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Methods capable of distributing antitumour therapeutics uniformly throughout an entire tumour and that can suppress metastasis at the same time, would be of great significance in improving cancer treatment. Bacteria-mediated synergistic therapies have been explored for better specificity, temporal and spatial controllability, as well for providing regulation of the immune microenvironment, in order to provide improved cancer treatment. To achieve this goal, here we developed an engineered bacteria delivery system (GDOX@HSEc) using synthetic biology and interfacial chemistry technologies. The engineered bacteria were concurrently modified to express heparin sulfatase 1 (HSulf-1) inside (HSEc), to attach doxorubicin-loaded glycogen nanoparticles (GDOX NPs) on their surface. Here we demonstrate that HSEc can actively target and colonise tumour sites resulting in HSulf-1 overexpression, thereby suppressing angiogenesis and metastasis. Simultaneously, the GDOX NPs were able to penetrate into tumour cells, leading to intracellular DNA damage. Our results confirmed that a combination of biotherapy and chemotherapy using GDOX@HSEc resulted in significant melanoma suppression in murine models, with reduced side effects. This study provides a powerful platform for the simultaneous delivery of biomacromolecules and chemotherapeutic drugs to tumours, representing an innovative strategy potentially more effective in treating solid tumours. An original engineered bacteria-based system (GDOX@HSEc) was developed using synthetic biology and interfacial chemistry technologies to concurrently produce naturally occurring heparin sulfatase 1 (HSulf-1) inside and anchor doxorubicin-loaded glycogen nanoparticles on the surface. GDOX@HSEc allowed for combined local delivery of chemotherapeutic agents along with the enzymes and immunostimulatory bacterial adjuvants, which resulted in a synergistic action in the inhibition of tumour growth and metastasis. The study provides a potential therapeutic approach that allows therapeutic agents to be distributed in a spatiotemporally controllable manner in tumours for combinatorial enhanced therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Periprosthetic fracture following knee arthroplasty is a rare but devastating complication associated with significant morbidity. With unicompartmental knee arthroplasty being performed far less frequently than total knee arthroplasty, periprosthetic fracture following unicompartmental knee arthroplasty presents a particular challenge to orthopaedic surgeons, due to clinical unfamiliarity and sparsity of literature. An up-to-date review of the epidemiology, risk factors, and management strategies for PPF after UKA is presented. [ABSTRACT FROM AUTHOR]

Community resilience determines a communities' ability to prepare for disruptions, absorb their effects, recover, and adapt if the situation requires it. This meta-analysis of pre-pandemic (1980–2017) academic literature in military and non-military contexts to examine community resilience interventions and performance outcomes or community functioning. The study also incorporates the role of cohesion because this emerged as a strong theme in the literature. The analysis aims specifically to identify benefits of resilience interventions for military communities that are frequently subjects of disruptions. The analysis connects interventions to the phases of resilience to identify which are well-covered by existing interventions, as well as gaps in that could indicate the need to update existing interventions or establishing new interventions. The recovery phase of resilience is strongly represented in interventions, while interventions to improve planning and adaptation capacities were sparsely represented in pre-pandemic literature. [ABSTRACT FROM AUTHOR]

Decellularized nerve, or acellular nerve allografts (ANAs), are an increasingly used alternative to nerve autografts to repair nerve gaps to facilitate regeneration. The adaptive immune system, specifically T cells, plays a role in promoting regeneration upon these ANA scaffolds. However, how T cells promote regeneration across ANAs is not clear. Here, we show that T cells accumulate within ANAs repairing nerve gaps resulting in regulation of cytokine expression within the ANA environment. This in turn ultimately leads to robust nerve regeneration and functional recovery. Nerve regeneration across ANAs and functional recovery in Rag1KO mice was limited compared to wild-type (WT) mice. Prior to appreciable nerve regeneration, ANAs from Rag1KO mice contained fewer eosinophils and reduced IL-4 expression compared to ANAs from WT mice. During this period, both T cells and eosinophils regulated IL-4 expression within ANAs. Eosinophils represented the majority of IL-4 expressing cells within ANAs, while T cells regulated IL-4 expression. Finally, an essential role for IL-4 during nerve regeneration across ANAs was confirmed as nerves repaired using ANAs had reduced regeneration in IL-4 KO mice compared to WT mice. Our data demonstrate T cells regulate the expression of IL-4 within the ANA environment via their effects on eosinophils. The immune system has been emerging as a critical component for tissue regeneration, especially when regeneration is supported upon biomaterials. The role of T cells, and their roles in the regeneration of nerve repaired with biomaterials, is still unclear. We demonstrated that when nerves are repaired with decellularized nerve scaffolds, T cells contribute to regeneration by regulating cytokines. We focused on their regulation of cytokine IL-4. Unexpectedly, T cells do not produce IL-4, but instead regulate IL-4 by recruiting eosinophils, which are major cellular sources of IL-4 within these scaffolds. Thus, our work demonstrated how IL-4 is regulated in a model biomaterial, and has implications for improving the design of biomaterials and understanding immune responses to biomaterials. Image, graphical abstract [ABSTRACT FROM AUTHOR]

• Fluoride-responsive degradable unit can be incorporated into PUs with a range of adhesive properties. • The mechanical properties can be tuned by varying structure and density of H-bonding monomers. • Introducing crystallinity into the adhesives can lower the bonding temperature to 50 °C. • The adhesives undergo depolymerisation to facilitate debonding on addition of fluoride ions. This paper reports the solvent-free synthesis of a series of six fluoride responsive debond-on-demand polyurethane (PU) adhesives that contain a silyl functionalised degradable unit (DU). To optimise the adhesion strength and debonding nature of the adhesives, the chemical composition of the PUs was varied according to the structure of the polyol or the diisocyanate component in the polymer mainchain. 1H NMR spectroscopy was used to study the depolymerisation behaviour in solution state. It showed that tetra -butylammonium fluoride (TBAF) triggered the breakdown of the DU unit without fragmenting the polyol mainchain indiscriminately. On exposure to fluoride ions, the PUs underwent depolymerisation with reductions in M n ranging from 64 to 90% as measured by GPC analysis. The morphology and thermal properties of the PUs were characterised by differential scanning calorimetry (DSC), rheology and variable temperature (VT) SAXS/WAXS analysis. Each technique demonstrated the reversibility of the supramolecular polymer network under thermal stimuli. PUs containing poly(butadiene) soft segments were amorphous with glass transition and viscoelastic transition temperatures dependent on the nature of the soft segment and diisocyanate starting materials. The PU containing a polyester soft segment exhibited a defined melting point at 49 °C. Mechanical stress-strain analysis of the series of PUs showed each exhibited greater than 70% reduction in toughness after treatment with TBAF for 30 min as a consequence of the chemo-responsive degradation of the polymer mainchain. The material featuring an ester-based polyol demonstrated excellent adhesion at bonding temperatures as low as 60 °C. Moreover, this material could be thermally rebonded if broken by force without loss in adhesion strength over three debond-rebond cycles. Lap shear adhesion tests showed a reduction in adhesive strength of approximately 40% (from 11.4 MPa to 7.3 MPa) on exposure to fluoride ions. [ABSTRACT FROM AUTHOR]

Periprosthetic acetabular fractures are rare but potentially devastating complications of total hip arthroplasty. As the number of total hip arthroplasties performed annually increases, so has the incidence of periprosthetic fractures, with the topic being spotlighted more frequently in the orthopaedic community. There is a particular sparsity of literature regarding periprosthetic acetabular fractures, with periprosthetic femoral fractures after total hip arthroplasty being traditionally far more commonly reported. This article aims to provide an up-to-date review of the epidemiology, risk factors, diagnostic challenges, classifications, and management strategies for periprosthetic acetabular fractures after total hip arthroplasty. [ABSTRACT FROM AUTHOR]

Highlights • Microfluidic device recapitulates the axon entrapment in the "candy-store" effect. • GDNF-overexpressing SCs induce axon entrapment in the device as seen in vivo. • High concentration of GDNF is sufficient to induce axon entrapment. Abstract Background One potential treatment strategy to enhance axon regeneration is transplanting Schwann Cells (SCs) that overexpress glial cell line-derived neurotrophic factor (GDNF). Unfortunately, constitutive GDNF overexpression in vivo can result in failure of regenerating axons to extend beyond the GDNF source, a phenomenon termed the "candy-store" effect. Little is known about the mechanism of this axon entrapment in vivo. New Method We present a reproducible in vitro culture platform using a microfluidic device to model axon entrapment and investigate mechanisms by which GDNF causes axon entrapment. The device is comprised of three culture chambers connected by two sets of microchannels, which prevent cell soma from moving between chambers but allow neurites to grow between chambers. Neurons from dorsal root ganglia were seeded in one end chamber while the effect of different conditions in the other two chambers was used to study neurite entrapment. Results The results showed that GDNF-overexpressing SCs (G-SCs) can induce axon entrapment in vitro. We also found that while physiological levels of GDNF (100 ng/mL) promoted neurite extension, supra-physiological levels of GDNF (700 ng/mL) induced axon entrapment. Comparison with Existing Method All previous work related to the "candy-store" effect were done in vivo. Here, we report the first in vitro platform that can recapitulate the axonal entrapment and investigate the mechanism of the phenomenon. Conclusions This platform facilitates investigation of the "candy-store" effect and shows the effects of high GDNF concentrations on neurite outgrowth. [ABSTRACT FROM AUTHOR]

miRNAs are small, noncoding RNAs that not only regulate gene expression within cells, but might also constitute promising extracellular biomarkers for a variety of pathologies, including the progressive muscle-wasting disorder Duchenne Muscular Dystrophy (DMD). A set of muscle-enriched miRNAs, the myomiRs (miR-1, miR-133, and miR-206) are highly elevated in the serum of patients with DMD and in dystrophin-deficient animal models. Furthermore, circulating myomiRs might be used as pharmacodynamic biomarkers, given that their levels can be restored towards wild-type levels following exon skipping therapy in dystrophic mice. The relationship between muscle pathology and extracellular myomiR release is complex, and incompletely understood. Here, we discuss current progress leading towards the clinical utility of extracellular miRNAs as putative DMD biomarkers, and their possible contribution to muscle physiology. [ABSTRACT FROM AUTHOR]

Objective: This study examines the influence of weight bias and health consciousness on eating and dietary behavior; it also investigates the role of normative influences.Design and Methods: A sample of adults living in South-East England (N=498) completed anonymous questionnaires about their diet, attitudes and beliefs towards obese people, health consciousness and normative influences. The survey included validated measures of anti-fat attitudes, and beliefs about obese people.Results: The findings demonstrate anti-fat attitudes are positively related to self-perceived dietary behavior. Surprisingly, self-perceived dietary behavior is negatively related to health consciousness and activities designed to enable healthy eating, for example meal planning. Significant differences exist between people with, or without, obese family members.Conclusions: Attempts to improve eating behavior by raising health consciousness and offering related support activities may fail; promoting health eating may also contribute to weight bias in society. However, interventions which focus on the negative impact of obesity itself may have a positive effect. [ABSTRACT FROM AUTHOR]

• 8 Novel series of rearranged tricyclic terpanes reported for first time. • Four series of rearranged hopanes reported for first time in oils and source rocks of the Anadarko Basin. • Similar rearrangement reactions possible for both the tricyclic terpanes and hopanes. • Presence controlled primarily by clay mineral content. • Oxicity of the depositional environment, maturity, and biodegradation probably do not play a role in the actual formation of these compounds. An ongoing study of oils and Paleozoic source rock extracts from the Anadarko Basin, Oklahoma, revealed the presence of multiple series of novel tricyclic terpanes in addition to the commonly observed series of 13β(H),14α(H) tricyclic terpanes. The precise structures of these novel tricyclic compounds are not known but several proposed spectral and chromatographic similarities with known compounds suggests the tentatively identified analytes are rearranged and structural isomers of the 13β(H),14α(H) tricyclic terpanes. The occurrences and relative abundances of these compounds are predominantly lower in more carbonate-rich formations, which implies a potential role of clay minerals in their formation. The presence and distributions of these unique tricyclic terpane configurations are seemingly unaffected by thermal maturation, although relative concentrations may increase as a result of preferential thermal degradation of the less thermally-stable hopanes. Many of the samples bearing the novel rearranged tricyclic terpanes also contain varying proportions of four previously reported series of rearranged hopanes, which are formed via rearrangement reactions catalyzed by clay minerals. The rearranged hopanes include the commonly observed Ts and C 30 diahopanes in addition to 9,15-dimethyl rearranged hopanes and 21-methyl-28,30-dinorhopanes (28-norspergulanes) that have been previously reported in a number of basins worldwide but not the Anadarko Basin. No apparent relationship was identified between the presence of the rearranged tricyclic terpanes and the rearranged hopanes. Both groups require the presence of clay minerals, as determined from empirical relationships with source rock lithology, and are observed to co-occur in many of the samples studied. Still, the lack of a clear correlation between rearranged tricyclic terpanes and rearranged hopanes suggests additional controls, beyond lithology, on their genesis and preservation in the geologic record. [ABSTRACT FROM AUTHOR]

Despite the discovery more than two decades ago that antisense oligonucleotides (ASOs) could be used to modulate protein expression, there have been only two antisense drugs approved for clinical use till date. Despite this low success rate, the antisense field is undergoing resurgence due to the development of more potent and nuclease resistant chemistries, as well as nanoparticle delivery systems that enhance delivery to target tissues. In this review, we introduce the predominant therapeutic strategies in the antisense field whilst highlighting recent clinical findings that demonstrate the significant potential of these approaches for development of novel therapies in several diseases. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are natural nanoparticles that mediate intercellular transfer of RNA and proteins and are of great medical interest; serving as novel biomarkers and potential therapeutic agents. However, there is little consensus on the most appropriate method to isolate high-yield and high-purity EVs from various biological fluids. Here, we describe a systematic comparison between two protocols for EV purification: ultrafiltration with subsequent liquid chromatography (UF-LC) and differential ultracentrifugation (UC). A significantly higher EV yield resulted from UF-LC as compared to UC, without affecting vesicle protein composition. Importantly, we provide novel evidence that, in contrast to UC-purified EVs, the biophysical properties of UF-LC-purified EVs are preserved, leading to a different in vivo biodistribution, with less accumulation in lungs. Finally, we show that UF-LC is scalable and adaptable for EV isolation from complex media types such as stem cell media, which is of huge significance for future clinical applications involving EVs. From the Clinical Editor Recent evidence suggests extracellular vesicles (EVs) as another route of cellular communication. These EVs may be utilized for future therapeutics. In this article, the authors compared ultrafiltration with size-exclusion liquid chromatography (UF-LC) and ultra-centrifugation (UC) for EV recovery. [ABSTRACT FROM AUTHOR]

In this report we summarize the many dark matter searches currently being pursued through four complementary approaches: direct detection, indirect detection, collider experiments, and astrophysical probes. The essential features of broad classes of experiments are described, each with their own strengths and weaknesses. The complementarity of the different dark matter searches is discussed qualitatively and illustrated quantitatively in two simple theoretical frameworks. Our primary conclusion is that the diversity of possible dark matter candidates requires a balanced program drawing from all four approaches. [ABSTRACT FROM AUTHOR]

The most fundamental roles of non-coding RNAs (ncRNAs) and epigenetic mechanisms are the guidance of cellular differentiation in development and the regulation of gene expression in adult tissues. In brain, both ncRNAs and the various epigenetic gene regulatory mechanisms play a fundamental role in neurogenesis and normal neuronal function. Thus, epigenetic chromatin remodelling can render coding sites transcriptionally inactive by DNA methylation, histone modifications or antisense RNA interactions. On the other hand, microRNAs (miRNAs) are ncRNA molecules that can regulate the expression of hundreds of genes post-transcriptionally, typically recognising binding sites in the 3′ untranslated region (UTR) of mRNA transcripts. Furthermore, there are a myriad of interactions in the interface of miRNAs and epigenetics. For example, epigenetic mechanisms can silence miRNA coding sites, and miRNAs can be the effectors of transcriptional gene silencing, targeting complementary promoters or silencing the expression of epigenetic modifier genes like MECP2 and EZH2 leading to global changes in the epigenome. Alterations in this regulatory machinery play a key role in the pathology of complex disorders including cancer and neurological diseases. For example, miRNA genes are frequently inactivated by epimutations in gliomas. Here we describe the interactions between epigenetic and ncRNA regulatory systems and discuss therapeutic potential, with an emphasis on tumors, cognitive disorders and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Abstract: Transportation vehicles, whether they are passenger vehicles or heavy trucks and transport vehicles, rely upon rubber tires to negotiate the roadways and surfaces on which they are driven. These tires have the potential of sudden rupture resulting from various causes including but not limited to over-pressurization, sidewall failures, or punctures from roadway debris. These rupture events can and do occur while the vehicles are stationary (e.g., during servicing) or are being driven, and often occur without notice. While the phenomenon of sudden tire failure has been documented for several decades, the potential bodily injury which can occur when an individual is in close proximity to such a sudden rupture has only more recently been documented. Aside from anecdotal mention in case studies, there has been little quantitative information available on the acoustic levels during these failures. Our study provides measured acoustic levels as a function of distance for such catastrophic tire failures. [Copyright &y& Elsevier]

Summary: Animal models of nerve compression, crush, and transection injuries of peripheral nerves have been subject to extensive study in order to understand the mechanisms of injury and axon regeneration and to investigate methods to promote axon regeneration and improve functional outcomes following nerve injury. Six outcome measures of regenerative success including axon and neuron counts, muscle and motor unit contractile forces, and behavior are reviewed in the context of nerve injury types, crush, transection and nerve repair by direct coaptation, or transection and repair via a nerve graft or conduit. The measures are evaluated for sciatic, tibial, common peroneal, femoral, single nerve branches such as the soleus nerve, and facial nerves. Their validity is discussed in the context of study objectives and the nerve branch. The case is made that outcome measures of axon counts and muscle contractile forces may be valid during the early phases of axon regeneration when regenerating sprouts emerge asynchronously from the proximal nerve stump and regenerate towards their denervated targets. However, care must be taken especially when experimental interventions differentially affect how many neurons regenerate axons and the number of axons per neuron that sprout from the proximal nerve stumps. Examples of erroneous conclusions are given to illustrate the need for researchers to ensure that the appropriate outcome measures are used in the evaluation of the success of peripheral nerve regeneration. [ABSTRACT FROM AUTHOR]

RNA mis-splicing diseases account for up to 15% of all inherited diseases, ranging from neurological to myogenic and metabolic disorders. With greatly increased genomic sequencing being performed for individual patients, the number of known mutations affecting splicing has risen to 50–60% of all disease-causing mutations. During the past 10years, genetic therapy directed toward correction of RNA mis-splicing in disease has progressed from theoretical work in cultured cells to promising clinical trials. In this review, we discuss the use of antisense oligonucleotides to modify splicing as well as the principles and latest work in bifunctional RNA, trans-splicing and modification of U1 and U7 snRNA to target splice sites. The success of clinical trials for modifying splicing to treat Duchenne muscular dystrophy opens the door for the use of splicing modification for most of the mis-splicing diseases. [Copyright &y& Elsevier]

Purpose: To determine the effect of a motor-specific neurotrophic factor, glial-derived neurotrophic factor (GDNF) on motor nerve regeneration. Methods: We used a nerve conduit filled with a fibrin-based delivery system that provided controlled release of GDNF during nerve regeneration. The motor branch of the rat femoral nerve was used to assess motor nerve regeneration across a 5-mm gap. Four experimental groups (n=4 to n=8) were evaluated. These included GDNF with the fibrin-based delivery system (GDNF-DS), fibrin alone, empty conduit (negative control), and nerve isograft (positive control). Nerves were harvested at 5 weeks for analysis by histomorphometry and electron microscopy. Results: At 5 mm distal to the conduit or isografts, the GDNF-DS group was not significantly different from the nerve isograft group in the following histomorphometric measures: total nerve fibers, percentage of neural tissue, and nerve density. Both the GDNF-DS and isograft groups had significantly more fibers and a higher percentage of neural tissue than fibrin alone and empty conduit groups. There were no differences in fiber width among all groups. By electron microscopy, the GDNF-DS and isograft groups also demonstrated more organized nerve architecture than the fibrin alone and empty conduit groups. Conclusions: The delivery of GDNF from the fibrin-based delivery system promotes motor nerve regeneration at a level similar to an isograft in the femoral motor nerve model. This study gives insight into the potential beneficial role of GDNF in the treatment of motor nerve injuries. [ABSTRACT FROM AUTHOR]

Abstract: We review the main silvicultural interventions used when managing Eucalyptus plantations for solid-wood products, including fertilising, pruning and thinning. The growth of a plantation and the quality of the wood produced is closely linked to the development of the tree crowns. These silvicultural interventions influence crown dynamics and can interact with each other, as well as the species, site and the age at which they are applied. This review focuses on the growth and physiological responses observed in Eucalyptus plantations, particularly from an Australian perspective. The implications for wood quality, while given some attention, are beyond the scope of this review. [Copyright &y& Elsevier]

Dominantly inherited polyglutamine disorders are chronic neurodegenerative diseases therapeutically amenable to gene-specific silencing strategies. Several compelling nucleic acid-based approaches have recently been developed to block the expression of mutant proteins and prevent toxic neurodegenerative sequelae. With such approaches, avoiding potential side effects caused by the concomitant ablation of the normal protein is an important objective. Therefore, allele-specific gene silencing is highly desirable; however, retaining wild type function is complex given that the common CAG mutation cannot be directly targeted, and might not be necessary or justifiable in all cases. Insights from polyglutamine gene function studies and the further development of allele-specific and other gene silencing methodologies will be important to determine the optimal therapeutic strategy for each polyglutamine disorder. [Copyright &y& Elsevier]

Abstract: The anisotropic mechanical properties of magnetically aligned fibrin gels were measured by magnetic resonance elastography (MRE) and by a standard mechanical test: unconfined compression. Soft anisotropic biomaterials are notoriously difficult to characterize, especially in vivo. MRE is well-suited for efficient, non-invasive, and non-destructive assessment of shear modulus. Direction-dependent differences in shear modulus were found to be statistically significant for gels polymerized at magnetic fields of 11.7 and 4.7T compared to control gels. Mechanical anisotropy was greater in the gels polymerized at the higher magnetic field. These observations were consistent with results from unconfined compression tests. Analysis of confocal microscopy images of gels showed measurable alignment of fibrils in gels polymerized at 11.7T. This study provides direct, quantitative measurements of the anisotropy in mechanical properties that accompanies fibril alignment in fibrin gels. [Copyright &y& Elsevier]

Gene therapy covers a broad spectrum of applications, from gene replacement and knockdown for genetic or acquired diseases such as cancer, to vaccination, each with different requirements for gene delivery. Viral vectors and synthetic liposomes have emerged as the vehicles of choice for many applications today, but both have limitations and risks, including complexity of production, limited packaging capacity, and unfavorable immunological features, which restrict gene therapy applications and hold back the potential for preventive gene therapy. While continuing to improve these vectors, it is important to investigate other options, particularly nonviral biological agents which include bacteria, bacteriophage, virus-like particles (VLPs), erythrocyte ghosts, and exosomes. Exploiting the natural properties of these biological entities for specific gene delivery applications will expand the repertoire of gene therapy vectors available for clinical use. Here, we review the prospects for nonviral biological delivery vehicles as gene therapy agents with focus on their unique evolved biological properties and respective limitations and potential applications. The potential of these nonviral biological entities to act as clinical gene therapy delivery vehicles has already been shown in clinical trials using bacteria-mediated gene transfer and with sufficient development, these entities will complement the established delivery techniques for gene therapy applications.Molecular Therapy (2009) 17 5, 767–777 doi:10.1038/mt.2009.41 [ABSTRACT FROM AUTHOR]

Abstract: Glial-derived neurotrophic factor (GDNF) promotes both sensory and motor neuron survival. The delivery of GDNF to the peripheral nervous system has been shown to enhance regeneration following injury. In this study, we evaluated the effect of affinity-based delivery of GDNF from a fibrin matrix in a nerve guidance conduit on nerve regeneration in a 13mm rat sciatic nerve defect. Seven experimental groups were evaluated which received GDNF or nerve growth factor (NGF) with the delivery system within the conduit, control groups excluding one or more components of the delivery system, and nerve isografts. Nerves were harvested 6 weeks after treatment for analysis by histomorphometry and electron microscopy. The use of the delivery system (DS) with either GDNF or NGF resulted in a higher frequency of nerve regeneration vs. control groups, as evidenced by a neural structure spanning the 13mm gap. The GDNF DS and NGF DS groups were also similar to the nerve isograft group in measures of nerve fiber density, percent neural tissue and myelinated area measurements, but not in terms of total fiber counts. In addition, both groups contained a significantly greater percentage of larger diameter fibers, with GDNF DS having the largest in comparison to all groups, suggesting more mature neural content. The delivery of GDNF via the affinity-based delivery system can enhance peripheral nerve regeneration through a silicone conduit across a critical nerve gap and offers insight into potential future alternatives to the treatment of peripheral nerve injuries. [Copyright &y& Elsevier]

Team-sport athletes who normally reside at sea level occasionally play games at altitudes sufficient to impair endurance performance. To investigate the effect of intermittent normobaric hypoxic exposure on performance in generic and game-specific tests at altitude, 22 senior club level rugby players performed baseline tests before single-blind random assignment to one of three groups: hypoxia-altitude (n=9), normoxia-altitude (n=6), and normoxia-sea level (n=7). The hypoxia-altitude group underwent 9-13 sessions of intermittent hypoxic exposure (concentration of inspired oxygen=13-10%) over 15 days, then repeated the performance tests within 12h of travelling to 1550m. The normoxia-altitude group underwent placebo exposures by breathing room air before repeating the tests at altitude, whereas the normoxia-sea level group underwent placebo exposures before repeating the tests at sea level. Hypoxic exposure consisted of alternately breathing 6min hypoxic gas and 4min ambient air for 1h at rest. Performance measures gathered at each testing session were maximum speed, sub-maximum heart-rate speed and sub-maximum lactate speed during a 20-m incremental running test, mean time in six 70-m sprints, repetitive explosive power and other measures from seven 5.5-min circuits of a rugby simulation. Repetitive explosive power ( approximately -16%) and 20-m shuttle performance ( approximately -3%) decreased substantially at altitude compared to sea level. Acclimatisation to hypoxia had a beneficial effect on sub-maximum heart rate and lactate speed but little effect on other performance measures. In conclusion, 1550-m altitude substantially impaired some measures of performance and the effects of prior adaptation via 9-13 sessions of intermittent hypoxia were mostly unclear. [ABSTRACT FROM AUTHOR]

The sufABCDSE operon of the Gram-negative bacterium Escherichia coli is induced by oxidative stress and iron deprivation. To examine the biochemical roles of the Suf proteins, we purified all of the proteins and assayed their effect on SufS cysteine desulfurase activity. Here we report that the SufE protein can stimulate the cysteine desulfurase activity of the SufS enzyme up to 8-fold and accepts sulfane sulfur from SufS. This sulfur transfer process from SufS to Sure is sheltered from the environment based on its resistance to added reductants and on the analysis of available crystal structures of the proteins. We also found that the SufB, SufC, and SufD proteins associate in a stable complex and that, in the presence of SufE, the SufBCD complex further stimulates SufS activity up to 32-fold. Thus, the SufE protein and the SufBCD complex act synergistically to modulate the cysteine desulfurase activity of SufS. We propose that this sulfur transfer mechanism may be important for limiting sulfide release during oxidative stress conditions in vivo. [ABSTRACT FROM AUTHOR]

Poor sleep quality is associated with age-related cognitive decline, and whether reversal of these alterations is possible is unknown. In this study, we report how sleep deprivation (SD) affects hippocampal representations, sleep patterns, and memory in young and old mice. After training in a hippocampus-dependent object-place recognition (OPR) task, control animals sleep ad libitum , although experimental animals undergo 5 h of SD, followed by recovery sleep. Young controls and old SD mice exhibit successful OPR memory, whereas young SD and old control mice are impaired. Successful performance is associated with two cellular phenotypes: (1) "context" cells, which remain stable throughout training and testing, and (2) "object configuration" cells, which remap when objects are introduced to the context and during testing. Additionally, effective memory correlates with spindle counts during non-rapid eye movement (NREM)/rapid eye movement (REM) sigma transitions. These results suggest SD may serve to ameliorate age-related memory deficits and allow hippocampal representations to adapt to changing environments. [Display omitted] • Sleep deprivation improves memory in old mice but worsens it in young ones • Sleep deprivation decreases hippocampal flexibility and spindle counts in young mice • Increased spindle counts are associated with improved memory in old mice • Sleep deprivation improves the quality of hippocampal representations in old mice Age-related cognitive decline is associated with poor sleep quality. Yuan et al. show that acute sleep deprivation has beneficial effects on sleep microarchitecture, memory, and hippocampal representations in old mice and has opposite effects in young animals. These findings suggest that acute sleep deprivation may serve to mitigate age-related cognitive decline. [ABSTRACT FROM AUTHOR]

• 18α(H)-Oleanane is reported in Pennsylvanian and Mississippian rock extracts. • Identity of 18α(H)-oleanane was confirmed by GCMS, GCMSMS and coinjection. • 18α(H)-Oleanane present in multiple wells and depth sequence from one well. • Results suggest angiosperms split from gymnosperms earlier than previously proposed. • Alternatively a previously unidentified source(s) is responsible for the oleanane. • 1,2,7-Trimethylnaphthalene present in all samples containing 18α(H)-oleanane. Analyses of multiple Mississippian and Pennsylvanian aged source rock samples in the Anadarko Basin, Oklahoma, revealed the presence of a compound that was tentatively identified as 18α(H)-oleanane. The identity of the 18α(H)-oleanane was subsequently confirmed by GCMS, GCMSMS, and coinjection with a sample known to contain 18α(H)-oleanane. The approach to identifying 18α(H)-oleanane was similar to that described in previous publications that have noted the presence of 18α(H)-oleanane in pre-Cretaceous samples. The presence of 18α(H)-oleanane in an Early Mississippian Kinderhookian sample appears to be the earliest reported occurrence to date. 18α(H)-Oleanane has typically been reported to be derived from a Late Cretaceous/Early Tertiary angiosperm source which would appear unlikely in this case since there are no Cretaceous or Tertiary aged source rocks in Oklahoma. This paper discusses possible sources for 18α(H)-oleanane including the suggestion that angiosperms, or angiosperm related species, split off from the gymnosperms far earlier than previously proposed. It is proposed that the data and methods discussed in this paper clearly show the presence of a compound identified as 18α(H)-oleanane in Mississippian and Pennsylvanian age samples. However, the source of the 18α(H)-oleanane still remains unclear. [ABSTRACT FROM AUTHOR]

In this article, the authors examines a study by X. Zhuang and colleagues which describes the use of exosomes to deliver anti-inflammatory drugs to the brain through a noninvasive intranasal route. The authors state that the study demonstrates an association between exosomes and curcumin following coincubation. They note that the study need further validation of the potential of exosomes as drug delivery vehicles.

Food webs are a fundamental concept in ecology in which parasites have been virtually ignored. In a recent article, Lafferty et al. address this imbalance, finding that the inclusion of parasites in food webs could be of greater importance to ecosystem stability than was previously thought. Furthermore, the bottom of the food chain is perhaps no longer the most dangerous place to be. [Copyright &y& Elsevier]

The ecological mechanisms underlying the dispersal of parasites are poorly understood, which is of particular concern in view of currently emerging infectious diseases. In a new study, Pérez-Tris and Bensch examined the distribution and prevalence of avian malaria in a migratory bird across Western Europe. They concluded that repeated independent evolution of year-round transmission has enabled some avian malaria lineages to become more widespread, and more prevalent, than lineages that are transmitted only during the summer. This study blurs the boundaries of evolutionary ecology, epidemiology and macroecology with great potential for cross-disciplinary research. [Copyright &y& Elsevier]

In this issue of Structure, report the structure of the redox-sensing repressor from the gram-positive bacterium Thermus aquaticus (T-Rex), a protein that links gene expression to oxygen limitation and the metabolic state of the cell. [Copyright &y& Elsevier]

Gross total resection of arteriovenous malformations (AVMs) of the central nervous system confirmed by formal angiography is accepted as a cure for patients. In some cases, this may not be possible. Even though in these cases other treatment modalities such as endovascular embolization and radiotherapy can be used, long-term follow-up is lacking in the literature. Here we report a case of a 57-year-old woman with history of a right-sided parieto-occipital/periatrial AVM, initially treated with a combination of endovascular embolization and radiotherapy. The patient subsequently presented (12 years later) with a symptomatic, enlarging, contrast-enhancing mass at the same location that was angiographically occult but ultimately proven to be an AVM on a background of reactive changes on pathology. [ABSTRACT FROM AUTHOR]