Does "ichthyosis uteri" have malignant potential? : A case report of squamous cell carcinoma of endometrium associated with extensive ichthyosis uteri

This short report discusses a case of solitary colonic polypoid ganglioneuroma associated with melanosis coli in a woman with no systemic manifestations. To our knowledge this is the first ganglioneuroma reported in the literature in association with melanosis coli. The nature and significance of this event remains unclear, although this may be coincidental due to the laxative intake. Further investigation is necessary to clarify this point. The interest of this case lies moreover in the rarity of this entity and its endoscopic and histologic resemblance to sessile polyps frequent in the clinical practice.     

NOV story: the way to CCN3

The principal aim of this historical review- the first in a new series- is to present the basic concepts that led to the discovery of NOV and to show how our ideas evolved regarding the role and functions of this new class of proteins. It should prove particularly useful to the new comers and to students who are engaged in this exciting field. It is also a good opportunity to acknowledge the input of those who participated in the development of this scientific endeavour     

Multi-functional T-DNA/Ds tomato lines designed for gene cloning and molecular and physical dissection of the tomato genome

In order to make the tomato genome more accessible for molecular analysis and gene cloning, we have produced 405 individual tomato (Lycopersicon esculentum) lines containing a characterized copy of pJasm13, a multifunctional T-DNA/modifiedDs transposon element construct. Both the T-DNA and the Ds element in pJasm13 harbor a set of selectable marker genes to monitor excision and reintegration of Ds and additionally, target sequences for rare cutting restriction enzymes (I-PpoI, SfiI, NotI) and for site-specific recombinases (Cre, FLP, R). Blast analysis of flanking genomic sequences of 174 T-DNA inserts revealed homology to transcribed genes in 69 (40%), of which about half are known or putatively identified as genes and ESTs. The map position of 140 individual inserts was determined on the molecular genetic map of tomato. These inserts are distributed over the 12 chromosomes of tomato, allowing targeted and non-targeted transposon tagging, marking of closely linked genes of interest and induction of chromosomal rearrangements including translocations or creation of saturation-deletions or inversions within defined regions linked to the T-DNA insertion site. The different features of pJasm13 were successfully tested in tomato and Arabidopsis thaliana, thus providing a new tool for molecular/genetic dissection studies, including molecular and physical mapping, mutation analysis and cloning strategies in tomato and potentially, in other plants as well.Equal contributors to this workEqual contributors to this workEqual contributors to this workEqual contributors to this workEqual contributors to this workEqual contributors to this workEqual contributors to this workEqual contributors to this workEqual contributors to this workEqual contributors to this workEqual contributors to this workEqual contributors to this work     

Liposomes surface conjugated with human hemoglobin target delivery to macrophages

Current strategies to deliver therapeutic molecules to specific cell and tissue types rely on conjugation of antibodies and other targeting ligands directly to the therapeutic molecule itself or its carrier. This work describes a novel strategy to deliver therapeutic molecules into macrophages that takes advantage of the native hemoglobin (Hb) scavenging activity of plasma haptoglobin (Hp) and the subsequent uptake of the Hb-Hp complex into macrophages via CD163 receptor-mediated endocytosis. The drug delivery system described in this work consists of Hb decorated liposomes that can encapsulate any therapeutic molecule of interest, in this case the model fluorescent dye calcein was used in this study. The results of this study clearly demonstrate that this delivery system is specific towards macrophages and demonstrates the feasibility of using this approach in targeted drug delivery.     

Bone marrow suppression and severe anaemia associated with persistent Plasmodium falciparum infection in African children with microscopically undetectable parasitaemia

In sub-Saharan Africa the highest overlap between malaria and HIV infections occurs in female adolescents. Yet control activities for these infections are directed to different target groups, using disparate channels. This reflects the lack of priority given to adolescents and the absence of an accepted framework for delivering health and health-related interventions to this high-risk group. In this paper it is argued that female adolescents require a continuum of care for malaria and HIV – prior to conception, during and after pregnancy and that this should be provided through adolescent services. The evidence for this conclusion is presented. A number of African countries are commencing to formulate and implement adolescent-friendly policies and services and disease control programs for malaria and HIV will need to locate their interventions within such programs to ensure widespread coverage of this important target group. Failure to prioritize adolescent health in this way will seriously limit the success of disease control programs for malaria and HIV prevention.     

An Atg13 protein-mediated self-association of the Atg1 protein kinase is important for the induction of autophagy

Autophagy pathways in eukaryotic cells mediate the turnover of a diverse set of cytoplasmic components, including damaged organelles and abnormal protein aggregates. Autophagy-mediated degradation is highly regulated, and defects in these pathways have been linked to a number of human disorders. The Atg1 protein kinase appears to be a key site of this control and is targeted by multiple signaling pathways to ensure the appropriate autophagic response to changing environmental conditions. Despite the importance of this kinase, relatively little is known about the molecular details of Atg1 activation. In this study we show that Atg13, an evolutionarily conserved regulator of Atg1, promotes the formation of a specific Atg1 self-interaction in the budding yeast, Saccharomyces cerevisiae. The appearance of this Atg1-Atg1 complex is correlated with the induction of autophagy, and conditions that disrupt this complex result in diminished levels of both autophagy and Atg1 kinase activity. Moreover, the addition of a heterologous dimerization domain to Atg1 resulted in elevated kinase activity both in vivo and in vitro. The formation of this complex appears to be an important prerequisite for the subsequent autophosphorylation of Thr-226 in the Atg1 activation loop. Previous work indicates that this modification is necessary and perhaps sufficient for Atg1 kinase activity. Interestingly, this Atg1 self-association does not require Atg17, suggesting that this second conserved regulator might activate Atg1 in a manner mechanistically distinct from that of Atg13. In all, this work suggests a model whereby this self-association stimulates the autophosphorylation of Atg1 within its activation loop.     

A potential model for early stages of chromosomal evolution via concentric Robertsonian fans: a large area of polymorphism in southern short-tailed shrews (Blarina carolinensis)

Western Tennessee contains unusually highly polymorphic populations of southern short-tailed shrews (Blarina carolinensis). We previously documented eight Robertsonian translocations (ROBs) accounting for a variation in diploid number from 46 in most of this species' range to 34-40 in western Tennessee. We have now expanded our study to include data from adjacent areas in Tennessee and Mississippi, 10 localities in all. The new data show a variation in diploid number ranging from 31 to 41, four new ROBs (for a total of 12), and the novel finding of monobrachial translocations in this group. All animals collected from this large area (extending over 12, 000 km(2)) had some level of ROBs, and none represented the 2n = 46 form seen in other parts of the range of this species. Because other species of shrews (genus Sorex) are not affected in the same area, the factors and/or selective forces causing this extensive polymorphism in B. carolinensis must be unique to this species and to this geographic area. Some ROBs were found throughout this large area of over 12,000 km(2). Other translocations (including those with monobrachial homology) were located in one or two localities in this large area, and still other translocations were intermediate in their distribution. There was a concentric pattern to the evolution and presumed spreading of the ROBs. This allowed us to expand the concept of a Robertsonian "fan," introduced by Matthey (1970), to that of concentric evolution of multiple fusion fans: ROBs likely arose independently, separated temporally and geographically, and radiated into surrounding populations to create this complex zone of polymorphism. This is an active process in its infancy, and it is not as mature as that seen in European studies of Mus and Sorex.     

Theory of cooperative transitions in protein molecules. I. Why denaturation of globular protein is a first-order phase transition

A theory of equilibrium denaturation of proteins is suggested. According to this theory, a cornerstone of protein denaturation is disruption of tight packing of side chains in protein core. Investigation of this disruption is the object of this paper. It is shown that this disruption is an "all-or-none" transition (independent of how compact is the denatured state of a protein and independent of the protein-solvent interactions) because expansion of a globule must exceed some threshold to release rotational isomerization of side chains. Smaller expansion cannot produce entropy compensation of nonbonded energy loss; this is the origin of a free-energy barrier (transition state) between the native and denatured states. The density of the transition state is so high that the solvent cannot penetrate into protein in this state. The results obtained in this paper make it possible to present in the following paper a general phase diagram of protein molecule in solution.     

A step toward barcoding life: a model-based, decision-theoretic method to assign genes to preexisting species groups

A major part of the barcoding of life problem is assigning newly sequenced or sampled individuals to existing groups that are preidentified externally (by a taxonomist, for example). This problem involves evaluating the statistical evidence towards associating a sequence from a new individual with one group or another. The main concern of our current research is to perform this task in a fast and accurate manner. To accomplish this we have developed a model-based, decision-theoretic framework based on the coalescent theory. Under this framework, we utilized both distance and the posterior probability of a group, given the sequences from members of this group and the sequence from a newly sampled individual to assign this new individual. We believe that this approach makes efficient use of the available information in the data. Our preliminary results indicated that this approach is more accurate than using a simple measure of distance for assignment.     

Teaching "Species"

A clear understanding of the term "species" is fundamental to the subject of evolution. However, introductory textbooks often fail to address this topic until one of the later chapters, after having used the term species in all preceding chapters. Furthermore, definitions of terms critical to a clear understanding of this subject are often vague or absent in chapters on species concepts. We feel the popular notion of a "species problem" has been unnecessarily inflated by this less-than-effective educational approach. Clearly addressing this essential subject at the beginning of a course on evolution will prepare students to learn the details and complexities of evolution. Here we provide the background for an alternative approach to this foundational topic, followed by an outlined lesson plan. We emphasize early introduction of this subject in texts and courses using unambiguous terminology and including the historical development of species concepts.     

盾壳霉在油菜菌核病菌生物防治中的应用

油菜核病菌(Sclerotiniasclerotiorum)是一种世界性病原菌,其分布广、危害大、难根治。盾壳霉(Coniothyriumminitans)是该病原菌的破坏性寄生真菌,可以有效、专一地降低病原菌菌核的形成与萌发,在该病原菌的生物防治方面具有较大的应用潜力。从油菜核盘菌的致病过程与特点、盾壳霉的生长特性、盾壳霉和油菜核盘菌间相互作用的规律及途径等几个方面阐述了盾壳霉对油菜核盘菌的生防特性,讨论了盾壳霉在生产实践中的应用潜力及存在问题,并提出了一些解决问题的可能途径及需要进一步研究的内容与方向 。     

History of methods for estimating body height by skeletal findings. Recommendations for estimating body height by skeletal findings up to the middle of the 20th century

Up to now no historical review concerning the methods to estimate body height from skeletons has been given. As well no collection of the formulae relevant to this subject, which would save laborious search in the wide-scattered literature, is available hitherto. This study tries to fill this gap. The anthropological and statistical treatment of the populations under study will not be discussed in this connection, because this has to be left to a separate study.     

The role of a beta-bulge in the folding of the beta-hairpin structure in ubiquitin

It is known that the peptide corresponding to the N-terminal beta-hairpin of ubiquitin, U(1-17), can populate the monomeric beta-hairpin conformation in aqueous solution. In this study, we show that the Gly-10 that forms the bulge of the beta-turn in this hairpin is very important to the stability of the hairpin. The deletion of this residue to desG10(1-16) unfolds the structure of the peptide in water. Even under denaturing conditions, this bulge appears to be important in maintaining the residual structure of ubiquitin, which involves tertiary interactions within the sequence 1 to 34 in the denatured state. We surmise that this residual structure functions as one of the nucleation centers in the folding process and is important in stabilizing the transition state. In accordance with this idea, deleting Gly-10 slows down the refolding and unfolding rate by about one half.     

The sodium pump. Its molecular properties and mechanics of ion transport.

The sodium pump (Na(+)/K(+)-ATPase; sodium- and potassium-activated adenosine 5'-triphosphatase; EC 3.6.1.37) has been under investigation for more than four decades. During this time, the knowledge about the structure and properties of the enzyme has increased to such an extent that specialized groups have formed within this field that focus on specific aspects of the active ion transport catalyzed by this enzyme. Taking this into account, this review, while somewhat speculative, is an attempt to summarize the information regarding the enzymology of the sodium pump with the hope of providing to interested readers from outside the field a concentrated overview and to readers from related fields a guide in their search for gathering specific information concerning the structure, function, and enzymology of this enzyme.     

Genetic identification of hybrid camelids

North American zoos in 1984 had the first opportunity in many years to obtain South American camelids after a long embargo on imports. The Rio Grande Zoo in Albuquerque, New Mexico, purchased two alpacas and one presumptive llama during this period. The llama, however, appeared to be phenotypically intermediate between a llama and an alpaca. In an attempt to ascertain the identity of this animal, it and purebred individuals of llama and alpaca were compared at 22 presumptive genic loci using starch-gel electrophoresis. Genic differences between llama and alpaca suggest this animal to be a hybrid. If further tests prove consistent with the findings of this study, this technique will provide a simple assay using easily obtained blood for identifying llama and alpaca. The use of genetic management techniques such as this in zoos holds great potential for helping to preserve pure breeding lines of closely related interfertile animals.     

Synthesis of 4-azasteroids by an intramolecular Ugi reaction

In this paper we report the use of an intramolecular Ugi reaction to synthesize new 4-azacholestanes diversely substituted both at N-4 and C-5. Both the scope and the stereochemical outcome of this approach were studied by varying the nature of the components necessary for this multicomponent reaction. In sight of our results we concluded that this methodology can be applied to obtain 4-azasteroids targeted to find new biologically active compounds.     

Social-ecological Resilience Modeling: Water Stress Effects in the Bighorn Sheep Management System in Baja California Sur,Mexico

Bighorn sheep (Ovis canadensis) management involves ecological and socioeconomic aspects, creating a social-ecological system (SES). Social-ecological thresholds can be identified in the system to assess its specific resilience in response to climate stressors. Thus, the aim of this study is to build a dynamic model to assess whether this system is resilient to a particular stressor (water stress). In this study, the SES is considered resilient if the bighorn population is sufficiently large to provide economic revenue to landowners and promote conservation action. We validate and formalize this model by conducting semistructured interviews to Bonfil ejido landowners located in Baja California Sur (BCS), Mexico, and to experts in the field of recreational hunting and wildlife management. To explore the changes in specific resilience in this SES, we conduct simulations to assess the impact of rainfall variability patterns on the system. Our results indicate that rainfall variations with respect to the historical record have the potential to disrupt both the species and the local economy and that the lack of adaptive capacity in both harvest and conservation strategies may affect the dynamics of the whole SES. Finally, this paper explores how adaptive wildlife conservation management strategies can enhance the resilience of both subsystems in this SES.     

The effects of temperature upon the toxicity of chemicals to aquatic organisms

Although rather extensive bibliographies give the impression that there is a vast amount of literature on the effects of temperature on aquatic organisms, when one tries to apply this information to specific interactions, such as the effects of temperature changes on chemical toxicity to aquatic organisms, often very little of the evidence is applicable. Although the most useful information on this relationship has been acquired in laboratory situations even this body of literature (which forms the bulk of this paper) is not adequate to make any scientifically justifiable generalizations. Field data on this relationship is almost non-existent and it is unlikely that much will become available unless specific studies are initiated which are directed toward this end. This is equally true of the laboratory information although it seems more likely that this will be generated as a spinoff from other research activities. In order to develop water quality management programs for steam-electric power plants one should understand the relationship between temperature and the response of aquatic organisms to toxic chemicals. Not only do some power plants discharge chlorine and other similar materials as well as heated waste water but those that discharge the latter only may be located near discharges of toxic chemicals. Since temperature and chemical stress to aquatic organisms are most commonly discussed independently we felt a paper covering this relationship would be useful.     

Melanization immune responses in mosquito vectors

The production and deposition of melanin pigments on invading pathogens and parasites represents a unique, innate immune response in the phylum Arthropoda. This immune response has started to receive considerable attention because of the potential to exploit this mechanism to control mosquito-borne diseases. In this article, we summarize knowledge about this complex biochemistry, the use of melanin biosynthesis in diverse physiological processes and the gaps in knowledge that must be addressed if this immune process is to be manipulated in genetic-based control strategies.     

Information Filtering via Heterogeneous Diffusion in Online Bipartite Networks

The rapid expansion of Internet brings us overwhelming online information, which is impossible for an individual to go through all of it. Therefore, recommender systems were created to help people dig through this abundance of information. In networks composed by users and objects, recommender algorithms based on diffusion have been proven to be one of the best performing methods. Previous works considered the diffusion process from user to object, and from object to user to be equivalent. We show in this work that it is not the case and we improve the quality of the recommendation by taking into account the asymmetrical nature of this process. We apply this idea to modify the state-of-the-art recommendation methods. The simulation results show that the new methods can outperform these existing methods in both recommendation accuracy and diversity. Finally, this modification is checked to be able to improve the recommendation in a realistic case.