On the mechanism of chromatin loss induced by the B chromosome of maize

Knobbed regions of the regular maize complement frequently are eliminated at the second microspore division in spores which have two or more B chromosomes. Evidence is presented that no or little loss occurs in spores with one B and that the rate is not increased in spores with more than two B's.—The B chromosomes from an unrelated strain proved as effective in inducing loss as did the B's of the original high loss stock.—Chromatin loss induced by B's is restricted to knobbed A chromosomes and occurs only at the second microspore division. Knobbed chromosomes 3, 5, and 9 have been tested and all interact with B's to give loss. Chromosomes with large knobs are more frequently broken than are those with smaller knobs and knobless chromosomes show negligible loss.—Although knobs and B's are essential for chromatin elimination, modifying genes can markedly affect the rate of loss.——Two knobbed heterologous chromosomes undergo simultaneous loss more frequently than expected from independent events. The data indicate that joint loss occurs in competent cells and that preferential assortment of the two deficient chromosomes to specific poles is unlikely.—B chromosomes and deficient chromosomes assort independently at the second microspore anaphase.—Genetic data from crosses with marker genes in both arms of chromosome 3 show that breakage of the postulated dicentric bridge does not occur solely at the centric region since a variety of deficient chromosomes were recovered.—Nondisjunction of B chromosomes and elimination of knobbed chromatin take place during the second microspore mitosis. The argument is advanced that the two phenomena result from faulty replication of heterochromatic segments. The position of the nonreplicating segment in the two kinds of chromosomes determines whether nondisjunction or breakage takes place.—Finally, it is suggested that all of the reported effects of the B chromosome can be accounted for if the B is a parasitic entity having no genetic function other than controlling the replication of its proximal heterochromatic knob and increasing the ability of B-containing sperm cells to compete successfully for fertilization of the egg.     

Nifedipine and atenolol singly and combined for treatment of essential hypertension: comparative multicentre study in general practice in the United Kingdom

A randomised double blind parallel group study was performed to compare the efficacy and acceptability of slow release nifedipine (maximum dose 40 mg twice a day) with those of atenolol (maximum dose 100 mg once a day) as single agents for the treatment of essential hypertension. Of 410 patients recruited almost exclusively from general practices in 22 centres in the United Kingdom 210 received nifedipine and 200 atenolol. Both drugs significantly reduced blood pressure, and control—a reduction of the diastolic pressure to less than 95 mm Hg—was obtained in about 65% of patients. Those who received nifedipine had more pronounced reductions in systolic pressure than those who received atenolol. One hundred and forty nine patients who failed to respond adequately to either atenolol or nifedipine in low doses were given both drugs once daily for eight weeks in a fixed combination capsule that contained atenolol 50 mg and nifedipine 20 mg. All patients showed further reductions in blood pressure, although those who were taking β atenolol before the combination capsule had more pronounced reductions in systolic pressures. Twenty six patients (12%) were withdrawn because of adverse effects while taking nifedipine compared with 19 (10%) taking atenolol. Flushing and oedema were more common after the calcium antagonist, whereas diarrhoea and dyspepsia were more common after atenolol. The frequencies of headaches, dizziness, fatigue, and dyspnoea were equally distributed between the two groups. When the fixed combination capsule was taken side effects such as flushing and oedema continued.Nifedipine was more effective than atenolol in lowering systolic blood pressure, although neither drug used alone controlled the pressure of more than two thirds of the patients studied. When used in a fixed combination slightly better control of blood pressure was achieved with a lower dose of each drug.     

A NEW ANTIHYPERTENSIVE AGENT—Clinical Evaluation of a Rauwolfia-Flumethiazide Combination (Rautrax?)

Twenty-eight patients were treated with Rautrax,® a combination of flumethiazide, rauwolfia and potassium chloride for from one to seven months. The average mean blood pressure for the group declined from 135 mm. of mercury to 107 mm. All but two of the patients had a decrease in blood pressure and 19 became normotensive. Associated symptoms of headache, dyspnea, edema and angina were completely relieved or improved in the majority of patients with these complaints. On the basis of the blood pressure response and the clinical effects seen in the patient, therapeutic results were classified as good to excellent in 22 of the 28 patients, fair in two, and poor in three. No evaluation was made in the remaining patient in the series because further adjustment in dosage was required.Three patients had side effects—moderate gastrointestinal upset in one case, headache and a sensation of the bladder''s having been “wrung out” in another, and headache and paresthesia of the legs in the third. Only the third patient had persisting symptoms after the drug was discontinued. In the other two reduction of dosage sufficed.     

Factors Affecting Work Load in General Practice—II

The second part of a survey studying factors that affect a general practitioner''s work load considers the effects of age, sex, social class and time on list. Women, the old, and the young created the most work for the doctor and his paramedical team. Patients in the lower social classes also generated more work, even though a larger proportion of the higher social classes used the resources of the general practice—and more fully. Newly-registered patients generated slightly more work than the more permanent residents. Not only the size of a doctor''s list, therefore, but also the demographic features of the community should be taken into account in determining the size and structure of the general-practice team needed for an area.     

Anti-Cancer Vaccines — A One-Hit Wonder?

Immunization against common bacterial and viral diseases has helped prevent millions of deaths worldwide. More recently, the concept of vaccination has been developed into a potentially novel strategy to treat and prevent cancer formation, progression, and spread. Over the past few years, a handful of anti-cancer vaccines have been licensed and approved for use in clinical practice, thus providing a breakthrough in the field. However, the path has not always been easy, with many hurdles that have had to be overcome in order to reach this point. Nevertheless, with more anti-cancer vaccines currently in development, there is still hope that they can eventually become routine tools used in the treatment and prevention of cancer in the future. This review will discuss in detail both types of anti-cancer vaccine presently used in clinical practice — therapeutic and preventive — before considering some of the more promising anti-cancer vaccines that are currently in development. Finally, the issue of side effects and the debate surrounding the overall cost-effectiveness of anti-cancer vaccines will be examined.     

The Role of Family Environment in Depressive Symptoms among University Students: A Large Sample Survey in China

Objective

To explore the relationship between family environment and depressive symptoms and to evaluate the influence of hard and soft family environmental factors on depression levels in a large sample of university students in China.

Methods

A multi-stage stratified sampling procedure was used to select 6,000 participants. The response rate was 88.8%, with 5,329 students completing the Beck Depression Inventory (BDI) and the Family Environment Scale Chinese Version (FES-CV), which was adapted for the Chinese population. Differences between the groups were tested for significance by the Student’s t-test; ANOVA was used to test continuous variables. The relationship between soft family environmental factors and BDI were tested by Pearson correlation analysis. Hierarchical linear regression analysis was conducted to model the effects of hard environmental factors and soft environmental factors on depression in university students.

Results

A total of 11.8% of students scored above the threshold of moderate depression(BDI≧14). Hard family environmental factors such as parent relationship, family economic status, level of parental literacy and non-intact family structure were associated with depressive symptoms. The soft family environmental factors—conflict and control—were positively associated with depression, while cohesion was negatively related to depressive symptom after controlling for other important associates of depression. Hierarchical regression analysis indicated that the soft family environment correlates more strongly with depression than the hard family environment.

Conclusions

Soft family environmental factors—especially cohesion, conflict and control—appeared to play an important role in the occurrence of depressive symptoms. These findings underline the significance of the family environment as a source of risk factors for depression among university students in China and suggest that family-based interventions and improvement are very important to reduce depression among university students.     

Microbiologic contamination of bovine semen.

Candida tropicalis was found in five infertile uteri with endometritis and in two dead fetuses in utero. C. tropicalis was also found in the commercial frozen semen used on this ranch. The source of contamination was traced to the green dye used by the semen processor to identify the semen.Routine culturing of commericial frozen semen revealed a variety of both quality and quantity of microbiologic contamination. This can be eliminated by hygenic collection of semen as was demonstrated at one bull stud. A check list of collection procedures is included.     

Components of placebo effect: randomised controlled trial in patients with irritable bowel syndrome

Objective To investigate whether placebo effects can experimentally be separated into the response to three components—assessment and observation, a therapeutic ritual (placebo treatment), and a supportive patient-practitioner relationship—and then progressively combined to produce incremental clinical improvement in patients with irritable bowel syndrome. To assess the relative magnitude of these components.Design A six week single blind three arm randomised controlled trial.Setting Academic medical centre.Participants 262 adults (76% women), mean (SD) age 39 (14), diagnosed by Rome II criteria for and with a score of ≥150 on the symptom severity scale.Interventions For three weeks either waiting list (observation), placebo acupuncture alone (“limited”), or placebo acupuncture with a patient-practitioner relationship augmented by warmth, attention, and confidence (“augmented”). At three weeks, half of the patients were randomly assigned to continue in their originally assigned group for an additional three weeks.Main outcome measures Global improvement scale (range 1-7), adequate relief of symptoms, symptom severity score, and quality of life.Results At three weeks, scores on the global improvement scale were 3.8 (SD 1.0) v 4.3 (SD 1.4) v 5.0 (SD 1.3) for waiting list versus “limited” versus “augmented,” respectively (P<0.001 for trend). The proportion of patients reporting adequate relief showed a similar pattern: 28% on waiting list, 44% in limited group, and 62% in augmented group (P<0.001 for trend). The same trend in response existed in symptom severity score (30 (63) v 42 (67) v 82 (89), P<0.001) and quality of life (3.6 (8.1) v 4.1 (9.4) v 9.3 (14.0), P<0.001). All pairwise comparisons between augmented and limited patient-practitioner relationship were significant: global improvement scale (P<0.001), adequate relief of symptoms (P<0.001), symptom severity score (P=0.007), quality of life (P=0.01).Results were similar at six week follow-up.Conclusion Factors contributing to the placebo effect can be progressively combined in a manner resembling a graded dose escalation of component parts. Non-specific effects can produce statistically and clinically significant outcomes and the patient-practitioner relationship is the most robust component.Trial registration Clinical Trials NCT00065403.     

THE USE OF BANTHINE IN THE TREATMENT OF DIGESTIVE DISTURBANCES

Banthine® was used in the treatment of patients with various diseases, organic and functional, of the gastrointestinal tract. Good response was obtained in a high proportion of cases of duodenal, stomal and gastric ulcer, and of hypertrophic gastritis. In some instances, patients who did not have good response at first were relieved later when the size of doses and the dosage schedule were adjusted to fit their particular needs.Some patients “felt so well” during Banthine therapy that they departed from prescribed diet and violated injunctions against use of alcohol and tobacco, and symptoms recurred.Nine patients with history of recurrent bouts of pain from ulcer for several years took small doses of Banthine constantly, or occasionally at times of stress, as a prophylactic measure after the symptoms were relieved by therapeutic doses. None of them had recurrence while following the prophylactic regimen.In most of the cases of peptic ulcer in which the response was recorded as “poor,” it was because distressing side-effects dictated discontinuance of the drug. Several elderly male patients had severe urinary retention. Paralytic ileus developed postoperatively in one patient who was receiving Banthine. Less severe side reactions—dry mouth, blurring of vision, urinary slowing — were for the most part transient.Few patients with functional indigestion, chronic non-specific colitis or regional enteritis were relieved. Most of the patients with functional indigestion reported exacerbation of symptoms when Banthine was given. This was believed to be based on emotional reaction to the hypomotility induced by the drug.     

A Controlled Clinical Trial Using Placebos in Normal Subjects: A Teaching Exercise

An exercise for medical students was designed to illustrate one method of setting up a clinical trial and incidentally to demonstrate some effects of placebos. Twelve groups of four students participated: one in each group was the “recorder”, the other three (volunteers) were randomly assigned to the treatment A, treatment B, or untreated groups. Subjects performed seven psychomotor or mental tests before taking medication and 30 and 60 minutes after medication. The time taken for the tests and the errors made were recorded. Treatment A was one green and yellow gelatin capsule filled with lactose, taken with water; treatment B was a red and white capsule containing lactose; untreated subjects received a drink of water. No large changes in performance occurred and no evidence of fatigue or learning was noted, although the B''s took significantly longer to perform the arithmetic test after medication than before. Treated subjects were instructed to check any of 29 listed side effects that they experienced. A total of 44 side effects was reported: 8 of 12 in A group and 10 of 12 in B checked one or more symptoms. Indications are that the results of the trial will not soon be forgotten.     

Bighorn sheep show similar in‐host responses to the same pathogen strain in two contrasting environments

Ecological context—the biotic and abiotic environment, along with its influence on population mixing dynamics and individual susceptibility—is thought to have major bearing on epidemic outcomes. However, direct comparisons of wildlife disease events in contrasting ecological contexts are often confounded by concurrent differences in host genetics, exposure histories, or pathogen strains. Here, we compare disease dynamics of a Mycoplasma ovipneumoniae spillover event that affected bighorn sheep populations in two contrasting ecological contexts. One event occurred on the herd''s home range near the Rio Grande Gorge in New Mexico, while the other occurred in a captive facility at Hardware Ranch in Utah. While data collection regimens varied, general patterns of antibody signal strength and symptom emergence were conserved between the two sites. Symptoms appeared in the captive setting an average of 12.9 days postexposure, average time to seroconversion was 24.9 days, and clinical signs peaked at approximately 36 days postinfection. These patterns were consistent with serological testing and subsequent declines in symptom intensity in the free‐ranging herd. At the captive site, older animals exhibited more severe declines in body condition and loin thickness, higher symptom burdens, and slower antibody response to the pathogen than younger animals. Younger animals were more likely than older animals to clear infection by the time of sampling at both sites. The patterns presented here suggest that environment may not be a major determinant of epidemiological outcomes in the bighorn sheep—M. ovipneumoniae system, elevating the possibility that host‐ or pathogen‐factors may be responsible for observed variation.     

Sulfhydryl groups and the structure of hemoglobin

1. Addition of 2 moles of mersalyl, mercuric chloride, p-chloromercuribenzoate (PCMB), or methyl mercury hydroxide per mole of hemoglobin greatly reduces heme-heme interactions (n), yet these substances have quite different effects on the oxygen affinity (-log p₅₀). Mersalyl and mercuric chloride at this concentration each increase the oxygen affinity, while PCMB and methyl mercury have little or no effect on the oxygen affinity. These effects are primarily associated with the binding of —SH groups, and are largely reversed on the addition of glutathione. —SH groups do not appear to be responsible for the Bohr effect. 2. Evidence is presented for the belief that the two hemes of each half-molecule of horse hemoglobin are situated on either side of a cluster of—SH groups. 3. The mechanism of interaction between the hemes is discussed. It is concluded that the reorganization of the protein architecture which accompanies oxygenation plays a central role in this interaction, in agreement with the views of Pauling and Wyman.     

CANCER OF THE LUNG IN WOMEN

Cancer of the lung in women has the same signs and symptoms as in men, but the disease seems to advance more rapidly. Of 35 female patients, half were under radiation therapy (for inoperable tumor) within four months after the first manifestation. In three of the five who had no symptoms, the cancer when diagnosed was inoperable.Scalene node biopsy confirmed metastasis in nine of the eleven cases in which it was used, and this procedure should be used after diagnosis whenever metastasis is not evident.Of the 35 women, two received only chemotherapy, 32 radiotherapy. Only four were alive at the time of report—one without evidence of disease at 20 months, one with symptoms of disease at 11 months, two under chemotherapy at two months, For 29 who received palliative or radical irradiation to the primary tumor site, the median survival time was 26 weeks.     

Genetic Effects of Acute Spermatogonial X-Irradiation of the Laboratory Rat

The genetic effects of one generation of spermatogonial X-irradiation in rats, by a single dose of 600r in one experiment and by a fractionated dose of 450r in another, were measured in three generations of their descendants. Estimates of dominant lethal mutation rates—(2 to 3) x 10 ^-4/gamete/r—from litter size differences between irradiated and nonirradiated stock were consistent with previous estimates from rats and mice. Similar consistency was found for estimates of sex-linked recessive mutation rates—(1 to 2) x 10^-4 chromosome/r—from male proportions within strains; however, when measured in crossbreds the proportion of males was higher in the irradiated than in the nonirradiated lines. This inconsistency in results is in keeping with the contradictory results reported for recessive sex-linked lethal mutation rates in mice. The effects used to estimate recessive lethal mutation rates which were unusually high—(2 to 14) x 10^-4/gamete/r—were not significant. Other factors that could have contributed to the observed effects are postulated.     

DNA repair inhibition by UVA photoactivated fluoroquinolones and vemurafenib

Cutaneous photosensitization is a common side effect of drug treatment and can be associated with an increased skin cancer risk. The immunosuppressant azathioprine, the fluoroquinolone antibiotics and vemurafenib—a BRAF inhibitor used to treat metastatic melanoma—are all recognized clinical photosensitizers. We have compared the effects of UVA radiation on cultured human cells treated with 6-thioguanine (6-TG, a DNA-embedded azathioprine surrogate), the fluoroquinolones ciprofloxacin and ofloxacin and vemurafenib. Despite widely different structures and modes of action, each of these drugs potentiated UVA cytotoxicity. UVA photoactivation of 6-TG, ciprofloxacin and ofloxacin was associated with the generation of singlet oxygen that caused extensive protein oxidation. In particular, these treatments were associated with damage to DNA repair proteins that reduced the efficiency of nucleotide excision repair. Although vemurafenib was also highly phototoxic to cultured cells, its effects were less dependent on singlet oxygen. Highly toxic combinations of vemurafenib and UVA caused little protein carbonylation but were nevertheless inhibitory to nucleotide excision repair. Thus, for three different classes of drugs, photosensitization by at least two distinct mechanisms is associated with reduced protection against potentially mutagenic and carcinogenic DNA damage.     

distAngsd: Fast and Accurate Inference of Genetic Distances for Next-Generation Sequencing Data

Commonly used methods for inferring phylogenies were designed before the emergence of high-throughput sequencing and can generally not accommodate the challenges associated with noisy, diploid sequencing data. In many applications, diploid genomes are still treated as haploid through the use of ambiguity characters; while the uncertainty in genotype calling—arising as a consequence of the sequencing technology—is ignored. In order to address this problem, we describe two new probabilistic approaches for estimating genetic distances: distAngsd-geno and distAngsd-nuc, both implemented in a software suite named distAngsd. These methods are specifically designed for next-generation sequencing data, utilize the full information from the data, and take uncertainty in genotype calling into account. Through extensive simulations, we show that these new methods are markedly more accurate and have more stable statistical behaviors than other currently available methods for estimating genetic distances—even for very low depth data with high error rates.     

Recollection-Based Retrieval Is Influenced by Contextual Variation at Encoding but Not at Retrieval

In this article, we investigated the effects of variations at encoding and retrieval on recollection. We argue that recollection is more likely to be affected by the processing that information undergoes at encoding than at retrieval. To date, manipulations shown to affect recollection were typically carried out at encoding. Therefore, an open question is whether these same manipulations would also affect recollection when carried out at retrieval, or whether there is an inherent connection between their effects on recollection and the encoding stage. We therefore manipulated, at either encoding or retrieval, fluency of processing (Experiment 1)—typically found not to affect recollection—and the amount of attentional resources available for processing (Experiments 2 and 3)—typically reported to affect recollection. We found that regardless of the type of manipulation, recollection was affected more by manipulations carried out at encoding and was essentially unaffected when these manipulations were carried out at retrieval. These findings suggest an inherent dependency between recollection-based retrieval and the encoding stage. It seems that because recollection is a contextual-based retrieval process, it is determined by the processing information undergoes at encoding—at the time when context is bound with the items—but not at retrieval—when context is only recovered.     

Microbial Degradation of Natural Rubber Vulcanizates

An actinomycete, Nocardia sp. strain 835A, grows well on unvulcanized natural rubber and synthetic isoprene rubber, but not on other types of synthetic rubber. Not only unvulcanized but also various kinds of vulcanized natural rubber products were more or less utilized by the organism as the sole source of carbon and energy. The thin film from a latex glove was rapidly degraded, and the weight loss reached 75% after a 2-week cultivation period. Oligomers with molecular weights from 10⁴ to 10³ were accumulated during microbial growth on the latex glove. The partially purified oligomers were examined by infrared and ¹H nuclear magnetic resonance and ¹³C nuclear magnetic resonance spectroscopy, and the spectra were those expected of cis-1, 4-polyisoprene with the structure, OHC—CH₂—[—CH₂—C(—CH₃)=CH —CH₂—]_n—CH₂—C(=O)— CH₃, with average values of n of about 114 and 19 for the two oligomers.     

Multiple-Locus Sequence Typing Analysis of Bacillus cereus and Bacillus thuringiensis Reveals Separate Clustering and a Distinct Population Structure of Psychrotrophic Strains

We used multilocus sequence typing (MLST) to characterize phylogenetic relationships for a collection of Bacillus cereus group strains isolated from forest soil in the Paris area during a mild winter. This collection contains multiple strains isolated from the same soil sample and strains isolated from samples from different sites. We characterized 115 strains of this collection and 19 other strains based on the sequences of the clpC, dinB, gdpD, panC, purF, and yhfL loci. The number of alleles ranged from 36 to 53, and a total of 93 allelic profiles or sequence types were distinguished. We identified three major strain clusters—C, T, and W—based on the comparison of individual gene sequences or concatenated sequences. Some less representative clusters and subclusters were also distinguished. Analysis of the MLST data using the concept of clonal complexes led to the identification of two, five, and three such groups in clusters C, T, and W, respectively. Some of the forest isolates were closely related to independently isolated psychrotrophic strains. Systematic testing of the strains of this collection showed that almost all the strains that were able to grow at a low temperature (6°C) belonged to cluster W. Most of these strains, including three independently isolated strains, belong to two clonal complexes and are therefore very closely related genetically. These clonal complexes represent strains corresponding to the previously identified species Bacillus weihenstephanensis. Most of the other strains of our collection, including some from the W cluster, are not psychrotrophic. B. weihenstephanensis (cluster W) strains appear to comprise an effectively sexual population, whereas Bacillus thuringiensis (cluster T) and B. cereus (cluster C) have clonal population structures.     

NON-TOXIC GOITER TREATMENT WITH I-TRIIODOTHYRONINE AND I-THYROXINE

Twenty-one patients with goiters—four diffuse and 17 nodular—were treated with I-triiodothyronine and I-thyroxine in doses to tolerance. The four diffuse goiters were barely palpable at the end of the treatment. The average dose of I-triiodothyronine required was 100 mcg. per day. The average dose of I-thyroxine was 0.3 mg. per day. Of the 17 multinodular goiters, 11 showed at least a 50 per cent reduction in size. The average dose of I-triiodothyronine used was 125 mcg. In six cases the gland did not change in size; in three of the six the lesion was diagnosed, at operation, as microfollicular and macrofollicular colloid goiter.Hypermetabolic symptoms may occur when doses of 100 mcg. or more of I-triiodothyronine are used.Results indicated that suppressive therapy with thyroid hormone to tolerance is effective in diffuse goiters. It is only partially effective in the treatment of multinodular goiters. In the cases in which operation was done, no change in the basic histological goiter structure was observed.