Research Articles (Biochemistry, Genetics and Microbiology (BGM))

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Characterizing the quick-killing mechanism of action of azithromycin analogs against malaria parasites
(American Society for Microbiology, 2025-09) Mao, Emma Y.; Nguyen, William; Jana, Gouranga P.; Maity, Bikash C.; Pazicky, Samuel; Giannangelo, Carlo; Reader, Janette; Famodimu, Mufuliat T.; Birkholtz, Lyn-Marie; Delves, Michael J.; Creek, Darren J.; Bozdech, Zbynek; Laleu, Benoit; Burrows, Jeremy N.; Sleebs, Brad E.; Gancheva, Maria R.; Wilson, Danny W.
Drug resistance is steadily undermining the efficacy of frontline anti-malarials, highlighting the urgent need for novel therapies with alternative mechanisms of action. The chemical addition of different moieties to azithromycin yields compounds with improved quick-killing potency against malaria parasites, with the most active analogs typically containing a chloroquinoline group. Here, we investigated the quick-killing mechanism of five azithromycin analogs, two of which contain differentially oriented chloroquinoline moieties. The improvement in quick-killing activity over azithromycin for non-chloroquinoline analogs was around 10 -to 42-fold, with chloroquinoline-containing analogs showing a further 2- to 17-fold improvement over non-chloroquinoline compounds. Chemical inhibition of hemoglobin digestion and chloroquine's inhibitory effect against heme polymerization linked analogs with both chloroquinoline and non-chloroquinoline modifications to a chloroquine-like mechanism of action. However, none of the analogs showed a significant reduction in efficacy against chloroquine-resistant asexual blood-stage parasites. Multiple attempts at selecting for azithromycin analog-resistant parasites to elucidate the mechanism of quick-killing were unsuccessful. Application of cellular thermal shift proteomics revealed that azithromycin analogs significantly stabilized 34-155 different proteins in trophozoites, a high number that showed minimal overlap with chloroquine. Additionally, our most potent chloroquinoline-containing analog demonstrated a significant improvement in gametocytocidal activity over azithromycin and further maintained moderate inhibition of chloroquine-insensitive late-stage gametocytes. These findings support that this class of azithromycin analogs kills malaria parasites through a broad range of potential mechanisms, making them promising candidates for optimization as fast and broad-acting anti-malarials.
Plant pathogen name game : Cross Kingdom Review for the naming of biotic agents associated with plants
(Annual Reviews, 2025-09) Bull, Carolee T.; Salgado-Salazar, Catalina; Romberg, Megan K.; Allen, Cavan; Kantor, Mihail; Handoo, Zafar; Aboughanem-Sabanadzovic, Nina; Sabanadzovic, Sead; Coutinho, Teresa A.
To communicate across scientific disciplines, regulatory bodies, and the agricultural community, the naming of plant pathogens assigned to specific taxa is critical. Here, we provide an overview of the nomenclatural systems governing the naming of plant-pathogenic nematodes, fungi, oomycetes, prokaryotes, and viruses. Although we focus on the nature of the nomenclatural codes, we briefly discuss fundamental principles of taxonomy, including classification and identification. Key elements of the codes of nomenclature that ensure stability and clarity when naming species of pathogens are defined. When comparing the practice of nomenclature across different kingdoms, the classification and nomenclatural systems differ, and thus unique challenges are faced. We provide guidance from the codes and current practice for naming novel species. When there are nomenclatural conflicts, international committees play a critical role in their resolution. They also play a role in updating the codes to reflect new advancements in science. With this review, we aim to assist plant pathologists, journal editors, and those in related fields by providing an entrée to the legalistic requirements of the codes. Authors must consult and follow the rules of the appropriate code for any proposal of new or new combinations of names. To those interested in naming new species (or renaming the current ones), we recommend collaborations with experts in the field of taxonomy to ensure that rules for accurate and consistent naming practices and procedures are followed and to increase the likelihood that the proposed nomenclature is correct and acceptable.
Cryphonectriaceae : biodiverse and threatening tree pathogens in the tropics and southern hemisphere
(Annual Reviews, 2025-09) Wingfield, Michael J.; Pham, Nam Q.; Marincowitz, Seonju; Wingfield, Brenda D.; mike.wingfield@fabi.up.ac.za
The chestnut blight pathogen Cryphonectria parasitica is well-known for the devastation it caused to North American forests. It is less well recognized that numerous other fungi in the Cryphonectriaceae are emerging as threats to native and planted forests in the tropics and Southern Hemisphere. Unlike C. parasitica, these fungi, such as Chrysoporthe cubensis, initially gained attention due to a canker disease in plantations of non-native Eucalyptus. More than four decades of research have revealed a wide diversity of Cryphonectriaceae species that infect many other tree genera in the Myrtales. These fungi often exist as endophytes but become problematic when trees are planted outside their native range. Growing numbers of species are also undergoing host shifts from native to susceptible trees such as Eucalyptus, posing serious risks to both natural and planted forests. These fungi provide an example of the biodiversity of tree-infecting fungi that is understudied, despite their significant potential to harm forest ecosystems.
Breed-specific genetic recombination analysis in South African Bonsmara and Nguni cattle using genomic data
(MDPI, 2025-08) Magagula, Nozipho A.; Mtileni, Bohani; Ncube, Keabetswe T.; Khanyile, Khulekani S.; Zwane, Avhashoni Agnes
South African cattle comprise diverse breeds with distinct evolutionary histories, potentially reflecting differences in recombination landscapes. This study assessed genome-wide recombination rates and hotspots in Bonsmara (n = 190) and Nguni (n = 119) cattle using three-generation half-sib pedigrees genotyped with the Illumina Bovine SNP50 BeadChip. Phasing across 29 autosomes was conducted using SHAPEIT v2, and crossover events were inferred using the DuoHMM algorithm. The total number of crossover events detected was higher in Nguni (n = 8982) than in Bonsmara (n = 7462); however, the average recombination rate per 1 Mb window was significantly higher in Bonsmara (0.31) compared to Nguni (0.18) (p < 0.01). This apparent discrepancy reflects differences in genomic distribution and crossover clustering across breeds, rather than overall recombination frequency. A critical limitation of the study is the reliance on half-sib families with small family sizes, which may underestimate recombination rates due to limited meiotic sampling and increased variance in crossover detection. We identified 407 recombination hotspots in Bonsmara and 179 in Nguni, defined as intervals exceeding 2.5 standard deviations above the mean recombination rate. Genes such as PDE1B and FP which are associated with productions traits were located within hotspot-enriched regions. However, functional causality between these genes and local recombination activity remains unverified. Our results provide statistically supported evidence for breed-specific recombination patterns and hotspot distributions, underscoring the importance of incorporating recombination architecture into genetic improvement strategies for South African cattle.
Investigating bark, ambrosia and nitidulid beetle (Coleoptera : Scolytinae and Nitidulidae) communities and their potential role in the movement of Ceratocystis manginecans in commercial forestry plantations in Riau, Indonesia
(Wiley, 2025-11) Lynn, Kira Mary Theresa; Wingfield, Michael J.; Tarigan, Marthin; Duran, Alvaro; Santos, Samuel A.; Nel, Wilma Janine; Barnes, Irene; irene.barnes@fabi.up.ac.za
Ceratocystis Canker and Wilt Disease (CCWD), caused by the fungal pathogen Ceratocystis manginecans, poses a significant threat to Acacia and Eucalyptus plantations in Indonesia. Infections typically occur through wounds on the main stems of trees, and infected trees, particularly Acacia, are often co-infested by various wood-associated beetles. The aim of this study was to identify the beetle species associated with Ceratocystis-infected trees and to assess their potential role in dispersing C. manginecans. Beetle and frass samples were collected from Ceratocystis-infected compartments of Acacia and Eucalyptus propagated as monocultures in Riau, Indonesia, either by using traps or by direct collection from infected trees. The samples were screened for the presence and viability of Ceratocystis propagules using a quantitative polymerase chain reaction-high-resolution melting analysis (qPCR-HRMA) diagnostic tool and a carrot baiting technique, respectively. Fourteen beetle species, predominantly collected from traps, representing nine genera of the Scolytinae and Nitidulidae, were identified from the two plantation types. The qPCR tool detected the presence of Ceratocystis DNA on 13 of the 14 beetle species at concentrations as low as 0.015–0.0019 ng. However, viable Ceratocystis propagules could not be recovered from these beetles using culture-based methods. Of the 105 frass samples screened, qPCR detected Ceratocystis DNA in 67 samples; however, only one Ceratocystis isolate was obtained using the carrot baiting method. The results of this study suggest that the beetles and beetle frass can harbour Ceratocystis propagules, as indicated by the detection of fungal DNA. However, the viability of the propagules and the ability of the beetles and/or beetle frass to spread C. manginecans requires further investigation.
Early detection of Phytophthora root rot in Eucalyptus using hyperspectral reflectance and machine learning
(Elsevier, 2025-10) Esterhuizen, Hendrik J.; Slippers, Bernard; Bosman, Anna Sergeevna; Roux, Jolanda; Jones, Wayne; Bose, Tanay; Hammerbacher, Almuth; tanay.bose@fabi.up.ac.za
The rising prevalence of Phytophthora diseases in forests highlights the need for rapid, non-invasive detection methods. Early-stage root infections are difficult to detect due to the absence of visible above-ground symptoms, while current diagnostics remain slow and invasive. This study investigated whether hyperspectral leaf reflectance could detect root rot caused by Phytophthora alticola in Eucalyptus benthamii. Nineteen commercially planted families were inoculated, and leaf spectra were collected using an ASD FieldSpec 4 sensor. A machine learning pipeline was developed to identify diagnostic spectral signals. Key wavelengths were identified using permutation importance, a genetic algorithm, and self-attention network (SAN) scores. Spectral signals linked to root rot revealed that infection was correlated with leaf pigment accumulation and moisture stress. Three algorithms, random forest (RF), support vector machine (SVM), and SAN, were trained on hyperspectral data to predict P. alticola infection. The SAN achieved 97 % accuracy on a reduced dataset, which included the diagnostic wavelengths from the feature selection step, surpassing the RF (96 %) and SVM (94 %) models. This study demonstrates hyperspectral sensing as an effective tool for detecting Phytophthora root rot using spectra from the foliage and highlights the application of advanced machine learning techniques for plant disease classification. HIGHLIGHTS • Hyperspectral sensing detects Phytophthora root rot before symptoms appear. • SAN model achieved 97 % accuracy using selected wavelengths from leaf spectra. • Key wavelengths correlated with pigment shifts and moisture stress in leaves. • Machine learning identified spectral markers for early disease detection. • Vegetation indices NDNI and MSI are strongly linked to infection status.
Chemodiversity of penicillium isolated from alpine and arctic environments, including ten new species
(Westerdijk Fungal Biodiversity Institute, 2025-08-01) Overy, D.P.; Frisvad, J.C.; Witte, T.E.; Hicks, C.L.; Hermans, A.; Sproule, A.; Louis-Seize, G.; Seifer, K.A.; Yilmaz, Neriman; Price, Jodi; Van Vuuren, Nicole Innike; Visagie, Cobus M.; cobus.visagie@fabi.up.ac.za
Polar, high altitude montane and cold desert environments harbour only sparse plant life and often remain frozen for extended periods. Because of their remoteness, often combined with restricted access, such regions are rarely visited and the fungal biodiversity of the soils is scarcely studied. Despite this, when such studies are undertaken, psychrophilic Penicillium species are often reported and the isolates exhibit a high spectrum of biologically active compounds of biotechnological interest. Small molecule profiling by mass spectrometry (often called ‘metabolomics’) can supplement phylogenetic species concepts and provide information to characterize variation within species or populations. During large scale fungal isolation surveys exploring new psychrophilic fungi from high altitude alpine and arctic tundra soils, several undescribed Penicillium species were discovered. A polyphasic taxonomic approach was adopted to formally describe ten new species using multigene phylogenetic analyses and phenotypic characterizations including secondary metabolite production, colony characters, and microscopic analysis of morphological structures. Using untargeted metabolomics and molecular networking tools, an emphasis was made to characterize, compare and discuss in depth, the chemical diversity associated with these new Penicillium species.
Epigenetic background of lineage-specific gene expression landscapes of four Staphylococcus aureus hospital isolates
(Public Library of Science, 2025-05) Korotetskiy, Ilya S.; Shilov, Sergey V.; Kuznetsova, Tatyana V.; Zubenko, Natalya; Ivanova, Lyudmila; Reva, Oleg N.; oleg.reva@up.ac.za
Bacteria with similar genomes can exhibit different phenotypes due to alternative gene expression patterns. In this study, we analysed four antibiotic-resistant Staphylococcus aureus hospital isolates using transcriptomics, PacBio genome sequencing, and methylomics analyses. Transcriptomic data were obtained from cultures exposed to gentamicin, the iodine-alanine complex CC-196, and their combination. We observed strain-specific expression patterns of core and accessory genes that remained stable under antimicrobial stress – a phenomenon we term the Clonal Gene Expression Stability (CGES) that is the main discovery of the paper. An involvement of epigenetic mechanisms in stabilization of the CGES was hypothesized and statistically verified. Canonical methylation patterns controlled by type I restriction-modification systems accounted for ~ 10% of epigenetically modified adenine residues, whereas multiple non-canonically modified adenines were distributed sporadically due to imperfect DNA targeting by methyltransferases. Protein-coding sequences were characterized by a significantly lower frequency of modified nucleotides. Epigenetic modifications near transcription start codons showed a statistically significant negative association with gene expression levels. While the role of epigenetic modifications in gene regulation remains debatable, variations in non-canonical modification patterns may serve as markers of CGES.
Subolesin gene structure and mRNA isoform diversity in South African R. microplus ticks : relevance for understanding subolesin-based tick vaccines
(Elsevier, 2025-07) Rabie, Elsje Christine; Maritz-Olivier, Christine; christine.maritz@up.ac.za
Designing a universal vaccine against ticks, capable of protecting a wide range of species, has long been an appealing goal. One antigen that has been proposed for a universal tick vaccine is Subolesin. Despite its intracellular and mostly nuclear location, this antigen has seen some success in bovine vaccine trials. The mechanism behind the observed efficacy remains elusive and may be due to various isoforms being produced in tick cells. By means of RNA sequencing and mapping to the annotated genome of R. microplus, this study confirms the presence of a single subolesin gene along with four distinct transcripts, resulting in three protein variants. However, none of the putative protein variants have extracellular location signals or known functional motifs. Furthermore, this study offers insights into the antigenic diversity of Subolesin isoforms and their expression across multiple life stages in R. microplus ticks from South Africa. This study also raise the question regarding the contrast between Subolesin's nuclear location, function, and its observed efficacy in bovine vaccine trials as an antigen accessible to the host immune system. Future studies evaluating antisera cross-reactivity with other tick proteins is therefore essential to fully understand subolesin as a protective antigen.
Factors that influence the flight activity, abundance and infestation severity of the polyphagous shot hole borer beetle (PSHB, Euwallacea fornicatus) in an urban-agricultural fringe setting
(Elsevier, 2025-10) Roberts, Elise; Paap, Trudy; Roets, Francois
The polyphagous shot hole borer (PSHB, Euwallacea fornicatus) has invaded multiple countries, including South Africa. Along with its fungal mutualist, PSHB has caused the death of a wide range of tree species. Unmitigated costs of invasion in South Africa are estimated to be high. This study consisted of a 26-month PSHB monitoring programme using baited traps in an urban-agricultural fringe setting in the Western Cape province, focusing on revealing the factors most important to flight activity, beetle abundance, and infestation severity. It also tested the validity of felling infested trees as a management option to reduce beetle numbers (propagule pressure). More than half of the 94 study plots evaluated had PSHB-infested trees. Beetle flight activity was highest in summer and negligible in winter, with flight activity being positively correlated with temperature, beetle developmental degree days and beetle flight hours. The surrounding abundance of infested hosts was positively correlated with beetle abundance and infestation levels, though “saturation” in the infestation of a focal host tree may be a deterrent to dispersing beetles. Trees in plots that experience water stress (seasonal flooding) had higher dispersing beetle abundance and infestation levels, suggesting that tree stress might play a role in attracting beetles or making trees more vulnerable to infestation. Beetle activity during tree felling echoed the overall seasonal trend, and higher numbers of dispersing beetles on the day of tree felling in summer suggest that felling activities should best be conducted in winter. For three host tree species, infestation severity increased with decreasing tree size, which may be due to larger trees having thicker bark or other better defence systems. This study provides insight into the ecology of PSHB in this region of South Africa, which is important for developing monitoring and management strategies.
The effect of semiorganic iodine-containing compounds on the antibiotic susceptibility of pathogenic microorganisms
(MDPI, 2025-08) Kenesheva, Sabina T.; Turganbay, Seitzhan; Jumagaziyeva, Ardak B.; Askhatkyzy, Gaukhar; Askarova, Dana A.; Azembayev, Amir A.; Ilin, Alexandr I.; Reva, Oleg N.; Karpenyuk, Tatyana A.; oleg.reva@up.ac.za
OBJECTIVES : The global rise in multidrug resistance underscores the urgent need for the development of novel and effective antimicrobial agents. Semi-organic iodine-containing complexes, owing to their unique properties, low likelihood of resistance development, and stability under various conditions, represent a promising avenue for the design of new therapeutic strategies. This study describes the synthesis of semi-organic iodine-containing complexes and the in vitro evaluation of their impact on antibiotic susceptibility modulation in the multidrug-resistant pathogenic microorganisms S. aureus and E. coli. METHODS: The physicochemical properties of the semiorganic compounds were characterized using UV-Vis spectroscopy, potentiometric, and titrimetric methods. Evaluation of antimicrobial activity was obtained according to CLSI protocols. The impact of semiorganic compounds on the in vitro susceptibility of MDR strains was evaluated by the disk diffusion method. RESULTS : This study evaluated the effects of iodine-containing complexes KC-270 and KC-271 on the antibiotic susceptibility of Staphylococcus aureus BAA-39 and Escherichia coli BAA-196. The most pronounced effect was observed with KC-270 applied during the lag phase, which enhanced the activity of several antibiotics and, in some cases, restored susceptibility. KC-271 exhibited a weaker and more limited impact. The findings suggest that KC-270 has potential as a modulator of antibiotic susceptibility, particularly when administered at early stages of bacterial growth. CONCLUSIONS : The results support the ability of amino acid-based iodine coordination compounds to influence the antibiotic susceptibility of pathogenic bacteria, highlighting their potential as adjuvant agents to improve the effectiveness of current antimicrobial therapies. However, although changes in susceptibility were detected, neither compound fully eliminated resistance in the multidrug-resistant strains, indicating the necessity for further research into their mechanisms of action and possible synergistic interactions with antibiotics.
In vitro photoprotective and skin aging-related enzyme in-hibitory activities of Cylindrospermum alatosporum (NR125682) and Loriellopsis cavernicola (NR117881) extracts
(MDPI, 2025-09) Sithole, Siphesihle Z.; Ikhane, Albert O.; Osunsanmi, Foluso Oluwagbemiga; Mosa, Rebamang Anthony; Opoku, Andrew Rowland; rebamang.mosa@up.ac.za
The use of cyanobacteria has gained considerable interest in many industries, including the cosmetic industry, due to its rich array of bioactive metabolites. This study evaluates the in vitro photoprotective properties and the effect of Cylindrospermum alatosporum (NR125682) and Loriellopsis cavernicola (NR117881) extracts on slowing down the enzymes associated with skin aging. Various crude extracts were prepared using hexane, dichloromethane, and ethanol solvents. The resulting crude extract solvents were completely distilled to obtain their bioactive compounds, based on selected polarities. The sulfhydryl content of the crude extracts was determined and the aging-associated enzymes’ activity (collagenase, elastase, hyaluronidase, and tyrosinase) in the crude extracts was investigated. Furthermore, the in vitro photoprotective activity of the extracts was assessed by measuring UVA and UVB photoprotection. Most of the extracts contained varying amounts of sulfhydryl compounds (10.88–78.15 mg/g). All of the extracts demonstrated in vitro inhibitory activity against tyrosinase, hyaluronidase (IC50 6 µg/mL), and collagenase (IC50 50–70 µg/mL); weak elastase inhibitory activities were also observed. The crude extracts also showed appreciable UVA and UVB photoprotective activity. Meanwhile, L. cavernicola extracts demonstrated the highest UVB photoprotective activity (SPF 14.67–78.96). It is noteworthy that the crude extracts possessed anti-skin-aging potency with notable photoprotective capability.
Understanding the genetics of sex determination in insects and its relevance to genetic pest management
(Wiley, 2025-06) Ashmore, Jade Sabrina; Slippers, Bernard; Duong, Tuan A.; Dittrich-Schroder, Gudrun; gudrun.dittrich@fabi.up.ac.za
Sex determination pathways regulate male and female-specific development and differentiation and offer potential targets for genetic pest management methods. Insect sex determination pathways are comprised of primary signals, relay genes and terminal genes. Primary signals of coleopteran, dipteran, hymenopteran and lepidopteran species are highly diverse and regulate the sex-specific splicing of relay genes based on the primary signal dosage, amino acid composition or the interaction with paternally inherited genes. In coleopterans, hymenopterans and some dipterans, relay genes are Transformer orthologs from the serine-arginine protein family that regulate sex-specific splicing of the terminal genes. Alternative genes regulate the splicing of the terminal genes in dipterans that lack Transformer orthologs and lepidopterans. Doublesex and Fruitless orthologs are the terminal genes. Doublesex and Fruitless orthologs are highly conserved zinc-finger proteins that regulate the expression of downstream proteins influencing physical traits and courtship behaviours in a sex-specific manner. Genetic pest management methods can use different mechanisms to exploit or disrupt female-specific regions of different sex determination genes. Female-specific regions of sex determination genes can be exploited to produce a lethal gene only in females or disrupted to impede female development or fertility. Reducing the number of fertile females in pest populations creates a male-biased sex ratio and eventually leads to the local elimination of the pest population. Knowledge on the genetic basis of sex determination is important to enable these sex determination pathways to be exploited for genetic pest management.
Ferrocenyl quinoline-benzimidazole hybrids : a multistage strategy to combat drug-resistant malaria
(American Chemical Society, 2025-07) Golding, Taryn M.; Garnie, Larnelle F.; Rabie, Tayla Anne; Reader, Janette; Birkholtz, Lyn-Marie; Wicht, Kathryn J.; Smith, Gregory S.
Molecular hybridization and metal incorporation are widely employed strategies for drug development aimed at enhancing pharmacological efficacy while mitigating the emergence of drug resistance. The effectiveness of these approaches is supported by numerous studies demonstrating their success against a range of diseases. Despite the deployment of malaria vaccines, effective treatment remains hindered by the persistent emergence of drug-resistant Plasmodium falciparum strains, contributing to an alarming global disease burden. Inspired by the antimalarial candidate ferroquine, this study focused on the design and synthesis of ferrocenyl-based quinoline-benzimidazole molecular hybrids. The hybrids were evaluated for their in vitro blood-stage antiplasmodial activity against drug-sensitive NF54 and multidrug-resistant K1 P. falciparum strains, exhibiting potent submicromolar activity. Notably, incorporating an N,N-dimethylaminomethyl side chain significantly enhanced activity against both strains. Further assays revealed a compound with multistage antiplasmodial activity, targeting both immature and mature gametocytes. Mechanistic studies implicated the inhibition of hemozoin formation as a key mode of action, supported by in vitro cellular heme fractionation analysis. Additionally, fluorescence assays indicated the generation of reactive oxygen species under oxidative conditions, suggesting a complementary pathway contributing to the compounds’ antiplasmodial activity. These findings highlight the potential of ferrocenyl-based molecular hybrids as promising candidates in antiplasmodial drug development.
Genetic variants associated with suspected neonatal hypoxic ischaemic Encephalopathy : a study in a South African context
(MDPI, 2025-03) Foden, Caroline J.; Durant, Kevin; Mellet, Juanita; Joubert, Fourie; Van Rensburg, Jeanne; Masemola, Mogomane Yvonne Khomotso; Velaphi, Sithembiso C.; Nakwa, Firdose L.; Horn, Alan R.; Pillay, Shakti; Kali, Gugu; Coetzee, Melantha; Ballot, Daynia E.; Kalua, Thumbiko; Babbo, Carina; Pepper, Michael Sean; NESHIE Working Group; michael.pepper@up.ac.za
Neonatal encephalopathy suspected to be due to hypoxic ischaemic encephalopathy (NESHIE) carries the risk of death or severe disability (cognitive defects and cerebral palsy). Previous genetic studies on NESHIE have predominantly focused on exomes or targeted genes. The objective of this study was to identify genetic variants associated with moderate–severe NESHIE through whole-genome, unbiased analysis. Variant filtering and prioritization were performed, followed by association testing both on a case–control basis and to compare the grades of severity and/or progression. Association testing on neonates with NESHIE (N = 172) and ancestry-matched controls (N = 288) produced 71 significant genetic variants (false discovery rate corrected p-value < 6.2 × 10−4), all located in non-coding regions and not previously implicated in NESHIE. Disease-associated variants in non-coding regions are considered to affect regulatory functions, possibly by modifying gene expression, promoters, enhancers, or DNA structure. The most significant variant was at position 6:162010973 in the Parkin RBR E3 ubiquitin protein ligase (PRKN) intron. Intronic variants were also identified in genes involved in inflammatory processes (SLCO3A1), DNA repair (ZGRF1), synaptogenesis (CNTN5), haematopoiesis (ASXL2), and the transcriptional response to hypoxia (PADI4). Ten variants were associated with a higher severity or lack of improvement in NESHIE, including one in ADAMTS3, which encodes a procollagen amino protease with a role in angiogenesis and lymphangiogenesis. This analysis represents one of the first efforts to analyze whole-genome data to investigate the genetic complexity of NESHIE in diverse ethnolinguistic groups of African origin and provides direction for further study.
Combination of citrus peel-derived essential oils with acarbose to inhibit amylolytic enzymes – a potential type II diabetes treatment approach
(Elsevier, 2025-05) Tshiyoyo, Kadima Samuel; Rabbad, Ali; Yusuf, Abdullahi Ahmed; Malgas, Samkelo; samkelo.malgas@up.ac.za
Type 2 diabetes (T2D) can be managed by inhibiting amylolytic enzymes, α-amylase and α-glucosidase, reducing the impact of dietary carbohydrates on blood glucose elevation. Acarbose, a current α-glucose inhibitor (AGI), has excessive α-amylase inhibition, resulting in side effects associated with large amounts of undigested starch being fermented in the colon. This study evaluated the AGI efficacy of citrus peel-derived essential oils, where they were first tested in silico against the target amylolytic enzymes, and then their AGI activity was tested in vitro. The synergistic effects of the essential oils with acarbose against amylolytic enzymes were also determined. In silico and in vitro data of the efficacy of the essential oils as AGIs correlated positively; lower Ki values correlated with more negative binding affinity. Furthermore, molecular dynamic simulations of the most potent compounds were evaluated and indicated relative flexibility and stability induced upon ligand interactions with the protein. The standard AGI drug, acarbose, had the lowest Ki (0.10 ± 0.01 mg/mL) and more negative binding affinity (−7.5 kcal/mol) than the essential oils for α-glucosidase; however, the essential oils only showed potent inhibition against α-glucosidase, with the most potent essential oils being valencene (Ki = 0.33 ± 0.04 mg/mL), carveol (Ki = 0.53 ± 0.02 mg/mL) and geraniol (Ki = 0.56 ± 0.02 mg/mL). The essential oils and acarbose displayed competitive inhibition of α-glucosidase. Furthermore, a combination of acarbose with carveol or geraniol at a ratio of 12.5 μg/mL: 2 mg/mL exhibited antagonistic (CI > 10) and synergistic (CI < 0.7) effects on α-amylase and α-glucosidase inhibition, respectively. Carveol or geraniol can be considered as potentially therapeutic in managing T2D, as it may display lowered AGI-associated side effects. HIGHLIGHTS • Terpenes were identified from Citrus peel-derived essential oils. • Some individual essential oils tolerably inhibited amylolytic enzymes. • Synergism of essential oils with acarbose against amylolytic enzymes was established. • Essential oils inhibited glucose release with reduced starch residues.
The genome and population genomics of allopolyploid Coffea arabica reveal the diversification history of modern coffee cultivars
(Nature Research, 2024-04-15) Salojärvi, Jarkko; Rambani, Aditi; Yu, Zhe; Guyot , Romain; Strickler, Susan; Lepelley, Maud; Wang, Cui; Rajaraman, Sitaram; Rastas , Pasi; Zheng, Chunfang; Muñoz, Daniella Santos; Meidanis , João; Paschoal , Alexandre Rossi; Krabbenhoft, Trevor J.; Bawin, Yves; Wang, Zhen Qin; Fleck , Steven J.; Aussel, Rudy; Bellanger, Laurence; Charpagne, Aline; Fournier, Coralie; Kassam, Mohamed; Lefebvre, Gregory; Métairon , Sylviane; Moine, Déborah; Rigoreau, Michel; Stolte, Jens; Hamon, Perla; Couturon, Emmanuel; Tranchant-Dubreuil, Christine; Mukherjee , Minakshi; Lan, Tianying; Engelhardt , Jan; Stadler, Peter; Correia De Lemos, Samara Mireza; Suzuki , Suzana Ivamoto; Sumirat, Ucu; Wai , Ching Man; Dauchot , Nicolas; Orozco-Arias, Simon; Garavito , Andrea; Kiwuka, Catherine; Musoli, Pascal; Nalukenge, Anne; Guichoux, Erwan; Reinout, Havinga; Smit, Martin; Carretero-Paulet, Lorenzo; Filho, Oliveiro Guerreiro; Braghini, Masako Toma; Padilha, Lilian; Sera, Gustavo Hiroshi; Ruttink, Tom; Henry, Robert; Marraccini, Pierre; Van de Peer, Yves ; Andrade, Alan; Domingues , Douglas; Giuliano , Giovanni; Mueller, Lukas; Pereira, Luiz Filipe; Plaisance, Stephane; Poncet , Valerie; Rombauts , Stephane; Sankoff, David; Albert, Victor A.; Crouzillat , Dominique; De Kochko , Alexandre; Descombes, Patrick
Coffea arabica, an allotetraploid hybrid of Coffea eugenioides and Coffea canephora, is the source of approximately 60% of coffee products worldwide, and its cultivated accessions have undergone several population bottlenecks. We present chromosome-level assemblies of a di-haploid C. arabica accession and modern representatives of its diploid progenitors, C. eugenioides and C. canephora. The three species exhibit largely conserved genome structures between diploid parents and descendant subgenomes, with no obvious global subgenome dominance. We find evidence for a founding polyploidy event 350,000–610,000 years ago, followed by several pre-domestication bottlenecks, resulting in narrow genetic variation. A split between wild accessions and cultivar progenitors occurred ~30.5 thousand years ago, followed by a period of migration between the two populations. Analysis of modern varieties, including lines historically introgressed with C. canephora, highlights their breeding histories and loci that may contribute to pathogen resistance, laying the groundwork for future genomics-based breeding of C. arabica.
Monitoring of species’ genetic diversity in Europe varies greatly and overlooks potential climate change impacts
(Nature Research, 2024-01-15) Pearman, Peter B.; Broennimann , Olivier; Aavik, Tsipe; Albayrak, Tamer; Alves, Paulo C.; Aravanopoulos, F.A.; Bertola , Laura D.; Biedrzycka, Aleksandra; Buzan , Elena; Cubric-Curik , Vlatka; Djan , Mihajla; Fedorca, Ancuta; Fuentes-Pardo, Angela P.; Fussi , Barbara; Godoy , José A.; Gugerli , Felix; Hoban , Sean; Holderegger, Rolf; Hvilsom, Christina; Iacolina , Laura; Stroil , Belma Kalamujic; Klinga , Peter; Konopiński, Maciej K.; Kopatz, Alexander; Laikre , Linda; Lopes-Fernandes, Margarida; McMahon, Barry John; Mergeay, Joachim; Neophytou , Charalambos; Pálsson, Snæbjörn; Paz-Vinas , Ivan; Posledovich, Diana; Primmer, Craig R.; Raeymaekers , Joost A.M.; Rinkevich, Baruch; Rolečková , Barbora; Ruņģis, Dainis; Schuerz , Laura; Segelbacher , Gernot; Sonnenschein , Katja Kavčič; Stefanovic , Milomir; Thurfjell , Henrik; Träger, Sabrina; Tsvetkov, Ivaylo N.; Velickovic, Nevena; Vergeer , Philippine; Vernesi, Cristiano; Vilà , Carles; Westergren , Marjana; Zachos, Frank E.; Guisan, Antoine; Bruford, Michael W.
Genetic monitoring of populations currently attracts interest in the context of the Convention on Biological Diversity but needs long-term planning and investments. However, genetic diversity has been largely neglected in biodiversity monitoring, and when addressed, it is treated separately, detached from other conservation issues, such as habitat alteration due to climate change. We report an accounting of efforts to monitor population genetic diversity in Europe (genetic monitoring effort, GME), the evaluation of which can help guide future capacity building and collaboration towards areas most in need of expanded monitoring. Overlaying GME with areas where the ranges of selected species of conservation interest approach current and future climate niche limits helps identify whether GME coincides with anticipated climate change effects on biodiversity. Our analysis suggests that country area, financial resources and conservation policy influence GME, high values of which only partially match species’ joint patterns of limits to suitable climatic conditions. Populations at trailing climatic niche margins probably hold genetic diversity that is important for adaptation to changing climate. Our results illuminate the need in Europe for expanded investment in genetic monitoring across climate gradients occupied by focal species, a need arguably greatest in southeastern European countries. This need could be met in part by expanding the European Union’s Birds and Habitats Directives to fully address the conservation and monitoring of genetic diversity.
Rapid establishment of species barriers in plants compared with that in animals
(American Association for the Advancement of Science, 2025-09) Monnet, Francois; Postel, Zoe; Touzet, Pascal; Fraisse, Christelle; Van de Peer, Yves; Vekemans, Xavier; Roux, Camille
Speciation, the process by which new reproductively isolated species emerge from ancestral populations, results from the gradual accumulation of barriers to gene flow within genomes. To date, the notion that interspecific genetic exchange (introgression) occurs more frequently between plant species than animals has gained a strong footing in scientific discourse. By examining the dynamics of gene flow across a continuum of divergence in both kingdoms, we observed the opposite relationship: Plants experience less introgression than animals at the same level of genetic divergence, suggesting that species barriers are established more rapidly in plants. This pattern raises questions about which differences in microevolutionary processes between plants and animals influence the dynamics of reproductive isolation establishment at the macroevolutionary scale.
Cryphonectria Canker on Eucalyptus in Florida reconsidered
(Wiley, 2025-08) Pham, Nam Q.; Wingfield, Brenda D.; Marincowitz, Seonju; Brawner, Jeremy T.; Hulcr, Jiri; Wingfield, Michael J.; nam.pham@fabi.up.ac.za
Cryphonectria canker is one of the most important diseases of plantation-grown Eucalyptus spp. in the tropics and Southern Hemisphere. The disease has been known in Florida, USA, for many years, and the causal agents are attributed to two known canker pathogens, Chrysoporthe cubensis (≡ Cryphonectria cubensis) and Microthia havanensis (≡ Endothia havanensis). These identifications were based on morphological characteristics, which are inadequate to recognise cryptic species in the Cryphonectriaceae. In this study, we visited various sites in Florida where Eucalyptus grandis and E. amplifolia trees are cultivated and investigated the presence of cankers. Isolations were made from fungal structures on symptomatic tissues associated with cankers. A total of 41 cultures resembling Cryphonectriaceae spp. were isolated. The isolates were identified based on DNA sequences for the ITS region of the rRNA and sections of the β-tubulin gene, and confirmed as the three species of Cryphonectriaceae, namely Microthia havanensis, Chrysoporthe cubensis and Chrysoporthe doradensis. Of these, Chrysoporthe doradensis was discovered for the first time in the USA. In addition, this study represents the first record of any Cryphonectriaceae on E. amplifolia , a Eucalyptus species that is poorly studied in terms of disease. Pathogenicity trials on Eucalyptus showed that all three Cryphonectriaceae species could cause disease on these trees, with Chrysoporthe spp. being more aggressive. These findings highlight the importance of continuous monitoring and surveillance to detect emerging pathogens and safeguard the sustainability of Eucalyptus in non-native forestry systems.

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