Zinc concentration in erythrocyte membranes in normal volunteers and in patients with taste and smell dysfunction

Erythrocyte membrane zinc concentration was measured in 14 normal volunteers and in 36 patients with taste and smell dysfunction, and compared with zinc concentration in erythrocyte cytosol and blood plasma in the normal volunteers and with zinc concentration in erythrocyte cytosol, blood serum, urine, and parotid saliva in the patients. A A significant negative correlation was found between age and membrane zinc concentration in the normals. A significant positive correlation was found between parotid saliva zinc and erythrocyte membrane zinc concentrations in the patients. Concentration of zinc in the erythrocyte membrane is 50% greater than its concentration in cytosol, and three times greater than the zinc concentration in plasma or serum; membrane zinc concentration in humans is approximately one-half that reported in the dog or in the mouse.     

Organ and isotype distribution of plasma cells producing specific antibody after oral immunization: evidence for a generalized secretory immune system.

Mice were induced to produce IgA antibodies against ferritin after oral immunization. Such antibodies were detected by immunofluorescence in plasma cells in the intestinal mucosa as well as in secretory sites located elsewhere, such as the lactating mammary gland, salivary gland, and respiratory tract. The observation suggested that cells immunized locally via the gut could home to distant secretory sites. To confirm this hypothesis, lymphocyte transfer studies were done with mesenteric node (MN) versus peripheral node (PN) cells from orally immunized donors into nonimmunized recipients. IgA anti-ferritin cells from MN homed to exocrine targets, whereas IgM and IgG anti-ferritin cells homed to PN. The findings overall support the concept of a generalized and interrelated secretory immune system.     

Life in lights: Tracking mitochondrial delivery to lysosomes in vivo

The past decade has seen an intensive and concerted research effort into the molecular regulation of mitophagy, the selective autophagy of mitochondria. Cell-based studies have implicated mitophagy in the pathology of diverse conditions ranging from cancer to neurodegeneration. However, a definitive link between mitophagy and the etiology of human disease remains to be demonstrated. Moreover, we do not know how pervasive mammalian mitophagy is in vivo and fundamental questions remain unanswered. For example, is mitophagy common to all tissues under basal conditions or does it only occur in highly oxidative tissues under stress? This paucity of knowledge is largely due to a lack of experimentally tractable tools that can measure and monitor mitophagy in tissues. Our recent work describes the development of mito-QC, a mouse model to study mitophagy at single cell resolution in vivo.     

Reversible blunting of arousal from sleep in response to intermittent hypoxia in the developing rat

Arousal is an important survival mechanism when infants are confronted with hypoxia during sleep. Many sudden infant death syndrome (SIDS) infants are exposed to repeated episodes of hypoxia before death and have impaired arousal mechanisms. We hypothesized that repeated exposures to hypoxia would cause a progressive blunting of arousal, and that a reversal of this process would occur if the hypoxia was terminated at the time of arousal. P5 (postnatal age of 5 days), P15, and P25 rat pups were exposed to either eight trials of hypoxia (3 min 5% O(2) alternating with room air) (group A), or three hypoxia trials as in group A, followed by five trials in which hypoxia was terminated at arousal (group B). In both groups A and B, latency increased over the first four trials of hypoxia, but reversed in group B animals during trials 5-8. Progressive arousal blunting was more pronounced in the older pups. The effects of intermittent hypoxia on heart rate also depended on age. In the older pups, heart rate increased with each hypoxia exposure. In the P5 pups, however, heart rate decreased during hypoxia and did not return to baseline between exposures, resulting in a progressive fall of baseline values over successive hypoxia exposures. In the group B animals, heart rate changes during trials 1-4 also reversed during trials 5-8. We conclude that exposure to repeated episodes of hypoxia can cause progressive blunting of arousal, which is reversible by altering the exposure times to hypoxia and the period of recovery between hypoxia exposures.     

A modified tyrosinase-related protein 2 epitope generates high-affinity tumor-specific T cells but does not mediate therapeutic efficacy in an intradermal tumor model

The generation of tumor-specific T cells is hampered by the presentation of poorly immunogenic tumor-specific epitopes by the tumor. Here, we demonstrate that, although CD8+ T cells specific for the self/tumor Ag tyrosinase-related protein 2 (TRP2) are readily detected in tumor-bearing hosts, vaccination of either tumor-bearing or naive mice with an epitope derived from TRP2 fails to generate significant numbers of tetramer-staining TRP2-specific T cells or antitumor immunity. We identified an altered peptide epitope, called deltaV, which elicits T cell responses that are cross-reactive to the wild-type TRP2 epitope. Immunization with deltaV generates T cells with increased affinity for TRP2 compared with immunization with the wild-type TRP2 epitope, although TRP2 immunization often generates a greater number of TRP2-specific T cells based on intracellular IFN-gamma analysis. Despite generating higher affinity responses, deltaV immunization alone fails to provide any greater therapeutic efficacy against tumor growth than TRP2 immunization. This lack of tumor protection is most likely a result of both the deletion of high affinity and functional tolerance induction of lower affinity TRP2-specific T cells. Our data contribute to a growing literature demonstrating the ability of variant peptide epitopes to generate higher affinity T cell responses against tumor-specific Ags. However, consistent with most clinical data, simple generation of higher affinity T cells is insufficient to mediate tumor immunity.     

A Crucial Role for Kupffer Cell-Derived Galectin-9 in Regulation of T Cell Immunity in Hepatitis C Infection

Approximately 200 million people throughout the world are infected with hepatitis C virus (HCV). One of the most striking features of HCV infection is its high propensity to establish persistence (∼70–80%) and progressive liver injury. Galectins are evolutionarily conserved glycan-binding proteins with diverse roles in innate and adaptive immune responses. Here, we demonstrate that galectin-9, the natural ligand for the T cell immunoglobulin domain and mucin domain protein 3 (Tim-3), circulates at very high levels in the serum and its hepatic expression (particularly on Kupffer cells) is significantly increased in patients with chronic HCV as compared to normal controls. Galectin-9 production from monocytes and macrophages is induced by IFN-γ, which has been shown to be elevated in chronic HCV infection. In turn, galectin-9 induces pro-inflammatory cytokines in liver-derived and peripheral mononuclear cells; galectin-9 also induces anti-inflammatory cytokines from peripheral but not hepatic mononuclear cells. Galectin-9 results in expansion of CD4⁺CD25⁺FoxP3⁺CD127^low regulatory T cells, contraction of CD4⁺ effector T cells, and apoptosis of HCV-specific CTLs. In conclusion, galectin-9 production by Kupffer cells links the innate and adaptive immune response, providing a potential novel immunotherapeutic target in this common viral infection.     

The effects of dietary linoleic acid and hydrophilic antioxidants on basal,peak, and sustained metabolism in flight‐trained European starlings

Dietary micronutrients have the ability to strongly influence animal physiology and ecology. For songbirds, dietary polyunsaturated fatty acids (PUFAs) and antioxidants are hypothesized to be particularly important micronutrients because of their influence on an individual's capacity for aerobic metabolism and recovery from extended bouts of exercise. However, the influence of specific fatty acids and hydrophilic antioxidants on whole‐animal performance remains largely untested. We used diet manipulations to directly test the effects of dietary PUFA, specifically linoleic acid (18:2n6), and anthocyanins, a hydrophilic antioxidant, on basal metabolic rate (BMR), peak metabolic rate (PMR), and rates of fat catabolism, lean catabolism, and energy expenditure during sustained flight in a wind tunnel in European starlings (Sturnus vulgaris). BMR, PMR, energy expenditure, and fat metabolism decreased and lean catabolism increased over the course of the experiment in birds fed a high (32%) 18:2n6 diet, while birds fed a low (13%) 18:2n6 diet exhibited the reverse pattern. Additionally, energy expenditure, fat catabolism, and flight duration were all subject to diet‐specific effects of whole‐body fat content. Dietary antioxidants and diet‐related differences in tissue fatty acid composition were not directly related to any measure of whole‐animal performance. Together, these results suggest that the effect of dietary 18:2n6 on performance was most likely the result of the signaling properties of 18:2n6. This implies that dietary PUFA influence the energetic capabilities of songbirds and could strongly influence songbird ecology, given their availability in terrestrial systems.     

Annual-Cycle Movements and Phenology of Black Scoters in Eastern North America

Sea ducks exhibit complex movement patterns throughout their annual cycle; most species use distinct molting and staging sites during migration and disjunct breeding and wintering sites. Although research on black scoters (Melanitta americana) has investigated movements and habitat selection during winter, little is known about their annual-cycle movements. We used satellite telemetry to identify individual variation in migratory routes and breeding areas for black scoters wintering along the Atlantic Coast, to assess migratory connectivity among wintering, staging, breeding, and molt sites, and to examine effects of breeding site attendance on movement patterns and phenology. Black scoters occupied wintering areas from Canadian Maritime provinces to the southeastern United States. Males used an average of 2.5 distinct winter areas compared to 1.1 areas for females, and within-winter movements averaged 1,256 km/individual. Individuals used an average of 2.1 staging sites during the 45-day pre-breeding migration period, and almost all were detected in the Gulf of St. Lawrence. Males spent less time at breeding sites and departed them earlier than females. During post-breeding migration, females took approximately 25 fewer days than males to migrate from breeding sites to molt and staging sites, and then wintering areas. Most individuals used molt sites in James and Hudson bays before migrating directly to coastal wintering sites, which took approximately 11 days and covered 1,524 km. Males tended to arrive at wintering areas 10 days earlier than females. Individuals wintering near one another did not breed closer together than expected by chance, suggesting weak spatial structuring of the Atlantic population. Females exhibited greater fidelity (4.5 km) to previously used breeding sites compared to males (60 km). A substantial number of birds bred west of Hudson Bay in the Barrenlands, suggesting this area is used more widely than believed previously. Hudson and James bays provided key habitat for black scoters that winter along the Atlantic Coast, with most individuals residing for >30% of their annual cycle in these bays. Relative to other species of sea duck along the Atlantic Coast, the Atlantic population of black scoter is more dispersed and mobile during winter but is more concentrated during migration. These results could have implications for future survey efforts designed to assess population trends of black scoters. © 2021 The Wildlife Society.     

Home Range,Body Condition,and Survival of Rehabilitated Raccoons (Procyon lotor) During Their First Winter

The effects of raccoon (Procyon lotor) rehabilitation on postrelease survivorship are unknown. Raccoon rehabilitation success was measured as differences in prewinter body condition, home range size, distance to manmade structures, and during-winter survival between raccoons in the wild and those who have been rehabilitated. Prewinter body condition did not differ between wild and rehabilitated raccoons, but there was a trend for rehabilitated raccoons to have better body conditions. There was no difference between wild and rehabilitated raccoon adaptive kernel (AK) home range for 95% and 90% AK home ranges, or for core (50% AK) use areas. There was no sex difference in distance traveled from the release site within rehabilitated raccoons. However, rehabilitated raccoons were found significantly closer (49.4 ± 4.7 m) to manmade structures than wild raccoons (92.2 ± 14.4 m), and female raccoons were found significantly closer (64.8 ± 4.5 m) to manmade structures than male raccoons (72.3 ± 17.6 m). The results of this study indicate that raccoons can be successfully rehabilitated, but they may occupy habitat closer to manmade structures than wild raccoons.     

Reduced body mass gain in small passerines during migratory stopover under simulated heat wave conditions

For birds that migrate long distances, maximizing the rate of refueling at stopovers is advantageous, but ambient conditions may adversely influence this vital process. We simulated a 3-day migratory stopover for garden warblers (Sylvia borin) and compared body temperatures (T(b)) and rates of refueling under conditions of a heat wave (T(a)=40 °C by day, and 15 °C at night) with those under more moderate conditions (T(a)=27 °C by day, and 15 °C at night). We measured T(b) with implanted thermo-sensitive radio transmitters. Birds had significantly lower rates of body mass gain on the first day of stopover (repeated measures mixed model ANOVA, p=0.002) affecting body mass during the entire stopover (p=0.034) and higher maximum T(b) during the day when exposed to high T(a) than when exposed to moderate T(a) (p=0.002). In addition, the birds exposed to high T(a) by day had significantly lower minimum T(b) at night than those exposed to moderate daytime T(a) (p=0.048), even though T(a) at night was the same for both groups. We interpret this lower nighttime T(b) to be a means of saving energy to compensate for elevated daytime thermoregulatory requirements, while higher T(b) by day may reduce protein turnover. All effects on T(b) were significantly more pronounced during the first day of stopover than on days two and three, which may be linked to the rate of renewal of digestive function during stopover. Our results suggest that environmental factors, such as high T(a), constrain migratory body mass gain. Extreme high T(a) and heat waves are predicted to increase due to global climate change, and thus are likely to pose increasing constraints on regaining body mass during stopover and therefore migratory performance in migratory birds.