Immunomodulatory roles of polysaccharide capsules in the intestine

The interplay between the immune system and the microbiota in the human intestine dictates states of health vs. disease. Polysaccharide capsules are critical elements of bacteria that protect bacteria against environmental and host factors, including the host immune system. This review summarizes the mechanisms by which polysaccharide capsules from commensal and pathogenic bacteria in the gut microbiota modulate the innate and adaptive immune systems in the intestine. A deeper understanding of the roles of polysaccharide capsules in microbiota-immune interactions will provide a basis to harness their therapeutic potential to advance human health

Deficit or difference: African American children\u27s linguistic paths towards a Theory of Mind

The present paper raises one of many major problems with past research. More specifically, the question is raised with regard to how the presumption of language deficits has been studied, especially the use of language deemed necessary for the development of a theory of mind. The data used to argue that there are deficits in the quality of language encountered in working-class African American households, namely the reduced frequency of references to the mind and mental states, results from language transcripts where simple counts of mental verb usage are recorded for different race/class groups. While such a coding scheme lends a gross measure of mental verb usage, it tells us nothing about the syntactic structures in which such verbs were used. Yet recent theories argue that it is not just the amount of mental verb usage that is the necessary precursor to the development of a theory of mind. Rather, it is maintained that it is the mastery of complement sentences with mental verbs that enable the ultimate development of a theory of mind (Astington and Jenkins, 1995; de Villiers and Pyers, 1997; de Villiers and de Villiers, 2000). The theory of complement sentences also includes communication verbs as a possible linguistic route to a theory of mind because such verbs allow for the same syntactic structures as mental verbs (Astington and Jenkins, 1997; de Villiers and Pyers, 1997; de Villiers and de Villiers, 2000)

4-H STEM Curriculum Challenges: A Delphi study

Science, technology, engineering and math (STEM) skills have become essential for today’s youth. STEM-literate individuals are a necessity to fill the ever-growing STEM employment pipeline. Employers are expecting applicants with STEM skills. 4-H programs across the nation have recognized the importance of educating STEM-minded youth. As STEM programs become more prevalent within 4-H, it is essential to address challenges Extension educators and 4-H volunteers face when teaching STEM curriculum. In this study the Delphi technique was utilized to collect the opinions of a geographically dispersed group of 4-H Extension educators and volunteers. Each group served on a separate panel and were asked the question, “What challenges do you face when teaching STEM curriculum?” After three rounds of study, both the educator and volunteer panels identified 2 challenges faced when teaching STEM curriculum. Through identification of these challenges, Oklahoma state 4-H staff can better address the professional development needs of educators and volunteers within the organization, and support the desired scientific literacy outcomes of 4-H youth

Cigarette Smoke Impairs A2A Adenosine Receptor Mediated Wound Repair through Up-regulation of Duox-1 Expression.

Cigarette smoke (CS) exposure and intrinsic factors such as the NADPH oxidases produce high levels of reactive oxygen species (ROS), ensuing inflammatory tissue injury. We previously demonstrated that CS-generated ROS, particularly hydrogen peroxide (H2O2), impaired adenosine stimulated wound repair. We hypothesized that CS exposure modulates expression of Dual oxidase 1 (Duox-1), a NADPH oxidases known to generate H2O2. To test this hypothesis, we used human bronchial epithelial cell line Nuli-1 and C57BL/6 mice. Cells were treated with 5% CS extract (CSE) for various periods of time, and mice were exposed to whole body CS for six weeks. Both CSE and CS treatment induced increased expression of Duox-1, and silencing of Doux-1 improved the rate of cell wound repair induced by CSE treatment. Nuli-1 cells pretreated with thapsigargin but not calcium ionophore exhibited increased Duox-1 mRNA expression. CSE treatment stimulated PKCα activation, which was effectively blocked by pretreatment with diphenylene iodonium, a NADPH oxidase inhibitor. Compared to control, lungs from CS-exposed mice showed a significant increase in PKCα activity and Duox-1 expression. Collectively, the data demonstrated that CS exposure upregulates expression of Duox-1 protein. This further leads to H2O2 production and PKCα activation, inhibiting A2AAR-stimulated wound repair

An asteroidal origin for water in the Moon

The Apollo-derived tenet of an anhydrous Moon has been contested following measurement of water in several lunar samples that require water to be present in the lunar interior. However, significant uncertainties exist regarding the flux, sources and timing of water delivery to the Moon. Here we address those fundamental issues by constraining the mass of water accreted to the Moon and modelling the relative proportions of asteroidal and cometary sources for water that are consistent with measured isotopic compositions of lunar samples. We determine that a combination of carbonaceous chondrite-type materials were responsible for the majority of water (and nitrogen) delivered to the Earth–Moon system. Crucially, we conclude that comets containing water enriched in deuterium contributed significantly <20% of the water in the Moon. Therefore, our work places important constraints on the types of objects impacting the Moon ~4.5–4.3 billion years ago and on the origin of water in the inner Solar System

Genome-wide changes in genetic diversity in a population of Myotis lucifugus affected by white-nose syndrome

Novel pathogens can cause massive declines in populations, and even extirpation of hosts. But disease can also act as a selective pressure on survivors, driving the evolution of resistance or tolerance. Bat white-nose syndrome (WNS) is a rapidly spreading wildlife disease in North America. The fungus causing the disease invades skin tissues of hibernating bats, resulting in disruption of hibernation behavior, premature energy depletion, and subsequent death. We used whole-genome sequencing to investigate changes in allele frequencies within a population of Myotis lucifugus in eastern North America to search for genetic resistance to WNS. Our results show low F-ST values within the population across time, i.e., prior to WNS (Pre-WNS) compared to the population that has survived WNS (Post-WNS). However, when dividing the population with a geographical cut-off between the states of Pennsylvania and New York, a sharp increase in values on scaffold GL429776 is evident in the Post-WNS samples. Genes present in the diverged area are associated with thermoregulation and promotion of brown fat production. Thus, although WNS may not have subjected the entire M. lucifugus population to selective pressure, it may have selected for specific alleles in Pennsylvania through decreased gene flow within the population. However, the persistence of remnant sub-populations in the aftermath of WNS is likely due to multiple factors in bat life history.Peer reviewe

VH1-69 Utilizing Antibodies Are Capable of Mediating Non-neutralizing Fc-Mediated Effector Functions Against the Transmitted/Founder gp120

Multiple antibody effector functions arise in HIV-1 infection that could be harnessed to protect against infection or clear the persistent reservoir. Here, we have investigated the genetic and functional memory B cell and antibody landscape present during early infection in six individuals infected with either subtype A, C, or an A/C recombinant HIV-1. These individuals demonstrated varying levels of plasma autologous neutralization (nAb) against the transmitted/founder envelope (T/F Env) pseudovirus and non-neutralizing Fc-mediated effector function (nnFc) antibody-dependent cell-mediated cytotoxicity (ADCC) against the T/F Env gp120 protein at ~7 months after infection. Genetic analysis of the immunoglobulin heavy (VH) and light (VL) chain variable domain gene segments from 352 autologous T/F Env gp120-specific single B cells recovered at this same 7-month time-point revealed an over-representation of the VH1-69 germline in five of six individuals. A defining feature of the VH1-69 utilizing gp120-specific antibodies was their significantly more hydrophobic complementarity-determining region-2 (CDRH2) regions compared to other VH CDRH2 sequences from each individual. While none of the VH1-69 antibodies possessed strong neutralizing activity against virions pseudotyped with the autologous T/F Env, almost a third were capable of mediating high ADCC activity, as assayed by intracellular granzyme B activity in CEM.NKr.CCR5 target cells coated with autologous T/F Env gp120. High ADCC mediating VH1-69 antibodies exhibited shorter complementarity-determining region-3 (CDRH3) lengths and a more neutral isoelectric point than antibodies lacking this function. In the individual that developed the highest autologous ADCC responses, the high granzyme B producing antibodies bound to surface expressed envelope in the absence of CD4 and were not enhanced by the addition of soluble CD4. Overall, VH1-69 utilizing antibodies are commonly induced against gp120 in diverse HIV-1 infections and a subset of these antibodies can mediate ADCC functions, serving as a bridge between the innate and adaptive immune response to HIV-1

Reversing cortical porosity: Cortical pore infilling in preclinical models of chronic kidney disease

Purpose Chronic kidney disease (CKD) patients have a high incidence of fracture due in part to cortical porosity. The goal of this study was to study cortical pore infilling utilizing two rodent models of progressive CKD. Methods Exp 1: Female C57Bl/6J mice (16-week-old) were given dietary adenine (0.2%) to induce CKD for 10 weeks after which calcium water supplementation (Ca-H2O; 1.5% and 3%) was given to suppress PTH for another 4 weeks. Exp 2: Male Cy/+ rats were aged to ~30 weeks with baseline porosity assessed using in vivo μCT. A second in vivo scan followed 5-weeks of Ca-H2O (3%) supplementation. Results Exp 1: Untreated adenine mice had elevated blood urea nitrogen (BUN), parathyroid hormone (PTH), and cortical porosity (~2.6% porosity) while Ca-H2O lowered PTH and cortical porosity (0.5–0.8% porosity). Exp 2: Male Cy/+ rats at baseline had variable porosity (0.5%–10%), but after PTH suppression via Ca-H2O, cortical porosity in all rats was lower than 0.5%. Individual pore dynamics measured via a custom MATLAB code demonstrated that 85% of pores infilled while 12% contracted in size. Conclusion Ca-H2O supplementation causes net cortical pore infilling over time and imparted mechanical benefits. While calcium supplementation is not a viable clinical treatment for CKD, these data demonstrate pore infilling is possible and further research is required to examine clinically relevant therapeutics that may cause net pore infilling in CKD