Minocycline attenuates HIV‐1 infection and suppresses chronic immune activation in humanized NOD/LtsZ‐scidIL‐2Rγnull mice

More than a quarter of a century of research has established chronic immune activation and dysfunctional T cells as central features of chronic HIV infection and subsequent immunodeficiency. Consequently, the search for a new immunomodulatory therapy that could reduce immune activation and improve T‐cell function has been increased. However, the lack of small animal models for in vivo HIV study has hampered progress. In the current study, we have investigated a model of cord blood haematopoietic progenitor cells (CB‐HPCs) ‐transplanted humanized NOD/LtsZ‐scidIL‐2Rγ^null mice in which progression of HIV infection is associated with widespread chronic immune activation and inflammation. Indeed, HIV infection in humanized NSG mice caused up‐regulation of several T‐cell immune activation markers such as CD38, HLA‐DR, CD69 and co‐receptor CCR5. T‐cell exhaustion markers PD‐1 and CTLA‐4 were found to be significantly up‐regulated on T cells. Moreover, increased plasmatic levels of lipopolysaccharide, sCD14 and interleukin‐10 were also observed in infected mice. Treatment with minocycline resulted in a significant decrease of expression of cellular and plasma immune activation markers, inhibition of HIV replication and improved T‐cell counts in HIV‐infected humanized NSG mice. The study demonstrates that minocycline could be an effective, low‐cost adjunctive treatment to regulate chronic immune activation and replication of HIV.     

Ultra-small palladium nano-particles synthesized using bulky S/Se and N donor ligands as a stabilizer: application as catalysts for Suzuki–Miyaura coupling

Two chalcogenated ligands L1 and L2 containing anthracene core and amine functionality have been synthesized. Both the ligands have been characterized using ¹H and ¹³C{¹H} NMR techniques. The structure of L1 has also been corroborated by single crystal X-ray diffraction. Application of L1 and L2 as stabilizers for palladium nano-particles (NPs) has been explored and six different types of NPs 1–6 have been prepared by varying the quantity of stabilizer. The nano-particles have been characterized by PXRD, EDX, and HRTEM techniques. The size of NPs has been found to be in the range of ∼1–2 nm, 2–3 nm, 4–6 nm, 1–2 nm, 1–2 nm and 3–5 nm for 1–6 respectively. The catalytic activities of 1–6 have been explored for Suzuki–Miyaura coupling of phenyl boronic acid with various aryl halides. These NPs showed good catalytic activity for various aryl chlorides/bromides at low catalyst loading (5 mg). Among 1–6, the highest activity has been observed for NPs 1, probably due to their relatively small size and high uniformity in the dispersion. The recyclability of the NPs upto 5 catalytic cycles is a distinct advantage.

Monodispersed ultrasmall Pd nanoparticles synthesized utilizing bulky organochalcogen secondary amines as stabilizers and application in Suzuki coupling of aryl chlorides at low catalyst loading.     

Development of a fused imidazo[1,2-a]pyridine based fluorescent probe for Fe3+ and Hg2+ in aqueous media and HeLa cells

A new fluorescent sensor 5 based on a fused imidazopyridine scaffold has been designed and synthesized via cascade cyclization. The reaction features the formation of three different C–N bonds in sequence. Imidazopyridine based fluorescent probe 5 exhibits highly sensitive and selective fluorescent sensing for Fe³⁺(‘turn-on’) and Hg²⁺(‘turn-off’). The excellent selectivity of imidazopyridine for Fe³⁺/Hg²⁺ was not hampered in the presence of any of the competing cations. The limit of detection (LOD) of 5 toward Fe³⁺ and Hg²⁺ has been estimated to be 4.0 ppb and 1.0 ppb, respectively, with a good linear relationship (R² = 0.99). Notably, 5 selectively detects Fe³⁺/Hg²⁺ through fluorescence enhancement signalling both in vitro and in HeLa cells.

A new fluorescent sensor 5 having fused imidazopyridine scaffold has been synthesized via cascade cyclization. It exhibits highly sensitive and selective detection of Fe³⁺ (‘turn-on’) and Hg²⁺ (‘turn-off’) in vitro and in HeLa cells.     

Nutritional Rehabilitation of Children < 6 mo with Severe Acute Malnutrition

The authors studied the outcome of 108 infants <??6 mo with severe acute malnutrition (SAM) admitted in the Nutritional Rehabilitation Centres (NRC) at a teaching hospital. The most common symptom that the children presented with, was acute diarrhoea (35.2 %) followed by failure to gain weight (26.9 %). Seventy five (69.4 %) infants were cured after nutritional rehabilitation and 29 (26.8 %) were non responders. Fifty two (48 %) infants showed good weight gain after proper counseling or supplementary suckling technique alone.     

Genetic Study of an Indian Family with Cherubism

Cherubism (OMIM : 118400) is an autosomal dominant disorder affecting mainly facial bones leading to disfigurement of face needing medical and surgical attention besides impairing the self esteem of person. At present, there is no medical cure and there is limited indication for surgery in such cases. So, correct diagnosis is of paramount importance to both treating physician and family. Here, the authors report a family with two affected members (mother and daughter) who were tested positive for a known pathogenic mutation and thus offered timely treatment and adequate genetic counseling.     

Thermal unfolding and refolding of a lytic polysaccharide monooxygenase from Thermoascus aurantiacus

Lytic polysaccharide monooxygenases (LPMOs) are copper-containing enzymes which promote the degradation of recalcitrant polysaccharides like cellulose or chitin. Here, we have investigated the thermostability of an LPMO from Thermoascus aurantiacus (TaLPMO9A). TaLPMO9A was found to retain most of its initial activity after incubating at 100 °C while its apparent melting temperature (T_m) is 69 °C at neutral pH. Interestingly, our studies show that holoTaLPMO9A, apoTaLPMO9A and deglycosylated TaLPMO9A can fold back to their original conformation upon lowering the temperature. In the presence of β-mercaptoethanol the protein does not refold. Activity of TaLPMO9A and refolded TaLPMO9A was studied by an Amplex® Red assay as well as by TaLPMO9A catalysed oxidation of phosphoric acid swollen cellulose (PASC). These studies confirm the functional regain of TaLPMO9A activity upon going through one cycle of unfolding and refolding. The thermal unfolding and refolding of TaLPMO9A was measured spectroscopically. Utilizing the two-state model, detailed thermodynamic parameters were obtained for holoTaLPMO. Furthermore, we have investigated the kinetics of TaLPMO9A unfolding and refolding. Our results have implications in understanding LPMO stability, which is crucial for the efficient application of LPMOs as biocatalysts during biomass degradation.

TaLPMO9A regains its catalytic power after a thermal unfolding and refolding cycle.     

Screw-worm myiasis of prolapsed rectum

Background

Wound myiasis in the Indian subcontinent is most commonly caused by old world screw-worm (Chrysomya bezziana).

Case Report and management

A 4-yearold malnourished girl presented with full thickness rectal prolapse following acute diarrhea with a large wound and screwworm myiasis of the rectum. Turpentine oil was applied to immobilize the maggots followed by manual extraction. Prolapse was successfully treated by manual reduction followed by strapping of the buttocks.

Outcome

Child was thriving well and gained 2 kg weight in follow up after two weeks.

Message

Parents should be educated about taking care of prolapsed rectum.