Genomic imputation of ancient Asian populations contrasts local adaptation in pre- and post-agricultural Japan.

Early modern humans lived as hunter-gatherers for millennia before agriculture, yet the genetic adaptations of these populations remain a mystery. Here, we investigate selection in the ancient hunter-gatherer-fisher Jomon and contrast pre- and post-agricultural adaptation in the Japanese archipelago. Building on the successful validation of imputation with ancient Asian genomes, we identify selection signatures in the Jomon, particularly robust signals from KITLG variants, which may have influenced dark pigmentation evolution. The Jomon lacks well-known adaptive variants (EDAR, ADH1B, and ALDH2), marking their emergence after the advent of farming in the archipelago. Notably, the EDAR and ADH1B variants were prevalent in the archipelago 1,300 years ago, whereas the ALDH2 variant could have emerged later due to its absence in other ancient genomes. Overall, our study underpins local adaptation unique to the Jomon population, which in turn sheds light on post-farming selection that continues to shape contemporary Asian populations.

An unusual configuration of two anomalies in the extensor digitorum profundus complex in a human.

The extensor digitorum profundus complex underwent degeneration of the ulnar segments during primate adaptation and evolution. This process resulted in the preservation of only the extensor pollicis longus and extensor indicis in some apes, including humans. Consequently, anatomical variations within the digitorum profundus complex in modern humans have been well-documented, with detailed reports on their frequency and patterns in previous studies. Here, we report an unusual arrangement involving two anomalies in the extensor digitorum profundus complex, identified in a 66-year-old Japanese male cadaver. In this cadaver, two accessory muscles differentiated from both the extensor pollicis longus and extensor indicis. Notably, the latter muscle featured a tendon bifurcating towards both the thumb and index fingers, referred to as the extensor pollicis et indicis communis. Under the extensor retinaculum, the tendon of the accessory extensor pollicis longus passed through an independent compartment, whereas that of the extensor pollicis et indicis communis traversed a compartment shared by the extensor indicis and the extensor digitorum communis. Both muscles were innervated by the posterior interosseous nerve. Previous studies have reported that the accessory slip of the extensor pollicis longus and extensor pollicis et indicis communis appear at frequencies of 0.6% and 0.4-1.4%, respectively. However, to the best of our knowledge, a configuration in which both appear simultaneously has not been reported. The data from this case could provide essential insights into the variations in the extensor digitorum profundus complex in humans and non-human primates.

Genomic insights into a tripartite ancestry in the Southern Ryukyu Islands.

A tripartite structure for the genetic origin of Japanese populations states that present-day populations are descended from three main ancestors: (1) the indigenous Jomon hunter-gatherers; (2) a Northeast Asian component that arrived during the agrarian Yayoi period; and (3) a major influx of East Asian ancestry in the imperial Kofun period. However, the genetic heterogeneity observed in different regions of the Japanese archipelago highlights the need to assess the applicability and suitability of this model. Here, we analyse historic genomes from the southern Ryukyu Islands, which have unique cultural and historical backgrounds compared with other parts of Japan. Our analysis supports the tripartite structure as the best fit in this region, with significantly higher estimated proportions of Jomon ancestry than mainland Japanese. Unlike the main islands, where each continental ancestor was directly brought by immigrants from the continent, those who already possessed the tripartite ancestor migrated to the southern Ryukyu Islands and admixed with the prehistoric people around the eleventh century AD, coinciding with the emergence of the Gusuku period. These results reaffirm the tripartite model in the southernmost extremes of the Japanese archipelago and show variability in how the structure emerged in diverse geographic regions.

Ancient genomics reveals tripartite origins of Japanese populations.

Prehistoric Japan underwent rapid transformations in the past 3000 years, first from foraging to wet rice farming and then to state formation. A long-standing hypothesis posits that mainland Japanese populations derive dual ancestry from indigenous Jomon hunter-gatherer-fishers and succeeding Yayoi farmers. However, the genomic impact of agricultural migration and subsequent sociocultural changes remains unclear. We report 12 ancient Japanese genomes from pre- and postfarming periods. Our analysis finds that the Jomon maintained a small effective population size of ~1000 over several millennia, with a deep divergence from continental populations dated to 20,000 to 15,000 years ago, a period that saw the insularization of Japan through rising sea levels. Rice cultivation was introduced by people with Northeast Asian ancestry. Unexpectedly, we identify a later influx of East Asian ancestry during the imperial Kofun period. These three ancestral components continue to characterize present-day populations, supporting a tripartite model of Japanese genomic origins.

Impact of Hands-on Experience of a Cadaver Dissection on the Professional Identity Formation of Health Sciences Students.

BACKGROUND: In Japan, some nursing and health science universities that train nurses and/or clinical laboratory technicians have a curriculum in which students observe medical students performing a cadaver dissection. Observing a cadaver dissection is believed to affect the formation of a student's professional identity. This study aimed to investigate the effects of observing a cadaver dissection on the professional identity of nursing and clinical laboratory science students to find an effective educational support system for developing professional identity. METHODS: Sophomores majoring in nursing science or clinical laboratory science were asked to complete a questionnaire with a professional identity scale before and after hands-on experience of a cadaver dissection performed by medical students. After their hands-on session was complete, they responded to a free-answer question about acquiring a professional identity. RESULTS: The professional identity score of nursing students significantly decreased after the hands-on experience of the cadaver dissection. No significant change in professional identity score was observed in the clinical laboratory science students. However, the effect size (r) was moderate. CONCLUSION: Although professional identity formation fluctuates immediately after the experience of the hands-on experience of a cadaver dissection, the findings do suggest that these hands-on sessions will be effective for developing their professional identity if educational support is provided to help them utilize what they learned through reflection.

A paleopathological approach to early human adaptation for wet-rice agriculture: The first case of Neolithic spinal tuberculosis at the Yangtze River Delta of China.

The earliest evidence of human tuberculosis can be traced to at least the early dynastic periods, when full-scaled wet-rice agriculture began or entered its early developmental stages, in circum-China countries (Japan, Korea, and Thailand). Early studies indicated that the initial spread of tuberculosis coincided with the development of wet-rice agriculture. It has been proposed that the adaptation to agriculture changed human social/living environments, coincidentally favoring survival and spread of pathogenic Mycobacterial strains that cause tuberculosis. Here we present a possible case of spinal tuberculosis evident in the remains of a young female (M191) found among 184 skeletal individuals who were Neolithic wet-rice agriculturalists from the Yangtze River Delta of China, associated with Songze culture (3900-3200 B.C.). This early evidence of tuberculosis in East Asia serves as an example of early human morbidity following the adoption of the wet-rice agriculture.

THE DISPERSION OF HERBACEOUS PLANT POLLEN IN ITO CITY, SHIZUOKA.

BACKGROUND: Airborne pollen was examined in Ito City, Shizuoka for the purpose of treatment and prophylaxis pollen allergies because the patients with pollen allergy to herbaceous plants have recently increased. METHODS: Setting up a Durham's sampler, we measured airborne pollen identified and classified: Poaceae, Polygonaceae, Amaranthaceae, Urticaceae, Cannabaceae, Ambrosia and Artemisia indica.We studied whether each airborne pollen count has something to do with weather condition (2004-2015). RESULTS: Average total airborne Poaceae pollen count and standard deviation from January to June was 19.4±5.5 cells/cm(2), average total airborne Polygonaceae pollen count and standard deviation from April to September was 11.6±13.4 cells/cm(2). Airborne Poaceae, Amaranthaceae, Cannabaceae, Uriticaceae. Ambrosia and Artamisia indica pollen count from July to Deccember in order: 34.0±15.5 cells/cm(2), 1.3±1.1 cells/cm(2), 8.7±6.4cells/cm(2), 4.9±6.4 cells/cm(2), 10.5±7.8 cells/cm(2), and 13.6±16.3 cells/cm(2).Cannabaceae admitted that its airborne pollen count has negative correlation to the rainfall.Artemisia indica admitted that its airborne pollen count has negative correlation to the average temperature. CONCLUSION: Herbaceous plants pollen doesn't cause allergies because it is much less than tree pollen in ItoCity.It is thought that the diversity of the plants keep the people from having a serious allergy to pollen with awarm weather in this area.

Inhibition of MEK and GSK3 supports ES cell-like domed colony formation from avian and reptile embryos.

As amniotes diversified, mammals may have modified mechanisms of cellular pluripotency along with the acquisition of a placenta. What then defined pluripotent states in the ancestral amniotes? To study the evolutionary background of pluripotency in amniotes, we tested the effects of extracellular effectors on primary culture cells from avian and reptile embryos in serum-free medium. When treated with a combination of a MEK inhibitor and a GSK3 inhibitor (2i condition), chicken early embryos formed domed colonies (DCs), which were morphologically indistinguishable from the colonies formed by mouse and rat naïve embryonic stem cells. However, no DCs formed when cells from further-developed embryos were cultured in the 2i condition, indicating that there is a clear boundary of DC-forming ability at around the stage of primitive streak elongation. Quail embryos at the blastoderm and cleavage stages also formed DCs in the 2i condition, which is consistent with the notion that the appearance of DCs corresponds with the presence of pluripotent cells in embryos. Gecko blastoderms also formed DCs in the 2i condition, but gastrulas did not. ERK activation by bFGF caused an effect opposite to that of the 2i condition, namely, it dispersed colonies of cells even from early embryos in all species examined. These results suggest that the regulation of pluripotency by FGF/ERK signaling may date back at least to the common ancestor of mammals, birds, and reptiles. However, gene expression analysis indicated the possibility that mammalian pluripotency transcription factors function differently in non-mammalian amniotes.

A missense mutation in the ITGA8 gene, a cell adhesion molecule gene, is associated with schizophrenia in Japanese female patients.

BACKGROUND: Cell adhesion molecules (CAMs) play pivotal role in the development of the central nervous system (CNS) and have also been reported to play role in the pathophysiology of schizophrenia. Missense mutations in the CAMs genes might alter the binding of their ligands, increasing the vulnerability to develop schizophrenia. METHODS: We selected 15 missense mutations in the CAMs genes of the CNS reported in the Kyoto Encyclopedia of Genes and Genomes (KEGG) and examined the association between these mutations and schizophrenia in 278 patients and 284 control subjects (first batch). We also genotyped the positive single nucleotide polymorphisms (SNPs) in 567 patients and 710 control subjects (second batch) and in 635 patients and 639 control subjects (replication samples). RESULTS: Genotypic and allelic distributions of rs2298033 in the ITGA8 gene between the schizophrenia and control groups were significantly different in the first batch (p=0.005 and 0.007, respectively). Gender-based analysis revealed that the allelic and genotypic distributions of rs2298033 in the ITGA8 were significantly different between the schizophrenia and control groups among females in both batches (p=0.010, 0.011 and 0.0086, 0.010, respectively) but not among males. Combine analysis of rs2298033 with the replication samples revealed a more significant differences (p=0.0032; 0.0035 in the overall subjects and p=0.0024; 0.0025 in the female subjects, respectively). The significant differences for rs2802808 of the NFASC gene were only observed in the female subgroup of the first batch. CONCLUSION: These results suggest that the ITGA8 gene might have gender-specific roles in the development of schizophrenia. Further replication and functional studies are required to confirm these findings.

[Tree pollen dispersion in Ito City, Shizuoka Prefecture].

BACKGROUND: The authors investigated the atmospheric tree pollen dispersion in Ito City, Shizuoka Prefecture for 12 years for the purpose of the prophylaxis and treatment of pollinosis. METHODS: We set up a Durham sampler on the rooftop of the three-story building in Ito City, and counted atmospheric pollen grouping first, Taxodiaceae and Cupressaceae; second, Pinaceae and Podocarpaceae; third, Betulaceae and Ulmaceae; last, Fagaceae. The counts of atmospheric tree pollen on season and the weather from January to June were treated statistically and analyzed on the computer program Microsoft Excel. RESULTS: Each average and SD of total pollen count was, in order, 7079±6503 count/cm(2), 502±146 count/cm(2), 891±480 count/cm(2), 906±481 count/cm(2). The last summer weather correlates to the atmospheric pollen count of Taxodiaceae, Cupressaceae, Betulaceace and Ulmaceae. The atmospheric pollen count of Taxodiaceae and Cupressaceae in spring is influenced by the weather; their atmospheric pollen count is reduced by a heavy rain or a heavy snow out of season. The atmospheric pollen count of Pinaceae, Podocarpaceae and Fagaceae does not relate to the weather. CONCLUSION: As a result of having examined the relations between the count of the atmospheric pollen and the weather in Ito City, I recognized relations in Taxodiaceae, Cupressaceae, Pinaceae and Podocarpaceae, but there were not the relations of intentionality in Betulaceae, Ulmaceae and Fagaceae.

Nuclear Smad7 Overexpressed in Mesenchymal Cells Acts as a Transcriptional Corepressor by Interacting with HDAC-1 and E2F to Regulate Cell Cycle.

Smad family proteins are essential intracellular mediators that regulate transforming growth factor-ß (TGF-ß) ligand signaling. In response to diverse stimuli, Smad7 is rapidly expressed and acts as a cytoplasmic inhibitor that selectively interferes with signals elicited from TGF-ß family receptors. In addition, earlier works have indicated that retrovirally transduced Smad7 induces long-lasting cell proliferation arrest in a variety of mesenchymal cells through down-regulation of G1 cyclins. However, the molecular mechanisms underlying the cytostatic effects of Smad7 remain unknown. We show here that Smad7 can form a complex with endogenous histone deacetylase proteins HDAC-1 and HDAC-3 in NIH 3T3 mouse fibroblast cells. By contrast, forced expression of a dominant-negative variant of HDAC-1 efficiently protected cells against Smad7 proliferation inhibition, suggesting that Smad7 depends on the deacetylase activity of its associated HDAC-1 to arrest the cell cycle. Furthermore, Smad7 caused HDAC-1 bind to E2F-1 to form a ternary complex on chromosomal DNA containing an E2F-binding motif and leading to repression in the activity of the E2F target genes. Smad7 mutations that prevented its binding to either HDAC-1 or E2F-1 resulted in a significant decrease in Smad7-mediated inhibition of cell proliferation. The present results strongly suggest that nuclear Smad7 is a transcriptional corepressor for E2F, providing a molecular basis for the Smad7-induced arrest of the cell cycle.

Developmental variation in ecogeographic body proportions.

While ecogeographic variation in adult human body proportions has been extensively explored, relatively less attention has been paid to the effect of Bergmann's and Allen's rules on human body shape during growth. The relationship between climate and immature body form is particularly important, as immature mortality is high, mechanisms of thermoregulation differ between young and mature humans, and immature body proportions fluctuate due to basic parameters of growth. This study explores changes in immature ecogeographic body proportions via analyses of anthropometric data from children included in Eveleth and Tanner's (1976) Worldwide Variation in Human Growth, as well as limb proportion measurements in eight different skeletal samples. Moderate to strong correlations exist between climatic data and immature stature, weight, BMI, and bi-iliac breadth; these relationships are as strong, if not stronger, in immature individuals as they are in adults. Correlations between climate and trunk height relative to stature are weak or nonexistent. Altitude also has significant effects on immature body form, with children from higher altitudes displaying smaller statures and lower body weights. Brachial and crural indices remain constant over the course of growth and display consistent, moderate correlations with latitude across ontogeny that are just as high as those detected in adults. The results of this study suggest that while some features of immature body form, such as bi-iliac breadth and intralimb indices, are strongly dictated by ecogeographic principles, other characteristics of immature body proportions are influenced by intrinsic and extrinsic factors such as nutrition and basic constraints of growth.

[Pollen dispersion of Cryptomeria japonica and Cupressaceae in Ito city during 10 years].

BACKGROUND: For a period of 10 years, ending in 2010, the authors investigated atmospheric pollen dispersion of Cryptomeria japonica and Cupressaceae in Ito City. We expect this investigation useful in treating patients with pollen allergy. METHODS: We set up a Durham sampler on a rooftop of the three-story building in Ito City and counted atmospheric pollen day by day. The results and the local weather conditions were treated statistically on the computer program Microsoft Excel. RESULTS: During the 10 years, in average, initial pollen was observed at January 3; pollen began to release was observed at February 6; final pollen was observed at May 12. The spring seasonal total pollen counts was 5683 grain/cm2. This pollen counts and the previous early winter seasonal pollen counts were correlated statistically. The pollen counts were related with the local weather conditions significantly. CONCLUSION: The investigations of the atmospheric pollen dispersion of Cryptomeria japonica and Cupressaceae and the weather conditions in the local area are useful to treat patients with the pollen allergy.

Ontogeny of limb proportions in late through final Jomon period foragers.

This study reports on developmental patterning in the intralimb indices of Late/Final Jomon period (4000-2300 BP) people. Jomon foragers represent the descendants of migrants from Northeast Asia, who arrived in the Japanese Islands around 20,000 BP. Among adults, Jomon brachial indices are elevated and similar to warm adapted, low latitude people, while crural indices are intermediate and similar to people from moderate latitudes. Two hypotheses regarding the development of intralimb indices among Jomon period foragers are tested: (1) intralimb indices of Jomon people maintain predicted ecogeographic relationships over ontogeny; (2) greater evolvability will be observed in the brachial index, while greater developmental constraint will be observed in the crural index. Changes in intralimb proportions in a Jomon skeletal growth series are compared to those in two contrasting samples: Inuit from Point Hope (cold adapted) and Nubians from Kulubnarti (warm adapted). A quadratic equation best describes the ontogeny of brachial and crural indices, with high indices in infancy followed by a decline in childhood and an increase in adolescence. Despite these shifts, ecogeographically predicted differences and similarities in the indices are maintained between samples throughout ontogeny. In addition, radial relative to humeral length is significantly less correlated than tibial relative to femoral length. These results suggest genetic conservation of intralimb indices over the course of development. However, radial and humeral lengths are less correlated than tibial and femoral lengths among Jomon subadults and adults, potentially suggesting greater evolvability of the brachial index and more developmental constraint on the crural index.

Basic study of a diagnostic modality employing a new electrical impedance tomography (EIT) method for noninvasive measurement in localized tissues.

The objective of this study is to develop a device for noninvasive local tissue electrical impedance tomography (EIT) using divided electrodes with guard electrodes and to validate its effectiveness using bioequivalent phantoms. For this purpose, we prepared a measurement device and bioequivalent phantoms, measured the electrical characteristics of the phantoms, and validated the method using the phantoms. Monolayer phantoms mimicking the brain and muscle and bilayer phantoms consisting of muscle and brain layers were prepared. The relative differences between the measured electrical conductivities of the monolayer brain and muscle phantoms and the true values determined by the 4-electrode method were both less than 10%. The relative differences between the measured and true values in the bilayer phantoms were less than 20% in both layers. The biological impedance measurement device that we developed was confirmed to be effective for impedance measurement in bilayer phantoms with different electrical impedances. To develop a device for the early diagnosis of breast diseases, the development of a multi-layer phantom and demonstration of the effectiveness of the device for its examination are necessary. If the device that we developed makes impedance measurement in breast tumors possible, it may be used as a new diagnostic modality for breast diseases.

An exploratory study on perceptions of seismic risk and mitigation in two districts of Istanbul.

Istanbul is one of the world's cities most vulnerable to seismic events. According to seismologists, the probability of a severe earthquake in the next 30 years is approximately 40 per cent. Following an outline of the seismicity of this vital Turkish city and a summary of current seismic risks and mitigation studies, this paper presents the results of a survey conducted in two districts of Istanbul, Avcilar and Bakirkoy. The survey comprised some 60 questions on the seismic risk perceptions of individuals and requested basic personal data, such as on age, education level, employment type, financial income, and gender. Despite various differences among the survey population, such as academic background and level of financial income, responses were surprisingly similar, especially in terms of having no plan for a safer house. The data may help those planning mitigation programmes and public awareness campaigns on preparedness and particularly mitigation in highly vulnerable regions.

Current status of breast cancer screening in the world.

The mortality associated with breast cancer is decreasing in Europe and the United States. There are various reasons for these trends, including an increase in detection of early-stage breast cancers due to increased use of mammographic screening and the establishment of standardized systemic treatments based on evidence-based medicine. However, in Japanese women, both the morbidity and the mortality of breast cancer are increasing. In this manuscript, we describe the current status of mammographic screening in Europe and the United States, and the status of breast cancer screening in Japan. Quality control systems are also introduced, and the need for practical measures, such as implementation of quality control systems aimed at improving the cancer screening rate (with a target of 50%) and population-based screening (organized screening), based on the Cancer Control Act, is described. Current countermeasures for dense breasts in women in their 40s, both overseas and in Japan, are also described, together with discussions of the diagnostic capability of digital mammography, the usefulness of screening combined with computer-aided diagnosis, and the current status of screening using MRI in Europe and the United States.

Smad7 induces G0/G1 cell cycle arrest in mesenchymal cells by inhibiting the expression of G1 cyclins.

The major Smad pathways serve in regulating the expression of genes downstream of TGFbeta signals. In this study, we examined the effects of sustained Smad7 expression in cultured cells. Interestingly, Smad7 caused various mesenchymal cells, including NIH3T3 fibroblast and ST2 bone-marrow stromal cells, to undergo a marked morphological alteration into a flattened cell shape, but kept them alive for as long as 60 days. Furthermore, Smad7 arrested the proliferation of the cells even before they reached confluence. These cells became quiescent in G0/G1 phase and accumulated a hypophosphorylated form of retinoblastoma. The cytostatic effect of Smad7 was closely associated with a preceding decrease in the levels of G1 cyclins, such as cyclin D1 and cyclin E. Accordingly, ectopic cyclin E was able to overcome the Smad7-induced arrest of proliferation. These results indicate that Smad7 functions upstream of G1 cyclins and suggest a novel role for Smad7 as an antiproliferative factor. In contrast to the growth of mesenchymal cells, that of epithelial cells was little susceptible to Smad7. The present findings raise the possibility that a link between Smad7 and the G1 to S phase transition may also contribute to the cell cycle control by certain Smad7-inducing stimuli in a cell-type-dependent fashion.

Crystallization and preliminary X-ray analysis of the Pax6 paired domain bound to the Pax6 gene enhancer.

Pax6 is a member of the Pax family of transcription factors and is essential for eye development. Pax6 has two DNA-binding domains: the paired domain and the homeodomain. The Pax6 paired domain is involved in Pax6 gene autoregulation by binding to its enhancer. In this study, crystallization and preliminary X-ray diffraction analysis of the mammalian Pax6 paired domain in complex with the Pax6 gene enhancer was attempted. The Pax6 paired domain complexed with an optimized 25 bp DNA fragment was crystallized by the hanging-drop vapour-diffusion method. The crystal diffracted synchrotron radiation to 3.0/3.7 A resolution and belongs to the monoclinic space group P2(1), with unit-cell parameters a = 62.21, b = 70.69, c = 176.03 A, beta = 90.54 degrees. Diffraction data were collected to 3.7 A resolution.