Glycosylation as a tool for rational vaccine design

The discovery of broadly neutralizing antibodies that can neutralize multiple strains or subtypes of a pathogen has renewed interest in the development of broadly protective vaccines. To that end, there has been an interest in designing immunofocusing strategies to direct the immune response to specific, conserved regions on antigenic proteins. Modulation of glycosylation is one such immunofocusing strategy; extensive glycosylation is often exploited by pathogens for immune evasion. Masking epitopes on protein immunogens with “self” glycans can also shield the underlying protein surface from humoral immune surveillance. We review recent advances in applying glycosylation as an immunofocusing tool. We also highlight recent interesting work in the HIV-1 field involving the identification and elicitation of broadly neutralizing antibodies that incorporate glycans into their binding epitopes.     

Unconventional protein secretion: an evolving mechanism

The process by which proteins are secreted without entering the classical endoplasmic reticulum (ER)–Golgi complex pathway, in eukaryotic cells, is conveniently called unconventional protein secretion. Recent studies on one such protein called Acb1 have revealed a number of components involved in its secretion. Interestingly, conditions that promote the secretion of Acb1 trigger the biogenesis of a new compartment called CUPS (Compartment for Unconventional Protein Secretion). CUPS form near the ER exit site but lack ER‐specific proteins. Other proteins that share some of the features common with the secretion of Acb1 are interleukin‐1β and tissue transglutaminase. Here I will review recent advances made in the field and propose a new model for unconventional protein secretion.     

Hospitalization-induced exacerbation of the ill effects of chemotherapy on rest-activity rhythm and quality of life of breast cancer patients: a prospective and comparative cross-sectional follow-up study

ABSTRACT

Chemotherapy administration may result in the disruption of circadian rhythms and impairment of quality of life (QoL) of cancer patients. Nevertheless, we have little knowledge on the long-term consequences of chemotherapy and the effects of hospitalization. In the present study, we employed the two-factor repeated-measure cross-sectional design to determine the effects of chemotherapy and hospitalization on rest-activity (RA) rhythm and QoL of breast cancer patients. Initially, we randomly selected 39 inpatients and 42 outpatients, scheduled to receive six cycles of chemotherapy, from the Regional Cancer Center (RCC), Raipur, India. Finally, 30 patients in each group were included in the current study. We monitored circadian RA rhythm and QoL using wrist actigraphy and QLQ-C30 and QLQ-BR23, respectively, during the 1st (C1), 3rd (C3) and 6th (C6) chemotherapy cycles. Results revealed that with the progression of chemotherapy cycles (from C1 to C6), all rhythm parameters, namely mesor, amplitude, acrophase, rhythm quotient (RQ), circadian quotient (CQ), peak activity (PA), dichotomy index and autocorrelation coefficient, significantly decreased in both cancer in- and outpatients. In both groups of patients and during C1–C6, all functional and global QoL measures of QLQ-C30 and QLQ-BR23 significantly decreased and the symptoms significantly increased, except constipation, body image, sexual functioning and future perspectives in outpatients. The hospitalization exacerbated the problems associated with the RA rhythm and the QoL of the patients. In conclusion, the current study highlighted the negative consequences of hospitalization among inpatients, irrespective of the stage of cancer. We, therefore, recommend that cancer patients should be administered with chemotherapy as outpatients. The proposed protocol might have a covert bearing on the expression of better physiological state leading to satisfactory treatment outcomes.     

Alterations of the Characteristics of the Circadian Rest‐Activity Rhythm of Cancer In‐Patients

The aim of the present study was to evaluate the characteristics of the circadian rest‐activity rhythm of cancer patients. Thirty‐one in‐patients, consisting of 19 males and 12 females, were randomly selected from the Regional Cancer Center, Pandit Jawaharlal Nehru Medical College, Raipur, India. The rest‐activity rhythm was studied non‐invasively by wrist actigraphy, and compared with 35 age‐matched apparently healthy subjects (22 males and 13 females). All subjects wore an Actiwatch (AW64, Mini Mitter Co. Inc., USA) for at least 4–7 consecutive days. Fifteen‐second epoch length was selected for gathering actigraphy data. In addition, several sleep parameters, such as time in bed, assumed sleep, actual sleep time, actual wake time, sleep efficiency, sleep latency, sleep bouts, wake bouts, and fragmentation index, were also recorded. Data were analyzed using several statistical techniques, such as cosinor rhythmometry, spectral analysis, ANOVA, Duncan's multiple‐range test, and t‐test. Dichotomy index (I<O) and autocorrelation coefficient (r24) were also computed. The results validated a statistically significant circadian rhythm in rest‐activity with a prominent period of 24 h for most cancer patients and control subjects. Results of this study further revealed that cancer patients do experience a drastic alteration in the circadian rest‐activity rhythm parameters. Both the dichotomy index and r24 declined in the group of cancer patients. The occurrence of the peak (acrophase, Ø) of the rest‐activity rhythm was earlier (p<0.001) in cancer patients than age‐ and gender‐matched control subjects. Results of sleep parameters revealed that cancer patients spent longer time in bed, had longer assumed and actual sleep durations, and a greater number of sleep and wake bouts compared to control subjects. Further, nap frequency, total nap duration, average nap, and total nap duration per 1 h awake span were statistically significantly higher in cancer patients than control subjects. In conclusion, the results of the present study document the disruption of the circadian rhythm in rest‐activity of cancer in‐patients, with a dampening of amplitude, lowering of mean level of activity, and phase advancement. These alterations of the circadian rhythm characteristics could be attributed to disease, irrespective of variability due to gender, sites of cancer, and timings of therapies. These results might help in designing patient‐specific chronotherapeutic protocols.     

Eragrostis nilgiriensis sp. nov. (Poaceae) from Nilgiri district,Tamil Nadu,India

A new species of the grass genus Eragrostis Wolf, E. nilgiriensis C. P. Vivek, G. V. S. Murthy & V. J. Nair sp. nov. from Nilgiri district, Tamil Nadu, India is described and illustrated. The species is allied to E. barrelieri, but differs from it mainly by the primary panicle branches not spiculate up to base, leaves not glaucous, lemma shorter and acute and by a much smaller caryopsis. The new species is morphologically similar also to E. minor and E. nigra. A table listing differences between these species is provided.     

Methylerythritol phosphate pathway to isoprenoids: Kinetic modeling and in silico enzyme inhibitions in Plasmodium falciparum

The methylerythritol phosphate (MEP) pathway of Plasmodium falciparum (P. falciparum) has become an attractive target for anti-malarial drug discovery. This study describes a kinetic model of this pathway, its use in validating 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR) as drug target from the systemic perspective, and additional target identification, using metabolic control analysis and in silico inhibition studies. In addition to DXR, 1-deoxy-d-xylulose 5-phosphate synthase (DXS) can be targeted because it is the first enzyme of the pathway and has the highest flux control coefficient followed by that of DXR. In silico inhibition of both enzymes caused large decrement in the pathway flux. An added advantage of targeting DXS is its influence on vitamin B1 and B6 biosynthesis. Two more potential targets, 2-C-methyl-d-erythritol 2,4-cyclodiphosphate synthase and 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate synthase, were also identified. Their inhibition caused large accumulation of their substrates causing instability of the system.     

Plant proteomics in India and Nepal: current status and challenges ahead

Plant proteomics has made tremendous contributions in understanding the complex processes of plant biology. Here, its current status in India and Nepal is discussed. Gel-based proteomics is predominantly utilized on crops and non-crops to analyze majorly abiotic (49 %) and biotic (18 %) stress, development (11 %) and post-translational modifications (7 %). Rice is the most explored system (36 %) with major focus on abiotic mainly dehydration (36 %) stress. In spite of expensive proteomics setup and scarcity of trained workforce, output in form of publications is encouraging. To boost plant proteomics in India and Nepal, researchers have discussed ground level issues among themselves and with the International Plant Proteomics Organization (INPPO) to act in priority on concerns like food security. Active collaboration may help in translating this knowledge to fruitful applications.     

Dual on-off and off-on switchable oligoaziridine biosensor

A water-soluble biocompatible aziridine-based biosensor with pendant anthracene units was synthesized by radicalar polymerization of N-substituted aziridines in supercritical carbon dioxide. The binding ability of the sensor towards a series of metal ions was examined by comparing the fluorescence intensities of the solutions before and after the addition of 100 equivalents of a solution of the metal ion chloride salt. A fast, simple and highly optical sensitive dual behavior, "off-on" and "on-off" response, was observed after the biosensor was exposed to the metal cations in aqueous solution. Zinc presented the highest fluorescence enhancement (turn-on) and copper presented the highest fluorescence quenching (turn-off). The response time was found to be instantaneous and the detection limit was achieved even in the presence of excess metal cation competitors. By using immunofluorescence microscopy it was also shown that oligoaziridine acts as an "on-off" probe through highly sensitive (detection limit of 1.6nM), selective and reversible binding to copper anions under physiologic conditions using living Human Fibroblast cells. The stoichiometry for the reaction of the biosensor with Cu(2+) was determined by a Job plot and indicates the formation of an oligoaziridine-Cu(2+) 1:2 adduct.     

Wild Asian elephants distinguish aggressive tiger and leopard growls according to perceived danger

Prey species exhibit antipredator behaviours such as alertness, aggression and flight, among others, in response to predators. The nature of this response is variable, with animals reacting more strongly in situations of increased vulnerability. Our research described here is the first formal study to investigate night-time antipredator behaviour in any species of elephants, Asian or African. We examined the provocative effects of elephant-triggered tiger and leopard growls while elephants attempted to crop-raid. Tigers opportunistically prey on elephant calves, whereas leopards pose no threat; therefore, we predicted that the elephant response would be reflective of this difference. Elephants reacted similarly cautiously to the simulated presence of felids of both species by eventually moving away, but differed markedly in their more immediate behavioural responses. Elephants retreated silently to tiger-growl playbacks, whereas they responded with aggressive vocalizations, such as trumpets and grunts, to leopard-growl playbacks. Elephants also lingered in the area and displayed alert or investigative behaviours in response to leopard growls when compared with tiger growls. We anticipate that the methods outlined here will promote further study of elephant antipredator behaviour in a naturalistic context, with applications for conservation efforts as well.