Author Correction: The solute carrier SLC9C1 is a Na+/H+-exchanger gated by an S4-type voltage-sensor and cyclic-nucleotide binding.

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The solute carrier SLC9C1 is a Na+/H+-exchanger gated by an S4-type voltage-sensor and cyclic-nucleotide binding.

Voltage-sensing (VSD) and cyclic nucleotide-binding domains (CNBD) gate ion channels for rapid electrical signaling. By contrast, solute carriers (SLCs) that passively redistribute substrates are gated by their substrates themselves. Here, we study the orphan sperm-specific solute carriers SLC9C1 that feature a unique tripartite structure: an exchanger domain, a VSD, and a CNBD. Voltage-clamp fluorimetry shows that SLC9C1 is a genuine Na+/H+ exchanger gated by voltage. The cellular messenger cAMP shifts the voltage range of activation. Mutations in the transport domain, the VSD, or the CNBD strongly affect Na+/H+ exchange, voltage gating, or cAMP sensitivity, respectively. Our results establish SLC9C1 as a phylogenetic chimaera that combines the ion-exchange mechanism of solute carriers with the gating mechanism of ion channels. Classic SLCs slowly readjust changes in the intra- and extracellular milieu, whereas voltage gating endows the Na+/H+ exchanger with the ability to produce a rapid pH response that enables downstream signaling events.

Deletion of a single hydrogen bonding atom from the MS2 RNA operator leads to dramatic rearrangements at the RNA-coat protein interface.

The MS2 coat protein binds specifically to an RNA hairpin formed within the viral genome. By soaking different RNA fragments into crystals of MS2 coat protein capsids it is possible to determine the X-ray structure of the RNA-protein complexes formed. Here we present the structure to 2.85 A resolution of a complex between a chemically modified RNA hairpin variant and the MS2 coat protein. This RNA variant has a substitution at the -5 base position, which has been shown previously to be pyrimidine-specific and is a uracil in the wild-type RNA. The modified RNA hairpin contains a pyridin-4-one base (4one) at this position that lacks the exocyclic 2-oxygen eliminating the possibility of forming a hydrogen bond to asparagine A87 in the protein. The 4one complex structure shows an unprecedented major conformational change in the loop region of the RNA, whereas there is almost no change in the conformation of the protein.

Sediment reference concentrations of seldom monitored trace elements (Ag, Be, In, Ga, Sb, Tl) in four Swedish boreal lakes--comparison with commonly monitored elements.

This paper presents reference and recent acid-leachable concentrations of some seldom monitored trace elements (SMTE; Ag, Be, Ga, In, Sb and Tl) in sediments from four boreal oligotrophic lakes in a south to north transect in Sweden. For comparison commonly monitored trace elements (As, Cd, Co, Cr, Cu, Ni, Pb and Zn) are included as well as those of relevance for redistribution processes (Al, Ca, Fe, Mg and Mn). Pore water pH and the corresponding solid/solution distribution coefficients (Kd) indicated that redistribution of the elements due to acidification is minor. The depth of impact was defined as the level in the sediment where the mean values became constant on successive exclusion of metal concentrations in overlying strata. Reference concentrations were calculated below the depth of impact. The present concentration changes are estimated by the ratio between the average concentration above the depth of impact and the reference concentration. Reference concentration ranges for the SMT-elements are (mg/kg, dry wt.): Ag 0.16-0.66; Be 1.6-3.7; Ga 2.0-5.1; In 0.05-0.22; Sb 0.05-0.11 and Tl 0.17-0.70. The concentration ratios for these elements ranged in the two most southern lakes from 1.5 to 4.5 and in the two northern ones from 0.6 to 1.6. A high correlation between Kd for the SMT-elements, and iron, except for Sb and Tl, infer that the biogeochemistry of iron is quantitatively important for the accumulation of these elements. The reference concentration ranges for the commonly monitored trace elements are (mg/kg, dry wt.): As 7.0-29.6; Cd 0.33-0.98; Co 5.7-23.8; Cr 15.2-26.1; Cu 27.6-58.4; Ni 5.4-20.8; Pb 44-96. The corresponding concentration ratios were 1.2-18 (second highest 3.9) in the two most southern lakes and 0.8-1.6 in the two northern ones. Declining ratios were found from south to north, most obvious for cobalt and zinc. The copper ratios did not show a regional pattern, partly because of the impact from old mine waste. Increased concentrations of Ag, Be, Ga, In, Sb and Tl in recent sediments up to 4.5 times the reference levels in combination with the geographical pattern infer an elevated loading of these elements.

Effect of milk and fermented milk on iron absorption in ileostomy subjects.

This study was undertaken to determine whether milk with its high calcium content adversely affects the absorption of nonheme iron from the diet as greatly as single-meal studies indicate. Nine ileostomy subjects ate a low-fiber, low-phytate diet for 8 consecutive weeks. During the first and eight weeks they drank a 250-mL soft drink with three main meals and an evening snack each day (0.16 g Ca/d). During the two intervening 3-wk periods, they drank the same amount of low-fat milk or fermented low-fat milk (Verum; Hälsofil, Norrmejerier, Umeä, Sweden) according to a formally randomized crossover design (1.4 g Ca/d). During the last 2 d in each of the four periods, apparent iron absorption (balance) from a test diet together with that period's beverage was measured and the plasma ferritin concentration was determined. There was no decrease in apparent iron absorption during the milk diet periods.

Antimicrobial factors in saliva: ontogeny and relation to oral health.

Antimicrobial agents (antibody and non-antibody) present in human saliva protect oral tissues by a variety of mechanisms, such as prevention of bacterial adhesion, agglutination of micro-organisms, and inhibition of multiplication and metabolism. However, studies in which the concentrations of various salivary antimicrobial agents have been correlated to the presence and severity of oral diseases--of dental caries, in particular--have produced controversial data, and it seems evident, also on the basis of the present study, that no single salivary antimicrobial factor (except flow rate) affects oral health to a significant degree. In the present study, we report the levels of some selected salivary antimicrobial agents in predentate and dentate human infants, with a comparison to the levels found in young adults' saliva. Salivary lysozyme, peroxidase, and hypothiocyanite concentrations were already at the adult level at the time when the primary teeth erupt, whereas immunoglobulin (IgA, IgG, and IgM), lactoferrin, myeloperoxidase, and thiocyanate concentrations were significantly lower in children than in adults. Dentate children had more IgG, thiocyanate, and protein in whole saliva than did predentate children.

Effects of low-fat milk and fermented low-fat milk on cholesterol absorption and excretion in ileostomy subjects.

OBJECTIVE: To study small bowel cholesterol absorption and sterol excretion in order to explain possible serum cholesterol-lowering mechanisms of low-fat milk products. DESIGN: Two 24-h sterol balance studies with 1 litre of low-fat milk or one litre of fermented milk, in random order, added to a controlled diet. [3H]Cholesterol absorption was measured during each period. The results were compared to those on two 24-h periods with isocaloric amounts of lemonade given to the same basic diet, before and after the study. One litre of the two milk products was also consumed in addition to their normal diets in a cross-over design of 3 weeks and with run-in and run-out periods of 2 weeks each with 1000 ml of lemonade preceding the balance studies: SETTING: Outpatient clinic, where the subjects were eating their meals during the day and ileostomy bags collected. SUBJECTS: Nine ileostomy subjects, who have earlier participated in similar studies, volunteered for the study. All subjects completed the study. RESULTS: Cholesterol absorption was highest (66%) in the lemonade period, intermediate in the low-fat milk period (61%) and lowest in the fermented low-fat period (55%) (P < 0.05 for differences). Net cholesterol excretion (excretion minus intake) and calculated endogenous cholesterol excretion were significantly (P < 0.05 for differences) higher in the low-fat milk period than in the lemonade period and the fermented low-fat milk period. No significant change in serum cholesterol was, however, seen after 3 weeks on each milk regimen. CONCLUSION: Assimilation of cholesterol by microorganisms could possibly explain the reduced uptake of cholesterol with fermented milk. The mechanism behind the increased endogenous cholesterol excretion, induced by low-fat milk, is unclear.

Interfering alpha-streptococci as a protection against recurrent streptococcal tonsillitis in children.

Recurrent streptococcal tonsillitis/pharyngitis is a great problem, especially in certain epidemiological situations. Patients treated with antibiotics often have a disturbed normal throat flora and may lack, e.g., alpha-streptococci known in vitro to have an interfering activity against group A streptococci. Thirty-one patients with recurrent streptococcal tonsillitis were given antibiotics for 10 days. At the end of this treatment they were sprayed in their mouths with four selected alpha-streptococcal strains known to have strong growth inhibiting activity in vitro against most beta-streptococci group A. The follow-up period after this colonization was 3 months. After alpha-streptococcal treatment, none of the patients attracted a new tonsillitis during the follow-up period while 8% of the controls had a second tonsillitis. Treatment of streptococcal tonsillitis/pharyngitis with antibiotics followed by recolonization with alpha-streptococci seems to hinder further recurrences.

Historical pollution of seldom monitored trace elements in Sweden--Part A: sediment properties and chronological indicators.

Sediment cores from four small oligotrophic boreal lakes, with minor acidification, in remote regions of central Sweden were used for historical interpretation of their metal content, with focus on Cu, Cd, Pb and Zn in Lake Stensjön, which has the longest sediment record (at least two centuries according to (210)Pb dating). Comparison is made with the other three lakes. Major and trace elements in lake water, porewater and the acid-leached (HNO(3)) solid sediment phase was analysed with ICP-MS. In addition, general lake water chemistry, TOC and principal anions were measured in the aqueous phases. Redistribution processes were interpreted from geochemical modelling. The solid/solution distribution of pe/pH sensitive elements, indicates a minor diagenetic redistribution and the concentration profiles are therefore suitable for chronological evaluation. The ratios of Al, Ti, Sc and V, indicated a qualitative shift of sedimenting material a century ago, which did not have any impact on the retention of trace elements. Lead had a concentration profile, supported by the (206)Pb/(207)Pb ratio, where it was possible to distinguish preindustrial conditions, early industrialisation in Europe, industrialisation in Sweden, and the use of leaded petrol after the Second World War. Cadmium showed a similar concentration pattern. The zinc profile resembled that of cadmium, but with less enrichment. Local lithogenic sources are believed to be quantitatively important. The solid/solution distribution (K(d)) was independent of depth for all four elements. The sediment concentrations of copper and zinc are not related to early industrialisation but its concentration has doubled since the Second World War.

Historical pollution of seldom monitored trace elements in Sweden--Part B: sediment analysis of silver, antimony, thallium and indium.

Sediment cores from four boreal and remote lakes in a south to north transect in central Sweden were analysed for acid leachable silver, antimony, thallium and indium in the solid sediment phase and the corresponding porewater. Dating of the cores was made by their content of acid leachable lead and the (206)Pb/(207)Pb ratio, in one lake also by (210)Pb. The impact of diagenesis on element redistribution in the sediments was included and found to be minor except for thallium. The results show lowered concentrations towards the north and most intense accumulation after the Second World War, which is taken as evidence for atmospheric deposition being the primary source. Indium has declining concentrations in recent strata while silver and antimony increase. Thallium has lowered acid-leachable concentrations in recent strata. For all metals the impact of domestic industrialisation as well as the early industrialisation of central Europe is discernible. Only thallium appears to reach a geological background at depths that correspond to the late 18th century. For the other metals elevated levels are concluded.

Bacterial interference in streptococcal tonsillitis.

On the basis of the presented results and those published by other investigators it can be stated that in the throat (i) bacterial interference is a multifaceted phenomenon; (ii) bacterial interference not only varies individually but also fluctuates in the individual by time and the epidemiological situation; (iii) bacterial interference among the microbes in the normal flora apparently helps the individual to combat the invading microorganisms; (iv) bacteriocins, if present, in the invading bacteria represent an important virulence factor; (v) bacterial interference as a factor of the host resistance to infection can be influenced negatively by antibiotic therapy; (vi) bacterial interference can act synergistically with antibiotics given in optimal doses saving the normal flora.

Bacterial interference in the throat flora during a streptococcal tonsillitis outbreak in an apartment house area.

During an outbreak of streptococcal tonsillitis in an apartment house area the interfering capacity of alpha-hemolytic streptococci isolated from the inhabitants' throat flora on the beta-hemolytic streptococcal strains recovered during the outbreak was investigated. Strains of alpha-streptococci with an inhibiting capacity on beta-streptococci were isolated mainly from individuals seemingly resistant to streptococcal tonsillitis while patients with repeated tonsillitis often had beta-streptococcal strains inhibiting the growth of the patients own alpha-streptococcal flora. Inhibiting alpha-streptococcal strains were isolated in high frequency in healthy patients that had recently recovered from tonsillitis.

The effect of penicillin on bacterial interference in vivo.

The study was designed to analyse the effect of penicillin on interference between alfa-streptococci and group A streptococci in vivo. Tissue cages were implanted subcutaneously in 9 rabbits and inoculated with 10(5) cfu of alfa- and beta-streptococci together as well as separately. Both streptococci were recovered 96 h after the inoculation in the untreated rabbits. Alfa-streptococci inhibiting the growth of beta-streptococci in vitro retained this capacity under the experimental in vivo conditions. Higher penicillin concentration did not increase the killing rate of beta-streptococci grown separately while a faster killing was observed with low penicillin levels in the presence of inhibiting alfa-streptococci, indicating synergistic effect.

Penicillin concentration in saliva and its influence on bacterial interference.

The aim of the investigation was to study the influence of various penicillin levels on the interference between alfa- and beta-streptococci based on antibiotic levels registered after oral intake of penicillin tablets. It was found that penicillin was released from ordinary sugar coated tablets already in the mouth resulting in concentrations in saliva above the MIC of most penicillin sensitive microorganisms during the first 2 min. This was followed by a decrease of the alfa-streptococcal flora. It was also shown that penicillin levels above the MIC of alfa-streptococci resulted in prolonged survival of beta-streptococci as compared to that noted at penicillin levels above the MIC of beta-streptococci but below that of the alfa-strains. At this latter level a synergistic effect between penicillin and interfering alfa-streptococcal strains could be demonstrated.

Alpha-streptococci as supplementary treatment of recurrent streptococcal tonsillitis: a randomized placebo-controlled study.

Recurrences are a common finding after antibiotic treatment of acute group A streptococcal tonsillitis. This has been attributed to several factors, among others a disturbed normal throat flora and especially a lack of alpha-streptococci. It thus seems logical in patients with recurrent streptococcal tonsillitis, to restore the normal alpha-streptococcal flora by reimplantation of alpha-streptococci. This was performed in a double blinded, randomized, placebo-controlled study. 36 patients with recurrent streptococcal group A tonsillitis were treated with antibiotics followed by either placebo (19 patients) or a pool of 4 selected alpha-streptococcal strains (17 patients) with good interfering activity against clinical isolates of beta-streptococci. No patient recurred during the first 2 months of follow-up in the alpha-treated group, but 7 in those treated with antibiotics and placebo. After 3 months 1 in the patient group treated with antibiotics and alpha-streptococci and 11 in the placebo-treated group recurred. These results are statistically highly significant and show that recolonisation with alpha-streptococci seems to offer a new way to lower the rate of recurrence in streptococcal throat infections.

The Woronets trait: a new familial erythrocyte anomaly.

A dominantly inherited abnormality of the red blood cells is described. It is characterized by the presence of a small population of markedly distorted red blood cells resembling keratocytes. In addition, many of the red cells show minor deformities resembling the beginning stages of formation of echinocytes. Red cell lifespan is normal, and the severely deformed cells appear to represent the senescent population. Inappropriate increases in activities of some, but not all, age-dependent red cell enzymes were observed. The anomaly appeared to be entirely benign; no abnormal clinical findings were associated with this defect. It has been designated the Woronets trait.

Pharmacokinetics of phenoxymethylpenicillin in tonsils.

The pharmacokinetics of phenoxymethylpenicillin in tonsillar tissue was studied in 33 patients who underwent tonsillectomy, mainly because of repeated tonsillitis or peritonsillitis. The patients were operated on 30-240 min after an oral penicillin dose of 12.5 mg/kg body weight. The mean serum concentration was 2.8 micrograms/ml for 10 patients operated upon 80-95 min after drug administration. The mean tissue concentration for these patients at the same time was 0.6 micrograms/g. The mean concentration of penicillin in tissue after 240 min was 0.05 micrograms/g. 19% of the serum concentration was recovered in the tonsillar tissue. No significant difference between penicillin concentration in the centre or surface of the tonsils was found. The tissue concentration was calculated to be above 0.03 micrograms/ml for at least 4-5 h. 30% of the patients harboured penicillinase producing bacteria on their tonsils, mainly Staphylococcus aureus. These patients had a lower tissue concentration than those lacking the bacteria, but the difference was not statistically significant (p = 0.095).

Evaluation of beta-lactamase activity and microbial interference in treatment failures of acute streptococcal tonsillitis.

Out of 169 patients with streptococcal tonsillitis treated with phenoxymethylpenicillin, 13 (8%) developed a new clinical infection with the same streptococcal strain within 2 weeks of completing the therapy (clinical treatment failure) and 24 (14%) were clinically healthy but harboured the same streptococcal strain after treatment (bacterial treatment failure). Patients with clinical treatment failure showed beta-lactamase activity in their saliva pellet significantly more often than patients with bacterial treatment failure, healed streptococcal tonsillitis or non-streptococcal tonsillitis as well as healthy controls. In an interference study, clinical treatment failures were compared with healthy streptococcal carriers, i.e. persons living in the same household and harbouring the same beta-streptococcal strain. 11/12 healthy carriers had alpha-streptococci with interfering activity against their own beta-streptococcal strain, while the corresponding figure for the clinical treatment failures was 2/13. Furthermore, 6/12 healthy carriers had beta-streptococci inhibiting their own alpha-strains, while the streptococci in 11/13 clinical treatment failures had this ability. The beta-lactamase activity and the interference between alpha- and beta-streptococci may be a contributory cause to treatment failure in streptococcal tonsillitis.