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1.
Geriatrics (Basel) ; 8(5)2023 Sep 25.
Article in English | MEDLINE | ID: mdl-37887968

ABSTRACT

Gait speed is a simple, effective indicator of age-related disease and disability. We sought to examine the prevalence and trends of slow gait speed in older Americans. Our unweighted analytic sample included 12,427 adults aged ≥ 65 years from the 2006-2016 waves of the Health and Retirement Study. Gait speed was measured in participant residences. Persons with gait speed < 0.8 or <0.6 m/s were slow. Sample weights were used to generate nationally representative estimates. The overall estimated prevalence of slow gait speed with the <0.8 m/s cut-point was 48.6% (95% confidence interval (CI): 47.4-49.8) in the 2006-2008 waves yet was 45.7% (CI: 44.3-47.1) in the 2014-2016 waves, but this downward trend was not statistically significant (p = 0.06). The estimated prevalence of slowness with the <0.6 m/s cut-point was 21.3% (CI: 20.4-22.3) for the 2006-2008 waves, 18.5% (CI: 17.5-19.4) for the 2010-2012 waves, and 19.2% (CI: 18.2-20.2) for the 2014-2016 waves, but there were again no significant trends (p = 0.61). Our findings showed that the estimated prevalence of slow gait speed in older Americans is pronounced, and different cut-points largely inform how slowness is categorized. Continued surveillance of slowness over time will help guide screening for disablement and identify sub-populations at greatest risk for targeted interventions.

2.
Proc Natl Acad Sci U S A ; 120(39): e2307638120, 2023 09 26.
Article in English | MEDLINE | ID: mdl-37722052

ABSTRACT

Photosynthetic carbon (C) fixation by phytoplankton in the Southern Ocean (SO) plays a critical role in regulating air-sea exchange of carbon dioxide and thus global climate. In the SO, photosynthesis (PS) is often constrained by low iron, low temperatures, and low but highly variable light intensities. Recently, proton-pumping rhodopsins (PPRs) were identified in marine phytoplankton, providing an alternate iron-free, light-driven source of cellular energy. These proteins pump protons across cellular membranes through light absorption by the chromophore retinal, and the resulting pH energy gradient can then be used for active membrane transport or for synthesis of adenosine triphosphate. Here, we show that PPR is pervasive in Antarctic phytoplankton, especially in iron-limited regions. In a model SO diatom, we found that it was localized to the vacuolar membrane, making the vacuole a putative alternative phototrophic organelle for light-driven production of cellular energy. Unlike photosynthetic C fixation, which decreases substantially at colder temperatures, the proton transport activity of PPR was unaffected by decreasing temperature. Cellular PPR levels in cultured SO diatoms increased with decreasing iron concentrations and energy production from PPR photochemistry could substantially augment that of PS, especially under high light intensities, where PS is often photoinhibited. PPR gene expression and high retinal concentrations in phytoplankton in SO waters support its widespread use in polar environments. PPRs are an important adaptation of SO phytoplankton to growth and survival in their cold, iron-limited, and variable light environment.


Subject(s)
Diatoms , Rhodopsin , Rhodopsin/genetics , Phytoplankton/genetics , Protons , Antarctic Regions , Ion Transport , Diatoms/genetics
3.
J Strength Cond Res ; 37(12): 2484-2490, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-37639680

ABSTRACT

ABSTRACT: McGrath, R, FitzSimmons, S, Andrew, S, Black, K, Bradley, A, Christensen, BK, Collins, K, Klawitter, L, Kieser, J, Langford, M, Orr, M, and Hackney, KJ. Prevalence and trends of weakness among middle-aged and older adults in the United States. J Strength Cond Res 37(12): 2484-2490, 2023-Muscle weakness, which is often determined with low handgrip strength (HGS), is associated with several adverse health conditions; however, the prevalence and trends of weakness in the United States is not well-understood. We sought to estimate the prevalence and trends of weakness in Americans aged at least 50 years. The total unweighted analytic sample included 22,895 Americans from the 2006-2016 waves of the Health and Retirement Study. Handgrip strength was measured with a handgrip dynamometer. Men with weakness were below at least one of the absolute or normalized (body mass, body mass index) cut points: <35.5 kg, <0.45 kg/kg, <1.05 kg/kg/m 2 . The presence of any weakness in women was also identified as being below one of the absolute or normalized HGS cut points: <20.0 kg, <0.34 kg/kg, or <0.79 kg/kg/m 2 . There was an increasing trend in the prevalence of any weakness over time ( p < 0.001). The prevalence of weakness was 45.1% (95% confidence interval [CI]: 44.0-46.0) in the 2006-2008 waves and 52.6% (CI: 51.5-53.7) in the 2014-2016 waves. Weakness prevalence was higher for older (≥65 years) Americans (64.2%; CI: 62.8-65.5) compared with middle-aged (50-64 years) Americans (42.2%; CI: 40.6-43.8) in the 2014-2016 waves. Moreover, the prevalence of weakness in the 2014-2016 waves was generally higher in women (54.5%; CI: 53.1-55.9) than in men (50.4%; CI: 48.7-52.0). Differences existed in weakness prevalence across races and ethnicities. The findings from our investigation suggest that the prevalence of weakness is overall pronounced and increasing in Americans. Efforts for mitigating and better operationalizing weakness will elevate in importance as our older American population grows.


Subject(s)
Hand Strength , Retirement , Male , Middle Aged , Humans , Female , United States/epidemiology , Aged , Hand Strength/physiology , Prevalence , Muscle Weakness/epidemiology , Body Mass Index
4.
ISME Commun ; 2(1): 97, 2022 Oct 03.
Article in English | MEDLINE | ID: mdl-37938401

ABSTRACT

Southern Ocean (SO) diatoms play an important role in global carbon flux, and their influence on carbon export is directly linked to interactions with epiphytic bacteria. Bacterial symbionts that increase diatom growth promote atmospheric carbon uptake, while bacterial degraders divert diatom biomass into the microbial loop where it can then be released as carbon dioxide through respiration. To further explore SO diatom-bacterial associations, a natural model system is needed that is representative of these diverse and important interactions. Here, we use concurrent cultivation to isolate a species of the ecologically-important SO diatom, Pseudo-nitzschia subcurvata, and its co-occurring bacteria. Although vitamin-depleted, axenic Pseudo-nitzschia grew poorly in culture, addition of a co-isolated Roseobacter promoted diatom growth, while addition of a co-isolated Flavobacterium negatively impacted diatom growth. Microscopy revealed both bacterial isolates are physically associated with diatom cells and genome sequencing identified important predicted functions including vitamin synthesis, motility, cell attachment mechanisms, and diverse antimicrobial weapons that could be used for interbacterial competition. These findings revealed the natural coexistence of competing symbiotic strategies of diatom-associated bacteria in the SO, and the utility of this tripartite system, composed of a diatom and two bacterial strains, as a co-culture model to probe ecological-relevant interactions between diatoms and the bacteria that compete for access to the phycosphere.

5.
Genet Med ; 20(6): 608-613, 2018 06.
Article in English | MEDLINE | ID: mdl-29758563

ABSTRACT

PurposeTo determine feasibility and utility of newborn screening for spinal muscular atrophy (SMA) in New York State.MethodsWe validated a multiplex TaqMan real-time quantitative polymerase chain reaction assay using dried blood spots for SMA. From January 2016 to January 2017, we offered, consented, and screened 3,826 newborns at three hospitals in New York City and tested newborns for the deletion in exon 7 of SMN1.ResultsNinety-three percent of parents opted in for SMA screening. Overall the SMA carrier frequency was 1.5%. We identified one newborn with a homozygous SMN1 deletion and two copies of SMN2, which strongly suggests the severe type 1 SMA phenotype. The infant was enrolled in the NURTURE clinical trial and was first treated with Spinraza at age 15 days. She is now age 12 months, meeting all developmental milestones, and free of any respiratory issues.ConclusionOur pilot study demonstrates the feasibility of population-based screening, the acceptance by families, and the benefit of newborn screening for SMA. We suggest that SMA be considered for addition to the national recommended uniform screening panel.


Subject(s)
Muscular Atrophy, Spinal/diagnosis , Neonatal Screening/methods , Survival of Motor Neuron 1 Protein/genetics , Exons , Female , Gene Deletion , Gene Dosage , Humans , Infant , Infant, Newborn , Male , Muscular Atrophy, Spinal/genetics , New York , Pilot Projects , Survival of Motor Neuron 1 Protein/physiology
6.
Curr Protoc Immunol ; Chapter 2: 2.9.1-2.9.8, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19347846

ABSTRACT

This unit describes two classical protocols for the purification of IgM-dialysis of ascites fluid, tissue culture medium, or bioreactor supernatants against distilled water to precipitate pure IgM, and ammonium sulfate precipitation. Both protocols can be followed by size-exclusion chromatography to obtain a highly purified product. Recently, an affinity method for purification of IgM has been developed using mannan-binding protein, and is described here. The third approach presented is a one-step IgD purification method, designed specifically for murine derived samples, that uses Sepharose coupled to lectin derived from the seeds of Griffonia simplicifolia-1. This represents a simple, rapid, and gentle, approach to isolating this highly labile immunoglobulin from IgD-containing ascites or hybridoma sources.


Subject(s)
Chromatography, Affinity/methods , Immunoglobulin D/isolation & purification , Immunoglobulin M/isolation & purification , Ammonium Sulfate , Animals , Ascitic Fluid , Cell Culture Techniques , Chemical Precipitation , Chromatography, Agarose , Chromatography, Gel , Humans , Hybridomas , Immunoglobulin D/immunology , Immunoglobulin M/immunology , Mannose-Binding Lectin , Mice , Plant Lectins
7.
Biochem Biophys Res Commun ; 324(2): 511-7, 2004 Nov 12.
Article in English | MEDLINE | ID: mdl-15474457

ABSTRACT

There are an increasing number of studies reporting the presence of Hsps in human serum. We have investigated the release of Hsp70 into blood and culture medium from peripheral blood mononuclear cells (PBMCs), and whether this release is due to cell damage or active secretion from the cells. Intact Hsp70 was released from cells within whole blood and from purified PBMCs under normal culture conditions. Hsp70 release was rapid (0.1 ng/10(6) cells/h) over the first 2 h of culture and continued at a reduced rate up to 24 h (<0.025 ng/10(6) cells/h). Using viable cell counts and lactate dehydrogenase release we were able to confirm that the release of Hsp70 was not due to cellular damage. Hsp70 release was inhibited by monensin, methyl-beta-cyclodextrin, and methylamine, but not by brefeldin A. These data suggest that Hsp70 is released from cells via a non-classical pathway, possibly involving lysosomal lipid rafts.


Subject(s)
HSP70 Heat-Shock Proteins/blood , Leukocytes, Mononuclear/cytology , B-Lymphocytes/metabolism , Blotting, Western , Brefeldin A/pharmacology , Cell Survival , Culture Media/pharmacology , HSP70 Heat-Shock Proteins/metabolism , Humans , L-Lactate Dehydrogenase/metabolism , Leukocytes, Mononuclear/metabolism , Lysosomes/metabolism , Membrane Microdomains/metabolism , Methylamines/chemistry , Monensin/metabolism , Protein Synthesis Inhibitors/pharmacology , RNA, Messenger/metabolism , T-Lymphocytes/metabolism , Temperature , Time Factors , beta-Cyclodextrins/metabolism
8.
Curr Protoc Cell Biol ; Chapter 16: Unit 16.4, 2003 Feb.
Article in English | MEDLINE | ID: mdl-18228421

ABSTRACT

For some purposes, fragments of the IgG molecule are preferred. The F(c) portion is useful for studies of biological effect-binding to the F(c) receptor, mediating antibody-dependent cellular cytotoxicity, and complement fixation. The bivalent F(ab')(2) produced by digestion with pepsin and the monovalent Fab produced by digestion with papain are useful for studies based on the interaction between antibody binding site(s) with antigen. This unit also describes alternative methods for preparing F(ab')(2) fragments.


Subject(s)
Immunoglobulin Fab Fragments/chemistry , Immunoglobulin Fc Fragments/chemistry , Immunoglobulin Fragments/chemistry , Immunoglobulin G/chemistry , Animals , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/immunology , Antigen-Antibody Complex/immunology , Binding Sites , Cattle , Chickens , Electrophoresis, Polyacrylamide Gel , Ficain/chemistry , Goats , Guinea Pigs , Horses , Humans , Immunoglobulin Fab Fragments/immunology , Immunoglobulin Fab Fragments/isolation & purification , Immunoglobulin Fc Fragments/immunology , Immunoglobulin Fc Fragments/isolation & purification , Immunoglobulin Fragments/immunology , Immunoglobulin Fragments/isolation & purification , Immunoglobulin G/immunology , Immunoglobulin G/isolation & purification , Mice , Papain/chemistry , Pepsin A/chemistry , Rats , Sheep
9.
Early Hum Dev ; 66(2): 89-100, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11872313

ABSTRACT

Numerous studies have postulated a link between recent infection and Sudden Infant Death Syndrome (SIDS). In this study we contrasted arousal responses from sleep in infants on the day of discharge from hospital following an infection with those when fully recovered and also with well age-matched control infants. Thirteen term infants comprised the infection group and nine well infants acted as age-matched controls. All infants were studied using daytime polysomnography and multiple measurements of arousal threshold (cm H(2)O) in response to air-jet stimulation applied alternately to the nares were made in both active sleep (AS) and quiet sleep (QS). All infants were studied on two occasions: firstly, immediately before discharge from the Paediatric ward, and secondly, 10-15 days later when they were completely well in the case of the infection group.Arousal thresholds in QS in the infection group were significantly elevated on the day of discharge (262 +/- 48 cm H(2)O) compared with 10-15 days later (205 +/- 31 cm H(2)O, p<0.05). Thresholds in the control group were not different between studies. This study provides evidence that arousability from QS is impaired following an infection and we postulate that this may explain the increased risk for SIDS following infection observed in previous studies.


Subject(s)
Arousal/physiology , Communicable Diseases/physiopathology , Sleep/physiology , Sudden Infant Death/etiology , Body Temperature/physiology , Female , Heart Rate/physiology , Humans , Infant , Male , Polysomnography , Respiration , Skin Temperature/physiology
10.
Curr Protoc Toxicol ; Appendix 3: A.3H.1-5, 2002 Feb.
Article in English | MEDLINE | ID: mdl-20976673

ABSTRACT

Conventional dialysis separates small molecules from large molecules by allowing diffusion of only the small molecules through selectively permeable membranes. Dialysis is usually used to change the salt (small-molecule) composition of a macromolecule-containing solution. The solution to be dialyzed is placed in a sealed dialysis membrane and immersed in a selected buffer; small solute molecules then equilibrate between the sample and the dialysate. Concomitant with the movement of small solutes across the membrane, however, is the movement of solvent in the opposite direction. There are several simple and relatively inexpensive methods for concentrating protein solutions. Dialysis against Aquacide 11A (Calbiochem), which removes water through the dialysis tubing, may be used. After concentration, the solution must be redialyzed into the appropriate buffer. Another method is to use Immersible-CX Ultrafilters (Millipore) which, when connected to a vacuum, remove everything below their molecular weight cutoff (MWCO). Alternatively, centrifugal concentrators, which are operated with the aid of ordinary laboratory centrifuges may be used.


Subject(s)
Dialysis/methods , Proteins , Microchemistry/methods , Osmolar Concentration , Peptides , Toxicology/methods
11.
Curr Protoc Immunol ; Chapter 2: 2.10A.1-2.10A.5, 2001 May.
Article in English | MEDLINE | ID: mdl-18432762

ABSTRACT

Fragmentation of IgM antibodies may be necessary because of the large molecular weight of the native molecule (900 kDa). IgMs fragments resemble IgG in size and structure, but they may have a decreased binding affinity. The Fc portion of IgM can have powerful biological effector functions such as complement activation. Because some T cells have receptors for IgM, it may be desirable to produce fragments of IgM for both cytotoxicity studies and for in vivo use. A protocol is presented for digestion of IgM with pepsin to produce F(ab')(2)micro. The fragment can be reduced to produce the monovalent F(ab')u, if desired. IgM can also be reduced and alkylated in a single step, as described, using cysteine to produce IgMs, the bivalent monomer or subunit of IgM.


Subject(s)
Immunoglobulin Fab Fragments/chemistry , Immunoglobulin M/chemistry , Pepsin A/chemistry , Animals , Antibody-Dependent Cell Cytotoxicity/immunology , Complement Activation/immunology , Humans , Immunoglobulin G/chemistry , Immunoglobulin G/immunology , Immunoglobulin M/immunology , T-Lymphocytes/immunology
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