Functional importance of a highly elastic ligament on the mammalian diaphragm.

The diaphragm of mammals is a musculotendinous dome separating the thoracic and abdominal cavities. With no skeletal elements to stretch it, the diaphragm has the problem of positioning its muscle fibres at a length appropriate for the onset of an inspiratory contraction. This is achieved through a negative intrapleural pressure, resulting from the opposing elastic recoil of the ribcage and lungs, which sucks the diaphragm into the thorax and extends the muscle fibres. A consequence of this negative pressure is that the diaphragm muscle is under tension when inactive during expiration. This is an unusual condition for skeletal muscles, which can suffer irreversible changes when stretched to long length, or they may respond by growing longer. We now describe a highly elastic and resilient diaphragmatic ligament which sets a sarcomere length enabling the muscle to use its full operating range, reduces stress on the diaphragm muscle fibres, and assists shortening of the diaphragm muscle at the onset of inspiration by means of elastic recoil.     

The mammalian endocytic cytoskeleton

Clathrin-mediated endocytosis (CME) is the major route through which cells internalise various substances and recycle membrane components. Via the coordinated action of many proteins, the membrane bends and invaginates to form a vesicle that buds off—along with its contents—into the cell. The contribution of the actin cytoskeleton to this highly dynamic process in mammalian cells is not well understood. Unlike in yeast, where there is a strict requirement for actin in CME, the significance of the actin cytoskeleton to mammalian CME is variable. However, a growing number of studies have established the actin cytoskeleton as a core component of mammalian CME, and our understanding of its contribution has been increasing at a rapid pace. In this review, we summarise the state-of-the-art regarding our understanding of the endocytic cytoskeleton, its physiological significance, and the questions that remain to be answered.     

The mammalian pseudoautosomal region

Despite being morphologically dissimilar, mammalian sex chromosomes pair in male meiosis. Molecular studies of the X and Y chromosomes in humans and mice have identified the pseudoautosomal region, a genetically unique region of shared, recombining sequences that fall within the meiotic pairing region. Complete meiotic and physical maps of the human pseudoautosomal region have been produced and the pseudoautosomal boundary has been cloned and sequenced. These studies have provided clues to mammalian sex chromosome function and evolution.     

The mammalian circadian clock

Organisms populating the earth are under the steady influence of daily and seasonal changes resulting from the planet's rotation and orbit around the sun. This periodic pattern most prominently manifested by the light-dark cycle has led to the establishment of endogenous circadian timing systems that synchronize biological functions to the environment. The mammalian circadian system is composed of many individual, tissue-specific clocks. To generate coherent physiological and behavioral responses, the phases of this multitude of clocks are orchestrated by the master circadian pacemaker residing in the suprachiasmatic nuclei of the brain. Genetic, biochemical and genomic approaches have led to major advances in understanding the molecular and cellular basis of mammalian circadian clock components and mechanisms.     

The mammalian centromere organization

Routine and recently obtained data on the pattern and functions of the mammalian centromeres and kinetochores have been reviewed. Several problems of kinetochore formation (centromere recognition, anaphase checkpoint) are specially discussed, in addition to the role played by centromere DNA in the interphase nucleus consideration.     

The function of the coracoacromial ligament

The function of the coracoacromial ligament was investigated in 8 dissecting-room scapulae. Strain gauges were attached around the coracoid process and the acromion, and tension (50 or 100 N) applied through the remaining muscle stumps. The results showed that, after division of the ligament, significantly more distortion could be measured in the acromion than in the coracoid process, which suggests that the 'stay' effect of the coracoacromial ligament is stronger for the former. Since the degree of distortion is largely dependent on the direction of pull, the ligament is interpreted as a dynamic brace between the two processes of the scapula.     

The mammalian TRPC cation channels

Transient Receptor Potential-Canonical (TRPC) channels are mammalian homologs of Transient Receptor Potential (TRP), a Ca(2+)-permeable channel involved in the phospholipase C-regulated photoreceptor activation mechanism in Drosophila. The seven mammalian TRPCs constitute a family of channels which have been proposed to function as store-operated as well as second messenger-operated channels in a variety of cell types. TRPC channels, together with other more distantly related channel families, make up the larger TRP channel superfamily. This review summarizes recent findings on the structure, regulation and function of the apparently ubiquitous TRPC cation channels.     

The mammalian clock and chronopharmacology

Increases in our understanding of the molecular control of circadian rhythms and subsequent signaling pathways has allowed for new therapeutic drug targets to be identified as well as for a better understanding of how to more efficaciously and safely utilize current drugs. Here, we review recent advances in targeting components of the molecular clock in mammals for the development of novel therapeutics as well as describe the impact of the circadian rhythm on drug efficacy and toxicity.