Targeting OsNIP3;1 via CRISPR/Cas9: A strategy for minimizing arsenic accumulation and boosting rice resilience.

Arsenic (As) contamination in rice poses a significant threat to human health due to its toxicity and widespread consumption. Identifying and manipulating key genes governing As accumulation in rice is crucial for reducing this threat. The large NIP gene family of aquaporins in rice presents a promising target due to functional redundancy, potentially allowing for gene manipulation without compromising plant growth. This study aimed to utilize genome editing to generate knock-out (KO) lines of genes of NIP family (OsLsi1, OsNIP3;1) and an anion transporter family (OsLsi2), in order to assess their impact on As accumulation and stress tolerance in rice. KO lines were created using CRISPR/Cas9 technology, and the As accumulation patterns, physiological performance, and grain yield were compared against wild-type (WT) under As-treated conditions. KO lines exhibited significantly reduced As accumulation in grain compared to WT. Notably, Osnip3;1 KO line displayed reduced As in xylem sap (71-74%) and grain (32-46%) upon treatment. Additionally, these lines demonstrated improved silicon (23%) uptake, photosynthetic pigment concentrations (Chl a: 77%; Chl b: 79%, Total Chl: 79% & Carotenoid: 49%) overall physiological and agronomical performance under As stress compared to WT. This study successfully utilized genome editing for the first time to identify OsNIP3;1 as a potential target for manipulating As accumulation in rice without compromising grain yield or plant vigor.

Allylsilane as a versatile handle in photoredox catalysis.

Organosilanes have secured a special place in the synthetic world for several decades. However, among them, allylsilanes are a choice reagent for organic chemists to develop novel organic transformations. In recent years researchers have proved that visible-light photoredox catalysis has emerged as one of the most mild, sustainable, straightforward, and efficient strategies to construct simple to complex molecules with or without enantioselectivity. This review provides an in-depth analysis of recent advances and strategies employed in visible-light photoredox catalysis for allylsilane and its analogues for the development of various organic transformations. The review is divided into sections, each focused on a specific reactivity of allylsilane under light irradiation with C(sp2) center arene or alkene, C(sp2) center carbonyl, and C(sp3) center carbon functionality. In this review, we present optimization data, reaction scope, and mechanistic aspects to bring forward specific reactivity and selectivity trends of allylsilane in photoredox conditions.

Internet-based cognitive behavioral therapy intervention for youth with type 1 diabetes and depressive symptoms: a pilot and feasibility study.

Depression is more common in youth with type 1 diabetes (T1D) compared to youth without diabetes. This study aims to assess the efficacy of Competent Adulthood Transition with Cognitive Humanistic and Interpersonal Teaching (CATCH-IT), an internet-based cognitive behavioral therapy (CBT) intervention, in adolescents with T1D and depressive symptoms. Adolescents (13 to 17 years old) with T1D and mild (score 5-9) or moderate (score 10-14) depressive symptoms on Patient Health Questionnaire-Adolescent (PHQ-A) screening assessment were recruited to participate and received online access to the CATCH-IT modules for 6 months (requested to complete in 12 weeks). Statistical analyses included paired t-test for changes in Center for Epidemiologic Studies Depression Scale (CES-D), PHQ-A, Problem Areas in Diabetes-Teen version (PAID-T), and hemoglobin A1c (HbA1c). Nineteen patients were consented, 15 met inclusion criteria and received the intervention. In the seven participants that completed the modules, there was a trend towards improvements in PHQ-A, CES-D and HbA1c. Participants provided robust qualitative feedback on the modules and areas for improvement in subsequent iterations, such as inclusion of diabetes-related content. Given the prevalence of depression in diabetes, feasible, low resource interventions are needed. Internet programs such as CATCH-IT can serve as an effective first line intervention in this high-risk population. A modified version of CATCH-IT tailored for adolescents with T1D may be beneficial in this patient population.

Gender-Affirming Medical Treatments.

Individuals with gender dysphoria (as defined by Diagnostic and Statistical Manual of Mental Disorders or DSM-V) experience a marked incongruence between the sex assigned at birth and the experienced gender resulting in significant distress or impairment in social, occupational, or other important areas of functioning. For transgender and gender diverse minors, the Endocrine Society recommends a multidisciplinary approach to gender-affirming medical treatment that involves a physician and a mental health provider, also consistent with the World Professional Association for Transgender Health Standard of Care 8th Edition recommendations. This article will outline the role of medical providers in implementing safe and effective gender-affirming medical treatments in youth.

Photochemical Sonogashira coupling reactions: beyond traditional palladium-copper catalysis.

Sonogashira coupling is one of the Nobel reactions discovered in 1975 to form a C-C bond using palladium and copper as co-catalysts. Incorporating alkyne functionalities either in macro or micro molecules by using this Sonogashira reaction has already proven its viability and relevance in the sphere of synthetic chemistry. While aiming for sustainable chemistry, in recent years, visible light photoredox catalysts have appeared as an advanced tool in this regard. In this review, we aim to portray a comprehensive summary of modern visible light photo redox catalyzed Sonogashira reaction, which will leave space for the readers to rethink alternative strategies to conduct the Sonogashira reaction. This review briefly describes the implementation of various metal-based nanomaterial photocatalysts, developing either copper or palladium-free photocatalytic methods, and organo-photolytic and bioinspired photocatalysts for the Sonogashira coupling reactions. Besides, this review also gives a concise overview of the mechanistic aspects and highlights selective examples for substrate scope.

Evaluation of the Antimicrobial Activity of Magnetized Water and Its Comparison with Chlorhexidine 0.2% in Young Children for 3 Weeks.

AIM: The goal of this study was to compare the effects of magnetized water and 0.2% chlorhexidine mouthwash on gingivitis and plaque prevention in children aged 12-15 years for a period of 21 days. MATERIALS AND METHODS: A total of 24 youngsters between the ages of 12 and 15 years were chosen. A computer-generated random number sequence was used to split the research participants into two groups. Magnetized water was utilized as a mouthrinse in Category 1, while 0.2% chlorhexidine was employed in Category 2. Water purified with reverse osmosis was stored in glass bottles, which were then put near the magnets to create magnetic water. The magnets had 1000 Gauss power. The bottles were put for a period of 24 hours. The youngsters were given 140 mL of mouthrinse. These mouthrinses were to be used at home, they were told. The Gilmore Turesky adaptation of Quigley Hein's plaque index was used to assess the plaque whereas the gingival index recommended by Loe and Sillness was utilized to assess the gingiva. The plaque index and gingival index were analyzed at baseline, 14 days, and 21 days, as well as history and examination for adverse effects such as bitter taste, brownish discoloration, and so on, were recorded. The trial lasted 21 days with a follow-up period of another 21 days. RESULTS: Both magnetic water and chlorhexidine were similarly successful in managing periodontal and gingival infections; however, magnetized water had less side effects, such as a bitter metallic taste and brown stains. CONCLUSION: Because of its well-accepted flavor, softer nature, and lower frequency of brown stains, magnetized water can be a safer and more acceptable alternative to chlorhexidine mouthwashes, especially in youngsters. CLINICAL SIGNIFICANCE: The use of chlorhexidine as a mouthrinse in the oral cavity has been linked to side effects. These side effects are mostly localized, such as brownish discoloration of teeth, alterations in taste perception, and erosion of the oral mucosa. As chlorhexidine has such negative side effects, it was necessary to do research, particularly in children, to identify a replacement that is similarly efficient against germs but does not have these side effects. Water treated with a magnetic field (magnetized water) was compared with chlorhexidine in the current study.

Evaluation of Inflammatory Acute Phase Protein Level and Different Leukocyte Counts in Chronic Periodontitis Normolipidemic Patients after Nonsurgical Periodontal Therapy.

AIM AND OBJECTIVE: To evaluate the effect of nonsurgical periodontal therapy on periodontal parameters, serum C-reactive protein (CRP) level, total leukocyte count (TLC), and differential leukocyte count (DLC) in normolipidemic patients with generalized chronic periodontitis. MATERIALS AND METHODS: A total of 60 subjects (38 males and 22 females) between 20 and 55 years of age were included in this study. Twenty subjects with generalized chronic gingivitis were assigned group I. Forty subjects with generalized chronic periodontitis were randomly divided into test groups, i.e., group II (n = 20) and control group, i.e., group III (n = 20). At baseline, clinical parameters (plaque and gingival indices, clinical attachment loss) were recorded and blood collected for lipid profile test, TLC, DLC, and CRP estimation. Patients with lipid values in the normal range continued the study. Groups I and II were provided nonsurgical periodontal therapy. Follow-up clinical examination and blood examination were done for CRP level, TLC, and DLC after 1 and 2 months. RESULTS: A significant improvement in the clinical parameters was evident following scaling and root planning in group II as compared to group III. A decrease in serum CRP and TLC count was also observed, but the difference was not significant. Moreover, a reduction was observed in neutrophils, monocytes, eosinophils post therapeutically in group II but the decrease was significant only for monocyte count. CONCLUSION: Based on the findings of the study, it can be concluded that nonsurgical periodontal therapy can reduce the inflammatory component. CLINICAL SIGNIFICANCE: Periodontal diseases comprise a wide range of inflammatory conditions affecting the supporting structures of teeth. Effect of nonsurgical periodontal therapy on chronic periodontitis can be evaluated by measuring the CRP and leukocyte concentration.

miRNAs play critical roles in response to abiotic stress by modulating cross-talk of phytohormone signaling.

One of the most interesting signaling molecules that regulates a wide array of adaptive stress responses in plants are the micro RNAs (miRNAs) that are a unique class of non-coding RNAs constituting novel mechanisms of post-transcriptional gene regulation. Recent studies revealed the role of miRNAs in several biotic and abiotic stresses by regulating various phytohormone signaling pathways as well as by targeting a number of transcription factors (TFs) and defense related genes. Phytohormones are signal molecules modulating the plant growth and developmental processes by regulating gene expression. Studies concerning miRNAs in abiotic stress response also show their vital roles in abiotic stress signaling. Current research indicates that miRNAs may act as possible candidates to create abiotic stress tolerant crop plants by genetic engineering. Yet, the detailed mechanism governing the dynamic expression networks of miRNAs in response to stress tolerance remains unclear. In this review, we provide recent updates on miRNA-mediated regulation of phytohormones combating various stress and its role in adaptive stress response in crop plants.

Effect of Intracanal Medicaments (Modified Triple Antibiotic Paste, Calcium Hydroxide, and Aloe Vera) on Microhardness of Root Dentine: An In Vitro Study.

AIM: To compare the effect of three different intracanal medicaments, namely, modified triple antibiotic paste (MTAP), calcium hydroxide (Ca(OH)2), and aloe vera, on the root dentine microhardness. MATERIALS AND METHODS: A total of 50 extracted mandibular bicuspids were prepared using ProTaper Next rotary files. The roots of the bicuspids were alienated to three groups (n = 10 each) and one control group (untreated; n = 20). In three groups, the root canals were filled with MTAP, Ca(OH)2, and aloe vera medicaments. After 21 days, medicaments were removed by Endo activator. Mean Knoop hardness numbers were calculated after treatment and compared with the untreated control group. Data were evaluated using the Student's t test (paired), ANOVA (one-way) followed, and the post hoc test. RESULTS: All treated groups except the aloe vera group had shown significant reduction (p < 0.05) in microhardness of the root dentin as compared with the untreated control group. The aloe vera group showed least reduction of microhardness and was statistically insignificant (p > 0.05). CONCLUSION: Aloe vera shows promising results in terms of fewer effects on microhardness of the root dentin compared to MTAP and Ca(OH)2. CLINICAL SIGNIFICANCE: Elimination of most of the bacterial infection from the root canal and very minimum to no effect on the microhardness of the dentin in the root part are the basics of success in any endodontic treatment. Further in vivo studies are required to compare the efficacy of these intracanal medicaments.

Correlation of dental caries and dermatoglyphic patterns: A study in pediatric population.

INTRODUCTION: Dental caries is the most prevalent chronic disease among children worldwide irrespective of the advancements in oral healthcare. The basis of considering dermatoglyphic patterns as marker for dental caries is that the epithelium of finger buds and enamel are both ectodermal in origin and develop during the same period of intrauterine life. AIM AND OBJECTIVE: To record and evaluate the dermatoglyphic patterns, its correlation with early childhood caries (ECC) and to predict its efficacy in assessing the caries risk. METHOD: The study was carried out on 100 school going children within the age group of 36-71 months. Study population was divided into two groups comprising of 50 individuals each on the basis of def score, experimental group (def ≥ 1) and control group (def score 0). Dermatoglyphic patterns of all ten palmar digits were recorded using Cummins and Midlo method and assessed using a magnifying glass (2×). RESULTS: Statistically significant increase in number of whorls was found in ECC group, whereas higher number of loops was seen in control group. In ECC group, value of both, the mean axial t triradius angle and mean total ridge count was low as compared to the caries-free group. CONCLUSION: There is definite variation in dermatoglyphics between the ECC and caries-free group, indicating that dermatoglyphic patterns can be used as a non-invasive predictive tool for children with ECC.

Inguinal Lymph Node Dissection Does Not Improve Overall Survival in Anal Cancer Nodal Disease.

BACKGROUND: Anal SCC is a rare disease mainly treated with chemoradiation. Abdominoperineal resection (APR), once the mainstay of treatment for anal cancer, now serves a role as salvage therapy for persistent or recurrent disease after chemoradiation. In addition, clinically positive nodes are currently treated by extending the radiation field to the groin. The role of inguinal lymph node dissection in recurrent or persistent anal SCC is unclear. The aim of the study is to determine the role of inguinal lymph node dissection in the management of inguinal lymph node metastasis for anal squamous cell carcinoma (SCC). METHODS: Retrospective analysis of patients with anal SCC in the National Cancer Database with positive inguinal nodes undergoing salvage APR between 2004 and 2014 was performed. A comparison of overall survival between patients who underwent APR with lymph node dissection versus APR only was analyzed using Kaplan-Meier plot. RESULTS: A total of 3424 patients underwent salvage APR, with 274 (8%) having clinically positive nodes. Within the subgroup that had clinically positive nodes, 195 (71%) underwent APR, whereas 79 (29%) underwent both APR and node dissection. Kaplan-Meier analysis demonstrates no difference in overall survival in the two groups (P = 0.99). Five-year survival for both groups was similar (36% versus 42%; P = 0.987). No significant difference was found when adjusted for age, gender, and Tumor Node Metastasis staging. CONCLUSIONS: Inguinal lymph node dissection does not appear to improve overall survival in patients with advanced-stage anal cancer requiring salvage APR. Proper patient selection for node dissection is essential to spare patients from additional morbid procedures.

Auxin-salicylic acid cross-talk ameliorates OsMYB-R1 mediated defense towards heavy metal, drought and fungal stress.

The MYB TF family is an immensely large and functionally diverse class of proteins involved in the regulation of cell cycle, cell morphogenesis to stress signaling mechanism. The present study deciphered the hormonal cross-talk of wound inducible and stress-responsive OsMYB-R1 transcription factor in combating abiotic [Cr(VI) and drought/PEG] as well as biotic (Rhizoctonia solani) stress. OsMYB-R1 over-expressing rice transgenics exhibit a significant increase in lateral roots, which may be associated with increased tolerance under Cr(VI) and drought exposure. In contrast, its loss-of-function reduces stress tolerance. Higher auxin accumulation in the OsMYB-R1 over-expressed lines further strengthens the protective role of lateral roots under stress conditions. RNA-seq. data reveals over-representation of salicylic acid signaling molecule calcium-dependent protein kinases, which probably activate the stress-responsive downstream genes (Peroxidases, Glutathione S-transferases, Osmotins, Heat Shock Proteins, Pathogenesis Related-Proteins). Enzymatic studies further confirm OsMYB-R1 mediated robust antioxidant system as catalase, guaiacol peroxidase and superoxide dismutase activities were found to be increased in the over-expressed lines. Our results suggest that OsMYB-R1 is part of a complex network of transcription factors controlling the cross-talk of auxin and salicylic acid signaling and other genes in response to multiple stresses by modifying molecular signaling, internal cellular homeostasis and root morphology.

Comparison and Evaluation of Linear Dimensional Accuracy of Three Elastomeric Impression Materials at Different Time Intervals Using Vision Inspection System: An In Vitro Study.

BACKGROUND: Making an impression represents a crucial step in fabrication of a prosthesis. Elastomers are the most commonly used materials for precise and accurate recording and reproduction of tooth morphology and surrounding soft tissue. AIMS AND OBJECTIVE: The aim of this study was to compare and evaluate the linear dimensional accuracy of three elastomeric impression materials: addition silicone, condensation silicone, and polyether at different time intervals up to 15 days using a vision inspection system. MATERIALS AND METHODS: Dimensional accuracy of impression materials was measured at certain designated time periods using stainless steel die. The impressions of die were made using one representative material of each type of elastomeric impression material. The die along with the impression material in the mold was held using a clamp and put in a water bath maintained at mouth temperature. The linear dimensional changes taking place in each material with time were measured using the vision inspection system. RESULTS: On comparison with master die impression at 30min, 1h, and 1½ h time interval, a significant decreased mean dimension of condensation silicone was observed, whereas addition silicone and polyether showed statistically nonsignificant difference. At 2, 3, 4, and 12h time span, a significant difference in mean dimension of addition and condensation silicone was noted, whereas polyether showed a nonsignificant difference. At 24h, 1 week, and 15 days duration, on comparison with the master die, a significant reduction in mean dimension of condensation silicone was discovered, whereas addition silicone and polyether showed nonsignificant difference. CONCLUSION: Polyether showed significantly lesser dimensional changes among all three materials, though the differences were small enough to be considered clinically acceptable.

Perception, awareness, and practice among patients seeking orthodontic treatment toward maintenance of periodontal health and factors affecting the same among patients visiting dental clinics in Patna.

BACKGROUND: During the orthodontic treatment, maintenance of periodontal health is of utmost importance; hence, this study was conducted to explore the perception and awareness of patients seeking orthodontic treatment toward maintenance of periodontal health and factors affecting the same. MATERIALS AND METHODS: It was a cross-sectional descriptive questionnaire study conducted among134 patients seeking orthodontic treatment from 16 private clinics in Patna. The study was conducted in the month of June 2019. The city was divided into four directions east, west, north, and south and four clinics were selected from each directions randomly. A close-ended questionnaire was prepared consists of demographic details and questions regarding their perception, awareness, and practice to maintain periodontal health from the start of orthodontic treatment. RESULTS: Majority of study participants {74 (55.22%)} were between the age group of 11 and 15 years. Among all study participants, females {81 (60.45%)} were more than males. It was determined that 112 (83.58%) of patients were using tooth brush and tooth paste/powder for cleaning teeth. There was moderate awareness, negative perception, and fair practice of majority of study participants seeking orthodontic treatment toward maintenance of periodontal health. Awareness of study participants was significantly (P-value ≤ 0.05*) associated with practice. CONCLUSION: There was moderate awareness, negative perception, and fair practice of majority of study participants seeking orthodontic treatment toward maintenance of periodontal health. Education of study participants was significantly associated with awareness and practice regarding maintenance of periodontal health. There is further need to educate the orthodontic patients toward maintenance of periodontal health.

Aurora A site specific TACC3 phosphorylation regulates astral microtubule assembly by stabilizing γ-tubulin ring complex.

BACKGROUND: Astral microtubules emanating from the mitotic centrosomes play pivotal roles in defining cell division axis and tissue morphogenesis. Previous studies have demonstrated that human transforming acidic coiled-coil 3 (TACC3), the most conserved TACC family protein, regulates formation of astral microtubules at centrosomes in vertebrate cells by affecting γ-tubulin ring complex (γ-TuRC) assembly. However, the molecular mechanisms underlying such function were not completely understood. RESULTS: Here, we show that Aurora A site-specific phosphorylation in TACC3 regulates formation of astral microtubules by stabilizing γ-TuRC assembly in human cells. Mutation of the most conserved Aurora A targeting site, Ser 558 to alanine (S558A) in TACC3 results in robust loss of astral microtubules and disrupts localization of the γ-tubulin ring complex (γ-TuRC) proteins at the spindle poles. Under similar condition, phospho-mimicking S558D mutation retains astral microtubules and the γ-TuRC proteins in a manner similar to control cells expressed with wild type TACC3. Time-lapse imaging reveals that S558A mutation leads to defects in positioning of the spindle-poles and thereby causes delay in metaphase to anaphase transition. Biochemical results determine that the Ser 558- phosphorylated TACC3 interacts with the γ-TuRC proteins and further, S558A mutation impairs the interaction. We further reveal that the mutation affects the assembly of γ-TuRC from the small complex components. CONCLUSIONS: The results demonstrate that TACC3 phosphorylation stabilizes γ- tubulin ring complex assembly and thereby regulates formation of centrosomal asters. They also implicate a potential role of TACC3 phosphorylation in the functional integrity of centrosomes/spindle poles.

Protein lysine 43 methylation by EZH1 promotes AML1-ETO transcriptional repression in leukemia.

The oncogenic fusion protein AML1-ETO retains the ability of AML1 to interact with the enhancer core DNA sequences, but blocks AML1-dependent transcription. Previous studies have shown that post-translational modification of AML1-ETO may play a role in its regulation. Here we report that AML1-ETO-positive patients, with high histone lysine methyltransferase Enhancer of zeste homolog 1 (EZH1) expression, show a worse overall survival than those with lower EZH1 expression. EZH1 knockdown impairs survival and proliferation of AML1-ETO-expressing cells in vitro and in vivo. We find that EZH1 WD domain binds to the AML1-ETO NHR1 domain and methylates AML1-ETO at lysine 43 (Lys43). This requires the EZH1 SET domain, which augments AML1-ETO-dependent repression of tumor suppressor genes. Loss of Lys43 methylation by point mutation or domain deletion impairs AML1-ETO-repressive activity. These findings highlight the role of EZH1 in non-histone lysine methylation, indicating that cooperation between AML1-ETO and EZH1 and AML1-ETO site-specific lysine methylation promote AML1-ETO transcriptional repression in leukemia.

ErbB3-binding protein 1 (EBP1) represses HNF4α-mediated transcription and insulin secretion in pancreatic ß-cells.

HNF4α (hepatocyte nuclear factor 4α) is one of the master regulators of pancreatic ß-cell development and function, and mutations in the HNF4α gene are well-known monogenic causes of diabetes. As a member of the nuclear receptor family, HNF4α exerts its gene regulatory function through various molecular interactions; however, there is a paucity of knowledge of the different functional complexes in which HNF4α participates. Here, to find HNF4α-binding proteins in pancreatic ß-cells, we used yeast two-hybrid screening, a mammalian two-hybrid assay, and glutathione S-transferase pulldown approaches, which identified EBP1 (ErbB3-binding protein 1) as a factor that binds HNF4α in a LXXLL motif-mediated manner. In the ß-cells, EBP1 suppressed the expression of HNF4α target genes that are implicated in insulin secretion, which is impaired in HNF4α mutation-driven diabetes. The crystal structure of the HNF4α ligand-binding domain in complex with a peptide harboring the EBP1 LXXLL motif at 3.15Å resolution hinted at the molecular basis of the repression. The details of the structure suggested that EBP1's LXXLL motif competes with HNF4α coactivators for the same binding pocket and thereby prevents recruitment of additional transcriptional coactivators. These findings provide further evidence that EBP1 plays multiple cellular roles and is involved in nuclear receptor-mediated gene regulation. Selective disruption of the HNF4α-EBP1 interaction or tissue-specific EBP1 inactivation can enhance HNF4α activities and thereby improve insulin secretion in ß-cells, potentially representing a new strategy for managing diabetes and related metabolic disorders.

Dimerization defective MODY mutations of hepatocyte nuclear factor 4α.

HNF4α is a culprit gene product for a monogenic and dominantly-inherited form of diabetes, referred to as MODY1 (Maturity Onset Diabetes of the Young type 1). Reduced HNF4α activities have been linked to impaired insulin secretion and ß-cell function. Numerous mutations have been identified from the patients and they have been instructive as to the individual residue's role in protein structure-function and dysfunction. As a member of the nuclear receptor (NR) superfamily, HNF4α is made of characteristic modular domains and it functions exclusively as a homodimer despite its sequence homology to RXR, a common heterodimer partner of non-steroidal NRs. Transcription factors commonly dimerize to enhance their molecular functions mainly by facilitating the recognition of double helix target DNAs that display an intrinsic pseudo-2-fold symmetry and the recruitment of the remainder of the main transcriptional machinery. HNF4α is no exception and its dimerization is maintained by the ligand binding domain (LBD) mainly through the leucine-zipper-like interactions at the stalk of two interacting helices. Although many MODY1 mutations have been previously characterized, including DNA binding disruptors, ligand binding disruptors, coactivator binding disruptors, and protein stability disruptors, protein dimerization disruptors have not been formally reported. In this report, we present a set of data for the two MODY1 mutations found right at the dimerization interface (L332 P and L328del mutations) which clearly exhibit the disruptive effects of directly affecting dimerization, protein stability, and transcriptional activities. These data reinforced the fact that MODY mutations are loss-of-function mutations and HNF4α dimerization is essential for its optimal function and normal physiology.

Tubulin Posttranslational Modifications and Emerging Links to Human Disease.

Tubulin posttranslational modifications are currently emerging as important regulators of the microtubule cytoskeleton and thus have a strong potential to be implicated in a number of disorders. Here, we review the latest advances in understanding the physiological roles of tubulin modifications and their links to a variety of pathologies.

SnapShot: Functions of Tubulin Posttranslational Modifications.

Post-translational modification of tubulin offers a mechanism for functional diversification of microtubules and regulation in a variety of physiological contexts. This SnapShot recaps the current state of understanding of tubulin posttranslational modifications and their functions in the regulation of biological processes. To view this SnapShot, open or download the PDF.