Prenatal exposure to polycyclic aromatic hydrocarbons is not associated with behavior problems in preschool and early school-aged children: A prospective multi-cohort study.

BACKGROUND: Epidemiological study findings are inconsistent regarding associations between prenatal polycyclic aromatic hydrocarbon (PAH) exposures and childhood behavior. This study examined associations of prenatal PAH exposure with behavior at age 4-6 years in a large, diverse, multi-region prospective cohort. Secondary aims included examination of PAH mixtures and effect modification by child sex, breastfeeding, and child neighborhood opportunity. METHODS: The ECHO PATHWAYS Consortium pooled 1118 mother-child dyads from three prospective pregnancy cohorts in six U.S. cities. Seven PAH metabolites were measured in prenatal urine. Child behavior was assessed at age 4-6 using the Total Problems score from the Child Behavior Checklist (CBCL). Neighborhood opportunity was assessed using the socioeconomic and educational scales of the Child Opportunity Index. Multivariable linear regression was used to estimate associations per 2-fold increase in each PAH metabolite, adjusted for demographic, prenatal, and maternal factors and using interaction terms for effect modifiers. Associations with PAH mixtures were estimated using Weighted Quantile Sum Regression (WQSR). RESULTS: The sample was racially and sociodemographically diverse (38% Black, 49% White, 7% Other; household-adjusted income range $2651-$221,102). In fully adjusted models, each 2-fold increase in 2-hydroxynaphthalene was associated with a lower Total Problems score, contrary to hypotheses (b = -0.80, 95% CI = -1.51, -0.08). Associations were notable in boys (b = -1.10, 95% CI = -2.11, -0.08) and among children breastfed 6+ months (b = -1.31, 95% CI = -2.25, -0.37), although there was no statistically significant evidence for interaction by child sex, breastfeeding, or neighborhood child opportunity. Associations were null for other PAH metabolites; there was no evidence of associations with PAH mixtures from WQSR. CONCLUSION: In this large, well-characterized, prospective study of mother-child pairs, prenatal PAH exposure was not associated with child behavior problems. Future studies characterizing the magnitude of prenatal PAH exposure and studies in older childhood are needed.

Linking Sensory Integration and Processing With Mental Health in Autism: A Retrospective Review of Survey Data.

IMPORTANCE: Although a central tenet of occupational therapy practice, evidence-based practice is at times overrepresented by research and can overlook the contributions of clinical expertise, the lived experience, and context. This survey affords the occupational therapy practitioner the opportunity to understand sensory integration and processing (SI/P) as experienced by autistic adults. OBJECTIVE: To explore the following research question through a retrospective analysis of an internet-based survey: What is the relationship between the SI/P differences and mental health concerns reported by autistic adults? DESIGN: Nonexperimental; retrospective analysis of data collected from September 2018 through June 2019. The analysis team joined the project after the survey had been launched. SETTING: The Grand Sensory Survey (GSS) was available internationally through the websites and social media accounts of the Autistic Empire and STAR Institute for Sensory Processing. PARTICIPANTS: The sample included 440 total responses. Excluding responses from participants ages ≤18 yr (n = 24), 416 responses were included: n = 189 identified as autistic, n = 147 identified as nonautistic, and n = 80 did not provide a response to this query. OUTCOMES AND MEASURES: The GSS included questions about demographics, mental health, and sensory experiences. RESULTS: Both SI/P disruptions and sensory sensitivity predicted anxiety and depression (p < .001). CONCLUSIONS AND RELEVANCE: Differences in SI/P are significant factors in mental health for autistic adults. What This Article Adds: We implicate multiple aspects of SI/P and their influence on mental health among autistic adults. The autistic-led design of the survey ensures representation of issues that are pivotal to the autistic community, broadening the template for aspects of SI/P that should be considered when looking at client factors in autism and influence on function and participation. Positionality Statement: The authors deliberately use identity first language in keeping with requests from the autistic community (see https://autisticadvocacy.org/about-asan/identity-first-language/). This language is favored by autistic communities and self-advocates and has been adopted by health care professionals and researchers (Bottema-Beutel et al., 2021; Kenny et al., 2016). This article is written from the perspective of the social model of disability and a neurodiversity affirming frame of reference. Three of the five authors are autistic.

Feasibility of Using Electrical Impedance Spectroscopy for Assessing Biological Cell Damage during Freezing and Thawing.

This study was performed to test bioimpedance as a tool to detect the effect of different thawing methods on meat quality to aid in the eventual creation of an electric impedance-based food quality monitoring system. The electric impedance was measured for fresh pork, thawed pork, and during quick and slow thawing. A clear difference was observed between fresh and thawed samples for both impedance parameters. Impedance was different between the fresh and the frozen-thawed samples, but there were no impedance differences between frozen-thawed samples and the ones that were frozen-thawed and then stored at +3 °C for an additional 16 h after thawing. The phase angle was also different between fresh and the frozen-thawed samples. At high frequency, there were small, but clear phase angle differences between frozen-thawed samples and the samples that were frozen-thawed and subsequently stored for more than 16 h at +3 °C. Furthermore, the deep learning model LSTM-RNN (long short-term memory recurrent neural network) was found to be a promising way to classify the different methods of thawing.

Microwave Sensors for In Situ Monitoring of Trace Metals in Polluted Water.

Thousands of pollutants are threatening our water supply, putting at risk human and environmental health. Between them, trace metals are of significant concern, due to their high toxicity at low concentrations. Abandoned mining areas are globally one of the major sources of toxic metals. Nowadays, no method can guarantee an immediate response for quantifying these pollutants. In this work, a novel technique based on microwave spectroscopy and planar sensors for in situ real-time monitoring of water quality is described. The sensors were developed to directly probe water samples, and in situ trial measurements were performed in freshwater in four polluted mining areas in the UK. Planar microwave sensors were able to detect the water pollution level with an immediate response specifically depicted at three resonant peaks in the GHz range. To the authors' best knowledge, this is the first time that planar microwave sensors were tested in situ, demonstrating the ability to use this method for classifying more and less polluted water using a multiple-peak approach.

Real-Time Water Quality Monitoring with Chemical Sensors.

Water quality is one of the most critical indicators of environmental pollution and it affects all of us. Water contamination can be accidental or intentional and the consequences are drastic unless the appropriate measures are adopted on the spot. This review provides a critical assessment of the applicability of various technologies for real-time water quality monitoring, focusing on those that have been reportedly tested in real-life scenarios. Specifically, the performance of sensors based on molecularly imprinted polymers is evaluated in detail, also giving insights into their principle of operation, stability in real on-site applications and mass production options. Such characteristics as sensing range and limit of detection are given for the most promising systems, that were verified outside of laboratory conditions. Then, novel trends of using microwave spectroscopy and chemical materials integration for achieving a higher sensitivity to and selectivity of pollutants in water are described.

Integrating optogenetic and pharmacological approaches to study neural circuit function: current applications and future directions.

Optogenetic strategies to control genetically distinct populations of neurons with light have been rapidly evolving and widely adopted by the neuroscience community as one of the most important tool sets to study neural circuit function. Although optogenetics have already reshaped neuroscience by allowing for more precise control of circuit function compared with traditional techniques, current limitations of these approaches should be considered. Here, we discuss several strategies that combine optogenetic and contemporary pharmacological techniques to further increase the specificity of neural circuit manipulation. We also discuss recent advances that allow for the selective modulation of cellular function and gene expression with light. In addition, we outline a novel application of optogenetic circuit analysis for causally addressing the role of pathway-specific neural activity in mediating alterations in postsynaptic transcriptional processing in genetically defined neurons. By determining how optogenetic activation of specific neural circuits causally contributes to alterations in gene expression in a high-throughput fashion, novel biologic targets for future pharmacological intervention may be uncovered. Lastly, extending this experimental pipeline to selectively target pharmacotherapies to genetically defined neuronal populations or circuits will not only provide more selective control of neural circuits, but also may lead to the development of neural circuit specific pharmacological therapeutics.

Theoretical Basis and Application for Measuring Pork Loin Drip Loss Using Microwave Spectroscopy.

During cutting and processing of meat, the loss of water is critical in determining both product quality and value. From the point of slaughter until packaging, water is lost due to the hanging, movement, handling, and cutting of the carcass, with every 1% of lost water having the potential to cost a large meat processing plant somewhere in the region of €50,000 per day. Currently the options for monitoring the loss of water from meat, or determining its drip loss, are limited to destructive tests which take 24-72 h to complete. This paper presents results from work which has led to the development of a novel microwave cavity sensor capable of providing an indication of drip loss within 6 min, while demonstrating good correlation with the well-known EZ-Driploss method (R² = 0.896).

Activation of prefrontal cortical parvalbumin interneurons facilitates extinction of reward-seeking behavior.

Forming and breaking associations between emotionally salient environmental stimuli and rewarding or aversive outcomes is an essential component of learned adaptive behavior. Importantly, when cue-reward contingencies degrade, animals must exhibit behavioral flexibility to extinguish prior learned associations. Understanding the specific neural circuit mechanisms that operate during the formation and extinction of conditioned behaviors is critical because dysregulation of these neural processes is hypothesized to underlie many of the maladaptive and pathological behaviors observed in various neuropsychiatric disorders in humans. The medial prefrontal cortex (mPFC) participates in the behavioral adaptations seen in both appetitive and aversive-cue-mediated responding, but the precise cell types and circuit mechanisms sufficient for driving these complex behavioral states remain largely unspecified. Here, we recorded and manipulated the activity of parvalbumin-positive fast spiking interneurons (PV+ FSIs) in the prelimbic area (PrL) of the mPFC in mice. In vivo photostimulation of PV+ FSIs resulted in a net inhibition of PrL neurons, providing a circuit blueprint for behavioral manipulations. Photostimulation of mPFC PV+ cells did not alter anticipatory or consummatory licking behavior during reinforced training sessions. However, optical activation of these inhibitory interneurons to cues associated with reward significantly accelerated the extinction of behavior during non-reinforced test sessions. These data suggest that suppression of excitatory mPFC networks via increased activity of PV+ FSIs may enhance reward-related behavioral flexibility.

Label free detection of specific protein binding using a microwave sensor.

The specific binding of streptavidin to biotinylated protein A was demonstrated using a microwave detection system. In control experiments, the degree of non-specific binding was negligible. The method of detection was used to monitor the adsorption of two other proteins, cytochrome c and glucose oxidase, on to the IDE microwave sensor surface. The response of the sensor was also examined on different substrate materials, with detection of protein binding observed obtained on both smooth, conductive (gold) and on rough, insulating (hydroxyapatite) surfaces.

Prenatal exposure to polycyclic aromatic hydrocarbons and cognition in early childhood.

BACKGROUND: Epidemiological evidence for gestational polycyclic aromatic hydrocarbon (PAH) exposure and adverse child cognitive outcomes is mixed; little is known about critical windows of exposure. OBJECTIVE: We investigated associations between prenatal PAH exposure and child cognition in a large, multi-site study. METHODS: We included mother-child dyads from two pooled prospective pregnancy cohorts (CANDLE and TIDES, N = 1,223) in the ECHO-PATHWAYS Consortium. Seven urinary mono-hydroxylated PAH metabolites were measured in mid-pregnancy in both cohorts as well as early and late pregnancy in TIDES. Child intelligence quotient (IQ) was assessed between ages 4-6. Associations between individual PAH metabolites and IQ were estimated with multivariable linear regression. Interaction terms were used to examine effect modification by child sex and maternal obesity. We explored associations of PAH metabolite mixtures with IQ using weighted quantile sum regression. In TIDES, we averaged PAH metabolites over three periods of pregnancy and by pregnancy period to investigate associations between PAH metabolites and IQ. RESULTS: In the combined sample, PAH metabolites were not associated with IQ after full adjustment, nor did we observe associations with PAH mixtures. Tests of effect modification were null except for the association between 2-hydroxynaphthalene and IQ, which was negative in males (ßmales = -0.67 [95%CI:-1.47,0.13]) and positive in females (ßfemales = 0.31 [95%CI:-0.52,1.13])(pinteraction = 0.04). In analyses across pregnancy (TIDES-only), inverse associations with IQ were observed for 2-hydroxyphenanthrene averaged across pregnancy (ß = -1.28 [95%CI:-2.53,-0.03]) and in early pregnancy (ß = -1.14 [95%CI:-2.00,-0.28]). SIGNIFICANCE: In this multi-cohort analysis, we observed limited evidence of adverse associations of early pregnancy PAHs with child IQ. Analyses in the pooled cohorts were null. However, results also indicated that utilizing more than one exposure measures across pregnancy could improve the ability to detect associations by identifying sensitive windows and improving the reliability of exposure measurement. More research with multiple timepoints of PAH assessment is warranted.

Improving hydrogen adsorption enthalpy through coordinatively unsaturated cobalt in porous polymers.

The design and synthesis of a new porous organic polymer (POP) incorporated with cobalt carbonyl complexes through built-in bipyridinic coordination sites for hydrogen storage are described. A thermal activation process was developed to remove the ligated carbonyl and carbon dioxide in order to expose the cobalt atomically inside of porous structure. Various spectroscopic and physical characterization techniques were used to study the coordinated Co sites and the POP's surface property. Upon thermal activation, this new cobalt-containing POP showed improved hydrogen uptake capacity and isosteric heat of adsorption.

Public attitudes towards bystander CPR and their association with social deprivation: Findings from a cross sectional study in North England.

Background: Bystander cardiopulmonary resuscitation (BCPR) is undertaken in only 40% of out of hospital cardiac arrests (OHCAs) in the UK. Lower rates of BCPR and public access defibrillator (PAD) use have been correlated with lower socio-economic status (SES). The aim of this study was to examine knowledge and attitudes towards BCPR and PAD's using a study specific questionnaire, and to understand how these potentially interact with individual characteristics and SES. Methods: Cross-sectional study between July-December 2021 across areas of varying SES in North England. Results: Six hundred and one individuals completed the survey instrument (mean age = 51.9 years, 52.2 % female). Increased age was associated with being less willing to call 999 (p < 0.001) and follow call handler advice (p < 0.001). Female respondents were less comfortable performing BCPR than male respondents (p = 0.006). Individuals from least deprived areas were less likely to report comfort performing CPR, (p = 0.016) and less likely to know what a PAD is for, (p = 0.025). Higher education level was associated with increased ability to recognise OHCA (p = 0.005) and understanding of what a PAD is for (p < 0.001). Individuals with higher income were more likely to state they would follow advice regarding BCPR (p = 0.017) and report comfort using a PAD (p = 0.029). Conclusion: Individual characteristics such as age and ethnicity, rather than SES, are indicators of knowledge, willingness, and perceived competency to perform BCPR. Policy makers should avoid using SES alone to target interventions. Future research should examine how cultural identity and social cohesion intersect with these characteristics to influence willingness to perform BCPR.

Pigs: A stepwise RGB-D novel pig carcass cutting dataset.

This paper presents a pig carcass cutting dataset, captured from a bespoke frame structure with 6 Intel® RealSense™ Depth Camera D415 cameras attached, and later recorded from a single camera attached to a robotic arm cycling through the positions previously defined by the frame structure. The data is composed of bags files recorded from the Intel's SDK, which includes RGB-D data and camera intrinsic parameters for each sensor. In addition, ten JSON files with the transformation matrix for each camera in relation to the left/front camera in the structure are provided, five JSON files for the data recorded with the bespoke frame and five JSON files for the data captured with the robotic arm.

Cohort profile: the ECHO prenatal and early childhood pathways to health consortium (ECHO-PATHWAYS).

PURPOSE: Exposures early in life, beginning in utero, have long-term impacts on mental and physical health. The ECHO prenatal and early childhood pathways to health consortium (ECHO-PATHWAYS) was established to examine the independent and combined impact of pregnancy and childhood chemical exposures and psychosocial stressors on child neurodevelopment and airway health, as well as the placental mechanisms underlying these associations. PARTICIPANTS: The ECHO-PATHWAYS consortium harmonises extant data from 2684 mother-child dyads in three pregnancy cohort studies (CANDLE [Conditions Affecting Neurocognitive Development and Learning in Early Childhood], TIDES [The Infant Development and Environment Study] and GAPPS [Global Alliance to Prevent Prematurity and Stillbirth]) and collects prospective data under a unified protocol. Study participants are socioeconomically diverse and include a large proportion of Black families (38% Black and 51% White), often under-represented in research. Children are currently 5-15 years old. New data collection includes multimodal assessments of primary outcomes (airway health and neurodevelopment) and exposures (air pollution, phthalates and psychosocial stress) as well as rich covariate characterisation. ECHO-PATHWAYS is compiling extant and new biospecimens in a central biorepository and generating the largest placental transcriptomics data set to date (N=1083). FINDINGS TO DATE: Early analyses demonstrate adverse associations of prenatal exposure to air pollution, phthalates and maternal stress with early childhood airway outcomes and neurodevelopment. Placental transcriptomics work suggests that phthalate exposure alters placental gene expression, pointing to mechanistic pathways for the developmental toxicity of phthalates. We also observe associations between prenatal maternal stress and placental corticotropin releasing hormone, a marker of hormonal activation during pregnancy relevant for child health. Other publications describe novel methods for examining exposure mixtures and the development of a national spatiotemporal model of ambient outdoor air pollution. FUTURE PLANS: The first wave of data from the unified protocol (child age 8-9) is nearly complete. Future work will leverage these data to examine the combined impact of early life social and chemical exposures on middle childhood health outcomes and underlying placental mechanisms.

Genomic, Habitat, and Leaf Shape Analyses Reveal a Possible Cryptic Species and Vulnerability to Climate Change in a Threatened Daisy.

Olearia pannosa is a plant species listed as vulnerable in Australia. Two subspecies are currently recognised (O. pannosa subsp. pannosa (silver daisy) and O. pannosa subsp. cardiophylla (velvet daisy)), which have overlapping ranges but distinct leaf shape. Remnant populations face threats from habitat fragmentation and climate change. We analysed range-wide genomic data and leaf shape variation to assess population diversity and divergence and to inform conservation management strategies. We detected three distinct genetic groupings and a likely cryptic species. Samples identified as O. pannosa subsp. cardiophylla from the Flinders Ranges in South Australia were genetically distinct from all other samples and likely form a separate, range-restricted species. Remaining samples formed two genetic clusters, which aligned with leaf shape differences but not fully with current subspecies classifications. Levels of genetic diversity and inbreeding differed between the three genetic groups, suggesting each requires a separate management strategy. Additionally, we tested for associations between genetic and environmental variation and carried out habitat suitability modelling for O. pannosa subsp. pannosa populations. We found mean annual maximum temperature explained a significant proportion of genomic variance. Habitat suitability modelling identified mean summer maximum temperature, precipitation seasonality and mean annual rainfall as constraints on the distribution of O. pannosa subsp. pannosa, highlighting increasing aridity as a threat for populations located near suitability thresholds. Our results suggest maximum temperature is an important agent of selection on O. pannosa subsp. pannosa and should be considered in conservation strategies. We recommend taxonomic revision of O. pannosa and provide conservation management recommendations.

Intact gastro-intestinal tract removal from pig carcasses in a novel Meat Factory Cell approach.

Conventional automated slaughter lines for pigs are organised as disassembly lines with many specialised machines. High costs and capacities make them relevant only for large scale meat production. The ambition with the novel Meat Factory Cell (MFC) concept is to provide the meat industry with a robust and flexible automation platform that is also relevant for smaller scale production. The MFC process deviates radically from conventional processing of pig carcasses after singeing. In MFC, the limbs are removed first. Then the dorsal muscles along the spinal axis from tail to head are removed with the column and rind in one meat cut, followed by removal of the viscera. Finally, the cut ribs and belly are removed. Such approaches to automation in pig abattoirs and cutting plants are highly needed in smaller scale production, and they should produce meat and offal as hygienically as conventional factories. This case study reports the evisceration of 37 pigs in 9 trials performed in 2019. Several approaches were tested with a prototype carcass holding unit. Evisceration could be undertaken without the need to cut through the gastrointestinal tract from tongue to rectum, reducing the probability of accidental faecal contamination of pork carcasses from the gut content. The Meat Factory Cell procedure is an advance towards automated evisceration of pig carcasses which is both simple and hygienic. The traditional separation of internal organs into a pluck set and a set of stomach and bowels was more prone to leakages.

A liposome-micelle-hybrid (LMH) oral delivery system for poorly water-soluble drugs: Enhancing solubilisation and intestinal transport.

A novel liposome-micelle-hybrid (LMH) carrier system was developed as a superior oral drug delivery platform compared to conventional liposome or micelle formulations. The optimal LMH system was engineered by encapsulating TPGS micelles in the aqueous core of liposomes and its efficacy for oral delivery was demonstrated using lovastatin (LOV) as a model poorly soluble drug with P-gp (permeability glycoprotein) limited intestinal absorption. LOV-LMH was characterised as unilamellar, spherical vesicles encapsulating micellar structures within the interior aqueous core and showing an average diameter below 200 nm. LMH demonstrated enhanced drug loading, water apparent solubility and extended/controlled release of LOV compared to conventional liposomes and micelles. LMH exhibited enhanced LOV absorption and transportation in a Caco-2 cell monolayer model of the intestine by inhibiting the P-gp transporter system compared to free LOV. The LMH system is a promising novel oral delivery approach for enhancing bioavailability of poorly water-soluble drugs, especially those presenting P-gp effluxes limited absorption.

Detectability of the degree of freeze damage in meat depends on analytic-tool selection.

Novel freezing solutions are constantly being developed to reduce quality loss in meat production chains. However, there is limited focus on identifying the sensitive analytical tools needed to directly validate product changes that result from potential improvements in freezing technology. To benchmark analytical tools relevant to meat research and production, we froze pork samples using traditional (-25 °C, -35 °C) and cryogenic freezing (-196 °C). Three classes of analyses were tested for their capacity to separate different freeze treatments: thaw loss testing, bioelectrical spectroscopy (nuclear magnetic resonance, microwave, bioimpedance) and low-temperature microscopy (cryo-SEM). A general effect of freeze treatment was detected with all bioelectrical methods. Yet, only cryo-SEM resolved quality differences between all freeze treatments, not only between cryogenic and traditional freezing. The detection sensitivity with cryo-SEM may be explained by testing meat directly in the frozen state without prior defrosting. We discuss advantages, shortcomings and cost factors in using analytical tools for quality monitoring in the meat sector.

Real-Time Monitoring of Tetraselmis suecica in A Saline Environment as Means of Early Water Pollution Detection.

Biological water pollution, including organic pollutants and their possible transportation, via biofouling and ballast water, has the potential to cause severe economic and health impacts on society and environment. Current water pollution monitoring methods are limited by transportation of samples to the laboratory for analysis, which could take weeks. There is an urgent need for a water quality monitoring technique that generates real-time data. The study aims to assess the feasibility of three sensing techniques to detect and monitor the concentrations of the model species Tetraselmis suecica in real-time using eleven samples for each method. Results showed UV-Vis spectrophotometer detected increasing concentration of Tetraselmis suecica with R² = 0.9627 and R² = 0.9672, at 450 nm and 650 nm wavelengths, respectively. Secondly, low-frequency capacitance measurements showed a linear relationship with increasing concentration of Tetraselmis suecica at 150 Hz (R² = 0.8463) and 180 Hz (R² = 0.8391). Finally, a planar electromagnetic wave sensor measuring the reflected power S11 amplitude detected increasing cell density at 4 GHz (R² = 0.8019).

Environmental control of kisspeptin: implications for seasonal reproduction.

The KiSS-1 gene encodes the peptide hormone kisspeptin, which acts as a principal positive regulator of the reproductive axis by directly stimulating GnRH neuron activity. To gain insight into a potential role for kisspeptin in integrating and relaying reproductively relevant stimuli to the GnRH system, we investigated changes in kisspeptin peptide expression associated with photoperiodic changes in reproductive state as well as pituitary and gonadal responses to peripheral kisspeptin injections. Seasonally breeding rodents undergo pronounced fluctuations in reproductive state in response to changing day lengths. In common with other rodent species, a majority of male Siberian hamsters (Phodopus sungorus) exhibit reproductive decline after exposure to short-day lengths. A subset of individuals fails to respond to day length information, however, and maintains their reproductive function. We exploited these individual differences to examine whether kisspeptin may act at the interface between external stimuli and the reproductive system. After extended exposure to short days, animals with a quiescent reproductive axis displayed a marked reduction in kisspeptin cell labeling in the anteroventral periventricular nucleus but robust kisspeptin-immunoreactive staining in the arcuate nucleus. In contrast, animals with functional reproductive systems displayed high numbers of kisspeptin-immunoreactive neurons in the anteroventral periventricular nucleus but a paucity of expression in the arcuate nucleus. Kisspeptin injections significantly elevated LH over preinjection levels regardless of photoperiod or reproductive state. Collectively, these findings suggest an important role for kisspeptin in coordinating and relaying environmentally relevant information to the reproductive axis as well as a role for this peptide in regulating seasonal changes in reproductive function.