AXL-TBK1 driven AKT3 activation promotes metastasis.

The receptor tyrosine kinase AXL promotes tumor progression, metastasis, and therapy resistance through the induction of epithelial-mesenchymal transition (EMT). Here, we found that activation of AXL resulted in the phosphorylation of TANK-binding kinase 1 (TBK1) and the downstream activation of AKT3 and Snail, a transcription factor critical for EMT. Mechanistically, we showed that TBK1 directly bound to and phosphorylated AKT3 in a manner dependent on the multiprotein complex mTORC1.

ApoE Gene Polymorphism and Clinical, Biochemical, and Sociodemographic Characteristics of Alzheimer's Disease Patients From Northern and Southern Regions of Kazakhstan.

Background: Alzheimer's disease (AD) is the most frequent cause of dementia in seniors and is also one of the critical social issues of modern healthcare. Since AD is considered a multifactorial disease, the significance of particular risk factors in different ethnic populations is constantly reevaluated.

Method: The study group consisted of 181 patients with AD, and the control group included 244 healthy seniors comparable in sex and age to the dementia group.

Inflammatory Manifestations Associated With Gut Dysbiosis in Alzheimer's Disease.

Recent studies strongly suggest that gut microbiome can influence brain functions and contribute to the development of Alzheimer's disease (AD). However, reported changes in the gut microbiomes in AD patients from different countries are not similar, and more research is needed to reveal the relationships between human microbiomes and AD in diverse ethnic populations. There is also an assumption that microbiome-associated peripheral inflammation might drive the development of sporadic AD.

Oral Microbiome Stamp in Alzheimer's Disease.

Recent studies have suggested that periodontal disease and alterations in the oral microbiome may be associated with cognitive decline and Alzheimer's disease (AD) development. Here, we report a case-control study of oral microbiota diversity in AD patients compared to healthy seniors from Central Asia. We have characterized the bacterial taxonomic composition of the oral microbiome from AD patients (n = 64) compared to the healthy group (n = 71) using 16S ribosomal RNA sequencing.

Association of Insomnia with Anxiety and Depression in Type 2 Diabetic Patients: A Cross-Sectional Study.

Background: Type 2 diabetes mellitus (T2DM) is associated with sleep disorders, which in turn may lead to anxiety and depression. Sleep deprivation impairs glucose metabolism causing a decrease in insulin sensitivity and glucose tolerance. The present study aimed to determine the association of insomnia with anxiety and depression in patients with T2DM.

Circulating adiponectin levels, expression of adiponectin receptors, and methylation of adiponectin gene promoter in relation to Alzheimer's disease.

Background: The role of adiponectin (ADIPOQ) in Alzheimer's disease (AD) has been documented, however, demonstrating controversial results. In this study, we investigated blood serum ADIPOQ levels, methylation of the adiponectin gene promoter, and adiponectin receptors (AdipoR1 and AdipoR2) expression in blood samples isolated from AD patients and healthy controls.

Methods: We performed a case-control study including 248 subjects (98 AD patients and 150 healthy controls); ADIPOQ serum levels, AdipoR1, and AdipoR2 levels in PBMC were measured by ELISA Kits, and ADIPOQ gene methylation was analyzed using methyl-specific PCR.

Study of gut microbiota alterations in Alzheimer's dementia patients from Kazakhstan.

We have investigated the diversity and composition of gut microbiotas isolated from AD (Alzheimer's disease) patients (n = 41) and healthy seniors (n = 43) from Nur-Sultan city (Kazakhstan). The composition of the gut microbiota was characterized by 16S ribosomal RNA sequencing. Our results demonstrated significant differences in bacterial abundance at phylum, class, order, and genus levels in AD patients compared to healthy aged individuals.

The ORF45 Protein of Kaposi Sarcoma-Associated Herpesvirus Is an Inhibitor of p53 Signaling during Viral Reactivation.

Kaposi sarcoma-associated herpesvirus (KSHV) is a carcinogenic double-stranded DNA virus and the etiological agent of Kaposi sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD). To prevent premature apoptosis and support its replication cycle, KSHV expresses a series of open reading frames (ORFs) that regulate signaling by the p53 tumor suppressor protein. Here, we describe a novel viral inhibitor of p53 encoded by KSHV ORF45 and identify its mechanism of action.

Novel modulators of p53-signaling encoded by unknown genes of emerging viruses.

The p53 transcription factor plays a key role both in cancer and in the cell-intrinsic response to infections. The ORFEOME project hypothesized that novel p53-virus interactions reside in hitherto uncharacterized, unknown, or hypothetical open reading frames (orfs) of human viruses. Hence, 172 orfs of unknown function from the emerging viruses SARS-Coronavirus, MERS-Coronavirus, influenza, Ebola, Zika (ZIKV), Chikungunya and Kaposi Sarcoma-associated herpesvirus (KSHV) were de novo synthesized, validated and tested in a functional screen of p53 signaling.

T cell inactivation by poxviral B22 family proteins increases viral virulence.

Infections with monkeypox, cowpox and weaponized variola virus remain a threat to the increasingly unvaccinated human population, but little is known about their mechanisms of virulence and immune evasion. We now demonstrate that B22 proteins, encoded by the largest genes of these viruses, render human T cells unresponsive to stimulation of the T cell receptor by MHC-dependent antigen presentation or by MHC-independent stimulation. In contrast, stimuli that bypass TCR-signaling are not inhibited.

Modulation of the host immune response by cowpox virus.

Cowpox virus, a zoonotic poxvirus endemic to Eurasia, infects a large number of host species which makes its eradication impossible. The elimination of world-wide smallpox vaccination programs renders the human population increasingly susceptible to infection by orthopoxviruses resulting in a growing number of zoonotic infections including CPXV transmitted from domestic animals to humans. The ability of CPXV to infect a wide range of mammalian host is likely due to the fact that, among the orthopoxviruses, CPXV encodes the most complete set of open reading frames expected to encode immunomodulatory proteins.

Cowpox virus inhibits the transporter associated with antigen processing to evade T cell recognition.

Cowpox virus encodes an extensive array of putative immunomodulatory proteins, likely contributing to its wide host range, which includes zoonotic infections in humans. Unlike Vaccinia virus, cowpox virus prevents stimulation of CD8(+) T cells, a block that correlated with retention of MHC class I in the endoplasmic reticulum by the cowpox virus protein CPXV203. However, deletion of CPXV203 did not restore MHC class I transport or T cell stimulation.

A host cell membrane protein, golgin-97, is essential for poxvirus morphogenesis.

Acquisition of the membrane and genome encapsidation is an important step in the replication of enveloped viruses. The biogenesis of the poxviral primary membrane and the core as well as the mechanisms of their maturation are poorly understood. Using RNA interference approach, we demonstrate that a cellular trans-Golgi network membrane protein, golgin-97, is essential for virus replication.

Virion tails of Beet yellows virus: Coordinated assembly by three structural proteins.

Filamentous virions of Beet yellows virus contain a long body formed by a major capsid protein and a short tail that is assembled by a minor capsid protein (CPm), an Hsp70-homolog (Hsp70h), a 64-kDa protein (p64), and a 20-kDa protein (p20). Using mutation analysis and newly developed in planta assays, here we investigate the genetic requirements for the tail assembly. We show that the inactivation of CPm dramatically reduces incorporation of both Hsp70h and p64.

A trans-Golgi network resident protein, golgin-97, accumulates in viral factories and incorporates into virions during poxvirus infection.

Poxviruses are the only DNA viruses known to replicate and assemble in the cytoplasm of infected cells. Poxvirus morphogenesis is a complicated process in which four distinct infectious forms of the virus are produced: intracellular mature virus, intracellular enveloped virus, cell-associated enveloped virus, and extracellular enveloped virus. The source of primary membrane wrapping the intracellular mature virus, the first infectious form, is still unknown.

The 64-kilodalton capsid protein homolog of Beet yellows virus is required for assembly of virion tails.

The filamentous virion of the closterovirus Beet yellows virus (BYV) consists of a long body formed by the major capsid protein (CP) and a short tail composed of the minor capsid protein (CPm) and the virus-encoded Hsp70 homolog. By using nano-liquid chromatography-tandem mass spectrometry and biochemical analyses, we show here that the BYV 64-kDa protein (p64) is the fourth integral component of BYV virions. The N-terminal domain of p64 is exposed at the virion surface and is accessible to antibodies and mild trypsin digestion.

Cell-to-cell movement and assembly of a plant closterovirus: roles for the capsid proteins and Hsp70 homolog.

Diverse animal and plant viruses are able to translocate their virions between neighboring cells via intercellular connections. In this work, we analyze the virion assembly and cell-to-cell movement of a plant closterovirus and reveal a strong correlation between these two processes. The filamentous virions of a closterovirus possess a long body formed by the major capsid protein (CP) and a short tail formed by the minor capsid protein (CPm).

Site-specific nickase from bacillus species strain d6.

Three site-specific endonucleases were found in thermophilic strain Bacillus species D6. One of them, BspD6II, is an isoschizomer of Eco57I. The second, BspD6III, is present in the strain in very small amount; therefore, it has not been characterized.

Genetic analysis of the cell-to-cell movement of beet yellows closterovirus.

A beet yellows closterovirus (BYV) variant expressing green fluorescent protein and leaves of BYV local lesion host Claytonia perfoliata were used to reveal genetic requirements for BYV cell-to-cell movement in leaf epidermis and mesophyll. A series of mutations targeting genes that are not involved in amplification of the viral positive-strand RNA was analyzed. The products of genes coding for a 6-kDa hydrophobic protein (p6) and a 64-kDa protein (p64), as well as for minor and major capsid proteins, were found to be essential for intercellular translocation of BYV.

Thermophilic strain Bacillus species AA contains several site-specific endonucleases.

Thermophilic strain Bacillus species AA contains several site-specific endonucleases and three of them have been identified. BspAAI recognizes the sequence 5'-C downward arrow TCGAG-3' and cleaves it after the first "C" forming 4-nucleotide 5'-ends and is an isoschizomer of XhoI. BspAAII recognizes the sequence 5'-T downward arrow CTAGA-3' and cleaves it after the first "T" forming 4-nucleotide 5'-ends and is an isoschizomer of XbaI.

Isolation and characterization of site-specific endonuclease Bsp123 I from thermophilic strain Bacillus species 123.

The preparation of site-specific endonuclease Bsp123 I was isolated and purified from the thermophilic strain Bacillus species 123. Endonuclease Bsp123 I recognizes the sequence CGCG and cleaves it in the middle between nucleotides G and C, producing blunt ends. Thus, Bsp123 I is an isoschizomer of FnuDII.