Sterol and bile acid metabolism during development: 2. Identification of 3β-hydroxy-5-cholenoic acid (an intermediate in alternate pathway of bile acid synthesis) in newborn and fetal guinea pig

3β-hydroxy-5-cholenoic acid was found in the bile and feces of new-born and fetal guinea pigs. The identity of this compound was confirmed by gas chromatography and mass spectrometry. This finding suggests that the formation of chenodeoxycholic acid through 3β-hydroxy-5-cholenoic acid is intermediate in the early life of guinea pigs. Thus, it provides a useful model for studying the details of regulatory factors and significance of this pathway. This study also revealed that, unlike the adult guinea pig, the newborn guinea pig has significant amounts of glycine conjugates of bile acid.     

Associations of <Emphasis Type="Italic">CTLA4</Emphasis> +49 A/G Dimorphism and HLA-DRB1*/DQB1* Alleles With Type 1 Diabetes from South India

The aim of present study was to elucidate the association of CTLA4 +49 A/G and HLA-DRB1*/DQB1* gene polymorphism in south Indian T1DM patients. The patients and controls (n?=?196 each) were enrolled for CTLA4 and HLA-DRB1*/DQB1* genotyping by RFLP/PCR-SSP methods. The increased frequencies of CTLA4 ‘AG’ (OR?=?1.99; p?=?0.001), ‘GG’ (OR?=?3.94; p?=?0.001) genotypes, and ‘G’ allele (OR?=?2.42; p?=?9.26?×?10^?8) were observed in patients. Reduced frequencies of ‘AA’ (OR?=?0.35; p?=?7.19?×?10^?7) and ‘A’ (OR?=?0.41; p?=?9.26?×?10^?8) in patients revealed protective association. Among HLA-DRB1*/DQB1* alleles, DRB1*04 (OR?=?3.29; p?=?1.0?×?10^?5), DRB1*03 (OR?=?2.81; p?=?1.9?×?10^?6), DQB1*02:01 (OR?=?2.93; p?=?1.65?×?10^?5), DQB1*02:02 (OR?=?3.38; p?=?0.0003), and DQB1*03:02 (OR?=?7.72; p?=?0.0003) were in susceptible association. Decreased frequencies of alleles, DRB1*15 (OR?=?0.32; p?=?2.55?×?10^?7), DRB1*10 (OR?=?0.45; p?=?0.002), DQB1*06:01 (OR?=?0.43; p?=?0.0001), and DQB1*05:02 (OR?=?0.28; p?=?2.1?×?10^?4) in patients were suggested protective association. The combination of DRB1*03+AG (OR?=?5.21; p?=?1.4?×?10^?6), DRB1*04+AG (OR?=?2.14; p?=?0.053), DRB1*04+GG (OR?=?5.21; p?=?0.036), DQB1*02:01+AG (OR?=?4.44; p?=?3.6?×?10^?5), DQB1*02:02+AG (OR?=?20.9; p?=?9.5?×?10^?4), and DQB1*02:02+GG (OR?=?4.06; p?=?0.036) revealed susceptible association. However, the combination of DRB1*10+AA (OR?=?0.35; p?=?0.003), DRB1*15+AA (OR?=?0.22; p?=?5.3?×?10^?7), DQB1*05:01+AA (OR?=?0.45; p?=?0.007), DQB1*05:02+AA (OR?=?0.17; p?=?1.7?×?10^?4), DQB1*06:01+AA (OR?=?0.40; p?=?0.002), and DQB1*06:02+AG (OR?=?0.34; p?=?0.001) showed decreased frequency in patients, suggesting protective association. In conclusion, CTLA4/HLA-DR/DQ genotypic combinations revealed strong susceptible/protective association toward T1DM in south India. A female preponderance in disease associations was also documented.     

Site,trigger, quenching mechanism and recovery of non-photochemical quenching in cyanobacteria: recent updates

Femtosecond transient absorption was used to study excitation decay in monomeric and trimeric cyanobacterial Photosystem I (PSI) being prepared in three states: (1) in aqueous solution, (2) deposited and dried on glass surface (either conducting or non-conducting), and (3) deposited on glass (conducting) surface but being in contact with aqueous solvent. The main goal of this contribution was to determine the reason of the acceleration of the excitation decay in dried PSI deposited on the conducting surface relative to PSI in solution observed previously using time-resolved fluorescence (Szewczyk et al., Photysnth Res 132(2):111–126, 2017). We formulated two alternative working hypotheses: (1) the acceleration results from electron injection from PSI to the conducting surface; (2) the acceleration is caused by dehydration and/or crowding of PSI proteins deposited on the glass substrate. Excitation dynamics of PSI in all three types of samples can be described by three main components of subpicosecond, 3–5, and 20–26 ps lifetimes of different relative contributions in solution than in PSI-substrate systems. The presence of similar kinetic components for all the samples indicates intactness of PSI proteins after their deposition onto the substrates. The kinetic traces for all systems with PSI deposited on substrates are almost identical and they decay significantly faster than the kinetic traces of PSI in solution. We conclude that the accelerated excitation decay in PSI-substrate systems is caused mostly by dense packing of proteins.     

Distribution of Trichaleurina javanica (Rehm) M. Carbone,Agnello & P. Alvarado (Chorioactidaceae) in India

During the recent field visits to Saurashtra regions of Western India, one of the interesting fungi i.e. Trichaleurina javanica (Rehm) M. Carbone, Agnello & P. Alvarado (Chorioactidaceae, order Pezizales) was collected from Sarkhadiya Hanuman and Sasan (Gir Forest, India). Further confirmation of the identity was carried out by using molecular methods with its DNA barcoding. Review of literature showed that this species was previously reported from India under a different name; the collection here studied is the first one molecularly confirmed. Nucleotide sequence obtained during molecular analysis is submitted into NCBI and is the first record at BOLD data system for its DNA barcode (BOLD ID KSRF-0019).     

Horizontal gene transfer accelerates genome innovation and evolution

Horizontal gene transfer (HGT) spreads genetic diversity by moving genes across species boundaries. By rapidly introducing newly evolved genes into existing genomes, HGT circumvents the slow step of ab initio gene creation and accelerates genome innovation. However, HGT can only affect organisms that readily exchange genes (exchange communities). In order to define exchange communities and understand the internal and external environmental factors that regulate HGT, we analyzed approximately 20,000 genes contained in eight free-living prokaryotic genomes. These analyses indicate that HGT occurs among organisms that share similar factors. The most significant are genome size, genome G/C composition, carbon utilization, and oxygen tolerance.     

An optimization-based sampling scheme for phylogenetic trees

Much modern work in phylogenetics depends on statistical sampling approaches to phylogeny construction to estimate probability distributions of possible trees for any given input data set. Our theoretical understanding of sampling approaches to phylogenetics remains far less developed than that for optimization approaches, however, particularly with regard to the number of sampling steps needed to produce accurate samples of tree partition functions. Despite the many advantages in principle of being able to sample trees from sophisticated probabilistic models, we have little theoretical basis for concluding that the prevailing sampling approaches do in fact yield accurate samples from those models within realistic numbers of steps. We propose a novel approach to phylogenetic sampling intended to be both efficient in practice and more amenable to theoretical analysis than the prevailing methods. The method depends on replacing the standard tree rearrangement moves with an alternative Markov model in which one solves a theoretically hard but practically tractable optimization problem on each step of sampling. The resulting method can be applied to a broad range of standard probability models, yielding practical algorithms for efficient sampling and rigorous proofs of accurate sampling for heated versions of some important special cases. We demonstrate the efficiency and versatility of the method by an analysis of uncertainty in tree inference over varying input sizes. In addition to providing a new practical method for phylogenetic sampling, the technique is likely to prove applicable to many similar problems involving sampling over combinatorial objects weighted by a likelihood model.     

Changes in the stability and biomechanics of P22 bacteriophage capsid during maturation

The capsid of P22 bacteriophage undergoes a series of structural transitions during maturation that guide it from spherical to icosahedral morphology. The transitions include the release of scaffold proteins and capsid expansion. Although P22 maturation has been investigated for decades, a unified model that incorporates thermodynamic and biophysical analyses is not available. A general and specific model of icosahedral capsid maturation is of significant interest to theoreticians searching for fundamental principles as well as virologists and material scientists seeking to alter maturation to their advantage. To address this challenge, we have combined the results from orthogonal biophysical techniques including differential scanning fluorimetry, atomic force microscopy, circular dichroism, and hydrogen-deuterium exchange mass spectrometry. By integrating these results from single particle and population measurements, an energy landscape of P22 maturation from procapsid through expanded shell to wiffle ball emerged, highlighting the role of metastable structures and the thermodynamics guiding maturation. The propagation of weak quaternary interactions across symmetric elements of the capsid is a key component for stability in P22. A surprising finding is that the progression to wiffle ball, which lacks pentamers, shows that chemical and thermal stability can be uncoupled from mechanical rigidity, elegantly demonstrating the complexity inherent in capsid protein interactions and the emergent properties that can arise from icosahedral symmetry. On a broader scale, this work demonstrates the power of applying orthogonal biophysical techniques to elucidate assembly mechanisms for supramolecular complexes and provides a framework within which other viral systems can be compared.