Enzyme activity and dynamics in near-anhydrous conditions

Water is widely assumed to be essential for life 1, although the exact molecular basis of this requirement is unclear 2-4. Water facilitates protein motions 5-9 and although enzyme activity has been demonstrated at low hydrations in organic solvents 10-13, such non-aqueous solvents may allow the necessary motions for catalysis. To examine enzyme function in the absence of solvation and bypass diffusional constraints we have tested the ability of an esterase to catalyse alcoholysis as an anhydrous powder, using a closed reaction system in which the substrates and products of the enzyme reaction are gaseous 14-15, and where the water content can be well defined 16. At hydrations equivalent to 3 (±2) molecules of water per molecule of enzyme, activity is observed that is several orders of magnitude greater than non-enzymatic catalysis. Neutron spectroscopy indicates that the fast (≤nanosecond) global anharmonic dynamics of the anhydrous functional enzyme are heavily suppressed. The results indicate that neither hydration water nor the solvent-activated fast anharmonic dynamics are required for enzyme function. An implication of these results is that one of the essential requirements of water for life may lie with its role as a diffusion medium rather than any of its more specific properties

A rare case of beta-ketothiolase deficiency in identical twins

Betaketothiolase deficiency is a rare defect of isoleucine and ketone body metabolism which manifests as severe metabolic acidosis following common viral illnesses. A set of 1 year, 8 month-old identical male twins presented with similar symptoms in different time frames. Both of them had severe metabolic acidosis, hypoglycemia, and altered sensorium. Both twins tested positive for beta-ketothiolase deficiency by urine gas chromatography-mass spectrometry. The children responded to symptomatic treatment and are now growing well on a protein-restricted diet. Beta-ketothiolase deficiency is a rare disorder of amino acid metabolism with a favorable outcome if preventive measures are taken early

The prevalence of insulin resistance in polycystic ovarian syndrome cases at a tertiary care hospital: a cross sectional study

Background: Insulin resistance (IR) is defined clinically as the inability of a known quantity of exogenous or endogenous insulin to increase glucose uptake and utilization in an individual as much as it does in a normal population PCOS is a disease of heterogeneous disturbance of reproductive, endocrine and metabolic functions. The objective of the study was to study the prevalence of insulin resistance in polycystic ovarian syndrome cases.Methods: The present cross sectional study was carried out at Obstetrics and Gynecology department, MGM medical college, Kalamboli, Navi Mumbai for a period of 2 years from 2011 to 2013 on total of 50 women aged between 16-39 years, coming to OPD with complaints of menstrual irregularities, infertility or hirsutism. After initial assessment, pelvic ultrasonography was done in these women to confirm the diagnosis of polycystic ovaries.Results: Majority 26 (52%) cases were in age group of 16-25 years and, majority 19 (38%) cases were in overweight (25-29.99) group. There were 21 (42%) women with insulin resistance When chi square test was applied to assess the association between BMI and insulin resistance, it was found to be statistically significant. (p=0.01).Conclusions: The prevalence of abnormal glucose tolerance, dyslipidemia, insulin resistance and metabolic syndrome was observed to be high in PCOS. We conclude that physician should consider that early recognition to reduce the incidence and severity of associated potential sequelae

A rare presentation of heteropagus conjoined twin: a case report with review of literature

Conjoined twins are a rare occurrence with an incidence of about 1 in 100000 pregnancies. Our case is that of a 32 year old multigravida patient who came to us at 17 weeks gestation with a scan done at 14 weeks suggestive of severe spinal dysraphism with lumbar meningomyelocele spina bifida at multiple levels with protuberant abdomen. The patient opted for medical termination of pregnancy which was carried out after due to consent. The patient aborted after 12 hours. Further inspection of the abortus revealed it to be conjoined twins with one apparently normal head and thorax with a large omphalocele with 4 lower limbs. There were two caudal halves along with two sets of lower limbs and external genitalia arising from the abortus perpendicular to it on either side of the thorax. One set of arms was attached to the thorax and yet another arm and a limb bud were arising from the other end of the fetus attached to a rudimentary head like structure. Heteropagus tetrapus twins are an extremely rare form of parasitic twins. Inspite of advances in surgical techniques and methods, the morbidity endured by the affected neonates is very high. Thus prenatal diagnosis of conjoined twins along with the option of termination of pregnancy is of utmost importance.

Recurrent hydatiform mole: a rare case report

Molar pregnancy is characterized histologically by abnormalities of the chorionic villi that consist of trophoblastic proliferation and oedema of villous stroma. The incidence of hydatiform moles in India is 1 in 1000. The incidence of recurrence is 1 in 60 in a subsequent pregnancy and 1 in 65 in the third pregnancy after two molar pregnancies. The occurrence of hydatiform mole is related to a few risk factors such as smoking, increased paternal or maternal age, and previous history of abortions. Here we report a case of a 29 year old woman with history of four partial moles and two first trimester abortions and her management. The patient finally opted for adoption

Hydration Effect on Low-Frequency Protein Dynamics Observed in Simulated Neutron Scattering Spectra

Hydration effects on protein dynamics were investigated by comparing the frequency dependence of the calculated neutron scattering spectra between full and minimal hydration states at temperatures between 100 and 300 K. The protein boson peak is observed in the frequency range 1–4 meV at 100 K in both states. The peak frequency in the minimal hydration state shifts to lower than that in the full hydration state. Protein motions with a frequency higher than 4 meV were shown to undergo almost harmonic motion in both states at all temperatures simulated, whereas those with a frequency lower than 1 meV dominate the total fluctuations above 220 K and contribute to the origin of the glass-like transition. At 300 K, the boson peak becomes buried in the quasielastic contributions in the full hydration state but is still observed in the minimal hydration state. The boson peak is observed when protein dynamics are trapped within a local minimum of its energy surface. Protein motions, which contribute to the boson peak, are distributed throughout the whole protein. The fine structure of the dynamics structure factor is expected to be detected by the experiment if a high resolution instrument (<∼20 μeV) is developed in the near future

Structure and Dynamics of Biological Systems: Integration of Neutron Scattering with Computer Simulation

The combination of molecular dynamics simulation and neutron scattering techniques has emerged as a highly synergistic approach to elucidate the atomistic details of the structure, dynamics and functions of biological systems. Simulation models can be tested by calculating neutron scattering structure factors and comparing the results directly with experiments. If the scattering profiles agree the simulations can be used to provide a detailed decomposition and interpretation of the experiments, and if not, the models can be rationally adjusted. Comparison with neutron experiment can be made at the level of the scattering functions or, less directly, of structural and dynamical quantities derived from them. Here, we examine the combination of simulation and experiment in the interpretation of SANS and inelastic scattering experiments on the structure and dynamics of proteins and other biopolymers

Low-energy unphysical saddle in polynomial molecular potentials

Vibrational spectra of polyatomic molecules are often obtained from a polynomial expansion of the adiabatic potential around a minimum. For several molecules, we show that such an approximation displays an unphysical saddle point of comparatively small energy, leading to a region where the potential is negative and unbounded. This poses an upper limit for a reliable evaluation of vibrational levels. We argue that the presence of such saddle points is general.Comment: The preprint version of the published Mol. Phys. paper, 19 pages, 3 figure

Multiplication of microbes below 0.690 water activity: implications for terrestrial and extraterrestrial life

Since a key requirement of known life-forms is available water (water-activity; aw), searches for signatures of past life in terrestrial and extraterrestrial environments have recently targeted places known to have contained significant quantities of biologically available water. The lower limit of water activity that enables cell division is ~0.605 which, until now, was only known to be exhibited by a single eukaryote; the sugar-tolerant, fungal xerophile Xeromyces bisporus. The first forms of life on Earth were, however, prokaryotic. Furthermore, early life on Earth inhabited high-salt environments, suggesting an ability to withstand low water activity. Recent evidence indicates that some halophilic Archaea and Bacteria have water activity limits more or less equal to those of X. bisporus. Regardless of species, cellular systems are sensitive to minute differences in water activity (of w-units) so there is a need to determine water-activity values to three decimal places. We discuss water activity in relation to the limits of Earth’s present-day biosphere; the possibility of microbial multiplication by utilizing water from thin, aqueous films or non-liquid sources; whether prokaryotes were the first organisms able to multiply at the 0.605-aw limit; and whether extraterrestrial aqueous milieu of ≥0.605 aw can resemble fertile microbial habitats found on Earth