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Abstract Behavior is a useful trait for comparative studies that provide the comprehension of phylogenetic relationships among species. Here, we present a description of two spiny-rats species’ behavioral repertoire, Clyomys laticeps and Trinomys setosus (Rodentia: Echimyidae). The affiliative and agonistic behavioral patterns were sampled during a three-year study of captive populations of wild animals. Observational data were collected in two phases under different arrangements of individuals in groups. We also compare the behavioral traits of T. setosus and C. laticeps with the known behavioral patterns of Trinomys yonenagae. We add categories to the previous descriptions of T. setosus and a standard ethogram for C. laticeps. Trinomys setosus showed a visual and vocal display we called foot-trembling, which was not described in this form and function for other species studied until now. We discuss the differences in their sociality levels and similarities and differences among behavior patterns and repertoires. Resumo O comportamento é uma característica útil para estudos comparativos que fornecem a compreensão das relações filogenéticas entre as espécies. Apresentamos aqui uma descrição do repertório comportamental de duas espécies de ratos-de-espinho Clyomys laticeps and Trinomys setosus (Rodentia: Echimyidae). Os padrões comportamentais afiliativos e agonísticos foram amostrados durante um estudo de três anos em populações de animais silvestres em cativeiro. Os dados foram coletados em duas fases sob diferentes arranjos de indivíduos em grupos sociais. Comparamos as características comportamentais de T. setosus e C. laticeps com as da espécie mais conhecida, T. yonenagae. Adicionamos categorias às descrições anteriores de T. setosus, e um etograma padrão para C. laticeps. Trinomys setosus mostrou uma exibição visual e vocal que chamamos de saltitar, que não foi descrito nesta forma e função para outras espécies do gênero estudado até agora. Discutimos diferenças nos níveis de socialidade e similaridades e diferenças entre os padrões comportamentais e repertórios.

Lymphocyte-rich classic Hodgkin lymphoma (LR-CHL) is a rare subtype of Hodgkin lymphoma. Recent technical advances have allowed for the characterization of specific cross-talk mechanisms between malignant Hodgkin Reed-Sternberg (HRS) cells and different normal immune cells in the tumor microenvironment (TME) of CHL. However, the TME of LR-CHL has not yet been characterized at single-cell resolution. Here, using single-cell RNA sequencing (scRNA-seq), we examined the immune cell profile of 8 cell suspension samples of LR-CHL in comparison to 20 samples of the mixed cellularity (MC, 9 cases) and nodular sclerosis (NS, 11 cases) subtypes of CHL, as well as 5 reactive lymph node controls. We also performed multicolor immunofluorescence (MC-IF) on tissue microarrays from the same patients and an independent validation cohort of 31 pretreatment LR-CHL samples. ScRNA-seq analysis identified a unique CD4⁺ helper T cell subset in LR-CHL characterized by high expression of Chemokine C-X-C motif ligand 13 (CXCL13) and PD-1. PD-1⁺CXCL13⁺ T cells were significantly enriched in LR-CHL compared to other CHL subtypes, and spatial analyses revealed that in 46%of the LR-CHL cases these cells formed rosettes surrounding HRS cells. MC-IF analysis revealed CXCR5⁺ normal B cells in close proximity to CXCL13⁺ T cells at significantly higher levels in LR-CHL. Moreover, the abundance of PD-1⁺CXCL13⁺ T cells in the TME was significantly associated with shorter progression-free survival in LR-CHL (P = 0.032). Taken together, our findings strongly suggest the pathogenic importance of the CXCL13/CXCR5 axis and PD-1⁺CXCL13⁺ T cells as a treatment target in LR-CHL.

Vertebrate genomes contain fewer CG dinucleotides than would be expected by chance, and this pattern is mimicked by many viruses; HIV-1 derivatives mutated to contain more CG dinucleotides are targeted by the human antiviral protein ZAP, suggesting that CG suppression has evolved in viruses to evade recognition. Viruses evade the ZAP Many virus genomes possess lower than expected numbers of 5′-CG-3′ dinucleotides, mimicking the CG suppression of their vertebrate hosts. The reason for this has been unclear, but Paul Bieniasz and colleagues now show that viruses use CG suppression to avoid recognition by the zinc-finger antiviral protein ZAP. They show that CG suppression is essential for HIV-1 replication; otherwise, the virus genome is recognized by ZAP and targeted for degradation. Vertebrate genomes exhibit marked CG suppression—that is, lower than expected numbers of 5′-CG-3′ dinucleotides 1 . This feature is likely to be due to C-to-T mutations that have accumulated over hundreds of millions of years, driven by CG-specific DNA methyl transferases and spontaneous methyl-cytosine deamination. Many RNA viruses of vertebrates that are not substrates for DNA methyl transferases mimic the CG suppression of their hosts 2 , 3 , 4 . This property of viral genomes is unexplained 4 , 5 , 6 . Here we show, using synonymous mutagenesis, that CG suppression is essential for HIV-1 replication. The deleterious effect of CG dinucleotides on HIV-1 replication was cumulative, associated with cytoplasmic RNA depletion, and was exerted by CG dinucleotides in both translated and non-translated exonic RNA sequences. A focused screen using small inhibitory RNAs revealed that zinc-finger antiviral protein (ZAP) 7 inhibited virion production by cells infected with CG-enriched HIV-1. Crucially, HIV-1 mutants containing segments whose CG content mimicked random nucleotide sequence were defective in unmanipulated cells, but replicated normally in ZAP-deficient cells. Crosslinking–immunoprecipitation–sequencing assays demonstrated that ZAP binds directly and selectively to RNA sequences containing CG dinucleotides. These findings suggest that ZAP exploits host CG suppression to identify non-self RNA. The dinucleotide composition of HIV-1, and perhaps other RNA viruses, appears to have adapted to evade this host defence.

The WD40-containing E3 ubiquitin ligase RFWD3 has been recently linked to the repair of DNA damage by homologous recombination (HR). Here we have shown that an RFWD3 mutation within the WD40 domain is connected to the genetic disease Fanconi anemia (FA). An individual presented with congenital abnormalities characteristic of FA. Cells from the patient carrying the compound heterozygous mutations c.205_206dupCC and c.1916T>A in RFWD3 showed increased sensitivity to DNA interstrand cross-linking agents in terms of increased chromosomal breakage, reduced survival, and cell cycle arrest in G2 phase. The cellular phenotype was mirrored in genetically engineered human and avian cells by inactivation of RFWD3 or introduction of the patient-derived missense mutation, and the phenotype was rescued by expression of wild-type RFWD3 protein. HR was disrupted in RFWD3-mutant cells as a result of impaired relocation of mutant RFWD3 to chromatin and defective physical interaction with replication protein A. Rfwd3 knockout mice appear to have increased embryonic lethality, are subfertile, show ovarian and testicular atrophy, and have a reduced lifespan resembling that of other FA mouse models. Although RFWD3 mutations have thus far been detected in a single child with FA, we propose RFWD3 as an FA gene, FANCW, supported by cellular paradigm systems and an animal model.

Although a defect in the DNA polymerase POLQ leads to ionizing radiation sensitivity in mammalian cells, the relevant enzymatic pathway has not been identified. Here we define the specific mechanism by which POLQ restricts harmful DNA instability. Our experiments show that Polq-null murine cells are selectively hypersensitive to DNA strand breaking agents, and that damage resistance requires the DNA polymerase activity of POLQ. Using a DNA break end joining assay in cells, we monitored repair of DNA ends with long 3' single-stranded overhangs. End joining events retaining much of the overhang were dependent on POLQ, and independent of Ku70. To analyze the repair function in more detail, we examined immunoglobulin class switch joining between DNA segments in antibody genes. POLQ participates in end joining of a DNA break during immunoglobulin class-switching, producing insertions of base pairs at the joins with homology to IgH switch-region sequences. Biochemical experiments with purified human POLQ protein revealed the mechanism generating the insertions during DNA end joining, relying on the unique ability of POLQ to extend DNA from minimally paired primers. DNA breaks at the IgH locus can sometimes join with breaks in Myc, creating a chromosome translocation. We found a marked increase in Myc/IgH translocations in Polq-defective mice, showing that POLQ suppresses genomic instability and genome rearrangements originating at DNA double-strand breaks. This work clearly defines a role and mechanism for mammalian POLQ in an alternative end joining pathway that suppresses the formation of chromosomal translocations. Our findings depart from the prevailing view that alternative end joining processes are generically translocation-prone.

The ~9.5 kilobase HIV-1 genome contains RNA sequences and structures that control many aspects of viral replication, including transcription, splicing, nuclear export, translation, packaging and reverse transcription. Nonetheless, chemical probing and other approaches suggest that the HIV-1 genome may contain many more RNA secondary structures of unknown importance and function. To determine whether there are additional, undiscovered cis-acting RNA elements in the HIV-1 genome that are important for viral replication, we undertook a global silent mutagenesis experiment. Sixteen mutant proviruses containing clusters of ~50 to ~200 synonymous mutations covering nearly the entire HIV-1 protein coding sequence were designed and synthesized. Analyses of these mutant viruses resulted in their division into three phenotypic groups. Group 1 mutants exhibited near wild-type replication, Group 2 mutants exhibited replication defects accompanied by perturbed RNA splicing, and Group 3 mutants had replication defects in the absence of obvious splicing perturbation. The three phenotypes were caused by mutations that exhibited a clear regional bias in their distribution along the viral genome, and those that caused replication defects all caused reductions in the level of unspliced RNA. We characterized in detail the underlying defects for Group 2 mutants. Second-site revertants that enabled viral replication could be derived for Group 2 mutants, and generally contained point mutations that reduced the utilization of proximal splice sites. Mapping of the changes responsible for splicing perturbations in Group 2 viruses revealed the presence of several RNA sequences that apparently suppressed the use of cryptic or canonical splice sites. Some sequences that affected splicing were diffusely distributed, while others could be mapped to discrete elements, proximal or distal to the affected splice site(s). Overall, our data indicate complex negative regulation of HIV-1 splicing by RNA elements in various regions of the HIV-1 genome that enable balanced splicing and viral replication.

Spatiotemporal distributions of anthropogenic radionuclides in marine surface sediments off Miyagi, Fukushima, and Ibaraki Prefectures were analyzed on the basis of data collected during the monitoring program launched by the Japanese Ministry of Education, Sports, Science and Technology in 2011 right after the Fukushima Dai-ichi Nuclear Power Plant accident began. Concentrations of 137Cs in the surface sediments varied spatially by two orders of magnitude, from 1.7 to 580 Bq kg-dry−1, and there was no obvious correlation between 137Cs concentration and the proximity of the sampling location to the accident site. The total inventory of 137Cs accumulated in the upper 3 cm of surface sediments in the monitoring area was estimated to be 3.78 × 1013 Bq, that is, 0.1–2% of the total 137Cs flux from the plant to the ocean as a result of the accident (the percentage depends on the model used to estimate the total flux). The spatial variations of 137Cs concentration and inventory depended on two main factors: the 137Cs concentration in the overlying water during the first several months after the accident and the physical characteristics of the sediments (water content and bulk density). The temporal variations of the concentrations of other anthropogenic radionuclides (90Sr, 95Nb, 110 mAg, 125Sb, 129Te, and 129 mTe) in the sediments were also investigated. Activity ratios of these nuclides to 137Cs suggest that the nuclides themselves were not homogenized before they were removed from seawater to the sediments.

The Sun rotates faster at its equator than at its poles. This process is known as differential rotation and is seen in the motion of sunspots. Helioseismology has shown that the effect extends into the Sun's interior. It has not been possible to measure whether other stars also experience equivalent differential rotation. Benomar et al. used the Kepler spacecraft to monitor stellar oscillations of a group of Sun-like stars. By decomposing the oscillations into separate frequencies, they searched for signs of differential rotation. Several stars do indeed seem to have equators that spin faster than their poles, and none indicated the opposite pattern. Science , this issue p. 1231 Stellar oscillations show that some solar-type stars spin faster at their equators than their poles. The differentially rotating outer layers of stars are thought to play a role in driving their magnetic activity, but the underlying mechanisms that generate and sustain differential rotation are poorly understood. We report the measurement using asteroseismology of latitudinal differential rotation in the convection zones of 40 Sun-like stars. For the most significant detections, the stars’ equators rotate approximately twice as fast as their midlatitudes. The latitudinal shear inferred from asteroseismology is much larger than predictions from numerical simulations.

DNA polymerase ν (pol ν), encoded by the POLN gene, is an A-family DNA polymerase in vertebrates and some other animal lineages. Here we report an in-depth analysis of pol ν-defective mice and human cells. POLN is very weakly expressed in most tissues, with the highest relative expression in testis. We constructed multiple mouse models for Poln disruption and detected no anatomic abnormalities, alterations in lifespan, or changed causes of mortality. Mice with inactive Poln are fertile and have normal testis morphology. However, pol ν-disrupted mice have a modestly reduced crossover frequency at a meiotic recombination hot spot harboring insertion/deletion polymorphisms. These polymorphisms are suggested to generate a looped-out primer and a hairpin structure during recombination, substrates on which pol ν can operate. Pol ν-defective mice had no alteration in DNA end-joining during immunoglobulin class-switching, in contrast to animals defective in the related DNA polymerase θ (pol θ). We examined the response to DNA crosslinking agents, as purified pol ν has some ability to bypass major groove peptide adducts and residues of DNA crosslink repair. Inactivation of Poln in mouse embryonic fibroblasts did not alter cellular sensitivity to mitomycin C, cisplatin, or aldehydes. Depletion of POLN from human cells with shRNA or siRNA did not change cellular sensitivity to mitomycin C or alter the frequency of mitomycin C-induced radial chromosomes. Our results suggest a function of pol ν in meiotic homologous recombination in processing specific substrates. The restricted and more recent evolutionary appearance of pol ν (in comparison to pol θ) supports such a specialized role.

Background The genus Trypanosoma Gruby, 1843 is constituted by terrestrial and aquatic phylogenetic lineages both harboring understudied trypanosomes from reptiles including an increasing diversity of crocodilian trypanosomes. Trypanosoma clandestinus Teixeira & Camargo, 2016 of the aquatic lineage is transmitted by leeches to caimans. Trypanosoma grayi Novy, 1906 of the terrestrial lineage is transmitted by tsetse flies to crocodiles in Africa, but the vectors of Neotropical caiman trypanosomes nested in this lineage remain unknown. Results Our phylogenetic analyses uncovered crocodilian trypanosomes in tabanids from South America and Africa, and trypanosomes other than T. grayi in tsetse flies. All trypanosomes found in tabanids clustered in the crocodilian clade (terrestrial lineage) forming six clades: Grayi (African trypanosomes from crocodiles and tsetse flies); Ralphi (trypanosomes from caimans, African and Brazilian tabanids and tsetse flies); Terena (caimans); Cay03 (caimans and Brazilian tabanids); and two new clades, Tab01 (Brazilian tabanid and tsetse flies) and Kaiowa. The clade Kaiowa comprises Trypanosoma kaiowa n. sp. and trypanosomes from African and Brazilian tabanids, caimans, tsetse flies and the African dwarf crocodile. Trypanosoma kaiowa n. sp. heavily colonises tabanid guts and differs remarkably in morphology from other caiman trypanosomes. This species multiplied predominantly as promastigotes on log-phase cultures showing scarce epimastigotes and exhibited very long flagellates in old cultures. Analyses of growth behavior revealed that insect cells allow the intracellular development of Trypanosoma kaiowa n. sp. Conclusions Prior to this description of Trypanosoma kaiowa n. sp., no crocodilian trypanosome parasitic in tabanid flies had been cultured, morphologically examined by light, scanning and transmission microscopy, and phylogenetically compared with other crocodilian trypanosomes. Additionally, trypanosomes thought to be restricted to caimans were identified in Brazilian and African tabanids, tsetse flies and the dwarf crocodile. Similar repertoires of trypanosomes found in South American caimans, African crocodiles and tabanids from both continents support the recent diversification of these transcontinental trypanosomes. Our findings are consistent with trypanosome host-switching likely mediated by tabanid flies between caimans and transoceanic migrant crocodiles co-inhabiting South American wetlands at the Miocene.