23,245 research outputs found
Data for 'Revisiting rough-wall turbulent boundary layers over sandgrain roughness'
No full textThis dataset presents the experimental data described in "Gul and Ganapathisubramani, Revisiting rough-wall turbulent boundary layers over sandgrain roughness, Journal of Fluid Mechanics, 2020”.</span
Investigating TRPM3 Modulation and Cyst Reversibility in Ex Vivo and Organoid Models of Autosomal Dominant Polycystic Kidney Disease (ADPKD)
No full textAutosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease, affecting approximately 1 in 1000 live births. It is characterised by multiple fluid-filled cysts in renal tubules. ADPKD is associated with mutations in the PKD1 and PKD2 genes, which encode the proteins polycystin 1 (PC1) and polycystin 2 (PC2). PC1 is a transmembrane protein that acts as a mechano-sensor, while PC2 is a non-selective cation channel that belongs to the transient receptor potential (TRP) superfamily. PC1 and PC2 form a heterodimer complex in the primary cilium, crucial for regulating intracellular calcium levels. Recent research suggests that TRPM3, another TRP family member, is necessary for PC2's ciliary function. Therefore, I analysed the impact of TRPM3 activators (nifedipine and CIM0216) and inhibitors (isosakuranetin, primidone, and diclofenac) on cyst formation in cultured E12.5 mouse kidneys which were exposed to various concentrations of forskolin, a compound known to induce cyst formation in kidney cultures. The results indicated that cyst formation occurred at lower forskolin concentrations in kidney rudiments treated with TRPM3 antagonists. In contrast, TRPM3 agonists significantly reduced cyst formation, especially at high forskolin concentrations, compared to kidneys treated with forskolin alone. Among the TRPM3 agonists tested, nifedipine—an FDA-approved antihypertensive drug—showed potential as a therapeutic for ADPKD.
Isosakuranetin was the TRPM3 antagonist that most significantly increased forskolin sensitivity. I generated a drug-induced PKD model by treating mouse kidney rudiments with isosakuranetin and forskolin to analyse cyst reversibility. Cysts in my PKD model originated from proximal tubules and showed disrupted apical-basal polarity. Upon isosakuranetin and forskolin withdrawal, cysts shrank and eventually disappeared with no detectable cell death.
I showed that siRNA-based downregulation was not a useful technique for designing a reversible cyst-forming organoid model, at least in my experimental conditions.
To test whether similar results in cyst reversibility could be achieved in mutant human systems, I developed a CRISPR/Cas13b-based reversible gene downregulation system for future studies. This tool has the potential for the analysis of cyst regression in human organoid studies by inducing cyst formation through controlled downregulation of PKD1 or PKD2 genes, followed by gene re-expression.
Overall, the study suggests that TRPM3 could be a viable target for ADPKD treatment, and nifedipine may be a promising therapeutic option. The findings also provide detailed findings into cyst regression in an early developmental stage. However, it should be noted that all results obtained in these studies were from ex vivo mouse kidney rudiments. To obtain more reliable results, the data here should be confirmed in human ADPKD models. In this context, nifedipine can be tested in ADPKD patient-derived organoids or PKD1 or PKD2 mutant human organoid models
Gul-i-bakawuli /
No full textA version by Nihal Cand Lahauri, originally published in Urdu under the title Mazhab-i ʻishq, of the Gul-i Bakāvalī, Izzatul̄lah's version of a tale in Hindi.Mode of access: Internet
Targeting TRPM3 As a Potential Therapeutic Approach for Autosomal Dominant Polycystic Kidney Disease
No full textAbstract
Cystic diseases, especially autosomal dominant polycystic kidney disease (ADPKD; incidence approx. 1/1000), are a leading cause of renal failure, caused by appearance and growth of renal cysts that can lead to renal failure in middle age. Most ADPKD cases are caused by mutations in PKD1 or PKD2, encoding polycystin-1 (PC1) and polycystin-2 (PC2). PC1 is a mechanosensor that controls PC2, a Ca2+-permeable cation channel that, by regulating cytoplasmic Ca2+, prevents adenylyl cyclase producing cyst-promoting concentrations of cAMP. In other systems, there is evidence for PC2 interacts with TRPM3. We therefore examined the effect of pharmacological activators and inhibitors of TRPM3 on cyst formation in cultured mouse kidney rudiments exposed to a range of concentrations of forskolin, a cAMP-elevating drug commonly used experimentally to induce cysts in cultured kidneys. We found that TRPM3 inhibitors (isosakuranetin, primidone, diclofenac) increased cyst formation, while TRPM3 activators (CIM0216 and nifedipine) greatly reduced cyst formation and reduced the sensitivity of kidneys to forskolin. These preclinical, in-vitro data suggest that TRPM3 may be a promising target in ADPKD management
GUL Herbaryumu'nun Ranunculaceae Familyası Envanteri
No full textÖzet: Bu çalışma, GUL Herbaryumu'nda bulunan Ranunculaceae familyası örneklerinin yeniden düzenlenmesi, internet sitesinde veri tabanı hazırlanması, teşhis edilmemiş örneklerin teşhis edilmesi, teşhislilerin mevcut literatür ışığında kontrol edilmesi esasına dayanmaktadır. Bu çalışma ile GUL Herbaryumu'nda Ranunculaceae familyasına bağlı 16 cins ve bu cinslere ait 132 takson belirlenmiştir. Bu taksonlardan 26'ısı Türkiye için endemiktir. Endemizm oranı ise % 19,6'dır. GUL'daki Ranunculaceae familyasının tür zenginliği yönünden ilk 5 sıradaki cinsleri: Ranunculus (62 takson), Delphinium (17 takson), Consolida (16 takson), Nigella (6 takson), Thalictrum (6 takson)'dur. Bunlardan; 17 takson LR, 9 takson VU, 3 takson EN ve 1 takson ise CR kategorisindedir.
Anahtar kelimeler: Ranunculaceae, GUL herbaryumu, envanter, biyolojik çeşitlilik, Isparta, Türkiye.
Ranunculaceae Family Inventory of Herbarium Gul
Abstract: This study is based on the rearrangement of Ranunculaceae family samples which are included in Herbarium GUL, the preparation of datebase in the website, the diagnosis of the samples which have not been diagnoised, checking the diagnosed ones according to present literature and the properties that don't comply with the definitions in the basic systematic works. With this study, 16 genara in Ranunculaceae family in Herbarium GUL and 132 taxa belong to these genara have been determined. 26 of these taxa are endemics for Türkiye and endemism ratio is % 19,6. The top 5 genera in term of kind abundance in Ranunculaceae family in Herbarium GUL are Ranunculus (62 taxa), Delphinium (17 taxa), Consolida (16 taxa), Nigella (6 taxa), Thalictrum (6 taxa). 17 taxa belong to LR category, 9 taxa belong to VU category, 3 taxa belong to EN category ve 1taxon belong to CR category.
Key words: Ranunculaceae, herbarium GUL, inventory, biodiversity, Isparta, Türkiye
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Transcription: Retelling of Limpi Kisar
No full textTranscription of Gul Nasreen reciting "Limpi Kisar," a popular story in the Hunza dialect of Burushaski. In this popular story Limpi Kisar was married to a woman, and she was stolen on their wedding day by an ogre. He travels up mountains to get his wife back. Transcription done in Burushaski with translations in English
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Barguunmo Ghar
No full textTranscription and translation of the recording of Gul Nasreen, a speaker of Hunza Burushaski, discussing the folk song of Barguun with other Burushaski speakers
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Interlinear-glossed text: Retelling of Limpi Kisar
No full textTranscription, translation and linguistic analysis of Gul Nasreen reciting "Limpi Kisar," a popular story in the Hunza dialect of Burushaski. In this popular story Limpi Kisar was married to a woman, and she was stolen on their wedding day by an ogre. He travels up mountains to get his wife back. Transcription done in Burushaski with translations and analysis in English
Women leaders in trade unions of Pakistan : stories of struggle and leadership
No full textFriedrich-Ebert-Stiftung, Pakistan Office ; author: Saba Gul Khattak ; illustrators Abdullah Shahid, Aiman Saleem, Areeban Shaukat Qureshi [und weitere
The avoidance of statutory benefits to employees by Hong Kong employers
No full textAuthor name used in this publication: Gul, Reza Jashen.Author name used in this publication: Sun, Sunny.2012-2013 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishedPublisher permissio
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