Comprehensive review of environmental factors influencing the performance of photovoltaic panels: Concern over emissions at various phases throughout the lifecycle.

Recently, solar photovoltaic (PV) technology has shown tremendous growth among all renewable energy sectors. The attractiveness of a PV system depends deeply of the module and it is primarily determined by its performance. The quantity of electricity and power generated by a PV cell is contingent upon a number of parameters that can be intrinsic to the PV system itself, external or environmental. Thus, to improve the PV panel performance and lifetime, it is crucial to recognize the main parameters that directly influence the module during its operational lifetime. Among these parameters there are numerous factors that positively impact a PV system including the temperature of the solar panel, humidity, wind speed, amount of light, altitude and barometric pressure. On the other hand, the module can be exposed to simultaneous environmental stresses such as dust accumulation, shading and pollution factors. All these factors can gradually decrease the performance of the PV panel. This review not only provides the factors impacting PV panel's performance but also discusses the degradation and failure parameters that can usually affect the PV technology. The major points include: 1) Total quantity of energy extracted from a photovoltaic module is impacted on a daily, quarterly, seasonal, and yearly scale by the amount of dust formed on the surface of the module. 2) Climatic conditions as high temperatures and relative humidity affect the operation of solar cells by more than 70% and lead to a considerable decrease in solar cells efficiency. 3) The PV module current can be affected by soft shading while the voltage does not vary. In the case of hard shadowing, the performance of the photovoltaic module is determined by whether some or all of the cells of the module are shaded. 4) Compared to more traditional forms of energy production, PV systems offer a significant number of advantages to the environment. Nevertheless, these systems can procure greenhouse gas emissions, especially during the production stages. In conclusion, this study underlines the importance of considering multiple parameters while evaluating the performance of photovoltaic modules. Environmental factors can have a major impact on the performance of a PV system. It is critical to consider these factors, as well as intrinsic and other intermediate factors, to optimize the performance of solar energy systems. In addition, continuous monitoring and maintenance of PV systems is essential to ensure maximum efficiency and performance.

TRAF3IP2-IL-17 Axis Strengthens the Gingival Defense against Pathogens.

Recent genome-wide association studies have suggested novel risk loci associated with periodontitis, which is initiated by dysbiosis in subgingival plaque and leads to destruction of teeth-supporting structures. One such genetic locus was the tumor necrosis factor receptor-associated factor 3 interacting protein 2 (TRAF3IP2), a gene encoding the gate-keeping interleukin (IL)-17 receptor adaptor. In this study, we first determined that carriers of the lead exonic variant rs13190932 within the TRAF3IP2 locus combined with a high plaque microbial burden was associated with more severe periodontitis than noncarriers. We then demonstrated that TRAF3IP2 is essential in the IL-17-mediated CCL2 and IL-8 chemokine production in primary gingival epithelial cells. Further analysis suggested that rs13190932 may serve a surrogate variant for a genuine loss-of-function variant rs33980500 within the same gene. Traf3ip2 null mice (Traf3ip2-/-) were more susceptible than wild-type (WT) mice to the Porphyromonas gingivalis-induced periodontal alveolar bone loss. Such bone loss was associated with a delayed P. gingivalis clearance and an attenuated neutrophil recruitment in the gingiva of Traf3ip2-/- mice. Transcriptomic data showed decreased expression of antimicrobial genes, including Lcn2, S100a8, and Defb1, in the Traf3ip2-/- mouse gingiva in comparison to WT mice prior to or upon P. gingivalis oral challenge. Further 16S ribosomal RNA sequencing analysis identified a distinct microbial community in the Traf3ip2-/- mouse oral plaque, which was featured by a reduced microbial diversity and an overabundance of Streptococcus genus bacteria. More P. gingivalis was observed in the Traf3ip2-/- mouse gingiva than WT control animals in a ligature-promoted P. gingivalis invasion model. In agreement, neutrophil depletion resulted in more local gingival tissue invasion by P. gingivalis. Thus, we identified a homeostatic IL-17-TRAF3IP2-neutrophil axis underpinning host defense against a keystone periodontal pathogen.

Comparison of shear bond strength of composite resin, compomer, and resin-modified glass-ionomer cements in primary teeth: An in-vitro study.

OBJECTIVE: The contemporary esthetic restorative materials such as composite resin and glass-ionomer cements and their modifications have all been developed keeping in mind the requirements of permanent teeth. There have been plenty of studies that have focused on the characteristics of these materials in relation to permanent teeth with a relative dearth of such studies as regard to the primary teeth. The present study was undertaken to compare and evaluate the shear bond strength of composite resin, compomer, and resin-modified glass-ionomer cements in primary teeth. METHODS: Thirty non-carious primary molars that were indicated for extraction because of physiological resorption or, for orthodontic reasons, were selected. The selected teeth were randomly allocated to three groups of 10 each for composite, compomer, and resin-modified glass-ionomer cements. The enamel from the occlusal surface of all teeth was removed to expose the superficial dentin and was wet polished with 400 grit sand paper. Composite, compomer, and resin-modified glass-ionomer stubs were bonded on to the occlusal surfaces using a plastic tube as a template. All samples were, then, subjected to thermocycling and evaluation of shear bond strength using the universal testing machine at a cross-head speed of 0.5 mm/min, whereas the results obtained were subjected to statistical analysis. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) version 17.0 (SPSS Inc., Chicago, IL, USA), whereas one-way analysis of variance (ANOVA) and Tukey's multiple post-hoc procedures were used for statistical analysis. A P < 0.05 was considered statistically significant. RESULTS: The mean shear bond strength values for Groups I, II, and III were found to be 11.7 ± 3.07 MPa, 7.74 ± 4.16 Mpa, and 4.43 ± 2.08 Mpa, respectively, whereas one-way ANOVA and Tukey's multiple post-hoc procedures indicated that there were remarkable differences among the three groups with the results being statistically significant (P < 0.05). CONCLUSIONS: Composite resin showed the highest shear bond strength in relation to primary dentin when compared to compomer and resin-modified glass-ionomer cements.

Effects of branched-chain amino acids on glucose uptake and lactose synthesis rates in bovine mammary epithelial cells and lactating mammary tissue slices.

Even though supplementations of essential AA (EAA) are often related to increased lactose yields in dairy cows, underlying mechanisms connecting EAA availability to the mammary glands and lactose synthesis are poorly understood. The objective of this study was to examine the effects of branched-chain AA (BCAA) including Leu, Ile, and Val on (1) glucose transporter (GLUT1) abundance and glucose uptake, (2) the abundance of proteins regulating lactose synthesis pathway, and (3) fractional synthesis rates of lactose (FSR) using bovine mammary epithelial cells (BMEC) and mammary tissues slices (MTS). The BMEC (n = 4) were allocated randomly to regular Dulbecco's Modified Eagle Medium with Ham's F12 (DMEM/F12) medium (+EAA) or +EAA deficient (by 90%) in all EAA (-EAA), all BCAA (-BCAA), only Leu (-Leu), only Ile (-Ile) or only Val (-Val). Western immunoblotting analyses, depletion of glucose in media, and a proteomic analysis were performed to determine the abundance of GLUT1 in the cell membrane, net glucose uptake, and the abundance of enzymes involved in lactose synthesis pathway in BMEC, respectively. The MTS (n = 6) were allocated randomly to DMEM/F12 medium having all EAA and 13C-glucose at concentrations similar to plasma concentrations of cows (+EAAp), and +EAAp deprived of all BCAA (-BCAAp) or only Leu (-Leup) for 3 h. The 13C enrichments of free glucose pool in MTS (EGlu-free) and the enrichments of glucose incorporated into lactose in MTS and media [ELactose-bound (T&M)] were determined and used in calculating FSR. In BMEC, -BCAA increased the fraction of total GLUT1 translocated to the cell membrane and the fraction that was potentially glycosylated compared with +EAA. Among individual BCAA, only -Leu was associated with a 63% increase in GLUT1 translocated to the cell membrane and a 40% increase in glucose uptake of BMEC. The -BCAA tended to be related to a 75% increase in the abundance of hexokinase in BMEC. Deprivation of Leu tended to increase glucose uptake of MTS but did not affect EGlu-free, ELactose-bound (T&M), or FSR relative to +EAAp. On the other hand, -BCAAp did not affect glucose uptake of MTS but was related to lower ELactose-bound (T&M), or FSR relative to +EAAp. Considering together, decreasing Leu supply to mammary tissues enhances GLUT1 and thus glucose uptake, which, however, does not affect lactose synthesis rates. Moreover, the deficiency of other BCAA, Ile, and Val alone or together with the deficiency of Leu seemed to decrease lactose synthesis rates without affecting glucose uptake. The data also emphasize the importance of addressing the effect of the supply of other nutrients to the mammary glands than the precursor supply in describing the synthesis of a milk component.

Dynamic diffusion lung capacity of carbon monoxide (DLCO) as a predictor of pulmonary microangiopathy and its association with extra pulmonary microangiopathy in patients with type II diabetes mellitus.

BACKGROUND AND AIM: Lung as a target end organ for microvascular disease often remains underdiagnosed. This study aims to assess occurrence of pulmonary microangiopathy among Type 2 diabetes mellitus (T2DM) using dynamic diffusion lung capacity of carbon monoxide (DLCO). METHODS: A total of 120 participants aged >18 years were enrolled in this study. Group 1 comprised T2DM with microangiopathy (n = 40), group 2 include T2DM without microangiopathy (n = 40), group 3 were healthy controls (n = 40). Individuals with underlying lung disease, smoking history, heart failure, urinary tract infection, macrovascular complications of diabetes, microalbuminuria due to other causes were excluded from the study. Using electronic spirometry, Forced Expiratory Volume in first second (FEV1), Forced Vital Capacity (FVC) was measured and FEV1/FVC ratio calculated. DLCO (%predicted) using single breath method was measured in sitting position followed by supine position and delta DLCO was calculated. DLCO measured was compared between the three groups. RESULTS: DLCO (median [IQR]) in sitting (78 [70-82.75]) and supine position (70 [62-84]) among group one was significantly decreased when compared to other two groups (p value < 0.001, p value < 0.001 respectively). Delta DLCO (median, [IQR]) among patients with diabetic microangiopathy (-6 [-8 to -2]) was significant on comparison with group two (4[2,6]) and control group (5[4,6]) (p < 0.001). Negative delta DLCO reflecting pulmonary microangiopathy was significantly associated with extrapulmonary microangiopathy (p value = 0.027). CONCLUSION: Postural variation in DLCO is a useful non-invasive test for identifying pulmonary microangiopathy among T2DM patients. Presence of pulmonary microangiopathy has significant association with diabetic nephropathy and retinopathy.

Real-world application of tumor mutational burden-high (TMB-high) and microsatellite instability (MSI) confirms their utility as immunotherapy biomarkers.

INTRODUCTION: Microsatellite instability (MSI) testing and tumor mutational burden (TMB) are genomic biomarkers used to identify patients who are likely to benefit from immune checkpoint inhibitors. Pembrolizumab was recently approved by the Food and Drug Administration for use in TMB-high (TMB-H) tumors, regardless of histology, based on KEYNOTE-158. The primary objective of this retrospective study was real-world applicability and use of immunotherapy in TMB/MSI-high patients to lend credence to and refine this biomarker. METHODS: Charts of patients with advanced solid tumors who had MSI/TMB status determined by next generation sequencing (NGS) (FoundationOne CDx) were reviewed. Demographics, diagnosis, treatment history, and overall response rate (ORR) were abstracted. Progression-free survival (PFS) was determined from Kaplan-Meier curves. PFS1 (chemotherapy PFS) and PFS2 (immunotherapy PFS) were determined for patients who received immunotherapy after progressing on chemotherapy. The median PFS2/PFS1 ratio was recorded. RESULTS: MSI-high or TMB-H [≥20 mutations per megabase (mut/MB)] was detected in 157 adults with a total of 27 distinct tumor histologies. Median turnaround time for NGS was 73 days. ORR for most recent chemotherapy was 34.4%. ORR for immunotherapy was 55.9%. Median PFS for patients who received chemotherapy versus immunotherapy was 6.75 months (95% confidence interval, 3.9-10.9 months) and 24.2 months (95% confidence interval, 9.6 months to not reached), respectively (P = 0.042). Median PFS2/PFS1 ratio was 4.7 in favor of immunotherapy. CONCLUSION: This real-world study reinforces the use of TMB as a predictive biomarker. Barriers exist to the timely implementation of NGS-based biomarkers and more data are needed to raise awareness about the clinical utility of TMB. Clinicians should consider treating TMB-H patients with immunotherapy regardless of their histology.

Variations in Canal Morphology, Shapes, and Positions of Major Foramen in Maxillary and Mandibular Teeth.

CONTEXT AND AIM: A plethora of studies have revealed that there is a lack of general consensus in the precise anatomic detailing of the canals and the major foramen in both the maxillary and mandibular teeth while emphasizing the significance of the same for a successful endodontic treatment. The aim of the present study was to determine the variations in canal morphology, shapes, and positions of major foramen in maxillary and mandibular teeth. MATERIALS AND METHODS: In the present study, 420 extracted human maxillary and mandibular teeth with completely formed apices were included. The specimens were cleaned for surface debris including remnants of periodontal tissue and were stored in saline. Examination of the apices was performed with the help of stereomicroscope for their exact shapes and configurations and precise anatomic location. Comparison of different parameters within the group was done using Chi-square test while P < 0.05 was considered statistically significant. RESULTS: The results of the present study indicated that apical foramen in mandibular teeth showed higher degree of deviation with a prevalence of 70.2% while flat shape of apical foramen was observed only in maxillary teeth. Furthermore, maximum deviation in maxillary teeth was recorded in the canines with a prevalence of 90% while, in mandibular teeth, maximum deviation was recorded with mandibular second premolars with a prevalence of 79.12%. CONCLUSIONS: The results of the present study revealed that deviation of apical foramen from the root apex was seen in 68.2% of the specimens. Furthermore, deviation was greater in the mandibular than the maxillary teeth.

Assessment of the viability of human periodontal ligament cells in black tea, lime juice, and passion fruit concentrate - A comparative in vitro study.

BACKGROUND: Tooth avulsion is considered as a severe form of dental trauma, causing damage to the periodontium. Hence, the preservation of healthy periodontal ligament (PDL) cells in the storage medium are pivotal for the success of replantation. AIM AND OBJECTIVE: The aim of this study is to assess the viability of human PDL cells in black tea, lime juice, and passion fruit concentrate. METHODS: Human periodontal cells were cultured and stored in three experimental media - black tea, lime juice, and passion fruit concentrate and subjected to 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay for 1 h and the cell viability was determined. Mean and standard deviation were statistically analyzed using one-way analysis of variance to identify the significant groups. RESULTS: The human PDL cells showed 100% viability in lime juice and passion fruit concentrate, followed by 98% viability in black tea. CONCLUSION: Black tea, lime juice, and passion fruit concentrate can be used effectively as storage media for maintaining PDL cells viability in avulsed teeth, with 100% viability exhibited by lime juice and passion fruit concentrate.

Poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) and polyvinylidene fluoride blend doped with oxydianiline-based thiourea derivatives as a novel and modest gel electrolyte system for dye-sensitized solar cell applications.

Unique symmetrical thiourea derivatives with an oxydianiline core were synthesized using cost-effective and simple methods. A new gel electrolyte system was prepared using these thiourea additives along with a highly conductive PEG-PPG-PEG block copolymer, PVDF, and an iodide/triiodide redox couple. The PEG units present in the electrolyte are well-known for their intense segmental motion of ions, which can degrade the recombination rate and favour the charge transfer. The thiourea additives interacted well with the redox couple to limit iodine sublimation and their adsorption induced a negative potential shift for TiO2. The highest efficiency attained by utilizing such gel polymer electrolytes was 5.75%, especially with 1,1'-(oxybis(4,1-phenylene))bis(3-(6-methylpyridin-2-yl) thiourea) (OPPT), under an irradiation of 100 mW cm-2. The electrochemical impedance spectroscopy, UV-vis absorption spectroscopy, differential scanning calorimetry, and FTIR spectroscopy data of such gel polymer electrolytes favoured the PCE order of the additives used in DSSCs. The improvement in the DSSC performance with symmetrical thioureas having electron-rich atoms was practically attributed to the reduction of back electron transfer, dye regeneration, and hole transport.

Compressive three-dimensional super-resolution microscopy with speckle-saturated fluorescence excitation.

Nonlinear structured illumination microscopy (nSIM) is an effective approach for super-resolution wide-field fluorescence microscopy with a theoretically unlimited resolution. In nSIM, carefully designed, highly-contrasted illumination patterns are combined with the saturation of an optical transition to enable sub-diffraction imaging. While the technique proved useful for two-dimensional imaging, extending it to three-dimensions is challenging due to the fading of organic fluorophores under intense cycling conditions. Here, we present a compressed sensing approach that allows 3D sub-diffraction nSIM of cultured cells by saturating fluorescence excitation. Exploiting the natural orthogonality of speckles at different axial planes, 3D probing of the sample is achieved by a single two-dimensional scan. Fluorescence contrast under saturated excitation is ensured by the inherent high density of intensity minima associated with optical vortices in polarized speckle patterns. Compressed speckle microscopy is thus a simple approach that enables 3D super-resolved nSIM imaging with potentially considerably reduced acquisition time and photobleaching.

Hybrid capture-based genomic profiling of circulating tumor DNA from patients with estrogen receptor-positive metastatic breast cancer.

BACKGROUND: Genomic changes that occur in breast cancer during the course of disease have been informed by sequencing of primary and metastatic tumor tissue. For patients with relapsed and metastatic disease, evolution of the breast cancer genome highlights the importance of using a recent sample for genomic profiling to guide clinical decision-making. Obtaining a metastatic tissue biopsy can be challenging, and analysis of circulating tumor DNA (ctDNA) from blood may provide a minimally invasive alternative. PATIENTS AND METHODS: Hybrid capture-based genomic profiling was carried out on ctDNA from 254 female patients with estrogen receptor-positive breast cancer. Peripheral blood samples were submitted by clinicians in the course of routine clinical care between May 2016 and March 2017. Sequencing of 62 genes was carried out to a median unique coverage depth of 7503×. Genomic alterations (GAs) in ctDNA were evaluated and compared with matched tissue samples and genomic datasets of tissue from breast cancer. RESULTS: At least 1 GA was reported in 78% of samples. Frequently altered genes were TP53 (38%), ESR1 (31%) and PIK3CA (31%). Temporally matched ctDNA and tissue samples were available for 14 patients; 89% of mutations detected in tissue were also detected in ctDNA. Diverse ESR1 GAs including mutation, rearrangement and amplification, were observed. Multiple concurrent ESR1 GAs were observed in 40% of ESR1-altered cases, suggesting polyclonal origin; ESR1 compound mutations were also observed in two cases. ESR1-altered cases harbored co-occurring GAs in PIK3CA (35%), FGFR1 (16%), ERBB2 (8%), BRCA1/2 (5%), and AKT1 (4%). CONCLUSIONS: GAs relevant to relapsed/metastatic breast cancer management were identified, including diverse ESR1 GAs. Genomic profiling of ctDNA demonstrated sensitive detection of mutations found in tissue. Detection of amplifications was associated with ctDNA fraction. Genomic profiling of ctDNA may provide a complementary and possibly alternative approach to tissue-based genomic testing for patients with estrogen receptor-positive metastatic breast cancer.

Characterizing effects of feed restriction and glucagon-like peptide 2 administration on biomarkers of inflammation and intestinal morphology.

Inadequate feed consumption reduces intestinal barrier function in both ruminants and monogastrics. Objectives were to characterize how progressive feed restriction (FR) affects inflammation, metabolism, and intestinal morphology, and to investigate if glucagon-like peptide 2 (GLP2) administration influences the aforementioned responses. Twenty-eight Holstein cows (157 ± 9 d in milk) were enrolled in 2 experimental periods. Period 1 [5 d of ad libitum (AL) feed intake] served as baseline for period 2 (5 d), during which cows received 1 of 6 treatments: (1) 100% of AL feed intake (AL100; n = 3), (2) 80% of AL feed intake (n = 5), (3) 60% of AL feed intake (n = 5), (4) 40% of AL feed intake (AL40; n = 5), (5) 40% of AL feed intake + GLP2 administration (AL40G; 75 µg/kg of BW s.c. 2×/d; n = 5), or (6) 20% of AL feed intake (n = 5). As the magnitude of FR increased, body weight and milk yield decreased linearly. Blood urea nitrogen and insulin decreased, whereas nonesterified fatty acids and liver triglyceride content increased linearly with progressive FR. Circulating endotoxin, lipopolysaccharide binding protein, haptoglobin, serum amyloid A, and lymphocytes increased or tended to increase linearly with advancing FR. Circulating haptoglobin decreased (76%) and serum amyloid A tended to decrease (57%) in AL40G relative to AL40 cows. Cows in AL100, AL40, and AL40G treatments were euthanized to evaluate intestinal histology. Jejunum villus width, crypt depth, and goblet cell area, as well as ileum villus height, crypt depth, and goblet cell area, were reduced (36, 14, 52, 22, 28, and 25%, respectively) in AL40 cows compared with AL100 controls. Ileum cellular proliferation tended to be decreased (14%) in AL40 versus AL100 cows. Relative to AL40, AL40G cows had improved jejunum and ileum morphology, including increased villus height (46 and 51%), villus height to crypt depth ratio (38 and 35%), mucosal surface area (30 and 27%), cellular proliferation (43 and 36%), and goblet cell area (59 and 41%). Colon goblet cell area was also increased (48%) in AL40G relative to AL40 cows. In summary, progressive FR increased circulating markers of inflammation, which we speculate is due to increased intestinal permeability as demonstrated by changes in intestinal architecture. Furthermore, GLP2 improved intestinal morphology and ameliorated circulating markers of inflammation. Consequently, FR is a viable model to study consequences of intestinal barrier dysfunction and administering GLP2 appears to be an effective mitigation strategy to improve gut health.

Short-term heat stress causes altered intracellular signaling in oxidative skeletal muscle.

Heat stress (HS) causes morbidities and mortalities, in part by inducing organ-specific injury and dysfunction. Further, HS markedly reduces farm animal productivity, and this is especially true for lean tissue accretion. The purpose of this investigation was to determine the extent to which short-term HS caused muscle dysfunction in skeletal muscle. We have previously found increased free radical injury in skeletal muscle following 24 h of HS. Thus, we hypothesized that HS would lead to apoptosis, autophagy, and decreased mitochondrial content in skeletal muscle. To test this hypothesis, crossbred gilts were divided into 3 groups ( = 8/group): thermal neutral (TN: 21°C), HS (37°C), and pair-fed thermal neutral (PFTN: feed intake matched with heat-stressed animals). Following 12 h of treatment, animals were euthanized and red (STR) and white (STW) portions of the semitendinosus were recovered. Heat stress did not alter intracellular signaling in STW. In STR, the oxidative stress marker malondialdehyde protein and concentration were increased in HS ( = 0.007) compared to TN and PFTN, which was matched by an inadequate antioxidant response, including an increase in superoxide dismutase (SOD) I ( = 0.03) and II relative protein abundance ( = 0.008) and total SOD activity ( = 0.02) but a reduction ( = 0.006) in catalase activity in HS compared to TN. Further, B-cell lymphoma 2-associated X protein ( = 0.02) and apoptotic protease activating factor 1 ( = 0.01) proteins were increased by HS compared to TN and PFTN. However, caspase 3 activity was similar between groups, indicating a lack of apoptotic execution. Despite increased initiation, autophagy appeared to be inhibited by HS as the microtubule-associated protein A/B light chain 3 II/I ratio and mitofusin-2 proteins were decreased ( < 0.03) and sequestosome 1(p62) protein abundance was increased ( = 0.001) in HS compared to TN and PFTN. Markers of mitochondrial content cytochrome c, cytochrome c oxidase IV, voltage-dependent anion channel, pyruvate dehydrogenase, and prohibitins 1 were increased ( < 0.05) in HS compared to TN, whereas mitochondrial biogenesis and mitophagy markers were similar between groups. These data demonstrate that HS caused aberrant intracellular signaling, which may contribute to HS-mediated muscle dysfunction.

The Abl-1 Kinase is Dispensable for NK Cell Inhibitory Signalling and is not Involved in Murine NK Cell Education.

Natural killer (NK) cell responsiveness in the mouse is determined in an education process guided by inhibitory Ly49 and NKG2A receptors binding to MHC class I molecules. It has been proposed that inhibitory signalling in human NK cells involves Abl-1 (c-Abl)-mediated phosphorylation of Crk, lowering NK cell function via disruption of a signalling complex including C3G and c-Cbl, suggesting that NK cell education might involve c-Abl. Mice deficient in c-Abl expression specifically in murine NK cells displayed normal inhibitory and activating receptor repertoires. Furthermore, c-Abl-deficient NK cells fluxed Ca2+ normally after triggering of ITAM receptors, killed YAC-1 tumour cells efficiently and showed normal, or even slightly elevated, capacity to produce IFN-γ after activating receptor stimulation. Consistent with these results, c-Abl deficiency in NK cells did not affect NK cell inhibition via the receptors Ly49G2, Ly49A and NKG2A. We conclude that signalling downstream of murine inhibitory receptors does not involve c-Abl and that c-Abl plays no major role in NK cell education in the mouse.

Regulation of spindle integrity and mitotic fidelity by BCCIP.

Centrosomes together with the mitotic spindle ensure the faithful distribution of chromosomes between daughter cells, and spindle orientation is a major determinant of cell fate during tissue regeneration. Spindle defects are not only an impetus of chromosome instability but are also a cause of developmental disorders involving defective asymmetric cell division. In this work, we demonstrate BCCIP, especially BCCIPα, as a previously unidentified component of the mitotic spindle pole and the centrosome. We demonstrate that BCCIP localizes proximal to the mother centriole and participates in microtubule organization and then redistributes to the spindle pole to ensure faithful spindle architecture. We find that BCCIP depletion leads to morphological defects, disoriented mitotic spindles, chromosome congression defects and delayed mitotic progression. Our study identifies BCCIP as a novel factor critical for microtubule regulation and explicates a mechanism utilized by BCCIP in tumor suppression.

Age-related macular degeneration in a South Indian population, with and without diabetes.

PurposeTo elucidate the prevalence and risk factors of age-related macular degeneration (AMD) in people with diabetes.MethodsOf the 5495 subjects ≥60 years of age recruited in the population-based study in south India, 4791 subjects with gradable images on 30° three-field retinal photographs were analyzed. AMD and diabetic retinopathy (DR) were graded based on the International ARM Epidemiological Study Group classification and International Clinical Diabetic Retinopathy Disease Severity Scale, respectively. All subjects underwent a detailed history, physical examination, and a comprehensive ocular examination.ResultsOf the 4791 subjects, 1256 had diabetes. In those with diabetes, 166 (13.2%) had DR: of which, 9.6% had AMD. Of those with diabetes but no DR, 15.6% had AMD. Presence of DR (OR=0.57, 95% CI: 0.33-0.99, P=0.046) was a protective factor for AMD in diabetes. When adjusted for potential confounding factors, those with AMD and diabetes were from urban areas (OR=1.65, 95% CI: 1.09-2.49, P=0.018), had raised systolic blood pressure (OR=1.02, 95% CI: 1.00-1.03, P=0.01), higher BMI (OR=1.06, 95% CI: 1.02-1.10, P=0.005), and higher serum triglycerides (OR=1.00, 95% CI: 1.00-1.01, P=0.011). A higher level of high-density lipoprotein (HDL) (OR=0.98, 95% CI: 0.96-0.99, P=0.038) was a protective factor for AMD in subjects with diabetes.ConclusionsThe presence of DR and higher serum HDL are protective factors whereas obesity and higher systolic blood pressure are risk factors for AMD in subjects with diabetes.

Contrast sensitivity and its determinants in people with diabetes: SN-DREAMS-II, Report No 6.

PurposeTo assess contrast sensitivity (CS) and to elucidate the factors associated with CS among subjects with type 2 diabetes in a cross-sectional population-based study.Patients and methodsSubjects were recruited from a follow-up cohort, Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular genetics Study (SN-DREAMS II). Of 958 subjects who were followed up in SN-DREAMS II, a subset of 653 subjects was included in the analysis. All subjects underwent a comprehensive eye examination, which included CS assessment using the Pelli-Robson chart. The cross-sectional association between CS and independent variables was assessed using stepwise linear regression analysis. A P-value of <0.05 was considered statistically significant.ResultsThe mean age of the study sample was 58.7±9.41 (44-87) years. Mean CS of the study sample was 1.32±0.20 (range: 0-1.65) log units. CS was negatively and significantly correlated with age, duration of diabetes, hemoglobin level, vibration perception threshold (VPT) value, albuminuria, best corrected visual acuity (BCVA), refractive error, total error score (TEM) of FM 100 hue test, and mean retinal sensitivity. In multiple regression analysis, after adjusting for all the related factors, CS was significantly associated with BCVA (ß=-0.575; P<0.001), VPT (ß=-0.003; P=0.010), severity of cataract (ß=-0.018; P=0.032), diabetic retinopathy (ß=-0.016; P=0.019), and age (ß=-0.002; P=0.029). These factors explained about 29.3% of the variation in CS.ConclusionAmong the factors evaluated, differences in BCVA were associated with the largest predicted differences in CS. This association of CS with visual acuity highlights the important role of visual assessment in type 2 diabetes.

Looking beyond drivers and passengers in cancer genome sequencing data.

Cancer arises as a result of acquired changes in the DNA sequence of the genome of somatic cells. A subset of the genetic changes, dubbed driver mutations, propels tumor growth, and the remaining changes are passengers, apparently inconsequential for neoplastic transformation. Massive genome sequencing of thousands of tumors from all major cancer types has enabled cataloging of the so-called driver and passenger mutations, and facilitated molecular classification of cancer, guiding precision medicine approach for the patients. Nonetheless, innovative analyses of cancer genomics data has led to novel, sometimes serendipitous findings that have aided to our understanding of other aspects of the biology of the disease and opened up new frontiers. For instance, emerging findings show that mutational patterns in cancer genomes can help detect signatures of known and novel DNA damage and repair processes, provide a likely chronological account of genomic changes in cancer genomes, and allow revisiting the models of cancer evolution. These findings have stimulated original approaches to identify disease etiology, stratify patients, target the disease, and monitor patient responses, complementing driver-mutation centric approaches. In this review, we discuss these emerging approaches and unexpected breakthroughs, and their implications for basic cancer research and clinical practices.

Biochemical assessment of human uterine cervix by micro-Raman mapping.

Raman spectroscopy and mapping are capable of probing the molecular changes due to oncogenesis. Here Raman maps of cervical tissues under different pathological conditions were studied. Multivariate analytical methods were utilized to reconstruct these Raman maps and were compared with Hematoxylin and Eosin stained histological images. The maps showed clear differences between the different regions of the tissue and there were spectral changes associated with neoplasia and malignancy. A semi-quantitative biochemical modeling was carried out to quantify these spectral changes and the relative contributions of the biochemicals. This method revealed gradual biochemical changes (nucleus to cytoplasm ratio, glycogen, collagen, lipids, protein and carotene) associated with the progression of cervical cancer. These biomolecules extracted for the disease prognosis would have greater significance for cervical cancer diagnosis.