Skeletal Class III malocclusion with maxillary deficiency is a severe maxillofacial disease with unclear pathogenic mechanisms. We recruited a Han Chinese family who was clinically diagnosed with skeletal Class III malocclusion and maxillary deficiency. Using whole exome sequencing, a missense variant in ADAMTS2 (NM_014244: c.3506G>T: p.G1169V) was identified and predicted as deleterious by in silico tools. We also found ADAMTS2 variants associated with deficient maxillary development in a cohort. ADAMTS2 expression in HEK293 cells showed significant decrease due to the variant, which was also consistent in dental pulp stem cells from the proband and a healthy control. In the adamts2-knockdown zebrafish model, the length and width of the ethmoid plate, as well as the length of the palatoquadrate became significantly shorter than the control group (p < 0.001), while there was no significant difference in the length and width of the mandible. The expression of Sox3, which was required in early embryonic craniofacial development, was significantly downregulated in the adamts2-knockdown zebrafish embryos. Bioinformatic and cellular studies showed that the decreased expression of ADAMTS2 may inhibit downstream ErbB signaling pathway transduction and restrain subsequent osteogenesis in human adult mesenchymal stromal cells. Collectively, these data showed that ADAMTS2 (c.3506G>T: p.G1169V) may confer susceptibility to risk of skeletal Class III malocclusion with maxillary deficiency.

Nodal is a transforming growth factor-β (TGF-β) superfamily member that plays a number of critical roles in mammalian embryonic development. Nodal is essential for the support of the peri-implantation epiblast in the mouse embryo and subsequently acts to specify mesendodermal fate at the time of gastrulation and, later, left-right asymmetry. Maintenance of human pluripotent stem cells (hPSCs) in vitro is dependent on Nodal signaling. Because it has proven difficult to prepare a biologically active form of recombinant Nodal protein, Activin or TGFB1 are widely used as surrogates for NODAL in hPSC culture. Nonetheless, the expression of the components of an endogenous Nodal signaling pathway in hPSC provides a potential autocrine pathway for the regulation of self-renewal in this system. Here we review recent studies that have clarified the role of Nodal signaling in pluripotent stem cell populations, highlighted spatial restrictions on Nodal signaling, and shown that Nodal functions in vivo as a heterodimer with GDF3, another TGF-β superfamily member expressed by hPSC. We discuss the role of this pathway in the maintenance of the epiblast and hPSC in light of these new advances.

The methods used to study human growth and development (auxology) have not previously been applied within the setting of hominin maturation (ontogeny). Ontogeny is defined here as the pattern of biological change into an adult form, both at the individual and species level. The hominin fossil record has a lack of recovered immature materials, due to such factors as taphonomic processes that destroy pre-adults; the fragility of immature compared to adult bone; and the lower mortality rates of juveniles compared to adults. The recent discovery of pre-adult hominin skeletal material from a single, homogeneous Homo naledi species from the Rising Star cave system in South Africa provides the opportunity for a broader application of auxology methods and thus the need to understand their use in a modern context. Human auxology studies benefit from a robust database, across multiple populations, and with longitudinal studies in order to assess the patterns and variations in typical growth, development and life history stages. Here, we review the approach, vocabulary, and methods of these human studies, investigate commonalities in data with the fossil record, and then advance the reconstruction of ontogeny for the extinct hominin species H. naledi. To this end, we apply an auxology model into the paleontological context to broadly predict H. naledi birthweight of the offspring at 2.06 kg with a range (±1 SD) of 1.89 to 2.24 kg, with a length at birth 45.5 cm. We estimate a H. naledi juvenile partial skeleton DH7 to be a height of 111-125 cm at death.

This case report describes the collaborative management of an extensive combined endodontic-periodontal lesion related to a long palato-radicular groove (PRG) on a maxillary lateral incisor. Cases with similar severity have been reported minimally in the endodontic journals but even less in the periodontal journals. This case report illustrates the result of multidisciplinary treatment of the combined lesions associated with PRG.
A 63-year-old patient presented with a periapical radiolucency on tooth #10. After evaluation, the patient was diagnosed with an endodontic-periodontal lesion associated with PRG. After being informed of a guarded prognosis, the patient consented to a surgical procedure in an effort to retain the tooth. Management of the case involved a combination of endodontic therapy, odontoplasty under dental operating microscopy to attempt to eliminate the root anomaly, and periodontal regenerative procedures with allografts and a resorbable barrier membrane. Clinical examination and the cone-beam computed tomography scan at a 2-year postoperative visit revealed a substantial reduction in probing depth and significant bone fill of the defect.
In the past, a long PRG in combination with a periapical lesion often resulted in extraction of the tooth. With accurate assessment of the etiology of the defect, patient education, and a multidisciplinary approach, teeth with a PRG may be retained with a stable outcome for years.

This paper offers the first ever published discussion of the ethical treatise Harmonie: Versuch einer monistischen Ethik [Harmony: an attempt at a monistic ethics] by Heinrich Schmidt (1874-1935), one of the leading figures in the circle of Ernst Haeckel. Published near the end of Schmidt\'s life (1931), it constituted a kind of summation of decades of intense involvement in the \"project\" of German monism that found its epicentre in Jena, and in Haeckel\'s attempts at founding it on Darwinian and Goethian lines. After a brief description of Schmidt\'s life and works, we summarize the main lines of Haeckel\'s evolutionary thought and their expression in his sparse ethical writings. A detailed description of Harmonie follows, in which we seek to demonstrate Schmidt\'s close adherence to Haeckel\'s monist foundations, as well as indicate where he expanded his own thinking in directions beyond Haeckel\'s. Lastly, we suggest that Harmonie, perhaps contrary to Schmidt\'s wishes after 1933, nevertheless offers textual evidence of the deep incompatibility of Schmidt\'s understanding of ethics to the sociopolitical ideology of National Socialism. This is consistent with the historical record of how Haeckel\'s monism, together with those like Schmidt who worked tirelessly to promote it, was negatively regarded by the NSDAP.

Plunging ranulas are rare; report of this condition is particularly limited in our environment. We present case series in children; with all cases having both oral and cervical components. It is important to note this type of presentation of plunging ranula and their appropriate management.

One of the main goals of Chromosome-Centric Human Proteome Project is to identify protein evidence for missing proteins (MPs). Here, we present a case study of the role of Y chromosome genes in organ development and how to overcome the challenges facing MPs identification by employing human pluripotent stem cell differentiation into cells of different organs yielding unprecedented biological insight into adult silenced proteins. Y chromosome is a male-specific sex chromosome which escapes meiotic recombination. From an evolutionary perspective, Y chromosome has preserved 3% of ancestral genes compared to 98% preservation of the X chromosome based on Ohno\'s law. Male specific region of Y chromosome (MSY) contains genes that contribute to central dogma and govern the expression of various targets throughout the genome. One of the most well-known functions of MSY genes is to decide the male-specific characteristics including sex, testis formation, and spermatogenesis, which are majorly formed by ampliconic gene families. Beyond its role in sex-specific gonad development, MSY genes in coexpression with their X counterparts, as single copy and broadly expressed genes, inhibit haplolethality and play a key role in embryogenesis. The role of X-Y related gene mutations in the development of hereditary syndromes suggests an essential contribution of sex chromosome genes to development. MSY genes, solely and independent of their X counterparts and/or in association with sex hormones, have a considerable impact on organ development. In this Review, we present major recent findings on the contribution of MSY genes to gonad formation, spermatogenesis, and the brain, heart, and kidney development and discuss how Y chromosome proteome project may exploit developmental biology to find missing proteins.

For decades, mammalian developmental genetic studies have focused almost entirely on two laboratory models: Mus and Rattus, species that breed readily in the laboratory and for which a wealth of molecular and genetic resources exist. These species alone, however, do not capture the remarkable diversity of morphological, behavioural and physiological traits seen across rodents, a group that represents >40% of all mammal species. Due to new advances in molecular tools and genomic technologies, studying the developmental events underlying natural variation in a wide range of species for a wide range of traits has become increasingly feasible. Here we review several recent studies and discuss how they not only provided technical resources for newly emerging rodent models in developmental genetics but also are instrumental in further encouraging scientists, from a wide range of research fields, to capitalize on the great diversity in development that has evolved among rodents.

An analysis of more than 1000 research articles in biology reveals that the name of the species being studied is not mentioned in the title or abstract of many articles. Consequently, such data are not easily accessible in the PubMed database. These omissions can mislead readers about the true nature of developmental processes and delay the acceptance of valid species differences. To improve the accuracy of the scientific record, I suggest that journals should require that authors include the name of the species being studied in the title or abstract of submitted papers.

BACKGROUND: The syndrome of horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare human disease and while its association with scoliosis was first reported in 1974, thirty years later the responsible genetic mutations are being elucidated. This progress was due to the reporting of single interesting cases.
METHODS: We present the case of a 27 year-old male patient who was admitted for elective scoliosis correction surgery and who represented after an uncomplicated discharge with headache and vomiting; because of a gaze palsy he underwent brain imaging that confirmed a brainstem abnormality, consistent with the syndrome of horizontal gaze palsy with progressive scoliosis (HGPPS), a rare autosomal recessive human disease.
CONCLUSIONS: This rare syndrome is a good example of how single case reports can lead to advances in laboratory research and genetic characterisation of diseases, together with implications for neurodevelopment. Vigilance in the neurological examination in an otherwise \'non-neurological\' scoliosis will help identify potential such cases, whilst further genetic/molecular analysis may shed further light into neuro-embryological development and patterning.