Background
As the rate of crime is constantly increasing, the workload on the forensic analyst also piles up. The availability of a limited number of seized samples makes it crucial to directly ...analyze the sample, thereby preventing wastage in the prior steps of sample preparation. Due to such needs, the forensic community is consistently working on broadening the usage of direct analysis in real-time mass spectrometry (DART-MS). DART-MS is a relatively new technique for rapid mass spectral analysis. Its use for chemical analysis credits its ability to analyze the sample at atmospheric pressure.
Main body
This article gives insight into the ionization mechanisms, data analysis tools, and the use of hyphenated techniques like thermal-desorption-DART-MS, infrared-thermal-desorption-DART-MS, Joule-heating thermal-desorption-DART-MS, etc. This review summarizes the applications of DART-MS in the field of Forensic Science reported from 2005 to 2021. The applications include analysis of drugs, warfare agents, gun-shot residues, ink differentiation, and other forensically relevant samples. The paper also presents the relation between the type of DART-MS technique and the ionization mode used for a particular class of compounds.
Conclusion
The review follows that the high-resolution mass-spectrometers or low-resolution mass-spectrometers systems in the positive or negative mode were highly dependent on the type of analyte under investigation. Drugs, inks, dyes, and paints were mainly analyzed using the positive ionization mode in the HRMS technique. The examinations of fire accelerants predominantly used the positive ionization mode in the LRMS technique. Moreover, the limit of detection values obtained from the qualitative screening of street drugs were of ppb level, indicating high sensitivity of DART-MS. Considering the work done in the past years, there are potential future research needs of this technology, especially in forensic science.
Graphical Abstract
Introduction: The Dynamic Neuromuscular Stabilisation (DNS) technique uses feed forward feedback to involuntarily activate the diaphragm and deep abdominal muscles prior to purposeful movement in ...humans. It is an efficient approach for facilitating deep core muscle activation of the underactive muscle chain consisting of the Internal Oblique (IO), transverse abdominals and diaphragm, thereby enhancing age appropriate jumping, walking and standing, in participants with Spastic Diplegic Cerebral Palsy (SDCP), whereas the primary goal of Neurodevelopmental Therapy (NDT) is to facilitate more normal movement patterns for performing performance skills and rectifying abnormal postural tone. Need of the study: Even though studies have been done in the past, utilising DNS and NDT in children with diplegic CP, for improving core stability, balance, posture and diaphragmatic movement; however, Gross Motor Function (GMF) and trunk control are the aspects that have not been aimed with DNS. There is scarcity in the literature related to impact of DNS on GMF and trunk control in children with diplegic CP. As DNS has specific role on core strength it can be a valuable in the management of trunk control. Because no study comparing the impact of DNS and NDT on trunk control and functions of gross motor in diplegic children has been found; there is a strong need to perform a study to evaluate the same. Aim: To compare the impact of DNS to NDT on gross motor performance and trunk control in children with SDCP. Materials and Methods: It will be a Randomised Clinical Trial (RCT) with the assessor blinded, conducted in the Outpatient Department of Physiotherapy, AVBRH Sawangi, Meghe, Wardha, Maharashtra, India, from July 2022 to April 2023. Following the baseline assessments, children with SDCP (n=36) will be enlisted and randomly assigned into two groups, groups A and group B. Group A will be treated using conventional therapy along with NDT; group B will be given conventional therapy as well as DNS. Treatment will be given for four weeks, five days a week. On the first and the last day of the intervention, primary outcome measures Gross Motor Function Measure-88 (GMFM-88), Trunk Impairment Scale (TIS) and secondary outcome measure Modified Ashworth Scale (MAS) will be employed (on the first day and after the completion of four weeks). Mini-mental Scale Examination (MMSE) will be used as inclusion criteria for the children. Statistical analysis will be carried out using Statistical Package for the Social Sciences (SPSS) software version 27.0. Conclusion: The present study is expected to prove that DNS approach to be successful in enhancing the control of the trunk and gross motor abilities in children with SDCP.
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor survival rates and frequently carries oncogenic KRAS mutation. However, KRAS has thus far not been a viable therapeutic ...target. We found that the abundance of YAP mRNA, which encodes Yes-associated protein (YAP), a protein regulated by the Hippo pathway during tissue development and homeostasis, was increased in human PDAC tissue compared with that in normal pancreatic epithelia. In genetically engineered Kras(G12D) and Kras(G12D):Trp53(R172H) mouse models, pancreas-specific deletion of Yap halted the progression of early neoplastic lesions to PDAC without affecting normal pancreatic development and endocrine function. Although Yap was dispensable for acinar to ductal metaplasia (ADM), an initial step in the progression to PDAC, Yap was critically required for the proliferation of mutant Kras or Kras:Trp53 neoplastic pancreatic ductal cells in culture and for their growth and progression to invasive PDAC in mice. Yap functioned as a critical transcriptional switch downstream of the oncogenic KRAS-mitogen-activated protein kinase (MAPK) pathway, promoting the expression of genes encoding secretory factors that cumulatively sustained neoplastic proliferation, a tumorigenic stromal response in the tumor microenvironment, and PDAC progression in Kras and Kras:Trp53 mutant pancreas tissue. Together, our findings identified Yap as a critical oncogenic KRAS effector and a promising therapeutic target for PDAC and possibly other types of KRAS-mutant cancers.
Abstract Objective Nitric oxide (NO) is one of the most important signaling molecules produced within the body. Continuous generation of NO is essential for the integrity of the cardiovascular ...system. The aim of this study was to assess whether oral intake of a nitrate (NO3 ˉ)-rich dietary supplement (amaranth extract) is able to increase NO3 ˉ and nitrite (NO2 ˉ) levels in blood plasma and saliva of healthy adults. Methods In the present study, bioavailability and pharmacokinetics of NO3 ˉ and NO2 ˉ from amaranth extract (2 g as single dose) was studied in 16 healthy individuals and compared with placebo in a crossover design. The NO3 ˉ and NO2 ˉ levels in plasma as well as saliva were measured up to 24 h. Results After administration of amaranth extract, the NO3 ˉ levels in plasma as well as saliva were found to be significantly ( P < 0.001) higher than in the placebo group. The NO2 ˉ level in plasma was slightly higher ( P < 0.05) in the amaranth group (test group) compared with that in the placebo group, whereas the saliva NO2 ˉ level was significantly high ( P < 0.001) in the amaranth extract–treated group than the placebo group. Conclusions These results clearly indicate that a single oral dose of amaranth extract is able to increase the NO3 ˉ and NO2 ˉ levels in the body for at least 8 h. The increase in NO3 ˉ and NO2 ˉ levels can help to improve the overall performance of people involved in vigorous physical activities or sports.
Respiratory allergy triggered by pollen allergens is increasing at an alarming rate worldwide. Sunflower pollen is thought to be an important source of inhalant allergens. Present study aims to ...identify the prevalence of sunflower pollinosis among the Indian allergic population and characterizes the pollen allergens using immuno-proteomic tools.
Clinico-immunological tests were performed to understand the prevalence of sensitivity towards sunflower pollen among the atopic population. Sera from selected sunflower positive patients were used as probe to detect the IgE-reactive proteins from the one and two dimensional electrophoretic separated proteome of sunflower pollen. The antigenic nature of the sugar moiety of the glycoallergens was studied by meta-periodate modification of IgE-immunoblot. Finally, these allergens were identified by mass-spectrometry.
Prevalence of sunflower pollen sensitization was observed among 21% of the pollen allergic population and associated with elevated level of specific IgE and histamine in the sera of these patients. Immunoscreening of sunflower pollen proteome with patient sera detected seven IgE-reactive proteins with varying molecular weight and pI. Hierarchical clustering of 2D-immunoblot data highlighted three allergens characterized by a more frequent immuno-reactivity and increased levels of IgE antibodies in the sera of susceptible patients. These allergens were considered as the major allergens of sunflower pollen and were found to have their glycan moiety critical for inducing IgE response. Homology driven search of MS/MS data of these IgE-reactive proteins identified seven previously unreported allergens from sunflower pollen. Three major allergenic proteins were identified as two pectate lyases and a cysteine protease.
Novelty of the present report is the identification of a panel of seven sunflower pollen allergens for the first time at immuno-biochemical and proteomic level, which substantiated the clinical evidence of sunflower allergy. Further purification and recombinant expression of these allergens will improve component-resolved diagnosis and therapy of pollen allergy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Protein profile was analyzed by 1D and 2D gel electrophoresis, followed by immunoblotting with 15 individual sensitized patients' sera and identification by mass spectrometry using MALDI-TOF/TOF. ...Results Histamine release, specific IgE, and skin sensitivity were found in higher amount in susceptible patients. 2D immunoblot revealed sixteen IgE reactive spots which were identified by MALDI-TOF/TOF.
Covalent attachment of a synthetic triantennary N-acetylagalactosamine (GalNAc) ligand to chemically modified siRNA has enabled asialoglycoprotein (ASGPR)-mediated targeted delivery of ...therapeutically active siRNAs to hepatocytes in vivo. This approach has become transformative for the delivery of RNAi therapeutics as well as other classes of investigational oligonucleotide therapeutics to the liver. For efficient functional delivery of intact drug into the desired subcellular compartment, however, it is critical that the nucleic acids are stabilized against nucleolytic degradation. Here, we compared two siRNAs of the same sequence but with different modification pattern resulting in different degrees of protection against nuclease activity. In vitro stability studies in different biological matrices show that 5'-exonuclease is the most prevalent nuclease activity in endo-lysosomal compartments and that additional stabilization in the 5'-regions of both siRNA strands significantly enhances the overall metabolic stability of GalNAc-siRNA conjugates. In good agreement with in vitro findings, the enhanced stability translated into substantially improved liver exposure, gene silencing efficacy and duration of effect in mice. Follow-up studies with a second set of conjugates targeting a different transcript confirmed the previous results, provided additional insights into kinetics of RISC loading and demonstrated excellent translation to non-human primates.
Airborne fungal spores are well documented to trigger respiratory allergy. The present study provides baseline information on the quantitative and qualitative aspects of aerospores for the first time ...in a typical urban area of Kolkata metropolis, India. An aeromonitoring was performed by Burkard volumetric 7-day sampler for two consecutive years (August 2012–July 2014). Total concentration, seasonal variations and intradiurnal periodicities of fungal spores were estimated. Spearman’s rank correlation analysis was performed using various weather parameters. The prevalence of fungal spore allergy was investigated among patients reporting to the Department of Allergy and Asthma, Mediland Diagnostics, Kolkata. A retrospective review of patients was conducted with a standard questionnaire and performing skin prick test with 20 fungal extracts. Thirty-eight fungal genera were identified with the highest spore concentration in August. Relative humidity and rainfall were found to be positively correlated with spore concentration. A comparatively higher frequency of sufferers was observed for males and 15–35-year age group. Patients with an atopic family history and insidious onset of symptoms were prone to suffer more, and bronchial asthma was diagnosed in most. Out of 742 patients, 592 patients noticed to have positive skin reactivity toward one or more fungal extracts.
Aspergillus fumigatus
followed by
Curvularia pallescens
and
Fusarium lateritium
elicited maximum sensitization. Each of these genera also represented a considerable fraction of the total aeromycota, thereby indicating potential risk to the sensitized individuals. Further serological analysis along with the identification of fungal allergens would pave the way of immunotherapy.
It has been established that regulation of chromatin structure through post-translational modification of histone proteins, primarily histone H3 phosphorylation and acetylation, is an important early ...step in the induction of synaptic plasticity and formation of long-term memory. In this study, we investigated the contribution of another histone modification, histone methylation, to memory formation in the adult hippocampus. We found that trimethylation of histone H3 at lysine 4 (H3K4), an active mark for transcription, is upregulated in hippocampus 1 h following contextual fear conditioning. In addition, we found that dimethylation of histone H3 at lysine 9 (H3K9), a molecular mark associated with transcriptional silencing, is increased 1 h after fear conditioning and decreased 24 h after context exposure alone and contextual fear conditioning. Trimethylated H3K4 levels returned to baseline levels at 24 h. We also found that mice deficient in the H3K4-specific histone methyltransferase, Mll, displayed deficits in contextual fear conditioning relative to wild-type animals. This suggests that histone methylation is required for proper long-term consolidation of contextual fear memories. Interestingly, inhibition of histone deacetylases (HDACs) with sodium butyrate (NaB) resulted in increased H3K4 trimethylation and decreased H3K9 dimethylation in hippocampus following contextual fear conditioning. Correspondingly, we found that fear learning triggered increases in H3K4 trimethylation at specific gene promoter regions (Zif268 and bdnf) with altered DNA methylation and MeCP2 DNA binding. Zif268 DNA methylation levels returned to baseline at 24 h. Together, these data demonstrate that histone methylation is actively regulated in the hippocampus and facilitates long-term memory formation.
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