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  • Krebs Martens posted an update 1 day, 11 hours ago

    Appropriate pectin deposition in cell walls is important for cell growth in plants. Rhamnogalacturonan II (RG-II) is a portion of pectic polysaccharides; its borate crosslinking is essential for maintenance of pectic networks. However, the overall process of RG-II synthesis is not fully understood. To identify a novel factor for RG-II deposition or dimerization in cell walls, we screened Arabidopsis mutants with altered boron (B)-dependent growth. The mutants exhibited alleviated disorders of primary root and stem elongation, and fertility under low B, but reduced primary root lengths under sufficient B conditions. Altered primary root elongation was associated with cell elongation changes caused by loss of function in AtTMN1 (Transmembrane Nine 1)/EMP12, which encodes a Golgi-localized membrane protein of unknown function that is conserved among eukaryotes. Mutant leaf and root dry weights were lower than those of wild-type plants, regardless of B conditions. In cell walls, AtTMN1 mutations reduced concentrations of B, RG-II specific 2-keto-3-deoxy monosaccharides, and rhamnose largely derived from rhamnogalacturonan I (RG-I), suggesting reduced RG-II and RG-I. Together, our findings demonstrate that AtTMN1 is required for the deposition of RG-II and RG-I for cell growth and suggest that pectin modulates plant growth under low B conditions.Carbohydrates play important and diverse roles in the fundamental processes of life. We have established a method for accurately and a large-scale synthesis of functional carbohydrates with diverse properties using a unique enzymatic method. Furthermore, various artificial glycan-conjugated molecules have been developed by adding these synthetic carbohydrates to macromolecules and to middle- and low-molecular-weight molecules with different properties. These glycan-conjugated molecules have biological activities comparable to or higher than those of natural compounds and present unique functions. In this review, several synthetic glycan-conjugated molecules are taken as examples to show design, synthesis, and function.

    Safety-net hospitals (SNHs) operate under limited financial resources and have had challenges providing high-quality care. Medicaid expansion under the Affordable Care Act led to improvements in hospital finances, but whether this was associated with better hospital quality, particularly among SNHs given their baseline financial constraints, remains unknown.

    To compare changes in quality from 2012 to 2018 between SNHs in states that expanded Medicaid vs those in states that did not.

    Using a difference-in-differences analysis in a cohort study, performance on quality measures was compared between SNHs, defined as those in the highest quartile of uncompensated care in the pre-Medicaid expansion period, in expansion vs nonexpansion states, before and after the implementation of Medicaid expansion. A total of 811 SNHs were included in the analysis, with 316 in nonexpansion states and 495 in expansion states. The study was conducted from January to November 2020.

    Time-varying indicators for Medicaid expansprovements in operating margins, there appears to be little evidence of quality improvement among SNHs in states that expanded Medicaid compared with those in states that did not.

    This difference-in-differences cohort study found that despite reductions in uncompensated care and improvements in operating margins, there appears to be little evidence of quality improvement among SNHs in states that expanded Medicaid compared with those in states that did not.

    Before reviewing drug applications, the US Food and Drug Administration (FDA) conducts “filing reviews” to assess whether they are complete enough for full review. If the applications are incomplete, the FDA issues refuse-to-file (RTF) letters identifying deficiencies. The FDA does not make these RTF letters public at the time of issuance. Why the FDA issues RTF letters and how often the letters and their contents are made publicly available are unknown.

    To quantitatively analyze the FDA’s reasons for issuing RTF letters and assess the public transparency of RTF letters and their contents.

    This cross-sectional study analyzes RTF letters issued in response to new drug applications and efficacy supplements (applications for new indications or patient populations for already approved drugs) submitted to the FDA between January 1, 2008, and December 31, 2017. Statistical analysis was conducted in July 2019.

    Two types of information were extracted and cataloged from RTF letters (1) the reasons why the FDA ). Applicants publicly disclosed the existence of 16 of 103 RTF letters (15.5%); however, only 5.4% of applicant-disclosed reasons (35 of 644) matched the refusal reasons that the FDA had provided in the RTF letters.

    This cross-sectional study found that the FDA refused to file applications for substantive reasons related to quality, safety, and efficacy, and applicants’ disclosure of those reasons was incomplete. This work sheds light on the FDA’s regulatory decision-making processes and the RTF reasons that could delay availability of therapies to patients.

    This cross-sectional study found that the FDA refused to file applications for substantive reasons related to quality, safety, and efficacy, and applicants’ disclosure of those reasons was incomplete. This work sheds light on the FDA’s regulatory decision-making processes and the RTF reasons that could delay availability of therapies to patients.The synergy between the organic component of two-dimensional (2D) metal halide layered perovskites and flexible polymers offers an unexplored window to tune their optical properties at low mechanical stress. Thus, there is a significant interest in exploiting their PL anisotropy by controlling their orientation and elucidating their interactions. Here, we apply this principle to platelet structures of micrometre lateral size that are synthesized in situ into free-standing polymer films. We study the photoluminescence of the resulting films under cyclic mechanical stress and observe an enhancement in the emission intensity up to ∼2.5 times along with a switch in the emission profile when stretching the films from 0% to 70% elongation. All the films recovered their initial emission intensity when releasing the stress throughout ca. check details 15 mechanical cycles. We hypothesize a combined contribution from reduced reabsorption, changes on in-plane and out-of-plane dipole moments that stem from different orientation of the platelets inside the film, and relative sliding of platelets within oriented stacks while stretching the films.