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Mitochondrial DNA. Part B, Resources 2024The two commonest kelp-encrusting bryozoans, and , are difficult to distinguish morphologically. Molecular studies of should thus be helpful for the identification of...
The complete mitochondrial genome of Hincks, 1880 (Bryozoa: Gymnolaemata: Cheilostomatida): phylogenetic relationship of two kelp-encrusting bryozoans within the suborder Membraniporina.
The two commonest kelp-encrusting bryozoans, and , are difficult to distinguish morphologically. Molecular studies of should thus be helpful for the identification of both species because the mitogenome of was already sequenced. The complete mitogenome of collected from Sinjido was determined in this study through Illumina NovaSeq sequencing. Maximum-likelihood (ML) analysis was based on concatenated 13 protein-coding genes dataset from nine bryozoan species. The mitogenome length was 15,407 bp, and its gene arrangement was similar to those of the mitogenome of other membraniporids, having 13 PCGs, two ribosomal RNAs, and 22 tRNAs. It had an overall A + T content of 63.7% (29.7% A, 16.7% C, 19.6% G, and 34.0% T). and showed sequence differences of 20% for the total length of mitogenome and 16.1.% for 13 PCGs. Molecular data definitely consider them to be separate species. Phylogenetic analyses based on the amino acids of 13 PCGs indicated that has the closest relationship with another kelp-encrusting bryozoan, of membraniporids. The phylogenetic position of genera and families within the suborder Membraniporina coincides with the Bayesian phylogenetic analysis of the mixed concatenated alignment consisting of three partitions.
PubMed: 38903544
DOI: 10.1080/23802359.2024.2364755 -
Mitochondrial DNA. Part B, Resources 2024, an annual potherb belonging to the family Amaranthaceae, has been widely used in traditional Chinese and Japanese medicine for over 2000 years. Herein, we presented...
, an annual potherb belonging to the family Amaranthaceae, has been widely used in traditional Chinese and Japanese medicine for over 2000 years. Herein, we presented its complete chloroplast. The chloroplast genome sequence was 151,278 bp in length with a 36.6% content of GC. The genome showed the typical quadripartite structure, comprising a pair of inverted repeat (IR) regions (24,353 bp) separated by a large single-copy (LSC) region (84,067 bp) and a small single-copy (SSC) region (18,505 bp). This chloroplast genome harbored 133 predicted genes, including 88 protein-coding genes, 37 transfer RNA (tRNA) genes, and eight ribosomal RNA (rRNA) genes. The phylogenetic analysis indicated that was closely related to . This newly sequenced chloroplast genome not only enhances our understanding of the genome of but also provides valuable insights for the evolutionary study of the family Amaranthaceae.
PubMed: 38903543
DOI: 10.1080/23802359.2024.2364959 -
Frontiers in Plant Science 2024Maize, a salt-sensitive crop, frequently suffers severe yield losses due to soil salinization. Enhancing salt tolerance in maize is crucial for maintaining yield...
Maize, a salt-sensitive crop, frequently suffers severe yield losses due to soil salinization. Enhancing salt tolerance in maize is crucial for maintaining yield stability. To address this, we developed an introgression line (IL76) through introgressive hybridization between maize wild relatives , , and inbred Zheng58, utilizing the tri-species hybrid MTP as a genetic bridge. Previously, genetic variation analysis identified a polymorphic marker on (designated as ZmSC), which encodes a vesicle-sorting protein described as a salt-tolerant protein in the NCBI database. To characterize the identified polymorphic marker, we employed gene cloning and homologous cloning techniques. Gene cloning analysis revealed a non-synonymous mutation at the 1847th base of , where a guanine-to-cytosine substitution resulted in the mutation of serine to threonine at the 119th amino acid sequence (using as the reference sequence). Moreover, homologous cloning demonstrated that the variation site derived from . Functional analyses showed that transgenic lines overexpressing exhibited significant reductions in leaf number, root length, and pod number, alongside suppression of the expression of genes in the SOS and CDPK pathways associated with Ca signaling. Similarly, fission yeast strains expressing displayed inhibited growth. In contrast, the allele from alleviated these negative effects in both and yeast, with the lines overexpressing exhibiting significantly higher abscisic acid (ABA) content compared to those overexpressing . Our findings suggest that ZmSC negatively regulates salt tolerance in maize by suppressing downstream gene expression associated with Ca2+ signaling in the CDPK and SOS pathways. The allele from , however, can mitigate this negative regulatory effect. These results provide valuable insights and genetic resources for future maize salt tolerance breeding programs.
PubMed: 38903442
DOI: 10.3389/fpls.2024.1361422 -
Research Square Mar 2024Broadly neutralizing antibodies (bNAbs) are promising candidates for the treatment and prevention of HIV-1 infection. Despite their critical importance, automatic...
Broadly neutralizing antibodies (bNAbs) are promising candidates for the treatment and prevention of HIV-1 infection. Despite their critical importance, automatic detection of HIV-1 bNAbs from immune repertoire is still lacking. Here, we developed a straightforward computational method for apid utomatic dentification of bAbs ) based on Machine Learning methods. In contrast to other approaches using one-hot encoding amino acid sequences or structural alignment for prediction, RAIN uses a combination of selected sequence-based features for accurate prediction of HIV-1 bNAbs. We demonstrate the performance of our approach on non-biased, experimentally obtained sequenced BCR repertoires from HIV-1 immune donors. RAIN processing leads to the successful identification of novel HIV-1 bNAbs targeting the CD4-binding site of the envelope glycoprotein. In addition, we validate the identified bNAbs using neutralization assay and we solve the structure of one of them in complex with the soluble native-like heterotrimeric envelope glycoprotein by single-particle cryo-electron microscopy (cryo-EM). Overall, we propose a method to facilitate and accelerate HIV-1 bNAbs discovery from non-selected immune repertoires.
PubMed: 38903123
DOI: 10.21203/rs.3.rs-4023897/v1 -
BioRxiv : the Preprint Server For... Feb 2024Endosomal Sorting Complexes Required for Transport (ESCRT) play key roles in protein sorting between membrane-bounded compartments of eukaryotic cells. Homologs of many...
UNLABELLED
Endosomal Sorting Complexes Required for Transport (ESCRT) play key roles in protein sorting between membrane-bounded compartments of eukaryotic cells. Homologs of many ESCRT components are identifiable in various groups of archaea, especially in Asgardarchaeota, the archaeal phylum that is currently considered to include the closest relatives of eukaryotes, but not in bacteria. We performed a comprehensive search for ESCRT protein homologs in archaea and reconstructed ESCRT evolution using the phylogenetic tree of Vps4 ATPase (ESCRT IV) as a scaffold, using sensitive protein sequence analysis and comparison of structural models to identify previously unknown ESCRT proteins. Several distinct groups of ESCRT systems in archaea outside of Asgard were identified, including proteins structurally similar to ESCRT-I and ESCRT-II, and several other domains involved in protein sorting in eukaryotes, suggesting an early origin of these components. Additionally, distant homologs of CdvA proteins were identified in Thermoproteales which are likely components of the uncharacterized cell division system in these archaea. We propose an evolutionary scenario for the origin of eukaryotic and Asgard ESCRT complexes from ancestral building blocks, namely, the Vps4 ATPase, ESCRT-III components, wH (winged helix-turn-helix fold) and possibly also coiled-coil, and Vps28-like domains. The Last Archaeal Common Ancestor likely encompassed a complex ESCRT system that was involved in protein sorting. Subsequent evolution involved either simplification, as in the TACK superphylum, where ESCRT was co-opted for cell division, or complexification as in Asgardarchaeota. In Asgardarchaeota, the connection between ESCRT and the ubiquitin system that was previously considered a eukaryotic signature was already established.
IMPORTANCE
All eukaryotic cells possess complex intracellular membrane organization. ESCRT (Endosomal Sorting Complexes Required for Transport) plays a central role in membrane remodeling which is essential for cellular functionality in eukaryotes. Recently, it has been shown that Asgard archaea, the archaeal phylum that includes the closest known relatives of eukaryotes, encode homologs of many components of the ESCRT systems. We employed protein sequence and structure comparisons to reconstruct the evolution of ESCRT systems in archaea and identified several previously unknown homologs of ESCRT subunits, some of which can be predicted to participate in cell division. The results of this reconstruction indicate that the Last Archaeal Common ancestor already encoded a complex ESCRT system that was involved in protein sorting. In Asgard archaea, ESCRT systems evolved towards greater complexity, and in particular, the connection between ESCRT and the ubiquitin system that was previously considered a eukaryotic signature was established.
PubMed: 38903064
DOI: 10.1101/2024.02.06.579148 -
BMC Genomics Jun 2024The genotype-by-environment interaction (GxE) in beef cattle can be investigated using reaction norm models to assess environmental sensitivity and, combined with...
BACKGROUND
The genotype-by-environment interaction (GxE) in beef cattle can be investigated using reaction norm models to assess environmental sensitivity and, combined with genome-wide association studies (GWAS), to map genomic regions related to animal adaptation. Including genetic markers from whole-genome sequencing in reaction norm (RN) models allows us to identify high-resolution candidate genes across environmental gradients through GWAS. Hence, we performed a GWAS via the RN approach using whole-genome sequencing data, focusing on mapping candidate genes associated with the expression of reproductive and growth traits in Nellore cattle. For this purpose, we used phenotypic data for age at first calving (AFC), scrotal circumference (SC), post-weaning weight gain (PWG), and yearling weight (YW). A total of 20,000 males and 7,159 females genotyped with 770k were imputed to the whole sequence (29 M). After quality control and linkage disequilibrium (LD) pruning, there remained ∼ 2.41 M SNPs for SC, PWG, and YW and ∼ 5.06 M SNPs for AFC.
RESULTS
Significant SNPs were identified on Bos taurus autosomes (BTA) 10, 11, 14, 18, 19, 20, 21, 24, 25 and 27 for AFC and on BTA 4, 5 and 8 for SC. For growth traits, significant SNP markers were identified on BTA 3, 5 and 20 for YW and PWG. A total of 56 positional candidate genes were identified for AFC, 9 for SC, 3 for PWG, and 24 for YW. The significant SNPs detected for the reaction norm coefficients in Nellore cattle were found to be associated with growth, adaptative, and reproductive traits. These candidate genes are involved in biological mechanisms related to lipid metabolism, immune response, mitogen-activated protein kinase (MAPK) signaling pathway, and energy and phosphate metabolism.
CONCLUSIONS
GWAS results highlighted differences in the physiological processes linked to lipid metabolism, immune response, MAPK signaling pathway, and energy and phosphate metabolism, providing insights into how different environmental conditions interact with specific genes affecting animal adaptation, productivity, and reproductive performance. The shared genomic regions between the intercept and slope are directly implicated in the regulation of growth and reproductive traits in Nellore cattle raised under different environmental conditions.
Topics: Animals; Cattle; Genome-Wide Association Study; Reproduction; Polymorphism, Single Nucleotide; Female; Whole Genome Sequencing; Gene-Environment Interaction; Male; Genotype; Phenotype; Quantitative Trait Loci; Linkage Disequilibrium
PubMed: 38902640
DOI: 10.1186/s12864-024-10520-x -
Nature Communications Jun 2024A major challenge in protein design is to augment existing functional proteins with multiple property enhancements. Altering several properties likely necessitates...
A major challenge in protein design is to augment existing functional proteins with multiple property enhancements. Altering several properties likely necessitates numerous primary sequence changes, and novel methods are needed to accurately predict combinations of mutations that maintain or enhance function. Models of sequence co-variation (e.g., EVcouplings), which leverage extensive information about various protein properties and activities from homologous protein sequences, have proven effective for many applications including structure determination and mutation effect prediction. We apply EVcouplings to computationally design variants of the model protein TEM-1 β-lactamase. Nearly all the 14 experimentally characterized designs were functional, including one with 84 mutations from the nearest natural homolog. The designs also had large increases in thermostability, increased activity on multiple substrates, and nearly identical structure to the wild type enzyme. This study highlights the efficacy of evolutionary models in guiding large sequence alterations to generate functional diversity for protein design applications.
Topics: beta-Lactamases; Protein Engineering; Evolution, Molecular; Mutation; Models, Molecular; Amino Acid Sequence; Enzyme Stability; Protein Conformation
PubMed: 38902262
DOI: 10.1038/s41467-024-49119-x -
Nature Communications Jun 2024mRNA therapeutics are revolutionizing the pharmaceutical industry, but methods to optimize the primary sequence for increased expression are still lacking. Here, we...
mRNA therapeutics are revolutionizing the pharmaceutical industry, but methods to optimize the primary sequence for increased expression are still lacking. Here, we design 5'UTRs for efficient mRNA translation using deep learning. We perform polysome profiling of fully or partially randomized 5'UTR libraries in three cell types and find that UTR performance is highly correlated across cell types. We train models on our datasets and use them to guide the design of high-performing 5'UTRs using gradient descent and generative neural networks. We experimentally test designed 5'UTRs with mRNA encoding megaTAL gene editing enzymes for two different gene targets and in two different cell lines. We find that the designed 5'UTRs support strong gene editing activity. Editing efficiency is correlated between cell types and gene targets, although the best performing UTR was specific to one cargo and cell type. Our results highlight the potential of model-based sequence design for mRNA therapeutics.
Topics: RNA, Messenger; Deep Learning; 5' Untranslated Regions; Humans; Gene Editing; Polyribosomes; Cell Line; HEK293 Cells; Protein Biosynthesis
PubMed: 38902240
DOI: 10.1038/s41467-024-49508-2 -
Microbiology Resource Announcements Jun 2024The draft genome of NIH1002, a 2011 isolate from a case of disseminated disease, was sequenced using PacBio long-read and HiSeq short-read technologies. The genome has...
The draft genome of NIH1002, a 2011 isolate from a case of disseminated disease, was sequenced using PacBio long-read and HiSeq short-read technologies. The genome has 43 contigs, an N50 of 2.65 Mb, and 13,295 protein-coding genes. It is the most complete genome to date.
PubMed: 38899875
DOI: 10.1128/mra.00062-24 -
Journal of Experimental Orthopaedics Jul 2024Establishing zonal tendon-to-bone attachment could accelerate the anterior cruciate ligament reconstruction (ACLR) rehabilitation schedule and facilitate an earlier...
PURPOSE
Establishing zonal tendon-to-bone attachment could accelerate the anterior cruciate ligament reconstruction (ACLR) rehabilitation schedule and facilitate an earlier return to sports. KI24RGDS is a self-assembling peptide hydrogel scaffold (SAPS) with the RGDS amino acid sequence. This study aimed to elucidate the therapeutic potential of KI24RGDS in facilitating zonal tendon-to-bone attachment after ACLR.
METHODS
Sixty-four C57BL/6 mice were divided into the ACLR + SAPS and ACLR groups. ACLR was performed using the tail tendon. To assess the maturation of tendon-to-bone attachment, we quantified the area of mineralized fibrocartilage (MFC) in the tendon graft with demeclocycline. Immunofluorescence staining of α-smooth muscle actin (α-SMA) was performed to evaluate progenitor cell proliferation. The strength of tendon-to-bone attachment was evaluated using a pull-out test.
RESULTS
The MFC and maximum failure load in the ACLR + SAPS group were remarkably higher than in the ACLR group on Day 14. However, no significant difference was observed between the two groups on Day 28. The number of α-SMA-positive cells in the tendon graft was highest on Day 7 after ACLR in both the groups and was significantly higher in the ACLR + SAPS group than in the ACLR group.
CONCLUSION
This study highlighted the latent healing potential of KI24RGDS in facilitating early-stage zonal attachment of tendon grafts and bone tunnels post-ACLR. These findings may expedite rehabilitation protocols and shorten the timeline for returning to sports.
LEVEL OF EVIDENCE
Not applicable.
PubMed: 38899049
DOI: 10.1002/jeo2.12061