The current model of murine innate lymphoid cell (ILC) development holds that mouse ILCs are derived downstream of the common lymphoid progenitor through lineage-restricted progenitors. However, ...corresponding lineage-restricted progenitors in humans have yet to be discovered. Here we identified a progenitor population in human secondary lymphoid tissues (SLTs) that expressed the transcription factor RORγt and was unique in its ability to generate all known ILC subsets, including natural killer (NK) cells, but not other leukocyte populations. In contrast to murine fate-mapping data, which indicate that only ILC3s express Rorγt, these human progenitor cells as well as human peripheral blood NK cells and all mature ILC populations expressed RORγt. Thus, all human ILCs can be generated through an RORγt+ developmental pathway from a common progenitor in SLTs. These findings help establish the developmental signals and pathways involved in human ILC development.
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•All human innate lymphoid cell subsets express RORγt•RORγt is expressed in a subset of CD34+CD45RA+ progenitors found in human SLT•The human RORγt+CD34+CD45RA+ progenitor is restricted to ILC development
Human innate lymphoid cells (ILCs) mediate responses against pathogens and cancer; how they develop is unclear. Freud and colleagues identify a human RORγt+ progenitor that selectively resides in secondary lymphoid tissues and exclusively generates all ILCs, including NK cells. These findings help define the pathways involved in human ILC development.
Human natural killer (NK) cells develop in secondary lymphoid tissues (SLTs) through distinct stages. We identified two SLT lineage (Lin)−CD34−CD117+/−CD94+CD16− “stage 4” subsets according to ...expression of the C-type lectin-like surface-activating receptor, NKp80: NKp80− (stage “4a”) and NKp80+ (stage “4b”). Whereas stage 4b cells expressed more of the transcription factors T-BET and EOMES, produced interferon-gamma, and were cytotoxic, stage 4a cells expressed more of the transcription factors RORγt and AHR and produced interleukin-22, similar to SLT Lin−CD34−CD117+CD94−CD16− “stage 3” cells, whose phenotype overlaps with that of group 3 innate lymphoid cells (ILC3s). Co-culture with dendritic cells or transplantation into immunodeficient mice produced mature NK cells from stage 3 and stage 4a populations. These data identify NKp80 as a marker of NK cell maturity in SLTs and support a model of human NK cell development through a stage 4a intermediate with ILC3-associated features.
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•NKp80 is expressed on a subset of CD94+ NK cells in secondary lymphoid tissues•CD94+NKp80− NK cells have ILC3-associated features•CD94+NKp80+ NK cells produce IFN-γ and kill MHC class I− target cells•CD94+NKp80− NK cells are precursors to CD94+NKp80+ NK cells
Human natural killer (NK) cells have potent effector functions against cancer; how NK cells develop in humans is unclear. Freud et al. demonstrate that NKp80 expression marks functionally mature NK cells as they develop in secondary lymphoid tissues. These findings help define the pathway of human NK cell development.
We have developed a rapid negative selection method to enrich rare mononuclear cells from human tissues. Unwanted and antibody-tethered cells are selectively depleted during a Ficoll separation step, ...and there is no need for magnetic-based reagents and equipment. The new method is fast, customizable, inexpensive, remarkably efficient, and easy to perform, and per sample the overall cost is less than one-tenth the cost associated with a magnetic column-based method.
Zinc is an essential micro-nutrient involved in numerous physiological functions. The high content of zinc in the hippocampus, coupled with the integral involvement of the hippocampus in memory, ...strongly implicates zinc in memory processing. The hypothesis of the current study was that dietary zinc restriction influenced short-term memory in postweaned rats, and this influence was age-dependent. Male rats (43 days to 18 months old) were divided into five experimental groups based on age, and fed zinc-adequate (zinc at 20 mg/kg as zinc chloride) or zinc-deficient (zinc less than 1–2 mg/kg) diets for a minimum of 3 weeks. Short-term memory was assessed using the distal-cue version of the Morris water maze (MWM). All rats fed the zinc-restricted diet exhibited cyclic anorexia, decreased weight gain, and significantly lower liver and femur zinc concentrations compared to age-matched controls. Further, whole brain, hippocampal, and cerebral wet weights were significantly reduced in the zinc-restricted treatment groups of all the age groups. Only zinc-restricted rats that were less than 62 days of age at the start of zinc restriction demonstrated significantly prolonged escape latencies in the water maze, indicating deficits in short-term memory. Regression analyses confirmed that the short-term memory deficits were correlated with significantly lower hippocampal and cerebral zinc concentrations compared to age-matched control and pair-fed rats. These results emphasize the significance of a critical age of influence for dietary zinc in memory processing, and the importance of considering age when studying zinc nutriture and CNS function.
Zinc, an essential dietary element, modulates neurotransmission in brain regions associated with cognition. Cognitive dysfunction has been reported in offspring of female rats fed zinc-restricted ...diets during gestation and/or lactation. Studies on the cognitive effects of zinc restriction during young adulthood are limited. After a 3-wk period of dietary zinc restriction, male rats (71–75 d old) were repleted with zinc chloride alone, or zinc chloride supplemented with L-histidine, and short-term memory was measured using the Morris water maze. During restriction, zinc-restricted rats demonstrated significantly longer (86.0%) retrieval latencies than nonrestricted controls, and significantly lower liver (25.5%), bone (32.5%) and hippocampal (3.2%) zinc concentrations. During subsequent repletion, rats repleted with zinc chloride supplemented with L-histidine improved their retrieval latencies to the extent that they were no longer significantly different from controls by repletion d 3. This was associated with a return of hippocampal zinc concentrations to control values by repletion d 3. The mean retrieval escape latencies of the zinc chloride–repleted rats remained significantly prolonged (75.0%). Collectively, these data indicate the following: 1) feeding a zinc-restricted diet for 3 wk impairs short-term memory in young adult male rats, and 2) repletion with dietary zinc supplemented with L-histidine improves short-term memory function more efficiently than dietary zinc chloride alone. The latter point suggests that dietary zinc supplemented with L-histidine is more bioavailable to the brain than zinc provided as zinc chloride alone. These findings are important in that they highlight the importance of both dietary zinc formulation and the use of functional assessments in determining zinc nutriture.
The current model of murine innate lymphoid cell (ILC) development holds that mouse ILCs are derived downstream of the common lymphoid progenitor through lineage-restricted progenitors. However, ...corresponding lineage-restricted progenitors in humans have yet to be discovered. Here we identified a progenitor population in human secondary lymphoid tissues (SLTs) that expressed the transcription factor RORγt and was unique in its ability to generate all known ILC subsets, including natural killer (NK) cells, but not other leukocyte populations. In contrast to murine fate-mapping data, which indicate that only ILC3s express Rorγt, these human progenitor cells as well as human peripheral blood NK cells and all mature ILC populations expressed RORγt. Thus, all human ILCs can be generated through an RORγt+developmental pathway from a common progenitor in SLTs. These findings help establish the developmental signals and pathways involved in human ILC development.
My students always enjoyed working in groups. They begged to be with their friends whenever I assigned a group project. In general, I dreaded allowing students to work in groups. I feared the ...classroom disruption from students who could not stay on task. And I wondered if students would do their best work in a group. Yet, I had to admit that as a graduate student, I found that some of my best work resulted from work in a group setting.
Although the rate of alcohol use among adolescents has declined, it remains their drug of choice. Parent and peer alcohol use are powerful risk factors for youth alcohol use. However, questions ...remain about how these factors influence underage drinking. The present study investigates the relationship between exposure to parent or peer alcohol use and two stages of adolescent drinking—onset and escalation—overall and at five age points during adolescence. Participants were 9348 adolescents in Waves I (WI) and II (WII) of the National Longitudinal Study of Adolescent Health, whose parents completed interviews at WI, and who identified themselves as either non-drinkers or experimental drinkers at WI. Reports of WII alcohol use were used to measure onset among WI non-drinkers and escalation among WI experimenters. Risk ratios were calculated to assess the overall impact of exposure to parent or peer alcohol use on onset and escalation, and at five age points (i.e., ≤ 13, 14, 15, 16, and ≥ 17). Findings show that exposure to either parent or friend alcohol use increased the risk of onset and escalation. Age-based analyses reveal a more nuanced relationship, showing variability in the nature and strength of influence by stage of drinking and by age. This study highlights the relevance of both parent and peer modeling on youth drinking throughout adolescence. Implications in advancing prevention and treatment include parental education about the impact of their own behaviors and the importance of monitoring teens’ friendships.
Four fishers (Martes pennanti) from an insular population in the southern Sierra Nevada Mountains, California, USA died as a consequence of an infection with canine distemper virus (CDV) in 2009. ...Three fishers were found in close temporal and spatial relationship; the fourth fisher died 4 mo later at a 70 km distance from the initial group. Gross lesions were restricted to hyperkeratosis of periocular skin and ulcera-tion of footpads. All animals had necrotizing bronchitis and bronchiolitis with syncytia and intracytoplasmic inclusion bodies. Inclusion bodies were abundant in the epithelia of urinary bladder and epididymis but were infrequent in the renal pelvis and the female genital epithelia. No histopathologic or immu-nohistochemical evidence for virus spread to the central nervous system was found. One fisher had encephalitis caused by Sarcocystis neurona and another had severe head trauma as a consequence of predation. The H gene nucleo-tide sequence of the virus isolates from the first three fishers was identical and was 99.6% identical to the isolate from the fourth fisher. Phylogenetically, the isolates clustered with other North American isolates separate from classical European wildlife lineage strains. These data suggest that the European wildlife lineage might consist of two separate subgroups that are genetically distinct and endemic in different geographic regions. The source of infection as well as pertinent transmission routes remained unclear. This is the first report of CDV in fishers and underscores the significance of CDV as a pathogen of management concern.
The characteristics and dynamics of primary producer communities of Silver Springs was examined to compare with that observed by Odum Odum, H.T., 1957. Trophic structure and productivity of Silver ...Springs, Florida. Ecol. Monogr. 27, 55–112. as a means of evaluating the impacts of changes that have occurred over time. The Silver Springs ecosystem is considered an ecosystem at risk, where nitrate levels have more than doubled over the past 50 years. The spatial and temporal abundance and distribution of above-sediment primary producers in Silver Springs, FL, USA, was estimated on a system-wide basis using a GIS platform. The results of study suggest that while the
Sagittaria component of Silver Springs has remained relatively stable, epiphyte and benthic algal mat community biomass has expanded, particularly benthic forms, like
Lyngbya. However, we argue for caution in weighing the significance of long-term comparisons of system-wide biomass in light of considerable spatial heterogeneity in aquatic primary producer communities.
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