Functional organization of TRPC-Ca2+ channels and regulation of calcium microdomains

TRP family of proteins are components of unique cation channels that are activated in response to diverse stimuli ranging from growth factor and neurotransmitter stimulation of plasma membrane receptors to a variety of chemical and sensory signals. This review will focus on members of the TRPC sub-family (TRPC1-TRPC7) which currently appear to be the strongest candidates for the enigmatic Ca(2+) influx channels that are activated in response to stimulation of plasma membrane receptors which result in phosphatidyl inositol-(4,5)-bisphosphate (PIP(2)) hydrolysis, generation of IP(3) and DAG, and IP(3)-induced Ca(2+) release from the intracellular Ca(2+) store via inositol trisphosphate receptor (IP(3)R). Homomeric or selective heteromeric interactions between TRPC monomers generate distinct channels that contribute to store-operated as well as store-independent Ca(2+) entry mechanisms. The former is regulated by the emptying/refilling of internal Ca(2+) store(s) while the latter depends on PIP(2) hydrolysis (due to changes in PIP(2) per se or an increase in diacylglycerol, DAG). Although the exact physiological function of TRPC channels and how they are regulated has not yet been conclusively established, it is clear that a variety of cellular functions are controlled by Ca(2+) entry via these channels. Thus, it is critical to understand how cells coordinate the regulation of diverse TRPC channels to elicit specific physiological functions. It is now well established that segregation of TRPC channels mediated by interactions with signaling and scaffolding proteins, determines their localization and regulation in functionally distinct cellular domains. Furthermore, both protein and lipid components of intracellular and plasma membranes contribute to the organization of these microdomains. Such organization serves as a platform for the generation of spatially and temporally dictated [Ca(2+)](i) signals which are critical for precise control of downstream cellular functions.     

Comparison,alignment, and synchronization of cell line information between CLO and EFO

Background

The Experimental Factor Ontology (EFO) is an application ontology driven by experimental variables including cell lines to organize and describe the diverse experimental variables and data resided in the EMBL-EBI resources. The Cell Line Ontology (CLO) is an OBO community-based ontology that contains information of immortalized cell lines and relevant experimental components. EFO integrates and extends ontologies from the bio-ontology community to drive a number of practical applications. It is desirable that the community shares design patterns and therefore that EFO reuses the cell line representation from the Cell Line Ontology (CLO). There are, however, challenges to be addressed when developing a common ontology design pattern for representing cell lines in both EFO and CLO.

Results

In this study, we developed a strategy to compare and map cell line terms between EFO and CLO. We examined Cellosaurus resources for EFO-CLO cross-references. Text labels of cell lines from both ontologies were verified by biological information axiomatized in each source. The study resulted in the identification 873 EFO-CLO aligned and 344 EFO unique immortalized permanent cell lines. All of these cell lines were updated to CLO and the cell line related information was merged. A design pattern that integrates EFO and CLO was also developed.

Conclusion

Our study compared, aligned, and synchronized the cell line information between CLO and EFO. The final updated CLO will be examined as the candidate ontology to import and replace eligible EFO cell line classes thereby supporting the interoperability in the bio-ontology domain. Our mapping pipeline illustrates the use of ontology in aiding biological data standardization and integration through the biological and semantics content of cell lines.

     

The photosynthetic pathway of the roots of twelve epiphytic orchids with CAM leaves

The photosynthetic pathway of the roots (both the white velamentous main portions and the green, nonvelamentous tips) was investigated in twelve taxa (natural species and intergeneric hybrid cultivars) of epiphytic orchids having CAM leaves. All organs contained chlorophyll, and the a/b ratios indicate that the organs, especially the roots, are likely shade-adapted. Stable carbon isotope ratios of the tissues were near −15‰ for all organs, a value typical of obligate (constitutive) CAM plants. Values for root tissues were slightly lower (more negative) than those of the leaves. The presence of CAM in the leaves of these orchids did not ensure that their roots performed CAM photosynthesis. Further work is needed to address the questions raised in this study and to determine if the photosynthetic roots of these taxa are capable of assimilating atmospheric CO₂.     

Molecular variants of human papillomavirus type 16 from four continents suggest ancient pandemic spread of the virus and its coevolution with humankind.

We have amplified by the polymerase chain reaction, cloned, and sequenced genomic segments of 118 human papillomavirus type 16 (HPV-16) isolates from 76 cervical biopsy, 14 cervical smear, 3 vulval biopsy, 2 penile biopsy, 2 anal biopsy, and 1 vaginal biopsy sample and two cell lines. The specimens were taken from patients in four countries--Singapore, Brazil, Tanzania, and Germany. The sequence of a 364-bp fragment of the long control region of the virus revealed 38 variants, most of which differed by one or several point mutations. Phylogenetic trees were constructed by distance matrix methods and a transformation series approach. The trees based on the long control region were supported by another set based on the complete E5 protein-coding region. Both sets had two main branches. Nearly all of the variants from Tanzania were assigned to one (African) branch, and all of the German and most of the Singaporean variants were assigned to the other (Eurasian) branch. While some German and Singaporean variants were identical, each group also contained variants that formed unique branches. In contrast to the group-internal homogeneity of the Singaporean, German, and Tanzanian variants, the Brazilian variants were clearly divided between the two branches. Exceptions to this were the seven Singaporean isolates with mutational patterns typical of the Tanzanian isolates. The data suggest that HPV-16 evolved separately for a long period in Africa and Eurasia. Representatives of both branches may have been transferred to Brazil via past colonial immigration. The comparable efficiencies of transfer of the African and the Eurasian variants to the New World suggest pandemic spread of HPV-16 in past centuries. Representatives of the African branch were possibly transferred to the Far East along old Arab and Indonesian sailing routes. Our data also support the view that HPV-16 is a well-defined virus type, since the variants show only a maximal genomic divergence of about 5%. The small amount of divergence in any one geographic location and the lack of marked divergence between the Tanzanian and Brazilian African genome variants two centuries after their likely introduction into the New World suggest a very slow rate of viral evolution. The phylogenetic tree therefore probably represents a minimum of several centuries of evolution, if not an age equal to that of the respective human races.     

Protein Composition and Biomedical Potential of the Skin Secretion of Hylarana erythraea (Schlegel, 1837) (Anura: Ranidae) from Langkawi Archipelago,Kedah, Peninsular Malaysia

International Journal of Peptide Research and Therapeutics - The skin secretion of amphibians is known for its high content of bioactive compounds. These bioactive compounds are essential for the...     

Detecting and Characterizing Genomic Signatures of Positive Selection in Global Populations

Natural selection is a significant force that shapes the architecture of the human genome and introduces diversity across global populations. The question of whether advantageous mutations have arisen in the human genome as a result of single or multiple mutation events remains unanswered except for the fact that there exist a handful of genes such as those that confer lactase persistence, affect skin pigmentation, or cause sickle cell anemia. We have developed a long-range-haplotype method for identifying genomic signatures of positive selection to complement existing methods, such as the integrated haplotype score (iHS) or cross-population extended haplotype homozygosity (XP-EHH), for locating signals across the entire allele frequency spectrum. Our method also locates the founder haplotypes that carry the advantageous variants and infers their corresponding population frequencies. This presents an opportunity to systematically interrogate the whole human genome whether a selection signal shared across different populations is the consequence of a single mutation process followed subsequently by gene flow between populations or of convergent evolution due to the occurrence of multiple independent mutation events either at the same variant or within the same gene. The application of our method to data from 14 populations across the world revealed that positive-selection events tend to cluster in populations of the same ancestry. Comparing the founder haplotypes for events that are present across different populations revealed that convergent evolution is a rare occurrence and that the majority of shared signals stem from the same evolutionary event.     

Occurrence of Regulated and Emerging Iodinated DBPs in the Shanghai Drinking Water

Drinking water chlorination plays a pivotal role in preventing pathogen contamination against water-borne disease. However, chemical disinfection leads to the formation of halogenated disinfection by products (DBPs). Many DBPs are highly toxic and are of health concern. In this study, we conducted a comprehensive measurements of DBPs, including iodoacetic acid (IAA), iodoform (IF), nine haloacetic acids and four trihalomethanes in drinking waters from 13 water plants in Shanghai, China. The results suggested that IAA and IF were found in all the water treatment plants, with maximum levels of 1.66 µg/L and 1.25 µg/L for IAA and IF, respectively. Owing to deterioration of water quality, the Huangpu River has higher IAA and IF than the Yangtze River. Our results also demonstrated that low pH, high natural organic matter, ammonia nitrogen, and iodide in source waters increased IAA and IF formation. Compared to chlorine, chloramines resulted in higher concentration of iodinated DBP, but reduced the levels of trihalomethanes. This is the first study to reveal the widespread occurrence of IAA and IF in drinking water in China. The data provide a better understanding on the formation of iodinated disinfection byproducts and the findings should be useful for treatment process improvement and disinfection byproducts controls.     

Single Sustained Inflation followed by Ventilation Leads to Rapid Cardiorespiratory Recovery but Causes Cerebral Vascular Leakage in Asphyxiated Near-Term Lambs

BackgroundA sustained inflation (SI) rapidly restores cardiac function in asphyxic, bradycardic newborns but its effects on cerebral haemodynamics and brain injury are unknown. We determined the effect of different SI strategies on carotid blood flow (CaBF) and cerebral vascular integrity in asphyxiated near-term lambs.MethodsLambs were instrumented and delivered at 139 ± 2 d gestation and asphyxia was induced by delaying ventilation onset. Lambs were randomised to receive 5 consecutive 3 s SI (multiple SI; n = 6), a single 30 s SI (single SI; n = 6) or conventional ventilation (no SI; n = 6). Ventilation continued for 30 min in all lambs while CaBF and respiratory function parameters were recorded. Brains were assessed for gross histopathology and vascular leakage.ResultsCaBF increased more rapidly and to a greater extent during a single SI (p = 0.01), which then decreased below both other groups by 10 min, due to a higher cerebral oxygen delivery (p = 0.01). Blood brain barrier disruption was increased in single SI lambs as indicated by increased numbers of blood vessel profiles with plasma protein extravasation (p = 0.001) in the cerebral cortex. There were no differences in CaBF or cerebral oxygen delivery between the multiple SI and no SI lambs.ConclusionsVentilation with an initial single 30 s SI improves circulatory recovery, but is associated with greater disruption of blood brain barrier function, which may exacerbate brain injury suffered by asphyxiated newborns. This injury may occur as a direct result of the initial SI or to the higher tidal volumes delivered during subsequent ventilation.