Occupational dermatitis due to 1,2-benzisothiazolin-3-one in the pottery industry

Three men working as mouldmakers in the pottery industry acquired a contact allergic dermatitis to a releasing oil. All three were shown to he sensitized to the biocide (1,2-benzisothinzolin-3-one) in the oil.     

Monitoring of DNA damage in foundry and pottery workers exposed to silica by the alkaline comet assay

BACKGROUND: Workers in foundry and pottery are exposed to a mixture of chemicals and silica, which is suspected to cause genetic alterations. METHODS: To investigate the potential hazard associated with the occupational exposure to silica, DNA damage in the peripheral lymphocytes of 30 foundry and 22 pottery workers were examined by the alkaline single-cell gel electrophoresis or Comet Assay, and compared to 52 healthy subjects with no history of occupational silica or chemical exposure. RESULTS: The DNA damage observed in the lymphocytes of both foundry and pottery workers was significantly higher than that in their controls. Cigarette smoking was also related to DNA damage since the DNA damage observed in smoking silica-exposed workers compared with the non-smoking workers was significantly higher. CONCLUSIONS: Occupational exposure of silica from foundry and pottery workplaces has been associated with the increased DNA damage and smoking which represents an additional risk factor and must be avoided.     

Zika virus employs the host antiviral RNase L protein to support replication factory assembly

Infection with the flavivirus Zika virus (ZIKV) can result in tissue tropism, disease outcome, and route of transmission distinct from those of other flaviviruses; therefore, we aimed to identify host machinery that exclusively promotes the ZIKV replication cycle, which can inform on differences at the organismal level. We previously reported that deletion of the host antiviral ribonuclease L (RNase L) protein decreases ZIKV production. Canonical RNase L catalytic activity typically restricts viral infection, including that of the flavivirus dengue virus (DENV), suggesting an unconventional, proviral RNase L function during ZIKV infection. In this study, we reveal that an inactive form of RNase L supports assembly of ZIKV replication factories (RFs) to enhance infectious virus production. Compared with the densely concentrated ZIKV RFs generated with RNase L present, deletion of RNase L induced broader subcellular distribution of ZIKV replication intermediate double-stranded RNA (dsRNA) and NS3 protease, two constituents of ZIKV RFs. An inactive form of RNase L was sufficient to contain ZIKV genome and dsRNA within a smaller RF area, which subsequently increased infectious ZIKV release from the cell. Inactive RNase L can interact with cytoskeleton, and flaviviruses remodel cytoskeleton to construct RFs. Thus, we used the microtubule-stabilization drug paclitaxel to demonstrate that ZIKV repurposes RNase L to facilitate the cytoskeleton rearrangements required for proper generation of RFs. During infection with flaviviruses DENV or West Nile Kunjin virus, inactive RNase L did not improve virus production, suggesting that a proviral RNase L role is not a general feature of all flavivirus infections.

The flavivirus genus contains arthropod-transmitted viruses with a positive-sense single-stranded RNA (ssRNA) genome, including Zika virus (ZIKV), dengue virus (DENV), and West Nile virus (WNV). These viruses are transmitted by mosquitos and globally distributed, with high associated morbidity and mortality in humans (1–3). More recently, ZIKV sexual and vertical transmission has been recognized, the latter involving transplacental migration of the virus, potentially resulting in fetal microcephaly (4–9). Due to diversity in ZIKV tissue tropism, disease, and route of transmission as compared with other flaviviruses, it is possible that variances in ZIKV infection at the molecular level confer the observed shifts in clinical outcome at the organismal level. For this reason, we are interested in host machinery that supports the ZIKV replication cycle but not that of other flaviviruses, as this may improve our understanding of the molecular determinants of ZIKV pathogenesis.After entry into the host cell, the flavivirus genome, which also serves as the messenger RNA (mRNA), is directly translated at the endoplasmic reticulum (ER). Proximal to sites of translation, flaviviruses create replication factories (RFs) through extensive cytoskeletal rearrangements that generate invaginations in the folds of the ER membrane, within which new genome synthesis occurs (10–15). These RFs contain ZIKV replication complex proteins, including the NS3 protease, the replication intermediate double-stranded RNA (dsRNA), as well as template genomic ssRNA. New genome is packaged into compartments at opposite ER folds, and new virions traffic through the transgolgi network and eventually bud from the plasma membrane (16). RFs therefore enable efficient throughput of key viral processes as centers of new genome synthesis linked with viral protein translation as well as new virus assembly. In addition, RFs serve as a protective barrier to impede cytosolic innate immune sensing, as flavivirus RNA predominantly resides within RFs during the bulk of the intracellular replication cycle.Innate immune sensors within the cytoplasm of the infected cell detect viral RNA to activate antiviral responses, including the type I interferon (IFN) and oligoadenylate synthetase/ribonuclease L (OAS/RNase L) pathways. Extensive research has demonstrated that flaviviruses, including ZIKV, have evolved strategies for counteracting the type I IFN response (17–22). Since OAS genes are IFN-stimulated genes and therefore up-regulated by type I IFN signaling, the OAS/RNase L pathway can also be potentiated by type I IFN production. However, activation of RNase L can occur in the absence of type I IFN responses when basal OAS expression is sufficient (23, 24). In either event, OAS sensors detect viral dsRNA and generate 2''-5''-oligoadenylates (2-5A). RNase L, which is constitutively expressed in an inactive form, homodimerizes upon 2-5A binding to become catalytically active (25). Active RNase L cleaves both host and viral ssRNA within the cell (Fig. 1). While there are three OAS isoforms, we have shown that the OAS3 isoform is the predominant activator of RNase L during infection with a variety of viruses including ZIKV (23, 26). Activated RNase L cleavage of host ribosomal RNA (rRNA) and mRNA as well as viral ssRNA ultimately inhibits virus infection (26–31).Open in a separate windowFig. 1.Noncanonical RNase L function promotes infectious ZIKV production. (Left) Canonical RNase L antiviral activity. Viral dsRNA is detected by OAS3, which produces the small molecule 2-5A that binds inactive RNase L, inducing its homodimerization and catalytic activation, resulting in cleavage of host and viral ssRNA, leading to inhibition of viral infection. (Right) RNase L activity during ZIKV infection. ZIKV dsRNA is recognized by OAS3, which activates RNase L resulting in ssRNA cleavage; however, ZIKV production is improved with RNase L expression.Once activated, RNase L can restrict infection of a diverse range of DNA and RNA viruses, including flaviviruses DENV and WNV (30, 32–34). Many viruses have subsequently developed mechanisms for evading RNase L antiviral effects, most of which target this pathway upstream of RNase L activation through sequestration of dsRNA, which prevents OAS activation, or by degradation of 2-5A (32, 35–40). We recently showed that ZIKV avoids antiviral effects of activated RNase L and that this evasion strategy requires assembly of RFs to protect genome from RNase L cleavage (23). Despite substantial RNase L–mediated cleavage of intracellular ZIKV genome, a portion of uncleaved genome was shielded from activated RNase L within RFs. This genome was sufficient to produce high levels of infectious virus particles, as infectious ZIKV released from wild-type (WT) cells was significantly higher than from RNase L knockout (KO) cells. Unlike ZIKV, infectious DENV production was decreased by canonical RNase L antiviral activity (23, 33). These results indicated that RNase L expression was ultimately proviral during ZIKV infection (Fig. 1). As this was the initial report of viral resistance to catalytically active RNase L during infection, we sought to isolate the differences between ZIKV RFs and those constructed by other flaviviruses, to identify factors that enable this ZIKV evasion mechanism.In this study, we focused on elucidating how RNase L increases ZIKV production. An earlier study reported that an inactive form of RNase L interacts with the actin cytoskeleton to reorganize cellular framework during viral infection (41). Since flaviviruses reorganize the cellular cytoskeletal and organellar network during infection (11), we investigated the possibility that RNase L was exploited by ZIKV to assemble protective RFs that dually serve as a barrier against host sensors in addition to providing sites of replication.     

Thomas Hastie Bryce (1862-1946)--a lesson in the power of observation

Thomas Hastie Bryce was Regius Professor of Anatomy at the University of Glasgow from 1909 to 1935. In Anatomy, he is remembered as an embryologist and as an editor of the 11th edition of Quain's Elements of Anatomy. His most-lasting scientific contribution, however, was in archaeology where he defined the Clyde Group of Neolithic cairns in south-west Scotland. He showed that the Neolithic people of Arran were of short stature and were dolichocephalic, distinct from those of the Bronze Age. Also, Bryce was the first to appreciate the importance of pottery in analyzing the movement of ancient peoples across Europe, and defined Beacharra ware, a class of Neolithic pottery unique to the west of Scotland. As in anatomy, archaeological discoveries are made by study of morphology and relationships with careful attention to detail and a sound knowledge of the literature.     

Evidence of tungiasis in pre-Hispanic America

Ancient parasites of the genus Tunga originated in America and, during the first half of the 19th century, were transported to the Eastern Hemisphere on transatlantic voyages. Although they were first documented by Spanish chroniclers after the arrival of Columbus, little is known about their presence in pre-Hispanic America. To evaluate the antiquity of tungiasis in America, we assessed several kinds of early documentation, including written evidence and pre-Incan earthenware reproductions. We identified 17 written documents and 4 anthropomorphic figures, of which 3 originated from the Chimu culture and 1 from the Maranga culture. Tungiasis has been endemic to Peru for at least 14 centuries. We also identified a pottery fragment during this study. This fragment is the fourth representation of tungiasis in pre-Hispanic America identified and provides explicit evidence of disease endemicity in ancient Peru.