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Orthoflaviviruses are positive-sense single-stranded RNA viruses that hijack host proteins to promote their own replication. Zika virus (ZIKV) is infamous among orthoflaviviruses for its association with severe congenital birth defects, notably microcephaly. We previously mapped ZIKV-host protein interactions and identified the interaction between ZIKV non-structural protein 4A (NS4A) and host microcephaly protein ankyrin repeat and LEM domain-containing 2 (ANKLE2). Using a fruit fly model, we showed that NS4A induced microcephaly in an ANKLE2-dependent manner. Here, we explore the role of ANKLE2 in ZIKV replication to understand the biological significance of the interaction from a viral perspective. We observe that ANKLE2 localization is drastically shifted to sites of NS4A accumulation during infection and that knockout of ANKLE2 reduces ZIKV replication in multiple human cell lines. This decrease in virus replication is coupled with a moderate increase in innate immune activation. Using microscopy, we observe dysregulated formation of virus-induced endoplasmic reticulum rearrangements in ANKLE2 knockout cells. Knockdown of the ANKLE2 ortholog in Aedes aegypti cells also decreases virus replication, suggesting ANKLE2 is a beneficial replication factor across hosts. Finally, we show that NS4A from four other orthoflaviviruses physically interacts with ANKLE2 and is also beneficial to their replication. Thus, ANKLE2 likely promotes orthoflavivirus replication by regulating membrane rearrangements that serve to accelerate viral genome replication and protect viral dsRNA from immune detection. Taken together with our previous results, our findings indicate that ZIKV and other orthoflaviviruses hijack ANKLE2 for a conserved role in replication, and this drives unique pathogenesis for ZIKV since ANKLE2 has essential roles in developing tissues.IMPORTANCEZIKV is a major concern due to its association with birth defects, including microcephaly. We previously identified a physical interaction between ZIKV NS4A and host microcephaly protein ANKLE2. Mutations in ANKLE2 cause congenital microcephaly, and NS4A induces microcephaly in an ANKLE2-dependent manner. Here, we establish the role of ANKLE2 in ZIKV replication. Depletion of ANKLE2 from cells significantly reduces ZIKV replication and disrupts virus-induced membrane rearrangements. ANKLE2's ability to promote ZIKV replication is conserved in mosquito cells and for other related mosquito-borne orthoflaviviruses. Our data point to an overall model in which ANKLE2 regulates virus-induced membrane rearrangements to accelerate orthoflavivirus replication and avoid immune detection. However, ANKLE2's unique role in ZIKV NS4A-induced microcephaly is a consequence of ZIKV infection of important developing tissues in which ANKLE2 has essential roles., Competing Interests: The authors declare no conflict of interest.

Background: Diabetes is a condition characterized by a loss of pancreatic β-cell function which results in the dysregulation of insulin homeostasis. Using a partial pancreatectomy model in axolotl, we aimed to observe the pancreatic response to injury., Results: Here we show a comprehensive histological assessment of pancreatic islets in axolotl. Following pancreatic injury, no apparent blastemal structure was observed. We found a significant, organ-wide increase in cellular proliferation post-resection in the pancreas compared to sham-operated controls. This proliferative response was most robust at the site of injury. We found that β-cells actively contributed to the increased rates of proliferation upon injury. β-cell proliferation manifested in increased β-cell mass in injured tissue at two weeks post injury. At four weeks post injury, we found organ-wide proliferation to be extinguished while proliferation at the injury site persisted, corresponding to pancreatic tissue recovery. Similarly, total β-cell mass was comparable to sham after four weeks., Conclusions: Our findings suggest a non-blastema-mediated regeneration process takes place in the pancreas, by which pancreatic resection induces whole-organ β-cell proliferation without the formation of a blastemal structure. This process is analogous to other models of compensatory growth in axolotl, including liver regeneration., Competing Interests: Declaration of Interests JLW is a co-founder of Matice Biosciences. Other authors declare no competing interests.

Previous studies have reported that amputation invokes body-wide responses in regenerative organisms, but most have not examined the implications of these changes beyond the region of tissue regrowth. Specifically, long-range epidermal responses to amputation are largely uncharacterized, with research on amputation-induced epidermal responses in regenerative organisms traditionally being restricted to the wound site. Here, we investigate the effect of amputation on long-range epidermal permeability in two evolutionarily distant, regenerative organisms: axolotls and planarians. We find that amputation triggers a long-range increase in epidermal permeability in axolotls, accompanied by a long-range epidermal downregulation in MAPK signaling. Additionally, we provide functional evidence that pharmacologically inhibiting MAPK signaling in regenerating planarians increases long-range epidermal permeability. These findings advance our knowledge of body-wide changes due to amputation in regenerative organisms and warrant further study on whether epidermal permeability dysregulation in the context of amputation may lead to pathology in both regenerative and non-regenerative organisms., Competing Interests: CONFLICT OF INTEREST J.L.W. is a co-founder of Matice Biosciences. Other authors declare no conflicts of interest.

Ankyrin repeat and LEM domain-containing 2 (ANKLE2) is a scaffolding protein with established roles in cell division and development, the dysfunction of which is increasingly implicated in human disease. ANKLE2 regulates nuclear envelope disassembly at the onset of mitosis and its reassembly after chromosome segregation. ANKLE2 dysfunction is associated with abnormal nuclear morphology and cell division. It regulates the nuclear envelope by mediating protein-protein interactions with barrier to autointegration factor (BANF1; also known as BAF) and with the kinase and phosphatase that modulate the phosphorylation state of BAF. In brain development, ANKLE2 is crucial for proper asymmetric division of neural progenitor cells. In humans, pathogenic loss-of-function mutations in ANKLE2 are associated with primary congenital microcephaly, a condition in which the brain is not properly developed at birth. ANKLE2 is also linked to other disease pathologies, including congenital Zika syndrome, cancer and tauopathy. Here, we review the molecular roles of ANKLE2 and the recent literature on human diseases caused by its dysfunction., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Approximately 80% of sorghum phenolic compounds are linked to arabinoxylans by ester bonds, which are capable of resisting the digestion process in the upper gastrointestinal tract, compromising their bioaccessibility and biological potential. The aim of this study was to evaluate the effect of the extrusion process on the content of phenolic compounds in sorghum bran and its impact on phenolic compounds and antiradical and anti-inflammatory capacity. Results revealed that the extrusion process increased total phenol content in sorghum bran compared to nonextruded sorghum, particularly for extrusion at 180°C with 20% moisture content (2.0222 ± 0.0157 versus 3.0729 ± 0.0187 mg GAE/g +52%), which positively affected antiradical capacity measured by the DPPH and TEAC assays. The percentage of inhibition of nitric oxide (NO) production by RAW cells due to the presence of extruded sorghum bran extract was significantly higher than that of nonextruded sorghum bran extract (90.2 ± 1.9% versus 76.2 ± 1.3%). The results suggest that extruded sorghum bran could be used as a functional ingredient and provide advantages to consumers by reducing diseases related to oxidative stress and inflammation., Competing Interests: The authors declare that there are no competing interests.

Food safety has acquired great attention by food importer and exporters. Food rejection or acceptance across international borders is based on the compliance with international food regulations. Due to the lack of recent data on pesticide residues in Mexican grains, this study focused on detecting and quantifying insecticide residues in stored wheat, corn, chickpeas, and beans, as well as to determine their mutagenic potential. Grains were sampled from primary storage sites in Sonora, Mexico. Malathion, chlorpyrifos, deltamethrin, cypermethrin, 4,4-DDE, 4,4-DDD and 4,4-DDT were analyzed in 135 samples. Grain samples were not mutagenic and most pesticide levels were within regulation limits.

Background: Most clinical studies assume that the subgingival microbiota is similar from one geographic location to another. The purpose of the present investigation was to examine the composition of the subgingival microbiota in chronic periodontitis subjects from four countries., Method: Subjects with chronic periodontitis (N, Sweden=101; USA=115; Brazil=58; Chile=26) were recruited. Subjects were measured at baseline for plaque, gingivitis, bleeding on probing (BOP), suppuration, pocket depth (PD) and attachment level (AL) at six sites per tooth. Subgingival plaque samples taken from the mesial aspect of each tooth at baseline were individually analyzed for their content of 40 bacterial species using checkerboard DNA-DNA hybridization (total samples=6036). % DNA probe counts comprised by each species was determined for each site and averaged across sites in each subject. Significance of differences in proportions of each species among countries was determined using ancova adjusting for age, mean pocket depth, gender and smoking status. p-Values were adjusted for multiple comparisons., Results: On average, all species were detected in samples from subjects in the four countries. Thirteen species differed significantly in adjusted mean proportions among countries even after adjusting for multiple comparisons. Porphyromonas gingivalis, one species that differed in proportions among countries, comprised adjusted means of 7.5, 11.9, 1.6 and 6.6% of the microbiota in subjects from Brazil, Chile, Sweden and USA (p<0.001), while mean proportions of Treponema denticola were 6.7, 4.2, 0.8 and 2.3, respectively (p<0.001). In contrast, a key periodontal pathogen, Tannerella forsythensis, exhibited mean proportions ranging from 6.2-8.5% and did not differ significantly among countries. Besides these species, prominent species in Brazil were Actinomyces naeslundii genospecies 1 and 2 (8.4%, 7.2%) and Prevotella intermedia (6.5%); in Chile, Prevotella melaninogenica (6.4%) and Neisseria mucosa (5.3%); in Sweden A. naeslundii genospecies 2 (8.4%), Capnocytophaga gingivalis (7.1%) and Peptostreptococcus micros (5.0%); in USA A. naeslundii genospecies 2 (7.5%), P. intermedia (6.8%) and C. gingivalis (6.1%)., Conclusions: The microbial profiles of subgingival plaque samples from chronic periodontitis subjects in four countries showed surprisingly marked differences. These differences persisted after adjusting for age, mean pocket depth, gender and smoking status., ((c) Blackwell Munksgaard, 2004)

There has been significant concern that the dental curriculum and system of clinical education, in particular, is not designed to take advantage of the explosion in knowledge in biomedical science and its application to the health of the public. Although there are some examples of innovations in dental education on a global scale that have the capacity to increase the assimilation of basic and clinical knowledge, most of the dental education models are mired in the traditional '2 + 2' approach to education. This can be seen in North America and the European '2 + 3' model or the stomatological '4 + 2' approach. In each of these systems, the basic and behavioural science courses continue to be perceived as hurdles over which students must leap in order to reach the clinical programmes where there is little opportunity to use basic science information to advance patient care and treatment. Examples of issues that are not well represented include: innovations in imaging; diagnosis; bio-materials; science-based approaches to clinical practice; novel approaches to therapeutics; interactions between the oral, dental and craniofacial complex and systemic health and disorders; the role of oral infections and systemic disease; the increasing appreciation of chronic diseases and disorders such as osteoporosis and diabetes that affect oral tissues; the promise of bioengineering, tissue engineering and biomimetics; the potential use of saliva as a diagnostic tool; the understanding of oral complications of cancer treatment; the treatments of HIV/AIDS diseases and hepatitis; the use of dental and dental hygiene staff on health-care teams to deal with issues such as birth defects, orofacial trauma, head and neck cancer, chronic pain management and so on. There seems to be an excessive emphasis on restorative dentistry and, to a lesser extent, on the more biological approaches to diagnosis, prevention and therapeutics. This continued lack of integration of basic and clinical sciences in the curriculum continues to foster a dental workforce that is highly technically competent to provide specific clinical services but poorly equipped to evaluate and implement new biological approaches to diagnosis, therapeutics and intervention. Unfortunately, after many attempts by organized dental symposia aimed at the integration of basic and clinical sciences, there has been little discernible curricular change. It appears that there is an opportunity through this global congress to identify the best practices in the various global curricula that could change this paradigm in dental education and lead us toward the education of a more scientifically orientated practitioner-one who can take advantage of innovations in new and emerging technologies in their application to patient care. It is the challenge of this section to try to ascertain the best method or methods by which dental education promotes research to the dental student and what research represents in terms of critical thinking and evidence-based approaches to dental education and clinical practice.

A CPITN survey involving Chileans aged 35-44 and 65-74 was conducted. A random, stratified sample by age, gender, socio-economic status and educational level was obtained, comprising 1150 individuals. Prevalence of chronic inflammatory periodontal disease (Codes 3 + 4) was 90.89 per cent in subjects aged 35-44, and 100 per cent in subjects aged 65-74. The total prevalence for both age cohorts was 92.19 per cent. Prevalence of periodontal disease was slightly lower in females but severity was significantly higher in males. A significant association between socio-economic status and periodontal health was found. Prevalence (Code 3 + 4) was 56.44 per cent in subjects of high, 98 per cent in subjects of middle, and 100 per cent in subjects of low socio-economic status. Also, the mean number of sextants with pockets > 6 mm (1.12) and mean number of excluded sextants (1.43) were significantly higher in subjects of low socio-economic status. An association between educational level and periodontal health was apparent. The only subjects who were periodontally healthy were in the group with university education. Prevalence of CITN (Code 3 + 4) was also significantly lower in subjects with university education. There was also a significant association between educational level and loss of teeth. Concerning missing teeth, 22 per cent were lost due to periodontal disease and 77 per cent due to caries. The prevalence of periodontal disease found in this adult representative Chilean population indicates that the entire population needs oral hygiene instruction and scaling, and that 45.70 per cent need complex periodontal treatment.

In a joint clinical and histological research, carried out in humans of both sexes, it was attempted to establish some of the differences between the effects of curettage and root planing as procedures to accomplish remission of gingival inflammation. In 10 patients, 210 teeth were treated (103 curetted and 98 root planed). Sixty useful samples and 2132 histological sections were obtained. Six different staining techniques were used to study the samples. Clinical and histological evaluations were made of the results obtained with both procedures.

The inflammatory potential of diseased cementum was studied by implanting 70 autogenous fragments from periodontally involved roots into the mucosa of 56 patients. The implants were divided into groups depending upon the type of preparation the root received prior to implantation. Fifteen healthy root fragments implanted into 15 patients served as controls. Histologic results showed that implanted fragments from roots that had been scaled caused the most response with acute inflammation up to 14 days and chronic inflammation to 21 days. In cases in which these fragments were autoclaved the acute inflammation was not as severe. In the cases in which the roots were planed and autoclaved, even less acute inflammation was seen in the 7-day specimens while some chronic inflammation persisted in the 21-day specimens. Implants from healthy roots evoked no response. The inflammation caused by the autoclaved diseased cementum was attributed to thermo-stable endotoxin. It was concluded that in advanced periodontal disease it is necessary to remove all of the cementum exposed to the pocket to eliminate its potential for inducing inflammation.