Structural Interconversion Based on Intramolecular Boroxine Formation.

A novel structural interconversion unit based on intramolecular boroxine formation has been developed. A macrocyclic triboronic acid consisting of three phenylboronic acid units linked by covalent linkers preferentially underwent intramolecular rather than intermolecular boroxine formation, resulting in a quantitative formation of tricyclic boroxine. This structural transformation was accompanied by changes in the polarity, flexibility, and size of the molecule. Dynamic interconversion between the macrocyclic triboronic acid and the tricyclic boroxine was achieved by simple heating/cooling, whereas no boroxine formation occurred upon heating when three boronic acid units were not connected by linkers. Thermodynamic analysis revealed that the entropic advantage of the intramolecular boroxine formation process resulted in these unique features. The entropically stabilized tricyclic boroxine also shows high stability with respect to hydrolysis.

Boroxine template for macrocyclization and postfunctionalization.

A novel synthetic strategy for large macrocyclic molecules using boroxine formation was developed. For this, the threefold intramolecular olefin metathesis of 3,5-bis(alkenyloxy)phenylboroxines with various lengths of alkenyl chains, formed by the dehydration of the corresponding boronic acid substrates, together with treatment with pinacol, was used to produce 39-, 45-, and 51-membered macrocyclic compounds with three boronate units. The boroxine moiety functions as a covalent template but can also be used to postmodify the macrocycle. Boroxine-templated macrocyclization implemented in this way does not require the addition of template molecules and simplifies the synthetic procedure.

The mammalian red nucleus and its role in motor systems, including the emergence of bipedalism and language.

The human red nucleus consists of the well-developed parvicellular red nucleus (pNr) and the rudimentary magnocellular red nucleus (mNr). It is believed that the human pNr is separated from the nucleus accessorius medialis of Bechterew (NB), which, generally speaking, is located in the ventral central gray. It was initially suggested that the "rolled sheet" model of the human pNr that we proposed included the view that the human NB does not occupy the ventral central gray but is placed in the dorsomedial part of the red nucleus. It is perhaps more appropriate to state that the NB, the origin of the medial tegmental tract (MTT), over time became displaced from the ventral central gray and was in part shifted to the adjacent reticular formation. The majority of the MTT tract however remained in its established location. Evolutionarily speaking, this separation of the NB and the nucleus of Darkschewitsch (ND), and the translocation of the position of the NB just referred to, might have begun within the lineage of the apes prior to the emergence of man. Furthermore it is generally believed that the human mNr consists of a scattered few groups of giant-to-large neurons situated among the fiber bundles of the superior cerebellar peduncle at the level of the oculomotor nerve fibers. It has long been considered impossible to clearly draw an outline of the human mNr such that it could be seen as a self-contained structural entity. However, we now demonstrate just such an outline of the rudimentary human adult mNr through employment of the concepts of the so-called "Mannen's closed nucleus" and "Ogawa's human mNr": descriptions that exclude the associated area that contains neurons which possess melanin pigment. Interestingly, recent studies have shown that the human fetus and newborns have a well-developed semilunar mNr, and this observation raises the possibility that the associated transient but well-developed rubrospinal tract seen in the perinatal state might have had an important role for the development of upright bipedalism in hominids. The well-developed human prefrontal-NB-olivo-lateral cerebellar circuit might possibly have resulted in the emergence of language.

Carbocyanine dye usage in demarcating boundaries of the aged human red nucleus.

BACKGROUND: Though the adult human magnocellular Red nucleus (mNr) is essentially vestigial and its boundaries with neighbouring structures have never been well demarcated, human studies in utero have shown a well developed semilunar mNr wrapping around the caudal parvicellular Red nucleus (pNr), similar to what is seen in quadrupeds. In the present study, we have sought to better delineate the morphological determinants of the adult human Red nucleus (ahRn). METHODS AND FINDINGS: Serial sections of ahRn show fine myelinated fibers arising from pNr and turning toward the central tegmental tract. DiI was deposited within a well restricted region of ahRn at the fasciculus retroflexus level and the extent of label determined. Nissl-stained serial sections allowed production of a 3-D mNr model, showing rudimentary, vestigial morphology compared with its well developed infant homologue. DiI within this vestigial mNr region at the level of the oculomotor nerve showed labeled giant/large mNr neurons, coarse fiber bundles at the ventral tegmental decussation and lateral lemniscal label. CONCLUSIONS: Large amounts of DiI and a long incubation time have proven useful in aged human brain as a marker of long axons and large cell bodies of projecting neurons such as the rubrospinal projection and for clarifying nuclear boundaries of closed nuclei (e.g., the large human pNr). Our 3D model of adult human mNr appeared shrunken in shape and axially rotated compared with the infant mNr, the rotation being a common feature among mammalian mNr.

A comparative neuroanatomical study of the red nucleus of the cat, macaque and human.

BACKGROUND: The human red nucleus (Nr) is comparatively less well-studied than that of cats or monkeys. Given the functional importance of reticular and midbrain structures in control of movement and locomotion as well as from an evolutionary perspective, we investigated the nature and extent of any differences in Nr projections to the olivary complex in quadrupedal and bipedal species. Using neuroanatomical tract-tracing techniques we developed a "neural sheet" hypothesis allowing us to propose how rubro-olivary relations differ among the three species. METHODS AND FINDINGS: Wheat germ agglutinin-horseradish peroxidase staining supports findings that the cat's nucleus accessories medialis of Bechtrew (NB) projects mainly to the lateral bend of the principal olive. We clarified boundaries among nucleus of Darkschewitsch (ND), NB and parvicellular red nucleus (pNr) of the cat's neural sheet. The macaque's ND-medial accessory olivary projection is rostro-caudally organized and the dorsomedial and ventrolateral parts of the macaque's pNr may project to the principal olive's rostral and caudal dorsal lamella; in cat it projects as well to pNr. Myelin- and Nissl-stained sections show that a well-developed dorsomedial part of the human Nr consists of densely packed cells, deriving small myelinated fibers that continue into the medial central tegmental tract. CONCLUSIONS: Based on these findings we suggest there are distinct bipedal-quadrupedal differences for Nr projections to the olivary complex. We propose the Nr of cats and monkeys comprise the ND, NB and pNr in a zonal sheet-like structure, retaining clear nuclear boundaries and an isolated, well-developed mNr. The human NB may be distinguished from its more specialised ND (ND lies alongside a well-developed pNr) in the human central gray. Phylogenetically, the NB may have been translocated into a roll-shaped Nr in the reticular formation, the dorsomedial portion of which might correspond to the cat's and monkey's NB.

Olivary projection from the rostral part of the nucleus of Darkschewitsch in the postnatal rat as revealed through the use of a carbocyanine dye.

Using a carbocyanine dye in postnatal rats, we have shown that the rostral part of the nucleus of Darkschewitsch (ND), consisting of a subnucleus of the so-called "area parafascicularlis prerubralis " and excluded from the rat's ND proper, projects ipsilaterally to the rostral part of the medial accessory olive. The present study suggests the existence of a precise topographic organization from subnuclei of the area parafascicularlis prerublaris to subnuclei of the inferior olive.