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Objective: The current study sought to clarify and harness the incremental validity of emotional dysregulation and unawareness (EDU) in emerging adulthood, beyond ADHD symptoms and with respect to concurrent classification of impairment and co-occurring problems, using machine learning techniques. Method: Participants were 1,539 college students (M[subscript age] = 19.5, 69% female) with self-reported ADHD diagnoses from a multisite study who completed questionnaires assessing ADHD symptoms, EDU, and co-occurring problems. Results: Random forest analyses suggested EDU dimensions significantly improved model performance (ps < 0.001) in classifying participants with impairment and internalizing problems versus those without, with the resulting ADHD + EDU classification model demonstrating acceptable to excellent performance (except in classification of Work Impairment) in a distinct sample. Variable importance analyses suggested inattention sum scores and the Limited Access to Emotional Regulation Strategies EDU dimension as the most important features for facilitating model classification. Conclusion: Results provided support for EDU as a key deficit in those with ADHD that, when present, helps explain ADHD's co-occurrence with impairment and internalizing problems. Continued application of machine learning techniques may facilitate actuarial classification of ADHD-related outcomes while also incorporating multiple measures.

Abstract Developing strategies to systematically increase the critical current, the threshold current below which the superconductivity exists, is an important goal of materials science. Here, the concept of quantum phase transition is employed to enhance the critical current of a kagome superconductor CsV3Sb5, which exhibits a charge density wave (CDW) and superconductivity that are both affected by hydrostatic pressure. As the CDW phase is rapidly suppressed under pressure, a large enhancement in the self‐field critical current (Ic, sf) is recorded. The observation of a peak‐like enhancement of Ic, sf at the zero‐temperature limit (Ic, sf(0)) centered at p* ≈ 20 kbar, the same pressure where the CDW phase transition vanishes, further provides strong evidence of a zero‐temperature quantum anomaly in this class of pressure‐tuned superconductor. Such a peak in Ic, sf(0) resembles the findings in other well‐established quantum‐critical superconductors, hinting at the presence of enhanced quantum fluctuations associated with the CDW phase in CsV3Sb5.

Abstract Vaccination has successfully controlled several infectious diseases although better vaccines remain desirable. Host response to vaccination studies have identified correlates of vaccine immunogenicity that could be useful to guide development and selection of future vaccines. However, it remains unclear whether these findings represent mere statistical correlations or reflect functional associations with vaccine immunogenicity. Functional associations, rather than statistical correlates, would offer mechanistic insights into vaccine-induced adaptive immunity. Through a human experimental study to test the immunomodulatory properties of metformin, an anti-diabetic drug, we chanced upon a functional determinant of neutralizing antibodies. Although vaccine viremia is a known correlate of antibody response, we found that in healthy volunteers with no detectable or low yellow fever 17D viremia, metformin-treated volunteers elicited higher neutralizing antibody titers than placebo-treated volunteers. Transcriptional and metabolomic analyses collectively showed that a brief course of metformin, started 3 days prior to YF17D vaccination and stopped at 3 days after vaccination, expanded oxidative phosphorylation and protein translation capacities. These increased capacities directly correlated with YF17D neutralizing antibody titers, with reduced reactive oxygen species response compared to placebo-treated volunteers. Our findings thus demonstrate a functional association between cellular respiration and vaccine-induced humoral immunity and suggest potential approaches to enhancing vaccine immunogenicity.

Abstract Bacteria adapt to selective pressure in their immediate environment in multiple ways. One mechanism involves the acquisition of independent mutations that disable or modify a key pathway, providing a signature of adaptation via convergent evolution. Extra-intestinal pathogenic Escherichia coli (ExPEC) belonging to sequence type 95 (ST95) represent a global clone frequently associated with severe human infections including acute pyelonephritis, sepsis, and neonatal meningitis. Here, we analysed a publicly available dataset of 613 ST95 genomes and identified a series of loss-of-function mutations that disrupt cellulose production or its modification in 55.3% of strains. We show the inability to produce cellulose significantly enhances ST95 invasive infection in a rat model of neonatal meningitis, leading to the disruption of intestinal barrier integrity in newborn pups and enhanced dissemination to the liver, spleen and brain. Consistent with these observations, disruption of cellulose production in ST95 augmented innate immune signalling and tissue neutrophil infiltration in a mouse model of urinary tract infection. Mutations that disrupt cellulose production were also identified in other virulent ExPEC STs, Shigella and Salmonella, suggesting a correlative association with many Enterobacteriaceae that cause severe human infection. Together, our findings provide an explanation for the emergence of hypervirulent Enterobacteriaceae clones.

Abstract The Lifshitz–Kosevich (LK) theory is the pillar of magnetic quantum oscillations, which have been extensively applied to characterise a wide range of metallic states. In this study, we focus on the Shubnikov–de Haas (SdH) effect observed in SmSb, a rare-earth monopnictide. We observed a significant departure from the expected LK theory near T N = 2.4 K: both a peak-like anomaly and an enhancement in the temperature dependence of quantum oscillation amplitude are seen in SmSb. Moreover, we discovered a remarkable sensitivity of the SdH amplitudes to sample purity. By adjusting the sample purity, we were able to tune the temperature dependence of the α band’s SdH amplitudes from a peak-like anomalous behaviour to an enhancement. Therefore, SdH oscillations from the α band connect the two well-known non-LK behaviours, controllable through varying the sample purity, paving the way for developing further understanding of the mechanism leading to the anomalous quantum oscillations.

Two-dimensional (2D) materials have gained increasing prominence not only in fundamental research but also in daily applications. However, to fully harness their potential, it is crucial to optimize their properties with an external parameter and track the electronic structure simultaneously. Magnetotransport over a wide magnetic field range is a powerful method to probe the electronic structure and, for metallic 2D materials, quantum oscillations superimposed on the transport signals encode Fermi surface parameters. In this manuscript, we utilize biaxial strain as an external tuning parameter and investigate the effects of strain on the electronic properties of two quasi-2D superconductors, MoTe2 and RbV3Sb5, by measuring their magnetoresistance in pulsed magnetic fields up to 60 T. With a careful selection of insulating substrates, we demonstrate the possibility of both the compressive and tensile biaxial strains imposed on MoTe2 and RbV3Sb5, respectively. For both systems, the applied strain has led to superconducting critical temperature enhancement compared to their free-standing counterparts, proving the effectiveness of this biaxial strain method at cryogenic temperatures. Clear quantum oscillations in the magnetoresistance—the Shubnikov–de Haas (SdH) effect—are obtained in both samples. In strained MoTe2, the magnetoresistance exhibits a nearly quadratic dependence on the magnetic field and remains non-saturating even at the highest field, whereas in strained RbV3Sb5, two SdH frequencies showed a substantial enhancement in effective mass values, hinting at a possible enhancement of charge fluctuations. Our results demonstrate that combining biaxial strain and pulsed magnetic field paves the way for studying 2D materials under unprecedented conditions.

Abstract Introduction Visual assessment and imaging of the donor liver are inaccurate in predicting fibrosis and remain surrogates for histopathology. We demonstrate that 3‐s scans using a handheld near‐infrared‐spectroscopy (NIRS) instrument can identify and quantify fibrosis in fresh human liver samples. Methods We undertook NIRS scans on 107 samples from 27 patients, 88 from 23 patients with liver disease, and 19 from four organ donors. Results Liver disease patients had a median immature fibrosis of 40% (interquartile range [IQR] 20–60) and mature fibrosis of 30% (10%–50%) on histopathology. The organ donor livers had a median fibrosis (both mature and immature) of 10% (IQR 5%–15%). Using machine learning, this study detected presence of cirrhosis and METAVIR grade of fibrosis with a classification accuracy of 96.3% and 97.2%, precision of 96.3% and 97.0%, recall of 96.3% and 97.2%, specificity of 95.4% and 98.0% and area under receiver operator curve of 0.977 and 0.999, respectively. Using partial‐least square regression machine learning, this study predicted the percentage of both immature (R2 = 0.842) and mature (R2 = 0.837) with a low margin of error (root mean square of error of 9.76% and 7.96%, respectively). Conclusion This study demonstrates that a point‐of‐care NIRS instrument can accurately detect, quantify and classify liver fibrosis using machine learning.

Abstract Streptococcus agalactiae, also known as Group B Streptococcus (GBS) is a frequent cause of infections, including bacteraemia and other acute diseases in adults and immunocompromised individuals. We developed a novel system to study GBS within human monocytes to define the co-transcriptome of intracellular GBS (iGBS) and host cells simultaneously using dual RNA-sequencing (RNA-seq) to better define how this pathogen responds to host cells. Using human U937 monocytes and genome-sequenced GBS reference strain 874,391 in antibiotic protection assays we validated a system for dual-RNA seq based on measures of GBS and monocyte viability to ensure that the bacterial and host cell co-transcriptome reflected mainly intracellular (iGBS) rather than extracellular GBS. Elucidation of the co-transcriptome revealed 1119 dysregulated transcripts in iGBS with most genes, including several that encode virulence factors (e.g., scpB, hvgA, ribD, pil2b) exhibiting activation by upregulated expression. Infection with iGBS resulted in significant remodelling of the monocyte transcriptome, with 7587 transcripts differentially expressed including 7040 up-regulated and 547 down-regulated. qPCR confirmed that the most strongly activated genes included sht, encoding Streptococcal Histidine Triad Protein. An isogenic GBS mutant strain deficient in sht revealed a significant effect of this gene on phagocytosis of GBS and survival of the bacteria during systemic infection in mice. Identification of a novel contribution of sht to GBS virulence shows the co-transcriptome responses elucidated in GBS-infected monocytes help to shape the host–pathogen interaction and establish a role for sht in the response of the bacteria to phagocytic uptake. This study provides comprehension of concurrent transcriptional responses that occur in GBS and human monocytes that shape the host–pathogen interaction.

Streptococcus agalactiae, also known as group B Streptococcus, is an important human and animal pathogen. Zinc (Zn) is an essential trace element for normal bacterial physiology but intoxicates bacteria at high concentrations. Molecular systems for Zn detoxification exist in S. agalactiae, however the degree to which Zn detoxification may vary among different S. agalactiae isolates is not clear. We measured resistance to Zn intoxication in a diverse collection of clinical isolates of S. agalactiae by comparing the growth of the bacteria in defined conditions of Zn stress. We found significant differences in the ability of different S. agalactiae isolates to resist Zn intoxication; some strains such as S. agalactiae 18RS21 were able to survive and grow at 3.8-fold higher levels of Zn stress compared to other reference strains such as BM110 (6.4mM vs 1.68mM Zn as inhibitory, respectively). We performed in silico analysis of the available genomes of the S. agalactiae isolates used in this study to examine the sequence of czcD, which encodes an efflux protein for Zn that supports resistance in S. agalactiae. Interestingly, this revealed the presence of a mobile insertion sequence (IS) element, termed IS1381, in the 5′ region of czcD in S. agalactiae strain 834, which was hyper-resistant to Zn intoxication. Interrogating a wider collection of S. agalactiae genomes revealed identical placement of IS1381 in czcD in other isolates from the clonal-complex-19 (CC19) 19 lineage. Collectively, these results show a resistance spectrum among S. agalactiae isolates enables survival in varying degrees of Zn stress, and this phenotypic variability has implications for understanding bacterial survival in metal stress.

A type-II Weyl semimetal candidate MoTe2, which superconducts at Tc ∼0.1 K, is one of the promising candidates for realizing topological superconductivity. However, the exceedingly low Tc is associated with a small upper critical field (Hc2), implying a fragile superconducting phase that only exists on a small region of the H–T phase diagram. Here, we describe a simple and versatile approach based on the differential thermal expansion between dissimilar materials to subject a thin single crystalline MoTe2 to biaxial strain. With this approach, we successfully enhance the Tc of MoTe2 by fivefold and consequently expand the superconducting region on the H–T phase diagram significantly. To demonstrate the relative ease of studying the superconductivity in the biaxially strained MoTe2, we further present the magnetotransport data, enabling the study of the temperature-dependent Hc2 and the anisotropy of the superconducting state, which would otherwise be difficult to obtain in a free-standing MoTe2. Our work shows that biaxial strain is an effective knob to tune the electronic properties of MoTe2. Due to the simplicity of our methodology to apply biaxial strain, we anticipate its direct applicability to a wider class of quantum materials.

AV _3 Sb _5 (A = Cs, K, Rb) is a recently discovered superconducting system ( $T_\mathrm{c}\sim0.9$ –2.5 K) in which the vanadium atoms adopt the kagome structure. Intriguingly, these systems enter a charge-density-wave (CDW) phase ( $T_\mathrm{CDW}\sim80$ –100 K), and further evidence shows that the time-reversal symmetry is broken in the CDW phase. Concurrently, the anomalous Hall effect (AHE) has been observed in KV _3 Sb _5 and CsV _3 Sb _5 inside the novel CDW phase. Here, we report a comprehensive study of a high-quality RbV _3 Sb _5 single crystal with magnetotransport measurements. Our data demonstrate the emergence of the AHE in RbV _3 Sb _5 when the CDW state develops. The magnitude of the anomalous Hall resistivity in the low temperature limit is comparable to the reported values in KV _3 Sb _5 and CsV _3 Sb _5 . The magnetoresistance channel further reveals a rich spectrum of quantum oscillation frequencies, many of which have not been reported before. In particular, a large quantum oscillation frequency (2235 T), which occupies ∼56% of the Brillouin zone area, was recorded. For the quantum oscillation frequencies with sufficient signal-to-noise ratio, we further perform field angle-dependent measurements, and our data indicate two-dimensional Fermi surfaces in RbV _3 Sb _5 . Our results provide indispensable information for understanding the AHE and band structure in kagome metal AV _3 Sb _5 .

The definitive diagnosis of Alzheimer's Disease (AD) without the need for neuropathological confirmation remains a challenge in AD research today, despite efforts to uncover the molecular and biological underpinnings of the disease process. Furthermore, the potential for therapeutic intervention is limited upon the onset of symptoms, providing motivation for studying and treating the AD precursor mild cognitive impairment (MCI), the prodromal stage of AD instead. Applying machine learning classification to transcriptomic data of MCI, AD, and cognitively normal (CN) control patients, we identified differentially expressed genes that serve as biomarkers for the characterization and classification of subjects into MCI or AD groups. Predictive models employing these biomarker genes exhibited good classification performances for CN, MCI, and AD, significantly above random chance. The PI3K-Akt, IL-17, JAK-STAT, TNF, and Ras signaling pathways were also enriched in these biomarker genes, indicating their diagnostic potential and pathophysiological roles in MCI and AD. These findings could aid in the recognition of MCI and AD risk in clinical settings, allow for the tracking of disease progression over time in individuals as part of a therapeutic approach, and provide possible personalized drug targets for early intervention of MCI and AD.

Pedestrian link-ways are important street facility for first-/last-mile mobility. This study compared pedestrians’ walking experiences on sheltered/unsheltered link-ways by collecting their perceived walking time/distance. It is found that, first, pedestrians (51 along sheltered and 49 along unsheltered link-ways) generally walk at a faster pace along unsheltered link-ways as compared to sheltered link-way. Second, participants are found to more likely over-perceive walking times and distances (with odds of three to one) along unsheltered link-way than sheltered link-way, and with more extreme deviations on unsheltered link-ways. Third, sheltered link-ways accrued better Level of Service (LOS) ratings on factors such as weather protection, distance, accessibility/user-friendliness, comfort, safety and level of crowdedness. The study demonstrates value-add application of cognitive bias approach for examining the walking experience, and provides human-centric indicators to justify the provision of shelters to the link-way for the benefits of pedestrian users.

Breast cancer is now the most common cancer worldwide, and it is also the main cause of cancer-related death in women. Survival rates for female breast cancer have significantly improved due to early diagnosis and better treatment. Nevertheless, for patients with advanced or metastatic breast cancer, the survival rate is still low, reflecting a need for the development of new therapies. Mechanistic insights into metastatic breast cancer have provided excellent opportunities for developing novel therapeutic strategies. Although high-throughput approaches have identified several therapeutic targets in metastatic disease, some subtypes such as triple-negative breast cancer do not yet have an apparent tumor-specific receptor or pathway to target. Therefore, exploring new druggable targets in metastatic disease is a high clinical priority. In this review, we summarize the emerging intrinsic therapeutic targets for metastatic breast cancer, including cyclin D-dependent kinases CDK4 and CDK6, the PI3K/AKT/mTOR pathway, the insulin/IGF1R pathway, the EGFR/HER family, the JAK/STAT pathway, poly(ADP-ribose) polymerases (PARP), TROP-2, Src kinases, histone modification enzymes, activated growth factor receptors, androgen receptors, breast cancer stem cells, matrix metalloproteinases, and immune checkpoint proteins. We also review the latest development in breast cancer immunotherapy. Drugs that target these molecules/pathways are either already FDA-approved or currently being tested in clinical trials.

Extra-intestinal pathogenic Escherichia coli (ExPEC) belong to a critical priority group of antibiotic resistant pathogens. ExPEC establish gut reservoirs that seed infection of the urinary tract and bloodstream, but the mechanisms of gut colonisation remain to be properly understood. Ucl fimbriae are attachment organelles that facilitate ExPEC adherence. Here, we investigated cellular receptors for Ucl fimbriae and Ucl expression to define molecular mechanisms of Ucl-mediated ExPEC colonisation of the gut. We demonstrate differential expression of Ucl fimbriae in ExPEC sequence types associated with disseminated infection. Genome editing of strains from two common sequence types, F11 (ST127) and UTI89 (ST95), identified a single nucleotide polymorphism in the ucl promoter that changes fimbriae expression via activation by the global stress-response regulator OxyR, leading to altered gut colonisation. Structure-function analysis of the Ucl fimbriae tip-adhesin (UclD) identified high-affinity glycan receptor targets, with highest affinity for sialyllacto-N-fucopentose VI, a structure likely to be expressed on the gut epithelium. Comparison of the UclD adhesin to the homologous UcaD tip-adhesin from Proteus mirabilis revealed that although they possess a similar tertiary structure, apart from lacto-N-fucopentose VI that bound to both adhesins at low-micromolar affinity, they recognize different fucose- and glucose-containing oligosaccharides. Competitive surface plasmon resonance analysis together with co-structural investigation of UcaD in complex with monosaccharides revealed a broad-specificity glycan binding pocket shared between UcaD and UclD that could accommodate these interactions. Overall, our study describes a mechanism of adaptation that augments establishment of an ExPEC gut reservoir to seed disseminated infections, providing a pathway for the development of targeted anti-adhesion therapeutics.

Background: Minimally invasive pancreatic surgeries (MIPS) are increasingly adopted worldwide. However, it remains uncertain if these reported experiences are reproducible throughout the world today. This study examines the safety and evolution of MIPS at a single institution in Southeast Asia. Methods: This is a retrospective review of 150 consecutive patients who underwent MIPS between 2006 and 2018 of which 135 cases (90%) were performed since 2012. To determine the evolution of MIPS, the study population was stratified into 3 equal groups of 50 patients. Comparison was also made between pancreatoduodenectomies (PD), distal pancreatectomies (DP) and other pancreatic surgeries. Results: One hundred and fifty patients underwent MIPS (103 laparoscopic, 45 robotic and 2 hand-assisted). Forty-three patients underwent PD, 93 DP and 14 other MIPS. There were 21 (14.0%) open conversions. There was an exponential increase in caseload over the study period. Comparison across the 3 time periods demonstrated that patients were significantly more likely to have a higher American Society of Anesthesiologists score, older, undergo PD and a longer operation time. The conversion rate decreased from 28% to 0% and increased again to 14% across the 3 time periods. Comparison between the various types of MIPS demonstrated that patients who underwent PD were significantly older, more likely to have symptomatic tumours, had longer surgery time, increased blood loss, increased frequency of extended pancreatectomies, increased frequency of hybrid procedures, longer post-operative stay, increased post-operative morbidity rate and increased post-operative major morbidity rate. Conclusion: The case volume of MIPS increased rapidly at our institution over the study period. Furthermore, although the indications for MIPS expanded to include more complex procedures in higher risk patients, there was no change in key perioperative outcomes.

Biophysical parameters such as substrate topography and stiffness have been shown independently to elicit profound effects on neuronal differentiation and maturation from neural progenitor cells (NPCs) yet have not been investigated in combination. Here, the effects of various micrograting and stiffness combinations on neuronal differentiation and maturation were investigated using a polyacrylamide and N-acryloyl-6-aminocaproic acid copolymer (PAA-ACA) hydrogel with tunable stiffness. Whole laminin was conjugated onto the PAA-ACA surface indirectly or directly to facilitate long-term mouse and human NPC-derived neuron attachment. Three micrograting dimensions (2–10 µm) were patterned onto gels with varying stiffness (6.1–110.5 kPa) to evaluate the effects of topography, stiffness, and their interaction. The results demonstrate that the extracellular matrix (ECM)-modified PAA-ACA gels support mouse and human neuronal cell attachment throughout the differentiation and maturation stages (14 and 28 days, respectively). The interaction between topography and stiffness is shown to significantly increase the proportion of β-tubulin III (TUJ1) positive neurons and microtubule associated protein-2 (MAP2) positive neurite branching and length. Thus, the effects of topography and stiffness cannot be imparted. These results provide a novel platform for neural mechanobiology studies and emphasize the utility of optimizing numerous biophysical cues for improved neuronal yield in vitro.

ABSTRACTThe emergence of neurotropic Zika virus (ZIKV) raised a public health emergency of global concern. ZIKV can cross the placental barrier and infect foetal brains, resulting in microcephaly, but the pathogenesis of ZIKV is poorly understood. With recent findings reporting AXL as a type I interferon antagonist rather than an entry receptor, the exact entry mechanism remains unresolved. Here we report that cell surface sialic acid plays an important role in ZIKV infection. Removal of cell surface sialic acid by neuraminidase significantly abolished ZIKV infection in Vero cells and human induced-pluripotent stem cells-derived neural progenitor cells. Furthermore, knockout of the sialic acid biosynthesis gene encoding UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase resulted in significantly less ZIKV infection of both African and Asian lineages. Huh7 cells deficient in α2,3-linked sialic acid through knockout of ST3 β-galactoside-α2,3-sialyltransferase 4 had significantly reduced ZIKV infection. Removal of membrane-bound, un-internalized virus with pronase treatment revealed the role of sialic acid in ZIKV internalization but not attachment. Sialyllactose inhibition studies showed that there is no direct interaction between sialic acid and ZIKV, implying that sialic acid could be mediating ZIKV-receptor complex internalization. Identification of α2,3-linked sialic acid as an important host factor for ZIKV internalization provides new insight into ZIKV infection and pathogenesis.

1T-TaS_{2} is a prototypical charge-density-wave system with a Mott insulating ground state. Usually, a Mott insulator is accompanied by an antiferromagnetic state. However, the antiferromagnetic order had never been observed in 1T-TaS_{2}. Here, we report the stabilization of the antiferromagnetic order by the intercalation of a small amount of Fe into the van der Waals gap of 1T-TaS_{2}, i.e., forming 1T-Fe_{0.05}TaS_{2}. Upon cooling from 300 K, the electrical resistivity increases with a decreasing temperature before reaching a maximum value at around 15 K, which is close to the Néel temperature determined from our magnetic susceptibility measurement. The antiferromagnetic state can be fully suppressed when the sample thickness is reduced, indicating that the antiferromagnetic order in Fe_{0.05}TaS_{2} has a non-negligible three-dimensional character. For the bulk Fe_{0.05}TaS_{2}, a comparison of our high pressure electrical transport data with that of 1T-TaS_{2} indicates that, at ambient pressure, Fe_{0.05}TaS_{2} is in the nearly commensurate charge-density-wave phase near the border of the Mott insulating state. The temperature-pressure phase diagram thus reveals an interesting decoupling of the antiferromagnetism from the Mott insulating state.

Giant clams live in symbiosis with extracellular zooxanthellae and display high rates of growth and shell formation (calcification) in light. Light-enhanced calcification requires an increase in the supply of Ca2+ to, and simultaneously an augmented removal of H+ from, the extrapallial fluid where shell formation occurs. We have obtained the complete coding cDNA sequence of Plasma Membrane Ca2+-ATPase (PMCA) from the thin and whitish inner mantle, which is in touch with the extrapallial fluid, of the giant clam Tridacna squamosa. The deduced PMCA sequence consisted of an apical targeting element. Immunofluorescence microscopy confirmed that PMCA had an apical localization in the shell-facing epithelium of the inner mantle, whereby it can actively secrete Ca2+ in exchange for H+. More importantly, the apical PMCA-immunofluorescence of the shell-facing epithelium of the inner mantle increased significantly after 12 h of exposure to light. The transcript and protein levels of PMCA/PMCA also increased significantly in the inner mantle after 6 or 12 h of light exposure. These results offer insights into a light-dependable mechanism of shell formation in T. squamosa and a novel explanation of light-enhanced calcification in general. As the inner mantle normally lacks light sensitive pigments, our results support a previous proposition that symbiotic zooxanthellae, particularly those in the colorful and extensible outer mantle, may act as light-sensing elements for the host clam.