3D enamel thickness in Neandertal and modern human permanent canines

Enamel thickness figures prominently in studies of human evolution, particularly for taxonomy, phylogeny, and paleodietary reconstruction. Attention has focused on molar teeth, through the use of advanced imaging technologies and novel protocols. Despite the important results achieved thus far, further work is needed to investigate all tooth classes. We apply a recent approach developed for anterior teeth to investigate the 3D enamel thickness of Neandertal and modern human (MH) canines. In terms of crown size, the values obtained for both upper and lower unworn/slightly worn canines are significantly greater in Neandertals than in Upper Paleolithic and recent MH. The 3D relative enamel thickness (RET) is significantly lower in Neandertals than in MH. Moreover, differences in 3D RET values between the two groups appear to decrease in worn canines beginning from wear stage 3, suggesting that both the pattern and the stage of wear may have important effects on the 3D RET value. Nevertheless, the 3D average enamel thickness (AET) does not differ between the two groups. In both groups, 3D AET and 3D RET indices are greater in upper canines than in lower canines, and overall the enamel is thicker on the occlusal half of the labial aspect of the crown, particularly in MH. By contrast, the few early modern humans investigated show the highest volumes of enamel while for all other components of 3D enamel, thickness this group holds an intermediate position between Neandertals and recent MH. Overall, our study supports the general findings that Neandertals have relatively thinner enamel than MH (as also observed in molars), indicating that unworn/slightly worn canines can be successfully used to discriminate between the two groups. Further studies, however, are needed to understand whether these differences are functionally related or are the result of pleiotropic or genetic drift effects

Counseling Update: A Flexible Monitoring Method for the Client and Practitioner

Recent years have seen a number of articles questioning both the utility and practicality of single-case designs. The authors propose a flexible monitoring method for practice evaluation. The proposed method is presented as a dynamic model, one that utilizes the existing evaluative procedures of the practitioner. This flexible method is proposed within the general outlines of developmental research. It is proposed as a method designed to lead practitioners toward an empirical model of practice. Some case examples are provided to substantiate the utility and value of the model.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68429/2/10.1177_104973159300300203.pd

The lncRNA HOTAIR transcription is controlled by HNF4α-induced chromatin topology modulation

The expression of the long noncoding RNA HOTAIR (HOX Transcript Antisense Intergenic RNA) is largely deregulated in epithelial cancers and positively correlates with poor prognosis and progression of hepatocellular carcinoma and gastrointestinal cancers. Furthermore, functional studies revealed a pivotal role for HOTAIR in the epithelial-to-mesenchymal transition, as this RNA is causal for the repressive activity of the master factor SNAIL on epithelial genes. Despite the proven oncogenic role of HOTAIR, its transcriptional regulation is still poorly understood. Here hepatocyte nuclear factor 4-α (HNF4α), as inducer of epithelial differentiation, was demonstrated to directly repress HOTAIR transcription in the mesenchymal-to epithelial transition. Mechanistically, HNF4α was found to cause the release of a chromatin loop on HOTAIR regulatory elements thus exerting an enhancer-blocking activity

Exploring the DNA2-PNA heterotriplex formation in targeting the Bcl-2 gene promoter: A structural insight by physico-chemical and microsecond-scale MD investigation

Peptide Nucleic Acids (PNAs) represent a promising tool for gene modulation in anticancer treatment. The uncharged peptidyl backbone and the resistance to chemical and enzymatic degradation make PNAs highly advantageous to form stable hybrid complexes with complementary DNA and RNA strands, providing higher stability than the corresponding natural analogues. Our and other groups’ research has successfully shown that tailored PNA sequences can effectively downregulate the expression of human oncogenes using antigene, antisense, or anti-miRNA approaches. Specifically, we identified a seven bases-long PNA sequence, complementary to the longer loop of the main G-quadruplex structure formed by the bcl2midG4 promoter sequence, capable of downregulating the expression of the antiapoptotic Bcl-2 protein and enhancing the anticancer activity of an oncolytic adenovirus. Here, we extended the length of the PNA probe with the aim of including the double-stranded Bcl-2 promoter among the targets of the PNA probe. Our investigation primarily focused on the structural aspects of the resulting DNA2-PNA heterotriplex that were determined by employing conventional and accelerated microsecond-scale molecular dynamics simulations and chemical-physical analysis. Additionally, we conducted preliminary biological experiments using cytotoxicity assays on human A549 and MDA-MB-436 adenocarcinoma cell lines, employing the oncolytic adenovirus delivery strategy

The Snail repressor recruits EZH2 to specific genomic sites through the enrollment of the lncRNA HOTAIR in epithelial-to-mesenchymal transition

The transcription factor Snail is a master regulator of cellular identity and epithelial-to-mesenchymal transition (EMT) directly repressing a broad repertoire of epithelial genes. How chromatin modifiers instrumental to its activity are recruited to Snail-specific binding sites is unclear. Here we report that the long non-coding RNA (lncRNA) HOTAIR (for HOX Transcript Antisense Intergenic RNA) mediates a physical interaction between Snail and enhancer of zeste homolog 2 (EZH2), an enzymatic subunit of the polycomb-repressive complex 2 and the main writer of chromatin-repressive marks. The Snail-repressive activity, here monitored on genes with a pivotal function in epithelial and hepatic morphogenesis, differentiation and cell-type identity, depends on the formation of a tripartite Snail/HOTAIR/EZH2 complex. These results demonstrate an lncRNA-mediated mechanism by which a transcriptional factor conveys a general chromatin modifier to specific genes, thereby allowing the execution of hepatocyte transdifferentiation; moreover, they highlight HOTAIR as a crucial player in the Snail-mediated EMT.Oncogene advance online publication, 25 July 2016; doi:10.1038/onc.2016.260

Primary cerebral alveolar rhabdomyosarcoma in adult

Primary cerebral rhabdomyosarcomas are very rare and malignant tumors that occur predominantly in the posterior fossa of pediatric patients. We report a rare case of primary cerebral rhabdomyosarcoma located in the supratentorial compartment of a 51 year-old woman together with a review of the pertinent Literature especially regarding the histological diagnosis and pitfalls

2021 Update of the International Council for Standardization in Haematology Recommendations for Laboratory Measurement of Direct Oral Anticoagulants

International audienceIn 2018, the International Council for Standardization in Haematology (ICSH) published a consensus document providing guidance for laboratories on measuring direct oral anticoagulants (DOACs). Since that publication, several significant changes related to DOACs have occurred, including the approval of a new DOAC by the Food and Drug Administration, betrixaban, and a specific DOAC reversal agent intended for use when the reversal of anticoagulation with apixaban or rivaroxaban is needed due to life-threatening or uncontrolled bleeding, andexanet alfa. In addition, this ICSH Working Party recognized areas where additional information was warranted, including patient population considerations and updates in point-of-care testing. The information in this manuscript supplements our previous ICSH DOAC laboratory guidance document. The recommendations provided are based on (1) information from peer-reviewed publications about laboratory measurement of DOACs, (2) contributing author's personal experience/expert opinion and (3) good laboratory practice

XQR-30: the ultimate XSHOOTER quasar sample at the reionization epoch

The final phase of the reionization process can be probed by rest-frame UV absorption spectra of quasars at z>6, shedding light on the properties of the diffuse intergalactic medium within the first Gyr of the Universe. The ESO Large Programme "XQR-30: the ultimate XSHOOTER legacy survey of quasars at z~5.8-6.6" dedicated ~250 hours of observations at the VLT to create a homogeneous and high-quality sample of spectra of 30 luminous quasars at z~6, covering the rest wavelength range from the Lyman limit to beyond the MgII emission. Twelve quasar spectra of similar quality from the XSHOOTER archive were added to form the enlarged XQR-30 sample, corresponding to a total of ~350 hours of on-source exposure time. The median effective resolving power of the 42 spectra is R~11400 and 9800 in the VIS and NIR arm, respectively. The signal-to-noise ratio per 10 km/s pixel ranges from ~11 to 114 at $\lambda \simeq 1285$ \AA rest frame, with a median value of ~29. We describe the observations, data reduction and analysis of the spectra, together with some first results based on the E-XQR-30 sample. New photometry in the H and K bands are provided for the XQR-30 quasars, together with composite spectra whose characteristics reflect the large absolute magnitudes of the sample. The composite and the reduced spectra are released to the community through a public repository, and will enable a range of studies addressing outstanding questions regarding the first Gyr of the Universe.Comment: 21 pages, 10 figures. Revised version resubmitted to MNRAS after minor referee repor

XQR-30: The ultimate XSHOOTER quasar sample at the reionization epoch

The final phase of the reionization process can be probed by rest-frame UV absorption spectra of quasars at z ≳ 6, shedding light on the properties of the diffuse intergalactic medium within the first Gyr of the Universe. The ESO Large Programme 'XQR-30: the ultimate XSHOOTER legacy survey of quasars at z ≃ 5.8-6.6' dedicated ∼250 h of observations at the VLT to create a homogeneous and high-quality sample of spectra of 30 luminous quasars at z ∼6, covering the rest wavelength range from the Lyman limit to beyond the Mg ii emission. Twelve quasar spectra of similar quality from the XSHOOTER archive were added to form the enlarged XQR-30 sample, corresponding to a total of ∼350 h of on-source exposure time. The median effective resolving power of the 42 spectra is R ≃ 11 400 and 9800 in the VIS and NIR arm, respectively. The signal-to-noise ratio per 10 km s-1 pixel ranges from ∼11 to 114 at λ ≃ 1285 Å rest frame, with a median value of ∼29. We describe the observations, data reduction, and analysis of the spectra, together with some first results based on the E-XQR-30 sample. New photometry in the H and K bands are provided for the XQR-30 quasars, together with composite spectra whose characteristics reflect the large absolute magnitudes of the sample. The composite and the reduced spectra are released to the community through a public repository, and will enable a range of studies addressing outstanding questions regarding the first Gyr of the Universe