MAR1-a Regulator of the HMa and HMalpha Loci in SACCHAROMYCES CEREVISIAE

A mutation in the MAR1 (mating-type regulator) locus causing sterility in Saccharomyces cerevisiae is reported. The mutation maps on the left arm of linkage group IV between trp1 and cdc2 at a distance of about 27 cM from trp1 and about 31 cM from cdc2. Haploid strains with genotype MATalpha HMalpha HMa mar1-1 and MATa HMalpha HMamar1-1 are sterile. However, MATalpha hmalpha HMa mar1-1 and MATa HMalpha hma mar1-1 strains exhibit alpha and a mating type, respectively. The sterile strains can be "rare mated" with standard strains as a consequence of mutational changes at HMa and HMalpha. It is proposed that the MAR1 locus blocks the expression of MATalpha and MATa information thought to exist at HMa and HMalpha loci, respectively (Hicks, Strathern and Herskowitz, 1977). In a mar1-1 mutant, the expression of both HMalpha and HMa information leads to a nonmating phenotype similar to that of MATa/MATalpha diploids. The genetic evidence reported here is consistent with a central feature of the "cassette model", namely that HMalpha and hma carry MATa information and HMa and hmalpha carry MATalpha information.     

A mixed finite element formulation for a non-linear,transversely isotropic material model for the cardiac tissue

In this paper we present a mixed finite element method for modeling the passive properties of the myocardium. The passive properties are described by a non-linear, transversely isotropic, hyperelastic material model, and the myocardium is assumed to be almost incompressible. Single-field, pure displacement-based formulations are known to cause numerical difficulties when applied to incompressible or slightly compressible material cases. This paper presents an alternative approach in the form of a mixed formulation, where a separately interpolated pressure field is introduced as a primary unknown in addition to the displacement field. Moreover, a constraint term is included in the formulation to enforce (almost) incompressibility. Numerical results presented in the paper demonstrate the difficulties related to employing a pure displacement-based method, applying a set of physically relevant material parameter values for the cardiac tissue. The same problems are not experienced for the proposed mixed method. We show that the mixed formulation provides reasonable numerical results for compressible as well as nearly incompressible cases, also in situations of large fiber stretches. There is good agreement between the numerical results and the underlying analytical models.     

Patterns of Human Papillomavirus Types in Multiple Infections: An Analysis in Women and Men of the High Throughput Human Papillomavirus Monitoring Study

Background

To evaluate the pattern of co-infection of human papillomavirus (HPV) types in both sexes in Sweden.

Methods

Cell samples from genital swabs, first-void urine, and genital swabs immersed in first-void urine were collected in the present cross-sectional High Throughput HPV Monitoring study. Overall, 31,717 samples from women and 9,949 from men (mean age 25) were tested for 16 HPV types using mass spectrometry. Multilevel logistic regression was used to estimate the expected number of multiple infections with specific HPV types, adjusted for age, type of sample, and accounting for correlations between HPV types due to unobserved risk factors using sample-level random effects. Bonferroni correction was used to allow for multiple comparisons (120).

Results

Observed-to-expected ratio for any multiple infections was slightly above unity in both sexes, but, for most 2-type combinations, there was no evidence of significant departure from expected numbers. HPV6/18 was found more often and HPV51/68 and 6/68 less often than expected. However, HPV68 tended to be generally underrepresented in co-infections, suggesting a sub-optimal performance of our testing method for this HPV type.

Conclusions

We found no evidence for positive or negative clustering between HPV types included in the current prophylactic vaccines and other untargeted oncogenic types, in either sex.     

Calcium ions and osteoclastogenesis initiate the induction of bone formation by coral‐derived macroporous constructs

Coral-derived calcium carbonate/hydroxyapatite macroporous constructs of the genus Goniopora with limited hydrothermal conversion to hydroxyapatite (7% HA/CC) initiate the induction of bone formation. Which are the molecular signals that initiate pattern formation and the induction of bone formation? To evaluate the role of released calcium ions and osteoclastogenesis, 7% HA/CC was pre-loaded with either 500 μg of the calcium channel blocker, verapamil hydrochloride, or 240 μg of the osteoclast inhibitor, biphosphonate zoledronate, and implanted in the rectus abdominis muscle of six adult Chacma baboons Papio ursinus. Generated tissues on days 15, 60 and 90 were analysed by histomorphometry and qRT-PCR. On day 15, up-regulation of type IV collagen characterized all the implanted constructs correlating with vascular invasion. Zoledronate-treated specimens showed an important delay in tissue patterning and morphogenesis with limited bone formation. Osteoclastic inhibition yielded minimal, if any, bone formation by induction. 7% HA/CC pre-loaded with the Ca⁺⁺ channel blocker verapamil hydrochloride strongly inhibited the induction of bone formation. Down-regulation of bone morphogenetic protein-2 (BMP-2) together with up-regulation of Noggin genes correlated with limited bone formation in 7% HA/CC pre-loaded with either verapamil or zoledronate, indicating that the induction of bone formation by coral-derived macroporous constructs is via the BMPs pathway. The spontaneous induction of bone formation is initiated by a local peak of Ca⁺⁺ activating stem cell differentiation and the induction of bone formation.     

As Facts and Chats Go Online,What Is Important for Adolescents with Type 1 Diabetes?

Background

Continued refinement of resources for patient information, education and support is needed. Considering the rapid development of new communication practices, the perspectives of young people themselves warrant more attention using a wide research focus. The purpose of this study was to understand information-seeking behaviours, Internet use and social networking online in adolescents with type 1 diabetes (T1DM). This applied to their everyday life, including the context of diabetes and their experiences and need of contact with T1DM peers.

Methodology/Principal Findings

Twenty-four adolescents aged 10–17 years with T1DM were recruited from a county hospital in the south-east of Sweden. Qualitative data were obtained using eight focus groups, wherein each participant engaged in a 60–90 minute video/audio-recorded session. The focus group data were transcribed and analysed using qualitative content analysis. Some demographic and medical information was also collected. The three main categories that were identified; Aspects of Security, Updating, and Plainness and their sub-categories gave significant information about how to enhance information retrieval and peer contacts related to T1DM. Regarding the persons'' information-seeking behaviour, Internet use, and use of social media some differences could be identified depending on gender and age.

Conclusions/Significance

Sensitivity and adaptation to users'' needs and expectations seem crucial in the development of future online resources for adolescents with T1DM. To start with, this could mean applying a wider range of already existing information and communication technologies. Health practitioners need to focus on the areas of security of information and communication, frequency of updating, and simplicity of design-less is more.     

Unbiased Approach for Virus Detection in Skin Lesions

To assess presence of virus DNA in skin lesions, swab samples from 82 squamous cell carcinomas of the skin (SCCs), 60 actinic keratoses (AKs), paraffin-embedded biopsies from 28 SCCs and 72 kerathoacanthomas (KAs) and fresh-frozen biopsies from 92 KAs, 85 SCCs and 92 AKs were analyzed by high throughput sequencing (HTS) using 454 or Ion Torrent technology. We found total of 4,284 viral reads, out of which 4,168 were Human Papillomavirus (HPV)-related, belonging to 15 known (HPV8, HPV12, HPV20, HPV36, HPV38, HPV45, HPV57, HPV59, HPV104, HPV105, HPV107, HPV109, HPV124, HPV138, HPV147), four previously described putative (HPV 915 F 06 007 FD1, FA73, FA101, SE42) and two putatively new HPV types (SE46, SE47). SE42 was cloned, sequenced, designated as HPV155 and found to have 76% similarity to the most closely related known HPV type. In conclusion, an unbiased approach for viral DNA detection in skin tumors has found that, although some new putative HPVs were found, known HPV types constituted most of the viral DNA.     

Catalytic Turnover Triggers Exchange of Subunits of the Magnesium Chelatase AAA+ Motor Unit

The ATP-dependent insertion of Mg²⁺ into protoporphyrin IX is the first committed step in the chlorophyll biosynthetic pathway. The reaction is catalyzed by magnesium chelatase, which consists of three gene products: BchI, BchD, and BchH. The BchI and BchD subunits belong to the family of AAA+ proteins (ATPases associated with various cellular activities) and form a two-ring complex with six BchI subunits in one layer and six BchD subunits in the other layer. This BchID complex is a two-layered trimer of dimers with the ATP binding site located at the interface between two neighboring BchI subunits. ATP hydrolysis by the BchID motor unit fuels the insertion of Mg²⁺ into the porphyrin by the BchH subunit. In the present study, we explored mutations that were originally identified in semidominant barley (Hordeum vulgare L.) mutants. The resulting recombinant BchI proteins have marginal ATPase activity and cannot contribute to magnesium chelatase activity although they apparently form structurally correct complexes with BchD. Mixing experiments with modified and wild-type BchI in various combinations showed that an exchange of BchI subunits in magnesium chelatase occurs during the catalytic cycle, which indicates that dissociation of the complex may be part of the reaction mechanism related to product release. Mixing experiments also showed that more than three functional interfaces in the BchI ring structure are required for magnesium chelatase activity.     

The function of Notch signalling in segment formation in the crustacean Daphnia magna (Branchiopoda)

Ten years ago we showed for the first time that Notch signalling is required in segmentation in spiders, indicating the existence of similar mechanisms in arthropod and vertebrate segmentation. However, conflicting results in various arthropod groups hampered our understanding of the ancestral function of Notch in arthropod segmentation. Here we fill a crucial data gap in arthropods and analyse segmentation in a crustacean embryo. We analyse the expression of homologues of the Drosophila and vertebrate segmentation genes and show that members of the Notch signalling pathway are expressed at the same time as the pair-rule genes. Furthermore, inactivation of Notch signalling results in irregular boundaries of the odd-skipped-like expression domains and affects the formation of segments. In severe cases embryos appear unsegmented. We suggest two scenarios for the function of Notch signalling in segmentation. The first scenario agrees with a segmentation clock involving Notch signalling, while the second scenario discusses an alternative mechanism of Notch function which is integrated into a hierarchical segmentation cascade.