Effectiveness of a community football programme on improving physiological markers of health in a hard-to-reach male population: the role of exercise intensity

© 2015 Taylor & Francis. The present study evaluated the effectiveness of participation in recreational football during a community health programme, on physiological markers of health within a hard to reach population. Nine men (Age: 33 ± 9 years, Mass: 75.4 ± 13.7 kg, Height: 1.74 ± 0.07 m and Body Fat: 19 ± 2%) were recruited to participate in the study in collaboration with an English Premier League Football Club. Participants completed the 12-week football-based programme which included two coached football sessions each week. Physiological tests for blood pressure, resting heart rate, cholesterol and an anthropometrical test for body composition were completed at three time points during the study (Weeks – 1, 6 and 12) in an attempt to evaluate the impact of the intervention on health. During each training session, measurements of intensity (%HRmax, identified from the yoyo intermittent level 1 test), duration and rating of perceived exertion were made. The 12-week programme (mean HRmax throughout programme = 75 ± 4% beats min−1; mean RPE throughout programme = 6 ± 1) elicited few changes in physiological markers of health with the only significant change been a decrease in resting heart rate from weeks 6 to 12 (87 ± 22 beats min−1 at week-6, to 72 ± 17 beats min−1; p < 0.05). These data would suggest that the current community football-related health project was not effective in improving physiological markers of health, but was able to maintain their level of health. A lack of improvement may be due to the low intensity of sessions and a lack of coach education for the promotion of sessions that aim to improve health

SENP1 participates in the dynamic regulation of Elk-1 SUMOylation

The modification of proteins with SUMO (small ubiquitin-related modifier) plays an important role in determining their functional properties. Importantly though, SUMOylation is a highly dynamic process enabling transient responses to be elicited. This dynamism is controlled by two competing conjugating and deconjugating activities. The latter activity is mediated by the SENP [SUMO1/sentrin/SMT3 (suppressor of mif two 3 homologue 1)-specific peptidase] family of SUMO-specific proteases. The transcription factor Elk-1 [ETS (E twenty-six)-like 1] undergoes rapid de-SUMOylation following cellular stimulation with growth factors, and this contributes to its conversion from a SUMO-dependent repressor into a potent transcriptional activator. In the present study we demonstrate an important role for SENP1 in the de-SUMOylation of Elk-1, and therefore an integral role in determining the Elk-1-dependent transcriptional programme. Among the SENPs, Elk-1 preferentially forms a complex with SENP1. This preferential binding is reflected by the higher efficiency of SENP1 in promoting Elk-1 transactivation. Moreover, depletion of SENP1 causes a reciprocal effect and reduces the transactivation properties of Elk-1. Partial redundancy of function with SENP2 is revealed by combinatorial knockdown studies. Importantly, depletion of SENP1 also reduces the activation of the Elk-1 target gene c-FOS. Taken together, these results therefore reveal an important role for SENP1 in the regulation of Elk-1-mediated gene expression in response to mitogenic signalling cues

Veterinary trypanocidal benzoxaboroles are peptidase-activated prodrugs

Livestock diseases caused by Trypanosoma congolense, T. vivax and T. brucei, collectively known as nagana, are responsible for billions of dollars in lost food production annually. There is an urgent need for novel therapeutics. Encouragingly, promising antitrypanosomal benzoxaboroles are under veterinary development. Here, we show that the most efficacious subclass of these compounds are prodrugs activated by trypanosome serine carboxypeptidases (CBPs). Drug-resistance to a development candidate, AN11736, emerged readily in T. brucei, due to partial deletion within the locus containing three tandem copies of the CBP genes. T. congolense parasites, which possess a larger array of related CBPs, also developed resistance to AN11736 through deletion within the locus. A genome-scale screen in T. brucei confirmed CBP loss-of-function as the primary mechanism of resistance and CRISPR-Cas9 editing proved that partial deletion within the locus was sufficient to confer resistance. CBP re-expression in either T. brucei or T. congolense AN11736-resistant lines restored drug-susceptibility. CBPs act by cleaving the benzoxaborole AN11736 to a carboxylic acid derivative, revealing a prodrug activation mechanism. Loss of CBP activity results in massive reduction in net uptake of AN11736, indicating that entry is facilitated by the concentration gradient created by prodrug metabolism.</p

A blood atlas of COVID-19 defines hallmarks of disease severity and specificity.

Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description of specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying COVID-19 severity in an integrated comparison with influenza and sepsis patients versus healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity involved cells, their inflammatory mediators and networks, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism, and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Systems-based integrative analyses including tensor and matrix decomposition of all modalities revealed feature groupings linked with severity and specificity compared to influenza and sepsis. Our approach and blood atlas will support future drug development, clinical trial design, and personalized medicine approaches for COVID-19

PIPELINES AND TIGHT RHYMES: VIRTUAL MEDIA AND HIP-HOP IN JAPAN & NEW ZEALAND

This thesis looks at hip-hop as a contemporary pop cultural phenomena and its relationship with media in the construction of underground hip-hop communities in Japanese and New Zealand settings. My work on hip-hop in Japan illustrates how global networks influence a traditionally mono-cultural society reckoning with a style connected to African-American experience. A New Zealand setting illustrates how virtual networks allow connections to wider hip-hop culture from a geographically isolated setting and legitimises the local scene. In looking at both settings side-by-side, this thesis underscores the various ways that virtual networks and their increased visibility are used contemporaneously in the construction of local hip-hop scenes as a tool to understand and promote hip-hop music. Based on a mix of virtual fieldwork, fieldwork in New Zealand, as well as fieldwork in Japan, this thesis shows that questions of authenticity in hip-hop have become more complex through different manifestations of hip-hop culture that challenge traditional understandings of the genre’s meaning. This is a result of the varying levels of user-agency in virtual networks. In a Japanese setting, we see an increased importance placed on virtual networks, allowing hip-hop fans and musicians alike to be part of the immediate conversation. Language barriers to hip-hop’s dominant English vernacular mean that this conversation is generally filtered through the most dominant networks and ‘mainstream’ culture. These impressions of hip-hop are the driving forces of style for the Japanese scene, leading to a collapse of the dichotic underground/mainstream divide seen in the earlier generations of Japanese hip-hop. In a New Zealand setting, virtual networks are used to connect with English speaking hip-hop musicians overseas, allowing musicians to operate in ‘underground’ virtual communities that are not physically manifested in New Zealand. By drawing attention to the ways that hip-hop culture is formed, legitimized, and understood in these two geographic and cultural settings, this thesis demonstrates that hip-hop culture exists in an integral relationship with virtual media and explores questions of appropriation, imitation, and authenticity

PIPELINES AND TIGHT RHYMES: VIRTUAL MEDIA AND HIP-HOP IN JAPAN & NEW ZEALAND

This thesis looks at hip-hop as a contemporary pop cultural phenomena and its relationship with media in the construction of underground hip-hop communities in Japanese and New Zealand settings. My work on hip-hop in Japan illustrates how global networks influence a traditionally mono-cultural society reckoning with a style connected to African-American experience. A New Zealand setting illustrates how virtual networks allow connections to wider hip-hop culture from a geographically isolated setting and legitimises the local scene. In looking at both settings side-by-side, this thesis underscores the various ways that virtual networks and their increased visibility are used contemporaneously in the construction of local hip-hop scenes as a tool to understand and promote hip-hop music. Based on a mix of virtual fieldwork, fieldwork in New Zealand, as well as fieldwork in Japan, this thesis shows that questions of authenticity in hip-hop have become more complex through different manifestations of hip-hop culture that challenge traditional understandings of the genre’s meaning. This is a result of the varying levels of user-agency in virtual networks. In a Japanese setting, we see an increased importance placed on virtual networks, allowing hip-hop fans and musicians alike to be part of the immediate conversation. Language barriers to hip-hop’s dominant English vernacular mean that this conversation is generally filtered through the most dominant networks and ‘mainstream’ culture. These impressions of hip-hop are the driving forces of style for the Japanese scene, leading to a collapse of the dichotic underground/mainstream divide seen in the earlier generations of Japanese hip-hop. In a New Zealand setting, virtual networks are used to connect with English speaking hip-hop musicians overseas, allowing musicians to operate in ‘underground’ virtual communities that are not physically manifested in New Zealand. By drawing attention to the ways that hip-hop culture is formed, legitimized, and understood in these two geographic and cultural settings, this thesis demonstrates that hip-hop culture exists in an integral relationship with virtual media and explores questions of appropriation, imitation, and authenticity.</p

PIPELINES AND TIGHT RHYMES: VIRTUAL MEDIA AND HIP-HOP IN JAPAN & NEW ZEALAND

This thesis looks at hip-hop as a contemporary pop cultural phenomena and its relationship with media in the construction of underground hip-hop communities in Japanese and New Zealand settings. My work on hip-hop in Japan illustrates how global networks influence a traditionally mono-cultural society reckoning with a style connected to African-American experience. A New Zealand setting illustrates how virtual networks allow connections to wider hip-hop culture from a geographically isolated setting and legitimises the local scene. In looking at both settings side-by-side, this thesis underscores the various ways that virtual networks and their increased visibility are used contemporaneously in the construction of local hip-hop scenes as a tool to understand and promote hip-hop music. Based on a mix of virtual fieldwork, fieldwork in New Zealand, as well as fieldwork in Japan, this thesis shows that questions of authenticity in hip-hop have become more complex through different manifestations of hip-hop culture that challenge traditional understandings of the genre’s meaning. This is a result of the varying levels of user-agency in virtual networks. In a Japanese setting, we see an increased importance placed on virtual networks, allowing hip-hop fans and musicians alike to be part of the immediate conversation. Language barriers to hip-hop’s dominant English vernacular mean that this conversation is generally filtered through the most dominant networks and ‘mainstream’ culture. These impressions of hip-hop are the driving forces of style for the Japanese scene, leading to a collapse of the dichotic underground/mainstream divide seen in the earlier generations of Japanese hip-hop. In a New Zealand setting, virtual networks are used to connect with English speaking hip-hop musicians overseas, allowing musicians to operate in ‘underground’ virtual communities that are not physically manifested in New Zealand. By drawing attention to the ways that hip-hop culture is formed, legitimized, and understood in these two geographic and cultural settings, this thesis demonstrates that hip-hop culture exists in an integral relationship with virtual media and explores questions of appropriation, imitation, and authenticity