Helices in peptoids of alpha- and beta-peptides

Peptoids of alpha- and beta-peptides (alpha- and beta-peptoids) can be obtained by shifting the amino acid side chains from the backbone carbon atoms of the monomer constituents to the peptide nitrogen atoms. They are, therefore, N-substituted poly-glycines and poly-beta-alanines, respectively. Due to the substituted nitrogen atoms, the ability for hydrogen bond formation between peptide bonds gets lost. It may be very interesting to see whether such non-natural oligomers could be regarded as foldamers, which fold into definite backbone conformers. In this paper, we provide a complete overview on helix formation in alpha- and beta-peptoids on the basis of systematic theoretical conformational analyses employing the methods of ab initio molecular orbital (MO) theory. It can be shown that the alpha- and beta-peptoid structures form helical structures with both trans and cis peptide bonds despite the missing hydrogen bonds. Obviously, the conformational properties of the backbone are more important for folding than the possibility of hydrogen bonding. There are close relationships between the helices of alpha-peptoids and poly-glycine and poly-proline helices of alpha-peptides, whereas the helices of beta-peptoids correspond to the well-known helical structures of beta-peptides as, for instance, the 3(1)-helix of beta-peptides with 14-membered hydrogen-bonded rings. Thus, alpha- and beta-peptoids enrich the field of foldamers and may be used as useful tools in peptide and protein design.     

Beta-peptoid "foldamers"--why the additional methylene unit?

The field of peptoid (i.e., N-alkylglycine) research has been thriving since the first publications on this molecular design appeared in 1992. A highly efficient and modular synthetic platform, which is compatible with automation and ready generation of combinatorial libraries, was published the same year. This has enabled the investigation of numerous compounds with this architecture, and ligands with a wide variety of interesting biological targets have thus been discovered. Furthermore, detailed biophysical and structural studies focusing on the investigation of the conformational space adopted and three-dimensional folding of these peptide mimics have been undertaken. The same is true for beta-peptides (i.e., oligomers composed of beta-amino acids). Since the first publication describing peptide mimics combining these two structural modifications [the N-alkyl-beta-alanines (beta-peptoids)] in 1998, on the other hand, the application of this backbone construct has appeared much more sparsely in the literature. The present perspective article will provide an overview of the data obtained for beta-peptoid-containing peptide mimics as well as a discussion of the future challenges associated with this type of backbone modification.     

血清Visfatin、PRDX1水平与克罗恩病患者活动度指标和肠道菌群的相关性分析

摘要 目的：分析血清内脂素（Visfatin）、过氧化物还原蛋白1（PRDX1）水平与克罗恩病（CD）患者活动度指标和肠道菌群的相关性。方法：选取2019年4月~2022年12月期间联勤保障部队第九一〇医院收治的146例CD患者，根据简化克罗恩病疾病活动指数（CDAI）将所有CD患者分为中重度活动组（n=36）、轻度活动组（n=49）、缓解期组（n=61）。对比三组血清Visfatin、PRDX1、C反应蛋白（CRP）水平、血沉（ESR）、肠道菌群数量。采用Pearson相关性分析血清Visfatin、PRDX1与 CDAI、 CRP、ESR和肠道菌群数量的相关性。结果：中重度活动组、轻度活动组的血清Visfatin、PRDX1水平高于缓解期组，且中重度活动组血清Visfatin、PRDX1水平高于轻度活动组（P<0.05）。中重度活动组、轻度活动组的CRP、ESR高于缓解期组，且中重度活动组CRP、ESR高于轻度活动组（P<0.05）。中重度活动组、轻度活动组的肠球菌、大肠杆菌高于缓解期组，且中重度活动组的肠球菌、大肠杆菌高于轻度活动组（P<0.05），中重度活动组、轻度活动组的双歧杆菌、类杆菌低于缓解期组，且中重度活动组的双歧杆菌、类杆菌低于轻度活动组（P<0.05）。Pearson相关性分析显示，血清Visfatin、PRDX1、 CRP水平与 肠球菌、大肠杆菌菌群数量、CDAI、ESR呈正相关，而与双歧杆菌、类杆菌菌群数量呈负相关（P<0.05）。结论：CD患者的血清Visfatin、PRDX1升高，可导致疾病进展，肠道菌群紊乱加重。     

Anaphylactoid and anti-ovulatory activities of LHRH antagonists in rats

Studies were conducted with LHRH antagonists examining the relationship of structure to anaphylactoid-like activity and the relationship of anaphylactoid-like activity to anti-ovulatory activity in rats. Substitution of basic amino acids appeared to enhance the anaphylactoid-like activity of these peptides but other complex structural characteristics may also be involved. Anaphylactoid and anti-ovulatory activities were clearly independent and potent LHRH antagonists with minimal anaphylactoid-like activity were identified.     

Superoxide dismutase activity of Helicobacter pylori per se from 158 clinical isolates and the characteristics

We investigated the correlation between the SOD activity of Helicobacter pylori (H. pylori) and gastroduodenal diseases and the characteristics of strains exposed to oxidative stress. Two sequenced strains, 26695 and J99, and clinical isolates from 156 Japanese patients with gastroduodenal diseases such as gastric cancer (n= 59) and non-cancer (n= 97) were used. SOD activities of all 158 isolates were measured and were divided into three groups: high-SOD activity (>0.22, n= 2), moderate-SOD activity (0.15≦≦0.22, n= 16) and low-SOD activity (<0.15, n= 140). Expressions of H. pylori Fe-SOD were examined by western blotting with anti-H. pylori Fe-SOD antibody prepared inhouse, and the profiles of Fe-SOD activity were investigated by zymogram with activity staining in native-PAGE. The characteristics of strains from high-SOD and low-SOD groups were examined under oxidative stress by paraquat. The average of H. pylori SOD activity was significantly higher in the cancer group than in the non-cancer group (P < 0.05). However, irrespective of SOD activity level, the amount of Fe-SOD expressed was variable among individual strains. Zymogram revealed a single band in moderate-SOD and low-SOD strains, but multiple bands in high-SOD strains were observed. These bands were confirmed as H. pylori Fe-SOD. Under oxidative stress with paraquat, low-SOD strains were drastically eliminated without inducible SOD activity; however, high-SOD strains were still viable with increased SOD activity. This study is the first to exhibit the characteristics of high-SOD activity strains representing multiple bands in zymograms and the correlation between H. pylori SOD activity and gastric cancer.     

华根霉脂肪酶有机相合成酶活的研究

通过比较7种微生物脂肪酶的有机相合成酶活、水相水解酶活及在正庚烷中催化己酸乙酯合成的能力,证明了合成酶活与水解酶活相关性不高,合成酶活比水解酶活更能反映脂肪酶的合成能力。通过比较两株华根霉(Rhizopus chinensis)脂肪酶酶活,发现合成酶活相差较大,表明相同种属微生物的脂肪酶合成酶活存在不同。对．Rhizopus chinensis-2液态发酵产脂肪酶进程研究发现,水解酶活高峰先于合成酶活高峰大约12h。将不同培养时间的Rhizopus chinensis-2全细胞脂肪酶用于催化己酸乙酯合成,具有高合成酶活的全细胞脂肪酶催化己酸乙酯合成反应较快。因此,全细胞脂肪酶用于催化有机相酯合成反应时,具有高脂肪酶合成酶活的菌体具有较好的催化酯合成能力。     

The dynamics of neuron activity level in the striatum of the monkey brain in relation to the realization of multistage behavior

Level of the unit activity was studied in the monkey putamen during multistage behavior. Two groups of neuron activity patterns were distinguished. The first one involved patterns of low level neuron activity less exceeding the background level than the second one; the other group involved patterns of high level neuron activity exceeding the background level in the second time. These kinds of patterns were behavior-related. Patterns with low level neuron activity were recorded preferentially in relation to the trigger stimuli and reward. Patterns of high level neuron activity were recorded in relation to the decision-making, movements of arms in the left and right directions. Besides, their number rose in relation to the auditory cue reported to right realization of the task. It was established that the number of patterns of high level neuron activity rose in key moments of behavior, while the number of the patterns of low level neuron activity decreased.     

Day time wheel running activity in laboratory rats following geomagnetic event of 5–6 July 1974

Albino laboratory rats that were given free access to running wheels while maintained on a 12:12 h L:D schedule were observed to display marked increases in day cycle activity following an unusually intense geomagnetic storm. The activity changes were not immediate but peaked one day to several days after the storm. Two less intense geomagnetic storm conditions during the 51 day observation period were associated with less marked activity increases. Ambient room temperature fluctuations were not significantly correlated with either geomagnetic activity or day cycle activity measures.     

Rubella virus antigens: localization of epitopes involved in hemagglutination and neutralization by using monoclonal antibodies.

Monoclonal antibodies (MAbs) against the rubella virion were used to locate epitopes involved in hemagglutination and neutralization. The MAbs exhibiting high-level hemagglutination-inhibiting activity were shown by Western blot analysis to be specific for the E1 polypeptide; this is consistent with the presence of the hemagglutinin on the E1 polypeptide. Some of the E1-specific MAbs also neutralized viral infectivity. However, hemagglutination-inhibiting activity and neutralizing activity did not always correlate. Three distinct functional epitopes were identified on the E1 polypeptide by competition analyses: one which reacted with MAbs with high-level hemagglutination-inhibiting activity and with neutralizing activity, one which reacted with MAbs with low-level hemagglutination-inhibiting activity and with neutralizing activity, and one which reacted with MAbs with only hemagglutination-inhibiting activity. A MAb specific for the E2 polypeptide exhibited neutralizing activity. This E2-specific MAb and two E1-specific MAbs with neutralizing activity were capable of precipitating intact virus which indicates that at least three epitopes involved in neutralization are accessible on the surface of the virion.     

Circadian Temperature and Activity Rhythms in Mice under Free-Running and Entrained Conditions; Assessment after Purification of the Temperature Rhythm

Six female mice were studied separately for six weeks, first in constant light (300 lx), and then on a 12 : 12 L : D schedule (light on 07:00–19:00–h). Food and water were available ad libitum. Abdominal temperature and spontaneous locomotor activity were measured every 10 min. In constant light, the animals free-ran with both temperature and activity records showing circadian rhythms that were significantly greater than 24 h; by contrast, in the LD schedule, the circadian rhythms had become entrained and showed a stable phase relation to this schedule. The direct masking effects upon raw temperatures caused by bursts of activity were clearly seen, and could be removed by a process of ‘purification’. A comparison of the activity profiles during the entrained and free-running phases showed that the imposed light-dark cycle resulted in decreased activity in the light, increased activity in the dark, and bursts of activity at the light-dark and dark-light transitions. Masking effects due to the activity profile were present in the raw temperature profile, and many could be removed by purification using the activity profile; however, there was evidence that other masking effects, independent of activity, were present also. The efficacy of thermoregulatory compensation, as assessed from the rise of core temperature produced by spontaneous locomotor activity, was, in comparison with the free-running condition, increased in the dark phase and decreased in the light phase; this would appear to be one way to limit the temperature rise that occurs in the active phase of the rest-activity cycle.     

The residual enzymatic phosphorylation activity of hexokinase II mutants is correlated with glucose repression in Saccharomyces cerevisiae.

Saccharomyces cerevisiae mutants containing different point mutations in the HXK2 gene were used to study the relationship between phosphorylation by hexokinase II and glucose repression in yeast cells. Mutants showing different levels of hexokinase activity were examined for the degree of glucose repression as indicated by the levels of invertase activity. The levels of hexokinase activity and invertase activity showed a strong inverse correlation, with a few exceptions attributable to very unstable hexokinase II proteins. The in vivo hexokinase II activity was determined by measuring growth rates, using fructose as a carbon source. This in vivo hexokinase II activity was similarly inversely correlated with invertase activity. Several hxk2 alleles were transferred to multicopy plasmids to study the effects of increasing the amounts of mutant proteins. The cells that contained the multicopy plasmids exhibited less invertase and more hexokinase activity, further strengthening the correlation. These results strongly support the hypothesis that the phosphorylation activity of hexokinase II is correlated with glucose repression.     

Effects of oxygen and chloramphenicol on Frankia nitrogenase activity

The kinetics of asymbiotic nitrogenase activity in three strains of the actinomycete Frankia were studied. Decay rates for enzyme activity were determined by adding chloramphenicol to active acetylene-reducing cells and measuring the time required for all activity to cease. Synthesis rates were measured by bubbling oxygen through actively-reducing cells (which totally destroyed all activity) and then measuring the time required for activity to return to normal. Decay rates (t _1/2) for these three strains were approximately 30 to 40 min. Synthesis rates were slower and initial nitrogenase activities were recorded about 110 min (DDB 011610) or 210 min (DDB 020210 and WgCc1.17) after return to air-equilibrated cultures. Frankia strain WgCc1.17 showed a greater sensitivity to oxygen and nitrogenase activity was totally lost when cells were bubbled only with atmospheric concentrations of oxygen. The results presented here indicate that nitrogenase activity turnover time is relatively rapid, on the order of minutes rather than hours or days. However, regulation of nitrogenase activity will differ from one strain to another and asmmbiotic characterization will be useful for understanding nitrogenase regulation in the bacterial-plant symbiosis.Contribution no. 879 from the Battelle-Kettering Laboratory     

A double-blind investigation of the relationship between seizure activity and the sleep EEG following EEG biofeedback training

The sleep EEGs of eight medically refractory epileptic patients were examined as part of a double-blind, ABA crossover study designed to determine the effectiveness of EEG biofeedback for the control of seizures. The patients were initially reinforced for one of three EEG criteria recorded from electrodes placed over sensorimotor cortex: (a) suppression of 3- to 7-Hz activity, (b) enhancement of 12- to 15-Hz activity, or (c) simultaneous suppression of 3- to 7-Hz and enhancement of 11- to 19-Hz activity. Reinforcement contingencies were reversed during the second or B phase, and then reinstated in their original form during the final A′ phase. All-night polysomnographic recordings were obtained at the end of each conditioning phase and were subjected to both visual and computer-based power spectral analyses. Four of the patients showed changes in their nocturnal paroxysmal activity that were either partially or totally consistent with the ABA′ contingencies of the study. The spectral data proved difficult to interpret, though two trends emerged from the analyses. Decreases in nocturnal 4- to 7-Hz activity were correlated with decreases in seizure activity, and increases in 8- to 11-Hz activity were correlated with decreases in seizure activity. These findings were shown to strengthen the hypothesis that EEG biofeedback may produce changes in the sleep EEG that are related to seizure incidence.     

Circadian Temperature and Activity Rhythms in Mice under Free-Running and Entrained Conditions; Assessment after Purification of the Temperature Rhythm

Six female mice were studied separately for six weeks, first in constant light (300 lx), and then on a 12 : 12 L : D schedule (light on 07:00-19:00-h). Food and water were available ad libitum. Abdominal temperature and spontaneous locomotor activity were measured every 10 min. In constant light, the animals free-ran with both temperature and activity records showing circadian rhythms that were significantly greater than 24 h; by contrast, in the LD schedule, the circadian rhythms had become entrained and showed a stable phase relation to this schedule. The direct masking effects upon raw temperatures caused by bursts of activity were clearly seen, and could be removed by a process of 'purification'. A comparison of the activity profiles during the entrained and free-running phases showed that the imposed light-dark cycle resulted in decreased activity in the light, increased activity in the dark, and bursts of activity at the light-dark and dark-light transitions. Masking effects due to the activity profile were present in the raw temperature profile, and many could be removed by purification using the activity profile; however, there was evidence that other masking effects, independent of activity, were present also. The efficacy of thermoregulatory compensation, as assessed from the rise of core temperature produced by spontaneous locomotor activity, was, in comparison with the free-running condition, increased in the dark phase and decreased in the light phase; this would appear to be one way to limit the temperature rise that occurs in the active phase of the rest-activity cycle.     

Typology of activity bouts and effect of fearfulness on behaviour in meat-type chickens

Increased physical exercise is known to prevent leg problems in meat-type chickens. Our aims were to study in detail the organisation of general and locomotor activity, to determine how physical exercise could be promoted and to investigate the effects of tonic immobility (TI) duration on spontaneous activity. Chicks were allocated to two groups according to their TI duration at 3 and 20 days (fearful birds, HF, n=11; non-fearful birds, LF, n=14). The behaviour patterns expressed by awake birds were recorded as 'activity bouts'. Activity bouts were then classified into five classes according to the most long-lasting activity in the bout. The behaviour patterns were similar in both groups. The FORAGING class contained long-lasting bouts with high levels of locomotor activity which decreased considerably with age, when bouts of EATING and DRINKING classes became more and more numerous. Bouts in the PREENING and NONE classes contained low activity. In conclusion, the level of activity in home pens was poorly related to TI. Categorisation of bouts into five classes is valuable to understand the general organisation of activity in chickens. The FORAGING class included bouts with high levels of locomotion and it could thus be used as a general indicator of activity.     

Time course of exercise induced alterations in daily activity in chronic fatigue syndrome

In a previous study we demonstrated that while people with CFS had lower daily activity levels than control subjects, they were able to increase daily activity via a daily walking program. We reanalyzed our data to determine the time course of activity changes during the walking program. Daily activity assessed via an accelometer worn at the hip was divided into sleep, active, and walking periods. Over the first 4–10 days of walking the subjects with CFS were able to reach the prescribed activity goals each day. After this time, walking and total activity counts decreased. Sedentary controls subjects were able to maintain their daily walking and total activity goals throughout the 4 weeks. Unlike our previous interpretation of the data, we feel this new analysis suggests that CFS patients may develop exercise intolerance as demonstrated by reduced total activity after 4–10 days. The inability to sustain target activity levels, associated with pronounced worsening of symptomology, suggests the subjects with CFS had reached their activity limit.     

Activity of broad-spectrum and reduced-risk insecticides on various life stages of cranberry fruitworm (Lepidoptera: Pyralidae) in highbush blueberry

Laboratory and semifield bioassays were conducted to determine the life-stage activity of insecticides for controlling cranberry fruitworm, Acrobasis vaccinii Riley (Lepidoptera: Pyralidae), a key lepidopteran pest of highbush blueberry, Vaccinium corymbosum L. The organophosphates azinphosmethyl and phosmet, the pyrethroid esfenvalerate, and the carbamate methomyl were lethal to all life stages. The neonicotinoids thiacloprid and acetamiprid demonstrated strong larvicidal and ovicidal activity but were somewhat weaker adulticides than the conventional broad-spectrum compounds. Bacillus thuringiensis, indoxacarb, and emamectin benzoate were shown to control A. vacinii primarily through their larvicidal activity. Spinosad was toxic to all life stages, including eggs laid on top of residues and those that were treated topically, but larvicidal activity was short lived. The growth regulators pyriproxyfen and novaluron had strong ovicidal activity when eggs were laid on top of residues but had limited larvicidal activity. Tebufenozide was not directly toxic to eggs, but demonstrated larvicidal activity, and ovilarvicidal activity when topically applied to eggs. Azinphosmethyl, phosmet, indoxacarb, thiacloprid, and acetamiprid were all toxic to the egg parasitoid Trichogramma minutum Riley. In contrast pyriproxyfen, emamectin benzoate, methomyl, novaluron, and spinosad did not negatively affect the survival of T. minutum within Acrobasis vacinii eggs. These results help inform the ongoing development of integrated strategies for insect management in blueberry.     

Desulphation of heparin by mice and guinea pig leukocytes

Leukocytes from mice and guinea pigs were tested for their sulphate-splitting activity on heparin. Mouse macrophages showed the highest degrading activity while mouse neutrophils and lymphocytes were less active. In comparison, guinea pig spleen cells and leukocytes showed only a weak degrading activity. Mouse macrophages maintained in tissue culture were also found to degrade heparin, the amount of sulphate released increasing with time up to 96 h. Spleen extracts were found to neutralize the anticoagulatory activity of heparin.     

Long-term electromyographic activity in upper trapezius and low back muscles of women with moderate physical activity.

The habitual activity patterns of trapezius and postural back muscles (multifidus, iliocostalis, longissimus) of 23 female subjects with moderate physical activity were studied. Bilateral surface electromyographic (sEMG) recordings from start of work until bedtime were analyzed. The activity level was calibrated as percentage of root mean square-detected muscle activity at maximal voluntary contraction (EMG(max)). Sixty-six previous trapezius recordings of women with moderate physical activity were included in some analyses to pursue the full range of variation in trapezius activity. Twenty-six of these were recorded twice, separated by 16-28 mo. Median activity level and duration of periods with sEMG activity of <0.5% EMG(max) ("rest time"; only trapezius) and exceeding 2 ("burst time"), 10, 30, and 50% EMG(max) was determined. The trapezius median activity level ranged from 0.6 to 8.8% EMG(max), burst time from 9 to 84%, and rest time from 2 to 84%. The activity patterns of the back muscles showed similar large interindividual variation. Repeated trapezius recordings of the same subject showed high consistency; intraclass correlation coefficients ranged from 0.62 to 0.79 for different sEMG variables. Periods with high sEMG amplitude were of short duration; 7% of the trapezius recordings did not present time intervals (0.2-s duration) above 50% EMG(max). The activity patterns of the postural muscles, despite large interindividual variability, were distinctly different from activity patterns of upper and lower limb muscles reported by others (e.g., mean burst time 40-50 vs. 10-20%). We conclude that postural trunk muscles show idiosyncratic activity patterns with large interindividual variation. High-threshold motor units are activated to a very minor extent.     

Phospholipid-dependence of oestrone UDP-glucuronyltransferase and p-nitrophenol UDP-glucuronyltransferase.

Hepatic UDP-glucuronyltransferase activity was resolved into two fractions, one exhibiting oestrone glucuronyltransferase activity and the other exhibiting p-nitrophenol glucuronyltransferase activity. Hydroxyapatite-column chromatography removed greater than 95% of the phospholipids from both preparations. The partially purified delipidated enzymes were essentially devoid of catalytic activity, but activities were restored by the addition of phospholipids or phosphatidylcholine mixtures containing various saturated and unsaturated fatty acids. Both oestrone and p-nitrophenol glucuronyl-transferase activities were reconstituted to similar degrees with the phosphatidylcholine mixtures. When purified phospholipids were tested, phosphatidylcholine and lysophosphatidylcholine were most effective in restoring activity, whereas phosphatidylethanolamine was the least effective. These results further suggest that oestrone and p-nitrophenol UDP-glucuronyltransferases are dependent on phospholipids for their activity.