Neurotopographical Transformations: Dissecting Cortical Reconfigurations in Auditory Deprivation.

Within the intricate matrices of cognitive neuroscience, auditory deprivation acts as a catalyst, propelling a cascade of neuroanatomical adjustments that have, until now, been suboptimally articulated in extant literature. Addressing this gap, our study harnesses high-resolution 3 T MRI modalities to unveil the multifaceted cortical transformations that emerge in tandem with congenital auditory deficits. We conducted a rigorous cortical surface analysis on a cohort of 90 congenitally deaf individuals, systematically compared with 90 normoacoustic controls. Our sample encompassed both male and female participants, ensuring a gender-inclusive perspective in our analysis. Expected alterations within prototypical auditory domains were evident, but our findings transcended these regions, spotlighting modifications dispersed across a gamut of cortical and subcortical structures, thereby epitomizing the cerebral adaptive dynamics to sensory voids. Crucially, the study's innovative methodology integrated two pivotal variables: the duration of auditory deprivation and the extent of sign language immersion. By intersecting these metrics with structural changes, our analysis unveiled nuanced layers of cortical reconfigurations, elucidating a more granulated understanding of neural plasticity. This intersectional approach bestows a unique advantage, allowing for a discerning exploration into how varying durations of sensory experience and alternative communication modalities modulate the brain's morphological terrain. In encapsulating the synergy of neuroimaging finesse and incisive scientific rigor, this research not only broadens the current understanding of adaptive neural mechanisms but also paves the way for tailored therapeutic strategies, finely attuned to individual auditory histories and communicative repertoires.

Neural adaptations to congenital deafness: enhanced tactile discrimination through cross-modal neural plasticity - an fMRI study.

BACKGROUND: This study explores the compensatory neural mechanisms associated with congenital deafness through an examination of tactile discrimination abilities using high-resolution functional magnetic resonance imaging (fMRI). OBJECTIVE: To analyze the neural substrates underlying tactile processing in congenitally deaf individuals and compare them with hearing controls. METHODS: Our participant pool included thirty-five congenitally deaf individuals and thirty-five hearing controls. All participants engaged in tactile discrimination tasks involving the identification of common objects by touch. We utilized an analytical suite comprising voxel-based statistics, functional connectivity multivariate/voxel pattern analysis (fc-MVPA), and seed-based connectivity analysis to examine neural activity. RESULTS: Our findings revealed pronounced neural activity in congenitally deaf participants within regions typically associated with auditory processing, including the bilateral superior temporal gyrus, right middle temporal gyrus, and right rolandic operculum. Additionally, unique activation and connectivity patterns were observed in the right insula and bilateral supramarginal gyrus, indicating a strategic reorganization of neural pathways for tactile information processing. Behaviorally, both groups demonstrated high accuracy in the tactile tasks, exceeding 90%. However, the deaf participants outperformed their hearing counterparts in reaction times, showcasing significantly enhanced efficiency in tactile information processing. CONCLUSION: These insights into the brain's adaptability to sensory loss through compensatory neural reorganization highlight the intricate mechanisms by which tactile discrimination is enhanced in the absence of auditory input. Understanding these adaptations can help develop strategies to harness the brain's plasticity to improve sensory processing in individuals with sensory impairments, ultimately enhancing their quality of life through improved tactile perception and sensory integration.

Human epidermal growth factor receptor 2/neu expression in urothelial carcinomas.

Introduction: Urothelial carcinomas of the bladder are more common in males, making them the sixth-most common cancer in men and the tenth-most common cancer overall, worldwide. Current guidelines do not recommend routine testing for human epidermal growth factor receptor (HER2/neu) expression on the biopsy specimens of patients with urothelial carcinoma. This study was aimed at determining the expression pattern of HER2/neu and its usefulness in muscle-invasive and nonmuscle-invasive urothelial carcinoma. Methods: HER2/neu expression was assessed in 89 specimens of urothelial cancer by immunohistochemistry (IHC), and equivocal cases were subjected to fluorescent in situ hybridization (FISH). Results: On IHC for HER2/neu, 17.9% (7/39) of the muscle-invasive bladder cancers (MIBCs) showed a 3+ expression, whereas 22% (11/50) of the non-muscle invasive cancers were positive with a score of 3+. A significant correlation between HER2/neu status and muscle invasion could not be established in the current study (P = 0.74, Fisher's exact test). Three cases of muscle-invasive (7.7%) and 2 cases (4%) among nonmuscle invasive cancers showed equivocal expression. All the cases with equivocal (2+) expression on IHC were subjected to FISH and none showed gene amplification on hybridization and were considered as negative. Conclusion: Overexpression of HER-2/neu was seen in 17.9% of MIBCs and 22% of non-MIBCs. There are no norms for routine testing of HER2/neu expression in the biopsy specimens of urothelial carcinoma. There is an unmet need to establish guidelines for HER2/neu scoring, similar to that for breast and gastric cancers, to determine the proportion of positive cases and help in identification of those who may benefit from targeted therapies.

Drought stress in maize: stress perception to molecular response and strategies for its improvement.

Given the future demand for food crops, increasing crop productivity in drought-prone rainfed areas has become essential. Drought-tolerant varieties are warranted to solve this problem in major crops, with drought tolerance as a high-priority trait for future research. Maize is one such crop affected by drought stress, which limits production, resulting in substantial economic losses. It became a more serious issue due to global climate change. The most drought sensitive among all stages of maize is the reproductive stages and the most important for overall maize production. The exact molecular basis of reproductive drought sensitivity remains unclear due to genes' complex regulation of drought stress. Understanding the molecular biology and signaling of the unexplored area of reproductive drought tolerance will provide an opportunity to develop climate-smart drought-tolerant next-generation maize cultivars. In recent decades, significant progress has been made in maize to understand the drought tolerance mechanism. However, improving maize drought tolerance through breeding is ineffective due to the complex nature and multigenic control of drought traits. With the help of advanced breeding techniques, molecular genetics, and a precision genome editing approach like CRISPR-Cas, candidate genes for drought-tolerant maize can be identified and targeted. This review summarizes the effects of drought stress on each growth stage of maize, potential genes, and transcription factors that determine drought tolerance. In addition, we discussed drought stress sensing, its molecular mechanisms, different approaches to developing drought-resistant maize varieties, and how molecular breeding and genome editing will help with the current unpredictable climate change.

Large Solitary Fibrous Tumor (SFT) of the penis- a case report and review of literature.

BACKGROUND: Solitary fibrous tumors (SFTs) are very rare spindle cell neoplasms of mesenchymal origin with largely benign course of disease. Genital SFT's can be managed providing excellent functional and psychological outcomes by timely intervention. CASE PRESENTATION: We report the largest and possibly the second only reported case of penile SFT in a 34 year male presenting with a gradually increasing perineal mass with clinically normal appearing phallus. MRI revealed a 9.8 × 3.2 cm soft tissue mass arising from left corpora cavernosae, the mass was excised en-bloc via a perineal approach under spinal anaesthesia. Histopathology revealed spindle cell tumor embedded in myxohyaline stroma along with hyalinized vascular channels demonstrating IHC positivity for CD34 and STAT6. The patient is disease free post 2 years of resection with no sexual or urinary dysfunctions. CONCLUSION: Genital SFTs, although rare, should be considered in the differential diagnosis of well-circumscribed, painless, slow growing solid masses and histopathologists must be vigilant of its malignant characteristics.

Evaluation of modified RENAL nephrometry score in the prediction of perioperative outcomes of open partial nephrectomy.

Introduction: RENAL nephrometry score (RNS) is a standardized system to grade the complexity of renal masses, but it does not correlate well with the perioperative outcomes of open partial nephrectomy (OPN). To overcome these shortcomings, a modified RNS (MRNS) has been proposed. In this study, we evaluated the MRNS and its role in predicting the perioperative outcomes of OPN. Methods: This was a prospective observational study performed at a tertiary care hospital to evaluate the efficacy of MRNS in predicting the perioperative outcomes of OPN. Sixty-four cases were included in the study. Demographic parameters, tumor characteristics, and perioperative outcomes were analyzed. Correlation with the post-operative outcomes and the strengths of MRNS were compared with various other nephrometry scores. Results: The mean age of the patients was 52.89 years, 60.9% were male and 53.1% had a right-sided mass. The comorbidities, body mass index, and performance scores were evenly distributed across the complexity groups (P > 0.05). The mean tumor size was 4.13 cm and the mean MRNS and RNS were 9.45 and 6.1, respectively. 60.9% of the cases had no complications. Major complications (Clavien-Dindo grade [CDG] 3+) were noted in five cases (7.8%). The trifecta of neargin, ischemia, and complications (MICs) score was achieved in 85.9% and was achieved in 71.9% of the cases. MRNS was found to be an independent predictor of the trifecta outcomes (P = 0.04). Receiver-operating characteristic curve of MRNS analyzing the major complications as per the CDG showed an area under the curve of. 804, indicating good prediction of complications by the MRNS. Conclusions: MRNS improves the predicting power of RNS by attributing enhanced scores to key elements and by adding new elements. Also, MRNS has good ability to predict the achievement of the trifecta and MIC.

Flexible microtubule anchoring modulates the bi-directional motility of the kinesin-5 Cin8.

Two modes of motility have been reported for bi-directional kinesin-5 motors: (a) context-dependent directionality reversal, a mode in which motors undergo persistent minus-end directed motility at the single-molecule level and switch to plus-end directed motility in different assays or under different conditions, such as during MT gliding or antiparallel sliding or as a function of motor clustering; and (b) bi-directional motility, defined as movement in two directions in the same assay, without persistent unidirectional motility. Here, we examine how modulation of motor-microtubule (MT) interactions affects these two modes of motility for the bi-directional kinesin-5, Cin8. We report that the large insert in loop 8 (L8) within the motor domain of Cin8 increases the MT affinity of Cin8 in vivo and in vitro and is required for Cin8 intracellular functions. We consistently found that recombinant purified L8 directly binds MTs and L8 induces single Cin8 motors to behave according to context-dependent directionality reversal and bi-directional motility modes at intermediate ionic strength and according to a bi-directional motility mode in an MT surface-gliding assay under low motor density conditions. We propose that the largely unstructured L8 facilitates flexible anchoring of Cin8 to the MTs. This flexible anchoring enables the direct observation of bi-directional motility in motility assays. Remarkably, although L8-deleted Cin8 variants exhibit a strong minus-end directed bias at the single-molecule level, they also exhibit plus-end directed motility in an MT-gliding assay. Thus, L8-induced flexible MT anchoring is required for bi-directional motility of single Cin8 molecules but is not necessary for context-dependent directionality reversal of Cin8 in an MT-gliding assay.

Autoinducer N-(3-oxododecanoyl)-l-homoserine lactone induces calcium and reactive oxygen species-mediated mitochondrial damage and apoptosis in blood platelets.

Acylated homoserine lactones (AHL) such as N-(3-oxododecanoyl)-l-homoserine lactone (3-oxo-C12 HSL) and N-butyryl-l-homoserine lactone (C4 HSL) are the most common autoinducer molecules in Pseudomonas aeruginosa. These AHL molecules not only regulate the expression of virulence factors but also have been shown to interfere with the host cell and modulate its functions. Recently, we reported that 3-oxo-C12 HSL but not C4 HSL causes cytosolic Ca2+ rise and ROS production in platelets. In this study, we examined the potential of AHLs to induce apoptosis in the human blood platelet. Our result showed that 3-oxo-C12 HSL but not C4 HSL causes phosphatidylserine (PS) exposure, mitochondrial dysfunction (mitochondrial transmembrane potential loss, and mitochondrial permeability transition pore (mPTP) formation). Besides, 3-oxo-C12 HSL also inhibited thrombin-induced platelet aggregation and clot retraction. The pretreatment of an intracellular calcium chelator BAPTA-AM or ROS inhibitor (DPI) significantly attenuated the 3-oxo-C12 HSL induced apoptotic characters such as PS exposure and mitochondrial dysfunctions. These data, including our previous findings, confirmed that 3-oxo-C12 HSL induced intracellular Ca2+ mediated ROS production results in the activation and subsequent induction of apoptotic features in platelets. Our results demonstrated that the 3-oxo-C12 HSL modulates the functions of platelets that may cause severe thrombotic complications in P. aeruginosa infected individuals.

Mechanisms by Which Kinesin-5 Motors Perform Their Multiple Intracellular Functions.

Bipolar kinesin-5 motor proteins perform multiple intracellular functions, mainly during mitotic cell division. Their specialized structural characteristics enable these motors to perform their essential functions by crosslinking and sliding apart antiparallel microtubules (MTs). In this review, we discuss the specialized structural features of kinesin-5 motors, and the mechanisms by which these features relate to kinesin-5 functions and motile properties. In addition, we discuss the multiple roles of the kinesin-5 motors in dividing as well as in non-dividing cells, and examine their roles in pathogenetic conditions. We describe the recently discovered bidirectional motility in fungi kinesin-5 motors, and discuss its possible physiological relevance. Finally, we also focus on the multiple mechanisms of regulation of these unique motor proteins.

Bidirectional motility of kinesin-5 motor proteins: structural determinants, cumulative functions and physiological roles.

Mitotic kinesin-5 bipolar motor proteins perform essential functions in mitotic spindle dynamics by crosslinking and sliding antiparallel microtubules (MTs) apart within the mitotic spindle. Two recent studies have indicated that single molecules of Cin8, the Saccharomyces cerevisiae kinesin-5 homolog, are minus end-directed when moving on single MTs, yet switch directionality under certain experimental conditions (Gerson-Gurwitz et al., EMBO J 30:4942-4954, 2011; Roostalu et al., Science 332:94-99, 2011). This finding was unexpected since the Cin8 catalytic motor domain is located at the N-terminus of the protein, and such kinesins have been previously thought to be exclusively plus end-directed. In addition, the essential intracellular functions of kinesin-5 motors in separating spindle poles during mitosis can only be accomplished by plus end-directed motility during antiparallel sliding of the spindle MTs. Thus, the mechanism and possible physiological role of the minus end-directed motility of kinesin-5 motors remain unclear. Experimental and theoretical studies from several laboratories in recent years have identified additional kinesin-5 motors that are bidirectional, revealed structural determinants that regulate directionality, examined the possible mechanisms involved and have proposed physiological roles for the minus end-directed motility of kinesin-5 motors. Here, we summarize our current understanding of the remarkable ability of certain kinesin-5 motors to switch directionality when moving along MTs.

NMR elucidation of monomer-dimer transition and conformational heterogeneity in histone-like DNA binding protein of Helicobacter pylori.

Helicobacter pylori (H. pylori) colonizes under harsh acidic/oxidative stress conditions of human gastrointestinal tract and can survive there for infinitely longer durations of host life. The bacterium expresses several harbinger proteins to facilitate its persistent colonization under such conditions. One such protein in H. pylori is histone-like DNA binding protein (Hup), which in its homo-dimeric form binds to DNA to perform various DNA dependent cellular activities. Further, it also plays an important role in protecting the genomic DNA from oxidative stress and acidic denaturation. Legitimately, if the binding of Hup to DNA is suppressed, it will directly impact on the survival of the bacterium, thus making Hup a potential therapeutic target for developing new anti-H. pylori agents. However, to inhibit the binding of Hup to DNA, it is necessary to gain detailed insights into the molecular and structural basis of Hup-dimerization and its binding mechanism to DNA. As a first step in this direction, we report here the nuclear magnetic resonance (NMR) assignments and structural features of Hup at pH 6.0. The study revealed the occurrence of dynamic equilibrium between its monomer and dimer conformations. The dynamic equilibrium was found to shifting towards dimer both at low temperature and low pH; whereas DNA binding studies evidenced that the protein binds to DNA in its dimeric form. These preliminary investigations correlate very well with the diverse functionality of protein and will form the basis for future studies aiming to develop novel anti-H. pylori agents employing structure-based-rational drug discovery approach.

Molecular characterization of novel immunodominant molybdenum cofactor biosynthesis protein C1 (Rv3111) from Mycobacterium tuberculosis H37Rv.

BACKGROUND: In the molybdenum cofactor biosynthesis pathway, MoaA and MoaC catalyze the first step of transformation of GTP to cPMP. In M. tuberculosis H37Rv, three different genes (Rv3111, Rv0864 and Rv3324c) encode for MoaC homologs. Out of these three only MoaC1 (Rv3111) is secretory in nature. METHODS: We have characterized MoaC1 protein through biophysical, in-silico, and immunological techniques. RESULTS: We have characterized the conformation and thermodynamic stability of MoaC1, and have established its secretory nature by demonstrating the presence of anti-MoaC1 antibodies in human tuberculosis patients' sera. Further, MoaC1 elicited a dominant Th1 immune response in mice characterized by increased induction of IL-2 and IFN-γ. CONCLUSION: Integrating these results, we conclude that MoaC1 is a structured secretory protein capable of binding with GTP and eliciting induced immune response. GENERAL SIGNIFICANCE: This study would be useful for the development of vaccines against tuberculosis and to improve methods used for diagnosis of tuberculosis.

Characterization of culture filtrate proteins Rv1197 and Rv1198 of ESAT-6 family from Mycobacterium tuberculosis H37Rv.

BACKGROUND: We have characterized two immunogenic proteins, Rv1197 and Rv1198, of the Esx-5 system of the ESAT-6 family of Mycobacterium tuberculosis H37Rv. METHODS: The complex formation between Rv1197 and Rv1198 was characterized by biophysical techniques. The reactivity of serum from TB patients towards these proteins was characterized by ELISA. Lymphocyte proliferation and cytokine induction were followed in restimulated splenocytes from immunized mice by using MTT assay and CBA flowcytometry, respectively. RESULTS: Rv1197 and Rv1198 strongly interact to form a heterodimeric complex under reducing conditions, which is characterized by a dissociation constant of 97×10-9M and melting temperature, Tm, of 50.5°C. Strong humoral responses to Rv1197, Rv1198, CFP-10 and MoaC1 (Rv3111) antigens were found in Indian patients with active pulmonary tuberculosis (n=44), in comparison to non-infected healthy individuals (n=20). The seroreactivity to Rv1198 was characterized by a sensitivity of 75% and specificity of 90%. In BALB/c mice, immunization with Rv1198-FIA induced a pro-inflammatory response with elevated levels of TNF and IL-6, along with low induction of IFN-γ, IL-2 and IL-10, but no induction of IL-4. CONCLUSION: Rv1197 and Rv1198 form a stable complex, which is regulated by the redox state of Rv1198. Rv1198 is immunogenic with highly specific seroreactivity towards TB patients' serum. Rv1198 elicits a pro-inflammatory recall response in immunized mice. GENERAL SIGNIFICANCE: This study characterizes the interaction of Rv1197 and Rv1198, and establishes the immunogenic nature of Rv1198.

Exploration of anti-Malassezia potential of Nyctanthes arbor-tristis L. and their application to combat the infection caused by Mala s1 a novel allergen.

BACKGROUND: Malassezia commensal yeasts along with multitude of antigens have been found to be associated with various skin disorders including Pityriasis versicolor (PV). Amongst them Mala s1, a 37 kDa protein has been proved to be a major allergen reacting with a large panel of sera. However, there exists no therapeutic alternative to combat such problems in form of plant based natural compounds. The purpose of this study is in the first place, to determine the anti-Malassezia activity of Nyctanthes arbor-tristis L. (NAT) ethanolic leaf extract through turbidimetric growth curves, disruption of plasma membrane and secondly, it aims to present in silico validation of its active constituents over Mala s1a novel allergen. METHODS: The antifungal susceptibility 50 % ethanolic extract of NAT was determined by broth microdilution method according to CLSI guidelines. Further MICs and IC50 were determined spectrophotometrically using the software SoftMax® Pro-5 (Molecular Devices, USA). Active constituents mediated disruption of plasma membrane was studied through flowcytometry by permeabilization of fluorescent dye Propidium Iodide (PI). Antioxidant activity of the extract was determined using the DPPH stable radical. Molecular validation of fungal DNA from the extract was observed using PCR amplification. In silico analysis of its active constituents over Mala s1 was performed using HEX software and visualized through Pymol. RESULTS: The anti-Malassezia potential of NAT leaf extracts reflected moderate MIC 1.05 µg/µl against M. globosa, while least effective against M. restricta with MIC 1.47 µg/µl. A linear correlation coefficient R (2) = 0.866 was obtained in case of M. globosa while minimum was observed in M. restricta with R (2) = 0.732. The flow cytometric data reveal ~ 75 % cell death when treated with active constituents ß-Sitosterol and Calceolarioside A. The docking confirmations and the interaction energies between Mala s1 and the active constituents (ß-Sitosterol and Calceolarioside A) from extracts showed an effective binding which suggests Mala s1 as efficient allergen for site specific targeting. CONCLUSIONS: This study revealed that Nyctanthes arbor-tristis L. (NAT) extracts possess high anti-Malassezia potential which is driven mainly by disruption of plasma membrane. Also in silico validation and molecular modeling studies establishes Mala s1 as a novel allergen that could be a potential target in disease treatment. Our results would also provide a foundation for the development of new therapeutic approach using NAT extract as lead compound with high antioxidant property as an added trait for skin care.

Outcomes of laparoscopic cholecystectomy done with surgical energy versus done without surgical energy: a prospective-randomized control study.

OBJECTIVE: Laparoscopic cholecystectomy (LC), a gold standard procedure can be done without energized dissection (ED). We did a randomized study for the outcomes of LC done with ED or without ED, i.e., with cold dissection (CD). METHODS AND PROCEDURES: At a tertiary level institution, open-ended prospective-randomized control study was conducted between September 2008 and June 2013. Consecutive, unselected, consenting candidates for LC were enrolled following standard ethics, informed consent, anesthesia, and clinical pathway protocol. They were allocated to control group (LC with ED) or study group (LC with CD, as per our published technique with the option for rescue ED). The study points were based upon Clavien-Dindo grading of postoperative complications. They were either, peri-operative events potentially affecting, hospital stay (Grade I) or Grade II-V, e.g., peri-operative hemodynamic instability, needing intervention/blood transfusion, injury to biliary ducts/hollow viscous, postoperative biliary leak, postoperative re-intervention, re-hospitalization, mortality, and any adverse event during a 90-day follow-up period. The data were prospectively collected in an integrated "hospital information system" that could be retrieved only by independent external coordinators. RESULTS: Demographics, co-morbidities, and gallbladder inflammation profile of the control group (n = 361) and study group (n = 384) were comparable. There was no rescue ED usage in the study group. Hospital stay (Grade I adverse outcome dependent) was longer, i.e., 1.6 ± 1.03 in the control versus 1.35 ± 1.2 days in the study group (p < 0.001). Grade II-IV complications were significantly more (p < 0.009) in control group. There was one common bile duct (CBD) injury in each group. The index bilio-enteric anastomosis for CBD injury in control group failed and needed a revision with multiple interventions. There was one grade V adverse outcome, i.e., mortality in the control group. CONCLUSION: Avoiding the use of ED in LC is associated with better outcomes.

Using ALE coordinate-based meta-analysis to observe resting-state brain abnormalities in subjective tinnitus.

The origin of tinnitus remains a topic of discussion; however, numerous resting-state functional magnetic resonance imaging (rsfMRI) studies interpret it as a disruption in neural functional connectivity. Yet, there's notable inconsistency in the resting-state data across these studies. To shed light on this discrepancy, we conducted a meta-analysis of extant rsfMRI studies, aiming to identify potential regions that consistently signify core abnormalities in individuals with tinnitus. METHODS: A systematic search on MEDLINE/PubMed, Google Scholar, and Scopus databases was performed to identify rsfMRI studies on tinnitus published up to October 2022. Coordinates related to the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) brain maps that showed significant differences between tinnitus patients and controls were extracted. Meta-analysis was performed using the activation likelihood estimation method. Data were included from 17 rsfMRI studies that reported a total of 63 distinct foci in ALFF and 46 foci in ReHo. RESULTS: Our meta-analysis revealed several regions where tinnitus patients demonstrated increased ALFF and ReHO values, both individually and collectively, when compared to control subjects. These regions encompassed the insula, middle temporal gyrus, and inferior frontal gyrus on both sides. Additionally, increased activity was also noted in the cerebellum posterior lobe bilaterally and the right superior frontal gyrus. CONCLUSIONS: This meta-analysis demonstrates a unique pattern of resting-state brain abnormalities involving both the auditory and non-auditory brain regions as neuroimaging markers, which helps understand the neuro-pathophysiological mechanisms of tinnitus.

Mapping the unique neural engagement in deaf individuals during picture, word, and sign language processing: fMRI study.

Employing functional magnetic resonance imaging (fMRI) techniques, we conducted a comprehensive analysis of neural responses during sign language, picture, and word processing tasks in a cohort of 35 deaf participants and contrasted these responses with those of 35 hearing counterparts. Our voxel-based analysis unveiled distinct patterns of brain activation during language processing tasks. Deaf individuals exhibited robust bilateral activation in the superior temporal regions during sign language processing, signifying the profound neural adaptations associated with sign comprehension. Similarly, during picture processing, the deaf cohort displayed activation in the right angular, right calcarine, right middle temporal, and left angular gyrus regions, elucidating the neural dynamics engaged in visual processing tasks. Intriguingly, during word processing, the deaf group engaged the right insula and right fusiform gyrus, suggesting compensatory mechanisms at play during linguistic tasks. Notably, the control group failed to manifest additional or distinctive regions in any of the tasks when compared to the deaf cohort, underscoring the unique neural signatures within the deaf population. Multivariate Pattern Analysis (MVPA) of functional connectivity provided a more nuanced perspective on connectivity patterns across tasks. Deaf participants exhibited significant activation in a myriad of brain regions, including bilateral planum temporale (PT), postcentral gyrus, insula, and inferior frontal regions, among others. These findings underscore the intricate neural adaptations in response to auditory deprivation. Seed-based connectivity analysis, utilizing the PT as a seed region, revealed unique connectivity pattern across tasks. These connectivity dynamics provide valuable insights into the neural interplay associated with cross-modal plasticity.

Detection and molecular characterization of 'Candidatus Phytoplasma australasiaticum' in Aegle marmelos: a fruit of high medicinal values in India.

In surveys conducted from 2020 to 2022, five leaf samples each from symptomatic Agele marmelos trees and seedlings, along with five samples from asymptomatic trees and seedlings, were collected in Ayodhya, Uttar Pradesh, India. The DNA extraction from all the samples was subjected to nested PCR assays, using the universal phytoplasma-specific primers set (P1/P7 followed by R16F2n/R16R2). The resulting 1.2 kb amplified products were observed in all the symptomatic samples but not in the asymptomatic samples. Bael phytoplasma strain sequences from the trees and seedlings were found 100% identical within themselves and only two representative sequences (one each from tree and seedling) were deposited in GenBank (NCBI) as PP415872 (AmA-1) and PP415873 (AmA-2). BLASTn searches revealed the maximum (100%) sequence identity with a phytoplasma strain from murraya little leaf strain of Faizabad (GenBank Acc.no. OP984129) and lowest (99.84%) with arecanut crown choking of Shimoga (GenBank Acc. no. OM417502) from Karnataka. Phylogenetic analysis clustered the bael phytoplasma isolates with peanut witches' broom group phytoplasma strains. Virtual RFLP analysis confirmed their identity as 'Ca. P. australasiaticum', a 16SrII-D subgroup strain. This study presents the first identification of a phytoplasma strain in A. marmelos, emphasizing its potential threat to fruit crops and the need for vigilance in nursery practices to prevent further dissemination.

In Vitro Assessment of Antimicrobial Activity of Novel Fluoroquinolone, Levonadifloxacin (WCK 771) Against Multi-Drug-Resistant Clinical Isolates from Cancer Patients in India.

Introduction: Rapid increase in antimicrobial-resistance is leading to urgent need for newer broad-spectrum antimicrobials. Therefore, we have evaluated the antimicrobial résistance spectrum of India-discovered novel antibiotics (levonadifloxacin) against clinical isolates recovered from cancer patients. Materials and Methods: The study was conducted in the microbiology department, over a period of 1 year between May 2021 and June 2022 and 374 consecutive and nonduplicate Gram-positive (GPC) and MDR Gram Negative Bacteria (GNB) isolate were analyzed from 3,880 cancer patients in study. The identification and antimicrobial sensitivities of bacterial isolates were performed according to standard laboratory protocols by using automated identification system (VITEK-2-8.01; BioMérieux, Germany). The activity of levonadifloxacin and comparator antibiotics was evaluated using disk diffusion methods as per Clinical and Laboratory Standards Institute 2022 guidelines. Results: The mean age of the patients were 51.6 ± 14.59 years with male: female ratio of 1.2:1. The prevalence of GPC was 167 (44.65%) and MDR-GNB was 207 (55.34%). The most common GPC was Staphylococcus aureus; 97 (58.08%) followed by Enterococcus species 66 (39.52%). In GNB, Escherichia coli; 93 (44.92%) was the most common followed by Klebsiella pneumoniae; 45 (21.73%). Levonadifloxacin susceptibility was present in 98.7% methicillin-resistant S. aureus and 96% methicillin-susceptible S. aureus and 77.1% Enterococcus-species. Additionally, all the fluoroquinolones-resistant S. aureus isolates were susceptible to levonadifloxacin (WCK-771) except one isolate. Also, levonadifloxacin-(WCK-771) exhibits 100% susceptibility fluoroquinolone susceptible GNB, such as E. coli, K. pneumoniae, Pseudomonas species, and Acinetobacter species. Interestingly, all fluoroquinolones-resistant Salmonella species and Stenotrophomonas maltophilla exhibited 100% susceptibility to levonadifloxacin (WCK-771). Conclusion: Levonadifloxacin (WCK-771) possesses potent activity against all the MDR Gram-positive pathogens including the coverage of susceptible Enterobacterales and MDR S. maltophilla and Burkholderia cepacia suggesting its potential utility in the management of polymicrobial infections.

Ecological and human health risk assessment of pharmaceutical compounds in the Sirsa River of Indian Himalayas.

The Baddi-Barotiwala-Nalagarh (BBN) region of Indian Himalayas is one of the most important pharmaceutical industrial clusters in Asia. This study investigated the distribution, and ecological and human health risks of four most frequently used pharmaceuticals [ciprofloxacin (CIP), norfloxacin (NOR), cetirizine (CTZ) and citalopram oxalate (ECP)] when co-occurring with metal ions in the Sirsa river water of the BBN region. The concentration range of the selected pharmaceuticals was between 'not detected' to 50 µgL-1 with some exception for CIP (50-100 µgL-1) and CTZ (100-150 µgL-1) in locations directly receiving wastewater discharges. A significant correlation was found between the occurrences of NOR and Al (r2 = 0.65; p = 0.01), and CTZ and K (r2 = 0.50; p = 0.01) and Mg (r2 = 0.50; p = 0.01). A high-level ecological risk [risk quotient (RQ) > 1] was observed for algae from all the pharmaceuticals. A medium-level risk (RQ = 0.01-0.1) was observed for Daphnia from CIP, NOR and ECP, and a high-level risk from CTZ. A low-level risk was observed for fishes from CIP and NOR, whereas CTZ and ECP posed a high-level risk to fishes. The overall risk to ecological receptors was in the order: CTZ > CIP > ECP > NOR. Samples from the river locations receiving water from municipal drains or situated near landfill and pharmaceutical factories exhibited RQ > 1 for all pharmaceuticals. The average hazard quotient (HQ) values for the compounds followed the order: CTZ (0.18) > ECP (0.15) > NOR (0.001) > CIP (0.0003) for children (0-6 years); ECP (0.49) > CTZ (0.29) > NOR (0.005) > CIP (0.001) for children (7-17 years), and ECP (0.34) > CTZ (0.21) > NOR (0.007) > CIP (0.001) for adults (>17 years). The calculated risk values did not readily confirm the status of water as safe or unsafe because the values of predicted no-effect concentration (PNEC) would depend on various other environmental factors such as quality of the toxicity data, and species sensitivity and distribution, which warrants further research.