Infection-induced lysine lactylation enables herpesvirus immune evasion.

Aerobic glycolysis is a hallmark of many viral infections, leading to substantial accumulation of lactate. However, the regulatory roles of lactate during viral infections remain poorly understood. Here, we report that human cytomegalovirus (HCMV) infection leverages lactate to induce widespread protein lactylation and promote viral spread.

Tapioca: a platform for predicting de novo protein-protein interactions in dynamic contexts.

Protein-protein interactions (PPIs) drive cellular processes and responses to environmental cues, reflecting the cellular state. Here we develop Tapioca, an ensemble machine learning framework for studying global PPIs in dynamic contexts. Tapioca predicts de novo interactions by integrating mass spectrometry interactome data from thermal/ion denaturation or cofractionation workflows with protein properties and tissue-specific functional networks.

Sirtuin 2 promotes human cytomegalovirus replication by regulating cell cycle progression.

This study expands the growing understanding that protein acetylation is a highly regulated molecular toggle of protein function in both host anti-viral defense and viral replication. We describe a pro-viral role for the human enzyme SIRT2, showing that its deacetylase activity supports HCMV replication. By integrating quantitative proteomics, flow cytometry cell cycle assays, microscopy, and functional virology assays, we investigate the temporality of SIRT2 functions and substrates.

Orchestration of Mitochondrial Function and Remodeling by Post-Translational Modifications Provide Insight into Mechanisms of Viral Infection.

The regulation of mitochondria structure and function is at the core of numerous viral infections. Acting in support of the host or of virus replication, mitochondria regulation facilitates control of energy metabolism, apoptosis, and immune signaling. Accumulating studies have pointed to post-translational modification (PTM) of mitochondrial proteins as a critical component of such regulatory mechanisms.

A TRUSTED targeted mass spectrometry assay for pan-herpesvirus protein detection.

The presence and abundance of viral proteins within host cells are part of the essential signatures of the cellular stages of viral infections. However, methods that can comprehensively detect and quantify these proteins are still limited, particularly for viruses with large protein coding capacity. Here, we design and experimentally validate a mass spectrometry-based Targeted herpesviRUS proTEin Detection (TRUSTED) assay for monitoring human viruses representing the three Herpesviridae subfamilies-herpes simplex virus type 1, human cytomegalovirus (HCMV), and Kaposi sarcoma-associated herpesvirus.

Virus-host protein interactions as footprints of human cytomegalovirus replication.

Human cytomegalovirus (HCMV) is a pervasive β-herpesvirus that causes lifelong infection. The lytic replication cycle of HCMV is characterized by global organelle remodeling and dynamic virus-host interactions, both of which are necessary for productive HCMV replication. With the advent of new technologies for investigating protein-protein and protein-nucleic acid interactions, numerous critical interfaces between HCMV and host cells have been identified.

[Lung cancer and COPD - growing clinical problem].

A spread of the addiction of tobacco smoking is valued on near 1 billion of people in the world, that involves growing number of morbidity and mortality by the reason of smoke related diseases. Lung cancer and chronic obstructive pulmonary disease (COPD) are the most serious and incurable diseases which are leading to a permanent disability as well as to premature death. There are factors that naturally increase the vulnerability of an individual on the coincidence of above disorders, such as pathophysiological conditions, systemic inflammation, bronchitis, emphysema, respiratory obstructive disease and precise genetic predispositions for COPD and lung cancer.

KDM2A integrates DNA and histone modification signals through a CXXC/PHD module and direct interaction with HP1.

Functional genomic elements are marked by characteristic DNA and histone modification signatures. How combinatorial chromatin modification states are recognized by epigenetic reader proteins and how this is linked to their biological function is largely unknown. Here we provide a detailed molecular analysis of chromatin recognition by the lysine demethylase KDM2A.

Structural plasticity of histones H3-H4 facilitates their allosteric exchange between RbAp48 and ASF1.

The mechanisms by which histones are disassembled and reassembled into nucleosomes and chromatin structure during DNA replication, repair and transcription are poorly understood. A better understanding of the processes involved is, however, crucial if we are to understand whether and how histone variants and post-translationally modified histones are inherited in an epigenetic manner. To this end we have studied the interaction of the histone H3-H4 complex with the human retinoblastoma-associated protein RbAp48 and their exchange with a second histone chaperone, anti-silencing function protein 1 (ASF1).

Distinct roles of the mTOR components Rictor and Raptor in MO7e megakaryocytic cells.

Objective: During megakaryopoiesis, hematopoietic progenitor cells in the bone marrow proliferate and ultimately differentiate in mature megakaryocytes (MK). We and others have recently described a role for the mammalian target of Rapamycin (mTOR) in proliferation and differentiation of MK cells. Two non-redundant complexes of mTOR have been described; mTORC1 containing rapamycin-associated TOR protein (Raptor) and mTORC2 containing Rapamycin-insensitive companion of mTOR (Rictor).

Downregulation of signal transducer and activator of transcription 5 (STAT5) in CD34+ cells promotes megakaryocytic development, whereas activation of STAT5 drives erythropoiesis.

Although it has been proposed that the common myeloid progenitor gives rise to granulocyte/monocyte progenitors and megakaryocyte/erythroid progenitors (MEP), little is known about molecular switches that determine whether MEPs develop into either erythrocytes or megakaryocytes. We used the thrombopoietin receptor c-Mpl, as well as the megakaryocytic marker CD41, to optimize progenitor sorting procedures to further subfractionate the MEP (CD34(+)CD110(+)CD45RA(-)) into erythroid progenitors (CD34(+)CD110(+)CD45RA(-)CD41(-)) and megakaryocytic progenitors (CD34(+)CD110(+)CD45RA(-)CD41(+)) from peripheral blood. We have identified signal transducer and activator of transcription 5 (STAT5) as a critical denominator that determined lineage commitment between erythroid and megakaryocytic cell fates.

HIV-1-Associated Cognitive-Motor Disorders: A Research-Based Approach to Diagnosis and Treatment.

The diagnosis of human immunodeficiency virus type 1 (HIV-1)-associated cognitive-motor disorder--either minor cognitive-motor disorder (MCMD) or HIV-1-associated dementia (HAD)--is fraught with potential pitfalls for the clinician. Before making such a diagnosis, clinicians should exclude other etiologies by using neuroimaging, lumbar puncture, and serum chemistries to screen for opportunistic and non-opportunistic infections of the brain and meninges. Clinicians should also consider psychoneurotoxicity (caused from the use of psychoactive substances and prescribed medications) and psychopathology, such as mood, anxiety, and other disorders.

Chemical characterisation of three haemolytic compounds from the microalgal species Fibrocapsa japonica (Raphidophyceae).

The molecular structures of the three main haemolytic compounds (Fj1, Fj2 and Fj3) isolated from the ichthyotoxic microalgal species Fibrocapsa japonica have been investigated by NMR, LC-ESI-MS, ESI-MS-MS, IR, GC-MS and GC-HRMS methods. They are polyunsaturated fatty acids which we identified as: 6,9,12,15-octadecatetraenoic acid (OTA, C18:4omega3), 5,8,11,14,17-eicosapentaenoic acid (EPA, C20:5omega3) and 5,8,11,14-eicosatetraenoic acid (arachidonic acid AA, C20:4omega6). The identity of the latter two was confirmed on the basis of commercial standards (C20:5omega3 and C20:4omega6).