Observations on the chemistry of the waters of the Bay of Bengal off Madras city during 1948-1949

The study of the fundamental problem of the productivity of the sea involves knowledge of the composition of the sea water, particularly with reference to those inorganic compounds which form a valuable link in the food chain of life in the sea. The most important among these are th~ compounds of phosphorus, nitrogen and silicon. Studies on the distribution and seasoml varia tion of these compounds, commonly referred to as 'nutrients', form an essential preliminary to a more detailed biological investigation of the sea

Jacques Monod and the advent of the age of operons

"In Science, self satisfaction is death. Personal self satisfaction is the death of the scientist. Collective self satisfaction is the death of research. It is the restlessness, anxiety, dissatisfaction, agony of mind that nourish Science"

Phase variation and adaptation in bacteria: a 'Red Queen's Race'

In nature, bacteria are constantly exposed to many stressful conditions of life. This is particularly true of pathogens. Survival and adaptation under stressful conditions demand multiple strategies, genetic as well as phenotypic. Bacteria have many, pre-programmed, phenotypic stress response systems which can handle a limited number of stresses. Genetically, heritable as well as transient hypermutability mechanisms have been found to facilitate bacterial adaptation to varied and unpredictable stresses; these processes are not reviewed here. Instead, this article will focus on processes which do not increase global mutation rates but cause localized hypermutability in specific loci called contingency genes which have been identified particularly in pathogenic bacteria. These processes are collectively called phase and antigenic variations. Most of the contingency genes are involved in the synthesis or modification of surface-associated structures and enzymes. Phase variation in these genes involves high frequency, reversible, switching of their expression (on to off and off to on). The mechanisms of this switching are reviewed. However, some phase variable genes are not involved in the synthesis or modification of surface structures but are components of type I and type III restriction-modification (RM) systems. The on/off switching of these genes (type III RM genes) leads to regulation of expression of many unlinked genes, impacting several properties of cells. This novel type of control of multiple gene expression by phase variation has been named 'phasevarion'. The adaptive advantages of phase variation in contingency genes and phasevarions in the evasion of host immunity, virulence, niche adaptation and other phenomena are reviewed with some illustrative examples. Phase variation and bacterial adaptation have been likened to the 'Red Queen's Race' in Lewis Carrol's classic Through the Looking Glass

Seymour Benzer and T4 rII: running the map into the ground

One of the goals of genetics is to understand genes in as much detail as possible. For instance, with respect to a given gene, one would like to know its chromosomal location, its physical and genetic size, its neighbours, the number of mutations/alleles defining the gene, the order of mutations, the genetic/physical distance between them, etc. Thus, rather than focusing on the whole genome, one focuses on the finer details of a given genetic segment. The exercise of probing such details is called 'fine structure genetic analysis'. There are several pioneers who have contributed enormously to this area in many bacterial and phage systems. Two stalwarts, Seymour Benzer and Charles Yanofsky, stand preeminent among them. In the following pages I present briefly Benzer's outstanding work on the fine structure of the rII region of bacteriopage T4. These path-breaking studies contributed significantly to our understanding of the structure, organization and function of genes

Hypermutation and stress adaptation in bacteria

Hypermutability is a phenotype characterized by a moderate to high elevation of spontaneous mutation rates and could result from DNA replication errors, defects in error correction mechanisms and many other causes. The elevated mutation rates are helpful to organisms to adapt to sudden and unforeseen threats to survival. At the same time hypermutability also leads to the generation of many deleterious mutations which offset its adaptive value and therefore disadvantageous. Nevertheless, it is very common in nature, especially among clinical isolates of pathogens. Hypermutability is inherited by indirect (second order) selection along with the beneficial mutations generated. At large population sizes and high mutation rates many cells in the population could concurrently acquire beneficial mutations of varying adaptive (fitness) values. These lineages compete with the ancestral cells and also among themselves for fixation. The one with the 'fittest' mutation gets fixed ultimately while the others are lost. This has been called 'clonal interference' which puts a speed limit on adaptation. The original clonal interference hypothesis has been modified recently. Nonheritable (transient) hypermtability conferring significant adaptive benefits also occur during stress response although its molecular basis remains controversial. The adaptive benefits of heritable hypermutability are discussed with emphasis on host-pathogen interactions

Mutators and hypermutability in bacteria: the Escherichia coli paradigm

Mutators (also called hypermutators) are mutants which show higher than normal spontaneous mutation frequencies, ranging from 10-20 fold to 100-1000 fold higher, or sometimes even more, than wild-type cells. Being a mutator is advantageous to the organism when adapting to environmental changes or stressful situations, such as moving from one habitat to another, one host to another, exposure to antibiotics etc. However, this advantage is only a short-term benefit. In the long run, hypermutability leads to a fitness disadvantage due to accumulation of deleterious mutations or antagonistic pleiotropy or both. Contrary to intuitive expectations, hypermutability is commonly encountered in natural bacterial populations, especially among clinical isolates. It is believed to be involved in the emergence of antibiotic resistance and a hindrance to the treatment of infectious diseases. Here, I review the state of knowledge on the common mechanisms of hypermutability such as errors/defects in DNA replication, proof reading, mismatch repair, oxidative DNA damage, mistranslation etc., as well as phenomena associated with these processes, using Escherichia coli as a paradigmatic organism

The fit genes and transcription control in Escherichia coli

This article reviews the work done in the author's laboratory on the genetics and physiology of thefit mutants ofEscherichia coli. Isolaton of thefit mutants, genetic mapping, transcription abnormalities of thefit mutants, the possible involvement of thefit gene products in transcription control and identity of the fitA gene as pheS are described

A study on diagnostic significance of nerve conduction studies in early detection of Pure Neuritic Hansen’s disease

INTRODUCTION: Hansen's disease is diagnosed by presence of skin lesions. However, in case of pure neuritic hansen's the diagnosis is delayed because of absence of skin lesions. The delay in diagnosis leads to delay in treatment which leads to formation of deformities. This study is aim that whether nerve conduction studies are helpful in subjecting the patient to early nerve biopsy. AIM OF THE STUDY: To study the diagnostic significance of nerve conduction studies in early detection of pure neuritic hansen's disease. MATERIALS AND METHODS: This study is a descriptive study of analysing the patients with clinical suspicion of pure neuritic Hansen's electro physiologically and later corrlating with the nerve biopsy results. 70 patients attending neurology OPD with clinical suspicion of pure neuritic hansen's disease were selected. Patients were evaluated for other diseases which can mimic Hansen's disease. Patients were subjected to sural nerve biopsy and then the findings were correlated with electro physiology. RESULTS: 16 out of 70 patients were diagnosed to have Hansen's disease by biopsy. The most common mimickers for Hansen's were Diabetic Neuropathy, HMSN and connective tissue disorders. Nerve conduction studies including sympathetic skin response were abnormal in all patients with Hansen's disease. It was also abnormal in other diseases like Diabetic Neuropathy and connective tissue disorders. CONCLUSION: All the patients with biopsy proven Hansen's disease showed abnormal nerve conduction studies. Since nerve conduction studies were also abnormal in other diseases it is not specific for Hansen's and based on that alone we cannot subject the patients for nerve biopsy. Nerve biopsy clinches the diagnosis

Low cycle fatigue of MAR-M 200 single crystals at 760 and 870 deg C

Fully reversed low cycle fatigue tests were conducted on single crystals of the nickel-base superalloys Mar-M 200 at 760 C and 870 C. At 760 C, planar slip (octahedral) lead to orientation-dependent strain hardening and cyclic lives. Multiple slip crystals strain hardened the most, resulting in relatively high stress ranges and low lives. Single slip crystals strain hardened the least, resulting in relatively low stress ranges and higher lives. A preferential crack initiation site which was related to slip plane geometry was observed in single slip orientated crystals. At 870 C, the trends were quite different, and the slip character was much more homogeneous. As the tensile axis orientation deviated from 001 , the stress ranges increased and the cyclic lives decreased. Two possible mechanisms were proposed to explain the behavior: one is based on Takeuchi and Kuramoto's cube cross-slip model, and the other is based on orientation-dependent creep rates