Sex Differences in the Disease Progression of FTD vs AD

Abigail Mitchell, Danielle Frances, Chase Metzger Sex Differences in the Disease Progression of FTD vs AD. Abstract Neurodegenerative diseases are on the rise in aging populations due to the upper tier of the population getting larger in that age group (Zheng & Chen, 2022). Knowing this, there is great benefit in more accurate and early diagnosis of conditions like frontotemporal dementia (FTD) and Alzheimer’s disease (AD). Particularly, it is important to understand which variables may contribute to differences in disease burden and progression of associated sequalae, with one of those variables being biological sex. The current study investigated sex differences in the disease progression of Frontotemporal dementia (FTD) verses Alzheimer’s (AD) over time. All data for this study was extracted from open datasets provided by the National Alzheimer’s Coordinating Center (NACC). Disease progression is quantified by deficits in cognitive ability as well as volumetric loss in the brain. In particular, voxel-based morphometry analyses on high-resolution T1 MRI scans extracted whole grey matter volumes (GM) at 2 timepoints, separated by years, as well as regionally-specific volumetric measures of the insula for FTD, hippocampus for AD and the cingulate cortex for both conditions. Coping ability outcomes, measured by traditional clinical assessments at matching timepoints to the MRI acquisitions include the Clinical Dementia Rating scale sum of boxes (CDRsb), Mini-mental state exam (MMSE), and Montreal cognitive assessment (MOCA). The current study expects to replicate existing findings in the field, with FTD and AD female patients revealing faster disease progression than males, as measure by volumetric analyses. However, it is expected that FTD females will reveal better coping abilities compared to males, and that AD females will have worse coping abilities in a similar sex comparison. The data is currently being analyzed and the results will be presented a

A protein quality control pathway at the mitochondrial outer membrane.

Maintaining the essential functions of mitochondria requires mechanisms to recognize and remove misfolded proteins. However, quality control (QC) pathways for misfolded mitochondrial proteins remain poorly defined. Here, we establish temperature-sensitive (ts-) peripheral mitochondrial outer membrane (MOM) proteins as novel model QC substrates in Saccharomyces cerevisiae. The ts- proteins sen2-1HAts and sam35-2HAts are degraded from the MOM by the ubiquitin-proteasome system. Ubiquitination of sen2-1HAts is mediated by the ubiquitin ligase (E3) Ubr1, while sam35-2HAts is ubiquitinated primarily by San1. Mitochondria-associated degradation (MAD) of both substrates requires the SSA family of Hsp70s and the Hsp40 Sis1, providing the first evidence for chaperone involvement in MAD. In addition to a role for the Cdc48-Npl4-Ufd1 AAA-ATPase complex, Doa1 and a mitochondrial pool of the transmembrane Cdc48 adaptor, Ubx2, are implicated in their degradation. This study reveals a unique QC pathway comprised of a combination of cytosolic and mitochondrial factors that distinguish it from other cellular QC pathways

Ruthenium Metal–Organic Frameworks with Different Defect Types: Influence on Porosity, Sorption, and Catalytic Properties

By employing the mixed-component, solid-solution approach, various functionalized ditopic isophthalate (ip) defect-generating linkers denoted 5-X-ipH(2), where X = OH (1), H (2), NH2 (3), Br (4), were introduced into the mixed-valent ruthenium analogue of [Cu-3(btc)(2)](n) (HKUST-1, btc = benzene-1,3,5-tricarboxylate) to yield Ru-DEMOFs (defect-engineered metal-organic frameworks) of the general empirical formula [Ru-3(btc)(2-x)(5-X-ip)(x)Y-y](n). Framework incorporation of 5-X-ip was confirmed by powder XRD, FTIR spectroscopy, ultrahigh-vacuum IR spectroscopy, thermogravimetric analysis, H-1 NMR spectroscopy, N-2 sorption, and X-ray absorption near edge structure. Interestingly, Ru-DEMOF 1c with 32% framework incorporation of 5-OH-ip shows the highest BET surface area (approximate to 1300 m(2) g(-1), N-2 adsorption, 77 K) among all materials (including the parent framework [Ru-3(btc)(2)Y-y](n)). The characterization data are consistent with two kinds of structural defects induced by framework incorporation of 5-X-ip: modified paddlewheel nodes featuring reduced ruthenium sites (Ru delta+, 0 Plus at Ruhr-University Bochum for the support of her PhD project and funding of an internship at UC Berkeley at the group of Prof. Jeffrey. R. Long and collaboration with D.J.X. and M.I.G. including Douglas Reed for the collection of CO isotherms (298 K). W.Z. also thanks Dr. Raghavender Medishetty for the fruitful discussions. P.G. acknowledges the support of the EU innovative Training Network "DEFect NETwork materials science and engineering" (DEFNET). The authors further thank the team at DELTA synchrotron facility at the TU Dortmund for the support with the X-ray absorption spectroscopy experiments performed at beam lines BL8 and the PXRD data collection at beam lines BL9.Zhang, W.; Kauer, M.; Halbherr, O.; Epp, K.; Guo, P.; Gonzalez, MI.; Xiao, DJ.... (2016). Ruthenium Metal–Organic Frameworks with Different Defect Types: Influence on Porosity, Sorption, and Catalytic Properties. Chemistry - A European Journal. 22(40):14297-14307. https://doi.org/10.1002/chem.2016026411429714307224

6S RNA regulation of relA alters ppGpp levels in early stationary phase

6S RNA is a small, non-coding RNA that interacts directly with σ70-RNA polymerase and regulates transcription at many σ70-dependent promoters. Here, we demonstrate that 6S RNA regulates transcription of relA, which encodes a ppGpp synthase. The 6S RNA-dependent regulation of relA expression results in increased ppGpp levels during early stationary phase in cells lacking 6S RNA. These changes in ppGpp levels, although modest, are sufficient to result in altered regulation of transcription from σ70-dependent promoters sensitive to ppGpp, including those promoting expression of genes involved in amino acid biosynthesis and rRNA. These data place 6S RNA as another player in maintaining appropriate gene expression as cells transition into stationary phase. Independent of this ppGpp-mediated 6S RNA-dependent regulation, we also demonstrate that in later stationary phase, 6S RNA continues to downregulate transcription in general, and specifically at a subset of the amino acid promoters, but through a mechanism that is independent of ppGpp and which we hypothesize is through direct regulation. In addition, 6S RNA-dependent regulation of σS activity is not mediated through observed changes in ppGpp levels. We suggest a role for 6S RNA in modulating transcription of several global regulators directly, including relA, to downregulate expression of key pathways in response to changing environmental conditions

Catching Element Formation In The Act

Gamma-ray astronomy explores the most energetic photons in nature to address some of the most pressing puzzles in contemporary astrophysics. It encompasses a wide range of objects and phenomena: stars, supernovae, novae, neutron stars, stellar-mass black holes, nucleosynthesis, the interstellar medium, cosmic rays and relativistic-particle acceleration, and the evolution of galaxies. MeV gamma-rays provide a unique probe of nuclear processes in astronomy, directly measuring radioactive decay, nuclear de-excitation, and positron annihilation. The substantial information carried by gamma-ray photons allows us to see deeper into these objects, the bulk of the power is often emitted at gamma-ray energies, and radioactivity provides a natural physical clock that adds unique information. New science will be driven by time-domain population studies at gamma-ray energies. This science is enabled by next-generation gamma-ray instruments with one to two orders of magnitude better sensitivity, larger sky coverage, and faster cadence than all previous gamma-ray instruments. This transformative capability permits: (a) the accurate identification of the gamma-ray emitting objects and correlations with observations taken at other wavelengths and with other messengers; (b) construction of new gamma-ray maps of the Milky Way and other nearby galaxies where extended regions are distinguished from point sources; and (c) considerable serendipitous science of scarce events -- nearby neutron star mergers, for example. Advances in technology push the performance of new gamma-ray instruments to address a wide set of astrophysical questions.Comment: 14 pages including 3 figure

Nuclear dependence of the transverse single-spin asymmetry in the production of charged hadrons at forward rapidity in polarized p+pp+p, p+p+Al, and p+p+Au collisions at sNN=200\sqrt{s_{_{NN}}}=200 GeV

We report on the nuclear dependence of transverse single-spin asymmetries (TSSAs) in the production of positively-charged hadrons in polarized $p^{\uparrow}+p$, $p^{\uparrow}+$Al and $p^{\uparrow}+$Au collisions at $\sqrt{s_{_{NN}}}=200$ GeV. The measurements have been performed at forward rapidity ($1.4<\eta<2.4$) over the range of $1.8<p_{T}<7.0$ GeV$/c$ and $0.1<x_{F}<0.2$. We observed a positive asymmetry $A_{N}$ for positively-charged hadrons in \polpp collisions, and a significantly reduced asymmetry in $p^{\uparrow}$+$A$ collisions. These results reveal a nuclear dependence of charged hadron $A_N$ in a regime where perturbative techniques are relevant. These results provide new opportunities to use \polpA collisions as a tool to investigate the rich phenomena behind TSSAs in hadronic collisions and to use TSSA as a new handle in studying small-system collisions.Comment: 303 authors from 66 institutions, 9 pages, 2 figures, 1 table. v1 is version accepted for publication in Physical Review Letters. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Nuclear dependence of the transverse-single-spin asymmetry for forward neutron production in polarized pp++AA collisions at sNN=200\sqrt{s_{_{NN}}}=200 GeV

During 2015 the Relativistic Heavy Ion Collider (RHIC) provided collisions of transversely polarized protons with Au and Al nuclei for the first time, enabling the exploration of transverse-single-spin asymmetries with heavy nuclei. Large single-spin asymmetries in very forward neutron production have been previously observed in transversely polarized $p$$+$$p$ collisions at RHIC, and the existing theoretical framework that was successful in describing the single-spin asymmetry in $p$$+$$p$ collisions predicts only a moderate atomic-mass-number ($A$) dependence. In contrast, the asymmetries observed at RHIC in $p$$+$$A$ collisions showed a surprisingly strong $A$ dependence in inclusive forward neutron production. The observed asymmetry in $p$$+$Al collisions is much smaller, while the asymmetry in $p$$+$Au collisions is a factor of three larger in absolute value and of opposite sign. The interplay of different neutron production mechanisms is discussed as a possible explanation of the observed $A$ dependence.Comment: 315 authors, 8 pages, 4 figures, 1 table. v2 is version accepted for publication in Phys. Rev. Lett. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm