Sensory Perception: Lessons from Synesthesia: Using Synesthesia to Inform the Understanding of Sensory Perception

Synesthesia, the conscious, idiosyncratic, repeatable, and involuntary sensation of one sensory modality in response to another, is a condition that has puzzled both researchers and philosophers for centuries. Much time has been spent proving the condition’s existence as well as investigating its etiology, but what can be learned from synesthesia remains a poorly discussed topic. Here, synaesthesia is presented as a possible answer rather than a question to the current gaps in our understanding of sensory perception. By first appreciating the similarities between normal sensory perception and synesthesia, one can use what is known about synaesthesia, from behavioral and imaging studies, to inform our understanding of “normal” sensory perception. In particular, in considering synesthesia, one can better understand how and where the different sensory modalities interact in the brain, how different sensory modalities can interact without confusion ― the binding problem ― as well as how sensory perception develops.     

Some Factors Affecting Survival of Desiccation by Infective Juveniles of Orrina phyllobia

The survival of desiccation by J4 Orrina phyllobia was examined at controlled relative humidities. When nematodes were transferred from water to air at 10% relative humidity (rh), 80% died within 30 minutes. When nematodes were transferred from water to air with rh at 70% or greater for ca. 15 minutes prior to being transferred to 10% rh, more than 90% of them survived desiccation. This phenomenon is referred to as preconditioning and occurred at much faster rates (2-30 minutes) than has been observed for other nematode species (24 hours). Differences in preconditioning rates may be due to technique-dependent variations in boundary layer resistance around nematodes during desiccation.     

Host Suitability and Susceptibility of Glycine max cv. Bedford to Race 1 of Heterodera glycines

Populations of Heterodera glycines identifiable as race 1 reproduced on the race 1 resistant ''Bedford'' soybean. A Beaufort County, North Carolina, population had an index of parasitism of 112% on Bedford in greenhouse tests. Indices of parasitism for this population on race 1 resistant cultivars Pickett 71, Centennial, and Forrest were less than 10%. The Beaufort County population had significantly greater reproduction on Bedford in microplots than did populations of race 3 or race 4. In field tests, a race 1 population suppressed yields of Bedford but not yields of Centennial. Based on these data, Bedford is no longer recommended in North Carolina as a race 1 resistant cultivar.     

Morphometric and Serologic Comparisons of a Number of Populations of Cyst Nematodes

Thirty-five populations of Heterodera glycines and populations of 15 other Heterodera, Globodera, and Punctodera species were studied morphometrically and some were compared serologically. There was a wide range of each measurement within each nematode population. Except for one soybean cyst nematode population from Indiana, which was a tetraploid and considerably larger than the others, morphometric measurements overlapped. In a discriminant function comparison most of the populations were closely grouped but at least three were rather distinctly separated. Morphometrically H. fici, H. cruciferae, H. schachtii, and H. trifolii were closely associated with H. glycines. Serology indicated a close relationship between H. glycines, H. lespedezae, H. trifolii, H. schachtii, and the Heterodera sp. from Rumex, while H. betulae appeared to be more distantly related.     

The Water Channel Aquaporin 1 Is a Novel Molecular Target of Polychlorinated Biphenyls for in Utero Anomalies

Despite serious health risks in humans and wild life, the underlying mechanisms that explain the gene-environment effects of chemical toxicants are largely unknown. Polychlorinated biphenyls (PCBs) are one of the most ubiquitous environmental toxicants worldwide, with reported epidemiological evidence for reproductive and neurocognitive anomalies in humans. Here, we show that Aroclor 1254, a mixture of structurally distinct PCBs, causes preterm birth in interleukin (IL)-10^-/- mice at a dose that does not show any adverse effects in wild type mice, highlighting the significance of IL-10 as an anti-toxicant cytokine. Aroclor 1254-treated IL-10^-/- mice demonstrated increased amniotic fluid, intrauterine growth restriction, and reduced litter size with postnatal neuromotor defects. Further, our results identify aquaporin 1 (AQP1), a potent effector of fluid volume regulation and angiogenic activity, as a novel placental target of PCBs. In vivo or in vitro exposure to Aroclor 1254 coupled with IL-10 deficiency significantly reduced the protein content of AQP1. Reduced uterine AQP1 levels were associated with defective spiral artery transformation. Importantly, recombinant IL-10 reversed PCB-induced in vivo and in vitro effects. These data demonstrate for the first time that the IL-10-AQP1 axis is a novel regulator of PCB-induced in utero effects.The health consequences of environmental toxicants are likely to have critical effects during in utero fetal development because of the complex signaling cascades, high cellular proliferation rates, and differentiation events. Mammalian reproduction involves a complex but highly choreographed sequence of molecular processes. These processes include interactions between the hormonally stimulated uterus and the developing blastocyst, implantation, placental and fetal development, and parturition (1, 2). Although the hormonal milieu, metabolic changes, and placental microenvironment are programmed in a pregnancy compatible manner, pregnancy presents itself as an immunological and hormonal paradox (3, 4). The role of steroid hormones is well known in uterine receptivity, implantation, local immune modulation, and pregnancy success (5). If not temporally produced and regulated, their dysfunction lead to infertility or pregnancy loss. Man-made chemicals like polychlorinated biphenyls (PCBs)² act like hormones and interfere with their cognate receptor functions impacting normal biological processes (6, 7). Although the genotoxic effects of PCBs have been investigated intensively and epidemiological studies have highlighted their health risks (6, 7), the mechanisms responsible for reproductive and neurodevelopmental effects still remain enigmatic. The overarching goal of our studies is to identify unknown pathways and targets that impart adverse effects on pregnancy. In this study, we directed our efforts toward establishing an experimental system to evaluate the in utero gene-environment effects of PCBs using wild type mice and their counterparts deficient in pregnancy compatible anti-inflammatory cytokines such as interleukin 10 (IL-10).IL-10 is a potent anti-inflammatory cytokine that controls inflammatory insult in most organs, particularly at the maternal-fetal interface. IL-10 is produced by gestational tissue and maternal immune cells in the intrauterine microenvironment in humans (8, 9) and in mice (10). We and others have reported that IL-10^-/- mice experience preterm birth and resorptions in response to low doses of inflammatory triggers such as lipopolysaccharide (LPS) (11, 12) or poly(I-C) (13). Importantly, the pregnancy outcome in treated IL-10^-/- mice can be rescued by giving an exogenous dose of IL-10 (11, 14). We have also demonstrated poor IL-10 production in placental and decidual tissues from preterm labor deliveries and missed abortions (15, 16). These data suggest that an inflammatory environment coupled with genetic stress (IL-10 deficiency) may lead to adverse pregnancy outcomes. In consideration of these observations, we hypothesize that exposure to toxicants such as PCBs mimics the physiological counterpart of inflammation that predisposes to adverse pregnancy outcomes when combined with genetic deficiency in loci crucial for pregnancy success such as IL-10.PCBs are chlorinated aromatic hydrocarbon compounds consisting of a group of 209 structurally diverse congeners, identified based on the position of chlorine atoms (7). Since the start of their manufacture in the 1920s until their ban in late 1970s, PCBs were globally valued for their noninflammability and high heat and chemical stability and thus were used widely in a multitude of commercial and industrial applications (7, 17). Improper disposal and accidental release of these compounds led to their introduction into the environment, placing them in the list of widespread environmental contaminants. Subsequently, their lipophilicity facilitated their bioaccumulation in the food chain and bio-concentration at successively higher levels (6, 18-21). PCBs have now been detected globally, in different environmental matrices, wild life, food, and humans (6, 18, 20). Convincing evidence exist for their toxicity, both in humans as well as in laboratory animals (7). From epidemiological studies in humans it has been observed that exposure to PCBs causes various reproductive anomalies that include irregular and shorter menstrual cycles, delayed conception, miscarriage, reduced lactating time, low birth weight, preterm birth, small for gestational age infants, and higher incidence of still-births and mortality among children (22-27). PCB congeners may work in an aryl hydrocarbon receptor-dependent or -independent pathway (6, 7, 28). Despite the knowledge that PCBs affect either aryl hydrocarbon receptor or estrogen receptor signaling, there is a paucity of molecular mechanisms underlying the most sensitive developmental effects of PCBs, and thus new pathways and targets need to be identified.Aroclor 1254 is a mixture of more than one hundred different PCB congeners and may impart cumulative adverse effects on female reproductive health (29, 30). In this study, we show that Aroclor 1254 exposure induces preterm birth in IL-10^-/- mice with reduced litter size and birth weight, increased amniotic fluid, and postnatal neurocognitive defects. Importantly, we have identified aquaporin 1 (AQP1) as a novel target of PCB action at the maternal-fetal interface. Our findings for the first time provide direct experimental evidence for a protective role of IL-10 against PCB exposure. These findings may have implications for the understanding and management of environmental toxicant-induced female reproductive anomalies in humans.     

Acute dacryocystitis: another clinical manifestation of sporotrichosis

Sporotrichosis associated with exposure to domestic cats is hyperendemic in Rio de Janeiro, Brazil. A review of the clinical records at our institute revealed four patients with clinical signs of dacryocystitis and a positive conjunctival culture for Sporothrix who were diagnosed with Sporothrix dacryocystitis. Three patients were children (< 13 years of age) and one patient was an adult. Two patients reported contact with a cat that had sporotrichosis. Dacryocystitis was associated with nodular, ulcerated lesions on the face of one patient and with granulomatous conjunctivitis in two patients; however, this condition manifested as an isolated disease in another patient. All of the patients were cured of the fungal infections, but three patients had chronic dacryocystitis and one patient developed a cutaneous fistula. Sporotrichosis is usually a benign disease, but may cause severe complications when the eye and the adnexa are affected. Physicians, especially ophthalmologists in endemic areas, should be aware of the ophthalmological manifestations and complications of sporotrichosis.     

Unusual Non-Occupational Exposure to Metals

Exposure to metals at workplaces is well known and in many cases occupational studies led to an adoption of limit values. For airborne concentrations of substances as metals refer to the “Maximaleo Arbeitsplatz-Konzentration” (MAK) in Germany or the “Threshold Limit Value” (TLV) in USA. Biological monitoring consists of an assessment of overall exposure to chemicals at the workplace and in the environment. The “Biologischer Arbeitsstoff Toleranzwert” (BAT) in Germany and the “Biological Exposure Index” in the USA serve as reference values. Besides these occupational limit values, reference values exist in Germany for the background exposure of the non occupationally exposed general population. In some cases the reference values are exceeded without any occupational exposure. Several cases of unusual environmental exposure to cobalt, mercury and manganese are reported. In such cases, it is often difficult to evaluate the measured concentration. In Germany, therefore, the “Human-Biomonitoring-Werte” (HBMValues) have been adopted in order to evaluate such high background exposures. The HBM-concept is presented. Environmental exposure to metals is usual within some limits. Reference values are helpful for an assessment. Unusual exposure occurs and the physician should be alert to symptoms of poisoning.     

Kinesin Adapter JLP Links PIKfyve to Microtubule-based Endosome-to-Trans-Golgi Network Traffic of Furin

JIPs (c-Jun N-terminal kinase interacting proteins), which scaffold JNK/p38 MAP kinase signaling modules, also bind conventional kinesins and are implicated in microtubule-based membrane trafficking in neuronal cells. Here we have identified a novel splice variant of the Jip4 gene product JLP_L (JNK-interacting leucine zipper protein) in yeast-two hybrid screens with the phosphoinositide kinase PIKfyve. The interaction was confirmed by pulldown and coimmunoprecipitation assays in native cells. It engages the PIKfyve cpn60_TCP1 consensus sequence and the last 75 residues of the JLP C terminus. Subpopulations of both proteins cofractionated and populated similar structures at the cell perinuclear region. Because PIKfyve is essential in endosome-to-trans-Golgi network (TGN) cargo transport, we tested whether JLP is a PIKfyve functional partner in this trafficking pathway. Short interfering RNA (siRNA)-mediated depletion of endogenous JLP or PIKfyve profoundly delayed the microtubule-based transport of chimeric furin (Tac-furin) from endosomes to the TGN in a CHO cell line, which was rescued upon ectopic expression of siRNA-resistant JLP or PIKfyve constructs. Peptides from the contact sites in PIKfyve and JLP, or a dominant-negative PIKfyve mutant introduced into cells by ectopic expression or microinjection, induced a similar defect. Because Tac-TGN38 delivery from endosomes to the TGN, unlike that of Tac-furin, does not require intact microtubules, we monitored the effect of JLP and PIKfyve depletion or the interacting peptides administration on Tac-TGN38 trafficking. Remarkably, neither maneuver altered the Tac-TGN38 delivery to the TGN. Our data indicate that JLP interacts with PIKfyve and that both proteins and their association are required in microtubule-based, but not in microtubule-independent, endosome-to-TGN cargo transport.In mammalian cells, the endosomal/endocytic system comprises an interconnected and morphologically complex network of membrane organelles that supports fundamental functions such as nutrient entry and delivery for degradation, removal and degradation of plasma membrane or Golgi proteins, regulation and integration of signaling pathways, and protein recycling to the cell surface or the TGN² (1–4). From the plasma membrane, the endocytosed cargo is first delivered to early endosomes/sorting endosomes. Cargoes destined for recycling to the cell surface then enter the endocytic recycling compartment, whereas others, intended for degradation, remain in early endosomes. Early endosomes undergo a series of changes, known as maturation, to give rise to maturing transport intermediates (herein ECV/MVBs; also Ref. 5) and to late endosomes that fuse with lysosomes to deliver cargo for degradation. Recycling or degradation is not the only outcome of the cell surface-originated cargoes. A set of internalized transmembrane proteins, including intracellular sorting receptors, enzymes, and toxins, are retrieved from the endosomal system and transported to the TGN. The endosome-to-TGN trafficking of the acid-hydrolase-sorting receptor, CI-MPR, the endopeptidase furin, and the putative cargo receptor TGN38 are the best studied examples. These cargoes are highly enriched in the TGN at steady state but arrive there from different compartments, utilizing distinct mechanisms. Thus, TGN38 enters the TGN from the endocytic recycling compartment by an iterative removal from the latter compartment, furin reaches the TGN by exiting the early/late endosomal system, and CI-MPR implements features of both pathways (4, 6–9).Whereas the detailed molecular and cellular mechanisms underlying the membrane progression in the course of cargo transport through the endosomal system or retrieval from early/late endosomes to the TGN is still elusive, experimental evidence has been accumulating to implicate PIKfyve, the sole enzyme for PtdIns(3,5)P₂ synthesis (10). Thus, PIKfyve has been found to interact with the late endosome-to-TGN transport factor Rab9 effector p40 (11). Furthermore, disruption of the PtdIns(3,5)P₂ homeostatic mechanism by means of expression of dominant-negative kinase-deficient point mutants of PIKfyve, protein depletion, or pharmacological inhibition of PIKfyve activity was found to impair the exit of a subset of cargoes from early endosomes to the TGN and late endosomes or from the late endosomes (12–16). Phenotypically, these defects are manifested by progressive endosome swelling and cytoplasmic vacuolation, first seen by expression of dominant-negative PIKfyve^K1831E in a number of mammalian cell types (17) and confirmed thereafter by other maneuvers inhibiting PIKfyve protein expression or activity (14, 16). In vitro reconstitution assays indicate that PIKfyve enzymatic activity is required in endosome processing in two ways. It triggers the formation/fission (or maturation) of ECV/MVBs from early endosomes and arrests the rate of fusion events in the endosomal system (18, 19). It is thus conceivable that impaired PIKfyve and PtdIns(3,5)P₂ functioning in the fission and fusion events mechanistically underlies the constraints in the trafficking pathways traversing endosomes.Microtubules aided by the microtubule-associated motor protein families of kinesin and dynein are required for proper performance of the endosomal/endocytic membrane system. Although their role is rather complex and not completely understood, in vivo and in vitro studies implicate microtubule-based dynamics in multiple aspects of the endocytic trafficking, including sorting of endocytic contents, fission/fusion events at early or late endosomes, early endosome maturation, and efficient motility of the transport vesicles to their destination (20–27). Accumulating evidence indicates that the binding of motor proteins to organelles or carrier vesicles is regulated by motor protein adapters. Intriguingly, this newly emerging adapter function has been found to be executed by proteins known as scaffolds of stress signaling enzymes. One such adapter for conventional kinesins is the group of JIPs that scaffold the JNK/p38 MAP kinase signaling modules (28–31). A mutation that causes mislocalization of synaptic vesicles and aberrant axonal transport in Drosophila and Caenorhabditis elegans affects the JIP3 homologs Sunday driver (dSYD) and Unc16, respectively (32, 33). In mammalian cells, JIPs are represented by four proteins (JIP1–4) derived from separate genes and several alternatively spliced variants. JIP1, the founding member, is structurally related to JIP2 (34, 35). JIP3 (also known as Unc16/JSAP1/dSYD) is structurally unrelated to JIP1 or JIP2, but as those two, it is abundant in neuronal cells (30, 32, 36). The latest addition to the group is JIP4 that occurs in three splice variants known thus far: JLP and JIP4 in mouse and SPAG9 in humans (31, 37, 38). JIP4, JLP, and SPAG9 (gene symbol, SPAG9) are structurally homologous to JIP3 but display broader distribution (37–39). Remarkably, all four members of the JIP group interact with the kinesin1 light chain, and potential cargoes for microtubule-based vesicle transport have been proposed for JIP1–JIP3 (32, 33, 38, 40–43). The role of JLP/JIP4 in the context of cargo transport or membrane trafficking events, however, has never been investigated. In the present study we report that JLP is a PIKfyve physical and functional partner in microtubule-based endosome-to-TGN trafficking. The interaction is identified by a yeast two-hybrid screen with the PIKfyve cpn60_TCP1 consensus sequence and mapped to the 75-aa peptide fragment of the extreme JLP C terminus. By monitoring divergent routes of cargo delivery to the TGN, differing by the requirement of microtubule-dependent early endosome maturation, we have determined that JLP assists PIKfyve selective functionality in microtubule-based endosome-to-TGN trafficking.     

Gaseous Requirements for Postparasitic Development of Romanomermis culicivorax

The development of postparasitic stages of Romanomermis culicivorax was studied under various concentrations of oxygen and carhon dioxide. The nematode developed poorly if only nitrogen was supplied; only one-third molted and all died eventually. In the presence of 5% CO₂ - 95% N₂, development was normal; most nematodes molted and oviposited with respective mean developmental times of 32 and 50 d. Addition of 0.2% O₂ stimulated development; molting and oviposition commenced at days 18 and 41, respectively. There was an additional stimulation of development by increasing amounts of O₂ up to 1%, but concentrations greater than 1% produced no additional stimulation. Carbon dioxide was required for development after exsheathment under anaerobic conditions or O₂ concentrations less than 1%. Oxygen or CO₂ were not required for embryological development or egg hatch. It is suggested that post-parasitic stages function as facultative anaerobes,     

Development of Four Populations of Meloidogyne hapla on Two Cultivars,of Cucumber at Different Temperatures

The infectivity and development of four populations of Meloidogyne hapla were compared, at three temperatures, on tomato and two varieties of cucumber. A population from Canada produced few root-galls on cucumber and, except at 24 C, no larvae developed into adult females and produced egg masses. In contrast, a population with 45 chromosomes from America produced many galls on cucumber and small proportions of larvae became females and produced egg masses at 20 and 24 C. At 18 C this population produced no egg masses on cucumber, but a population from Britain and one from America with 17 chromosomes produced more egg masses at this temperature than at 20 or 24 C. Dissection of the galls showed that on cucumber many larvae died or their growth and development was slowed.     

wrinkled1: A Novel, Low-Seed-Oil Mutant of Arabidopsis with a Deficiency in the Seed-Specific Regulation of Carbohydrate Metabolism

During oil deposition in developing seeds of Arabidopsis, photosynthate is imported in the form of carbohydrates into the embryo and converted to triacylglycerols. To identify genes essential for this process and to investigate the molecular basis for the developmental regulation of oil accumulation, mutants producing wrinkled, incompletely filled seeds were isolated. A novel mutant locus, wrinkled1 (wri1), which maps to the bottom of chromosome 3 and causes an 80% reduction in seed oil content, was identified. Wild-type and homozygous wri1 mutant plantlets or mature plants were indistinguishable. However, developing homozygous wri1 seeds were impaired in the incorporation of sucrose and glucose into triacylglycerols, but incorporated pyruvate and acetate at an increased rate. Because the activities of several glycolytic enzymes, in particular hexokinase and pyrophosphate-dependent phosphofructokinase, are reduced in developing homozygous wri1 seeds, it is suggested that WRI1 is involved in the developmental regulation of carbohydrate metabolism during seed filling.     

Nematode Temperature Responses: a Niche Dimension In Populations of Bacterial-Feeding Nematodes

The optimum temperatures for population development were determined for six species of bacterial-feeding nematodes from among eight temperatures, ranging from 5 to 40 C. Four of the species are cohabiting species. The range of temperatures over which population development occurs (temperature niche breadth) is different for the cohabiting species. This difference may be a means of reducing competition between species, thus increasing temperatures over which habitats can be exploited.