Presentation and diagnosis of neonatal tuberous sclerosis complex: A case report and literature review.

Tuberous sclerosis is an uncommon neurocutaneous syndrome characterized by hamartomatous growths with unpredictable progression. Diagnosing and managing neonatal tuberous sclerosis can be challenging. We report a rare case of a 30-day-old male born out of a non-consanguineous marriage who presented with poor suckling and persistent abnormal body movement, required prolonged intensive care, and was diagnosed with tuberous sclerosis with multisystem involvement.

Hemangioblastoma: An Uncommon Cause of Polycythemia in a Child.

Polycythemia is a rare condition in children. Myeloproliferative neoplasms, including polycythemia vera although rare, is an important cause of childhood primary polycythemia. Secondary polycythemia is more common in children due to conditions causing hypoxia or due to pathologic erythropoietin production in malignancies like renal cell carcinoma, Wilms tumor or Hepatocellular carcinoma. Central nervous system hemangioblastoma is one of the rare causes of polycythemia. We report a 13-year-old girl with primarily neurological symptoms identified to be polycythemic during routine evaluation. Clinical examination and neuroimaging subsequently confirmed an intracranial space occupying lesion which was excised. Hemoglobin level normalized after tumor excision. This case report emphasizes the need for thorough systemic evaluation including central nervous system examination in children identified to be polycythemic. Keywords: CNS tumor; hemangioblastoma; polycythemia.

Transcriptional regulation of tomato fruit ripening.

An intrinsic and genetically determined ripening program of tomato fruits often depends upon the appropriate activation of tissue- and stage-specific transcription factors in space and time. The past two decades have yielded considerable progress in detailing these complex transcriptional as well as hormonal regulatory circuits paramount to fleshy fruit ripening. This non-linear ripening process is strongly controlled by the MADS-box and NOR family of proteins, triggering a transcriptional response associated with the progression of fruit ripening. Deepening insights into the connection between MADS-RIN and plant hormones related transcription factors, such as ERFs and ARFs, further conjugates the idea that several signaling units work in parallel to define an output fruit ripening transcriptome. Besides these TFs, the role of other families of transcription factors such as MYB, GLK, WRKY, GRAS and bHLH have also emerged as important ripening regulators. Other regulators such as EIN and EIL proteins also determine the transcriptional landscape of ripening fruits. Despite the abundant knowledge of the complex spectrum of ripening networks in the scientific domain, identifying more ripening effectors would pave the way for a better understanding of fleshy fruit ripening at the molecular level. This review provides an update on the transcriptional regulators of tomato fruit ripening.

A Preliminary Study on the Impact of Household Air Pollution on Adult Respiratory Health in Urban and Rural Settings of Jaipur, India.

Background: This study aimed to investigate the association between household air pollution and chronic respiratory illness (CRI) in Jaipur, India. Materials and Methods: A total of 147 participants over 18 years of age from 45 households were randomly included in the study, and follow-up visits were conducted once every fortnight over a three-month period. Spirometry tests were conducted using a portable hand-held digital spirometer. A self-designed, pretested, semi-structured questionnaire was utilized to collect socio-demographic information from the participants. Statistical tests, such as t-tests were used to analyze the association between household air pollution and CRI. Results: The prevalence of COPD and bronchial asthma was 2% and 4%, respectively. Various risk factors for CRI were identified within households, and only 4 episodes of acute exacerbation of chronic respiratory illness were observed, resulting in no incidence density calculation. The mean values of forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) were significantly lower in females (P < 0.001) Also, the mean values of FVC and FEV1 were significantly lower in rural areas (P < 0.005) than urban areas. Conclusion: Our findings highlight the importance of government and stakeholder action to implement clean air policies and protect respiratory health. Further studies are needed to expand on these findings and delve deeper into understanding the complex interactions between various risk factors and respiratory health in this population.

Antidiuretic hormone deficiency secondary to inactive hydrocephalus: a case report.

BACKGROUND: Diabetes insipidus is a syndrome characterized by polyuria, which is almost always associated with polydipsia. The most frequent cause is central diabetes insipidus, which is the result of an inadequate secretion of the antidiuretic hormone, and diagnosis involves differentiating it from other causes of polyuria and polydipsia. CASE PRESENTATION: Here, we present a clinical case of a previously healthy 13-year-old Nepali boy, who, in December 2022, was found to have intense polydipsia accompanied by polyuria. He had bilateral lower limb weakness at the time of presentation. Biochemical evaluation demonstrated raised serum sodium (181 mEq/L), serum creatinine (78 µmol/L), and serum uric acid (560 µmol/L) with suppressed serum potassium (2.7 mEq/L), which was the major concern to the clinicians. Further laboratory workup revealed an increased serum osmolarity (393.6 mOsm/kg) with reduced urine osmolarity (222.7 mOsm/kg). On contrast magnetic resonance imaging of the brain, a thick-walled third ventricular cyst with bilateral foramen obstruction, thin membrane-like structure at top of aqueduct of Sylvius with gross obstructive hydrocephalus (inactive), and compressed and thinned pituitary gland with no bright spot was observed. The laboratory findings, radiological findings, and case presentation provided the provisional diagnosis of diabetes insipidus due to hydrocephalus and third ventricular cyst. CONCLUSIONS: Central diabetes insipidus due to hydrocephalus, though rare, can have serious complications including the predilection to develop a deficit of other pituitary hormones. Thus, even if hydrocephalus is dormant with normal intracranial pressure, it must be addressed during investigations of central diabetes insipidus.

Comprehensive assessment of nutritional and functional status of patients with ulcerative colitis and their impact on quality of life.

INTRODUCTION: Patients with ulcerative colitis (UC) are likely to have poor nutritional intake and increased gut losses. This study was designed to study the prevalence and predictors of nutritional deficiencies in patients with UC and their impact on the quality of life (QOL). METHODS: A prospective study was conducted among consenting patients with UC (cases) and healthy relatives of the cases (controls) visiting a university teaching hospital. They were assessed for clinical, demographic, endoscopic (Mayo score) and histological profile (Robart's score). They were assessed for the presence of macronutrient and micronutrient deficiency, anthropometry, functional status (muscle strength by dynamometer and sit-to-stand test) and the quality of life (short inflammatory bowel disease questionnaire [SIBDQ]). A SIBDQ score of ≤ 50 was considered poor QOL. RESULTS: We studied 126 cases and 57 healthy controls (age [mean ± SD] 37.7 ± 13.2 years vs. 34.40 ± 11.05 years; [p = 0.10] females [38.1% vs. 38.7%]; p = 0.94). Cases more often were underweight (28% vs. 3.5%; p < 0.001), had low mid arm circumference (45% vs. 12%; p < 0.0001), lower functional status in the form of weaker hand grip strength (67% vs. 45.6%; p = 0.007) and weaker lower limb strength (80% vs. 42%; p < 0.0001). Cases more often had the evidence of macronutrient deficiencies: total serum protein deficiency (31% vs. 3.5%; p < 0.0001), serum albumin deficiency (25.4% vs. 0.00%; p < 0.0001) and cholesterol deficiency (63% vs. 28%; p < 0.0001). Micronutrient deficiencies were highly prevalent among cases: calcium (44%), phosphate (21%), magnesium (11%), zinc (76%), iron (87%), folate (16%), vitamin B12 (10%) and vitamin D (81%). Most cases had a poor quality of life (85/126; 67.5%). Factors associated with poor QOL were low hemoglobin, serum albumin, zinc and vitamin D levels and histologically active disease. On multi-variate analysis, low vitamin D levels (odds ratio [OR] = 6.1; 95% confidence interval [CI]: 1.9-19.7) and histologically active disease (OR = 4.0; 95% CI: 1.6-9.9) were identified as independent predictors of poor QOL. CONCLUSIONS: Macronutrient deficiency, micronutrient deficiency, lower functional status and poorer QOL are highly prevalent among patients with UC. The independent predictors of poor QOL were histologically active disease and low serum vitamin D levels. Identifying and correcting the deficiencies may help in improving the QOL of patients with UC.

RegX3-dependent transcriptional activation of kdpDE and repression of rv0500A are linked to potassium homeostasis in Mycobacterium tuberculosis.

Ionic homeostasis is essential for the survival and replication of Mycobacterium tuberculosis within its host. Low potassium ion concentrations trigger a transition of M. tuberculosis into dormancy. Our current knowledge of the transcriptional regulation mechanisms governing genes involved in potassium homeostasis remains limited. Potassium transport is regulated by the constitutive Trk system and the inducible Kdp system in M. tuberculosis. The two-component system KdpDE (also known as KdpD/KdpE) activates expression of the kdpFABC operon, encoding the four protein subunits of the Kdp potassium uptake system (KdpFABC). We show that, under potassium deficiency, expression of the two-component system senX3/regX3 is upregulated, and bacterial survival is compromised in a regX3-inactivated mutant, ΔregX3. Electrophoretic mobility shift assays (EMSAs), promoter reporter assays and chromatin immunoprecipitation (ChIP) show that RegX3 binds to the kdpDE promoter and activates it under potassium deficiency, whereas RegX3 (K204A), a DNA binding-deficient mutant, fails to bind to the promoter. Mutation of the RegX3 binding motifs on the kdpDE promoter abrogates RegX3 binding. In addition, EMSAs and ChIP assays show that RegX3 represses Rv0500A, a repressor of kdpFABC, by binding to consensus RegX3 binding motifs on the rv0500A promoter. Our findings provide important insight into two converging pathways regulated by RegX3; one in which it activates an activator of kdpFABC, and the other in which it represses a repressor of kdpFABC, during potassium insufficiency. This culminates in increased expression of the potassium uptake system encoded by kdpFABC, enabling bacterial survival. These results further expand the growing transcriptional network in which RegX3 serves as a central node to enable bacterial survival under stress.

Fyn, Blk, and Lyn kinase inhibitors: A mini-review on medicinal attributes, research progress, and future insights.

Fyn, Blk, and Lyn are part of a group of proteins called Src family kinases. They are crucial in controlling cell communication and their response to the growth, changes, and immune system. Blocking these proteins with inhibitors can be a way to treat diseases where these proteins are too active. The primary mode of action of these inhibitors is to inhibit the phosphorylation of Fyn, Blk, and Lyn receptors, which in turn affects how signals pass within the cells. This review shows the structural and functional aspects of Fyn, Blk, and Lyn kinases, highlighting the significance of their dysregulation in diseases such as cancer and autoimmune disorders. The discussion encompasses the design strategies, SAR analysis, and chemical characteristics of effective inhibitors, shedding light on their specificity and potency. Furthermore, it explores the progress of clinical trials of these inhibitors, emphasizing their potential therapeutic applications.

Strengthening breast cancer screening program through health education of women and capacity building of primary healthcare providers.

Background: Globally and in India, breast cancer is a prevalent malignancy. India saw 178,361 new cases and 90,000 deaths in 2020. Timely detection is vital, highlighting the importance of Breast Self-Examination (BSE), especially in low-income settings. Strengthening BSE in awareness and screening efforts is urgent. Despite awareness, practical application lags due to women's reluctance. Effective execution demands partnerships, a multi-sectoral strategy, and training grassroots workers. Objective: To address these challenges, the present study aims to strengthen the breast cancer screening program using BSE strategy and adopting a referral mechanism for the diagnosis and treatment of suspect cases. Methods: A community-based study occurred in specific districts of Rajasthan (2017-2022), enhancing breast cancer screening for women aged 30-65. It involved healthcare providers and local women, utilizing tools like the MT-DM-GP6620 Breast Inspection Model, educational booklets, and semi-structured schedules. The strategy encompassed knowledge assessment, capacity building for healthcare providers, BSE training, increasing women's breast cancer awareness, suspect case referrals, and phone-based follow-up. Results: Our study encompassed 157,225 women aged 30-65 in Jodhpur, Jalore, and Pali districts. Initial breast self-examination (BSE) awareness was below 1%. BSE training reached 218,978 women using booklets and demonstrations, with 72% aged 30-65 and the rest 15-30. Follow-ups reinforced BSE, leading to 745 identified suspect breast cancer cases, mostly due to painless lumps (332 cases). Capacity-building workshops involving 824 medical and paramedical staff strengthened early breast cancer detection in Jodhpur and Jalore, in collaboration with the district health department. Conclusion: The study model's success suggests its applicability in other Rajasthan districts, Indian states, and global breast cancer prevention programs. While positive outcomes were evident, challenges related to culture, cost, and benefits warrant consideration. The approach prioritized early detection through community engagement, reducing patient and government burdens. Community involvement and healthcare engagement were pivotal, with breast self-examination proving effective for enhancing awareness and early detection. Promoting BSE education can significantly enhance breast cancer awareness and early detection.

Functions of Phytochrome-Interacting Factors (PIFs) in the regulation of plant growth and development: A comprehensive review.

Transcription factors play important roles in governing plant responses upon changes in their ambient conditions. Any fluctuation in the supply of critical requirements for plants, such as optimum light, temperature, and water leads to the reprogramming of gene-signaling pathways. At the same time, plants also evaluate and shift their metabolism according to the various stages of development. Phytochrome-Interacting Factors are one of the most important classes of transcription factors that regulate both developmental and external stimuli-based growth of plants. This review focuses on the identification of PIFs in various organisms, regulation of PIFs by various proteins, functions of PIFs of Arabidopsis in diverse developmental pathways such as seed germination, photomorphogenesis, flowering, senescence, seed and fruit development, and external stimuli-induced plant responses such as shade avoidance response, thermomorphogenesis, and various abiotic stress responses. Recent advances related to the functional characterization of PIFs of crops such as rice, maize, and tomato have also been incorporated in this review, to ascertain the potential of PIFs as key regulators to enhance the agronomic traits of these crops. Thus, an attempt has been made to provide a holistic view of the function of PIFs in various processes in plants.

The two faces of DJ-1D proteins.

Despite the documented bi-enzymatic mode of methylglyoxal detoxification, the single-step catalysis of methylglyoxal by DJ-1/Pfp-I domain containing proteins has been in the limelight. Prasad et al. recently discovered another functional facet of these moonlighting proteins: the deglycase potential of DJ-1D to repair the glycated DNA, RNA, and proteins in plants.

Efficacy and Safety of Stempeucel in Osteoarthritis of the Knee: A Phase 3 Randomized, Double-Blind, Multicenter, Placebo-Controlled Study.

BACKGROUND: Osteoarthritis is a chronic, progressive, and degenerative condition with limited therapy options. Recently, biologic therapies have been an evolving option for the management of osteoarthritis. PURPOSE: To assess whether allogenic mesenchymal stromal cells (MSCs) have the potential to improve functional parameters and induce cartilage regeneration in patients with osteoarthritis. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A total of 146 patients with grade 2 and 3 osteoarthritis were randomized to either an MSC group or placebo group with a ratio of 1:1. There were 73 patients per group who received either a single intra-articular injection of bone marrow-derived MSCs (BMMSCs; 25 million cells) or placebo, followed by 20 mg per 2 mL of hyaluronic acid under ultrasound guidance. The primary endpoint was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score. The secondary endpoints were WOMAC subscores for pain, stiffness, and physical function; the visual analog scale score for pain; and magnetic resonance imaging findings using T2 mapping and cartilage volume. RESULTS: Overall, 65 patients from the BMMSC group and 68 patients from the placebo group completed 12-month follow-up. The BMMSC group showed significant improvements in the WOMAC total score compared with the placebo group at 6 and 12 months (percentage change: -23.64% [95% CI, -32.88 to -14.40] at 6 months and -45.60% [95% CI, -55.97 to -35.23] at 12 months P < .001; percentage change, -44.3%). BMMSCs significantly improved WOMAC pain, stiffness, and physical function subscores as well as visual analog scale scores at 6 and 12 months (P < .001). T2 mapping showed that there was no worsening of deep cartilage in the medial femorotibial compartment of the knee in the BMMSC group at 12-month follow-up, whereas in the placebo group, there was significant and gradual worsening of cartilage (P < .001). Cartilage volume did not change significantly in the BMMSC group. There were 5 adverse events that were possibly/probably related to the study drug and consisted of injection-site swelling and pain, which improved within a few days. CONCLUSION: In this small randomized trial, BMMSCs proved to be safe and effective for the treatment of grade 2 and 3 osteoarthritis. The intervention was simple and easy to administer, provided sustained relief of pain and stiffness, improved physical function, and prevented worsening of cartilage quality for ≥12 months. REGISTRATION: CTRI/2018/09/015785 (National Institutes of Health and Clinical Trials Registry-India).

Identification of universal stress proteins in wheat and functional characterization during abiotic stress.

KEY MESSAGE: TaUSPs are localized in Endoplasmic reticulum and form homo and hetero dimers within themselves. They play significant role in multiple abiotic stress responses in yeast heterologous system and in plants. Universal Stress Proteins are stress responsive proteins present in a variety of life forms ranging from bacteria to multicellular plants and animals. In this study we have identified 85 TaUSP genes in the wheat genome and have characterised their abiotic stress responsive members in yeast under different stress conditions. Localization and Y2H studies suggest that wheat, USP proteins are localized in the ER complex, and extensively crosstalk amongst themselves through forming hetero and homodimers. Expression analysis of these TaUSP genes suggests their role in adaptation to multiple abiotic stresses. TaUSP_5D-1 was found to have some DNA binding activity in yeast. Certain abiotic stress responsive TaUSP genes are found to impart tolerance to temperature stress, oxidative stress, ER stress (DTT treatment) and LiCl2 stress in the yeast heterologous system. TaUSP_5D-1 overexpression in A. thaliana imparts drought tolerance via better lateral root network in transgenic lines. The TaUSP represents an important repertoire of genes for engineering abiotic stress responsiveness in crop plants.

Pancreatic Dysfunction and Reduction in Quality of Life Is Common After Pancreaticoduodenectomy.

BACKGROUND: Improvements in survival after pancreaticoduodenectomy has increased the number of patients potentially at risk of pancreatic insufficiency. AIMS: We studied long-term (> 1 year) pancreatic functions (endocrine and exocrine) after pancreaticoduodenectomy and aimed to recognize the impact of various clinicopathological factors and postoperative complications on pancreatic functions. METHODS: All patients who underwent pancreaticoduodenectomy at least 1 year prior were recruited from July 2020 to December 2021. Endocrine function was assessed using HbA1c, fasting blood sugar and postprandial blood sugar levels. Pancreatic exocrine function was assessed clinically with history of steatorrhea and objectively with quantitative estimation of fecal elastase-1 levels in stool samples. Volume of remnant pancreas, parenchymal thickness and duct diameter were assessed by computed tomography. Quality of life assessment was done using SF-36 questionnaire. RESULTS: Of the 106 patients assessed, 64 patients met the inclusion criteria. Endocrine insufficiency was noted in 51.6%, and 34.3% had new onset diabetes mellitus. The incidence of pancreatic exocrine insufficiency was 87.5% and severe insufficiency was found in 62.5% of patients. Twenty-nine (45.3%) patients had both exocrine and endocrine insufficiency. Patients with CRPOPF had higher risk of severe exocrine insufficiency (5 vs. 2, OR 1.57(0.28-8.81) p = 0.6). The SF-36 scores were lower than general population especially in role limitation due to physical health, role limitation due to emotional problems, energy/fatigue, general health perception and health change domains. CONCLUSION: Post-pancreaticoduodenectomy patients have a high frequency of pancreatic insufficiency and should be screened for same. The post-operative pancreatic fistula increases the risk of pancreatic exocrine insufficiency.

Uncovering the role of microRNA671-5p/CDCA7L/monoamine oxidase-A signaling in Helicobacter pylori mediated apoptosis in gastric epithelial cells.

Helicobacter pylori is a gram-negative microaerophilic bacterium and is associated with gastrointestinal diseases ranging from peptic ulcer and gastritis to gastric cancer and mucosa-associated lymphoid tissue lymphoma. In our laboratory, the transcriptomes and miRnomes of AGS cells infected with H. pylori have been profiled, and an miRNA-mRNA network has been constructed. MicroRNA 671-5p is upregulated during H. pylori infection of AGS cells or of mice. In this study, the role of miR-671-5p during infection has been investigated. It has been validated that miR-671-5p targets the transcriptional repressor CDCA7L, which is downregulated during infection (in vitro and in vivo) concomitant with miR-671-5p upregulation. Further, it has been established that the expression of monoamine oxidase A (MAO-A) is repressed by CDCA7L, and that MAO-A triggers the generation of reactive oxygen species (ROS). Consequently, miR-671-5p/CDCA7L signaling is linked to the generation of ROS during H. pylori infection. Finally, it has been demonstrated that ROS-mediated caspase 3 activation and apoptosis that occurs during H. pylori infection, is dependent on the miR-671-5p/CDCA7L/MAO-A axis. Based on the above reports, it is suggested that targeting miR-671-5p could offer a means of regulating the course and consequences of H. pylori infection.

Elevated methylglyoxal levels inhibit tomato fruit ripening by preventing ethylene biosynthesis.

Methylglyoxal (MG), a toxic compound produced as a by-product of several cellular processes, such as respiration and photosynthesis, is well known for its deleterious effects, mainly through glycation of proteins during plant stress responses. However, very little is known about its impact on fruit ripening. Here, we found that MG levels are maintained at high levels in green tomato (Solanum lycopersicum L.) fruits and decline during fruit ripening despite a respiratory burst during this transition. We demonstrate that this decline is mainly mediated through a glutathione-dependent MG detoxification pathway and primarily catalyzed by a Glyoxalase I enzyme encoded by the SlGLYI4 gene. SlGLYI4 is a direct target of the MADS-box transcription factor RIPENING INHIBITOR (RIN), and its expression is induced during fruit ripening. Silencing of SlGLYI4 leads to drastic MG overaccumulation at ripening stages of transgenic fruits and interferes with the ripening process. MG most likely glycates and inhibits key enzymes such as methionine synthase and S-adenosyl methionine synthase in the ethylene biosynthesis pathway, thereby indirectly affecting fruit pigmentation and cell wall metabolism. MG overaccumulation in fruits of several nonripening or ripening-inhibited tomato mutants suggests that the tightly regulated MG detoxification process is crucial for normal ripening progression. Our results underpin a SlGLYI4-mediated regulatory mechanism by which MG detoxification controls fruit ripening in tomato.

OsCRY2 and OsFBO10 co-regulate photomorphogenesis and photoperiodic flowering in indica rice.

Cryptochromes (CRYs) are a class of photoreceptors that perceive blue/ultraviolet-A light of the visible spectrum to mediate a vast number of physiological responses in bacteria, fungi, animals and plants. In the present study, we have characterized OsCRY2 in a photoperiod sensitive indica variety, Basmati 370, by generating and analyzing overexpression (OE) and knock-down (KD) transgenic lines. The OsCRY2OE lines displayed dwarfism as shown in their reduced plant height and leaf length, attributed largely by an overall reduction in their cell size. The OsCRY2OE lines flowered significantly earlier and showed shorter and broader seeds with an overall reduced seed weight. The OsCRY2KD lines showed contrasting phenotypes, such as increased plant height and delayed flowering, however, decreased seed size and weight were also observed in the KD lines, along with reduced spikelet fertility and high seed shattering rate in mature panicles. Novel interactions were confirmed between OsCRY2 and members of ZEITLUPE family of blue/ultraviolet-A light photoreceptors, encoded by OsFBO8, OsFBO9 and OsFBO10 which are orthologous to ZEITLUPE (ZTL), LOV KELCH PROTEIN2 (LKP2) and FLAVIN BINDING, KELCH REPEAT F-BOX1 (FKF1), respectively, of Arabidopsis thaliana. Since FKF1 is known to play a role in regulating photoperiodic flowering, OsFBO10 was chosen for further studies. OsCRY2 and OsFBO10 interacted in the nucleus and cytoplasm of the cell and cross-regulated the expression of each other. They were also found to regulate the expression of several genes involved in photoperiodic flowering in rice. Both OsCRY2 and OsFBO10 played a positive role in photomorphogenic responses in different light conditions. The physical interaction of OsCRY2 with OsFBO10, their involvement in common physiological and developmental pathways and their cross-regulation of each other suggest that the two photoreceptors may regulate common developmental pathways in plants, either jointly or redundantly.

Levosimendan: mechanistic insight and its diverse future aspects in cardiac care.

Inotropic agents are generally recommended to use in patients with acute decompensated heart failure (HF) with reduced ejection fraction (HFrEF) concurrent to end-organ dysfunction. However, due to certain pharmacological limitations like developing life threatening arrhythmia and tolerance, cannot be employed as much as needed. Meanwhile, Calcium ion (Ca2+) sensitisers exhibits their inotropic action by increasing the sensitivity of the cardiomyocyte to intracellular Ca2+ ion and have been reported as emerging therapeutic alternative in HF cases. Levosimendan (LEVO) is an inodilator and with its unique pharmacology justifying its use in a wide range of cardiac alterations in HF particularly in undergoing cardiac surgery. It is also reported to be better than classical inotropes in maintaining cardiac mechanical efficacy and reducing congestion in acute HF with hypotension. This review paper was designed to compile various evidence about basic pharmacology and potential clinical aspects of LEVO in cardiac surgery and other HF associated alterations. This will benefit directly to the researcher in initiating research and to fill the gaps in the area of thrust.

SCFOsFBK1 E3 ligase mediates jasmonic acid-induced turnover of OsATL53 and OsCCR14 to regulate lignification of rice anthers and roots.

The rice F-box protein OsFBK1, which mediates the turnover of a cinnamoyl CoA-reductase, OsCCR14, has previously been shown to regulate anther and root lignification. Here, we identify OsATL53, a member of the ATL family of RING-H2 proteins that interacts with OsCCR14 in the cytoplasm. OsATL53 was identified in the same yeast two-hybrid library screening as reported previously for OsCCR14, and we show it to have cytoplasmic localization and E3 ligase ubiquitination properties. SCFOsFBK1 mediates turnover of OsATL53 in the cytoplasm and the nucleus, and that of OsCCR14 only in the nucleus, as shown by cell-free degradation assays. Confocal fluorescence lifetime imaging microscopy analyses demonstrate that in presence of jasmonic acid (JA), which plays a role in anther dehiscence, OsATL53-OsCCR14 undergoes conformational changes that trigger the complex to accumulate around the nuclear periphery and signals OsFBK1 to initiate degradation of the proteins in the respective cellular compartments. OsATL53 decreases the enzymatic activity of OsCCR14 and sequesters it in the cytoplasm, thereby regulating the lignification process. Transgenic rice with knockdown of OsATL53 display increased lignin deposition in the anthers and roots compared to the wild type, whilst knockdown of OsCCR14 results in decreased lignin content. Our results show that OsATL53 affects the activity of OsCCR14, and that their JA-induced degradation by SCFOsFBK1 regulates lignification of rice anthers and roots.

A glutathione-independent DJ-1/PfpI domain-containing tomato glyoxalaseIII2, SlGLYIII2, confers enhanced tolerance under salt and osmotic stresses.

In plants, glyoxalase enzymes are activated under stress conditions to mitigate the toxic effects of hyperaccumulated methylglyoxal (MG), a highly reactive carbonyl compound. Until recently, a glutathione-dependent bi-enzymatic pathway involving glyoxalase I (GLYI) and glyoxalase II (GLYII) was considered the primary MG-detoxification system. Recently, a new glutathione-independent glyoxalase III (GLYIII) mediated direct route was also reported in plants. However, the physiological significance of this new pathway remains to be elucidated across plant species. This study identified the full complement of 22 glyoxalases in tomato. Based on their strong induction under multiple abiotic stresses, SlGLYI4, SlGLYII2 and SlGLYIII2 were selected candidates for further functional characterisation. Stress-inducible overexpression of both glutathione-dependent (SlGLYI4 + SlGLYII2) and independent (SlGLYIII2) pathways led to enhanced tolerance in both sets of transgenic plants under abiotic stresses. However, SlGLYIII2 overexpression (OE) plants outperformed the SlGLYI4 + SlGLYII2 OE counterparts for their stress tolerance under abiotic stresses. Further, knockdown of SlGLYIII2 resulted in plants with exacerbated stress responses than those silenced for both SlGLYI4 and SlGLYII2. The superior performance of SlGLYIII2 OE tomato plants for better growth and yield under salt and osmotic treatments could be attributed to better GSH/GSSG ratio, lower reactive oxygen species levels, and enhanced antioxidant potential, indicating a prominent role of GLYIII MG-detoxification pathway in abiotic stress mitigation in this species.