Adenine nucleotide transporters in organelles: novel genes and functions

In eukaryotes, cellular energy in the form of ATP is produced in the cytosol via glycolysis or in the mitochondria via oxidative phosphorylation and, in photosynthetic organisms, in the chloroplast via photophosphorylation. Transport of adenine nucleotides among cell compartments is essential and is performed mainly by members of the mitochondrial carrier family, among which the ADP/ATP carriers are the best known. This work reviews the carriers that transport adenine nucleotides into the organelles of eukaryotic cells together with their possible functions. We focus on novel mechanisms of adenine nucleotide transport, including mitochondrial carriers found in organelles such as peroxisomes, plastids, or endoplasmic reticulum and also mitochondrial carriers found in the mitochondrial remnants of many eukaryotic parasites of interest. The extensive repertoire of adenine nucleotide carriers highlights an amazing variety of new possible functions of adenine nucleotide transport across eukaryotic organelles.     

The histidine triad nucleotide-binding protein 1 supports mu-opioid receptor–glutamate NMDA receptor cross-regulation

A series of pharmacological and physiological studies have demonstrated the functional cross-regulation between MOR and NMDAR. These receptors coexist at postsynaptic sites in midbrain periaqueductal grey (PAG) neurons, an area implicated in the analgesic effects of opioids like morphine. In this study, we found that the MOR-associated histidine triad nucleotide-binding protein 1 (HINT1) is essential for maintaining the connection between the NMDAR and MOR. Morphine-induced analgesic tolerance is prevented and even rescued by inhibiting PKC or by antagonizing NMDAR. However, in the absence of HINT1, the MOR becomes supersensitive to morphine before suffering a profound and lasting desensitization that is refractory to PKC inhibition or NMDAR antagonism. Thus, HINT1 emerges as a key protein that is critical for sustaining NMDAR-mediated regulation of MOR signaling strength. Thus, HINT1 deficiency may contribute to opioid-intractable pain syndromes by causing long-term MOR desensitization via mechanisms independent of NMDAR.     

Visual perception and memory systems: from cortex to medial temporal lobe

Visual perception and memory are the most important components of vision processing in the brain. It was thought that the perceptual aspect of a visual stimulus occurs in visual cortical areas and that this serves as the substrate for the formation of visual memory in a distinct part of the brain called the medial temporal lobe. However, current evidence indicates that there is no functional separation of areas. Entire visual cortical pathways and connecting medial temporal lobe are important for both perception and visual memory. Though some aspects of this view are debated, evidence from both sides will be explored here. In this review, we will discuss the anatomical and functional architecture of the entire system and the implications of these structures in visual perception and memory.     

Novel macrophage polarization model: from gene expression to identification of new anti-inflammatory molecules

Plasticity is a well-known property of macrophages that is controlled by different changes in environmental signals. Macrophage polarization is regarded as a spectrum of activation phenotypes adjusted from one activation extreme, the classic (M1), to the other, the alternative (M2) activation. Here we show, in vitro and in vivo, that both M1 and M2 macrophage phenotypes are tightly coupled to specific patterns of gene expression. Novel M2-associated markers were characterized and identified as genes controlling the extracellular metabolism of ATP to generate pyrophosphates (PPi). Stimulation of M1 macrophages with PPi dampens both NLR and TLR signaling and thus mediates cytokine production. In this context extracellular PPi enhanced the resolution phase of a murine peritonitis model via a decrease in pro-inflammatory cytokine production. Therefore, our study reveals an additional level of plasticity modulating the resolution of inflammation.     

Comparative life history for populations of the Sceloporus grammicus complex (Squamata: Phrynosomatidae)

A Teotihuacán population of the Sceloporus grammicus complex was compared with other previously studied populations (Parque Nacional Zoquiapan [PNZ], Monte Alegre Ajusco [MAA], Pedregal San Angel [PSA], Cantimplora [CA], Capulín, Laguna, Paredon, Michilia, and south Texas) for variations in several life history characteristics (SVL at sexual maturity, reproductive period, ovulation and gestation time, and litter size). Mean body size at sexual maturity of females from Teotihuacán was larger than PNZ, MAA, CA, and Capulín. Reproductive period (vitellogenesis, ovulation, gestation, and birth) for the Teotihuacán population was the shortest of all populations. In the Teotihuacán population, gestation time was similar to the Capulínand MAA populations but was shorter than all other populations except the Michilia population. Embryonic development at ovulation varied among populations, with Teotihuacán and Capulín showing earlier stages (stages 1) at ovulation than all other populations. Teotihuacán, PSA, PNZ, and Texas all showed similar litter size, which were larger than Laguna, Paredon, MAA, Capulín, and CA populations. Differences in reproductive characteristics of these populations could indicate phylogenetically constrained, reproductively isolated populations, or they may be explained as merely responses to different environments.     

Demography of the Yarrow's spiny lizard, Sceloporus jarrovii , from the central Chihuahuan Desert

The demography of a population of Yarrow's spiny lizard, Sceloporus jarrovii , was examined from 2004 to 2006 in the canyon Las Piedras Encimadas, located in Gomez Palacio, Durango, México. Lizards were studied using a mark-recapture technique. Reproduction in females occurred between November and May, coinciding with dry conditions. Reproductive activity was highest (percent of females with vitellogenic follicles or embryos) in the middle of the dry season (November and December). Thirteen percent of females reached sexual maturity at an average age of 8.5 months. The population structure was similar in spring and fall, but not in summer. A notable feature of summer, coinciding with the wet season, was the greater number of hatchlings and juveniles. The overall sex ratio did not differ from 1:1. The density of adults varied from 12 to 62 animals ? 0.5 ha –1 . Temperate and arid-adapted populations of S. jarrovii exhibited broad similarity in timing of the reproductive season, whereas factors such as density, growth, age at sexual maturity, and survivorship differed.     

Rediscovered population of Mexican Plateau spotted whiptail lizard, Aspidoscelis septemvittata , from México, D.F.

Multiple surveys carried out by herpetologists in México, D.F., during the 1980s failed to find specimens of Aspidoscelis septemvitatta (Squamata: Teiidae). However, 10 specimens were recently collected to the east of México, D.F., inside a protected area, Sierra de Santa Catarina. The Sierra de Santa Catarina has been heavily modified by human activity and habitation. Morphological and natural history information about the specimens are presented, as well as notes on locality.     

A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition

Mutations affecting ciliary components cause ciliopathies. As described here, we investigated Tectonic1 (Tctn1), a regulator of mouse Hedgehog signaling, and found that it is essential for ciliogenesis in some, but not all, tissues. Cell types that do not require Tctn1 for ciliogenesis require it to localize select membrane-associated proteins to the cilium, including Arl13b, AC3, Smoothened and Pkd2. Tctn1 forms a complex with multiple ciliopathy proteins associated with Meckel and Joubert syndromes, including Mks1, Tmem216, Tmem67, Cep290, B9d1, Tctn2 and Cc2d2a. Components of this complex co-localize at the transition zone, a region between the basal body and ciliary axoneme. Like Tctn1, loss of Tctn2, Tmem67 or Cc2d2a causes tissue-specific defects in ciliogenesis and ciliary membrane composition. Consistent with a shared function for complex components, we identified a mutation in TCTN1 that causes Joubert syndrome. Thus, a transition zone complex of Meckel and Joubert syndrome proteins regulates ciliary assembly and trafficking, suggesting that transition zone dysfunction is the cause of these ciliopathies.     

Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease

Using variants from the 1000 Genomes Project pilot European CEU dataset and data from additional resequencing studies, we densely genotyped 183 non-HLA risk loci previously associated with immune-mediated diseases in 12,041 individuals with celiac disease (cases) and 12,228 controls. We identified 13 new celiac disease risk loci reaching genome-wide significance, bringing the number of known loci (including the HLA locus) to 40. We found multiple independent association signals at over one-third of these loci, a finding that is attributable to a combination of common, low-frequency and rare genetic variants. Compared to previously available data such as those from HapMap3, our dense genotyping in a large sample collection provided a higher resolution of the pattern of linkage disequilibrium and suggested localization of many signals to finer scale regions. In particular, 29 of the 54 fine-mapped signals seemed to be localized to single genes and, in some instances, to gene regulatory elements. Altogether, we define the complex genetic architecture of the risk regions of and refine the risk signals for celiac disease, providing the next step toward uncovering the causal mechanisms of the disease.     

Microhabitat selection in the sand recluse spider (Sicarius thomisoides): the effect of rock size and temperature

In spiders, temperature is considered an important environmental variable for microhabitat selection. In this study, we evaluated the effect of temperature and rock size on the presence of the sand recluse spider Sicarius thomisoides and the degree of selectivity in different locations. This species is a large spider that lives under rocks in desert and semi-desert climates and is particularly active during the summer. In Chile, these spiders can be found at both coastal and inland locations under different thermal conditions, where usually the temperatures are lower near the coast. If large-scale climatic conditions are important for this species, they may be expected to select lower rock temperatures on the coast than at inland locations. In addition, we would expect that the spiders would choose larger rocks in inland compared to coast locations, which reduce the effect of high temperatures. We found that the probability of finding individuals of this species increased according to rock temperature and rock size in the field. Our results suggest that S. thomisoides prefers larger and warmer rocks to shelter under during the day, this selectivity being similar at both coastal and inland locations. Thus, this species tends to select rocks with the same thermal and structural conditions, independent of the climatic conditions.