Where Do Core Thalamocortical Axons Terminate in Mammalian Neocortex When There Is No Cytoarchitecturally Distinct Layer 4?

Although the mammalian cerebral cortex is most often described as a hexalaminar structure, there are cortical areas (primary motor cortex) and species (elephants, cetaceans, and hippopotami), where a cytoarchitecturally indistinct, or absent, layer 4 is noted. Thalamocortical projections from the core, or first order, thalamic system terminate primarily in layers 4/inner 3. We explored the termination sites of core thalamocortical projections in cortical areas and in species where there is no cytoarchitecturally distinct layer 4 using the immunolocalization of vesicular glutamate transporter 2, a known marker of core thalamocortical axon terminals, in 31 mammal species spanning the eutherian radiation. Several variations from the canonical cortical column outline of layer 4 and core thalamocortical inputs were noted. In shrews/microchiropterans, layer 4 was present, but many core thalamocortical projections terminated in layer 1 in addition to layers 4 and inner 3. In primate primary visual cortex, the sublaminated layer 4 was associated with a specialized core thalamocortical projection pattern. In primate primary motor cortex, no cytoarchitecturally distinct layer 4 was evident and the core thalamocortical projections terminated throughout layer 3. In the African elephant, cetaceans, and river hippopotamus, no cytoarchitecturally distinct layer 4 was observed and core thalamocortical projections terminated primarily in inner layer 3 and less densely in outer layer 3. These findings are contextualized in terms of cortical processing, perception, and the evolutionary trajectory leading to an indistinct or absent cortical layer 4.

Species-specific histological characterizations of renal tubules and collecting ducts in the kidneys of cats and dogs.

The histomorphological features of normal kidneys in cats and dogs have been revealed despite the high susceptibility of cats to tubulointerstitial damage. Herein, the histological characteristics of the two species were compared. Cytoplasmic lipid droplets (LDs) were abundant in the proximal convoluted tubules (PCTs) of cats aged 23-27 months but scarce in dogs aged 24-27 months. LDs were rarely observed in the distal tubules (DTs) and collecting ducts (CDs) of either species, as visualized by the expression of Tamm-Horsfall protein 1, calbindin-D28K, and aquaporin 2. The occupational area ratio of proximal tubules (PTs) in the renal cortex was higher, but that of DTs or CDs was significantly lower in adult cats than in dogs. Single PT epithelial cells were larger, but PCT, DT, and CD lumens were significantly narrower in adult cats than in dogs. Unlike adults, young cats at 6 months exhibited significantly abundant cytoplasmic LDs in proximal straight tubules, indicating lipid metabolism-related development. Histochemistry of the 21 lectins also revealed variations in glycosylation across different renal tubules and CDs in both species. Sodium-glucose cotransporter 2 was expressed only in PTs, excluding the proximal straight tubules with few LDs in adult cats or the PCTs of young cats and adult dogs. These findings are crucial for understanding species-specific characteristics of renal histomorphology and pathogenesis.

Taxonomic revision of two species in the genus Ptychorhynchus Simpson, 1900 (Bivalvia: Unionidae: Gonideinae), with description of a new species.

Accurate identification and precise classification of freshwater mussel species that are among the most threatened freshwater taxa in the world, play a crucial role in informing conservation and management efforts for these organisms. However, due to the variability in shell morphology, relying solely on shell characteristics for species taxonomy poses significant challenges, thereby impeding effective conservation planning and management. The freshwater mussel genus Ptychorhynchus Simpson, 1900 is one such group in need of study. We integrate molecular phylogeny, shell morphology and soft-body anatomy to examine the classification of Ptychorhynchus denserugata (Haas, 1910) and Ptychorhynchus resupinatus (von Martens, 1902). The COI barcoding data support the clustering of P. denserugata and Nodularia douglasiae within a single clade, and P. denserugata shares the diagnostic feature of the genus Nodularia , i.e. knobs or bumps on the inner mantle surface in the excurrent aperture. Therefore, by integrating molecular data and anatomical characteristics, we confirm that the nominal species P. denserugata syn. nov. is a new synonym for N. douglasiae . The multi-locus (COI + ND1 + 16S rRNA + 18S rRNA + 28S rRNA ) phylogeny and mitochondrial phylogenomics support the transfer of P. resupinatus from Ptychorhynchus to the newly elevated genus Cosmopseudodon stat. rev., as Cosmopseudodon resupinatus stat. rev. that is still considered the designated type species. We also describe a new species based on integrative taxonomy, i.e. Cosmopseudodon wenshanensis sp. nov. The comprehensive understanding of the taxonomy and diversity of the revised Cosmopseudodon species, and shell heteromorphism of N. douglasiae (=P. denserugata syn. nov.), will serve as a crucial foundation for further scientific assessment and conservation strategies pertaining to these taxa. ZooBank: urn:lsid:zoobank.org:pub:E48968B1-DF0F-42AD-8F31-B8C95F23CE57.

Identification of Southeast Asian Anopheles mosquito species using MALDI-TOF mass spectrometry.

Malaria elimination in Southeast Asia remains a challenge, underscoring the importance of accurately identifying malaria mosquitoes to understand transmission dynamics and improve vector control. Traditional methods such as morphological identification require extensive training and cannot distinguish between sibling species, while molecular approaches are costly for extensive screening. Matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF MS) has emerged as a rapid and cost-effective tool for Anopheles species identification, yet its current use is limited to few specialized laboratories. This study aimed to develop and validate an online reference database for MALDI-TOF MS identification of Southeast Asian Anopheles species. The database, constructed using the in-house data analysis pipeline MSI2 (Sorbonne University), comprised 2046 head mass spectra from 209 specimens collected at the Thailand-Myanmar border. Molecular identification via COI and ITS2 DNA barcodes enabled the identification of 20 sensu stricto species and 5 sibling species complexes. The high quality of the mass spectra was demonstrated by a MSI2 median score (min-max) of 61.62 (15.94-77.55) for correct answers, using the best result of four technical replicates of a test panel. Applying an identification threshold of 45, 93.9% (201/214) of the specimens were identified, with 98.5% (198/201) consistency with the molecular taxonomic assignment. In conclusion, MALDI-TOF MS holds promise for malaria mosquito identification and can be scaled up for entomological surveillance in Southeast Asia. The free online sharing of our database on the MSI2 platform (https://msi.happy-dev.fr/) represents an important step towards the broader use of MALDI-TOF MS in malaria vector surveillance.

Woody plant species richness and productivity relationship in a subtropical forest: The predominant role of common species.

A long-standing key issue for examining the relationships between biodiversity and ecosystem functioning (BEF), such as forest productivity, is whether ecosystem functions are influenced by the total number of species or the properties of a few key species. Compared with controlled ecosystem experiments, the BEF relationships in secondary forest remain unclear, as do the effects of common species richness and rare species richness on the variation in ecosystem functions. To address this issue, we conducted field surveys at five sampling sites (1 ha each) with subtropical secondary evergreen broad-leaved forest vegetation. We found (1) a positive correlation between species richness and standing aboveground biomass (AGB); (2) that common species were primarily responsible for the distribution patterns of species abundance and dominance; although they accounted for approximately 25% of the total species richness on average, they represented 86-91% of species abundance and 88-97% of species dominance; and (3) that common species richness could explain much more of the variation in AGB than total species richness (common species plus rare species) at both the site and plot scales. Because rare species and common species were not equivalent in their ability to predict productivity in the biodiversity-ecosystem productivity model, redundant information should be eliminated to obtain more accurate results. Our study suggested that woody plant species richness and productivity relationship in subtropical forest ecosystem can be explained and predicted by a few common species.

Redescription of Taeniacanthus aulacocephali (Copepoda: Cyclopoida: Taeniacanthidae) parasitic on Uranoscopus japonicus Houttuyn (Uranoscopidae) from Pacific coast, Japan, with adaptation of the non-destructive DNA technique.

Taeniacanthus aulacocephali Izawa, 2021 (Copepoda: Cyclopoida: Taeniacanthidae) was redescribed from the branchial cavity and gill filaments of Uranoscopus japonicus Houttuyn (Perciformes: Uranoscopidae) collected from the Pacific coast of the Kochi and Wakayama prefectures, Japan. This is the second record of the copepod, and the finding from U. japonicus represents the new host record. The species is characterized by several distinguishing features: 1) a decrease in the width of the habitus between the second and fourth pedigerous segments; 2) the ratio of prosome/body length; 3) the presence of eight setae on the exopodal terminal segment of leg 2; 4) an un-bifurcated maxilliped claw surrounded by 14-28 transverse ridges; and 5) the presence of an inner coxal seta on legs 2 and 3. The newly collected specimens were subjected to a modified non-destructive DNA extraction method and morphological description based on the same copepod individual, while preserving a morphologically describable specimen. Sequences of 18S rDNA, 28S rDNA and the mitochondrial cytochrome c oxidase subunit 1 mitochondrial gene (cox1) were obtained.

Description of Sandythoa gen. nov., a fish parasitic branchial cymothoid (Crustacea: Isopoda: Cymothoidae) from the Indian Ocean, with five species including one new species.

The comparative analysis of records of Elthusa samariscii (Shiino, 1951) from Japan and India, alongside corresponding illustrations, indicates that the records of E. samariscii from Samaris cristatus Gray in India represent a distinct and previously undescribed species. This study introduces Sandythoa tiranga gen. and sp. nov., providing comprehensive descriptions of various lifecycle stages, including the female, male, transitional, premanca, and manca larvae. The following combinations of characters identify the genus: cephalon anterior margin with acute rostrum; pleonite 1 is distinctly narrow, not extending laterally; presence of a narrow gap between pleonites; antenna with more than 10 articles; maxilliped with oostegital lobe. Sandythoa tiranga sp. nov. is specifically identified along the southwest coast of India. Furthermore, we propose transferring the following species from Elthusa: Sandythoa arnoglossi (Trilles and Justine 2006) comb. nov.; Sandythoa parabothi (Trilles and Justine, 2004) comb. nov.; Sandythoa samariscii (Shiino, 1951) comb. nov.; Sandythoa moritakii (Saito and Yamauchi, 2016) comb. nov. A revised key to the global marine branchial cymothoid genera is provided.

Molecular phylogenetic position and description of a new genus and species of freshwater Chaetonotidae (Gastrotricha: Chaetonotida: Paucitubulatina), and the annotation of its mitochondrial genome.

Chaetonotidae is the most diversified family of the entire phylum Gastrotricha; it comprises ~430 species distributed across 16 genera. The current classification, established mainly on morphological traits, has been challenged in recent years by phylogenetic studies, indicating that the cuticular ornamentations used to discriminate among species may be misleading when used to identify groupings, which has been the practice until now. Therefore, a consensus is developing toward implementing novel approaches to better define species identity and affiliation at a higher taxonomic ranking. Using an integrative morphological and molecular approach, including annotation of the mitogenome, we report on some freshwater gastrotrichs characterised by a mixture of two types of cuticular scales diagnostic of the genera Aspidiophorus and Heterolepidoderma . Our specimens' overall anatomical characteristics find no correspondence in the taxa of these two genera, calling for their affiliation to a new species. Phylogenetic analyses based on the sequence of the ribosomal RNA genes of 96 taxa consistently found the new species unrelated to Aspidiophorus or Heterolepidoderma but allied with Chaetonotus aff. subtilis, as a subset of a larger clade, including mostly planktonic species. Morphological uniqueness and position along the non-monophyletic Chaetonotidae branch advocate erecting a new genus to accommodate the current specimens; consequently, the name Litigonotus ghinii gen. nov., sp. nov. is proposed. The complete mitochondrial genome of the new taxon resulted in a single circular molecule 14,384 bp long, including 13 protein-coding genes, 17 tRNA genes and 2 rRNAs genes, showing a perfect synteny and collinearity with the only other gastrotrich mitogenome available, a possible hint of a high level of conservation in the mitochondria of Chaetonotidae. ZooBank: urn:lsid:zoobank.org:pub:9803F659-306F-4EC3-A73B-8C704069F24A.

Right ventricular diastolic adaptation to pressure overload in different rat strains.

Different rat strains are used in various animal models of pulmonary hypertension and right ventricular (RV) failure. No systematic assessment has been made to test differences in RV response to pressure overload between rat strains. We compared RV adaptation to pulmonary trunk banding (PTB) in Wistar (W), Sprague Dawley (SD), and Fischer344 (F) rats by hemodynamic profiling focusing on diastolic function. Age-matched male rat weanlings were randomized to sham surgery (W-sham, n = 5; SD-sham, n = 4; F-sham, n = 4) or PTB (W-PTB, n = 8; SD-PTB, n = 8; F-PTB, n = 8). RV function was evaluated after 5 weeks by echocardiography, cardiac MRI, and invasive pressure-volume measurements. PTB caused RV failure and increased RV systolic pressures four-fold in all three PTB groups compared with sham. W- and SD-PTB had a 2.4-fold increase in RV end-systolic volume index compared with sham, while F-PTB rats were less affected. Diastolic and right atrial impairment were evident by increased RV end-diastolic elastance, filling pressure, and E/e' in PTB rats compared with sham, again F-PTB the least affected. In conclusions, PTB caused RV failure with signs of diastolic dysfunction. Despite a similar increase in RV systolic pressure, F-PTB rats showed less RV dilatation and a more preserved diastolic function compared with W- and SD-PTB.

Enhanced Genomic and Transcriptomic Resources for Trichinella pseudospiralis and T. spiralis to Underpin the Discovery of Molecular Differences between Stages and Species.

Nematodes of the genus Trichinella are important pathogens of humans and animals. This study aimed to enhance the genomic and transcriptomic resources for T. pseudospiralis (non-encapsulated phenotype) and T. spiralis (encapsulated phenotype) and to explore transcriptional profiles. First, we improved the assemblies of the genomes of T. pseudospiralis (code ISS13) and T. spiralis (code ISS534), achieving genome sizes of 56.6 Mb (320 scaffolds, and an N50 of 1.02 Mb) and 63.5 Mb (568 scaffolds, and an N50 value of 0.44 Mb), respectively. Then, for each species, we produced RNA sequence data for three key developmental stages (first-stage muscle larvae [L1s], adults, and newborn larvae [NBLs]; three replicates for each stage), analysed differential transcription between stages, and explored enriched pathways and processes between species. Stage-specific upregulation was linked to cellular processes, metabolism, and host-parasite interactions, and pathway enrichment analysis showed distinctive biological processes and cellular localisations between species. Indeed, the secreted molecules calmodulin, calreticulin, and calsyntenin-with possible roles in modulating host immune responses and facilitating parasite survival-were unique to T. pseudospiralis and not detected in T. spiralis. These insights into the molecular mechanisms of Trichinella-host interactions might offer possible avenues for developing new interventions against trichinellosis.

Tree species explain only half of explained spatial variability in plant water sensitivity.

Spatiotemporal patterns of plant water uptake, loss, and storage exert a first-order control on photosynthesis and evapotranspiration. Many studies of plant responses to water stress have focused on differences between species because of their different stomatal closure, xylem conductance, and root traits. However, several other ecohydrological factors are also relevant, including soil hydraulics, topographically driven redistribution of water, plant adaptation to local climatic variations, and changes in vegetation density. Here, we seek to understand the relative importance of the dominant species for regional-scale variations in woody plant responses to water stress. We map plant water sensitivity (PWS) based on the response of remotely sensed live fuel moisture content to variations in hydrometeorology using an auto-regressive model. Live fuel moisture content dynamics are informative of PWS because they directly reflect vegetation water content and therefore patterns of plant water uptake and evapotranspiration. The PWS is studied using 21,455 wooded locations containing U.S. Forest Service Forest Inventory and Analysis plots across the western United States, where species cover is known and where a single species is locally dominant. Using a species-specific mean PWS value explains 23% of observed PWS variability. By contrast, a random forest driven by mean vegetation density, mean climate, soil properties, and topographic descriptors explains 43% of observed PWS variability. Thus, the dominant species explains only 53% (23% compared to 43%) of explainable variations in PWS. Mean climate and mean NDVI also exert significant influence on PWS. Our results suggest that studies of differences between species should explicitly consider the environments (climate, soil, topography) in which observations for each species are made, and whether those environments are representative of the entire species range.

Echolocating bats show species-specific variation in susceptibility to acoustic forward masking.

Echolocating bats rely on precise auditory temporal processing to detect echoes generated by calls that may be emitted at rates reaching 150-200 Hz. High call rates can introduce forward masking perceptual effects that interfere with echo detection; however, bats may have evolved specializations to prevent repetition suppression of auditory responses and facilitate detection of sounds separated by brief intervals. Recovery of the auditory brainstem response (ABR) was assessed in two species that differ in the temporal characteristics of their echolocation behaviors: Eptesicus fuscus, which uses high call rates to capture prey, and Carollia perspicillata, which uses lower call rates to avoid obstacles and forage for fruit. We observed significant species differences in the effects of forward masking on ABR wave 1, in which E. fuscus maintained comparable ABR wave 1 amplitudes when stimulated at intervals of <3 ms, whereas post-stimulus recovery in C. perspicillata required 12 ms. When the intensity of the second stimulus was reduced by 20-30 dB relative to the first, however, C. perspicillata showed greater recovery of wave 1 amplitudes. The results demonstrate that species differences in temporal resolution are established at early levels of the auditory pathway and that these differences reflect auditory processing requirements of species-specific echolocation behaviors.

Evolution of threat response-related polymorphisms at the SLC6A4 locus in callitrichid primates.

Variation in an upstream repetitive region at the SLC6A4 locus, which encodes the serotonin transporter, is associated with anxiety-related behaviour in a few primate species, including humans and rhesus macaques, and has been suggested to be related to ecological adaptability among macaques. In this study, we investigate evolution of SLC6A4 polymorphisms associated with anxiety-related behaviour in common marmosets (Callithrix jacchus). Assaying variation in the SLC6A4 repeat region across 14 species in eight genera of callitrichid primates (marmosets and tamarins), we find large interspecific variation in the number of repeats present (24-43). The black tufted-ear marmoset (C. penicillata) has sequence polymorphisms similar to those found in the common marmoset, which is its sister species, and no other species has intraspecific variation at these sites. We conclude that, similar to humans and macaques, the functional polymorphism at SLC6A4 in common marmosets has a recent evolutionary origin, and that the anxiety-related allele is evolutionarily derived. Common/black tufted-ear marmosets and rhesus/bonnet macaques share high ecological adaptability and behavioural flexibility that we propose may be related to the maintenance of the polymorphism.

Nocturnal substrate association of four coral reef fish groups (parrotfishes, surgeonfishes, groupers and butterflyfishes) in relation to substrate architectural characteristics.

Although numerous coral reef fish species utilize substrates with high structural complexities as habitats and refuge spaces, quantitative analysis of nocturnal fish substrate associations has not been sufficiently examined yet. The aims of the present study were to clarify the nocturnal substrate associations of 17 coral reef fish species (nine parrotfish, two surgeonfish, two grouper and four butterflyfish) in relation to substrate architectural characteristics. Substrate architectural characteristics were categorized into seven types: (1) eave-like space, (2) large inter-branch space, (3) overhang by protrusion of fine branching structure, (4) overhang by coarse structure, (5) uneven structure without large space or overhang, (6) flat and (7) macroalgae. Overall, fishes were primarily associated with three architectural characteristics (eave-like space, large inter-branch space and overhang by coarse structure). The main providers of these three architectural characteristics were tabular and corymbose Acropora, staghorn Acropora, and rock. Species-specific significant positive associations with particular architectural characteristics were found as follows. For the nine parrotfish species, Chlorurus microrhinos with large inter-branch space and overhang by coarse structure; Ch. spilurus with eave-like space and large inter-branch space; Hipposcarus longiceps with large inter-branch space; Scarus ghobban with overhang by coarse structure; five species (Scarus forsteni, S. niger, S. oviceps, S. rivulatus and S. schlegeli) with eave-like space. For the two surgeonfish species, Naso unicornis with overhang by coarse structure; N. lituratus with eave-like space. For the two grouper species, Plectropomus leopardus with eave-like space; Epinephelus ongus with overhang by coarse structure. For the four butterflyfish species, Chaetodon trifascialis with eave-like space and large inter-branch space; C. lunulatus and C. ephippium with large inter-branch space; C. auriga showed no significant associations with any architectural characteristics. Four species (Ch. microrhinos, H. longiceps, S. niger and N. unicornis) also showed clear variations in substrate associations among the different fish size classes. Since parrotfishes, surgeonfishes and groupers are main fisheries targets in coral reefs, conservation and restoration of coral species that provide eave-like space (tabular and corymbose Acropora) and large inter-branch space (staghorn Acropora) as well as hard substrates with coarse structure that provide overhang (rock) should be considered for effective fisheries management in coral reefs. For butterflyfishes, coral species that provide eave-like space (tabular Acropora) and large inter-branch space (staghorn Acropora) should also be conserved and restored for provision of sleeping sites.

Physiological thermal responses of three Mexican snakes with distinct lifestyles.

The impact of temperature on reptile physiology has been examined through two main parameters: locomotor performance and metabolic rates. Among reptiles, different species may respond to environmental temperatures in distinct ways, depending on their thermal sensitivity. Such variation can be linked to the ecological lifestyle of the species and needs to be taken into consideration when assessing the thermal influence on physiology. This is particularly relevant for snakes, which are a very functionally diverse group. In this study, our aim was to analyze the thermal sensitivity of locomotor performance and resting metabolic rate (RMR) in three snake species from central Mexico (Crotalus polystictus, Conopsis lineata, and Thamnophis melanogaster), highlighting how it is influenced by their distinctive behavioral and ecological traits. We tested both physiological parameters in five thermal treatments: 15 °C, 25 °C, 30 °C, 33 °C, and 36 °C. Using the performance data, we developed thermal performance curves (TPCs) for each species and analyzed the RMR data using generalized linear mixed models. The optimal temperature for locomotion of C. polystictus falls near its critical thermal maximum, suggesting that it can maintain performance at high temperatures but with a narrow thermal safety margin. T. melanogaster exhibited the fastest swimming speeds and the highest mass-adjusted RMR. This aligns with our expectations since it is an active forager, a high energy demand mode. The three species have a wide performance breadth, which suggests that they are thermal generalists that can maintain performance over a wide interval of temperatures. This can be beneficial to C. lineata in its cold habitat, since such a characteristic has been found to allow some species to maintain adequate performance levels in suboptimal temperatures. RMR increased along with temperature, but the proportional surge was not uniform since thermal sensitivity measured through Q10 increased at the low and high thermal treatments. High Q10 at low temperatures could be an adaptation to maintain favorable performance in suboptimal temperatures, whereas high Q10 at high temperatures could facilitate physiological responses to heat stress. Overall, our results show different physiological adaptations of the three species to the environments they inhabit. Their different activity patterns and foraging habits are closely linked to these adaptations. Further studies of other populations with different climatic conditions would provide valuable information to complement our current understanding of the effect of environmental properties on snake physiology.

Development of ocular dominance columns across rodents and other species: revisiting the concept of critical period plasticity.

The existence of cortical columns, regarded as computational units underlying both lower and higher-order information processing, has long been associated with highly evolved brains, and previous studies suggested their absence in rodents. However, recent discoveries have unveiled the presence of ocular dominance columns (ODCs) in the primary visual cortex (V1) of Long-Evans rats. These domains exhibit continuity from layer 2 through layer 6, confirming their identity as genuine ODCs. Notably, ODCs are also observed in Brown Norway rats, a strain closely related to wild rats, suggesting the physiological relevance of ODCs in natural survival contexts, although they are lacking in albino rats. This discovery has enabled researchers to explore the development and plasticity of cortical columns using a multidisciplinary approach, leveraging studies involving hundreds of individuals-an endeavor challenging in carnivore and primate species. Notably, developmental trajectories differ depending on the aspect under examination: while the distribution of geniculo-cortical afferent terminals indicates matured ODCs even before eye-opening, consistent with prevailing theories in carnivore/primate studies, examination of cortical neuron spiking activities reveals immature ODCs until postnatal day 35, suggesting delayed maturation of functional synapses which is dependent on visual experience. This developmental gap might be recognized as 'critical period' for ocular dominance plasticity in previous studies. In this article, I summarize cross-species differences in ODCs and geniculo-cortical network, followed by a discussion on the development, plasticity, and evolutionary significance of rat ODCs. I discuss classical and recent studies on critical period plasticity in the venue where critical period plasticity might be a component of experience-dependent development. Consequently, this series of studies prompts a paradigm shift in our understanding of species conservation of cortical columns and the nature of plasticity during the classical critical period.

Inter-Species Pharmacokinetic Modeling and Scaling for Drug Repurposing of Pyronaridine and Artesunate.

Even though several new targets (mostly viral infection) for drug repurposing of pyronaridine and artesunate have recently emerged in vitro and in vivo, inter-species pharmacokinetic (PK) data that can extend nonclinical efficacy to humans has not been reported over 30 years of usage. Since extrapolation of animal PK data to those of humans is essential to predict clinical outcomes for drug repurposing, this study aimed to investigate inter-species PK differences in three animal species (hamster, rat, and dog) and to support clinical translation of a fixed-dose combination of pyronaridine and artesunate. PK parameters (e.g., steady-state volume of distribution (Vss), clearance (CL), area under the concentration-time curve (AUC), mean residence time (MRT), etc.) of pyronaridine, artesunate, and dihydroartemisinin (an active metabolite of artesunate) were determined by non-compartmental analysis. In addition, one- or two-compartment PK modeling was performed to support inter-species scaling. The PK models appropriately described the blood concentrations of pyronaridine, artesunate, and dihydroartemisinin in all animal species, and the estimated PK parameters in three species were integrated for inter-species allometric scaling to predict human PKs. The simple allometric equation (Y = a × Wb) well explained the relationship between PK parameters and the actual body weight of animal species. The results from the study could be used as a basis for drug repurposing and support determining the effective dosage regimen for new indications based on in vitro/in vivo efficacy data and predicted human PKs in initial clinical trials.

First identification of canine parvovirus -2a/2b variant in unvaccinated domestic dogs with gastrointestinal signs in Türkiye.

BACKGROUND: Canine parvovirus type 2 (CPV-2) is the most common enteric virus that infects canids. CPV is the causative agent of a contagious disease defined mostly by clinical gastrointestinal signs in dogs. During the late 1970s, CPV-2 emerged as a new virus capable of infecting domestic dogs and growing across the world. The VP2 gene stands out as a key determinant in the pathogenicity, antigenicity, and host interactions of CPV-2. AIMS: The molecular characterization of the VP2 gene is crucial for understanding CPV evolution and epidemiology. MATERIALS & METHODS: Genes encoding the VP2 protein were sequenced and compared to reference strains worldwide. The maximum likelihood method was used to build a phylogenetic tree using CPV VP2 gene nucleotide sequences. RESULTS: Our phylogenetic analysis of the VP2 gene revealed that five strains were very similar and clustered together, and three strains were in the 2b clade, whereas the other two were in the 2a/2b clade. DISCUSSION: This paper reports the molecular characterization of two novel CPV-2a/2b subtypes in dogs with gastrointestinal symptoms. Genetic analysis was conducted on a CPV genomic region encompassing one of the open reading frames (ORFs) encoding the structural protein VP2. Sequence analysis indicates new and unreported sequence changes, mainly affecting the VP2 gene, which includes the mutations Ser297Ala and Leu87Met. This study represents the first evidence of a new CPV-2a/2b subtype in Türkiye. Due to VP2's crucial role in encoding the capsid protein of CPV-2 and its significant involvement in the host-virus interaction, it is critical to closely monitor its evolutionary changes and be cautious while searching for novel or pre-existing subtypes. CONCLUSION: This study highlights the significance of continuous molecular research for acquiring more insights on the circulation of novel CPV mutants.

An integrative approach to the study of Kempnyia Klapálek, 1914 (Plecoptera: Perlidae) from Brazil: Support for the description of four new species and a basis for future studies.

Kempnyia (Plecoptera: Perlidae) is an endemic genus of Brazilian stoneflies that has 36 valid species and is distributed primarily in the Atlantic Forest and the mountainous areas of Central Brazil, particularly in Goiás and Tocantins states. Despite being the Brazilian genus with the most DNA sequences available on GenBank, integrative studies on the genus began only recently, in 2014. In this context, herein we studied the morphology and molecular data of Kempnyia specimens deposited in the Aquatic Biology Laboratory (UNESP, Assis) and the Entomology Museum of the Federal University of Viçosa (UFVB, Viçosa) collections. For the integrative approach adopted, in addition to studying the specimens morphologically, we used sequences of the COI mitochondrial gene combined with the following species delimitation methods: Automatic Barcode Gap Discovery (ABGD), both primary (ABGDp) and recursive (ABGDr) partitions; Assemble Species by Automatic Partitioning (ASAP); Poisson Tree Processes (PTP) and the Bayesian implementation of the Poisson Tree Processes (bPTP). As a result, we provided 28 new COI sequences of 21 species and support the description of four new species, namely, K. guarani sp. nov., K. tupiniquim sp. nov., K. una sp. nov., and K. zwickii sp. nov., consequently increasing the known diversity of the genus to 40 species. We also discuss the morphological variations observed in other species of the genus and provide several new geographic records. Therefore, our study brings new insights into the values of intra- and interspecific molecular divergence within Kempnyia, serving as a basis for new studies.

Diagnosis of Chagas Disease by Detecting Species-Specific Repetitive Genomic DNA from Filtered Human Urine Samples.

INTRODUCTION: Chagas disease caused by Trypanosoma cruzi (T cruzi) found in the Americas is often missed during the early stage of infection due to lack of sensitive diagnostic tests. The classic immunological and parasitological tests often fail in the acute phase due to the nonspecific and low antibody level nature of the infection and in the chronic phase due to low levels of trypanosomes in the blood. For successful control strategies, there must be a sensitive and specific diagnostic test. OBJECTIVE/METHODS: We have demonstrated the possibility (proof of concept) of detecting T cruzi-specific repeat DNA via polymerase chain reaction (PCR) by (1) spiking 15 urine samples collected from volunteers free of prior infection with 3 different concentrations of T cruzi (3 strains), Trypanosoma brucei, and Trypanosoma rhodesiense (African strain) genomic DNA and (2) from filtered collected clinical samples from Argentina. Three sets of primers were used. RESULTS: Our approach detected repeat DNA specific for T cruzi strains from 1 clinical sample by 2 sets of primer and from spiked urine by all 3 sets of primer but not the African species. A serial dilution (spiking) also was performed on T cruzi strains to detect sensitivities of the assay. One set of primers constantly detected satellite DNA for all T cruzi strains from 70 pg/µl to 175 fg/µl. CONCLUSIONS: We were able to demonstrate the feasibility of detecting T cruzi-specific DNA from filtered urine samples by sensitive and specific PCR assay. Besides the evident increased sensitivity and specificity of primers, our approach can be used to explore Chagas prevalence in endemic areas - especially in congenital Chagas newborn screening - and in the acute phase.