A chemical inhibitor of IST1-CHMP1B interaction impairs endosomal recycling and induces noncanonical LC3 lipidation.

The endosomal sorting complex required for transport (ESCRT) machinery constitutes multisubunit protein complexes that play an essential role in membrane remodeling and trafficking. ESCRTs regulate a wide array of cellular processes, including cytokinetic abscission, cargo sorting into multivesicular bodies (MVBs), membrane repair, and autophagy. Given the versatile functionality of ESCRTs, and the intricate organizational structure of the ESCRT machinery, the targeted modulation of distinct ESCRT complexes is considerably challenging. This study presents a pseudonatural product targeting IST1-CHMP1B within the ESCRT-III complexes. The compound specifically disrupts the interaction between IST1 and CHMP1B, thereby inhibiting the formation of IST1-CHMP1B copolymers essential for normal-topology membrane scission events. While the compound has no impact on cytokinesis, MVB sorting, or biogenesis of extracellular vesicles, it rapidly inhibits transferrin receptor recycling in cells, resulting in the accumulation of transferrin in stalled sorting endosomes. Stalled endosomes become decorated by lipidated LC3, suggesting a link between noncanonical LC3 lipidation and inhibition of the IST1-CHMP1B complex.

Visual Acuity Screening in North Indian Schools: Testing Accuracy and Cost of Alternate Screening Models.

PURPOSE: Our study compares the sensitivity, specificity and cost of visual acuity screening as performed by all class teachers (ACTs), selected teachers (STs) and vision technicians (VTs) in north Indian schools. METHODS: Prospective cluster randomized control studies are conducted in schools in a rural block and an urban-slum of north India. Consenting schools, with a minimum of 800 students aged 6 to 17 years, within a defined study region in both locations, were randomised into three arms: ACTs, STs or VTs. Teachers were trained to test visual acuity. Reduced vision was defined as unable to read equivalent of 20/30. Optometrists, who were masked to results of initial screening, examined all children. Costs were measured for all three arms. RESULTS: The number of students screened were 3410 in 9 ACT schools, 2999 in 9 ST schools and 3071 in 11 VT schools. Vision deficit was found in 214 (6.3%), 349 (11.6%) and 207 (6.7%), (p < .001) children in the ACT, ST and VT arms, respectively. The positive predictive value of VT screening for vision deficit (81.2%) was significantly higher than that of ACTs (42.5%) and STs (30.1%), (p < .001). VTs had significantly higher sensitivity of 93.3% and specificity of 98.7%, compared to ACTs (36.0% and 96.1%) and STs (44.3% and 91.2%). The cost of screening children with actual visual deficit by ACTs, STs and VTs, was found to be $9.35, $5.79 and $2.82 per child, respectively. CONCLUSION: Greater accuracy and lower cost favours school visual acuity screening by visual technicians in this setting, when they are available.

Corrigendum: The pulmonary extracellular matrix is a bactericidal barrier against Haemophilus influenzae in chronic obstructive pulmonary disease (COPD): implications for an in vivo innate host defense function of collagen VI.

[This corrects the article DOI: 10.3389/fimmu.2018.01988.].

An investigation of luminescence properties of CaF2: Dy nanophosphor irradiated with gamma rays and low energy proton beams.

This paper reports the luminescence properties of nanocrystalline calcium fluoride doped with dysprosium (CaF2: Dy). The nanophosphor has been synthesized by the chemical co-precipitation technique and the dopant concentration has been optimized at 0.3 mol% using thermoluminescence (TL) intensity emitted post 50Gy gamma dose irradiation of samples doped with different dopant concentrations. X-ray diffraction shows the formation of crystalline particles with an average size of 49.233 nm. Photoluminescence (PL) emission spectrum shows the characteristic peaks at 455 nm, 482 nm, 573 nm corresponding to 4I15/2 to 6H15/2, 4F9/2 to 6H15/2 and 4F9/2 to 6H13/2 Dy3+ transitions respectively. PL excitation spectrum shows a peak at 327 nm which corresponds to the Dy3+ transition of 6H15/2 to 4L19/2. Gamma (of 1.25 MeV) and low energy proton beam (of 30 keV) irradiated nanophosphor shows a variation in TL glow curve structure and peak position with an increase in radiation dose/fluence. However, the nanophosphor shows a wide linear dose response for 60Co gamma radiation in the range 10 Gy - 1.5 kGy and for low energy proton beam in the fluence range of 1012-1014 ions/cm2. Srim 2013 has been used to calculate the ion beam parameters including the range of protons in CaF2: Dy 0.3 mol%. The nanophosphor CaF2: Dy could be further investigated as a potential dosimeter for gamma rays and proton beam by studying its TL properties for different energies of these radiations.

Door-to-door Screening as a New Model Augmenting School Eye Screening: Reaching Out to School Age Children in the Midst of a Pandemic.

PURPOSE: Explore door-to-door eye screening in India as a model to reach school age children in need of eye care, especially during school closures due to the Covid-19 pandemic. METHODS: Children between 5 and 18 years were screened in an urban-slum of Delhi from September 2020 to March 2021. Screening included capturing ocular complaints, visual acuity and conducting a torchlight examination. Children with any eye-related complaints, gross abnormality or a LogMAR acuity of more than 0.2 in either eye were referred to the nearby vision centre. Data were disaggregated by gender and age group. Reporting after referral and proportion of true positives referrals were used to assess the model. RESULTS: 32,857 children were screened. 55% were boys. Only 917 children (2.8%) had previous eye examinations. 1814 (5.5%) children were referred. Overall compliance rate amongst those referred was 59% (1070 of 1814) and compliance was significantly higher (72%) amongst those referred with poor vision as compared to those with only ocular morbidities (38%). Overall compliance was significantly higher amongst older age group (64% vs 50%) and amongst girls than boys (61% vs 56%). 3.9% children were detected with refractive error (RE) and 2.5% with uncorrected RE which was significantly higher in girls and in older age group. Of 1070 children reporting after referral, 85% had confirmed diagnosis for RE or other ocular pathology. CONCLUSION: Door-to-door screening had good referral compliance and positive predictive value. We recommend this model as a supplement to school screening especially in regions with low enrolment and high absenteeism in schools.

Correction: Effect of Door-to-Door Screening and Awareness Generation Activities in the Catchment Areas of Vision Centers on Service Use: Protocol for a Randomized Experimental Study.

[This corrects the article DOI: 10.2196/31951.].

Effect of Door-to-Door Screening and Awareness Generation Activities in the Catchment Areas of Vision Centers on Service Use: Protocol for a Randomized Experimental Study.

BACKGROUND: A vision center (VC) is a significant eye care service model to strengthen primary eye care services. VCs have been set up at the block level, covering a population of 150,000-250,000 in rural areas in North India. Inadequate use by rural communities is a major challenge to sustainability of these VCs. This not only reduces the community's vision improvement potential but also impacts self-sustainability and limits expansion of services in rural areas. The current literature reports a lack of awareness regarding eye diseases and the need for care, social stigmas, low priority being given to eye problems, prevailing gender discrimination, cost, and dependence on caregivers as factors preventing the use of primary eye care. OBJECTIVE: Our organization is planning an awareness-cum-engagement intervention-door-to-door basic eye checkup and visual acuity screening in VCs coverage areas-to connect with the community and improve the rational use of VCs. METHODS: In this randomized, parallel-group experimental study, we will select 2 VCs each for the intervention arm and the control arm from among poor, low-performing VCs (ie, walk-in of ≤10 patients/day) in our 2 operational regions (Vrindavan, Mathura District, and Mohammadi, Kheri District) of Uttar Pradesh. Intervention will include door-to-door screening and awareness generation in 8-12 villages surrounding the VCs, and control VCs will follow existing practices of awareness generation through community activities and health talks. Data will be collected from each VC for 4 months of intervention. Primary outcomes will be an increase in the number of walk-in patients, spectacle advise and uptake, referral and uptake for cataract and specialty surgery, and operational expenses. Secondary outcomes will be uptake of refraction correction and referrals for cataract and other eye conditions. Differences in the number of walk-in patients, referrals, uptake of services, and cost involved will be analyzed. RESULTS: Background work involved planning of interventions and selection of VCs has been completed. Participant recruitment has begun and is currently in progress. CONCLUSIONS: Through this study, we will analyze whether our door-to-door intervention is effective in increasing the number of visits to a VC and, thus, overall sustainability. We will also study the cost-effectiveness of this intervention to recommend its scalability. TRIAL REGISTRATION: ClinicalTrials.gov NCT04800718; https://clinicaltrials.gov/ct2/show/NCT04800718. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/31951.

Peptidoglycan-Binding Anchor Is a Pseudomonas aeruginosa OmpA Family Lipoprotein With Importance for Outer Membrane Vesicles, Biofilms, and the Periplasmic Shape.

The outer membrane protein A (OmpA) family contains an evolutionary conserved domain that links the outer membrane in Gram-negative bacteria to the semi-rigid peptidoglycan (PG) layer. The clinically significant pathogen Pseudomonas aeruginosa carries several OmpA family proteins (OprF, OprL, PA0833, and PA1048) that share the PG-binding domain. These proteins are important for cell morphology, membrane stability, and biofilm and outer membrane vesicle (OMV) formation. In addition to other OmpAs, in silico analysis revealed that the putative outer membrane protein (OMP) with gene locus PA1041 is a lipoprotein with an OmpA domain and, hence, is a potential virulence factor. This study aimed to evaluate PA1041 as a PG-binding protein and describe its effect on the phenotype. Clinical strains were confirmed to contain the lipoprotein resulting from PA1041 expression with Western blot, and PG binding was verified in enzyme-linked immunosorbent assay (ELISA). By using a Sepharose bead-based ELISA, we found that the lipoprotein binds to meso-diaminopimelic acid (mDAP), an amino acid in the pentapeptide portion of PGs. The reference strain PAO1 and the corresponding transposon mutant PW2884 devoid of the lipoprotein were examined for phenotypic changes. Transmission electron microscopy revealed enlarged periplasm spaces near the cellular poles in the mutant. In addition, we observed an increased release of OMV, which could be confirmed by nanoparticle tracking analysis. Importantly, mutants without the lipoprotein produced a thick, but loose and unorganized, biofilm in flow cells. In conclusion, the lipoprotein from gene locus PA1041 tethers the outer membrane to the PG layer, and mutants are viable, but display severe phenotypic changes including disordered biofilm formation. Based upon the phenotype of the P. aeruginosa PW2884 mutant and the function of the protein, we designate the lipoprotein with locus tag PA1041 as "peptidoglycan-binding anchor" (Pba).

Exploring the bacterial nano-universe.

Since the days of the first acknowledged microscopist, Antonie van Leeuwenhoek, the 'animalcules', that is, bacteria and other microbes have been subject to increasingly detailed visualization. With the currently most sophisticated molecular imaging method; cryo electron tomography (Cryo-ET), we are reaching the milestone of being able to image an entire organism in a single dataset at nanometer resolution. Cryo-ET will enable the next revolution in our understanding of bacterial cells, their ultra-structure and intricate molecular nanomachines. Here, we highlight recent research discoveries based on constantly progressing technology developments. We discuss advantages and challenges of using Cryo-ET to visualize spatial structure of microorganisms and macromolecular complexes in their native environment.

Compliance to the secondary prophylaxis and awareness of rheumatic heart disease: A cross-sectional study in low-income province of India.

BACKGROUND: Rheumatic heart disease is a preventable problem and regular secondary prophylaxis and proper awareness about this disease among common people may reduce the burden of this disease in any region. OBJECTIVES: To find out compliance to the secondary prophylaxis of Rheumatic heart disease and awareness about this disease among common people of Bihar. METHODOLOGY: This was a questionnaire based cross sectional study to find out compliance to the secondary prophylaxis and awareness of Rheumatic heart disease, conducted at two tertiary care referral hospitals of Bihar. RESULT: 19/41 (46%) study participants were non-compliant to regular secondary prophylaxis. Most of the participants (34/42,81%) had poor knowledge of Rheumatic heart disease. Low socioeconomic condition was not a statistically significant risk factor for poor adherence to the secondary prophylaxis (odds ratio-5.29,95% CI- 0.55-50.08, P-0.11). Low level of education was not a statistically significant risk factor for poor awareness as compared to the participants with education of 10th standard or above (odds ratio 4.0, 95% CI- 0.65-24.24, P- 0.15). CONCLUSION: Approximately half of the participants of this study were non-compliant to the regular secondary prophylaxis of rheumatic heart disease and most of them had poor awareness of this disease. Ensuring regular secondary prophylaxis and improving awareness to Rheumatic heart disease among common people may reduce its prevalence in regions with significant burden of Rheumatic heart disease.

Luminescence properties of tricalcium phosphate doped with dysprosium.

Tricalcium phosphate having effective atomic number Zeff = 15.785, equivalent to that of bones was studied for its thermoluminescence (TL) and photoluminescence (PL) properties. Different samples with varied concentrations of the dopant Dy3+ (0.1, 0.2, 0.3, 0.4, 0.5, and 0.6 mol %) were synthesized by the chemical co-precipitation technique. Phase and compound confirmations were done using X-Ray Diffraction (XRD) and the phosphors' crystallite size was calculated using Scherrer's formula which was found to range between 27 nm and 49 nm. The surface morphological study was done using Field Emission-Scanning Electron Microscopy (FE-SEM). Other characterization techniques used for compound confirmation included Energy Dispersive X-Ray Spectroscopy (EDX) and Fourier Transform Infrared Spectroscopy (FTIR). Samples were further irradiated by gamma rays (emitted from Co-60) with dose varying from 10 Gy to 5 kGy in order to study their TL properties. Concentration optimization of the given phosphor was done in terms of its TL intensity and was found to be 0.5 mol %. The TL dose response of the phosphor was linear over a wide range of dose (10 Gy-3 kGy). Deconvolution was performed on the glow curve for 10 Gy dose, giving six peaks (at 127o, 153o, 185o, 218o, 313o and 335oC) suggesting the presence of six different types of traps. Other characteristics of the TL material i.e. repeatability and fading were also studied. Overall, the phosphor showed promising results for its utility in TL dosimetry. In addition to the TL, PL further confirmed the presence of dopant in the phosphor. Moreover, the dopant concentration was optimized in terms of the nanophosphor's PL intensity. The Commission International de l'Éclairage (CIE) was used to calculate chromaticity coordinates, colour rendering index and colour temperature in order to investigate the phosphor's application in white LEDs.

Effect of γ-irradiation on thermal and thermoluminescence properties of polystyrene/europium (III) oxide composite film.

In the present study, polystyrene:europium (III) oxide polymer films at a ratio of 95:5 wt% were prepared using a solution casting technique. These polymeric films were irradiated with 5, 25 and 50 kGy γ-radiation doses and their thermoluminescence (TL) and thermal properties were studied as a function of radiation dose. Analysis of Fourier transform infrared spectra revealed different modes of vibration and polymer-filler interaction. Reduction of vibrational modes with radiation dose was observed. The TL glow curve intensity was observed to increase with increasing radiation dose and to become broader in the 378 K and 444 K regions. Detrapping of electrons implied by the glow curve was caused by thermally induced macromolecular motion, concurrent with ß-relaxation in polystyrene. The TL glow curve parameters were computed using a glow curve deconvolution method. Differential scanning calorimetry analysis indicated that the glass transition temperature (Tg ) increased with increase in dose, suggesting crosslinking of the polymer chain. Scanning electron microscopy analysis evidenced the change in surface morphology due to γ-irradiation.

The Laminin Interactome: A Multifactorial Laminin-Binding Strategy by Nontypeable Haemophilus influenzae for Effective Adherence and Colonization.

Laminin is a well-defined component of the airway basement membrane (BM). Efficient binding of laminin via multiple interactions is important for nontypeable Haemophilus influenzae (NTHi) colonization in the airway mucosa. In this study, we identified elongation factor thermo-unstable (EF-Tu), l-lactate dehydrogenase (LDH), protein D (PD), and peptidoglycan-associated lipoprotein P6 as novel laminin-binding proteins (Lbps) of NTHi. In parallel with other well-studied Lbps (protein 4 [P4], protein E [PE], protein F [PF], and Haemophilus adhesion and penetration protein [Hap]), EF-Tu, LDH, PD, and P6 exhibited interactions with laminin, and mediated NTHi laminin-dependent adherence to pulmonary epithelial cell lines. More importantly, the NTHi laminin interactome consisting of the well-studied and novel Lbps recognized laminin LG domains from the subunit α chains of laminin-111 and -332, the latter isoform of which is the main laminin in the airway BM. The NTHi interactome mainly targeted multiple heparin-binding domains of laminin. In conclusion, the NTHi interactome exhibited a high plasticity of interactions with different laminin isoforms via multiple heparin-binding sites.

Assays for Studying the Role of Vitronectin in Bacterial Adhesion and Serum Resistance.

Bacteria utilize complement regulators as a means of evading the host immune response. Here, we describe protocols for evaluating the role vitronectin acquisition at the bacterial cell surface plays in resistance to the host immune system. Flow cytometry experiments identified human plasma vitronectin as a ligand for the bacterial receptor outer membrane protein H of Haemophilus influenzae type f. An enzyme-linked immunosorbent assay was employed to characterize the protein-protein interactions between purified recombinant protein H and vitronectin, and binding affinity was assessed using bio-layer interferometry. The biological importance of the binding of vitronectin to protein H at the bacterial cell surface in evasion of the host immune response was confirmed using a serum resistance assay with normal and vitronectin-depleted human serum. The importance of vitronectin in bacterial adherence was analyzed using glass slides with and without vitronectin coating, followed by Gram staining. Finally, bacterial adhesion to human alveolar epithelial cell monolayers was investigated. The protocols described here can be easily adapted to the study of any bacterial species of interest.

The Pulmonary Extracellular Matrix Is a Bactericidal Barrier Against Haemophilus influenzae in Chronic Obstructive Pulmonary Disease (COPD): Implications for an in vivo Innate Host Defense Function of Collagen VI.

Non-typeable Haemophilus influenzae (NTHi) is a Gram-negative human commensal commonly residing in the nasopharynx of preschool children. It occasionally causes upper respiratory tract infection such as acute otitis media, but can also spread to the lower respiratory tract causing bronchitis and pneumonia. There is increasing recognition that NTHi has an important role in chronic lower respiratory tract inflammation, particularly in persistent infection in patients suffering from chronic obstructive pulmonary disease (COPD). Here, we set out to assess the innate protective effects of collagen VI, a ubiquitous extracellular matrix component, against NTHi infection in vivo. In vitro, collagen VI rapidly kills bacteria through pore formation and membrane rupture, followed by exudation of intracellular content. This effect is mediated by specific binding of the von Willebrand A (VWA) domains of collagen VI to the NTHi surface adhesins protein E (PE) and Haemophilus autotransporter protein (Hap). Similar observations were made in vivo specimens from murine airways and COPD patient biopsies. NTHi bacteria adhered to collagen fibrils in the airway mucosa and were rapidly killed by membrane destabilization. The significance in host-pathogen interplay of one of these molecules, PE, was highlighted by the observation that it confers partial protection from bacterial killing. Bacteria lacking PE were more prone to antimicrobial activity than NTHi expressing PE. Altogether the data shed new light on the carefully orchestrated molecular events of the host-pathogen interplay in COPD and emphasize the importance of the extracellular matrix as a novel branch of innate host defense.

Genetic predisposition to infection in a case of atypical hemolytic uremic syndrome.

Most cases of hemolytic uremic syndrome (HUS) are caused by infection with enterohemorrhagic Escherichia coli (EHEC). Genetic defects causing uncontrolled complement activation are associated with the more severe atypical HUS (aHUS). Non-EHEC infections can trigger the disease, however, complement defects predisposing to such infections have not yet been studied. We describe a 2-month-old patient infected with different Gram-negative bacterial species resulting in aHUS. Serum analysis revealed slow complement activation kinetics. Rare variant R229C was found in complement inhibitor vitronectin. Recombinant mutated vitronectin showed enhanced complement inhibition in vitro and may have been a predisposing factor for infection. Our work indicates that genetic changes in aHUS can not only result in uncontrolled complement activation but also increase vulnerability to infections contributing to aHUS.

A review of the genus Lordiphosa Basden in India, with descriptions of four new species from the Himalayan region (Diptera, Drosophilidae).

All Indian species of the genus Lordiphosa Basden are reviewed, with descriptions of four new species, L. curva Fartyal & Toda, sp. n. of the denticeps species group and L. ayarpathaensis Kandpal & Singh, sp. n., L. makaibarensis Pradhan & Chatterjee, sp. n. and L. srinagarensis Sati & Fartyal, sp. n. of the nigricolor species group. Two of the new species, L. ayarpathaensis and L. makaibarensis, were found visiting flowers of Hedychium spicatum and Datura suaveolens, respectively. This is the first record of flower visitation in Lordiphosa flies. In addition, L. parantillaria (Kumar & Gupta, 1990), syn. n. is synonymized with L. antillaria (Okada, 1984). Supplementary and revised descriptions for L. antillaria and L. neokurokawai (Singh & Gupta, 1981) and a key to all Indian species of Lordiphosa are provided.

The Rickettsia conorii Adr1 Interacts with the C-Terminus of Human Vitronectin in a Salt-Sensitive Manner.

Spotted fever group (SFG) Rickettsia species are inoculated into the mammalian bloodstream by hematophagous arthropods. Once in the bloodstream and during dissemination, the survival of these pathogens is dependent upon the ability of these bacteria to evade serum-borne host defenses until a proper cellular host is reached. Rickettsia conorii expresses an outer membrane protein, Adr1, which binds the complement inhibitory protein vitronectin to promote resistance to the anti-bacterial effects of the terminal complement complex. Adr1 is predicted to consist of 8 transmembrane beta sheets that form a membrane-spanning barrel with 4 peptide loops exposed to the extracellular environment. We previously demonstrated that Adr1 derivatives containing either loop 3 or 4 are sufficient to bind Vn and mediate resistance to serum killing when expressed at the outer-membrane of E. coli. By expressing R. conorii Adr1 on the surface of non-pathogenic E. coli, we demonstrate that the interaction between Adr1 and vitronectin is salt-sensitive and cannot be interrupted by addition of heparin. Additionally, we utilized vitroenctin-derived peptides to map the minimal Adr1/vitronectin interaction to the C-terminal region of vitronectin. Furthermore, we demonstrate that specific charged amino acid residues located within loops 3 and 4 of Adr1 are critical for mediating resistance to complement-mediated killing. Interestingly, Adr1 mutants that were no longer sufficient to mediate resistance to serum killing still retained the ability to bind to Vn, suggesting that Adr1-Vn interactions responsible for resistance to serum killing are more complex than originally hypothesized. In summary, elucidation of the mechanisms governing Adr1-Vn binding will be useful to specifically target this protein-protein interaction for therapeutic intervention.

PRELP Enhances Host Innate Immunity against the Respiratory Tract Pathogen Moraxella catarrhalis.

Respiratory tract infections are one of the leading causes of mortality worldwide urging better understanding of interactions between pathogens causing these infections and the host. Here we report that an extracellular matrix component proline/arginine-rich end leucine-rich repeat protein (PRELP) is a novel antibacterial component of innate immunity. We detected the presence of PRELP in human bronchoalveolar lavage fluid and showed that PRELP can be found in alveolar fluid, resident macrophages/monocytes, myofibroblasts, and the adventitia of blood vessels in lung tissue. PRELP specifically binds respiratory tract pathogens Moraxella catarrhalis, Haemophilus influenzae, and Streptococcus pneumoniae, but not other bacterial pathogens tested. We focused our study on M. catarrhalis and found that PRELP binds the majority of clinical isolates of M. catarrhalis (n = 49) through interaction with the ubiquitous surface protein A2/A2H. M. catarrhalis usually resists complement-mediated serum killing by recruiting to its surface a complement inhibitor C4b-binding protein, which is also a ligand for PRELP. We found that PRELP competitively inhibits binding of C4b-binding protein to bacteria, which enhances membrane attack complex formation on M. catarrhalis and thus leads to increased serum sensitivity. Furthermore, PRELP enhances phagocytic killing of serum-opsonized M. catarrhalis by human neutrophils in vitro. Moreover, PRELP reduces Moraxella adherence to and invasion of human lung epithelial A549 cells. Taken together, PRELP enhances host innate immunity against M. catarrhalis through increasing complement-mediated attack, improving phagocytic killing activity of neutrophils, and preventing bacterial adherence to lung epithelial cells.

The crystal structure of PD1, a Haemophilus surface fibril domain.

The Haemophilus surface fibril (Hsf) is an unusually large trimeric autotransporter adhesin (TAA) expressed by the most virulent strains of H. influenzae. Hsf is known to mediate adhesion between pathogen and host, allowing the establishment of potentially deadly diseases such as epiglottitis, meningitis and pneumonia. While recent research has suggested that this TAA might adopt a novel `hairpin-like' architecture, the characterization of Hsf has been limited to in silico modelling and electron micrographs, with no high-resolution structural data available. Here, the crystal structure of Hsf putative domain 1 (PD1) is reported at 3.3 Šresolution. The structure corrects the previous domain annotation by revealing the presence of an unexpected N-terminal TrpRing domain. PD1 represents the first Hsf domain to be solved, and thus paves the way for further research on the `hairpin-like' hypothesis.