Spin-Direction-Spin Coupling of Quasiguided Modes in Plasmonic Crystals.

We report an unusual spin-direction-spin coupling phenomenon of light using the leaky quasiguided modes of a waveguided plasmonic crystal. This is demonstrated as simultaneous input spin-dependent directional guiding of waves (spin-direction coupling) and wave-vector-dependent spin acquisition (direction-spin coupling) of the scattered light. These effects, manifested as the forward and the inverse spin Hall effect of light in the far field, and other accompanying spin-orbit interaction effects are observed and analyzed using a momentum (k) domain polarization Mueller matrix. Resonance-enabled enhancement of these effects is also demonstrated by utilizing the spectral Fano resonance of the hybridized modes. The fundamental origin and the unconventional manifestation of the spin-direction-spin coupling phenomenon from a relatively simple system, ability to probe and interpret the resulting spin-orbit phenomena in the far field through momentum-domain polarization analysis, and their regulated control in plasmonic-photonic crystals open up exciting avenues in spin-orbit-photonic research.

"Dial-In" Emission from a Unique Flexible Material with Polarization Tuneable Spectral Intensity.

The development of organic photoluminescent materials, which show promising roles as catalysts, sensors, organic light-emitting diodes, logic gates, etc., is a major demand and challenge for the global scientific community. In this context, a photoclick polymerization method is adopted for the growth of a unique photoluminescent three-dimensional (3D) polymer film, E, as a model system that shows emission tunability over the range 350-650 nm against the excitation range 295-425 nm. The DFT analysis of energy calculations and π-stacking supports the spectroscopic observations for the material exhibiting a broad range of emission owing to newly formed chromophoric units within the film. Full polarization spectroscopic Mueller matrix studies were employed to extract and quantify the molecular orientational order of both the ground (excitation) and excited (emission) state anisotropies through a set of newly defined parameters, namely the fluorescence diattenuation and fluorescence polarizance. The information contained in the recorded fluorescence Mueller matrix of the organic polymer material provided a useful way to control the spectral intensity of emission by using pre- and post-selection of polarization states. The observation was based on the assumption that the longer lifetime of the excited dipolar orientation is attributed to the compactness of the film.

Consensus on "Basal insulin in the management of Type 2 Diabetes: Which, When and How?"

INTRODUCTION: Type 2 diabetes mellitus (T2DM) has attained epidemic proportions and continues to increase despite the availability of a number of oral antidiabetic medications and major advances made in insulin delivery since its discovery nearly a hundred years ago. One, amongst many other reasons responsible for the inability to achieve adequate glycaemic control in a substantial proportion of T2DM patients is the delayed initiation and inappropriate intensification of insulin treatment. Appropriate initiation and intensification of insulin is critical for the successful achievement of tight glycaemic control. OBJECTIVE: To provide simple and easily implementable guidelines to primary care physicians on basal insulin initiation and intensification, along with use of basal insulin in special situations (hepatic failure, renal failure and gestational diabetes mellitus). METHODS: Each consensus statement on basal insulin initiation, intensification and use of basal insulin in special situations was evaluated for dosing and titration based on established guidelines, data from approved pack inserts, prescribing information or summary of product characteristics for each insulin type, and published scientific literature. These evaluations were then factored into the national context based not only on the clinical experience of the expert committee representatives' but also based on the common therapeutic practices followed in India to successfully achieve optimal glucose control. RESULTS: Recommendations on initiation and intensification of basal insulin, and its use in special situations, have been developed. The key recommendations are to initiate basal insulin when 2 or 3 oral antidiabetic medications fail to achieve target glycaemic control, or in symptomatic patients with glycated haemoglobin value greater than 9%. Depending upon patient characteristics, any of the four available basal insulins [Neutral protamine Hagedorn (NPH), Glargine (IGlar), Detemir (IDet), Degludec (IDeg)] can be used. However, IDeg has a longer duration of action, comparatively lesser hypoglycaemia (both overall and nocturnal) and more flexibility in administration timing compared to IGlar) and IDet. Inability to maintain glycaemic control should lead to prompt intensification of basal insulin treatment by adding mealtime insulin, consisting of one to three injections of either rapid-acting insulin analog or regular insulin; depending upon patient characteristics, intensification can also be achieved by transition from basal insulin to twice daily premixed insulin analogs/premixed human insulin/insulin co-formulations. IDeg/IDet can be used in all grades of renal and hepatic impairment; and IDet has been approved for use in gestational diabetes mellitus. CONCLUSIONS: We hope that these consensus based recommendations shall be a useful reference tool for health care practitioners and help them in initiating and intensifying insulin therapy in T2DM patients in order to achieve optimal glycaemic control.

Transverse spin and transverse momentum in scattering of plane waves.

We study the near field to the far field evolution of spin angular momentum (SAM) density and the Poynting vector of the scattered waves from spherical scatterers. The results show that at the near field, the SAM density and the Poynting vector are dominated by their transverse components. While the former (transverse SAM) is independent of the helicity of the incident circular polarization state, the latter (transverse Poynting vector) depends upon the polarization state. It is further demonstrated that the interference of the transverse electric and transverse magnetic scattering modes enhances both the magnitudes and the spatial extent of the transverse SAM and the transverse momentum components.

An overview of therapeutic options of obesity management in India: the Integrated Diabetes and Endocrinology Academy (IDEA) 2023 Congress update.

INTRODUCTION: With newer anti-obesity medications (AOMs) being introduced at a rapid pace, it is prudent to make a concise and updated clinical practice document that may help busy clinicians in daily clinical practice. A group of metabolic physicians, diabetologists, endocrinologists, and bariatric surgeons assembled during the Integrated Diabetes and Endocrine Academy 2023 Congress (IDEACON, July 2023, Kolkata, India) to compile an update of pharmacotherapeutic options for managing people with obesity in India. AREAS COVERED: After an extensive review of the literature by experts in different domains, this update provides all available information on the management of obesity, with a special emphasis on both currently available and soon-to-be-available AOMs, in people with obesity. EXPERT OPINION: Several newer AOMs have been shown to reduce body weight significantly, thus poised to make a paradigm shift in the management of obesity. While the tolerability and key adverse events associated with these AOMs appear to be acceptable in randomized controlled trials, pharmacovigilance is vital in real-world settings, given the absence of sufficiently long-term studies. The easy availability and affordability of these drugs is another area of concern, especially in developing countries like India.

Observation of nonvanishing optical helicity in thermal radiation from symmetry-broken metasurfaces.

Spinning thermal radiation is a unique phenomenon observed in condensed astronomical objects, including the Wolf-Rayet star EZ-CMa and the red degenerate star G99-47, due to the existence of strong magnetic fields. Here, by designing symmetry-broken metasurfaces, we demonstrate that spinning thermal radiation with a nonvanishing optical helicity can be realized even without applying a magnetic field. We design nonvanishing optical helicity by engineering a dispersionless band that emits omnidirectional spinning thermal radiation, where our design reaches 39% of the fundamental limit. Our results firmly suggest that metasurfaces can impart spin coherence in the incoherent radiation excited by thermal fluctuations. The symmetry-based design strategy also provides a general pathway for controlling thermal radiation in its temporal and spin coherence.

Protein restriction in adults with chronic kidney disease, with or without diabetes: Integrated Diabetes and Endocrine Academy (IDEA) consensus statement for Indian patients.

BACKGROUND AND AIMS: Most guidelines recommend protein restriction in adults with chronic kidney disease (CKD), with or without diabetes. However, advising protein restriction for every person with CKD is controversial. We aim to arrive at a consensus on this topic, especially among Indian adults with CKD. METHODS: A systematic literature search in the PubMed electronic database was undertaken using specific keywords and MeSH terms until May 1, 2022. All the retrieved literature was circulated and rigorously deliberated upon by the panel members. RESULTS: Seventeen meta-analyses that evaluated the outcomes of protein restriction in adults with CKD, with or without diabetes, met our inclusion criteria and were analyzed. A low-protein diet (LPD) in people with stages 3-5 of CKD (who are not on haemodialysis [HD]) reduces the severity of uremic symptoms and the rate of decline in glomerular filtration rate, leading to a delay in dialysis initiation. However, LPD in patients on maintenance HD may not be desirable because HD-induced protein catabolism may lead to protein-energy malnutrition. Since the average protein intake among Indians is much lower than recommended, this must be taken into consideration before recommending LPD for all Indian adults with CKD, particularly those on maintenance HD. CONCLUSION: It is essential to assess the nutritional status of people with CKD, particularly in countries like India where average daily protein intake is poor, before recommending guideline-directed protein restriction. The prescribed diet, including the quantity and quality of proteins, should be tailored to the person's habits, tastes, and needs.

Diattenuation and retardance signature of plasmonic gold nanorods in turbid media revealed by Mueller matrix polarimetry.

Plasmonic gold nanorods (GNRs) are finding increasing use in biomedicine due to their unique electromagnetic properties, optical contrast enhancement and biocompatibility; they also show promise as polarization contrast agents. However, quantification of their polarization-enhancing properties within heterogeneous turbid media remains challenging. We report on polarization response in controlled tissue phantoms consisting of dielectric microsphere scatterers with varying admixtures of GRNs. Experimental Mueller matrix measurements and polarization sensitive Monte-Carlo simulations show excellent agreement. Despite the GNRs' 3D random orientation and distribution in the strong multiply scattering background, significant linear diattenuation and retardance were observed. These exclusive measurable characteristics of GNRs suggest their potential uses as contrast enhancers for polarimetric assessment of turbid biological tissue.

Reduced Neurog3 Gene Dosage Shifts Enteroendocrine Progenitor Towards Goblet Cell Lineage in the Mouse Intestine.

BACKGROUND & AIMS: Transient expression of Neurog3 commits intestinal secretory progenitors to become enteroendocrine-biased progenitors and hence drive enteroendocrine differentiation. Loss of Neurog3 in mouse resulted in the depletion of intestinal enteroendocrine cells (EECs) and an increase in goblet cells. Earlier studies in developing mouse pancreas identified a role of Neurog3 gene dosage in endocrine and exocrine cell fate allocation. We aimed to determine whether Neurog3 gene dosage controls fate choice of enteroendocrine progenitors. METHODS: We acquired mutant Neurog3 reporter mice carrying 2, 1, or null Neurog3 alleles to study Neurog3 gene dosage effect by lineage tracing. Cell types arising from Neurog3+ progenitors were determined by immunohistochemistry using antibodies against intestinal lineage-specific markers. RNA sequencing of sorted Neurog3+/+, Neurog3+/-, or bulk intestinal cells were performed and differentially expressed genes were analyzed. RESULTS: We identified 2731 genes enriched in sorted Neurog3+/+-derived cells in the Neurog3+/+EYFP mouse intestine when compared with bulk duodenum epithelial cells. In the intestine of Neurog3+/-EGFP heterozygous mouse, we observed a 63% decrease in EEC numbers. Many Neurog3-derived cells stained for goblet marker Mucin 2. RNA sequencing of sorted Neurog3+/- cells uncovered enriched expression of genes characteristic for both goblet and enteroendocrine cells, indicating the mixed lineages arose from Neurog3+ progenitors. Consistent with this hypothesis, deletion of both Neurog3 alleles resulted in the total absence of EECs. All Neurog3+-derived cells stained for Mucin 2. CONCLUSIONS: We identified that the fate of Neurog3+ enteroendocrine progenitors is dependent on Neurog3 gene dosage. High Neurog3 gene dosage enforces the commitment of secretory progenitors to an EE lineage, while constraining their goblet cell lineage potential. Transcriptome profiling data was deposited to Gene Ontology omnibus, accession number: GSE149203.

Assessing prevalence and predictors of depression in Type 2 Diabetes Mellitus (DM) patients - The DEPDIAB study.

OBJECTIVES: Depression is common in diabetes and has significant impact on health outcomes. Suicidal ideation also forms a part of the spectrum of diabetes and coexistent depression. To assess the predictors of depression as well as its prevalence in Type 2 Diabetes Mellitus (T2DM) patients, we conducted a cross sectional study entitled "DEPression in DIABetes" (DEPDIAB). MATERIAL AND METHODS: A cohort of consecutive 1371 T2DM patients from Eastern India suffering from diabetes greater than 1 year was assessed in a cross- sectional survey in 9 different hospitals and medical polyclinics in Kolkata, India for depression by administering the 9-item PHQ - 9 and Beck depression scales. Socioeconomic status was assessed by the "Revised Kuppuswamy and B G Prasad socio-economic scales for 2016", a validated scoring system for assessing the socioeconomic status of Indian patients. RESULTS: In our study 836 patients (60.9%) were male and 535 (39.02%) were female. 56 patients (4.1%) met the criteria for major depression and 494 patients (36.16%) for minor depression. No sign of depression was found in 816 patients (59.74%). Depression was strongly associated with younger age (18-40 years vs. >60 years) [OR-2.09; 95% CI 1.11-3.96], female sex [OR-1.31; 95% CI 1.11-2.01], low socioeconomic status [OR-2.69; 95% CI 1.34-3.79], poor compliance [OR- 5.05; 95% CI 2.79-8.13], hypoglycemia [OR 1.466; 95% CI 1.076-1.999] and difficulty in managing day-to-day activities [OR- 4.648; 95% CI 3.450-6.262] Suicidal ideation was detected in 201 patients (14.8%). Among patients who had repeated attacks of hypoglycemia (>1 episode per month), 22% experienced suicidal ideation. This was significantly higher than in patients who had not suffered from hypoglycemia (12%) (p < 0.0001). Patients with HbA1C of 7% or lower experienced statistically significantly lesser suicidal ideation than patients with a higher HbA1C (12% vs. 16.8% {p = 0.016}). Suicidal ideation did not correlate withbody mass index (BMI), fasting plasma glucose (FPG) or insulin usage. CONCLUSIONS: We found a high prevalence of depression in T2DM patients in Eastern India. Younger age, female sex, lower socio-economic status, poor compliance, hypoglycemia, and difficulty in managing day to day activities emerged as significant predictors of depression in this study. Recurrent episodes of hypoglycemia were an independent risk factor for suicidal ideation in patients with depression. Depression was not significantly associated with co morbidities associated with T2D and surprisingly insulin usage was not associated with increased depression.

Testosterone replacement therapy in men with type 2 diabetes mellitus and functional hypogonadism -an Integrated Diabetes and Endocrine Academy (IDEA) consensus guideline.

BACKGROUND: Though testosterone replacement therapy in men with organic hypogonadism is established, its role in men with type 2 diabetes mellitus (T2DM) and functional hypogonadism is unclear. METHODS: Thirteen experts addressed ten topic-specific questions after an in-depth review of literature, where all relevant issues were critically evaluated. RESULTS: Ten recommendations concerning diagnosis and management of men with T2DM and functional hypogonadism have been put forward. CONCLUSION: Routine measurement of serum testosterone in all, and inappropriate replacement of testosterone in asymptomatic T2DM men with functional hypogonadism and borderline low serum testosterone values, is not recommended.

Effects of a Technology-Assisted Integrated Diabetes Care Program on Cardiometabolic Risk Factors Among Patients With Type 2 Diabetes in the Asia-Pacific Region: The JADE Program Randomized Clinical Trial.

Importance: Many health care systems lack the efficiency, preparedness, or resources needed to address the increasing number of patients with type 2 diabetes, especially in low- and middle-income countries. Objective: To examine the effects of a quality improvement intervention comprising information and communications technology and contact with nonphysician personnel on the care and cardiometabolic risk factors of patients with type 2 diabetes in 8 Asia-Pacific countries. Design, Setting, and Participants: This 12-month multinational open-label randomized clinical trial was conducted from June 28, 2012, to April 28, 2016, at 50 primary care or hospital-based diabetes centers in 8 Asia-Pacific countries (India, Indonesia, Malaysia, the Philippines, Singapore, Taiwan, Thailand, and Vietnam). Six countries were low and middle income, and 2 countries were high income. The study was conducted in 2 phases; phase 1 enrolled 7537 participants, and phase 2 enrolled 13 297 participants. Participants in both phases were randomized on a 1:1 ratio to intervention or control groups. Data were analyzed by intention to treat and per protocol from July 3, 2019, to July 21, 2020. Interventions: In both phases, the intervention group received 3 care components: a nurse-led Joint Asia Diabetes Evaluation (JADE) technology-guided structured evaluation, automated personalized reports to encourage patient empowerment, and 2 or more telephone or face-to-face contacts by nurses to increase patient engagement. In phase 1, the control group received the JADE technology-guided structured evaluation and automated personalized reports. In phase 2, the control group received the JADE technology-guided structured evaluation only. Main Outcomes and Measures: The primary outcome was the incidence of a composite of diabetes-associated end points, including cardiovascular disease, chronic kidney disease, visual impairment or eye surgery, lower extremity amputation or foot ulcers requiring hospitalization, all-site cancers, and death. The secondary outcomes were the attainment of 2 or more primary diabetes-associated targets (glycated hemoglobin A1c <7.0%, blood pressure <130/80 mm Hg, and low-density lipoprotein cholesterol <100 mg/dL) and/or 2 or more key performance indices (reduction in glycated hemoglobin A1c≥0.5%, reduction in systolic blood pressure ≥5 mm Hg, reduction in low-density lipoprotein cholesterol ≥19 mg/dL, and reduction in body weight ≥3.0%). Results: A total of 20 834 patients with type 2 diabetes were randomized in phases 1 and 2. In phase 1, 7537 participants (mean [SD] age, 60.0 [11.3] years; 3914 men [51.9%]; 4855 patients [64.4%] from low- and middle-income countries) were randomized, with 3732 patients allocated to the intervention group and 3805 patients allocated to the control group. In phase 2, 13 297 participants (mean [SD] age, 54.0 [11.1] years; 7754 men [58.3%]; 13 297 patients [100%] from low- and middle-income countries) were randomized, with 6645 patients allocated to the intervention group and 6652 patients allocated to the control group. In phase 1, compared with the control group, the intervention group had a similar risk of experiencing any of the primary outcomes (odds ratio [OR], 0.94; 95% CI, 0.74-1.21) but had an increased likelihood of attaining 2 or more primary targets (OR, 1.34; 95% CI, 1.21-1.49) and 2 or more key performance indices (OR, 1.18; 95% CI, 1.04-1.34). In phase 2, the intervention group also had a similar risk of experiencing any of the primary outcomes (OR, 1.02; 95% CI, 0.83-1.25) and had a greater likelihood of attaining 2 or more primary targets (OR, 1.25; 95% CI, 1.14-1.37) and 2 or more key performance indices (OR, 1.50; 95% CI, 1.33-1.68) compared with the control group. For attainment of 2 or more primary targets, larger effects were observed among patients in low- and middle-income countries (OR, 1.50; 95% CI, 1.29-1.74) compared with high-income countries (OR, 1.20; 95% CI, 1.03-1.39) (P = .04). Conclusions and Relevance: In this 12-month clinical trial, the use of information and communications technology and nurses to empower and engage patients did not change the number of clinical events but did reduce cardiometabolic risk factors among patients with type 2 diabetes, especially those in low- and middle-income countries in the Asia-Pacific region. Trial Registration: ClinicalTrials.gov Identifier: NCT01631084.

Safeguarding long-lived excitons from excimer traps in H-aggregated dye-assemblies.

The fate of perylene bisimide (PBI) H-aggregates as energy-harvesting materials depends on the ability to circumvent an extremely deleterious but efficient self-trapping process that scavenges the long-lived excitons to form deep excimeric traps. We present the first ever report of an ambient-stable, bright, steady-state photoluminescence (PL) from the long-lived exciton of an H-aggregated PBI crystal. The crystal structure reveals a rotationally displaced H-aggregated arrangement of PBI chromophores, in which transition from the lowest energy exciton state is partially allowed. Polarized absorption spectroscopy on single microcrystals confirms an unusually large exciton splitting of ∼1265 cm-1 that stabilizes the lower exciton state, and inhibits excimer formation. A PL Mueller matrix study shows an increase in the excited state polarization anisotropy, indicating a strong localization of the nascent exciton, which further safeguards it from the self-trapping process. Finally, the possibility of achieving excimer-free excitonic PL in solution self-assembly is also demonstrated.

Intestinal Neurod1 expression impairs paneth cell differentiation and promotes enteroendocrine lineage specification.

Transcription factor Neurod1 is required for enteroendocrine progenitor differentiation and maturation. Several earlier studies indicated that ectopic expression of Neurod1 converted non- neuronal cells into neurons. However, the functional consequence of ectopic Neurod1 expression has not been examined in the GI tract, and it is not known whether Neurod1 can similarly switch cell fates in the intestine. We generated a mouse line that would enable us to conditionally express Neurod1 in intestinal epithelial cells at different stages of differentiation. Forced expression of Neurod1 throughout intestinal epithelium increased the number of EECs as well as the expression of EE specific transcription factors and hormones. Furthermore, we observed a substantial reduction of Paneth cell marker expression, although the expressions of enterocyte-, tuft- and goblet-cell specific markers are largely not affected. Our earlier study indicated that Neurog3+ progenitor cells give rise to not only EECs but also Goblet and Paneth cells. Here we show that the conditional expression of Neurod1 restricts Neurog3+ progenitors to adopt Paneth cell fate, and promotes more pronounced EE cell differentiation, while such effects are not seen in more differentiated Neurod1+ cells. Together, our data suggest that forced expression of Neurod1 programs intestinal epithelial cells more towards an EE cell fate at the expense of the Paneth cell lineage and the effect ceases as cells mature to EE cells.

The retinoblastoma protein, RB, is required for gastrointestinal endocrine cells to exit the cell cycle, but not for hormone expression.

Important functions of the RB family proteins include inhibition of cell cycle progression and regulation of terminal differentiation. We have examined the role of RB and the related protein, p107, in regulating cell cycle activity and differentiation of gastrointestinal endocrine cells, a relatively quiescent cell population, by conditionally disrupting the RB gene in neurogenin3 (Ngn3)-expressing cells in both p107(+/+) and p107(-/-) mice. Endocrine cells in the small intestine, colon, pancreas, and stomach were present in normal numbers in RB and RB-p107 mutants except for an increase in serotonin cells and decrease in ghrelin cells in the antral stomach. Deletion of RB resulted in a dramatic increase in proliferating serotonin cells in the antral stomach and intestine, whereas other enteroendocrine cell types exhibited much lower cell cycle activity or remained quiescent. The related p107 protein appears dispensable for enteroendocrine differentiation and does not functionally compensate for the loss of RB. Our results suggest that RB is required for enteroendocrine cells, particularly serotonin cells, to undergo cell cycle arrest as they terminally differentiate. RB has relatively subtle effects on enteroendocrine cell differentiation and is not required for the expression of the normal repertoire of hormones in the gastrointestinal tract.

Energy homeostasis and gastrointestinal endocrine differentiation do not require the anorectic hormone peptide YY.

The gastrointestinal hormone peptide YY is a potent inhibitor of food intake and is expressed early during differentiation of intestinal and pancreatic endocrine cells. In order to better understand the role of peptide YY in energy homeostasis and development, we created mice with a targeted deletion of the peptide YY gene. All intestinal and pancreatic endocrine cells developed normally in the absence of peptide YY with the exception of pancreatic polypeptide (PP) cells, indicating that peptide YY expression was not required for terminal differentiation. We used recombination-based cell lineage trace to determine if peptide YY cells were progenitors for gastrointestinal endocrine cells. Peptide YY(+) cells gave rise to all L-type enteroendocrine cells and to islet partial differential and PP cells. In the pancreas, approximately 40% of pancreatic alpha and rare beta cells arose from peptide YY(+) cells, suggesting that most beta cells and surprisingly the majority of alpha cells are not descendants of peptide YY(+)/glucagon-positive/insulin-positive cells that appear during early pancreagenesis. Despite the anorectic effects of exogenous peptide YY(3-36) following intraperitoneal administration, mice lacking peptide YY showed normal growth, food intake, energy expenditure, and responsiveness to peptide YY(3-36). These observations suggest that targeted disruption of the peptide YY gene does not perturb terminal endocrine cell differentiation or the control of food intake and energy homeostasis.

The zinc finger protein ras-responsive element binding protein-1 is a coregulator of the androgen receptor: implications for the role of the Ras pathway in enhancing androgenic signaling in prostate cancer.

Androgen receptor (AR) plays an important role in normal prostate function as well as in the etiology of prostate cancer. Activation of AR is dictated by hormone binding and by interactions with coregulators. Several of these coregulators are known targets of Ras-related signals. Recent evidence suggests that Ras activation may play a causal role in the progression of prostate cancer toward a more malignant and hormone-insensitive phenotype. In the present study, we used a transcription factor-transcription factor interaction array method to identify the zinc finger protein Ras-responsive element binding protein (RREB-1) as a partner and coregulator of AR. In LNCaP prostate cancer cells, RREB-1 was found to be present in a complex with endogenous AR as determined by coimmunoprecipitation, glutathione S-transferase pull down, and immunofluorescence analyses. RREB-1 bound to the prostate-specific antigen (PSA) promoter as assessed by chromatin immunoprecipitation. Transient expression of RREB-1 down-regulated AR-mediated promoter activity and suppressed expression of PSA protein. The repressor activity of RREB-1 was significantly attenuated by cotransfection of activated Ras. Moreover, expression of the dominant-negative N-17-Ras or, alternatively, use of the MAPK kinase inhibitor PD98059 [2-(2-amino-3-methyoxyphenyl)-4H-1-benzopyran-4-one] abolished the effect of Ras in attenuating RREB-1-mediated repression. Furthermore, inhibition of RREB-1 expression by RNA interference enhanced the effect of Ras on PSA promoter activity and PSA expression. In addition, activation of the Ras pathway depleted AR from the RREB-1/AR complex. Collectively, our data for the first time identify RREB-1 as a repressor of AR and further implicate the Ras/MAPK kinase pathway as a likely antagonist of the inhibitory effects of RREB-1 on androgenic signaling.

Novel transcriptional potentiation of BETA2/NeuroD on the secretin gene promoter by the DNA-binding protein Finb/RREB-1.

The basic helix-loop-helix protein BETA2/NeuroD activates transcription of the secretin gene and is essential for terminal differentiation of secretin-producing enteroendocrine cells. However, in heterodimeric complexes with its partner basic helix-loop-helix proteins, BETA2 does not appear to be a strong activator of transcription by itself. Mutational analysis of a proximal enhancer in the secretin gene identified several cis-acting elements in addition to the E-box binding site for BETA2. We identified by expression cloning the zinc finger protein RREB-1, also known to exist as a longer form, Finb, as the protein binding to one of the mutationally sensitive elements. Finb/RREB-1 lacks an intrinsic activation domain and by itself did not activate secretin gene transcription. Here we show that Finb/RREB-1 can associate with BETA2 to enhance its transcription-activating function. Both DNA binding and physical interaction of Finb/RREB-1 with BETA2 are required to potentiate transcription. Thus, Finb/RREB-1 does not function as a classical activator of transcription that recruits an activation domain to a DNA-protein complex. Finb/RREB-1 may be distinguished from coactivators, which increase transcription without sequence-specific DNA binding. We suggest that Finb/RREB-1 should be considered a potentiator of transcription, representing a distinct category of transcription-regulating proteins.

Oligomeric form of C-terminal-binding protein coactivates NeuroD1-mediated transcription.

The mechanism underlying transcriptional coactivation by the corepressor C-terminal-binding protein (CtBP) is not established. We previously found that CtBP co-occupies several actively transcribed endocrine genes with the transcription factor NeuroD1 to paradoxically increase transcription by recruiting KDM1A and CoREST. While the importance of the oligomeric form of CtBP for corepression is well established, the role of oligomerization in transcriptional coactivation has received little attention. Here, we examined the importance of the oligomeric state of CtBP for coactivation of NeuroD1-dependent transcription by expressing a CtBP dimerization mutant in cells depleted of endogenous CtBP. Dimerization mutants failed to increase transcription or to associate with KDM1A and CoREST, suggesting that oligomeric, but not monomeric CtBP is required to recruit other proteins needed to activate transcription.

Polarization-Tailored Fano Interference in Plasmonic Crystals: A Mueller Matrix Model of Anisotropic Fano Resonance.

Fano resonance is observed in a wide range of micro- and nano-optical systems and has been a subject of intensive investigations due to its numerous potential applications. Methods that can control or modulate Fano resonance by tuning some experimentally accessible parameters are highly desirable for realistic applications. Here we present a simple yet elegant approach using the Mueller matrix formalism for controlling the Fano interference effect and engineering the resulting asymmetric spectral line shape in an anisotropic optical system. The approach is founded on a generalized model of anisotropic Fano resonance, which relates the spectral asymmetry to physically meaningful and experimentally accessible parameters of interference, namely, the Fano phase shift and the relative amplitudes of the interfering modes. The differences in these parameters between orthogonal linear polarizations in an anisotropic system are exploited to desirably tune the Fano spectral asymmetry using pre- and postselection of optimized polarization states. The concept is demonstrated on waveguided plasmonic crystals using Mueller matrix-based polarization analysis. The approach enabled tailoring of several exotic regimes of Fano resonance in a single device, including the complete reversal of the spectral asymmetry, and shows potential for applications involving control and manipulation of electromagnetic waves at the nanoscale.