Targeting PI3K/AKT/mTOR and MAPK Signaling Pathways in Gastric Cancer.

Gastric cancer (GC) is the fourth leading cause of death worldwide, with more than 1 million cases diagnosed every year. Helicobacter pylori represents the main risk factor, being responsible for 78% of the cases. Increased amounts of salt, pickled food, red meat, alcohol, smoked food, and refined sugars negatively affect the stomach wall, contributing to GC development. Several gene mutations, including PIK3CA, TP53, ARID1A, CDH1, Ras, Raf, and ERBB3 are encountered in GC pathogenesis, leading to phosphatidylinositol 3-kinase (PI3K) protein kinase B (AKT)/mammalian target of rapamycin (mTOR)-PI3K/AKT/mTOR-and mitogen-activated protein kinase (MAPK) signaling pathway activation and promoting tumoral activity. Helicobacter pylori, growth factors, cytokines, hormones, and oxidative stress also activate both pathways, enhancing GC development. In clinical trials, promising results have come from monoclonal antibodies such as trastuzumab and ramucirumab. Dual inhibitors targeting the PI3K/AKT/mTOR and MAPK signaling pathways were used in vitro studies, also with promising results. The main aim of this review is to present GC incidence and risk factors and the dysregulations of the two protein kinase complexes together with their specific inhibitors.

Adiponectin - stratification biomarker in diastolic cardiac dysfunction.

This study does not propose to elucidate how adiponectin secretion is regulated, but how its adiponectin concentration is an indicator of heart disease. About adiponectin, it is not known whether it is functionally an enzyme, or very likely a cytokine/chemokine/hormone, secreted by fat cells/adipocytes in the abdomen. Abdominal fat secretes 67 hormones, and all of which cause disease. For example, adiponectin generates diabetes and ischaemic heart disease via dyslipidemia. Based on clinical symptoms, electrocardiographic and echocardiographic parameters, a group of 208 patients with diastolic cardiac dysfunction with or without preserved systolic function, developed on a background of painful chronic ischaemic heart disease, stable angina on exertion, was constituted. The serum levels of adiponectin, total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides were measured. Using the identified values, it was appreciated whether adiponectin correlates with the type of any of the two conditions, so that it can be recognised as a diagnostic and risk stratification marker.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) - possible diagnostic and risk biomarker in chronic ischaemic heart disease.

In a group of 208 patients with chronic ischaemic heart disease, the variation of A2-associated-LDL phosphatase (Lp-PLA2) serum concentration values was analysed in dynamics at a two-week interval. The conclusion of the study is that the values of serum concentration of Lp-PLA2 can be accepted as a biomarker with diagnostic specificity for chronic ischaemic heart disease, a parameter of real utility in medical practice, both in situations where the patient, although clinically reporting the existence of angina pectoris, does not show specific changes on an EKG, and for the assessment of the response to personalised therapy.

Osteopontin - a biomarker of disease, but also of stage stratification of the functional myocardial contractile deficit by chronic ischaemic heart disease.

The study analyses the significance of the plasmatic values of the OPN dosed to 91 people suffering from diastolic cardiac dysfunction with preserved ejection fraction, thus revealing significant growths of its level compared to the normal value. Despite being a clinical research, its conclusions are a breakthrough, differing from the results of other studies published in the relevant medical literature. We can make this assertion because this study analyses the clinical information given by the circulating values of the OPN, based on experimental models (animals), or on patients with congestive heart failure, which can be identified with the existence of a low systolic flow. The results of our study allow us to assert that the plasmatic values of this glycoprotein lead to its acceptance in the medical practice as a new biomarker that provides indicators regarding the stratification of risk with the patients suffering from heart failure of the diastolic dysfunction type, but whose systolic flow is preserved.

Development of a highly efficient oil degumming process using a novel phosphatidylinositol-specific phospholipase C enzyme.

Enzymatic degumming using phospholipase C (PLC) enzymes may be used in environmentally friendly processes with improved oil recovery yields. In this work, phosphatidylinositol-specific phospholipase C (PIPLC) candidates obtained from an in silico analysis were evaluated for oil degumming. A PIPLC from Lysinibacillus sphaericus was shown to efficiently remove phosphatidylinositol from crude oil, and when combined with a second phosphatidylcholine and phosphatidylethanolamine-specific phospholipase C, the three major phospholipids were completely hydrolyzed, providing an extra yield of oil greater than 2.1%, compared to standard methods. A remarkably efficient fed-batch Escherichia coli fermentation process producing ∼14 g/L of the recombinant PIPLC enzyme was developed, which may facilitate the adoption of this cost-effective oil-refining process.

Abrasion and dental pulp morphological changes in occlusal dysfunction.

AIM: The authors set out to assess if the presence and the degree of severity of the abrasion, as a consequence of the occlusal dysfunction, determine further morphological changes in the dental pulp. MATERIALS AND METHODS: Study group included teeth dental pulp from 45 cases with occlusal dysfunction, subsequently divided into two subgroups: 24 cases with abrasion (AB) and 21 cases without abrasion (NONAB). The set of morphological parameters of dental pulp were thicknesses of the outer layer, inner layer and entire peripheral pulp zone, the presence of pulpal calcifications and their extent within the dental pulp, the presence of interstitial fibrosis and its extent within the dental pulp and the vascular density (VD) of pulpal capillary network. Tissue samples were fixed in 10% buffered formalin, embedded in paraffin, and sectioned off at 4 µm. Serial slides were stained with Hematoxylin-Eosin (HE), Masson's trichrome (MT) and anti-cluster of differentiation 34 (CD34) antibodies labeled with 3,3'-Diaminobenzidine (DAB) and transformed into virtual slides on which the above-mentioned parameters were studied comparatively with the help of a dedicated in-house software, realized in MATLAB (MathWorks, USA). The numerical values of the assessed parameters were also stratified in classes, thus obtaining score scales for each parameter. Statistical tools used were Lilliefors test, t-test (two-sample assuming equal variances), Mann-Whitney test, Pearson's correlation test, one-way analysis of variance (ANOVA) test and χ² (chi-squared) test. RESULTS AND DISCUSSIONS: Both peripheral zone (PZ) and its layers individually tended to be thicker in the teeth with abrasion than in those without abrasion. Also, teeth with abrasion tended to develop larger amounts of calcium deposits in their dental pulp than teeth without abrasion. On the other hand, fibrotic tissue in dental pulp had no relationship with the presence or absence of abrasion. PZ as a whole and its layers evolved together in the same way, with a stronger correlation in the group of teeth without abrasion. Deposits of calcium evolved in the opposite direction to both the amount of fibrous tissue and the capillaries density of the dental pulp. Consequently, the amount of fibrous tissue and VD evolved together in the same way, more pronounced in the teeth without abrasion. CONCLUSIONS: Our preliminary study pointed out that different components of the dental pulp showed slight to moderate changes depending on the degree of abrasion in teeth with occlusal dysfunction.

Clinical and Histopathological Aspects of MRONJ in Cancer Patients.

Medication-related osteonecrosis of the jaw (MRONJ) is a major complication of bisphosphonate treatment in cancer patients, and its etiology is not completely clarified. The study's goal is to find connections between the clinical and histopathological characteristics of osteonecrosis and bisphosphonates in a cohort of cancer patients who had osteonecrosis treated surgically. The retrospective study includes 51 patients of both sexes, aged 46 to 85 years, who underwent surgical treatment for MRONJ in two oral and maxillofacial surgery clinics (Craiova and Constanța). Demographic, clinical, and imaging data from the records of patients with osteonecrosis were analyzed. The surgical treatment removed the necrotic bone, and the harvested fragments were analyzed from a histopathological perspective. The histopathological examination data were evaluated and statistically processed to look for viable bone, granulation tissue, bacterial colonies, and inflammatory infiltrate. In the study groups, MRONJ was found particularly in the posterior regions of the mandible. Tooth extraction, but also periapical or periodontal infections, represented the trigger factors in most of the cases. The surgical therapy consisted of sequestrectomy or bone resection, and the histopathological examination of the fragments revealed osteonecrosis-specific features, such as the lack of bone cells, the development of an inflammatory infiltrate, and the existence of bacterial colonies. MRONJ in cancer patients receiving zoledronic acid is a severe complication that significantly lowers quality of life. Since these patients are not usually monitored by the dentist, they are identified in advanced stages of MRONJ. For these patients, thorough dental monitoring could reduce the incidence of osteonecrosis and its related complications.

Risk Factors for Medication-Related Osteonecrosis of the Jaw-A Binomial Analysis of Data of Cancer Patients from Craiova and Constanta Treated with Zoledronic Acid.

MRONJ (Medication-Related Osteonecrosis of the Jaw) is a condition observed in a subset of cancer patients who have undergone treatment with zoledronic acid in order to either prevent or treat bone metastases. The primary aim of this research was to establish the importance of risk factors in the development of medication-related osteonecrosis of the jaw in cancer patients receiving zoledronic acid therapy for bone metastases. The present study is an observational retrospective investigation conducted at two university centers, namely, Craiova and Constanța, and included cancer patients treated with zoledronic acid. The medical records of the patients were obtained over a four-year timeframe spanning from June 2018 to June 2022. The data analysis was carried out between January 2021 and October 2022. Patients were treated for cancer, bone metastases, and MRONJ according to the international guidelines. The research investigated a cohort of 174 cancer patients (109 females and 65 males) aged between 22 and 84 years (with a mean age 64.65 ± 10.72 years) seeking treatment at oncology clinics situated in Craiova and Constanța. The study conducted a binomial logistic regression to analyze ten predictor variables, namely, gender, age, smoking status, treatment duration, chemotherapy, radiotherapy, endocrine therapy, presence of diabetes mellitus (DM), obesity, and hypertension (HT). The results of the analysis revealed that only five of the ten predictor variables were statistically significant for MRONJ occurrence: duration of treatment (p < 0.005), chemotherapy (p = 0.007), and hypertension (p = 0.002) as risk factors, and endocrine therapy (p = 0.001) and obesity (p = 0.024) as protective factors.

Increasing Vaccine Uptake during Pregnancy by Using Prenatal Education Classes: An Effective Tool for Health Communication and Promotion.

Childbirth education classes represent an antenatal tool for supporting pregnant women and couples in increasing knowledge on pregnancy, delivery, breastfeeding, and newborn care. The aim of this study was to investigate the impact of an additional lesson during the prenatal course regarding the advantage of vaccination to mitigation of maternal anxiety. An observational study was designed that included participants in childbirth education classes and compared courses enhanced by the extra lesson on vaccination during pregnancy versus those who did not receive it. Assessment of the impact of prenatal educational on vaccination was measured by using validated questionnaires (State-Trait Anxiety Inventory, STAI; Perceived Stress Scale, PSS; World Health Organization- Five Well-Being Index, WHO-5). A total of 145 pregnant women participated to the investigation by answering to the online survey. Of them, 33 patients (22.8%) belonged to the course without a lesson on vaccine, while 112 (77.2%) participated to online prenatal education that included an additional meeting on the usefulness of getting vaccinated during pregnancy. No statistical differences were found between study groups in terms of demographics and perinatal outcomes. Participants in the enriched course reported lower basal anxiety levels than those without the vaccine lesson (STAI-State, normal score < 40, 30 vs. 19%, p-value 0.041; STAI-State, mild score 40-50, 78 vs. 67%, p-value 0.037). With reference to the prior two weeks, maternal wellbeing level was improved by the added class (score > 13 as measurement of wellbeing: 62% vs. 80%, p-value < 0.05). Moderate perceived stress assessed by PSS was found in those pregnant women without prenatal education on vaccination (64 vs. 50%, p-value 0.042). The introduction of a lesson regarding vaccination during pregnancy in the program of prenatal education courses improved maternal anxiety levels and wellbeing, in addition to reducing perceived stress.

Systemic inflammation factors as survival prognosis markers in ovarian neoplasm and the relationship with cancer-associated inflammatory mediators-a review.

At the level of the genital system, ovarian neoplasm is the most frequent cause of morbidity and mortality. In the specialized literature, the coexistence of an inflammatory process is admitted from the early stages of the evolution of this pathology. Starting from the importance of this process, both in determinism and in the evolution of carcinogenesis and summarizing the field of knowledge, for this study we considered two objectives: the first was the presentation of the pathogenic mechanism, through which chronic +ovarian inflammation is involved in the process of carcinogenesis, and the second is the justification of the clinical utility of the three parameters, accepted as biomarkers of systemic inflammation: neutrophil-lymphocyte ratio, platelet lymphocyte ratio, and lymphocyte-monocyte ratio in the assessment of prognosis. The study highlights the acceptance of these hematological parameters, with practical utility, as prognostic biomarkers in ovarian cancer, based on the intrinsic link with cancer-associated inflammatory mediators. Based on the data from the specialized literature, the conclusion is that in ovarian cancer, the inflammatory process induced by the presence of the tumor, induces changes in the types of circulating leukocytes, with immediate effects on the markers of systemic inflammation.

The Yin and Yang dualistic features of autophagy in thermal burn wound healing.

Burn healing should be regarded as a dynamic process consisting of two main, interrelated phases: (a) the inflammatory phase when neutrophils and monocytes infiltrate the injury site, through localized vasodilation and fluid extravasation, and (b) the proliferative-remodeling phase, which represents a key event in wound healing. In the skin, both canonical autophagy (induced by starvation, oxidative stress, and environmental aggressions) and non-canonical or selective autophagy have evolved to play a discrete, but, essential, "housekeeping" role, for homeostasis, immune tolerance, and survival. Experimental data supporting the pro-survival roles of autophagy, highlighting its Yang, luminous and positive feature of this complex but insufficient explored molecular pathway, have been reported. Autophagic cell death describes an "excessive" degradation of important cellular components that are necessary for normal cell function. This deadly molecular mechanism brings to light the darker, concealed, Yin feature of autophagy. Autophagy seems to perform dual, conflicting roles in the angiogenesis context, revealing once again, its Yin-Yang features. Autophagy with its Yin-Yang features remains the shadow player, able to decide quietly whether the cell survives or dies.

Specific interaction between E2F1 and Sp1 regulates the expression of murine CTP:phosphocholine cytidylyltransferase alpha during the S phase.

CTP:phosphocholine cytidylyltransferase alpha (CCTalpha) is a key enzyme for phosphatidylcholine biosynthesis in mammalian cells. This enzyme plays an essential role in all processes that require membrane biosynthesis such as cell proliferation and viability. Thus, CCTalpha activity and expression fluctuate during the cell cycle to achieve PtdCho requirements. We demonstrated, for the first time, that CCTalpha is localized in the nucleus in cells transiting the S phase, whereas it is localized in the cytoplasm of G(0)-arrested cells, suggesting a specific role of nuclear CCTalpha during the S phase. We also investigated how E2F1 influences the regulation of the CCTalpha-promoter during the S phase; we demonstrated that E2F1 is necessary, but not sufficient, to activate CCTalpha expression when this factor is over-expressed. However, when E2F1 and Sp1 were over-expressed, the transcription from the CCTalpha-promoter reporter construct was super-activated. Transient transfection studies demonstrated that E2F1 could super-activate Sp1-dependent transcription in a promoter containing only the Sp1 binding sites "B" or "C", and that Sp1 could activate Sp1-dependent transcription in a promoter containing the E2F site, thus, further demonstrating a functional interaction of these factors. In conclusion, the present results allowed us to portray the clearest picture of the CCTalpha-gene expression in proliferating cells, and understand the mechanism by which cells coordinate cell cycle progression with the requirement for phosphatidylcholine.

Role of phosphatidylcholine during neuronal differentiation.

Neuronal differentiation is characterized by neuritogenesis and neurite outgrowth, processes, which are critically dependent on membrane biosynthesis, and therefore, on the expression and regulation of enzymes involved in phospholipid biosynthesis. During the last decade a great effort was made to clarify where membrane lipids are synthesized, how the newly synthesized membrane components reach the membrane and are inserted during neuritogenesis and to elucidate the mechanism by which the supply of new membrane components is coordinated with the demand for growth. Phosphatidylcholine is the principal and essential component for mammalian membranes. This review updates the mechanism by which phosphatidylcholine biosynthesis takes place and how it is coordinately regulated during neuronal differentiation.

Ixodes ricinus ticks (Acari: Ixodidae): vectors for Lyme disease spirochetes in Romania.

In this study 1,868 questing Ixodes ricinus ticks (nymphs and adults), collected in six sites from three counties--Giurgiu, Sibiu, and Tulcea--in Romania, were examined by polymerase chain reaction (PCR) followed by reverse line blot (RLB) for detection of Borrelia burgdorferi sensu lato presence. The bacteria were found in 18% of the investigated ticks. The prevalence of infection did not differ significantly between nymphs (19.1%) and adults (15.4%). Three B. burgdorferi s.l. genospecies were detected: B. afzelii (61.1%), B. garinii (31.2%), and B. valaisiana (7.7%). No mixed infections were detected. The highest infection prevalence in nymphs was detected at Cristian (Sibiu County)--22.0%, whereas in adults it was at Comana (Giurgiu County)--19.8%. This preliminary study provides evidence that Lyme disease spirochetes are present in various regions of Romania, and at a relatively high prevalence in their vectors, thus posing a risk of infection to human subjects in the areas infested by ticks.

First report of lyme disease spirochetes in ticks from Romania (Sibiu County).

We examined 200 questing Ixodes ricinus ticks (nymphs and adults) collected in three different sites in Sibiu County, Romania by polymerase chain reaction (PCR) followed by reverse line blot (RLB) for Borrelia burgdorferi s.l.. We detected the bacteria in 19% of the investigated ticks. The prevalence of infection was higher in nymphs (27%) than in adults (12%). Two B. burgdorferi sensu lato genospecies were detected: B. garinii (20%) and B. afzelii (80%). We did not detect any mixed infections in the investigated ticks. In two of the investigated sites B. burgdorferi prevalence values were comparable (25%), while in the third site the prevalence was lower ( approximately 7%). Our preliminary study provides evidence that Lyme disease spirochetes are present in various areas and at a relatively high prevalence in their vectors, thus posing a risk of infection to human subjects that undergo work or leisure activities in those areas.

Characterization of the murine CTP:phosphocholine cytidylyltransferase beta gene promoter.

CTP:phosphocholine cytidylyltransferase (CCT) is a key regulatory enzyme in phosphatidylcholine (PtdCho) biosynthesis by the Kennedy pathway. In mammals, there are two genes that encode the enzyme isoforms that catalyze this reaction: Pcyt1a for CCTalpha and Pcyt1b for CCTbeta. In mouse tissues two different CCTbeta variants named CCTbeta2 and CCTbeta3 have been identified. Although little is known about Pcyt1b gene expression, recent data from cell lines propose a distinct role for CCTbeta2 in neuronal differentiation. Also, gonadal dysfunction in the CCTbeta2 knockout mouse suggests a role for this protein in ovary maturation and the maintenance of sperm production. This work defines and characterizes two alternative promoters that drive the expression of the two murine CCTbeta isoforms. The promoter activities were measured in Neuro-2a (mouse neuroblastoma), TM4 (mouse Sertoli) and C3H10T1/2 (mouse embryo fibroblast) cell lines. The transcriptional start points of each transcript and the promoter regions essential for the expression of each isoform were determined. Analysis of the CCTbeta2 promoter sequence suggested the transcription factor AP-1 as a potential regulator of CCTbeta2 expression in neuronal cells. However, CCTbeta3 was not detected in this cell line suggesting a different role or regulation. The activities of alternative promoters provide for greater flexibility in the control of CCTbeta isoform expression.

Spotted fever rickettsiae in wild-living rodents from south-western Poland.

BACKGROUND: Rickettsiae are obligate intracellular alpha-proteobacteria. They are transmitted via arthropod vectors, which transmit the bacteria between animals and occasionally to humans. So far, much research has been conducted to indicate reservoir hosts for these microorganisms, but our knowledge is still non-exhaustive. Therefore, this survey was undertaken to investigate the presence of Rickettsia spp. in wild-living small rodents from south-western Poland. RESULTS: In total, 337 samples (193 from spleen and 144 from blood) obtained from 193 wild-living rodents: Apodemus agrarius, Apodemus flavicollis, and Myodes glareolus were tested by qPCR for Rickettsia spp. based on a fragment of gltA gene. The prevalence of infection was 17.6% (34/193). Subsequently, the positive samples were analysed by conventional PCR targeting the gltA gene fragment. The genus Rickettsia was confirmed by sequence analysis in four samples from the blood. In two blood samples from A. agrarius, the identified pathogen was Rickettsia helvetica. The Rickettsia obtained from A. flavicollis was assigned to Rickettsia felis-like organisms group. One isolate from A. agrarius could be determined only to the genus level. CONCLUSIONS: This study shows the presence of Rickettsia DNA in tissues of wild-living rodents, suggesting some potential role of these animals in temporarily maintaining and spreading the bacteria in enzootic cycles.

Ticks and Borrelia in urban and peri-urban green space habitats in a city in southern England.

Ticks are becoming increasingly recognised as important vectors of pathogens in urban and peri-urban areas, including green space used for recreational activities. In the UK, the risk posed by ticks in such areas is largely unknown. In order to begin to assess the risk of ticks in urban/peri-urban areas in southern England, questing ticks were collected from five different habitat types (grassland, hedge, park, woodland and woodland edge) in a city during the spring, summer and autumn of 2013/2014 and screened for Borrelia burgdorferi sensu lato. In addition, seasonal differences in B. burgdorferi s.l. prevalence were also investigated at a single site during 2015. Ixodes ricinus presence and activity were significantly higher in woodland edge habitat and during spring surveys. DNA of Borrelia burgdorferi s.l. was detected in 18.1% of nymphs collected across the 25 sites during 2013 and 2014 and two nymphs also tested positive for the newly emerging tick-borne pathogen B. miyamotoi. Borrelia burgdorferi s.l. prevalence at a single site surveyed in 2015 were found to be significantly higher during spring and summer than in autumn, with B. garinii and B. valaisiana most commonly detected. These data indicate that a range of habitats within an urban area in southern England support ticks and that urban Borrelia transmission cycles may exist in some of the urban green spaces included in this study. Sites surveyed were frequently used by humans for recreational activities, providing opportunity for exposure to Borrelia infected ticks in an urban/peri-urban space that might not be typically associated with tick-borne disease transmission.

Post-medication Stevens-Johnson syndrome in a girl hospitalized for a norovirus and rotavirus infection.

Stevens-Johnson syndrome (SJS) is a cutaneous mucosal disorder characterized by extended necrosis and detachment of the epidermis affecting <10% of the body surface, caused by drugs or infections. The authors report a case of a girl with Depakine resistant epilepsy, who develops a SJS in the third week of introducing lamotrigine. The girl also presents an acute diarrheal disease with double viral etiology - rotavirus and norovirus. The clinical image comprises polymorphic erythematous maculopapular exanthema with vesicular and bullous elements, with ulcerations and desquamations at the level of the eyelids, mouth, anogenital area and tegument denuding at the level of the abdomen and limbs. The SCORTEN score (SCORe of Toxic Epidermal Necrosis) for establishing the seriousness is 1. The evolution of the disease is slowly favorable under conservative treatment, which does not involve the use of corticotherapy or intravenous immunoglobulins. Although there is a low incidence of this syndrome in pediatrics, it may occur as complication of using some drugs - mostly anti-epileptics or antibiotics, corroborated or not with an infectious process.

Nested coevolutionary networks shape the ecological relationships of ticks, hosts, and the Lyme disease bacteria of the Borrelia burgdorferi (s.l.) complex.

BACKGROUND: The bacteria of the Borrelia burgdorferi (s.l.) (BBG) complex constitute a group of tick-transmitted pathogens that are linked to many vertebrate and tick species. The ecological relationships between the pathogens, the ticks and the vertebrate carriers have not been analysed. The aim of this study was to quantitatively analyse these interactions by creating a network based on a large dataset of associations. Specifically, we examined the relative positions of partners in the network, the phylogenetic diversity of the tick's hosts and its impact on BBG circulation. The secondary aim was to evaluate the segregation of BBG strains in different vectors and reservoirs. RESULTS: BBG circulates through a nested recursive network of ticks and vertebrates that delineate closed clusters. Each cluster contains generalist ticks with high values of centrality as well as specialist ticks that originate nested sub-networks and that link secondary vertebrates to the cluster. These results highlighted the importance of host phylogenetic diversity for ticks in the circulation of BBG, as this diversity was correlated with high centrality values for the ticks. The ticks and BBG species in each cluster were not significantly associated with specific branches of the phylogeny of host genera (R 2 = 0.156, P = 0.784 for BBG; R 2 = 0.299, P = 0.699 for ticks). A few host genera had higher centrality values and thus higher importance for BBG circulation. However, the combined contribution of hosts with low centrality values could maintain active BBG foci. The results suggested that ticks do not share strains of BBG, which were highly segregated among sympatric species of ticks. CONCLUSIONS: We conclude that BBG circulation is supported by a highly redundant network. This network includes ticks with high centrality values and high host phylogenetic diversity as well as ticks with low centrality values. This promotes ecological sub-networks and reflects the high resilience of BBG circulation. The functional redundancy in BBG circulation reduces disturbances due to the removal of vertebrates as it allows ticks to fill other biotic niches.