Central tolerance matters

In this issue of Immunity, Anderson et al. provide another clue to the riddle that is Aire--why do human beings and mice lacking Aire develop diffuse and pathogenic autoimmunity? They find that Aire influences central tolerance not only by promoting the expression of peripheral self-proteins in thymic medullary epithelial cells (MECs) but also by furnishing these cells with the apparatus for effective antigen presentation ().     

Dystrophin gene deletions in South Indian Duchenne muscular dystrophy patients

66 unrelated patients from Southern India with Duchenne Muscular Dystrophy (DMD) were studied for intragenic deletion in 18 exons and Pm region of the DMD gene using multiplex PCR. Of these 41 (62.1%) showed intragenic deletions. 78% of the deletions were located at the distal hotspot region (44-55 exons) and 22% of the deletions were located at the proximal region (exon 2-19). Exon 50 is most frequently deleted. Deletions in isolated cases were significantly more compared to familial cases. The lower incidence reported from South India compared to North India, is suggestive of variations in the Southern and Northern population.     

Precision Tracing of Household Dengue Spread Using Inter- and Intra-Host Viral Variation Data,Kamphaeng Phet,Thailand

Dengue control approaches are best informed by granular spatial epidemiology of these viruses, yet reconstruction of inter- and intra-household transmissions is limited when analyzing case count, serologic, or genomic consensus sequence data. To determine viral spread on a finer spatial scale, we extended phylogenomic discrete trait analyses to reconstructions of house-to-house transmissions within a prospective cluster study in Kamphaeng Phet, Thailand. For additional resolution and transmission confirmation, we mapped dengue intra-host single nucleotide variants on the taxa of these time-scaled phylogenies. This approach confirmed 19 household transmissions and revealed that dengue disperses an average of 70 m per day between households in these communities. We describe an evolutionary biology framework for the resolution of dengue transmissions that cannot be differentiated based on epidemiologic and consensus genome data alone. This framework can be used as a public health tool to inform control approaches and enable precise tracing of dengue transmissions.     

Effect of silica coating and laser treatment on the flexural strength,surface characteristics,and bond strength of a dental zirconia

This study investigated the effect of irradiation with an erbium‐doped yttrium aluminium garnet (Er:YAG) laser and coating with silica on the surface characteristics, bond strength, and flexural strength of dental zirconia. Three hundred and forty‐three standard zirconia specimens were created, and 49 were assigned to each of seven surface treatment groups: (i) no treatment; Er:YAG laser (80 mJ/2 Hz) with pulse widths of 50 μs (ii), 100 μs (iii), 300 μs (iv), or 600 μs (v); or tribochemical silica coating at the partially sintered stage (vi) or after sintering was complete (vii). All specimens were sintered after the surface treatments, except for the group in which specimens were sintered before treatment. The study outcomes were roughness, surface loss, microshear bond strength (μSBS), and biaxial flexural strength (BFS). Mean roughness and surface loss values were significantly higher in specimens from irradiated groups than in those from silica‐coated groups. Regarding μSBS, after aging, specimens from all experimental groups presented very low and similar μSBS values, irrespective of the surface treatment. Silica coating after sintering yielded the highest BFS (1149.5 ± 167.6 MPa), while coating partially sintered specimens with silica resulted a BFS (826.9 ± 60.9 MPa) similar to that of the untreated control group (794.9 ± 101.7 MPa). Laser treatments, irrespective of pulse width used, significantly decreased the BFS. In the group treated with laser at 300 μs pulse width, specimens exhibited the lowest BFS value (514.1 ± 71.5 MPa). Adhesion to zirconia was not stable after aging, regardless of the surface treatment implemented.     

Which Parameters Affect Biofilm Removal with Acoustic Cavitation? A Review

Bacterial biofilms are a cause of contamination in a wide range of medical and biological areas. Ultrasound is a mechanical energy that can remove these biofilms using cavitation and acoustic streaming, which generate shear forces to disrupt biofilm from a surface. The aim of this narrative review is to investigate the literature on the mechanical removal of biofilm using acoustic cavitation to identify the different operating parameters affecting its removal using this method. The properties of the liquid and the properties of the ultrasound have a large impact on the type of cavitation generated. These include gas content, temperature, surface tension, frequency of ultrasound and acoustic pressure. For many of these parameters, more research is required to understand their mechanisms in the area of ultrasonic biofilm removal, and further research will help to optimise this method for effective removal of biofilms from different surfaces.     

An enzyme-linked immunosorbent assay to characterize dengue infections where dengue and Japanese encephalitis co-circulate

The diagnostic sensitivity and specificity of detection of anti-dengue IgM by antibody capture enzyme-linked immunosorbent assay (ELISA) was investigated in dengue infections in a variety of clinical settings. Sera from uninfected controls were uniformly negative. Serial specimens from experimental and natural infections showed that viremia and fever terminated as anti-dengue IgM became detectable. Anti-dengue IgM appeared in most cases by the 3rd afebrile day of illness and declined to undetectable levels after 30-60 days. Assay sensitivity was 78% in admission sera (924/1,183; 95% CI = 75-81%) and 97% in paired sera (1,030/1,062; 95% CI = 96-98%) thus exceeding or matching the performance of the hemagglutination-inhibition assay. Measurement of the anti-dengue IgM to anti-Japanese encephalitis IgM ratio correctly identified all sera from 112 patients with strictly defined Japanese encephalitis and 98% (307/312; 95% CI = 96-99%) of sera from patients whose dengue infections were confirmed by virus isolation. Dengue infections could be classified as primary or secondary by determining the ratio of units of dengue IgM to IgG antibody. We propose that measurement of dengue and Japanese encephalitis IgM and IgG antibodies upon admission and discharge from hospital care should replace the hemagglutination inhibition assay as the standard dengue serologic technique in regions where these 2 viruses co-circulate.     

Epidemiology and control of dengue virus infections in Thai villages in 1987

A severe epidemic of dengue hemorrhagic fever (DHF) in Nakhon Ratchasima, Thailand in August of 1987 prompted a field investigation. DHF rates of 0.4-6.5 cases per 1,000 residents in subdistricts and 2-15 cases per 1,000 residents in 10 villages investigated were reported. Epidemics peaked in neighboring villages at different times; in June and July, and in August before the rainy season began late in the month. In 4 primary schools representing 6 villages, sera from groups of randomly selected children were tested for dengue IgM with the antibody capture ELISA test. Rates of recent dengue infection were 10-65% in the schools and correlated closely with reported rates of DHF. In an effort to control vectors, malathion fog and temephos (1% abate sand granules) were applied. Villagers were educated in prevention and were urged to cover water receptacles. The percentage of houses with larvae dropped from 67 to 20, the percentage of containers with larvae decreased from 30 to 5, and the number of containers with larvae per 100 households decreased from 221 to 33. This was a serious epidemic in which conventional control measures were only moderately effective.     

Hypoxia drives murine neutrophil protein scavenging to maintain central carbon metabolism

Limiting dysfunctional neutrophilic inflammation while preserving effective immunity requires a better understanding of the processes that dictate neutrophil function in the tissues. Quantitative mass-spectrometry identified how inflammatory murine neutrophils regulated expression of cell surface receptors, signal transduction networks, and metabolic machinery to shape neutrophil phenotypes in response to hypoxia. Through the tracing of labeled amino acids into metabolic enzymes, proinflammatory mediators, and granule proteins, we demonstrated that ongoing protein synthesis shapes the neutrophil proteome. To maintain energy supplies in the tissues, neutrophils consumed extracellular proteins to fuel central carbon metabolism. The physiological stresses of hypoxia and hypoglycemia, characteristic of inflamed tissues, promoted this extracellular protein scavenging with activation of the lysosomal compartment, further driving exploitation of the protein-rich inflammatory milieu. This study provides a comprehensive map of neutrophil proteomes, analysis of which has led to the identification of active catabolic and anabolic pathways that enable neutrophils to sustain synthetic and effector functions in the tissues.