Substrate binding plasticity revealed by Cryo-EM structures of SLC26A2.

SLC26A2 is a vital solute carrier responsible for transporting essential nutritional ions, including sulfate, within the human body. Pathogenic mutations within SLC26A2 give rise to a spectrum of human diseases, ranging from lethal to mild symptoms. The molecular details regarding the versatile substrate-transporter interactions and the impact of pathogenic mutations on SLC26A2 transporter function remain unclear. Here, using cryo-electron microscopy, we determine three high-resolution structures of SLC26A2 in complexes with different substrates. These structures unveil valuable insights, including the distinct features of the homodimer assembly, the dynamic nature of substrate binding, and the potential ramifications of pathogenic mutations. This structural-functional information regarding SLC26A2 will advance our understanding of cellular sulfate transport mechanisms and provide foundations for future therapeutic development against various human diseases.

Plasmonic Sensors beyond the Phase Matching Condition: A Simplified Approach.

The conventional approach to optimising plasmonic sensors is typically based entirely on ensuring phase matching between the excitation wave and the surface plasmon supported by the metallic structure. However, this leads to suboptimal performance, even in the simplest sensor configuration based on the Otto geometry. We present a simplified coupled mode theory approach for evaluating and optimizing the sensing properties of plasmonic waveguide refractive index sensors. It only requires the calculation of propagation constants, without the need for calculating mode overlap integrals. We apply our method by evaluating the wavelength-, device length- and refractive index-dependent transmission spectra for an example silicon-on-insulator-based sensor of finite length. This reveals all salient spectral features which are consistent with full-field finite element calculations. This work provides a rapid and convenient framework for designing dielectric-plasmonic sensor prototypes-its applicability to the case of fibre plasmonic sensors is also discussed.

Behavioral and Molecular Consequences of Chronic Sleep Restriction During Development in Fragile X Mice.

Sleep is critical for brain development and synaptic plasticity. In male wild-type mice, chronic sleep restriction during development results in long-lasting impairments in behavior including hypoactivity, decreased sociability, and increased repetitive behavior. Disordered sleep is characteristic of many neurodevelopmental disorders. Moreover, the severity of behavioral symptoms is correlated with the degree of disordered sleep. We hypothesized that chronic developmental sleep restriction in a mouse model of fragile X syndrome (FXS) would exacerbate behavioral phenotypes. To test our hypothesis, we sleep-restricted Fmr1 knockout (KO) mice for 3 h per day from P5 to P52 and subjected mice to behavioral tests beginning on P42. Contrary to our expectations, sleep restriction improved the hyperactivity and lack of preference for social novelty phenotypes in Fmr1 KO mice but had no measurable effect on repetitive activity. Sleep restriction also resulted in changes in regional distribution of myelin basic protein, suggesting effects on myelination. These findings have implications for the role of disrupted sleep in the severity of symptoms in FXS.

PT-Symmetric Topological Edge-Gain Effect.

We demonstrate a non-Hermitian topological effect that is characterized by having complex eigenvalues only in the edge states of a topological material, despite the fact that the material is completely uniform. Such an effect can be constructed in any topological structure formed by two gapped subsystems, e.g., a quantum spin-Hall system, with a suitable non-Hermitian coupling between the spins. The resulting complex-eigenvalued edge state is robust against defects due to the topological protection. In photonics, such an effect can be used for the implementation of topological lasers, in which a uniform pumping provides gain only in the edge lasing state. Furthermore, such a topological lasing model is reciprocal and is thus compatible with standard photonic platforms.

Nonreciprocal Metamaterial Obeying Time-Reversal Symmetry.

We introduce a class of non-Hermitian systems that break electromagnetic reciprocity while preserving time-reversal symmetry, and describe its novel polarization dynamics. We show that this class of systems can be realized using van der Waals heterostructures involving transition-metal dichalcogenides (TMDs). Our work provides a path towards achieving strong optical nonreciprocity and polarization-dependent directional amplification using compact, large-area and magnet-free structures.

Sex-Selective Effects on Behavior in a Mouse Model of Tuberous Sclerosis Complex.

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder that is caused by a mutation in either TSC1 or TSC2 TSC affects multiple systems of the body, and patients with TSC display a range of neurologic and behavioral manifestations including seizures, intellectual disability, autism spectrum disorders, attention deficit hyperactivity disorder, anxiety, and mood disorders. Whereas behavioral phenotypes of many mouse models have been studied, the effects of sex have, for the most part, not been explored. We studied adult male and female Tsc2 heterozygous and control mice to investigate the influence of sex and genotype on behavior. On a test of social preference, Tsc2 heterozygous mice, regardless of sex, demonstrated lower preference for the stranger mouse than control mice. In the open field, Tsc2 heterozygous males and control females habituated to the open field with decreasing anxiety-like behavior over time, whereas Tsc2 heterozygous females did not show habituation to the open field environment. We did not find any statistically significant effects of genotype on open field activity, learning and memory or motor function. Our results highlight phenotype differences in Tsc2 heterozygous mice, some of which are influenced by sex. A consideration of how sex influences the behavioral phenotypes of TSC is critical to develop a more complete understanding of the disorder and better target future pharmacological treatments.

Disruption of cholinergic neurotransmission, within a cognitive challenge paradigm, is indicative of Aß-related cognitive impairment in preclinical Alzheimer's disease after a 27-month delay interval.

BACKGROUND: Abnormal beta-amyloid (Aß) is associated with deleterious changes in central cholinergic tone in the very early stages of Alzheimer's disease (AD), which may be unmasked by a cholinergic antagonist (J Prev Alzheimers Dis 1:1-4, 2017). Previously, we established the scopolamine challenge test (SCT) as a "cognitive stress test" screening measure to identify individuals at risk for AD (Alzheimer's & Dementia 10(2):262-7, 2014) (Neurobiol. Aging 36(10):2709-15, 2015). Here we aim to demonstrate the potential of the SCT as an indicator of cognitive change and neocortical amyloid aggregation after a 27-month follow-up interval. METHODS: Older adults (N = 63, aged 55-75 years) with self-reported memory difficulties and first-degree family history of AD completed the SCT and PET amyloid imaging at baseline and were then seen for cognitive testing at 9, 18, and 27 months post-baseline. Repeat PET amyloid imaging was completed at the time of the 27-month exam. RESULTS: Significant differences in both cognitive performance and in Aß neocortical burden were observed between participants who either failed vs. passed the SCT at baseline, after a 27-month follow-up period. CONCLUSIONS: Cognitive response to the SCT (Alzheimer's & Dementia 10(2):262-7, 2014) at baseline is related to cognitive change and PET amyloid imaging results, over the course of 27 months, in preclinical AD. The SCT may be a clinically useful screening tool to identify individuals who are more likely to both have positive evidence of amyloidosis on PET imaging and to show measurable cognitive decline over several years.

Absence of unidirectionally propagating surface plasmon-polaritons at nonreciprocal metal-dielectric interfaces.

In the presence of an external magnetic field, the surface plasmon polariton that exists at the metal-dielectric interface is believed to support a unidirectional frequency range near the surface plasmon frequency, where the surface plasmon polariton propagates along one but not the opposite direction. Recent works have pointed to some of the paradoxical consequences of such a unidirectional range, including in particular the violation of the time-bandwidth product constraint that should otherwise apply in general in static systems. Here we show that such a unidirectional frequency range is nonphysical using both a general thermodynamic argument and a detailed calculation based on a nonlocal hydrodynamic Drude model for the metal permittivity. Our calculation reveals that the surface plasmon-polariton at metal-dielectric interfaces remains bidirectional for all frequencies.

Sleep Duration in Mouse Models of Neurodevelopmental Disorders.

Sleep abnormalities are common in patients with neurodevelopmental disorders, and it is thought that deficits in sleep may contribute to the unfolding of symptoms in these disorders. Appreciating sleep abnormalities in neurodevelopmental disorders could be important for designing a treatment for these disorders. We studied sleep duration in three mouse models by means of home-cage monitoring: Tsc2+/- (tuberous sclerosis complex), oxytocin receptor (Oxtr) knockout (KO) (autism spectrum disorders), and Shank3 e4-9 KO (Phelan-McDermid syndrome). We studied both male and female mice, and data were analyzed to examine effects of both genotype and sex. In general, we found that female mice slept less than males regardless of genotype or phase. We did not find any differences in sleep duration in either Tsc2+/- or Oxtr KO mice, compared to controls. In Shank3 e4-9 KO mice, we found a statistically significant genotype x phase interaction (p = 0.002) with a trend that Shank3e4-9 KO mice regardless of sex slept more than control mice in the active phase. Our results have implications for the management of patients with Phelan-McDermid syndrome.

Blood Pressure Variability and Cerebral Small Vessel Disease: A Systematic Review and Meta-Analysis of Population-Based Cohorts.

Background and Purpose- Blood pressure (BP) variability may increase the risk of stroke and dementia. It remains inconclusive whether BP variability is associated with cerebral small vessel disease, a common and potentially devastating subclinical disease that contributes significantly to both stroke and dementia. Methods- A systematic review and meta-analysis of prospective cohort studies that examined the association between BP variability and the presence or progression of established markers of cerebral small vessel disease, including white matter hyperintensities, lacunes, and microbleeds on magnetic resonance imaging. We searched MEDLINE, EMBASE, and Web of Science. Ten studies met the criteria for qualitative synthesis and 7 could be included in the meta-analysis. Data were synthetized using random-effect models. Results- These studies included a total of 2796 individuals aged 74 (mean) ±4 (SD) years, with a median follow-up of 4.0 years. A one SD increase in systolic BP variability was associated with increased odds of the presence or progression of white matter hyperintensities (odds ratio, 1.26 [95% CI, 1.06-1.50]). The association of systolic BP variability with the presence of lacunes (odds ratio, 0.93 [95% CI, 0.74-1.16]) and the presence of microbleeds (odds ratio, 1.13 [95% CI, 0.89-1.44]) were not statistically significant. Conclusions- A larger BP variability may be associated with a higher risk of having a higher burden of white matter hyperintensities. Targeting large BP variability has the potential to prevent cerebral small vessel disease and thereby reducing the risk of stroke and dementia. The potential issue of reverse causation and the heterogeneity in the assessment of cerebral small vessel disease markers should be better addressed in future studies.

Chronic Sleep Restriction in Developing Male Mice Results in Long Lasting Behavior Impairments.

Sleep abnormalities are prevalent in autism spectrum disorders (ASD). Moreover, the severity of ASD symptoms are correlated with the degree of disturbed sleep. We asked if disturbed sleep during brain development itself could lead to ASD-like symptoms, particularly behavioral manifestations. We reasoned that sleep is known to be important for normal brain development and plasticity, so disrupted sleep during development might result in changes that contribute to behavioral impairments associated with ASD. We sleep-restricted C57BL/6J male mice [beginning at postnatal day 5 (P5) and continuing through P52] 3 h per day by means of gentle handling and compared the data with a stress group (handled every 15 min during the 3-h period) and a control group (no additional handling). From P42-P52, we assessed the behavioral effects of sleep-restriction in this pre-recovery phase. Then, we allowed the mice to recover for 4 weeks and tested behavior once again. Compared to the control group, we found that sleep restricted-mice had long-lasting hypoactivity, and impaired social behavior; repetitive behavior was unaffected. These behavior changes were accompanied by an increase in the downstream signaling products of the mammalian target of rapamycin pathway. These data affirm the importance of undisturbed sleep during development and show that, at least in this model, sleep-restriction can play a causative role in the development of behavioral abnormalities. Assessing and treating sleep abnormalities in ASD may be important in alleviating some of the symptoms.

Spectrally Selective Nanocomposite Textile for Outdoor Personal Cooling.

Outdoor heat stress poses a serious public health threat and curtails industrial labor supply and productivity, thus adversely impacting the wellness and economy of the entire society. With climate change, there will be more intense and frequent heat waves that further present a grand challenge for sustainability. However, an efficient and economical method that can provide localized outdoor cooling of the human body without intensive energy input is lacking. Here, a novel spectrally selective nanocomposite textile for radiative outdoor cooling using zinc oxide nanoparticle-embedded polyethylene is demonstrated. By reflecting more than 90% solar irradiance and selectively transmitting out human body thermal radiation, this textile can enable simulated skin to avoid overheating by 5-13 °C compared to normal textile like cotton under peak daylight condition. Owing to its superior passive cooling capability and compatibility with large-scale production, this radiative outdoor cooling textile is promising to widely benefit the sustainability of society in many aspects spanning from health to economy.

Broadband Control of Topological Nodes in Electromagnetic Fields.

We study topological nodes (phase singularities) in electromagnetic wave interactions with structures. We show that, when the nodes exist, it is possible to bind certain nodes to a specific plane in the structure by a combination of mirror and time-reversal symmetry. Such binding does not rely on any resonances in the structure. As a result, the nodes persist on the plane over a wide wavelength range. As an implication of such broadband binding, we demonstrate that the topological nodes can be used for hiding of metallic objects over a broad wavelength range.

Warming up human body by nanoporous metallized polyethylene textile.

Space heating accounts for the largest energy end-use of buildings that imposes significant burden on the society. The energy wasted for heating the empty space of the entire building can be saved by passively heating the immediate environment around the human body. Here, we demonstrate a nanophotonic structure textile with tailored infrared (IR) property for passive personal heating using nanoporous metallized polyethylene. By constructing an IR-reflective layer on an IR-transparent layer with embedded nanopores, the nanoporous metallized polyethylene textile achieves a minimal IR emissivity (10.1%) on the outer surface that effectively suppresses heat radiation loss without sacrificing wearing comfort. This enables 7.1 °C decrease of the set-point compared to normal textile, greatly outperforming other radiative heating textiles by more than 3 °C. This large set-point expansion can save more than 35% of building heating energy in a cost-effective way, and ultimately contribute to the relief of global energy and climate issues.Energy wasted for heating the empty space of the entire building can be saved by passively heating the immediate environment around the human body. Here, the authors show a nanophotonic structure textile with tailored infrared property for passive personal heating using nanoporous metallized polyethylene.

How jet lag impairs Major League Baseball performance.

Laboratory studies have demonstrated that circadian clocks align physiology and behavior to 24-h environmental cycles. Examination of athletic performance has been used to discern the functions of these clocks in humans outside of controlled settings. Here, we examined the effects of jet lag, that is, travel that shifts the alignment of 24-h environmental cycles relative to the endogenous circadian clock, on specific performance metrics in Major League Baseball. Accounting for potential differences in home and away performance, travel direction, and team confounding variables, we observed that jet-lag effects were largely evident after eastward travel with very limited effects after westward travel, consistent with the >24-h period length of the human circadian clock. Surprisingly, we found that jet lag impaired major parameters of home-team offensive performance, for example, slugging percentage, but did not similarly affect away-team offensive performance. On the other hand, jet lag impacted both home and away defensive performance. Remarkably, the vast majority of these effects for both home and away teams could be explained by a single measure, home runs allowed. Rather than uniform effects, these results reveal surprisingly specific effects of circadian misalignment on athletic performance under natural conditions.

Negative Effects of Chronic Rapamycin Treatment on Behavior in a Mouse Model of Fragile X Syndrome.

Fragile X syndrome (FXS), the most common form of inherited intellectual disability, is also highly associated with autism spectrum disorders (ASD). It is caused by expansion of a CGG repeat sequence on the X chromosome resulting in silencing of the FMR1 gene. This is modeled in the mouse by deletion of Fmr1 (Fmr1 KO). Fmr1 KO mice recapitulate many of the behavioral features of the disorder including seizure susceptibility, hyperactivity, impaired social behavior, sleep problems, and learning and memory deficits. The mammalian target of rapamycin pathway (mTORC1) is upregulated in Fmr1 KO mice and is thought to be important for the pathogenesis of this disorder. We treated Fmr1 KO mice chronically with an mTORC1 inhibitor, rapamycin, to determine if rapamycin treatment could reverse behavioral phenotypes. We performed open field, zero maze, social behavior, sleep, passive avoidance, and audiogenic seizure testing. We found that pS6 was upregulated in Fmr1 KO mice and normalized by rapamycin treatment, but, except for an anxiogenic effect, it did not reverse any of the behavioral phenotypes examined. In fact, rapamycin treatment had an adverse effect on sleep and social behavior in both control and Fmr1 KO mice. These results suggest that targeting the mTOR pathway in FXS is not a good treatment strategy and that other pathways should be considered.

A dual-mode textile for human body radiative heating and cooling.

Maintaining human body temperature is one of the most basic needs for living, which often consumes a huge amount of energy to keep the ambient temperature constant. To expand the ambient temperature range while maintaining human thermal comfort, the concept of personal thermal management has been recently demonstrated in heating and cooling textiles separately through human body infrared radiation control. Realizing these two opposite functions within the same textile would represent an exciting scientific challenge and a significant technological advancement. We demonstrate a dual-mode textile that can perform both passive radiative heating and cooling using the same piece of textile without any energy input. The dual-mode textile is composed of a bilayer emitter embedded inside an infrared-transparent nanoporous polyethylene (nanoPE) layer. We demonstrate that the asymmetrical characteristics of both emissivity and nanoPE thickness can result in two different heat transfer coefficients and achieve heating when the low-emissivity layer is facing outside and cooling by wearing the textile inside out when the high-emissivity layer is facing outside. This can expand the thermal comfort zone by 6.5°C. Numerical fitting of the data further predicts 14.7°C of comfort zone expansion for dual-mode textiles with large emissivity contrast.

Radiative human body cooling by nanoporous polyethylene textile.

Thermal management through personal heating and cooling is a strategy by which to expand indoor temperature setpoint range for large energy saving. We show that nanoporous polyethylene (nanoPE) is transparent to mid-infrared human body radiation but opaque to visible light because of the pore size distribution (50 to 1000 nanometers). We processed the material to develop a textile that promotes effective radiative cooling while still having sufficient air permeability, water-wicking rate, and mechanical strength for wearability. We developed a device to simulate skin temperature that shows temperatures 2.7° and 2.0°C lower when covered with nanoPE cloth and with processed nanoPE cloth, respectively, than when covered with cotton. Our processed nanoPE is an effective and scalable textile for personal thermal management.