Conserved motifs reveal details of ancestry and structure in the small tim chaperones of the mitochondrial intermembrane space

The mitochondrial inner and outer membranes are composed of a variety of integral membrane proteins, assembled into the membranes posttranslationally. The small translocase of the inner mitochondrial membranes (TIMs) are a group of ∼10 kDa proteins that function as chaperones to ferry the imported proteins across the mitochondrial intermembrane space to the outer and inner membranes. In yeast, there are 5 small TIM proteins: Tim8, Tim9, Tim10, Tim12, and Tim13, with equivalent proteins reported in humans. Using hidden Markov models, we find that many eukaryotes have proteins equivalent to the Tim8 and Tim13 and the Tim9 and Tim10 subunits. Some eukaryotes provide "snapshots" of evolution, with a single protein showing the features of both Tim8 and Tim13, suggesting that a single progenitor gene has given rise to each of the small TIMs through duplication and modification. We show that no "Tim12" family of proteins exist, but rather that variant forms of the cognate small TIMs have been recently duplicated and modified to provide new functions: the yeast Tim12 is a modified form of Tim10, whereas in humans and some protists variant forms of Tim9, Tim8, and Tim13 are found instead. Sequence motif analysis reveals acidic residues conserved in the Tim10 substrate-binding tentacles, whereas more hydrophobic residues are found in the equivalent substrate-binding region of Tim13. The substrate-binding region of Tim10 and Tim13 represent structurally independent domains: when the acidic domain from Tim10 is attached to Tim13, the Tim8–Tim13¹⁰ complex becomes essential and the Tim9–Tim10 complex becomes dispensable. The conserved features in the Tim10 and Tim13 subunits provide distinct binding surfaces to accommodate the broad range of substrate proteins delivered to the mitochondrial inner and outer membranes

Die Jemandssprache : Plädoyer für eine Deutsche Philologie unter besonderer Berücksichtigung von Heinrich von Morungen, Paul Celan und der "Auslandsgermanistik"

Der Titel „Jemandssprache“ bezieht sich kontrafaktisch auf Paul Celans Gedichtband „Die Niemandsrose“. (...) [In dem ersten Teil seine Aufsatzes bezieht sich Volker Mertens] auf die aktuelle Situation im Fach, in einem zweiten (...) [votiert er] für eine spezifische Gegenstandsbestimmung und einen bestimmten Umgang mit den methodischen Paradigmen, in einem dritten für eine Überwindung der Schwelle zwischen Älterer und Neuerer Literatur, (...), in einem vierten (...) [gibt er] eine vergleichende Interpretation je eines Gedichts von Heinrich von Morungen und von Paul Celan als Beispiel für eine Überschreitung der im Fach institutionalisierten Epochengrenze

Long-term effects of nutrient and CO2 enrichment on the temperate coral Astrangia poculata (Ellis and Solander, 1786)

Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Journal of Experimental Marine Biology and Ecology 386 (2010): 27-33, doi:10.1016/j.jembe.2010.02.007.Zooxanthellate colonies of the scleractinian coral Astrangia poculata were grown under combinations of ambient and elevated nutrients (5 μM NO3 -, 0.3 μM PO4 -3, and 2 nM Fe+2) and CO2 (~780 ppmv) treatments for a period of 6 months. Coral calcification rates, estimated from buoyant weights, were not significantly affected by moderately elevated nutrients at ambient CO2 and were negatively affected by elevated CO2 at ambient nutrient levels. However, calcification by corals reared under elevated nutrients combined with elevated CO2 was not significantly different from that of corals reared under ambient conditions, suggesting that CO2 enrichment can lead to nutrient limitation in zooxanthellate corals. A conceptual model is proposed to explain how nutrients and CO2 interact to control zooxanthellate coral calcification. Nutrient limited corals are unable to utilize an increase in dissolved inorganic carbon (DIC) as nutrients are already limiting growth, thus the effect of elevated CO2 on saturation state drives the calcification response. Under nutrient replete conditions, corals may have the ability to utilize more DIC, thus the calcification response to CO2 becomes the product of a negative effect on saturation state and a positive effect on gross carbon fixation, depending upon which dominates, the calcification response can be either positive or negative. This may help explain how the range of coral responses found in different studies of ocean acidification can be obtained.Funding for this work was provided by the Ocean Life Institute, NSF OCE-0648157, and an International Society for Reef Studies / Ocean Conservancy Fellowship. This material is based upon work supported under a National Science Foundation Graduate Research Fellowship

SPICES: Spectro-Polarimetric Imaging and Characterization of Exoplanetary Systems

SPICES (Spectro-Polarimetric Imaging and Characterization of Exoplanetary Systems) is a five-year M-class mission proposed to ESA Cosmic Vision. Its purpose is to image and characterize long-period extrasolar planets and circumstellar disks in the visible (450 - 900 nm) at a spectral resolution of about 40 using both spectroscopy and polarimetry. By 2020/22, present and near-term instruments will have found several tens of planets that SPICES will be able to observe and study in detail. Equipped with a 1.5 m telescope, SPICES can preferentially access exoplanets located at several AUs (0.5-10 AU) from nearby stars ($<$25 pc) with masses ranging from a few Jupiter masses to Super Earths ($\sim$2 Earth radii, $\sim$10 M$_{\oplus}$) as well as circumstellar disks as faint as a few times the zodiacal light in the Solar System

SPICES: Spectro-Polarimetric Imaging and Characterization of Exoplanetary Systems - From Planetary Disks To Nearby Super Earths

SPICES (Spectro-Polarimetric Imaging and Characterization of Exoplanetary Systems) is a five-year M-class mission proposed to ESA Cosmic Vision. Its purpose is to image and characterize long-period extrasolar planets and circumstellar disks in the visible (450-900 nm) at a spectral resolution of about 40 using both spectroscopy and polarimetry. By 2020/2022, present and near-term instruments will have found several tens of planets that SPICES will be able to observe and study in detail. Equipped with a 1.5 m telescope, SPICES can preferentially access exoplanets located at several AUs (0.5-10 AU) from nearby stars (less than 25 pc) with masses ranging from a few Jupiter masses to Super Earths (approximately 2 Earth radii, approximately 10 mass compared to Earth) as well as circumstellar disks as faint as a few times the zodiacal light in the Solar System

Formal System Processing of Juveniles: Effects on Delinquency

Justice practitioners have tremendous discretion on how to handle juvenile offenders. Police officers, district attorneys, juvenile court intake officers, juvenile and family court judges, and other officials can decide whether the juvenile should be “officially processed” by the juvenile justice system, diverted from the system to a program, counseling or some other services, or to do nothing at all (release the juvenile altogether). An important policy question is which strategy leads to the best outcomes for juveniles. This is an important question in the United States, but many other nations are concerned with the decision to formally process or divert juvenile offenders. There have been a number of randomized experiments in the juvenile courts that have examined the impact of juvenile system processing that should be gathered together in a systematic fashion to provide rigorous evidence about the impact of this decision on subsequent offending by juveniles. Our objective is to answer the question: Does juvenile system processing reduce subsequent delinquency? Based on the evidence presented in this report, juvenile system processing appears to not have a crime control effect, and across all measures appears to increase delinquency. This was true across measures of prevalence, incidence, severity, and self-report. Given the additional financial costs associated with system processing (especially when compared to doing nothing) and the lack of evidence for any public safety benefit, jurisdictions should review their policies regarding the handling of juveniles

BIN1 protein isoforms are differentially expressed in astrocytes, neurons, and microglia: neuronal and astrocyte BIN1 are implicated in tau pathology

Background Identified as an Alzheimer’s disease (AD) susceptibility gene by genome wide-association studies, BIN1 has 10 isoforms that are expressed in the Central Nervous System (CNS). The distribution of these isoforms in different cell types, as well as their role in AD pathology still remains unclear. Methods Utilizing antibodies targeting specific BIN1 epitopes in human post-mortem tissue and analyzing mRNA expression data from purified microglia, we identified three isoforms expressed in neurons and astrocytes (isoforms 1, 2 and 3) and four isoforms expressed in microglia (isoforms 6, 9, 10 and 12). The abundance of selected peptides, which correspond to groups of BIN1 protein isoforms, was measured in dorsolateral prefrontal cortex, and their relation to neuropathological features of AD was assessed. Results Peptides contained in exon 7 of BIN1’s N-BAR domain were found to be significantly associated with AD-related traits and, particularly, tau tangles. Decreased expression of BIN1 isoforms containing exon 7 is associated with greater accumulation of tangles and subsequent cognitive decline, with astrocytic rather than neuronal BIN1 being the more likely culprit. These effects are independent of the BIN1 AD risk variant. Conclusions Exploring the molecular mechanisms of specific BIN1 isoforms expressed by astrocytes may open new avenues for modulating the accumulation of Tau pathology in AD

Clinical history and management recommendations of the smooth muscle dysfunction syndrome due to ACTA2 arginine 179 alterations

Smooth muscle dysfunction syndrome (SMDS) due to heterozygous ACTA2 arginine 179 alterations is characterized by patent ductus arteriosus, vasculopathy (aneurysm and occlusive lesions), pulmonary arterial hypertension, and other complications in smooth muscle-dependent organs. We sought to define the clinical history of SMDS to develop recommendations for evaluation and management. Medical records of 33 patients with SMDS (median age 12 years) were abstracted and analyzed. All patients had congenital mydriasis and related pupillary abnormalities at birth and presented in infancy with a patent ductus arteriosus or aortopulmonary window. Patients had cerebrovascular disease characterized by small vessel disease (hyperintense periventricular white matter lesions; 95%), intracranial artery stenosis (77%), ischemic strokes (27%), and seizures (18%). Twelve (36%) patients had thoracic aortic aneurysm repair or dissection at median age of 14 years and aortic disease was fully penetrant by the age of 25 years. Three (9%) patients had axillary artery aneurysms complicated by thromboembolic episodes. Nine patients died between the ages of 0.5 and 32 years due to aortic, pulmonary, or stroke complications, or unknown causes. Based on these data, recommendations are provided for the surveillance and management of SMDS to help prevent early-onset life-threatening complications

Combining genomic and epidemiological data to compare the transmissibility of SARS-CoV-2 variants Alpha and Iota.

SARS-CoV-2 variants shaped the second year of the COVID-19 pandemic and the discourse around effective control measures. Evaluating the threat posed by a new variant is essential for adapting response efforts when community transmission is detected. In this study, we compare the dynamics of two variants, Alpha and Iota, by integrating genomic surveillance data to estimate the effective reproduction number (Rt) of the variants. We use Connecticut, United States, in which Alpha and Iota co-circulated in 2021. We find that the Rt of these variants were up to 50% larger than that of other variants. We then use phylogeography to show that while both variants were introduced into Connecticut at comparable frequencies, clades that resulted from introductions of Alpha were larger than those resulting from Iota introductions. By monitoring the dynamics of individual variants throughout our study period, we demonstrate the importance of routine surveillance in the response to COVID-19