Novel Denisovan and Neanderthal Retroviruses

Following the recent availability of high-coverage genomes for Denisovan and Neanderthal hominids, we conducted a screen for endogenized retroviruses, identifying six novel, previously unreported HERV-K(HML2) elements (HERV-K is human endogenous retrovirus K). These elements are absent from the human genome (hg38) and appear to be unique to archaic hominids. These findings provide further evidence supporting the recent activity of the HERV-K(HML2) group, which has been implicated in human disease. They will also provide insights into the evolution of archaic hominids.     

Morphological,anatomical, and ultrastructural changes (visualized through scanning electron microscopy) inducedin Triticum aestivum by Pb2+ treatment

Lead (Pb) causes severe damage to crops, ecosystems, and humans, and alters the physiology and biochemistry of various plant species. It is hypothesized that Pb-induced metabolic alterations could manifest as structural variations in the roots of plants. In light of this, the morphological, anatomical, and ultrastructural variations (through scanning electron microscopy, SEM) were studied in 4-day-old seedlings of Triticum aestivum grown under Pb stress (0, 8, 16, 40, and 80 mg Pb²⁺ l^?1; mild to highly toxic). The toxic effect was more pronounced in radicle growth than on the plumule growth. The SEM of the root of T. aestivum depicted morphological alterations and surface ultrastructural changes. Compared to intact and uniform surface cells in the control roots, cells were irregular and desiccated in Pb²⁺-treated roots. In Pb²⁺-treated roots, the number of root hairs increased manifold, showing dense growth, and these were apparently longer. Apart from the deformity in surface morphology and anatomy of the roots in response to Pb²⁺ toxicity, considerable anatomical alterations were also observed. Pb²⁺-treated root exhibited signs of injury in the form of cell distortion, particularly in the cortical cells. The endodermis and pericycle region showed loss of uniformity post Pb²⁺ exposure (at 80 mg l^?1 Pb²⁺). The cells appeared to be squeezed with greater depositions observed all over the tissue. The study concludes that Pb²⁺ treatment caused structural anomalies and induced anatomical and surface ultrastructural changes in T. aestivum.     

Ni<Superscript>+2</Superscript>-inhibited radicle growth in germinating wheat seeds involves alterations in sugar metabolism

Nickel (Ni) is a trace element essential for the growth and development of plants. Conversely, when in excess, Ni inhibits seed germination and reduces seedling growth. Therefore, we investigated the effect of Ni⁺² (5–50 μM; supplied as nickel sulfate: NiSO₄·6H₂O) on the activity of enzymes involved in sugar metabolism of wheat (Triticum aestivum L.) seedlings after 96 h of exposure to the metal. Ni⁺² treatment reduced root and coleoptile length of emerging wheat seedlings and the effect was more pronounced on the root length. Ni⁺² (5–50 μM) treatment significantly enhanced carbohydrate content by 21–100 % over that of the control. In contrast, protein and reducing sugar contents declined by 17–43 and 22–69 %, respectively. The reduction in total protein content was confirmed by SDS-PAGE analysis. The activities of starch-metabolizing enzymes declined upon Ni⁺² stress in a concentration-dependent manner. Activities of α- and β-amylases, acid and alkaline invertases, acid and alkaline phosphatases, and starch phosphorylase declined by 18–74 and 24–85 %, 42–76 and 21–73 %, 15–54 and 28–72 %, and 50–83 %, respectively, when compared to the control. The study concludes that Ni⁺² impairs sugar metabolism as indicated by decline in the activity of sucrose and starch hydrolyzing enzymes. It resulted in decrease in the availability of biochemical energy and sugars required for the synthesis, leading to inhibition of radicle growth in germinating wheat seeds.     

Reactive oxygen species generation and antioxidant defense system in hydroponically grown wheat (Triticum aestivum) upon β-pinene exposure: an early time course assessment

We investigated the effect of β-pinene on reactive oxygen species (ROS: lipid peroxidation, membrane integrity, hydrogen peroxide and superoxide ions) generation and activity of antioxidant defense system during early hours of treatment (4, 8, 16 and 24 h) in hydroponically grown Triticum aestivum (wheat). β-Pinene reduced the root and shoot growth of the hydroponically grown wheat. However, the reduction was more pronounced in root length than in shoot length. β-Pinene enhanced ROS generation as indicated by increased levels of malondialdehyde (20–87 %), hydrogen peroxide (9–45 %) and superoxide ion (23–179 %) content, thereby suggesting lipid peroxidation and induction of oxidative stress in a time- and concentration-dependent manner. The oxidative damage was more pronounced at ≥10 µM β-pinene and at ≥8 h after exposure. β-Pinene caused a severe electrolyte leakage from wheat roots indicating membrane disruption and loss of integrity. Enhanced lipid peroxidation and loss of membrane integrity were confirmed by in situ histochemical studies. β-Pinene provoked increase in the activity of lipoxygenase and upregulation in the activities of antioxidant enzymes: catalases, superoxide dismutases, ascorbate peroxidases, guaiacol peroxidases and glutathione reductases. The enhanced activity of lipoxygenases evoked by β-pinene paralleled higher accumulation of MDA, thereby suggesting that antioxidant defense mechanism was not able to prevent β-pinene-induced lipid peroxidation.     

Primary Cutaneous Mucormycosis in a Patient with Burn Wounds Due to Lichtheimia ramosa

Mucormycosis is usually an invasive mycotic disease caused by fungi in the class mucormycetes. Here we report a case of cutaneous mucormycosis due to Lichtheimia ramosa in a 20-year-old female patient with burn injuries. She was admitted to the hospital with accidental flame burns covering 60 % total burn surface area. After 15 days of admission to hospital, the burn wound showed features of fungal infection. Culture showed white cottony growth belonging to the Mucorales order. Morphological identification confirmed it as L. ramosa. She was managed surgically and medically with the help of amphotericin B. Patient survived due to prompt diagnosis and appropriate medical and surgical treatment. Early diagnosis is critical in prevention of morbidity and mortality associated with the disease. Fungal infection in burn wounds can be difficult to diagnose and manage.     

The Interaction of N-Glycans in Fcγ Receptor I α-Chain with Escherichia coli K1 Outer Membrane Protein A for Entry into Macrophages: EXPERIMENTAL AND COMPUTATIONAL ANALYSIS*

Neonatal meningitis, caused by Escherichia coli K1, is a serious central nervous system disease. We have established that macrophages serve as permissive niches for E. coli K1 to multiply in the host and for attaining a threshold level of bacterial load, which is a prerequisite for the onset of the disease. Here, we demonstrate experimentally that three N-glycans in FcγRIa interact with OmpA of E. coli K1 for binding to and entering the macrophages. Adoptive transfer of FcγRIa^−/− bone marrow-derived macrophages transfected with FcγRIa into FcγRIa^−/− newborn mice renders them susceptible to E. coli K1-induced meningitis. In contrast, mice that received bone marrow-derived macrophages transfected with FcγRIa in which N-glycosylation sites 1, 4, and 5 are mutated to alanines exhibit resistance to E. coli K1 infection. Our molecular dynamics and simulation studies predict that N-glycan 5 exhibits strong binding at the barrel site of OmpA formed by loops 3 and 4, whereas N-glycans 1 and 4 interact with loops 1, 3, and 4 of OmpA at tip regions. Molecular modeling data also suggest no role for the IgG binding site in the invasion process. In agreement, experimental mutations in IgG binding site had no effect on the E. coli K1 entry into macrophages in vitro or on the onset of meningitis in newborn mice. Together, this integration of experimental and computational studies reveals how the N-glycans in FcγRIa interact with the OmpA of E. coli K1 for inducing the disease pathogenesis.     

Protection of Shrimp Penaeus monodon from WSSV Infection Using Antisense Constructs

White spot syndrome caused by white spot syndrome virus (WSSV) is one of the most threatening diseases of shrimp culture industry. Previous studies have successfully demonstrated the use of DNA- and RNA-based vaccines to protect WSSV infection in shrimp. In the present study, we have explored the protective efficacy of antisense constructs directed against WSSV proteins, VP24, and VP28, thymidylate synthase (TS), and ribonucleotide reductase-2 (RR2) under the control of endogenous shrimp histone-3 (H3) or penaedin (Pn) promoter. Several antisense constructs were generated by inserting VP24 (pH3–VP24, pPn–VP24), VP28 (pH3–VP28, pPn–VP28), TS (pH3–TS, pPn–TS), and RR2 (pH3–RR2) in antisense orientation. These constructs were tested for their protective potential in WSSV infected cell cultures, and their effect on reduction of the viral load was assessed. A robust reduction in WSSV copy number was observed upon transfection of antisense constructs in hemocyte cultures derived from Penaeus monodon and Scylla serrata. When tested in vivo, antisense constructs offered a strong protection in WSSV challenged P. monodon. Constructs expressing antisense VP24 and VP28 provided the best protection (up to 90 % survivability) with a corresponding decrease in the viral load. Our work demonstrates that shrimp treated with antisense constructs present an efficient control strategy for combating WSSV infection in shrimp aquaculture.     

Cytokines and anti-cytokine biologicals in autoimmunity: present and future

The increasing understanding of the role of cytokines in autoimmunity, and the observation that tumour necrosis factor alpha (TNFalpha) is central to the inflammatory and destructive process common to several human autoimmune diseases, has led to a new generation of therapeutics, the TNFalpha blocking agents. In this article, we review the current knowledge of the role of cytokines in autoimmunity as unravelled by studies both in the laboratory and the clinic. In addition, we discuss future prospects of the anti-TNFalpha therapy that may involve combination therapy with other anti-cytokine or anti-T cell biologicals, or the use of small chemicals targeting molecules involved in TNFalpha production such as NF-kappaB and p38 MAPK. The future developments of anti-TNFalpha and anti-cytokine therapy in general will be interesting.     

Caffeic acid inhibits in vitro rooting in mung bean [Vigna radiata (L.) Wilczek] hypocotyls by inducing oxidative stress

Caffeic acid (CA), which is ubiquitously present in plants, is a potent phytotoxin affecting plant growth and physiology. The aim of our study was to investigate whether CA-induced inhibition of adventitious root formation (ARF) in mung bean {Vigna radiata (L.) Wilczek [Phaseolus aureus Roxb.]} involves the induction of conventional stress responses. The effect of CA (0–1000 μM) on ARF in mung bean was determined by measuring the generation of reactive oxygen species (ROS) in terms of malondialdehyde and hydrogen peroxide (H₂O₂) content, root oxidizability and changes in levels of antioxidant enzymes. Our results show that CA significantly enhanced MDA content, indicating severe lipid peroxidation, and increased H₂O₂ accumulation and root oxidizability in the lower rooted hypocotylar region (LRHR) of mung bean, thereby inducing oxidative stress and cellular damage. In response to CA, there was a significant upregulation in the activities of scavenging enzymes, such as superoxide dismutase, ascorbate peroxidase, guaiacol peroxidase, catalase and glutathione reductase, in LRHRs of mung bean. Based on these results, we conclude that CA inhibits ARF in mung bean hypocotyls by inducing ROS-generated oxidative stress and upregulating the activities of antioxidant enzymes.