Terpene synthase genes originated from bacteria through horizontal gene transfer contribute to terpenoid diversity in fungi

Fungi are successful eukaryotes of wide distribution. They are known as rich producers of secondary metabolites, especially terpenoids, which are important for fungi-environment interactions. Horizontal gene transfer (HGT) is an important mechanism contributing to genetic innovation of fungi. However, it remains unclear whether HGT has played a role in creating the enormous chemical diversity of fungal terpenoids. Here we report that fungi have acquired terpene synthase genes (TPSs), which encode pivotal enzymes for terpenoid biosynthesis, from bacteria through HGT. Phylogenetic analysis placed the majority of fungal and bacterial TPS genes from diverse taxa into two clades, indicating ancient divergence. Nested in the bacterial TPS clade is a number of fungal TPS genes that are inferred as the outcome of HGT. These include a monophyletic clade of nine fungal TPS genes, designated as BTPSL for bacterial TPS-like genes, from eight species of related entomopathogenic fungi, including seven TPSs from six species in the genus Metarhizium. In vitro enzyme assays demonstrate that all seven BTPSL genes from the genus Metarhizium encode active enzymes with sesquiterpene synthase activities of two general product profiles. By analyzing the catalytic activity of two resurrected ancestral BTPSLs and one closely related bacterial TPS, the trajectory of functional evolution of BTPSLs after HGT from bacteria to fungi and functional divergence within Metarhizium could be traced. Using M. brunneum as a model species, both BTPSLs and typical fungal TPSs were demonstrated to be involved in the in vivo production of terpenoids, illustrating the general importance of HGT of TPS genes from bacteria as a mechanism contributing to terpenoid diversity in fungi

Higher risk of intracranial aneurysms and subarachnoid haemorrhage in siblings of families with intracranial aneurysms

Introduction: First-degree relatives of patients with familial aneurysmal subarachnoid hemorrhage have an increased risk of unruptured intracranial aneurysms and aneurysmal subarachnoid hemorrhage. We assessed whether the type of kinship of first-degree relatives of aneurysmal subarachnoid hemorrhage patients influences this risk. Patients and methods: We used all available data from the prospectively collected database of families consulting our outpatient clinic between 1994-2016. We constructed pedigrees for all families with ≥2 first-degree relatives with aneurysmal subarachnoid hemorrhage or unruptured intracranial aneurysms. The proband was defined as the first family member with aneurysmal subarachnoid hemorrhage who sought medical attention. We compared both the proportion of aneurysmal subarachnoid hemorrhage and unruptured intracranial aneurysms in proband's first-degree relatives by calculating relative risks (RR) with children as the reference. Results: We studied 154 families with 1,105 first-degree relatives of whom 146 had aneurysmalsubarachnoid hemorrhage. Unruptured intracranial aneurysms were identified in 63 (19%) of the 326 screened relatives. Siblings had a higher risk of aneurysmal subarachnoid hemorrhage (RR:1.62, 95% CI:1.12–2.38) and parents a lower risk (RR:0.44, 95% CI:0.24–0.81) than children. Siblings also had a higher risk of unruptured intracranial aneurysms (RR:2.28, 95% CI:1.23–4.07, age-adjusted RR:2.04, 95% CI:1.07–3.92) than children. Conclusion: Siblings of patients with aneurysmal subarachnoid hemorrhage have a significanthigher risk of both unruptured intracranial aneurysms and aneurysmal subarachnoid hemorrhage and parents have a lower risk of aneurysmal subarachnoid hemorrhage than children. Discussion: Type of kinship is a relevant factor to consider in risk prediction and screening advice in families with familial aneurysmal subarachnoid hemorrhage

Spinal arteriovenous shunts presenting as intracranial subarachnoid haemorrhage

Item does not contain fulltextBACKGROUND: In approximately 5% of patients with intracranial subarachnoid haemorrhage (SAH), the cause is another than a ruptured aneurysm or perimesencephalic haemorrhage. One of these causes is a spinal arteriovenous shunt (SAVS). The aim of this study was to investigate the characteristics of patients with SAVS who present with intracranial SAH without symptoms and signs suggesting a spinal cause. METHODS: We systematically reviewed the literature and searched the SAH database of the University Medical Center Utrecht, The Netherlands, for patients with SAVS presenting with intracranial SAH and studied the characteristics of patients with SAVS whose clinical presentation mimicked intracranial SAH caused by rupture of a saccular aneurysm. RESULTS: Thirty-five patients were identified after a review of the literature. In our SAH database, comprising 2142 patients included in the period 1985-2004, we found one patient (0.05%, 95 % CI 0.006- 0.3%). SAH due to SAVS occurred at any age (4-72 years). The SAVS was located at the craniocervical junction in 14 patients, at the cervical level in 11, and at the thoracolumbar level in the remaining 11 patients. The majority of patients (n = 26, 72%) had no disabling deficits at discharge or follow-up. CONCLUSION: Rupture of a SAVS presenting as intracranial SAH is rare and can occur at any age. The SAVS can be located not only at the craniocervical junction or cervical level but also in the thoracolumbar region. Most patients with SAVS presenting as intracranial SAH have a good recovery

n- исчисление – реалистичная формализация класса переписывающих систем

Предложен новый формализм типизированного η-исчисления в качестве теоретической основы для по-строения специальных классов систем программирования на основе переписывающих правил. Форма-лизм использует упорядоченные неконфлюэнтные множества правил переписывания и взаимодействие с программным окружением, что позволяет расширить возможности программирования динамических приложений

Size of third and fourth ventricle in obstructive and communicating acute hydrocephalus after aneurysmal subarachnoid hemorrhage

In patients with acute hydrocephalus after aneurysmal subarachnoid haemorrhage (SAH), lumbar drainage is possible if the obstruction is in the subarachnoid space (communicating hydrocephalus). In case of intraventricular obstruction (obstructive hydrocephalus), ventricular drainage is the only option. A small fourth ventricle is often considered a sign of obstructive hydrocephalus. We investigated whether the absolute or relative size of the fourth ventricle can indeed distinguish between these two types of hydrocephalus. On CT-scans of 76 consecutive patients with acute headache but normal CT and CSF, we measured the cross-sectional surface of the third and fourth ventricle to obtain normal planimetric values. Subsequently we performed the same measurements on 117 consecutive SAH patients with acute hydrocephalus. These patients were divided according to the distribution of blood on CT-scan into three groups: mainly intraventricular blood (n = 15), mainly subarachnoid blood (n = 54) and both intraventricular and subarachnoid blood (n = 48). The size of the fourth ventricle exceeded the upper limit of normal in 2 of the 6 (33%) patients with intraventricular blood but without haematocephalus, and in 15 of the 54 (28%) patients with mainly subarachnoid blood. The mean ratio between the third and fourth ventricle was 1.45 (SD 0.66) in patients with intraventricular blood and 1.42 (SD 0.91) in those with mainly subarachnoid blood. Neither fourth ventricular size nor the ratio between the third and fourth ventricles discriminates between the two groups. A small fourth ventricle does not necessarily accompany obstructive hydrocephalus and is therefore not a contraindication for lumbar drainage

Secondary infarction in single or in multiple vascular territories: two different entities following subarachnoid hemorrhage?

The pathogenesis of secondary infarctions (SI) after aneurysmal subarachnoid hemorrhage (SAH) is poorly understood. To assess whether SI in single (SSI) or multiple (MSI) vascular territories represent different disease entities, we compared clinical profiles of patients with these patterns of SI. CT/MRI-examinations of 448 patients were reviewed for new infarctions within 28 days after SAH, and categorized into SSI or MSI. Only patients with adequate follow-up imaging excluding any new infarctions were included for analysis (269 patients). Procedure-related infarctions were excluded. Odds ratios (ORs) with corresponding 95% confidence intervals (CI) were calculated for patients with SSI or MSI versus patients without SI to analyze differences in demographic characteristics, vascular risk factors, disease-related characteristics and treatment modalities. Thirty-six patients had SSI, 53 MSI and 180 no SI. ORs in MSI-patients were >1.5 times higher compared with ORs in SSI-patients for multiple vascular risk factors [MSI:5.4 (2.3–13) versus SSI:1.2 (0.5–2.8)], poor clinical condition on admission [MSI:4.6 (2.4–8.9) versus SSI:2.4 (1.1–5.2)], initial loss of consciousness [MSI:2.6 (1.3–5.3) versus SSI:1.1 (0.5–2.3)] and large amounts of intraventricular blood [MSI:2.9 (1.4–5.8) versus SSI:1.5 (0.7–3.2)]. In multivariate analysis ORs remained higher in MSI for presence of multiple vascular risk factors [MSI:1.9 (1.2–2.9) versus SSI:1.1 (0.8–1.7)] and initial loss of consciousness [MSI:3.0 (1.0–8.9) versus SSI:1.6 (0.6–4.0)]. Our findings suggest that SSI and MSI after SAH are not distinct disease entities. MSI was related to the same characteristics as SSI but to a larger extent, specifically to the presence of multiple vascular risk factors, initial loss of consciousness, larger amounts of intraventricular blood, and poor clinical status on admission