Inteins are mobile genetic elements that apply standard enzymatic strategies to excise themselves post-translationally from the precursor protein via protein splicing. Since their discovery in the 1990s, recent advances in intein technology allow for them to be implemented as a modern biotechnological contrivance. Radical improvement in the structure and catalytic framework of cis- and trans-splicing inteins devised the development of engineered inteins that contribute to various efficient downstream techniques. Previous literature indicates that implementation of intein-mediated splicing has been extended to in vivo systems. Besides, the homing endonuclease domain also acts as a versatile biotechnological tool involving genetic manipulation and control of monogenic diseases. This review orients the understanding of inteins by sequentially studying the distribution and evolution pattern of intein, thereby highlighting a role in genetic mobility. Further, we include an in-depth summary of specific applications branching from protein purification using self-cleaving tags to protein modification, post-translational processing and labelling, followed by the development of intein-based biosensors. These engineered inteins offer a disruptive approach towards research avenues like biomaterial construction, metabolic engineering and synthetic biology. Therefore, this linear perspective allows for a more comprehensive understanding of intein function and its diverse applications.
Inteins are auto-processing domains that implement a multi-step biochemical reaction termed protein splicing, marked by cleavage and formation of peptide bonds. They excise from a precursor protein, generating a functional protein via covalent bonding of flanking exteins. We report the kinetic study of splicing and cleavage reaction in a [Fe-S] cluster assembly protein SufB from Mycobacterium tuberculosis. Although it follows a canonical intein splicing pathway, distinct features are added by extein residues present in the active site. Sequence analysis identified two conserved histidines in the N-extein region; His-5 and His-38. Kinetic analyses of His-5Ala and His-38Ala SufB mutants exhibited significant reductions in splicing and cleavage rates relative to the SufB wild-type precursor protein. Structural analysis and molecular dynamics simulations suggested that Mtu SufB displays a unique mechanism where two remote histidines work concurrently to facilitate N- cleavage reaction. His-5, which is exposed outside, because of the random push of water molecules forces His-38 towards the N-cleavage site. Thus, His-5 stabilizes the position of His-38 which in turn activates N-S acyl shift via direct interaction with catalytic Cys1. Understanding intein~extein partnership in an essential mycobacterial protein may diversify into intein-based applied research along with the development of pathogen-specific novel antimicrobials.
A Pilot study was Carried out to study the association of consanguinity marriage with depression. It was observed that the consanguinity of marriage was associated with depression. The odds ratio was 5.66 (CI: 2.42-13.54). The age and sex had an association with depression. The age and sex adjusted odds ratio of consanguinity marriage was 7.66 (CI: 3.93-19.45) indicating that it is independently associated with depression.
COVID-19 remains a matter of global public health concern. Previous research suggested the association between local environmental factors and viral transmission. We present a multivariate observational analysis of SARS-CoV-2 transmission in the state of Odisha, India, hinting at a seasonal activity. We aim to investigate the demographic characteristics of COVID-19 in the Indian state of Odisha for two specific timelines in 2020 and 2021. For a comparative outlook, we chose similar datasets from the state of New York, USA. Further, we present a critical analysis pertaining to the effects of environmental factors and the emergence of variants on SARS-CoV-2 transmission and persistence. We assessed the datasets for confirmed cases, death, age, and gender for 29 February 2020 to 31 May 2020, and 1 March 2021 to 31 May 2021. We determined the case fatalities, crude death rates, sex ratio, and incidence rates for both states along with monthly average temperature analysis. A yearlong epi-curve analysis was conducted to depict the coronavirus infection spread pattern in the respective states. The Indian state of Odisha reported a massive 436,455 confirmed cases and 875 deaths during the 2021 timeline as compared to a mere 2223 cases and 7 deaths during the 2020 timeline. We further discuss the demographic and temperature association of SARS-CoV-2 transmission during early 2020 and additionally comment on the variant-associated massive rise in cases during 2021. Along with the rapid rise of variants, the high population density and population behavior seem to be leading causes for the 2021 pandemic, whereas factors such as age group, gender, and average local temperature were prominent during the 2020 spread. A seasonal occurrence of SARS-CoV-2 transmission is also observed from the yearlong epidemiological plot. The recent second wave of COVID-19 is a lesson that emphasizes the significance of continuous epidemiological surveillance to predict the relative risk of viral transmission for a specific region.
Background and Aim:
The COVID pandemic necessitated the use of masks to reduce the propagation of coronavirus by airborne transmission. This research was conducted in healthy volunteers to assess the changes in noninvasive measurable physiological variables over 45 min at rest.
Methods:
This was a prospective randomized controlled crossover trial. Twenty-one healthy volunteers were monitored for pulse rate (PR), peripheral oxygen saturation (SpO
2
), systolic blood pressure (SBP), diastolic blood pressure (DBP), respiratory rate (RR), inspired carbon dioxide and expired carbon dioxide (ECO
2
), inspired (FiO
2
) and expired oxygen (FeO
2
), every 15 min for 45 minute (min) with N95 respirator, N95 respirator with surgical mask (SM), N95 with SM and visor (V), SM with N95, and N95 respirator with visor.
Results:
Repeated measures analysis of variance (ANOVA) of PR, RR, SpO
2
, SBP, and DBP over time within the group and intragroup was calculated and found statistically insignificant.
P
value for comparison of mean value within the group was calculated by paired
t
-test with Bonferroni correction. There was a significant rise in ECO
2
in the N95 group over time, and repeated measures ANOVA showed
P
= 0.04 at 30 min between the N95 + V group and the N95 + SM + V group. Inspired CO
2
was statistically significant over time in the N95 + SM + V with
P
= 0.02.
Conclusion:
N95 alone or in combination with a SM and visor does not cause any clinically significant measurable physiological derangements. The inspired CO
2
may be implicated in the symptoms manifested by individuals.
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