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Objectives: Grotta‐Riparo di Uluzzo C (Apulia, southern Italy) is a pivotal site for investigating the evolution of the Middle Paleolithic and the earliest phases of the Upper Paleolithic in southern Italy, as the extensive stratigraphic record of this site includes a thick Mousterian sequence followed by the Uluzzian. Here, we investigate the taxonomic affinity of seven unpublished deciduous human teeth retrieved from the site of Uluzzo C in 1960. Materials and Methods: The teeth are represented by seven plaster dental casts, which are housed at the Museo Civico di Paleontologia e Paletnologia in Maglie (Lecce, Apulia). The location of the original specimens remains unknown, rendering these casts the only human remains evidence yielded by Uluzzo C to date. Based on occlusal‐view photographs and digital models of the casts, we examined the external morphology and morphometry of the teeth, comparing them to Homo sapiens and H. neanderthalensis samples. Through geometric morphometric methods and statistical analyses, we analyzed the crown outline of the deciduous molars. Results: The teeth show morphological and morphometric features that are variably found in H. neanderthalensis, H. sapiens, or both. Specifically, crown outline analysis shows that all molars fall within H. neanderthalensis variability, except for Uluzzo 853 (lower right deciduous first molar), which falls within H. sapiens variability. Discussion: This study provides the first taxonomic assessment of the hominin teeth from Uluzzo C. The results contribute additional insights into the Paleolithic peopling of southern Italy during a crucial period marked by the persistence of post‐Tyrrhenian Neanderthal techno‐complexes and the arrival of H. sapiens. [ABSTRACT FROM AUTHOR]

The human fibular shape has been scarcely analyzed in anthropology. However, studies on athletes and human archaeological samples suggest the importance of including fibular structural properties to reconstruct mobility patterns in past populations. This study analyzes human fibular variation in relation to mobility patterns, environmental conditions, subsistence economies, and shoe use to further explore the role of this bone in reconstructing mobility patterns in past populations. The sample consists of 173 individuals from Italian archaeological and modern skeletal collections spanning the Mid-Late Upper Paleolithic to the twentieth century and includes hunter-gatherers, agriculturalists, herders, and post-industrialists. Virtual three-dimensional models of left fibulae were acquired by computer tomography and surface scanning. Fibular proximal and distal epiphyseal morphologies were investigated through 3D semilandmark-based geometric morphometric methods and compared among populations and mobility categories. Our analysis reveals a trend separating groups based on their subsistence strategy and chronology. Some fibular traits (e.g., horizontal proximal tibiofibular joint and tilted distal talofibular articular surface, robust interosseous membrane, broad malleolar fossa, projecting m. biceps femoris insertion) indicate greater mobility of fibular joints and load sharing during ankle and knee excursion in foraging groups, which are presumably highly active, frequently traversing uneven terrain with absent/minimalist foot coverings. Stiffer fibular joints (e.g., obliquely oriented tibiofibular and vertical talofibular articular surfaces) are observed in sedentary populations, which may suggest a restricted ankle excursion and limited lower limb loading and use, consistent with their sedentary lifestyle in plain urban settlements with hard-shoe coverings. Other fibular traits (e.g., shorter subcutaneous triangular surface, projecting and anteriorly-facing malleolus, concave peroneal groove and proximal peroneal insertion) might indicate for mobile groups a more everted foot posture with increased moment arm in eversion, more efficient for barefoot/minimal footwear running in a forefoot-strike gait and concurring in the stabilization of the first metatarsophalangeal ray. These results further stress the functional role of fibular morphology and its importance in studies investigating past population mobility patterns. [ABSTRACT FROM AUTHOR]

Entheses are acknowledged as skeletal markers capable of revealing several biological and behavioral aspects of past individuals and populations. However, entheseal changes (ECs) of juvenile individuals have not yet been studied with a systematic approach. This contribution aims at investigating the morphological changes occurring at the femoral insertion of the gluteus maximus and tibial origin of the soleus muscles to highlight a potential link between the morphological features of those entheses and skeletal maturity in relation to sex, age, and locomotor developmental patterns. The sample consisted of 119 skeletons (age‐at‐death: 0–30 years) belonging to the Documented Human Skeletal Collection of the Certosa Cemetery (Bologna, Italy). The entheseal variation during the last stages of skeletal maturation in young adults was assessed using existing recording standards. A recording protocol for each enthesis was developed for immature individuals to subdivide the morphological variability into discrete categories. Univariate, bivariate, and multivariate statistical analyses were performed to investigate the variation of entheseal morphologies and measurements in relation to bone metrics, degree of epiphyseal closure, sex, age, and locomotor developmental patterns. A statistically significant relationship was observed between ECs morphological patterns and age for both entheses, while sexual differences were negligible. A relationship between ECs morphological pattern and locomotor milestones emerged only for the gluteus maximus. Even though further testing is needed on other documented skeletal collections, our protocol could be usefully applied in forensic and archaeological fields and serving as important reference for evolutionary investigations. [ABSTRACT FROM AUTHOR]

Objectives: We perform a comparative assessment of shape variation of the proximal fibula in extant humans and great apes, intending to investigate the possible link between proximal fibular shape and locomotor patterns. Methods: Our sample includes 94 fibulae of 37 Homo sapiens, 15 Gorilla, 17 Pongo, and 25 Pan. Fibular morphology was investigated through three‐dimensional (semi)landmark‐based geometric morphometric methods. Results: We found unique features of the human fibular head compared to that of great apes (i.e., oblique articular surface, the presence of the styloid process, specific morphology of muscle attachment sites), supporting the functional role of this bone in relation to human obligate bipedalism. Great apes also showed distinctive traits in their proximal fibula morphology, in agreement with differences in locomotor behavior. Conclusion: The morphology of the proximal fibula in extant humans and great apes is indicative of locomotor behavior, offering the potential for the comparative analysis of fossil hominin remains. [ABSTRACT FROM AUTHOR]

This article discusses the evolution of human bipedalism and its connection to anatomical variation in modern humans and our close relatives. It explores the musculoskeletal adaptations of early hominins and the factors that influenced the development of bipedalism, such as subsistence economy, choice of footwear, and biological factors. The article also examines the role of age-related changes in bone density and the scaling patterns of muscles in ape locomotor behaviors. Additionally, it discusses the impact of activity levels, footwear, and sedentary lifestyles on the morphology of foot bones. The research topic includes 10 peer-reviewed original research articles that contribute to our understanding of bipedalism. The article emphasizes the interdisciplinary nature of studying bipedalism and endorses a pluralistic approach to research. [Extracted from the article]

The evolution of the medial longitudinal arch (MLA) is one of the most impactful adaptations in the hominin foot that emerged with bipedalism. When and how it evolved in the human lineage is still unresolved. Complicating the issue, clinical definitions of flatfoot in living Homo sapiens have not reached a consensus. Here we digitally investigate the navicular morphology of H. sapiens (living, archaeological, and fossil), great apes, and fossil hominins and its correlation with the MLA. A distinctive navicular shape characterises living H. sapiens with adult acquired flexible flatfoot, while the congenital flexible flatfoot exhibits a 'normal' navicular shape. All H. sapiens groups differentiate from great apes independently from variations in the MLA, likely because of bipedalism. Most australopith, H. naledi, and H. floresiensis navicular shapes are closer to those of great apes, which is inconsistent with a human-like MLA and instead might suggest a certain degree of arboreality. Navicular shape of OH 8 and fossil H. sapiens falls within the normal living H. sapiens spectrum of variation of the MLA (including congenital flexible flatfoot and individuals with a well-developed MLA). At the same time, H. neanderthalensis seem to be characterised by a different expression of the MLA. A GM study diachronically examined evolution of the medial longitudinal arch and variation as expressed by the navicular bone, identifying navicular traits associated with particular locomotor behaviors, subsistence strategies, and foot types [ABSTRACT FROM AUTHOR]

The Iron Age is characterized by an extended interweaving of movements by Celts in Europe. Several waves of Celts from Western and Central Europe migrated southeast and west from the core area of the La Téne culture (between Bourgogne and Bohemia). Through the analysis of non-metric dental traits, this work aims to understand the biological relationship among Celtic groups arrived in Italy and the Carpathian Basin, as well as between local populations and Celtic newcomers. A total of 10 non-metric dental traits were analyzed to evaluate biological affinities among Celts (Sopron-Krautacker and Pilismarót-Basaharc) and Scythians-related populations from Hungary (Tápiószele), Celts from continental Europe (Switzerland and Austria), two Iron Age Etruscan-Celtic sites from northern Italy (Monterenzio Vecchio and Monte Bibele), 13 Iron Age central-southern Italic necropolises, and the northern Italian Bronze Age necropolis of Scalvinetto. Strontium isotopes were measured on individuals from the necropolis of Monte Bibele to infer their local or non-local origin. Results highlight the existence of statistically significant differences between Celts and autochthonous Italian groups. Celtic groups from Hungary and Italy (i.e., non-local individuals of Monterenzio Vecchio and Monte Bibele) share a similar biological background, supporting the historical records mentioning a common origin for Celts migrated to the eastern and southern borders of today's Europe. The presence of a supposed Steppean ancestry both in Celts from Hungary and Celts from northern Italy corroborates the hypothesis of the existence of a westward migration of individuals and genes from the Steppe towards northern Italy during the Bronze and Iron Age, which contributed to the biological variability of pre-Celtic and later Celtic populations, respectively. Conversely, individuals from central-southern Italy show an autochthonous pre-Iron Age background. Lastly, this work supports the existence of Celtic migratory routes in northern Italy, as shown by biological and cultural admixture between Celts and Italics living together. [ABSTRACT FROM AUTHOR]

The present study examines the prehistoric human skeletal remains retrieved starting from the 1920s in the deposit of the Farneto rock shelter, situated in the area of the ‘Parco dei Gessi Bolognesi e Calanchi dell’Abbadessa’ (San Lazzaro di Savena, Bologna, northern Italy). An exact dating and a reliable interpretation of the assemblage had not been reached so far because of the lack of contextual data useful for dating purposes, the inaccurate recovery procedures of the remains and their state of preservation. In fact, the skeletal remains from the Farneto rock shelter are highly fragmented and commingled, whereas reliable information about their original position and their recovery procedures are not available. Despite these difficulties, radiocarbon analyses allowed the precise dating of the remains to a final phase of the Neolithic and an early phase of the Eneolithic period in Emilia Romagna (northern Italy). The study of the assemblage enabled to clarify the use of the context for funerary purposes. Moreover, the anthropological and taphonomic analyses of the skeletal remains shed light on the biological profile of the individuals and on some events that occurred after their death. In particular, the analysis of perimortem lesions highlighted the existence of intentional interventions related to corpse treatment, referable to dismembering/disarticulation and scarnification, i.e. cleaning of bones from soft tissues. Finally, the comparison with other Italian and European Neo/Eneolithic funerary contexts enabled a better understanding of these complex ritual practices. [ABSTRACT FROM AUTHOR]

Bacterial drug resistance is one of the major challenges to present and future human health, as the continuous selection of multidrug resistant bacteria poses at serious risk the possibility to treat infectious diseases in the near future. One of the infection at higher risk to become incurable is tuberculosis, due to the few drugs available in the market against Mycobacterium tuberculosis. Drug resistance in this species is usually due to point mutations in the drug target or in proteins required to activate prodrugs. However, another interesting and underexplored aspect of bacterial physiology with important impact on drug susceptibility is represented by the changes in transcriptional regulation following drug exposure. The main regulators involved in this phenomenon in M. tuberculosis are the sigma factors, and regulators belonging to the WhiB, GntR, XRE, Mar and TetR families. Better understanding the impact of these regulators in survival to drug treatment might contribute to identify new drug targets and/or to design new strategies of intervention. [ABSTRACT FROM AUTHOR]

Objectives: The study of the development of human bipedalism can provide a unique perspective on the evolution of morphology and behavior across species. To generate new knowledge of these mechanisms, we analyze changes in both internal and external morphology of the growing human talus in a sample of modern human juveniles using an innovative approach. Materials and Methods: The sample consists of high‐resolution microCT scans of 70 modern juvenile tali, aged between 8 postnatal weeks and 10 years old, from a broad chronological range from Middle/Late Neolithic, that is, between 4800 and 4500 BCE, to the 20th century. We applied geometric morphometric and whole‐bone trabecular analysis (bone volume fraction, degree of anisotropy, trabecular number, thickness, and spacing) to all specimens to identify changes in the external and internal morphology during growth. Morphometric maps were also generated. Results: During the first year of life, the talus has an immature and globular shape, with a dense, compact, and rather isotropic trabecular architecture, with numerous trabeculae packed closely together. This pattern changes while children acquire a more mature gait, and the talus tends to have a lower bone volume fraction, a higher anisotropy, and a more mature shape. Discussion: The changes in talar internal and external morphologies reflect the different loading patterns experienced during growth, gradually shifting from an "unspecialized" morphology to a more complex one, following the development of bipedal gait. Our research shows that talar plasticity, even though genetically driven, may show mechanical influences and contribute to tracking the main locomotor milestones. [ABSTRACT FROM AUTHOR]

Bacterial drug resistance is one of the major challenges to present and future human health, as the continuous selection of multidrug resistant bacteria poses at serious risk the possibility to treat infectious diseases in the near future. One of the infection at higher risk to become incurable is tuberculosis, due to the few drugs available in the market against Mycobacterium tuberculosis. Drug resistance in this species is usually due to point mutations in the drug target or in proteins required to activate prodrugs. However, another interesting and underexplored aspect of bacterial physiology with important impact on drug susceptibility is represented by the changes in transcriptional regulation following drug exposure. The main regulators involved in this phenomenon in M. tuberculosis are the sigma factors, and regulators belonging to the WhiB, GntR, XRE, Mar and TetR families. Better understanding the impact of these regulators in survival to drug treatment might contribute to identify new drug targets and/or to design new strategies of intervention. [ABSTRACT FROM AUTHOR]

Objectives: During the middle‐to‐upper Paleolithic transition (50,000 and 40,000 years ago), interaction between Neanderthals and Homo sapiens varied across Europe. In southern Italy, the association between Homo sapiens fossils and non‐Mousterian material culture, as well as the mode and tempo of Neanderthal demise, are still vividly debated. In this research, we focus on the study of two human teeth by using 3D geometric morphometric approaches for a reliable taxonomical attribution as well as obtaining new radiometric dates on the archeological sequence. Material and Methods: This work presents two lower deciduous molars uncovered at Roccia San Sebastiano (Mondragone‐Caserta, Italy), stratigraphically associated with Mousterian (RSS1) and Uluzzian (RSS2) artifacts. To obtain a probabilistic attribution of the two RSS teeth to each reference taxa group composed of Neanderthals and Homo sapiens, we performed and compared the performance of three supervised learning algorithms (flexible discriminant analysis, multiadaptive regression splines, and random forest) on both crown and cervical outlines obtained by virtual morphometric methods. Results: We show that RSS1, whose Mousterian context appears more recent than 44,800–44,230 cal BP, can be attributed to a Neanderthal, while RSS2, found in an Uluzzian context that we dated to 42,640–42,380 cal BP, is attributed to Homo sapiens. Discussion: This site yields the most recent direct evidence for a Neanderthal presence in southern Italy and confirms a later shift to upper Paleolithic technology in southwestern Italy compared to the earliest Uluzzian evidence at Grotta del Cavallo (Puglia, Italy). [ABSTRACT FROM AUTHOR]

This work aims to test accuracy and comparability of 3D models of human skeletal fibulae generated by clinical CT and laser scanner virtual acquisitions. Mesh topology, segmentation and smoothing protocols were tested to assess variation among meshes generated with different scanning methods and procedures, and to evaluate meshes‐interchangeability in 3D geometric morphometric analysis. A sample of 13 left human fibulae were scanned separately with Revolution Discovery CT dual energy (0.625 mm resolution) and ARTEC Space Spider 3D structured light laser scanner (0.1 mm resolution). Different segmentation methods, including half‐maximum height (HMH) and MIA‐clustering protocols, were compared to their high‐resolution standard generated with laser‐scanner by calculating topological surface deviations. Different smoothing algorithms were also evaluated, such as Laplacian and Taubin smoothing. A total of 142 semilandmarks were used to capture the shape of both proximal and distal fibular epiphyses. After Generalized Procrustes superimposition, the Procrustes coordinates of the proximal and distal fibular epiphyses were used separately to assess variation due to scanning methods and the operator error. Smoothing algorithms at low iteration do not provide significant variation among reconstructions, but segmentation protocol may influence final mesh quality (0.09–0.24 mm). Mean deviation among CT‐generated meshes that were segmented with MIA‐clustering protocol, and laser scanner‐generated ones, is optimal (0.42 mm, ranging 0.35–0.56 mm). Principal component analysis reveals that homologous samples scanned with the two methods cluster together for both the proximal and distal fibular epiphyses. Similarly, Procrustes ANOVA reveals no shape differences between scanning methods and replicates, and only 1.38–1.43% of shape variation is due to scanning device. Topological similarities support the comparability of CT‐ and laser scanner‐generated meshes and validate its simultaneous use in shape analysis with potential clinical relevance. We precautionarily suggest that dedicated trials should be performed in each study when merging different data sources prior to analyses. [ABSTRACT FROM AUTHOR]

Simple Summary: The extremities of the fibula may reflect differences between males and females, although so far only few studies included this bone for post-cranial sex assessment. Our work explored shape and size variation between sexes in identified skeletal samples comprising different populations from Italy and South Africa and showed that fibular extremities are significantly smaller, with narrower articular surfaces in females than in males. Consistent sex-related differences are revealed in fibular form and size in Italians but not in South Africans. Potential application in forensic and bioarcheological contexts may benefit from the use of this approach. Fibular metric variations have revealed their potential in distinguishing between males and females; however the fibula remains scarcely analyzed in studies of sexual dimorphism. This work aims at investigating sexually dimorphic features in fibular proximal and distal epiphyses through geometric morphometrics methods. A total of 136 left fibulae, from two Italian and one South African identified skeletal collections were virtually acquired through CT and laser scanning and analyzed using geometric morphometric methods. Statistical analyses were performed on shape, form, and size variables. Results show that fibular epiphyses are smaller with narrower articular surfaces in females than in males in both extremities. Relevant sexual differences emerge in fibular form and size for the two Italian samples but not for the South African one, likely for its small sample size. Discriminant analysis on form principal components (PCs) offers accuracy above 80% when the samples are pooled, and reaches accuracy of 80–93% when the Italian samples are considered separately. However, our method on form PCs was not successful for the South African sample (50–53% accuracy), possibly due to the small sample size. These results show relevant morphological variation in relation to fibular form and size, with a degree of accuracy that indicates the utility of the present method for sexing human fibulae in both forensic and bioarchaeological contexts for Italian samples. [ABSTRACT FROM AUTHOR]

We present the results of a multi-disciplinary investigation on a deciduous human tooth (Pradis 1), recently recovered from the Epigravettian layers of the Grotte di Pradis archaeological site (Northeastern Italian Prealps). Pradis 1 is an exfoliated deciduous molar (Rdm2), lost during life by an 11–12-year-old child. A direct radiocarbon date provided an age of 13,088–12,897 cal BP (95% probability, IntCal20). Amelogenin peptides extracted from tooth enamel and analysed through LC–MS/MS indicate that Pradis 1 likely belonged to a male. Time-resolved 87Sr/86Sr analyses by laser ablation mass spectrometry (LA-MC-ICPMS), combined with dental histology, were able to resolve his movements during the first year of life (i.e. the enamel mineralization interval). Specifically, the Sr isotope ratio of the tooth enamel differs from the local baseline value, suggesting that the child likely spent his first year of life far from Grotte di Pradis. Sr isotopes are also suggestive of a cyclical/seasonal mobility pattern exploited by the Epigravettian human group. The exploitation of Grotte di Pradis on a seasonal, i.e. summer, basis is also indicated by the faunal spectra. Indeed, the nearly 100% occurrence of marmot remains in the entire archaeozoological collection indicates the use of Pradis as a specialized marmot hunting or butchering site. This work represents the first direct assessment of sub-annual movements observed in an Epigravettian hunter-gatherer group from Northern Italy. [ABSTRACT FROM AUTHOR]

This project aims to test whether geometric morphometric (GM) and trabecular analyses may be useful tools in identifying talar characteristics related to hypochondroplasia. We quantified the external and internal talar morphology of a hypochondroplasic dwarf (T17) from Modena (northern Italy) dated to the sixth century AD. External talar morphology of T17 was compared with a broad sample of modern human tali (n = 159) using GM methods. Additionally, a subsample of these tali (n = 41) was used to investigate whole talar trabecular changes in T17. Our results show that GM and trabecular analyses identify a combination of traits linked to the dwarfing disorder of hypochondroplasia. These traits include decreased scaled talar dimensions compared with normal‐sized individuals, presence of an accessory antero‐lateral talar facet, high bone volume fraction, and high anisotropy values throughout the entire talus. In our case study, hypochondroplasia does not appear to substantially modify external talar morphology probably due to the fast growth of the talus. We suggest that small talar dimensions are associated with hypochondroplasia. An antero‐lateral talar facet may result from the talus and calcaneus coalition (i.e., talocalcaneal abnormal bridging) possibly related to an everted foot posture that was limited by overgrowth of the fibula. We suggest that high talar trabecular density and strut orientation provide insights into pathological development of the trabecular plates in T17. Finally, our study suggests that high talar trabecular density and strut orientation, and small talar dimensions, may be added as possible concomitant talar hallmarks for hypochondroplasia. [ABSTRACT FROM AUTHOR]

Teeth fusion is a developmental anomaly characterized by the union of two and, more rarely, three adjacent teeth. The fusion is caused by the physical pressure between two adjacent teeth during their development due to congenital, inherited, acquired or idiopathic factors. Nowadays, fused teeth occur with a frequency ratio between 0.1% and 1% in permanent dentition and 0.5% and 2.5% in primary dentition, and with an equal distribution between males and females. Fused teeth are a rare clinical finding, so there are not standardized clinical protocols and each case should be treated independently. This condition is rare in archaeological populations, likely due to taphonomic processes that cause the lack of information, as well as for the general low occurrence of the defect itself. In the European archaeological literature, there are no reports of two permanent fused teeth so far. Therefore, the present paper represents the first case study of two fused permanent incisors in the past Europe populations as this anomaly has been recognized in an adult man buried in the Longobard cemetery of Guidizzolo (VI–VII century A.D., northern Italy). [ABSTRACT FROM AUTHOR]

An isolated human cranium, dated to the early Eneolithic period, was discovered in 2015 at the top of a vertical shaft in the natural Marcel Loubens gypsum Cave (Bologna area, northern Italy). No other anthropological or archaeological remains were found inside the cave. In other caves of the same area anthropic and funerary use are attested from prehistory to more recent periods. We focused on investigating the circumstances surrounding the death of this individual, since the cranium shows signs of some lesions that appear to be the results of a perimortem manipulation probably carried out to remove soft tissues. Anthropological analyses revealed that the cranium belonged to a young woman. We analysed the taphonomic features and geological context to understand how and why the cranium ended up (accidentally or intentionally) in the cave. The analyses of both the sediments accumulated inside the cranium and the incrustations and pigmentation covering its outer surface suggested that it fell into the cave, drawn by a flow of water and mud, likely from the edges of a doline. The accidental nature of the event is also seemingly confirmed by some post-mortem lesions on the cranium. The comparison with other Eneolithic archaeological sites in northern Italy made it possible to interpret the find as likely being from a funerary or ritual context, in which corpse dismemberment (in particular the displacement of crania) was practiced. [ABSTRACT FROM AUTHOR]

An emerging body of research is revealing the microbiota pivotal involvement in determining the health or disease state of several human niches, and that of vitamin D also in extra-skeletal regions. Nevertheless, much of the oral microbiota and vitamin D reciprocal impact in oropharyngeal squamous cell carcinogenesis (OPSCC) is still mostly unknown. On this premise, starting from an in-depth scientific bibliographic analysis, this narrative literature review aims to show a detailed view of the state of the art on their contribution in the pathogenesis of this cancer type. Significant differences in the oral microbiota species quantity and quality have been detected in OPSCC-affected patients; in particular, mainly high-risk human papillomaviruses (HR-HPVs), Fusobacterium nucleatum, Porphyromonas gingivalis, Pseudomonas aeruginosa, and Candida spp. seem to be highly represented. Vitamin D prevents and fights infections promoted by the above identified pathogens, thus confirming its homeostatic function on the microbiota balance. However, its antimicrobial and antitumoral actions, well-described for the gut, have not been fully documented for the oropharynx yet. Deeper investigations of the mechanisms that link vitamin D levels, oral microbial diversity and inflammatory processes will lead to a better definition of OPSCC risk factors for the optimization of specific prevention and treatment strategies. [ABSTRACT FROM AUTHOR]

Objectives: The primate talus is known to have a shape that varies according to differences in locomotion and substrate use. While the modern human talus is morphologically specialized for bipedal walking, relatively little is known on how its morphology varies in relation to cultural and environmental differences across time. Here we compare tali of modern human populations with different subsistence economies and lifestyles to explore how cultural practices and environmental factors influence external talar shape. Materials and Methods: The sample consists of digital models of 142 tali from 11 archaeological and post‐industrial modern human groups. Talar morphology was investigated through 3D (semi)landmark based geometric morphometric methods. Results: Our results show distinct differences between highly mobile hunter‐gatherers and more sedentary groups belonging to a mixed post‐agricultural/industrial background. Hunter‐gatherers exhibit a more "flexible" talar shape, everted posture, and a more robust and medially oriented talar neck/head, which we interpret as reflecting long‐distance walking strictly performed barefoot, or wearing minimalistic footwear, along uneven ground. The talus of the post‐industrial population exhibits a "stable" profile, neutral posture, and a less robust and orthogonally oriented talar neck/head, which we interpret as a consequence of sedentary lifestyle and use of stiff footwear. Discussion: We suggest that talar morphological variation is related to the adoption of constraining footwear in post‐industrial society, which reduces ankle range of motion. This contrasts with hunter‐gatherers, where talar shape shows a more flexible profile, likely resulting from a lack of footwear while traversing uneven terrain. We conclude that modern human tali vary with differences in locomotor and cultural behavior. [ABSTRACT FROM AUTHOR]

Sex determination is a pivotal step in forensic and bioarchaeological fields. Generally, scholars focus on metric or qualitative morphological features, but in the last few years several contributions have applied geometric-morphometric (GM) techniques to overcome limitations of traditional approaches. In this study, we explore sexual dimorphism in modern human tali from three early 20th century populations (Sassari and Bologna, Italy; New York, USA) at intra- and interspecific population levels using geometric morphometric (GM) methods. Statistical analyses were performed using shape, form, and size variables. Our results do not show significant differences in shape between males and females, either considering the pooled sample or the individual populations. Differences in talar morphology due to sexual dimorphism are mainly related to allometry, i.e. size-related changes of morphological traits. Discriminant function analysis using form space Principal Components and centroid size correctly classify between 87.7% and 97.2% of the individuals. The result is similar using the pooled sample or the individual population, except for a diminished outcome for the New York group (from 73.9% to 78.2%). Finally, a talus from the Bologna sample (not included in the previous analysis) with known sex was selected to run a virtual resection, followed by two digital reconstructions based on the mean shape of both the pooled sample and the Bologna sample, respectively. The reconstructed talus was correctly classified with a Ppost between 99.9% and 100%, demonstrating that GM is a valuable tool to cope with fragmentary tali, which is a common occurrence in forensic and bioarchaeological contexts. [ABSTRACT FROM AUTHOR]

Background: Despite vaccination and screening measures, anogenital cancer, mainly promoted by HPV16 oncoproteins, still represents the fourth tumor and the second cause of death among women. Cell replication fidelity is the result of the host DNA damage response (DDR). Unlike many DNA viruses that promote their life cycle through the DDR inactivation, HR-HPVs encourage cells proliferation despite the DDR turned on. Why and how it occurs has been only partially elucidated. During HPV16 infection, E6 links and degrades p53 via the binding to the E6AP LXXLL sequence; unfortunately, E6 direct role in the DDR response has not clearly identified yet. Similarly, E7 increases DDR by competing with E2F1-pRb interaction, thus leading to the inactivation of pRb, and promotion, E2F1 mediated, of DDR genes translation, by binding to the pRb-like proteins CBP/p300 and p107, that also harbour LXXLL sequence, and via the interaction and activation of several DDR proteins. Methods: To gain information regarding E6 and E7 contribution in DDR activation, we produced an in vitro 3D HPV16-E6E7 infected epithelium, already consolidated study model for HPVs, and validated it by assessing H&E staining and BrdU, HPV16 DNA, E6E7 proteins and γH2A.X/53BP1 double-strand break (DSBs) sensors expression; then we made an immuno-colocalization of E6 and E7 with cyclin E2 and B1. Since 53BP1, like E6 and E7, also binds p53 and pRb, we supposed their possible direct binding. To explore this hypothesis, we performed a double immunofluorescence of E6 and E7 with 53BP1, a sequence analysis of 53BP1 within its BRCT2 domain and then an in situ PLA within CaSki, E6E7HPV16 NHEKs and the 3D model. Results: The in vitro epithelium resembled the histology and the events typical of in vivo infected tissues. E6E7HPV16 were both expressed in basal and differentiated strata and induced H2A.X phosphorylation and 53BP1 increment into nuclear foci. After highlighting E6 and E7 co-expression with 53BP1 and a LKVLL sequence within the 53BP1 BRCT2 domain, we demonstrated the bindings via the PLA technique. Conclusions: Our results reinforce E6 and E7 role in cellular function control providing potentially new insights into the activity of this tumor virus. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Exact symmetry and perfect balance between opposite jaw halves, as well as between antagonistic teeth, is not frequently observed in natural masticatory systems. Research results show that asymmetry in our body, skull, and jaws is often related to genetic, epigenetic, environmental and individual ontogenetic factors. Our study aims to provide evidence for a significant link between masticatory asymmetry and occlusal contact between antagonist teeth by testing the hypothesis that tooth inclination is one of the mechanisms driving distribution of wear in masticatory phases in addition to dietary and cultural habits. Materials and Methods: The present work investigates the relationship between dental macrowear patterns and tooth inclinations on a sample of complete maxillary and mandibular 3D models of dental arches from 19 young and adult Yuendumu Aboriginal individuals. The analysis was carried out on first molars (M1) from all quadrants. Occlusal Fingerprint Analysis was used for the quantification of macrowear patterns, and 2D cross‐sectional geometric analysis was carried out to investigate asymmetry in dental arches. Results: The asymmetry is highly variable on both arches, and it is associated with differences in the inclination of upper M1 crowns. Each molar has variable inclination (buccal/lingual) which influence tooth to tooth contact, producing greater or lesser variation in wear pattern. Interindividual variability of morphological variation of the occlusal relationship has to be considered in macrowear analysis. Discussion: Our results suggest that overall asymmetry in the masticatory apparatus in modern humans affects occlusal contact areas between antagonist teeth influencing macrowear and chewing efficiency during ontogeny. [ABSTRACT FROM AUTHOR]

The 4th century BC marks the main entrance of Celtic populations in northern Italy. Their arrival has been suggested based on the presence of Celtic customs in Etruscan mortuary contexts, yet up to now few bioarchaeological data have been examined to support or reject the arrival of these newcomers. Here we use strontium isotopes, non-metric dental traits and funerary patterns to unravel the biocultural structure of the necropolis of Monterenzio Vecchio (Bologna, Italy). Subsamples of our total sample of 38 individuals were analyzed based on different criteria characterizing the following analyses: 1) strontium isotope analysis to investigate migratory patterns and provenance; 2) non-metric dental traits to establish biological relationships between Monterenzio Vecchio, 13 Italian Iron age necropolises and three continental and non-continental Celtic necropolises; 3) grave goods which were statistically explored to detect possible patterns of cultural variability. The strontium isotopes results indicate the presence of local and non-local individuals, with some revealing patterns of mobility. The dental morphology reveals an affinity between Monterenzio Vecchio and Iron Age Italian samples. However, when the Monterenzio Vecchio sample is separated by isotopic results into locals and non-locals, the latter share affinity with the sample of non-continental Celts from Yorkshire (UK). Moreover, systematic analyses demonstrate that ethnic background does not retain measurable impact on the distribution of funerary elements. Our results confirm the migration of Celtic populations in Monterenzio as archaeologically hypothesized on the basis of the grave goods, followed by a high degree of cultural admixture between exogenous and endogenous traits. This contribution shows that combining different methods offers a more comprehensive perspective for the exploration of biocultural processes in past and present populations. [ABSTRACT FROM AUTHOR]

Peri-implantitis is a severe condition affecting the success of transmucosal dental implants: tissue healing is severely limited by the inflammatory processes that come about to control homeostasis in the surrounding tissues. The main cause of peri-implantitis is bacterial biofilm infection; gingival fibroblasts play a pivotal role in regulating the inflammatory cascades. A new technology aimed at preventing bacterial colonization of titanium (Ti) implants, and enhancing the spread of gingival fibroblasts, is presented. Using electro-spinning, mirror-polished Ti disks were uniformly coated with keratin fibers obtained from discarded wool via sulfitolysis. The keratin-coated surfaces were then doped with silver (Ag) to introduce antibacterial properties, using different concentrations of silver nitrate as a precursor (0.01, 0.05 and 0.1 M). The resulting specimens were characterized in terms of morphology and chemical composition by FESEM, FTIR and XPS, revealing silver concentrations between 1.7 and 1.9%. Silver release into the medium was evaluated in the presence of cells (α-MEM) or bacteria (LB) by ICP; release was 0.2–1.4 mg l−1 for α-MEM, and 10–40 mg l−1 for LB. The antibacterial properties of the Ag-doped specimens were tested against a multidrug-resistant Staphylococcus aureus biofilm through morphology (FESEM) and metabolic assay (XTT); reduction in viability was significant (p ＜ 0.05; ＞80% reduction within 72 h). Lastly, the cytocompatibility of the specimens was confirmed using human primary gingival fibroblasts, whose viability, spread and matrix deposition were found to be comparable to those of untreated Ti polished controls (p ＞ 0.05). Thus, Ag surface enrichment was effective in reducing viability and maturation of S. aureus biofilm, without compromising human cell viability. Moreover, cell spread was found to be very sensitive to keratin fiber stimulation. The strategy thus appears to be very promising to introduce surface features in line with the main requirements for transmucosal dental implants. [ABSTRACT FROM AUTHOR]

Several studies have documented the ability of flavonoids to sensitize cancer cells to chemotherapeutics and reverse multidrug resistance by inhibition of efflux pumps (adenosine triphosphate-binding cassette transporters), apoptosis activation, and cell cycle arrest. In this study, the flavonoid rutin (quercetin 3-O-β-d-rutinoside) was investigated as chemosensitizer towards two different human epithelial breast cancer cell lines: (i) MB-MDA-231, selected as representative for triple-negative breast cancer and (ii) MCF-7 used as a well-characterized model of HER2-negative breast cancer. To assess the cytocompatibility of rutin against non-cancer cells, primary human mammary fibroblasts were used as control and non-target cells. In MDA-MB-231 cells, 20 μM rutin enhanced cytotoxicity related to cyclophosphamide and methotrexate. Rutin significantly (p < 0.05) increased the anticancer activity of both chemotherapeutics, at 24-48-72 h, and decreased the activity of the adenosine triphosphate-binding cassette transporters, namely, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Flow cytometry analysis showed 20 μM and 50 μM rutin arrested cell cycle at G2/M and G0/G1 phases, respectively, significantly promoting cell apoptosis. Rutin, via non-selective inhibition of P-gp and BCRP pumps, efficiently reverses multidrug resistance and restores chemosensitivity to cyclophosphamide and cyclophosphamide of human chemoresistant, triple-negative breast cancer cells, successfully arresting cell cycle progression. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objectives Early evidence for the treatment of dental pathology is found primarily among food-producing societies associated with high levels of oral pathology. However, some Late Pleistocene hunter-gatherers show extensive oral pathology, suggesting that experimentation with therapeutic dental interventions may have greater antiquity. Here, we report the second earliest probable evidence for dentistry in a Late Upper Paleolithic hunter-gatherer recovered from Riparo Fredian (Tuscany, Italy). Materials and Methods The Fredian 5 human consists of an associated maxillary anterior dentition with antemortem exposure of both upper first incisor (I1) pulp chambers. The pulp chambers present probable antemortem modifications that warrant in-depth analyses and direct dating. Scanning electron microscopy, microCT and residue analyses were used to investigate the purported modifications of external and internal surfaces of each I1. Results The direct date places Fredian 5 between 13,000 and 12,740 calendar years ago. Both pulp chambers were circumferentially enlarged prior to the death of this individual. Occlusal dentine flaking on the margin of the cavities and striations on their internal aspects suggest anthropic manipulation. Residue analyses revealed a conglomerate of bitumen, vegetal fibers, and probable hairs adherent to the internal walls of the cavities. Discussion The results are consistent with tool-assisted manipulation to remove necrotic or infected pulp in vivo and the subsequent use of a composite, organic filling. Fredian 5 confirms the practice of dentistry-specifically, a pathology-induced intervention-among Late Pleistocene hunter-gatherers. As such, it appears that fundamental perceptions of biomedical knowledge and practice were in place long before the socioeconomic changes associated with the transition to food production in the Neolithic. [ABSTRACT FROM AUTHOR]

Chlorhexidine (CHX), one of the most effective drugs administered for periodontal treatment, presents collateral effects including toxicity when used for prolonged periods; here, we have evaluated the bactericidal potency and the cytocompatibility of Juniperus excelsa M. Bieb essential oil (EO) in comparison with 0.05% CHX. The EO was extracted from berries by hydrodistillation and components identified by gas chromatography and mass spectrometry. Bacterial inhibition halo analysis, quantitative cell viability 2,3-bis(2-methoxy-4-nitro-5-sulphophenyl)-5-[(phenyl amino) carbonyl]-2H-tetrazolium hydroxide assay (XTT), and colony forming unit (CFU) count were evaluated against the two biofilm formers Aggregatibacter actinomycetemcomitans and Streptococcus mutans. Finally, cytocompatibility was assessed with human primary gingival fibroblasts (HGF) and mucosal keratinocytes (HK). The resulting EO was mainly composed of monoterpene hydrocarbons and oxygenated monoterpenes. An inhibition halo test demonstrated that both bacteria were sensitive to the EO; XTT analysis and CFU counts confirmed that 10-fold-diluted EO determined a statistically significant (p < 0.05) reduction in bacteria count and viability towards both biofilm and planktonic forms in a comparable manner to those obtained with CHX. Moreover, EO displayed higher cytocompatibility than CHX (p < 0.05). In conclusion, EO exhibited bactericidal activity similar to CHX, but a superior cytocompatibility, making it a promising antiseptic alternative to CHX. [ABSTRACT FROM AUTHOR]

Recent work has disclosed the critical role played by enamel peptides in sex classification of old skeletal remains. In particular, protein AMELY (amelogenin isoform Y) is present in the enamel dental tissue of male individuals only, while AMELX (isoform X) can be found in both sexes. AMELY can be easily detected by LC-MS/MS in the ion extracted chromatograms of the SM(ox)IRPPY peptide (monoisotopic [M + 2 H]+2 mass = 440.2233 m/z). In this paper, we exploited the dimorphic features of the amelogenin protein to determine the sex of the so-called 'Lovers of Modena', two Late Antique individuals whose skeletons were intentionally buried hand-in-hand. Upon discovery, mass media had immediately assumed they were a male-female couple, even if bad preservation of the bones did not allow an effective sex classification. We were able to extract proteins from the dental enamel of both individuals (~1600 years old) and to confidently classify them as males. Results were compared to 14 modern and archaeological control samples, confirming the reliability of the ion chromatogram method for sex determination. Although we currently have no information on the actual relationship between the 'Lovers of Modena' (affective? Kin-based?), the discovery of two adult males intentionally buried hand-in-hand may have profound implications for our understanding of funerary practices in Late Antique Italy. [ABSTRACT FROM AUTHOR]

A possible strategy in regenerative medicine is cell-sheet engineering (CSE), i.e., developing smart cell culture surfaces from which to obtain intact cell sheets (CS). The main goal of this study was to develop 3D printing via extrusion-based bioprinting of methylcellulose (MC)-based hydrogels. Hydrogels were prepared by mixing MC powder in saline solutions (Na2SO4 and PBS). MC-based hydrogels were analyzed to investigate the rheological behavior and thus optimize the printing process parameters. Cells were tested in vitro on ring-shaped printed hydrogels; bulk MC hydrogels were used for comparison. In vitro tests used murine embryonic fibroblasts (NIH/3T3) and endothelial murine cells (MS1), and the resulting cell sheets were characterized analyzing cell viability and immunofluorescence. In terms of CS preparation, 3D printing proved to be an optimal approach to obtain ring-shaped CS. Cell orientation was observed for the ring-shaped CS and was confirmed by the degree of circularity of their nuclei: cell nuclei in ring-shaped CS were more elongated than those in sheets detached from bulk hydrogels. The 3D printing process appears adequate for the preparation of cell sheets of different shapes for the regeneration of complex tissues. [ABSTRACT FROM AUTHOR]