Evaluation of cortical bone density using clinical computed tomography images: Detection of cortical porosity areas or transitional zones in human femoral diaphyses.

Age-related changes in human trabecular bone and cortical bone are known to vary. Although the porosity of cortical bone has been suggested to increase the risk of bone fracture, most of the currently available instruments for osteoporosis testing target trabecular bone. In this study, we evaluated cortical bone density using clinical computed tomography (CT) and compared the reliability of the cortical bone density index (CDI) with that of a polished male femoral bone from the same region. CDI images revealed that the porous area of cortical bone was extended in low CDI values. Moreover, this method was used to semi-quantitatively evaluate the cortical bones of the diaphysis of male femur specimens (n = 46). We found that there was a significant relationship (r = 0.70, p < 0.01) between the value of the cortical index (the ratio of cortical bone area to the cross-sectional area of the femoral diaphysis) and the average of CDI in the low signal area. Our findings suggest that the smaller the cortical bone occupancy, the more areas of consequential bone density loss were present. This may be the first step toward using clinical CT to assess cortical bone density.

Morphological divergence in the curvature of human femoral diaphyses: Tracing the central mass distributions of cross-sections.

The diaphysis of the human femoral bone has a physiological anterior curvature; additionally, there is a curvature to the medial side or lateral side. In addition to compression stress from gravity during standing, walking, and running, these bones are continuously exposed to complex stresses from the traction forces of the various strong muscles attached to them. The femoral diaphysis is subjected to these mechanical stresses, and the direction and size of its curvature are defined according to Wolff's law and the mechanostat theory of Frost. The purpose of this study was to quantitatively evaluate the curvature of the femoral diaphysis in Japanese skeletons by determining the curve connecting the central mass distributions (CMD) of cross-sectional images. A total of 90 right femora (46 males and 44 females) were randomly selected from modern Japanese skeletal specimens. Full-length images of these bones were acquired using a clinical computed tomography scanner. The range between the lower end of the lesser trochanter and the adductor tubercle of each femur was divided at regular intervals to obtain ten planes, and nine levels were analyzed. The CMD curve was determined by connecting the CMDs of each of the nine cross-sections. First, the CMD of a cross-section in each of the nine slices was calculated, and the nine trajectories were superimposed from above. Then, by converting the shape of the entire CMD curve to superimpose the coordinates of the endpoint on the starting point, a closed arc representing the curvature of the femur was determined. For both males and females, the patterns varied from mostly medial to largely lateral curvature. The size of the curvature also varied for individuals. By analyzing only the coordinates of the vertex of the CMD curve of each femoral bone, the outlines of the diaphyseal curvatures could be recognized. The femora were thereby divided into two groups: medial bending and lateral bending. Considering males and females together, the number in the lateral-curvature group (n = 51) was larger than that in the medial-curvature group (n = 39). Moreover, the average age of the lateral-curvature group was significantly higher than that of the medial-curvature group (p < 0.05). In males, with an increase in the cortical bone proportion of the cross-sectional area, the anterior vertex of diaphyseal bending tended to be more prominent. This cortical proportion was significantly higher in the medial-curvature groups than in the lateral-curvature group (p < 0.01). The phenomena observed in this study may be related to pathophysiologies such as atypical fractures of the femur and osteoarthritis of the knee joints.

Nuclear receptor TLX stimulates hippocampal neurogenesis and enhances learning and memory in a transgenic mouse model.

The role of the nuclear receptor TLX in hippocampal neurogenesis and cognition has just begun to be explored. In this study, we generated a transgenic mouse model that expresses TLX under the control of the promoter of nestin, a neural precursor marker. Transgenic TLX expression led to mice with enlarged brains with an elongated hippocampal dentate gyrus and increased numbers of newborn neurons. Specific expression of TLX in adult hippocampal dentate gyrus via lentiviral transduction increased the numbers of BrdU(+) cells and BrdU(+)NeuN(+) neurons. Furthermore, the neural precursor-specific expression of the TLX transgene substantially rescued the neurogenic defects of TLX-null mice. Consistent with increased neurogenesis in the hippocampus, the TLX transgenic mice exhibited enhanced cognition with increased learning and memory. These results suggest a strong association between hippocampal neurogenesis and cognition, as well as significant contributions of TLX to hippocampal neurogenesis, learning, and memory.

E2A and CBP/p300 act in synergy to promote chromatin accessibility of the immunoglobulin κ locus.

V(D)J recombination of Ig and TCR genes is strictly regulated in a lineage- and stage-specific manner by the accessibility of target gene chromatin to the recombinases RAG1 and RAG2. It has been shown that enforced expression of the basic helix-loop-helix protein, E2A, together with RAG1/2 in a nonlymphoid cell line BOSC23 can induce V(D)J recombination in endogenous Igκ and TCR loci by increasing chromatin accessibility of target gene segments. In this study, we demonstrate that ectopically expressed E2A proteins in BOSC23 cells have the ability to bind directly to the promoter and recombination signal sequence of Vκ genes and to recruit histone acetyltransferase CBP/p300. Overexpression of CBP/p300 in conjunction with E2A results in enhancement of E2A-induced histone acetylation, germline transcription, and Igκ rearrangement. Conversely, knockdown of endogenous CBP/p300 expression by small interfering RNA leads to a decrease in histone acetylation, germline transcription and Igκ rearrangement. Furthermore, analyses using a mouse pre-B cell line revealed that endogenous E2A proteins also bind to a distinct set of Vκ genes and regulatory regions in the mouse Igκ locus and act to increase histone acetylation by recruiting p300, confirming the similar findings observed with BOSC23 cells. These observations indicate that E2A plays critical roles in inducing Igκ rearrangement by directly binding to and increasing chromatin accessibility at target gene segments.

Cross-sectional geometry of the femoral diaphyseal cortical bones: analysis of central mass distribution.

A detailed analysis of differences in skeletal shape among many individuals is expected to reveal the mechanical significance behind various morphological features. To confirm the distribution of the cortical bone region in cross sections, the relative position of the central mass distribution (CMD) of the cortical bone region to the CMD of the entire cross section was examined. A total of 90 right human femoral skeletons were examined using clinical multi-slice computed tomography. For nine cross sections of each femur, we determined the CMD of the whole area, including both cortical bone and medullary areas, as CMD-W, and that of the cortical bone region in the same cross section as CMD-C, and they were compared. The medial and anterior portion of the cortex was relatively thick just below the lesser trochanter. The posterior cortical bone tended to be relatively thick in the region from the center to the distal part of the diaphysis. Females had a significantly more medially deviated CMD than males throughout the entire diaphysis. These results suggest that femurs with advanced cortical bone thinning tend to have a concentration of cortical bone in their medial portion. CMD-C was located farther from the diaphysis axis as the degree of medial bending increased. Conversely, the greater the lateral bending of the diaphysis, the closer CMD-C was to the diaphysis axis. As the amount of bone decreases with age, self-adjustment could occur so that the cortical bone's critical area remains to prevent a decrease in mechanical strength.

The risk of Creutzfeldt-Jakob disease infection in cadaveric surgical training.

The usefulness of cadaver surgical training in the clinical field is already well known. In Japan, the number of universities introducing cadaver surgical training is increasing. In addition to formalin fixation, various fixation methods are used, such as the Thiel method, saturated salt solution method, N-vinyl-2-pyrrolidone method, and fresh-frozen cadavers. Although protection against infections during fixation and cadaver surgical training has been implemented in most universities, it is currently inadequate. Furthermore, the possibility of undiagnosed infectious diseases in donors cannot be excluded. Prion diseases, such as Creutzfeldt-Jakob disease, are relatively rare, but they are fatal, with no effective treatment. The abnormal prion protein that causes prion diseases is resistant to formaldehyde and cannot be inactivated by all methods of cadaver fixation presently in use. Recently developed real-time quaking-induced conversion has been reported to be a useful screening method for prion infection. In addition, this article aims to raise awareness of prion diseases in cadaver surgical training by reviewing the current understanding of prion diseases in cadavers and their screening methods.

Application of Methods for a Morphological Analysis of the Femoral Diaphysis Based on Clinical CT Images to Prehistoric Human Bone: Comparison of Modern Japanese and Jomon Populations from Hegi Cave, Oita, Japan.

A morphological analysis of ancient human bones is essential for understanding life history, medical history, and genetic characteristics. In addition to external measurements, a three-dimensional structural analysis using CT will provide more detailed information. The present study examined adult male human skeletons excavated from Hegi cave, Nakatsu city, Oita Prefecture. CT images were taken from the femurs of adult males (Initial/Early Jomon Period (n = 10) and Late Jomon Period (n = 5)). Cross-sectional images of the diaphysis from below the lesser trochanter to above the adductor tubercle were obtained using the method established by Imamura et al. (2019) and Imamura et al. (2021). Using Excel formulas and macros, the area of cortical bone, thickness, and degree of curvature were quantitatively analyzed. The results were compared with data on modern Japanese. The maximum thickness of cortical bone in the diaphysis and the degree of the anterior curvature were significantly greater in Late Jomon humans than in the other groups. In contrast to modern humans, the majority of Jomon femurs showed the S-shaped curvature with the medial side at the top position and the lateral side at the lower position. The present results demonstrate that Late Jomon humans had a wider range of activity than the other groups and also provide insights into diseases in the hip and knee joints of Jomon humans.

Similarities and Differences in Bone Mineral Density between Multiple Sites in the Same Individual: An Elderly Cadaveric Study.

Bone mineral density (BMD) is known to vary based on various factors, and the degree of variation is site-specific. However, few studies have investigated the relationship between bone density at trabecular bone-rich and cortical bone-rich sites in the same individual. In this study, we attempted to measure BMD at multiple sites using whole-body computed tomography images taken immediately after death and to clarify the similarities and differences between skeletal sites. Additionally, we aimed to examine the factors that influence changes in BMD, such as the loading environment, bone microstructure, and the ossification process of each skeletal region. A 3D model containing BMD data of the skull, clavicle, lumbar vertebrae, and femur (neck and diaphysis) was created using computed tomography images taken immediately after the death of 60 individuals (28 men and 32 women, average age: 84.0 years) who consented to participate in the study before death. Arbitrary measurement sites were defined, and bone density was measured at each site. We found that the BMDs of all regions were negatively correlated with age, but this correlation was weaker in the skull than in other regions. The negative correlation was especially pronounced in areas with more trabecular bones in men and in areas with more cortical bones in women. Furthermore, these findings suggest that factors, such as the loading environment, bone microstructure, and the ossification process of the skeletal sites, affect the BMD. Furthermore, our results suggest that it is important to assess the BMD of cortical bone in older women.

Gα subunit coordinates with ephrin-B to balance self-renewal and differentiation in neural progenitor cells.

Proper development of the mammalian brain requires that neural progenitor cells balance self-renewal and differentiation under precise temporal and spatial regulation, but the underlying mechanisms are not well understood. In this study, we identify Gα subunit as a positive regulator of mammalian neurogenesis, working with the regulator of G protein signaling (RGS)-mediated ephrin-B signaling pathway as two opposing forces to maintain a balance between self-renewal and differentiation in the developing mouse cerebral cortex. Multiple Gα(i) subunits are expressed by cortical neural progenitor cells during the course of cortical neurogenesis. Activation of Gα(i) signaling, through in utero electroporation-mediated expression of wild-type and constitutively active Gα(i) subunits, counteracts the function of ephrin-B in cortical neural progenitors to induce differentiation. Genetic knock-in of an RGS-insensitive G184SGα(i2) causes early cell cycle exit and a reduction of cortical neural progenitor cells and leads to a defect in the production of late born cortical neurons, similar to what is observed in mutant mice with deficiency in ephrin-B reverse signaling pathway. This study reveals a role of Gα subunit in mammalian neurogenesis and uncovers a developmental mechanism, coordinated by the Gα and ephrin-B signaling pathways, for control of the balance between self-renewal and differentiation in neural progenitor cells.

Gross anatomical investigation of the muscular head between the vastus lateralis and intermedius in the Japanese population: a cadaver study.

Unlike the general understanding of the quadriceps femoris, the existence of a new muscular head between the vastus lateralis and the vastus intermedius was reported, and named the tensor of the vastus intermedius in the Swedish population. The purpose of this study was to investigate the presence and form of the muscular head in the Japanese population and to clarify its structure by gross anatomical approaches. A total of 35 thighs of 20 Japanese cadavers were investigated. We searched for the muscular head and classified it into four types. In addition, nerve fiber analysis was performed for each classification type. Regarding classification, 11% were the independent type, 29% were the common type, 37% were the vastus lateralis type, and 23% were the vastus intermedius type. Based on nerve fiber analysis, in the common type, the muscular head was under dual nerve supply from the vastus lateralis and intermedius. The other three types were innervated only by nerves from the vastus lateralis. The target muscular head may always be present in Japanese. The nerves from the vastus lateralis were always distributed in the target muscular head based on nerve fiber analysis; therefore, this muscular head may be most closely related to the vastus lateralis. The name of this muscular head should be "the accessory head of the vastus lateralis" rather than "the tensor of the vastus intermedius."

Significant Asymmetry of the Bilateral Upper Extremities of a Skeleton Excavated from the Mashiki-Azamabaru Site, Okinawa Island, Japan.

The human skeleton of a young adult male with marked asymmetry of the bilateral upper extremities was excavated from the Mashiki-Azamabaru site (3000-2000 BCE) on the main island of Okinawa in the southwestern archipelago of Japan. The skeleton was buried alone in a corner of the cemetery. In this study, morphological and radiographic observations were made on this skeleton, and the pathogenesis of the bone growth disorder observed in the left upper limb was discussed. The maximum diameter of the midshaft of the humerus was 13.8 mm on the left and 21.2 mm on the right. The long bones comprising the left upper extremity lost the structure of the muscle attachments except for the deltoid tubercle of the humerus. The bone morphology of the right upper extremity and the bilateral lower extremities was maintained and was close to the mean value of females from the Ohtomo site in northwestern Kyushu, Japan, during the Yayoi period. It is assumed that the anomalous bone morphology confined to the left upper extremity was secondary to the prolonged loss of function of the muscles attached to left extremity bones. In this case, birth palsy, brachial plexus injury in childhood, and acute grey matter myelitis were diagnosed. It was suggested that this person had survived into young adulthood with severe paralysis of the left upper extremity due to injury or disease at an early age.

ZHX2 Interacts with Ephrin-B and regulates neural progenitor maintenance in the developing cerebral cortex.

Neural progenitor cells in the ventricular zone of the developing mammalian cerebral cortex give rise to specialized cortical cell types via consecutive rounds of proliferation and differentiation, but the mechanisms by which progenitor cell self-renewal and differentiation are regulated during cortical development are not well understood. Here, we show that zinc-finger and homeodomain protein 2 (ZHX2) is specifically expressed in neural progenitor cells during cortical neurogenesis. ZHX2 binds to the cytoplasmic domain of ephrin-B1, which is expressed in cortical neural progenitors and plays a role in neural progenitor cell maintenance. ZHX2 acts as a transcriptional repressor in cell, and its repressor activity is enhanced by coexpression of an ephrin-B1 intracellular domain. Blocking ZHX2 function in cultured neural progenitor cells or in the embryonic cortex causes neuronal differentiation, whereas overexpression of ZHX2 and an ephrin-B1 intracellular domain disrupts the normal differentiation of cortical neural progenitor cells. This study identifies ZHX2 as a novel regulator of neural progenitor cell maintenance and suggests a potential nuclear mechanism of the ephrin-B function in the cortex.

Spindle Orientation-Independent Control of Cell Fate Determination by RGS3 and KIF20A.

It was proposed that similar to its role in the invertebrate nervous system, mitotic spindle orientation (or cell cleavage plane orientation) of a dividing neural progenitor cell specifies the fate of daughter cells in the mammalian brain, modulating the production of neurons via symmetric versus asymmetric cell divisions during the course of neurogenesis. Experimental tests of the sufficiency of spindle/cleavage plane orientation in mammalian cell fate determination have yielded conflicting results. On the other hand, the necessity of spindle/cleavage plane orientation in mammalian cell fate determination has not yet been addressed. Here we examined the necessity of spindle/cleavage plane orientation during cortical neurogenesis in mice with loss-of-function of the RGS3-KIF20A interaction axis. We present evidence that while inactivation of RGS3 or KIF20A was linked to a shift in neural progenitor cells from proliferative to differentiative divisions in the developing cortex, these genetic mutations did not lead to anticipated alteration in the orientation of spindle/cleavage plane. Our results indicate that the RGS3-KIF20A axis regulates the balance between proliferation and differentiation in the mammalian cortex employing a mechanism independent of spindle/cleavage plane orientation. These data also caution against using spindle/cleavage plane orientation as the synonym for cell fate determination.

Reduced cortical bone thickness increases stress and strain in the female femoral diaphysis analyzed by a CT-based finite element method: Implications for the anatomical background of fatigue fracture of the femur.

The incidence of hip fractures is increasing in Japan and is high among women older than 70 years. While osteoporosis has been identified as one of the causative factors of fracture, atypical femoral fracture has emerged as a potential complication of bisphosphonate therapy. Atypical femoral fracture is prevalent among Asian women and has been attributed to morphological parameters. Age-related decreases in the morphological parameters of the femoral diaphysis, such as cortical bone thickness, cortical cross-sectional area, and the cortical index, were reported in Japanese women prior to bisphosphonate drugs being approved for treatment. Thus, in the present study, the relationships between biomechanical and morphological parameters were analyzed using a CT-based finite element method. Finite element models were constructed from 44 femurs of Japanese women aged 31-87 years using CT data. Loading conditions were set as the single-leg configuration and biomechanical parameters, maximum and minimum principal stresses, Drucker-Prager equivalent stress, maximum and minimum strains, and strain energy density were calculated in 7 zones from the subtrochanteric region to distal diaphysis. Pearson's correlation coefficient test was performed to investigate relationships with morphological parameters. While absolute stresses gradually decreased from the subtrochanteric region to distal diaphysis, absolute strains markedly declined in the proximal diaphysis and were maintained at the same levels as those in the distal regions. All types of stresses and minimum principal strain in the femoral diaphysis scored higher absolute values in the high-risk group (≥70 years, n = 28) than in the low-risk group (<70 years, n = 16) (p < 0.05). The distribution patterns of equivalent stress and strain energy density were similar to that of Young's modulus, except for the region of the linea aspera. All biomechanical parameters correlated with morphological parameters and correlation efficiencies, with the reciprocal of cortical bone thickness showing the strongest correlation. The present results demonstrated that biomechanical parameters may be predicted by calculating the cortical bone thickness of femurs not treated with bisphosphonates. Furthermore, strain appeared to be repressed at a low level despite differences in stress intensities among the regions by bone remodeling. This remodeling is considered to be regulated by Wolff's law driven by equivalent stress and strain energy densities from the proximal to distal femur. The present results will promote further investigations on the contribution of morphological parameters in the femoral diaphysis to the onset of atypical femoral fracture.

The Accessory Muscular Head of the Triceps Brachii Muscle with Tendinous Attachment / Cabeza Muscular Accesoria del Músculo Triceps Braquial con Inserción Tendinosa

SUMMARY: Variations in the triceps brachii muscle are uncommon, and especially limited reports exist on the accessory heads of tendinous origin that attach near the upper medial part of the humerus. During anatomical training at Nagasaki University School of Medicine, the accessory head of the triceps brachii muscle was observed on the right upper arm of a 72-year-old Japanese female. It arose tendinously from the medial side of the upper humerus, then formed a muscle belly and joined the distal side of the long head. This accessory head had independent nerve innervation, and the innervating nerve branched from a bundle of the radial nerve, which divided the nerve innervating the long head and the posterior brachial cutaneous nerve. The origin of the innervation of the accessory head was the basis for determining that this muscle head was an accessory muscle to the long head of the triceps brachii muscle. Embryologically, we discuss that part of the origin of the long head of the triceps brachii muscle was separated early in development by the axillary nerve and the posterior brachial circumflex artery, and it slipped into the surgical neck of the humerus and became fixed there. The accessory head crossed the radial nerve and deep brachial artery. When clinicians encounter compression of the radial nerve or profunda brachii artery, they should consider the presence of accessory muscles as a possible cause.

Las variaciones en el músculo tríceps braquial son poco comunes y existen informes especialmente limitados sobre las cabezas accesorias de origen tendinoso que se insertan cerca de la parte medial superior del húmero. Durante un entrenamiento anatómico en la Facultad de Medicina de la Universidad de Nagasaki, se observó la cabeza accesoria del músculo tríceps braquial en la parte superior del brazo derecho de una mujer japonesa de 72 años. Se originaba tendinosamente desde el lado medial de la parte superior del húmero, luego formaba un vientre muscular y se unía al lado distal de la cabeza larga. Esta cabeza accesoria tenía inervación nerviosa independiente, cuyo nervio se ramificaba a partir de un ramo del nervio radial, que dividía el nervio que inervaba la cabeza larga y el nervio cutáneo braquial posterior. El origen de la inervación de la cabeza accesoria fue la base para determinar que esta cabeza muscular era un músculo accesorio de la cabeza larga del músculo tríceps braquial. Embriológicamente, discutimos que parte del origen de la cabeza larga del músculo tríceps braquial se separó temprananamente en el desarrollo por el nervio axilar y la arteria circunfleja braquial posterior, y se deslizó hacia el cuello quirúrgico del húmero y quedó fijado allí. La cabeza accesoria cruzaba el nervio radial y la arteria braquial profunda. Cuando los médicos encuentran compresión del nervio radial o de la arteria braquial profunda, deben considerar la presencia de mús- culos accesorios como una posible causa.

N-Acyldopamine induces aggresome formation without proteasome inhibition and enhances protein aggregation via p62/SQSTM1 expression.

Accumulation of ubiquitinated protein aggregates is a common pathology associated with a number of neurodegenerative diseases and selective autophagy plays a critical role in their elimination. Although aging-related decreases in protein degradation properties may enhance protein aggregation, it remains unclear whether proteasome dysfunction is indispensable for ubiquitinated-protein aggregation in neurodegenerative diseases. Here, we show that N-oleoyl-dopamine and N-arachidonyl-dopamine, which are endogenous brain substances and belong to the N-acyldopamine (AcylDA) family, generate cellular inclusions through aggresome formation without proteasome inhibition. Although AcylDA itself does not inhibit proteasome activity in vitro, it activates the rearrangement of vimentin distribution to form a vimentin cage surrounding aggresomes and sequesters ubiquitinated proteins in aggresomes. The gene transcription of p62/SQSTM1 was significantly increased by AcylDAs, whereas the transcription of other ubiquitin-dependent autophagy receptors was unaffected. Genetic depletion of p62 resulted in the loss of ubiquitinated-protein sequestration in aggresomes, indicating that p62 is a critical component of aggresomes. Furthermore, AcylDAs accelerate the aggregation of mutant huntingtin exon 1 proteins. These results suggest that aggresome formation does not require proteasome dysfunction and AcylDA-induced aggresome formation may participate in forming cytoplasmic protein inclusions.

KIF20A/MKLP2 regulates the division modes of neural progenitor cells during cortical development.

Balanced symmetric and asymmetric divisions of neural progenitor cells (NPCs) are crucial for brain development, but the underlying mechanisms are not fully understood. Here we report that mitotic kinesin KIF20A/MKLP2 interacts with RGS3 and plays a crucial role in controlling the division modes of NPCs during cortical neurogenesis. Knockdown of KIF20A in NPCs causes dislocation of RGS3 from the intercellular bridge (ICB), impairs the function of Ephrin-B-RGS cell fate signaling complex, and leads to a transition from proliferative to differentiative divisions. Germline and inducible knockout of KIF20A causes a loss of progenitor cells and neurons and results in thinner cortex and ventriculomegaly. Interestingly, loss of function of KIF20A induces early cell cycle exit and precocious neuronal differentiation without causing substantial cytokinesis defect or apoptosis. Our results identify a RGS-KIF20A axis in the regulation of cell division and suggest a potential link of the ICB to regulation of cell fate determination.

Double-sided superior vena cava: developmental considerations associated with the thymic veins / Vena cava superior de doble cara: consideraciones de desarrollo asociadas con las venas tímicas

SUMMARY: The superior vena cava is usually located only on the right side, but persistence of the left superior vena cavais observed in about 0.3 to 0.5 % of adults. A routine dissection of the cadaver of a 91-year-old Japanese female, whose cause of death was sepsis due to cholecystitis, was performed at Nagasaki University and revealed a double-sided superior vena cava. On the right side, the superior vena cava opened to the right atrium, while on the left, it opened into the extended coronary sinus. Veins in the left head, neck and upper limb regions joined to form the persistent left superior vena cava, with eventual drainage into the expanded coronary vein. An anastomosing branch occurred between each superior vena cava, and two thymic veins opened to the anastomosing branch. The azygos vein in the azygos venous system opened into the right superior vena cava, whereas a hemi-azygos vein opened into the azygos vein. The accessory hemi-azygos vein also opened into the azygos vein and opened cranially into the left superior vena cava. The left supreme intercostal vein also opened into the left superior vena cava. Several studies have reported a persistent left superior vena cava and the various considerations for its occurrence. Here, we propose a new hypothesis for the embryonic development of the persistent left superior vena cava with the thymic vein. This hypothesis essentially states that the left brachiocephalic vein fails to mature due to inadequate venous return from the thymic vein during the embryonic period, and the left superior vena cava then remains to maintain venous return from the left head, neck and upper limb. We also discuss the clinical significance of the persistent left superior vena cava.

RESUMEN: Usualmente la vena cava superior se localiza solo en el lado derecho, sin embargo en aproximadamente 0,3 a 0,5 % de los adultos se observa la persistencia de la vena cava superior izquierda. En la Universidad de Nagasaki se realizó una disección de rutina del cadáver de una mujer japonesa de 91 años, cuya causa de muerte fue sepsis debido a una colecistitis. El cuerpo presentaba una vena cava superior doble. En el lado derecho, la vena cava superior llegaba al atrio derecho, mientras que en el lado izquierdo drenaba al seno coronario. Las venas de las regiones de la cabeza, el cuello y del miembro superior izquierdo formaban la vena cava superior izquierda persistente, con drenaje hacia la vena coronaria. Se observó una rama anastomótica entre cada vena cava superior y dos venas tímicas drenaban a la rama anastomótica. La vena ácigos drenaba a la vena cava superior derecha, mientras que una vena hemiácigos drenaba a la vena ácigos. La vena hemiácigos accesoria también drnaba en la vena ácigos y cranealmente lo hacia la vena cava superior izquierda. La vena intercostal suprema izquierda drenaba en la vena cava superior izquierda. Varios estudios han informado una vena cava superior izquierda persistente y las diversas consideraciones para su aparición. Aquí, proponemos una nueva hipótesis para el desarrollo embrionario de la vena cava superior izquierda persistente con la vena tímica, que esencialmente establece que la vena braquiocefálica izquierda no se dearrolla debido a un retorno venoso inadecuado de la vena tímica durante el período embrionario, y se mantiene la vena cava superior izquierda para el retorno venoso de la cabeza, el cuello y el miembro superior izquierdo. Además se informa de la importancia clínica de la persistencia de la vena cava superior izquierda.

The neural repressor NRSF/REST binds the PAH1 domain of the Sin3 corepressor by using its distinct short hydrophobic helix.

In non-neuronal cells and neuronal progenitors, many neuron-specific genes are repressed by a neural restrictive silencer factor (NRSF)/repressor element 1 silencing transcription factor (REST), which is an essential transcriptional repressor recruiting the Sin3-HDAC complex. Sin3 contains four paired amphipathic helix (PAH) domains, PAH1, PAH2, PAH3 and PAH4. A specific target repressor for Sin3 is likely to bind to one of them independently. So far, only the tertiary structures of PAH2 domain complexes, when bound to the Sin3-interacting domains of Mad1 and HBP1, have been determined. Here, we reveal that the N-terminal repressor domain of NRSF/REST binds to the PAH1 domain of mSin3B, and determine the structure of the PAH1 domain associated with the NRSF/REST minimal repressor domain. Compared to the PAH2 structure, PAH1 holds a rather globular four-helix bundle structure with a semi-ordered C-terminal tail. In contrast to the amphipathic alpha-helix of Mad1 or HBP1 bound to PAH2, the short hydrophobic alpha-helix of NRSF/REST is captured in the cleft of PAH1. A nuclear hormone receptor corepressor, N-CoR has been found to bind to the PAH1 domain with a lower affinity than NRSF/REST by using its C-terminal region, which contains fewer hydrophobic amino acid residues than the NRSF/REST helix. For strong binding to a repressor, PAH1 seems to require a short alpha-helix consisting of mostly hydrophobic amino acid residues within the repressor. Each of the four PAH domains of Sin3 seems to interact with a characteristic helix of a specific repressor; PAH1 needs a mostly hydrophobic helix and PAH2 needs an amphipathic helix in each target repressor.