Cryo-tomography and 3D Electron Diffraction Reveal the Polar Habit and Chiral Structure of the Malaria Pigment Crystal Hemozoin.

Detoxification of heme in depends on its crystallization into hemozoin. This pathway is a major target of antimalarial drugs. The crystalline structure of hemozoin was established by X-ray powder diffraction using a synthetic analog, β-hematin.

Visualization of Organelles In Situ by Cryo-STEM Tomography.

Cryogenic electron microscopy (cryo-EM) relies on the imaging of biological or organic specimens embedded in their native aqueous medium; water is solidified into a glass (i.e., vitrified) without crystallization.

Correlating cryo-super resolution radial fluctuations and dual-axis cryo-scanning transmission electron tomography to bridge the light-electron resolution gap.

Visualization of organelles and their interactions with other features in the native cell remains a challenge in modern biology. We have introduced cryo-scanning transmission electron tomography (CSTET), which can access 3D volumes on the scale of 1 micron with a resolution of nanometers, making it ideal for this task. Here we introduce two relevant advances: (a) we demonstrate the utility of multi-color super-resolution radial fluctuation light microscopy under cryogenic conditions (cryo-SRRF), and (b) we extend the use of deconvolution processing for dual-axis CSTET data.

Diffraction contrast in cryo-scanning transmission electron tomography reveals the boundary of hemozoin crystals .

Malaria is a potentially fatal infectious disease caused by the obligate intracellular parasite . The parasite infects human red blood cells (RBC) and derives nutrition by catabolism of hemoglobin. As amino acids are assimilated from the protein component, the toxic heme is released.

20S proteasomes secreted by the malaria parasite promote its growth.

Mature red blood cells (RBCs) lack internal organelles and canonical defense mechanisms, making them both a fascinating host cell, in general, and an intriguing choice for the deadly malaria parasite Plasmodium falciparum (Pf), in particular. Pf, while growing inside its natural host, the human RBC, secretes multipurpose extracellular vesicles (EVs), yet their influence on this essential host cell remains unknown. Here we demonstrate that Pf parasites, cultured in fresh human donor blood, secrete within such EVs assembled and functional 20S proteasome complexes (EV-20S).

Association of With the Apical Domain of Hepatocytes Is Necessary for the Parasite's Liver Stage Development.

parasites undergo a dramatic transformation during the liver stage of their life cycle, amplifying over 10,000-fold inside infected hepatocytes within a few days. Such a rapid growth requires large-scale interactions with, and manipulations of, host cell functions. Whereas hepatocyte polarity is well-known to be critical for liver function, little is presently known about its involvement during the liver stage of development.

Nanomechanics of Extracellular Vesicles Reveals Vesiculation Pathways.

Extracellular vesicles (EVs) are emerging as important mediators of cell-cell communication as well as potential disease biomarkers and drug delivery vehicles. However, the mechanical properties of these vesicles are largely unknown, and processes leading to microvesicle-shedding from the plasma membrane are not well understood. Here an in depth atomic force microscopy force spectroscopy study of the mechanical properties of natural EVs is presented.

Electrophilicity of pyridazine-3-carbonitrile, pyrimidine-2-carbonitrile, and pyridine-carbonitrile derivatives: a chemical model to describe the formation of thiazoline derivatives in human liver microsomes.

Certain aromatic nitriles are well-known inhibitors of cysteine proteases. The mode of action of these compounds involves the formation of a reversible or irreversible covalent bond between the nitrile and a thiol group in the active site of the enzyme. However, the reactivity of these aromatic nitrile-substituted heterocycles may lead inadvertently to nonspecific interactions with DNA, protein, glutathione, and other endogenous components, resulting in toxicity and complicating the use of these compounds as therapeutic agents.

Knowledge and perceptions of residents regarding case management of acute diarrhea.

The knowledge and perceptions about case management of acute diarrhea were studied amongst 330 resident doctors working in Pediatric Departments of various Medical Colleges in the country. Our observations highlight the inadequacies in the medical curriculum and deficient clinical training in the management of acute diarrhea in the teaching institutions. Knowledge of signs of dehydration was correctly perceived by only 79.

Icterometer: a useful screening tool for neonatal jaundice.

One hundred and sixty one jaundiced newborns were investigated for the usefulness of perspex icterometer as a screening tool for neonatal jaundice. Along with serum bilirubin estimation, icterometer score was simultaneously obtained in all the cases. The correlation between serum bilirubin and icterometer score was high (r = 0.

Breath holding spells: an analysis of 50 cases.

Of 50 preschool children having breath holding spells (M:F::3:1) (BHS), 80.0% were less than 18 months of age (mean age 16 +/- 5 mo). More children came from a lower social class (70.

Plain radiograph skull: is it really needed in epilepsy?

One hundred and three children with seizure disorder were studied. Plain radiograph skull was normal in all the cases. CT scan skull done in 34 patients, showed abnormalities in 24 cases.

Alopecia with rickets: an end organ unresponsiveness to 1,25-dihydroxyvitamin D--a case report.

Two siblings of a rare syndrome of vitamin D dependent type II rickets are reported for the first time from India. The clinical and biochemical picture was characterised by florid rickets, alopecia, hypocalcemia and resistance to therapy with high dosages of vitamin D3. Due to lack of facilities for estimation of 1,25(OH)2D, alopecia remains the only clue to the diagnosis of this rare syndrome in association with resistant rickets.

Premature infant feeding: role of diluted formula.

The role of half strength, double volume milk feeds for initiating feeding in preterm newborn infants was evaluated. Thirty eight premature infants were included in the study and divided into Groups A and B having 20 and 18 babies, respectively. Group A babies were fed half strength (10 cal/oz) formula feeds but the volume was doubled, while Group B babies were fed full strength formula feeds (20 cal/oz) with standard volume.

Temper tantrums. Prevalence and etiology in a non-referral outpatient setting.

Of a total of 800 children (aged 3-12 years) attending a pediatric outpatient department, 182 (22.8%) were found to be having temper tantrums (mean age, 4.7 years).

Spinal muscular atrophy: some easy clues to diagnosis.

Seven cases of benign form of spinal muscular atrophy were studied to evaluate the importance of detecting hand tremors, muscle fasciculation, evertion of foot and ECG tremors to distinguish these cases from muscular dystrophy. Taken in combination, diagnosis of all the seven cases was possible without the need for application of more sophisticated and invasive investigations, e.g.

Epidemiological evaluation of BCG vaccine efficacy in Delhi--1989.

A field evaluation of efficacy of BCG vaccine to prevent tubercular meningitis was undertaken in a case control study in Delhi during 1988-89. Each case of tubercular meningitis was matched by age and neighbourhood with 2 controls from the community. Thirty-seven cases of tubercular meningitis were matched with 74 controls and thus 37 triplets were analysed.

Immune status following measles vaccination in infants and evaluation for the need of revaccination.

In this prospective study, immune status of children vaccinated in infancy was determined at age 12-18 months. In 200 children, preimmunization protective measles hemagglutination (HI) antibody titres (greater than or equal to 1:8) were present in 38.5% of children of 6-8 months, the frequency decreased to 17.

Immunoglobulins profile of measles.

Immunoglobulins profile was carried out in 60 cases of measles (30 each with and without complications) and 30 age and sex matched controls. Antibody titres and immunoglobulins levels (IgG, IgM and IgA) were determined by hemagglutination inhibition and single radial immunodiffusion techniques, respectively. Though higher IgG and IgM levels were found in complicated cases compared to controls, more importantly lower IgA levels were seen in these cases.

Outcome of low birth weight babies with special reference to some maternal factors.

Neonatal outcome of 178 low birth weight (LBW) babies in this study was associated with 26.4% neonatal mortality. A significantly higher mortality rate was noted in presence of adverse maternal factors, birth weight less than 1.