Human papillomavirus E2 regulates SRSF3 (SRp20) to promote capsid protein expression in infected differentiated keratinocytes

The human papillomavirus (HPV) life cycle is tightly linked to differentiation of the infected epithelial cell suggesting a sophisticated interplay between host cell metabolism and virus replication. Previously we demonstrated in differentiated keratinocytes in vitro and in vivo that HPV16 infection caused increased levels of the cellular SR splicing factors (SRSFs) SRSF1 (ASF/SF2), SRSF2 (SC35) and SRSF3 (SRp20). Moreover, the viral E2 transcription and replication factor that is expressed at high levels in differentiating keratinocytes could bind and control activity of the SRSF1 gene promoter. Here we reveal that E2 proteins of HPV16 and HPV31 control expression of SRSFs 1, 2 and 3 in a differentiation-dependent manner. E2 has the greatest trans-activation effect on expression of SRSF3. siRNA depletion experiments in two different models of the HPV16 life cycle (W12E and NIKS16) and one model of the HPV31 life cycle (CIN612-9E) revealed that only SRSF3 contributed significantly to regulation of late events in the virus life cycle. Increased levels of SRSF3 are required for L1 mRNA and capsid protein expression. Capsid protein expression was regulated specifically by SRSF3 and appeared independent of other SRSFs. Taken together these data suggest a significant role of the HPV E2 protein in regulating late events in the HPV life cycle through transcriptional regulation of SRSF3 expression. IMPORTANCE Human papillomavirus replication is accomplished in concert with differentiation of the infected epithelium. Virus capsid protein expression is confined to the upper epithelial layers so as to avoid immune detection. In this study we demonstrate that the viral E2 transcription factor activates the promoter of the cellular SRSF3 RNA processing factor. SRSF3 is required for expression of the E4̂L1 mRNA and so controls expression of the HPV L1 capsid protein. Thus we reveal a new dimension of virus-host interaction crucial for production of infectious virus. SRSF proteins are known drug targets. Therefore, this study provides an excellent basis for developing strategies to regulate capsid protein production in the infected epithelium and production of new virions

Specht modules and semisimplicity criteria for Brauer and Birman--Murakami--Wenzl Algebras

A construction of bases for cell modules of the Birman--Murakami--Wenzl (or B--M--W) algebra $B_n(q,r)$ by lifting bases for cell modules of $B_{n-1}(q,r)$ is given. By iterating this procedure, we produce cellular bases for B--M--W algebras on which a large abelian subalgebra, generated by elements which generalise the Jucys--Murphy elements from the representation theory of the Iwahori--Hecke algebra of the symmetric group, acts triangularly. The triangular action of this abelian subalgebra is used to provide explicit criteria, in terms of the defining parameters $q$ and $r$, for B--M--W algebras to be semisimple. The aforementioned constructions provide generalisations, to the algebras under consideration here, of certain results from the Specht module theory of the Iwahori--Hecke algebra of the symmetric group

Vertical migration maintains phytoplankton position in a tidal channel with residual flow

A tidal channel can retain phytoplankton, despite a residual flow, if the phytoplankton migrate vertically with a daily rhythm. Tidal currents are slowed down by bed friction and so plankton experience faster flow when higher in the water column. The lateral movement of the plankton depends on the nature of the vertical migration, particularly the time spent near the surface and the phase of the tide. A model of this process accorded with observations of chlorophyll derived from in situ fluorescence at a mooring in a tidal channel. Peaks in chlorophyll at the end of the flood tide indicated the presence of a phytoplankton bloom downstream of the mooring. Peaks in chlorophyll at the ends of the morning flood tides were 3 to 4 times larger than at the ends of the evening floods, over several days. In contrast, well-mixed particulates were removed from the channel by the residual flow in just 2 d. Both the day-night asymmetry and the sustained presence of chlorophyll were explained by allowing for vertical migration of the phytoplankton and constraining the period during which they were near the surface. Tidal channels retaining phytoplankton that migrate vertically can be ecologically more diverse and yield higher commercial output of farmed bivalves. The natural timings of some phytoplankton blooms in tidal channels are controlled by the nature of the migration. Although a by-product of vertical migration, longer residence in the tidal channel affords the phytoplankton more nutrients than phytoplankton that advect offshore

A powerful intervention: general practitioners' use of sickness certification in depression

<b>Background</b> Depression is frequently cited as the reason for sickness absence, and it is estimated that sickness certificates are issued in one third of consultations for depression. Previous research has considered GP views of sickness certification but not specifically in relation to depression. This study aimed to explore GPs views of sickness certification in relation to depression.<p></p> <b>Methods</b> A purposive sample of GP practices across Scotland was selected to reflect variations in levels of incapacity claimants and antidepressant prescribing. Qualitative interviews were carried out between 2008 and 2009.<p></p> <b>Results</b> A total of 30 GPs were interviewed. A number of common themes emerged including the perceived importance of GP advocacy on behalf of their patients, the tensions between stakeholders involved in the sickness certification system, the need to respond flexibly to patients who present with depression and the therapeutic nature of time away from work as well as the benefits of work. GPs reported that most patients with depression returned to work after a short period of absence and that it was often difficult to predict which patients would struggle to return to work.<p></p> <b>Conclusions</b> GPs reported that dealing with sickness certification and depression presents distinct challenges. Sickness certificates are often viewed as powerful interventions, the effectiveness of time away from work for those with depression should be subject to robust enquiry

Seasonal nutrient co-limitation in a temperate shelf sea: A modelling approach

Nutrient limitation on phytoplankton growth plays a critical role in ocean productivity, the functioning of marine ecosystems, and the ocean carbon cycle. In the Celtic Sea, a temperate shelf sea, many studies have shown the importance of nitrate on phytoplankton growth focusing on the seasonal cycle of nitrate and feedbacks with the physical environment; but only recently has it been demonstrated, through discrete measurements, that dissolved iron also plays an important role in the ecosystem of the region. A well-established one-dimensional model has been developed to analyse the nutrient co-limitation between dissolved iron and dissolved inorganic nitrogen in the Celtic Sea. This model allows us to study the full seasonal cycle and inter-annual variability of these two nutrients. Simulations show that dissolved iron is an important nutrient for the development of the spring bloom, while nitrate plays a more important role during the summer season. Sensitivity analyses show that these results are robust when varying the nutrient-related parameters; the largest variability observed for primary production was observed when varying the nutrient sediment flux rates for dissolved iron and nitrate while less impact on phytoplankton production occurs when changing the half saturation constants. Here, we demonstrate that dissolved iron is an important nutrient for the development of the spring bloom and it should not be neglected as a state variable when modelling the Celtic Sea or other temperate shelf seas

Gaps in detailed knowledge of human papillomavirus (HPV) and the HPV vaccine among medical students in Scotland

<p>Background: A vaccination programme targeted against human papillomavirus (HPV) types16 and 18 was introduced in the UK in 2008, with the aim of decreasing incidence of cervical disease. Vaccine roll out to 12–13 year old girls with a catch-up programme for girls aged up to 17 years and 364 days was accompanied by a very comprehensive public health information (PHI) campaign which described the role of HPV in the development of cervical cancer.</p> <p>Methods: A brief questionnaire, designed to assess acquisition of knowledge of HPV infection and its association to cervical cancer, was administered to two different cohorts of male and female 1st year medical students (school leavers: 83% in age range 17–20) at a UK university. The study was timed so that the first survey in 2008 immediately followed a summer's intensive PHI campaign and very shortly after vaccine roll-out (150 students). The second survey was exactly one year later over which time there was a sustained PHI campaign (213 students).</p> <p>Results: We addressed three research questions: knowledge about three specific details of HPV infection that could be acquired from PHI, whether length of the PHI campaign and/or vaccination of females had any bearing on HPV knowledge, and knowledge differences between men and women regarding HPV. No female student in the 2008 cohort had completed the three-dose vaccine schedule compared to 58.4% of female students in 2009. Overall, participants’ knowledge regarding the sexually transmitted nature of HPV and its association with cervical cancer was high in both year groups. However, in both years, less than 50% of students correctly identified that HPV causes over 90% of cases of cervical cancer. Males gave fewer correct answers for these two details in 2009. In 2008 only around 50% of students recognised that the current vaccine protects against a limited subset of cervical cancer-causing HPV sub-types, although there was a significant increase in correct response among female students in the 2009 cohort compared to the 2008 cohort.</p> <p>onclusions: This study highlights a lack of understanding regarding the extent of protection against cervical cancer conferred by the HPV vaccine, even among an educated population in the UK who could have a vested interest in acquiring such knowledge. The intensive PHI campaign accompanying the first year of HPV vaccination seemed to have little effect on knowledge over time. This is one of the first studies to assess detailed knowledge of HPV in both males and females. There is scope for continued improvements to PHI regarding the link between HPV infection and cervical cancer.</p&gt

Janina Maria Sokołowska (1945): the first woman veterinary surgeon from the Royal (Dick) Veterinary College, Edinburgh

Internationally, almost all the students who qualified as veterinary surgeons prior lo 1900 were men. However, in the last two decades of the nineteenth century women were expressing their wishes to be similarly qualified. One of the first women to achieve that ambition was Stephania Kruszevska, from Warsaw, Poland, who acquired her veterinary degree in Zurich in 1889. ln Scotland, in 1894, William Williams of the New Veterinary College, Elm Row, Edinburgh accepted the apptication or Aleen Cust (1868-1937). She enrolled in the college under the name A.l. Custance to study veterinary medicine. Despite examination entitlement impediments placed in her way by the lawyers of the Royal College of Veterinary Surgeons, Williams gave her a testimonial in 1900 at the end of her coursework in his college, expressing his satisfaction that she was now a qualified veterinary surgeon