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Peroxisomes are membrane-bound organelles harboring metabolic enzymes. In humans, peroxisomes are required for normal development, yet the genes regulating peroxisome function remain unclear. We performed a genome-wide CRISPRi screen to identify novel factors involved in peroxisomal homeostasis. We found that inhibition of RNF146, an E3 ligase activated by poly(ADP-ribose), reduced the import of proteins into peroxisomes. RNF146-mediated loss of peroxisome import depended on the stabilization and activity of the poly(ADP-ribose) polymerases TNKS and TNKS2, which bind the peroxisomal membrane protein PEX14. We propose that RNF146 and TNKS/2 regulate peroxisome import efficiency by PARsylation of proteins at the peroxisome membrane. Interestingly, we found that the loss of peroxisomes increased TNKS/2 and RNF146-dependent degradation of non-peroxisomal substrates, including the ß-catenin destruction complex component AXIN1, which was sufficient to alter the amplitude of ß-catenin transcription. Together, these observations not only suggest previously undescribed roles for RNF146 in peroxisomal regulation but also a novel role in bridging peroxisome function with Wnt/ß-catenin signaling during development.

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The endoplasmic reticulum (ER) is a single-copy organelle that cannot be generated de novo, suggesting coordination between the mechanisms overseeing ER integrity and those controlling the cell cycle to maintain organelle inheritance. The Unfolded Protein Response (UPR) is a conserved signaling network that regulates ER homeostasis. Here, we show that pharmacological and genetic inhibition of the UPR sensors IRE1, ATF6, and PERK in unstressed cells delays the cell cycle, with PERK inhibition showing the most penetrant effect, which was associated with a slowdown of the G1-to-S/G2 transition. Treatment with the small molecule ISRIB to bypass the effects of PERK-dependent phosphorylation of the translation initiation factor eIF2α had no such effect, suggesting that cell cycle timing depends on PERK's kinase activity but is independent of eIF2α phosphorylation. Using complementary light and electron microscopy and flow cytometry-based analyses, we also demonstrate that the ER enlarges before mitosis. Together, our results suggest coordination between UPR signaling and the cell cycle to maintain ER physiology during cell division.

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Aquaporin-1 (Aqp1), a water channel, has garnered significant interest for cell-based medicine and in vivo synthetic biology due to its ability to be genetically encoded to produce magnetic resonance signals by increasing the rate of water diffusion in cells. However, concerns regarding the effects of Aqp1 overexpression and increased membrane diffusivity on cell physiology have limited its widespread use as a deep-tissue reporter. In this study, we present evidence that Aqp1 generates strong diffusion-based magnetic resonance signals without adversely affecting cell viability or morphology in diverse cell lines derived from mice and humans. Our findings indicate that Aqp1 overexpression does not induce ER stress, which is frequently associated with heterologous expression of membrane proteins. Furthermore, we observed that Aqp1 expression had no detrimental effects on native biological activities, such as phagocytosis, immune response, insulin secretion, and tumor cell migration in the analyzed cell lines. These findings should serve to alleviate any lingering safety concerns regarding the utilization of Aqp1 as a genetic reporter and should foster its broader application as a noninvasive reporter for in vivo studies.

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Aquaporin-1 (Aqp1), a water channel, has garnered significant interest for cell-based medicine and in vivo synthetic biology due to its ability to be genetically encoded to produce magnetic resonance signals by increasing the rate of water diffusion in cells. However, concerns regarding the effects of Aqp1 overexpression and increased membrane diffusivity on cell physiology have limited its widespread use as a deep-tissue reporter. In this study, we present evidence that Aqp1 generates strong diffusion-based magnetic resonance signals without adversely affecting cell viability or morphology in diverse cell lines derived from mice and humans. Our findings indicate that Aqp1 overexpression does not induce ER stress, which is frequently associated with heterologous expression of membrane proteins. Furthermore, we observed that Aqp1 expression had no detrimental effects on native biological activities, such as phagocytosis, immune response, insulin secretion, and tumor cell migration in the analyzed cell lines. These findings should serve to alleviate any lingering safety concerns regarding the utilization of Aqp1 as a genetic reporter and should foster its broader application as a noninvasive reporter for in vivo studies.

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Acetaldehyde in a dilute aqueous solution gets hydrated to produce a geminal diol under atmospheric conditions. The acetaldehyde-water ice system under high pressure also converts to a geminal diol, and therefore, its stable clathrate hydrate (CH) phase, which in most systems forms at high pressures, is unknown. In the present study, we showed that acetaldehyde CH exists in ultrahigh vacuum (10-10 mbar) under cryogenic conditions (below 140 K) and continues to exist at 115 K for periods well over 1 day. Decomposition of acetaldehyde CH at 130-135 K produces water ice in its cubic crystalline form. The mechanism and kinetics involved in the process have also been studied. Reflection absorption infrared spectroscopy and temperature-programmed desorption mass spectrometry were utilized to confirm the CH formation. Our study establishes the possibility of a stable CH phase for acetaldehyde in interstellar and cometary environments.

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Restricted migration of reactive species limits chemical transformations within interstellar and cometary ices. We report the migration of CO2 from clathrate hydrate (CH) cages to amorphous solid water (ASW) in the presence of tetrahydrofuran (THF) under ultrahigh vacuum (UHV) and cryogenic conditions. Thermal annealing of sequentially deposited CO2 and H2O ice, CO2@H2O, to 90 K resulted in the partitioning of CO2 in 512 and 51262 CH cages (CO2@512, CO2@51262). However, upon preparing a composite ice film composed of CO2@512, CO2@51262 and THF distributed in the water matrix at 90 K, and annealing the mixture for 6 h at 130 K produced mixed CO2-THF CH, where THF occupied the 51264 cages (THF@51264) exclusively while CO2 in 51262 cages (CO2@51262) got transferred to the ASW matrix and CO2 in the 512 cages (CO2@512) remained as is. This cage-matrix exchange may create a more conducive environment for chemical transformations in interstellar environments.

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Ti-based alloys have been commonly employed in manufacturing implants for orthopedic applications. Binary Titanium-Niobium (Ti-25Nb) alloy is a promising material for potential applications in orthopedics because of their lower elastic moduli and superior biocompatibility than the conventional Ti-based alloys. Implants with porous structures encourage bone ingrowth and reduce the effect of stress-shielding further. This study is aimed at establishing the relationship between the mechanical performance and structural parameters of porous body-centered-cubic (BCC) structures made up of Ti-25Nb (25% by wt.). Solid models of BCC porous structures were constructed (unit cell size: 2 mm; overall size: 8 × 8 × 8 mm3). Finite element analysis (FEA) of the BCC structures with porosity ranging from 29% to 79% (seven porosities) was conducted under tension, bending, and torsional loads. The Gibson-Ashby model and Exponential regression model were also employed to determine the stiffness of the above porous structures. The functional relationships between effective Young's modulus, effective yield strength, and porosity generated from both the models were found to match the FEA results well. Results indicated that porosity in the range of 50%-70% can be used to design graded porous stems to mimic the mechanical properties of cortical bone.

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A 60 year old woman presented in gynecology department with bleeding per vagina and subsequently histotpathologically, it was diagnosed as malignant melanoma of the vagina. She underwent excision biopsy. On metastatic work-up, Positron emission tomography (PET) scan proved that she had distant metastasis and received palliative radiotherapy and chemotherapy, with temozolamide. She is alive after one year.