Osteoporosis is the most prevalent metabolic bone disease that affects half the women in the sixth and seventh decade of life. Osteoporosis is characterized by uncoupled bone resorption that leads to low bone mass, compromised microarchitecture and structural deterioration that increases the likelihood of fracture with minimal trauma, known as fragility fractures. Several factors contribute to osteoporosis in men and women. In women, menopause – the cessation of ovarian function, is one of the leading causes of primary osteoporosis. Over the past three decades there has been growing appreciation that the adaptive immune system plays a fundamental role in the development of postmenopausal osteoporosis, both in humans and in mouse models. In this review, we highlight recent data on the interactions between T cells and the skeletal system in the context of postmenopausal osteoporosis. Finally, we review recent studies on the interventions to ameliorate osteoporosis.

Cyanobacteria are photosynthetic organisms and are the only prokaryotes known to have a circadian lifestyle. Unicellular diazotrophic cyanobacteria such asCyanothecesp. ATCC 51142 produce oxygen and can also fix atmospheric nitrogen, a process exquisitely sensitive to oxygen. To accommodate such antagonistic processes, the intracellular environment ofCyanotheceoscillates between aerobic and anaerobic conditions during a day–night cycle. This is accomplished by temporal separation of the two processes: photosynthesis during the day and nitrogen fixation at night. Although previous studies have examined periodic changes in transcript levels for a limited number of genes inCyanotheceand other unicellular diazotrophic cyanobacteria, a comprehensive study of transcriptional activity in a nitrogen-fixing cyanobacterium is necessary to understand the impact of the temporal separation of photosynthesis and nitrogen fixation on global gene regulation and cellular metabolism. We have examined the expression patterns of nearly 5,000 genes inCyanothece51142 during two consecutive diurnal periods. Our analysis showed that ≈30% of these genes exhibited robust oscillating expression profiles. Interestingly, this set included genes for almost all central metabolic processes inCyanothece51142. A transcriptional network of all genes with significantly oscillating transcript levels revealed that the majority of genes encoding enzymes in numerous individual biochemical pathways, such as glycolysis, oxidative pentose phosphate pathway, and glycogen metabolism, were coregulated and maximally expressed at distinct phases during the diurnal cycle. These studies provide a comprehensive picture of how a physiologically relevant diurnal light–dark cycle influences the metabolism in a photosynthetic bacterium.

Cyanobacteria are key contributors to global photosynthetic productivity, and iron availability is essential for cyanobacterial proliferation. While iron is abundant in the earth's crust, its unique chemical properties render it a limiting factor for photoautotrophic growth. As compared to other nonphotosynthetic organisms, oxygenic photosynthetic organisms such as cyanobacteria, algae, and green plants need large amounts of iron to maintain functional PSI complexes in their photosynthetic apparatus. Ferritins and bacterioferritins are ubiquitously present iron-storage proteins. We have found that in the cyanobacterium Synechocystis sp. PCC 6803 (Synechocystis 6803), bacterioferritins are responsible for the storage of as much as 50% of cellular iron. Synechocystis 6803, as well as many other cyanobacterial species, have two bacterioferritins, BfrA and BfrB, in which either the heme binding or di-iron center ligating residues are absent. Purified bacterioferritin complex from Synechocystis 6803 has both BfrA and BfrB proteins. Targeted mutagenesis of each of the two bacterioferritin genes resulted in poor growth under iron-deprived conditions. Inactivation of both genes did not result in a more severe phenotype. These results support the presence of a heteromultimeric structure of Synechocystis bacterioferritin, in which one subunit ligates a di-iron center while the other accommodates heme binding. Notably, the reduced internal iron concentrations in the mutant cells resulted in a lower content of PSI. In addition, they triggered iron starvation responses even in the presence of normal levels of external iron, thus demonstrating a central role of bacterioferritins in iron homeostasis in these photosynthetic organisms.

Unicellular cyanobacteria have recently been recognized for their contributions to nitrogen fixation in marine environments, a function previously thought to be filled mainly by filamentous cyanobacteria such as Trichodesmium . To begin a systems level analysis of the physiology of the unicellular N ₂ -fixing microbes, we have sequenced to completion the genome of Cyanothece sp. ATCC 51142, the first such organism. Cyanothece 51142 performs oxygenic photosynthesis and nitrogen fixation, separating these two incompatible processes temporally within the same cell, while concomitantly accumulating metabolic products in inclusion bodies that are later mobilized as part of a robust diurnal cycle. The 5,460,377-bp Cyanothece 51142 genome has a unique arrangement of one large circular chromosome, four small plasmids, and one linear chromosome, the first report of a linear element in the genome of a photosynthetic bacterium. On the 429,701-bp linear chromosome is a cluster of genes for enzymes involved in pyruvate metabolism, suggesting an important role for the linear chromosome in fermentative processes. The annotation of the genome was significantly aided by simultaneous global proteomic studies of this organism. Compared with other nitrogen-fixing cyanobacteria, Cyanothece 51142 contains the largest intact contiguous cluster of nitrogen fixation-related genes. We discuss the implications of such an organization on the regulation of nitrogen fixation. The genome sequence provides important information regarding the ability of Cyanothece 51142 to accomplish metabolic compartmentalization and energy storage, as well as how a unicellular bacterium balances multiple, often incompatible, processes in a single cell.