Antibodies Generated against Conserved Antigens Expressed by Bacteria and Allergen-Bearing Fungi Suppress Airway Disease

There has been a sharp rise in allergic asthma and asthma-related deaths in the developed world, in contrast to many childhood illnesses that have been reduced or eliminated. The hygiene hypothesis proposes that excessively sanitary conditions early in life result in autoimmune and allergic phenomena because of a failure of the immune system to receive proper microbial stimulation during development. We demonstrate that Abs generated against conserved bacterial polysaccharides are reactive with and dampen the immune response against chitin and Aspergillus fumigatus. A reduction in Ag uptake, cell influx, cell activation, and cytokine production occurred in the presence of anti-polysaccharide Abs, resulting in a striking decrease in the severity of allergic airway disease in mice. Overall, our results suggest that Ag exposure-derived from environmental sources, self-antigens, or vaccination-during the neonatal period has dramatic effects on the adult Ab response and modifies the development of allergic airway disease.     

Fast‐forward genetics by radiation hybrids to saturate the locus regulating nuclear–cytoplasmic compatibility in Triticum

The nuclear‐encoded species cytoplasm specific (scs) genes control nuclear–cytoplasmic compatibility in wheat (genus Triticum). Alloplasmic cells, which have nucleus and cytoplasm derived from different species, produce vigorous and vital organisms only when the correct version of scs is present in their nucleus. In this study, bulks of in vivo radiation hybrids segregating for the scs phenotype have been genotyped by sequencing with over 1.9 million markers. The high marker saturation obtained for a critical region of chromosome 1D allowed identification of 3318 reads that mapped in close proximity of the scs. A novel in silico approach was deployed to extend these short reads to sequences of up to 70 Kb in length and identify candidate open reading frames (ORFs). Markers were developed to anchor the short contigs containing ORFs to a radiation hybrid map of 650 individuals with resolution of 288 Kb. The region containing the scs locus was narrowed to a single Bacterial Artificial Chromosome (BAC) contig of Aegilops tauschii. Its sequencing and assembly by nano‐mapping allowed rapid identification of a rhomboid gene as the only ORF existing within the refined scs locus. Resequencing of this gene from multiple germplasm sources identified a single nucleotide mutation, which gives rise to a functional amino acid change. Gene expression characterization revealed that an active copy of this rhomboid exists on all homoeologous chromosomes of wheat, and depending on the specific cytoplasm each copy is preferentially expressed. Therefore, a new methodology was applied to unique genetic stocks to rapidly identify a strong candidate gene for the control of nuclear–cytoplasmic compatibility in wheat.     

On Sanctuary

The author reflects on a sanctuary site in Davao City, Philippines, where 750 Lumad—indigenous peoples from several mountain tribes of Mindanao—sought sanctuary from the violent, lawless forms of militarization and paramilitarization that overwhelmed their communities in 2015. Dizon weaves interviews done with Lumad at the sanctuary site with the Lumad’s long history of struggle against corporate globalization; and also with a summary of contemporary media artists from the Philippines and its diaspora who are working to document the vibrant resistance of Lumad to their violent displacement and dispossession. She reflects on her practice as a USA-based media artist from that diaspora, and on why she forges solidarities with those who are most vulnerable to the processes of globalization today.     

Disruption of Type I Interferon Induction by HIV Infection of T Cells

Our main objective of this study was to determine how Human Immunodeficiency Virus (HIV) avoids induction of the antiviral Type I Interferon (IFN) system. To limit viral infection, the innate immune system produces important antiviral cytokines such as the IFN. IFN set up a critical roadblock to virus infection by limiting further replication of a virus. Usually, IFN production is induced by the recognition of viral nucleic acids by innate immune receptors and subsequent downstream signaling. However, the importance of IFN in the defense against viruses has lead most pathogenic viruses to evolve strategies to inhibit host IFN induction or responses allowing for increased pathogenicity and persistence of the virus. While the adaptive immune responses to HIV infection have been extensively studied, less is known about the balance between induction and inhibition of innate immune defenses, including the antiviral IFN response, by HIV infection. Here we show that HIV infection of T cells does not induce significant IFN production even IFN I Interferon production. To explain this paradox, we screened HIV proteins and found that two HIV encoded proteins, Vpu and Nef, strongly antagonize IFN induction, with expression of these proteins leading to loss of expression of the innate immune viral RNA sensing adaptor protein, IPS-1 (IFN-β promoter stimulator-1). We hypothesize that with lower levels of IPS-1 present, infected cells are defective in mounting antiviral responses allowing HIV to replicate without the normal antiviral actions of the host IFN response. Using cell lines as well as primary human derived cells, we show that HIV targeting of IPS-1 is key to limiting IFN induction. These findings describe how HIV infection modulates IFN induction providing insight into the mechanisms by which HIV establishes infection and persistence in a host.     

DETERMINING PREGNANCY FROM BLUBBER IN THREE SPECIES OF DELPHINIDS

We quantified progesterone in 110 blubber samples from dolphins of known reproductive status in order to test the accuracy of a method to determine pregnancy status in wild cetaceans. The samples were collected from fishery‐bycaught delphinids of three species (Delphinus delphis, Lissodelphis borealis, and Lagenorhynchus obliquidens). We ascertained that blubber progesterone concentrations could clearly distinguish pregnant D. delphis (range 132–415 ng/g, mean 261 ng/g) from non‐pregnant mature and immature ones (range 0.92–48.2 ng/g, mean 15.2 ng/g). We found similar dramatic differences in L. borealis and L. obliquidens. These results were insensitive to various blubber sampling depths and anatomical sampling locations on the body, suggesting relative homogeneity of progesterone levels throughout the blubber. However, no trend was found in blubber progesterone concentration with fetal length, indicating that although blubber progesterone appears to distinguish pregnancy status, it is unlikely to differentiate pregnancy stage. Based on the findings presented here we suggest that this method, when coupled with projectile biopsy procedures, can be used to assess the pregnancy status of free‐ranging cetaceans and thus provide a new tool to determine pregnancy rates of wild populations.     

The peroxin loss-of-function mutation abstinence by mutual consent disrupts male-female gametophyte recognition

In eukaryotes, fertilization relies on complex and specialized mechanisms that achieve the precise delivery of the male gamete to the female gamete and their subsequent union [1-4]. In flowering plants, the haploid male gametophyte or pollen tube (PT) [5] carries two nonmotile sperm cells to the female gametophyte (FG) or embryo sac [6] during a long assisted journey through the maternal tissues [7-10]. In Arabidopsis, typically one PT reaches one of the two synergids of the FG (Figure 1A), where it terminates its growth and delivers the sperm cells, a poorly understood process called pollen-tube reception. Here, we report the isolation and characterization of the Arabidopsis mutant abstinence by mutual consent (amc). Interestingly, pollen-tube reception is impaired only when an amc pollen tube reaches an amc female gametophyte, resulting in pollen-tube overgrowth and completely preventing sperm discharge and the development of homozygous mutants. Moreover, we show that AMC is strongly and transiently expressed in both male and female gametophytes during fertilization and that AMC functions in gametophytes as a peroxin essential for protein import into peroxisomes. These findings show that peroxisomes play an unexpected key role in gametophyte recognition and implicate a diffusible signal emanating from either gametophyte that is required for pollen-tube discharge.     

Transgenic mice with green fluorescent protein-labeled pancreatic beta -cells

We have generated transgenic mice that express green fluorescent protein (GFP) under the control of the mouse insulin I gene promoter (MIP). The MIP-GFP mice develop normally and are indistinguishable from control animals with respect to glucose tolerance and pancreatic insulin content. Histological studies showed that the MIP-GFP mice had normal islet architecture with coexpression of insulin and GFP in the beta-cells of all islets. We observed GFP expression in islets from embryonic day E13.5 through adulthood. Studies of beta-cell function revealed no difference in glucose-induced intracellular calcium mobilization between islets from transgenic and control animals. We prepared single-cell suspensions from both isolated islets and whole pancreas from MIP-GFP-transgenic mice and sorted the beta-cells by fluorescence-activated cell sorting based on their green fluorescence. These studies showed that 2.4 +/- 0.2% (n = 6) of the cells in the pancreas of newborn (P1) and 0.9 +/- 0.1% (n = 5) of 8-wk-old mice were beta-cells. The MIP-GFP-transgenic mouse may be a useful tool for studying beta-cell biology in normal and diabetic animals.     

Phylogeography, intraspecific structure and sex-biased dispersal of Dall's porpoise, Phocoenoides dalli, revealed by mitochondrial and microsatellite DNA analyses

Mitochondrial DNA (mtDNA) control-region sequences and microsatellite loci length polymorphisms were used to estimate phylogeographical patterns (historical patterns underlying contemporary distribution), intraspecific population structure and gender-biased dispersal of Phocoenoides dalli dalli across its entire range. One-hundred and thirteen animals from several geographical strata were sequenced over 379 bp of mtDNA, resulting in 58 mtDNA haplotypes. Analysis using F(ST) values (based on haplotype frequencies) and phi(ST) values (based on frequencies and genetic distances between haplotypes) yielded statistically significant separation (bootstrap values P < 0.05) among most of the stocks currently used for management purposes. A minimum spanning network of haplotypes showed two very distinctive clusters, differentially occupied by western and eastern populations, with some common widespread haplotypes. This suggests some degree of phyletic radiation from west to east, superimposed on gene flow. Highly male-biased migration was detected for several population comparisons. Nuclear microsatellite DNA markers (119 individuals and six loci) provided additional support for population subdivision and gender-biased dispersal detected in the mtDNA sequences. Analysis using F(ST) values (based on allelic frequencies) yielded statistically significant separation between some, but not all, populations distinguished by mtDNA analysis. R(ST) values (based on frequencies of and genetic distance between alleles) showed no statistically significant subdivision. Again, highly male-biased dispersal was detected for all population comparisons, suggesting, together with morphological and reproductive data, the existence of sexual selection. Our molecular results argue for nine distinct dalli-type populations that should be treated as separate units for management purposes.     

UNOBSERVED KILL OF NURSING DOLPHIN CALVES IN A TUNA PURSE-SEINE FISHERY

The kill of dolphins ( Stenella attenuata and S. longirostris ) in the eastern tropical Pacific tuna purse-seine fishery has been underestimated because of unobserved deaths of nursing calves due to separation from their mothers during fishing. Based on an analysis of dolphins killed from 1973 to 1990, and depending on the length at which calves are assumed to become independent, there was a deficit of calves relative to the number of lactating females killed in 24%–32% of 1,847 spotted-dolphin sets and in 13%–19% of 563 spinner-dolphin sets. We found a deficit of 0.31–0.45 spotted dolphin and 0.15–0.26 spinner dolphin calves per set. If these missing calves were added to the observed kill, it would represent an increase in the kill of 10%–15% for spotted dolphins and 6%–10% for spinner dolphins in the sets we examined. We did not attempt to estimate the actual number of unobserved calf deaths due to purse-seine fishing on dolphins, either in the sets we examined or in all dolphin sets. The actual number of unobserved calf deaths is likely to be higher than the calf deficit we found. Separation of dolphin mothers from calves could occur at any of several points in the fishing process, but most of these would be invisible to us and not produce a calf deficit. Estimation of the actual number of unobserved calf deaths would require further information on how frequently permanent mother-calf separations occur, the fraction of calves that survive after separation, the fraction of lactating females set upon that are carrying calves, and the fraction of calves killed that are actually related to lactating females killed in the same set. In any case, the observation of a calf deficit indicates that the reported dolphin kill fails to measure the full impact of purse-seine fishing on spotted and spinner dolphin populations.