Astaxanthin is a bioactive natural pigment with antioxidant properties. It has extensive applications within the industrial sector as well as in human and animal health. Mucor circinelloides is a zygomycete fungus that accumulates β-carotene as the main carotenoid compound. M. circinelloides is a well-known model organism among Mucorales for studying carotenogenesis in fungi, which makes it a promising candidate for the biotechnological production of carotenoids. In this study, β-carotene hydroxylase (crtR-B) and ketolase (bkt) genes (codon-optimized) were coexpressed from Haematococcus pluvialis in M. circinelloides using two potent promoters gpd1 and zrt1 respectively to generate an astaxanthin-producing biofactory. Following 72 h of cultivation, the recombinant M. circinelloides Mc-57 obtained in this study produced 135 ± 8 µg/g of astaxanthin. This is the highest reported amount in M. circinelloides to date. The mRNA levels of crtR-B and bkt in Mc-57 were assayed using RT-qPCR. These levels showed a 5.7-fold increase at 72 h and a 5.5-fold increase at 24 h, respectively, compared to the control strain. This demonstrated the successful overexpression of both genes, which correlated with the production of astaxanthin in the Mc-57. Moreover, the addition of glutamate (2 g/L) and mevalonate (15 mM) resulted in an increase in astaxanthin production in the recombinant strain. The results showed that the combined addition of these metabolic precursors resulted in 281 ± 20 µg/g of astaxanthin, which is 2.08-fold higher than the control medium (135 ± 8 µg/g). The addition of metabolic precursors also positively impacted the biomass growth of Mc-57, reaching 11.2 ± 0.57 g/L compared to 9.1 ± 0.23 g/L (control medium). The study successfully addressed the challenge of balancing the accumulation of astaxanthin with biomass growth, which has been regarded as common bottleneck in the metabolic engineering of microbial cells. The development of a recombinant fungal strain of M. circinelloides not only increased astaxanthin content. Additionally, it provided a foundation for further improvement of the biotechnological production of astaxanthin in M. circinelloides.
A four-year-old female who was born term via spontaneous vaginal delivery (SVD) with a birth weight of 3.4 kg had an onset of persistent hypoglycaemia at the 6th hour of life. She was diagnosed with congenital hyperinsulinism based on high glucose load, negative ketone and a good response to glucagon. Genetic workup revealed the presence of ATP Binding Cassette Subfamily C Member 8 (ABCC8 genes) mutation which indicated a focal form of congenital hyperinsulinism. She was resistant to the standard dose of oral diazoxide but responded to subcutaneous somatostatin. At the age of 3 years and 6 months, multiple daily injections of somatostatin were replaced with a long-acting monthly somatostatin analogue. With the present treatment, she had better glycaemic control, normal growth and was able to stop tube feeding.
Matched MeSH terms: Drug Resistance/genetics; Sulfonylurea Receptors/genetics
The taxonomic classification of a falcon population found in the Mongolian Altai region in Asia has been heavily debated for two centuries and previous studies have been inconclusive, hindering a more informed conservation approach. Here, we generated a chromosome-level gyrfalcon reference genome using the Vertebrate Genomes Project (VGP) assembly pipeline. Using whole genome sequences of 49 falcons from different species and populations, including "Altai" falcons, we analyzed their population structure, admixture patterns, and demographic history. We find that the Altai falcons are genomic mosaics of saker and gyrfalcon ancestries, and carry distinct W and mitochondrial haplotypes that cluster with the lanner falcon. The Altai maternally-inherited haplotypes diverged 422,000 years before present (290,000-550,000 YBP) from the ancestor of sakers and gyrfalcons, both of which, in turn, split 109,000 YBP (70,000-150,000 YBP). The Altai W chromosome has 31 coding variants in 29 genes that may possibly influence important structural, behavioral, and reproductive traits. These findings provide insights into the question of Altai falcons as a candidate distinct species.
Matched MeSH terms: Chromosomes/genetics; Genetics, Population
p16INK4a is a crucial tumor suppressor and regulator of cellular senescence, forming a molecular bridge between aging and cancer. Dysregulated p16INK4a expression is linked to both premature aging and cancer progression, where non-coding RNAs (ncRNAs) such as long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and small interfering RNAs (siRNAs) play key roles in modulating its function. These ncRNAs interact with p16INK4a through complex post-transcriptional and epigenetic mechanisms, influencing pathways critical to senescence and tumor suppression. In this review, we explore ncRNAs, including ANRIL, MIR31HG, UCA1, MALAT1, miR-24, miR-30, and miR-141, which collectively regulate p16INK4a expression, promoting or inhibiting pathways associated with cancer and aging. ANRIL and MIR31HG modulate p16INK4a silencing via interactions with polycomb repressive complexes (PRC), while miRNAs such as miR-24 and miR-30 target p16INK4a to influence cellular proliferation and senescence. This regulatory interplay underscores the therapeutic potential of ncRNA-targeted strategies to restore p16INK4a function. We summarize recent studies supporting that ncRNAs that control p16INK4a may be diagnostic biomarkers and therapeutic targets for age-related diseases and cancer.
RNA interference regulates gene expression by selectively silencing target genes through the introduction of small RNA molecules, such as microRNA, small interfering RNA and short hairpin RNA. These molecules offer significant therapeutic potential for diverse human ailments like cancer, viral infections and neurodegenerative disorders. Whilst non-viral vectors like nanoparticles have been extensively explored for delivering these RNAs, viral vectors, with superior specificity and delivery efficiency, remain less studied. This review examines current viral vectors for small RNA delivery, focusing on design strategies and characteristics. It compares the advantages and drawbacks of each vector, aiding readers in selecting the optimal one for small RNA delivery.
Cuticles protect plants from water loss and pathogen attack. We address here the functional significance of SlGRAS9, SlZHD17, and SlMBP3 in regulating cutin formation in tomato fruit. The study unveils the role of the multipartite "SlGRAS9-SlZHD17-SlMBP3-SlMIXTA-like" transcription factor module in cutin biosynthesis. Plants deficient in SlGRAS9, SlZHD17, or SlMBP3 exhibit thickened cuticles and a higher accumulation of cutin monomers, conferring extended fruit shelf life and higher tolerance to postharvest fungal infection. SlGRAS9 regulation of cutin is mediated by SlZHD17, a negative regulator of SlCYP86A69. SlZHD17 acts synergistically with SlMBP3 to repress SlCYP86A69, and its interaction with SlMIXTA-like prevents the binding to the SlCYP86A69 promoter, thereby releasing the repression of cutin biosynthesis. SlZHD17 and SlMBP3 synergistically repress cutin biosynthesis, while SlMIXTA-like and SlCD2 act antagonistically to SlZHD17 and SlMBP3 on this metabolic pathway. The study defines targets for breeding strategies aimed at improving cuticle-associated traits in tomato and potentially other crops.
Background: The link between rheumatoid arthritis (RA) and schizophrenia (SZ) has long been a hot topic of deliberation among scientists from various fields. Especially when it comes to genetics, the connection between RA and SZ is still up for discussion, as can be observed in this study. The HLA genes are the most disputed in identifying a connection between the two diseases, but a more thorough investigation of other genes that may be ignored could yield something even more interesting. Thus, finding the genes responsible for this long-sought relationship will necessitate looking for them. Materials and Methods: Shared and overlapped associated genes involved between SZ and RA were extracted from four databases. The overlapping genes were examined using Database for Annotation, Visualization and Integrated Discovery (DAVID) and InnateDB to search the pertinent genes that concatenate between these two disorders. Results: A total of 91 overlapped genes were discovered, and that 13 genes, divided into two clusters, showed a similarity in function, suggesting that they may serve as an important meeting point. FCGR2A, IL18R, BTNL2, AGER, and CTLA4 are five non-HLA genes related to the immune system, which could lead to new discoveries about the connection between these two disorders. Conclusion: An in-depth investigation of these functionally comparable non-HLA genes that overlap could reveal new interesting information in both diseases. Understanding the molecular and immune-related aspects of RA and SZ may shed light on their etiology and inform future research on targeted treatment strategies.
The clawed lobster Nephrops norvegicus is an important commercial species in European waters. We have sequenced the complete mitochondrial genome of the species from a partial genome scan using Next-Gen sequencing. The N. norvegicus has a mitogenome of 16,132 base pairs (71.22% A+ T content) comprising 13 protein-coding genes, 2 ribosomal subunit genes, 21 transfer RNAs, and a putative 1259 bp non-coding AT-rich region. This mitogenome is the second fully characterized for the family Nephropidae and the first for the genus Nephrops. The mitogenome gene order is identical to the Maine lobster, Homarus americanus with the exception of the possible loss of the trnI gene.
High temperature tolerance is an important component of adaptation to arid and semiarid cropping environment in chili pepper. Two experiments were carried out to study the genetic variability among chili pepper for heat tolerance and morphophysiological traits and to estimate heritability and genetic advance expected from selection. There was a highly significant variation among the genotypes in response to high temperature (CMT), photosynthesis rate, plant height, disease incidence, fruit length, fruit weight, number of fruits, and yield per plant. At 5% selection intensity, high genetic advance as percent of the mean (>20%) was observed for CMT, photosynthesis rate, fruit length, fruit weight, number of fruits, and yield per plant. Similarly, high heritability (>60%) was also observed indicating the substantial effect of additive gene more than the environmental effect. Yield per plant showed strong to moderately positive correlations (r = 0.23-0.56) at phenotypic level while at genotypic level correlation coefficient ranged from 0.16 to 0.72 for CMT, plant height, fruit length, and number of fruits. Cluster analysis revealed eight groups and Group VIII recorded the highest CMT and yield. Group IV recorded 13 genotypes while Groups II, VII, and VIII recorded one each. The results showed that the availability of genetic variance could be useful for exploitation through selection for further breeding purposes.
The mitochondrial genome of the rock pool prawn (Palaemon serenus), is sequenced, making it the third for genera of the family Palaemonidae and the first for the genus Palaemon. The mitogenome is 15,967 base pairs in length and comprises 13 protein-coding genes, 2 ribosomal subunit genes, 22 transfer RNAs and a non-coding AT-rich region. The P. serenus mitogenome has an AT bias of 58.97% and a base composition of 29.79% for T, 24.14% for C, 29.18% for A, and 16.89% for G. The mitogenome gene order of P. serenus is identical to Exopalaemon carinicauda.
The mitochondrial genome sequence of the Australian freshwater shrimp, Paratya australiensis, is presented, which is the fourth for genera of the superfamily Atyoidea and the first atyid from the southern hemisphere. The base composition of the P. australiensis, mitogenome is 33.55% for T, 18.24% for C, 35.16% for A, and 13.06% for G, with an AT bias of 71.58%. It has a mitogenome of 15,990 base pairs comprised of 13 protein-coding, 2 ribosomal subunit and 22 transfer RNAs genes and a non-coding AT-rich region. The mitogenome gene order for the species is typical for atyid shrimps, which conform to the primitive pan crustacean model.
Rice blast disease, which is caused by the fungal pathogen Magnaporthe oryzae, is a recurring problem in all rice-growing regions of the world. The use of resistance (R) genes in rice improvement breeding programmes has been considered to be one of the best options for crop protection and blast management. Alternatively, quantitative resistance conferred by quantitative trait loci (QTLs) is also a valuable resource for the improvement of rice disease resistance. In the past, intensive efforts have been made to identify major R-genes as well as QTLs for blast disease using molecular techniques. A review of bibliographic references shows over 100 blast resistance genes and a larger number of QTLs (∼500) that were mapped to the rice genome. Of the blast resistance genes, identified in different genotypes of rice, ∼22 have been cloned and characterized at the molecular level. In this review, we have summarized the reported rice blast resistance genes and QTLs for utilization in future molecular breeding programmes to introgress high-degree resistance or to pyramid R-genes in commercial cultivars that are susceptible to M. oryzae. The goal of this review is to provide an overview of the significant studies in order to update our understanding of the molecular progress on rice and M. oryzae. This information will assist rice breeders to improve the resistance to rice blast using marker-assisted selection which continues to be a priority for rice-breeding programmes.
The mitogenome of the Australian freshwater blackfish, Gadopsis marmoratus was recovered coverage by genome skimming using the MiSeq sequencer (GenBank Accession Number: NC_024436). The blackfish mitogenome has 16,407 base pairs made up of 13 protein-coding genes, 2 ribosomal subunit genes, 22 transfer RNAs, and a 819 bp non-coding AT-rich region. This is the 5th mitogenome sequence to be reported for the family Percichthyidae.
Matched MeSH terms: Base Composition/genetics; Perciformes/genetics*; Base Pairing/genetics
The mitochondrial genome sequence of the Australian tadpole shrimp, Triops australiensis is presented (GenBank Accession Number: NC_024439) and compared with other Triops species. Triops australiensis has a mitochondrial genome of 15,125 base pairs consisting of 13 protein-coding genes, 2 ribosomal subunit genes, 22 transfer RNAs, and a non-coding AT-rich region. The T. australiensis mitogenome is composed of 36.4% A, 16.1% C, 12.3% G and 35.1% T. The mitogenome gene order conforms to the primitive arrangement for Branchiopod crustaceans, which is also conserved within the Pancrustacean.
Matched MeSH terms: Crustacea/genetics*; Larva/genetics; Base Pairing/genetics
Calamus palustris Griff. is an economically important dioecious rattan species in Southeast Asia. However, dioecy and onset of flowering at 3-4 years old render uncertainties in desired female:male seedling ratios to establish a productive seed orchard for this rattan species. We constructed a subtractive library for male floral tissue to understand the genetic mechanism for gender determination in C. palustris. The subtractive library produced 1536 clones with 1419 clones of high quality. Reverse Northern screening showed 313 clones with differential expression, and sequence analyses clustered them into 205 unigenes, including 32 contigs and 173 singletons. The subtractive library was further validated with reverse transcription-quantitative polymerase chain reaction analysis. Homology identification classified the unigenes into 12 putative functional proteins with 83% unigenes showing significant match to proteins in databases. Functional annotations of these unigenes revealed genes involved in male flower development, including MADS-box genes, pollen-related genes, phytohormones for flower development, and male flower organ development. Our results showed that the male floral genes may play a vital role in sex determination in C. palustris. The identified genes can be exploited to understand the molecular basis of sex determination in C. palustris.
The complete mitogenome of the ray Pastinachus atrus was recovered from a partial genome scan using the HiSeq sequencing system. The P. atrus mitogenome has 18,162 base pairs (61% A + T content) made up of 13 protein-coding genes, 2 ribosomal subunit genes, 22 transfer RNAs, and a 2516 bp non-coding AT-rich region. This mitogenome sequence is the first for a ray from Australian waters, the first for the Genus Pastinachus, and the 6th for the family Dasyatidae.
Hydrophobins are small secreted fungal proteins that play roles in growth and development of filamentous fungi, i.e. in the formation of aerial structures and the attachment of hyphae to hydrophobic surfaces. In Botrytis cinerea, three hydrophobin genes have been identified. Studies by Mosbach et al. (2011) showed that hydrophobins are neither involved in conferring surface hydrophobicity to conidia and aerial hyphae of B. cinerea, nor are they required for virulence. The present study investigated the role of hydrophobins in sclerotium and apothecium development. Expression analysis revealed high expression of the Bhp1 gene during different stages of apothecium development. Two Bhp1 splice variants were detected that differ by an internal stretch of 13 amino acid residues. Seven different mutants in which either a single, two or three hydrophobin genes were knocked out, as well as two wild type strains of opposite mating types, were characterized for sclerotium and apothecium development. No aberrant morphology was observed in sclerotium development when single deletion mutants in hydrophobin genes were analyzed. Sclerotia of double knock out mutant ΔBhp1/ΔBhp3 and the triple knock out mutant, however, showed easily wettable phenotypes. For analyzing apothecium development, a reciprocal crossing scheme was setup. Morphological aberrations were observed in crosses with two hydrophobin mutants. When the double knock out mutant ΔBhp1/ΔBhp2 and the triple knock out mutant were used as the maternal parent (sclerotia), and fertilized with wild type microconidia, the resulting apothecia were swollen, dark brown in color and had a blotched surface. After initially growing upwards toward the light source, the apothecia in many cases collapsed due to loss of structural integrity. Aberrant apothecium development was not observed in the reciprocal cross, when these same mutants were used as the paternal parent (microconidia). These results indicate that the presence of hydrophobins in maternal tissue is important for normal development of apothecia of B. cinerea.
For centuries, morphology-based fish identification has been applied without molecular evaluation. Many studies showed that specimens with a similar morphology are frequently found to be quite genetically distinct. One of the fish species that still remains taxonomically problematic is a commercial snapper species, Lutjanus johnii. Because of morphological ambiguities among local fish taxonomists in Malaysia, we examined the ability of the cytochrome oxidase I (COI) gene to genetically examine the taxonomic status of L. johnii. A 626-base pair COI region was successfully amplified and aligned with conspecific sequences that were retrieved from GenBank. The phylogenetic tree obtained showed two major clusters; the first cluster consists of L. johnii from Straits of Malacca, Thailand, Australia, and China while the second cluster comprises L. johnii from China and India. The latter group showed sequence divergence greater than 3.5%. After observing this, we suspected that there might be a cryptic species between the South China Sea and Indian Ocean. This is the first molecular report concerning the commercial species of snapper, L. johnii, in Malaysia, which had only gained provisional recognition from morphological examination.
Matched MeSH terms: Electron Transport Complex IV/genetics; DNA, Mitochondrial/genetics; Fishes/genetics*
The Kelantanese Malays who resided in the remote northeastern regions of the Malay Peninsula in the Kelantan state are believed to have a unique genetic signature. The objective of this review is to analyze the populational sub-structure of the Kelantanese Malays from historical, genetic and linguistic perspectives. Historical data suggest that the Semang were composed of the Jahai, Bateq and Kensiu sub-tribes, whereas the Senoi were composed of only the Temiar sub-tribe. The Mendriq sub-tribe is believed to be the first group of aborigines to land in Kelantan. Subsequently, genetic analysis showed that the Kelantanese Malays are an independent clade at the base of the phylogenetic tree and contain genetic material similar to that of the Semang, specifically the Jahai and the Kensiu sub-tribes. The genetic data are supported by the fact that the Aslian language, a branch of the Austroasiatic languages that is widely spoken by the Semang, was potentially transmitted through agricultural activities. However, the potential limitation of this mini-review is the lack of primary reliable sources covering the historical, linguistic and genetic features of the Kelantanese Malays.
We conducted a meta-analysis in order to investigate the relationships between PTEN gene mutations and the prognosis in glioma. The following electronic databases were searched for relevant articles without any language restrictions: Web of Science (1945 ~ 2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966 ~ 2013), EMBASE (1980 ~ 2013), CINAHL (1982 ~ 2013), and the Chinese Biomedical Database (CBM) (1982 ~ 2013). Meta-analyses were conducted using the STATA software (Version 12.0, Stata Corporation, College Station, Texas USA). Hazard ratio (HR) with its corresponding 95 % confidence interval (95%CI) was calculated. Six independent cohort studies with a total of 357 glioma patients met our inclusion criteria. Our meta-analysis results indicated that glioma patients with PTEN gene mutations exhibited a significantly shorter overall survival (OS) than those without PTEN gene mutations (HR = 3.66, 95%CI = 2.02 ~ 5.30, P < 0.001). Ethnicity-stratified subgroup analysis demonstrated that PTEN gene mutations were closely linked to poor prognosis in glioma among Americans (HR = 3.72, 95%CI = 1.72 ~ 5.73, P < 0.001), while similar correlations were not observed among populations in Sweden, Italy, and Malaysia (all P > 0.05). Our meta-analysis provides direct and strong evidences for the speculation of PTEN gene mutations' correlation with poor prognosis of glioma patients.