Virulence associated gene profiling and antimicrobial resistance pattern of Streptococcus suis isolated from clinically healthy pigs from North East India

This study revealed the prevalence of Streptococcus suis in 20·39% clinically healthy pigs from North East India. All these isolates were screened for the presence of virulence- associated genes such as suilysin (sly), muramidase released protein (mrp), extracellular protein factor (epf) and arginine deiminase (arcA). Of these 62 isolates, 29 isolates carried mrp gene, 17 isolates carried sly gene, 57 isolates carried arcA gene, whereas all isolates were negative for epf gene. The most prevalent genotype was mrp⁻ sly⁻ epf⁻ arcA⁺ (45·16%) followed by genotypes mrp⁺ sly⁻ epf⁻ arcA⁺ (27·41%), mrp⁺ sly⁺ epf⁻ arcA⁺ (19·35%) and mrp⁻ sly⁺ epf⁻ arcA⁻ (8·06%). High frequency of resistance was observed for antimicrobials such as tetracycline (93·54%), clindamycin (91·93%), co-trimoxazole (88·70%) and erythromycin (85·48%). Antimicrobial resistance patterns of the S. suis isolates revealed 16 resistance groups (R1 to R16), where 93·54% isolates showed multi-drug resistance (≥3 antimicrobial agents). It has also been observed that 57 (91·93%) isolates were resistant to at least four antimicrobials. The most predominant resistance pattern observed was CD-COT-E-TE, which accounted for 38·70% of the isolates. The occurrence of relatively high levels of resistance of S. suis to some antimicrobials (e.g., macrolides, tetracyclines, and sulphonamides) as observed in this study may represent a human health concern. In addition, a relatively higher percentage of S. suis isolated from clinically healthy pigs indicates a carrier status with risk of dissemination to other pigs in the herd as well as to humans.     

Clinically-Relevant Cutaneous Lesions by Nitrogen Mustard: Useful Biomarkers of Vesicants Skin Injury in SKH-1 Hairless and C57BL/6 Mice

A paucity of clinically applicable biomarkers to screen therapies in laboratory is a limitation in the development of countermeasures against cutaneous injuries by chemical weapon, sulfur mustard (SM), and its analog nitrogen mustard (NM). Consequently, we assessed NM-caused progression of clinical cutaneous lesions; notably, skin injury with NM is comparable to SM. Exposure of SKH-1 hairless and C57BL/6 (haired) mice to NM (3.2 mg) for 12–120 h caused clinical sequelae of toxicity, including microblister formation, edema, erythema, altered pigmentation, wounding, xerosis and scaly dry skin. These toxic effects of NM were similar in both mouse strains, except that wounding and altered pigmentation at 12–24 h and appearance of dry skin at 24 and 72 h post-NM exposure were more pronounced in C57BL/6 compared to SKH-1 mice. Conversely, edema, erythema and microblister formation were more prominent in SKH-1 than C57BL/6 mice at 24–72 h after NM exposure. In addition, 40–60% mortality was observed following 120 h of NM exposure in the both mouse strains. Overall, these toxic effects of NM are comparable to those reported in humans and other animal species with SM, and thus represent clinically-relevant cutaneous injury endpoints in screening and optimization of therapies for skin injuries by vesicating agents.     

Playing 20 Questions with the Mind: Collaborative Problem Solving by Humans Using a Brain-to-Brain Interface

We present, to our knowledge, the first demonstration that a non-invasive brain-to-brain interface (BBI) can be used to allow one human to guess what is on the mind of another human through an interactive question-and-answering paradigm similar to the “20 Questions” game. As in previous non-invasive BBI studies in humans, our interface uses electroencephalography (EEG) to detect specific patterns of brain activity from one participant (the “respondent”), and transcranial magnetic stimulation (TMS) to deliver functionally-relevant information to the brain of a second participant (the “inquirer”). Our results extend previous BBI research by (1) using stimulation of the visual cortex to convey visual stimuli that are privately experienced and consciously perceived by the inquirer; (2) exploiting real-time rather than off-line communication of information from one brain to another; and (3) employing an interactive task, in which the inquirer and respondent must exchange information bi-directionally to collaboratively solve the task. The results demonstrate that using the BBI, ten participants (five inquirer-respondent pairs) can successfully identify a “mystery item” using a true/false question-answering protocol similar to the “20 Questions” game, with high levels of accuracy that are significantly greater than a control condition in which participants were connected through a sham BBI.     

Quantitative Structure-Activity Relationship Study on Tetrahydro-β-carboline Antagonists of the Serotonin 2B (5HT 2B) Contractile Receptor in the Rat Stomach Fundus

The antagonist actions of three sub-series of tetrahydro- β -carbolines at the serotonin 2B (5HT 2B) contractile receptor in the rat stomach fundus are analyzed in relation to the physicochemical properties of the molecules. Significant correlations are obtained between the 5HT 2B receptor antagonist affinity and the hydrophobic, steric, electronic, hydrogen bond acceptor and some indicator variables of substituents. Based on these findings, the mode of actions of these congeneric series and future strategy to synthesize more potential compounds are discussed.     

Psychoneurochemical Investigations to Reveal Neurobiology of Memory Deficit in Epilepsy

Pentylenetetrazole-kindling induced memory deficit has been validated in our previous study. The present study attempts a neurochemical investigation to reveal possible targets for treatment of memory deficit associated with pentylenetetrazole-kindling. Kindling was induced by administering subconvulsive dose of pentylenetetrazole (35 mg/kg; i.p.) at an interval of 48 ± 2 h. Successfully kindled animals were divided into two groups (interictal and postictal group), while non-kindled (naive) animals served as naïve group. In postictal group, animals were challenged with pentylenetetrazole (35 mg/kg) on days 5, 10, 15 and 20. Learning and memory were evaluated in all experimental groups using elevated plus maze and passive shock avoidance paradigm on days 5, 10, 15 and 20. After behavioral evaluations on day 20, all animals were sacrificed to remove their brains. Neurochemical (glutamate, GABA, norepinephrine, dopamine and serotonin) changes and acetylcholinesterase activity and total nitrite level were estimated using HPLC-FD methods and microplate reader method respectively, in discrete brain parts. The results of the neurochemical estimation demonstrated the imbalance in excitatory/inhibitory tone, reduction in monoamine level, elevated nitrosative and acetylcholinesterase activity in the cortex and hippocampus, as responsible factors for the pathobiology of learning and memory deficit in epilepsy. Restoration of these changes may be targeted for the management of memory deficit in epileptic patients.     

Biocatalysts for multicomponent Biginelli reaction: bovine serum albumin triggered waste-free synthesis of 3,4-dihydropyrimidin-2-(1H)-ones

Bovine serum albumin (BSA) promoted simple and efficient one-pot procedure was developed for the direct synthesis of 3,4-dihydropyrimidin-2(1H)-ones including potent mitotic kinesin Eg5 inhibitor monastrol under mild reaction conditions. The catalyst recyclability and gram scale synthesis have also been demonstrated to enhance the practical utility of process.     

Force Generation in Lamellipodia Is a Probabilistic Process with Fast Growth and Retraction Events

Polymerization of actin filaments is the primary source of motility in lamellipodia and it is controlled by a variety of regulatory proteins. The underlying molecular mechanisms are only partially understood and a precise determination of dynamical properties of force generation is necessary. Using optical tweezers, we have measured with millisecond (ms) temporal resolution and picoNewton (pN) sensitivity the force-velocity (Fv) relationship and the power dissipated by lamellipodia of dorsal root ganglia neurons. When force and velocity are averaged over 3-5 s, the Fv relationships can be flat. On a finer timescale, random occurrence of fast growth and subsecond retractions become predominant. The maximal power dissipated by lamellipodia over a silica bead with a diameter of 1 μm is 10⁻¹⁶ W. Our results clarify the dynamical properties of force generation: i), force generation is a probabilistic process; ii), underlying biological events have a bandwidth up to at least 10 Hz; and iii), fast growth of lamellipodia leading edge alternates with local retractions.