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Biomedical subjects

J Niemi

Publications and source records attributed to J Niemi.

At least 19 recordsLinked to original sources

Trends of phosphorus, nitrogen and chlorophyll a concentrations in Finnish rivers and lakes in 1975-2000.

During recent decades the amounts of nutrients discharged to Finnish surface waters have markedly decreased. This has been achieved by considerable investments in water protection, which were made mainly to improve municipal and industrial wastewater purification. We investigated whether these water protection measures have decreased phosphorus and nitrogen concentrations in Finnish rivers and lakes. In addition, possible trends in chlorophyll a concentrations in lakes were studied. The data consisted of a total of over 68000 monitoring results of 22 rivers and 173 lakes (or sub-basins of lakes) with different types of catchment areas. The study period covered the years 1975-2000 and the non-parametric Kendall Tau b and Seasonal Kendall tests were applied for detecting trends. Decreasing nutrient concentration trends were typical in many lakes and rivers earlier polluted by municipal and industrial wastewaters. Increasing nutrient concentration trends were common in smaller rivers and lakes receiving diffuse loading from agriculture. The results show that the investments directed towards wastewater purification have effectively improved the quality of Finnish inland waters. However, no clear effects of decreasing non-point loading were found. Thus, more effective measures should be directed towards decreasing non-point source loading.

Chlorophyll↗

Modifications of aclacinomycin T by aclacinomycin methyl esterase (RdmC) and aclacinomycin-10-hydroxylase (RdmB) from Streptomyces purpurascens.

The genes rdmB and rdmC of Streptomyces purpurascens encoding aclacinomycin modifying enzymes RdmB and RdmC were expressed in Streptomyces lividans TK24. In contrast to the earlier suggestion that RdmC may be an esterase that causes the removal of the carbomethoxy group from the 10 position of aclacinomycins, RdmC functions as an aclacinomycin methyl esterase and catalyzes the removal of the methoxy group from the C-15 position of aclacinomycin T producing 15-demethoxyaclacinomycin T. RdmB acts upon C-10 of 15-demethoxyaclacinomycin T and is able to remove the carboxylic group from the C-10 position. It functions also as an aclacinomycin-10-hydroxylase being able to add a hydroxyl group at the same, C-10 position in vitro. Aclacinomycin methyl esterase was purified to apparent homogeneity from S. lividans carrying the rdmC and aclacinomycin-10-hydroxylase as a glutathione S-transferase fusion construct from Escherichia coli carrying the rdmB gene, respectively. Aclacinomycin methyl esterase functions as a monomer and aclacinomycin-10-hydroxylase as a tetramer. Aclacinomycin methyl esterase has an exceptionally high temperature stability and has an apparent K(m) for aclacinomycin T of 15.5 microM. The introduction of rdmC and rdmB in a Streptomyces galilaeus mutant HO38 produced the same modifications of aclacinomycin T in vivo as aclacinomycin methyl esterase and aclacinomycin-10-hydroxylase in vitro.

Aclarubicin↗

Characterization of aklavinone-11-hydroxylase from Streptomyces purpurascens.

Aklavinone-11-hydroxylase (RdmE) is a FAD monooxygenase participating in the biosynthesis of daunorubicin, doxorubicin and rhodomycins. The rdmE gene encodes an enzyme of 535 amino acids. The sequence of the Streptomyces purpurascens enzyme is similar to other Streptomyces aromatic polyketide hydroxylases. We overexpressed the gene in Streptomyces lividans and purified aklavinone-11-hydroxylase to apparent homogeneity with four chromatographic steps utilizing a kinetic photometric enzyme assay. The enzyme is active as the monomer with a molecular mass of 60 kDa; it hydroxylates aklavinone and other anthracyclinones. Aklavinone-11-hydroxylase can use both NADH and NADPH as coenzyme but it is slowly inactivated in the presence of NADH. The apparent Km for NADPH is 2 mM and for aklavinone 10 microM. The enzyme is inactivated in the presence of phenylglyoxal and 2,3-butanedione. NADPH protects against inactivation of aklavinone-11-hydroxylase by phenylglyoxal.

Anthracyclines↗

Modularity of prosody: autonomy of phonological quantity and intonation in aphasia.

The Finnish language is used here to enrich our conception of the dysprosody hypothesis of the output in Broca's agrammatism, i.e., of the claim that agrammatic speech is characterized by aberrant timing and intonation patterns. The native language of the two agrammatic aphasics of the present study places a high functional load on quantity (acoustically: timing/duration) in its phonology, as the short-long quantity opposition concerns both vowels and consonants. Moreover, the quantity opposition in Finnish is not local, i.e., syllable-internal as in many Germanic languages, because the phonetic quantity values are determined by a disyllabic sequence. In contrast to the high functional load of quantity in its lexical phonology, Finnish makes little, if any, grammatical use of intonation. In the present acoustic analyses it was noted that the two Broca's aphasics have preserved the disyllabically determined quantity oppositions, although the speech of the aphasics is characterized by long interword pauses, i.e., by syntactic dysprosody. In contrast to the asyntactic timing patterns, the declination line of intonation is retained in the output of the present aphasics in spite of the low grammatical value of intonation in the language. The present results further dispute the characterization of agrammatic speech output as being dysprosodic, or more specifically atemporal, as lexical quantity and syntactic tonal patterns can be retained in a speech mode that is replete with long interword pauses. More generally, the observations will corroborate the autonomy (modularity) of lexical and syntactic processes in oral language production.

Adult↗

A static shoulder model based on a time-dependent criterion for load sharing between synergistic muscles.

A static shoulder model including a novel muscular synergy principle for computing load sharing between the shoulder muscles is presented. This principle is feasible especially when analysing endurance-type activities. According to the principle, time elapsed from the start of the activity decreases the allowable muscle stress levels on the basis of the stress-endurance time curves of individual muscles. At low load levels the sum of the squared forces is minimized. At higher load levels the increase in the stress levels of individual muscles is counteracted in order to prevent fatigue. In the model the direction of the contact force in the glenohumeral joint is constrained. The stiffness of the shoulder can also be constrained to produce more muscular co-contraction in tasks with high precision demands.

Biomechanical Phenomena↗

Load-sharing patterns in the shoulder during isometric flexion tasks.

Patterns of load-sharing between the shoulder muscles during isometric flexion tasks were studied by using both a biomechanical shoulder model and electromyographic (EMG) recordings of ten subjects. The effect of changes in several model parameters and shoulder stiffness constraints on the predicted load-sharing patterns were studied, while the arm position, hand load and precision requirements of the tasks were varied. The results calculated using the model were, when compared to the EMG recordings, plausible predicting a high level of synergistic contraction of muscles of the shoulder muscles during flexion tasks. The trends of the model-predicted muscle forces corresponded well to the EMG recordings. At low hand load levels the increasing of the shoulder stiffness strongly increased the muscle force levels, thus increasing also the level of synergistic contraction of muscles. At higher load levels the increase in the muscle forces was not so high, because the model predicted a high level of simultaneous contraction of muscles already at a low level of shoulder stiffness. Cluster analysis of the EMG recordings revealed large inter-individual differences in the load distribution patterns during flexion tasks. The constraint angle of the glenohumeral joint contact force direction was found to be an important model parameter affecting both the predicted forces and the maximum force production ability of the shoulder.

Adult↗

Muscular synergy in the shoulder during a fatiguing static contraction.

The synergic operation of shoulder muscles during a fatiguing submaximal arm flexion task was studied using both a biomechanical 3-dimensional shoulder model and electromyographic recordings. A new optimization scheme aiming to maximize the task endurance time by constantly regulating the force output of each muscle is utilized in the model. The method can be used to simulate the muscle rotation phenomenon, which has been proposed to occur during an endurance type contraction. The model predictions on the fatigue order of the shoulder muscles were compared to results derived using the median frequencies of the electromyographic signals from nine muscles or muscle parts. In the test performed 10 men held until exhaustion a weight (4 kg) suspended on the wrist with the arm in horizontal flexion. The deltoid, infraspinatus, and supraspinatus muscles were the first to show electromyographic signs of fatigue. The times for detecting electromyographic changes in the trapezius muscle were longer than those in the muscles first showing electromyographic signs of fatigue. The biomechanical model used predicted the upper and lower infraspinatus and the anterior part of the deltoid to be the first to show signs of fatigue during the flexion task. The predictions of the biomechanical model on the order of fatigue of the nine shoulder muscles monitored also using electromyographic recordings corresponded to the electromyographic results. However, the accuracy of this comparison is limited by the fact that the electromyographic recordings did not cover all the muscles used in the model. No clear order was found for the development of electromyographic signs of muscle fatigue. RELEVANCE--:The biomechanical model and the developed optimization methods provide new tools for studying the synergic operation of shoulder muscles during fatiguing contractions. Our results will help in analysing and optimizing shoulder load in problematic functions both of work and leisure activities.

Journal Article↗

Nucleotide sequences and expression of genes from Streptomyces purpurascens that cause the production of new anthracyclines in Streptomyces galilaeus.

Six open reading frames, rdmA to rdmF, in a 6,077-bp segment of Streptomyces purpurascens DNA which caused the production of hybrid anthracyclines were identified. The minimal fragment that produced anthracyclines modified at the 10th position contained rdmB to rdmD; rdmE is the gene for aklavinone-11-hydroxylase. RdmC is similar to a putative open reading frame in the daunorubicin biosynthetic cluster of Streptomyces peucetius and is likely to participate in the removal of the side chain at the 10th position.

Amino Acid Sequence↗

Hybrid anthracycline antibiotics: production of new anthracyclines by cloned genes from Streptomyces purpurascens in Streptomyces galilaeus.

A DNA segment cloned from Streptomyces purpurascens ATCC 25489 close to a region that hybridized to a probe containing part of the actinorhodin polyketide synthase caused S. galilaeus ATCC 31615 to produce new anthracyclines. When transformed with certain sub-clones of this segment, the host produced glycosides of epsilon-rhodomycinone, beta-rhodomycinone, 10-demethoxycarbonylaklavinone and 11-deoxy-beta-rhodomycinone in addition to those of aklavinone, the natural anthracyclines of S. galilaeus. The first two compounds are S. purpurascens products and the other two are novel compounds that conceptually are structural hybrids between S. galilaeus and S. purpurascens products. Three glycosides of one of the novel aglycones, 11-deoxy-beta-rhodomycinone, were purified and found to possess cytotoxic activity against L1210 mouse leukaemia cells. Separate regions of the cloned S. purpurascens DNA are responsible for modification of the S. galilaeus host product at the 10- and 11-positions.

Acyltransferases↗

Isolation and characterization of aclacinomycin A-non-producing Streptomyces galilaeus (ATCC 31615) mutants.

Twelve mutants of Streptomyces galilaeus (ATCC 31615) blocked in the production of aclacinomycin A, an anthracycline antibiotic with significant antitumour activity, accumulated intermediates of the biosynthesis of aclacinomycins and several anthracyclines with variant sugar moieties. Three of these aklavinone glycosides have not been described before. Mutant strains H028, H061 and H036 were blocked before the formation of aklavinone, a common intermediate for most anthracyclines. Strain H039 accumulated aklavinone and H026, H035, H038 and H054 had mutations that changed glycosylation of aklavinone. Characterization of the mutants and their products is described.

Acetates↗

On the nature of naming difficulties in aphasia.

An extensive naming battery was administered to ten patients representing classical aphasia syndromes. The battery included traditional performance measures and error scoring, phonological cuing, multiple-choice tasks tapping semantic and phonological knowledge, and word repetition tests. Differences in the patients' performance profiles were interpreted as reflecting lexical-phonological, phoneme assembly or multiple deficits. The results suggest that the hypothesized naming deficits have complex relationships to classical aphasia syndromes.

Adult↗

abaA, a new pleiotropic regulatory locus for antibiotic production in Streptomyces coelicolor.

Production of the blue-pigmented antibiotic actinorhodin is greatly enhanced in Streptomyces lividans and Streptomyces coelicolor by transformation with a 2.7-kb DNA fragment from the S. coelicolor chromosome cloned on a multicopy plasmid. Southern analysis, restriction map comparisons, and map locations of the cloned genes revealed that these genes were different from other known S. coelicolor genes concerned with actinorhodin biosynthesis or its pleiotropic regulation. Computer analysis of the DNA sequence showed five putative open reading frames (ORFs), which were named ORFA, ORFB, and ORFC (transcribed in one direction) and ORFD and ORFE (transcribed in the opposite direction). Subcloning experiments revealed that ORFB together with 137 bp downstream of it is responsible for antibiotic overproduction in S. lividans. Insertion of a phi C31 prophage into ORFB by homologous recombination gave rise to a mutant phenotype in which the production of actinorhodin, undecylprodigiosin, and the calcium-dependent antibiotic (but not methylenomycin) was reduced or abolished. The nonproducing mutants were not affected in the timing or vigor or sporulation. A possible involvement of ORFA in antibiotic production in S. coelicolor is not excluded. abaA constitutes a new locus which, like the afs and abs genes previously described, pleiotropically regulates antibiotic production. DNA sequences that hybridize with the cloned DNA are present in several different Streptomyces species.

Amino Acid Sequence↗

Cloning and expression in a heterologous host of the complete set of genes for biosynthesis of the Streptomyces coelicolor antibiotic undecylprodigiosin.

A fragment of DNA carrying the hitherto unisolated members of the cluster of genes (red) for biosynthesis of the red-pigmented antibiotic undecylprodigiosin of Streptomyces coelicolor A3(2) was isolated. This was done by cloning random fragments of S. coelicolor DNA into the closely related Streptomyces lividans 66 and recovering a clone that caused overproduction of undecylprodigiosin. The effect was probably due to the presence of the cloned redD gene, which functions as a positive regulator of the expression of the red cluster, activating the normally poorly expressed red genes of S. lividans. Two fragments from either end of the red cluster were cloned adjacent to each other on a low-copy-number Streptomyces vector. Double crossing-over occurring between these plasmid-borne sequences and the chromosomal copy of the same DNA in S. coelicolor led to isolation of the entire red cluster as a single cloned fragment. Isolation of antibiotic biosynthetic genes by the effects of an activator in a self-cloning experiment, and in vivo reconstitution of a large cluster of genes by homologous recombination, may turn out to be usefully generalizable procedures.

Cloning, Molecular↗

Semantic errors in a deep dyslexic.

A case of a Swedish-speaking deep dyslexic is reported whose semantic paralexias appeared to result mainly from a lexical retrieval failure in oral reading. He was able to draw correct pictures of the written words for which he had simultaneously produced a semantically erroneous oral reading response. Repeated attempts to correct paralexic responses were common, indicating that the patient was often aware of the errors. His lexical retrieval problems and semantic errors extended to naming as well, and the results support Nolan and Caramazza's (1982, Brain and Language, 16, 237-264), dual-deficit model of deep dyslexia.

Adult↗

Fragile X speech phonology in Finnish.

Fragile X syndrome is a recently discovered relatively common syndrome linked with an anomaly of the X chromosome and causing handicaps of cognitive development especially in males. In the present phonological analysis we will discuss the sound patterns of two Finnish fragile X speakers, a five (borderline intelligence)- and an eight (mildly mentally retarded)-year-old boy. The fragile X syndrome is not necessarily linked with any anomalies of speech organs. The subjects could produce all Finnish speech sounds in isolated test words. However, in the present samples of connected speech they exhibited general dysphonology. What is noteworthy is that their phonological error patterns resembled each other to a great extent. Among the common features were the tendencies to substitute and omit phonemes. As for vowels, our results showed about one-half of the errors to be omissions. Labiality and quantity oppositions were quite resistant to substitution. Most substitution errors of place of consonants occurred in dentals. As for the feature of manner, /r/ and /s/ were the phonemes most prone for substitution. A tendency toward spirantization or /h/ sation was common for both patients. The number of additions was clearly lower than has been reported for English-speaking developmentally dyspraxic children and also for Finnish Broca's aphasics. The speech problems of our patients seemed to indicate higher level motor encoding problems of linguistic information rather than peripheral articulatory deficits.

Articulation Disorders↗

Grammatical morphology in aphasia: a case of errata or reader misinterpretations?

As convincing as the discussion presented by Elizabeth Bates, Angela Friederici and Beverly Wulfeck on grammatical morphology in aphasia in three languages may seem, we were at loss when trying to reconstruct the quantitative basis of their argumentation (see Bates et al., 1987, Grammatical morphology in aphasia: Evidence from three languages. Cortex, 23: 545-575). With the present notice we would like to lessen the possibility of reader misinterpretations that may easily confuse the thread of the argument of this article in the form in which it was originally presented.

Aphasia↗

Temporal delay and lexical retrieval in narratives: aphasiological observations.

Temporal delays in nonpathological speech have been mostly attributed to long-term planning and lexical access. In wake of the recent increased interest in lexicon in general, there have also been serious attempts to approach lexical processes through analyses of disrupted lexicon, most notably through the language of aphasics. In the present study we have analyzed the temporal delays and pauses associated with neologisms produced by Finnish posterior aphasics. It appears that delays and pauses correlate with the type of neology they precede. Moreover, the anomia theory of neologistic items will receive here further observational support.

Anomia↗

A new approach to high sensitivity differential hybridization.

We describe a new approach to differential hybridization, designed to identify cDNA clones representing rare mRNA species. Duplicate filters carrying a library of cDNA from phorbolmyristate acetate (PMA)-induced EL-4 cells in lambda gt11 were hybridized with high concentrations of unlabeled, cloned, single-stranded cDNA from induced and control EL-4 cells, respectively. Plaques binding single-stranded cDNA were revealed by a second round of hybridization with 35S-labeled DNA complementary to the vector moiety of the single-stranded cDNA. Plaques corresponding to PMA-induced mRNAs occurring at a level of about 1 part in 15,000 were isolated. We believe the method is at least ten times more sensitive than conventional differential hybridization.

Animals↗