understood. Here, we assess if DNA-based diet analysis allows tracking the consumption of seeds by carabids. Adult individuals of Harpalus rufipes were fed with seeds of Taraxacum officinale and Lolium perenne allowing them to digest for up to 3 days. Regurgitates were tested for the DNA of ingested seeds at eight different time points post-feeding using general and species-specific plant primers. The detection of seed DNA decreased with digestion time for both seed species, albeit in a species-specific manner. Significant differences in overall DNA detection rates were found with the general plant primers but not with the species-specific primers. This can have implications for the interpretation of trophic data derived from next-generation sequencing, which is based on the application of general primers. Our findings demonstrate that seed predation by carabids can be tracked, molecularly, on a species-specific level, providing a new way to unravel the mechanisms underlying in-field diet choice in granivores.

Detyrosinated tubulin is decreased in fetal vessels of preeclampsia placentas.

INTRODUCTION: Preeclampsia is a hypertensive, gestational disease, which is still the leading cause of pregnancy related morbidity and mortality. The impairment of placental angiogenesis and vascularization is discussed to be of etiopathologic relevance. Deytrosination and tyrosination of α-tubulin is important for the stability and dynamics of microtubules. An increase of α-tubulin detyrosination leads to microtubule stabilization, which is an essential prerequisite for physiologic vascular tube morphogenesis during angiogenesis. So far, little is known about the specific localization of detyrosinated (detyr) and tyrosinated (tyr) tubulin in the placenta and its relevance for preeclampsia. METHODS: Placental expression of detyr- and tyr-tubulin was analyzed by immunohistochemistry, immunofluorescence and western blot. For western blot quantification we used biopsies from healthy placentas (n = 21) and placentas from pregnancies complicated with small for gestational age (n = 5), preeclampsia (n = 5) or both (n = 5). RESULTS: Specific placental localization of detyr-tubulin was detected in the fetal endothelial cells of the placenta. Villous and extravillous trophoblasts as well as villous stroma cells were tyr-tubulin positive. Detyr-tubulin protein expression was significantly decreased in placentas complicated by preeclampsia. CONCLUSIONS: In summary, we report an accumulation of detyr-tubulin in villous vessels of the placenta and a significantly reduced level of detyr-tubulin in placental biopsies of preeclampsia cases. The reduction of placental detyr-tubulin in preeclampsia could suggest a deficit in villous vascular plasticity and might be associated with the impaired arborization of the disease.

The International Endometriosis Evaluation Program (IEEP Study) - A Systematic Study for Physicians, Researchers and Patients.

INTRODUCTION: Endometriosis is a heterogeneous disease characterized by a range of different presentations. It is usually diagnosed when patients present with pain and/or infertility, but it has also been diagnosed in asymptomatic patients. Because of the different diagnostic approaches and diverse therapies, time to diagnosis can vary considerably and the definitive diagnosis may be delayed, with some cases not being diagnosed for several years. Endometriosis patients have many unmet needs. A systematic registration and follow-up of endometriosis patients could be useful to obtain an insight into the course of the disease. The validation of biomarkers could contribute to the development of diagnostic and predictive tests which could help select patients for surgical assessment earlier and offer better predictions about patients who might benefit from medical, surgical or other interventions. The aim is also to obtain a better understanding of the etiology, pathogenesis and progression of the disease. MATERIAL AND METHODS: To do this, an online multicenter documentation system was introduced to facilitate the establishment of a prospective multicenter case-control study, the IEEP (International Endometriosis Evaluation Program) study. We report here on the first 696 patients with endometriosis included in the program between June 2013 and June 2015. RESULTS: A documentation system was created, and the structure and course of the study were mapped out with regard to data collection and the collection of biomaterials. CONCLUSION: The documentation system permits the history and clinical data of patients with endometriosis to be recorded. The IEEP combines this information with biomaterials and uses it for scientific studies. The recorded data can also be used to evaluate clinical quality control measures such as the certification parameters used by the EEL (European Endometriosis League) to assess certified endometriosis centers.

Implications of the consolidated Omnibus Budget Reconciliation "antidumping" legislation for emergency nurses.

Although the original intent of the law is to protect the indigent, the statute applies to any situation in which a patient is denied care or transferred to another facility before being medically stabilized. The data thus far indicate that financial motives may be only partially responsible for alleged COBRA violations and that other health care system issues are involved. Patient "dumping" may become better camouflaged against federal and state scrutiny, but until these other issues are identified and addressed dumping may continue to occur for a variety of reasons. To avoid the appearance of dumping, the emergency nurse and physician should meticulously record all aspects of every patient transfer. Particular attention should be given to documenting patient stability at the time of transfer, the risks versus benefits of the transfer, and the communication with and acceptance of the patient by the receiving facility. Emergency nurses, directors of nursing, and nursing quality assurance or risk managers should all be familiar with the COBRA requirements. For further information on the interpretation and application of COBRA, contact your state's acute care facility licensing authority or one of the HCFA Regional Offices listed in the Appendix.

Study of an order-disorder phase transition on an atomic scale: the example of decagonal Al-Ni-Co quasicrystals.

In the present paper we succeeded in studying structural phase transitions from an atomistic point of view by positron annihilation Doppler broadening. This differs and is complementary to conventionally used diffraction experiments with large coherence lengths. In the exemplary case of the 1140 K order-disorder transition in decagonal Al71.5Ni14Co14.5 quasicrystals the importance of this atomistic approach and its wide scope of application is demonstrated.

Use of a guide wire and a ureteral dilator as an aid to awake fibreoptic intubation.

We describe the successful use of a guide wire and ureteral dilator to pass a tracheal tube into the trachea through the mouth in an awake, sedated patient when attempts to pass a larger tube over an Olympus LF1 fibreoptic bronchoscope were unsuccessful. Since the ureteral and renal dilators are available in a variety of sizes, if too large a tube is inadvertently mounted on the instrument this technique allows an appropriate sized tube to be inserted without the need to re-endoscope the patient.