Freshwater occurrence of the extinct dolphin Parapontoporia (Cetacea: Lipotidae) from the upper Pliocene nonmarine Tulare Formation of California

The diminutive, extinct longirostrine dolphin Parapontoporia is one of the most abundantly represented late Neogene odontocetes from the eastern North Pacific and is widely known from numerous marine strata of late Miocene and Pliocene age in California, Baja California and possibly Japan. Parapontoporia has been identified as the sister taxon of the recently extinct Chinese river dolphin (Lipotes vexillifer); unlike Lipotes, which exclusively inhabited freshwater, the depositional context of Parapontoporia suggests it was marine. A newly identified petrosal of Parapontoporia sp. was preserved alongside terrestrial vertebrates in the nonmarine Tulare Formation (upper Pliocene to Pleistocene, 2.2–0.6 Ma), California, which was deposited under lacustrine and fluviodeltaic conditions. Abundantly preserved freshwater molluscs and rare marine taxa suggest predominantly freshwater settings with intermittent periods of estuarine conditions. This occurrence of Parapontoporia indicates its presence in the San Joaquin basin after the retreat of the inland sea and suggests that this extinct odontocete may have been freshwater tolerant and an inhabitant of marine and freshwater settings, heralding the exclusively freshwater existence of its Recent sister taxon Lipotes vexillifer.     

The role of the maternal immune system in the regulation of human birthweight

Human birthweight is subject to stabilizing selection. Large babies are at risk of obstetric complications such as obstructed labour, which endangers both mother and child. Small babies are also at risk with reduced survival. Fetal growth requires remodelling of maternal spiral arteries to provide an adequate maternal blood supply to the placenta. This arterial transformation is achieved by placental trophoblast cells, which invade into the uterine wall. Under-invasion is associated with fetal growth restriction; but if invasion is excessive large babies can result. A growing body of evidence suggests that this process is controlled by interactions between killer-cell immunoglobulin-like receptors (KIRs) expressed on maternal uterine natural killer cells (uNK) and their corresponding human leukocyte antigen-C (HLA-C) ligands on invading trophoblast. Mothers with the KIR AA genotype and a fetus with a paternal HLA-C2 allele tend to have small babies, because this combination inhibits cytokine secretion by uNK. Mothers with the activating KIR2DS1 gene and an HLA-C2 fetus are more likely to have large babies. When KIR2DS1 binds to HLA-C2 this increases secretion of cytokines that enhance trophoblast invasion. We conclude that specific combinations of the highly polymorphic gene systems, KIR and HLA-C, contribute to successful reproduction by maintaining birthweight between two extremes.     

Macrophage apoAI protects against dyslipidemia-induced dermatitis and atherosclerosis without affecting HDL

Tissue cholesterol accumulation, macrophage infiltration, and inflammation are features of atherosclerosis and some forms of dermatitis. HDL and its main protein, apoAI, are acceptors of excess cholesterol from macrophages; this process inhibits tissue inflammation. Recent epidemiologic and clinical trial evidence questions the role of HDL and its manipulation in cardiovascular disease. We investigated the effect of ectopic macrophage apoAI expression on atherosclerosis and dermatitis induced by the combination of hypercholesterolemia and absence of HDL in mice. Hematopoietic progenitor cells were transduced to express human apoAI and transplanted into lethally irradiated LDL receptor^−/−/apoAI^−/− mice, which were then placed on a high-fat diet for 16 weeks. Macrophage apoAI expression reduced aortic CD4⁺ T-cell levels (−39.8%), lesion size (−25%), and necrotic core area (−31.6%), without affecting serum HDL or aortic macrophage levels. Macrophage apoAI reduced skin cholesterol by 39.8%, restored skin morphology, and reduced skin CD4⁺ T-cell levels. Macrophage apoAI also reduced CD4⁺ T-cell levels (−32.9%) in skin-draining lymph nodes but had no effect on other T cells, B cells, dendritic cells, or macrophages compared with control transplanted mice. Thus, macrophage apoAI expression protects against atherosclerosis and dermatitis by reducing cholesterol accumulation and regulating CD4⁺ T-cell levels, without affecting serum HDL or tissue macrophage levels.