Phylogenetic position of a remarkable new fideliine bee from northern Chile (Hymenoptera: Megachilidae)

Fideliine bees are an archaic group with a disjunct distribution mostly restricted to deserts of South America and South Africa. This group was previously thought to be more diverse in Africa than in South America, where only one genus (Neofidelia) comprising five species is known. Here we describe a species belonging to a second South American genus: Xenofidelia colorada Packer gen. et sp.n. , from northern Chile. The species is illustrated and its phylogenetic position within Megachilidae is assessed using morphological, molecular and combined data. The 214 character morphological matrix includes 55 new characters with an additional 16 hitherto unexplored for megachilid phylogeny. The molecular dataset is based upon seven nuclear gene sequences, totalling 6439 bp, many of which are published for the first time for particular megachilid taxa. In all analyses, Xenofidelia was found as sister to Neofidelia (endemic to Chile and Peru). It differs from that genus most notably in its short mouthparts, absence of a glossal rod, unmodified female metabasitarsus and an elongate and horizontal dorsal surface of the metapostnotum. Morphological and combined data support a monophyletic Fideliinae (excluding Pararhophites), while molecular data alone failed to recover fideliine monophyly. Dating analyses suggest that Xenofidelia and Neofidelia diverged 34.3–40.6 Ma, indicating that New World fideliines were probably present in arid habitats of South America during the Eocene. This divergence time predates both the main orogenic events that resulted in the formation of the Andean mountains and the origin of hyperarid conditions in the Atacama Desert; it also corresponds to a period prior to the origin of the summer rainfall area in the far north of Chile where the new genus is found. These results support the view that arid habitats have been present continuously in South America since the Eocene. This published work has been registered in ZooBank, http://zoobank.org/urn:lsid:zoobank.org:pub:EA69BB4A‐6F59‐4A15‐AB44‐2A8949E3CF8F .     

A Single Conserved Residue Mediates Binding of the Ribonucleotide Reductase Catalytic Subunit RRM1 to RRM2 and Is Essential for Mouse Development

The ribonucleotide reductase (RNR) complex, composed of a catalytic subunit (RRM1) and a regulatory subunit (RRM2), is thought to be a rate-limiting enzymatic complex for the production of nucleotides. In humans, the Rrm1 gene lies at 11p15.5, a tumor suppressor region, and RRM1 expression in cancer has been shown to predict responses to chemotherapy. Nevertheless, whether RRM1 is essential in mammalian cells and what the effects of its haploinsufficiency are remain unknown. To model RNR function in mice we used a mutation previously described in Saccharomyces cerevisiae (Rnr1-W688G) which, despite being viable, leads to increased interaction of the RNR complex with its allosteric inhibitor Sml1. In contrast to yeast, homozygous mutant mice carrying the Rrm1 mutation (Rrm1^WG/WG) are not viable, even at the earliest embryonic stages. Proteomic analyses failed to identify proteins that specifically bind to the mutant RRM1 but revealed that, in mammals, the mutation prevents RRM1 binding to RRM2. Despite the impact of the mutation, Rrm1^WG/+ mice and cells presented no obvious phenotype, suggesting that the RRM1 protein exists in excess. Our work reveals that binding of RRM1 to RRM2 is essential for mammalian cells and provides the first loss-of-function model of the RNR complex for genetic studies.     

Multifunctional roles of the autoimmune disease-associated tyrosine phosphatase PTPN22 in regulating T cell homeostasis

The non-receptor tyrosine phosphatase PTPN22 has a vital function in inhibiting antigen-receptor signaling in T cells, while polymorphisms in the PTPN22 gene are important risk alleles in human autoimmune diseases. We recently reported that a key physiological function of PTPN22 was to prevent naïve T cell activation and effector cell responses in response to low affinity antigens. PTPN22 also has a more general role in limiting T cell receptor-induced proliferation. Here we present new data emphasizing this dual function for PTPN22 in T cells. Furthermore, we show that T cell activation modulates the expression of PTPN22 and additional inhibitory phosphatases. We discuss the implication of these findings for our understanding of the roles of PTPN22 in regulating T cell responses and in autoimmunity.     

Alterations in the Colonic Microbiota of Pigs Associated with Feeding Distillers Dried Grains with Solubles

In an effort to reduce feed costs, many pork producers have increased their use of coproducts of biofuel production in commercial pig diets, including increased feeding of distiller’s dried grains with solubles (DDGS). The inclusion of DDGS increases the insoluble fiber content in the ration, which has the potential to impact the colonic microbiota considerably as the large intestine contains a dynamic microenvironment with tremendous interplay between microorganisms. Any alteration to the physical or chemical properties of the colonic contents has the potential to impact the resident bacterial population and potentially favor or inhibit the establishment of pathogenic species. In the present study, colonic contents collected at necropsy from pigs fed either 30% or no DDGS were analyzed to examine the relative abundance of bacterial taxa associated with feeding this ingredient. No difference in alpha diversity (richness) was detected between diet groups. However, the beta diversity was significantly different between groups with feeding of DDGS being associated with a decreased Firmicutes:Bacteriodetes ratio (P = .004) and a significantly lower abundance of Lactobacillus spp. (P = .016). Predictive functional profiling of the microbiota revealed more predicted genes associated with carbohydrate metabolism, protein digestion, and degradation of glycans in the microbiota of pigs fed DDGS. Taken together, these findings confirm that alterations in dietary insoluble fiber significantly alter the colonic microbial profile of pigs and suggest the resultant microbiome may predispose to the development of colitis.     

Epigenetic silencing of TIMP4 in heart failure

Tissue inhibitor of matrix metalloprotease 4 (TIMP4) is endogenously one of the key modulators of matrix metalloprotease 9 (MMP9) and we have reported earlier that cardiac specific TIMP4 instigates contractility and helps in differentiation of cardiac progenitor cells. Although studies show that the expression of TIMP4 goes down in heart failure but the mechanism is unknown. This study aims to determine the mechanism of silencing of TIMP4 in heart failure progression created by aorta‐vena cava (AV) fistula. We hypothesize that there is epigenetic silencing of TIMP4 in heart failure. To validate this hypothesis, we created heart failure model by creating AV fistula in C57BL/6 mice and looked into the promoter methylation (methylation specific PCR, high resolution melting, methylation sensitive restriction enzyme and Na bisulphite treatment followed by sequencing), histone modification (ChIP assay) and microRNAs that regulate TIMP4 (mir122a) and MMP9 (mir29b and mir455‐5p). The physiological parameters in terms of cardiac function after AV fistula were assessed by echocardiography. We observed that there are 7 CpG islands in the TIMP4 promoter which get methylated during the progression of heart failure which leads to its epigenetic silencing. In addition, the up‐regulated levels of mir122a in part, contribute to regulation of TIMP4. Consequently, MMP9 gets up‐regulated and leads to cardiac remodeling. This is a novel report to explain the epigenetic silencing of TIMP4 in heart failure.     

Religious Affiliation Modulates Weekly Cycles of Cropland Burning in Sub-Saharan Africa

Vegetation burning is a common land management practice in Africa, where fire is used for hunting, livestock husbandry, pest control, food gathering, cropland fertilization, and wildfire prevention. Given such strong anthropogenic control of fire, we tested the hypotheses that fire activity displays weekly cycles, and that the week day with the fewest fires depends on regionally predominant religious affiliation. We also analyzed the effect of land use (anthrome) on weekly fire cycle significance. Fire density (fire counts.km^-2) observed per week day in each region was modeled using a negative binomial regression model, with fire counts as response variable, region area as offset and a structured random effect to account for spatial dependence. Anthrome (settled, cropland, natural, rangeland), religion (Christian, Muslim, mixed) week day, and their 2-way and 3-way interactions were used as independent variables. Models were also built separately for each anthrome, relating regional fire density with week day and religious affiliation. Analysis revealed a significant interaction between religion and week day, i.e. regions with different religious affiliation (Christian, Muslim) display distinct weekly cycles of burning. However, the religion vs. week day interaction only is significant for croplands, i.e. fire activity in African croplands is significantly lower on Sunday in Christian regions and on Friday in Muslim regions. Magnitude of fire activity does not differ significantly among week days in rangelands and in natural areas, where fire use is under less strict control than in croplands. These findings can contribute towards improved specification of ignition patterns in regional/global vegetation fire models, and may lead to more accurate meteorological and chemical weather forecasting.