How human papillomavirus replication and immune evasion strategies take advantage of the host DNA damage repair machinery

The DNA damage response (DDR) is a complex signalling network activated when DNA is altered by intrinsic or extrinsic agents. DDR plays important roles in genome stability and cell cycle regulation, as well as in tumour transformation. Viruses have evolved successful life cycle strategies in order to ensure a chronic persistence in the host, virtually avoiding systemic sequelae and death. This process promotes the periodic shedding of large amounts of infectious particles to maintain a virus reservoir in individual hosts, while allowing virus spreading within the community. To achieve such a successful lifestyle, the human papilloma virus (HPV) needs to escape the host defence systems. The key to understanding how this is achieved is in the virus replication process that provides by itself an evasion mechanism by inhibiting and delaying the host immune response against the viral infection. Numerous studies have demonstrated that HPV exploits both the ataxia-telangiectasia mutated (ATM) and ataxia-telangiectasia and rad3-related (ATR) DDR pathways to replicate its genome and maintain a persistent infection by downregulating the innate and cell-mediated immunity. This review outlines how HPV interacts with the ATM-and ATR-dependent DDR machinery during the viral life cycle to create an environment favourable to viral replication, and how the interaction with the signal transducers and activators of transcription (STAT) protein family and the deregulation of the Janus kinase (JAK)-STAT pathways may impact the expression of interferon-inducible genes and the innate immune responses

The Emerging Role of Microbial Biofilm in Lyme Neuroborreliosis

Lyme borreliosis (LB) is the most common tick-borne disease caused by the spirochete Borrelia burgdorferi in North America and Borrelia afzelii or Borrelia garinii in Europe and Asia, respectively. The infection affects multiple organ systems, including the skin, joints, and the nervous system. Lyme neuroborreliosis (LNB) is the most dangerous manifestation of Lyme disease, occurring in 10-15% of infected individuals. During the course of the infection, bacteria migrate through the host tissues altering the coagulation and fibrinolysis pathways and the immune response, reaching the central nervous system (CNS) within 2 weeks after the bite of an infected tick. The early treatment with oral antimicrobials is effective in the majority of patients with LNB. Nevertheless, persistent forms of LNB are relatively common, despite targeted antibiotic therapy. It has been observed that the antibiotic resistance and the reoccurrence of Lyme disease are associated with biofilm-like aggregates in B. burgdorferi, B. afzelii, and B. garinii, both in vitro and in vivo, allowing Borrelia spp. to resist to adverse environmental conditions. Indeed, the increased tolerance to antibiotics described in the persisting forms of Borrelia spp., is strongly reminiscent of biofilm growing bacteria, suggesting a possible role of biofilm aggregates in the development of the different manifestations of Lyme disease including LNB

Towards sustainable mining: exploiting raw materials from extractive waste facilities

The focus of the present research is on the exploitation of extractive waste to recover raw materials, considering the technological and economic factors, together with the environmental impacts, associated with extractive waste quarrying and dressing activities. The present study, based on a case history from Northern Italy (Montorfano and Baveno granite quarrying area), was intended to validate the presented interdisciplinary approach for evaluating economic and environmental impacts associated with extractive waste facility exploitation (from granite waste to products for the ceramic industry and by-products for the building industry). A shared methodology was applied to determine extractive waste characteristics (geochemistry, petrography, and mineralogy), waste volume (geophysical, topographic, and morphologic 3D characterization) and potential exploitable products and by-products. Meanwhile, a Life Cycle Assessment (LCA) was applied to determine the environmental impacts associated with the extraction and processing phases

Surgical approach and etiopathogenetic considerations to the umbilical tumefactions in cattle: Case review in twenty years (2000/2020)

B S T R A C T Objective: Our investigation was conducted to evaluate the incidence of umbilical pathologies and the result of related surgical interventions in Sicilian cattle. Study design: 320 (214 females, 106 males) cattle with umbilical lesions were collected, anesthetized, operated on and follow-up recorded. We evaluated the injury incidence rate. Population: The animals considered were: high productivity dairy cattle (Holstein Friesian and Brown Swiss); meat breeds (Charolaise and Limousine) and some crosses. Results: The highest injury rate was simple omphalocele, followed by purulent omphalitis. A high percentage was found in young cattle. Friesians are the most prone to navel diseases. The dairy breeds, compared to the meat breeds, and double aptitude and crosses, were the most affected. The most common was simple omphalocele, with a small hernial port (1 to 3 cm), while the rest was greater than 3 cm, with severe organs or complications. Methods: the most commonly used surgery was herniorraphy with autologous reinforcement, while classic su- tures and mesh sutures were used in the remaining cases. Follow-up demonstrated healing in most of the treated subjects. Conclusions: The study aimed to estimate some surgical clinical cases in Sicilian cattle. Most injuries are lower abdomen injuries, mostly simple or complicated umbilical hernias. Young dairy females were the most affected. Meaning/Impact: Radical surgery is the treatment of choice in the vast majority of symptomatic or asymptomatic umbilical diseases; moreover, the correct management and the choice of an appropriate surgical approach allow to obtain an effective treatment of the lesions. Simple summary: In cattle farm, the correct management of births is a fundamental step for the future of the breeding. In fact, there are numerous critical factors in this phase: calving area management, umbilical disin- fection, correct administration of colostrum, management of individual pens. Generally, after a few hours from birth, the calf is transferred in individual pens, the walls of this box allow visual and tactile contact but avoid the possibility of mutual sucking of the umbilical region, a risk factor, in that area, of infections and hernias. In the study have been collected umbilical interventions carried out over twenty years by a team operating in south- eastern Sicily: Ragusa. Out of a total of 320 cases, have been reported: the prevalence of types of umbilical tumefactions, anesthetic techniques and surgical techniques performed. The purpose of the work was to highlight any predispositions of race, sex, age regarding the lesion considered and above all, the effectiveness of the surgical therap

ErbB2 receptor over-expression improves post-traumatic peripheral nerve regeneration in adult mice.

In a transgenic mice (BALB-neuT) over-expressing ErbB2 receptor, we investigated the adult mouse median nerve in physiological and pathological conditions. Results showed that, in physiological conditions, the grip function controlled by the median nerve in BALB-neuT mice was similar to wild-type (BALB/c). Stereological assessment of ErbB2-overexpressing intact nerves revealed no difference in number and size of myelinated fibers compared to wild-type mice. By contrast, after a nerve crush injury, the motor recovery was significantly faster in BALB-neuT compared to BALB/c mice. Moreover, stereological assessment revealed a significant higher number of regenerated myelinated fibers with a thinner axon and fiber diameter and myelin thickness in BALB-neuT mice. At day-2 post-injury, the level of the mRNAs coding for all the ErbB receptors and for the transmembrane (type III) Neuregulin 1 (NRG1) isoforms significantly decreased in both BALB/c and BALB-neuT mice, as shown by quantitative real time PCR. On the other hand, the level of the mRNAs coding for soluble NRG1 isoforms (type I/II, alpha and beta) increased at the same post-traumatic time point though, intriguingly, this response was significantly higher in BALB-neuT mice with respect to BALB/c mice. Altogether, these results suggest that constitutive ErbB2 receptor over-expression does not influence the physiological development of peripheral nerves, while it improve