DMPPred: a tool for identification of antigenic regions responsible for inducing type 1 diabetes mellitus.

There are a number of antigens that induce autoimmune response against ß-cells, leading to type 1 diabetes mellitus (T1DM). Recently, several antigen-specific immunotherapies have been developed to treat T1DM. Thus, identification of T1DM associated peptides with antigenic regions or epitopes is important for peptide based-therapeutics (e.g. immunotherapeutic). In this study, for the first time, an attempt has been made to develop a method for predicting, designing, and scanning of T1DM associated peptides with high precision. We analysed 815 T1DM associated peptides and observed that these peptides are not associated with a specific class of HLA alleles. Thus, HLA binder prediction methods are not suitable for predicting T1DM associated peptides. First, we developed a similarity/alignment based method using Basic Local Alignment Search Tool and achieved a high probability of correct hits with poor coverage. Second, we developed an alignment-free method using machine learning techniques and got a maximum AUROC of 0.89 using dipeptide composition. Finally, we developed a hybrid method that combines the strength of both alignment free and alignment-based methods and achieves maximum area under the receiver operating characteristic of 0.95 with Matthew's correlation coefficient of 0.81 on an independent dataset. We developed a web server 'DMPPred' and stand-alone server for predicting, designing and scanning T1DM associated peptides (https://webs.iiitd.edu.in/raghava/dmppred/).

The heparin-binding hemagglutinin protein of Mycobacterium tuberculosis is a nucleoid-associated protein.

Nucleoid-associated proteins (NAPs) regulate multiple cellular processes such as gene expression, virulence, and dormancy throughout bacterial species. NAPs help in the survival and adaptation of Mycobacterium tuberculosis (Mtb) within the host. Fourteen NAPs have been identified in Escherichia coli; however, only seven NAPs are documented in Mtb. Given its complex lifestyle, it is reasonable to assume that Mtb would encode for more NAPs. Using bioinformatics tools and biochemical experiments, we have identified the heparin-binding hemagglutinin (HbhA) protein of Mtb as a novel sequence-independent DNA-binding protein which has previously been characterized as an adhesion molecule required for extrapulmonary dissemination. Deleting the carboxy-terminal domain of HbhA resulted in a complete loss of its DNA-binding activity. Atomic force microscopy showed HbhA-mediated architectural modulations in the DNA, which may play a regulatory role in transcription and genome organization. Our results showed that HbhA colocalizes with the nucleoid region of Mtb. Transcriptomics analyses of a hbhA KO strain revealed that it regulates the expression of ∼36% of total and ∼29% of essential genes. Deletion of hbhA resulted in the upregulation of ∼73% of all differentially expressed genes, belonging to multiple pathways suggesting it to be a global repressor. The results show that HbhA is a nonessential NAP regulating gene expression globally and acting as a plausible transcriptional repressor.

Role of serine/threonine protein phosphatase PrpN in the life cycle of Bacillus anthracis.

Reversible protein phosphorylation at serine/threonine residues is one of the most common protein modifications, widely observed in all kingdoms of life. The catalysts controlling this modification are specific serine/threonine kinases and phosphatases that modulate various cellular pathways ranging from growth to cellular death. Genome sequencing and various omics studies have led to the identification of numerous serine/threonine kinases and cognate phosphatases, yet the physiological relevance of many of these proteins remain enigmatic. In Bacillus anthracis, only one ser/thr phosphatase, PrpC, has been functionally characterized; it was reported to be non-essential for bacterial growth and survival. In the present study, we characterized another ser/thr phosphatase (PrpN) of B. anthracis by various structural and functional approaches. To examine its physiological relevance in B. anthracis, a null mutant strain of prpN was generated and shown to have defects in sporulation and reduced synthesis of toxins (PA and LF) and the toxin activator protein AtxA. We also identified CodY, a global transcriptional regulator, as a target of PrpN and ser/thr kinase PrkC. CodY phosphorylation strongly controlled its binding to the promoter region of atxA, as shown using phosphomimetic and phosphoablative mutants. In nutshell, the present study reports phosphorylation-mediated regulation of CodY activity in the context of anthrax toxin synthesis in B. anthracis by a previously uncharacterized ser/thr protein phosphatase-PrpN.

Design of Highly Selective Zn-Coordinated Polyampholyte for Cancer Treatment and Inhibition of Tumor Metastasis.

Developing anticancer agents with negligible cytotoxicity against normal cells while mitigating multidrug resistance and metastasis is challenging. Previously reported cationic polymers have effectively eradicated cancers but are clinically unsuitable due to their limited selectivity. Herein, a series of poly(l-lysine)- and nicotinic acid-based polymers were synthesized using varying amounts of dodecylsuccinic anhydride. Zn-coordinating polymers concealed their cationic charge and enhanced selectivity. These Zn-bound polymers were highly effective against liver and colon cancer cells (HepG2 and Colon 26, respectively) and prevented cancer cell migration. They also displayed potent anticancer activity against drug-resistant cell lines (COR-L23/R): their cationic structure facilitated cancer cell membrane disruption. Compared to these polymers, doxorubicin was less selective and less efficacious against drug-resistant cell lines and was unable to prevent cell migration. These polymers are potential cancer treatment agents, offering a promising solution for mitigating drug resistance and tumor metastasis and representing a novel approach to designing cancer therapeutics.

Quercetin in semen extenders curtails reactive oxygen and nitrogen species and improves functional attributes of cryopreserved buck semen.

Cryopreservation of goat spermatozoa is challenging due to several factors, including one of the most essential, i.e., oxidative stress. It is particularly essential in goat semen due to its scanty ejaculate volume and high sperm concentration. This leaves a narrow sperm-to-seminal plasma ratio owing to marginal antioxidant support; moreover, semen extension further dilutes the antioxidant level, leading to an imbalance of oxidant-antioxidant equilibrium. The present study aimed to evaluate the effect of quercetin on curtailing oxidative stress and its reflection on the post-thaw survivability and membrane integrity of goat spermatozoa. For this study, six bucks were selected. Six ejaculates from each buck totaling 36 ejaculates were collected, which were then split into five parts; furthermore, each part was added with a semen extender having a particular concentration of additive. Group C without quercetin and T1 containing Vit E at 3 mmol/mL were considered the control and positive control respectively, whereas T2, T3, and T4 contain 10, 20, and 30 µmol/mL of Quercetin respectively. The final sperm concentration of each group was kept at 200×106 spermatozoa/mL. All groups were subjected to equilibration at 4 °C for 4 hours, then filled in French mini (0.25 mL) straws, followed by sealing and cryopreservation. Samples after 72 hours of cryopreservation were subjected to evaluation of plasma membrane integrity and viability through staining, acrosomal integrity, and mitochondrial membrane activity through flowcytometry. Evaluation of sperm kinematics as well as the oxidant-antioxidant status of sperm (ROS and nitric oxide) and seminal plasma (SOD, CAT, GPx, FRAP, and lipid peroxidation through MDA estimation) were also carried out. Quercetin, when supplemented at 20 µmol/mL in buck semen extender, significantly (p<0.01) improved cryopreserved sperm functions in terms of plasma membrane integrity, viability, acrosomal integrity, mitochondrial membrane activity, and sperm kinematics of buck semen. Similarly, Quercetin supplementation at 20 µmol/mL significantly reduced reactive oxygen and nitrogen species (RONS) in sperm and improved the antioxidant status of seminal plasma, which was indicated by reduced oxidative damage and improved the antioxidant status of buck semen. In conclusion, Quercetin at 20 µmol/mL reduced oxidative stress, improved semen antioxidant status, and improved sperm membrane integrity and kinematics.

Robust Reconstruction of the Void Fraction from Noisy Magnetic Flux Density Using Invertible Neural Networks.

Electrolysis stands as a pivotal method for environmentally sustainable hydrogen production. However, the formation of gas bubbles during the electrolysis process poses significant challenges by impeding the electrochemical reactions, diminishing cell efficiency, and dramatically increasing energy consumption. Furthermore, the inherent difficulty in detecting these bubbles arises from the non-transparency of the wall of electrolysis cells. Additionally, these gas bubbles induce alterations in the conductivity of the electrolyte, leading to corresponding fluctuations in the magnetic flux density outside of the electrolysis cell, which can be measured by externally placed magnetic sensors. By solving the inverse problem of the Biot-Savart Law, we can estimate the conductivity distribution as well as the void fraction within the cell. In this work, we study different approaches to solve the inverse problem including Invertible Neural Networks (INNs) and Tikhonov regularization. Our experiments demonstrate that INNs are much more robust to solving the inverse problem than Tikhonov regularization when the level of noise in the magnetic flux density measurements is not known or changes over space and time.

Deciphering pressure-induced nanoarchitectonics in a monolayer of heterocoronene-based discotics at air-water and air-solid interfaces.

Understanding and control of molecular alignment at the nanoscale in self-assembled supramolecular structures is a prerequisite for the subsequent exploitation of molecules in functional devices. Here, we have clarified the surface-pressure induced molecular nanoarchitectures in a monolayer of a heterocoronene-based discotic liquid crystal (DLC) at air-water and air-solid interfaces using surface manometry, real-time Brewster angle microscopy, and real-space atomic force microscopy (AFM). Chloroform-spread DLCs at a concentration of ∼108 µM exhibit floating domains at the air-water interface comprising small aggregates of edge-on stacked molecules interacting via peripheral alkyl chains. Detailed analysis of surface manometry and relaxation measurements reveal that, upon compression, these domains coalesce to form a coherent monolayer which then undergoes irreversible structural transformations via mechanisms such as monolayer loss due to desorption and localized nucleation of defects. AFM images of the films transferred on a hydrophilic substrate reveal that with increasing surface-pressure, the nanoscale structure of the monolayer transforms from randomly oriented nanowires to tightly-packed nanowire domains, and finally to fragmented wire segments which diffuse locally above the film. These results provide a facile method for the preparation of compact, two-dimensional films of ambipolar DLC molecules with a tunable nanoarchitecture which will be crucial for their applications in nanoscale electronic devices.

Ultrasound appearance of regenerative peripheral nerve interface with clinical correlation.

OBJECTIVE: To describe the ultrasound (US) appearance of regenerative peripheral nerve interfaces (RPNIs) in humans, and correlate clinically and with histologic findings from rat RPNI. MATERIALS AND METHODS: Patients (≥ 18 years) who had undergone RPNI surgery within our institution between the dates of 3/2018 and 9/2019 were reviewed. A total of 21 patients (15 male, 6 female, age 21-82 years) with technically adequate US studies of RPNIs were reviewed. Clinical notes were reviewed for the presence of persistent pain after RPNI surgery. Histologic specimens of RPNIs in a rat model from prior studies were compared with the US findings noted in this study. RESULTS: There was a variable appearance to the RPNIs including focal changes involving the distal nerve, nerve-muscle graft junction, and area of the distal sutures. The muscle grafts varied in thickness with accompanying variable echogenic changes. No interval change was noted on follow-up US studies. Diffuse hypoechoic swelling with loss of the fascicular structure of the nerve within the RPNI and focal hypoechoic changes at the nerve-muscle graft junction were associated with clinical outcomes. US findings corresponded to histologic findings in the rat RPNI. CONCLUSION: Ultrasound imaging can demonstrate various morphologic changes involving the nerve, muscle, and interface between these two biological components of RPNIs. These changes correspond to expected degenerative and regenerative processes following nerve resection and muscle reinnervation and should not be misconstrued as pathologic in all cases. N5 and N1 morphologic type changes of the RPNI were found to be associated with symptoms.

Artificial intelligence-based prediction of lycopene content in raw tomatoes using physicochemical attributes.

INTRODUCTION: Lycopene consumption reduces risk and incidence of cancer and cardiovascular diseases. Tomatoes are a rich source of phytochemical compounds including lycopene as a major constituent. Lycopene estimation using high-performance liquid chromatography is time-consuming and expensive. OBJECTIVE: To develop artificial intelligence models for prediction of lycopene in raw tomatoes using 14 different physicochemical parameters including salinity, total dissolved solids (TDS), electrical conductivity (EC), firmness, pH, total soluble solids (TSS), titratable acidity (TA), colour values on Hunter scale (L, a, b), total phenolic content (TPC), total flavonoid content (TFC) and antioxidant activity (AOA). MATERIAL AND METHODS: The post-harvest data acquisition was collected through investigation for more than 100 raw tomatoes stored for 15 days. Linear multivariate regression (LMVR), principal component regression (PCR) and partial least squares regression (PLSR) models were developed by splitting data set into train and test datasets. The training of models was performed using 10-fold cross validation (CV). RESULTS: Principal component analysis showed strong positive association between lycopene, colour value 'a', TPC, TFC and AOA. The R2 (CV), root mean square error (RMSE) (CV) and RMSE (Test) for best LMVR model was observed to be at 0.70, 8.48 and 9.69 respectively. The PCR model revealed R2 (CV) at 0.59, RMSE (CV) at 8.91 and RMSE (Test) at 10.17 while PLSR model revealed R2 (CV) at 0.60, RMSE (CV) at 9.10 and RMSE (Test) at 10.11. CONCLUSION: Results of the present study show that epidemiological studies suggest fully ripened tomatoes are most beneficial for consumption to ensure recommended daily intake of lycopene content.

Rice husk biochar - A novel engineered bio-based material for transforming groundwater-mediated fluoride cycling in natural environments.

Biochar, a promising carbon-rich and carbon-negative material, can control water pollution, harness the synergy of sustainable development goals, and achieve circular economy. This study examined the performance feasibility of treating fluoride-contaminated surface and groundwater using raw and modified biochar synthesized from agricultural waste rice husk as problem-fixing renewable carbon-neutral material. Physicochemical characterizations of raw/modified biochars were investigated using FESEM-EDAX, FTIR, XRD, BET, CHSN, VSM, pHpzc, Zeta potential, and particle size analysis were analyzed to identify the surface morphology, functional groups, structural, and electrokinetic behavior. In fluoride (F-) cycling, performance feasibility was tested at various governing factors, contact time (0-120 min), initial F- levels (10-50 mg L-1), biochar dose (0.1-0.5 g L-1), pH (2-9), salt strengths (0-50 mM), temperatures (301-328 K), and various co-occurring ions. Results revealed that activated magnetic biochar (AMB) possessed higher adsorption capacity than raw biochar (RB) and activated biochar (AB) at pH 7. The results indicated that maximum F- removal (98.13%) was achieved using AMB at pH 7 for 10 mg L-1. Electrostatic attraction, ion exchange, pore fillings, and surface complexation govern F- removal mechanisms. Pseudo-second-order and Freundlich were the best fit kinetic and isotherm for F- sorption, respectively. Increased biochar dose drives an increase in active sites due to F- level gradient and mass transfer between biochar-fluoride interactions, which reported maximum mass transfer for AMB than RB and AB. Fluoride adsorption using AMB could be described through chemisorption processes at room temperature (301 K), though endothermic sorption follows the physisorption process. Fluoride removal efficiency reduced, from 67.70% to 53.23%, with increased salt concentrations from 0 to 50 mM NaCl solutions, respectively, due to increased hydrodynamic diameter. Biochar was used to treat natural fluoride-contaminated surface and groundwater in real-world problem-solving measures, showed removal efficiency of 91.20% and 95.61%, respectively, for 10 mg L-1 F- contamination, and has been performed multiple times after systematic adsorption-desorption experiments. Lastly, techno-economic analysis was analyzed for biochar synthesis and F- treatment performance costs. Overall, our results revealed worth output and concluded with recommendations for future research on F- adsorption using biochar.

Salinity responses and tolerance mechanisms in underground vegetable crops: an integrative review.

MAIN CONCLUSION: The present review gives an insight into the salinity stress tolerance responses and mechanisms of underground vegetable crops. Phytoprotectants, agronomic practices, biofertilizers, and modern biotechnological approaches are crucial for salinity stress management. Underground vegetables are the source of healthy carbohydrates, resistant starch, antioxidants, vitamins, mineral, and nutrients which benefit human health. Soil salinity is a serious threat to agriculture that severely affects the growth, development, and productivity of underground vegetable crops. Salt stress induces several morphological, anatomical, physiological, and biochemical changes in crop plants which include reduction in plant height, leaf area, and biomass. Also, salinity stress impedes the growth of the underground organs, which ultimately reduces crop yield. Moreover, salt stress is detrimental to photosynthesis, membrane integrity, nutrient balance, and leaf water content. Salt tolerance mechanisms involve a complex interplay of several genes, transcription factors, and proteins that are involved in the salinity tolerance mechanism in underground crops. Besides, a coordinated interaction between several phytoprotectants, phytohormones, antioxidants, and microbes is needed. So far, a comprehensive review of salinity tolerance responses and mechanisms in underground vegetables is not available. This review aims to provide a comprehensive view of salt stress effects on underground vegetable crops at different levels of biological organization and discuss the underlying salt tolerance mechanisms. Also, the role of multi-omics in dissecting gene and protein regulatory networks involved in salt tolerance mechanisms is highlighted, which can potentially help in breeding salt-tolerant underground vegetable crops.

Financial Toxicity in Breast Reconstruction: A National Survey of Women Who have Undergone Breast Reconstruction After Mastectomy.

BACKGROUND: Despite awareness regarding financial toxicity in breast cancer care, little is known about the financial strain associated with breast reconstruction. This study aims to describe financial toxicity and identify factors independently associated with financial toxicity for women pursuing post-mastectomy breast reconstruction. METHODS: A 33-item electronic survey was distributed to members of the Love Research Army. Women over 18 years of age and at least 1 year after post-mastectomy breast reconstruction were invited to participate. The primary outcome of interest was self-reported financial toxicity due to breast reconstruction, while secondary outcomes of interest were patient-reported out-of-pocket expenses and impact of financial toxicity on surgical decision making. RESULTS: In total, 922 women were included (mean age 58.6 years, standard deviation 10.3 years); 216 women (23.8%) reported financial toxicity from reconstruction. These women had significantly greater out-of-pocket medical expenses. When compared with women who did not experience financial toxicity, those who did were more likely to have debt due to reconstruction (50.9% vs. 3.2%, p < 0.001). Younger age, lower annual household income, greater out-of-pocket expenses, and a postoperative major complication were independently associated with an increased risk for financial toxicity. If faced with the same decision, women experiencing financial toxicity were more likely to decide against reconstruction (p < 0.001) compared with women not experiencing financial toxicity. CONCLUSIONS: Nearly one in four women experienced financial toxicity from breast reconstruction. Women who reported higher levels of financial toxicity were more likely to change their decisions about surgery. Identified factors predictive of financial toxicity could guide preoperative discussions to inform decision making that mitigates undesired financial decline.

Design of an Ice Recrystallization-Inhibiting Polyampholyte-Containing Graft Polymer for Inhibition of Protein Aggregation.

Freezing-induced damage to proteins, through osmotic stress and ice recrystallization, during protein processing and long-term storage is a serious concern and may lead to loss of protein activity owing to denaturation. In this study, graft copolymers composed of a cryoprotective polymer (capable of preventing osmotic stress) and poly(vinyl alcohol) (PVA; known for its high ice recrystallization inhibition (IRI) property) were developed. The polymers had high IRI activity, albeit slightly lower than that of PVA alone, but substantially higher than that of succinylated ε-poly-l-lysine (PLLSA) alone. The graft polymers showed an efficiency higher than that of PVA or PLLSA alone in protecting proteins from multiple freeze-thaw cycles, as well as during prolonged freezing, indicating a synergy between PVA and PLLSA. The PLLSA-based graft polymer is a promising material for use in protein biopharmaceutics for the long-term storage of proteins under freezing conditions.

Evaluation of efficacy of antioxidant-enriched sunscreen prodcuts against long wavelength ultraviolet A1 and visible light.

OBJECTIVE: The synergistic effects of VL and long wavelength UVA1 (VL + UVA1, 370-700 nm) on inducing pigmentation and erythema in skin have been demonstrated and linked to exacerbation of dermatologic conditions including melasma and post-inflammatory hyperpigmentation. This study aimed to compare the photoprotection of organic sunscreens enriched with antioxidant (AO) combinations against VL + UVA1 induced biologic effects. The efficacy was compared with that offered by a commercially available tinted sunscreen. METHODS: Ten healthy adult subjects with Fitzpatrick skin phototypes IV-VI were enrolled (nine completed). VL + UVA1 dose of 380 J/cm2 was utilized. Assessment methods were polarized photography, investigator global scoring and diffuse reflectance spectroscopy (DRS). Measurements were obtained at baseline and immediately, 24 h and 7 days after irradiation. RESULTS: Sites treated with tinted sunscreen product had significantly less pigmentation compared with untreated but irradiated skin at all time points. However, DRS results demonstrated that the 5-AO sunscreen performed comparably or better than all sunscreens tested with relatively lower dyschromia, delayed erythema and pigmentation. CONCLUSION: These results highlight the potential of AO-enriched sunscreens to be photoprotective against VL + UVA1. The combination of efficacy and the cosmetic appearance of this product may provide wider acceptability which is crucial considering the limited available means of protection against this waveband.

OBJECTIF: les effets synergiques de la lumière visible (LV) et des rayons ultraviolets long (UVA1) (LV + UVA1, 370 à 700 nm) sur l'induction de la pigmentation et de l'érythème cutané ont été démontrés et liés à l'exacerbation des affections dermatologiques, notamment le mélasma et l'hyperpigmentation post-inflammatoire. Cette étude visait à comparer la photoprotection des écrans solaires organiques enrichis en associations antioxydantes (AO) contre les effets biologiques induits par LV+UVA1. L'efficacité a été comparée à celle offerte par un écran solaire teinté disponible dans le commerce. MÉTHODES: dix sujets adultes en bonne santé présentant des phototypes cutanés de Fitzpatrick IV à VI ont été inclus (neuf ont terminé l'étude). On a utilisé une dose LV+UVA1 de 380 J/cm2. Les méthodes d'évaluation étaient la photographie polarisée, le score global de l'investigateur et la spectroscopie de réflectance diffuse (DRS). Les mesures ont été obtenues immédiatement à l'entrée dans l'étude et, 24 h et 7 jours après l'irradiation. RÉSULTATS: les sites traités avec un produit de protection solaire teinté présentaient une pigmentation significativement inférieure à celle de la peau non traitée mais irradiée, à toutes les heures de mesure. Cependant, les résultats de la DRS ont démontré que l'écran solaire 5-AO fonctionnait de manière comparable ou mieux que tous les écrans solaires testés avec une dyschromie, un érythème retardé et une pigmentation relativement plus faible. CONCLUSION: ces résultats mettent en évidence le potentiel des écrans solaires enrichis en AO comme facteur de photoprotection contre LV+UVA1. La combinaison de l'efficacité et de l'aspect esthétique de ce produit peut permettre une plus grande acceptabilité, ce qui est essentiel compte tenu de la disponibilité limitée des moyens de protection contre cette gamme d'ondes.

Effect of biostimulation on growth rate and reproductive development of Bos indicus dairy heifers.

The present study aimed to compare the growth rate, feeding behavior, reproductive development, and concentrations of GH and leptin in Sahiwal heifers exposed to direct bull contact, bull contact through a fenceline, or isolated from bulls. Overall, 24 heifers were allotted to three treatment groups (n = eight/group) based on birth weight, body weight, and age. Heifers from the non-exposed group (NBE) remained isolated from bulls; heifers stimulated by fenceline bull contact (FBE) remained continuously exposed to bulls through a fenceline, and heifers with direct bull contact (DBE+FBE) had direct contact with a bull during 6 h/day plus continuous fenceline bull exposure for the entire 24 h period. It was considered that heifers attained puberty when progesterone concentration was >1 ng/mL. Biostimulated heifers achieved puberty at both a lower age and body weight (P < 0.05) than NBE heifers. Overall, average daily gain (g/day) was greater in DBE+FBE (516.3 ± 4.5) and FBE (501.6 ± 4.3) than in NBE (441.8 ± 2.9, respectively; P < 0.01). Leptin and growth hormone concentrations were significantly greater in FBE and DBE+FBE than NBE heifers. Both groups of biostimulated heifers devoted more time eating than NBE heifers, P < 0.05). In conclusion, biostimulation of Sahiwal heifers, either by exposing them to bulls through a fenceline or by both fenceline exposure and direct contact, reduced the age of puberty and increased growth performance. Overall, fenceline bull exposure can be recommended as an easy handling management to stimulate reproductive precocity and growth rate in heifers.

Bacillus anthracis chain length, a virulence determinant, is regulated by membrane localized serine/threonine protein kinase PrkC.

Anthrax is a zoonotic disease caused by Bacillus anthracis, a spore-forming pathogen that displays a chaining phenotype. It has been reported that the chaining phenotype acts as a virulence factor in B. anthracis In this study, we identify a serine/threonine protein kinase of B. anthracis, PrkC, the only kinase localized at the bacteria-host interface, as a determinant of B. anthracis chain length. In vitro, prkC disruption strain (BAS ΔprkC) grew as shorter chains throughout the bacterial growth cycle. A comparative analysis between the parent strain and BAS ΔprkC indicated that the levels of proteins, BslO and Sap, associated with the regulation of the bacterial chain length, were upregulated in BAS ΔprkC BslO is a septal murein hydrolase that catalyzes daughter cell separation and Sap is an S-layer structural protein required for the septal localization of BslO. PrkC disruption also has a significant effect on bacterial growth, cell wall thickness, and septa formation. Upregulation of ftsZ in BAS ΔprkC was also observed. Altogether, our results indicate that PrkC is required for maintaining optimum growth, cell wall homeostasis and most importantly - for the maintenance of the chaining phenotype.IMPORTANCEChaining phenotype acts as a virulence factor in Bacillus anthracis This is the first study that identifies a 'signal transduction protein' with an ability to regulate the chaining phenotype in Bacillus anthracis We show that the disruption of the lone surface-localized serine/threonine protein kinase, PrkC, leads to the shortening of the bacterial chains. We report upregulation of the de-chaining proteins in the PrkC disruption strain. Apart from this, we also report for the first time that PrkC disruption results in an attenuated cell growth, a decrease in the cell wall thickness and aberrant cell septa formation during the logarithmic phase of growth - a growth phase where PrkC is expressed maximally.

Dual Blood-Brain Barrier-Glioma Targeting Peptide-Poly(levodopamine) Hybrid Nanoplatforms as Potential Near Infrared Phototheranostic Agents in Glioblastoma.

Combined chemo-phototherapy for boosting the efficacy of individual modalities by synergism for antiglioma treatments is in its embryonic stage and far away from effective clinical translation. Herein, moving a step closer, we recommend a facile stratagem to fabricate smart biocompatible and biodegradable multifunctional nanoplatforms comprising inherently fluorescent poly(levodopamine) nanoparticles (FLs) co-loaded with doxorubicin (DOX) and indocyanine green (ICG). The designed near-infrared (NIR) phototheranostic agents upon NIR laser irradiation helped precipitate combined chemo-phototherapy [both photothermal therapy (PTT) and photodynamic therapy (PDT)] and optical imaging under one roof. Excellent glioma-targeting ability was allocated to the nanoplatforms by conjugating them with a novel chimeric therapeutic peptide with glioma homing and antiglioma dual functionality. Further, DOX/ICG/peptide co-loaded nanoplatforms (FLDIPs) exhibited triggered drug release in response to multiple stimuli. Studies performed in 2D C6 glioma cells and 3D spheroids exhibited superior combined chemo-PDT/PTT effects (∼94% killing in cells and ∼87% in spheroids) of the designed FL based nanoplatforms compared to individual therapeutic components. Herein, the FL based multifunctional nanoplatforms with active targeting ability and stimuli responsive drug release behavior will further help in nullifying chemotherapy based adverse effects and mitigate chemo-resistance by adopting a combinatorial approach.

The Role of Autologous Flap Reconstruction in Patients with Crohn's Disease Undergoing Abdominoperineal Resection.

BACKGROUND: Patients with symptomatic Crohn's disease who undergo abdominoperineal resection can experience impaired postoperative wound healing. This results in significant morbidity, burdensome dressing changes, and increased postoperative pain. When abdominoperineal resection is performed for oncological reasons, autologous flap reconstruction is occasionally performed to optimize wound healing and reconstruction outcomes. However, the role of flap reconstruction after abdominoperineal resection for Crohn's disease has not been established. OBJECTIVE: This study examines the utility of flap reconstruction in patients with symptomatic Crohn's disease undergoing abdominoperineal resection. We hypothesize that patients with immediate flap reconstruction after abdominoperineal resection will demonstrate improved wound healing. DESIGN: This study is a retrospective chart review. SETTINGS: Eligible patients at our institution were identified from 2010 to 2018 by using a combination of Current Procedural Terminology, International Classification of Diseases, Ninth Revision, and International Classification of Diseases, Tenth Revision codes. PATIENTS: Of 40 adult patients diagnosed with Crohn's disease, 20 underwent abdominoperineal resection only and 20 underwent abdominoperineal resection with flap reconstruction. INTERVENTIONS: Immediate autologous flap reconstruction was performed after abdominoperineal resection. MAIN OUTCOME MEASURES: The primary outcomes measured were the presence of postoperative perineal wounds and postoperative wound care burden. RESULTS: Patients in the abdominoperineal resection with flap reconstruction group demonstrated significantly worse preoperative disease traits, including fistula burden, than patients in the abdominoperineal resection only group. A lower number of patients tended to be associated with a persistent perineal wound in the flap group at 30 days (abdominoperineal resection with flap reconstruction = 55% vs abdominoperineal resection only = 70%; p = 0.327) and at 6 months (abdominoperineal resection with flap reconstruction = 25% vs abdominoperineal resection only = 40%; p = 0.311) postoperatively. There was also a trend toward a lower incidence of complications in the flap group. Patients in the abdominoperineal resection with flap reconstruction group tended to experience lower postoperative pain than patients in the abdominoperineal resection only group. LIMITATIONS: This retrospective cohort study was limited by its reliance on data in electronic medical records, and by its small sample size and the fact that it was a single-institution study. CONCLUSIONS: In select patients who have severe perianal fistulizing Crohn's disease, there may be a benefit to immediate flap reconstruction after abdominoperineal resection to lower postoperative wound care burden without significant intraoperative or postoperative risk. In addition, flap reconstruction may lead to lower postoperative pain. See Video Abstract at http://links.lww.com/DCR/B416. EL ROL DE LA RECONSTRUCCIN CON COLGAJO AUTLOGO EN PACIENTES CON ENFERMEDAD DE CROHN SOMETIDOS A RESECCIN ABDOMINOPERINEAL: ANTECEDENTES:Los pacientes con enfermedad de Crohn sintomática que se someten a una resección abdominoperineal pueden experimentar una curación posoperatoria deficiente de la herida. Esto da como resultado una morbilidad significativa, cambios de apósito molestos y un aumento del dolor posoperatorio. Cuando se realiza una resección abdominoperineal por razones oncológicas, ocasionalmente se realiza una reconstrucción con colgajo autólogo para optimizar los resultados de la curación y reconstrucción de la herida. Sin embargo, no se ha establecido la función de la reconstrucción con colgajo después de la resección abdominoperineal para la enfermedad de Crohn.OBJETIVO:Este estudio examina la utilidad de la reconstrucción con colgajo en pacientes con enfermedad de Crohn sintomática sometidos a resección abdominoperineal. Presumimos que los pacientes con reconstrucción inmediata con colgajo después de la resección abdominoperineal demostrarán una mejor curación de la herida.DISEÑO:Revisión retrospectiva de expedientes.MARCO:Los pacientes elegibles en nuestra institución se identificaron entre 2010 y 2018 mediante una combinación de los códigos de Terminología actual de procedimientos, Clasificación internacional de enfermedades 9 y Clasificación internacional de enfermedades 10.PACIENTES:Cuarenta pacientes adultos diagnosticados con enfermedad de Crohn que se someten a resección abdominoperineal solamente (APR-solo = 20) y resección abdominoperineal con reconstrucción con colgajo (APR-colgajo = 20).INTERVENCIÓN (ES):Reconstrucción inmediata con colgajo autólogo después de la resección abdominoperineal.MEDIDAS DE RESULTADOS PRINCIPALES:Presencia de herida perineal posoperatoria y carga de cuidado de la herida posoperatoria.RESULTADOS:Los pacientes del grupo APR-colgajo demostraron rasgos de enfermedad preoperatoria significativamente peores, incluida la carga de la fístula, en comparación con los pacientes del grupo APR-solo. Un número menor de pacientes tendió a asociarse con una herida perineal persistente en el grupo de colgajo a los 30 días (APR-colgajo = 55% vs APR-solo = 70%; p = 0.327) y 6 meses (APR-colgajo = 25% vs APR-solo = 40%; p = 0.311) postoperatoriamente. También hubo una tendencia hacia una menor incidencia de complicaciones en el grupo APR-colgajo. Los pacientes del grupo APR-colgajo tendieron a experimentar menos dolor posoperatorio en comparación con el grupo APR-solo.LIMITACIONES:Estudio de cohorte retrospectivo basado en datos de historias clínicas electrónicas. Tamaño de muestra pequeño y estudio de una sola institución.CONCLUSIONES:En pacientes seleccionados que tienen enfermedad de Crohn fistulizante perianal grave, la reconstrucción inmediata del colgajo después de la resección abdominoperineal puede beneficiar a reducir la carga posoperatoria del cuidado de la herida sin riesgo intraoperatorio o posoperatorio significativo. Además, la reconstrucción con colgajo puede resultar un dolor posoperatorio menor. Consulte Video Resumen en http://links.lww.com/DCR/B416.

Mechanistic insights on melatonin-mediated drought stress mitigation in plants.

Drought stress imposes a serious threat to crop productivity and nutritional security. Drought adaptation mechanisms involve complex regulatory network comprising of various sensory and signaling molecules. In this context, melatonin has emerged as a potential signaling molecule playing a crucial role in imparting stress tolerance in plants. Melatonin pretreatment regulates various plant physiological processes such as osmoregulation, germination, photosynthesis, senescence, primary/secondary metabolism, and hormonal cross-talk under water deficit conditions. Melatonin-mediated regulation of ascorbate-glutathione (AsA-GSH) cycle plays a crucial role to scavenge reactive oxygen species generated in the cells during drought. Here, in this review, the current knowledge on the role of melatonin to ameliorate adverse effects of drought by modulating morphological, physiological, and redox regulatory processes is discussed. The role of melatonin to improve water absorption capacity of roots by regulating aquaporin channels and hormonal cross-talk involved in drought stress mitigation are also discussed. Overall, melatonin is a versatile bio-molecule involved in growth promotion and yield enhancement under drought stress that makes it a suitable candidate for eco-friendly crop production to ensure food security.

Raptor research during the COVID-19 pandemic provides invaluable opportunities for conservation biology.

Research is underway to examine how a wide range of animal species have responded to reduced levels of human activity during the COVID-19 pandemic. In this perspective article, we argue that raptors (i.e., the orders Accipitriformes, Cariamiformes, Cathartiformes, Falconiformes, and Strigiformes) are particularly well-suited for investigating potential 'anthropause' effects: they are sensitive to environmental perturbation, affected by various human activities, and include many locally and globally threatened species. Lockdowns likely alter extrinsic factors that normally limit raptor populations. These environmental changes are in turn expected to influence - mediated by behavioral and physiological responses - the intrinsic (demographic) factors that ultimately determine raptor population levels and distributions. Using this population-limitation framework, we identify a range of research opportunities and conservation challenges that have arisen during the pandemic, related to changes in human disturbance, light and noise pollution, collision risk, road-kill availability, supplementary feeding, and persecution levels. Importantly, raptors attract intense research interest, with many professional and amateur researchers running long-term monitoring programs, often incorporating community-science components, advanced tracking technology and field-methodological approaches that allow flexible timing, enabling continued data collection before, during, and after COVID-19 lockdowns. To facilitate and coordinate global collaboration, we are hereby launching the 'Global Anthropause Raptor Research Network' (GARRN). We invite the international raptor research community to join this inclusive and diverse group, to tackle ambitious analyses across geographic regions, ecosystems, species, and gradients of lockdown perturbation. Under the most tragic of circumstances, the COVID-19 anthropause has afforded an invaluable opportunity to significantly boost global raptor conservation.