From Here to Eternity—The Theory and Practice of a Really Long Experiment

In February 1988, Richard Lenski set up 12 replicate populations of a single genotype of Escherichia coli in a simple nutrient medium. He has been following their evolution ever since. Here, Lenski answers provocative questions from Jeremy Fox about his iconic "Long-Term Evolution Experiment" (LTEE). The LTEE is a remarkable case study of the interplay of determinism and chance in evolution—and in the conduct of science.     

Neglected Zoonotic Diseases—The Long and Winding Road to Advocacy

Background

Years of advocacy for the neglected tropical diseases (NTDs) have focused the world''s attention on these diseases of the poor, resulting most recently in the 2012 “London Declaration” and the recent World Health Assembly Resolution WHA66.12 on NTDs in May 2013. Control of the endemic neglected zoonotic diseases (NZDs) would benefit from a similar campaign, which needs the support of a global community.

Methodology/Principal Findings

The resolutions from all 66 World Health Assembly (WHA) meetings held between 1948 and 2013 were examined to determine how many contain a specific focus on any of the following eight NZDs as defined by the World Health Organisation (WHO): anthrax, bovine tuberculosis (TB), brucellosis, Taenia solium cysticercosis, cystic echinococcosis (hydatidosis), leishmaniasis, rabies, and zoonotic human African trypanosomiasis (HAT or sleeping sickness). Twenty-one resolutions adopted in the 16 assemblies between 1948 and 2013 targeted one or more of these eight NZDs, representing 4% of the total resolutions on infectious diseases passed to date. The 2013 adoption of Resolution WHA66.12 targeting all 17 NTDs marks a change in approach by the WHA. Whereas previous resolutions have targeted the NTDs as separate entities, the new approach of the combined resolution will help increase the overall momentum to target these ancient diseases as coendemic clusters in endemic countries. However, three major NZDs remain outside this recent resolution: anthrax, brucellosis, and bovine TB.

Conclusions and Significance

The recent adoption of a specific resolution at the WHA in 2013 that emphasises a One Health approach for the successful control of 17 NTDs is a major development in advocacy. However, recognition of the importance of three major NZDs to public health in endemic countries—anthrax, brucellosis, and bovine tuberculosis—is still lacking despite being prioritised by the WHA as early as the 1950s. Global advocacy for control of the NZDs as a whole would similarly benefit from adoption of a One Health approach as is promoted for the NTDs under WHA66.12.     

MANAGEMENT OF NEPHROSIS—The Use of Long Continued Hormone Therapy

The course of nephrosis in 36 children was evaluated. Twelve of 24 who received no treatment or short-term courses of steroids died. Eleven of the 24 had been well for six months to five years at the time of this report.Twelve patients received steroids by schedule over extended periods. One died and eleven had been free of signs and symptoms of nephrosis for four to eighteen months at the time of report. In only two cases was therapy discontinued. It seems evident that these patients are experiencing a better state of well-being. Whether or not the prognosis is being altered for any single patient cannot be determined.     

Protein Aggregation in E. coli?: Short Term and Long Term Effects of Nutrient Density

During exponential growth some cells of E. coli undergo senescence mediated by asymmetric segregation of damaged components, particularly protein aggregates. We showed previously that functional cell division asymmetry in E. coli was responsive to the nutritional environment. Short term exposure as well as long term selection in low calorie environments led to greater cell division symmetry and decreased frequency of senescent cells as compared to high calorie environments. We show here that long term selection in low nutrient environment decreased protein aggregation as revealed by fluorescence microscopy and proportion of insoluble proteins. Across selection lines protein aggregation was correlated significantly positively with the RNA content, presumably indicating metabolic rate. This suggests that the effects of caloric restriction on cell division symmetry and aging in E. coli may work via altered protein handling mechanisms. The demonstrable effects of long term selection on protein aggregation suggest that protein aggregation is an evolvable phenomenon rather than being a passive inevitable process. The aggregated proteins progressively disappeared on facing starvation indicating degradation and recycling demonstrating that protein aggregation is a reversible process in E. coli.     

Privileged Communications—The Effect of California's New Evidence Code As It Concerns Physicians and Psychotherapists

A physician has an ethical duty to hold in confidence communications made to him by his patient. A legal recognition of this ethical duty is found in the concept of privilege, which is the subject of this article. January 1967 will bring to California physicians a new protection for patients'' communications. The physician-patient privilege has been redefined to include confidential communications made during diagnostic evaluation, those made to non-licensed physicians, interns and medical aides, and those overheard by eavesdroppers. There has been added a psychotherapist-patient privilege designed to facilitate communications required in psychotherapy as well as in behavioral research.This paper first presents a brief historical background and discusses the protections and limitations afforded by the new California Evidence Code. There follows a section on the psychotherapist-patient privilege with the recommendation that in the context of psychotherapy, patients of physicians who are not psychiatrists should be afforded the additional benefits of the psychotherapist-patient privilege. Lastly, advice is given concerning the physician''s conduct in relation to his duty to claim privilege under the new code.     

The Role of Zinc in Thrombosis and Pulmonary Embolism in the Course of Antiphospholipid Syndrome (APS)—Short Review

Antiphospholipid antibodies may occur in the course of various diseases, but its presence is not necessarily associated with clinical symptoms. Zinc has multiple biological roles. For example, it stabilizes the cell’s membrane and regulates its functions by influencing the synthesis of phospholipids and its distribution. The present review focuses on the possible associations between zinc and antiphospholipid antibodies and with the symptoms of antiphospholipid syndrome.     

How Pancreatic β-Cells Discriminate Long and Short Timescale cAMP Signals

The translocation of catalytic protein kinase A (cPKA) in response to cyclic-adenosine mono-phosphate (cAMP) depends on the pattern of stimulus applied to the cell. Experiments with IBMX have shown that 1), sustained cAMP elevation is more effective than oscillations of cAMP at getting cPKA into the nucleus; and 2), cPKA enters the nucleus by diffusion. We constructed mathematical models of cAMP activation of cPKA and their diffusion in order to study nuclear translocation of cPKA, and conclude that hindered diffusion of cPKA through the nuclear membrane by a rapid-binding process, but not globally reduced diffusion, can explain the experimental data. Perturbation analysis suggests that normal physiological oscillations of glucose would not result in nuclear translocation, but chronically high glucose that produces extended calcium plateaus and/or chronic glucagonlike peptide-1 stimulation could result in elevated levels of nuclear cPKA.     

8-METHOXYPSORALEN—A Short Review and Comment

8-Methoxypsoralen is a purified extract of the root ammi majus lynn, which was used in a crude form for centuries in the Middle East in the treatment of various skin diseases. In recent years it has been found that the purified extract, when taken internally, increases all skin responses to sunlight, including tanning. When too much drug is taken or when the patient is exposed to sunlight too long, the preliminary erythema may be painful, and blistering may occur. In some patients with vitiligo, islands of pigmentation appear around the hair follicles when the drug is taken, and in favorable cases these islands may coalesce to form continuous areas of pigmented skin. The drug has been found nontoxic, but successful treatment of vitiligo takes place in only a small proportion of patients.Promiscuous use of the drug for cosmetic tanning is to be deplored. The constant irritation of the skin due to the increased action of sunlight when the drug is used may possibly increase the incidence of sun-induced skin cancers.A topical preparation is available, which, when used with great care, may help to repigment small areas of vitiligo.     

Short Communication—Effects of oligosaccharins on callus growth and saponin content of Panax notoginseng

This work provides some evidences for the saponin production of Panax notoginseng callus by using biologically active,wall-related oligosaccharins.In an appropriate concentration,three kinds of oligosaccharins stimulated saponin formation of callus growth.The concentration of DO,GO and CO for saponin production of Panax notoqinseng callus culture were 15ppm,15ppm aud 20ppm respectively by comparing saponin yield,It was very obvious for DO to increase saponin content when the concentration was 10ppm,and for GO to stimulate callus growth when the concentration was 20ppm,It would be a good way to produce sapoin by using oligosaccharins in large scale culture in the future.     

It Is Tough and Tiring but It Works—Children’s Experiences of Undergoing Radiotherapy

Approximately 300 children ages 0 to 18 are diagnosed with cancer in Sweden every year, and 80 to 90 of them undergo radiotherapy treatment. The aim was to describe children’s experiences of preparing for and undergoing radiotherapy, and furthermore to describe children’s suggestions for improvement. Thirteen children between the ages of 5 and 15 with various cancer diagnoses were interviewed. Data was analyzed using qualitative content analysis. The findings revealed five categories: positive and negative experiences with hospital stays and practical arrangements; age-appropriate information, communication, and guidance to various degrees; struggle with emotions; use of distraction and other suitable coping strategies; and children’s suggestions for improvement during radiotherapy. An overarching theme emerged: “It is tough and tiring but it works”. Some key areas were: explanatory visits, the need for information and communication, being afraid, discomfort and suffering, the need for media distraction, dealing with emotions, and the need for support. A systematic, family-centered preparation program could possible help families prepare and individualized distraction during radiotherapy could contribute to reducing distress. Further studies with interventions could clarify successful programs.     

ARTERIAL HOMOGRAFTS—Long Term Observation of Results

In 29 consecutive cases of resection and aortic homograft replacement done between 1954 and 1958, the only surgical mortality occurred 14 days postoperatively and was due to a rupture of the implanted vessel.Seven patients have died (after a survival time averaging 21 months postoperatively) of causes not directly related to the aortic disease or to the operation.Twenty-one patients were still living some three to six and a half years after the implantation procedure—all of them active and showing no clinical evidence of aneurysmal dilatation.Infant thoracic aorta was used for homograft in the femoropopliteal area in three cases. Two of the patients were still living at the time of last report, four and five years after operation, with no evidence of obstruction or dilatation. This is perhaps indicative of the superiority of this material over plastic prosthesis for this purpose.     

Electrorotation of lymphocytes—The influence of membrane events and nucleus

Electrorotation—the spin of cells in rotating high frequency electric fields—has been used to investigate properties of human peripheral blood lymphocytes. The rotation spectra of lymphocytes deviate from those of single shell spheres. The deviations are caused by the electrical properties of the nucleus in the cell interior.Electrorotation allows the distinction between successfully stimulated lymphocytes and unstimulated cells after application of concanavalin A. Notwithstanding the fact that only a proportion of the cells will be mitogenically stimulated we detected an enhanced cell membrane conductivity for the whole cell population immediately after the addition of mitogen.     

Little but Loud. The Diversity of Functions of Small Proteins and Peptides – Translational Products of Short Reading Frames

Biochemistry (Moscow) - Cell functioning is tightly regulated process. For many years, research in the fields of proteomics and functional genomics has been focused on the role of proteins in cell...