Prediction of HIV-1 virus-host protein interactions using virus and host sequence motifs

<p>Abstract</p> <p>Background</p> <p>Host protein-protein interaction networks are altered by invading virus proteins, which create new interactions, and modify or destroy others. The resulting network topology favors excessive amounts of virus production in a stressed host cell network. Short linear peptide motifs common to both virus and host provide the basis for host network modification.</p> <p>Methods</p> <p>We focused our host-pathogen study on the binding and competing interactions of HIV-1 and human proteins. We showed that peptide motifs conserved across 70% of HIV-1 subtype B and C samples occurred in similar positions on HIV-1 proteins, and we documented protein domains that interact with these conserved motifs. We predicted which human proteins may be targeted by HIV-1 by taking pairs of human proteins that may interact via a motif conserved in HIV-1 and the corresponding interacting protein domain.</p> <p>Results</p> <p>Our predictions were enriched with host proteins known to interact with HIV-1 proteins ENV, NEF, and TAT (p-value < 4.26E-21). Cellular pathways statistically enriched for our predictions include the T cell receptor signaling, natural killer cell mediated cytotoxicity, cell cycle, and apoptosis pathways. Gene Ontology molecular function level 5 categories enriched with both predicted and confirmed HIV-1 targeted proteins included categories associated with phosphorylation events and adenyl ribonucleotide binding.</p> <p>Conclusion</p> <p>A list of host proteins highly enriched with those targeted by HIV-1 proteins can be obtained by searching for host protein motifs along virus protein sequences. The resulting set of host proteins predicted to be targeted by virus proteins will become more accurate with better annotations of motifs and domains. Nevertheless, our study validates the role of linear binding motifs shared by virus and host proteins as an important part of the crosstalk between virus and host.</p

Building energy models with morphological urban-scale parameters: A case study in Turin

With a growing awareness around the importance of the optimization of building efficiency, being able to make accurate predictions of building energy demand is an invaluable asset for practitioners and designers. For this reason, it is important to continually improve existing models as well as introduce new methods that can help reduce the so-called energy performance gap, which separates predicted from actual consumption values. This is particularly true for urban scale simulations, where even small scenes can be very complex and carry the necessity of finding a reasonable balance between precision and computational efforts. The scope of this work is to present two different models that make use of morphological urban-scale parameters to improve their performances, taking into account the interactions between buildings and their surroundings. In order to do this, two neighbourhoods in the city of Turin (IT) were taken as case studies. The buildings studied present similar characteristics but are inserted in a different urban context. Several urban parameters were extracted using a GIS tool and used as input, alongside the building-scale features, for two different models: i) a bottom-up engineering approach that evaluates the energy balance of residential buildings and introduces some variables at block-of-buildings scale, ii) a machine learning approach based on the bootstrap aggregating (bagging) algorithm, which takes the same parameters used by the previous model as inputs and makes an estimation of the hourly energy consumption of each building. The main results obtained confirm that the urban context strongly influences the energy performance of buildings located in high built-up areas, and that introducing simple morphological urban-scale parameters in the models to take these effects into account can improve their performance while having a very low impact on the computational efforts

ACPD ligands for glutamic receptors : conformational analysis by NMR spectroscopy and molecular dynamics. Simulation in water of glutamic acid analogues containing a cyclopentane ring

The conformational analysis of two isomeric glutamic acid analogues cis and trans ACPD containing a cyclopentane ring, was carried out in an aqueous environment, by lH and 13C NMR spectroscopy, and molecular dynamics (MD) in water. These analogues interact on receptors of central nervous system (receptor metabotropic ACPD for the ligand trans ACPD and receptor ionotropic NMDA for the ligand cis ACPD) . This study show four conformational families I-IV with characteristic distances dl (αNH3+ - yCOO-) and d2 (αCOO- - YCOO-)

The Cryo-immunologic effect: A therapeutic advance in the treatment of glioblastomas?

International audienceThe immunotherapy of cerebral glioblastoma has become a hot topic. Immune checkpoint blockade antibodies have progressively acquired a role in the management of malignant tumors. A multimodal approach using surgery, radiotherapy, chemotherapy in combination with immunotherapy represent a potent weapon against glioblastomas. In parallel, clinical applications of cryotherapy-freezing tumors based on repetition of rapid freeze-slow thaw cycle-for various cancers such as skin, lung, breast, esophagus, hepatic, kidney, prostate and bone tumors were developed. The future immunomodulatory approaches might be combined with brain tumors cryoablation to increase the cryoimmune response. The objective of this study was to analyze from the literature the relationship between cerebral cryosurgery and immunomodulation using PRISMA method. The animals' studies demonstrate the dendritic cells maturation and activation with the enhancement of antigen-presenting function after cryotherapy suggesting the potential usefulness of the association of cryotherapy and immunomodulator in the management of gliomas

Risk of Deep vein thrombosis in neurosurgery: State of the art on prophylaxis protocols and best clinical practices.

ObjectiveTo analytically discuss some protocols in Deep vein thrombosis (DVT)/pulmonary Embolism (PE) prophylaxis currently use in Neurosurgical Departments around the world. Data sourcesAnalysis of the prophylaxis protocols in the English literature: An analytical and narrative review of literature concerning DVT prophylaxis protocols in Neurosurgery have been conducted by a PubMed search (back to 1978). Data extraction80 abstracts were reviewed, and 74 articles were extracted. Data analysisThe majority of DVT seems to develop within the first week after a neurosurgical procedure, and a linear correlation between the duration of surgery and DVT occurrence has been highlighted. The incidence of DVT seems greater for cranial (7.7%) than spinal procedures (1.5%). Although intermittent pneumatic compression (IPC) devices provided adequate reduction of DVT/PE in some cranial and combined cranial/spinal series, low-dose subcutaneous unfractionated heparin (UFH) or low molecular-weight heparin (LMWH) further reduced the incidence, not always of DVT, but of PE. Nevertheless, low-dose heparin-based prophylaxis in cranial and spinal series risks minor and major postoperative haemorrhages: 2–4% in cranial series, 3.4% minor and 3.4% major haemorrhages in combined cranial/spinal series, and a 0.7% incidence of major/minor haemorrhages in spinal series. ConclusionThis analysis showed that currently most of the articles are represented by case series and case reports. As long as clear guidelines will not be defined and universally applied to this diverse group of patients, any prophylaxis for DVT and PE should be tailored to the individual patient with cautious assessment of benefits versus risks.  </p

Intracranial Metastases from Prostate Carcinoma: Classification, Management, and Prognostication

Background: Prostate carcinomas rarely metastasize to the central nervous system but, when they do, dural localizations are as common as and far more aggressive than intraparenchymal ones. Those metastases can be further classified according to their extension toward the subdural or extradural space and can frequently simulate other pathologic conditions including chronic subdural hematomas, abscess, and primary bone tumors. Beside the challenges of the preoperative differential diagnostic and complexity of surgical planning and operative excision, subdural metastases seem to carry a much poorer prognosis. Methods: A series of consecutive patients admitted during a 12-year period through our oncall pathway for subdural/extradural collections or intraparenchymal lesions found, on histologic analysis, to represent intracranial prostate cancer metastases was retrospectively reviewed. Results: A total of 19 patients were included, but only 3 were diagnosed with small cell prostate carcinoma, while the majority had a primary prostate adenocarcinoma. Metastases could be classified as pure subdural space lesions, dural-based lesions, extradural/bony lesions, and pure intraparenchymal lesions. All patients with subdural metastases and 3 out of 5 patients with dural-based lesions required an emergency intervention due to rapidly deteriorating neurologic status. The mean follow-up in our series was 37 months; only subdural localizations had a remarkably unfavorable outcome. Conclusions: Supported by our experience and the review of the literature, we suggest that a low threshold for contrast-enhanced computed tomography/magnetic resonance imaging is advisable in case of suspicious subdural collection, even in an emergency setting, for patients with previous medical history of prostate cancer

Evolution of prophylaxis protocols for venous thromboembolism in neurosurgery: results from a prospective comparative study on low-molecular-weight heparin, elastic stockings, and intermittent pneumatic compression devices

Background The incidence of venous thromboembolism (VT) in neurosurgical practice is astonishingly high, representing a major cause of morbidity and mortality. Prophylaxis strategies include elastic stockings, low-molecular-weight heparin (LMWH), and intermittent pneumatic compression (IPC) devices. Objective To assess the safety and efficacy of 2 different VT prophylaxis protocols implemented in a European neurosurgical center. Methods All patients admitted for neurosurgical intervention between 2012 and 2016 were stratified as low, moderate, and high risk of VT and received a combination of elastic stockings and LMWH. The protocol was modified in 2014 with the inclusion of perioperative IPC devices for all patients and only in the high-risk group also postoperatively. Results At time of post-hoc analysis, data obtained from patients included in this study before 2014 (Protocol A, 3169 patients) were compared with those obtained after the introduction of IPC (Protocol B, 3818 patients). Among patients assigned to protocol A, 73 (2.3%) developed deep-vein thrombosis (DVT) and 28 (0.9%) developed pulmonary embolism (PE), 9 of which were fatal (0.3%). Among patients assigned to protocol B, 32 developed DVT (0.8%) and 7 (0.18%) developed PE, with 2 eventually resulting in the death of the patient. A post-hoc analysis confirmed that the use of preoperative LMWH was not associated with a statistically significant greater risk of postoperative bleeding. Conclusions This study, despite its limitations of the nonrandomized design, seems to suggest that perioperative IPC devices are a non-negligible support in the prophylaxis of clinically symptomatic DVT and PE