UBQLN4 Represses Homologous Recombination and Is Overexpressed in Aggressive Tumors

Genomic instability can be a hallmark of both human genetic disease and cancer. We identify a deleterious UBQLN4 mutation in families with an autosomal recessive syndrome reminiscent of genome instability disorders. UBQLN4 deficiency leads to increased sensitivity to genotoxic stress and delayed DNA double-strand break (DSB) repair. The proteasomal shuttle factor UBQLN4 is phosphorylated by ATM and interacts with ubiquitylated MRE11 to mediate early steps of homologous recombination-mediated DSB repair (HRR). Loss of UBQLN4 leads to chromatin retention of MRE11, promoting non-physiological HRR activity in vitro and in vivo. Conversely, UBQLN4 overexpression represses HRR and favors non-homologous end joining. Moreover, we find UBQLN4 overexpressed in aggressive tumors. In line with an HRR defect in these tumors, UBQLN4 overexpression is associated with PARP1 inhibitor sensitivity. UBQLN4 therefore curtails HRR activity through removal of MRE11 from damaged chromatin and thus offers a therapeutic window for PARP1 inhibitor treatment in UBQLN4-overexpressing tumors

Mucinous carcinoma of breast with neuroendocrine differentiation: a rare case report with review of literature

Mucinous carcinoma of the breast is a relatively rare malignancy accounting for 2% of all breast cancers. Mucinous carcinoma of the breast has a favourable prognosis and is usually seen in postmenopausal women. Here, we report a 60 year old female patient presented with right breast lump was diagnosed on cytology as ductal carcinoma of the breast, on histopathology diagnosed as mucinous carcinoma with neuroendocrine differentiation, which was subsequently confirmed on IHC marker synaptophysin and chromogranin A positive

Peritoneal Dialysis in Dengue Shock Syndrome May Be Detrimental

Dengue shock syndrome is the most severe form of Dengue that can be fatal. Nonresponders to standard therapy need intensive care. This paper outlines the clinical features, complications, and outcomes of Dengue Shock Syndrome not responding to standard therapies and needing supportive care in a tertiary referral intensive care unit of a developing country. Nearly one-third die within 3 days of admission to ICU. Peritoneal dialysis predicts the worst outcomes

Multivariate analysis of oil palm germplasm for vegetative and bunch yield traits

Multivariate analysis of oil palm germplasm for vegetative and bunch yield trait

Sequencing of the Cheese Microbiome and Its Relevance to Industry

peer-reviewedThe microbiota of cheese plays a key role in determining its organoleptic and other physico-chemical properties. It is essential to understand the various contributions, positive or negative, of these microbial components in order to promote the growth of desirable taxa and, thus, characteristics. The recent application of high throughput DNA sequencing (HTS) facilitates an even more accurate identification of these microbes, and their functional properties, and has the potential to reveal those microbes, and associated pathways, responsible for favorable or unfavorable characteristics. This technology also facilitates a detailed analysis of the composition and functional potential of the microbiota of milk, curd, whey, mixed starters, processing environments, and how these contribute to the final cheese microbiota, and associated characteristics. Ultimately, this information can be harnessed by producers to optimize the quality, safety, and commercial value of their products. In this review we highlight a number of key studies in which HTS was employed to study the cheese microbiota, and pay particular attention to those of greatest relevance to industry

Clinical Study Peritoneal Dialysis in Dengue Shock Syndrome May Be Detrimental

Dengue shock syndrome is the most severe form of Dengue that can be fatal. Nonresponders to standard therapy need intensive care. This paper outlines the clinical features, complications, and outcomes of Dengue Shock Syndrome not responding to standard therapies and needing supportive care in a tertiary referral intensive care unit of a developing country. Nearly one-third die within 3 days of admission to ICU. Peritoneal dialysis predicts the worst outcomes

Effect of growth regulators and micronutrients on quality parameters in cashew (Anacardium occidentale L.)

Cashew (Anacardium occidentale L.) is an important tropical nut crop of social and economic importance worldwide. However, the crop is threatened with the low yield. In the present study, an attempt was made to test the effects of plant growth hormones as well as micronutrients on nut and apple quality of cashew var. Bhaskara. Significant differences in kernel weight, shelling percentage, carbohydrates and starch content of cashew kernel and juice content of cashew apple were observed with the foliar application of growth hormones and micronutrients. The foliar application of ethrel @ 50 ppm increased shelling percentage (35.8%), carbohydrate content (21.63%), sugar content (6.26%), protein content (32.4%), starch content (31.42%), juice content (78.3%) and total soluble solids (120 Brix). Further, the foliar spray of zinc sulphate (0.5%) + borax (0.1%) increased shelling (36.13%), protein content (32.15%), starch content (32.03%) among all the treatments tested. Furthermore, higher cashew apple juice content (78%) and total soluble solids (120Brix) was also recorded with the foliar spray of zinc sulphate (0.5%) + borax (0.1%)

Scary Barbie: An Extremely Energetic, Long-Duration Tidal Disruption Event Candidate Without a Detected Host Galaxy at z = 0.995

We report multi-wavelength observations and characterization of the ultraluminous transient AT 2021lwx (ZTF20abrbeie; aka ``Barbie'') identified in the alert stream of the Zwicky Transient Facility (ZTF) using a Recommender Engine For Intelligent Transient Tracking (REFITT) filter on the ANTARES alert broker. From a spectroscopically measured redshift of 0.995, we estimate a peak observed pseudo-bolometric luminosity of log (L$_{\text{max}} / [\text{erg}/\text{s}]$) = 45.7 from slowly fading ztf-$\it{g}$ and ztf-$r$ light curves spanning over 1000 observer-frame days. The host galaxy is not detected in archival Pan-STARRS observations ($g > 23.3$ mag), implying a lower limit to the outburst amplitude of more than 5 mag relative to the quiescent host galaxy. Optical spectra from Lick and Keck Observatories exhibit strong emission lines with narrow cores from the H Balmer series and ultraviolet semi-forbidden lines of Si III] $\lambda$1892, C III] $\lambda$1909, and C II] $\lambda$2325. Typical nebular lines in AGN spectra from ions such as [O II] and [O III] are not detected. These spectral features, along with the smooth light curve that is unlike most AGN flaring activity, and the luminosity that exceeds any observed or theorized supernova, lead us to conclude that AT 2021lwx is most likely an extreme tidal disruption event (TDE). Modeling of ZTF photometry with MOSFiT suggests that the TDE was between a $\approx 14 M_{\odot}$ star and a supermassive black hole of mass $M_{\text{BH}} \sim$ $10^{8} M_{\odot}$. Continued monitoring of the still-evolving light curve along with deep imaging of the field once AT 2021lwx has faded can test this hypothesis and potentially detect the host galaxy.Comment: 15 pages, 4 figures, 1 Table; Version as published in The Astrophysical Journal Letters. Observations of AT 2021lwx published in the paper can be found at https://bsubraya.github.io/research

Assessing the ability of nisin A and derivatives thereof to inhibit gram-negative bacteria from the genus Thermus

peer-reviewNisin is a bacteriocin that is globally employed as a biopreservative in food systems to control gram-positive, and some gram-negative, bacteria. Here we tested the bioactivity of nisin A-producing Lactococcus lactis NZ9700 and producers of bioengineered variants thereof against representatives of the gram-negative genus Thermus, which has been associated with the pink discoloration defect in cheese. Starting with a total of 73 nisin variant-producing Lactococcus lactis, bioactivity against Thermus was assessed via agar diffusion assays, and 22 variants were found to have bioactivity greater than or equal to that of the nisin A-producing control. To determine to what extent this enhanced bioactivity was attributable to an increase in specific activity, minimum inhibitory concentrations were determined using the corresponding purified form of these 22 nisin A derivatives. From these experiments, nisin M17Q and M21F were identified as peptides with enhanced antimicrobial activity against the majority of Thermus target strains tested. In addition, several other peptide variants were found to exhibit enhanced specific activity against a subset of strains

Assessing the ability of nisin A and derivatives thereof to inhibit gram-negative bacteria from the genus Thermus

peer-reviewNisin is a bacteriocin that is globally employed as a biopreservative in food systems to control gram-positive, and some gram-negative, bacteria. Here we tested the bioactivity of nisin A-producing Lactococcus lactis NZ9700 and producers of bioengineered variants thereof against representatives of the gram-negative genus Thermus, which has been associated with the pink discoloration defect in cheese. Starting with a total of 73 nisin variant-producing Lactococcus lactis, bioactivity against Thermus was assessed via agar diffusion assays, and 22 variants were found to have bioactivity greater than or equal to that of the nisin A-producing control. To determine to what extent this enhanced bioactivity was attributable to an increase in specific activity, minimum inhibitory concentrations were determined using the corresponding purified form of these 22 nisin A derivatives. From these experiments, nisin M17Q and M21F were identified as peptides with enhanced antimicrobial activity against the majority of Thermus target strains tested. In addition, several other peptide variants were found to exhibit enhanced specific activity against a subset of strains