Pituitary macroadenoma with panhypopituitarism masquerading as schizophrenia: a diagnostic dilemma managed conservatively.

Introduction and importance: Secretory pituitary macroadenoma also known as prolactinoma are benign neoplasm comprising very minimal cases of intracranial masses. Among the various presentation suggestive of panhypopituitarism, psychosis, and features of schizophrenia is very rarely seen. In the majority of cases, neurosurgical intervention for the excision of tumor is considered a standard treatment modality but conservative management with dopamine agonist and steroids have also been shown to provide an optimal level of care also improving the quality of level of patient. Case presentation: A 42-year-old Asian male presented with a history of talking to self, delusion of persecution, over talkativeness, hallucination, increased suspiciousness, and history of lost and found in the streets where he was working as a migrant worker. The patient was initially managed in line of schizophrenia with the antipsychotics drug of choice. On further assessment there was no improvement of psychiatric symptoms but they further deteriorated with additional neuropsychiatric symptoms; hence, MRI brain was carried out. Following which, the diagnosis of pituitary macroadenoma was confirmed and further more hormonal analysis was done, which showed findings suggestive of panhypopituitarism. The patient was then managed conservatively with dopamine agonist and steroids, which showed rapid improvement of psychiatric symptoms with a massive reduction in the size of the pituitary macroadenoma. Clinical discussion: With the incidence of 100 per million cases pituitary adenomas are considered locally invading with the characteristic compression of the surrounding structure, presenting as visual hallucinations, olfactory hallucinations, episodes of losing time, apathy, and features suggestive of adrenal insufficiency, hypogonadotrophic hypogonadism, and symptoms secondary to hormonal imbalance such as hypothyroidism. Psychiatric symptomatic presentations are considered a very rare presentation in cases of pituitary macroadenoma. Also, psychiatric features and symptoms of psychosis are associated with prolcatinomas through idiopathic mechanism and the basic casualty has not been established. Surgical intervention such as trans-sphenoidal resection of the mass can be undertaken in case where mass effects is present but long-term remission and prognosis is found not to be fruitful. Conservative treatment with dopamine agonist such as cabergoline and steroids also plays a meaningful role in abrupt management in such cases. Conclusion: Pituitary macroadenoma presenting as a patient of schizophrenia is noted very rarely in medical literature; hence, investigations in view of neurosurgical diagnosis in cases presenting as psychosis should be considered for ideal holistic management. Conservative management can also be a breakthrough treatment modality in complete recovery of pituitary macroadenoma.

Physiological Functions of Phospholipid: Diacylglycerol Acyltransferases.

Triacylglycerol (TAG) is amongst the most energy dense storage form of reduced carbon in living systems. TAG metabolism plays critical roles in cellular energy balance, lipid homeostasis, cell growth and stress responses. In higher plants, microalgae and fungi, TAG is assembled by acyl-CoA-dependent and -independent pathways catalyzed by diacylglycerol:acyltransferase (DGAT) and phospholipid:diacylglycerol acyltransferase (PDAT), respectively. This review contains a summary of the current understanding of the physiological functions of PDATs. Emphasis is placed on their role in lipid remodeling and lipid homeostasis in response to abiotic stress or perturbations in lipid metabolism.

Regiospecific Cellulose Orientation and Anisotropic Mechanical Property in Plant Cell Walls.

Cellulose microfibrils (CMFs) are a major load-bearing component in plant cell walls. Thus, their structures have been studied extensively with spectroscopic and microscopic characterization methods, but the findings from these two approaches were inconsistent, which hampers the mechanistic understanding of cell wall mechanics. Here, we report the regiospecific assembly of CMFs in the periclinal wall of plant epidermal cells. Using sum frequency generation spectroscopic imaging, we found that CMFs are highly aligned in the cell edge region where two cells form a junction, whereas they are mostly isotropic on average throughout the wall thickness in the flat face region of the epidermal cell. This subcellular-level heterogeneity in the CMF alignment provided a new perspective on tissue-level anisotropy in the tensile modulus of cell wall materials. This finding also has resolved a previous contradiction between the spectroscopic and microscopic imaging studies, which paves a foundation for better understanding of the cell wall architecture, especially structure-geometry relationships.

The human milk component myo-inositol promotes neuronal connectivity.

Effects of micronutrients on brain connectivity are incompletely understood. Analyzing human milk samples across global populations, we identified the carbocyclic sugar myo-inositol as a component that promotes brain development. We determined that it is most abundant in human milk during early lactation when neuronal connections rapidly form in the infant brain. Myo-inositol promoted synapse abundance in human excitatory neurons as well as cultured rat neurons and acted in a dose-dependent manner. Mechanistically, myo-inositol enhanced the ability of neurons to respond to transsynaptic interactions that induce synapses. Effects of myo-inositol in the developing brain were tested in mice, and its dietary supplementation enlarged excitatory postsynaptic sites in the maturing cortex. Utilizing an organotypic slice culture system, we additionally determined that myo-inositol is bioactive in mature brain tissue, and treatment of organotypic slices with this carbocyclic sugar increased the number and size of postsynaptic specializations and excitatory synapse density. This study advances our understanding of the impact of human milk on the infant brain and identifies myo-inositol as a breast milk component that promotes the formation of neuronal connections.

Deficiency in the neural cell adhesion molecule 2 (NCAM2) reduces axonal levels of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), affects axonal organization in the hippocampus, and leads to behavioral deficits.

The neural cell adhesion molecule 2 (NCAM2) regulates axonal organization in the central nervous system via mechanisms that have remained poorly understood. We now show that NCAM2 increases axonal levels of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), a protease that regulates axonal guidance. In brains of NCAM2-deficient mice, BACE1 levels are reduced in hippocampal mossy fiber projections, and the infrapyramidal bundle of these projections is shortened. This abnormal axonal organization correlates with impaired short-term spatial memory and cognitive flexibility in NCAM2-deficient male and female mice. Self-grooming, rearing, digging and olfactory acuity are increased in NCAM2-deficient male mice, when compared with littermate wild-type mice of the same sex. NCAM2-deficient female mice also show increased self-grooming, but are reduced in rearing, and do not differ from female wild-type mice in olfactory acuity and digging behavior. Our results indicate that errors in axonal guidance and organization caused by impaired BACE1 function can underlie the manifestation of neurodevelopmental disorders, including autism as found in humans with deletions of the NCAM2 gene.

A chloroplast diacylglycerol lipase modulates glycerolipid pathway balance in Arabidopsis.

Two parallel pathways compartmentalized in the chloroplast and the endoplasmic reticulum contribute to thylakoid lipid synthesis in plants, but how these two pathways are coordinated during thylakoid biogenesis and remodeling remains unknown. We report here the molecular characterization of a homologous ADIPOSE TRIGLYCERIDE LIPASE-LIKE gene, previously referred to as ATGLL. The ATGLL gene is ubiquitously expressed throughout development and rapidly upregulated in response to a wide range of environmental cues. We show that ATGLL is a chloroplast non-regioselective lipase with a hydrolytic activity preferentially towards 16:0 of diacylglycerol (DAG). Comprehensive lipid profiling and radiotracer labeling studies revealed a negative correlation of ATGLL expression and the relative contribution of the chloroplast lipid pathway to thylakoid lipid biosynthesis. Additionally, we show that genetic manipulation of ATGLL expression resulted in changes in triacylglycerol levels in leaves. We propose that ATGLL, through affecting the level of prokaryotic DAG in the chloroplast, plays important roles in balancing the two glycerolipid pathways and in maintaining lipid homeostasis in plants.

Proteomic analysis response of rice (Oryza sativa) leaves to ultraviolet-B radiation stress.

Rice (Oryza sativa) is a human staple food and serves as a model organism for genetic and molecular studies. Few studies have been conducted to determine the effects of ultraviolet-B (UV-B) stress on rice. UV-B stress triggers morphological and physiological changes in plants. However, the underlying mechanisms governing these integrated responses are unknown. In this study, we conducted a proteomic response of rice leaves to UV-B stress using two-dimensional gel electrophoresis and identified the selected proteins by mass spectrometry analysis. Four levels of daily biologically effective UV-B radiation intensities were imposed to determine changes in protein accumulation in response to UV-B stress: 0 (control), 5, 10, and 15 kJ m-2 d-1in two cultivars, i.e., IR6 and REX. To mimic the natural environment, we conducted this experiment in Sunlit Soil-Plant-Atmosphere-Research (SPAR) chambers. Among the identified proteins, 11% of differentially expressed proteins were found in both cultivars. In the Rex cultivar, only 45% of proteins are differentially expressed, while only 27.5% were expressed in IR6. The results indicate that REX is more affected by UV-B stress than IR6 cultivars. The identified protein TSJT1 (spot 16) in both cultivars plays a crucial role in plant growth and development during stress treatment. Additionally, we found that UV-B stress altered many antioxidant enzymes associated with redox homeostasis and cell defense response. Another enzyme, the glyceraldehyde-3-phosphate dehydrogenase (GAPDH), has been identified as spot 15, which plays an essential role in glycolysis and cellular energy production. Another vital protein identified is glycosyl hydrolase (GH) as spot 9, which catalyzes the hydrolysis of glycosidic bonds in cell wall polymers and significantly affects cell wall architecture. Some identified proteins are related to photosynthesis, protein biosynthesis, signal transduction, and stress response. The findings of our study provide new insights into understanding how rice plants are tailored to UV-B stress via modulating the expression of UV-B responsive proteins, which will help develop superior rice breeds in the future to combat UV-B stress. Data are available via ProteomeXchange with identifier PXD032163.

Genetic Variability Assessment of Tropical Indica Rice (Oryza sativa L.) Seedlings for Drought Stress Tolerance.

Drought stress is one of the most devastating abiotic factors limiting plant growth and development. Devising an efficient and rapid screening method at the seedling stage is vital in identifying genotypes best suited under drought conditions. An experiment was conducted to assess 74 rice genotypes for drought tolerance using specially designed mini-hoop structures. Two treatments were imposed on rice seedlings, including 100% moisture and a 50% moisture regime. Several shoot morpho-physiological traits and root traits were measured and analyzed. The genotypes exhibited a wide range of variability for the measured traits, with the leaf area showing the most significant variation, followed by plant height, tiller number, and shoot dry weight. In contrast, the drought did not significantly affect most root traits. The germplasm was classified into different categories using cumulative drought stress response indices (CDSRI); 19 genotypes (26%) were identified as drought sensitive, and 33 (45%), 15 (20%), and 7 (9%) were determined as low, moderately, and highly drought-tolerant, respectively. Genotypes IR86638 and IR49830 were the most and least drought-tolerant, respectively. Overall, a poor correlation was observed between CDSRI, total shoot traits (R2 = 0.36), and physiological parameters (R2 = 0.10). A strong linear correlation was found between CDSRI and root traits (R2 = 0.81), suggesting that root traits are more crucial and better descriptors in screening for drought tolerance. This study can help rice breeders and scientists to accelerate breeding by adopting a mini-hoop rapid screening method. The tolerant genotypes could serve as appropriate donor parents, progenies, and potential genotypes for developing drought-tolerant commercial cultivars.

Silicon Enhances Plant Vegetative Growth and Soil Water Retention of Soybean (Glycine max) Plants under Water-Limiting Conditions.

Silicon has been implicated as a factor affecting the degree of resistance to abiotic stresses in several plant species. However, the role of silicon in soybean (Glycine max) under water-limiting conditions is not yet fully understood. This study was conducted to evaluate the effects of silicon application on the vegetative growth of two soybean cultivars (Asgrow 5332 and Progeny 5333) grown under water-limiting conditions. Silicon was provided by adding silicate to the soil. Water-limiting treatments were imposed on plants at two vegetative growth stages for 20 days by irrigating with a reduced amount of water (66% or 33% of the required water). Silicate application enhanced plant height, leaf area, and total dry weight of soybean plants. Significant increases in root volumes were observed in both the silicate-treated cultivars compared to the control plants under water-limiting conditions (33% irrigation). Net photosynthesis and stomatal conductance were decreased, but the quantum efficiency of photosystem II (Fv'/Fm') did not change under the same irrigation condition, which indicates photosynthesis downregulation through stomatal limitation. Silicate-treated plants in both cultivars had higher water use efficiency as compared to control plants under water-limiting conditions (irrigated with 66% or 33% of required water). Under water-limiting conditions, the soil moisture content was significantly higher in pots containing silicate than in those without added silicate, suggesting that silicon application improves water holding capacity. Taken together, the results from this study indicate that silicon application can improve the vegetative growth of soybeans under low water conditions by increasing the water use efficiency of plants and enhancing the soil's ability to retain moisture.

Alterations in the leaf lipidome of Brassica carinata under high-temperature stress.

BACKGROUND: Brassica carinata (A) Braun has recently gained increased attention across the world as a sustainable biofuel crop. B. carinata is grown as a summer crop in many regions where high temperature is a significant stress during the growing season. However, little research has been conducted to understand the mechanisms through which this crop responds to high temperatures. Understanding traits that improve the high-temperature adaption of this crop is essential for developing heat-tolerant varieties. This study investigated lipid remodeling in B. carinata in response to high-temperature stress. A commercial cultivar, Avanza 641, was grown under sunlit-controlled environmental conditions in Soil-Plant-Atmosphere-Research (SPAR) chambers under optimal temperature (OT; 23/15°C) conditions. At eight days after sowing, plants were exposed to one of the three temperature treatments [OT, high-temperature treatment-1 (HT-1; 33/25°C), and high-temperature treatment-2 (HT-2; 38/30°C)]. The temperature treatment period lasted until the final harvest at 84 days after sowing. Leaf samples were collected at 74 days after sowing to profile lipids using electrospray-ionization triple quadrupole mass spectrometry. RESULTS: Temperature treatment significantly affected the growth and development of Avanza 641. Both high-temperature treatments caused alterations in the leaf lipidome. The alterations were primarily manifested in terms of decreases in unsaturation levels of membrane lipids, which was a cumulative effect of lipid remodeling. The decline in unsaturation index was driven by (a) decreases in lipids that contain the highly unsaturated linolenic (18:3) acid and (b) increases in lipids containing less unsaturated fatty acids such as oleic (18:1) and linoleic (18:2) acids and/or saturated fatty acids such as palmitic (16:0) acid. A third mechanism that likely contributed to lowering unsaturation levels, particularly for chloroplast membrane lipids, is a shift toward lipids made by the eukaryotic pathway and the channeling of eukaryotic pathway-derived glycerolipids that are composed of less unsaturated fatty acids into chloroplasts. CONCLUSIONS: The lipid alterations appear to be acclimation mechanisms to maintain optimal membrane fluidity under high-temperature conditions. The lipid-related mechanisms contributing to heat stress response as identified in this study could be utilized to develop biomarkers for heat tolerance and ultimately heat-tolerant varieties.

Cell Adhesion Molecules and Protein Synthesis Regulation in Neurons.

Cell adhesion molecules (CAMs) mediate interactions of neurons with the extracellular environment by forming adhesive bonds with CAMs on adjacent membranes or via binding to proteins of the extracellular matrix. Binding of CAMs to their extracellular ligands results in the activation of intracellular signaling cascades, leading to changes in neuronal structure and the molecular composition and function of neuronal contacts. Ultimately, many of these changes depend on the synthesis of new proteins. In this review, we summarize the evidence showing that CAMs regulate protein synthesis by modulating the activity of transcription factors, gene expression, protein translation, and the structure and distribution of organelles involved in protein synthesis and transport.

Andrographis paniculata extract inhibit growth, biofilm formation in multidrug resistant strains of Klebsiella pneumoniae.

BACKGROUND AND AIM: Andrographis paniculata (Kalmegh), a valuable ancient medicinal herb is used in the treatment of several diseases in most Asian countries including India. Klebsiella pneumoniae is an opportunistic pathogen causing nosocomial infections in human. We have investigated the antimicrobial susceptibility and the presence of AmpC gene in K. pneumoniae strain isolated from the sputum of the patient. EXPERIMENTAL PROCEDURE: Antibiotic susceptibility test and phenotypic detection of AmpC/ESBL beta-lactamase were performed by combined disc diffusion test. The CEA of A. paniculata was analyzed for its antibacterial potential against susceptible and resistant strains of K. pneumoniae through the broth microdilution method. Molecular detection of AmpC gene was carried by polymerase chain reaction (PCR). RESULTS: Antibiotic susceptibility test displayed that the clinical isolate of K. pneumoniae were resistant towards cephalosporins, quinolone and monobactam but susceptible to carbapenems. Combined disk diffusion demonstrated AmpC+ve/ESBL-ve beta-lactamase. 250 µg/ml of CEA extract confirmed the inhibition of bacterial growth and biofilm formation compared to the antibiotic. CEA treated K. pneumoniae displayed a reduction of AmpC by polymerase chain reaction. CONCLUSION: The present study illustrates that CEA extract of A. paniculata demonstrated potentiality to control K. pneumoniae growth and biofilm formation. CEA was able to suppress the expression of gene encoding AmpC. This study proves to be an economical approach to control the growth of K. pneumoniae which causes serious infections.

Efficacy of Andrographis paniculata against extended spectrum ß-lactamase (ESBL) producing E. coli.

BACKGROUND: A. paniculata is widely known for its medicinal values and is traditionally used to treat a wide range of diseases such as cancer, diabetes, skin infections, influenza, diarrhoea, etc. The phytochemical constituents of this plant possess unique and interesting biological activities. The main focus of this study was to evaluate the antibacterial property of crude ethyl acetate (CEA) extract of A. paniculata against E. coli clinical isolates along with molecular docking of 10 different bioactive components from this plant with CTX-M-15. METHODS: CEA extract was subjected to phytochemical and FTIR analysis. The E. coli isolates were tested for antibiotic susceptibility through disk-diffusion method to observe their resistance pattern towards different antibiotics. Antibacterial activity and biofilm assay were performed through broth microdilution using a 96-well microplate. CEA extract was further utilized to observe its effect on the expression of a gene encoding CTX-M-15. Finally, in-silico studies were performed where 10 different bioactive compounds from A. paniculata were molecularly docked with CTX-M-15. RESULTS: Phytochemical and FTIR analysis detected the presence of various secondary metabolites and functional groups in CEA extract respectively. Molecular docking provided the number of residues and bond lengths together with a positive docking score. Antibiotic susceptibility showed the multi-drug resistance of all the clinical strains of E. coli. The antibacterial and antibiofilm efficiency of CEA extract (25, 50 and 100 µg/ml) was tested and 100 µg/ml of the extract was more effective in all the strains of E. coli. All 3 ESBL producing strains of E. coli were subjected to gene expression analysis through PCR. Strains treated with 100 µg/ml of the extract showed a downregulation of the gene encoding CTX-M-15 compared to untreated controls. CONCLUSIONS: The utilization of CEA extract of A. paniculata proved an economical way of controlling the growth and biofilm formation of ESBL strains of E. coli. CEA extract was also able to downregulate the expression of a gene encoding CTX-M-15. Molecular docking of 10 different bioactive compounds from A. paniculata with CTX-M-15 provided the residues and bond lengths with a positive docking score.

Effect of high-fat diet on cognitive impairment in triple-transgenic mice model of Alzheimer's disease.

High-fat diet (HFD)-induced obesity is a risk factor for cognitive impairment in Alzheimer's disease (AD). It has been reported that two typical neuropathological markers of AD, ß-amyloid (Aß) peptide and hyperphosphorylated protein tau can cause neuronal apoptosis via oxidative stress, which ultimately leads to cognitive dysfunction. In this study, we tried to explore the molecular pathway underlying memory impairment in young AD transgenic mice model in response to HFD. We maintained non-transgenic control mice (non-Tg) and triple transgenic AD (3xTg-AD) mice aged 8 weeks on either normal diet (ND) containing 10% fat or HFD (60% fat) for 16 weeks. Cognitive functions were evaluated by Morris water maze and Y-maze tests. Behavioral tests showed a significant memory impairment in 3xTg-AD mice fed with HFD. HFD did not alter the levels of Aß and phospho-tau protein in the cortical region regardless of groups. However, 3xTg-AD mice fed with HFD exhibited increased neuronal oxidative stress and apoptosis as assessed by augmentation of lipid peroxidation, activation of caspase-3 and elevated ratio of Bax/Bcl-2. Furthermore, HFD markedly reduced the activation of redox-sensitive transcription factor NF-E2-related factor 2 (Nrf2) by suppressing its up-stream regulatory protein kinase B/Akt as well as down-stream targets such as heme oxygenase-1 and manganese superoxide dismutase in these mice. Our findings suggest that HFD may accelerate cognitive impairment by enhancing oxidative stress and aggravating neuronal apoptosis via inactivation of Nrf2 signaling pathway.

Abscisic Acid and Abiotic Stress Tolerance in Crop Plants.

Abiotic stress is a primary threat to fulfill the demand of agricultural production to feed the world in coming decades. Plants reduce growth and development process during stress conditions, which ultimately affect the yield. In stress conditions, plants develop various stress mechanism to face the magnitude of stress challenges, although that is not enough to protect them. Therefore, many strategies have been used to produce abiotic stress tolerance crop plants, among them, abscisic acid (ABA) phytohormone engineering could be one of the methods of choice. ABA is an isoprenoid phytohormone, which regulates various physiological processes ranging from stomatal opening to protein storage and provides adaptation to many stresses like drought, salt, and cold stresses. ABA is also called an important messenger that acts as the signaling mediator for regulating the adaptive response of plants to different environmental stress conditions. In this review, we will discuss the role of ABA in response to abiotic stress at the molecular level and ABA signaling. The review also deals with the effect of ABA in respect to gene expression.