Characterization of a Myeloid Differentiation Factor 2-Derived Peptide that Facilitates THP-1 Macrophage-Mediated Phagocytosis of Gram-Negative Bacteria.

Myeloid differentiation factor 2 (MD2), the TLR4 coreceptor, has been shown to possess opsonic activity and has been implicated in phagocytosis and intracellular killing of Gram-negative bacteria. However, any MD2 protein segment involved in phagocytosis of Gram-negative bacteria is not yet known. A short synthetic MD2 segment, MD54 (amino acid regions 54 to 69), was shown to interact with a Gram-negative bacterial outer membrane component, LPS, earlier.

IL-17RA promotes pathologic epithelial inflammation in a mouse model of upper respiratory influenza infection.

The upper respiratory tract (nasopharynx or NP) is the first site of influenza replication, allowing the virus to disseminate to the lower respiratory tract or promoting community transmission. The host response in the NP regulates an intricate balance between viral control and tissue pathology. The hyper-inflammatory responses promote epithelial injury, allowing for increased viral dissemination and susceptibility to secondary bacterial infections.

Optimal Cut-Off Values for Body Mass Index and Fat Mass Index Based on Age in Physically Active Males Using Receiver Operating Characteristic Curve.

This study aims to redefine obesity cut-off points for body mass index (BMI) and fat mass index (FMI) according to the different age groups of physically active males. Healthy physically active volunteers (N = 1442) aged 18-57 years (y), with a mean BMI = 22.7 ± 2.

Interferon-γ promotes monocyte-mediated lung injury during influenza infection.

Influenza A virus (IAV) infection triggers an exuberant host response that promotes acute lung injury. However, the host response factors that promote the development of a pathologic inflammatory response to IAV remain incompletely understood. In this study, we identify an interferon-γ (IFN-γ)-regulated subset of monocytes, CCR2 monocytes, as a driver of lung damage during IAV infection.

A simplified and sensitive immunoprecipitation approach for the analysis of HSF1 in murine liver tissue.

Heat shock factor 1, HSF1, is one of several family members that recognize repeated nGAAn sequences associated with the heat shock element of heat shock and other genes. This transactivator is activated from a monomeric to trimeric form by oxidative, thermal and other stressors. Various studies show that HSF1 levels increase with cancer and decrease with aging and neurodegenerative disorders.

Augmentation of the heat shock axis during exceptional longevity in Ames dwarf mice.

How the heat shock axis, repair pathways, and proteostasis impact the rate of aging is not fully understood. Recent reports indicate that normal aging leads to a 50% change in several regulatory elements of the heat shock axis. Most notably is the age-dependent enhancement of inhibitory signals associated with accumulated heat shock proteins and hyper-acetylation associated with marked attenuation of heat shock factor 1 (HSF1)-DNA binding activity.

Deciphering Biochemical and Molecular Signatures Associated with Obesity in Context of Metabolic Health.

This study aims to identify the clinical and genetic markers related to the two uncommon nutritional statuses-metabolically unhealthy normal-weight (MUNW) and metabolically healthy overweight/obese (MHOW) individuals in the physically active individuals. Physically active male volunteers ( = 120) were recruited, and plasma samples were analyzed for the clinical parameters. Triglycerides, HDL-Cholesterol, LDL-cholesterol, total cholesterol, C-reactive protein, and insulin resistance were considered as markers of metabolic syndrome.

Tamoxifen restores extracellular trap formation in neutrophils from patients with chronic granulomatous disease in a reactive oxygen species-independent manner.

Tamoxifen induces autophagy-dependent NET formation in CGD patient neutrophils and improves their antimicrobial activity. Given the genetic defect in their ROS-generation machinery, this study highlights repurposing of tamoxifen to potentiate host defense in CGD patients.

Oxidant sensor cation channel TRPM2 regulates neutrophil extracellular trap formation and protects against pneumoseptic bacterial infection.

Neutrophil extracellular trap (NET) formation constitutes an important extracellular antimicrobial function of neutrophils that plays a protective role in bacterial pneumonia. Formation of reactive oxygen species (ROS) such as highly diffusible hydrogen peroxide (HO) is a hallmark of oxidative stress during inflammatory lung conditions including pneumonia. However, the impact of exogenous ROS on NET formation and the signaling pathway involved in the process is not completely understood.

NbO Nanostructure Evolution on Nb Surfaces via Low-Energy He Ion Irradiation.

We propose low-energy, broad-beam He ion irradiation as a novel processing technique for the generation of NbO surface nanostructures due to its relative simplicity and scalability in a commercial setting. Since there have been relatively few studies involving the interaction of high-fluence, low-energy He ion irradiation and Nb (or its oxidized states), this systematic study explores both effects of fluence and sample temperature during irradiation on resulting surface morphology. Detailed normal and cross-sectional scanning electron microscopy (SEM) studies reveal subsurface He bubble formation and elucidate potential driving mechanisms for nanostructure evolution.

Single Amino Acid Substitutions at Specific Positions of the Heptad Repeat Sequence of Piscidin-1 Yielded Novel Analogs That Show Low Cytotoxicity and In Vitro and In Vivo Antiendotoxin Activity.

Piscidin-1 possesses significant antimicrobial and cytotoxic activities. To recognize the primary amino acid sequence(s) in piscidin-1 that could be important for its biological activity, a long heptad repeat sequence located in the region from amino acids 2 to 19 was identified. To comprehend the possible role of this motif, six analogs of piscidin-1 were designed by selectively replacing a single isoleucine residue at a d (5th) position or at an a (9th or 16th) position with either an alanine or a valine residue.

Tetrahydrofuran amino acid-containing gramicidin S analogues with improved biological profiles.

Gramicidin S (GS) is a cyclic cationic antimicrobial peptide (CAP) with a wide spectrum of antibiotic activities whose usage has been limited to topical applications owing to its cytotoxic side effects. We have synthesized tetrahydrofuran amino acid (Taa)-containing GS analogues, and we have carried out conformational analysis and explored their structure activity relationships by evaluating their antitubercular, antibacterial and cytotoxic properties. Two of these analogues showed impressive as well as selective activity against Mycobacterium tuberculosis (MTB) without toxicity towards mammalian Vero cells or human RBCs, and are promising as potential leads.

Design and characterization of short antimicrobial peptides using leucine zipper templates with selectivity towards microorganisms.

Design of antimicrobial peptides with selective activity towards microorganisms is an important step towards the development of new antimicrobial agents. Leucine zipper sequence has been implicated in cytotoxic activity of naturally occurring antimicrobial peptides; moreover, this motif has been utilized for the design of novel antimicrobial peptides with modulated cytotoxicity. To understand further the impact of substitution of amino acids at 'a' and/or 'd' position of a leucine zipper sequence of an antimicrobial peptides on its antimicrobial and cytotoxic properties four short peptides (14-residue) were designed on the basis of a leucine zipper sequence without or with replacement of leucine residues in its 'a' and 'd' positions with D-leucine or alanine or proline residue.

Dynamics of physical interaction between HIV-1 Nef and ASK1: identifying the interacting motif(s).

FasL mediated preferential apoptosis of bystander CTLs while protection of infected CD4(+)T cells remains one of the hallmarks of immune evasion during HIV infection. The property of infected host cells to evade cell-autonomous apoptosis emanates from ability of HIV-1Nef-protein to physically interact with ASK-1 and thereby inhibit its enzymatic activity. The specific domains of HIV-1Nef through which it may interact with ASK1 and thereby impair the ASK1 activity remain unidentified so far and represent a major challenge towards developing clear understanding about the dynamics of this interaction.