CPAP promotes timely cilium disassembly to maintain neural progenitor pool

A mutation in the centrosomal‐P4.1‐associated protein (CPAP) causes Seckel syndrome with microcephaly, which is suggested to arise from a decline in neural progenitor cells (NPCs) during development. However, mechanisms of NPCs maintenance remain unclear. Here, we report an unexpected role for the cilium in NPCs maintenance and identify CPAP as a negative regulator of ciliary length independent of its role in centrosome biogenesis. At the onset of cilium disassembly, CPAP provides a scaffold for the cilium disassembly complex (CDC), which includes Nde1, Aurora A, and OFD1, recruited to the ciliary base for timely cilium disassembly. In contrast, mutated CPAP fails to localize at the ciliary base associated with inefficient CDC recruitment, long cilia, retarded cilium disassembly, and delayed cell cycle re‐entry leading to premature differentiation of patient iPS‐derived NPCs. Aberrant CDC function also promotes premature differentiation of NPCs in Seckel iPS‐derived organoids. Thus, our results suggest a role for cilia in microcephaly and its involvement during neurogenesis and brain size control.     

Azidobupramine,an Antidepressant-Derived Bifunctional Neurotransmitter Transporter Ligand Allowing Covalent Labeling and Attachment of Fluorophores

The aim of this study was to design, synthesize and validate a multifunctional antidepressant probe that is modified at two distinct positions. The purpose of these modifications was to allow covalent linkage of the probe to interaction partners, and decoration of probe-target complexes with fluorescent reporter molecules. The strategy for the design of such a probe (i.e., azidobupramine) was guided by the need for the introduction of additional functional groups, conveying the required properties while keeping the additional moieties as small as possible. This should minimize the risk of changing antidepressant-like properties of the new probe azidobupramine. To control for this, we evaluated the binding parameters of azidobupramine to known target sites such as the transporters for serotonin (SERT), norepinephrine (NET), and dopamine (DAT). The binding affinities of azidobupramine to SERT, NET, and DAT were in the range of structurally related and clinically active antidepressants. Furthermore, we successfully visualized azidobupramine-SERT complexes not only in SERT-enriched protein material but also in living cells stably overexpressing SERT. To our knowledge, azidobupramine is the first structural analogue of a tricyclic antidepressant that can be covalently linked to target structures and further attached to reporter molecules while preserving antidepressant-like properties and avoiding radioactive isotopes.     

An overview of the oxytocin-oxytocin receptor signaling network

Oxytocin, a nine amino acid long neuropeptide hormone, is synthesized in the hypothalamus and stored and released from the neural lobe of the pituitary gland. Although commonly known for its central role in the regulation of parturition and lactation, oxytocin signaling also plays a key role in modulating social behavior, evoking contentment, initiating maternal behavior, inducing trust, generosity and bonding in humans and animals. Oxytocin signaling can prove to be of great importance in therapeutics and drug targeting because of its diverse range of actions. However, a well annotated map of oxytocin signaling pathway is currently lacking in the publicly available pathway resources. Therefore, we systematically curated the available signaling information of oxytocin from published literature and collated the data to develop a more complete map. We cataloged 66 molecules belonging to oxytocin signaling pathway, which included 9 protein-protein interactions, 39 post-translational modifications, 14 protein translocation events and 22 activation/inhibition events. Further, Oxytocin signaling network data is made freely available to academic fraternity by integrating this into NetPath (http://www.netpath.org/), a freely available human signaling pathway resource developed previously by our group.     

Morphological divergence in Indian oil sardine,Sardinella longiceps Valenciennes, 1847– Does it imply adaptive variation?

The Indian oil sardine, Sardinella longiceps, is an important pelagic species in Indian waters, and shows divergent morphology while in sympatry. The reasons behind this divergent morphology were investigated using morphometric, genetic and nutritional analyses. Twenty‐one morphometric characters (as percentage of standard length) and eight meristic characters were studied in the three variants to assess whether they are significantly diverged. Distinct clustering of morphotypes was evident in the principal component analysis on log‐transformed ratios of morphological characters with PC1 and PC2, explaining 50.7% and 17.6% of the total morphological variation, respectively. PC1 was highly correlated with the distance from snout to anal origin, depth at dorsal, distance from snout to pelvic and distance from snout to first dorsal. PC2 was highly correlated with head length, caudal width and anal depth. Analysis of similarities (ANOSIM) was conducted using log‐transformed morphometric ratios, with the results showing the clusters to be well differentiated (R = 0.511; P < 0.01). Similarity of percentage analysis (SIMPER) analysis showed that the differences in depth at the dorsal, anal base length, caudal width, distance from pelvic to anal origin, anal depth and eye diameter accounted for 52% of variations between variant 1 and 2. Differences in caudal width, distance from pelvic to anal origin, anal base length, depth at dorsal and anal depth accounted for 56% of the variation between variant 2 and 3. Differences in caudal width, eye diameter, anal base length, anal depth, distance from pelvic to anal origin accounted for 50% of the variation between variant 1 and 3. Genetic divergence was not significantly based on mitochondrial cytochrome c oxidase I (COI) or control region sequences. Proximate composition analyses showed significantly high fat content in variants 1&3 and significantly high protein content in variant 2, probably due to dissimilar dietary preferences. The study shows that morphotypes of the Indian oil sardine may be the result of divergent selection and adaptive variations, which need further investigation using a long‐term sampling design.     

Unravelling the genome of Holy basil: an “incomparable” “elixir of life” of traditional Indian medicine

Background

Ocimum sanctum L. (O. tenuiflorum) family-Lamiaceae is an important component of Indian tradition of medicine as well as culture around the world, and hence is known as “Holy basil” in India. This plant is mentioned in the ancient texts of Ayurveda as an “elixir of life” (life saving) herb and worshipped for over 3000 years due to its healing properties. Although used in various ailments, validation of molecules for differential activities is yet to be fully analyzed, as about 80 % of the patents on this plant are on extracts or the plant parts, and mainly focussed on essential oil components. With a view to understand the full metabolic potential of this plant whole nuclear and chloroplast genomes were sequenced for the first time combining the sequence data from 4 libraries and three NGS platforms.

Results

The saturated draft assembly of the genome was about 386 Mb, along with the plastid genome of 142,245 bp, turning out to be the smallest in Lamiaceae. In addition to SSR markers, 136 proteins were identified as homologous to five important plant genomes. Pathway analysis indicated an abundance of phenylpropanoids in O. sanctum. Phylogenetic analysis for chloroplast proteome placed Salvia miltiorrhiza as the nearest neighbor. Comparison of the chemical compounds and genes availability in O. sanctum and S. miltiorrhiza indicated the potential for the discovery of new active molecules.

Conclusion

The genome sequence and annotation of O. sanctum provides new insights into the function of genes and the medicinal nature of the metabolites synthesized in this plant. This information is highly beneficial for mining biosynthetic pathways for important metabolites in related species.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1640-z) contains supplementary material, which is available to authorized users.     

What is the ultimate goal in acid-base regulation?

It is common to see chapters on acid-base physiology state that the goal of acid-base regulatory mechanisms is to maintain the pH of arterial plasma and not arterial Pco(2) (Pa(CO(2))) or plasma HCO(3). A hypothetical situation in which the Pa(CO(2)) of arterial plasma is 80 mmHg and the plasma HCO(3) concentration is 48 mM is presented and analyzed to get over this misconception. As per the modified Henderson equation, the pH of arterial plasma would be 7.4; however, we explain that this may be associated with intracellular acidosis due to intracellular hypercapnia and that derangement of homeostasis is evident from the occurrence of respiratory depression and, eventually, coma in the patient described. This suggests that the ultimate goal of acid-base regulatory mechanisms is not just the maintenance of the pH of arterial plasma but the maintenance of the steady-state pH of intracellular fluid as well.     

Indwelling catheter and vanishing intracardiac mass

A 36-year-old male was admitted for painful swelling of his right upper extremity. He had had an indwelling port-a-cath placed in his right subclavian vein eight months prior to admission. On admission the patient was afebrile and his vital signs were normal. His right upper extremity was swollen, erythematous and tender. Blood leucocyte count was normal and D-Dimer was elevated. Venous Doppler examination showed partial thrombosis of the distal right subclavian vein. Removal of the port-a-cath by interventional radiology was scheduled.     

Cyanobacterial KnowledgeBase (CKB), a Compendium of Cyanobacterial Genomes and Proteomes

Cyanobacterial KnowledgeBase (CKB) is a free access database that contains the genomic and proteomic information of 74 fully sequenced cyanobacterial genomes belonging to seven orders. The database also contains tools for sequence analysis. The Species report and the gene report provide details about each species and gene (including sequence features and gene ontology annotations) respectively. The database also includes cyanoBLAST, an advanced tool that facilitates comparative analysis, among cyanobacterial genomes and genomes of E. coli (prokaryote) and Arabidopsis (eukaryote). The database is developed and maintained by the Sub-Distributed Informatics Centre (sponsored by the Department of Biotechnology, Govt. of India) of the National Facility for Marine Cyanobacteria, a facility dedicated to marine cyanobacterial research. CKB is freely available at http://nfmc.res.in/ckb/index.html.     

Primers from the orders Osteoglossiform and Siluriform detect polymorphic microsatellite loci in sun-catfish, Horabagrus brachysoma (Teleostei: Bagridae)

Horabagrus brachysoma (sun‐catfish, Bagridae, Siluriformes) is a valuable ornamental and food fish. The stock structure of H. brachysoma, necessary to conserve its declining natural populations, is not known. Twenty‐five primers developed for four fish species belonging to the orders Siluriform (3) and Osteoglossiform (1) were tested and eight primers amplified microsatellite loci in H. brachysoma. The results demonstrate that cross‐priming between fish species belonging to different families and even to different orders can yield microsatellite loci. Five of eight primers each amplified two loci. However, the loci that had repeat motifs after sequencing were considered only for genotyping. Finally, eight loci were polymorphic with hree to seven alleles. Individual fish genotype data (n = 42; 21 each in two rivers) at each locus was analysed. Significant genetic heterogeneity was detected at six loci. The identified loci exhibited potential for use in population genetics application in H. brachysoma.     

Microsatellite DNA markers for population-genetic studies of Labeo dyocheilus (McClelland, 1839)

Fifty‐four primers published for six cyprinid fishes were tested to amplify homologous microsatellite loci in Labeo dyocheilus. Fifteen primers yielded successful amplification and seven were polymorphic with 3–9 alleles. To evaluate utility of the identified loci in population genetic study, 84 samples were analysed. The samples were collected from four rivers viz. Beas, Satluj, Yamuna and Jiabharali. The four sample sets displayed different diversity levels, with observed heterozygosity from 0.34 to 0.53. Significant genotype heterogeneity (P < 0.001) over all loci indicated that the samples are not drawn from the same genepool. The identified microsatellite loci are promising for use in fine‐scale population structure analysis of L. dyocheilus.