Proper Formation Research Articles

Understanding the influence of Manasika Bhavas on Stanya Kshaya: A Conceptual Study

Breast milk stands as the foremost source of nutrition in every individual's early life. According to Ayurveda, Stanya is considered an Upadhatu of Rasa and is pivotal for the nourishment and development of infants. Ayurveda defines decreased breast milk or lactation insufficiency as Stanya Kshaya, primarily attributed to emotions like anger, grief, and excessive affection, alongside dietary influences. Psychological factors such as emotional stress, anxiety, and maternal health also significantly impact milk production, necessitating both psychological and medical interventions. Any disruption in Agni affects Ahara Rasa, leading to disturbances in Rasa Dhatu, thereby affecting Stanya. Psychological aspects play a crucial role in the proper formation of Ahara Rasa. The significance of Manasika Bhavas lies in their advocacy of Soumanasya as a primary treatment for Ksheerajanana. This paper explores the correlation between psychological well-being and lactation outcomes, drawing on both contemporary psychological research and traditional Ayurvedic principles. Psychological stress, anxiety, depression, and maternal bonding are examined as key factors affecting hormonal balance and neuroendocrine pathways involved in lactation. Understanding these influences is crucial for holistic approaches to maternal health and breastfeeding support. The integration of psychological interventions alongside conventional medical treatments could enhance maternal lactation success rates and overall maternal-infant health outcomes. Thus, managing Stanya Kshaya requires thorough consideration of both psychological factors and dietary practices.

Comparative histological assessment of the effect of retinol palmitate preparations on aging skin

Background: Most often, the natural form of vitamin A (retinol palmitate) is used to prevent skin aging. There are two topical drugs on the Russian market that contain a high concentration of retinоl palmitate. This is the ointment "Videstim", which contains 0.5% retinol palmitate and ointment "RadevitАctive", which in addition to 1% retinol palmitate also includes cholecalciferol (0.005%) and tocopherol acetate (0.5%). The specific effects of these drugs on the structure of aging skin have not yet been fully studied. Aims: Comparative histological assessment of the effects of "Videstim" ointment and "RadevitАctive" ointmenton the epidermis and dermis of woman aged 40-55 years old. Materials and methods: The clinical study included 18 women aged 40 to 55 years old. Group I included 6 women who used "Videstim" ointment 2 times a day on the skin of the face. Group II consisted of 6 women who used "RadevitАctive" ointment 2 times a day on the skin of the face. Group III consisted of 6 women and was an intact comparison group. The observation period is 90 days. Patients underwent a punch biopsy with with histological examination of the skin before and after 90 days of using of the aforementioned drugs. Results: According to the results of the study, it was revealed that "Videstim" and "RadevitАctive" ointments they have a stimulating effect on the proliferation of keratinocytes of the epidermis, which manifested itself in an in increasing the number of rows of cells of the prickly layer. In addition, under the action of these drugs, the synthetic activity of keratinocytes of the granular layer increases, which contributes to the proper formation of the stratum corneum of the epidermis.. The use of ointments leads to a significant increase in the thickness of both the granular and prickly layers of the epidermis and the dermis. Conclusions: Ointments with a high concentration of retinol palmitate improve the structure of aging skin.

Substrate specificity and kinetic mechanism of 3-hydroxy-Δ5-C27-steroid oxidoreductase

Cholesterol is a key sterol whose homeostasis is primarily maintained through bile acid metabolism. Proper bile acid formation is vital for nutrient and fat-soluble vitamin absorption and emulsification of lipids. Synthesis of bile acids occurs through two main pathways, both of which rely on 3-hydroxy-5-C27 steroid oxidoreductase (HSD3B7) to begin epimerization of the 3β hydroxyl of cholesterol into its active 3α conformation. In this sequence HSD3B7 catalyzes the dehydrogenation of the 3β-hydroxy group followed by isomerization of the Δ5-cholestene-3-one. These reactions are some of the many steps that transform cholesterol for either storage or secretion. HSD3B7 has distinct activity from other 3β-HSD family members leaving significant gaps in our understanding of its mode of catalysis and substrate specificity. Additionally, the role of HSD3B7 in health and disease positions it as a metabolic vulnerability that could be harnessed as a therapeutic target. To this end, we evaluated the mechanism of HSD3B7 catalysis and reveal that HSD3B7 displays activity towards diverse 7α-hydroxylated oxysterols. HSD3B7 retains its catalytic efficiency towards these substrates, suggesting that its substrate binding pocket can withstand changes in polarity upon alterations to this hydrocarbon tail. Experiments aimed at determining substrate order are consistent with HSD3B7 catalyzing a sequential ordered bi bi reaction mechanism with the binding of NAD+ followed by 7α-hydroxycholesterol to form a central complex. HSD3B7 bifunctional activity is dependent on membrane localization through a putative membrane-associated helix giving insight into potential regulation of enzyme activity. We found strong binding of the NADH product thought to activate the isomerization reaction. Homology models of HSD3B7 reveal a potential substrate pocket that allows for oxysterol binding and mutagenesis was utilized to support this model. Together these studies offer an understanding of substrate specificity and kinetic mechanism of HSD3B7 which can be exploited for future drug development.

Synthesis and Characterization of Lauha Bhasma

The preparation of ayurvedic bhasma is particularly challenging, as mass production in modern facilities often lacks the standardized equipment needed to ensure consistent quality, leading to concerns about toxic elements like mercury and arsenic in the final products. Addressing these concerns necessitates the standardization of the synthesis process through the implementation of stringent quality control measures at every stage of preparation. This study is dedicated to the synthesis and comprehensive characterization of lauha (iron) bhasma, employing both traditional methodologies and advanced analytical techniques. The synthesis process began with samanya shodhana (general purification), followed by vishesh shodhana (special purification) and marana (incineration) The resultant product then underwent amrutikaran, involving heating with aloe vera extract at an elevated temperature of 750°C.The synthesized lauha bhasma was meticulously characterized using a combination of classical Ayurvedic techniques and modern analytical methods, including Fourier Transform Infrared Spectroscopy (FTIR), Atomic Absorption Spectroscopy (AAS), X-ray Diffraction (XRD), Brunauer-Emmett-Teller (BET) surface analysis, Scanning Electron Microscopy (SEM), Particle Size Distribution (PSD), and Energy Dispersive X-ray (EDX) analysis. The final product, post-Amrutikaran, successfully passed all traditional Ayurvedic evaluations, affirming the proper formation of bhasma. XRD analysis revealed the formation of rhombohedral α-Fe₂O₃ with only trace amounts of free iron, indicating high purity. SEM and PSD analyses demonstrated the creation of nanosized particles ranging from 50 to 200 nm, complemented by a specific surface area of 12.55 m²/g as determined by BET studies. Crucially, EDX analysis confirmed that the amrutikaran process effectively eliminated mercury from the bhasma, ensuring its safety and compliance with stringent quality standards.

F-BAR proteins CIP4 and FBP17 function in cortical neuron radial migration and process outgrowth.

During embryonic development, radial migration of newly born cortical neurons is a complex process that underlies the proper formation of the neocortex, the outermost layers of neurons in the brain. Disruptions in radial migration results in profound effects on cognitive function and can lead to devastating developmental disabilities. To better understand this critical process in brain development we examined two members of the F-BAR family of membrane bending proteins, CIP4 and FBP17, which are present in the developing brain. We demonstrate that intracellular concentrations of these proteins must be tightly regulated. Increasing or decreasing levels of either protein has profound effects on neuronal morphology and proper radial migration, suggesting they are key players in cortical development.

Geranylgeranyl diphosphate synthase inhibition impairs osteoclast differentiation, morphology and resorptive activity

Abstract Nitrogen bisphosphonates (NBPs), such as zoledronic acid, target the enzyme farnesyl diphosphate synthase (FDPS) in the isoprenoid biosynthetic pathway (IBP), and are the frontline treatment for osteolytic bone diseases. The strong affinity of these agents for bone limits their distribution out of the skeleton. Geranylgeranyl diphosphate synthase (GGDPS) is directly downstream to FDPS in the IBP and novel GGDPS inhibitors such as RAM2061 have been shown to have key drug-like features including prolonged half-life, metabolic stability, and systemic distribution. Furthermore, RAM2061 exerts anti-neoplastic benefits in mouse models of multiple myeloma and Ewing sarcoma. Therefore, we are interested in determining the potential impact of RAM2061 on osteoclast biology and bone remodeling. Studies utilizing undifferentiated RAW264.7 cells demonstrated that treatment with RAM2061 depletes cells of GGPP, impairs protein geranylgeranylation and induces markers of the unfolded protein response pathway and apoptosis. Differentiation of RAW264.7 cells to mature osteoclasts is disrupted by RAM2061, resulting in decreased numbers of mature osteoclasts, altered morphology and decreased tartrate resistant acid phosphatase activity. Treatment of fully differentiated RAW264.7 cells with RAM2061 led to decreased resorptive activity. Confocal microscopy studies revealed that RAM2061 disrupts Cdc42 localization, inhibiting proper actin ring formation in osteoclasts. No significant impact on bone turnover markers or bone histomorphology was observed following a 3-week treatment of CD-1 mice with RAM2061, although decreased numbers of osteoclasts were observed. Liquid chromatography–tandem mass spectrometry studies confirmed accumulation of RAM2061 in bone from the in vivo studies as well as hydroxyapatite binding in vitro. In conclusion, these studies are the first to demonstrate the anti-osteoclastic activity of GGDPS inhibitor treatment and support future studies exploring the therapeutic benefit of this novel therapy in the setting of pathological bone remodeling.

Human formin FHOD3-mediated actin elongation is required for sarcomere integrity in cardiomyocytes.

Contractility and cell motility depend on accurately controlled assembly of the actin cytoskeleton. Formins are a large group of actin assembly proteins that nucleate new actin filaments and act as elongation factors. Some formins may cap filaments, instead of elongating them, and others are known to sever or bundle filaments. The Formin HOmology Domain-containing protein (FHOD)-family of formins is critical to the formation of the fundamental contractile unit in muscle, the sarcomere. Specifically, mammalian FHOD3L plays an essential role in cardiomyocytes. Despite our knowledge of FHOD3L's importance in cardiomyocytes, its biochemical and cellular activities remain poorly understood. It has been proposed that FHOD-family formins act by capping and bundling, as opposed to assembling new filaments. Here, we demonstrate that FHOD3L nucleates actin and rapidly but briefly elongates filaments after temporarily pausing elongation, in vitro . We designed function-separating mutants that enabled us to distinguish which biochemical roles are req`uired in the cell. We found that human FHOD3L's elongation activity, but not its nucleation, capping, or bundling activity, is necessary for proper sarcomere formation and contractile function in neonatal rat ventricular myocytes. The results of this work provide new insight into the mechanisms by which formins build specific structures and will contribute to knowledge regarding how cardiomyopathies arise from defects in sarcomere formation and maintenance.

Poly(A)-Specific Ribonuclease Deficiency Leads to Deregulated Expression of Genes Involved in Sex Determination and Gonadal Maturation in Zebrafish

Abstract Background Deadenylation, the process of removal of poly (A) tail of messenger ribonucleic acids (mRNAs), is a rate-limiting step in mRNA stability, and poly(A)-specific ribonuclease (PARN) is the most important exonuclease involved in this process. Besides mRNA stability, PARN is also involved in several other processes including telomere maintenance, noncoding RNA maturation, ribosome biogenesis, and TP53 function. Previously, we have shown that zebrafish PARN null mutants are viable and fertile but turn out to only develop into males, indicating a role in oogenesis. The present study was focused on analyzing the expression of genes involved in sex determination and gonadal development in PARN mutant zebrafish. Materials and Methods Total RNA was extracted and quantitative real-time polymerase chain reaction was performed to determine the expression level of genes involved in gonad development in PARN mutant embryos (4 days postfertilization [dpf]) and adults (120 dpf) in comparison to their wild-type siblings. The expression levels were estimated by the ΔΔCT relative quantification method. Results At 4 dpf, the expression of germ cell-specific genes did not show any significant difference in the null mutants compared to the heterozygous and their wild-type siblings, suggesting no effect on germ cell differentiation due to the loss of PARN. However, the majority of the ovary-associated genes analyzed showed an increased expression in PARN null and heterozygous mutants compared to the wild-type siblings. Intriguingly, the expression of testis-associated genes showed decreased expression in the mutants compared to their wild-type siblings at 4 dpf. In adult stages, as expected, the expression of genes that jointly regulate the proper formation and function of ovaries and testes showed decreased expression in PARN null mutants. Interestingly, the expression of genes involved in the differentiation of testes, despite showing a decreased expression in the mutants, was comparable between the null and heterozygous mutants. Conclusion Taken together, these results suggest that the loss of PARN does not affect germ cell differentiation but affects the sexual differentiation that happens at later stages of development, particularly the process of oogenesis, in zebrafish.

Brassinosteroid signaling represses ZINC FINGER PROTEIN11 to regulate ovule development in Arabidopsis.

Brassinosteroid (BR) signaling and the C-class MADS-box gene AGAMOUS (AG) play important roles in ovule development in Arabidopsis (Arabidopsis thaliana). However, how BR signaling integrates with AG functions to control the female reproductive process remains elusive. Here, we showed that the regulatory role of BR signaling in proper ovule development is mediated by the transcriptional repressor gene ZINC FINGER PROTEIN 11 (ZFP11), which is a direct target of AG. ZFP11 expression initiates from the placenta upon AG induction and becomes prominent in the funiculus of ovule primordia. Plants harboring zfp11 mutations showed reduced placental length with decreased ovule numbers and some aborted ovules. During ovule development, the transcription factor BRASSINAZOLE-RESISTANT 1 (BZR1), which functions downstream of BR signaling, inhibits ZFP11 expression in the chalaza and nucellus. Weakened BR signaling leads to stunted integuments in ovules, resulting from the direct repression of INNER NO OUTER (INO) and WUSCHEL (WUS) by extended ZFP11 expression in the chalaza and nucellus, respectively. In addition, the zfp11 mutant shows reduced sensitivity to BR biosynthesis inhibitors and can rescue outer integument defects in brassinosteroid insensitive 1 (bri1) mutants. Thus, the precise spatial regulation of ZFP11, which is activated by AG in the placenta and suppressed by BR signaling in the central and distal regions of ovules, is essential for ensuring sufficient ovule numbers and proper ovule formation.

Nuclear deformability facilitates apical nuclear migration in the developing zebrafish retina.

Nuclear positioning is a crucial aspect of cell and developmental biology. One example is the apical movement of nuclei in neuroepithelia before mitosis, which is essential for proper tissue formation. While the cytoskeletal mechanisms that drive nuclei to the apical side have been explored, the influence of nuclear properties on apical nuclear migration is less understood. Nuclear properties, such as deformability, can be linked to lamin A/C expression levels, as shown in various invitro studies. Interestingly, many nuclei in early development, including neuroepithelial nuclei, express only low levels of lamin A/C. Therefore, we investigated whether increased lamin A expression in the densely packed zebrafish retinal neuroepithelium affects nuclear deformability and, consequently, migration phenomena. We found that overexpressing lamin A in retinal nuclei increases nuclear stiffness, which in turn indeed impairs apical nuclear migration. Interestingly, nuclei that do not overexpress lamin A but are embedded in a stiffer lamin A-overexpressing environment also exhibit impaired apical nuclear migration, indicating that these effects can be cell non-autonomous. Additionally, in the less crowded hindbrain neuroepithelium, only minor effects on apical nuclear migration are observed. Together, this suggests that the material properties of the nucleus influence nuclear movements in a tissue-dependent manner.

Experimental Verification of Inter Relation between Fowler–Nordheim and Millikan–Lauritsen Plot in Chemically Synthesized Zinc Oxide System

AbstractCold cathode emission or cold field emission (CFE) is a purely quantum mechanical phenomenon and a phenomenon of wonder. The exact science behind the observed current (I)–voltage (V) is yet to be pin pointed. For instance, a good cold emitter is very reasonably supposed to have low work function and good conductivity whereas a carbon allotropes like diamonds have just the reverse in both the cases, i.e., it is insulating in nature having very wide band gap as well as high work function yet it is considered to be an efficient field emitter. Since early of 20th century, till its middle a number of groups have suggested different equations or relations that can adequately describe the experimental CFE I–V characteristics adequately. Although they all fundamentally follow an exponential law, but so far, the relation suggests by Fowler and Nordheim (F–N) is the most accepted one. However, there is another relationship suggested by Millikan and Lauritsen (M–L) which is in spite of being reasonable not so common now a day to use. This work revisits different popular approaches for analyzing cold emission data. With this aim, the experimental CFE data obtained for chemically synthesized zinc oxide nanorods are chosen. The proper phase formation of ZnO is confirmed by XRD study whereas FESEM shows the rod like morphology. EDX confirms the proper stoichiometric ratio for the sample. After detail analysis it is confirmed that the theoretically proposed relation between F–N and M–L experimentally holds good as well and thus it would not be wrong to analyze the CFE data by simple M–L theory.

Silver Oxide Nanoparticle Decorated Carbon Nanotube as Efficient Electron Gun

AbstractAlthough there have been numerous great field emission reports of pure and hybrid carbon nanotubes (CNTs) with ultra‐low turn‐on field and ultra‐high emission stability, practically all of the reports indicate concern about CNT manufacture on a large scale. This is due to the fact that CNT experiments require high pressure, temperature, metal catalysis, and an inert environment, and even after meeting all of these perfect conditions, the yield is quite low. Furthermore, as CNT is relatively inert in nature, it is nearly hard to make it reactive with any other metal without adequate functionalization. Keeping this in mind, this work reports the synthesis of CNT in amorphous form by a simple low‐temperature solid‐state reaction between ammonium chloride and ferrocene. The as‐synthesized CNT is further functionalized by silver oxide nanoparticle without additional functionalization. X‐ray diffraction (XRD) confirms the proper phase formation as well as the successful functionalization of the pure and hybrid sample, electron microscopic images confirm the successful functionalization of the as‐prepared CNT whereas Fourier transformed infrared (FTIR) spectroscopic analysis gives the ideas about different bonding present in all the samples. It has been found that the hybrid sample gives much better field emission performance compare to the pure CNT with betterment in both turn‐on field and enhancement factor more than 100%. The betterment is believed to be due to the favorable band bending, larger number of emission sites, and sharp curvature of the silver particles.

Complex sporulation-specific expression of transcription termination factor Rho highlights its involvement in Bacillus subtilis cell differentiation

Termination factor Rho, responsible for the main factor-dependent pathway of transcription termination and the major inhibitor of antisense transcription, is an emerging regulator of various physiological processes in microorganisms. In Gram-positive bacterium Bacillus subtilis, Rho is involved in the control of cell adaptation to starvation and, in particular, in the control of sporulation, a complex differentiation program leading to formation of a highly resistant dormant spore. While the initiation of sporulation requires a decrease in Rho protein levels during the transition to stationary phase, the mechanisms regulating the expression of rho gene throughout the cell cycle remain largely unknown. Here we show that a drop in the activity of the vegetative SigA-dependent rho promoter causes the inhibition of rho expression in stationary phase. However, after the initiation of sporulation, rho gene is specifically reactivated in two compartments of the sporulating cell using distinct mechanisms. In the mother cell, rho expression occurs by read-through transcription initiated at the SigH-dependent promoter of the distal spo0F gene. In the forespore, rho gene is transcribed from the intrinsic promoter recognized by the alternative sigma factor SigF. These regulatory elements ensure the activity of Rho during sporulation, which appears important for the proper formation of spores. We provide experimental evidence that disruption of the spatiotemporal expression of rho during sporulation affects the resistance properties of spores, their morphology, and the ability to return to vegetative growth under favorable growth conditions.

Fmo5 plays a sex-specific role in goblet cell maturation and mucus barrier formation.

The intestine plays a key role in metabolism, nutrient and water absorption, and provides both physical and immunological defense against dietary and luminal antigens. The protective mucosal lining in the intestine is a critical component of intestinal barrier that when compromised, can lead to increased permeability, a defining characteristic of inflammatory bowel disease (IBD), among other intestinal diseases. Here, we define a new role for the flavin-containing monooxygenase (FMO) family of enzymes in maintaining a healthy intestinal epithelium. Using Caenorhabditis elegans we measure intestinal barrier function, actin expression, and intestinal damage response. In mice, we utilize an intestine-specific, tamoxifen- inducible knockout model of the mammalian homolog of Cefmo-2 , Fmo5, and assess histology, mucus barrier thickness, and goblet cell physiology. We also treat mice with the ER chaperone Tauroursodeoxycholic acid (TUDCA). In nematodes, we find Cefmo-2 is necessary and sufficient for intestinal barrier function, intestinal actin expression, and is induced by intestinal damage. In mice, we find striking changes to the intestine within two weeks following Fmo5 disruption. Alterations include sex-dependent changes in colon epithelial histology, goblet cell localization, and mucus barrier formation. These changes are significantly more severe in female mice, mirroring differences observed in IBD patients. Furthermore, we find increased protein folding stress in Fmo5 knockout animals and successfully rescue the severe female phenotype with addition of a chemical ER chaperone. Together, our results identify a highly conserved and novel role for Fmo5 in the mammalian intestine and support a key role for Fmo5 in maintenance of ER/protein homeostasis and proper mucus barrier formation.

EFFICIENCY OF MONETARY POLICY IMPLEMENTATION AS A BASIS FOR CENTRAL BANK STABILISATION POLICY UNDER MARTIAL LAW (UKRAINIAN AND ISRAELI PRACTICES)

The purpose of the paper is to summarise and present the anti-crisis practices of a central bank during martial law in the country, based on the experience of the National Bank of Ukraine and the Bank of Israel. The research methodology is based on an analysis of reports, guidelines, statistical data, scientific articles, legislation bases, and other relevant materials. One of the methodological aspects of this study is a comparison of the knowledge acquired about the regulations implemented by the two central banks after the introduction of martial law in the countries. The objective is to identify potential lessons learned for the banking regulations of Ukraine and the State of Israel. The results of the study show that the practical implementation of stabilisation measures by central banks is crucial for achieving financial stability of the state both during and after wartime, as well as the ability to predict possible deepening of crises and minimise their consequences. The tools and methods used by these central banks differ. In particular, the NBU's main monetary policy instrument was foreign exchange interventions, while the BoI actively used the key policy rate. The proper formation of international currency reserves and the possibility of using them during a war-related crisis is critical for both countries. This fact confirms that crisis management has different types of scenarios. Each anti-crisis scenario is unique. This paper highlights the practical need for interaction between monetary and macroprudential policies of the central bank in wartime. It demonstrates various combinations of methods and instruments of the central bank's monetary policy. This study also shows the interdependence of the economies of these two countries. Practical implementation. This analysis provides insight into the anti-crisis activities of central banks during unpredictable periods in a country's life, namely, during martial law. At the present stage, banking systems do not often face the challenges of war. Therefore, studying each case is important for improving theoretical knowledge and deepening practical research. Value / Originality. The author of the study collected the experience and practices of stabilisation activities of the central banks of Ukraine and Israel during the war.

Smad1/5 is acetylated in the dorsal aortae of the mouse embryo before the onset of blood flow, driving early arterial gene expression.

During embryonic development, arteriovenous (AV) differentiation ensures proper blood vessel formation and maturation. Defects in arterial or venous identity cause inappropriate fusion of vessels, resulting in atypical shunts, so-called arteriovenous malformations (AVM). Currently, the mechanism behind AVM formation remains unclear and treatment options are fairly limited. Mammalian AV differentiation is initiated before the onset of blood flow in the embryo; however, this pre-flow mechanism is poorly understood. Here, we aimed to unravel the role of Smad1/5 signalling in pre-flow arterial identity, and in the process uncovered an unexpected control mechanism of Smad1/5 signalling. We establish that despite Notch1 being expressed in the pre-flow mouse embryo, it is not activated, nor is it necessary for the expression of the earliest arterial genes in the dorsal aortae (i.e., Hey1 and Gja4). Furthermore, interrupting blood flow by using the Ncx1 KO model completely prevents the activation of Notch1 signalling, suggesting a strong role of shear stress in maintaining arterial identity. We demonstrate that early expression of Hey1 and Gja4 requires SMAD1/5 signalling. Using embryo cultures, we show that Smad1/5 signalling is activated through the Alk1/Alk5/TGFβR2 receptor complex, with TGFβ1 as a necessary ligand. Furthermore, our findings demonstrate that early arterial gene expression requires the acetylation of Smad1/5 proteins, rendering them more sensitive to TGFβ1 stimulation. Blocking acetyl-CoA production prevents pre-flow arterial expression of Hey1 and Gja4, while stabilizing acetylation rescues their expression. Our findings highlight the importance of the acetyl-CoA production in the cell and provide a novel control mechanism of Smad1/5 signalling involving protein acetylation. As disturbed canonical Smad1/5 signalling is involved in several vascular conditions, our results offer new insights in treatment options for circumventing canonical Smad1/5 signalling.

Drivers of vessel progenitor fate define intermediate mesoderm dimensions by inhibiting kidney progenitor specification

Proper organ formation depends on the precise delineation of organ territories containing defined numbers of progenitor cells. Kidney progenitors reside in bilateral stripes of posterior mesoderm that are referred to as the intermediate mesoderm (IM). Previously, we showed that the transcription factors Hand2 and Osr1 act to strike a balance between the specification of the kidney progenitors in the IM and the vessel progenitors in the laterally adjacent territory. Recently, the transcription factor Npas4l – an early and essential driver of vessel and blood progenitor formation – was shown to inhibit kidney development. Here we demonstrate how kidney progenitor specification is coordinated by hand2, osr1, and npas4l. We find that npas4l and the IM marker pax2a are transiently co-expressed in the posterior lateral mesoderm, and npas4l is necessary to inhibit IM formation. Consistent with the expression of npas4l flanking the medial and lateral sides of the IM, our findings suggest roles for npas4l in defining the IM boundaries at each of these borders. At the lateral IM border, hand2 promotes and osr1 inhibits the formation of npas4l-expressing lateral vessel progenitors, and hand2 requires npas4l to inhibit IM formation and to promote vessel formation. Meanwhile, npas4l appears to have an additional role in suppressing IM fate at the medial border: npas4l loss-of-function enhances hand2 mutant IM defects and results in excess IM generated outside of the lateral hand2-expressing territory. Together, our findings reveal that establishment of the medial and lateral boundaries of the IM requires inhibition of kidney progenitor specification by the neighboring drivers of vessel progenitor fate.

Reselling or agency selling? The impact of live-streaming on selling formats

PurposeChoosing the proper selling format for online retail has long been a critical issue for many platforms to consider, whereas the emergence and popularity of live-streaming have had a massive impact on the platform's business. As a result, selecting the suitable operating strategy for the live channel has become another critical issue for platforms. In such a context, what will be the impact of live-streaming on selling formats?Design/methodology/approachIn order to explore these issues, we identified two selling formats (wholesale reselling or agency selling) as well as two operating strategies (introduce or discard). Thereby, four channel-structures are constructed, namely the reselling-discard model (WN), the reselling-introduce model (WL), the agency-discard model (AN), and the agency-introduce model (AL). We comprehensively compare how different structures affect stakeholders' interests, consumer surplus, and social welfare through equilibrium analyses.FindingsThese results help clarify the impact of critical factors (e.g. self-effort attribute, cross-effort attribute, and commission ratio) on the choice of models. We find that regardless of the selling agreement between the manufacturer and the platform, the introduction of a live store is necessary; specifically, when the commission ratio is high, the platform's optimal decision is first to sign an agency agreement and then apply live selling (AL); conversely, when the commission ratio is low, the platform's optimal strategy is first to enable the live channel and then to select the reselling format (WL), together, this also reveals, from a theoretical perspective.Originality/valueOur study includes the dual analysis of selling formats and channel operations, considering the inherent dual attributes of service efforts and the external competitive environment.

Multiple guidance mechanisms control axon growth to generate precise T-shaped bifurcation during dorsal funiculus development in the spinal cord.

The dorsal funiculus in the spinal cord relays somatosensory information to the brain. It is made of T-shaped bifurcation of dorsal root ganglion (DRG) sensory axons. Our previous study has shown that Slit signaling is required for proper guidance during bifurcation, but loss of Slit does not affect all DRG axons. Here, we examined the role of the extracellular molecule Netrin-1 (Ntn1). Using wholemount staining with tissue clearing, we showed that mice lacking Ntn1 had axons escaping from the dorsal funiculus at the time of bifurcation. Genetic labeling confirmed that these misprojecting axons come from DRG neurons. Single axon analysis showed that loss of Ntn1 did not affect bifurcation but rather altered turning angles. To distinguish their guidance functions, we examined mice with triple deletion of Ntn1, Slit1, and Slit2 and found a completely disorganized dorsal funiculus. Comparing mice with different genotypes using immunolabeling and single axon tracing revealed additive guidance errors, demonstrating the independent roles of Ntn1 and Slit. Moreover, the same defects were observed in embryos lacking their cognate receptors. These in vivo studies thus demonstrate the presence of multi-factorial guidance mechanisms that ensure proper formation of a common branched axonal structure during spinal cord development.

Sustainable and environmentally friendly synthesis of ZnO semiconductor nanoparticles from Bauhinia forficata leaves extract and the study of their photocatalytic and antibacterial activity

The growing need to obtain nanomaterials has resulted in a trend to avoid environmentally harmful methodologies involving chemicals that damage ecosystems and health by searching for natural reducers and stabilizers with zero polluting impact. In this research, zinc oxide nanoparticles were synthesized following an environmentally friendly synthesis methodology by using a natural extract of Bauhinia forficata that, thanks to its phytochemical composition rich in organic molecules such as polyphenols and flavonoids, allows the correct formation of nanoparticles by acting as stabilizers. The results of the characterizations show the proper formation of the nanoparticles and a direct relationship between the percentage used to obtain the nanoparticles and their properties. The results obtained from XRD show a hexagonal zincite shape and crystallite sizes in the range of 22.25–31.05 nm. The appearance of a signal at ∼400 cm−1 obtained from FTIR confirms the formation of the Zn-O- bond. Subsequently, the removal of different organic dyes from polluted water was analyzed using zinc oxide semiconductor nanoparticles as photocatalysts under ultraviolet light. The results show outstanding degradation of the dyes, being able to remove at least 98.0 %, 84.4 %, 94.64 %, 95.5 %, and 98.2 % for methylene blue, methyl orange, rhodamine-B, Congo red, and malachite green, respectively. Additionally, the antibacterial effect of the obtained materials against multiple pathogenic bacteria was studied. All the synthesized nanoparticle samples showed an antibacterial effect, even at low concentrations for all the analyzed pathogens. The results show the feasibility of using Bauhinia forficata to obtain zinc oxide nanoparticles and its multiple applications due to its improved properties.