Cyanobacteria produce a high variety of hepatotoxic peptides in lichen symbiosis

Lichens are symbiotic associations between fungi and photosynthetic algae or cyanobacteria. Microcystins are potent toxins that are responsible for the poisoning of both humans and animals. These toxins are mainly associated with aquatic cyanobacterial blooms, but here we show that the cyanobacterial symbionts of terrestrial lichens from all over the world commonly produce microcystins. We screened 803 lichen specimens from five different continents for cyanobacterial toxins by amplifying a part of the gene cluster encoding the enzyme complex responsible for microcystin production and detecting toxins directly from lichen thalli. We found either the biosynthetic genes for making microcystins or the toxin itself in 12% of all analyzed lichen specimens. A plethora of different microcystins was found with over 50 chemical variants, and many of the variants detected have only rarely been reported from free-living cyanobacteria. In addition, high amounts of nodularin, up to 60 μg g(-1), were detected from some lichen thalli. This microcystin analog and potent hepatotoxin has previously been known only from the aquatic bloom-forming genus Nodularia. Our results demonstrate that the production of cyanobacterial hepatotoxins in lichen symbiosis is a global phenomenon and occurs in many different lichen lineages. The very high genetic diversity of the mcyE gene and the chemical diversity of microcystins suggest that lichen symbioses may have been an important environment for diversification of these cyanobacteria.     

Extreme sarcoplasmic reticulum volume loss and compensatory T-tubule remodeling after Serca2 knockout

Cardiomyocyte contraction and relaxation are controlled by Ca(2+) handling, which can be regulated to meet demand. Indeed, major reduction in sarcoplasmic reticulum (SR) function in mice with Serca2 knockout (KO) is compensated by enhanced plasmalemmal Ca(2+) fluxes. Here we investigate whether altered Ca(2+) fluxes are facilitated by reorganization of cardiomyocyte ultrastructure. Hearts were fixed for electron microscopy and enzymatically dissociated for confocal microscopy and electrophysiology. SR relative surface area and volume densities were reduced by 63% and 76%, indicating marked loss and collapse of the free SR in KO. Although overall cardiomyocyte dimensions were unaltered, total surface area was increased. This resulted from increased T-tubule density, as revealed by confocal images. Fourier analysis indicated a maintained organization of transverse T-tubules but an increased presence of longitudinal T-tubules. This demonstrates a remarkable plasticity of the tubular system in the adult myocardium. Immunocytochemical data showed that the newly grown longitudinal T-tubules contained Na(+)/Ca(2+)-exchanger proximal to ryanodine receptors in the SR but did not contain Ca(2+)-channels. Ca(2+) measurements demonstrated a switch from SR-driven to Ca(2+) influx-driven Ca(2+) transients in KO. Still, SR Ca(2+) release constituted 20% of the Ca(2+) transient in KO. Mathematical modeling suggested that Ca(2+) influx via Na(+)/Ca(2+)-exchange in longitudinal T-tubules triggers release from apposing ryanodine receptors in KO, partially compensating for reduced SERCA by allowing for local Ca(2+) release near the myofilaments. T-tubule proliferation occurs without loss of the original ordered transverse orientation and thus constitutes the basis for compensation of the declining SR function without structural disarrangement.     

Colonic methanogenesis in vivo and in vitro and fecal pH after resection of colorectal cancer and in healthy intact colon

Purpose  

We compared colonic methanogenesis in vivo and in vitro as well as fecal pH in healthy subjects and in patients with resected colorectal cancer thus without the possible confounding effects of the tumor.     

Thyroid effects of endocrine disrupting chemicals

In recent years, many studies of thyroid-disrupting effects of environmental chemicals have been published. Of special concern is the exposure of pregnant women and infants, as thyroid disruption of the developing organism may have deleterious effects on neurological outcome. Chemicals may exert thyroid effects through a variety of mechanisms of action, and some animal experiments and in vitro studies have focused on elucidating the mode of action of specific chemical compounds. Long-term human studies on effects of environmental chemicals on thyroid related outcomes such as growth and development are still lacking. The human exposure scenario with life long exposure to a vast mixture of chemicals in low doses and the large physiological variation in thyroid hormone levels between individuals render human studies very difficult. However, there is now reasonably firm evidence that PCBs have thyroid-disrupting effects, and there is emerging evidence that also phthalates, bisphenol A, brominated flame retardants and perfluorinated chemicals may have thyroid disrupting properties.     

The diagnostic accuracy of an incidental memory modification of the Boston Naming Test (memo-BNT) in differentiating between normal aging and mild Alzheimer's disease

Early Alzheimer's disease (AD) is associated with deficits in episodic memory. Semantic memory and naming have also been found to be affected, although to a lesser degree than episodic memory. Most episodic memory tests used in clinical settings assess intentional memory. The aim of the present paper was to present an incidental memory modification of the Boston Naming Test (memo-BNT) and to study the diagnostic accuracy of the BNT and the memo-BNT in differentiating between healthy old controls and AD patients. There were three groups in the study: 22 young controls (mean age 21.7), 23 normally aged old controls (mean age 70.6), and 23 patients with mild AD (mean age 74.0). There were no differences in the memo-BNT test scores between the old and young control participants. There were, however, significant differences between the AD patients and both control groups in several of the memo-BNT measures. Incidental free recall was the best measure in discriminating between the healthy aged controls and the AD patients (AUC?=?.939) and it had a better diagnostic accuracy than naming (AUC?=?880). The results indicate that the memo-BNT could be used in clinical settings especially to differentiate between normal aging and mild AD.     

Raised Activity of L-Type Calcium Channels Renders Neurons Prone to Form Paroxysmal Depolarization Shifts

Neuronal L-type voltage-gated calcium channels (LTCCs) are involved in several physiological functions, but increased activity of LTCCs has been linked to pathology. Due to the coupling of LTCC-mediated Ca²⁺ influx to Ca²⁺-dependent conductances, such as K_Ca or non-specific cation channels, LTCCs act as important regulators of neuronal excitability. Augmentation of after-hyperpolarizations may be one mechanism that shows how elevated LTCC activity can lead to neurological malfunctions. However, little is known about other impacts on electrical discharge activity. We used pharmacological up-regulation of LTCCs to address this issue on primary rat hippocampal neurons. Potentiation of LTCCs with Bay K8644 enhanced excitatory postsynaptic potentials to various degrees and eventually resulted in paroxysmal depolarization shifts (PDS). Under conditions of disturbed Ca²⁺ homeostasis, PDS were evoked frequently upon LTCC potentiation. Exposing the neurons to oxidative stress using hydrogen peroxide also induced LTCC-dependent PDS. Hence, raising LTCC activity had unidirectional effects on brief electrical signals and increased the likeliness of epileptiform events. However, long-lasting seizure-like activity induced by various pharmacological means was affected by Bay K8644 in a bimodal manner, with increases in one group of neurons and decreases in another group. In each group, isradipine exerted the opposite effect. This suggests that therapeutic reduction in LTCC activity may have little beneficial or even adverse effects on long-lasting abnormal discharge activities. However, our data identify enhanced activity of LTCCs as one precipitating cause of PDS. Because evidence is continuously accumulating that PDS represent important elements in neuropathogenesis, LTCCs may provide valuable targets for neuroprophylactic therapy.     

Acceptance of dental care following early extractions under rectal sedation with diazepam in preschool children

The aim of the study was to evaluate the effect of amnesia in preschool children on their later acceptance of dental care. Forty-six 4-6-year-old children, who between 2 and 4 years previously had had primary incisors extracted because of trauma, were reexamined for dental health and acceptance of dental care. The extractions had been performed under rectal sedation with diazepam (0.7 mg/kg body weight). Information about dental treatment and degree of cooperation during the intervening period was obtained from records at the referring clinic. The parents were interviewed about their child's experience of amnesia concerning the extractions, background variables, and experiences of dental care before the follow-up examination. Amnesia concerning the extractions was reported in 85% of the children. Twenty-nine percent had on some occasion exhibited behavior management problems (BMP) during the intervening period. Lack of amnesia was significantly associated with BMP (P < 0.002). Children without amnesia concerning the extractions tended to accept dental care less well at the reexamination. Parents were able to predict their child's acceptance of dental care at the follow-up with a significant degree of success (P = 0.02). In conclusion, amnesia in preschool children concerning extractions seems to be essential to facilitate positive acceptance of future dental care.     

The metabolic consequences of thyroxine replacement in adult hypopituitary patients

The metabolic consequences of thyroxine replacement in patients with central hypothyroidism (CH) need to be evaluated. The aim was to examine the outcome of thyroxine replacement in CH. Adult hypopituitary patients (n?=?1595) with and without CH from KIMS (Pfizer International Metabolic Database) were studied before and after 2?years of GH replacement. CH patients (CH, n?=?1080) were compared with TSH sufficient patients (TSHsuff n?=?515) as one group and divided by thyroxine dose/kg/day into tertiles (CHlow-mid-high). Anthropometry, fasting glucose, glycosylated haemoglobin (HbA1c), blood pressure, lipids, IGF-I SDS, quality of life and morbidity were studied. Analyses were standardized for gender, age, number and types of pituitary insufficiencies, stimulated GH peak, age at GH deficiency onset, aetiologies and, when appropriate, for weight and GH dose. At baseline, TSHsuff patients did not differ from CH or CHmid in any outcome. CHlow (≤1.18?μg thyroxine/kg/day) had increased weight, BMI and larger waist circumference (WC), CHhigh (≥1.58?μg thyroxine/kg/day) had lower weight, BMI, WC and IGF-I than TSHsuff and compared to their predicted weights, BMIs and WCs. For every 0.1?μg/kg/day increase of thyroxine dose, body weight decreased 1.0?kg, BMI 0.3?kg/m(2), and WC 0.65?cm. The GH sensitivity of the CH group was higher (0.76?±?0.56 SDS/mg GH) than that of TSHsuff patients (0.58?±?0.64 SDS/mg GH), P?相似文献