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Taxon-specific conserved signature indels (CSIs) in genes/proteins provide reliable molecular markers (synapomorphies) for unambiguous demarcation of taxa of different ranks in molecular terms and for genetic, biochemical and diagnostic studies. Because of their predictive abilities, the shared presence of known taxon-specific CSIs in genome sequences has proven useful for taxonomic purposes. However, the lack of a convenient method for identifying the presence of known CSIs in genome sequences has limited their utility for taxonomic and other studies. We describe here a web-based tool/server (AppIndels.com) that identifies the presence of known and validated CSIs in genome sequences and uses this information for predicting taxonomic affiliation. The utility of this server was tested by using a database of 585 validated CSIs, which included 350 CSIs specific for ≈45 Bacillales genera, with the remaining CSIs being specific for members of the orders Neisseriales , Legionellales and Chlorobiales , family Borreliaceae , and some Pseudomonadaceae species/genera. Using this server, genome sequences were analysed for 721 Bacillus strains of unknown taxonomic affiliation. Results obtained showed that 651 of these genomes contained significant numbers of CSIs specific for the following Bacillales genera/families: Alkalicoccus , ‘Alkalihalobacillaceae’, Alteribacter , Bacillus Cereus clade, Bacillus Subtilis clade, Caldalkalibacillus , Caldibacillus , Cytobacillus , Ferdinandcohnia, Gottfriedia , Heyndrickxia , Lederbergia , Litchfieldia , Margalitia , Mesobacillus , Metabacillus , Neobacillus , Niallia , Peribacillus , Priestia , Pseudalkalibacillus , Robertmurraya , Rossellomorea , Schinkia , Siminovitchia , Sporosarcina , Sutcliffiella , Weizmannia and Caryophanaceae . Validity of the taxon assignment made by the server was examined by reconstructing phylogenomic trees. In these trees, all Bacillus strains for which taxonomic predictions were made correctly branched with the indicated taxa. The unassigned strains likely correspond to taxa for which CSIs are lacking in our database. Results presented here show that the AppIndels server provides a useful new tool for predicting taxonomic affiliation based on shared presence of the taxon-specific CSIs. Some caveats in using this server are discussed.

The order Legionellales contains several clinically important microorganisms. Although members of this order are well-studied for their pathogenesis, there is a paucity of reliable characteristics distinguishing members of this order and its constituent genera. Genome sequences are now available for 73 Legionellales species encompassing ≈90% of known members from different genera. With the aim of understanding evolutionary relationships and identifying reliable molecular characteristics that are specific for this order and its constituent genera, detailed phylogenetic and comparative analyses were conducted on the protein sequences from these genomes. A phylogenomic tree was constructed based on 393 single copy proteins that are commonly shared by the members of this order to delineate the evolutionary relationships among its members. In parallel, comparative analyses were performed on protein sequences from Legionellales genomes to identify novel molecular markers consisting of conserved signature indels (CSIs) that are specific for different clades and genera. In the phylogenomic tree and in an amino acid identity matrix based on core proteins, members of the genera Aquicella, Coxiella, Legionella and Rickettsiella formed distinct clades confirming their monophyly. In these studies, Diplorickettsia massiliensis exhibited a close relationship to members of the genus Rickettsiella. The results of our comparative genomic analyses have identified 59 highly specific molecular markers consisting of CSIs in diverse proteins that are uniquely shared by different members of this order. Four of these CSIs are specific for all Legionellales species, except the two deeper-branching "Candidatus Berkiella" species, providing means for identifying members of this order in molecular terms. Twenty four, 7 and 6 CSIs are uniquely shared by members of the genera Legionella, Coxiella and Aquicella, respectively, identifying these groups in molecular terms. The descriptions of these three genera are emended to include information for their novel molecular characteristics. We also describe 12 CSIs that are uniquely shared by D. massiliensis and different members of the genus Rickettsiella. Based on these results, we are proposing an integration of the genus Diplorickettsia with Rickettsiella. Three other CSIs suggest that members of the genera Coxiella and Rickettsiella shared a common ancestor exclusive of other Legionellales. The described molecular markers, due to their exclusivity for the indicated taxa/genera, provide important means for the identification of these clinically important microorganisms and for discovering novel properties unique to them.

The genera Convivina , Fructobacillus , Leuconostoc , Oenococcus and Weissella , which formed the family Leuconostocaceae , have recently been merged within the family Lactobacillaceae . Using genome sequences for 47 of the 52 named species from these genera, we report here comprehensive phylogenomic and comparative analyses on protein sequences from these species using multiple approaches. In a phylogenomic tree based on concatenated sequences of 498 core proteins from these five genera, and in a 16S rRNA gene tree, members of the genera Fructobacillus , Leuconostoc and Oenococcus formed distinct strongly supported clades. In contrast, Weissella species grouped into two distinct unrelated clades designated as the ‘ Weissella main clade’ and ‘ Weissella clade 2’. The presence of these clades is also seen in a matrix of pairwise average amino acid identity based on core protein sequences. In parallel, comparative genomic studies on protein sequences from Leuconostocaceae genomes have identified 46 conserved signature indels (CSIs) in diverse proteins that are unique characteristics of the different observed species clades. Of these identified CSIs, five, five and 13 CSIs are uniquely present in members of the genera Fructobacillus , Leuconostoc and Oenococcus , respectively. We also report here six and five CSIs that are exclusively present in the species from the Weissella main clade and Weissella clade 2, respectively, providing independent evidence supporting their distinctness from each other. The remaining 12 identified CSIs are commonly shared by some or all of the species from the genera Convivina , Fructobacillus and Leuconostoc , clarifying their interrelationships. The identified CSIs provide novel and reliable means for the identification/circumscription of members of the genera Fructobacillus , Leuconostoc and Oenococcus as well as the two Weissella species clades in molecular terms. Based on the strong phylogenetic and molecular evidence presented here, we propose that the genus Weissella be limited to only the species from the Weissell a main clade, whereas the species forming Weissella clade 2 should be transferred to a new genus Periweissella gen. nov.

To clarify the evolutionary relationships and classification of Bacillus species, comprehensive phylogenomic and comparative analyses were performed on >300 Bacillus/Bacillaceae genomes. Multiple genomic-scale phylogenetic trees were initially reconstructed to identify different monophyletic clades of Bacillus species. In parallel, detailed analyses were performed on protein sequences of genomes to identify conserved signature indels (CSIs) that are specific for each of the identified clades. We show that in different reconstructed trees, most of the Bacillus species, in addition to the Subtilis and Cereus clades, consistently formed 17 novel distinct clades. Additionally, some Bacillus species reliably grouped with the genera Alkalicoccus, Caldalkalibacillus, Caldibacillus, Salibacterium and Salisediminibacterium . The distinctness of identified Bacillus species clades is independently strongly supported by 128 identified CSIs which are unique characteristics of these clades, providing reliable means for their demarcation. Based on the strong phylogenetic and molecular evidence, we are proposing that these 17 Bacillus species clades should be recognized as novel genera, with the names Alteribacter gen. nov., Ectobacillus gen. nov., Evansella gen. nov., Ferdinandcohnia gen. nov., Gottfriedia gen. nov., Heyndrickxia gen. nov., Lederbergia gen. nov., Litchfieldia gen. nov., Margalitia gen. nov., Niallia gen. nov., Priestia gen. nov., Robertmurraya gen. nov., Rossellomorea gen. nov., Schinkia gen. nov., Siminovitchia gen. nov., Sutcliffiella gen. nov. and Weizmannia gen. nov. We also propose to transfer ‘ Bacillus kyonggiensi s’ to Robertmurraya kyonggiensis sp. nov. (type strain: NB22=JCM 17569T=DSM 26768). Additionally, we report 31 CSIs that are unique characteristics of either the members of the Subtilis clade (containing the type species B. subtilis ) or the Cereus clade (containing B. anthracis and B. cereus ). As most Bacillus species which are not part of these two clades can now be assigned to other genera, we are proposing an emended description of the genus Bacillus to restrict it to only the members of the Subtilis and Cereus clades.

This response summarizes the highly disordered state of the Mollicutes taxonomy that existed until recently, where most Mollicutes taxa lacked proper circumscriptions and their names were not in accordance with the International Code of Nomenclature of Prokaryotes and illegitimate. We also summarize the comprehensive phylogenomic and comparative genomic studies forming the basis for the proposed changes in the classification of Mollicultes species. Our responses to the concerns raised by Balish et al., show that the proposed taxonomic changes do not violate any essential point of the Code. Instead the proposed name changes rectify numerous taxonomic anomalies that have long plagued the classification of Mollicute s species, leading to a better understanding of their evolutionary relationships and bringing their nomenclature in conformity with the Code.

The genus Bacillus, harbouring 293 species/subspecies, constitutes a phylogenetically incoherent group. In the absence of reliable means for grouping known Bacillus species into distinct clades, restricting the placement of new species into this genus has proven difficult. To clarify the evolutionary relationships among Bacillus species, 352 available genome sequences from the family Bacillaceae were used to perform comprehensive phylogenomic and comparative genomic analyses. Four phylogenetic trees were reconstructed based on multiple datasets of proteins including 1172 core Bacillaceae proteins, 87 proteins conserved within the phylum Firmicutes, GyrA-GyrB-RpoB-RpoC proteins, and UvrD-PolA proteins. All trees exhibited nearly identical branching of Bacillus species and consistently displayed six novel monophyletic clades encompassing 5-23 Bacillus species (denoted as the Simplex, Firmus, Jeotgali, Niacini, Fastidiosus and Alcalophilus clades), interspersed with other Bacillaceae species. Species from these clades also generally grouped together in 16S rRNA gene trees. In parallel, our comparative genomic analyses of Bacillus species led to the identification of 36 molecular markers comprising conserved signature indels in protein sequences that are specifically shared by the species from these six observed clades, thus reliably demarcating these clades based on multiple molecular synapomorphies. Based on the strong evidence from multiple lines of investigations supporting the existence of these six distinct 'Bacillus' clades, we propose the transfer of species from these clades into six novel Bacillaceae genera viz. Peribacillus gen. nov., Cytobacillus gen. nov., Mesobacillus gen. nov., Neobacillus gen. nov., Metabacillus gen. nov. and Alkalihalobacillus gen. nov. These results represent an important step towards clarifying the phylogeny/taxonomy of the genus Bacillus.

The genus Betacoronavirus, consisting of four main subgenera (Embecovirus, Merbecovirus, Nobecovirus, and Sarbecovirus), encompasses all clinically significant coronaviruses (CoVs), including SARS, MERS, and the SARS-CoV-2 virus responsible for current COVID-19 pandemic. Very few molecular characteristics are known that are specific for the genus Betacoronavirus or its different subgenera. In this study, our analyses of the sequences of four essential proteins of CoVs, viz., spike, nucleocapsid, envelope, and RNA-dependent RNA polymerase (RdRp), identified ten novel molecular signatures consisting of conserved signature indels (CSIs) in these proteins which are specific for the genus Betacoronavirus or its subgenera. Of these CSIs, two 14-aa-conserved deletions found within the heptad repeat motifs 1 and 2 of the spike protein are specific for all betacoronaviruses, except for their shared presence in the highly infectious avian coronavirus. Six additional CSIs present in the nucleocapsid protein and one CSI in the RdRp protein are distinctive characteristics of either the Merbecovirus, Nobecovirus, or Sarbecovirus subgenera. In addition, a 4-aa insert is present in the spike protein, which is uniquely shared by all viruses from the subgenera Merbecovirus, Nobecovirus, and Sarbecovirus, but absent in Embecovirus and all other genera of CoVs. This molecular signature provides evidence that viruses from the three subgenera sharing this CSI are more closely related to each other, and they evolved after the divergence of embecoviruses and other CoVs. As all CSIs specific for different groups of CoVs are flanked by conserved regions, their sequences provide novel means for identifying the above groups of CoVs and for developing novel diagnostic tests. Furthermore, our analyses of the structures of the spike and nucleocapsid proteins show that all identified CSIs are localized in the surface-exposed loops of these protein. It is postulated that these surface loops, through their interactions with other cellular proteins/ligands, play important roles in the biology/pathology of these viruses.

Both SARS-CoV-2 and SARS coronaviruses (CoVs) are members of the subgenus Sarbecovirus. To understand the origin of SARS-CoV-2, sequences for the spike and nucleocapsid proteins from sarbecoviruses were analyzed to identify molecular markers consisting of conserved inserts or deletions (termed CSIs) that are specific for either a particular clade of Sarbecovirus or are commonly shared by two or more clades of these viruses. Three novel CSIs in the N-terminal domain (NTD) of the spike protein S1-subunit (S1-NTD) are uniquely shared by SARS-CoV-2, Bat-CoV-RaTG13 and most pangolin CoVs (SARS-CoV-2r clade). Three other sarbecoviruses viz. bat-CoVZXC21, -CoVZC45 and -PrC31 (forming CoVZC/PrC31 clade), and a pangolin-CoV_MP789 also contain related CSIs in the same positions. In contrast to the S1-NTD, both SARS and SARS-CoV-2r viruses contain two large CSIs in the S1-C-terminal domain (S1-CTD) that are absent in the CoVZC/PrC31 clade. One of these CSIs, consisting of a 12 aa insert, is also present in the RShSTT clade (Cambodia-CoV strains). Sequence similarity studies show that the S1-NTD of SARS-CoV-2r viruses is most similar to the CoVZC/PrC31 clade, whereas their S1-CTD exhibits highest similarity to the RShSTT- (and the SARS-related) CoVs. Results from the shared presence of CSIs and sequence similarity studies on different CoV lineages support the inference that the SARS-CoV-2r cluster of viruses has originated by a genetic recombination between the S1-NTD of the CoVZC/PrC31 clade of CoVs and the S1-CTD of RShSTT/SARS viruses, respectively. We also present compelling evidence, based on the shared presence of CSIs and sequence similarity studies, that the pangolin-CoV_MP789, whose receptor-binding domain is most similar to the SARS-CoV-2 virus, has resulted from another independent recombination event involving the S1-NTD of the CoVZC/PrC31 CoVs and the S1-CTD of an unidentified SARS-CoV-2r related virus. The SARS-CoV-2 virus involved in this latter recombination event is postulated to be most similar to the SARS-CoV-2. Several other CSIs reported here are specific for other clusters of sarbecoviruses including a clade consisting of bat-SARS-CoVs (BM48-31/BGR/2008 and SARS_BtKY72). Structural mapping studies show that the identified CSIs form distinct loops/patches on the surface of the spike protein. It is hypothesized that these novel loops/patches on the spike protein, through their interactions with other host components, should play important roles in the biology/pathology of SARS-CoV-2 virus. Lastly, the CSIs specific for different clades of sarbecoviruses including SARS-CoV-2r clade provide novel means for the identification of these viruses and other potential applications.

The evolutionary relationships among species of the family

The evolutionary relationships among species of the family Pseudomonadaceae were examined based on 255 available genomes representing >85 % of the species from this family. In a phylogenetic tree based on concatenated sequences of 118 core proteins, most species of the genus Pseudomonas grouped within one large cluster which also included members of the genera Azotobacter and Azomonas . Within this large cluster 18–30 clades/subclades of species of the genus Pseudomonas consisting of between 1 and 36 species, were observed. However, a number of species of the genus Pseudomonas branched outside of this main cluster and were interspersed among other genera of the family Pseudomonadaceae . This included a strongly supported clade (Pertucinogena clade) consisting of 19 mainly halotolerant species. The distinctness of this clade from all other members of the family Pseudomonadaceae is strongly supported by 24 conserved signature indels (CSIs) in diverse proteins that are exclusively found in all members of this clade. Nine uncharacterized members of the genus Pseudomonas also shared these CSIs and they branched within the Pertucinogena clade, indicating their affiliation to this clade. On the basis of the strong evidence supporting the distinctness of the Pertucinogena clade, we are proposing transfer of species from this clade into a novel genus Halopseudomonas gen. nov. Pseudomonas caeni also branches outside of the main cluster and groups reliably with Oblitimonas alkaliphila and Thiopseudomonas denitrificans . Six identified CSIs are uniquely shared by these three species and we are proposing their integration into the emended genus Thiopseudomonas , which has priority over the name Oblitimonas . We are also proposing transfer of the deep-branching Pseudomonas hussainii , for which 22 exclusive CSIs have been identified, into the genus Atopomonas gen. nov. Lastly, we present strong evidence that the species Pseudomonas cissicola and Pseudomonas geniculata are misclassified into the genus Pseudomonas and that they are specifically related to the genera Xanthomonas and Stenotrophomonas , respectively. In addition, we are also reclassifying ‘Pseudomonas acidophila’ as Paraburkholderia acidicola sp. nov. (Type strain: G-6302=ATCC 31363=BCRC 13035).

The order Neisseriales contains 37 genera harboring 122 species with validly published names, which are placed into two families, Neisseriaceae and Chromobacteriaceae. Genome sequences are now available for 35 of the 37 Neisseriales genera for reliably determining their evolutionary relationships and taxonomy. We report here comprehensive phylogenomic and comparative analyses on protein sequences from 110 Neisseriales genomes plus 3 Chitinimonas genomes using multiple approaches. In a phylogenomic tree based on 596 core proteins, Neisseriales species formed 5 strongly supported clades. In addition to the clades for Neisseriaceae and Chromobacteriaceae families, three novel species clades designated as the “Chitinibacteraceae”, “Aquaspirillaceae”, and “Leeiaceae” were observed. The genus Chitinimonas grouped reliably with members of the “Chitinibacteraceae” clade. The major clades within the order Neisseriales can also be distinguished based on average amino acid identity analysis. In parallel, our comparative genomic studies have identified 30 conserved signature indels (CSIs) that are specific for members of the order Neisseriales or its five main clades. One of these CSIs is uniquely shared by all Neisseriales, whereas 8, 4, 9, 3 and 5 CSIs are distinctive characteristics of the Neisseriaceae, Chromobacteriaceae, “Chitinibacteraceae”, “Aquaspirillaceae” and “Leeiaceae” clades, respectively. Based on the strong phylogenetic and molecular evidence presented here, we are proposing that the three newly identified clades should be recognized as novel families (Chitinibacteraceae fam. nov., Aquaspirillaceae fam. nov. and Leeiaceae fam. nov.) within the order Neisseriales. In addition, we are also emending descriptions of the families Neisseriaceae and Chromobacteriaceae regarding their constituent genera and other distinguishing characteristics.

A rapidly increasing incidence of Diabetes mellitus throughout the world is a major concern in both developed and developing countries and the drawbacks associated with currently available treatments led to switching researcher's attention towards naturopathy. Since ancient time, herbal plants have been traditionally used for the treatment of diabetes as they consider to be less toxic and free from side effects than synthetic ones. In our previous studies, we had isolated two new compounds (Methyl 5-tridecyloctadec-4-enoate and Nonacosan-8-one), together with three known compounds (Lupeol, β-sitosterol and Stigmasterol) from chloroform fraction of stem bark of P. cineraria (CfPc). The present study aimed to determine the in vivo and in vivo antidiabetic activity of CfPc in streptozotocin induced experimental diabetes and also evaluated their possible mode of action. CfPc was orally administrated to STZ (55 mg/kg b.wt) induced diabetic rats at the doses of 50 and 100 mg/kg b.wt for 21 days. Treatment of CfPc significantly (p 0.05) lowered the level of blood glucose, glycosylated hemoglobin and also restored body weight, liver glycogen content and serum insulin level in diabetic rats in a dose-dependent manner. A significant (p 0.05) reduction in serum lipid profile markers and elevation in HDL-C after treatment with CfPc, also signifying the protective effects of CfPc in diabetes-associated complications. In addition, CfPc also promoted a significant inhibition of α-amylase enzyme activity with an IC

The genus Streptococcus comprises many important pathogens that impact human and animal health. Despite their widespread relevance, accurate classification and methods to reliably distinguish its members remain inadequate. Hence, we conducted comprehensive phylogenomics and comparative genomic analyses on 70 genome-sequenced members of this genus to delineate their interrelationships. Comprehensive phylogenetic trees were constructed based on multiple datasets of proteins, including 737 core proteins for the genus Streptococcus, 87 proteins conserved within the phylum Firmicutes, GyrA-GyrB, and RpoB-RpoC sequences. Based on the core proteins for Streptococcus species, genetic relatedness based on average amino acid identity was also determined. In parallel, comparative genomic analyses on protein sequences from this genus have identified 134 highly specific molecular markers in the form of conserved signature indels (CSIs) that are specifically shared by either the entire genus or its distinct clades/subclades. Based on the results from these multiple lines of investigations, a reliable picture of the overall evolutionary relationships within the genus Streptococcus has emerged. At the highest level, members of this genus form 2 main clades termed the "Mitis-Suis" and "Pyogenes-Equinus-Mutans" clades. Among these 2 major clades, 14 distinct subclades have been identified which include 4 previously identified species groups (viz. Pyogenes, Mutans, Salivarius and Equinus (or Bovis)); the Mitis clade, which is comprised of the Anginosus subclade and three novel subclades (viz. Pneumoniae, Gordonii and Parasanguinis), and six novel subclades termed the Suis, Sobrinus, Halotolerans, Porci, Entericus and Orisratti subclades. Members of the aforementioned subclades are reliably distinguished on the basis of their distinct branching in phylogenetic trees and multiple identified CSIs that are specifically shared by them. The molecular markers described here serve to dermarcate and clarify the interrelationships among different species groups of streptococci, and provide important means for developing novel diagnostic tests and functional studies on these bacteria which should enhance our understanding of them.

Spirochetes of the family Borreliaceae are, with one exception, tick-borne pathogens of a variety of vertebrates. The family at present comprises two genera: Borrelia (Swellengrebel), which includes the agents of relapsing fever, avian spirochetosis, and bovine borreliosis, and Borreliella (Gupta et al.), which includes the agents of Lyme disease and was formerly known as ‘Borrelia burgdorferi sensulato complex’. The two genera are distinguished not only by their disease associations but also biological features in the tick vector, including tissue location in unfed ticks and transovarial transmission. Borrelia species transmitted by argasid (soft) ticks tend to have more exclusive relationships with their tick vectors than do other Borrelia species and all Borreliella species that have ixodid (hard) ticks as vectors. The division of genera is supported by phylogenomic evidence from whole genomes and by several specific molecular markers. These distinguishing phylogenetic criteria also applied to three new species or isolates of Borrelia that were discovered in ixodid ticks of reptiles, a monotreme, and birds. Although the deep branching of the family from other spirochetes has been a challenge for inferences about evolution of the family, the discovery of related microorganisms in the gut microbiota of other arachnids suggests an ancestral origin for the family as symbionts of ticks and other arachnids.

Lack of representative and sufficient failure data is a common problem faced by researchers in the area of HVDC systems reliability analysis. To alleviate this problem, researchers usually resort to the collection of data from different publicly available sources, such as organizations reports and from other research articles. However, homogeneity of the information gathered in this way is not guaranteed, given the diverse sources; the generality of any conclusions based on this data is thus affected. In this paper, the adequacy of publicly available failure data for use in reliability analyses of LCC based HVDC systems is assessed. To this end, failure data available in public domain is first collated. Results from the reliability analysis of two bi-pole topologies of LCC based HVDC systems, with different levels of redundancy and operating voltages, are reported.

To clarify the evolutionary relationships and classification of

Both SARS-CoV-2 (COVID-19) and SARS coronaviruses (CoVs) are members of the subgenus Sarbecovirus. To understand the origin of SARS-CoV-2 and its relation to other viruses, protein sequences from sarbecoviruses were analyzed to identify conserved inserts or deletions (termed CSIs) demarcating either particular clusters/lineages of sarbecoviruses or those shared by specific lineages shedding light on their interrelationships. We report several clade-specific CSIs in the spike (S) and nucleocapsid (N) proteins that reliably demarcate distinct sarbecoviruses clades providing important insights into the origin and evolution of SARS-CoV-2. Two CSIs in the N-terminal domain (NTD) of S-protein are uniquely shared by SARS-CoV-2, BatCoV-RaTG13 and most pangolin CoVs (SARS-CoV-2r cluster); another CSI supports a closer relationship of SARS-CoV-2 to BatCov-RaTG13. Three additional CSIs in the NTD are specific for two Bat-SARS-like CoVs (viz. CoVZXC21 and CoVZC45; CoVZC cluster) which form an outgroup of the SARS-CoV-2r cluster. Interestingly, one of the pangolin-CoV-MP789 also shares these CSIs but lack the CSIs specific for the SARS-CoV-2r cluster. The N-terminal sequence (aa 1-320) of the S-protein for pangolin-CoV-MP789 shows highest similarity (85.94%) to the CoVZC cluster, while its C-terminal region including the receptor binding domain (RBD) is most similar (97-98% identity) to the SARS-CoV-2 virus. These observations indicate that the spike protein sequence for the strain MP789 is of chimeric origin. Multiple CSIs described here also distinguish two bat SARS-CoVs strains (BM48-31/BGR/2008 and SARS_BtKY72) from all others. Our work also clarifies that two large CSIs (5 aa and 13 aa) found in the RBD of S-protein are mainly specific for the SARS and SARS-CoV-2r clusters of CoVs. The surface loops formed by these CSIs are predicted to be important in the binding of S-protein with the human ACE-2 receptor. Lastly, we have mapped the locations of different CSIs in the structure of the S-protein. These studies reveal that the three CSIs specific for the SARS-CoV-2r cluster form distinct surface-exposed loops/patches on the S-protein. As the surface-exposed loops play important roles in mediating novel interactions, the novel lobes/patches formed by the SARS-CoV-2-specific CSIs in the spike protein are predicted to play important roles in the interaction of this protein with other surface-exposed components in the host cells thereby enhancing the binding/infectivity of this virus to humans.

The family Caryophanaceae/Planococcaceae is a taxonomically heterogeneous assemblage of >100 species classified within 13 genera, many of which are polyphyletic. Exhibiting considerable phylogenetic overlap with other families, primarily Bacillaceae, the evolutionary history of this family, containing the potent mosquitocidal species Lysinibacillus sphaericus, remains incoherent. To develop a reliable phylogenetic and taxonomic framework for the family Caryophanaceae/Planococcaceae and its genera, we report comprehensive phylogenetic and comparative genomic analyses on 124 genome sequences from all available Caryophanaceae/Planococcaceae and representative Bacillaceae species. Phylogenetic trees were constructed based on multiple datasets of proteins including 819 core proteins for this group and 87 conserved Firmicutes proteins. Using the core proteins, pairwise average amino acid identity was also determined. In parallel, comparative analyses on protein sequences from these species have identified 92 unique molecular markers (synapomorphies) consisting of conserved signature indels that are specifically shared by either the entire family Caryophanaceae/Planococcaceae or different monophyletic clades present within this family, enabling their reliable demarcation in molecular terms. Based on multiple lines of investigations, 18 monophyletic clades can be reliably distinguished within the family Caryophanaceae/Planococcaceae based on their phylogenetic affinities and identified molecular signatures. Some of these clades are comprised of species from several polyphyletic genera within this family as well as other families. Based on our results, we are proposing the creation of three novel genera within the family Caryophanaceae/Planococcaceae, namely Metalysinibacillus gen. nov., Metasolibacillus gen. nov., and Metaplanococcus gen. nov., as well as the transfer of 25 misclassified species from the families Caryophanaceae/Planococcaceae and Bacillaceae into these three genera and in Planococcus, Solibacillus, Sporosarcina, and Ureibacillus genera. These amendments establish a coherent taxonomy and evolutionary history for the family Caryophanaceae/Planococcaceae, and the described molecular markers provide novel means for diagnostic, genetic, and biochemical studies. Lastly, we are also proposing a consolidation of the family Planococcaceae within the emended family Caryophanaceae.

The genus Mycoplasma, including species earlier classified in the genera Eperythrozoon and Haemobartonella, contains ~ 120 species and constitutes an extensively polyphyletic assemblage of bacteria within the phylum Tenericutes. Due to their small genome sizes and lack of unique characteristics, the relationships among the mycoplasmas/Tenericutes are not reliably discerned. Using genome sequences for 140 Tenericutes, their evolutionary relationships were examined using multiple independent approaches. Phylogenomic trees were constructed for 63 conserved proteins, 45 ribosomal proteins, three main subunits of RNA polymerase and 16S rRNA gene sequences. In all of these trees, Tenericutes species reliably grouped into four main clades designated as the "Acholeplasma", "Spiroplasma", "Pneumoniae" and "Hominis" clusters. These clades are also distinguished based on a similarity matrix constructed based on 16S rRNA gene sequences. Mycoplasma species were dispersed across 3 of these 4 clades highlighting their extensive polyphyly. In parallel, our comparative genomic analyses have identified 100 conserved signature indels (CSIs) and 14 conserved signature proteins (CSPs), which are uniquely shared by the members of four identified clades, strongly supporting their monophyly and identifying them in molecular terms. Mycoplasma mycoides, the type species of the genus Mycoplasma, and a small number of other Mycoplasma species, formed a strongly supported clade within the "Spiroplasma" cluster. Nine CSIs and 14 CSPs reliably distinguish this clade from all other Mycoplasmatales species. The remainder of the Mycoplasmatales species are part of the "Pneumoniae" and "Hominis" clusters, which group together in phylogenetic trees. Here we are proposing that the order Mycoplasmatales should be emended to encompass only the Mycoplasma species within the "Spiroplasma" cluster and that a new order, Mycoplasmoidales ord. nov., should be created to encompass the other Mycoplasma species. The "Pneumoniae" and the "Hominis" clusters are proposed as two new families, Mycoplasmoidaceae fam. nov., which includes the genera Eperythrozoon, Ureaplasma, and the newly proposed genera Malacoplasma and Mycoplasmoides, and Metamycoplasmataceae fam. nov. to contain the newly proposed genera Metamycoplasma, Mycoplasmopsis, and Mesomycoplasma. The results presented here allow reliable discernment, both in phylogenetic and molecular terms, of the members of the two proposed families as well as different described genera within these families including members of the genus Eperythrozoon, which is comprised of uncultivable organisms. The taxonomic reclassifications proposed here, which more accurately portray the genetic diversity among the Tenericutes/Mycoplasma species, provide a new framework for understanding the biological and clinical aspects of these important microbes.

Homologs of the phosphatidylinositol-4-phosphate-5-kinase (PIP5K), which controls a multitude of essential cellular functions, contain a 8 aa insert in a conserved region that is specific for the Saccharomycetaceae family of fungi. Using structures of human PIP4K proteins as templates, structural models were generated of the Saccharomyces cerevisiae and human PIP5K proteins. In the modeled S. cerevisiae PIP5K, the 8 aa insert forms a surface exposed loop, present on the same face of the protein as the activation loop of the kinase domain. Electrostatic potential analysis indicates that the residues from 8 aa conserved loop form a highly positively charged surface patch, which through electrostatic interaction with the anionic portions of phospholipid head groups, is expected to play a role in the membrane interaction of the yeast PIP5K. To unravel this prediction, molecular dynamics (MD) simulations were carried out to examine the binding interaction of PIP5K, either containing or lacking the conserved signature insert, with two different membrane lipid bilayers. The results from MD studies provide insights concerning the mechanistic of interaction of PIP5K with lipid bilayer, and support the contention that the identified 8 aa conserved insert in fungal PIP5K plays an important role in the binding of this protein with membrane surface. Proteins 2017; 85:1454-1467. © 2017 Wiley Periodicals, Inc.

Diabetes is a serious metabolic disorder prevailing among people with ageing and sedentary lifestyle associated with rapidly growing urbanization and industrialization. Medicinal plants prescribed in thesaurus of Ayurveda and used by folklore have been a source of relief in controlling different types of diabetes all over the world. At the present time, the use of these herbal drugs is growing at high pace because of its cost effectiveness and free from the side effects over pharmaceutical hypoglycemic agents. The current review presents the profiles of approximately 35 plants having anti-diabetic activity and potential to reduce the oxidative stress, reported in the literature from 2005 to 2015. This review has been presented in such a fascinating manner which includes the plant along with its family, part used, phyto-constituents responsible for particular action in a tabulated form. Present study might provide a momentum to find newer antidiabetic entities.

The genus

The family Caryophanaceae/Planococcaceae is a taxonomically heterogeneous assemblage of >100 species classified within 13 genera, many of which are polyphyletic. Exhibiting considerable phylogenetic overlap with other families, primarily Bacillaceae, the evolutionary history of this family, containing the potent mosquitocidal species Lysinibacillus sphaericus, remains incoherent. To develop a reliable phylogenetic and taxonomic framework for the family Caryophanaceae/Planococcaceae and its genera, we report comprehensive phylogenetic and comparative genomic analyses on 124 genome sequences from all available Caryophanaceae/Planococcaceae and representative Bacillaceae species. Phylogenetic trees were constructed based on multiple datasets of proteins including 819 core proteins for this group and 87 conserved Firmicutes proteins. Using the core proteins, pairwise average amino acid identity was also determined. In parallel, comparative analyses on protein sequences from these species have identified 92 unique molecular markers (synapomorphies) consisting of conserved signature indels that are specifically shared by either the entire family Caryophanaceae/Planococcaceae or different monophyletic clades present within this family, enabling their reliable demarcation in molecular terms. Based on multiple lines of investigations, 18 monophyletic clades can be reliably distinguished within the family Caryophanaceae/Planococcaceae based on their phylogenetic affinities and identified molecular signatures. Some of these clades are comprised of species from several polyphyletic genera within this family as well as other families. Based on our results, we are proposing the creation of three novel genera within the family Caryophanaceae/Planococcaceae, namely Metalysinibacillus gen. nov., Metasolibacillus gen. nov., and Metaplanococcus gen. nov., as well as the transfer of 25 misclassified species from the families Caryophanaceae/Planococcaceae and Bacillaceae into these three genera and in Planococcus, Solibacillus, Sporosarcina, and Ureibacillus genera. These amendments establish a coherent taxonomy and evolutionary history for the family Caryophanaceae/Planococcaceae, and the described molecular markers provide novel means for diagnostic, genetic, and biochemical studies. Lastly, we are also proposing a consolidation of the family Planococcaceae within the emended family Caryophanaceae.