Slowing Down: Age-Related Neurobiological Predictors of Processing Speed

Processing speed, or the rate at which tasks can be performed, is a robust predictor of age-related cognitive decline and an indicator of independence among older adults. This review examines evidence for neurobiological predictors of age-related changes in processing speed, which is guided in part by our source based morphometry findings that unique patterns of frontal and cerebellar gray matter predict age-related variation in processing speed. These results, together with the extant literature on morphological predictors of age-related changes in processing speed, suggest that specific neural systems undergo declines and as a result slow processing speed. Future studies of processing speed – dependent neural systems will be important for identifying the etiologies for processing speed change and the development of interventions that mitigate gradual age-related declines in cognitive functioning and enhance healthy cognitive aging

To grab the stroma by the horns: From biology to cancer therapy with mesenchymal stem cells

Mesenchymal stem or stromal cells (MSCs) are precursor cells that play important roles in tumorigenesis. MSCs are recruited to tumors from local and distant sources to form part of the tumor microenvironment. MSCs influence tumor progression by interacting with cancer cells, endothelial cells, immune cells, and cancer stem cells, in a context-dependent network. This review aims to synthesize this emerging yet controversial field to identify key questions regarding the mechanisms of MSC mobilization and survival in blood; homing to tumors, metastases, and premetastatic sites; spatiotemporal organization and differentiation; and interaction with immune cells and cancer stem cells. Understanding the fundamental biology underlying mesenchymal stem cell and tumor interactions has the potential to inform our knowledge of cancer initiation and progression as well as lead to novel therapeutics for cancer. Furthermore, knowledge of endogenous mechanisms can be used to “program” exogenous MSCs for targeted chemotherapeutic delivery to tumors and metastases. Emerging studies will provide crucial insight into the mechanisms of tumor interactions with the whole organism including MSCs

Auditory cortex asymmetry associations with individual differences in language and cognition

This work was also supported by the National Institutes of Health (NIH)/Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD 069374) (Author MAE) and was conducted in a facility constructed with support from Research Facilities Improvement Program (C06 RR 014516) from the NIH/National Center for Research Resources.A longstanding cerebral lateralization hypothesis predicts that disrupted development of typical leftward structural asymmetry of auditory cortex explains why children have problems learning to read. Small sample sizes and small effects, potential sex-specific effects, and associations that are limited to specific dimensions of language are thought to have contributed inconsistent results. The large ABCD study dataset (baseline visit: N = 11,859) was used to test the hypothesis of significant associations between surface area asymmetry of auditory cortex and receptive vocabulary performance across boys and girls, as well as an oral word reading effect that was specific to boys. The results provide modest support (Cohen’s d effect sizes ≤ 0.10) for the cerebral lateralization hypothesis.Publisher PDFPeer reviewe

ECO and RESOLVE: Galaxy Disk Growth in Environmental Context

We study the relationships between galaxy environments and galaxy properties related to disk (re)growth, considering two highly complete samples that are approximately baryonic mass limited into the high-mass dwarf galaxy regime, the Environmental COntext (ECO) catalog (data release herein) and the B-semester region of the REsolved Spectroscopy Of a Local VolumE (RESOLVE) survey. We quantify galaxy environments using both group identification and smoothed galaxy density field methods. We use by-eye and quantitative morphological classifications plus atomic gas content measurements and estimates. We find that blue early-type (E/S0) galaxies, gas-dominated galaxies, and UV-bright disk host galaxies all become distinctly more common below group halo mass ~10^11.5 Msun, implying that this low group halo mass regime may be a preferred regime for significant disk growth activity. We also find that blue early-type and blue late-type galaxies inhabit environments of similar group halo mass at fixed baryonic mass, consistent with a scenario in which blue early types can regrow late-type disks. In fact, we find that the only significant difference in the typical group halo mass inhabited by different galaxy classes is for satellite galaxies with different colors, where at fixed baryonic mass red early and late types have higher typical group halo masses than blue early and late types. More generally, we argue that the traditional morphology-environment relation (i.e., that denser environments tend to have more early types) can be largely attributed to the morphology-galaxy mass relation for centrals and the color-environment relation for satellites.Comment: 26 pages and 28 figures; v2 contains minor figure and text updates to match final published version in ApJ; ECO data table release now available at http://resolve.astro.unc.edu/pages/data.ph

Age-Related Changes in Processing Speed: Unique Contributions of Cerebellar and Prefrontal Cortex

Age-related declines in processing speed are hypothesized to underlie the widespread changes in cognition experienced by older adults. We used a structural covariance approach to identify putative neural networks that underlie age-related structural changes associated with processing speed for 42 adults ranging in age from 19 to 79 years. To characterize a potential mechanism by which age-related gray matter changes lead to slower processing speed, we examined the extent to which cerebral small vessel disease influenced the association between age-related gray matter changes and processing speed. A frontal pattern of gray matter and white matter variation that was related to cerebral small vessel disease, as well as a cerebellar pattern of gray matter and white matter variation were uniquely related to age-related declines in processing speed. These results demonstrate that at least two distinct factors affect age-related changes in processing speed, which might be slowed by mitigating cerebral small vessel disease and factors affecting declines in cerebellar morphology

A whole-genome screen identifies Salmonella enterica serovar Typhi genes involved in fluoroquinolone susceptibility.

OBJECTIVES: A whole-genome screen at sub-gene resolution was performed to identify candidate loci that contribute to enhanced or diminished ciprofloxacin susceptibility in Salmonella enterica serovar Typhi. METHODS: A pool of over 1 million transposon insertion mutants of an S. Typhi Ty2 derivative were grown in a sub-MIC concentration of ciprofloxacin, or without ciprofloxacin. Transposon-directed insertion site sequencing (TraDIS) identified relative differences between the mutants that grew following the ciprofloxacin treatment compared with the untreated mutant pool, thereby indicating which mutations contribute to gain or loss of ciprofloxacin susceptibility. RESULTS: Approximately 88% of the S. Typhi strain's 4895 annotated genes were assayed, and at least 116 were identified as contributing to gain or loss of ciprofloxacin susceptibility. Many of the identified genes are known to influence susceptibility to ciprofloxacin, thereby providing method validation. Genes were identified that were not known previously to be involved in susceptibility, and some of these had no previously known phenotype. Susceptibility to ciprofloxacin was enhanced by insertion mutations in genes coding for efflux, other surface-associated functions, DNA repair and expression regulation, including phoP, barA and marA. Insertion mutations that diminished susceptibility were predominantly in genes coding for surface polysaccharide biosynthesis and regulatory genes, including slyA, emrR, envZ and cpxR. CONCLUSIONS: A genomics approach has identified novel contributors to gain or loss of ciprofloxacin susceptibility in S. Typhi, expanding our understanding of the impact of fluoroquinolones on bacteria and of mechanisms that may contribute to resistance. The data also demonstrate the power of the TraDIS technology for antibacterial research

The auditory evoked-gamma response and its relation with the N1m

This study explored the patterns of oscillatory activity that underpin the N1m auditory evoked response. Evoked gamma activity is a small and relatively rarely-reported component of the auditory evoked response, and the objective of this work was to determine how this component relates to the larger and more prolonged changes in lower frequency bands. An event-related beamformer analysis of MEG data from monaural click stimulation was used to reconstruct volumetric images and virtual electrode time series. Group analysis of localisations showed that activity in the gamma band originated from a source that was more medial than those for activity in the theta-to-beta band, and virtual-electrode analysis showed that the source of the gamma activity could be statistically dissociated from the lower-frequency response. These findings are in accordance with separate functional roles for the activity in each frequency band, and provide evidence that the oscillatory activity that underpins the auditory evoked response may contain important information about the physiological basis of the macroscopic signals recorded by MEG in response to auditory stimulation

Case Report: The Effect of Automated Manual Lymphatic Drainage Therapy on Lymphatic Contractility in 4 Distinct Cases

INTRODUCTION: Automated manual lymphatic drainage therapy (AMLDT) is available for home use in the form of a pneumatic mat of 16 pressurized air channels that inflate and deflate to mimic the stretch and release action of manual lymphatic drainage therapy. Four cases (a patient with complex regional pain syndrome and lymphedema, a healthy patient, a breast cancer survivor with chronic pain, and a patient with a history of abdominal surgery) underwent near-infrared fluorescence lymphatic imaging (NIRFLI) with AMLDT to evaluate the effect of AMLDT on lymphatic pumping and pain. METHODS: Each patient received 32-36 injections of 25 μg indocyanine green (ICG) on the anterior and posterior sides of their body and underwent 1 h of NIRFLI to assess the drainage of ICG laden lymph toward regional nodal basins at baseline. Each patient lay supine on the mat for 1 h of AMLDT with NIRFLI to assess lymphatic flow during treatment. A final NIFRFLI assessment was done 30-60 min posttreatment with the patient in the supine and prone position. Patients reported baseline and posttreatment pain using the Visual Analogue Scale. An imager analyzed NIRFLI images using ImageJ (US National Institutes of Health). Using time stamps of the first and last images to determine time lapsed and the number of pulses observed in a timeframe, pulsing frequency (pulses/min) was obtained to assess lymphatic function. RESULTS: All 4 cases completed the NIRFLI and AMLDT without complications; all 3 patients with baseline pain reported reduced pain posttreatment. AMLDT appeared to alter lymphatic contractility, with both increased and decreased pulsing frequencies observed, including in nonaffected limbs. Pulsing frequencies were very heterogeneous among patients and varied within anatomic regions of the same patient. DISCUSSION: This proof-of-concept study suggests that AMLDT may impact lymphatic contractility. Further research on its effect on lymphatic function is warranted

Human PrimPol is a highly error-prone polymerase regulated by single-stranded DNA binding proteins

PrimPol is a recently identified polymerase involved in eukaryotic DNA damage tolerance, employed in both re-priming and translesion synthesis mechanisms to bypass nuclear and mitochondrial DNA lesions. In this report, we investigate how the enzymatic activities of human PrimPol are regulated. We show that, unlike other TLS polymerases, PrimPol is not stimulated by PCNA and does not interact with it in vivo. We identify that PrimPol interacts with both of the major single-strand binding proteins, RPA and mtSSB in vivo. Using NMR spectroscopy, we characterize the domains responsible for the PrimPol-RPA interaction, revealing that PrimPol binds directly to the N-terminal domain of RPA70. In contrast to the established role of SSBs in stimulating replicative polymerases, we find that SSBs significantly limit the primase and polymerase activities of PrimPol. To identify the requirement for this regulation, we employed two forward mutation assays to characterize PrimPol's replication fidelity. We find that PrimPol is a mutagenic polymerase, with a unique error specificity that is highly biased towards insertion-deletion errors. Given the error-prone disposition of PrimPol, we propose a mechanism whereby SSBs greatly restrict the contribution of this enzyme to DNA replication at stalled forks, thus reducing the mutagenic potential of PrimPol during genome replication