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Loss of heterozygosity (LOH) on chromosome 17q21 has been detected in 30% of primary human breast tumours. The smallest common region deleted occurred in an interval between the D17S746 and D17S846 polymorphic sequences tagged sites that are located on two recombinant P1-bacteriophage clones of chromosome 17q21: 122F4 and 50H1, respectively. To identify the target gene for LOH, we defined a map of this chromosomal region. We found the following genes: JUP, FK506BP10, SC65, Gastrin (GAS) and HAP1. Of the genes that have been identified in this study, only JUP is located between D17S746 and D17S846. This was of interest since earlier studies have shown that JUP expression is altered in breast, lung and thyroid tumours as well as cell lines having LOH in chromosome 17q21. However, no mutations were detected in JUP using single-strand conformation polymorphism analysis of primary breast tumour DNAs having LOH at 17q21. We could find no evidence that the transcription promoter for JUP is methylated in tumour DNAs having LOH at 17q21. We suspect that the target gene for LOH in primary human breast tumours on chromosome 17q21 is either JUP and results in a haploinsufficiency for expression or may be an unidentified gene located in the interval between D17S846 and JUP.British Journal of Cancer (2004) 90, 2384-2389. doi:10.1038/sj.bjc.6601848 www.bjcancer.com Published online 25 May 2004 [ABSTRACT FROM AUTHOR]

The Order Pyrotheria is one of the most bizarre and least-known groups of South American native ungulates, and its biochron extends from the early? Eocene to the late Oligocene. The emblematic genus of this order is Pyrotherium, which is known by several maxillae, mandibles, and postcranial bones of adult individuals. In this paper, we describe the most complete juvenile mandible of Pyrotherium found to date, MPEF-PV 2581, which bears dp3–m1 and alveoli of di1–di2. The study of this specimen, re-study of previously published specimens (MACN-A 52-290 and MNHN-F-DES 104), and study of unpublished deciduous upper and lower cheek teeth from several collections allows us to designate MLP-PV 13-3 as the lectotype of P. romeroi, to establish dental age stages for Pyrotherium, to differentiate two juvenile stages (early and late), and to define differences between deciduous and permanent upper premolars. Our observations show that adult individuals of Pyrotherium have a narrower and posteriorly expanded mandible (due to the increase in the size of the tusk-like teeth) and a straighter mandibular incisura. We also observe that di1, di2, and dp2 are present in juveniles but not in adults, except for the i2. X-ray imaging suggests that delayed dental eruption is not present in the juvenile mandible, whereas cheek tooth wear suggests an anteroposterior eruption sequence in p3 through m3. This work adds new information about the dental age stages of Pyrotherium and proposes the following modified deciduous dental formula: dI ?/2, dC ?/0, dP 3/3. [ABSTRACT FROM AUTHOR]

Activities such as childbirth and breastfeeding can cause severe oxidative stress and inflammatory damage to the mother during early lactation, and can affect animal milk production, and the growth and development of offspring. Trehalose alleviates damage to the body by endowing it with stress resistance. In this study, we used trehalose combined with Lactobacillus plantarum, Bifidobacterium longum, Bacillus subtilis, and Saccharomyces cerevisiae to explore whether dietary intervention can alleviate oxidative stress and inflammatory damage in early lactation and to evaluate the growth ability, acid production ability, antioxidant ability, non-specific adhesion ability, antibacterial ability, and other parameters to determine the optimal combinations and proportions. The results showed that the synbiotics composed of 2.5% trehalose and 1 × 107 cfu/g of Bifidobacterium longum could regulate the gut microbiota, and promote mammary gland development in dams by reducing progesterone (PROG) content in the blood, increasing prolactin (PRL) and insulin-like growth factor-1 (IGF-1) content, enhancing their antioxidant and immune abilities, and effectively increasing the weight and lactation of early lactating dams. In addition, it can also affect the growth of offspring and the development of the intestinal barrier. These results indicate that trehalose synbiotics have great potential in alleviating oxidative stress and inflammatory damage in early lactation. [ABSTRACT FROM AUTHOR]

Fibrosis is a major medical challenge, as it leads to irreversible tissue remodeling and organ dysfunction. Its progression contributes significantly to morbidity and mortality worldwide, with limited therapeutic options available. Extensive research on the molecular mechanisms of fibrosis has revealed numerous factors and signaling pathways involved. However, the interactions between these pathways remain unclear. A comprehensive understanding of the entire signaling network that drives fibrosis is still missing. The TGF-β and Notch signaling pathways play a key role in fibrogenesis, and this review focuses on their functional interplay and molecular mechanisms. Studies have shown synergy between TGF-β and Notch cascades in fibrosis, but antagonistic interactions can also occur, especially in cardiac fibrosis. The molecular mechanisms of these interactions vary depending on the cell context. Understanding these complex and context-dependent interactions is crucial for developing effective strategies for treating fibrosis. [ABSTRACT FROM AUTHOR]

A refined analytical model of spatially resolved diffuse reflectance with small source-detector separations (SDSs) for the in vivo skin studies is proposed. Compared to the conventional model developed by Farrell et al., it accounts for the limited acceptance angle of the detector fiber. The refined model is validated in the wide range of optical parameters by Monte Carlo simulations of skin diffuse reflectance at SDSs of units of mm. Cases of uniform dermis and two-layered epidermis-dermis structures are studied. Higher accuracy of the refined model compared to the conventional one is demonstrated in the separate, constraint-free reconstruction of absorption and reduced scattering spectra of uniform dermis from the Monte Carlo simulated data. In the case of epidermis-dermis geometry, the recovered values of reduced scattering in dermis are overestimated and the recovered values of absorption are underestimated for both analytical models. Presumably, in the presence of a thin mismatched topical layer, only the effective attenuation coefficient of the bottom layer can be accurately recovered using a diffusion theory-based analytical model while separate reconstruction of absorption and reduced scattering fails due to the inapplicability of the method of images. These findings require implementation of more sophisticated models of light transfer in inhomogeneous media in the recovery algorithms. [ABSTRACT FROM AUTHOR]

During the past two decades evidence has been developed that indicates a handful of viruses with known oncogenic capacity, have potential roles in breast cancer. These viruses are mouse mammary tumour virus (MMTV - the cause of breast cancer in mice), high-risk human papilloma viruses (HPV-the cause of cervical cancer), Epstein Barr virus (EBV-the cause of lymphomas and naso-pharyngeal cancer) and bovine leukemia virus (BLV - the cause of cancers in cattle). These viruses may act alone or in combination. Each of these viruses are significantly more prevalent in breast cancers than in normal and benign breast tissue controls. The odds ratios for the prevalence of these viruses in breast cancer compared to normal and benign breast controls, are based on case control studies - MMTV 13·40, HPV 5.56, EBV 4·43 and BLV 2·57. The odds ratios for MMTV are much greater compared to the other three viruses. The evidence for a causal role for mouse mammary tumour virus and high risk for cancer human papilloma viruses in human breast cancer is increasingly comprehensive. The evidence for Epstein Barr virus and bovine leukemia virus is more limited. Overall the evidence is substantial in support of a viral cause of breast cancer. [ABSTRACT FROM AUTHOR]

Ever since the discovery of the first remains of Macrauchenia patachonica by Charles Darwin in 1834, this taxon has puzzled researchers with its peculiar anatomy. Being the best-known member of the family Macraucheniidae and with fossil records in extensive areas of South America between the Middle to Late Pleistocene/earliest Holocene, M. patachonica has been extensively studied over decades, and recently even included in molecular studies. However, there are some elements of its skeleton that have been inadvertently unstudied. One of these elements is the atlas of M. patachonica that due to a misidentification made 159 years ago by the prominent zoologist Hermann Burmeister, was not examined or illustrated by later researchers even with access to excellent specimens. Here, we describe and illustrate the atlas of M. patachonica for the first time, correcting Burmeister’s mistake. Overall, the anatomy of the atlas of M. patachonica is consistent with the anatomy of older macraucheniids. The atlas described by Burmeister as being M. patachonica probably corresponds to that of a bovid. It is noteworthy that most mounted skeletons of M. patachonica present today in museum exhibitions, display a correct atlas derived from a more complete specimen discovered ca. 1904 by the prominent palaeontologist Santiago Roth. [ABSTRACT FROM AUTHOR]

With their odd cranial features, glyptodonts, closely related to extant armadillos, are a highly diverse group of the South American megafauna. Doedicurus, Glyptodon, Panochthus, and Neosclerocalyptus were present in the “Pampean Formation” during the Pleistocene, and they are all exceptionally preserved in the Santiago Roth Collection, thus offering the possibility of investigating these four well-diversified genera. A total of 13 specimens (seven species) were analysed and compared in a qualitative/quantitative study of external cranial remains and endocranial reconstructions (i.e., braincase and associated cranial canals, and inner ears). We report on anatomical features that contribute to existing phylogenetic matrices; many of them are new potential synapomorphies supporting the current hypotheses regarding the evolutionary history of the Pleistocene glyptodonts. These include the anterior cranial shape, the position of the basicranium in respect to the whole cranium, the shape of the cranial roof, the position of the largest semicircular canal, and the inclination of the cerebrum. They may represent new shared-derived features among Glyptodon, Doedicurus, Neosclerocalyptus, and Panochthus. We also provide detailed comparative descriptions highlighting new potential convergences in respect to current phylogenies, concerning, for instance, the shape of the foramen magnum, the global shape of the cranium, orbital shape, cochlear position, and a strong protrusion of the zygomatic process of the squamosal. In light of these results, we discuss morphological transformations across phylogeny. The endocranial comparison brought insights on the phylogenetic patterns of cranial canal evolution. [ABSTRACT FROM AUTHOR]

Nearctic ungulates such as artiodactyls, perissodactyls, and proboscideans arrived in South America during the Great American Biotic Interchange. Among them are camelids, cervids, tayassuids, equids, tapirids and gomphotherids. A historical collection of Nearctic ungulates from Pleistocene deposits of the Pampean region in Argentina is here studied and described. The collection consists of specimens collected by Santiago Roth in the nineteenth century and brought to Europe, where they are housed in the paleontological collections of the University of Zurich and the Natural History Museum of Geneva. Among the taxa reported here are Notiomastodon platensis,Lama guanicoe, Hemiauchenia paradoxa, Tayassu pecari, Morenelaphus sp., Hippidion cf. H. principale, Equus cf. E. neogeus, and other indeterminate gomphotherids, camelids, tayassuids, cervids, and equids. The exact stratigraphic position of these fossils collected more than 130 years ago is in many cases uncertain. The historical collection is still relevant for taxonomic studies and for offering new insights into palaeobiogeography and palaeobiology of mammalian fauna of the region during the Pleistocene. [ABSTRACT FROM AUTHOR]

Safely maximizing brain cancer removal without injuring adjacent healthy tissue is crucial for optimal treatment outcomes. However, it is challenging to distinguish cancer from noncancer intraoperatively. This study aimed to explore the feasibility of diffuse reflectance spectroscopy (DRS) as a label‐free and real‐time detection technology for discrimination between brain cancer and noncancer tissues. Fifty‐five fresh cancer and noncancer specimens from 19 brain surgeries were measured with DRS, and the results were compared with co‐registered clinical standard histopathology. Tissue optical properties were quantitatively obtained from the diffuse reflectance spectra and compared among different types of brain tissues. A machine learning‐based classifier was trained to differentiate cancerous versus noncancerous tissues. Our method could achieve a sensitivity of 93% and specificity of 95% for discriminating high‐grade glioma from normal white matter. Our results showed that DRS has the potential to be used for label‐free, real‐time in vivo cancer detection during brain surgery. [ABSTRACT FROM AUTHOR]

We describe new Late Miocene mammalian specimens from the Maimará Formation (Late Miocene to Early Pliocene) exposed at Humahuaca Basin (23°–24°S), northwestern Argentina (NWA), and analyse their taxonomy and relevance for our understanding of the initial stages of the Great American Biotic Interchange (GABI). The stratigraphical and geochronological control of the studied specimens indicates a time window of c. 6.6–5.8 Ma. These data are crucial for establishing the oldest records of the Holarctic immigrants of the GABI. The first record of cricetid rodents from the Maimará Formation is reported. Moreover, with an age of c. 6 Ma it is the first appearance datum (FAD) of these rodents in South America. The age of the procyonid Cyonasua recorded in this unit is estimated between c. 6.6 and c. 6.4 Ma. The record of procyonids and cricetids in the same continuous sedimentary sequence suggests that the time interval between the dispersion of both groups into the continent during GABI was c. 1 myr. Of the autochthonous mammals from the Maimará Formation, the first records of litopterns, chlamyphorid and mylodontine xenarthrans, and caviomorph rodents (including new species Pithanotomys? solisae and Palaeocavia humahuaquense) are described. FADs of immigrant and autochthonous mammals in NWA suggest a major faunal turnover during GABI at the Messinian, probably linked to global climatic changes and the tectonic activity that affected the Humahuaca Basin at that time. Hypsodonty, a dominant feature among Maimaran mammals, may be related to a landscape strongly influenced by the Andean uplift. [ABSTRACT FROM AUTHOR]

We report herein a new genus and species of Pyrotheria, Berracotherium koimeterion, from the Quebrada de Los Colorados Formation (middle Eocene-early Oligocene), Salta Province (Argentina). Up to this contribution, pyrotheres had only been known from northwestern Argentina by a single fragmentary tusk referred to Propyrotherium from the Geste Formation (late Eocene), Catamarca Province. This new taxon is based on a right mandibular fragment with the roots of dp4–m1 and m2 in eruption, and it can be differentiated from other pyrotheres as follows: horizontal mandibular ramus high and robust; mandibular symphysis large that extends posteriorly to reach m1; lower cheek teeth longer than wide; m2 bilophodont; mesial and distal lophids completely separated at the labial and lingual ends; both lophids transverse, parallel, nearly straight, and low; crenulations on lophids; the cristid obliqua that connects mesial and labial lophids is conspicuous, almost perpendicular to both lophids, and it is labially placed; and well-expanded distal cingulum that forms a third lobe. A cladistic analysis was performed that recovers Berracotherium gen. nov. as a member of Pyrotheriidae and includes it within an unresolved clade with Griphodon, Propyrotherium, Baguatherium, and Pyrotherium. Berracotherium koimeterion gen. et sp. nov. increases the known diversity of Pyrotheria at both regional and global scales, as well as its geographic and stratigraphic distribution. [ABSTRACT FROM AUTHOR]

Mouse mammary tumor virus (MMTV) is a betaretrovirus that causes breast cancer in mice. The mouse mammary epithelial cells are the most permissive cells for MMTV, expressing the highest levels of virus upon infection and being the ones later transformed by the virus due to repeated rounds of infection/superinfection and integration, leading eventually to mammary tumors. The aim of this study was to identify genes and molecular pathways dysregulated by MMTV expression in mammary epithelial cells. Towards this end, mRNAseq was performed on normal mouse mammary epithelial cells stably expressing MMTV, and expression of host genes was analyzed compared with cells in its absence. The identified differentially expressed genes (DEGs) were grouped on the basis of gene ontology and relevant molecular pathways. Bioinformatics analysis identified 12 hub genes, of which 4 were up-regulated (Angp2, Ccl2, Icam, and Myc) and 8 were down-regulated (Acta2, Cd34, Col1a1, Col1a2, Cxcl12, Eln, Igf1, and Itgam) upon MMTV expression. Further screening of these DEGs showed their involvement in many diseases, especially in breast cancer progression when compared with available data. Gene Set Enrichment Analysis (GSEA) identified 31 molecular pathways dysregulated upon MMTV expression, amongst which the PI3-AKT-mTOR was observed to be the central pathway down-regulated by MMTV. Many of the DEGs and 6 of the 12 hub genes identified in this study showed expression profile similar to that observed in the PyMT mouse model of breast cancer, especially during tumor progression. Interestingly, a global down-regulation of gene expression was observed, where nearly 74% of the DEGs in HC11 cells were repressed by MMTV expression, an observation similar to what was observed in the PyMT mouse model during tumor progression, from hyperplasia to adenoma to early and late carcinomas. Comparison of our results with the Wnt1 mouse model revealed further insights into how MMTV expression could lead to activation of the Wnt1 pathway independent of insertional mutagenesis. Thus, the key pathways, DEGs, and hub genes identified in this study can provide important clues to elucidate the molecular mechanisms involved in MMTV replication, escape from cellular anti-viral response, and potential to cause cell transformation. These data also validate the use of the MMTV-infected HC11 cells as an important model to study early transcriptional changes that could lead to mammary cell transformation. [ABSTRACT FROM AUTHOR]

Polycomb-like proteins (PCLs) are a crucial group of proteins associated with the Polycomb repressive complex 2 (PRC2) and are responsible for setting up the PRC2.1 subcomplex. In the vertebrate system, three homologous PCLs exist: PHF1 (PCL1), MTF2 (PCL2), and PHF19 (PCL3). Although the PCLs share a similar domain composition, they differ significantly in their primary sequence. PCLs play a critical role in targeting PRC2.1 to its genomic targets and regulating the functionality of PRC2. However, they also have PRC2-independent functions. In addition to their physiological roles, their dysregulation has been associated with various human cancers. In this review, we summarize the current understanding of the molecular mechanisms of the PCLs and how alterations in their functionality contribute to cancer development. We particularly highlight the nonoverlapping and partially opposing roles of the three PCLs in human cancer. Our review provides important insights into the biological significance of the PCLs and their potential as therapeutic targets for cancer treatment. [ABSTRACT FROM AUTHOR]

Notch signaling is involved in cell fate determination and deregulated in human solid tumors. Hypoxia is an important feature in many solid tumors, which activates hypoxia-induced factors (HIFs) and their downstream targets to promote tumorigenesis and cancer development. Recently, HIFs have been shown to trigger the Notch signaling pathway in a variety of organisms and tissues. In this review, we focus on the pro- and anti-tumorigenic functions of Notch signaling and discuss the crosstalk between Notch signaling and cellular hypoxic response in cancer pathogenesis, including epithelia-mesenchymal transition, angiogenesis, and the maintenance of cancer stem cells. The pharmacological strategies targeting Notch signaling and hypoxia in cancer are also discussed in this review. [ABSTRACT FROM AUTHOR]

Thoracic aortic disease affects people of all ages and the majority of those aged <60 years have an underlying genetic cause. There is presently no effective medical therapy for thoracic aneurysm and surgery remains the principal intervention. Unlike abdominal aortic aneurysm, for which the inflammatory/atherosclerotic pathogenesis is well established, the mechanism of thoracic aneurysm is less understood. This paper examines the key cell signaling systems responsible for the growth and development of the aorta, homeostasis of endothelial and vascular smooth muscle cells and interactions between pathways. The evidence supporting a role for individual signaling pathways in pathogenesis of thoracic aortic aneurysm is examined and potential novel therapeutic approaches are reviewed. Several key signaling pathways, notably TGF-β, WNT, NOTCH, PI3K/AKT and ANGII contribute to growth, proliferation, cell phenotype and survival for both vascular smooth muscle and endothelial cells. There is crosstalk between pathways, and between vascular smooth muscle and endothelial cells, with both synergistic and antagonistic interactions. A common feature of the activation of each is response to injury or abnormal cell stress. Considerable experimental evidence supports a contribution of each of these pathways to aneurysm formation. Although human information is less, there is sufficient data to implicate each pathway in the pathogenesis of human thoracic aneurysm. As some pathways i.e., WNT and NOTCH, play key roles in tissue growth and organogenesis in early life, it is possible that dysregulation of these pathways results in an abnormal aortic architecture even in infancy, thereby setting the stage for aneurysm development in later life. Given the fine tuning of these signaling systems, functional polymorphisms in key signaling elements may set up a future risk of thoracic aneurysm. Multiple novel therapeutic agents have been developed, targeting cell signaling pathways, predominantly in cancer medicine. Future investigations addressing cell specific targeting, reduced toxicity and also less intense treatment effects may hold promise for effective new medical treatments of thoracic aortic aneurysm. [ABSTRACT FROM AUTHOR]

The concepts of integration and modularity refer to the degree of covariation between the components of a biological structure. Components that covariate strongly, but are relatively independent of other modules, are called morphological modules. Morphological integration is understood as the coordinated morphological variation of these components as a functional unit. In mandible case, four modules have been defined based on their differential embryonic origin: alveolar, basal body, coronoid and condylar. The aim was to test these four modular mandible bases using geometric morphometric techniques. The hypothesis of modularity of mandibular development, based on differential embryonic origins, was tested using digital pictures of hemimandibles in lateral form from 26 Araucan horses for those modules. Subsequently, the level of morphological integration between the modules defined above was evaluated using eight landmarks and 65 semi-landmarks, through an analysis of paired blocks of least squares. The divisions between those units presented a modular foundation and the respective level of morphological integration between all considered units. The results of our modular and integrative analysis can be very useful for the comparative study of adaptive processes of other equine breeds. [ABSTRACT FROM AUTHOR]

Background: Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer. Patient prognosis is poor, and the existing therapeutic strategies for LUAD are far from satisfactory. Recently, targeting N6-methyladenosine (m6A) modification of RNA has been suggested as a potential strategy to impede tumor progression. However, the roles of m6A modification in LUAD tumorigenesis is unknown. Methods: Global m6A levels and expressions of m6A writers, erasers and readers were evaluated by RNA methylation assay, dot blot, immunoblotting, immunohistochemistry and ELISA in human LUAD, mouse models and cell lines. Cell viability, 3D-spheroid generation, in vivo LUAD formation, experiments in cell- and patient-derived xenograft mice and survival analysis were conducted to explore the impact of m6A on LUAD. The RNA-protein interactions, translation, putative m6A sites and glycolysis were explored in the investigation of the mechanism underlying how m6A stimulates tumorigenesis. Results: The elevation of global m6A level in most human LUAD specimens resulted from the combined upregulation of m6A writer methyltransferase 3 (METTL3) and downregulation of eraser alkB homolog 5 (ALKBH5). Elevated global m6A level was associated with a poor overall survival in LUAD patients. Reducing m6A levels by knocking out METTL3 and overexpressing ALKBH5 suppressed 3D-spheroid generation in LUAD cells and intra-pulmonary tumor formation in mice. Mechanistically, m6A-dependent stimulation of glycolysis and tumorigenesis occurred via enolase 1 (ENO1). ENO1 mRNA was m6A methylated at 359 A, which facilitated it's binding with the m6A reader YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) and resulted in enhanced translation of ENO1. ENO1 positively correlated with METTL3 and global m6A levels, and negatively correlated with ALKBH5 in human LUAD. In addition, m6A-dependent elevation of ENO1 was associated with LUAD progression. In preclinical models, tumors with a higher global m6A level showed a more sensitive response to the inhibition of pan-methylation, glycolysis and ENO activity in LUAD. Conclusions: The m6A-dependent stimulation of glycolysis and tumorigenesis in LUAD is at least partially orchestrated by the upregulation of METTL3, downregulation of ALKBH5, and stimulation of YTHDF1-mediated ENO1 translation. Blocking this mechanism may represent a potential treatment strategy for m6A-dependent LUAD. [ABSTRACT FROM AUTHOR]

R‐spondins (RSPOs) are influential signaling molecules that promote the Wnt/β‐catenin pathway and self‐renewal of stem cells. Currently, RSPOs are emerging as clinically relevant oncogenes, being linked to cancer development in multiple organs. Although this has instigated the rapid development and testing of therapeutic antibodies targeting RSPOs, functional evidence that RSPO causally drives cancer has focused primarily on the intestinal tract. Here, we assess the oncogenic capacity of RSPO in breast cancer in a direct fashion by generating and characterizing a novel mouse model with conditional Rspo3 expression in the mammary gland. We also address the prevalence of RSPO gene alterations in breast cancer patients. We found that a quarter of breast cancer patients harbor RSPO2/RSPO3 copy number amplifications, which are associated with lack of steroid hormone receptor expression and reduced patient survival. Foremost, we demonstrate the causal oncogenic capacity of RSPO3 in the breast, as conditional Rspo3 overexpression consistently drives the development of mammary adenocarcinomas in our novel Rspo3 breast cancer model. RSPO3‐driven mammary tumors typically show poor differentiation, areas of epithelial‐to‐mesenchymal transition, and metastatic potential. Given the reported interplay in the Wnt/β‐catenin pathway, we comparatively analyzed RSPO3‐driven mouse mammary tumors versus classical WNT1‐driven analogues. This revealed that RSPO3‐driven tumors are distinct, as the poorly differentiated tumor morphology and metastatic potential were observed in RSPO3‐driven tumorigenesis exclusively, further substantiated by differentiating gene expression profiles. Co‐expression of Rspo3 and Wnt1 transduced mammary tumors with a mixed phenotype harboring morphological features characteristic of both transgenes. In summary, we report that a quarter of breast cancer patients harbor RSPO2/RSPO3 copy number gains, and these patients have a worse prognosis, whilst providing in vivo evidence that RSPO3 drives poorly differentiated invasive breast cancer in mice. Herewith, we establish RSPO3 as a driver of breast cancer with clinical relevance, proposing RSPO3 as a novel candidate target for therapy in breast cancer. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

A Human Betaretrovirus (HBRV) has been identified in humans, dating as far back as about 4500 years ago, with a high probability of it being acquired by our species around 10,000 years ago, following a species jump from mice to humans. HBRV is the human homolog of the MMTV (mouse mammary tumor virus), which is the etiological agent of murine mammary tumors. The hypothesis of a HMTV (human mammary tumor virus) was proposed about 50 years ago, and has acquired a solid scientific basis during the last 30 years, with the demonstration of a robust link with breast cancer and with PBC, primary biliary cholangitis. This article summarizes most of what is known about MMTV/HMTV/HBRV since the discovery of MMTV at the beginning of last century, to make evident both the quantity and the quality of the research supporting the existence of HBRV and its pathogenic role. Here, it is sufficient to mention that scientific evidence includes that viral sequences have been identified in breast-cancer samples in a worldwide distribution, that the complete proviral genome has been cloned from breast cancer and patients with PBC, and that saliva contains HBRV, as a possible route of inter-human infection. Controversies that have arisen concerning results obtained from human tissues, many of them outdated by new scientific evidence, are critically discussed and confuted. [ABSTRACT FROM AUTHOR]

Since its discovery as a milk factor, mouse mammary tumor virus (MMTV) has been shown to cause mammary carcinoma and lymphoma in mice. MMTV infection depends upon a viral superantigen (sag)-induced immune response and exploits the immune system to establish infection in mammary epithelial cells when they actively divide. Simultaneously, it avoids immune responses, causing tumors through insertional mutagenesis and clonal expansion. Early studies identified antigens and sequences belonging to a virus homologous to MMTV in human samples. Several pieces of evidence fulfill a criterion for a possible causal role for the MMTV-like virus in human breast cancer (BC), though the controversy about whether this virus was linked to BC has raged for over 40 years in the literature. In this review, the most important issues related to MMTV, from its discovery to the present days, are retraced to fully explore such a controversial issue. Furthermore, the hypothesis of an MMTV-like virus raised the question of a potential zoonotic mouse–man transmission. Several studies investigate the role of an MMTV-like virus in companion animals, suggesting their possible role as mediators. Finally, the possibility of an MMTV-like virus as a cause of human BC opens a new era for prevention and therapy. [ABSTRACT FROM AUTHOR]

A human betaretrovirus (HBRV) has been linked with the autoimmune liver disease, primary biliary cholangitis (PBC), and various cancers, including breast cancer and lymphoma. HBRV is closely related to the mouse mammary tumor virus, and represents the only exogenous betaretrovirus characterized in humans to date. Evidence of infection in patients with PBC has been demonstrated through the identification of proviral integration sites in lymphoid tissue, the major reservoir of infection, as well as biliary epithelium, which is the site of the disease process. Accordingly, we tested the hypothesis that patients with PBC harbor a transmissible betaretrovirus by co-cultivation of PBC patients' lymph node homogenates with the HS578T breast cancer line. Because of the low level of HBRV replication, betaretrovirus producing cells were subcloned to optimize viral isolation and production. Evidence of infection was provided by electron microscopy, RT-PCR, in situ hybridization, cloning of the HBRV proviral genome and demonstration of more than 3400 integration sites. Further evidence of viral transmissibility was demonstrated by infection of biliary epithelial cells. While HBRV did not show a preference for integration proximal to specific genomic features, analyses of common insertion sites revealed evidence of integration proximal to cancer associated genes. These studies demonstrate the isolation of HBRV with features similar to mouse mammary tumor virus and confirm that patients with PBC display evidence of a transmissible viral infection. [ABSTRACT FROM AUTHOR]

The felid species of South America are thought to have arrived on the continent during the Great American Biotic Interchange (GABI) in the Pleistocene. However, molecular and palaeontological data do not agree on how this event affected speciation in felids. Here, we determine both the number of colonization events and the period when felines first migrated from North America to South America. In addition, we evaluate whether similar evolutionary events could have affected the eight Neotropical cat species in their levels of genetic diversity, spatial genetic structure and demographic changes. We analysed four concatenated mitochondrial genes of the jaguar, ocelot, margay, tigrina, pampas cat, Andean cat, puma and jaguarundi. The samples were representative of a wide distribution of these species in Central and South America. Our analysis suggests either three or four colonization events from North America to South America over the past 3 Myr, followed by subsequent speciation events and the attainment of high or very high genetic diversity levels for seven of the species. No unique evolutionary process was detected for any of the current Neotropical cat species. [ABSTRACT FROM AUTHOR]

Aim: Mammalian carnivores are among the best studied groups in terms of evolutionary history. However, the effects of species interactions in shaping community assemblages remain poorly understood. We hypothesize that indirect interactions via ecological trait filtering play a key role in structuring carnivoran assemblages, mediate coexistence and thus should show high functional diversity (FD) in space and time at continental scales. Location: The Americas. Taxon Mammalian carnivores (Mammalia: Carnivora). Methods: We followed a macroecological perspective via ecological network analyses for indirect interactions and assessed the underlying FD across space and from the last interglacial to the present in the Americas. We analysed the potential distributions and six ecological traits of 88 species to establish possible mechanisms that enables species to coexist and the underlying diversity patterns. We compared the empirical results with two null models and two sensitivity analyses. Results: Co‐occurring carnivore species presented ecological segregation driven mainly by a size ratio (SR) relationship, called here the body size spatial anti‐clustering effect. The underlying FD patterns showed low redundancy towards the tropics and the poles during the times evaluated. However, during the last glacial maximum, shifts occurred primarily at high latitudes in North America. This shift affected the SR relationship and therefore changed FD patterns. These local‐to‐continental interactions mediated by the SR are significant from an ecological and biogeographic perspective, suggesting a robust and consistent trend in which carnivore species of similar size have a lower probability of occupying the same area unless they differentiate in other ecological trait spaces. Main conclusions: The SR relationship is potentially a primary mechanism limiting carnivore coexistence, reflecting functional filtering. The SR tends to be conservative across different ecological trait groups and through time and space. We propose that the body‐size spatial anti‐clustering effect can directly measure species' coexistence and mediate FD patterns in the Americas. [ABSTRACT FROM AUTHOR]

Luminal breast cancer (BrCa) has a favorable prognosis compared with other tumor subtypes. However, with time, tumors may evolve and lead to disease progression; thus, there is a great interest in unraveling the mechanisms that drive tumor metastasis and endocrine resistance. In this review, we focus on one of the many pathways that have been involved in tumor progression, the fibroblast growth factor/fibroblast growth factor receptor (FGFR) axis. We emphasize in data obtained from in vivo experimental models that we believe that in luminal BrCa, tumor growth relies in a crosstalk with the stromal tissue. We revisited the studies that illustrate the interaction between hormone receptors and FGFR. We also highlight the most frequent alterations found in BrCa cell lines and provide a short review on the trials that use FGFR inhibitors in combination with endocrine therapies. Analysis of these data suggests there are many players involved in this pathway that might be also targeted to decrease FGF signaling, in addition to specific FGFR inhibitors that may be exploited to increase their efficacy. [ABSTRACT FROM AUTHOR]

Outcomes in electronic health records (EHR)-derived cohorts can be compared to similarly treated clinical trial cohorts to estimate the efficacy-effectiveness gap, the discrepancy in performance of an intervention in a trial compared to the real world. However, because clinical trial data may only be available in the form of published summary statistics and Kaplan-Meier curves, survival data reconstruction methods are needed to recreate individual-level survival data. Additionally, marginal moment-balancing weights can adjust for differences in the distributions of patient characteristics between the trial and EHR cohorts. We evaluated bias in hazard ratio (HR) estimates by comparing trial and EHR cohorts using survival data reconstruction and marginal moment-balancing weights through simulations and analysis of real-world data. This approach produced nearly unbiased HR estimates. In an analysis of overall survival for patients with metastatic urothelial carcinoma treated with gemcitabine-carboplatin captured in the nationwide Flatiron Health EHR-derived de-identified database and patients enrolled in a trial of the same therapy, survival was similar in the EHR and trial cohorts after using weights to balance age, sex, and performance status (HR = 0.93, 95% confidence interval (0.74, 1.18)). Overall, we conclude that this approach is feasible for comparison of trial and EHR cohorts and facilitates evaluation of outcome differences between trial and real-world populations. [ABSTRACT FROM AUTHOR]

For many applications in tissue optics, knowledge of the scattering coefficient or at least the reduced scattering coefficient is essential. In addition, its spectral dependence is also an important feature, as this provides information about scatterer sizes. While the characterization of the spectral dependence should be a simple fit, experimental results show strong fluctuations even for the same tissue type. For in‐vivo measurements, this problem is even greater. Therefore, it is the aim of this study to analyze the instabilities of the scattering characterizations and find a solution for it by means of Bayesian inference. In this study, this behavior is investigated using the example of diffuse reflectance spectroscopy. It can be shown that the currently used fitting functions are unstable for the fitting as both parameters for characterizing the reduced scattering coefficient describe the spectral dependence as well as the scattering strength. However, by a simple coordinate transform, a stable mathematical description of the scattering is derived. By the fact that a posteriori probability of the reduced scattering coefficient narrows down significantly with the Bayesian inference, the new fitting function is verified. [ABSTRACT FROM AUTHOR]

Background: Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites (SRMS) is a non-receptor tyrosine kinase that has been found to be overexpressed in various tumors. However, the role of SRMS in colorectal cancer (CRC) has not been well established. Methods: We evaluated the expression levels of SRMS in CRC using GEPIA, Oncomine, and HPA datasets. Survival information and gene expression data of CRC were obtained from The Cancer Genome Atlas (TCGA). Then, the association between SRMS and clinicopathological features was analyzed using UALCAN dataset. LinkedOmics was used to determine co-expression and functional networks associated with SRMS. Besides, we used TISIDB to assess the correlation between SRMS and immune signatures, including tumor-infiltrating immune cells and immunomodulators. Lastly, protein-protein interaction network (PPI) was established and the function enrichment analysis of the SRMS-associated immunomodulators and immune cell marker genes were performed using the STRING portal. Results: Compared to normal colorectal tissues, SRMS was found to be overexpressed in CRC tissues, which was correlated with a poor prognosis. In colon adenocarcinoma (COAD), the expression levels of SRMS are significantly correlated with pathological stages and nodal metastasis status. Functional network analysis suggested that SRMS regulates intermediate filament-based processes, protein autophosphorylation, translational initiation, and elongation signaling through pathways involving ribosomes, proteasomes, oxidative phosphorylation, and DNA replication. In addition, SRMS expression was correlated with infiltrating levels of CD4+ T cells, CD56dim, MEM B, Neutrophils, Th2, Th17, and Act DC. The gene ontology (GO) analysis of SRMS-associated immunomodulators and immune cell marker genes showed that they were mainly enriched in the immune microenvironment molecule-related signals. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of these genes indicated that they are involved in multiple cancer-related pathways. Conclusions: SRMS is a promising prognostic biomarker and potential therapeutic target for CRC patients. In particular, SRMS regulates CRC progression by modulating cytokine-cytokine receptor interaction, chemokines, IL-17, and intestinal immune networks for IgA production signaling pathways among others. However, more studies are needed to validate these findings. [ABSTRACT FROM AUTHOR]

The Neotropical frog family Ceratophryidae is composed of wide-mouthed frogs with stout bodies. Living species of the family are consistently recovered as a monophyletic group, but with disparities among analyses regarding internal relationships. Ceratophryidae presents one of the richest fossil records in Anura. Nevertheless, phylogenetic analyses including both extant and extinct species are still scarce, and the position of fossils is persistently debated. In this sense, the systematics of the family has changed considerably in the last decade with the exclusion of Baurubatrachus pricei (Late Cretaceous), Beelzebufo ampinga (Late Cretaceous) and Wawelia gerholdi (early Miocene). Herein, a morphologically based phylogeny for Ceratophryidae, including living species (11 spp.) and fossil specimens (10 spp.), is used as a background to discuss the evolutionary history of the family and its classification. We phylogenetically placed Baurubatrachus pricei, Beelzebufo ampinga and Wawelia gerholdi as non-ceratophryids. We recovered a monophyletic Ceratophryidae: Lepidobatrachus and Ceratophrys form a clade, with Chacophrys as its sister group. Our analysis corroborates the C. cornuta and C. aurita groups. Among fossils, L. australis and C. sagani were recovered as valid species based on autapomorphies, and C. rusconii was found to be the sister of all Ceratophrys. Ceratophrys ensenadensis, C. ameghinorum, C. aurita NHMUK PV OR18895/6 and C. sagani belong to the C. aurita group. We also discuss homoplasies in Ceratophryidae, divergence-time estimates, and the evolution of ploidy and a dorsal shield in the family. [ABSTRACT FROM AUTHOR]

The Santa Cruz Formation (lower Miocene) has one of the richest fossil assemblages in South America (Vizcaíno et al., [38]). Sedimentology and fossil vertebrates of the Santa Cruz Formation (early Miocene) in Lago Posadas, southwestern Patagonia, Argentina. A, Location map of the fossil locality (star), in southern Santa Cruz province, Patagonia, Argentina (modified from Degrange et al., [14]). [Extracted from the article]

We have considered viruses and their contribution to breast cancer. Mouse mammary tumour virus: The prevalence of mouse mammary tumour virus (MMTV) is 15-fold higher in human breast cancer than in normal and benign human breast tissue controls. Saliva is the most plausible means of transmission. MMTV has been identified in dogs, cats, monkeys, mice and rats. The causal mechanisms include insertional oncogenesis and mutations in the protective enzyme ABOBEC3B. Human papilloma virus: The prevalence of high risk human papilloma viruses (HPV) is frequently six fold higher in breast cancer than in normal and benign breast tissue controls. Women who develop HPV associated cervical cancer are at higher than normal risk of developing HPV associated breast cancer. Koilocytes have been identified in breast cancers which is an indication of HPV oncogenicity. The causal mechanisms of HPVs in breast cancer appear to differ from cervical cancer. Sexual activity is the most common form of HPV transmission. HPVs are probably transmitted from the cervix to the breast by circulating extra cellular vesicles. Epstein Barr virus: The prevalence of Epstein Barr virus (EBV) is five fold higher in breast cancer than in normal and benign breast tissue controls. EBV is mostly transmitted from person to person via saliva. EBV infection predisposes breast epithelial cells to malignant transformation through activation of HER2/HER3 signalling cascades. EBV EBNA genes contribute to tumour growth and metastasis and have the ability to affect the mesenchymal transition of cells. Bovine leukemia virus: Bovine leukemia virus (BLV) infects beef and dairy cattle and leads to various cancers. The prevalence of BLV is double in human breast cancers compared to controls. Breast cancer is more prevalent in red meat eating and cow's milk consuming populations. BLV may be transmitted to humans from cattle by the consumption of red meat and cow's milk. Conclusion: The evidence that MMTV, high risk HPVs and EBVs have causal roles in human breast cancer is compelling. The evidence with respect to BLV is more limited but it is likely to also have a causal role in human breast cancer. [ABSTRACT FROM AUTHOR]

Accumulating evidences indicate that transforming acidic coiled-coil 3 (TACC3) is a tumor-related gene, was highly expressed in a variety of human cancers, which is involved in cancer development. However, the potential role of TACC3 in breast cancer remains largely unknown. In the present study, we found that TACC3 was highly-expressed in breast cancer tissues, and its level was positively correlated with the clinical features of breast cancer patients. Specifically, TACC3 expression was significantly associated with the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status, nodal status, the scarff-bloom-richardson (SBR) grade, nottingham prognostic index (NPI), age, subtypes, and triple-negative and basal-like status, suggesting that TACC3 may be a potential diagnostic indicator of breast cancer. Furthermore, functional studies have shown that inhibition of TACC3 can significantly promote the cell proliferation and viability of breast cancer cells. Moreover, TACC3 knockdown suppressed the expression of E-cadherin, but increased the expression of N-cadherin, Snail, ZEB1, and TWIST, which indicate that TACC3 may impact the migration of breast cancer cells in vitro. Taken together, these findings indicate that TACC3 may serve as a prognostic and therapeutic indicator of breast cancer. [ABSTRACT FROM AUTHOR]

Introduction: This study aims at exploring the expression and significance of recombination signal-binding protein for immunoglobulin kappa J region (RBP-Jκ) and C-X-C motif chemokine 11 (CXCL11) in human colon cancer tissues. Methods: The RBP-Jκ and CXCL11 expression levels were assessed by immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) in patients with colon cancer, and their prognostic significance was evaluated. Results: Through analyzing 342 samples of colon cancer patients treated at our institution, increased expression of RBP-Jκ and CXCL11 was found in human colon cancer specimens compared with matched paratumorous normal specimens (P< 0.001). A positive correlation was found between RBP-Jκ expression and CXCL11 expression (P< 0.001). High RBP-Jκ expression was significantly associated with poorly differentiated tumors (P=0.005), invasion beyond propria muscularis (P=0.025), lymph node metastases (P=0.005), distant metastasis (P< 0.001), advanced tumor-node-metastasis (TNM) stage (P=0.004), and a shorter overall survival (P< 0.001). An increase in CXCL11 protein expression was associated with poorly differentiated tumors (P=0.015), invasion beyond propria muscularis (P=0.029), lymph node metastases (P=0.031), distant metastasis (P=0.045), advanced TNM stage (P=0.026), and a shorter overall survival of patients (P< 0.001). In multivariate Cox regression analysis, RBP-Jκ protein expression (P=0.036), CXCL11 protein expression (P=0.001), differentiation (P< 0.001), depth of invasion (P=0.009), distant metastasis (P< 0.001), and TNM stage (P< 0.001) were independent prognostic indicators of colon cancer. Conclusion: High expression of RBP-Jκ is closely associated with high CXCL11 expression, which represents a risk factor for the poor overall survival of colon cancer patients. [ABSTRACT FROM AUTHOR]

The Miocene epoch (23.03–5.33 Ma) was a time interval of global warmth, relative to today. Continental configurations and mountain topography transitioned toward modern conditions, and many flora and fauna evolved into the same taxa that exist today. Miocene climate was dynamic: long periods of early and late glaciation bracketed a ∼2 Myr greenhouse interval—the Miocene Climatic Optimum (MCO). Floras, faunas, ice sheets, precipitation, pCO2, and ocean and atmospheric circulation mostly (but not ubiquitously) covaried with these large changes in climate. With higher temperatures and moderately higher pCO2 (∼400–600 ppm), the MCO has been suggested as a particularly appropriate analog for future climate scenarios, and for assessing the predictive accuracy of numerical climate models—the same models that are used to simulate future climate. Yet, Miocene conditions have proved difficult to reconcile with models. This implies either missing positive feedbacks in the models, a lack of knowledge of past climate forcings, or the need for re‐interpretation of proxies, which might mitigate the model‐data discrepancy. Our understanding of Miocene climatic, biogeochemical, and oceanic changes on broad spatial and temporal scales is still developing. New records documenting the physical, chemical, and biotic aspects of the Earth system are emerging, and together provide a more comprehensive understanding of this important time interval. Here, we review the state‐of‐the‐art in Miocene climate, ocean circulation, biogeochemical cycling, ice sheet dynamics, and biotic adaptation research as inferred through proxy observations and modeling studies. Plain Language Summary: During the Miocene time period (∼23–5 million years ago), Planet Earth looked similar to today, with some important differences: the climate was generally warmer and highly variable, while atmospheric CO2 was not much higher. Continental‐sized ice sheets were only present on Antarctica, but not in the northern hemisphere. The continents drifted to near their modern‐day positions, and plants and animals evolved into the many (near) modern species. Scientists study the Miocene because present‐day and projected future CO2 levels are in the same range as those reconstructed for the Miocene. Therefore, if we can understand climate changes and their biotic responses from the Miocene past, we are able to better predict current and future global changes. By comparing Miocene climate reconstructions from fossil and chemical data to climate simulations produced by computer models, scientists are able to test their understanding of the Earth system under higher CO2 and warmer conditions than those of today. This helps in constraining future warming scenarios for the coming decades. In this study, we summarize the current understanding of the Miocene world from data and models. We also identify gaps in our understanding that need further research attention in the future. Key Points: Miocene floras, faunas, and paleogeography were similar to today and provide plausible analogs for future climatic warmingThe Miocene saw great dynamism in biotic and climate systems, but the reasons for these shifts are still not well understoodThe pCO2‐temperature‐ice relationships during major Miocene climate oscillations and transitions warrant further research [ABSTRACT FROM AUTHOR]

Copyright of Intersecciones en Antropología is the property of Universidad Nacional del Centro de la Provincia de Buenos Aires, Facultad de Ciencias Sociales and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Understanding species distributions and the variation of assemblage structure in time and space are fundamental goals of biogeography and ecology. Here, we use an ecological niche modeling and macroecological approach in order to assess whether constraints patterns in carnivoran richness and composition structures in replicated assemblages through time and space should reflect environmental filtering through ecological niche constraints from the Last Inter-glacial (LIG), Last Glacial Maximum (LGM) to the present (C) time. Our results suggest a diverse distribution of carnivoran co-occurrence patterns at the continental scale as a result of spatial climatic variation as an important driver constrained by the ecological niches of the species. This influence was an important factor restructuring assemblages (more directly on richness than composition patterns) not only at the continental level, but also from regional and local scales and this influence was geographically different throughout the space in the continent. These climatic restrictions and disruption of the niche during the environmental changes at the LIG-LGM-C transition show a considerable shift in assemblage richness and composition across the Americas, which suggests an environmental filtering mainly during the LGM, explaining between 30 and 75% of these variations through space and time, with more accentuated changes in North than South America. LGM was likely to be critical in species functional adaptation and distribution and therefore on assemblage structuring and rearranging from continental to local scales through time in the continent. Still, extinction processes are the result of many interacting factors, where climate is just one part of the picture. [ABSTRACT FROM AUTHOR]

Background: Tumor models are critical for our understanding of cancer and the development of cancer therapeutics. The 4T1 murine mammary cancer cell line is one of the most widely used breast cancer models. Here, we present an integrated map of the genome, transcriptome, and immunome of 4T1. Results: We found Trp53 (Tp53) and Pik3g to be mutated. Other frequently mutated genes in breast cancer, including Brca1 and Brca2, are not mutated. For cancer related genes, Nav3, Cenpf, Muc5Ac, Mpp7, Gas1, MageD2, Dusp1, Ros, Polr2a, Rragd, Ros1, and Hoxa9 are mutated. Markers for cell proliferation like Top2a, Birc5, and Mki67 are highly expressed, so are markers for metastasis like Msln, Ect2, and Plk1, which are known to be overexpressed in triple-negative breast cancer (TNBC). TNBC markers are, compared to a mammary gland control sample, lower (Esr1), comparably low (Erbb2), or not expressed at all (Pgr). We also found testis cancer antigen Pbk as well as colon/gastrointestinal cancer antigens Gpa33 and Epcam to be highly expressed. Major histocompatibility complex (MHC) class I is expressed, while MHC class II is not. We identified 505 single nucleotide variations (SNVs) and 20 insertions and deletions (indels). Neoantigens derived from 22 SNVs and one deletion elicited CD8+ or CD4+ T cell responses in IFNγ-ELISpot assays. Twelve high-confidence fusion genes were observed. We did not observe significant downregulation of mismatch repair (MMR) genes or SNVs/indels impairing their function, providing evidence for 6-thioguanine resistance. Effects of the integration of the murine mammary tumor virus were observed at the genome and transcriptome level. Conclusions: 4T1 cells share substantial molecular features with human TNBC. As 4T1 is a common model for metastatic tumors, our data supports the rational design of mode-of-action studies for pre-clinical evaluation of targeted immunotherapies. [ABSTRACT FROM AUTHOR]

Vermilingua is a peculiar group of xenarthran placental mammals with well-established phylogenetic relationships based on morphological and molecular data, but until now, no combined analysis of those data types. Here we perform the first total-evidence phylogenetic analysis of Vermilingua and estimate divergence times for living and fossil anteaters with a tip-dating approach, using the Fossilized Birth-Death model in a Bayesian framework. Using combined analyses, we recovered as monophyletic the two families, Cyclopedidae and Myrmecophagidae, as in previous studies, although our revised morphological data alone do not support the monophyly of Cyclopedidae. We show how the combination of molecular and morphological data indirectly affects the position and support for fossil taxa even though molecular datasets do not contain direct information for them. The estimated divergence times of Palaeomyrmidon and Protamandua are much older than the ages of those fossils, reinforcing the scarcity of the vermilinguan fossil record. In addition, we obtained evidence that the extinct Neotamandua is an ancestor of the extant Myrmecophaga, not a sister taxon as in previous studies, that did not incorporate the possibility of anagenetic evolution between fossil and living taxa. [ABSTRACT FROM AUTHOR]

Tamandua mexicana is a mammal of the superorder Xenarthra geographically located between Mexico and Peru that remains insufficiently studied. These species are characterized by their movement, resting, and eating of termites and ants in arboreal and terrestrial environments, and therefore, their thoracic limbs have been adapted morphologically to move in these environments. Tamandua mexicana is a species constantly threatened by different causes, and their thoracic limbs can be affected in the scapular and shoulder regions as a result; therefore, specific anatomical knowledge of the scapula allows for better clinical procedures, surgical approaches, radiological diagnosis and muscular reconstructions in extinct species of anteaters. The main objective of this study was to report the anatomical and radiographic features of the scapula in juvenile and adult specimens of T. mexicana. Gross dissections and radiographic study were performed in six cadavers. The scapula had large differences compared with other mammals, such as two spines, a foramen for the suprascapular nerve, a long acromion, a cranial transverse scapular ligament and caudolateral fossa for the origin of the muscles teres major, tensor fasciae antebrachii and subscapular. In juvenile specimens, a scapular cartilage, an acromial cartilage, craniomedial and caudolateral coracoscapular ligaments forming the foramen for the suprascapular nerve, and progressive ossification of those ligaments and the cranial transverse scapular ligament were observed. These findings were corroborated by radiography; therefore, these characteristics change with age. The bony reliefs of the scapula of T. mexicana corroborate the specialization of the shoulder in this species. [ABSTRACT FROM AUTHOR]

A coupled diffuse-photon-density and thermal-wave model is developed for theoretical analysis of the photothermal field in demineralized teeth. Intact and demineralized layers of enamel, as well as dentin, are described as a layered one-dimensional system. The solution of the radiative transport equation in the limit of diffuse-photon-density field is considered as a source term in the thermal-wave field equation. The influence of optical parameters (absorption and scattering coefficients) and thermal parameters (thermal diffusivity and conductivity) of each layer on the diffuse-photon-density and thermal-wave depth profiles is analyzed using computer simulations, allowing the verification of accuracy and validity of the developed theory. The proposed model and simulations are intended for identifying the parameters most affecting the diffuse-photon-density and thermal-wave fields in turbid media, which leads to optimization of the fitting process of thermal and optical properties of teeth from experimental data obtained by frequency-domain photothermal radiometry. [ABSTRACT FROM AUTHOR]

We present an optical technique, point radiance spectroscopy, to directly recover chromophore concentrations and the reduced optical scattering coefficient spectrum from continuous wave interstitial point radiance measurements at a single-source-detector separation in turbid, tissuelike media. The method employs a spectral algorithm to fit the relative radiance data, using the P3 approximation, at only two detection angles (0° and 90°). The spectral fitting algorithm is applied to simulated data of relative point fluence and relative point radiance data with added 1% noise and shows that even under realistic experimental conditions, only point radiance information is able to provide quantitative information regarding chromophore concentrations and scattering power at distances greater than two to three mean free paths from the source. Furthermore, experimental measurements in tissue-simulating phantoms demonstrate that dye concentrations and scattering parameters can be recovered to within ¿10%. The developed point radiance technique bridges a technological gap between local surface reflectance and spatially resolved interstitial fluence methods in optical assessment of random media such as biological tissue. [ABSTRACT FROM AUTHOR]

Background: Subterranean mammals show a suite of musculoskeletal adaptations that enables efficient digging. However, little is known about their development. We assessed ontogenetic changes in functionally relevant skeletal traits, and ossification patterns (periosteal and endochondral bone modules) in a truly subterranean scratch‐digging rodent, Bathyergus. We studied 52 individuals (202 long bones) from a wild population by using a multiscale approach involving internal and external morphology. Results: Multivariate analysis showed significant morphological changes during ontogeny. A specialized phenotype is expressed perinatally (eg, greater external robustness and developed olecranon, teres major, and deltoid processes), whereas adults presented slender bones with significantly thicker cross‐sections. Ossification modules scaled mostly isometrically with body size parameters. Periosteal modules showed high variability and tended to grow faster than endochondral modules. Conclusions: Scratch‐digging adaptations appear at perinatal age and then specialize in subadults. Early development of agonistic and digging behaviors and onset of sexual maturation seems to contribute to its development, although genetic factors also seem to play an important role. Ontogenetic differences are probably a trade‐off to counteract weaker cortical bone properties and poor muscle development in juveniles, whereas slender but thicker cortical bones maximize bone resistance during burrow construction without compromising locomotor performance in adults. Key Findings: Marked phenotypic differences were found in the appendicular system of a solitary subterranean mammal during ontogeny.Inclusion of a multiscale approach allowed the identification of a novel morphological shift in bone design during ontogeny.Integration of developmental modules and allometric analysis provided valuable insights on the mechanisms underlying the generation of highly specialized phenotypes. [ABSTRACT FROM AUTHOR]

Copyright of Swiss Journal of Paleontology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We provide morphological, quantitative, and qualitative studies of cranial endocasts of mesotheriid notoungulates solving previous open debate on notoungulate endocasts. For that purpose, we use the most accurate digital reconstructions methods. We confirm that mesotheriids have endocasts similar in shape and gyrification to those of other rodent-like notoungulates (i.e., Hegetotheriidae and Interatheriidae) and living cavy rodents (e.g., Dolicavia minuscula, Hydrochoerus, and Cavia). We identify these similarities as evolutionary response to potentially similar ecological constraints. Based on the encephalization quotient (EQ) of several notoungulate families (i.e., Mesotheriidae, Interatheriidae, Notohippidae, Toxodontiidae, and Hegetotheriidae), there seems to be no increase in terms of EQ or neocortical complexity through time in that group. In addition, comparison with several Holarctic 'euungulates' leads us to propose differential predation pressure as a potential driver for EQ. Among notoungulates, braincase comparison between well-known Oligocene-Pleistocene mesotheriids and other families identifies lifestyle as an additional possible driver for EQ, with lower values for semifossorial taxa, in a similar way to rodents. Finally, the observed stability of mesotheriid EQ (from the Oligocene to the Pliocene) would match a conservative lifestyle further reflected by their highly invariant appendicular skeleton. [ABSTRACT FROM AUTHOR]

Here we describe two new megalonychid sloths from the late Miocene of the Urumaco Formation (Falcón State, Venezuela), Urumacocnus urbanii gen. et. sp. nov. and Pattersonocnus diazgameroi gen. et sp. nov. The recovery of these distinct taxa greatly improves our understanding of sloth diversity in the late Miocene of northern South America. A phylogenetic analysis based on the combination of cranial and postcranial elements (particularly the femur) partially supports previous interpretations of the relationships of genera within the Megalonychidae, but also suggests the existence of a more complex set of subclades within the family in South America, North America and the Antilles. http://zoobank.org/urn:lsid:zoobank.org:pub:594532F8-9E25-4282-B1AD-9FC5484DFD91 [ABSTRACT FROM AUTHOR]

Species distribution models (SDMs) are helpful for understanding actual and potential biogeographical traits of organisms. These models have recently started to be applied in the study of fossil xenarthrans. SDMs were generated for 15 South American late Pleistocene xenarthrans: eight Cingulata (Glyptodon clavipes, Doedicurus clavicaudatus, Panochthus tuberculatus, Neosclerocalyptus paskoensis, Pampatherium typum, Pampatherium humboldtii, Holmesina paulacoutoi, and Holmesina occidentalis) and seven Folivora (Glossotherium robustum, Lestodon armatus, Mylodon darwinii, Catonyx cuvieri, Catonyx (=Scelidodon) chilensis, Megatherium americanum, and Eremotherium laurillardi). Models were evaluated for three periods: the last interglacial (LIG), the last glacial maximum (LGM), and the Holocene climatic optimum (HCO). Co-occurrence records were studied based on the overlap of the potential distributions and compared with the available biome reconstructions of South America during the LGM to analyze species distribution patterns, ecological requirements, and possible interactions. Our results suggest the existence of provincialization within xenarthran megamammals grouped in at least three bioregions. Northern and southwestern taxa overlap in the Río de la Plata region where also some endemic taxa are found. We observed overlapping potential distributions but separated and continuous realized distributions between closely related xenarthrans suggesting competitive exclusion. A generalized reduction in potential habitats at the end of the Pleistocene was not obvious as some taxa show stable potential areas during HCO when comparing with LGM. Nonetheless, fragmentation of the most suitable areas due to climate variation and the impact of reduction in available land due to sea level changes cannot be ruled out as involved in the extinction. [ABSTRACT FROM AUTHOR]