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Abstract Background A positive relationship between diversification (i.e., speciation) and nucleotide substitution rates is commonly reported for angiosperm clades. However, the underlying cause of this relationship is often unknown because multiple intrinsic and extrinsic factors can affect the relationship, and these have confounded previous attempts infer causation. Determining which factor drives this oft-reported correlation can lend insight into the macroevolutionary process. Results Using a new database of 13 time-calibrated angiosperm phylogenies based on internal transcribed spacer (ITS) sequences, and controlling for extrinsic variables of life history and habitat, I evaluated several potential intrinsic causes of this correlation. Speciation rates (λ) and relative extinction rates (ε) were positively correlated with mean substitution rates, but were uncorrelated with substitution rate heterogeneity. It is unlikely that the positive diversification-substitution correlation is due to accelerated molecular evolution during speciation (e.g., via enhanced selection or drift), because punctuated increases in ITS rate (i.e., greater mean and variation in ITS rate for rapidly speciating clades) were not observed. Instead, fast molecular evolution likely increases speciation rate (via increased mutational variation as a substrate for selection and reproductive isolation) but also increases extinction (via mutational genetic load). Conclusions In general, these results predict that clades with higher background substitution rates may undergo successful diversification under new conditions while clades with lower substitution rates may experience decreased extinction during environmental stasis.

The kinetic and thermodynamic consequences of intrinsic disorder in protein-protein recognition are controversial. We address this by inducing one partner of the high-affinity colicin E3 rRNase domain-Im3 complex (K(d) ≈ 10(-12) M) to become an intrinsically disordered protein (IDP). Through a variety of biophysical measurements, we show that a single alanine mutation at Tyr507 within the hydrophobic core of the isolated colicin E3 rRNase domain causes the enzyme to become an IDP (E3 rRNase(IDP)). E3 rRNase(IDP) binds stoichiometrically to Im3 and forms a structure that is essentially identical to the wild-type complex. However, binding of E3 rRNase(IDP) to Im3 is 4 orders of magnitude weaker than that of the folded rRNase, with thermodynamic parameters reflecting the disorder-to-order transition on forming the complex. Critically, pre-steady-state kinetic analysis of the E3 rRNase(IDP)-Im3 complex demonstrates that the decrease in affinity is mostly accounted for by a drop in the electrostatically steered association rate. Our study shows that, notwithstanding the advantages intrinsic disorder brings to biological systems, this can come at severe kinetic and thermodynamic cost.

Strains of Clostridium difficile produce toxins A and B that can cause diarrhoea and pseudomembranous colitis. Currently, there is no preventative therapy for this infection but antibodies to the toxins provide protection, therefore a toxoid-based vaccine is needed. To evaluate thermal stability, a lyophilized and liquid formulation of toxoids A and B were stored at a range of temperatures for 5 weeks. Changes in toxoid structures and immune responses in an animal model before and after the incubation period were assessed. The structural integrity and the immune responses to liquid formulations were affected when stored at 56°C but the lyophilized formulation was thermally stable and same treatment did not result in significant loss of immunological responses when immunized in an animal model.

The cytotoxin colicin E3 targets the 30S subunit of bacterial ribosomes and specifically cleaves 16S rRNA at the decoding centre, thereby inhibiting translation. Although the cleavage site is well known, it is not clear which step of translation is inhibited. We studied the effects of colicin E3 cleavage on ribosome functions by analysing individual steps of protein synthesis. We find that the cleavage affects predominantly the elongation step. The inhibitory effect of colicin E3 cleavage originates from the accumulation of sequential impaired decoding events, each of which results in low occupancy of the A site and, consequently, decreasing yield of elongating peptide. The accumulation leads to an almost complete halt of translation after reading of a few codons. The cleavage of 16S rRNA does not impair monitoring of codon-anticodon complexes or GTPase activation during elongation-factor Tu-dependent binding of aminoacyl-tRNA, but decreases the stability of the codon-recognition complex and slows down aminoacyl-tRNA accommodation in the A site. The tRNA-mRNA translocation is faster on colicin E3-cleaved than on intact ribosomes and is less sensitive to inhibition by the antibiotic viomycin.

Colicins are a family of antibacterial cytotoxins produced by Escherichia coli and released into the environment to reduce competition from other bacterial strains. Colicins kill the target cell by a variety of effects that include depolarisation of the cytoplasmic membrane, a non-specific DNase activity, a highly specific RNase activity or by inhibition of murein synthesis. This review summarises some important findings that implicate colicins as potential anti-tumor agents. Colicins appear to inhibit proliferation of tumor cell lines in a colicin-type--and cell line-dependent fashion and are more toxic to tumor cells than to normal cells within the body. This opens a potential for using bacterial colicins in combating cancer and raises a number of questions concerning the mechanism of action of colicins in targeting tumor cells, their specificity and applicability as anti-tumor therapeutics.

Patients with renal failure often succumb to infection. Alterations in the immune system of these patients, whether inherent to the disease process or precipitated by therapeutic regimens, undermine the promotion of wellness. Part 1 of this article provides a comprehensive understanding of normal immune system function. Part 2 discusses common immune abnormalities related to renal failure and its treatment. In addition, there is an overview of assessment techniques that can assist nephrology nurses in identifying alterations in a patient's immunologic status and direct care to prevent complications from altered immune function.

Patients with renal failure often succumb to infection. Alterations in the immune system of these patients, whether inherent to the disease process or precipitated by therapeutic regimens, undermine the promotion of wellness. This article provides a comprehensive understanding of common immune abnormalities, and assessment techniques that can assist nephrology nurses in identifying problems in a patient's immunologic status and direct care to prevent infections, to treat or prevent organ rejection, and to monitor for signs and symptoms of malignancies.

This article has discussed major concepts essential to an understanding of tissue and organ transplantation, rejection, and immune modulation. The reader is encouraged to review and understand these basic concepts to understand and appreciate the complexities of specific tissue and organ transplants described in this issue.

The systematic nursing process is an essential prerequisite for providing effective care for patients in shock. Nurses use assessment skills to identify actual and potential collaborative problems and nursing diagnoses. Once collaborative problems and nursing diagnoses are identified, the nurse develops appropriate individualized patient outcomes and plans care to accomplish the outcomes and resolve the problems. Nursing actions from the three domains may be included in the care plan. The evaluation phase assesses the adequacy of nursing actions in accomplishing the stated goals and returns the process to the stage of assessment. Application of the nursing care planning process to the patient in shock can be somewhat difficult because of the critical nature of the illness, complex assessment data, and rapidly changing interventions. It is indeed a challenge for the critical care nurse to integrate sound principles of nursing care planning into the busy intensive care environment, but the outcome of improved patient care is worth the effort.

When the MAP decreases below approximately 75 mm Hg, renal autoregulatory processes are no longer effective. Decreased renal blood flow often leads to ATN and its related uremic syndrome. The patient with ATN typically experiences four successive phases as the ATN progresses and then eventually resolves. During the oliguricanuric phase of ATN, multiple organ systems and physiologic processes are affected by the alterations occurring as the result of severely altered renal function. With appropriate treatment, such as fluid-electrolyte and acid-base control, nutritional support, and renal replacement therapy, a return to normal renal function is often possible.

The kidneys have primary responsibility for regulating the body's water and solute balance. Of the 180 L per day that are filtered at the glomerulus, about 98 to 99 per cent is reabsorbed throughout the course of the renal tubule. The kidney can produce a concentrated urine or a dilute urine, depending on the needs of the body. Several hormones, notably aldosterone, ADH, PTH, and calcitonin, as well as vitamin D, are important in the regulation of water and solutes. This article has not discussed other important renal functions as noted in the introduction.