Microbial sulfur metabolism contributes to biogeochemical cycling on global scales. Sulfur metabolizing microbes are infected by phages that can encode auxiliary metabolic genes (AMGs) to alter ...sulfur metabolism within host cells but remain poorly characterized. Here we identified 191 phages derived from twelve environments that encoded 227 AMGs for oxidation of sulfur and thiosulfate (dsrA, dsrC/tusE, soxC, soxD and soxYZ). Evidence for retention of AMGs during niche-differentiation of diverse phage populations provided evidence that auxiliary metabolism imparts measurable fitness benefits to phages with ramifications for ecosystem biogeochemistry. Gene abundance and expression profiles of AMGs suggested significant contributions by phages to sulfur and thiosulfate oxidation in freshwater lakes and oceans, and a sensitive response to changing sulfur concentrations in hydrothermal environments. Overall, our study provides fundamental insights on the distribution, diversity, and ecology of phage auxiliary metabolism associated with sulfur and reinforces the necessity of incorporating viral contributions into biogeochemical configurations.
The human cerebral cortex depends for its normal development and size on a precisely controlled balance between self-renewal and differentiation of diverse neural progenitor cells. Specialized ...progenitors that are common in humans but virtually absent in rodents, called outer radial glia (ORG), have been suggested to be crucial to the evolutionary expansion of the human cortex. We combined progenitor subtype-specific sorting with transcriptome-wide RNA sequencing to identify genes enriched in human ORG, which included targets of the transcription factor neurogenin and previously uncharacterized, evolutionarily dynamic long noncoding RNAs. Activating the neurogenin pathway in ferret progenitors promoted delamination and outward migration. Finally, single-cell transcriptional profiling in human, ferret and mouse revealed more cells coexpressing proneural neurogenin targets in human than in other species, suggesting greater neuronal lineage commitment and differentiation of self-renewing progenitors. Thus, we find that the abundance of human ORG is paralleled by increased transcriptional heterogeneity of cortical progenitors.
High-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride concentrations are heritable risk factors for vascular disease, but their role in the ...progression of chronic kidney disease (CKD) is unclear.
2-sample Mendelian randomization analysis of data derived from the largest published lipid and CKD studies.
Effect of independent genetic variants significantly associated with lipid concentrations was obtained from the Global Lipids Genetics Consortium (n=188,577), and the effect of these same variants on estimated glomerular filtration rate (eGFR), CKD (defined as eGFR<60mL/min/1.73m2), and albuminuria was obtained from the CKD Genetics Consortium (n=133,814).
Using conventional, multivariable, and Egger Mendelian randomization approaches, we assessed the causal association between genetically determined lipid concentrations and kidney traits.
eGFR, dichotomous eGFR<60mL/min/1.73m2, and albuminuria.
In multivariable analysis, a 17-mg/dL higher HDL cholesterol concentration was associated with an 0.8% higher eGFR (95% CI, 0.4%-1.3%; P=0.004) and lower risk for eGFR<60mL/min/1.73m2 (OR, 0.85; 95% CI, 0.77-0.93; P<0.001), while Egger analysis showed no evidence of pleiotropy. There was no evidence for a causal relationship between LDL cholesterol concentration and any kidney disease measure. Genetically higher triglyceride concentrations appeared associated with higher eGFRs, but this finding was driven by a single pleiotropic variant in the glucokinase regulator gene (GCKR). After exclusion, genetically higher triglyceride concentration was not associated with any kidney trait.
Individual patient–level phenotype and genotype information were unavailable.
2-sample Mendelian randomization analysis of data from the largest lipid and CKD cohorts supports genetically higher HDL cholesterol concentration as causally associated with better kidney function. There was no association between genetically altered LDL cholesterol or triglyceride concentration and kidney function. Further analysis of CKD outcomes in HDL cholesterol intervention trials is warranted.
Highlights • Single-cell RNA sequencing revolutionizes systematic classification of neurons. • Classification by scRNA-seq reveals new neuronal subtypes. • Matching transcriptionally and classically ...defined subtypes is challenging. • Developmental classifications need larger sample sizes across many time-points.
Purpose
This study aimed to investigate the effects of multi-strain probiotics supplementation on gastrointestinal permeability, systemic markers of inflammation and running performance when ...exercising in the heat.
Methods
Ten male runners were randomized to 4 weeks of daily supplementation with a probiotics capsule (45 billion CFU of
Lactobacillus
,
Bifidobacterium
and
Streptococcus
strains) or placebo, separated by a washout period (double-blind, cross-over trial). After each treatment, the runners exercised to fatigue at 80 % of their ventilatory threshold at 35 °C and 40 % humidity. To assess gastrointestinal permeability, runners ingested lactulose and rhamnose before exercise and post-exercise urine was collected to measure sugar concentrations. Venous blood samples were collected before, immediately after and 1 h after exercise, and core temperature was monitored during exercise.
Results
Probiotics supplementation significantly increased run time to fatigue (min:s 37:44 ± 2:42 versus 33:00 ± 2:27;
P
= 0.03,
d
= 0.54). Average core temperature during exercise was similar between trials (probiotic 38.1 ± 0.2 °C, placebo 38.1 ± 0.1 °C;
P
= 0.77,
d
= 0.13). Serum lipopolysaccharide concentration increased post-exercise (
P
< 0.001), while there was a moderate to large reduction in pre-exercise (
d
= 0.70) and post-exercise (
d
= 1.24) concentration following probiotics supplementation. Plasma concentrations of IL-6, IL-10 and IL-1ra increased after exercise (
P
< 0.01), but there was no significant difference between trials (
P
> 0.05). There was a small to moderate reduction (
d
= 0.35) in urine lactulose:rhamnose and a small reduction (
d
= 0.25) in symptoms of gastrointestinal discomfort following probiotics supplementation (both
P
= 0.25).
Conclusion
Four weeks of supplementation with a multi-strain probiotic increased running time to fatigue in the heat. Further studies are required to elucidate the exact mechanisms for this performance benefit.
•Neural circuits mediating prosocial behaviors are being defined using modern methods.•Modulation of mesolimbic reward circuitry plays a key role in promoting sociability.•Social memory involves ...specific subregions of the hippocampus.•Prosocial behavior is deficient in rodent models of autism, depression, and addiction.
Prosocial behaviors are essential for group cooperation, which enrich life experience and enhance survival. These complex behaviors are governed by intricate interactions between numerous neural circuits functioning in concert. Impairments in prosocial interactions result from disruptions of this coordinated brain activity and are a prominent feature of several pathological conditions including autism spectrum disorder, depression and addiction. Here we highlight recent studies that use advanced techniques to anatomically map, monitor and manipulate neural circuits that influence prosocial behavior. These recent findings provide important clues to unravel the complexities of the neural mechanisms that mediate prosocial interactions and offer insights into new strategies for the treatment of aberrant social behavior.
Dehydration in older adults contributes to increased morbidity and mortality during hospitalization. As such, early diagnosis of dehydration may improve patient outcome and reduce the burden on ...healthcare. This prospective study investigated the diagnostic accuracy of routinely used physical signs, and noninvasive markers of hydration in urine and saliva.
Prospective diagnostic accuracy study.
Hospital acute medical care unit and emergency department.
One hundred thirty older adults 59 males, 71 females, mean (standard deviation) age = 78 (9) years.
Participants with any primary diagnosis underwent a hydration assessment within 30 minutes of admittance to hospital. Hydration assessment comprised 7 physical signs of dehydration tachycardia (>100 bpm), low systolic blood pressure (<100 mm Hg), dry mucous membrane, dry axilla, poor skin turgor, sunken eyes, and long capillary refill time (>2 seconds), urine color, urine specific gravity, saliva flow rate, and saliva osmolality. Plasma osmolality and the blood urea nitrogen to creatinine ratio were assessed as reference standards of hydration with 21% of participants classified with water-loss dehydration (plasma osmolality >295 mOsm/kg), 19% classified with water-and-solute-loss dehydration (blood urea nitrogen to creatinine ratio >20), and 60% classified as euhydrated.
All physical signs showed poor sensitivity (0%-44%) for detecting either form of dehydration, with only low systolic blood pressure demonstrating potential utility for aiding the diagnosis of water-and-solute-loss dehydration diagnostic odds ratio (OR) = 14.7. Neither urine color, urine specific gravity, nor saliva flow rate could discriminate hydration status (area under the receiver operating characteristic curve = 0.49-0.57, P > .05). In contrast, saliva osmolality demonstrated moderate diagnostic accuracy (area under the receiver operating characteristic curve = 0.76, P < .001) to distinguish both dehydration types (70% sensitivity, 68% specificity, OR = 5.0 (95% confidence interval 1.7-15.1) for water-loss dehydration, and 78% sensitivity, 72% specificity, OR = 8.9 (95% confidence interval 2.5-30.7) for water-and-solute-loss dehydration).
With the exception of low systolic blood pressure, which could aid in the specific diagnosis of water-and-solute-loss dehydration, physical signs and urine markers show little utility to determine if an elderly patient is dehydrated. Saliva osmolality demonstrated superior diagnostic accuracy compared with physical signs and urine markers, and may have utility for the assessment of both water-loss and water-and-solute-loss dehydration in older individuals. It is particularly noteworthy that saliva osmolality was able to detect water-and-solute-loss dehydration, for which a measurement of plasma osmolality would have no diagnostic utility.
Wearable assistive devices have demonstrated the potential to improve mobility outcomes for individuals with disabilities, and to augment healthy human performance; however, these benefits depend on ...how effectively power is transmitted from the device to the human user. Quantifying and understanding this power transmission is challenging due to complex human-device interface dynamics that occur as biological tissues and physical interface materials deform and displace under load, absorbing and returning power.
Here we introduce a new methodology for quickly estimating interface power dynamics during movement tasks using common motion capture and force measurements, and then apply this method to quantify how a soft robotic ankle exosuit interacts with and transfers power to the human body during walking. We partition exosuit end-effector power (i.e., power output from the device) into power that augments ankle plantarflexion (termed augmentation power) vs. power that goes into deformation and motion of interface materials and underlying soft tissues (termed interface power).
We provide empirical evidence of how human-exosuit interfaces absorb and return energy, reshaping exosuit-to-human power flow and resulting in three key consequences: (i) During exosuit loading (as applied forces increased), about 55% of exosuit end-effector power was absorbed into the interfaces. (ii) However, during subsequent exosuit unloading (as applied forces decreased) most of the absorbed interface power was returned viscoelastically. Consequently, the majority (about 75%) of exosuit end-effector work over each stride contributed to augmenting ankle plantarflexion. (iii) Ankle augmentation power (and work) was delayed relative to exosuit end-effector power, due to these interface energy absorption and return dynamics.
Our findings elucidate the complexities of human-exosuit interface dynamics during transmission of power from assistive devices to the human body, and provide insight into improving the design and control of wearable robots. We conclude that in order to optimize the performance of wearable assistive devices it is important, throughout design and evaluation phases, to account for human-device interface dynamics that affect power transmission and thus human augmentation benefits.
We previously reported that the activity of mesolimbic dopamine neurons of the ventral tegmental area (VTA) is a key determinant of behavioral susceptibility vs resilience to chronic social defeat ...stress. However, this was based solely on ex vivo measurements, and the in vivo firing properties of VTA dopamine neurons in susceptible and resilient mice, as well as the effects of antidepressant treatments, remain completely unknown. Here, we show that chronic (10 d) social defeat stress significantly increased the in vivo spontaneous firing rates and bursting events in susceptible mice but not in the resilient subgroup. Both the firing rates and bursting events were significantly negatively correlated with social avoidance behavior, a key behavioral abnormality induced by chronic social defeat stress. Moreover, the increased firing rates, bursting events, and avoidance behavior in susceptible mice were completely reversed by chronic (2 week), but not acute (single dose), treatments with the antidepressant medication fluoxetine (20 mg/kg). Chronic social defeat stress increased hyperpolarization-activated cation current (I(h)) in VTA dopamine neurons, an effect that was also normalized by chronic treatment with fluoxetine. As well, local infusion of I(h) inhibitors ZD7288 (0.1 μg) or DK-AH 269 (0.6 μg) into the VTA exerted antidepressant-like behavioral effects. Together, these data suggest that the firing patterns of mesolimbic dopamine neurons in vivo mediate an individual's responses to chronic stress and antidepressant action.
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