Nonsterile immunity to cryptosporidiosis in infants is associated with mucosal IgA against the sporozoite and protection from malnutrition

We conducted a longitudinal study of cryptosporidiosis from birth to three years of age in an urban slum of Dhaka Bangladesh. Fecal DNA was extracted from monthly surveillance samples and diarrheal stool samples collected from 392 infants from birth to three years. A pan-Cryptosporidium qPCR assay was used to identify sub-clinical and symptomatic cryptosporidiosis. Anthropometric measurements were collected quarterly to assess child nutritional status. 31% (121/392) of children experienced a single and 57% (222/392) multiple infections with Cryptosporidium. Repeat infections had a lower burden of parasites in the stool (Cq slope = -1.85; p<0.0001) and were more likely to be sub-clinical (Chi square test for trend; p = 0.01). Repeat infections were associated with the development of growth faltering (Pearson correlation = -0.18; p = 0.0004). High levels of fecal IgA antibodies against the Cryptosporidium Cp23 sporozoite protein at one year of life were associated with a delay in reinfection and amelioration of growth faltering through three years of life (HAZ IgA high responders -1.323 ± 0.932 versus HAZ -1.731 ± 0.984 p = 0.0001). We concluded that nonsterile immunity to cryptosporidiosis in young children was associated with high levels of mucosal IgA anti-Cp23 and protection from diarrhea and growth faltering.Trial Registration: {"type":"clinical-trial","attrs":{"text":"NCT02764918","term_id":"NCT02764918"}}NCT02764918.     

Recognition of partially concealed leopards by wild bonnet macaques (Macaca radiata). The role of the spotted coat

Wild bonnet macaques (Macaca radiata) have been shown to recognize models of leopards (Panthera pardus), based on their configuration and spotted yellow coat. This study examined whether bonnet macaques could recognize the spotted and dark melanic morph when partially concealed by vegetation. Seven troops were studied at two sites in southern India, the Mudumalai Wildlife Sanctuary and the Kalakad-Mundanthurai Tiger Reserve. The forequarters and hindquarters of the two leopard morphs were presented from behind thick vegetation to individuals at feeding stations 25 m away. Flight reaction times and frequency of flight were obtained from video for only those individuals who oriented towards the models prior to hearing alarm calls. Bonnet macaques exhibited faster reaction times and greater frequency of flight after looking at the spotted morph's forequarter than after looking at either its spotted hindquarter or the dark morph's forequarter. The hindquarter of the dark morph was ignored completely. Artificial neural network modeling examined the perceptual aspects of leopard face recognition and the role of spots as camouflage. When spots were integrated into the pattern recognition process via network training, these spots contributed to leopard face recognition. When networks were not trained with spots, spots did not act as camouflage by disrupting facial features.     

Comparative genomics of the pennate diatom Phaeodactylum tricornutum

Diatoms are one of the most important constituents of phytoplankton communities in aquatic environments, but in spite of this, only recently have large-scale diatom-sequencing projects been undertaken. With the genome of the centric species Thalassiosira pseudonana available since mid-2004, accumulating sequence information for a pennate model species appears a natural subsequent aim. We have generated over 12,000 expressed sequence tags (ESTs) from the pennate diatom Phaeodactylum tricornutum, and upon assembly into a nonredundant set, 5,108 sequences were obtained. Significant similarity (E < 1E-04) to entries in the GenBank nonredundant protein database, the COG profile database, and the Pfam protein domains database were detected, respectively, in 45.0%, 21.5%, and 37.1% of the nonredundant collection of sequences. This information was employed to functionally annotate the P. tricornutum nonredundant set and to create an internet-accessible queryable diatom EST database. The nonredundant collection was then compared to the putative complete proteomes of the green alga Chlamydomonas reinhardtii, the red alga Cyanidioschyzon merolae, and the centric diatom T. pseudonana. A number of intriguing differences were identified between the pennate and the centric diatoms concerning activities of relevance for general cell metabolism, e.g. genes involved in carbon-concentrating mechanisms, cytosolic acetyl-Coenzyme A production, and fructose-1,6-bisphosphate metabolism. Finally, codon usage and utilization of C and G relative to gene expression (as measured by EST redundance) were studied, and preferences for utilization of C and CpG doublets were noted among the P. tricornutum EST coding sequences.     

Synthesis and evaluation of anti-HIV activity of isatin beta-thiosemicarbazone derivatives

On the basis of pharmacophoric modelling studies of existing NNRTIs, a series of isatin beta-thiosemicarbazone derivatives was synthesized and evaluated for their anti-HIV activity in HTLV-III(B) strain in the CEM cell line. Three compounds showed significant anti-HIV activity, whereupon compound 6 was found to be the most active compound with an EC(50) value of 2.62 microM and a selectivity index of 17.41, while not being cytotoxic to the cell line at a CC(50) value of 44.90 microM. Other tested compounds exhibited marked activity below their toxicity threshold.     

The Solution Structure of a Cyclic Analog of Neuropeptide Y with High Y<Subscript>1</Subscript> Receptor Affinity by NMR,CD and MD Simulations

The conformation of a cyclic analog of neuropeptide Y [Tyr¹--Lys--Gly--Arg--cyclo^5/8-(Glu⁵--Tyr--Ile--Lys⁸)--Leu--Ile¹⁰--Thr--Arg--Pro--Arg--Tyr¹⁵--NH₂; cEK-NPY] with high Y₁ receptor affinity was studied using ¹H, ¹³C and ¹⁵N 2D-NMR and CD in three diverse media-viz. DMSO-d₆, water (pH 4.0) and 50% hexafluoroacetone (HFA). The conformation of cEK-NPY was interpreted based on chemical shift (¹H, ¹³C and ¹⁵N), temperature coefficients of the NH chemical shifts, ³J_NHα coupling constants and the pattern of intra and inter-residue NOE’s and the CD spectrum. In both DMSO and water, there is a preponderance of a β-strand structure, while HFA promotes an α-helical structure, which is discontinuous in the mid-region of the peptide, due to the constraints of the lactam ring. The solution structures were generated using Restrained Molecular Dynamics simulations and further refined by Mardigras to R factors between 0.55 and 0.65. The role of its conformations in its biological activity is discussed.     

Coordinate regulation of forskolin-induced cellular proliferation in macrophages by protein kinase A/cAMP-response element-binding protein (CREB) and Epac1-Rap1 signaling: effects of silencing CREB gene expression on Akt activation

In this study, we have examined the role of two cAMP downstream effectors protein kinase A (PKA) and Epac, in forskolin-induced macrophage proliferation. Treatment of macrophages with forskolin enhanced [(3)H]thymidine uptake and increased cell number, and both were profoundly reduced by prior treatment of cells with H-89, a specific PKA inhibitor. Incubation of macrophages with forskolin triggered the activation of Akt, predominantly by phosphorylation of Ser-473, as measured by Western blotting and assay of its kinase activity. Akt activation was significantly inhibited by LY294002 and wortmannin, specific inhibitors of phosphatidylinositol 3-kinase, but not by H-89. Incubation of macrophages with forskolin also increased Epac1 and Rap1.GTP. Immunoprecipitation of Epac1 in forskolin-stimulated cells co-immunoprecipitated Rap1, p-Akt(Thr-308), and p-Akt(Ser-473). Silencing of CREB gene expression by RNA interference prior to forskolin treatment not only decreased CREB protein and its phosphorylation at Ser-133, but also phosphorylation of Akt at Ser-473, and Thr-308. Concomitantly, this treatment inhibited [(3)H]thymidine uptake and reduced forskolin-induced proliferation of macrophages. Forskolin treatment also inhibited activation of the apoptotic mechanism while promoting up-regulation of the anti-apoptotic pathway. We conclude that forskolin mediates cellular proliferation via cAMP-dependent activation of both PKA and Epac.     

A novel acetabular alignment guide for THR using selective anatomic landmarks on the pelvis

This paper presents a novel approach for acetabular alignment during the implant of a prosthetic hip joint in a natural pelvis. The alignment instrument uses selective anatomic bony landmarks on the pelvis, which are accessible in surgery, to guide the placement of the acetabular component in the appropriate orientation. A closed form solution, involving both a forward and reverse analysis, is presented to relate the parameters of the device with the abduction and anteversion angles. Using mathematical models, this device should allow the surgeon to place the acetabular component with an orientation between 10.9 degrees and 19.1 degrees anteversion and 35.7 degrees and 44.3 degrees abduction with 95% confidence in a male/left specimen for the commonly accepted target of 15 degrees anteversion and 40 degrees abduction. This device is currently being used successfully by one of the authors in THR surgery.     

Ribosome inactivating proteins and apoptosis

Ribosome inactivating proteins (RIPs) are protein toxins that are of plant or microbial origin that inhibit protein synthesis by inactivating ribosomes. Recent studies suggest that RIPs are also capable of inducing cell death by apoptosis. Though many reports are available on cell death induced by RIPs, the mechanism involved is not well studied. Comparison of pathways of apoptosis and cellular events induced by various RIPs suggests a central role played by mitochondria, probably acting as an integrator of cellular stress and cell death. The purpose of this review is to compare the various apoptotic pathways that may be involved and propose a general pathway in RIP-induced cell death.     

Pigmented pheochromocytoma: report of a case with diagnosis by fine needle aspiration

BACKGROUND: Pheochromocytoma is a common tumor of the adrenal medulla, but its pigmented variant is rare. CASE REPORT: A 38-year-old woman presented with complaints of abdominal pain. Ultrasound revealed a right suprarenal mass. Fine needle aspiration (FNA) smears showed the characteristic cytomorphology of pheochromocytoma, with melanin pigment in the cytoplasm. Melanin was differentiated from lipofuschin and hemosiderin by various histochemical stains. Histopathologic findings and immunohistochemical stains confirmed the diagnosis. To our knowledge, this is the first reported case of pigmented pheochromocytoma diagnosed on FNA. CONCLUSION: FNA has proven to be a rapid and conclusive method of diagnosing pigmented pheochromocytoma, with no complications.