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Tropheryma whipplei, is an actinobacterium that causes different infections in humans, including Whipple's disease. The bacterium infects and replicates in macrophages, leading to a Th2-biased immune response. selleck chemicals Previous studies have shown that T. whipplei harbors complex surface glycoproteins with evidence of sialylation. However, the exact contribution of these glycoproteins for infection and survival remains obscure. To address this, we characterized the bacterial glycoprofile and evaluated the involvement of human β-galactoside-binding lectins, Galectin-1 (Gal-1) and Galectin-3 (Gal-3) which are highly expressed by macrophages as receptors for bacterial glycans. Tropheryma whipplei glycoproteins harbor different sugars including glucose, mannose, fucose, β-galactose and sialic acid. Mass spectrometry identification revealed that these glycoproteins were membrane- and virulence-associated glycoproteins. Most of these glycoproteins are highly sialylated and N-glycosylated while some of them are rich in poly-N-acetyllactosamine (Poly-LAcNAc) and bind Gal-1 and Gal-3. In vitro, T. whipplei modulates the expression and cellular distribution of Gal-1 and Gal-3. Although both galectins promote T. whipplei infection by enhancing bacterial cell entry, only Gal-3 is required for optimal bacterial uptake. Finally, we found that serum levels of Gal-1 and Gal-3 were altered in patients with T. whipplei infections as compared to healthy individuals, suggesting that galectins are also involved in vivo. Among T. whipplei membrane-associated proteins, poly-LacNAc rich-glycoproteins promote infection through interaction with galectins. T. whipplei modulates the expression of Gal-1 and Gal-3 both in vitro and in vivo. Drugs interfering with galectin-glycan interactions may provide new avenues for the treatment and diagnosis of T. whipplei infections.Ligand binding and temperature play important roles in riboswitch RNAs' structures and functions. However, most studies focused on studying structural dynamics or gene-regulation function of riboswitches from the aspect of ligand, instead of temperature. Here we combined NMR, ITC, stopped-flow and in vivo assays to investigate the ligand-triggered switch of adenine riboswitch from 10 to 45°C. Our results demonstrated that at single-nucleotide resolution, structural regions sensed ligand and temperature diversely. Temperature had opposite effects on ligand-binding and gene-regulation of adenine riboswitch. Compared with higher temperature, the RNA bound with its cognate ligand obviously stronger, while its regulatory capacity was weakened at lower temperature. In addition, application of specific-labelled RNAs to the stopped-flow experiments identified the real-time folding of the specific positions upon ligand addition at different temperatures. The kissing loop and internal loop at the riboswitch responded to ligand and temperature differently. The distinct thermo-dynamics of adenine riboswitch exposed here may contribute to the fields of RNA sensors and drug design.Formation of higher-order supramolecular complexes has emerged as a common principle underlying activity of a number of immune and regulated cell-death signalling pathways in animals, plants and fungi. Some of these signalosomes employ functional amyloid motifs in their assembly process. The description of such systems in fungi finds its origin in earlier studies on a fungal prion termed [Het-s], originally identified as a non-Mendelian cytoplasmic infectious element. Janine Beisson has been a key contributor to such early studies. Recent work on this and related systems offers a more integrated view framing this prion in a broader picture including related signalling systems described in animals. We propose here an auto-commentary centred on three recent studies on amyloid signalling in microbes. Collectively, these studies increase our understanding of fold conservation in functional amyloids and the structural basis of seeding, highlight the relation of fungal amyloid motifs to mammalian RHIM (RIP homotypic interaction motif) and expand the concept of Nod-like receptor-based amyloid signalosomes to the prokaryote reign.
In central auditory disorders caused by damage of the cerebral hemispheres, there are cortical deafness and auditory agnosia. Although clinical cases of cortical deafness have been reported, little is known about the hearing problems and localized lesions associated with cortical deafness.

The aims of our research are to elucidate lesion sites associated with cortical deafness and to clarify why patients with cerebral lesions are not aware of any sound at all.

Three patients diagnosed as having total loss of hearing participated in this study. We conducted pure-tone audiometry, speech audiometry, distortion product otoacoustic emission (DPOAE), auditory brainstem response (ABR), and brain magnetic resonance imaging (MRI) to diagnose cortical deafness with aphasia tests of these patients.

Our studies showed that waves VI and VII as well as waves I to V have normal peak latencies in ABRs in all three patients. In brain MRI, we found complete damage of proximal parts of bilateral auditory radiations in the three patients.

We propose 'subcortical deafness' as a subtype of auditory agnosia.
We propose 'subcortical deafness' as a subtype of auditory agnosia.
To explore and understand young people's perspectives of fixed orthodontic treatment. In particular, understanding how young people perceived and experienced having a fixed appliance and how their experiences can change during their treatment.

Qualitative study carried out longitudinally.

In-depth qualitative interviews carried out in participants' homes, video diaries recorded by participants when and where they wish.

Fifteen patients aged 10-15 years undergoing NHS fixed appliance treatment.

Data were collected by in-depth interviews and video diaries throughout the participants' course of orthodontic treatment. Data were analysed using thematic analysis.

Young people's friends, family and social media influenced how young people felt about the appearance of their teeth. Young people can perceive negative social judgements are made about them based on the appearance of their teeth; however, the appearance of the brace was not a concern. For some of the young people, the presence of the brace formed a rite of passage throughout adolescence.
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