Esophageal lung associated with VACTERL anomaly: a case report

Esophageal lung is an extremely rare type of bronchopulmonary foregut malformation in which the main stem bronchus is anomalously connected to the esophagus instead of the trachea and is supplied by branches of pulmonary artery. Less than 25 cases have been reported so far in literature. We hereby report first case of esophageal lung associated with VACTREL anomaly. An 8-month-old female child with weight of 4.7 kg presented with recurrent lower respiratory infections. She was diagnosed to have esophageal lung on basis of clinical examination, chest X-ray f/b computed tomogram of chest and esophagobronchoscopy. There was a bifid vertebra at D9 level with scoliosis, an ectopic left kidney and dextrocardia with patent foramen ovale. Thus, this case was classified as having VACTREL association. Patient was successfully operated for excision of the hypoplastic lung via thoracotomy. She recovered well and gaining weight at 3 months f/u without any respiratory infection since surgery. High index of suspicion is necessary for the diagnosis of esophageal lung when common causes of recurrent respiratory infections are ruled out.

\u3cem\u3eN-Acetyltransferase 9 \u3c/em\u3eameliorates Aβ42-mediated neurodegeneration in the \u3cem\u3eDrosophila \u3c/em\u3eeye

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, manifests as accumulation of amyloid-beta-42 (Aβ42) plaques and intracellular accumulation of neurofibrillary tangles (NFTs) that results in microtubule destabilization. Targeted expression of human Aβ42 (GMR \u3e Aβ42) in developing Drosophila eye retinal neurons results in Aβ42 plaque(s) and mimics AD-like extensive neurodegeneration. However, there remains a gap in our understanding of the underlying mechanism(s) for Aβ42-mediated neurodegeneration. To address this gap in information, we conducted a forward genetic screen, and identified N-acetyltransferase 9 (Mnat9) as a genetic modifier of GMR \u3e Aβ42 neurodegenerative phenotype. Mnat9 is known to stabilize microtubules by inhibiting c-Jun-N- terminal kinase (JNK) signaling. We found that gain-of-function of Mnat9 rescues GMR \u3e Aβ42 mediated neurodegenerative phenotype whereas loss-of-function of Mnat9 exhibits the converse phenotype of enhanced neurodegeneration. Here, we propose a new neuroprotective function of Mnat9 in downregulating the JNK signaling pathway to ameliorate Aβ42-mediated neurodegeneration, which is independent of its acetylation activity. Transgenic flies expressing human NAT9 (hNAT9), also suppresses Aβ42-mediated neurodegeneration thereby suggesting functional conservation in the interaction of fly Mnat9 or hNAT9 with JNK-mediated neurodegeneration. These studies add to the repertoire of molecular mechanisms that mediate cell death response following accumulation of Aβ42 and may provide new avenues for targeting neurodegeneration

Determination of Toxic Metals in Indian Smokeless Tobacco Products

This study targets the lesser-known ingredients of smokeless tobacco products, i.e., the toxic metals, in Indian brands. The metals selected in the study included lead (Pb), cadmium (Cd), arsenic (As), copper (Cu), mercury (Hg), and selenium (Se). The differential pulse anodic stripping voltammetry (DPASV) technique was used for estimating the metals Pb, Cd, and Cu; square wave voltammetry for As; and the cold vapor atomic absorption technique for Hg. The resulting levels of the metals were compared to the daily consumption of the smokeless tobacco products. It was observed that almost 30% of gutkha brand samples exceeded the permissible levels of metals Pb and Cu, when compared to the provisional tolerable intake limits determined by the FAO/WHO. The reliability of data was assured by analyzing standard reference materials

A Positive Feedback Loop of Hippo- and c-Jun-Amino-Terminal Kinase Signaling Pathways Regulates Amyloid-Beta-Mediated Neurodegeneration

Alzheimer\u27s disease (AD, OMIM: 104300) is an age-related disorder that affects millions of people. One of the underlying causes of AD is generation of hydrophobic amyloid-beta 42 (Aβ42) peptides that accumulate to form amyloid plaques. These plaques induce oxidative stress and aberrant signaling, which result in the death of neurons and other pathologies linked to neurodegeneration. We have developed a Drosophila eye model of AD by targeted misexpression of human Aβ42 in the differentiating retinal neurons, where an accumulation of Aβ42 triggers a characteristic neurodegenerative phenotype. In a forward deficiency screen to look for genetic modifiers, we identified a molecularly defined deficiency, which suppresses Aβ42-mediated neurodegeneration. This deficiency uncovers hippo (hpo) gene, a member of evolutionarily conserved Hippo signaling pathway that regulates growth. Activation of Hippo signaling causes cell death, whereas downregulation of Hippo signaling triggers cell proliferation. We found that Hippo signaling is activated in Aβ42-mediated neurodegeneration. Downregulation of Hippo signaling rescues the Aβ42-mediated neurodegeneration, whereas upregulation of Hippo signaling enhances the Aβ42-mediated neurodegeneration phenotypes. It is known that c-Jun-amino-terminal kinase (JNK) signaling pathway is upregulated in AD. We found that activation of JNK signaling enhances the Aβ42-mediated neurodegeneration, whereas downregulation of JNK signaling rescues the Aβ42-mediated neurodegeneration. We tested the nature of interactions between Hippo signaling and JNK signaling in Aβ42-mediated neurodegeneration using genetic epistasis approach. Our data suggest that Hippo signaling and JNK signaling, two independent signaling pathways, act synergistically upon accumulation of Aβ42 plaques to trigger cell death. Our studies demonstrate a novel role of Hippo signaling pathway in Aβ42-mediated neurodegeneration

Phytochemicals as weapons against drug resistance

Phytochemicals are plant-based products with high medicinal value. These metabolites effectively target disease-causing microbes. Drug-resistant pathogens have developed mechanisms to sustain themselves even with inhibitors. Drug resistance has emerged as a global giant, causing all available treatment options to fail. The solution to this problem is in the phytochemicals of plants with antibacterial and drug resistance modulation properties. Phytochemicals might be able to get rid of efflux pumps, drug-modulating enzymes, resistance genes, quorum sensing, and biofilm, all of which cause pathogens to be resistant to drugs. Moreover, anti-obesogenic and cardioprotective properties are also observed in phytochemicals. Additionally, studies show the success of phytochemical-based nanoparticles in drug resistance regulation. This review emphasizes phytochemicals' different mechanisms of action and their derivatives in curbing drug-resistant pathogens and cancer cells

Acireductone Dioxygenase 1 (ARD1) Is an Effector of the Heterotrimeric G Protein Subunit in Arabidopsis

Heterotrimeric G protein complexes are conserved from plants to mammals, but the complexity of each system varies. Arabidopsis thaliana contains one Gα, one Gβ (AGB1), and at least three Gγ subunits, allowing it to form three versions of the heterotrimer. This plant model is ideal for genetic studies because mammalian systems contain hundreds of unique heterotrimers. The activation of these complexes promotes interactions between both the Gα subunit and the Gβγ dimer with enzymes and scaffolds to propagate signaling to the cytoplasm. However, although effectors of Gα and Gβ are known in mammals, no Gβ effectors were previously known in plants. Toward identifying AGB1 effectors, we genetically screened for dominant mutations that suppress Gβ-null mutant (agb1-2) phenotypes. We found that overexpression of acireductone dioxygenase 1 (ARD1) suppresses the 2-day-old etiolated phenotype of agb1-2. ARD1 is homologous to prokaryotic and eukaryotic ARD proteins; one function of ARDs is to operate in the methionine salvage pathway. We show here that ARD1 is an active metalloenzyme, and AGB1 and ARD1 both control embryonic hypocotyl length by modulating cell division; they also may contribute to the production of ethylene, a product of the methionine salvage pathway. ARD1 physically interacts with AGB1, and ARD enzymatic activity is stimulated by AGB1 in vitro. The binding interface on AGB1 was deduced using a comparative evolutionary approach and tested using recombinant AGB1 mutants. A possible mechanism for AGB1 activation of ARD1 activity was tested using directed mutations in a loop near the substrate-binding site