Bioconjugation of Green Fluorescent Protein via an Unexpectedly Stable Cyclic Sulfonium Intermediate

Bioconjugation of superfolder GFP involving the formation of an unusually stable, and unprecedented, cyclic sulfonium species is described. This sulfonium can undergo smooth reaction with a range of nucleophiles to give sulfur-, selenium- and azide-modified GFP derivatives in high conversions

Optimisation of the dibromomaleimide (DBM) platform for native antibody conjugation by accelerated post-conjugation hydrolysis

Disulfide bridging offers a convenient approach to generate site-selective antibody conjugates from native antibodies. To optimise the reagents available to achieve this strategy, we describe here the use of dibromomaleimides designed to undergo accelerated post-conjugation hydrolysis. Conjugation and hydrolysis, which serve to 'lock' the conjugates as robustly stable maleamic acids, is achieved in just over 1 h. This dramatic acceleration is also shown to infer significant improvements in homogeneity, as demonstrated by mass spectrometry analysis

Multiparticulate Drug Delivery Systems for Controlled Release

Pharmaceutical invention and research are increasingly focusing on delivery systems which enhance desirable therapeutic objectives while minimising side effects. Recent trends indicate that multiparticulate drug delivery systems are especially suitable for achieving controlled or delayed release oral formulations with low risk of dose dumping, flexibility of blending to attain different release patterns as well as reproducible and short gastric residence time. The release of drug from microparticles depends on a variety of factors including the carrier used to form the multiparticles and the amount of drug contained in them. Consequently, multiparticulate drug delivery systems provide tremendous opportunities for designing new controlled and delayed release oral formulations, thus extending the frontier of future pharmaceutical development. Keywords: Dose dumping, Microparticles, Multiparticulate delivery system, Delayed release Tropical Journal of Pharmaceutical Research Vol. 7 (3) 2008: pp. 1067-107

Current indications for open Kuntscher nailing of femoral shaft fractures

We retrospectively reviewed 32 patients with fractures of the femoral shaft treated with open Kuntscher nailing. All fractures were simple transverse, short oblique or Winquist-Hensen type I and 11 comminuted diaphyseal fractures. Average operating time was 45 minutes (35 to 55 minutes). Patients were discharged from the hospital within 7 days of surgery. All fractures healed within 12-14 weeks and the union rate was 100%. One patient developed superficial wound infection. Two nails were too long proximally and two nails protruded into the knee joints. There were no rotational deformities nor shortening. One patient had limited knee flexion (less than 60o) and one fracture united in 8o varus. We concluded that open Kuntscher nailing is still indicated in the following situations: in hospitals with no traction table and image intensifier, in obese patients, in Grade I and II compound fractures, in polytrauma patients, in irreducible fractures and in patients with vascular injuries.Keywords: Kuntscher nail, intramedullary nail, femoral fractur

Time-traveling seeds reveal that plant regeneration and growth traits are responding to climate change

Studies assessing the biological impacts of climate change typically rely on long-term, historic data to measure trait responses to climate through time. Here, we overcame the problem of absent historical data by using resurrected seeds to capture historic plant-trait data for a number of plant regeneration and growth traits. We collected seed and seedling trait measurements from resurrected historic seeds and compared these with modern seed and seedling traits collected from the same species in the same geographic location. We found a total of 43 species from southeastern Australia for which modern/historic seed pairs could be located. These species were located in a range of regions that have undergone different amounts of climate change across a range of temperature, precipitation, and extreme measures of climate. There was a correlation between the amount of change in climate metrics, and the amount of change in plant traits. Using stepwise model selection, we found that for all regeneration and growth trait changes (except change in stem density), the most accurate model selected at least two measures of climate change. Changes in extreme measures of climate, such as heat-wave duration and changes in climate variability, were more strongly related to changes in regeneration and growth traits than changes in mean climate metrics. Across our species, for every 5% increase in temperature variability, there was a threefold increase in the probability of seed viability and seed germination success. An increase of 1 d in the maximum duration of dry spells through time led to a 1.5-fold decrease in seed viability and seeds became 30% flatter/thinner. Regions where the maximum heat-wave duration had increased by 10 d saw a 1.35-cm decrease in seedling height and a 1.04-g decrease in seedling biomass. Rapid responses in plant traits to changes in climate may be possible; however, it is not clear whether these changes will be fast enough for plants to keep pace with future climate change

Southern hemisphere plants show more delays than advances in flowering phenology

Shifts in flowering phenology have been studied in detail in the northern hemisphere and are a key plant response to climate change. However, there are relatively fewer data on species' phenological shifts in the southern hemisphere. We combined historic field data, data from herbarium specimens dating back to 1842 and modern field data for 37 Australian species to determine whether species were flowering earlier in the year than they had in the past. We also combined our results with data compiled in the southern and northern hemispheres, respectively, to determine whether southern hemisphere species are showing fewer advances in flowering phenology through time. Across our study species, we found that 12 species had undergone significant shifts in flowering time, with four species advancing their flowering and eight species delaying their flowering. The remaining 25 species showed no significant shifts in their flowering phenology. These findings are important because delays or lack of shifts in flowering phenology can lead to mismatches in trophic interactions between plants and pollinators or seed dispersers, which can have substantial impacts on ecosystem functioning and primary productivity. Combining our field results with data compiled from the literature showed that only 58.5% of southern hemisphere species were advancing their flowering time, compared with 81.6% of species that were advancing their flowering time in the northern hemisphere. Our study provides further evidence that it is not adequate for ecologists to assume that southern hemisphere ecosystems will respond to future climate change in the same way as ecosystems north of the Equator. Synthesis. Field data and data from the literature indicate that southern hemisphere species are showing fewer advances in their flowering phenology through time, especially in comparison to northern hemisphere species

The role of the future physician: building on shifting sands

The role of the future physician in the NHS is of interest to current doctors, patients, policymakers and the wider public. Amid the COVID-19 pandemic, it has never been more clear that the healthcare needs of the population, and the technical and scientific advances with which to solve them, are rapidly evolving and the medical workforce must adapt to these changes to deliver personalised healthcare. This article considers the current challenges that need to be addressed to deliver a future physician-led healthcare service that works for its patients. Key themes are expanded upon, including the changing healthcare workforce, digital and technological innovation, service delivery, complex conditions and changing patient demographics. The impact and challenges of the ongoing COVID-19 pandemic on these factors are highlighted. Avenues for development are suggested, both in postgraduate medical training and the health service as a whole. These changes will be required to deliver the physicians of the future, imbued with the skills and attributes they will need to provide a high standard of care in the mid-21st century

Management of pregnancy in women with rheumatoid arthritis

Rheumatoid arthritis (RA) disease activity may improve during pregnancy but postpartum flares are common. Patients taking disease-modifying antirheumatic drugs should be counselled about effective contraception. Knowledge about drug safety in pregnancy is limited but the Therapeutic Goods Administration categories and online resources are a guide to the data currently available. Begin prepregnancy counselling as early as possible to allow for cessation of teratogenic medications and optimisation of RA disease control. For unplanned pregnancies, cease teratogenic medications immediately and refer to a genetic counsellor and maternal–fetal medicine specialist for risk assessment and advice

Limited range shifting in biocrusts despite climate warming: A 25-year resurvey

The ranges of many species globally have already shifted to maintain climatic equilibrium in the face of climate change. Biocrusts—soil surface dwelling communities of lichens, bryophytes and microbes—play important functional roles in many ecosystems, particularly in drylands. Compared to better studied animal and plant taxa, dryland biocrusts have different establishment requirements and have never been assessed for historical range shifts. Here, we revisited the sites (N = 204) of a 25-year-old biocrust survey across a large area (400,000 km2) of drylands in south-eastern Australia. We used quadratic models to quantify changes in the climate niches of 15 lichen, eight moss and five liverwort taxa, as well as biocrust cover and richness. Our models showed that the observed climatic niches of most taxa have become hotter and drier in the past quarter century, yet the responses of the vast majority of taxa are consistent with remaining in the same geographic space. A similar pattern was observed at the community level, where the peak of biocrust cover and richness now occurs in a hotter, drier environment. Notable exceptions were the liverwort Riccia lamellosa and lichens in the genera Cladonia and Xanthoparmelia, which showed signs of contraction at their arid range edges. Unlike more mobile taxa, most biocrust species have yet to shift geographically and may already be lagging behind the pace of climate change. One explanation for the mortality lag is that long-term climate variability in the system is extensive, which may have selected for the ability to withstand multi-year warm periods as long as there is an eventual return to milder conditions. However, no forecasts of future climate include a return to milder conditions, suggesting there will be an eventual loss of ecosystem multifunctionality at the contracting front. Expansion lags are most likely due to delays in the mortality of competing vascular plants. Synthesis: Our study provides a valuable contribution to the knowledge of range shifts in understudied taxa and highlights a future need to promote the expansion of biocrusts to maintain the provision of ecosystem functions and services across their range

alpha,alpha '-Dihydroxyketone formation using aromatic and heteroaromatic aldehydes with evolved transketolase enzymes

Transketolase mutants have been identified that accept aromatic acceptors with good stereoselectivities, in particular benzaldehyde for which the wild type enzyme showed no activity