Solution structure of a repeated unit of the ABA-1 nematode polyprotein allergen of ascaris reveals a novel fold and two discrete lipid-binding sites

Parasitic nematode worms cause serious health problems in humans and other animals. They can induce allergic-type immune responses, which can be harmful but may at the same time protect against the infections. Allergens are proteins that trigger allergic reactions and these parasites produce a type that is confined to nematodes, the nematode polyprotein allergens (NPAs). These are synthesized as large precursor proteins comprising repeating units of similar amino acid sequence that are subsequently cleaved into multiple copies of the allergen protein. NPAs bind small lipids such as fatty acids and retinol (Vitamin A) and probably transport these sensitive and insoluble compounds between the tissues of the worms. Nematodes cannot synthesize these lipids, so NPAs may also be crucial for extracting nutrients from their hosts. They may also be involved in altering immune responses by controlling the lipids by which the immune and inflammatory cells communicate. We describe the molecular structure of one unit of an NPA, the well-known ABA-1 allergen of Ascaris and find its structure to be of a type not previously found for lipid-binding proteins, and we describe the unusual sites where lipids bind within this structur

How binding of small molecule and peptide ligands to HIV-1 TAR alters the RNA motional landscape

The HIV-1 TAR RNA represents a well-known paradigm to study the role of dynamics and conformational change in RNA function. This regulatory RNA changes conformation in response to binding of Tat protein and of a variety of peptidic and small molecule ligands, indicating that its conformational flexibility and intrinsic dynamics play important roles in molecular recognition. We have used 13C NMR relaxation experiments to examine changes in the motional landscape of HIV-1 TAR in the presence of three ligands of different affinity and specificity. The ligands are argininamide, a linear peptide mimic of the Tat basic domain and a cyclic peptide that potently inhibits Tat-dependent activation of transcription. All three molecules induce the same motional characteristics within the three nucleotides bulge that represents the Tat-binding site. However, the cyclic peptide has a unique motional signature in the apical loop, which represents a binding site for the essential host co-factor cyclin T1. These results suggest that all peptidic mimics of Tat induce the same dynamics in TAR within this protein binding site. However, the new cyclic peptide mimic of Tat represents a new class of ligands with a unique effect on the dynamics and the structure of the apical loop

Phage therapy as an approach to prevent Vibrio anguillarum infections in fish larvae production

Fish larvae in aquaculture have high mortality rates due to pathogenic bacteria, especially the Vibrio species, and ineffective prophylactic strategies. Vaccination is not feasible in larvae and antibiotics have reduced efficacy against multidrug resistant bacteria. A novel approach to controlling Vibrio infections in aquaculture is needed. The potential of phage therapy to combat vibriosis in fish larvae production has not yet been examined. We describe the isolation and characterization of two bacteriophages capable of infecting pathogenic Vibrio and their application to prevent bacterial infection in fish larvae. Two groups of zebrafish larvae were infected with V. anguillarum (∼106 CFU mL-1) and one was later treated with a phage lysate (∼108 PFU mL-1). A third group was only added with phages. A fourth group received neither bacteria nor phages (fish control). Larvae mortality, after 72 h, in the infected and treated group was similar to normal levels and significantly lower than that of the infected but not treated group, indicating that phage treatment was effective. Thus, directly supplying phages to the culture water could be an effective and inexpensive approach toward reducing the negative impact of vibriosis in larviculture

PROTOCOL: Family group decision making for children at risk of abuse and neglect

This is the final version of an article published by Campbell Systematic Reviews. This work is licensed under the Creative Commons Attribution- NonCommercial 4.0 International License. To view a copy of this license, visit https://creativecommons.org/licenses/by-nd/4.0

MRI volumetry for prediction of tumour response to neoadjuvant chemotherapy followed by chemoradiotherapy in locally advanced rectal cancer

Objective: To investigate if MRI-assessed tumour volumetry correlates with histological tumour response to neoadjuvant chemotherapy (NACT) and subsequent chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC). Methods: Data from 69 prospectively enrolled patients with LARC receiving NACT followed by CRT and radical surgery were analysed. Whole-tumour volumes were contoured in T2 weighted MR images obtained pre-treatment (VPRE), after NACT (VNACT) and after the full course of NACT followed by CRT (VCRT). VPRE, VNACT and tumour volume changes relative to VPRE, ΔVNACT and ΔVCRT were calculated and correlated to histological tumour regression grade (TRG). Results: 61% of good histological responders (TRG 1–2) to NACT followed by CRT were correctly predicted by combining VPRE  −78.2% and VNACT < 3.3 cm3. The highest accuracy was found for VNACT, with 55.1% sensitivity given 100% specificity. The volume regression after completed NACT and CRT (VCRT) was not significantly different between good and poor responders (TRG 1–2 vs TRG 3–5). Conclusion: MRI-assessed small tumour volumes after NACT correlated with good histological tumour response (TRG 1–2) to the completed course of NACT and CRT. Furthermore, by combining tumour volume measurements before, during and after NACT, more good responders were identified

SPINAL BLOCKS WITH AND WITHOUT MORPHINE IN WOMEN UNDERGOING HYSTERECTOMIES- A RANDOMIZED STUDY

To study whether a group of patients going through abdominal hysterectomies under general anesthesia could reduce their time of discharge and consumption of parenteral opioids by adding morphine to an intrathecal block. Methods: Sixty seven healthy women, undergoing abdominal hysterectomies. Patients had general anesthesia in combination with spinal blocks. Randomization between intrathecal blocks with morphine (group 1) and without morphine (group 2), in combination with either postoperative intermittent (group 1) or patient controlled analgesia (group 2). Results: The median time to discharge in group 1 was 53 hours and in group two 69 hours. Time of discharge was not statistically significant (p = 0.51). The patients in group 2 had significantly higher visual analogue scores for pain postoperatively. More postoperative opioids were also consumed in that group (p&lt;0.0001). Furthermore, significantly more patients in group 2 compared to group1 indicated that they had suffered from major nausea (p=0.01)