Zn(2+) modulation of neuronal transient K(+) current: fast and selective binding to the deactivated channels

Modulation of voltage-dependent transient K(+) currents (A type K(+) or K(A) current) by Zn(2+) was studied in rat hippocampal neurons by the whole-cell patch-clamp technique. It is found that Zn(2+) selectively binds to the resting (deactivated or closed) K(A) channels with a dissociation constant (K(d)) of approximately 3 &mgr;M, whereas the affinity between Zn(2+) and the inactivated K(A) channels is 1000-fold lower. Zn(2+) therefore produces a concentration-dependent shift of the K(A) channel inactivation curve and enhances the K(A) current elicited from relatively positive holding potentials. It is also found that the kinetics of Zn(2+) action are fast enough to compete with the transition rates between different gating states of the channel. The rapid and selective binding of Zn(2+) to the closed K(A) channels keeps the channel in the closed state and explains the ion's concentration-dependent slowing effect on the activation of K(A) current. This in turn accounts for the inhibitory effect of Zn(2+) on the K(A) current elicited from hyperpolarized holding potentials. Because the molecular mechanisms underlying these gating changes are kinetic interactions between the binding-unbinding of Zn(2+) and the intrinsic gating processes of the channel, the shift of the inactivation curve and slowing of K(A) channel activation are quantitatively correlated with ambient Zn(2+) over a wide concentration range without "saturation"; i.e., The effects are already manifest in micromolar Zn(2+), yet are not saturated even in millimolar Zn(2+). Because the physiological concentration of Zn(2+) could vary over a similarly wide range according to neural activities, Zn(2+) may be a faithful physiological "fine tuner," controlling and controlled by neural activities through its effect on the K(A) current.     

Floral Assemblages and Patterns of Insect Herbivory during the Permian to Triassic of Northeastern Italy

To discern the effect of the end-Permian (P-Tr) ecological crisis on land, interactions between plants and their insect herbivores were examined for four time intervals containing ten major floras from the Dolomites of northeastern Italy during a Permian–Triassic interval. These floras are: (i) the Kungurian Tregiovo Flora; (ii) the Wuchiapingian Bletterbach Flora; (iii) three Anisian floras; and (iv) five Ladinian floras. Derived plant–insect interactional data is based on 4242 plant specimens (1995 Permian, 2247 Triassic) allocated to 86 fossil taxa (32 Permian, 56 Triassic), representing lycophytes, sphenophytes, pteridophytes, pteridosperms, ginkgophytes, cycadophytes and coniferophytes from 37 million-year interval (23 m.yr. Permian, 14 m.yr. Triassic). Major Kungurian herbivorized plants were unaffiliated taxa and pteridosperms; later during the Wuchiapingian cycadophytes were predominantly consumed. For the Anisian, pteridosperms and cycadophytes were preferentially consumed, and subordinately pteridophytes, lycophytes and conifers. Ladinian herbivores overwhelming targeted pteridosperms and subordinately cycadophytes and conifers. Throughout the interval the percentage of insect-damaged leaves in bulk floras, as a proportion of total leaves examined, varied from 3.6% for the Kungurian (N = 464 leaves), 1.95% for the Wuchiapingian (N = 1531), 11.65% for the pooled Anisian (N = 1324), to 10.72% for the pooled Ladinian (N = 923), documenting an overall herbivory rise. The percentage of generalized consumption, equivalent to external foliage feeding, consistently exceeded the level of specialized consumption from internal feeding. Generalized damage ranged from 73.6% (Kungurian) of all feeding damage, to 79% (Wuchiapingian), 65.5% (pooled Anisian) and 73.2% (pooled Ladinian). Generalized-to-specialized ratios show minimal change through the interval, although herbivore component community structure (herbivore species feeding on a single plant-host species) increasingly was partitioned from Wuchiapingian to Ladinian. The Paleozoic plant with the richest herbivore component community, the coniferophyte Pseudovoltzia liebeana, harbored four damage types (DTs), whereas its Triassic parallel, the pteridosperm Scytophyllum bergeri housed 11 DTs, almost four times that of P. liebeana. Although generalized DTs of P. liebeana were similar to S. bergeri, there was expansion of Triassic specialized feeding types, including leaf mining. Permian–Triassic generalized herbivory remained relatively constant, but specialized herbivores more finely partitioned plant-host tissues via new feeding modes, especially in the Anisian. Insect-damaged leaf percentages for Dolomites Kungurian and Wuchiapingian floras were similar to those of lower Permian, north-central Texas, but only one-third that of southeastern Brazil. Global herbivore patterns for Early Triassic plant–insect interactions remain unknown.     

Genetic variation in TIMP1 but not MMPs predict excess FEV1 decline in two general population-based cohorts

Background

An imbalance in Matrix MetalloProteases (MMPs) and Tissue Inhibitors of MMPs (TIMPs) contributes to Chronic Obstructive Pulmonary Disease (COPD) development. Longitudinal studies investigating Single Nucleotide Polymorphisms (SNPs) in MMPs and TIMPs with respect to COPD development and lung function decline in the general population are lacking.

Methods

We genotyped SNPs in MMP1 (G-1607GG), MMP2 (-1306 C/T), MMP9 (3 tagging SNPs), MMP12 (A-82G and Asn357Ser) and TIMP1 (Phe124Phe and Ile158Ile) in 1390 Caucasians with multiple FEV₁ measurements from a prospective cohort study in the general population. FEV₁ decline was analyzed using linear mixed effect models adjusted for confounders. Analyses of the X-chromosomal TIMP1 gene were stratified according to sex. All significant associations were repeated in an independent general population cohort (n = 1152).

Results

MMP2 -1306 TT genotype carriers had excess FEV₁ decline (-4.0 ml/yr, p = 0.03) compared to wild type carriers. TIMP1 Ile158Ile predicted significant excess FEV₁ decline in both males and females. TIMP1 Phe124Phe predicted significant excess FEV₁ decline in males only, which was replicated (p = 0.10) in the second cohort. The MMP2 and TIMP1 Ile158Ile associations were not replicated. Although power was limited, we did not find associations with COPD development.

Conclusions

We for the first time show that TIMP1 Phe124Phe contributes to excess FEV₁ decline in two independent prospective cohorts, albeit not quite reaching conventional statistical significance in the replication cohort. SNPs in MMPs evidently do not contribute to FEV₁ decline in the general population.     

A well-preserved aneuretopsychid from the Jehol Biota of China (Insecta, Mecoptera, Aneuretopsychidae)

The Aneuretopsychidae is an unspeciose and enigmatic family of long-proboscid insects that presently consist of one known genus and three species from the Late Jurassic to Early Cretaceous of north-central Asia. In this paper, a new genus and species of fossil aneuretopsychid is described and illustrated, Jeholopsyche liaoningensisgen. et sp. n. Fossils representing this new taxon were collected from mid Early Cretaceous strata of the well known Jehol Biota in Liaoning Province, China. This finding documents the first formal record of fossil Aneuretopsychidae in China. In addition, this well-preserved and new material reveals previously unknown and detailed morphological structure of the mouthparts, antennae, head, thorax, legs and abdomen of this distinctive insect lineage.     

A tetravalent dengue nanoparticle stimulates antibody production in mice

Background

Dengue is a major public health problem worldwide, especially in the tropical and subtropical regions of the world. Infection with a single Dengue virus (DENV) serotype causes a mild, self-limiting febrile illness called dengue fever. However, a subset of patients experiencing secondary infection with a different serotype progresses to the severe form of the disease, dengue hemorrhagic fever/dengue shock syndrome. Currently, there are no licensed vaccines or antiviral drugs to prevent or treat dengue infections. Biodegradable nanoparticles coated with proteins represent a promising method for in vivo delivery of vaccines.

Findings

Here, we used a murine model to evaluate the IgG production after administration of inactivated DENV corresponding to all four serotypes adsorbed to bovine serum albumin nanoparticles. This formulation induced a production of anti-DENV IgG antibodies (p < 0.001). However, plaque reduction neutralization assays with the four DENV serotypes revealed that these antibodies have no neutralizing activity in the dilutions tested.

Conclusions

Our results show that while the nanoparticle system induces humoral responses against DENV, further investigation with different DENV antigens will be required to improve immunogenicity, epitope specicity, and functional activity to make this platform a viable option for DENV vaccines.     

Distribution and natural infection status of synantrophic triatomines (Hemiptera: Reduviidae), vectors of Trypanosoma cruzi,reveals new epidemiological scenarios for chagas disease in the Highlands of Colombia

IntroductionUpdating the distribution and natural infection status of triatomine bugs is critical for planning, prioritizing, and implementing strategies to control Chagas disease (CD), especially after vector reduction programs. After carrying out a control program, the Department of Boyaca contains the highest number of Colombian municipalities certified by PAHO to be free of intradomiciliary transmission of Trypanosoma cruzi by Rhodnius prolixus. The present work describes the spatial distribution, natural infection (NI), and molecular characterization of T. cruzi in synanthropic triatomines from the Department of Boyaca in 2017 and 2018.Materials and methodsAn entomological survey was conducted in 52 municipalities in Boyaca known to have had previous infestations of triatomine bugs. Insects were collected through active searches carried out by technical personnel from the Secretary of Health and community members using Triatomine Collection Stations (PITs-acronym in Spanish). For evaluation of natural infection, triatomines were identified morphologically and grouped in pools of one to five individuals of the same species collected in the same household. DNA derived from the feces of each pool of insects was analyzed by PCR for the presence of T. cruzi using primers flanking the satellite DNA of the parasite. SL-IR primers were used to differentiate TCI from the other DTUs and to identify different genotypes. The distribution of the collected triatomines was analyzed to determine any vector hotspots using spatial recreation.ResultsA total of 670 triatomine bugs was collected, belonging to five species: Triatoma dimidiata (73.2%), Triatoma venosa (16.7%), Panstrongylus geniculatus (5.7%), Rhodnius prolixus (4.4%), and Panstrongylus rufotuberculatus (0.4%), from 29 of the 52 municipalities. In total, 71.6% of the bugs were collected within houses (intradomiciliary) and the rest around the houses (peridomiciliary). Triatoma dimidiata was the most widely distributed species and had the highest natural infection index (37.8%), followed by T. venosa and P. geniculatus. TcI was the only DTU found, with the TcI Dom genotype identified in 80% of positive samples and TcI sylvatic in the other insects. Spatial analysis showed clusters of T. dimidiata and T. venosa in the northeast and southwest regions of Boyaca.ConclusionsAfter some municipalities were certified free of natural transmission within houses (intradomiciliary transmission) of T. cruzi by R. prolixus, T. dimidiata has become the most prevalent vector present, and represents a significant risk of resurgent CD transmission. However, T. venosa, P. geniculatus, and P. rufotuberculatus also contribute to the increased risk of transmission. The presence of residual R. prolixus may undo the successes achieved through vector elimination programs. The molecular and spatial analysis used here allows us to identify areas with an ongoing threat of parasite transmission and improve entomological surveillance strategies.     

The natural history of oviposition on a ginkgophyte fruit from the Middle Jurassic of northeastern China

A distinctive pattern of oviposition lesions occurs on a ginkgoalean seed, Yimaia capituliformis,which likely was inflicted by a kalligrammatid lacewing with a long,sword-like,plant-piercing ovipositor.This newly recorded oviposition type,DT272, occurs in the 165 million-year-old Jiulongshan Formation,of Middle Jurassic age,in Northeastern China.DT272 consists from three to seven,approximately equally spaced lesions with surrounding callus tissue,the fabricator of which targeted fleshy outer and inner tissues ofa ginkgophyte fruit.This distinctive damage also is known from the fleshy attachment pad surfaces of basal bennettitalean bracts.Examination of the life history of this probable ginkgoalean-kalligrammatid oviposition interaction indicates that the spacing of the eggs in substrate tissues disfavored inter-larval contact,but little cart be said of defense and counterdefense strategies between the plant host and the newly hatched imrnatures.