TOM-1/tomosyn acts with the UNC-6/netrin receptor UNC-5 to inhibit growth cone protrusion in Caenorhabditis elegans

In the polarity/protrusion model of growth cone repulsion from UNC-6/netrin, UNC-6 first polarizes the growth cone of the VD motor neuron axon via the UNC-5 receptor, and then regulates protrusion asymmetrically across the growth cone based on this polarity. UNC-6 stimulates protrusion dorsally through the UNC-40/DCC receptor, and inhibits protrusion ventrally through UNC-5, resulting in net dorsal growth. Previous studies showed that UNC-5 inhibits growth cone protrusion via the flavin monooxygenases and potential destabilization of F-actin, and via UNC-33/CRMP and restriction of microtubule plus-end entry into the growth cone. We show that UNC-5 inhibits protrusion through a third mechanism involving TOM-1/tomosyn. A short isoform of TOM-1 inhibited protrusion downstream of UNC-5, and a long isoform had a pro-protrusive role. TOM-1/tomosyn inhibits formation of the SNARE complex. We show that UNC-64/syntaxin is required for growth cone protrusion, consistent with a role of TOM-1 in inhibiting vesicle fusion. Our results are consistent with a model whereby UNC-5 utilizes TOM-1 to inhibit vesicle fusion, resulting in inhibited growth cone protrusion, possibly by preventing the growth cone plasma membrane addition required for protrusion

Analyzing indications for caesarean delivery in a tertiary care facility in India by Robsons Ten Group Classification System: journey to reduce maternal mortality-audit caesarean rates: a prospective observational design

Background: Rising caesarean rates pose a challenge to obstetricians, the healthcare system, and the national economy. High rate of caesarean without clear evidence of a decrease in maternal and neonatal morbidity is matter of concern. The era of impatient obstetricians, and caesareans on demand are major contributing factors. The purpose of this study is to validateTGCS classification for indications of caesarean. This would help to audit and streamline the indications of caesarean. Standardization of indications is the need of the hour. Learning from what has happened in background of local situations is the main aim of this work. Methods: In a prospective observational design, 1140 women who underwent caesarean for varied indications in C R Gardi Hospital Ujjain were recruited. Patients were classified according to Robson’s Ten Group Classification System. Every woman was observed for post-cesarean morbidities like wound dehiscence, anemia, postpartum hemorrhage, and puerperal sepsis. Neonates were observed for NICU admission, low birth weight, prematurity, respiratory distress syndrome, meconium aspiration syndrome, and death. Chi- Square and student t test were used for analysis. Results: 45.8% of women were of group 5. Modifiable indications were 60.2% in the primary caesarean of group 5. PPH, puerperal sepsis, PNC anemia, wound dehiscence, DVT, rupture uterus and NICU admission, respiratory distress syndrome of neonates were significantly high in group 5 ( p= less than 0.05). Conclusions: Out of all caesarean 45.8% are second caesarean for previous one caesarean. PPH, puerperal sepsis, wound dehiscence and PNC anemia are significantly high in group 5

STANDARDIZATION AND COMPARATIVE EVALUATION OF AYURVEDIC POLYHERBAL GHRITA FORMULATION WITH MODERN EXTRACTION TECHNIQUE FOR EXTRACTION EFFICIENCY USING REVERSED PHASE-HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY

Objective: Sarasvata ghrita (SG) is a polyherbal formulation in Ayurvedic Indian medicinal system, in which ghee is the main ingredient used for extraction. Ghee is 100% lipid, thus its regular use is limited, and there is a lack of quality control profile of SG. Thus, the objective of the study is to develop quality control method for standardization of SG and to analyze manufacturing process of SG and an effective method of extraction to extract phytoconstituents from herbs used in SG to overcome the limitation of SG.Methods: SG was processed as per the traditional method, whereas ethanolic extract (EE) and hydroalcoholic extract (HAE) were obtained by the conventional method and lipid-based extract (LE) was prepared by modern extraction method. SG and all extracts were standardized using newly developed high-performance liquid chromatography (LC) with respect to bebeerine, piperine, 6-shogaol, β-asarone, and chebulinic acid. All extracts were analyzed for pesticides, and heavy metal content by LC/mass spectrometry (MS/MS) and inductively coupled plasma/MS, respectively, screened for total polyphenols and flavonoids content, in vitro antioxidant potential, and for assessing its stability over time.Results: The better extraction was observed with maceration extraction using ethanol compared to ayurvedic method and LE method. All extracts were found to have a negligible amount of pesticide and heavy metals and found to be stable for 6 months under accelerated storage condition. Better polyphenols and flavonoid content and in vitro antioxidant potential were resulted in EE.Conclusion: EE showed a better potential in comparison with SG and LE

Ispitivanje vosku sličnih svojstava ibuprofena kao veziva

The study investigates ibuprofen with wax-like properties as a multifunctional agent (as an active component and as a melt binder). Binding efficiency was compared with granules prepared by wet granulation using polyvinylpyrollidone (PVP K-30) as a binder for micromeritic, physical and mechanical properties such as angle of repose, particle size distribution Carr’s index, Hausner’s ratio, crushing strength, percentage fines, Heckel plot study and tensile strength. To check the binder distribution during melt granulation, content uniformity was determined. To check changes in the physical state of ibuprofen, XRPD, DSC and FTIR studies were carried out. The present study underlines the fact that ibuprofen may be adopted as a binder in ibuprofen formulations using the melt granulation techniqueSvrha rada je ispitivanje vosku sličnih svojstava ibuprofena, tvari s višeznačnom funkcijom (ljekovita tvar i vezivo pri granulaciji). Vezivna svojstva uspoređivana su s granulama pripravljenim vlažnom granulacijom s polivinilpirolidonom (PVP K-30) kao vezivom, ispitivanjem mikrometričkih, fizikalnih i mehaničkih svojstava kao što su sipkost materijala, Carrov indeks distribucije veličine čestica, Hausnerov parameter, otpornost na vlak. Da bi se ispitala distribucija veziva tijekom granulacije taljenjem određivana je ujednačenost sadržaja. Za praćenje promjena fizikalnih svojstava ibuprofena snimljeni su XRPD, DSC, FTIR spektri. Istraživanja ukazuju da se ibuprofen može koristiti kao vezivo u ljekovitim pripravcima ibuprofena u kojima se primjenjuje granulacija taljenjem

Ispitivanje vosku sličnih svojstava ibuprofena kao veziva

The study investigates ibuprofen with wax-like properties as a multifunctional agent (as an active component and as a melt binder). Binding efficiency was compared with granules prepared by wet granulation using polyvinylpyrollidone (PVP K-30) as a binder for micromeritic, physical and mechanical properties such as angle of repose, particle size distribution Carr’s index, Hausner’s ratio, crushing strength, percentage fines, Heckel plot study and tensile strength. To check the binder distribution during melt granulation, content uniformity was determined. To check changes in the physical state of ibuprofen, XRPD, DSC and FTIR studies were carried out. The present study underlines the fact that ibuprofen may be adopted as a binder in ibuprofen formulations using the melt granulation techniqueSvrha rada je ispitivanje vosku sličnih svojstava ibuprofena, tvari s višeznačnom funkcijom (ljekovita tvar i vezivo pri granulaciji). Vezivna svojstva uspoređivana su s granulama pripravljenim vlažnom granulacijom s polivinilpirolidonom (PVP K-30) kao vezivom, ispitivanjem mikrometričkih, fizikalnih i mehaničkih svojstava kao što su sipkost materijala, Carrov indeks distribucije veličine čestica, Hausnerov parameter, otpornost na vlak. Da bi se ispitala distribucija veziva tijekom granulacije taljenjem određivana je ujednačenost sadržaja. Za praćenje promjena fizikalnih svojstava ibuprofena snimljeni su XRPD, DSC, FTIR spektri. Istraživanja ukazuju da se ibuprofen može koristiti kao vezivo u ljekovitim pripravcima ibuprofena u kojima se primjenjuje granulacija taljenjem

A short isoform of the UNC-6/Netrin receptor UNC-5 is required for growth cone polarity and robust growth cone protrusion in Caenorhabditis elegans

Introduction: UNC-6/Netrin is a conserved bi-functional guidance cue which regulates dorsal-ventral axon guidance in C. elegans. In the Polarity/Protrusion model of UNC-6/Netrin mediated dorsal growth away from UNC-6/Netrin, The UNC-5 receptor first polarizes the VD growth cone such that filopodial protrusions are biased dorsally. Based on this polarity, the UNC-40/DCC receptor stimulates growth cone lamellipodial and filopodial protrusion dorsally. The UNC-5 receptor maintains dorsal polarity of protrusion, and inhibits growth cone protrusion ventrally, resulting in net dorsal growth cone advance.Methods: Growth cone imaging in mutants, combined with Cas9 genome editing and genetic analysis, were used to analyze the role of a novel short isoform on unc-5 in growth cone polarity and protrusion.Results: Work presented here demonstrates a novel role of a previously undescribed, conserved short isoform of UNC-5 (UNC-5B). UNC-5B lacks the cytoplasmic domains of UNC-5 long, including the DEATH domain, the UPA/DB domain, and most of the ZU5 domain. Mutations that specifically affect only the unc-5 long isoforms were hypomorphic, suggesting a role of unc-5B short. A mutation specifically affecting unc-5B caused loss of dorsal polarity of protrusion and reduced growth cone filopodial protrusion, the opposite of unc-5 long mutations. Transgenic expression of unc-5B partially rescued unc-5 axon guidance defects, and resulted in large growth cones. Tyrosine 482 (Y482) in the cytoplasmic juxtamembrane region has been shown to be important for UNC-5 function, and is present in both UNC-5 long and UNC-5B short. Results reported here show that Y482 is required for the function of UNC-5 long and for some functions of UNC-5B short. Finally, genetic interactions with unc-40 and unc-6 suggest that UNC-5B short acts in parallel to UNC-6/Netrin to ensure robust growth cone lamellipodial protrusion.Discussion: These results demonstrate a previously-undescribed role for the UNC-5B short isoform, which is required for dorsal polarity of growth cone filopodial protrusion and to stimulate growth cone protrusion, in contrast to the previously-described role of UNC-5 long in inhibiting growth cone protrusion

RAPD Analysis for Determination of Components in Herbal Medicine

In this study, the RAPD (Random Amplified Polymorphic DNA) technique was employed for determination of the components in an Ayurvedic herbal prescription, Rasayana Churna. One-hundred-and-twenty decamer oligonucleotide primers were screened in the RAPD analysis to identify three Ayurvedic medicines, dried stem of Tinospora cordifolia, dried fruit of Emblica officinalis and dried fruit of Tribulus terestris, the Ayurvedic prescription. Primer OPC-6 simultaneously generated three distinct amplicons, each specific to one component. The marker with 600 bp is specific to Tinospora cordifolia; the marker 500 bp is specific to Emblica officinalis and the remaining marker >1000 bp was present in Tribulus terestris. Presence of three herbal medicines was determined when RAPD reaction with OPC-6 was performed. The technique was proved to contribute to the identification of components in Ayurvedic herbal preparation and thus helping to serve as a complementary tool for quality control

Coupon scale Z-pinned IM7/8552 delamination tests under dynamic loading

Dynamic impact onto laminated composite structures can lead to large-scale delamination. This can be mitigated by the introduction of through-thickness reinforcement, such as z-pins. Here, mode I & II and mixed-mode delamination tests have been designed and conducted at high loading rate, for both unpinned and Z-pinned coupons to study the effect of rate of loading. It was found that the Z-pins were not effective in delaying the dynamic crack initiation or resisting the dynamic propagation of delaminations shorter than 5 mm. However, the further growth of cracks was substantially delayed by Z-pinning, especially for the pure mode I and mode I dominated failure modes. On the other hand, the effectiveness of Z-pins in shear tests was relatively modest. The mode I dominated delamination resistance of Z-pinned laminates was found to be sensitive to the loading rate