Genotype-dependent contribution of CBF transcription factors to long-term acclimation to high light and cool temperature.

When grown under cool temperature, winter annuals upregulate photosynthetic capacity as well as freezing tolerance. Here, the role of three cold-induced C-repeat-binding factor (CBF1-3) transcription factors in photosynthetic upregulation and freezing tolerance was examined in two Arabidopsis thaliana ecotypes originating from Italy (IT) or Sweden (SW), and their corresponding CBF1-3-deficient mutant lines it:cbf123 and sw:cbf123. Photosynthetic, morphological and freezing-tolerance phenotypes, as well as gene expression profiles, were characterized in plants grown from the seedling stage under different combinations of light level and temperature. Under high light and cool (HLC) growth temperature, a greater role of CBF1-3 in IT versus SW was evident from both phenotypic and transcriptomic data, especially with respect to photosynthetic upregulation and freezing tolerance of whole plants. Overall, features of SW were consistent with a different approach to HLC acclimation than seen in IT, and an ability of SW to reach the new homeostasis through the involvement of transcriptional controls other than CBF1-3. These results provide tools and direction for further mechanistic analysis of the transcriptional control of approaches to cold acclimation suitable for either persistence through brief cold spells or for maximisation of productivity in environments with continuous low temperatures.

Aerosol and droplet generation from orbital repair: Surgical risk in the pandemic era.

INTRODUCTION: The highly contagious COVID-19 has resulted in millions of deaths worldwide. Physicians performing orbital procedures may be at increased risk of occupational exposure to the virus due to exposure to secretions. The goal of this study is to measure the droplet and aerosol production during repair of the inferior orbital rim and trial a smoke-evacuating electrocautery handpiece as a mitigation device. MATERIAL AND METHODS: The inferior rim of 6 cadaveric orbits was approached transconjunctivally using either standard or smoke-evacuator electrocautery and plated using a high-speed drill. Following fluorescein inoculation, droplet generation was measured by counting under ultraviolet-A (UV-A) light against a blue background. Aerosol generation from 0.300-10.000 µm was measured using an optical particle sizer. Droplet and aerosol generation was compared against retraction of the orbital soft tissue as a negative control. RESULTS: No droplets were observed following the orbital approach using electrocautery. Visible droplets were observed after plating with a high-speed drill for 3 of 6 orbits. Total aerosol generation was significantly higher than negative control following the use of standard electrocautery. Use of smoke-evacuator electrocautery was associated with significantly lower aerosol generation in 2 of 3 size groups and in total. There was no significant increase in total aerosols associated with high-speed drilling. DISCUSSION AND CONCLUSIONS: Droplet generation for orbital repair was present only following plating with high-speed drill. Aerosol generation during standard electrocautery was significantly reduced using a smoke-evacuating electrocautery handpiece. Aerosols were not significantly increased by high-speed drilling.

Aerosol and droplet generation from mandible and midface fixation: Surgical risk in the pandemic era.

PURPOSE: The COVID-19 pandemic has led to concerns over transmission risk from healthcare procedures, especially when operating in the head and neck such as during surgical repair of facial fractures. This study aims to quantify aerosol and droplet generation from mandibular and midface open fixation and measure mitigation of airborne particles by a smoke evacuating electrocautery hand piece. MATERIALS AND METHODS: The soft tissue of the bilateral mandible and midface of two fresh frozen cadaveric specimens was infiltrated using a 0.1% fluorescein solution. Surgical fixation via oral vestibular approach was performed on each of these sites. Droplet splatter on the surgeon's chest, facemask, and up to 198.12 cm (6.5 ft) away from each surgical site was measured against a blue background under ultraviolet-A (UV-A) light. Aerosol generation was measured using an optical particle sizer. RESULTS: No visible droplet contamination was observed for any trials of mandible or midface fixation. Total aerosolized particle counts from 0.300-10.000 µm were increased compared to baseline following each use of standard electrocautery (n = 4, p < 0.001) but not with use of a suction evacuating electrocautery hand piece (n = 4, p = 0.103). Total particle counts were also increased during use of the powered drill (n = 8, p < 0.001). CONCLUSIONS: Risk from visible droplets during mandible and midface fixation is low. However, significant increases in aerosolized particles were measured after electrocautery use and during powered drilling. Aerosol dispersion is significantly decreased with the use of a smoke evacuating electrocautery hand piece.

The Effects of Age on the Neural Correlates of Recollection Success, Recollection-Related Cortical Reinstatement, and Post-Retrieval Monitoring.

Functional magnetic resonance imaging (fMRI) was used to investigate whether age-related differences in episodic memory performance are accompanied by a reduction in the specificity of recollected information. We addressed this question by comparing recollection-related cortical reinstatement in young and older adults. At study, subjects viewed objects and concrete words, making 1 of 2 different semantic judgments depending on the study material. Test items were words that corresponded to studied words or the names of studied objects. Subjects indicated whether each test item was recollected, familiar, or novel. Reinstatement of information differentiating the encoding tasks was quantified both with a univariate analysis of the fMRI signal and with a multivoxel pattern analysis, using a classifier that had been trained to discriminate between the 2 classes of study episode. The results of these analyses converged to suggest that reinstatement did not differ according to age. Thus, there was no evidence that specificity of recollected information was reduced in older individuals. Additionally, there were no age effects in the magnitude of recollection-related modulations in regional activity or in the neural correlates of post-retrieval monitoring. Taken together, the findings suggest that the neural mechanisms engaged during successful episodic retrieval can remain stable with advancing age.

Rfx6 directs islet formation and insulin production in mice and humans.

Insulin from the beta-cells of the pancreatic islets of Langerhans controls energy homeostasis in vertebrates, and its deficiency causes diabetes mellitus. During embryonic development, the transcription factor neurogenin 3 (Neurog3) initiates the differentiation of the beta-cells and other islet cell types from pancreatic endoderm, but the genetic program that subsequently completes this differentiation remains incompletely understood. Here we show that the transcription factor Rfx6 directs islet cell differentiation downstream of Neurog3. Mice lacking Rfx6 failed to generate any of the normal islet cell types except for pancreatic-polypeptide-producing cells. In human infants with a similar autosomal recessive syndrome of neonatal diabetes, genetic mapping and subsequent sequencing identified mutations in the human RFX6 gene. These studies demonstrate a unique position for Rfx6 in the hierarchy of factors that coordinate pancreatic islet development in both mice and humans. Rfx6 could prove useful in efforts to generate beta-cells for patients with diabetes.

Episodic retrieval involves early and sustained effects of reactivating information from encoding.

Several fMRI studies have shown a correspondence between the brain regions activated during encoding and retrieval, consistent with the view that memory retrieval involves hippocampally-mediated reinstatement of cortical activity. With the limited temporal resolution of fMRI, the precise timing of such reactivation is unclear, calling into question the functional significance of these effects. Whereas reactivation influencing retrieval should emerge with neural correlates of retrieval success, that signifying post-retrieval monitoring would trail retrieval. The present study employed EEG to provide a temporal landmark of retrieval success from which we could investigate the sub-trial time course of reactivation. Pattern-classification analyses revealed that early-onsetting reactivation differentiated the outcome of recognition-memory judgments and was associated with individual differences in behavioral accuracy, while reactivation was also evident in a sustained form later in the trial. The EEG findings suggest that, whereas prior fMRI findings could be interpreted as reflecting the contribution of reinstatement to retrieval success, they could also indicate the maintenance of episodic information in service of post-retrieval evaluation.

Electrophysiological evidence for strategically orienting retrieval toward the specific age of a memory.

For over a century, memory researchers have extensively studied the differences between retrieving memories that were encoded in the remote past as opposed to recently. Although this work has largely focused on the changes that these memory traces undergo over time, an unexplored issue is whether retrieval attempts and other strategic processes might be differentially oriented in order to effectively access memories of different ages. The current study addressed this issue by instructing participants to retrieve words that were encoded either one week (remote) or about 30 minutes earlier (recent). To maximize the possibility that participants adopted distinct retrieval orientations, separate blocks of the memory test employed exclusion task procedures in which the words from only one encoding period were targeted at a given time, in the face of distractors from the other period. Event-related potentials (ERPs) elicited by correctly-rejected new items were contrasted to minimize confounding effects of retrieval success. The new-item ERPs revealed differences according to the targeted week, such that the ERPs over posterior scalp were more positive-going for the recent compared to remote blocks. Furthermore, using multiple methods, these ERP effects were dissociated from differences in difficulty across the two conditions. The findings provide novel evidence that knowledge about when a memory was initially encoded leads to differences in the adoption of retrieval processing strategies.

Hippocampal activity during recognition memory co-varies with the accuracy and confidence of source memory judgments.

It has been proposed that the hippocampus selectively supports retrieval of contextual associations, but an alternative view holds that the hippocampus supports strong memories regardless of whether they contain contextual information. We employed a memory test that combined the 'Remember/Know' and source memory procedures, which allowed test items to be segregated both by memory strength (recognition accuracy) and, separately, by the quality of the contextual information that could be retrieved (indexed by the accuracy/confidence of a source memory judgment). As measured by fMRI, retrieval-related hippocampal activity tracked the quality of retrieved contextual information and not memory strength. These findings are consistent with the proposal that the hippocampus supports contextual recollection rather than recognition memory more generally.

The diminishing precision of memory for time.

Knowing when an event took place can provide several benefits to episodic memory, such as distinguishing among multiple traces, learning sequences of events, and guiding a search strategy. As a tool for understanding memory, time is particularly appealing given its ever-changing quality, the constant possibility to associate it with encoded events, and the ease with which it can be targeted at retrieval. Whereas studies of episodic retrieval typically employ categorical and probabilistic measures of retrieval success, characterizing a continuous feature such as time warrants measures particularly sensitive to the fidelity, or precision, of retrieved information. Here, we adapt a paradigm for assessing the fine-grained precision of retrieval to understand the nature of judging the time at which a memory was encoded. Subjects studied a series of pictures and then undertook a test in which they placed each picture, as precisely as possible, along a continuous time line representing the study list. Based on mixture-modeling analyses of the test response errors, the primary results were that temporal judgments were less accurate with passing time, and this change was due to diminished precision as opposed to an increased rate of guessing. Moreover, although we observed a negligible influence of guessing, subjects exhibited a clear effect of bias that favored recent responses. Together, in contrast to numerous studies of memory for other continuous features (e.g., color and location), our findings demonstrate a novel pattern of decision factors, suggesting that the retrieval of time might highlight distinct attributes of episodic memory.

Decrements in hippocampal activity with item repetition during continuous recognition: an fMRI study.

fMRI (1.5 mm isotropic voxels) was employed to investigate the relationship between hippocampal activity and memory strength in a continuous recognition task. While being scanned, subjects were presented with colored photographs that each appeared on four occasions. The requirements were to make one response when an item was presented for the first or the third time and to make a different response when an item appeared for the second or the fourth time. Consistent with prior findings, items presented for the first time elicited greater hippocampal and parahippocampal activity than repeated items. The activity elicited by repeated items declined linearly as a function of number of presentations ("graded" new > old effects). No medial-temporal lobe regions could be identified where activity elicited by repeated items exceeded that for new items or where activity elicited by repeated items increased with number of presentations. These findings are inconsistent with the proposal that retrieval-related hippocampal activity is positively correlated with memory strength. We also identified graded new > old effects in several cortical regions outside the medial-temporal lobe, including the left retrosplenial/posterior cingulate cortex and the right lateral occipito-temporal cortex. By contrast, graded old > new effects were evident in bilateral mid-intraparietal sulcus and precuneus.

Recollection-related hippocampal activity during continuous recognition: a high-resolution fMRI study.

We used high-resolution functional magnetic resonance imaging to investigate whether successful recollection during continuous recognition is associated with relative enhancement of hippocampal activity, consistent with prior findings from experiments employing separate study and test phases. While being scanned, subjects discriminated between new and repeated pictures. Each picture, which was repeated once after an interval of between 10 and 30 items, was surrounded by a frame that was colored gray, blue, or orange. When an item repeated, its frame color determined the correct response. Repeated items surrounded by a gray frame always required an "old" judgment. A repeated item surrounded by a blue or an orange frame required a different response depending whether it was represented in the same (Target) or a different (Nontarget) color from the first presentation. Consistent with the results from previous continuous recognition experiments, robust new > old effects were found in bilateral hippocampus. In addition, an across-subjects correlational analysis identified a cluster of voxels in right hippocampus where recollection-related activity (operationalized by the contrast between correctly vs. incorrectly judged Nontargets) was positively correlated with recollection performance. Thus, successful recollection during continuous recognition is associated with a relative enhancement of hippocampal activity.

Developing high performance lipoprotein density profiling for use in clinical studies relating to cardiovascular disease.

Early detection of the beginning stage of cardiovascular disease (CVD) is an approach to prevention because the process is reversible at this stage. Consequently, several methods for screening for CVD have been introduced in recent years incorporating different analytical methods for characterizing the population of blood-borne lipoprotein subclasses. The gold standard method for lipoprotein subclassification is based on lipoprotein density measured by sedimentation equilibrium using the ultracentrifuge. However, this method has not been adopted for clinical studies because of difficulties in achieving the precision required for distinguishing individuals with and without CVD particularly when statistical classification methods are used. The objective of this study was to identify and improve the major factors that influence the precision of measurement of lipoprotein density profile by sedimentation equilibrium analysis and labeling with a fluorescent probe. The study has two phases, each contributing to precision. The first phase focuses on the ultracentrifugation-related variables, and the second phase addresses those factors involved in converting the fluorescent lipoprotein density profile to a digital format compatible with statistical analysis. The overall improvement in precision was on the order of a factor of 5, sufficient to be effectively applied to ongoing classification studies relating to CVD risk assessment.

Aerosol and Droplet Generation from Open Rhinoplasty: Surgical Risk in the Pandemic Era.

Introduction: The coronavirus disease 2019 pandemic has led to concerns over transmission risk from head and neck operations including facial cosmetic surgeries. Objectives: To quantify droplet and aerosol generation from rhinoplasty techniques in a human anatomic specimen model using fluorescein staining and an optical particle sizer. Methods: Noses of human anatomic specimens were infiltrated using 0.1% fluorescein. Droplets and aerosols were measured during rhinoplasty techniques including opening the skin-soft tissue envelope, monopolar electrocautery, endonasal rasping, endonasal osteotomy, and percutaneous osteotomy. Results: No visible droplet contamination was observed for any rhinoplasty techniques investigated. Compared with the negative control of anterior rhinoscopy, total 0.300-10.000 µm aerosols were increased after monopolar electrocautery (p < 0.001) and endonasal rasp (p = 0.003). Opening the skin-soft tissue envelope, endonasal osteotomies, and percutaneous osteotomies did not generate a detectable increase in aerosols (p > 0.15). Discussion and Conclusions: In this investigation, droplets were not observed under ultraviolet light, and aerosol generation was noted only with cautery and endonasal rasping.

Meal patterns and hypothalamic NPY expression during chronic social stress and recovery.

In the present study, we examined meal patterns during and after exposure to the visible burrow system (VBS), a rodent model of chronic social stress, to determine how the microstructure of food intake relates to the metabolic consequences of social subordination. Male Long-Evans rats were housed in mixed-sex VBS colonies (4 male, 2 female) for 2 wk, during which time a dominance hierarchy formed [1 dominant male (DOM) and 3 subordinate males (SUB)], and then male rats were individually housed for a 3-wk recovery period. Controls were individually housed with females during the 2-wk VBS period and had no changes in ingestive behavior compared with a habituation period. During the hierarchy-formation phase of VBS housing, DOM and SUB had a reduced meal frequency, whereas SUB also had a reduced meal size. However, during the hierarchy-maintenance phase of VBS housing, DOM meal patterns did not differ from controls, whereas SUB continued to display a reduced food intake via less frequent meals. During recovery, DOM had comparable meal patterns to controls, whereas SUB had an increased meal size. Hypothalamic neuropeptide Y (NPY) mRNA levels were not different between these groups during the experimental period. Together, the results suggest that exposure to chronic social stress alters ingestive behavior both acutely and in the long term, which may influence the metabolic changes that accompany bouts of stress and recovery; however, these differences in meal patterns do not appear to be mediated by hypothalamic NPY.

Repetition attenuates the influence of recency on recognition memory: Behavioral and electrophysiological evidence.

Studies of recognition memory often demonstrate a recency effect on behavioral performance, whereby response times (RTs) are faster for stimuli that were previously presented recently as opposed to more remotely in the past. One account of this relationship between performance and presentation lag posits that memories are accessed by serially searching backward in time, such that RT indicates the self-terminating moment of such a process. Here, we investigated the conditions under which this serial search gives way to more efficient means of retrieving memories. Event-related potentials (ERPs) were recorded during a continuous recognition task, in which subjects made binary old/new judgments to stimuli that were each presented up to four times across a range of lags. Stimulus repetition and shorter presentation lag both gave rise to speeded RTs, consistent with previous findings, and we novelly extend these effects to a robust latency measure of the left parietal ERP correlate of retrieval success. Importantly, the relationship between repetition and recency was further elucidated, such that repetition attenuated lag-related differences that were initially present in both the behavioral and neural latency data. These findings are consistent with the idea that an effortful search through recent memory can quickly be abandoned in favor of relying on more efficient "time-independent" cognitive processes or neural signals.

Beta-adrenergic antagonism alters functional connectivity during associative processing in a preliminary study of individuals with and without autism.

Beta-adrenergic antagonism (e.g. propranolol) has been associated with cognitive/behavioral benefits following stress-induced impairments and for some cognitive/behavioral domains in individuals with autism spectrum disorder. In this preliminary investigation, we examined whether the benefits of propranolol are associated with functional properties in the brain. Adolescents/adults (mean age = 22.54 years) with (n = 13) and without autism spectrum disorder (n = 13) attended three sessions in which propranolol, nadolol (beta-adrenergic antagonist that does not cross the blood-brain barrier), or placebo was administered before a semantic fluency task during functional magnetic resonance imaging. Autonomic nervous system measures and functional connectivity between language/associative processing regions and within the fronto-parietal control, dorsal attention, and default mode networks were examined. Propranolol was associated with improved semantic fluency performance, which was correlated with the baseline resting heart rate. Propranolol also altered network efficiency of regions associated with semantic processing and in an exploratory analysis reduced functional differences in the fronto-parietal control network in individuals with autism spectrum disorder. Thus, the cognitive benefits from beta-adrenergic antagonism may be generally associated with improved information processing in the brain in domain-specific networks, but individuals with autism spectrum disorder may also benefit from additional improvements in domain-general networks. The benefits from propranolol may also be able to be predicted from baseline autonomic nervous system measures, which warrants further investigation.

Latent resting-state network dynamics in boys and girls with attention-deficit/hyperactivity disorder.

Neuroimaging studies of subjects with ADHD typically show altered functional connectivity in prefrontal, striatal, and several temporal brain regions. While the majority of studies have focused on connectivity that is averaged over time, we investigated the temporal dynamics of brain network changes in resting-state fMRI. Using the ADHD-200 consortium, we characterized the time course of latent state changes using Hidden Markov Modeling, and compared state changes between boys and girls with ADHD along with typically developing controls. Sex differences were found in latent state switching, with boys dwelling longer in a given state than girls, and concurrently having fewer overall state transitions. These sex differences were found in children with ADHD and in typically developing controls. Children with ADHD were also found to be more variable in terms of state transitions than controls. These findings add to the growing literature on neural sex differences and may be related to the sex difference in focal versus diffuse attention.

Multiple repetitions reveal functionally and anatomically distinct patterns of hippocampal activity during continuous recognition memory.

We used a continuous recognition procedure that included multiple presentations of test items, along with high-resolution functional magnetic resonance imaging (fMRI), to investigate the relationship between item novelty and recognition-related activity in the medial temporal lobe (MTL). In several regions of hippocampus and parahippocampal cortex, activity elicited by new items exceeded that for old items, whereas no MTL regions exhibited greater activity for old items. Critically, anatomically distinct regions of MTL were engaged by item novelty in two different ways, as evidenced by statistically dissociable profiles of activity. In bilateral medial hippocampus and left posterior parahippocampal cortex, activity followed a categorical profile in which it was greater for new than old items but did not differ further with additional presentations of old items. By contrast, effects in adjacent regions of right lateral hippocampus and left parahippocampal cortex were graded, whereby activity declined linearly with respect to each successive item presentation. These findings suggest that the relationship between hippocampal (and parahippocampal) activity and continuous psychological dimensions, such as item novelty, cannot be captured by a unitary function.

The relationship between the right frontal old/new ERP effect and post-retrieval monitoring: specific or non-specific?

Post-retrieval processes are thought to be engaged when the outcome of an attempt to retrieve information from long-term memory must be monitored or evaluated. Previous research employing event-related potentials (ERPs) has implicated a specific ERP modulation - the 'right frontal old/new effect' - as a correlate of post-retrieval processing. In two experiments we examined whether the right frontal effect is specifically associated with processing of the products of an episodic retrieval attempt. During study, subjects in both experiments made one of two semantic judgments on serially presented pictures. In experiment 1, one study phase was followed by a source memory task, in which subjects responded 'new' to unstudied pictures and signaled the semantic judgment made on each studied picture. A separate study phase was followed by a task in which the studied items required a judgment about their semantic attributes. Robust right frontal effects were elicited by old items in both tasks, indicating that the effects are not selective for the monitoring of the content of information retrieved from episodic memory. In experiment 2, separate study phases were followed by test phases where semantic judgments were made either on old items (as in experiment 1), or on new items. Right frontal effects were elicited by whichever class of items, old or new, required the semantic judgment. Together, these findings indicate that the right frontal old/new effect reflects generic monitoring or decisional processes, rather than processing dedicated to the evaluation of the products of an episodic retrieval attempt.

Encoding-retrieval overlap in human episodic memory: a functional neuroimaging perspective.

The principle of transfer-appropriate processing and the cortical reinstatement hypothesis are two influential theoretical frameworks, articulated at the psychological and neurobiological levels of explanation, respectively, that each propose that the processes supporting the encoding and retrieval of episodic information are strongly interdependent. Here, we integrate these two frameworks into a single model that generates predictions that can be tested using functional neuroimaging methods in healthy humans, and then go on to describe findings that are in accord with these predictions. Consistent with the transfer-appropriate processing and cortical reinstatement frameworks, the neural correlates of successful encoding vary according to how retrieval is cued, and the neural correlates of retrieval are modulated by how items are encoded. Thus, encoding and retrieval should not be viewed as separate stages of memory that can be investigated in isolation from one another.