DD-1 / Palau Pharma - LARVOL DELTA

Biotransformation of doxycycline by Brevundimonas naejangsanensis and Sphingobacterium mizutaii strains. (PubMed, J Hazard Mater) - "Two bacterial strains, Brevundimonas naejangsanensis DD1 and Sphingobacterium mizutaii DD2, were isolated from chicken litter and characterized for their biotransformation capability of DC. While hydrolysis converted DC to its isomer or epimer, the two bacterial strains converted DC to various biotransformation products through a series of demethylation, dehydration, decarbonylation and deamination. Findings from the study can be used to better predict the fate of DC in the environment."

Journal

Cl and H coupling properties and subcellular localizations of wildtype and disease-associated variants of the voltage-gated Cl/H exchanger ClC-5. (PubMed, J Biol Chem) - "Dent disease 1 (DD1) is caused by mutations in the CLCN5 gene encoding a voltage-gated electrogenic nCl/H exchanger ClC-5...The ClC-5:R345W variant exhibited slightly higher Cl/H transport than ClC-5:S244L, but co-localized with early endosomes, suggesting decreased ClC-5:R345W membrane trafficking is perhaps in a fully functional form. The truncated ClC-5:Q629* variant displayed the lowest Cl/H exchange and was retained in the endoplasmic reticulum and cis-Golgi, but not in early endosomes, suggesting the nonsense mutation affects ClC-5 maturation and trafficking."

Journal • Nephrology • Renal Disease

Factors Associated with the Remission of Type 1 Diastolic Dysfunction after Dapagliflozin Treatment in Patients with Type 2 Diabetes. (PubMed, J Clin Med) - "Patients with a T2DM duration of less than eight years have the additional benefit of DD1 remission associated with dapagliflozin treatment beyond the conventional benefits such as improvements in glycemic control, cardiovascular, renal, and hepatic risk reductions. In patients with T2DM, the remission of DD1 was associated with decrease of liver stiffness."

Clinical • Journal • Cardiovascular • Congestive Heart Failure • Diabetes • Fibrosis • Heart Failure • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • Metabolic Disorders • Renal Disease • Type 2 Diabetes Mellitus

Guided endodontic treatment of multiple teeth with dentin dysplasia: a case report. (PubMed, Head Face Med) - "In patients with dentin dysplasia, conventional endodontic therapy is challenging. GET considerably facilitates the root canal treatment of teeth affected by dentin dysplasia."

Clinical • Journal • Dental Disorders • Periodontitis

Isolation and evaluation of the plant growth promoting rhizobacterium Bacillus methylotrophicus (DD-1) for growth enhancement of rice seedling. (PubMed, Arch Microbiol) - "Thus, the B. methylotrophicus DD-1 enhances plant growth promotion by multifarious growth promoting and root colonization traits, thereby augmenting potassium level in soil. Henceforth, the potential bacterium could be exploited for the development of biological fertilizer, leading towards sustainable agronomy."

Journal

Cl and H coupling properties and subcellular localizations of wildtype and disease-associated variants of the voltage-gated Cl/H exchanger ClC-5. (PubMed, J Biol Chem) - "Dent disease 1 (DD1) is caused by mutations in the CLCN5 gene encoding a voltage-gated electrogenic nCl/H exchanger ClC-5...The ClC-5:R345W variant exhibited slightly higher Cl/H transport than ClC-5:S244L, but co-localized with early endosomes, suggesting decreased ClC-5:R345W membrane trafficking is perhaps in a fully functional form. The truncated ClC-5:Q629* variant displayed the lowest Cl/H exchange and was retained in the endoplasmic reticulum and cis-Golgi, but not in early endosomes, suggesting the nonsense mutation affects ClC-5 maturation and trafficking."

Journal • Nephrology • Renal Disease

"Localized reentry captured and recorded on two bipole pairs DD1-4 (~50% of TCL within 1.5 cm)" (@DrRoderickTung)

Genetic Analyses in Dent Disease and Characterization of CLCN5 Mutations in Kidney Biopsies. (PubMed, Int J Mol Sci) - "Dent disease (DD), an X-linked renal tubulopathy, is mainly caused by loss-of-function mutations in CLCN5 (DD1) and OCRL genes...In four DD3 patients, WES revealed 12 potentially pathogenic variants in three novel genes (SLC17A1, SLC9A3, and PDZK1), and in three genes known to be associated with monogenic forms of renal proximal tubulopathies (SLC3A, LRP2, and CUBN). The supposed third Dent disease-causing gene was not discovered."

Journal • Nephrology

Dent disease: A window into calcium and phosphate transport. (PubMed, J Cell Mol Med) - "A potential role for NHE3 dysfunction in the DD1 phenotype has never been investigated, either in DD models or in patients with DD1, even though patients with DD1 exhibit renal sodium and potassium wasting, especially when exposed to even a low dose of thiazide diuretic. Thus, insights from the rare disease DD1 may inform possible underlying mechanisms for the phenotype of hypercalciuria and idiopathic calcium stones."

Journal • Review • Chronic Kidney Disease • Metabolic Disorders • Nephrology • Rare Diseases • Renal Calculi • Renal Disease • Urolithiasis

Structural and energetic basis for the inhibitory selectivity of both catalytic domains of dimeric HDAC6. (PubMed, J Biomol Struct Dyn) - "In addition, its structural and energetic behavior was explored with each one of the catalytic domains in the molecular recognition of six selective HDAC6 inhibitors, HPOB, CAY10603, Nexturastat, Rocilinostat, Tubacin and Tubastatin A for DD2, and with the so-called 9-peptide which is DD1-HDAC6 selective substrate. However, 9-peptide showed a higher affinity for DD1, which agrees with experimental reports elsewhere. Principal component analysis provided important information about the structural changes linked to the molecular recognition process, whereas per-residue decomposition analysis revealed the energetic contribution of the key residues in the molecular binding and structural characteristics that could assist in drug design."

Journal • CNS Disorders • Oncology

Clinical approach to rhizomicry based on a case of dentine dysplasia type 1. (PubMed, J Stomatol Oral Maxillofac Surg) - "The diagnosis of DD-1 was first established before an orthognathic surgery to correct the facial skeletal deformity. We also reviewed the clinicopathological aspects of this disease and clinical dental implications for this patient group."

Clinical • Journal

---cnd-1/NeuroD1 Functions with the Homeobox Gene ceh-5/Vax2 and Hox Gene -ceh-13/Labial to Specify Aspects of RME and DD Neuron Fate in Caenorhabditis elegans. (PubMed, G3 (Bethesda)) - "We also show that cnd-1 functions redundantly with the Hox gene ceh-13/labial in defining the fate of DD1 and DD2 embryonic ventral nerve cord motorneurons. These data highlight the utility of comparative transcriptomes for identifying transcription factor targets and understanding gene regulatory networks."

Journal • Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Genetic Disorders • Psychiatry • Schizophrenia • HIF1A

"@CDCDirector 1 dd1 11 .21111helped" (@spencerpfreeman)

Anticancer effects of resveratrol in canine hemangiosarcoma cell lines. (PubMed, Vet Comp Oncol) - "Additional experiments showed that resveratrol augmented the growth-inhibitory and apoptotic effects of doxorubicin in both HSA cell lines. These findings suggest that resveratrol has pro-apoptotic effects in canine HSA cells; therefore, its use as a potential adjunct therapy in canine HSA patients warrants further investigation."

Journal • Biosimilar • Oncology • Sarcoma • Solid Tumor

Differential susceptibility of Xylella fastidiosa strains to synthetic bactericidal peptides. (PubMed, Phytopathology) - "There was a differential susceptibility to BP178 among strains, with DD1 being the most resistant and CFBP 8173 the most susceptible. Moreover, strains showed a proportion of cells under the viable but nonculturable state (VBNC), which was highly variable among strains. These findings may have implications for managing the diseases caused by X. fastidiosa."

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The unraveling of substrate specificity of histone deacetylase 6 domains using acetylome peptide microarrays and peptide libraries. (PubMed, FASEB J) - "Investigations of the substrate specificity of HDAC6 are confounded by the presence of 2 catalytically active deacetylase domains (DD1 and DD2)...Finally, the deacylation activity of HDAC6 was profiled by using a panel of acyl derivatives of the optimized peptide substrate and showed that HDAC6 acts as a proficient deformylase. Our data thus offer a detailed insight into the substrate preferences of the individual HDAC6 domains at the peptide level, and these findings can in turn help in elucidating the biologic roles of the enzyme and facilitate the development of new domain-specific inhibitors as research tools or therapeutic agents.-Kutil, Z., Skultetyova, L., Rauh, D., Meleshin, M., Snajdr, I., Novakova, Z., Mikesova, J., Pavlicek, J., Hadzima, M., Baranova, P., Havlinova, B., Majer, P., Schutkowski, M., Barinka, C. The unraveling of substrate specificity of histone deacetylase 6 domains using acetylome peptide microarrays and peptide libraries."

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FOXD3 Regulates VISTA Expression in Melanoma. (PubMed, Cell Rep) - "BRAF inhibition upregulates FOXD3 and reduces VISTA expression. Overall, this study demonstrates melanoma cell expression of VISTA and its regulation by FOXD3, contributing to the rationale for therapeutic strategies that combine targeted inhibitors with immune checkpoint blockade."

IO Biomarker • Journal • BRAF • PD-L1

Electrogenic Transport Function of Low Temperature Rescued CLC-5: R345W Mutation and Towards Dent Disease Novel Therapies (KIDNEY WEEK 2019) - "Conclusion These results establish a rationale and the tools to explore the effect of pharmacological chaperones to facilitate proper protein folding and maturation of DD1 mutations, including R345W. Results could suggest new therapies for some populations of DD1 patients who currently have no specific therapy available."

Two Coupled Circadian Oscillators Are Involved in Nonphotic Acceleration of Reentrainment to Shifted Light Cycles in Mice. (PubMed, J Biol Rhythms) - "Interestingly, the magnitude of phase-shifts of activity offset, but not of activity onset, in the following DD was negatively correlated with the extent of α compression in DD1. These findings indicate that the 2 circadian oscillators underlying activity onset and offset are involved in asymmetric phase-shifts and nonphotic acceleration of reentrainment."

Journal • Preclinical

Evaluation of left ventricular diastolic function based on flow energetic parameters in chronic kidney disease with diastolic dysfunction. (PubMed, Echocardiography) - "For CKD patient with LVDD and LVEF > 50%, effective LV filling and systolic ejection with optimized energy consumption have been impaired. As a new flow-derived index, EL can quantitatively evaluate LV diastolic function in terms of blood fluid dynamics in CKD with various LVDD."

Journal

Kinetic Analysis of Nano-Structures Formed by Enzyme-Instructed Intracellular Assemblies against Cancer Cells. (PubMed, ACS Nano) - "...Here, we design and synthesize three dipeptidic precursors (ld-1-SO, dl-1-SO, dd-1-SO), consisting of diphenylalanine (l-Phe-d-Phe, d-Phe-l-Phe, d-Phe-d-Phe, respectively) as the backbone, which are capped by 2-(naphthalen-2-yl)acetic acid at the N-terminal and by 2-(4-(2-aminoethoxy)-4-oxobutanamido)ethane-1-sulfonic acid at the C-terminal...As the first kinetic analysis of intracellular EISA, this work elucidates how the stereochemistry modulates EISA in the complex extra- and/or intracellular environment for developing anticancer molecular processes. Moreover, it provides insights for understanding the kinetics and cytotoxicity of aggregates of aberrant proteins or peptides formed inside and outside cells."

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