Disturbance Of Protein Synthesis Research Articles

Noise suppression in stochastic genetic circuits using PID controllers.

Inside individual cells, protein population counts are subject to molecular noise due to low copy numbers and the inherent probabilistic nature of biochemical processes. We investigate the effectiveness of proportional, integral and derivative (PID) based feedback controllers to suppress protein count fluctuations originating from two noise sources: bursty expression of the protein, and external disturbance in protein synthesis. Designs of biochemical reactions that function as PID controllers are discussed, with particular focus on individual controllers separately, and the corresponding closed-loop system is analyzed for stochastic controller realizations. Our results show that proportional controllers are effective in buffering protein copy number fluctuations from both noise sources, but this noise suppression comes at the cost of reduced static sensitivity of the output to the input signal. In contrast, integral feedback has no effect on the protein noise level from stochastic expression, but significantly minimizes the impact of external disturbances, particularly when the disturbance comes at low frequencies. Counter-intuitively, integral feedback is found to amplify external disturbances at intermediate frequencies. Next, we discuss the design of a coupled feedforward-feedback biochemical circuit that approximately functions as a derivate controller. Analysis using both analytical methods and Monte Carlo simulations reveals that this derivative controller effectively buffers output fluctuations from bursty stochastic expression, while maintaining the static input-output sensitivity of the open-loop system. In summary, this study provides a systematic stochastic analysis of biochemical controllers, and paves the way for their synthetic design and implementation to minimize deleterious fluctuations in gene product levels.

Calreticulin Deficiency Disturbs Ribosome Biogenesis and Results in Retardation in Embryonic Kidney Development.

Nephrogenesis is driven by complex signaling pathways that control cell growth and differentiation. The endoplasmic reticulum chaperone calreticulin (Calr) is well known for its function in calcium storage and in the folding of glycoproteins. Its role in kidney development is still not understood. We provide evidence for a pivotal role of Calr in nephrogenesis in this investigation. We show that Calr deficiency results in the disrupted formation of an intact nephrogenic zone and in retardation of nephrogenesis, as evidenced by the disturbance in the formation of comma-shaped and s-shaped bodies. Using proteomics and transcriptomics approaches, we demonstrated that in addition to an alteration in Wnt-signaling key proteins, embryonic kidneys from Calr−/− showed an overall impairment in expression of ribosomal proteins which reveals disturbances in protein synthesis and nephrogenesis. CRISPR/cas9 mediated knockout confirmed that Calr deficiency is associated with a deficiency of several ribosomal proteins and key proteins in ribosome biogenesis. Our data highlights a direct link between Calr expression and the ribosome biogenesis.

Функциональные методы диагностики нарушений гена CFTR и его продукта

Cystic fibrosis is a hereditary disease caused by the mutation of the CFTR gene, as a consequence of the mutation of the gene is a disturbance of protein synthesis, structure and function of protein of the transmembrane conduction regulator of cystic fibrosis (CFTR), as a result of which the chlorine channels become pathologically impenetrable for chloride ions. Diagnosis of cystic fibrosis is a complex process due to the variety of mutations and phenotypes. In the article, various methods of diagnostics in historical aspect are considered. The sweat test has stood the test of time and remains in routine clinical practice the main diagnostic test that determines the function of the CFTR protein. However, false-positive and false-negative results of the sweat test are found in 12–15% of all the tests, the diagnostic complexity takes place at the borderline test results. The new methods for diagnosing cystic fibrosis and evaluating the effectiveness of targeted therapy (modulators of the protein CFTR) in the Russian Federation are following: nasal potential difference and intestinal current measurement, as well as the method of intestinal organoids. These methods are also bio-analyzers of the CFTR function. Both potential difference measurement tests were standardized and proved useful in confirming or eliminating CFTR dysfunction and take a leading place in the diagnosis of cystic fibrosis at the boundary values of the sweat samples also in the presence of rare mutations with unclear clinical significance. The review describes a test of intestinal organoids that is not diagnostic, but it can be used to understand whether a rare mutation has clinical significance for the patient and whether the patient responds to the therapeutic effects of CFTR protein modulators.

Assessing the Combined Toxicity of BMAA and Its Isomers 2,4-DAB and AEG In Vitro Using Human Neuroblastoma Cells.

The non-protein amino acid (NPAA) ß-methylamino-L-alanine (BMAA) is produced by a diverse range of cyanobacteria, diatoms and dinoflagellates, and is present in both aquatic and terrestrial ecosystems globally. Exposure to BMAA has been implicated in the development of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD) and Parkinson's disease (PD). BMAA is often found in nature along with its structural isomers 2,4-diaminobutyric acid (2,4-DAB) and aminoethylglycine (AEG); however, the toxicity of these NPAAs in combination has not been examined. We have previously demonstrated that BMAA induces endoplasmic reticulum (ER) stress and increases caspase and cathepsin activity in human neuroblastoma cells (SH-SY5Y), effects consistent with proteotoxic stress due to disturbances in protein synthesis, folding or turnover. The current study investigates whether 2,4-DAB and AEG share a similar mechanism of toxicity to BMAA, and if simultaneous exposure of cells to BMAA and its isomers results in increased toxicity in vitro. We show that a 48-h treatment with both 500μM BMAA and 2,4-DAB decreases cell viability in vitro whereas AEG was not cytotoxic under the same conditions. Treatment of SH-SY5Y cells with 2,4-DAB did not increase expression of ER stress markers. Combined treatment of cells with BMAA and 2,4-DAB resulted in increased caspase activity and increased apoptosis above that of BMAA or 2,4-DAB on their own. These results suggest that 2,4-DAB does not share the same mechanism of toxicity as BMAA but the presence of 2,4-DAB increases the toxicity of BMAA to human cells in vitro.

Antimicrobial evaluation of new metallic complexes with xylitol active against P. aeruginosa and C. albicans: MIC determination, post-agent effect and Zn-uptake

Xylitol (xylH5) is metabolized via the pentose pathway in humans, but it is unsuitable as an energy source for many microorganisms where it produces a xylitol-induced growth inhibition and disturbance in protein synthesis. For this reason, xylitol is used in the prophylaxis of several infections. In the search of better antimicrobial agents, new copper and zinc complexes with xylitol were synthesized and characterized by analytical and spectroscopic methods: Na2[Cu3(xylH−4)2]·NaCl·4.5H2O (Cu-xyl) and [Zn4(xylH−4)2(H2O)2]·NaCl·3H2O (Zn-xyl). Both copper and zinc complexes presented higher MIC against Pseudomona aeruginosa than the free xylitol while two different behaviors were found against Candida albicans depending on the complex. The growth curves showed that Cu-xyl presented lower activity than the free ligand during all the studied period. In the case of Zn-xyl the growth curves showed that the inhibition of the microorganism growth in the first stage was equivalent to that of xylitol but in the second stage (after 18h) Zn-xyl inhibited more. Besides, the PAE (post agent effect) obtained for Zn-xyl and xyl showed that the recovery from the damage of microbial cells had a delay of 14 and 13h respectively. This behavior could be useful in prophylaxis treatments for infectious diseases where it is important that the antimicrobial effect lasts longer.With the aim to understand the microbiological activities the analysis of the particle size, lipophilicity and Zn uptake was performed.

Assessment of the toxic effect exerted by fluorescent pseudomonads on embryos and larvae of the sea urchin Strongylocentrotus nudus

Strains of bacteria capable of growing on artificial culture media were isolated from the fouling of brass plates submerged in Nha Trang Bay, South China Sea, and from tissues of the seastar Distolasterias nipon, caught in Peter the Great Bay, Sea of Japan. According to the complex of data of genetic and physiological/biochemical analyzes, two strains of cultivated bacteria were identified by us as the species Pseudomonas aeruginosa, two strains as Pseudomonas fluorescens, and one strain as Ruegeria sp. It was shown that the cultivated strains of P. aeruginosa released exotoxins, particularly phenazine pigments, into the environment. Production of the toxins did not depend on presence of a target organism in the system and was aimed at regulation of interactions in the microbial community. The toxicity of the studied natural isolates of fluorescent pseudomonads was analyzed by using embryos and larvae of the sea urchin Strongylocentrotus nudus, which are the sensitive and dynamic toxicological sea-urchin embryo test (SET) system. As was established, exotoxins produced by the strains of P. aeruginosa inhibit activity of cilia in sea urchin larvae, as well as disturb processes of cell differentiation in embryos and larvae. Their toxic influence is accompanied by disturbances of protein synthesis and the disruptions of cytoskeleton in the course of zygote cleavage and larval development. Unlike P. aeruginosa, the strains of P. fluorescens and Ruegeria sp. did not exert the toxic effect on SET. The obtained data allow considering objects of the environment as the natural reservoir of opportunistic microorganisms posing a potential threat to human, whereas the use of SET for determination of toxicity of isolated bacteria provides an opportunity to study the mechanisms of their interactions with organisms in marine ecosystems.

A 2-DE-based proteomic study on the toxicological effects of cisplatin in L02 cells

Cisplatin is a chemotherapeutic agent for the treatment of various cancers. In this study, cisplatin-induced effects were characterized in vitro model of human liver cells (L02) using 2-DE-based proteomics. Results indicated that different cisplatin treatments primarily induced disturbances in protein synthesis and oxidative stress via differential mechanisms. Since the experimental concentrations of cisplatin described a hormesis effect in cell proliferation of L02 cells, it was expected to reveal the hormesis effects using proteomic markers. However, only confilin-1 was commonly up-regulated in three concentrations of cisplatin treatments showing a hormesis effects with a U-shape regulation. These results were highly consistent with many other toxico-proteomic studies, indicating that the toxico-proteomic responses based on dose-dependent protein responses were incongruent with the theoretically linear or hormetic concentration–effect relationship. Our findings suggested that a macroscopic hormesis phenomenon on the cell proliferation could not be reflected by proteomic responses induced by cisplatin treatments.

Зміни у функціонуванні шлунка щура після інтрагастрального введення корвітину в підвищених дозах

Intragastric administration of corvitin at doses of 10, 20 and 40 mg/kg dose-dependently increased the volume of gastric juice and the total production of hydrochloric acid (HA). Amplification of hexosamines and cysteine production was observed only when the study drug was administered at a dose of 10 mg/kg. When corvitin was used at 20 and 40 mg/kg, these parameters were at the level of control values. Protein production increased in response to 10 and 20 mg/kg corvitin, but fell below the control values after administration of 40 mg/kg of the drug. The level of blood flow in the gastric mucosa increased following administration of 10 mg/kg corvitin, was not different from the baseline after 20 mg/kg of the drug and significantly decreased in response to 40 mg/kg of flavonoid. Our results indicate that a single intragastric application of corvitin at dose of 10 mg/kg activates gastric defense mechanisms. At 20 and 40 mg/kg, corvitin does not affect them but gradually reduces blood flow in gastric mucosa, causes a disturbance of protein synthesis and hypersecretion of HA into the cavity of the stomach, which can lead to disruption of the digestive process and the integrity of gastric mucosa.

Quantum molecular biological investigation of the onset of cancer

Accurate stereostructure of DNA in the nucleosomes has been established recently with the aid of more precise crystal structure investigations. Using this structure, Hartree–Fock crystal orbital calculations have been performed on the DNA parts of the nucleosomes. The obtained band structure was used to calculate the hole mobilities of the corresponding DNA parts. These results were used further to investigate the effect of Cl− ions which enter in the cell nucleus through channels in the nuclear membrane. Our results show how Cl− ions can weaken the DNA–protein interactions which can lead to the onset of cancer. Other molecules can also bind to DNA or photon can excite a nucleotide base in the stack. In both cases, a soliton can appear which causes long‐range effect (disturbance of protein synthesis, double strand breaking). © 2014 Wiley Periodicals, Inc.

Fullerene C<SUB>60</SUB> Prevents Neurotoxicity Induced by Intrahippocampal Microinjection of Amyloid-<I>β</I> Peptide

The dynamics of the state of hippocampal pyramidal neurons after intrahippocampal microinjections of (1) amyloid-beta25-35 (1.6 nmol/1 microl), (2) an aqueous molecule-colloidal solution of C60 (0.46 nmol/1 microl) and (3) an aqueous molecule-colloidal solution of C60 before amyloid-beta25-35 administration were analysed in rats. This model allowed us to study the role of amyloid-beta25-35 in the pathogenesis of Alzheimer's disease and to test anti-amyloid substances. Methods of fluorescent (acridine orange) and brightfield (cresyl violet and immunohistochemistry) microscopy were used. Acridine orange staining indicated changes in protein synthesis intensity due to alterations in the rRNA state of neuron ribosomes. One day after administration of amyloid-beta25-35, the intensity of protein synthesis in the population of morphologically intact cells decreased by 45%. By day 14, degeneration occurred in the majority of pyramidal cells, and amyloid-beta25-35 deposits were observed in the neuronal cytoplasm. In necrotic cells, acridine orange staining of the cytoplasm was drastically increased as a result of RNA degradation rather than due to an increase in protein synthesis. Because amyloid-beta25-35 administration provoked oxidative stress, we assumed that an aqueous molecule-colloidal solution of C60 administered before amyloid-beta25-35 prevented protein synthesis changes on day 1, while acting as an antioxidant, and by day 14 it inhibited neurodegeneration and amyloid-beta25-35 accumulation. Based on the data that an aqueous molecule-colloidal solution of C60 prevented amyloid-beta25-35 aggregation in in vitro experiments and based on our present evidence on the antitoxicity of an aqueous molecule-colloidal solution of C60, we suggest that functionalised C60 prevents/diminishes amyloid-beta25-35 aggregation in vivo as well. Thus, an aqueous molecule-colloidal solution of C60 administered at a low concentration before amyloid-beta2-35, prevented disturbances in protein synthesis, neurodegeneration and formation amyloid-beta25-35 deposits in hippocampal pyramidal neurons in vivo. This evidence gives promise that functionalised C60 can be used to develop anti-amyloid drugs combining antioxidant and anti-aggregative properties.

The most important stages of the mechanism of action in vivo of carcinogen diethylnitrosoamine and its effect on the synthesis of RNA, proteins, DNA, and deoxyribonucleotides

The mechanisms of nitric oxide (NO) generation from exogenous and endogenous sources, induced by the addition of the carcinogen diethylnitrosoamine (DENA) to rat organism have been studied. Within 15 h after the addition of DENA, the carcinogen itselt acts as an exogenous NO donor. The products of protein degradation (the process induced by DENA) act as endogenous donors of NO. It was shown that the generation of nitric oxide from diethylnitrosoamine leads to deep hemic and tissue hypoxia and induces the inactivation of oxygen-dependent enzymes, including ribonucleotide reductase, and the inhibition of ATP synthesis. Under these conditions, the protein synthesis and as a consequence the synthesis of deoxyribonucleotides and DNA are strongly suppressed; i.e., diethylnitrosoamine produces the effect similar to the action of the antibiotic cycloheximide, an inhibitor of translation. The administration of cycloheximide to the animal organism also led to the appearance of a considerable amount of nitric oxide in the blood. It is assumed that nitric oxide initiates (on the administration of the carcinogen) or at least enhances (on the administration of cycloheximide) the blockage of the synthesis of the protein, deoxyribonucleotides, and DNA. In response to the disturbance of protein synthesis, the complex of enzymes is activated that accomplish the utilization of the degradation products of proteins, including the inducible form of NO synthase.

Morphometric Changes Induced by Amino Acid Supplementation in Skeletal and Cardiac Muscles of Old Mice

Aging is associated with progressive structural disorganization of muscular and cardiac fibers, decreasing functional capacity, and increased rates of disease and death. Aging is also characterized by disturbances in protein synthesis with impaired cellular organelle functions, particularly in the mitochondria. The availability of amino acids is a key factor for the overall metabolism of mammals and exogenous supplements of amino acid mixtures (AAm) could be a valid therapeutic strategy to improve quality of life, avoiding malnutrition and muscle wasting in the elderly. We investigated the morphoquantitative effects of long-term AAm supplementation on the mitochondria and sarcomeres (by electron microscope) and on collagen matrix deposition (by histologic techniques) in both skeletal and cardiac muscles of young and aged mice. Our data showed that old animals have fewer mitochondria and massive fibrosis in both muscles. Long-term AAm supplementation increased the number and volume of mitochondria and sarcomeres and decreased fibrosis in both skeletal muscle and hearts in old rats. These findings indicate that AAm restored muscular morphologic parameters and probably improved the mechanical performance of these organs.

Increased tissue protein synthesis during spontaneous inflammatory bowel disease in HLA-B27 rats.

Inflammatory bowel diseases (IBDs) are associated with an increased whole-body protein turnover. In certain drug-induced experimental models of IBD, disturbances of protein synthesis in tissues have been reported recently, but it is unclear if similar disturbances occur in other chronic intestinal diseases. Therefore we investigated changes in protein synthesis in different tissues of HLA-B27 (human leucocyte antigen B27) transgenic rats that develop spontaneously chronic inflammation, with major involvement of the colon. Protein synthesis rate in HLA-B27 rats was shown to be higher in nine different tissues compared with control (Fisher 344) rats. The absolute rate of protein synthesis was highly stimulated at the main inflammatory site (+290% in the colon). However, liver, muscle and skin appeared to be major contributors to the increased protein synthesis observed at the whole-body level. Despite the increased protein synthesis, HLA-B27 rats presented a marked atrophy of muscles, which suggests an increased proteolysis. These results contrast with metabolic disturbances described in acute inflammation and colitis induced by drugs (i.e. dextran sodium sulphate). The present study suggests that the modifications of protein metabolism are strongly influenced by the type of the inflammatory diseases and thus by the underlying mechanisms, which result in different metabolic adaptations and specific nutritional requirements.

Ischemic depolarization monitoring: evaluation of protein synthesis in the hippocampal CA1 after brief unilateral ischemia in a gerbil model

The authors investigate whether depolarization monitoring is an accurate index of ischemic damage in a gerbil model of unilateral ischemia and assess the effects of brief cerebral ischemia on protein synthesis in this model. The authors evaluate the relationship between the duration of ischemic depolarization caused by unilateral carotid artery occlusion and ischemia-induced neuronal damage in the CA1 subregion 7 days after ischemia. When the depolarization period exceeded 210 seconds, some neuronal damage was detected, and almost complete neuronal damage was observed when the period exceeded 400 seconds. Uptake of [14C]valine was evaluated in ischemic and nonischemic CA1 subregions. Disturbances in protein synthesis were seen in all animals subjected to sublethal ischemia (< or = 210-second depolarization) after a 10-minute recirculation, and after 2 and 6 hours of recirculation in animals with 90 seconds or more of depolarization. Inhibition of protein synthesis was proportional to the length of the depolarization period. After 1 and 3 days of recirculation, protein synthesis returned to near normal, and some animals with depolarizations greater than 180 to 210 seconds showed an increase in protein synthesis. Protein synthesis in all animals returned to normal levels after 7 days of recirculation. In this study the authors demonstrate that monitoring of ischemic depolarization is a useful method to predict neuronal damage in the hippocampal CA1 in this model, and they identify subtle changes in protein synthesis after brief ischemia. Sublethal ischemia was divided into three categories by its depolarization period (< 90 seconds, 90-180 seconds, and > 180-210 seconds) with regard to changes in protein synthesis.

Effects of a traumatic neocortical lesion on cerebral metabolism and gene expression of rats.

The effects of a traumatic neocortical lesions, induced by transcranial cold injury, on brain metabolism and gene expression were examined. The surrounding of the lesions was characterized by increased glucose and lactate levels without major disturbances of protein synthesis or energy state. A transient pH decrease by 0.4 units was noticed 1 h post-injury, which shifted towards alkaline values by 3 h. The metabolic disturbances did not differ between injured animals with spontaneous spreading depressions (SD, n = 14) and those without SD (n = 7). In SD animals, c-fos mRNA was strongly elevated in the injury-remote cortex, but hsp72 mRNA was not enhanced. Thus, in contrast to focal ischemia, the metabolic dysfunction around traumatic cortical lesions is not aggravated by SD.

Acute cerebral infarct: physiopathology and modern therapeutic concepts

This review focuses on the pathophysiological changes in acute cerebral ischemia, with special emphasis on disturbances of the cerebral blood flow (CBF) and the associated penumbra concept. Alternatively, the model of peri-infarct depolarization is demonstrated. Metabolic and molecular changes caused by cerebral ischemia and reperfusion are discussed, namely energy failure, release of glutamate with an excitatoric burst, calcium influx in neurons, generation of free radicals, activation of different proteases, disturbances of protein synthesis, induction of gene expression and apoptosis, loss of membrane integrity, edema formation and microvascular disturbances. In summary, the pathophysiological changes after focal cerebral ischemia and reperfusion are most adequately described by a network of interacting different mechanisms of tissue alterations. The simple concept of a cascade of ischemic effects which would be easy to block seems to be less applicable. A time window of approximately 6 h for the acute stroke therapy is postulated on the base of the above mentioned pathophysiological changes. The recently introduced treatment regimen with optimized basic treatment, recanalization using thrombolysis and neuroprotection by different agents is presented. Different modes of a possible intervention are discussed. Modern concepts of stroke therapy including stroke-unit care and thrombolysis with add-on neuroprotection seem to have potential for improving the outcome of acute stroke patients.

The effect of global ischemia and recirculation of rat brain on protein synthesisin vitro

Transient cerebral ischemia causes long-lasting inhibition of protein synthesis despite recovery of energy metabolism. We investigated the question if this inhibition is due to the formation of a suppression factor which interferes with the function of the protein synthesizing machinery. For this purpose rats were submitted to 20 minutes four vessel-occlusion followed by recirculation times from 30 minutes to 7 days. Post-mitochondrial supernatant (PMS) from various brain regions was added to a self-contained, cell-free rabbit reticulocyte translational system, and the effect on in vitro protein synthesis was assessed by measuring 14C-leucine incorporation over a duration of 45 minutes. PMS prepared at the end of ischemia from hippocampus, striatum and cerebellum inhibited in vitro protein synthesis by 40%-60% but there was only a minor inhibition by PMS from cerebral cortex. During post-ischemic recirculation cortical PMS transiently induced inhibition of in vitro protein synthesis by 30% but this effect gradually disappeared within one week. The inhibition caused by PMS from hippocampus, striatum and cerebellum was not reversed during recirculation and still amounted to about 40% after 7 days. Inhibition of in vitro protein synthesis could be blocked by heating PMS to 100 degrees C, indicating that the suppressor factor is a protein. The comparison of the in vitro effect of postischemic PMS with previously described in vivo inhibition of protein synthesis demonstrates that the here observed suppressor factor is not able to explain the overall disturbance of protein synthesis in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding, Uptake, and Release of Nicotine by Human Gingival Fibroblasts

Previous studies of the effects of nicotine on fibroblasts have reported an altered morphology and attachment of fibroblasts to substrates and disturbances in protein synthesis and secretion. This altered functional and attachment response may be associated with changes in the cell membrane resulting from binding of the nicotine, or to disturbances in cell metabolism as a result of high intracellular levels of nicotine. The purpose of the present study, therefore, was to 1) determine whether gingival fibroblasts bound nicotine and if any binding observed was specific or non-specific in nature; 2) determine whether gingival fibroblasts internalized nicotine, and if so, at what rate; 3) determine whether gingival fibroblasts also released nicotine back into the extracellular environment; and 4) if gingival fibroblasts release nicotine intact or as a metabolite. Cultures of gingival fibroblasts were prepared from gingival connective tissue biopsies. Binding was evaluated at 4 degrees C using a mixture of 3H-nicotine and unlabeled nicotine. Specific binding was calculated as the difference between 3H-nicotine bound in the presence and absence of unlabeled nicotine. The cells bound 1.44 (+/- 0.42) pmols/10(6) cells in the presence of unlabeled nicotine and 1.66 (+/- 0.55) pmols/10(6) cells in the absence of unlabeled nicotine. The difference was not significant. Uptake of nicotine was measured at 37 degrees C after treating cells with 3H-nicotine for time periods up to 4 hours. Uptake in pmols/10(6) cells was 4.90 (+/- 0.34) at 15 minutes, 8.30 (+/- 0.75) at 30 minutes, 12.28 (+/- 2.62) at 1 hour and 26.31 (+/- 1.15) at 4 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Mimosine, a nonprotein amino acid, inhibits growth and enzyme systems in Tribolium castaneum

The potency of mimosine is much greater in inhibiting growth and development of first-instar larvae of Tribolium castaneum than of fourth-instar larvae as expressed in suppression of larval weight gain and retardation in pupation. Approximately 70% suppression in weight gain of first-instar larvae was obtained at 0.06% mimosine and close to 100% at 0.08%. A dose-dependent decrease in the activity of trehalase, invertase, and amylase of fourth-instar larvae was obtained in vivo with the increase in mimosine concentration. At 0.3% dietary concentration, reductions of 58, 63, and 25% in trehalase, invertase, and amylase activity, respectively, were obtained after 2 days' feeding on treated diet, and of 65, 83, and 35%, respectively, after 5 days' feeding. On the other hand, increases of 27, 77, and 93% in protease activity were obtained in larvae fed for 5 days on diet containing 0.1%, 0.2%, and 0.3% minosine, respectively. The reduced activity of the trehalase enzyme might hamper the energy supply needed for growth and development, and that of the invertase and amylase enzymes for the feeding process. At concentrations of 10 −4 and 10 −3 M, mimosine had no effect on any of the carbohydrase enzymes in vitro. Hence, the observed effect on these enzymes in vivo could result from disturbances in protein synthesis leading to alteration in enzyme activity. Our study indicates that mimosine is a potent suppressor of growth and development of T. castaneum and may promote the development of a new group of insecticides.

Recessive ichthyosis congenita type II

In the heterogeneous group of recessive congenital ichthyoses the disorder of desquamation seems to be a basic problem. Desquamation is strongly dependent on the normal lipid metabolism of the keratinocytes. We describe a group of patients who have a typical clinical picture of large scale ichthyosis and cholesterol clefts in the thickened corneal layer, evidencing a disturbance of the lipid metabolism of the skin. The corneocytes also show a thin or absent cornified envelope, which could indicate a disturbance of protein synthesis. These patients have a severe ichthyosis, but good general health and no associated symptoms. This disorder has recently been named 'ichthyosis congenita type II' by the Heidelberg group on the basis of electron microscopic findings. According to the present examination this group corresponds clinically to the currently used diagnosis 'lamellar ichthyosis'.