Systematic review of hormonal strategies to improve fertility in rams.

Reviewing the current state of knowledge on reproductive performance and productive traits in rams has many advantages. First, the compilation of this information will serve as a literature resource for scientists conducting research around the world and will contribute to the understanding of the data collected and interpreted by researchers on the different hormonal strategies used to improve reproductive performance in rams. Second, it will allow scientists to identify current knowledge gaps and set future research priorities in ram reproduction. Rams play an important role in the global flock economy, but their reproductive analysis has been limited in the use of hormonal technologies to increase the productivity of sheep flocks. In this review, we cite the most important works on six hormones that, in one way or another, modify the hypothalamus-pituitary-gonadal axis, at different doses, in and out of the reproductive season, breeds, application methods, among other factors. The overall aim is to increase the reproductive efficiency of rams in different scenarios and, in some cases, of other species due to the lack of limited information on rams.

Artificial neural networks reconstruct missing perikymata in worn teeth.

Dental evolutionary studies in hominins are key to understanding how our ancestors and close fossil relatives grew from the early stages of embryogenesis into adults. In a sense, teeth are like an airplane's 'black box' as they record important variables for assessing developmental timing, enabling comparisons within and between populations, species, and genera. The ability to discern this type of nuanced information is embedded in the nature of how tooth enamel and dentin form: incrementally and over years. This incremental growth leaves chronological indicators in the histological structure of enamel, visible on the crown surface as perikymata. These structures are used in the process of reconstructing the rate and timing of tooth formation. Unfortunately, the developmentally earliest growth lines in lateral enamel are quickly lost to wear once the tooth crown erupts. We developed a method to reconstruct these earliest, missing perilymata from worn teeth through knowledge of the later-developed, visible perikymata for all tooth types (incisors, canines, premolars, and molars) using a modern human dataset. Building on our previous research using polynomial regressions, here we describe an artificial neural networks (ANN) method. This new ANN method mostly predicts within 2 counts the number of perikymata present in each of the first three deciles of the crown height for all tooth types. Our ANN method for estimating perikymata lost through wear has two immediate benefits: more accurate values can be produced and worn teeth can be included in dental research. This tool is available on the open-source platform R within the package teethR released under GPL v3.0 license, enabling other researchers the opportunity to expand their datasets for studies of periodicity in histological growth, dental development, and evolution.

Tumor mutational load is prognostic for progression to therapy among high-count monoclonal B-cell lymphocytosis.

ABSTRACT: High-count monoclonal B-cell lymphocytosis (HCMBL) is a precursor condition to chronic lymphocytic leukemia (CLL). We have shown that among individuals with HCMBL, the CLL-International Prognostic Index (CLL-IPI) is prognostic for time-to-first therapy (TTFT). Little is known about the prognostic impact of somatically mutated genes among individuals with HCMBL. We sequenced DNA from 371 individuals with HCMBL using a targeted sequencing panel of 59 recurrently mutated genes in CLL to identify high-impact mutations. We compared the sequencing results with that of our treatment-naïve CLL cohort (N = 855) and used Cox regression to estimate hazard ratios and 95% confidence intervals (CIs) for associations with TTFT. The frequencies of any mutated genes were lower in HCMBL (52%) than CLL (70%). At 10 years, 37% of individuals with HCMBL with any mutated gene had progressed requiring treatment compared with 10% among individuals with HCMBL with no mutations; this led to 5.4-fold shorter TTFT (95% CI, 2.6-11.0) among HCMBL with any mutated gene vs none, independent of CLL-IPI. When considering individuals with low risk of progression according to CLL-IPI, those with HCMBL with any mutations had 4.3-fold shorter TTFT (95% CI, 1.6-11.8) vs those with none. Finally, when considering both CLL-IPI and any mutated gene status, we observed individuals with HCMBL who were high risk for both prognostic factors had worse prognosis than patients with low-risk CLL (ie, 5-year progression rate of 32% vs 21%, respectively). Among HCMBL, the frequency of somatically mutated genes at diagnosis is lower than that of CLL. Accounting for both the number of mutated genes and CLL-IPI can identify individuals with HCMBL with more aggressive clinical course.

Sexual dimorphism in the enamel-dentine junction (EDJ) of permanent canines of European modern humans.

OBJECTIVES: Dental anthropological investigations into sexual dimorphism have conventionally concentrated on evaluating the dimensions and configuration of the enamel cap of canines. However, the morphology of the crown dentine surface can be closely linked to that of the enamel surface. This link can facilitate examination of crown morphology even when the enamel surface is slightly worn. Here, we determine if the morphology of the enamel-dentine junction (EDJ) differs within (maxillary vs. mandibular) and between a sample of male (n = 26) and female (n = 21) contemporary human permanent canines from Europe. METHODS: The morphological data of the EDJ were gathered employing a template comprising 96 landmarks and sliding semilandmarks. Subsequently, the data underwent analysis through form space principal component analysis following Procrustes registration, utilizing standard 3D geometric morphometric techniques. RESULTS: Significant differences in the morphology of the EDJ were observed between the sexes, particularly concerning the overall shape of the crown, the symmetry of the mesial and distal edges, and the development of the distal accessory ridge. CONCLUSIONS: Sex differences in the morphology of the EDJ could relate in part to retention of the canine-premolar honing complex in males. Our results indicate that analyses of the permanent canine EDJ may potentially provide a novel method for estimating the sex of adult and nonadult skeletons.

Third National Registry of Cardiac Rehabilitation Programs in Mexico (RENAPREC III-2022) / Tercer Registro Nacional de Programas de Rehabilitación Cardiaca en México (RENAPREC III-2022)

Abstract Introduction: In Mexico, cardiac rehabilitation (CR) as an interdisciplinary intervention with therapeutic impact in patients with heart disease is growing. There is the need to know actual conditions of CR in our country. Objectives: The objective of this National Registry is to follow-up those existing and new CR units in Mexico through the comparison between the two previous registries, RENAPREC-2009 and RENAPREC II-2015 studies. This is a descriptive study focused on diverse CR activities such as assistance training, and certification of health professionals, barriers, reference, population attended, interdisciplinarity, permanence over time, growth prospects, regulations, post-pandemic condition, integrative characteristics, and scientific research. Results: Data were collected from 45 CR centers in the 32 states, 75.5% are private practice units, 67% are new, 33% were part of RENAPREC II-2015, and 17 have continued since 2009. With a better distribution of CR units along the territory, the median reference of candidates for CR programs is 9% with a significant reduction into tiempo of enrollment to Phase II admission (19 ± 11 days). Regarding to previous registries, the coverance of Phases I, II, and III is 71%, 100%, and 93%, respectively; and a coverance increases in evaluation, risk stratification, and prescription, more comprehensive attendance and prevention strategies. Conclusions: CR in Mexico has grown in the past 7 years. Even there is still low reference and heterogeneity in specific processes, there are strengths such as interdisciplinarity, scientific professionalization of specialists, national diversification, and an official society that are consolidated over time.

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Intensity-Dependent Optical Response of 2D LTMDs Suspensions: From Thermal to Electronic Nonlinearities.

The nonlinear optical (NLO) response of photonic materials plays an important role in the understanding of light-matter interaction as well as pointing out a diversity of photonic and optoelectronic applications. Among the recently studied materials, 2D-LTMDs (bi-dimensional layered transition metal dichalcogenides) have appeared as a beyond-graphene nanomaterial with semiconducting and metallic optical properties. In this article, we review most of our work in studies of the NLO response of a series of 2D-LTMDs nanomaterials in suspension, using six different NLO techniques, namely hyper Rayleigh scattering, Z-scan, photoacoustic Z-scan, optical Kerr gate, and spatial self-phase modulation, besides the Fourier transform nonlinear optics technique, to infer the nonlinear optical response of semiconducting MoS2, MoSe2, MoTe2, WS2, semimetallic WTe2, ZrTe2, and metallic NbS2 and NbSe2. The nonlinear optical response from a thermal to non-thermal origin was studied, and the nonlinear refraction index and nonlinear absorption coefficient, where present, were measured. Theoretical support was given to explain the origin of the nonlinear responses, which is very dependent on the spectro-temporal regime of the optical source employed in the studies.

[Third National Registry of Cardiac Rehabilitation Programs in Mexico (RENAPREC III-2022)]. / Tercer Registro Nacional de Programas de Rehabilitación Cardiaca en México (RENAPREC III-2022).

Introduction: In Mexico, cardiac rehabilitation (CR) as an interdisciplinary intervention with therapeutic impact in patients with heart disease is growing. There is the need to know actual conditions of CR in our country. Objectives: The objective of this National Registry is to follow-up those existing and new CR units in Mexico through the comparison between the two previous registries, RENAPREC-2009 and RENAPREC II-2015 studies. This is a descriptive study focused on diverse CR activities such as assistance training, and certification of health professionals, barriers, reference, population attended, interdisciplinarity, permanence over time, growth prospects, regulations, post-pandemic condition, integrative characteristics, and scientific research. Results: Data were collected from 45 CR centers in the 32 states, 75.5% are private practice units, 67% are new, 33% were part of RENAPREC II-2015, and 17 have continued since 2009. With a better distribution of CR units along the territory, the median reference of candidates for CR programs is 9% with a significant reduction into tiempo of enrollment to Phase II admission (19 ± 11 days). Regarding to previous registries, the coverance of Phases I, II, and III is 71%, 100%, and 93%, respectively; and a coverance increases in evaluation, risk stratification, and prescription, more comprehensive attendance and prevention strategies. Conclusions: CR in Mexico has grown in the past 7 years. Even there is still low reference and heterogeneity in specific processes, there are strengths such as interdisciplinarity, scientific professionalization of specialists, national diversification, and an official society that are consolidated over time.

Introducción: En México, la Rehabilitación Cardíaca (RC) como intervención interdisciplinaria con impacto terapéutico en paciente con cardiopatía está en crecimiento. Existe la necesidad de conocer las condiciones actuales de la RC en nuestro país. Objetivo: El objetivo de este Registro es dar seguimiento comparativo de las unidades nuevas y existentes entre los registros anteriores, RENAPREC-2009 y RENAPREC II-2015. Se trata de un estudio descriptivo centrado en diversas actividades de la RC: formación asistencial y certificación de sus profesionales, barreras, referencia, población atendida, interdisciplinariedad, permanencia en el tiempo, perspectivas de crecimiento, normativa, condición pospandemia, características integradoras e investigación. Resultados: Se recolectaron datos de 45 centros en los 32 estados, 67% son nuevos 75.5% son de práctica privada, 33% fueron parte de RENAPREC II-2015 y 17 desde 2009. Con una mejor distribución de las unidades de RC a lo largo del territorio, la mediana de referencia de pacientes candidatos a RC es ahora del 9% con reducción significativa del tiempo de admisión a Fase II (19 ± 11 días). Respecto a registros anteriores las coberturas de las Fases I, II y III son del 71%, 100% y 93%, respectivamente; con un aumento de la cobertura en evaluación, estratificación de riesgo y prescripción, atención más integral y estrategias de prevención. Conclusiones: La RC en México ha crecido en los últimos 7 años. Si bien aún existe baja referencia y heterogeneidad en procesos específicos, existen fortalezas como la interdisciplinariedad, la profesionalización científica de los especialistas, la diversificación nacional y una sociedad oficial que se consolida en el tiempo.

Near-infrared ultrafast third-order nonlinear optical response of 2D NbS2, NbSe2, ZrTe2, and MoS2.

By employing the optical Kerr gate technique at 800 nm with 180 fs pulses at 76 MHz, we evaluated the third-order nonlinear optical response of two-dimensional (2D) semiconducting MoS2, semimetallic ZrTe2, and metallic NbS2 and NbSe2. The modulus of the nonlinear refractive index was measured to range from 8.6 × 10-19 m2/W to 5.3 × 10-18 m2/W, with all materials' response time limited by the pulse duration. The physical mechanism to explain the ultrafast response time's origin considers the nature of the 2D material, as will be discussed.

[Time of ethics review of research proposals: results of an observational study]. / Tiempos de evaluación ética de protocolos de investigación: resultados de un estudio observacional.

The review of research protocols by Research Ethics Committees (RECs), essential to ensure the protection of participants, has been managed in the City of Buenos Aires through the PRIISA.BA electronic platform since January 2020. The aim of the present study was to describe ethical review times, their temporal evolution, and predictors of their duration. We conducted an observational study that included all the protocols reviewed between January 2020 and September 2021. Times to approval and to first observation were calculated. Temporal trends in times, and the multivariate association between these and protocol and IRB characteristics were evaluated. 2,781 protocols reviewed in 62 RECs were included. The median time to approval was 29.11 (RIQ 11.29 to 63.35) days, and time to first observation was 8.92 (RIQ 2.05 to 18.18) days. The times were significantly reduced throughout the study period. We detected as variables independently associated with shorter time to approval to be a COVID proposal, having funding and the number of centers to perform the study and having been reviewed by an RECs with more than 10 members. Making observations to the protocol was associated with more time. The results of the present work suggest that ethical review times were reduced during study period. In addition, variables associated with time were identified that could be the object of interventions to improve the process.

Tiempos de evaluación ética de protocolos de investigación: resultados de un estudio observacional / Time of ethics review of research proposals: results of an observational study

La evaluación de protocolos de investigación por Comités de Ética en Investigación (CEI), esencialpara garantizar la protección de los participantes, se gestiona en la Ciudad de Buenos Aires a través laplataforma electrónica PRIISA.BA desde enero del 2020. El objetivo del presente estudio fue describirlos tiempos de evaluación ética, su evolución temporal, y los predictores de su duración. Se realizóun estudio observacional que incluyó todos los protocolos evaluados entre enero de 2020 y septiem-bre de 2021. Se calcularon los tiempos al dictamen final y a la primera observación. Se evaluaron lastendencias temporales de los tiempos, y la asociación multivariada entre éstos y características de losprotocolos y de los CEI. Se incluyeron 2781 protocolos evaluados en 62 CEI. La mediana de tiempo aldictamen final fue de 29.11 (RIQ 11.29 a 63.35) días, y del tiempo a la primera observación de 8.92(RIQ 2.05 a 18.18) días. Los tiempos se redujeron significativamente a lo largo del período de estudio.Detectamos como variables independientemente asociadas a menor tiempo a la temática COVID, tenerfinanciamiento y el número de centros a realizarse el estudio y haber sido evaluado en un CEI con másde 10 miembros. La realización de observaciones al protocolo se asoció a mayor tiempo. Los resultadosdel presente trabajo sugieren que los tiempos de evaluación ética se redujeron durante el período deestudio. Además, se identificaron variables asociadas con los tiempos, que podrían ser objeto de inter-venciones para mejorar el proceso.(AU)

The review of research protocols by Research Ethics Committees (RECs), essential to ensure theprotection of participants, has been managed in the City of Buenos Aires through the PRIISA.BA elec-tronic platform since January 2020. The aim of the present study was to describe ethical review times,their temporal evolution, and predictors of their duration. We conducted an observational study thatincluded all the protocols reviewed between January 2020 and September 2021. Times to approvaland to first observation were calculated. Temporal trends in times, and the multivariate associationbetween these and protocol and IRB characteristics were evaluated. 2,781 protocols reviewed in 62RECs were included. The median time to approval was 29.11 (RIQ 11.29 to 63.35) days, and time to firstobservation was 8.92 (RIQ 2.05 to 18.18) days. The times were significantly reduced throughout thestudy period. We detected as variables independently associated with shorter time to approval to bea COVID proposal, having funding and the number of centers to perform the study and having beenreviewed by an RECs with more than 10 members. Making observations to the protocol was associatedwith more time. The results of the present work suggest that ethical review times were reduced duringstudy period. In addition, variables associated with time were identified that could be the object ofinterventions to improve the process.(AU)

Differential prognosis of single and multiple TP53 abnormalities in high-count MBL and untreated CLL.

TP53 aberrations, including mutations and deletion of 17p13, are important adverse prognostic markers in chronic lymphocytic leukemia (CLL) but are less studied in high count monoclonal B-cell lymphocytosis (HCMBL), an asymptomatic pre-malignant stage of CLL. Here we estimated the prevalence and impact of TP53 aberrations in 1,230 newly diagnosed treatment-naïve individuals (849 CLL, 381 HCMBL). We defined TP53 state as: wild-type (no TP53 mutations and normal 17p), single-hit (del(17p) or one TP53 mutation), or multi-hit (TP53 mutation and del(17p), TP53 mutation and loss of heterozygosity, or multiple TP53 mutations). Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for time to first treatment and overall survival by TP53 state. We found 64 (7.5%) CLL patients and 17 (4.5%) HCMBL individuals had TP53 mutations with variant allele fraction >10%. Del(17p) was present in 58 (6.8%) of CLL and 11 (2.9%) of HCMBL cases. Most individuals had wild-type (N=1,128, 91.7%) TP53 state, followed by multi-hit (N=55, 4.5%) and then single-hit (N=47, 3.8%) TP53 state. The risk of shorter time to therapy and death increased with the number of TP53 abnormalities. Compared to wild-type patients, multi-hit patients had 3-fold and single-hit patients had 1.5-fold increased risk of requiring therapy. Multi-hit patients also had 2.9-fold increased risk of death compared to wild-type. These results remained stable after accounting for other known poor prognostic factors. Both TP53 mutations and del(17p) may provide important prognostic information for HCMBL and CLL that would be missed if only one were measured.

Variability in Ethics Review for Multicenter Protocols in Buenos Aires, Argentina. An Observational Study.

It has been reported that significant variability in the ethics review process affects multisite studies. We analyzed 1,305 applications for multicenter studies (409 unique protocols), from 1st January 2020 to 20th September 2021. We examined the variability in the times to approval and the first observation and the variation in the level of risk assigned. The median [IQR] variabilities were 42.19 [15.23-82.36] days and 8.00 [3.12-16.68] days, for the times to approval and to the first observation, respectively. There was disagreement in the level of risk assigned by the Research Ethics Committee (REC) in 24.0% of cases. Independent predictors of variability included the number of REC members. In our study, we found substantial variability in the ethics review process among health research protocols. Also, we describe methods to readily measure the delays and the variations in the ethics review process.

Transcriptional profiles define drug refractory disease in myeloma.

Identifying biomarkers associated with disease progression and drug resistance are important for personalized care. We investigated the expression of 121 curated genes, related to immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) responsiveness. We analyzed 28 human multiple myeloma (MM) cell lines with known drug sensitivities and 130 primary MM patient samples collected at different disease stages, including newly diagnosed (ND), on therapy (OT), and relapsed and refractory (RR, collected within 12 months before the patients' death) timepoints. Our findings led to the identification of a subset of genes linked to clinical drug resistance, poor survival, and disease progression following combination treatment containing IMIDs and/or PIs. Finally, we built a seven-gene model (MM-IMiD and PI sensitivity-7 genes [IP-7]) using digital gene expression profiling data that significantly separates ND patients from IMiD- and PI-refractory RR patients. Using this model, we retrospectively analyzed RNA sequcencing (RNAseq) data from the Mulltiple Myeloma Research Foundation (MMRF) CoMMpass (n = 578) and Mayo Clinic MM patient registry (n = 487) to divide patients into probabilities of responder and nonresponder, which subsequently correlated with overall survival, disease stage, and number of prior treatments. Our findings suggest that this model may be useful in predicting acquired resistance to treatments containing IMiDs and/or PIs.

The protoconid: a key cusp in lower molars. Evidence from a recent modern human population.

BACKGROUND: The molar (M) size sequence in the genus Homo is decreasing and the general pattern in Homo sapiens is M1> M2 > M3. AIM: To gain a better understanding of the reduction patterns of M components (cusps), we aim to assess the area of the protoconid (Prd), the phylogenetically oldest cusp of the lower Ms. SUBJECT AND METHODS: We measured the Prd and the total crown area in the scaled photographs of a recent modern human sample of lower Ms (76 males and 39 females). The values were statistically analysed. RESULTS: The absolute size of the Prd increases significantly between M1 and M2/M3, whereas the relative size of this cusp increases significantly from M1 to M3. In the latter, reduction or disappearance of the cusps of the talonid is common. CONCLUSIONS: The results can be explained in the framework of the patterning cascade model. As the first cusp to appear developmentally, the Prd forms in response to signals from the primary enamel knot, likely contributing to its stability. Inhibitory signals emitted during the Prd formation may lead to the reduction or disappearance of the talonid cusps, if these do not have enough time to form before the end of the M morphogenetic process.

Similarities and differences in the dental tissue proportions of the deciduous and permanent canines of Early and Middle Pleistocene human populations.

The two- and three-dimensional assessment of dental tissues has become routine in human taxonomic studies throughout the years. Nonetheless, most of our knowledge of the variability of the enamel and dentine dimensions of the human evolutionary lineage comes from the study of permanent dentition, and particularly from molars. This leads to a biased view of the variability of these features. Due to their early formation and rapid development, the deciduous teeth allow more simplified inferences regarding the processes involved in the dental tissue development of each group. Therefore, their study could be very valuable in dental palaeohistology. In this research, we have explored the dental tissue proportions of the deciduous canines belonging to some human samples of the Early and Middle Pleistocene. The purpose of this was to discuss the meaning of the similarities and differences observed in their histological pattern, as well as to evaluate the degree of covariance with that observed in the permanent dentition of these populations. Our results show that, although there are some similarities in the dental tissue proportions between the deciduous and permanent canines of the study samples, the two dental classes do not provide a similar or comparable pictures of the dental tissue pattern present in the dentition of fossil hominins. Future works on the dental tissue patterns of the anterior and posterior dentition, including deciduous teeth, of fossil samples, may help to shed light on this hypothesis.

Dental remains of the Middle Pleistocene hominins from the Sima de los Huesos site (Sierra de Atapuerca, Spain): Mandibular dentition.

The Middle Pleistocene site of the Sima de los Huesos (Sierra de Atapuerca, northern Spain) has yielded a considerable number of human fossils during the period 1984-2020. Among them, up to 314 mandibular teeth have been identified. In this second paper dedicated to the dentition we present the description of the eight dental classes of the mandible following the Arizona State University Dental Anthropology System (ASUDAS) classification. In addition, we show the mean mesiodistal and buccolingual diameters obtained in these teeth compared to those of Neanderthals and a modern human sample. The morphology of both the anterior and posterior teeth suggests a close relationship of the Sima de los Huesos hominins with the populations of the second half of the Middle Pleistocene of Europe and the Near East, as well as with the so-called classic Neanderthals of Europe. The combination of dental traits in these populations is characteristic and diagnostic and suggests grouping the Sima de los Huesos hominins with the other paleodemes in a Neanderthal clade. The dental evidence of the Sima de los Huesos hominins is key to propose a complex model for the settlement of Europe during the Middle Pleistocene. In this period, different migrations of human groups probably coming from Southwest Asia, replacements, prolonged isolations, as well as hybridization and introgression processes would have contributed to the diversity of hominins in Europe.

Dental remains of the Middle Pleistocene hominins from the Sima de los Huesos site (Sierra de Atapuerca, Spain): Maxillary dentition.

The Middle Pleistocene site of the Sima de los Huesos (Sierra de Atapuerca, northern Spain) has yielded a considerable number of human fossils during the period 1984-2020. Among them, up to 253 maxillary teeth have been recovered. In this article, we present the description of the eight dental classes of the maxilla following the Arizona State University Dental Anthropology System classification. In addition, we present the mean mesiodistal and buccolingual diameters of these teeth compared to those of Neanderthals and a modern human sample. The morphology of both the anterior and posterior teeth suggests a close relationship of the Sima de los Huesos hominins with the populations of the second half of the Middle Pleistocene of Europe and the Near East, as well as with the so-called classic Neanderthals of Europe. Features with a recognizable taxonomic signal allow grouping the Sima de los Huesos hominins with different paleodemes into a Neanderthal clade. The dental evidence of the Sima de los Huesos hominins is key to suggest a complex model for the settlement of Europe during the Middle Pleistocene. During this period, different migrations of human groups probably coming from Southwest Asia, replacements, prolonged isolations, as well as hybridization and introgression processes would have contributed to the diversity of hominins in Europe.

Comparative dental study between Homo antecessor and Chinese Homo erectus: Nonmetric features and geometric morphometrics.

The Chinese Middle Pleistocene fossils from Hexian, Xichuan, Yiyuan, and Zhoukoudian have been generally classified as Homo erectus s.s. These hominins share some primitive features with other Homo specimens, but they also display unique cranial and dental traits. Thus, the Chinese Middle Pleistocene hominins share with other European and Asian hominin populations the so-called 'Eurasian dental pattern'. The late Early Pleistocene hominins from Gran Dolina-TD6.2 (Spain), representing the species Homo antecessor, also exhibit the Eurasian dental pattern, which may suggest common roots. To assess phylogenetic affinities of these two taxa, we evaluated and compared nonmetric and metric dental features and interpreted morphological differences within a comparative hominin framework. We determined that the robust roots of the molars, the shelf-like protostylid, the dendrite-like pattern of the enamel-dentine junction surface of the upper fourth premolars and molars, the strongly folded dentine of the labial surface of the upper incisors, and the rare occurrence of a mid-trigonid crest in the lower molars, are all characteristic of Chinese H. erectus. With regard to H. antecessor, we observed the consistent expression of a continuous mid-trigonid crest, the absence of a cingulum in the upper canines, a complex root pattern of the lower premolars, and a rhomboidal occlusal contour and occlusal polygon and protrusion in the external outline of a large a bulging hypocone in the first and second upper molars. Using two-dimensional geometric morphometrics, we further demonstrated that H. antecessor falls outside the range of variation of Chinese H. erectus for occlusal crown outline shape, the orientation of occlusal grooves, and relative locations of anterior and posterior foveae in the P4s, P3s, M1s, M2s, and M2s. Given their geographic and temporal separation, the differences between these two species suggest their divergence occurred at some point in the Early Pleistocene, and thereafter they followed different evolutionary paths.

The Ratón Pérez collection: Modern deciduous human teeth at the Centro Nacional de Investigación sobre la Evolución Humana (Burgos, Spain).

OBJECTIVES: The aim of this report is to present the large deciduous tooth collection of identified children that is housed at the National Research Center on Human Evolution (CENIEH) in Burgos, Spain. METHODS: Yearly, members of the Dental Anthropology Group of the CENIEH are in charge of collecting the teeth and registering all the relevant information from the donors at the time of collection. In compliance with Spanish Law 14/2007 of July 3, 2007, on Biomedical Research (BOE-A-2007-12945), all individuals are guaranteed anonymity and confidentiality. When the donor hands in the tooth, they fill out a Donor Information Form and sign the Informed Consent Form. At the same time, another person completes the data label for the transparent polyethylene zip lock bag where the tooth is temporarily stored. All teeth are then transferred to the CENIEH Restoration lab, where the specialists apply the same protocol as for the fossil remains. RESULTS: Although the sample is still growing, from the first collection campaign in 2014 to date it comprises 2977 teeth of children whose ages of tooth loss are between 2 and 15 years. Each tooth is associated with basic information of the individuals and their parents and grandparents (sex, date, and place of birth, ancestry, country of residence), as well as important data about early life history (pregnancy duration, breastfeeding, bottle-feeding) and other relevant information provided by the donors (such as if they are twins, dental loss, or dental extraction). CONCLUSIONS: Due to the scarcity of deciduous dental samples available, the Ratón Pérez collection represents a highly valuable sample for a wide range of disciplines such as forensic, dental, and anthropological fields among others.

Mapping of pseudouridine residues on cellular and viral transcripts using a novel antibody-based technique.

Pseudouridine (Ψ) is the most common noncanonical ribonucleoside present on mammalian noncoding RNAs (ncRNAs), including rRNAs, tRNAs, and snRNAs, where it contributes ∼7% of the total uridine level. However, Ψ constitutes only ∼0.1% of the uridines present on mRNAs and its effect on mRNA function remains unclear. Ψ residues have been shown to inhibit the detection of exogenous RNA transcripts by host innate immune factors, thus raising the possibility that viruses might have subverted the addition of Ψ residues to mRNAs by host pseudouridine synthase (PUS) enzymes as a way to inhibit antiviral responses in infected cells. Here, we describe and validate a novel antibody-based Ψ mapping technique called photo-crosslinking-assisted Ψ sequencing (PA-Ψ-seq) and use it to map Ψ residues on not only multiple cellular RNAs but also on the mRNAs and genomic RNA encoded by HIV-1. We describe 293T-derived cell lines in which human PUS enzymes previously reported to add Ψ residues to human mRNAs, specifically PUS1, PUS7, and TRUB1/PUS4, were inactivated by gene editing. Surprisingly, while this allowed us to assign several sites of Ψ addition on cellular mRNAs to each of these three PUS enzymes, Ψ sites present on HIV-1 transcripts remained unaffected. Moreover, loss of PUS1, PUS7, or TRUB1 function did not significantly reduce the level of Ψ residues detected on total human mRNA below the ∼0.1% level seen in wild-type cells, thus implying that the PUS enzyme(s) that adds the bulk of Ψ residues to human mRNAs remains to be defined.