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Author: Donna Huber

Progress Toward Eradication of Dracunculiasis (Guinea Worm Disease) – Worldwide, January 2024-June 2025

Dracunculiasis (Guinea worm disease), caused by the parasite Dracunculus medinensis, is acquired by drinking water containing small water fleas infected with D. medinensis larvae or eating inadequately cooked aquatic animals. Efforts to eradicate D. medinensis, including the Guinea Worm Eradication Program (GWEP), began at CDC in 1980. In 1986, with an estimated 3.5 million cases in 20 African and Asian countries, the World Health Assembly called for dracunculiasis elimination in specific geographic areas; this goal was later expanded to global eradication. GWEP has been led by The Carter Center since 1986 and is supported by countries with endemic dracunculiasis, CDC, the World Health Organization, UNICEF, and other partners. During 1986-2023, human dracunculiasis cases decreased by >99%, from an estimated 3.5 million to 14 worldwide. Since 2012, environmental contamination from infected animals has posed a new challenge to eradication, as have ongoing civil unrest and insecurity in some areas. As of June 2025, indigenous dracunculiasis transmission was occurring in six countries (Angola, Cameroon, Chad, Ethiopia, Mali, and South Sudan). Fifteen human cases and 664 animal infections were reported in 2024, including 299 canine infections in Cameroon and 234 in Chad; during January-June 2025, one human case and 550 animal infections were reported. Animal infections and public health personnel’s impeded access to the population due to civil unrest and insecurity in Mali, South Sudan, and Sudan threaten the near-term possibility of disease eradication. Nevertheless, countries and partners appear poised to reach zero human cases soon.

Donald R Hopkins, Adam J Weiss, Sarah Yerian, Ynes R Ortega, Yujing Zhao, Obiora A Eneanya, Vitaliano A Cama. MMWR Morb Mortal Wkly Rep. 2026 Jan 1;74(42):648-654. doi: 10.15585/mmwr.mm7442a2.

Global characterization of Dictyostelium discoideum gene and protein expression changes under hypoxic conditions

Six scientific charts and graphs display experimental data on cell density, RNA levels, turnover, transcriptomic changes, gene regulation, and Venn diagram group overlaps at various time points.
Fig.1 Global transcriptomic response to hypoxia over the time course

Background: Aerobic eukaryotes utilize O2 to oxidize metabolites and generate ATP. The response to oxygen deprivation leads to migration to locations with more favorable concentrations (aerotaxis), differentiation, metabolic reprogramming, or more global stress responses. In mammals, changes in gene expression are particularly well studied, with the involvement of the Hypoxia-Inducible Factor (HIF-1), which regulates the transcription of hundreds of genes. However, the protist kingdom lacks the HIF-dependent transcriptional response network to adapt to low O2 levels, and their hypoxic adaptation remains unexplored.

Results: To address the scale and scope of hypoxic responses in protists, we characterized transcriptomic and proteomic changes when the social amoeba Dictyostelium is subjected to low (1%) O2 under nutritive conditions over 24 h followed by reoxygenation. Remarkably, 32% of the transcripts quantified were differentially expressed during hypoxia, with greatest changes associated with early (1 h) and late phases (24 h). Protein changes were modestly correlated with and generally lagged behind transcriptional changes. Correlated changes were observed for transcripts and proteins associated with various metabolic, anabolic, and catabolic pathways, as well as chromosome organization, cell cycling, vesicular trafficking, and signaling. Interestingly, transcripts associated with the cAMP signaling pathway normally triggered by starvation were also up-regulated during chronic hypoxia. Additionally, we studied the molecular mechanisms driving the transcriptomic response. Analysis of 4 marker genes showed extremely rapid responses that were graded over a range of O2 levels, with differential responses to inhibitors affecting protein synthesis and mitochondria, suggesting multiple induction mechanisms driving the transcriptomic response.

Conclusion: Overall, the amoebal response to a low but non-toxic O2-level resulted in massive and temporal remodeling of the transcriptome and proteome. This complex expression changes extend beyond simple metabolic adaptation and point toward a multiprong adaptation strategy.

Julie Hesnard, Elisabet Gas-Pascual, Hanke van der Wel, Olivier Cochet-Escartin, Stephane Joly, Jean-Paul Rieu, Christopher M West, Christophe Anjard. BMC Genomics. 2025 Dec 29;26(1):1143. doi: 10.1186/s12864-025-12328-9.

Glycoregulation of E3(SCF) ubiquitin ligases in unicellular eukaryotes

Skp1 is an essential adaptor within the Skp1/Cul1/F-box (SCF) class of E3 polyubiquitin ligases that regulate protein degradation in all eukaryotes. Skp1 is also a target of a 5-enzyme glycosylation pathway in parasites and other unicellular eukaryotes. Glycosylation of Skp1 is contingent upon oxygen-dependent hydroxylation of a critical Pro residue by a homolog of the HIFα PHD2 oxygen sensor of animals. The resulting hydroxyproline is modified by a series of soluble, cytoplasmic, sugar nucleotide-dependent glycosyltransferases that vary among branches of protist evolution, and are evolutionarily related to counterparts in the Golgi and the cytoplasm of prokaryotes. Pair-wise gene fusions of the six enzymes occur in various protists, suggesting processing efficiency. The terminal glycosyltransferases exhibit a second site interaction with Skp1 that may modulate its function irrespective of glycosylation status. The pentasaccharide adopts a constrained fold that in turn promotes Skp1 conformations that inhibit sequestration by homodimerization and encourage binding to select F-box protein substrate receptors with varied effects on their expression levels. The occurrence of a second Skp1 copy in some protists that is resistant to modification indicates a mechanism to bypass glycoregulation. This review details evidence from the social amoeba Dictyostelium discoideum and the pathogens Toxoplasma gondii and Pythium ultimum for the specificity of the enzymes for Skp1 and their regulation, as support for a role in regulating protein turnover via E3(SCF) ubiquitin ligases, and in turn sensing oxygen at the cellular level.

Donovan A Cantrell, Hanke van der Wel, Christopher M West. Glycobiology. 2025 Dec 17;36(1):cwaf078. doi: 10.1093/glycob/cwaf078.

PGDD 2.0: Plant Genome Duplication Database with updated content and tools

graphical abstract

Polyploidy and small-scale duplication have repeatedly reshaped plant genomes, making synteny and colinearity indispensable for evolutionary inference. We present PGDD 2.0 (accessible at chibba.agtec.uga.edu and pgdd2.org), a major update to the Plant Genome Duplication Database (PGDD) that now aggregates >120 complete telomere-to-telomere (T2T) assemblies, including many chromosome-scale genomes spanning all major Viridiplantae lineages. Each genome sequence is processed with a standardized pipeline to call intra- and intergenomic colinear (syntenic) blocks, estimate Ks, and block score metrics and age distributions. PGDD 2.0 introduces (i) interactive synteny networks for pattern discovery across taxa, (ii) a “riparian” or synteny alignment view for visualizing mesosynteny and rearrangements, and (iii) an embedded SynVisio module for rendering user-supplied or PGDD-downloaded MCScanX results directly in the browser. Together, these advances support tasks from resolving ancient whole-genome duplication signatures to tracing the postduplication fates of specific gene families with T2T-level precision and beyond. PGDD 2.0 delivers an up-to-date, uniform, and user-centered platform for plant comparative genomics, accelerating discovery regarding polyploidy, gene duplication, and genome evolution.

Ankush Sharma, John E Bowers, Tae-Ho Lee, Mingrui Xu, Ramandeep Kaur, Jessica C Kissinger, Xin Qiao, Peng W Chee, Andrew H Paterson. Nucleic Acids Res. 2025 Nov 26:gkaf1287. doi: 10.1093/nar/gkaf1287.

Four nudivirus core genes present in the genome of Venturia canescens are required for virus-like particle formation and prevention of encapsulation of parasitoid wasp eggs

Fig 1 VcVLP morphogenesis in calyx cells from different aged pupae or newly emerged adults that were injected with ds-egfp when P1 pupae.
Fig 1 VcVLP morphogenesis in calyx cells from different aged pupae or newly emerged adults that were injected with ds-egfp when P1 pupae.

 

Venturia canescens is a parasitoid wasp that harbors a domesticated endogenous virus (DEV) and parasitizes host insects like Ephestia kuehniella. The V. canescens DEV evolved from an alphanudivirus and produces virus-like particles (VLPs) in females that protect wasp eggs from a host immune defense called encapsulation. In contrast, very few DEV genes required for VLP formation and function have been identified. In this study, we characterized five V. canescens DEV genes of unknown function that all nudiviruses encode. Three of these genes are single copy (OrNVorf18-likeOrNVorf61-like, and OrNVorf76-like), while OrNVorf41-like has expanded into a six-member family and OrNVorf47-like has expanded into a three-member family. Sequence analysis indicated all of these genes retain essential motifs present in nudivirus homologs, while transmission electron microscopy (TEM) studies characterized the timing of VLP formation during the wasp pupal stage. RNA interference (RNAi) assays identified OrNVorf18-likeOrNVorf61-likeOrNVorf41-like-1, and OrNVorf41-like-2 as genes that are required for normal VLP formation. Knockdown of OrNVorf47-like family members did not affect VLP formation but did disable binding of VLPs to V. canescens eggs and protection against encapsulation. Disabled formation of VLPs in response to RNAi knockdown of OrNVorf18-likeOrNVorf61-likeOrNVorf41-like-1, and OrNVorf41-like-2 also resulted in wasp eggs being encapsulated. In contrast, knockdown of OrNVorf76-like had no effect on VLP assembly, egg binding, or encapsulation. Altogether, reported results significantly advance our understanding of V. canescens VLP (VcVLP) formation and function.

Importance: Understanding how V. canescens coopted an alphanudivirus to produce VcVLPs is of interest to the study of virus evolution. Our results show that three nudivirus core genes have essential functions in VcVLP formation, while one is essential for the novel function of binding to wasp eggs and protection from encapsulation, which is the most important immune defense of insects against parasitoids.

Meng Mao, Corinne M Stouthamer, Ange Lorenzi, Michael R Strand, Gaelen R Burke. J Virol. 2025 Nov 20:e0130525. doi: 10.1128/jvi.01305-25.

Temporal Variation in Target Site Mutations Is Associated with Diamide Cross-Resistance in Diamondback Moth Populations (Lepidoptera: Plutellidae) from Florida and Georgia, USA

 Collection sites, dates, and coordinates for all diamondback moth populations in this study.
Collection sites, dates, and coordinates for all diamondback moth populations in this study.

The Diamondback moth (DBM), Plutella xylostella (L.), the most significant worldwide pest of Brassica crops, is notorious for resistance to a diverse number of insecticides. Field populations bioassayed in Georgia and Florida, USA, in 2018 were resistant to chlorantraniliprole but susceptible to cyantraniliprole. Subsequently, populations assayed in 2021, 2022, and 2023 were cross-resistant to both diamides. We used NextSeq analysis of the ryanodine receptor PxRyR, the target of diamides, to quantify target site mutations associated with resistance. Three populations sampled in 2018 had a high prevalence (75.0-98.3% of total reads) of the G4946E mutation, associated with resistance to chlorantraniliprole, and additionally, in one population, a very low (2.7%) prevalence of another mutation, I4790K, was associated with diamide cross-resistance. Populations sampled in 2021 had a decreased prevalence of G4946E (0.7 and 8.4%) and increased prevalence of I4790K (9.3 and 18.0%). The G4946E allele was almost absent (0.2% to 3.9%) in populations sampled in 2022 and 2023, while I4790K was present at frequencies from 34.1% to 84.0%. These data suggest a remarkable shift in PxRyR target site mutations, replacing G4946E with I4790K, which occurred between 2018 and 2022, and were associated with the recent occurrence of cross-resistance in DBM populations in the Southeastern USA.

Thomas P Dunn, Md Abdullah Al Baki, Paulo S G Cremonez, David G Riley, Alton N Sparks Jr, Hugh Smith, Donald E Champagne. Insects. 2025 Nov 19;16(11):1179. doi: 10.3390/insects16111179.

Calcium transfer from the ER to other organelles for optimal signaling in Toxoplasma gondii

Hypothetical model showing Ca2+ entry through two different types of Ca2+ channels, uptake by T. gondii sarco/endoplasmic reticulum Ca2+- ATPase (TgSERCA) into the endoplasmic reticulum (ER) and distribution to the other organelles via transfer from the ER to the mitochondria, Plant-Like Vacuolar Compartment (PLVAC), and apicoplast.
Hypothetical model showing Ca2+ entry through two different types of Ca2+ channels, uptake by T. gondii sarco/endoplasmic reticulum Ca2+- ATPase (TgSERCA) into the endoplasmic reticulum (ER) and distribution to the other organelles via transfer from the ER to the mitochondria, Plant-Like Vacuolar Compartment (PLVAC), and apicoplast.

 

Ca2+ signaling in cells begins with the opening of Ca2+ channels in either the plasma membrane (PM) or endoplasmic reticulum (ER), leading to a sharp increase in the physiologically low (<100 nM) cytosolic Ca2+ level. The temporal and spatial regulation of Ca²+ is crucial for the precise activation of key biological processes. In the apicomplexan parasite Toxoplasma gondii, which infects approximately one-third of the global population, Ca²+ signaling governs essential aspects of the parasite’s infection cycle. T. gondii relies on Ca²+ signals to regulate pathogenic traits, with several Ca²+-signaling components playing critical roles. Ca2+ entry from the extracellular environment has been demonstrated in T. gondii for both, extracellular parasites, exposed to high Ca2+, and intracellular parasites, which acquire Ca²+ from host cells during host Ca²+ signaling events. Active egress, an essential step of the parasite’s infection cycle, is preceded by a large increase in cytosolic Ca2+, most likely initiated by release from intracellular stores. However, extracellular Ca2+ is also necessary to reach a cytosolic Ca2+ threshold required for timely egress. In this study, we investigated the mechanism of intracellular Ca²+ store replenishment and identified a central role for the SERCA-Ca2+-ATPase in maintaining Ca²+ homeostasis within the ER and in other organelles. We demonstrate mitochondrial Ca2+ uptake, which occurs by transfer of Ca2+ from the ER, likely through membrane contact sites. Our findings suggest that the T. gondii ER plays a key role in sequestering and redistributing Ca²+ to intracellular organelles following Ca²+ influx at the PM.

Zhu-Hong Li, Beejan Asady, Le Chang, Myriam Andrea Hortua Triana, Catherine Li, Isabelle Coppens, Silvia N J Moreno. Elife. 2025 Nov 12:13:RP101894. doi: 10.7554/eLife.101894.

Selenocyanate-Containing Molecules as Trypanosoma cruzi Inhibitors: Impact of Regioisomerism, Conformational Restriction, and Second-Ring Substitution

graphical abstract

As a continuation of the project aimed at searching for new chemotherapeuticagents against Chagas disease or American trypanosomiasis, new selenocyanate derivatives are designed, synthesized, and biologically evaluated against the clinically more relevant dividing amastigote form of Trypanosoma cruzi, the etiologic agent of this illness. Furthermore, as all the title compounds are fluorine-containing molecules, it seemed to be reasonable to explore the role of fluorine atoms in the aromatic system and to determine the optimal position at the terminal phenoxy group, and therefore, various regioisomers are prepared. The conformationally restricted selenocyates structurally related to WC-9Se exhibited improved antiparasitic activity compared to the lead drugs, Out to be extremely potent inhibitors of T. cruzi growth. In particular, (±)-5-(3-fluorophenoxy)-2-(selenocyanatomethyl)-2,3-dihydrobenzofuran exhibited an EC50 value of 0.032 µM, which resulted in the most potent selenocyanate developed in the laboratory. The presence of the fluorine atom together with the rigidity of the molecules are beneficial for the anti-T. cruzi effect. The resulting antiparasitic activity provides further insight into the role of the selenocyanate group in its effective and putative anti-T. cruzi action.

Hugo S Steingrüber, Mayara S Bertolini, Margarita M Vallejos, Sergio H Szajnman, Roberto Docampo, Juan B Rodriguez. ChemMedChem. 2025 Nov 11:e202500658. doi: 10.1002/cmdc.202500658.

Genomic Characterization of Cryptosporidium spp. via iNextEra Library Preparation and Hybridization Bait Capture

Next-generation DNA sequencing (NGS) is used to study the genome sequences of Cryptosporidium spp., but NGS is challenging when pure Cryptosporidium oocysts are limited in number or not available. Varying levels of parasites present in fecal samples, combined with the abundance of host cells, bacterial and other microbial cells, and undigested food particles, often result in fecal DNA samples with ~0.1% Cryptosporidium DNA, making genome-scale sequencing of Cryptosporidium from such samples cost-prohibitive. DNA extractions from fecal samples are, however, widely available and commonly used for polymerase chain reaction (PCR)-based diagnostics which can detect fg levels of Cryptosporidium DNA in complex DNA mixtures. Here, we describe an Illumina NGS sample preparation protocol (iNextEra) that can generate libraries from a wide range of DNA input (<1 ng to >60 ng). We then use those libraries within a modified myBaits capture hybridization protocol using CryptoCap_100K baits to enrich Cryptosporidium genomic DNA from a complex DNA background to increase the percentage of generated sequence reads that map to target Cryptosporidium reference genome sequences. Thus, iNextEra libraries and capture hybridization facilitate genome-level sequencing of this critical pathogen from widely available samples with less cost, thereby opening new opportunities to understand the complex biology of this important pathogen.

Mohammad Imtiaj Uddin Bhuiyan, Fiifi Agyabeng-Dadzie, Amanda H Sullivan, Megan S Beaudry, Kelly N Petersen, Piotr T Tuczapski, Michael E Grigg, Jessica C Kissinger, Travis C Glenn. Methods Mol Biol. 2026:2978:41-64. doi: 10.1007/978-1-0716-4824-7_4.

More extraordinary model systems for regeneration

Fig. 3 The rat tapeworm Hymenolepis diminuta.

 

The ability of organisms to replace and regenerate anatomical structures following their loss or damage has piqued the curiosity of biologists for centuries. In addition to Development’s ‘Model systems for regeneration’ collection, which introduced some of the most well-studied model organisms in the field, we published a Perspective in 2024 highlighting some of the lesser-known species with extraordinary regenerative abilities from plants to vertebrates ( Accorsi et al., 2024). Here, we revisit this topic again, hearing the perspectives of five experts, each of whom studies an amazing species with remarkable regenerative potential.

José E García-Arrarás, Chunyi Li, Tania Rozario, Mansi Srivastava, Andrew Willoughby. Development. 2025 Oct 15;152(20):dev205215. doi: 10.1242/dev.205215.