The Use of a Cap-mounted Tri-axial Accelerometer for Measurement of Distance, Lap Times and Stroke Rates in Swim Training

This paper will report some of the findings from a trial which recorded accelerometer data from six elite level swimmers (three female and three male, varying primary event stroke and distance) over the course of a regular 15 week training block. Measurements from a head-mounted accelerometer are used to determine when the athlete is swimming, marking of turning points (and therefore distance and lap-time measurements), and is processed by frequency analysis to determine stroke-rate. Comparison with video where available, and with training plans and literature where not, have proven this method to be accurate and reliable for determining these performance metrics. The primary objective of this project was to develop a low-cost, simple and highly usable system for use in swim coaching, feedback from elite coaches has indicated that development of this could be an extremely useful addition to their training regime

Members of the chloride intracellular ion channel protein family demonstrate glutaredoxin-like enzymatic activity

© 2015 Al Khamici et al. The Chloride Intracellular Ion Channel (CLIC) family consists of six evolutionarily conserved proteins in humans. Members of this family are unusual, existing as both monomeric soluble proteins and as integral membrane proteins where they function as chloride selective ion channels, however no function has previously been assigned to their soluble form. Structural studies have shown that in the soluble form, CLIC proteins adopt a glutathione S-transferase (GST) fold, however, they have an active site with a conserved glutaredoxin monothiol motif, similar to the omega class GSTs. We demonstrate that CLIC proteins have glutaredoxin-like glutathione-dependent oxidoreductase enzymatic activity. CLICs 1, 2 and 4 demonstrate typical glutaredoxin-like activity using 2-hydroxyethyl disulfide as a substrate. Mutagenesis experiments identify cysteine 24 as the catalytic cysteine residue in CLIC1, which is consistent with its structure. CLIC1 was shown to reduce sodium selenite and dehydroascorbate in a glutathione-dependent manner. Previous electrophysiological studies have shown that the drugs IAA-94 and A9C specifically block CLIC channel activity. These same compounds inhibit CLIC1 oxidoreductase activity. This work for the first time assigns a functional activity to the soluble form of the CLIC proteins. Our results demonstrate that the soluble form of the CLIC proteins has an enzymatic activity that is distinct from the channel activity of their integral membrane form. This CLIC enzymatic activity may be important for protecting the intracellular environment against oxidation. It is also likely that this enzymatic activity regulates the CLIC ion channel function

Lipoprotein-associated phospholipase A2 (Lp-PLA2) as a therapeutic target to prevent retinal vasopermeability during diabetes

Lipoprotein-associated phospholipase A2 (Lp-PLA2) hydrolyses oxidized low-density lipoproteins into proinflammatory products, which can have detrimental effects on vascular function. As a specific inhibitor of Lp-PLA2, darapladib has been shown to be protective against atherogenesis and vascular leakage in diabetic and hypercholesterolemic animal models. This study has investigated whether Lp-PLA2 and its major enzymatic product, lysophosphatidylcholine (LPC), are involved in blood-retinal barrier (BRB) damage during diabetic retinopathy. We assessed BRB protection in diabetic rats through use of species-specific analogs of darapladib. Systemic Lp-PLA2 inhibition using SB-435495 at 10 mg/kg (i.p.) effectively suppressed BRB breakdown in streptozotocin-diabetic Brown Norway rats. This inhibitory effect was comparable to intravitreal VEGF neutralization, and the protection against BRB dysfunction was additive when both targets were inhibited simultaneously. Mechanistic studies in primary brain and retinal microvascular endothelial cells, as well as occluded rat pial microvessels, showed that luminal but not abluminal LPC potently induced permeability, and that this required signaling by the VEGF receptor 2 (VEGFR2). Taken together, this study demonstrates that Lp-PLA2 inhibition can effectively prevent diabetes-mediated BRB dysfunction and that LPC impacts on the retinal vascular endothelium to induce vasopermeability via VEGFR2. Thus, Lp-PLA2 may be a useful therapeutic target for patients with diabetic macular edema (DME), perhaps in combination with currently administered anti-VEGF agents

L,L-Diaminopimelate Aminotransferase from Chlamydomonas reinhardtii: A Target for Algaecide Development

In some bacterial species and photosynthetic cohorts, including algae, the enzyme l,l-diaminopimelate aminotransferase (DapL) (E.C. 2.6.1.83) is involved in the anabolism of the essential amino acid L-lysine. DapL catalyzes the conversion of tetrahydrodipicolinate (THDPA) to l,l-diaminopimelate (l,l-DAP), in one step bypassing the DapD, DapC and DapE enzymatic reactions present in the acyl DAP pathways. Here we present an in vivo and in vitro characterization of the DapL ortholog from the alga Chlamydomonas reinhardtii (Cr-DapL). The in vivo analysis illustrated that the enzyme is able to functionally complement the E. coli dap auxotrophs and was essential for plant development in Arabidopsis. In vitro, the enzyme was able to inter-convert THDPA and l,l-DAP, showing strong substrate specificity. Cr-DapL was dimeric in both solution and when crystallized. The structure of Cr-DapL was solved in its apo form, showing an overall architecture of a α/β protein with each monomer in the dimer adopting a pyridoxal phosphate-dependent transferase-like fold in a V-shaped conformation. The active site comprises residues from both monomers in the dimer and shows some rearrangement when compared to the apo-DapL structure from Arabidopsis. Since animals do not possess the enzymatic machinery necessary for the de novo synthesis of the amino acid l-lysine, enzymes involved in this pathway are attractive targets for the development of antibiotics, herbicides and algaecides

Osteoarticular Infection in Three Young Thoroughbred Horses Caused by a Novel Gram Negative Cocco-Bacillus

© 2020 Bernard J. Hudson et al. We describe three cases of osteoarticular infection (OAI) in young thoroughbred horses in which the causative organism was identified by MALDI-TOF as Kingella species. The pattern of OAI resembled that reported with Kingella infection in humans. Analysis by 16S rRNA PCR enabled construction of a phylogenetic tree that placed the isolates closer to Simonsiella and Alysiella species, rather than Kingella species. Average nucleotide identity (ANI) comparison between the new isolate and Kingella kingae and Alysiella crassa however revealed low probability that the new isolate belonged to either of these species. This preliminary analysis suggests the organism isolated is a previously unrecognised species

Imperfection works: Survival, transmission and persistence in the system of Heliothis virescens ascovirus 3h (HvAV-3h), Microplitis similis and Spodoptera exigua

Ascoviruses are insect-specific large DNA viruses that mainly infect noctuid larvae, and are transmitted by parasitoids in the fields. Heliothis virescens ascovirus 3h (HvAV-3h) has been recently isolated from Spodoptera exigua, without parasitoid vector identified previously. Here we report that Microplitis similis, a solitary endoparasitoid wasp, could transmit HvAV-3h between S. exigua larvae in the laboratory. When the female parasitoid wasp acquired the virus and served as a vector, the period of virion viability on the ovipositor was 4.1 ± 1.4 days. Infected host larvae were still acceptable for egg laying by parasitoids, and the parasitoids thereafter transmitted virus to healthy hosts. Virus acquisition occurred only from donor hosts between 3 and 9 days post infection. The peak of virus acquisition (80.9 ± 6.3%) was found when M. similis wasps oviposited in larvae that had been inoculated with the virus 7 days previously. When virus infection of the host took place during the life cycle of the parasitoid wasp, it caused 1- to 4-day-old immature parasitoids death in the host, whilst a small proportion of 5- to 6-day-old and the majority of 7-day-old parasitoids larvae survived from the virus-infected hosts. Viral contamination did not reduce the life span or fecundity of female M. similis

WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics

Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heterogeneous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treatment with WNT inhibitors reduced both prostasphere size and self-renewal. In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear Β-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer cells express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are consistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector Β-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen receptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit amplifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the self-renewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell characteristics and improve the therapeutic outcome.Peer reviewe

GROWTH OF CERRADO NATIVE SPECIES AND OF Vetiveria zizanioides IN COLLUVIUM OF GULLIES

Taxas de germina\ue7\ue3o de sementes, sobreviv\ueancia e crescimento de plantas, par\ue2metros estes avaliados no presente estudo, s\ue3o informa\ue7\uf5es essenciais para a caracteriza\ue7\ue3o do potencial biol\uf3gico de esp\ue9cies para uso em processos de recupera\ue7\ue3o de \ue1reas degradadas. A falta de conhecimento sobre tais aspectos em esp\ue9cies nativas t\ueam justificado o uso de plantas ex\uf3ticas na revegeta\ue7\ue3o de vo\ue7orocas em todo o Brasil. Entretanto, especialmente em locais sujeitos \ue0 grande sazonalidade clim\ue1tica e sobre solos oligotr\uf3ficos, esp\ue9cies ex\uf3ticas nem sempre apresentam bom desempenho, levando o empreendimento de revegeta\ue7\ue3o ao insucesso ou elevando consideravelmente a necessidade de aplica\ue7\ue3o de tratos culturais. Com o objetivo de ampliar os conhecimentos sobre o potencial biol\uf3gico para revegeta\ue7\ue3o em vo\ue7orocas de plantas nativas do cerrado e de uma gram\uednea ex\uf3tica, que vem sendo amplamente usada em projetos de conten\ue7\ue3o de eros\ue3o, pl\ue2ntulas e touceiras das esp\ue9cies nativas Cratylia argentea (Desv.) Kuntze e Echinolaena inflexa (Poir.) Chase, e da ex\uf3tica Vetiveria zizanioides (L.) Nash foram transferidas para o col\ufavio de uma vo\ue7oroca no munic\uedpio de Ouro Preto - MG, onde permaneceram durante a esta\ue7\ue3o seca de 2010 sem aplica\ue7\ue3o de fertilizantes ou irriga\ue7\ue3o. Em blocos ao acaso, parcelas de 1 x 1 m receberam aleatoriamente quatro tratamentos de plantio: touceiras de Echinolaena inflexa ou de Vetiveria zizanioides; e touceiras destas gram\uedneas em cons\uf3rcio com a leguminosa arbustiva Cratylia argentea. Todas as gram\uedneas e 73% das pl\ue2ntulas da leguminosa sobreviveram. Como esperado, a cobertura verde de Echinolaena Inflexa diminuiu ao longo da esta\ue7\ue3o seca, tendo, entretanto, rebrotado ap\uf3s as primeiras chuvas. Vetiveria zizanioides manteve a \ue1rea foliar ativa e apresentou crescimento significativo no per\uedodo. Cratylia argentea apresentou altas taxas de germina\ue7\ue3o de sementes e de crescimento, entretanto, nodula\ue7\ue3o ocorreu em apenas dois indiv\uedduos. Assim, n\ue3o houve influ\ueancia da leguminosa no crescimento das gram\uedneas. Os resultados indicam que tanto as esp\ue9cies nativas do cerrado como a gram\uednea ex\uf3tica possuem alto potencial para revegeta\ue7\ue3o em col\ufavio de vo\ue7oroca, tendo sobrevivido ao per\uedodo cr\uedtico de seca e sobre substrato oligotr\uf3fico sem adi\ue7\ue3o de fertilizantes ou irriga\ue7\ue3o.Rates of seed germination, plant survival and growth, as measured in the present study, are essential parameters to characterize the biological potential of species for the restoration of degraded areas. The lack of knowledge about these aspects in native species has justified the use of exotic plants in Brazilian gullies revegetation. However, especially in places subject to highly seasonal climate and on oligotrophic soils, exotic species do not always perform well, leading to revegetation failure or significantly increasing the cultivation care needs. To improve the knowledge concerning to the biological potencial of cerrado native species and of an exotic grass which has been used for erosion contention, in the present study, seedlings and clumps of native cerrado species, Cratylia argentea (Desv.) Kuntze and Echinolaena inflexa (Poir.) Chase, and of the exotic grass Vetiveria zizanioides (L.) Nash, were transferred to a gully colluvium in Ouro Preto, Minas Gerais state, where they remained during the dry season of 2010 without application of fertilizers or irrigation. In randomized block design, plots of 1 x 1 m received four planting treatments: clumps of Echinolaena inflexa or Vetiveria zizanioides, and clumps of these grasses intercropped with the legume Cratylia argentea. All grasses and 73% of the legume seedlings survived. As expected, the green cover of Echinolaena inflexa decreased throughout the dry season, however, showing regrowth after the first rains. Leaf area of Vetiveria zizanioides remained active and grew significantly in the period. Cratylia argentea showed high rates of germination and growth; however, nodulation occurred in only two individuals. Thus, there was no influence of the legume on grasses growth. Results indicate that both native species and the exotic grass tested are potential successful plants for gullies replanting. Plants survived and grew on low nutrient substrate and during the critical period of drought without any fertilizer or irrigation application

'Just’ punishment? Offenders’ views on the meaning and severity of punishment

In England and Wales, ‘punishment’ is a central element of criminal justice. What punishment entails exactly, however, and how it relates to the other aims of sentencing (crime reduction, rehabilitation, public protection and reparation), remains contested. This article outlines different conceptualizations of punishment and explores to what extent offenders subscribe to these perspectives. The analysis is supported by findings from two empirical studies on the subjective experiences of imprisonment and probation, respectively. Semi-structured interviews were conducted with 15 male and 15 female prisoners and seven male and two female probationers. Two primary conceptualizations of punishment were identified: ‘punishment as deprivation of liberty’ and ‘punishment as hard treatment’. The comparative subjective severity of different sentences and the collateral (unintended) consequences of punishment are also discussed. It is shown that there are large individual differences in the interpretation and subjective experience of punishment, which has implications for the concept of retributive proportionality, as well as the function of punishment more generally