Asymmetric trehalose analogues to probe disaccharide processing pathways in mycobacteria

The uptake and metabolism of the disaccharide trehalose by Mycobacterium tuberculosis is essential for the virulence of this pathogen. Here we describe the chemoenzymatic synthesis of new azido-functionalised asymmetric trehalose probes that resist degradation by mycobacterial enzymes and are used to probe trehalose processing pathways in mycobacteria

Supreme Court justices cooperate strategically to strengthen coalitions

The past year has seen major decisions by the Supreme Court on gay marriage and Obamacare. But what influences the coalitions of opinion in Supreme Court decisions? In new research that examines nearly 30,000 choices by Supreme Court justices over 40 years, Andrew J. O’Geen and Christopher M. Parker find that when a decision’s initial majority is small, justices are much less likely to write separate opinions in order to stabilize the shaky majority

The 5'-3' exoribonuclease Pacman (Xrn1) regulates expression of the heat shock protein Hsp67Bc and the microRNA miR-277-3p in Drosophila wing imaginal discs

Pacman/Xrn1 is a highly conserved exoribonuclease known to play a critical role in gene regulatory events such as control of mRNA stability, RNA interference and regulation via miRNAs. Although Pacman has been well studied in Drosophila tissue culture cells, the biologically relevant cellular pathways controlled by Pacman in natural tissues are unknown. This study shows that a hypomorphic mutation in pacman (pcm5) results in smaller wing imaginal discs. These tissues, found in the larva, are known to grow and differentiate to form wing and thorax structures in the adult fly. Using microarray analysis, followed by quantitative RT-PCR, we show that eight mRNAs were increased in level by >2 fold in the pcm5 mutant wing discs compared to the control. The levels of pre mRNAs were tested for five of these mRNAs; four did not increase in the pcm5 mutant, showing that they are regulated at the post-transcriptional level and therefore could be directly affected by Pacman. These transcripts include one that encodes the heat-shock protein Hsp67Bc, which is upregulated 11.9-fold at the post-transcriptional level and 2.3-fold at the protein level. One miRNA, miR-277-3p, is 5.6-fold downregulated at the post-transcriptional level in mutant discs, suggesting that Pacman affects its processing in this tissue. Together, these data show that a relatively small number of mRNAs and miRNAs substantially change in abundance in pacman mutant wing imaginal discs. Since Hsp67Bc is known to regulate autophagy and protein synthesis, it is possible that Pacman may control the growth of wing imaginal discs by regulating these processes

Improving Communication between Doctors and Parents after Newborn Screening

Background: Newborn screening (NBS) enables early treatment, and some consider it a natural vehicle for genetic screening. Bioethicists argue for caution since families of infants with carrier status can develop psychosocial complications. This paper describes the methods and feasibility of Wisconsin’s statewide project for quality improvement of communication and psychosocial outcomes after NBS. Methods: When NBS identifies carrier status for cystic fibrosis or sickle cell, we contact primary care providers (PCPs), answer questions, and invite them to rehearse informing the parents. Three months later, we telephone the parents, assess knowledge and psychosocial outcomes, provide counseling, and assist with self-referral to further resources. Afterward, evaluation surveys are provided to the parents, to be returned anonymously. Results: Birthing facilities provided accurate PCP names for 73% of 817 infants meeting inclusion criteria; we identified PCPs for 21% more. We reached 47.3% of PCPs in time to invite a rehearsal; 60% of these accepted. We successfully called 50.2% of eligible parents; 61% recalled a PCP explanation, and 48.5% evaluated the explanation favorably. Evaluations by parents with limited health literacy were less favorable. Conclusion: It is feasible to follow parents for psychosocial outcomes after NBS. Preliminary data about communication is mixed, but further data will describe psychosocial outcomes and investigate outcomes’ associations with communication

What needs to change to increase chlamydia screening in general practice in Australia? The views of general practitioners

<p>Abstract</p> <p>Background</p> <p>Australia is considering implementing a chlamydia screening program in general practice. The views of general practitioners (GPs) are necessary to inform the design of the program. This paper aimed to investigate Australian GPs' views on how chlamydia screening could work in the Australian context.</p> <p>Methods</p> <p>This project used both qualitative interviews and a quantitative questionnaire. GPs were randomly selected from a national database of medical practitioners for both the qualitative and quantitative components. Semi-structured interviews were conducted with GPs and a thematic analysis conducted. The results of the interviews were used to design a quantitative postal questionnaire for completion by a larger sample of GPs. Up to three reminders were sent to non-responders.</p> <p>Results</p> <p>Twenty one GPs completed an interview and 255 completed the postal questionnaire. The results of the postal survey were in strong concordance with those of the interview. GPs identified a number of barriers to increased screening including lack of time, knowledge of GPs and the public about chlamydia, patient embarrassment and support for partner notification. GPs felt strongly that screening would be easier if there was a national program and if the public and GPs had a greater knowledge about chlamydia. Incentive payments and mechanisms for recall and reminders would facilitate screening. Greater support for contact tracing would be important if screening is to increase.</p> <p>Conclusion</p> <p>Chlamydia screening in general practice is acceptable to Australian GPs. If screening is to succeed, policy makers must consider the facilitators identified by GPs.</p