The marine nitrogen cycle: recent discoveries,uncertainties and the potential relevance of climate change

The ocean''s nitrogen cycle is driven by complex microbial transformations, including nitrogen fixation, assimilation, nitrification, anammox and denitrification. Dinitrogen is the most abundant form of nitrogen in sea water but only accessible by nitrogen-fixing microbes. Denitrification and nitrification are both regulated by oxygen concentrations and potentially produce nitrous oxide (N₂O), a climate-relevant atmospheric trace gas. The world''s oceans, including the coastal areas and upwelling areas, contribute about 30 per cent to the atmospheric N₂O budget and are, therefore, a major source of this gas to the atmosphere. Human activities now add more nitrogen to the environment than is naturally fixed. More than half of the nitrogen reaches the coastal ocean via river input and atmospheric deposition, of which the latter affects even remote oceanic regions. A nitrogen budget for the coastal and open ocean, where inputs and outputs match rather well, is presented. Furthermore, predicted climate change will impact the expansion of the oceans'' oxygen minimum zones, the productivity of surface waters and presumably other microbial processes, with unpredictable consequences for the cycling of nitrogen. Nitrogen cycling is closely intertwined with that of carbon, phosphorous and other biologically important elements via biological stoichiometric requirements. This linkage implies that human alterations of nitrogen cycling are likely to have major consequences for other biogeochemical processes and ecosystem functions and services.     

Breast cancer at bone metastatic sites: recent discoveries and treatment targets

Breast carcinoma is the most common cancer of women. Bones are often involved with breast carcinoma metastases with the resulting morbidity and reduced quality of life. Breast cancer cells arriving at bone tissues mount supportive microenvironment by recruiting and modulating the activity of several host tissue cell types including the specialized bone cells osteoblasts and osteoclasts. Pathologically activated osteoclasts produce osteolytic lesions associated with bone pain, pathological fractures, cord compression and other complications of metastatic breast carcinoma at bone. Over the last decade there has been enormous growth of knowledge in the field of osteoclasts biology both in the physiological state and in the tumor microenvironment. This knowledge allowed the development and implementation of several targeted therapeutics that expanded the armamentarium of the oncologists dealing with the metastases-associated osteolytic disease. While the interactions of cancer cells with resident bone cells at the established metastatic gross lesions are well-studied, the preclinical events that underlie the progression of disseminated tumor cells into micrometastases and then into clinically-overt macrometastases are just starting to be uncovered. In this review, we discuss the established information and the most recent discoveries in the pathogenesis of osteolytic metastases of breast cancer, as well as the corresponding investigational drugs that have been introduced into clinical development.     

Lysine metabolism in mammalian brain: an update on the importance of recent discoveries

The lysine catabolism pathway differs in adult mammalian brain from that in extracerebral tissues. The saccharopine pathway is the predominant lysine degradative pathway in extracerebral tissues, whereas the pipecolate pathway predominates in adult brain. The two pathways converge at the level of ?¹-piperideine-6-carboxylate (P6C), which is in equilibrium with its open-chain aldehyde form, namely, α-aminoadipate δ-semialdehyde (AAS). A unique feature of the pipecolate pathway is the formation of the cyclic ketimine intermediate ?¹-piperideine-2-carboxylate (P2C) and its reduced metabolite l-pipecolate. A cerebral ketimine reductase (KR) has recently been identified that catalyzes the reduction of P2C to l-pipecolate. The discovery that this KR, which is capable of reducing not only P2C but also other cyclic imines, is identical to a previously well-described thyroid hormone-binding protein [μ-crystallin (CRYM)], may hold the key to understanding the biological relevance of the pipecolate pathway and its importance in the brain. The finding that the KR activity of CRYM is strongly inhibited by the thyroid hormone 3,5,3′-triiodothyronine (T₃) has far-reaching biomedical and clinical implications. The inter-relationship between tryptophan and lysine catabolic pathways is discussed in the context of shared degradative enzymes and also potential regulation by thyroid hormones. This review traces the discoveries of enzymes involved in lysine metabolism in mammalian brain. However, there still remain unanswered questions as regards the importance of the pipecolate pathway in normal or diseased brain, including the nature of the first step in the pathway and the relationship of the pipecolate pathway to the tryptophan degradation pathway.     

Evidence in hand: recent discoveries and the early evolution of human manual manipulation

For several decades, it was largely assumed that stone tool use and production were abilities limited to the genus Homo. However, growing palaeontological and archaeological evidence, comparative extant primate studies, as well as results from methodological advancements in biomechanics and morphological analyses, have been gradually accumulating and now provide strong support for more advanced manual manipulative abilities and tool-related behaviours in pre-Homo hominins than has been traditionally recognized. Here, I review the fossil evidence related to early hominin dexterity, including the recent discoveries of relatively complete early hominin hand skeletons, and new methodologies that are providing a more holistic interpretation of hand function, and insight into how our early ancestors may have balanced the functional requirements of both arboreal locomotion and tool-related behaviours.     

Phytochemical biopesticides: some recent developments

Synthetic pesticides in general, are highly toxic, persistent and their harmful residues contaminate crops, food commodities and pollute soils and groundwater. They adversely affect non-target organisms like pollinators, fish, birds, animals, and their excessive use results in increased resistance in pests. Phytochemical biopesticides on the other hand are less toxic, least persistent, environment friendly and safe to humans and non target organisms. Several phytochemical biopesticides like azadirachtin, nicotine, pyrethrins, rotenone, veratrum, annonins, rocaglamides, isobutylamides etc. have been successfully commercilalized in the past. In this review pesticidal products based on Madhuca indica (Mahua), Sapindus mukorossi (soapnut), Curcuma longa (turmeric), Pongamia glabra (karanja), Eupatorium adenophorum (Crofton weed), Tagetes erecta (marigold), Rheum emodi (Himalayan Rhubarb) and essential oil bearing plants have been discussed. Natural insecticide synergists derived from Anethum sowa and their semisynthetic derivatives have been used to prolong efficacy and counter resistance in insect pests.     

Seed traits and genes important for translational biology--highlights from recent discoveries

Seeds provide food, feed, fiber and fuel. They are also an important delivery system of genetic information, which is essential for the survival of wild species in ecosystems and the production of agricultural crops. In this review, seed traits and genes that are potentially important for agricultural applications are discussed. Over the long period of crop domestication, seed traits have been modified through intentional or unintentional selections. While most selections have led to seed traits favorable for agricultural consumption, such as larger seeds with higher nutritional value than the wild type, other manipulations in modern breeding sometimes led to negative traits, such as vivipary, precocious germination on the maternal plant or reduced seed vigor, as a side effect during the improvement of other characteristics. Greater effort is needed to overcome these problems that have emerged as a consequence of crop improvement. Seed biology researchers have characterized the function of many genes in the last decade, including those associated with seed domestication, which may be useful in addressing critical issues in modern agriculture, such as the prevention of vivipary and seed shattering or the enhancement of yields. Recent discoveries in seed biology research are highlighted in this review, with an emphasis on their potential for translational biology.     

Alpha-adrenoceptors: recent development and some comparative aspects

On anatomical and functional bases, alpha-adrenoceptors have been divided into pre- and postsynaptic alpha-adrenoceptors. Recently, alpha-adrenoceptors have been classified as alpha 1 and alpha 2 according to their pharmacological responses, irrespective of their anatomical location. The presynaptic alpha-adrenoceptors, which have been recognized as alpha 2, determine the frequency of the nerve impulses travelling along the axon and also the amount of transmitter released per nerve impulse from the varicose terminal. Postsynaptic alpha-adrenoceptors have been recognized in various tissues including smooth muscle, pancreatic islets, fat cells, platelets and other tissues. Both alpha 1- and alpha 2-adrenoceptors have been located postsynaptically. alpha-Adrenoceptors have been found also in the central nervous system. Generally, they fall into the same categories (alpha 1 and alpha 2) as the peripheral alpha-adrenoceptors. A new class of drugs, the so called calcium blockers, inhibit the postsynaptic response to alpha 2 stimulation but not the alpha 1-mediated response, indicating that the alpha 2-adrenoceptors are dependent on Ca2+ ions for their function. In the most primitive group of vertebrates, the fishes, alpha-adrenoceptors seem to be different in as much as they do not respond to many of the classical drugs employed to distinguish between alpha-adrenoceptors in mammals. In reptiles and amphibians alpha 2-adrenoceptors have been shown to exist. These receptors are involved in the regulation of melanocytes. In the most advanced non-mammalian vertebrates (birds) both peripheral and central alpha-adrenoceptors seem to be qualitatively similar to the mammalian types.     

Inducible degradation of hydroxyproline in Pseudomonas putida: pathway regulation and hydroxyproline uptake

Studies in Pseudomonas putida of the inducible degradation of hydroxyproline to alpha-ketoglutarate have indicated that either of the two epimers, hydroxy-l-proline or allohydroxy-d-proline, acts as an inducer of all the pathway enzymes. In a mutant lacking the first enzyme of the sequence, hydroxyproline-2-epimerase, which interconverts these two hydroxyproline epimers, either epimer is still equally active as an inducer of the remaining three enzymes, suggesting that each epimer has intrinsic inducer activity. The second and third enzymes of the sequence were induced coordinately. The induction process appeared to be insensitive to catabolite repression under a number of experimental conditions. The induced enzymes were stable even under conditions of nitrogen starvation and other conditions designed to increase protein turnover. In addition to inducing the degradative enzymes, the two hydroxyproline epimers were also found to induce an uptake system that concentrates hydroxyproline intracellularly. Either amino acid induced the uptake system for its epimer as well as for itself.     

The history of the capillary wall: doctors, discoveries, and debates

In 1628, William Harvey provided definitive evidence that blood circulates. The notion that blood travels around the body in a circle raised the important question of how nutrients pass between blood and underlying tissue. Perhaps, Harvey posited, arterial blood pours into the flesh as into a sponge, only then to find its way into the veins. Far from solving this problem, Marcello Malpighi's discovery of the capillaries in 1661 only added to the dilemma: surely, some argued, these entities are little more than channels drilled into tissues around them. As we discuss in this review, it would take over 200 years to arrive at a consensus on the basic structure and function of the capillary wall. A consideration of the history of this period provides interesting insights into not only the central importance of the capillary as a focus of investigation, but also the enormous challenges associated with studying these elusive structures.