Visualization of DNA G-quadruplexes in herpes simplex virus 1-infected cells

We have previously shown that clusters of guanine quadruplex (G4) structures can form in the human herpes simplex-1 (HSV-1) genome. Here we used immunofluorescence and immune-electron microscopy with a G4-specific monoclonal antibody to visualize G4 structures in HSV-1 infected cells. We found that G4 formation and localization within the cells was virus cycle dependent: viral G4s peaked at the time of viral DNA replication in the cell nucleus, moved to the nuclear membrane at the time of virus nuclear egress and were later found in HSV-1 immature virions released from the cell nucleus. Colocalization of G4s with ICP8, a viral DNA processing protein, was observed in viral replication compartments. G4s were lost upon treatment with DNAse and inhibitors of HSV-1 DNA replication. The notable increase in G4s upon HSV-1 infection suggests a key role of these structures in the HSV-1 biology and indicates new targets to control both the lytic and latent infection

Phantoms in medicine: the case of ophthalmology

Physical and in-silico phantoms have revealed extremely useful in the development of new surgical techniques and medical devices and for training purposes. The fabrication of eye phantoms requires knowledge of anatomy and physical principles beyond the eye physiology and medical instruments used in the clinical scenario. After a proper definition of phantoms and the discussion about their classification, the present work reviews the various phantoms developed in ophthalmology, illustrating the rationale of their design

Radiation therapy for oligometastatic oropharyngeal cancer

At presentation, isolated metastasis from oropharyngeal squamous cell carcinoma is rare. Liver is a relatively uncommon first site of failure, especially in the absence of other distant metastases, particularly without diagnosis of lung metastases. We report on a case of HPV-related oropharyngeal squamous cell carcinoma with synchronous liver metastasis treated with radiation therapy. This condition, defined as "oligometastatic state," describes a subset of patients with limited volume metastatic disease in whom favorable outcomes were reported with the use of local ablative therapies on both the primary tumor and metastatic sites. As a definitive treatment, we offered the patient, ineligible for other therapeutic approaches, exclusive radiation treatment on the head and neck region and a stereotactic ablative approach targeted to the liver metastasis

New insights on binary black hole formation channels after GWTC-2: young star clusters versus isolated binaries

With the recent release of the second gravitational-wave transient catalogue (GWTC-2), which introduced dozens of new detections, we are at a turning point of gravitational wave astronomy, as we are now able to directly infer constraints on the astrophysical population of compact objects. Here, we tackle the burning issue of understanding the origin of binary black hole (BBH) mergers. To this effect, we make use of state-of-the-art population synthesis and N-body simulations, to represent two distinct formation channels: BBHs formed in the field (isolated channel) and in young star clusters (dynamical channel). We then use a Bayesian hierarchical approach to infer the distribution of the mixing fraction $f$, with $f=0$ ($f=1$) in the pure dynamical (isolated) channel. %that controls the proportion of isolated and dynamical BBHs. We explore the effects of additional hyper-parameters of the model, such as the spread in metallicity $\sigma_{\text{Z}}$ and the parameter $\sigma_{\text{sp}}$, describing the distribution of spin magnitudes. We find that the dynamical model is slightly favoured with a median value of $f=0.26$, when $\sigma_{\text{sp}}=0.1$ and $\sigma_{\text{Z}}=0.4$. Models with higher spin magnitudes tend to strongly favour dynamically formed BBHs ($f\le{}0.1$ if $\sigma_{\text{sp}}=0.3$). Furthermore, we show that hyper-parameters controlling the rates of the model, such as $\sigma_{\rm Z}$, have a large impact on the inference of the mixing fraction, which rises from $0.18$ to $0.43$ when we increase $\sigma_{\text{Z}}$ from 0.2 to 0.6, for a fixed value of $\sigma_{\text{sp}}=0.1$. Finally, our current set of observations is better described by a combination of both formation channels, as a pure dynamical scenario is excluded at the $99\%$ credible interval, except when the spin magnitude is high.Comment: 13 pages, 10 figures, 2 tables, published in MNRA

A score that predicts aquaporin-4-IgG positivity in patients with longitudinally extensive transverse myelitis

Background: Longitudinally extensive transverse myelitis (LETM) associated with aquaporin-4 autoantibodies (AQP4-IgG) can cause severe disability. Early diagnosis and prompt treatment are critical to prevent relapses. We describe a novel score based on clinical and neuroimaging characteristics that predicts AQP4-IgG positivity in patients with LETM. Methods: Patients were enrolled both retrospectively and prospectively from multiple Italian centers. Clinical and neuroimaging characteristics of AQP4-IgG positive and negative patients were compared through univariate and multivariate analysis. Results: Sixty-six patients were included. Twenty-seven (41%) were AQP4-IgG positive and median age at onset was 45.5 years old (range 19-81, interquartile range 24). Female sex (odds ratio [OR] 17.9; 95% confidence interval [CI] 2.6-381.9; p=0.014), tonic spasms (OR 45.6; CI 3.1-2197; p=0.017) and lesion hypointensity on T1-weighted images (OR 52.9; CI 6.8-1375; p=0.002) were independently associated with AQP4-IgG positivity. The Aquaporin-4-IgG positivity in Myelitis (AIM) score predicted AQP4-IgG positivity with 85% sensitivity and 95% specificity. Positive and negative likelihood ratio were 16.6 and 0.2 respectively. The inter-rater and intra-rater agreement in the score application were both excellent. Conclusions: The AIM score predicts AQP4-IgG positivity with good sensitivity and specificity in patients with a first episode of LETM. The score may assist clinicians in early diagnosis and treatment of AQP4-IgG positive LETM

Diagnostic contribution of Magnetic Resonance Imaging in an atypical presentation of Motor Neuron Disease

Motor neuron disease (MND) is a neurodegenerative disease determining progressive and relentless motor deterioration involving both upper and lower motor neurons (UMN and LMN); several variants at onset are described. Here we describe a case of MND presenting as pure spastic monoparesis in which magnetic resonance imaging (MRI) gave a substantial contribution in confirming the diagnosis and assessing the severity of UMN involvement. An isolated pyramidal syndrome, with complete absence of LMN signs, is a rare phenotype in the context of MND (less than 4% of total cases), especially if restricted to only one limb. Several other elements made this case an unusual presentation of MND: the late age of onset (8th decade), the subacute evolution of symptoms (raising the suspicion of an ischemic or inflammatory, rather than degenerative, etiology), the patient’s past medical history (achalasia, erythema nodosum), the increase of inflammatory indices. Conventional MRI showed no focal lesions that could explain the clinical features; therefore, we used advanced MR sequences. Diffusion tensor imaging (DTI) evaluation evidenced bilateral impairment of corticospinal tract (CST) diffusion metrics, with clear right-left asymmetry, pointing to a neurodegenerative etiology, which clinically appeared less likely at that time. Magnetic resonance spectroscopy (MRS) showed a significant reduction of NAA/Cho + Cr ratio in the motor cortex (MC), further supporting the hypothesis of UMN degeneration. In conclusion, in this particular case of MND, whose nosographic framing has not been fully defined, advanced MRI techniques with DTI and MRS proved to be of great usefulness in confirming a diffuse UMN involvement, possibly at a more advanced stage than its clinical expression

The Dragon-II simulations -- I. Evolution of single and binary compact objects in star clusters with up to 1 million stars

We present the first results of the \textsc{Dragon-II} simulations, a suite of 19 $N$-body simulations of star clusters with up to $10^6$ stars, with up to $33\%$ of them initially paired in binaries. In this work, we describe the main evolution of the clusters and their compact objects (COs). All \textsc{Dragon-II} clusters form in their centre a black hole (BH) subsystem with a density $10-100$ times larger than the stellar density, with the cluster core containing $50-80\%$ of the whole BH population. In all models, the BH average mass steeply decreases as a consequence of BH burning, reaching values $\langle m_{\rm BH}\rangle < 15$ M$_\odot$ within $10-30$ relaxation times. Generally, our clusters retain only BHs lighter than $30$ M$_\odot$ over $30$ relaxation times. Looser clusters retain a higher binary fraction, because in such environments binaries are less likely disrupted by dynamical encounters. We find that BH-main sequence star binaries have properties similar to recently observed systems. Double CO binaries (DCOBs) ejected from the cluster exhibit larger mass ratios and heavier primary masses than ejected binaries hosting a single CO (SCOBs). Ejected SCOBs have BH masses $m_{\rm BH} = 3-20$ M$_\odot$, definitely lower than those in DCOBs ($m_{\rm BH} = 10-100$ M$_\odot$).Comment: 22 pages, 21 figures, 4 tables. Comments welcome. Submitted to MNRA

Respiratory Complex I dysfunction in cancer: from a maze of cellular adaptive responses to potential therapeutic strategies

Mitochondria act as key organelles in cellular bioenergetics and biosynthetic processes producing signals that regulate different molecular networks for proliferation and cell death. This ability is also preserved in pathologic contexts such as tumorigenesis, during which bioenergetic changes and metabolic reprogramming confer flexibility favoring cancer cells survival in a hostile microenvironment. Although different studies epitomize mitochondrial dysfunction as a pro-tumorigenic hit, genetic ablation or pharmacological inhibition of respiratory Complex I causing a severe impairment are associated with a low proliferative phenotype. In this scenario, it must be considered that despite the initial delay in growth, cancer cells may become able to resume proliferation exploiting molecular mechanisms to overcome growth arrest. Here we highlight the current knowledge on molecular responses activated by Complex I-defective cancer cells to bypass physiological control systems and to re-adapt their fitness during microenvironment changes. Such adaptive mechanisms could reveal possible novel molecular players in synthetic lethality with Complex I impairment, thus providing new synergistic strategies for mitochondria-based anti-cancer therapy

Aiding the conservation of two wooden Buddhist sculptures with 3D imaging and spectroscopic techniques

The conservation of Buddhist sculptures that were transferred to Europe at some point during their lifetime raises numerous questions: while these objects historically served a religious, devotional purpose, many of them currently belong to museums or private collections, where they are detached from their original context and often adapted to western taste. A scientific study was carried out to address questions from Museo d'Arte Orientale of Turin curators in terms of whether these artifacts might be forgeries or replicas, and how they may have transformed over time. Several analytical techniques were used for materials identification and to study the production technique, ultimately aiming to discriminate the original materials from those added within later interventions