Prenatal diagnosis and molecular cytogenetic characterization of a de novo proximal interstitial deletion of chromosome 4p (4p15.2→p14)

We present prenatal diagnosis of de novo proximal interstitial deletion of chromosome 4p (4p15.2→p14) and molecular cytogenetic characterization of the deletion using uncultured amniocytes. We review the phenotypic abnormalities of previously reported patients with similar proximal interstitial 4p deletions, and we discuss the functions of the genes of RBPJ, CCKAR, STIM2, PCDH7 and ARAP2 that are deleted within this region.     

A Japanese child with geleophysic dysplasia caused by a novel mutation of FBN1

Geleophysic dysplasia (GD) is a rare disorder characterized by severe short stature, short hands and feet, limited joint mobility, skin thickening, characteristic facial features (e.g., a “happy” face), and cardiac valvular disorders that often result in an early death. The genes ADAMTSL2 (a disintegrin-like and metalloprotease with thrombospondin type 1 motif-like 2) and FBN1 (fibrillin 1) were recently identified as causative genes for GD. Here, we describe a 10-year-old Japanese female with GD who was born to non-consanguineous parents. At the age of 11 months, she was referred to our hospital because of very short stature for her age (− 4.4 standard deviations of the age-matched value) and a “happy” face with full cheeks, a shortened nose, hypertelorism, and a long and flat philtrum, characteristic of GD. Her hands and feet were small, her skin was thickened, and her joint mobility was generally limited. She had cardiac valvular disorders and history of recurrent respiratory failure. Mutation analysis revealed no abnormalities in ADAMTSL2. However, analysis of FBN1 revealed a novel heterozygous mutation (c.5161T > T/G) in exon 41, which encodes transforming growth factor-β-binding protein-like domain 5 (TB5). GD is an extremely rare disorder and, to our knowledge, only one case of GD with an FBN1 mutation has been reported in Japan. Similar to the previously reported cases of GD, the mutation in the current patient was located in the TB5 domain, which suggests that abnormalities in this domain of FBN1 are responsible for GD.     

Thermal environment shapes cuticle melanism and melanin-based immunity in the ground cricket Allonemobius socius

The thermal melanin hypothesis posits that ectothermic individuals of larger size or from colder environments exhibit darker cuticles due to melanin’s efficacy in absorbing solar radiation. However, melanin is also a crucial component of arthropod immunity. Thus, thermal selection for increased cuticle darkness may profoundly influence melanin-based immune function. In this study, we address the relationships between the thermal environment (season length), cuticular melanism and two aspects of melanin-based immunity across nine thermally distinct populations of the cricket Allonemobius socius. We found that season length (i.e. degree days) and body size had a positive association with cuticle melanism in both sexes across populations, supporting the thermal melanism hypothesis. Despite their smaller size, males were found to have darker cuticles and superior melanin-based immunity. This pattern may be the result of additional selection on males due to sex-specific temperature-dependent activities, such as male calling song. Perhaps most interestingly, we found that short season length populations (i.e. colder) exhibited a greater phenoloxidase activity (aspect of the melanin-based immune system) in addition to darker cuticles in both sexes. This pattern is consistent with direct thermal selection on cuticular color, coupled with indirect selection on melanin-based immunity due to pleiotropy. Thus, thermal selection on cuticle darkness appears to indirectly shape the evolution of pathogen resistance in this system, and potentially for other terrestrial arthropod systems whose ranges encompass a significant thermal gradient.     

Sestrin 2 and AMPK Connect Hyperglycemia to Nox4-Dependent Endothelial Nitric Oxide Synthase Uncoupling and Matrix Protein Expression

Mesangial matrix accumulation is an early feature of glomerular pathology in diabetes. Oxidative stress plays a critical role in hyperglycemia-induced glomerular injury. Here, we demonstrate that, in glomerular mesangial cells (MCs), endothelial nitric oxide synthase (eNOS) is uncoupled upon exposure to high glucose (HG), with enhanced generation of reactive oxygen species (ROS) and decreased production of nitric oxide. Peroxynitrite mediates the effects of HG on eNOS dysfunction. HG upregulates Nox4 protein, and inhibition of Nox4 abrogates the increase in ROS and peroxynitrite generation, as well as the eNOS uncoupling triggered by HG, demonstrating that Nox4 functions upstream from eNOS. Importantly, this pathway contributes to HG-induced MC fibronectin accumulation. Nox4-mediated eNOS dysfunction was confirmed in glomeruli of a rat model of type 1 diabetes. Sestrin 2-dependent AMP-activated protein kinase (AMPK) activation attenuates HG-induced MC fibronectin synthesis through blockade of Nox4-dependent ROS and peroxynitrite generation, with subsequent eNOS uncoupling. We also find that HG negatively regulates sestrin 2 and AMPK, thereby promoting Nox4-mediated eNOS dysfunction and increased fibronectin. These data identify a protective function for sestrin 2/AMPK and potential targets for intervention to prevent fibrotic injury in diabetes.     

Comparison of Expression of Inflammatory Cytokines in the Spinal Cord Between Young Adult and Aged Beagle Dogs

Aging is an inevitable process that occurs in the whole body system accompanying with many functional and morphological changes. Inflammation is known as one of age-related factors, and inflammatory changes could enhance mortality risk. In this study, we compared immunoreactivities of inflammatory cytokines, such as interleukin (IL)-2 (a pro-inflammatory cytokine), its receptor (IL-2R), IL-4 (an anti-inflammatory cytokine), and its receptor (IL-4R) in the cervical and lumbar spinal cord of young adult (2–3 years old) and aged (10–12 years old) beagle dogs using immunohistochemistry and western blotting. IL-2 and IL-2R-immunoreactive nerve cells were found throughout the gray matter of the cervical and lumbar spinal cord of young adult and aged dogs. In the spinal cord neurons of the aged dog, immunoreactivity and protein levels were apparently increased compared with those in the young adult dog. Change patterns of IL-4- and IL-4R-immunoreactive cells and their protein levels were also similar to those in IL-2 and IL-2R; however, IL-4 and IL-4R immunoreactivity in the periphery of the neuronal cytoplasm in the aged dog was much stronger than that in the young adult dog. These results indicate that the increase of inflammatory cytokines and their receptors in the aged spinal cord might be related to maintaining a balance of inflammatory reaction in the spinal cord during normal aging.     

Phospholipase D1 Has a Pivotal Role in Interleukin-1β-Driven Chronic Autoimmune Arthritis through Regulation of NF-κB,Hypoxia-Inducible Factor 1α, and FoxO3a

Interleukin-1β (IL-1β) is a potent proinflammatory and immunoregulatory cytokine playing an important role in the progression of rheumatoid arthritis (RA). However, the signaling network of IL-1β in synoviocytes from RA patients is still poorly understood. Here, we show for the first time that phospholipase D1 (PLD1), but not PLD2, is selectively upregulated in IL-1β-stimulated synoviocytes, as well as synovium, from RA patients. IL-1β enhanced the binding of NF-κB and ATF-2 to the PLD1 promoter, thereby enhancing PLD1 expression. PLD1 inhibition abolished the IL-1β-induced expression of proinflammatory mediators and angiogenic factors by suppressing the binding of NF-κB or hypoxia-inducible factor 1α to the promoter of its target genes, as well as IL-1β-induced proliferation or migration. However, suppression of PLD1 activity promoted cell cycle arrest via transactivation of FoxO3a. Furthermore, PLD1 inhibitor significantly suppressed joint inflammation and destruction in IL-1 receptor antagonist-deficient (IL-1Ra^−/−) mice, a model of spontaneous arthritis. Taken together, these results suggest that the abnormal upregulation of PLD1 may contribute to the pathogenesis of IL-1β-induced chronic arthritis and that a selective PLD1 inhibitor might provide a potential therapeutic molecule for the treatment of chronic inflammatory autoimmune disorders.     

Root-zone CO2 and root-zone temperature effects on photosynthesis and nitrogen metabolism of aeroponically grown lettuce (Lactuca sativa L.) in the tropics

Effects of elevated root-zone (RZ) CO₂ concentration (RZ [CO₂]) and RZ temperature (RZT) on photosynthesis, productivity, nitrate (NO₃ ^?), total reduced nitrogen (TRN), total leaf soluble and Rubisco proteins were studied in aeroponically grown lettuce plants in a tropical greenhouse. Three weeks after transplanting, four different RZ [CO₂] concentrations (ambient, 360 ppm, and elevated concentrations of 2,000; 10,000; and 50,000 ppm) were imposed on plants at 20°C-RZT or ambient(A)-RZT (24–38°C). Elevated RZ [CO₂] resulted in significantly higher light-saturated net photosynthetic rate, but lower light-saturated stomatal conductance. Higher elevated RZ [CO₂] also protected plants from both chronic and dynamic photoinhibition (measured by chlorophyll fluorescence Fv/Fm ratio) and reduced leaf water loss. Under each RZ [CO₂], all these variables were significantly higher in 20°C-RZT plants than in A-RZT plants. All plants accumulated more biomass at elevated RZ [CO₂] than at ambient RZ [CO₂]. Greater increases of biomass in roots than in shoots were manifested by lower shoot/root ratios at elevated RZ [CO₂]. Although the total biomass was higher at 20°C-RZT, the increase in biomass under elevated RZ [CO₂] was greater at A-RZT. Shoot NO₃ ^? and TRN concentrations, total leaf soluble and Rubisco protein concentrations were higher in all elevated RZ [CO₂] plants than in plants under ambient RZ [CO₂] at both RZTs. Under each RZ [CO₂], total leaf soluble and Rubisco protein concentrations were significantly higher at 20°C-RZT than at A-RZT. Our results demonstrated that increased P _Nmax and productivity under elevated [CO₂] was partially due to the alleviation of midday water loss, both dynamic and chronic photoinhibition as well as higher turnover of Calvin cycle with higher Rubisco proteins.     

Making Sense of Human Ecology Mapping: An Overview of Approaches to Integrating Socio-Spatial Data into Environmental Planning

Ecosystem-based planning and management have stimulated the need to gather sociocultural values and human uses of land in formats accessible to diverse planners and researchers. Human Ecology Mapping (HEM) approaches offer promising spatial data gathering and analytical tools, while also addressing important questions about human-landscape connections. This article reviews and compares the characteristics of three HEM approaches that are increasingly used in natural resource management contexts, each focused on a particular aspect of human-environmental interactions. These aspects include tenure and resource use (TRU), local ecological knowledge (LEK), and sense of place (SOP). We discuss their origins, provide examples of their use, and identify challenges to their application. Our review serves as a guide for environmental managers, planners, and communities interested in gathering spatial data on aspects of human ecology important in ecosystem-based management and planning, and for scientists designing socioecological research.     

Hypoglycemic dipeptide cyclo (His-Pro) significantly altered plasma proteome in streptozocin-induced diabetic rats and genetically-diabetic (ob/ob) mice

The proteins in plasma perform many important functions in the body, and the protein profiles of the plasma vary under different physiological and pathological conditions. In an attempt to identify novel marker proteins for diabetes prognosis, we examined the effect of hypoglycemic dipeptide cyclo (His-Pro) (CHP) on the differential regulation of plasma proteins in streptozocin-induced diabetic rats and genetically-diabetic (ob/ob) mice. The orally-administrated CHP produced an excellent hypoglycemic effect in both animal models, lowering the average plasma glucose level by over 50 %. In the 2-DE analysis of the plasma, a total of 23 spots among 500 visualized spots were found to be differentially regulated, and they were identified by MALDI/TOF mass spectrometry. These proteins include the down-regulation of Apo E and the up-regulation of FGA, Apo A-I, Apo A-IV, and A1M in STZ-induced diabetic rats. Moreover, CHP significantly reduced the plasma protein levels of FGB, FGC, F12, C1QTNF5, and SPA3K, as well as increased the abundance of A1M, A2M, Apo E, and TTR in genetically-diabetic mice. In conclusion, alteration in the regulation of these proteins indicates that this treatment may be successful in overcoming the diabetic state. The present proteomic data can serve as the basis for the development of specific evidence-based interventions allowing for the prevention and treatment of diabetes.