B-cell Interleukin 1 Receptor 1 (IL1R1) modulates the female adipose tissue immune microenvironment during aging.

Myeloid cell production of interleukin-1β (IL-1β) drives inflammaging in visceral adipose tissue (vWAT) and contributes to the expansion of interleukin-1 receptor 1 (Il1r1) positive aged adipose B-cells (AABs). AABs promote metabolic dysfunction and inflammation under inflammatory challenges. However, it is unclear whether IL-1β contributes to AAB-associated inflammation during aging.

Developing transcriptomic signatures as a biomarker of cellular senescence.

Cellular senescence is a cell fate driven by different types of stress, where damaged cells exit from the cell cycle and, in many cases, develop an inflammatory senescence-associated secretory phenotype (SASP). Senescence has often been linked to driving aging and the onset of multiple diseases conferred by the harmful SASP, which disrupts tissue homeostasis and impairs the regular function of many tissues. This phenomenon was first observed in vitro when fibroblasts halted replication after approximately 50 population doublings.

Challenges and considerations for treating PTSD with medicinal cannabis: the Australian clinician's perspective.

Introduction: Preclinical and experimental research have provided promising evidence that medicinal cannabis may be efficacious in the treatment of posttraumatic stress disorder (PTSD). However, implementation of medicinal cannabis into routine clinical therapies may not be straightforward.

Areas Covered: In this review, we describe some of the clinical, practical, and safety challenges that must be addressed for cannabis-based treatment of PTSD to be feasible in a real-world setting.

Targeting Cellular Senescence with Senotherapeutics: Development of New Approaches for Skin Care.

Aging of the skin is evidenced by increased wrinkles, age spots, dryness, and thinning with decreased elasticity. Extrinsic and intrinsic factors including UV, pollution, and inflammation lead to an increase in senescent cells (SnCs) in skin with age that contribute to these observed pathological changes. Cellular senescence is induced by multiple types of damage and stress and is characterized by the irreversible exit from the cell cycle with upregulation of cell cycle-dependent kinase inhibitors p16INK4a and p21CIP1.

Cellular senescence: a key therapeutic target in aging and diseases.

Cellular senescence is a hallmark of aging defined by stable exit from the cell cycle in response to cellular damage and stress. Senescent cells (SnCs) can develop a characteristic pathogenic senescence-associated secretory phenotype (SASP) that drives secondary senescence and disrupts tissue homeostasis, resulting in loss of tissue repair and regeneration. The use of transgenic mouse models in which SnCs can be genetically ablated has established a key role for SnCs in driving aging and age-related disease.

Beef Steer Performance on Irrigated Monoculture Legume Pastures Compared with Grass- and Concentrate-Fed Steers.

Fall- or spring-born steers grazed monoculture irrigated birdsfoot trefoil (BFT; Lotus corniculatus L.) or cicer milkvetch (CMV; Astragalus cicer L.) pastures for approximately 12 weeks for 3 years and were compared with steers on concentrate diets.

Targeting cellular senescence with senotherapeutics: senolytics and senomorphics.

The concept of geroscience is that since ageing is the greatest risk factor for many diseases and conditions, targeting the ageing process itself will have the greatest impact on human health. Of the hallmarks of ageing, cellular senescence has emerged as a druggable therapeutic target for extending healthspan in model organisms. Cellular senescence is a cell state of irreversible proliferative arrest driven by different types of stress, including oncogene-induced stress.

Development of Ice-Shelf Estuaries Promotes Fractures and Calving.

As the global climate warms, increased surface meltwater production on ice shelves may trigger ice-shelf collapse and enhance global sea-level rise. The formation of surface rivers could help prevent ice-shelf collapse if they can efficiently evacuate meltwater. Here, we present observations of the evolution of a surface river into an ice-shelf estuary atop the Petermann Ice Shelf in northwest Greenland, and identify a second estuary at the nearby Ryder Ice Shelf.

Recent advances in the discovery of senolytics.

The demonstration in model organisms that cellular senescence drives aging and age-related diseases has led to widespread efforts to identify compounds able to selectively kill senescent cells, termed senolytics. Approaches used to identify senolytics include bioinformatic analysis of senescent cell anti-apoptotic pathways (SCAPs) for drug development and screening of drugs libraries on different senescent cell types in culture. Alternatively, cytotoxic compounds can be made specific to senescent cells through a prodrug strategy such as linking the compound to a galactose moiety where toxicity is activated by lysosomal β-galactosidase.

Greenland Ice Sheet surface melt amplified by snowline migration and bare ice exposure.

Greenland Ice Sheet mass loss has recently increased because of enhanced surface melt and runoff. Since melt is critically modulated by surface albedo, understanding the processes and feedbacks that alter albedo is a prerequisite for accurately forecasting mass loss. Using satellite imagery, we demonstrate the importance of Greenland's seasonally fluctuating snowline, which reduces ice sheet albedo and enhances melt by exposing dark bare ice.

Retail stability of three beef muscles from grass-, legume-, and feedlot-finished cattle.

This study aimed to determine the influence of finishing diet on beef appearance and lipid oxidation of three beef muscles. A total of 18 Angus steers were selected from three diet treatments: grass-finished (USUGrass), legume-finished (USUBFT), and grain-finished (USUGrain). After processing, longissimus thoracis (LT), triceps brachii (TB), and gluteus medius (GM) steaks were evaluated over a 7-d display period.

Direct measurements of meltwater runoff on the Greenland ice sheet surface.

Meltwater runoff from the Greenland ice sheet surface influences surface mass balance (SMB), ice dynamics, and global sea level rise, but is estimated with climate models and thus difficult to validate. We present a way to measure ice surface runoff directly, from hourly in situ supraglacial river discharge measurements and simultaneous high-resolution satellite/drone remote sensing of upstream fluvial catchment area. A first 72-h trial for a 63.

Consumer sensory evaluation and chemical composition of beef gluteus medius and triceps brachii steaks from cattle finished on forage or concentrate diets.

The objective of this study was to assess the impact of cattle finishing diet and muscle type on meat quality. Consumer sensory response, proximate composition, Warner-Bratzler shear force (WBSF), fatty acid composition, and volatile compounds were assessed from the gluteus medius (GM) and triceps brachii (TB) muscles of cattle ( = 6 per diet) which were grain-finished (USUGrain) on conventional feedlot or 2 forage diets, a perennial legume, birdsfoot trefoil-finished (USUBFT; ), and grass-finished (USUGrass; ). Diet had an interacting effect with muscle for all sensory attributes ( ≤ 0.

Legume finishing provides beef with positive human dietary fatty acid ratios and consumer preference comparable with grain-finished beef.

Consumer liking, proximate composition, pH, Warner-Bratzler shear force, fatty acid composition, and volatile compounds were determined from the LM (longissimus thoracis) of cattle ( = 6 per diet) finished on conventional feedlot (USUGrain), legume, and grass forage diets. Forage diets included a condensed tannin-containing perennial legume, birdsfoot trefoil (; USUBFT), and a grass, meadow brome ( Rehmann; USUGrass). Moreover, representative retail forage (USDA Certified Organic Grass-fed [OrgGrass]) and conventional beef (USDA Choice, Grain-fed; ChGrain) were investigated ( = 6 per retail type).

Efficient meltwater drainage through supraglacial streams and rivers on the southwest Greenland ice sheet.

Thermally incised meltwater channels that flow each summer across melt-prone surfaces of the Greenland ice sheet have received little direct study. We use high-resolution WorldView-1/2 satellite mapping and in situ measurements to characterize supraglacial water storage, drainage pattern, and discharge across 6,812 km(2) of southwest Greenland in July 2012, after a record melt event. Efficient surface drainage was routed through 523 high-order stream/river channel networks, all of which terminated in moulins before reaching the ice edge.

Comparison of two blanket surveys of arsenic in tubewells conducted 12 years apart in a 25 km(2) area of Bangladesh.

The arsenic (As) content of groundwater pumped from all tubewells within 61 contiguous villages of Araihazar, Bangladesh, was determined a first time in 2000-01 with laboratory measurements and a second time in 2012-13 using the ITS Arsenic Econo-Quick kit. The two surveys indicate that the total number of tubewells within the area almost doubled from 5560 to 10,879 over 12 years. The evolution of the distribution of well ages between the two surveys is consistent with a simple model that combines an annual increase of 42 wells/year in the rate of installations within the 61 villages starting in 1980 and a 7%/year rate of abandonment of wells as a function of well age.

Th17 cells induce ectopic lymphoid follicles in central nervous system tissue inflammation.

Ectopic lymphoid follicles are hallmarks of chronic autoimmune inflammatory diseases such as multiple sclerosis (MS), rheumatoid arthritis, Sjögren's syndrome, and myasthenia gravis. However, the effector cells and mechanisms that induce their development are unknown. Here we showed that in experimental autoimmune encephalomyelitis (EAE), the animal model of MS, Th17 cells specifically induced ectopic lymphoid follicles in the central nervous system (CNS).

Herpes simplex virus 1 ICP0 phosphorylation site mutants are attenuated for viral replication and impaired for explant-induced reactivation.

In cell culture experiments, phosphorylation appears to be a critical regulator of the herpes simplex virus 1 (HSV-1) immediate-early (IE) protein, ICP0, which is an E3 ubiquitin ligase that transactivates viral gene expression. Three major regions of phosphorylation in ICP0 (amino acids 224 to 232, 365 to 371, and 508 to 518) have been identified, and mutant viruses that block phosphorylation sites within each region (termed Phos 1, 2, and 3, respectively) have been constructed. Previous studies indicated that replication of Phos 1 is significantly reduced compared to that of wild-type virus in cell culture (C.

Trafficking of B cell antigen in lymph nodes.

The clonal selection theory first proposed by Macfarlane Burnet is a cornerstone of immunology (1). At the time, it revolutionized the thinking of immunologists because it provided a simple explanation for lymphocyte specificity, immunological memory, and elimination of self-reactive clones (2). The experimental demonstration by Nossal & Lederberg (3) that B lymphocytes bear receptors for a single antigen raised the central question of where B lymphocytes encounter antigen.

The role of innate immunity in B cell acquisition of antigen within LNs.

Over the past decade, it has become apparent that B cells acquire antigens primarily from membrane surfaces and that uptake is an active process involving a synapse between the B cell receptor, coreceptor, and the antigen surface. However, understanding how antigens are delivered to follicular dendritic cells (FDC), which are the primary depot for B cell antigen within the lymph node follicles, is only recently beginning to be dissected. The application of fluorescent-based imaging techniques such as multiphoton intravital microscopy to visualize trafficking of B cells and antigens into draining lymph nodes has provide insights that would not otherwise be made.

Complement-dependent transport of antigen into B cell follicles.

Since the original proposal by Fearon and Locksley (Fearon and Locksley. 1996. Science 272: 50-53) that the complement system linked innate and adaptive immunity, there has been a rapid expansion of studies on this topic.

Capture of influenza by medullary dendritic cells via SIGN-R1 is essential for humoral immunity in draining lymph nodes.

A major pathway for B cell acquisition of lymph-borne particulate antigens relies on antigen capture by subcapsular sinus macrophages of the lymph node. Here we tested whether this mechanism is also important for humoral immunity to inactivated influenza virus. By multiple approaches, including multiphoton intravital imaging, we found that antigen capture by sinus-lining macrophages was important for limiting the systemic spread of virus but not for the generation of influenza-specific humoral immunity.

Uncoupling CD21 and CD19 of the B-cell coreceptor.

Complement receptors (CRs) CD21 and CD35 form a coreceptor with CD19 and CD81 on murine B cells that when coligated with the B-cell receptor lowers the threshold of activation by several orders of magnitude. This intrinsic signaling role is thought to explain the impaired humoral immunity of mice bearing deficiency in CRs. However, CRs have additional roles on B cells independent of CD19, such as transport of C3-coated immune complexes and regulation of C4 and C3 convertase.