can be elicited by motivationally salient stimuli (e.g., appetitive rewards) or objects that support utilization behaviors. These action tendencies can benefit behavioral performance through speeded ...RTs in response tasks and improve detection accuracy in attentional capture tasks. However, action tendencies can be counterproductive when goals change (e.g., refraining from junk foods or abstaining from alcohol). Maintaining control over cue-elicited action tendencies is therefore critical for successful behavior modification. To better understand this relationship, we used transcranial magnetic stimulation to investigate the neural signatures of action tendencies in the presence of previously trained response cues. Participants were presented with a continuous letter stream and instructed to respond quickly to two target letters using two different response keys. Following this training phase, the target letters were embedded in a new task (test phase), and we applied transcranial magnetic stimulation to the motor cortex and measured motor evoked potentials as an index of corticospinal excitability (CSE). We found that CSE could be potentiated by a former response cue trained within a single experimental session, even when participants were instructed to withhold responses during the test phase. Critically, attention to the previously trained response cue was required to elicit the primed modulation in CSE, and successful control of this activity was accompanied by CSE suppression. These findings suggest that well-trained response cues can come to prime a
and provide a model for understanding how the implementation of cognitive control can override action automaticity.
Spider silk is a striking and robust natural material that has an unrivaled combination of strength and elasticity. There are two major problems in creating materials from recombinant spider silk ...proteins (rSSps): expressing sufficient quantities of the large, highly repetitive proteins and solvating the naturally self-assembling proteins once produced. To address the second problem, we have developed a method to rapidly dissolve rSSps in water in lieu of traditional organic solvents and accomplish nearly 100% solvation and recovery of the protein. Our method involves generating pressure and temperature in a sealed vial by using short, repetitive bursts from a conventional microwave. The method is scalable and has been successful with all rSSps used to date. From these easily generated aqueous solutions of rSSps, a wide variety of materials have been produced. Production of fibers, films, hydrogels, lyogels, sponges, and adhesives and studies of their mechanical and structural properties are reported. To our knowledge, ours is the only method that is cost-effective and scalable for mass production. This solvation method allows a choice of the physical form of product to take advantage of spider silks’ mechanical properties without using costly and problematic organic solvents.
Background
Decisions for operative or nonoperative management remain challenging for patients with spinal metastases, especially when life expectancy and quality of life are not easily predicted. ...This study evaluated the effects of operative and nonoperative management on maintenance of ambulatory function and survival for patients treated for spinal metastases.
Methods
Propensity matching was used to yield an analytic sample in which operatively and nonoperatively treated patients were similar with respect to key baseline covariates. The study included patients treated for spinal metastases between 2005 and 2017 who were 40 to 80 years old, were independent ambulators at presentation, and had fewer than 5 medical comorbidities. It evaluated the influence of operative care and nonoperative care on ambulatory function 6 months after presentation as the primary outcome. Survival at 6 months and survival at 1 year were secondary outcomes.
Results
Nine hundred twenty‐nine individuals eligible for inclusion were identified, with 402 (201 operative patients and 201 nonoperative patients) retained after propensity score matching. Patients treated operatively had a lower likelihood than those treated nonoperatively of being nonambulatory 6 months after presentation (3% vs 16%; relative risk RR, 0.16; 95% confidence interval CI, 0.06‐0.46) as well as a reduced risk of 6‐month mortality (20% vs 29%; RR, 0.69; 95% CI, 0.49‐0.98).
Conclusions
These results indicate that in a group of patients with similar demographic and clinical characteristics, those treated operatively were less likely to lose ambulatory function 6 months after presentation than those managed nonoperatively. For patients with spinal metastases, our data can be incorporated into discussions about the treatments that align best with patients’ preferences regarding surgical risk, mortality, and ambulatory status.
This cohort study uses propensity matching to yield an analytic sample in which operatively and nonoperatively treated patients are similar with respect to key baseline covariates, including the independent ambulatory status at presentation. The results indicate that patients treated operatively are less likely to lose ambulatory function 6 months after presentation than those managed nonoperatively.
Spider silk, which has remarkable mechanical properties, is a natural protein fiber produced by spiders. Spiders cannot be farmed because of their cannibalistic and territorial nature. Hence, large ...amounts of spider silk cannot be produced from spiders. Genetic engineering is an alternative approach to produce large quantities of spider silk. Our group has produced synthetic spider silk proteins in E. coli to study structure/function and to produce biomaterials comparable to the silks produced by orb-weaving spiders. Here we give a detailed description of our cloning, expression, and purification methods of synthetic spider silk proteins ranging from ~30 to ~200 kDa. We have cloned the relevant genes of the spider Nephila clavipes and introduced them into bacteria to produce synthetic spider silk proteins using small and large-scale bioreactors. We have optimized the fermentation process, and we have developed protein purification methods as well. The purified proteins are spun into fibers and are used to make alternative materials like films and adhesives with various possible commercial applications.
•Spider silk protein mechanical properties.•Genetic engineering approach to produce spider silk.•Fermentation process optimized for recombinant spider silk production.•High level of recombinant spider silk expressed in bacteria.
Abstract
The microbiome and associated metabolome of faecal samples were compared to those from the caecum and right dorsal colon of horses and ponies euthanised for nonresearch purposes by ...investigating the microbial population community structure as well as their functional metabolic products. Through the use of 16S rRNA gene dendrograms, the caecum microbiome was shown to cluster separately from the other gut regions. 16S rRNA gene-based quantitative PCR (q-PCR) also demonstrated differences between the caecum and the other gut regions. Metabolites as identified by Fourier transform infrared clustered in a similar way and specific metabolic products (volatile fatty acids and ammonia) also varied by region. Protozoal 18S rDNA concentration and archaeal mcrA gene concentration quantified by q-PCR were found in higher numbers in the colon than the other gut regions. Diversity calculations using Simpson and Shannon–Wiener indices demonstrated higher diversity in the right dorsal colon and faeces than in the caecum. All findings of this study suggest that faecal samples are likely to represent the microbial population of the right dorsal colon to some extent but not that of the caecum, indicating careful consideration is required when planning microbial investigations of the hindgut of the horse.
Two experiments used the peak procedure to examine timing of conditioned responses in a magazine approach paradigm with rats. A conditioned stimulus (CS) was reinforced with food on 50% of trials. ...Food was delivered at a fixed time, 20 s, 30 s, or 40 s into the CS presentation. Response rates were recorded during nonreinforced CS presentations that extended well beyond the scheduled time of food delivery. The mean response rate (averaged over many trials) increased during the CS, peaking at the expected time of reinforcement, and decreased again. Detailed analyses of the frequency distribution of response rates showed that responding was described by 2 distinct distributions, consistent with the rat being in a low response state on some trials and in a high response state on others. Modeling of frequency distributions showed that the systematic rise and fall in response rate across a trial was primarily explained by a change in the proportion of time that the rat spent in the low versus high response state. However, the change in responding was also explained in part by a continuous shift in the high response state, such that responding in that state increased and then decreased gradually across the trial. These results support accounts describing response timing as an abrupt change from low to high responding during the CS, but also provide evidence for a continuous change in conditioning strength across the duration of the CS. The implications of these findings for timing and associative theories of conditioning are discussed.
The New England Spinal Metastasis Score (NESMS) was proposed as an intuitive and accessible prognostic tool for predicting survival in patients with spinal metastases. We designed an appropriately ...powered, prospective, longitudinal investigation to validate the NESMS.
To prospectively validate the NESMS.
Prospective longitudinal observational cohort study.
Patients, aged 18 and older, presenting for treatment with spinal metastatic disease.
One-year mortality (primary); 6-month mortality and mortality at any time point following enrollment (secondary).
The date of enrollment was set as time zero for all patients. The NESMS was assigned based on data collected at the time of enrollment. Patients were prospectively followed to one of two predetermined end-points: death, or survival at 365 days following enrollment. Survival was visually assessed with Kaplan-Meier curves and then analyzed using multivariable logistic regression, followed by Bayesian regression to assess for robustness of point estimates and 95% confidence intervals (CI).
This study included 180 patients enrolled between 2017 and 2018. Mortality within 1-year occurred in 56% of the cohort. Using NESMS 3 as the referent, those with a score of 2 had significantly greater odds of mortality (odds ratio 7.04; 95% CI 2.47, 20.08), as did those with a score of 1 (odds ratio 31.30; 95% CI 8.82, 111.04). A NESMS score of 0 was associated with perfect prediction, as 100% of individuals with this score were deceased at 1-year. Similar determinations were encountered for mortality at 6-months and overall.
This study validates the NESMS and demonstrates its utility in prognosticating survival for patients with spinal metastatic disease, irrespective of selected treatment strategy. This is the first study to prospectively validate a prognostic utility for patients with spinal metastases. The NESMS can be directly applied to patient care, hospital-based practice and health-care policy.
Motor cortex dysfunction in problem gamblers Chowdhury, Nahian S.; Livesey, Evan J.; Blaszczynski, Alex ...
Addiction biology,
January 2021, 2021-01-00, 20210101, Volume:
26, Issue:
1
Journal Article
Peer reviewed
Impairments in response inhibition have been implicated in gambling psychopathology. This behavioral impairment may suggest that the neural mechanisms involved in response inhibition, such as ...GABAA‐mediated neurotransmission in the primary motor cortex (M1), are also impaired. The present study obtained paired‐pulse transcranial magnetic stimulation markers of GABAA and glutamate receptor activity from the left M1 of three groups—problem gamblers (n = 17, 12 males), at‐risk gamblers (n = 29, 19 males), and controls (n = 23, six males)—with each group matched for alcohol use, substance use, and attention‐deficit hyperactivity disorder (ADHD) symptomology. Response inhibition was measured using the stop signal task. Results showed that problem gamblers had weaker M1 GABAA receptor activity relative to controls and elevated M1 glutamate receptor activity relative to at‐risk gamblers and controls. Although there were no differences in response inhibition between the groups, poorer response inhibition was correlated with weaker M1 GABAA receptor activity. These findings are the first to show that problem gambling is associated with alterations in M1 GABAA and glutamate‐mediated neurotransmission.
Using paired pulse transcranial magnetic stimulation, we found that that GABA receptor‐mediated activity was weaker in problem gamblers relative to controls and that glutamate‐mediated receptor activity was elevated in problem gamblers relative to at‐risk gamblers and controls. Weaker GABA receptor‐mediated activity across all participants was associated with poorer response inhibition.
Paired-pulse Transcranial Magnetic Stimulation (TMS) is used to study inhibitory and excitatory mechanisms in the motor cortex through the measurement of short-interval intracortical inhibition ...(SICI), indicative of GABAergic activity, and intracortical facilitation (ICF), indicative of glutamatergic activity. In the present study, TMS was delivered to the left motor cortex of 40 participants while we measured SICI and ICF at rest. We were interested in whether variation between individuals in these modulatory mechanisms is related to inhibitory control over responding measured as stop signal reaction time (SSRT). Within the same group of participants, we investigated whether SICI, ICF, SSRT, and self-reported impulsivity, are impaired in participants identified as At-Risk gamblers (n = 20) compared to non-gambling controls (n = 20). We found a significant negative correlation between SICI strength and SSRT, but no correlation between ICF strength and SSRT after controlling for the correlation between SICI and SSRT. Thus, poor inhibitory control of responding was associated with weak GABAergic activity. When taking into account the effects of substance/alcohol use and attention-deficit hyperactivity disorder (ADHD) symptom severity, At-Risk gamblers showed elevated self-reported impulsivity, but did not differ from controls on SSRT or SICI/ICF. Our study is the first to show that individual differences in motor cortex inhibition can predict stopping performance, and the first to investigate paired-pulse TMS parameters (together with other impulse control measures) in a gambling population.
Recent research using paired-pulse transcranial magnetic stimulation (TMS) has shown that the speed with which people can stop an action is linked to GABAergic inhibitory activity in the motor ...system. Specifically, a significant proportion of the variance in stop signal reaction time (SSRT; a widely used measure of inhibitory control) is accounted for by short-interval cortical inhibition (SICI). It is still unclear whether this relationship reflects a broader link between GABAergic processes and executive functions, or a specific link between GABAergic processes and motor stopping ability. The current study sought to replicate the correlation between SSRT and SICI while investigating whether this association generalises to other measures of inhibitory control and working memory, and to long-interval cortical inhibition (LICI). Participants completed a battery of inhibition (Stop-Signal, Stroop, Flanker) and working memory (n-back, Digit Span, and Operation Span) tasks. We replicated the correlation between SICI and SSRT but found no other correlations between behavioural measures of executive control and the two cortical measures of inhibition. These findings indicate that the relationship between SSRT and SICI is specific to a particular property of response inhibition and likely reflects the function of local inhibitory networks mediated by GABAA.
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