Frequent burning promotes invasions of alien plants into a mesic African savanna

Fire is both inevitable and necessary for maintaining the structure and functioning of mesic savannas. Without disturbances such as fire and herbivory, tree cover can increase at the expense of grass cover and over time dominate mesic savannas. Consequently, repeated burning is widely used to suppress tree recruitment and control bush encroachment. However, the effect of regular burning on invasion by alien plant species is little understood. Here, vegetation data from a long-term fire experiment, which began in 1953 in a mesic Zimbabwean savanna, were used to test whether the frequency of burning promoted alien plant invasion. The fire treatments consisted of late season fires, lit at 1-, 2-, 3-, and 4-year intervals, and these regularly burnt plots were compared with unburnt plots. Results show that over half a century of frequent burning promoted the invasion by alien plants relative to areas where fire was excluded. More alien plant species became established in plots that had a higher frequency of burning. The proportion of alien species in the species assemblage was highest in the annually burnt plots followed by plots burnt biennially. Alien plant invasion was lowest in plots protected from fire but did not differ significantly between plots burnt triennially and quadrennially. Further, the abundance of five alien forbs increased significantly as the interval (in years) between fires became shorter. On average, the density of these alien forbs in annually burnt plots was at least ten times as high as the density of unburnt plots. Plant diversity was also altered by long-term burning. Total plant species richness was significantly lower in the unburnt plots compared to regularly burnt plots. These findings suggest that frequent burning of mesic savannas enhances invasion by alien plants, with short intervals between fires favouring alien forbs. Therefore, reducing the frequency of burning may be a key to minimising the risk of alien plant spread into mesic savannas, which is important because invasive plants pose a threat to native biodiversity and may alter savanna functioning

Regulation of neutrophil senescence by microRNAs

Neutrophils are rapidly recruited to sites of tissue injury or infection, where they protect against invading pathogens. Neutrophil functions are limited by a process of neutrophil senescence, which renders the cells unable to respond to chemoattractants, carry out respiratory burst, or degranulate. In parallel, aged neutrophils also undergo spontaneous apoptosis, which can be delayed by factors such as GMCSF. This is then followed by their subsequent removal by phagocytic cells such as macrophages, thereby preventing unwanted inflammation and tissue damage. Neutrophils translate mRNA to make new proteins that are important in maintaining functional longevity. We therefore hypothesised that neutrophil functions and lifespan might be regulated by microRNAs expressed within human neutrophils. Total RNA from highly purified neutrophils was prepared and subjected to microarray analysis using the Agilent human miRNA microarray V3. We found human neutrophils expressed a selected repertoire of 148 microRNAs and that 6 of these were significantly upregulated after a period of 4 hours in culture, at a time when the contribution of apoptosis is negligible. A list of predicted targets for these 6 microRNAs was generated from http://mirecords.biolead.org and compared to mRNA species downregulated over time, revealing 83 genes targeted by at least 2 out of the 6 regulated microRNAs. Pathway analysis of genes containing binding sites for these microRNAs identified the following pathways: chemokine and cytokine signalling, Ras pathway, and regulation of the actin cytoskeleton. Our data suggest that microRNAs may play a role in the regulation of neutrophil senescence and further suggest that manipulation of microRNAs might represent an area of future therapeutic interest for the treatment of inflammatory disease

Four theorems on the psychometric function

In a 2-alternative forced-choice (2AFC) discrimination task, observers choose which of two stimuli has the higher value. The psychometric function for this task gives the probability of a correct response for a given stimulus difference, Δx. This paper proves four theorems about the psychometric function. Assuming the observer applies a transducer and adds noise, Theorem 1 derives a convenient general expression for the psychometric function. Discrimination data are often fitted with a Weibull function. Theorem 2 proves that the Weibull "slope" parameter, β, can be approximated by [Formula: see text], where [Formula: see text] is the β of the Weibull function that fits best to the cumulative noise distribution, and [Formula: see text] depends on the transducer. We derive general expressions for [Formula: see text] and [Formula: see text], from which we derive expressions for specific cases. One case that follows naturally from our general analysis is Pelli's finding that, when [Formula: see text], [Formula: see text]. We also consider two limiting cases. Theorem 3 proves that, as sensitivity improves, 2AFC performance will usually approach that for a linear transducer, whatever the actual transducer; we show that this does not apply at signal levels where the transducer gradient is zero, which explains why it does not apply to contrast detection. Theorem 4 proves that, when the exponent of a power-function transducer approaches zero, 2AFC performance approaches that of a logarithmic transducer. We show that the power-function exponents of 0.4-0.5 fitted to suprathreshold contrast discrimination data are close enough to zero for the fitted psychometric function to be practically indistinguishable from that of a log transducer. Finally, Weibull β reflects the shape of the noise distribution, and we used our results to assess the recent claim that internal noise has higher kurtosis than a Gaussian. Our analysis of β for contrast discrimination suggests that, if internal noise is stimulus-independent, it has lower kurtosis than a Gaussian

Therapeutic DNA vaccine induces broad T cell responses in the gut and sustained protection from viral rebound and AIDS in SIV-infected rhesus macaques.

Immunotherapies that induce durable immune control of chronic HIV infection may eliminate the need for life-long dependence on drugs. We investigated a DNA vaccine formulated with a novel genetic adjuvant that stimulates immune responses in the blood and gut for the ability to improve therapy in rhesus macaques chronically infected with SIV. Using the SIV-macaque model for AIDS, we show that epidermal co-delivery of plasmids expressing SIV Gag, RT, Nef and Env, and the mucosal adjuvant, heat-labile E. coli enterotoxin (LT), during antiretroviral therapy (ART) induced a substantial 2-4-log fold reduction in mean virus burden in both the gut and blood when compared to unvaccinated controls and provided durable protection from viral rebound and disease progression after the drug was discontinued. This effect was associated with significant increases in IFN-γ T cell responses in both the blood and gut and SIV-specific CD8+ T cells with dual TNF-α and cytolytic effector functions in the blood. Importantly, a broader specificity in the T cell response seen in the gut, but not the blood, significantly correlated with a reduction in virus production in mucosal tissues and a lower virus burden in plasma. We conclude that immunizing with vaccines that induce immune responses in mucosal gut tissue could reduce residual viral reservoirs during drug therapy and improve long-term treatment of HIV infection in humans

The post-vaccine microevolution of invasive Streptococcus pneumoniae

The 7-valent pneumococcal conjugated vaccine (PCV7) has affected the genetic population of Streptococcus pneumoniae in pediatric carriage. Little is known however about pneumococcal population genomics in adult invasive pneumococcal disease (IPD) under vaccine pressure. We sequenced and serotyped 349 strains of S. pneumoniae isolated from IPD patients in Nijmegen between 2001 and 2011. Introduction of PCV7 in the Dutch National Immunization Program in 2006 preluded substantial alterations in the IPD population structure caused by serotype replacement. No evidence could be found for vaccine induced capsular switches. We observed that after a temporary bottleneck in gene diversity after the introduction of PCV7, the accessory gene pool re-expanded mainly by genes already circulating pre-PCV7. In the post-vaccine genomic population a number of genes changed frequency, certain genes became overrepresented in vaccine serotypes, while others shifted towards non-vaccine serotypes. Whether these dynamics in the invasive pneumococcal population have truly contributed to invasiveness and manifestations of disease remains to be further elucidated. We suggest the use of whole genome sequencing for surveillance of pneumococcal population dynamics that could give a prospect on the course of disease, facilitating effective prevention and management of IPD

Computer-assisted versus non-computer-assisted preoperative planning of corrective osteotomy for extra-articular distal radius malunions: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Malunion is the most common complication of distal radius fracture. It has previously been demonstrated that there is a correlation between the quality of anatomical correction and overall wrist function. However, surgical correction can be difficult because of the often complex anatomy associated with this condition. Computer assisted surgical planning, combined with patient-specific surgical guides, has the potential to improve pre-operative understanding of patient anatomy as well as intra-operative accuracy. For patients with malunion of the distal radius fracture, this technology could significantly improve clinical outcomes that largely depend on the quality of restoration of normal anatomy. Therefore, the objective of this study is to compare patient outcomes after corrective osteotomy for distal radius malunion with and without preoperative computer-assisted planning and peri-operative patient-specific surgical guides.</p> <p>Methods/Design</p> <p>This study is a multi-center randomized controlled trial of conventional planning versus computer-assisted planning for surgical correction of distal radius malunion. Adult patients with extra-articular malunion of the distal radius will be invited to enroll in our study. After providing informed consent, subjects will be randomized to two groups: one group will receive corrective surgery with conventional preoperative planning, while the other will receive corrective surgery with computer-assisted pre-operative planning and peri-operative patient specific surgical guides. In the computer-assisted planning group, a CT scan of the affected forearm as well as the normal, contralateral forearm will be obtained. The images will be used to construct a 3D anatomical model of the defect and patient-specific surgical guides will be manufactured. Outcome will be measured by DASH and PRWE scores, grip strength, radiographic measurements, and patient satisfaction at 3, 6, and 12 months postoperatively.</p> <p>Discussion</p> <p>Computer-assisted surgical planning, combined with patient-specific surgical guides, is a powerful new technology that has the potential to improve the accuracy and consistency of orthopaedic surgery. To date, the role of this technology in upper extremity surgery has not been adequately investigated, and it is unclear whether its use provides any significant clinical benefit over traditional preoperative imaging protocols. Our study will represent the first randomized controlled trial investigating the use of computer assisted surgery in corrective osteotomy for distal radius malunions.</p> <p>Trial registration</p> <p>NCT01193010</p

A Live-Attenuated HSV-2 ICP0− Virus Elicits 10 to 100 Times Greater Protection against Genital Herpes than a Glycoprotein D Subunit Vaccine

Glycoprotein D (gD-2) is the entry receptor of herpes simplex virus 2 (HSV-2), and is the immunogen in the pharmaceutical industry's lead HSV-2 vaccine candidate. Efforts to prevent genital herpes using gD-2 subunit vaccines have been ongoing for 20 years at a cost in excess of $100 million. To date, gD-2 vaccines have yielded equivocal protection in clinical trials. Therefore, using a small animal model, we sought to determine if a live-attenuated HSV-2 ICP0− virus would elicit better protection against genital herpes than a gD-2 subunit vaccine. Mice immunized with gD-2 and a potent adjuvant (alum+monophosphoryl lipid A) produced high titers of gD-2 antibody. While gD-2-immunized mice possessed significant resistance to HSV-2, only 3 of 45 gD-2-immunized mice survived an overwhelming challenge of the vagina or eyes with wild-type HSV-2 (MS strain). In contrast, 114 of 115 mice immunized with a live HSV-2 ICP0− virus, 0ΔNLS, survived the same HSV-2 MS challenges. Likewise, 0ΔNLS-immunized mice shed an average 125-fold less HSV-2 MS challenge virus per vagina relative to gD-2-immunized mice. In vivo imaging demonstrated that a luciferase-expressing HSV-2 challenge virus failed to establish a detectable infection in 0ΔNLS-immunized mice, whereas the same virus readily infected naïve and gD-2-immunized mice. Collectively, these results suggest that a HSV-2 vaccine might be more likely to prevent genital herpes if it contained a live-attenuated HSV-2 virus rather than a single HSV-2 protein

Heterogeneity of O6-alkylguanine DNA-alkyltransferase expression in human breast tumours

An important determinant of cellular resistance to chemotherapeutic O6-alkylating agents, which comprise methylating and chloroethylating agents, is the ability of cells to repair alkylation damage at the O6-position of guanine in DNA. This is achieved by a specific DNA repair enzyme O6-alkylguanine DNA-alkyltransferase. In this study O6-alkylguanine DNA-alkyltransferase expression was measured in human breast tumours using both biochemical and immunohistochemical techniques. O6-alkylguanine DNA-alkyltransferase activity was then compared with known clinical prognostic indices to assess the potential role of O6-alkylguanine DNA-alkyltransferase in predicting the behaviour of this common malignancy. The application of both biochemical and immunohistochemical techniques was feasible and practical. Most breast tumours expressed high levels of O6-alkylguanine DNA-alkyltransferase. Immunohistochemical analysis showed marked variation in expression not only between individuals but also within individual tumours, and in the same patient, between metastases and between primary tumour and metastatic site. O6-alkylguanine DNA-alkyltransferase activity in tissue extracts significantly correlated not only with immunohistochemical staining intensity determined by subjective quantitation, but also with measures of protein levels using a computerised image analysis system including mean grey (P<0.001), percentage of cells positive for O6-alkylguanine DNA-alkyltransferase (P<0.001), and integrated optical density (P<0.001). O6-alkylguanine DNA-alkyltransferase expression did not correlate with any of the established clinical prognostic indicators for current treatment regimens. However, immunohistochemical offers a rapid and convenient method for assessing potential utility of O6-alkylating agents or O6-alkylguanine DNA-alkyltransferase inactivating agents in future studies of breast cancer treatment

Carbon stock growth in a forest stand: the power of age

BACKGROUND: Understanding the relationship between the age of a forest stand and its biomass is essential for managing the forest component of the global carbon cycle. Since biomass increases with stand age, postponing harvesting to the age of biological maturity may result in the formation of a large carbon sink. This article quantifies the carbon sequestration capacity of forests by suggesting a default rule to link carbon stock and stand age. RESULTS: The age dependence of forest biomass is shown to be a power-law monomial where the power of age is theoretically estimated to be 4/5. This theoretical estimate is close to the known empirical estimate; therefore, it provides a scientific basis for a quick and transparent assessment of the benefits of postponing the harvest, suggesting that the annual magnitude of the sink induced by delayed harvest lies in the range of 1–2% of the baseline carbon stock. CONCLUSION: The results of this study imply that forest age could be used as an easily understood and scientifically sound measure of the progress in complying with national targets on the protection and enhancement of forest carbon sinks

A Survey on the Krein-von Neumann Extension, the corresponding Abstract Buckling Problem, and Weyl-Type Spectral Asymptotics for Perturbed Krein Laplacians in Nonsmooth Domains

In the first (and abstract) part of this survey we prove the unitary equivalence of the inverse of the Krein--von Neumann extension (on the orthogonal complement of its kernel) of a densely defined, closed, strictly positive operator, $S\geq \varepsilon I_{\mathcal{H}}$ for some $\varepsilon >0$ in a Hilbert space $\mathcal{H}$ to an abstract buckling problem operator. This establishes the Krein extension as a natural object in elasticity theory (in analogy to the Friedrichs extension, which found natural applications in quantum mechanics, elasticity, etc.). In the second, and principal part of this survey, we study spectral properties for $H_{K,\Omega}$, the Krein--von Neumann extension of the perturbed Laplacian $-\Delta+V$ (in short, the perturbed Krein Laplacian) defined on $C^\infty_0(\Omega)$, where $V$ is measurable, bounded and nonnegative, in a bounded open set $\Omega\subset\mathbb{R}^n$ belonging to a class of nonsmooth domains which contains all convex domains, along with all domains of class $C^{1,r}$, $r>1/2$.Comment: 68 pages. arXiv admin note: extreme text overlap with arXiv:0907.144