Epitope-tagged Pkhd1 tracks the processing, secretion, and localization of fibrocystin.

Mutations in the PKHD1 gene, which encodes fibrocystin, cause autosomal recessive polycystic kidney disease (ARPKD). Unfortunately, the lack of specific antibodies to the mouse protein impairs the study of splicing, post-translational processing, shedding, and temporal and spatial expression of endogenous fibrocystin at the cellular and subcellular level. Here, we report using a knock-in strategy to generate a null Pkhd1 strain and a strain that expresses fibrocystin along with two SV5-Pk epitope tags engineered in-frame into the third exon, immediately C-terminal to the signal-peptide cleavage site in a poorly conserved region.

Large kindred evaluation of mitofusin 2 novel mutation, extremes of neurologic presentations, and preserved nerve mitochondria.

Background: Mitofusin 2 (MFN2) is a mitochondrial membrane protein mediating mitochondrial fusion and function. Mutated MFN2 is responsible for Charcot-Marie-Tooth type 2A2. In small kindreds, specific MFN2 mutations have been reported to associate with severity of axonal neuropathy, optic atrophy, and involvement of the central nervous system.

Artificial gravity with ergometric exercise preserves the cardiac, but not cerebrovascular, functions during 4 days of head-down bed rest.

Cardiovascular and musculoskeletal deconditioning occurring in long-term spaceflight requires new strategies to counteract these adverse effects. We previously reported that a short-arm centrifuge produced artificial gravity (AG), together with ergometer, has an approving effect on promoting cardiovascular function. The current study sought to investigate whether the cardiac and cerebrovascular functions were maintained and improved using a strategy of AG combined with exercise training on cardiovascular function during 4-day head-down bed rest (HDBR).

Comparison of element concentrations in fir and rhododendron leaves and twigs along an altitudinal gradient.

Concentrations of 23 elements (Ca, K, Mg, P, Al, Cu, Fe, Mn, Mo, Na, Ni, Zn, Ag, Ba, Be, Cd, Co, Cr, Pb, Sb, Th, Tl, and V) in leaf and twig samples of a fir (Abies fabri) and a rhododendron (Rhododendron williamsianum) collected along an altitudinal gradient on Mount Gongga, China, are reported in the present study. Most of the macronutrients (K and P), micronutrients (Fe, Zn, Cu, Na, Ni, Mo, and Al), and trace elements (Pb, Tl, Ag, Cd, Ba, Co, V, Be, and Cr) are significantly enriched in fir when compared to rhododendron; however, Ca, Mg, Mn, Ba, and Cd are more enriched in rhododendron than in fir. Most of the elements in both plants are more significantly enriched in twigs than in leaves.

Copy number variation in the complement factor H-related genes and age-related macular degeneration.

Purpose: To determine the contribution of copy number variation (CNV) in the regulation of complement activation (RCA) locus to the development of age-related macular degeneration (AMD).

Methods: A multiplex ligation-dependent probe amplification assay was developed to quantify the number of copies of CFH, CFHR3, CFHR1, CFHR4, CFHR2, and CFHR5 in humans. Subjects with (451) and without (362) AMD were genotyped using the assay, and the impact on AMD risk was evaluated.

Platelet factor XIII gene expression and embolic propensity in atrial fibrillation.

Nearly 15% of patients with non-valvular atrial fibrillation (NVAF) have left atrial appendage thrombus (LAAT) by transesophageal echocardiography (TEE) and yet the annual stroke rate averages 5%. The aim of this study was to identify variables influencing embolic propensity of LAAT. Platelet RNA was extracted from platelet-rich regions within formalin-fixed, paraffin-embedded specimens obtained from NVAF patients during cardiac surgery (26 LAAT from 23 patients) or peripheral embolectomy (51 thrombi from 41 patients).

Gender difference of unconscious attentional bias in high trait anxiety individuals.

By combining binocular suppression technique and a probe detection paradigm, we investigated attentional bias to invisible stimuli and its gender difference in both high trait anxiety (HTA) and low trait anxiety (LTA) individuals. As an attentional cue, happy or fearful face pictures were presented to HTAs and LTAs for 800 ms either consciously or unconsciously (through binocular suppression). Participants were asked to judge the orientation of a gabor patch following the face pictures.

[Proteomic analysis of human fetal and adult brain cortex].

Objective: To study the differences of protein expression levels in the brain cortex of human fetus and adult with proteomics technique, and provide preliminary data on the change of proteins during brain development.

Methods: Proteins extracted from human temporal lobes in fetal (3 month and 5 month respectively) and adult (30 years old) brain were separated by two-dimensional gel electrophoresis (2DE). The proteins were then stained with colloidal Coomassie blue to produce a high-resolution map of the proteiome.

Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing loss.

DNA methyltransferase 1 (DNMT1) is crucial for maintenance of methylation, gene regulation and chromatin stability. DNA mismatch repair, cell cycle regulation in post-mitotic neurons and neurogenesis are influenced by DNA methylation. Here we show that mutations in DNMT1 cause both central and peripheral neurodegeneration in one form of hereditary sensory and autonomic neuropathy with dementia and hearing loss.

Artificial gravity with ergometric exercise as a countermeasure against cardiovascular deconditioning during 4 days of head-down bed rest in humans.

We have shown previously that combined short-arm centrifuge and aerobic exercise training preserved several physiologically important cardiovascular functions in humans. We hypothesized that artificial gravity (AG) and exercise is effective to prevent changes of physical problems during head-down bed rest (HDBR). To test this hypothesis, 12 healthy male subjects had undergone 4 days of 6° HDBR.

The neuropathies of Waldenström's macroglobulinemia (WM) and IgM-MGUS.

Background: Neuropathy is common in Waldenström's macroglobulinemia (WM, an IgM-associated lymphoplasmacytic lymphoma) and in IgM-monoclonal gammopathy of undetermined significance (IgM-MGUS). Paraneoplastic or paraimmune mechanisms are thought to be involved in the pathogenesis of these neuropathies. Attempts at distinguishing WM and IgM-MGUS neuropathies are lacking especially among bone marrow (BM) confirmed patients.

Germline PKHD1 mutations are protective against colorectal cancer.

The autosomal recessive polycystic kidney disease (ARPKD) gene, PKHD1, has been implicated in the genesis or growth of colorectal adenocarcinoma, as a high level of somatic mutations was found in colorectal tumor tissue. To determine whether carriers of a single PKHD1 mutation are at increased risk of colorectal carcinoma, we assessed the prevalence of the commonest European mutation, T36M. First, we assayed a European cohort of ARPKD patients and found T36M was responsible for 13.

Historical trends of heavy metal contamination and their sources in lacustrine sediment from Xijiu Lake, Taihu Lake catchment, China.

Concentrations of Cd, Cr, Cu, Pb, Zn and Hg in Xijiu Lake sediment from the Taihu Lake catchment, China, were analyzed. Their contamination state was investigated based on the geoaccumulation index and enrichment factors. Statistical analysis was used to differentiate the anthropogenic versus natural sources of heavy metals (HMs), and the anthropogenic accumulation fluxes were calculated to quantify anthropogenic contribution to HMs.

Prevalence of CDKN2A mutations in pancreatic cancer patients: implications for genetic counseling.

Germline mutations in CDKN2A have been reported in pancreatic cancer families, but genetic counseling for pancreatic cancer risk has been limited by lack of information on CDKN2A mutation carriers outside of selected pancreatic or melanoma kindreds. Lymphocyte DNA from consecutive, unselected white non-Hispanic patients with pancreatic adenocarcinoma was used to sequence CDKN2A. Frequencies of mutations that alter the coding of p16INK4 or p14ARF were quantified overall and in subgroups.

Combined short-arm centrifuge and aerobic exercise training improves cardiovascular function and physical working capacity in humans.

Background: Musculoskeletal and cardiovascular deconditioning occurring in long-term spaceflight gives rise to the needs to develop new strategies to counteract these adverse effects. Short-arm centrifuge combined with ergometer has been proposed as a strategy to counteract adverse effects of microgravity. This study sought to investigate whether the combination of short-arm centrifuge and aerobic exercise training have advantages over short-arm centrifuge or aerobic exercise training alone.

[Apoptosis in myocyte after repeated + Gz exposures in rats].

Objective: To observe the effects of repeated + Gz exposures on the apoptosis of myocyte in rats.

Methods: Twelve male Sprague-Dawley rats were randomly divided into three groups: Control group, + 6Gz group and + 10Gz group. The rats of + Gz groups were exposed to + 6Gz for 3 min, + 10Gz for 3 min respectively, 1 b/d, 1 week.

[Liposomal encapsulation of free anthraquinones in rhizoma et radix rhei and its quality control].

Objective: To encapsulate the free anthraquiones in Rhizoma et Radix Rhei (rhein, chrysophanol, physcione, emodin and aloeemodin) in liposomes and characterize the liposomes.

Methods: The liposomes were separated from free drug with sephadex G-50 with HPLC determination of the free anthraquinones in liposomes, then its entrapment efficiency was calculated. Ethanol injection method was used to prepare the liposomes with the addition of a suitable amount Ca2+ in the medium.

Methylation markers for small cell lung cancer in peripheral blood leukocyte DNA.

Introduction: Small cell lung cancer (SCLC) is the most aggressive form of lung malignancy.

Methods: To identify and validate potential DNA methylation markers for risk assessment and disease detection, we examined peripheral blood leukocyte DNA specimens for methylation differences between SCLC cases and controls. We tested 1505 CpG sites using the Illumina Beadchip assay and validated 9 CpG sites using pyrosequencing technology.

Perceptual fusion tendency of speech sounds.

To discriminate and to recognize sound sources in a noisy, reverberant environment, listeners need to perceptually integrate the direct wave with the reflections of each sound source. It has been confirmed that perceptual fusion between direct and reflected waves of a speech sound helps listeners recognize this speech sound in a simulated reverberant environment with disrupting sound sources. When the delay between a direct sound wave and its reflected wave is sufficiently short, the two waves are perceptually fused into a single sound image as coming from the source location.

Religious beliefs influence neural substrates of self-reflection in Tibetans.

Previous transcultural neuroimaging studies have shown that the neural substrates of self-reflection can be shaped by different cultures. There are few studies, however, on the neural activity of self-reflection where religion is viewed as a form of cultural expression. The present study examined the self-processing of two Chinese ethnic groups (Han and Tibetan) to investigate the significant role of religion on the functional anatomy of self-representation.

Cystic fibrosis transmembrane conductance regulator gene mutation and lung cancer risk.

The cystic fibrosis transmembrane conductance regulator (CFTR) holds an important role in retaining lung function, but its association with lung cancer is unclear. A case-control study was conducted to determine the possible associations of the genetic variants in the CFTR gene with lung cancer risk. Genotypes of the most common deletion DeltaF508, one functional SNP, and eight tag SNPs in the CFTR gene were determined in 574 lung cancer patients and 679 controls.

Scapuloperoneal spinal muscular atrophy and CMT2C are allelic disorders caused by alterations in TRPV4.

Scapuloperoneal spinal muscular atrophy (SPSMA) and hereditary motor and sensory neuropathy type IIC (HMSN IIC, also known as HMSN2C or Charcot-Marie-Tooth disease type 2C (CMT2C)) are phenotypically heterogeneous disorders involving topographically distinct nerves and muscles. We originally described a large New England family of French-Canadian origin with SPSMA and an American family of English and Scottish descent with CMT2C. We mapped SPSMA and CMT2C risk loci to 12q24.

Childhood exposure to secondhand smoke and functional mannose binding lectin polymorphisms are associated with increased lung cancer risk.

Background: Exposure to secondhand smoke during adulthood has detrimental health effects, including increased lung cancer risk. Compared with adults, children may be more susceptible to secondhand smoke. This susceptibility may be exacerbated by alterations in inherited genetic variants of innate immunity genes.

Top-down modulation of prepulse inhibition of the startle reflex in humans and rats.

Prepulse inhibition (PPI) is the attenuation of the startle reflex when the sudden intense startling stimulus is shortly preceded by a weaker, non-startling sensory stimulus (prepulse). PPI reflects a protective function of reducing disruptive influences to the processing of prepulse signals and is recognized as a model of sensorimotor gating. In humans, PPI is modulated by both attentional and emotional responses to prepulse, indicating that this early-stage gating is top-down modulated by higher-order cognitive processes.

Deficiencies in Chfr and Mlh1 synergistically enhance tumor susceptibility in mice.

Genetic instability, which leads to an accumulation of various genetic abnormalities, has been considered an essential component of the human neoplasic transformation process. However, the molecular basis of genomic instability during tumorigenesis remains incompletely understood. Growing evidence indicates that checkpoint with forkhead and ring finger domains (CHFR), a recently identified mitotic checkpoint protein, plays an important role in maintaining chromosome integrity and functions as a tumor suppressor.