When colors mislead: Genomics and bioacoustics prompt re-classification of Asian flycatcher radiation (Aves: Niltavinae).

Traditional classification of many animals, including birds, has been highly dependent on external morphological characters like plumage coloration. However, both bioacoustics and genetic or genomic data have revolutionized our understanding of the relationships of certain lineages and led to sweeping taxonomic re-organizations. In this study, we present a case of erroneous delimitation of genus boundaries in the species-rich flycatcher subfamily Niltavinae. Genera within this subfamily have historically been delineated based on blue versus brown male body plumage until recent studies based on a few mitochondrial and nuclear loci unearthed several cases of generic misclassification. Here we use extensive bioacoustic data from 43 species and genomic data from 28 species for a fundamental reclassification of species in the Niltavinae. Our study reveals that song is an important trait to classify these birds even at the genus level, whereas plumage traits exhibit ample convergence and have led to numerous historic misattributions. Our taxonomic re-organization leads to new biogeographic limits of major genera, such that the genus Cyornis now only extends as far east as the islands of Sulawesi, Sula, and Banggai, whereas Eumyias is redefined to extend far beyond Wallace's Line to the islands of Seram and Timor. Our conclusions advise against an over-reliance on morphological traits and underscore the importance of integrative datasets.

BRCA2-HSF2BP oligomeric ring disassembly by BRME1 promotes homologous recombination.

In meiotic homologous recombination (HR), BRCA2 facilitates loading of the recombinases RAD51 and DMC1 at the sites of double-strand breaks (DSBs). The HSF2BP-BRME1 complex interacts with BRCA2. Its absence causes a severe reduction in recombinase loading at meiotic DSB. We previously showed that, in somatic cancer cells ectopically producing HSF2BP, DNA damage can trigger HSF2BP-dependent degradation of BRCA2, which prevents HR. Here, we report that, upon binding to BRCA2, HSF2BP forms octameric rings that are able to interlock into a large ring-shaped 24-mer. Addition of BRME1 leads to dissociation of both of these ring structures and cancels the disruptive effect of HSF2BP on cancer cell resistance to DNA damage. It also prevents BRCA2 degradation during interstrand DNA crosslink repair in Xenopus egg extracts. We propose that, during meiosis, the control of HSF2BPBRCA2 oligomerization by BRME1 ensures timely assembly of the ring complex that concentrates BRCA2 and controls its turnover, thus promoting HR.

Inicio de artritis reumatoide posterior a infección por SARS-CoV-2 / no

Se han descrito casos de patologías autoinmunes de inicio posterior a la infección por el virus SARS-CoV-2. La relación causal aún no es clara, por lo que es importante la construcción de la literatura frente a esta incógnita. Reportamos el caso de una mujer de 44 años que 18 días luego de cursar con infección por SARS-CoV-2 sin hipoxemia, presenta poliartralgias inflamatorias y paraclínicos compatibles con un diagnóstico de artritis reumatoide. Este caso refuerza la posibilidad de una relación causal entre ambas entidades.

Cases of autoimmune pathologies with onset after infection by the SARS-CoV-2 virus have been described. The causal relationship is not yet clear. We report the case of a 44-year-old woman who, 18 days after presenting with SARS-CoV-2 infection without hypoxaemia, presented with a clinical picture compatible with a diagnosis of rheumatoid arthritis. This case reinforces the possibility of a causal relationship between both entities.

The biology and engineered modeling strategies of cancer-nerve crosstalk.

A recent finding critical to cancer aggravation is the interaction between cancer cells and nerves. There exist two main modes of cancer-nerve interaction: perineural invasion (PNI) and tumor innervation. PNI occurs when cancer cells infiltrate the adjacent nerves, and its relative opposite, tumor innervation, occurs when axons extend into tumor bodies. Like most cancer studies, these crosstalk interactions have mostly been observed in patient samples and animal models at this point, making it difficult to understand the mechanisms in a controlled manner. As such, in recent years in vitro studies have emerged that have helped identify various microenvironmental factors responsible for cancer-nerve crosstalk, including but not limited to neurotrophic factors, neurotransmitters, chemokines, cancer-derived exosomes, and Schwann cells. The versatility of in vitro systems warrants continuous development to increase physiological relevance to study PNI and tumor innervation, for example by utilizing biomimetic three-dimensional (3D) culture systems. Despite the wealth of 3D in vitro cancer models, comparatively there exists a lack of 3D in vitro models of nerve, PNI, and tumor innervation. Native-like 3D in vitro models of cancer-nerve interactions may further help develop therapeutic strategies to curb nerve-mediated cancer aggravation. As such, we provide an overview of the key players of cancer-nerve crosstalk and current in vitro models of the crosstalk, as well as cancer and nerve models. We also discuss a few future directions in cancer-nerve crosstalk research.

ATP-Driven Separation of Liquid Phase Condensates in Bacteria.

Liquid-liquid phase-separated (LLPS) states are key to compartmentalizing components in the absence of membranes; however, it is unclear whether LLPS condensates are actively and specifically organized in the subcellular space and by which mechanisms. Here, we address this question by focusing on the ParABS DNA segregation system, composed of a centromeric-like sequence (parS), a DNA-binding protein (ParB), and a motor (ParA). We show that parS and ParB associate to form nanometer-sized, round condensates. ParB molecules diffuse rapidly within the nucleoid volume but display confined motions when trapped inside ParB condensates. Single ParB molecules are able to rapidly diffuse between different condensates, and nucleation is strongly favored by parS. Notably, the ParA motor is required to prevent the fusion of ParB condensates. These results describe a novel active mechanism that splits, segregates, and localizes non-canonical LLPS condensates in the subcellular space.

Supplemental Trichomonas vaginalis testing is required to maintain control following a transition from Pap smear to HPV DNA testing for cervical screening: a mathematical modelling study.

OBJECTIVES: Using mathematical modelling, we have previously shown that the prevalence of infection with Trichomonas vaginalis (TV) is likely to increase in the general population in Australia with the transition from Pap smear-based cervical screening to human papillomavirus (HPV) DNA testing. Here we use the existing model to estimate the level of supplemental testing required to maintain TV control. METHODS: A compartmental mathematical model describing the transmission of TV in the general heterosexual population in Australia was used to evaluate the impact of a range of screening scenarios on TV prevalence over time following the transition to HPV DNA testing for cervical screening. Scenarios considered were the inclusion of a TV test with the HPV test and the addition of TV testing to routine chlamydia testing conducted in primary care. RESULTS: Our modelling suggests that with sufficient coverage, inclusion of TV testing with routine chlamydia screening in general practice, TV prevalence can be reduced over time, but at the current reported coverage will gradually increase following the transition to HPV testing. Inclusion of TV testing with HPV testing in the cervical screening programme is preferable to no supplemental testing but is considerably less effective in controlling TV. CONCLUSIONS: These findings support the inclusion of TV testing with routine chlamydia testing of young people.

Potassium chloride: impacts on soil microbial activity and nitrogen mineralization / Uso de cloreto de potássio: impacto na atividade microbiana do solo e mineralização do nitrogênio

ABSTRACT: Potassium chloride is the most widely used potassium source worldwide, and due to its continuous use, the accumulation of its salts in the soil and in plants is becoming more common. Excess available ions can cause a series of physiological disturbances in organisms and can become a biocide in the soil. The objective of this study was to evaluate the effects of the application of KCl and banana crop residues on soil chloride content, microbial activity, and soil ammonification. The experiment utilized a completely randomized 2 × 4 factorial design with four replicates. Treatments were as follows: two doses of vegetal residue (200 and 400 mg dm-3) × four doses of KCl (0, 167, 334, and 668 mg dm-3 of KCl) and a control (untreated soil). The CO2 emission, ammonium (N-NH4 +) and soil chloride (Cl-) content, and mineralization/immobilization rates of the soils in each treatment were measured 4, 45, and 130 days after incubation (dai). Higher KCl dosages reduced soil microbial activity at 4 dai, regardless of the residue dosage. Microbial activity was reduced at 130 dai in all treatments when compared to the initial period. Higher dosages of banana crop residues increased the Cl- content of the soil and promoted the immobilization of N-NH4 +. We concluded that dosages of KCl (above 400 mg dm-3), when applied to soils that already contain crop residues, reduce microbial activity and mineralization of N in the soil.

RESUMO: O cloreto de potássio (KCl) é a fonte de potássio mais utilizada mundialmente e, devido ao uso contínuo desse fertilizante, pode ocorrer acúmulo de sais no solo e nas plantas. O excesso de íons desencadeia uma série de distúrbios fisiológicos, tornando-se um potencial biocida no solo. Objetivou-se avaliar o efeito da aplicação de doses de KCl e de resíduos culturais da bananeira no teor de cloreto do solo, na atividade microbiana e na amonificação. O delineamento experimental foi inteiramente casualizado com quatro repetições. Os tratamentos foram arranjados em um fatorial 2 x 4: 2 doses de resíduo vegetal (200 e 400 mg dm-3) x 4 doses de KCl (0, 167, 334 e 668 mg dm-3), além de um controle (sem aplicação de KCl e resíduo). Foram quantificados o CO2, o teor de amônio (N-NH4 +) e de cloreto (Cl-) do solo e as taxas de mineralização/imobilização, aos 4, 45 e 130 dias após a incubação (dai). O aumento da dose de KCl reduziu a atividade microbiana, aos 4 dai, independentemente da dose de resíduo adicionada. A atividade microbiana diminuiu, aos 130 dai: em todos os tratamentos, quando comparados ao período inicial. O acréscimo das quantidades de resíduos culturais da bananeira aumentou o teor de Cl- do solo e promoveu a imobilização do N-NH4 +. Conclui-se que doses de KCl maiores que 400 mg dm-3, associadas a presença desse resíduo, reduzem a atividade microbiana e a mineralização do N do solo.

Revising the PLAC8 gene family: from a central role in differentiation, proliferation, and apoptosis in mammals to a multifunctional role in plants.

PLAC8 is a cysteine-rich protein described as a central mediator of tumor evolution in mammals; as such, it represents a promising candidate for diagnostic and therapeutic targeting. The human PLAC8 gene is also involved in contact hypersensitivity response and presents a role in psoriatic skin. In plants, PLAC8 motif-containing proteins are involved in the determination of organ size and growth, response to infection, Ca2+ influx, Cd resistance, and zinc detoxification. In general, PLAC8 motif-containing proteins present the conserved CCXXXXCPC or CLXXXXCPC region. However, there is no devised nomenclature for the PLAC8 motif-containing proteins. Here, through the analysis of 445 sequences, we show that PLAC8 motif-containing proteins constitute a unique gene family, and we propose a unified nomenclature. This is the first report indicating the existence of different groups of PLAC8 proteins, which we have called types I, II, and III. Type I genes are found in mammals, fungi, plants, and algae, and types II and III are exclusive to plants. Our study describes for the first time PLAC8 type III proteins. Whether these sequences maintain their known functional role or possess distinct functions of types I and II genes remains unclear.

Asociación entre tamización de cáncer de próstata, vinculación al sistema de salud y factores asociados en adultos mayores: análisis secundario de la encuesta SABE Bogotá, Colombia / Relationship between prostate cancer screening, linkage to the health system and associated factors in older adults from Bogotá, Colombia: Secondary analysis of the SABE survey

Introducción y objetivos El cáncer de próstata es una enfermedad con alta prevalencia en nuestra población. Su diagnóstico temprano es importante para mejorar el pronóstico de esta enfermedad. El objetivo de este artículo es evidenciar los factores asociados a la oportunidad de tamización en adultos mayores de la ciudad de Bogotá, Colombia. Métodos Se analizaron los datos del estudio Salud, Bienestar y Envejecimiento (SABE) Bogotá 2012, que incluyó a 736 hombres de 60 años o más. Se utilizó como variable dependiente el autorreporte de examen de próstata en los 2 últimos años y se evaluó con respecto a factores sociodemográficos por medio de un análisis multivariado. Resultados Se encontró una prevalencia de cáncer de próstata del 3,15%. El 57,8% de los hombres se habían realizado al menos un examen de próstata. Aquellos afiliados al régimen contributivo tenían mayor oportunidad para ser tamizados con respecto a los vinculados/no asegurados (OR: 8,81) (IC95%: 2,92-26,63) (p < 0,001), al igual que los del régimen subsidiado (OR: 3,70) (IC95%; 1,20-11,41) (p = 0,023). Conclusión Existe una inequidad en cuanto a la oportunidad de tamización de cáncer de próstata según el tipo de seguridad social, por lo que se deben optimizar las estrategias de detección temprana que fortalezcan la inclusión de toda la población. Se necesitan más estudios que brinden mayor información sobre esta problemática.

Introduction Prostate cancer is a high prevalence disease in our male population. Early diagnosis is important in order to improve its prognosis. The aim of this article is to describe the factors associated with prostate cancer screening of older adults in Bogotá, Colombia. Materials and methods The study used data from the Bogotá 2012 Health, Well-Being, and Ageing (Salud, Bienestar y Envejecimiento [SABE]) survey, which included 736 men aged 60 years or older. The dependent variable used was self-reported prostate screening in the last 2 years. An analysis was performed to determine the between this variable and socio-demographic variables and comorbidities using multivariate analysis. Results There was a prevalence of prostate cancer of 3.15%, with 57.8% of the population having had at least one prostate examination. Those affiliated to a health insurance scheme were more likely to be screened than the uninsured with an OR: 8.81, 95% CI: 2.92-26.63, P < .001, as those affiliated to subsidized social security health scheme OR: 3.70, 95% CI: 1.20-11.41, P = .023, respectively). Conclusion There is inequity in the opportunity of screening for prostate cancer according to the type of health insurance scheme. Early detection strategies must be strengthened in order to include the entire population. Further studies are needed to provide more information on this issue.

Anatomical distribution analysis reveals lack of Langerin+ dermal dendritic cells in footpads and tail of C57BL/6 mice.

Epidermal Langerhans cells (LCs) and dermal dendritic cells (dDCs) capture cutaneous antigens and present them to T-cells in lymph nodes (LNs). The function of LCs and Langerin+ dDCs was extensively studied in the mouse, but their anatomical repartition is unknown. Here, we found LCs in back skin, footpads and tail skin of C57BL/6, BALB/c, 129/Sv and CBA/J mice. Langerin+ dDCs were readily observed in back skin of all strains, but only in footpads and tail of BALB/c and CBA/J mice. Similarly, while LCs were equally present in all LNs and strains, Langerin+ dDCs were found in popliteal LNs (draining footpads) only in BALB/c and CBA/J mice. The sciatic LNs, which we identified as the major tail-draining lymphoid organ, were devoid of Langerin+ dDCs in all strains. Thus, functionally different DCs reside in different skin areas, with variations among mouse strains, implying a potential impact on the cutaneous immune reaction.

Prostate cancer and the increasing role of active surveillance.

Prostate cancer (PC) is the most often diagnosed non-skin cancer and the second leading cause of cancer-related death among men in the United States. As a result, for many years the American Urological Association (AUA) and the American Cancer Society have issued statements recommending screening for PC, resulting in its widespread implementation in the United States. Recently, the United States Preventative Services Task Force gave PC screening a recommendation of D, that is, against PC screening for all men. The AUA countered this recommendation, stating that since the development of PC screening using prostate-specific antigen, a reduction in PC-specific mortality has been seen, and that the risk reduction occurred in a setting in which many of the patients were not aggressively treated for prostate cancer. Active surveillance may be described as a method to potentially delay or obviate the need for treatment in men with clinically insignificant PC or PC thought to be at low risk for progression. Studies have shown no significant difference in outcome or pathology between men with low risk PC who receive treatment at the point of progression and those undergoing immediate treatment. Ongoing studies are evaluating the efficacy and utility of active surveillance for low-risk PC. Interim results of these studies have shown that approximately 30% of patients progress on active surveillance. However, "progression" does not necessarily mean treatment failure; rarely do patients develop locally advanced or metastatic disease. Active surveillance has also been shown to be cost-effective when compared with immediate treatment for PC. Longer follow-up may continue to show an increased benefit of active surveillance as a reasonable initial approach to the management of men with low-risk, clinically localized PC.

Identification of four new PITX2 gene mutations in patients with Axenfeld-Rieger syndrome.

PURPOSE: Axenfeld Rieger syndrome (ARS) is an autosomal dominant inherited disorder affecting development of the ocular anterior chamber, abdomen, teeth and facial structures. The PITX2 gene is a major gene encoding a major transcription factor associated with ARS. METHODS: ARS patients were collected from six unrelated families. Patients and their families were ophthalmologically phenotyped and their blood was collected for DNA extraction. We screened the coding region of human PITX2 gene by direct sequencing. The consequences of the mutations described were investigated by generating crystallographic representations of the amino acid changes. In order to better understand the occurrence of glaucoma in ARS patients, we studied the PITX2 gene expression in human embryonic and fetal ocular tissue sections. RESULTS: We identified four novel PITX2 genetic alterations in four unrelated families with ARS. These mutations included two nonsense mutations (E55X and Y121X), an eight nucleotides insertion (1251 ins CGACTCCT) and a substitution (F58L), in familial and sporadic cases of ARS. We also showed for the first time that PITX2 is expressed at early stages of the human embryonic and fetal periocular mesenchyme, as well as at later stages of human development in the fetal ciliary body, ciliary processes, irido corneal angle and corneal endothelium. The human fetal eye PITX2 gene expression pattern reported here for the first time provides a strong basis for explaining the frequent occurrence of glaucoma in patients affected by PITX2 gene mutations. CONCLUSIONS: Two mutations identified affect the homeodomain (E55X and F58L). The E55X nonsense mutation is likely to alter dramatically the DNA-binding capabilities of the PITX2 homeodomain. Furthermore, there is a complete loss of the carboxy-terminal part of the PITX2 protein beyond the site of the mutation. The phenylalanine F58 is known to contribute to the hydrophobic network of the homeodomain. The crystallographic representations of the mutation F58L show that this mutation may change the conformation of the helical core. The F58L mutation is very likely to modify the homeodomain conformation and probably alters the DNA binding properties of PITX2. The other mutations (Y121X and the eight-nucleotide insertion (1251 ins CGA CTC CT) CGA CTC CT, at position 224 in PITX2A) result in partial loss of the C-terminal domain of PITX2. Pitx2 synergistically transactivates the prolactin promoter in the presence of the POU homeodomain protein Pit-1. Pitx2 activity is regulated by its own C-terminal tail. This region contains a highly conserved 14-amino-acid element involved in protein-protein interactions. The C-terminal 39-amino-acid tail represses DNA binding activity and is required for Pitx2 interactions with other transcription factors, for Pitx2-Pit-1 interaction and Pit-1synergism. Pit-1 interaction with the Pitx2 C terminus masks the inhibitory effect and promotes increased DNA binding activity. Thus, the partial or complete loss of the C terminus tail can lead to decreased or absent DNA binding activity and trigger severe ARS phenotypes. Our in situ hybridization results obtained on human embryonic and fetal ocular tissue sections constitute the first molecular histological data providing an explanation for the occurrence of precocious glaucoma in human patients affected by ARS caused by PITX2 mutations. Further structural and biochemical studies are needed for understanding the wide spectrum of clinical phenotypes caused by the increasing number of new PITX2 mutations found in ARS affected patients.

A cylinder-shaped double ribbon structure formed by an amyloid hairpin peptide derived from the beta-sheet of murine PrP: an X-ray and molecular dynamics simulation study.

A structural model of the murine PrP small beta-sheet was obtained by synthesizing the RGYMLGSADPNGNQVYYRG peptide comprising the two beta-strands 127-133 and 159-164 linked by a four-residue sequence of high turn propensity. The DPNG turn sequence is a "short circuit" replacing the original protein sequence between the two strands. This 19-residue peptide spontaneously forms very long single fibrils as observed by electron microscopy. The X-ray diffraction patterns of a partially oriented sample reveals an average arrangement of the hairpin peptides into a structure which can be geometrically approximated by an empty-core cylinder. The hairpins are oriented perpendicular to the cylinder axis and a 130 A helix period is observed. Based on X-ray diffraction constraints and on more indirect general protein structure considerations, a precise and consistent fibril model was built. The structure consists of two beta-sheet ribbons wound around a cylinder and assembled into a single fibril with a hairpin orientation perpendicular to the fibril axis. Subsequent implicit and explicit solvent molecular dynamics simulations provided the final structure at atomic resolution and further insights into the stabilizing interactions. Particularly important are the zipper-like network of polar interactions between the edges of the two ribbons, including the partially buried water molecules. The hydrophobic core is not optimally compact explaining the low density of this region seen by X-ray diffraction. The present findings provide also a simple model for further investigating the sequence-stability relationship using a mutational approach with a quasi-independent consideration of the polar and apolar interactions.

YodA from Escherichia coli is a metal-binding, lipocalin-like protein.

We have determined the crystal structure of YodA, an Escherichia coli protein of unknown function. YodA had been identified under conditions of cadmium stress, and we confirm that it binds metals such as cadmium and zinc. We have also found nickel bound in one of the crystal forms. YodA is composed of two domains: a main lipocalin/calycin-like domain and a helical domain. The principal metal-binding site lies on one side of the calycin domain, thus making YodA the first metal-binding lipocalin known. Our experiments suggest that YodA expression may be part of a more general stress response. From sequence analogy with the C-terminal domain of a metal-binding receptor of a member of bacterial ATP-binding cassette transporters, we propose a three-dimensional model for this receptor and suggest that YodA may have a receptor-type partner in E. coli.