Low-noise supercontinuum generation in chiral all-normal dispersion photonic crystal fibers.

We present the advantages of supercontinuum generation in chiral, therefore circularly birefringent, all-normal dispersion fibers. Due to the absence of nonlinear power transfer between the polarization eigenstates of the fiber, chiral all-normal dispersion fibers do not exhibit any polarization instabilities and thus are an ideal platform for a low-noise supercontinuum generation. By pumping a chiral all-normal dispersion fiber at 802 nm, we obtained an octave-spanning, robustly circularly polarized supercontinuum with a low noise.

Tunable fiber source of entangled UV-C and infrared photons.

Pairs of entangled photons-biphotons-are indispensable in quantum applications. However, some important spectral ranges, like the ultraviolet, have been inaccessible to them so far. Here, we use four-wave mixing in a xenon-filled single-ring photonic crystal fiber to generate biphotons with one of the photons in the ultraviolet and its entangled partner in the infrared spectral range. We tune the biphotons in frequency by varying the gas pressure inside the fiber and thus tailoring the fiber dispersion landscape. The ultraviolet photons are tunable from 271 nm to 231 nm and their entangled partners, from 764 nm to 1500 nm, respectively. Tunability up to 192 THz is achieved by adjusting the gas pressure by only 0.68 bar. At 1.43 bar, the photons of a pair are separated by more than 2 octaves. The access to ultraviolet wavelengths opens the possibility for spectroscopy and sensing with undetected photons in this spectral range.

Single-pulse terahertz spectroscopy monitoring sub-millisecond time dynamics at a rate of 50 kHz.

Slow motion movies allow us to see intricate details of the mechanical dynamics of complex phenomena. If the images in each frame are replaced by terahertz (THz) waves, such movies can monitor low-energy resonances and reveal fast structural or chemical transitions. Here, we combine THz spectroscopy as a non-invasive optical probe with a real-time monitoring technique to demonstrate the ability to resolve non-reproducible phenomena at 50k frames per second, extracting each of the generated THz waveforms every 20 µs. The concept, based on a photonic time-stretch technique to achieve unprecedented data acquisition speeds, is demonstrated by monitoring sub-millisecond dynamics of hot carriers injected in silicon by successive resonant pulses as a saturation density is established. Our experimental configuration will play a crucial role in revealing fast irreversible physical and chemical processes at THz frequencies with microsecond resolution to enable new applications in fundamental research as well as in industry.

Unmasking of the von Willebrand A-domain surface adhesin CglB at bacterial focal adhesions mediates myxobacterial gliding motility.

The predatory deltaproteobacterium Myxococcus xanthus uses a helically-trafficked motor at bacterial focal-adhesion (bFA) sites to power gliding motility. Using total internal reflection fluorescence and force microscopies, we identify the von Willebrand A domain-containing outer-membrane (OM) lipoprotein CglB as an essential substratum-coupling adhesin of the gliding transducer (Glt) machinery at bFAs. Biochemical and genetic analyses reveal that CglB localizes to the cell surface independently of the Glt apparatus; once there, it is recruited by the OM module of the gliding machinery, a heteroligomeric complex containing the integral OM ß barrels GltA, GltB, and GltH, as well as the OM protein GltC and OM lipoprotein GltK. This Glt OM platform mediates the cell-surface accessibility and retention of CglB by the Glt apparatus. Together, these data suggest that the gliding complex promotes regulated surface exposure of CglB at bFAs, thus explaining the manner by which contractile forces exerted by inner-membrane motors are transduced across the cell envelope to the substratum.

Measurement of Minute Liquid Volumes of Chiral Molecules Using In-Fiber Polarimetry.

We report an optofluidic method that enables to efficiently measure the enantiomeric excess of chiral molecules at low concentrations. The approach is to monitor the optical activity induced by a Kagome-lattice hollow-core photonic crystal fiber filled with a sub-µL volume of chiral compounds. The technique also allows monitoring the enzymatic racemization of R-mandelic acid.

Bacterial Outer Membrane Polysaccharide Export (OPX) Proteins Occupy Three Structural Classes with Selective ß-Barrel Porin Requirements for Polymer Secretion.

Secretion of high-molecular-weight polysaccharides across the bacterial envelope is ubiquitous, as it enhances prokaryotic survival in (a)biotic settings. Such polymers are often assembled by Wzx/Wzy- or ABC transporter-dependent schemes implicating outer membrane (OM) polysaccharide export (OPX) proteins in cell-surface polymer translocation. In the social predatory bacterium Myxococcus xanthus, the exopolysaccharide (EPS) pathway WzaX, major spore coat (MASC) pathway WzaS, and biosurfactant polysaccharide (BPS) pathway WzaB were herein found to be truncated OPX homologues of Escherichia coli Wza lacking OM-spanning α-helices. Comparative genomics across all bacteria (>91,000 OPX proteins identified and analyzed), complemented with cryo-electron tomography cell-envelope analyses, revealed such "truncated" WzaX/S/B architecture to be the most common among three defined OPX-protein structural classes independent of periplasm thickness. Fold recognition and deep learning revealed the conserved M. xanthus proteins MXAN_7418/3226/1916 (encoded beside wzaX/S/B, respectively) to be integral OM ß-barrels, with structural homology to the poly-N-acetyl-d-glucosamine synthase-dependent pathway porin PgaA. Such bacterial porins were identified near numerous genes for all three OPX protein classes. Interior MXAN_7418/3226/1916 ß-barrel electrostatics were found to match properties of their associated polymers. With MXAN_3226 essential for MASC export, and MXAN_7418 herein shown to mediate EPS translocation, we have designated this new secretion machinery component "Wzp" (i.e., Wz porin), with the final step of M. xanthus EPS/MASC/BPS secretion across the OM now proposed to be mediated by WzpX/S/B (i.e., MXAN_7418/3226/1916). Importantly, these data support a novel and widespread secretion paradigm for polysaccharide biosynthesis pathways in which those containing OPX components that cannot span the OM instead utilize ß-barrel porins to mediate polysaccharide transport across the OM. IMPORTANCE Diverse bacteria assemble and secrete polysaccharides that alter their physiologies through modulation of motility, biofilm formation, and host immune system evasion. Most such pathways require outer membrane (OM) polysaccharide export (OPX) proteins for sugar-polymer transport to the cell surface. In the prototypic Escherichia coli Group-1-capsule biosynthesis system, eight copies of this canonical OPX protein cross the OM with an α-helix, forming a polysaccharide-export pore. Herein, we instead reveal that most OPX proteins across all bacteria lack this α-helix, raising questions as to the manner by which most secreted polysaccharides actually exit cells. In the model developmental bacterium Myxococcus xanthus, we show this process to depend on OPX-coupled OM-spanning ß-barrel porins, with similar porins encoded near numerous OPX genes in diverse bacteria. Knowledge of the terminal polysaccharide secretion step will enable development of antimicrobial compounds targeted to blocking polymer export from outside the cell, thus bypassing any requirements for antimicrobial compound uptake by the cell.

Evaluation of Azido 3-Deoxy-d-manno-oct-2-ulosonic Acid (Kdo) Analogues for Click Chemistry-Mediated Metabolic Labeling of Myxococcus xanthus DZ2 Lipopolysaccharide.

Metabolic labeling paired with click chemistry is a powerful approach for selectively imaging the surfaces of diverse bacteria. Herein, we explored the feasibility of labeling the lipopolysaccharide (LPS) of Myxococcus xanthus-a Gram-negative predatory social bacterium known to display complex outer membrane (OM) dynamics-via growth in the presence of distinct azido (-N3) analogues of 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo). Determination of the LPS carbohydrate structure from strain DZ2 revealed the presence of one Kdo sugar in the core oligosaccharide, modified with phosphoethanolamine. The production of 8-azido-8-deoxy-Kdo (8-N3-Kdo) was then greatly improved over previous reports via optimization of the synthesis of its 5-azido-5-deoxy-d-arabinose precursor to yield gram amounts. The novel analogue 7-azido-7-deoxy-Kdo (7-N3-Kdo) was also synthesized, with both analogues capable of undergoing in vitro strain-promoted azide-alkyne cycloaddition (SPAAC) "click" chemistry reactions. Slower and faster growth of M. xanthus was displayed in the presence of 8-N3-Kdo and 7-N3-Kdo (respectively) compared to untreated cells, with differences also seen for single-cell gliding motility and type IV pilus-dependent swarm community expansion. While the surfaces of 8-N3-Kdo-grown cells were fluorescently labeled following treatment with dibenzocyclooctyne-linked fluorophores, the surfaces of 7-N3-Kdo-grown cells could not undergo fluorescent tagging. Activity analysis of the KdsB enzyme required to activate Kdo prior to its integration into nascent LPS molecules revealed that while 8-N3-Kdo is indeed a substrate of the enzyme, 7-N3-Kdo is not. Though a lack of M. xanthus cell aggregation was shown to expedite growth in liquid culture, 7-N3-Kdo-grown cells did not manifest differences in intrinsic clumping relative to untreated cells, suggesting that 7-N3-Kdo may instead be catabolized by the cells. Ultimately, these data provide important insights into the synthesis and cellular processing of valuable metabolic labels and establish a basis for the elucidation of fundamental principles of OM dynamism in live bacterial cells.

Leveraging the Structure of DNAJA1 to Discover Novel Potential Pancreatic Cancer Therapies.

Pancreatic cancer remains one of the deadliest forms of cancer with a 5-year survival rate of only 11%. Difficult diagnosis and limited treatment options are the major causes of the poor outcome for pancreatic cancer. The human protein DNAJA1 has been proposed as a potential therapeutic target for pancreatic cancer, but its cellular and biological functions remain unclear. Previous studies have suggested that DNAJA1's cellular activity may be dependent upon its protein binding partners. To further investigate this assertion, the first 107 amino acid structures of DNAJA1 were solved by NMR, which includes the classical J-domain and its associated linker region that is proposed to be vital to DNAJA1 functionality. The DNAJA1 NMR structure was then used to identify both protein and ligand binding sites and potential binding partners that may suggest the intracellular roles of DNAJA1. Virtual drug screenings followed by NMR and isothermal titration calorimetry identified 5 drug-like compounds that bind to two different sites on DNAJA1. A pull-down assay identified 8 potentially novel protein binding partners of DNAJA1. These proteins in conjunction with our previously published metabolomics study support a vital role for DNAJA1 in cellular oncogenesis and pancreatic cancer.

COVID-19 quarantine in adolescents with autoimmune rheumatic diseases: mental health issues and life conditions.

OBJECTIVES: To assess mental health and life conditions in adolescents with autoimmune rheumatic diseases (ARDs) and healthy controls quarantined during COVID-19 pandemic. METHOD: A cross-sectional study included 155 ARD adolescents and 105 healthy controls. Online survey included self-reported strengths and difficulties questionnaire (SDQ), and a semi-structured questionnaire with demographic data, daily home and school routine, physical activities, and COVID-19 information during the pandemic. RESULTS: Among patients, 56% had juvenile idiopathic arthritis (JIA), 29% juvenile systemic lupus erythematosus (JSLE), and 15% juvenile dermatomyositis (JDM). No differences were found regarding sex, ethnicity, and current age between ARD patients and controls (p > 0.05). Abnormal emotional SDQ (38% vs. 35%, p = 0.653) were similar in both groups. Logistic regression analyses in ARD patients demonstrated that female (OR = 2.4; 95%CI 1.0-6.0; p = 0.044) was associated with severe emotional SDQ dysfunction, whereas sleep problems were considered as a risk factor for both worse total SDQ (OR = 2.6; 95%CI 1.2-5.5; p = 0.009) and emotional SDQ scores (OR = 4.6; 95%CI 2.2-9.7; p < 0.001). Comparisons between ARD patients with and without current prednisone use showed higher median scores of peer problems in the first group [3 (0-10) vs. 2 (0-7), p = 0.049], whereas similar median and frequencies between JIA, JSLE, and JDM (p > 0.05). CONCLUSIONS: Approximately one third of JIA, JSLE, and JDM patients presented abnormal total and emotional scores of SDQ during COVID-19 quarantine. Sleep problems were the main factor associated with emotional difficulties in these ARD adolescents. The knowledge of mental health issues rates in adolescents with ARD supports the development of prevention strategies, like sleep hygiene counseling, as well as the references of the affected patients to specialized mental health services, as necessary. Key Points • One third of ARD patients presented mental health issues during COVID-19 quarantine • Sleep problems were associated with emotional difficulties. • It is necessary to warn pediatric rheumatologists about the importance of sleep hygiene counseling.

Social impact of disease parameters and damage accrual in adult Brazilian patients with childhood-onset Systemic Lupus Erythematosus.

OBJECTIVES: To describe the frequency and investigate potential associations of unemployment, need of financial assistance and health-related quality of life in adult patients with childhood-onset Systemic Lupus Erythematosus (cSLE). METHODS: In this multicenter cross-sectional retrospective cohort study including cSLE adult patients, questionnaires were applied evaluating demographic characteristics, medical history, treatment, receipt of government financial assistance, work status, quality of life, economic classification, disease activity, and damage accrual. Disease activity and disease damage were measured at the study visit. RESULTS: Sixty-nine cSLE patients with a median age of 21 years from two Brazilian tertiary centers were included (median disease duration 9 years). Twenty-eight (40.6%) patients were unemployed and 16 (23.2%) were receiving financial assistance or retirement pension. Work unemployment was associated with higher damage scores (OR 1.83, 95% CI 1.08 to 3.09, p = 0.024), and the need of financial assistance was associated with longer disease duration (OR 1.15, 95% CI 1.00 to 1.31, p = 0.045) and worse economic score (OR 0.87, 95% CI 0.77 to 0.99, p = 0.038). Emotional health and body image perception were the most compromised domains of quality of life but showed no association with disease parameters. Disease activity, on the other hand, was inversely associated with symptoms scores (ß = -1.377, p = 0.014) and scores of adverse effects of medications (ß = -1.286, p = 0.020). CONCLUSION: cSLE is a disease with severe outcomes and high social burden that profoundly impacts patients. Damage accrual is a major contributor to unemployment during adulthood and its prevention must be central in the management of cSLE.

Poor Sleep quality and health-related quality of life impact in adolescents with and without chronic immunosuppressive conditions during COVID-19 quarantine.

OBJECTIVE: To assess the possible factors that influence sleep quality in adolescents with and without chronic immunosuppressive conditions quarantined during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: This cross-sectional study included 305 adolescents with chronic immunocompromised conditions and 82 healthy adolescents. Online surveys were completed, which included questions on socio-demographic data and self-rated healthcare routine during COVID-19 quarantine and the following validated questionnaires: the Pittsburgh Sleep Quality Index (PSQI), Pediatric Quality of Life Inventory 4.0 (PedsQL4.0), and Pediatric Outcome Data Collection Instrument (PODCI). RESULTS: The median current age [14 (10-18) vs. 15 (10-18) years, p=0.847] and frequency of female sex (62% vs. 58%, p=0.571) were similar in adolescents with chronic conditions compared with healthy adolescents. The frequency of poor sleep quality was similar in both groups (38% vs. 48%, p=0.118). Logistic regression analysis, including both healthy adolescents and adolescents with chronic conditions (n=387), demonstrated that self-reported increase in screen time (odds ratio [OR] 3.0; 95% confidence interval [CI] 1.3-6.8; p=0.008) and intrafamilial violence report (OR 2.1; 95% CI 1.2-3.5; p=0.008) were independently associated with poor sleep quality in these adolescents. However, the PODCI global function score was associated with a lower OR for poor sleep quality (OR 0.97; 95% CI 0.94-0.99; p=0.001). Further logistic regression, including only adolescents with chronic conditions (n=305), demonstrated that self-reported increase in screen time (OR 3.1; 95% CI 1.4-6.8; p=0.006) and intrafamilial violence report (OR 2.0; 95% CI 1.2-3.4; p=0.011) remained independently associated with poor quality of sleep, whereas a lower PODCI global function score was associated with a lower OR for sleep quality (OR 0.96; 95% CI 0.94-0.98; p<0.001). CONCLUSION: Self-reported increases in screen time and intrafamilial violence report impacted sleep quality in both healthy adolescents and those with chronic conditions. Decreased health-related quality of life was observed in adolescents with poor sleep quality.

Doppler optical frequency domain reflectometry for remote fiber sensing: erratum.

This erratum corrects a typographical error in Eq. (10) of our paper [Opt. Express29, 14615 (2021)10.1364/OE.421842].

Distributed functions of prefrontal and parietal cortices during sequential categorical decisions.

Comparing sequential stimuli is crucial for guiding complex behaviors. To understand mechanisms underlying sequential decisions, we compared neuronal responses in the prefrontal cortex (PFC), the lateral intraparietal (LIP), and medial intraparietal (MIP) areas in monkeys trained to decide whether sequentially presented stimuli were from matching (M) or nonmatching (NM) categories. We found that PFC leads M/NM decisions, whereas LIP and MIP appear more involved in stimulus evaluation and motor planning, respectively. Compared to LIP, PFC showed greater nonlinear integration of currently visible and remembered stimuli, which correlated with the monkeys' M/NM decisions. Furthermore, multi-module recurrent networks trained on the same task exhibited key features of PFC and LIP encoding, including nonlinear integration in the PFC-like module, which was causally involved in the networks' decisions. Network analysis found that nonlinear units have stronger and more widespread connections with input, output, and within-area units, indicating putative circuit-level mechanisms for sequential decisions.

Deep-UV-enhanced supercontinuum generated in a tapered gas-filled photonic crystal fiber.

We present the use of a linearly down-tapered gas-filled hollow-core photonic crystal fiber in a single stage, pumped with pulses from a compact infrared (IR) laser source, to generate a supercontinuum (SC) carrying significant spectral power in the deep ultraviolet (UV) [200-300 nm]. The generated SC extends from the near IR down to ∼213nm with 0.58 mW/nm and down to ∼220nm with 0.83 mW/nm in the deep UV.

Bacterial glycocalyx integrity drives multicellular swarm biofilm dynamism.

Exopolysaccharide (EPS) layers on the bacterial cell surface are key determinants of biofilm establishment and maintenance, leading to the formation of higher-order 3D structures that confer numerous survival benefits to a cell community. In addition to a specific cell-associated EPS glycocalyx, we recently revealed that the social δ-proteobacterium Myxococcus xanthus secretes a novel biosurfactant polysaccharide (BPS) to the extracellular milieu. Together, secretion of the two polymers (EPS and BPS) is required for type IV pilus (T4P)-dependent swarm expansion via spatio-specific biofilm expression profiles. Thus the synergy between EPS and BPS secretion somehow modulates the multicellular lifecycle of M. xanthus. Herein, we demonstrate that BPS secretion functionally alters the EPS glycocalyx via destabilization of the latter, fundamentally changing the characteristics of the cell surface. This impacts motility behaviors at the single-cell level and the aggregative capacity of cells in groups via cell-surface EPS fibril formation as well as T4P production, stability, and positioning. These changes modulate the structure of swarm biofilms via cell layering, likely contributing to the formation of internal swarm polysaccharide architecture. Together, these data reveal the manner by which the combined secretion of two distinct polymers induces single-cell changes that modulate swarm biofilm communities.

Fiber-based biphoton source with ultrabroad frequency tunability.

Tunable biphotons are highly important for a wide range of quantum applications. For some applications, especially interesting are cases where two photons of a pair are far apart in frequency. Here, we report a tunable biphoton source based on a xenon-filled hollow-core photonic crystal fiber. Tunability is achieved by adjusting the pressure of the gas inside the fiber. This allows us to tailor the dispersion landscape of the fiber, overcoming the principal limitations of solid-core fiber-based biphoton sources. We report a maximum tunability of 120 THz for a pressure range of 4 bar with a continuous shift of 30 THz/bar. At 21 bar, the photons of a pair are separated by more than one octave. Despite the large separation, both photons have large bandwidths. At 17 bar, they form a very broad (110 THz) band around the frequency of the pump.

Low muscle mass in older adults and mortality: A systematic review and meta-analysis.

Sarcopenia comprises a loss of muscle function and muscle mass. So far, the association between the later and mortality in older adults is inconsistent. A meta-analysis was performed to assess whether muscle mass measured by appendicular skeletal muscle mass index (ASMI) is associated with higher mortality in older adults. Articles of interest were searched for in two databases (PudMed® and Embase®). Cohort and case-control studies reporting ASMI and mortality and enrolling community-dwelling adults aged 65 years or more were included. Nine articles were eligible and included for analysis (n = 10,028). All but one study were considered of high quality by Newcastle-Ottawa Scale assessment. We calculated the standardized mean difference (SMD) for ASMI between dead and living individuals during follow-up across studies. A reduced pooled ASMI in individuals who died as compared to those who survived (ASMI SMD = -0.18, CI95% -0.23 to -0.12, REM) was found. A meta-regression was performed including ASMI SMD, grip strength SMD, body mass index (BMI), sex, study quality, method used to assess ASMI, site of study and age. BMI and ethnicity were found to significantly impact the difference in ASMI between dead and living individuals. These results reinforce the prognostic importance of assessing muscle mass in older adults.

Tumbling and anomalous alignment of optically levitated anisotropic microparticles in chiral hollow-core photonic crystal fiber.

The complex tumbling motion of spinning nonspherical objects is a topic of enduring interest, both in popular culture and in advanced scientific research. Here, we report all-optical control of the spin, precession, and nutation of vaterite microparticles levitated by counterpropagating circularly polarized laser beams guided in chiral hollow-core fiber. The circularly polarized light causes the anisotropic particles to spin about the fiber axis, while, regulated by minimization of free energy, dipole forces tend to align the extraordinary optical axis of positive uniaxial particles into the plane of rotating electric field. The end result is that, accompanied by oscillatory nutation, the optical axis reaches a stable tilt angle with respect to the plane of the electric field. The results reveal new possibilities for manipulating optical alignment through rotational degrees of freedom, with applications in the control of micromotors and microgyroscopes, laser alignment of polyatomic molecules, and study of rotational cell mechanics.

Doppler optical frequency domain reflectometry for remote fiber sensing.

Coherent optical frequency domain reflectometry has been widely used to locate static reflectors with high spatial resolution. Here, we present a new type of Doppler optical frequency domain reflectometry that offers simultaneous measurement of the position and speed of moving objects. The system is exploited to track optically levitated "flying" particles inside a hollow-core photonic crystal fiber. As an example, we demonstrate distributed temperature sensing with sub-mm-scale spatial resolution and a standard deviation of ∼10°C up to 200°C.

Investigation of dengue-malaria coinfection among febrile patients consulting at Ngaoundere Regional Hospital, Cameroon.

This study aimed at evaluating the seroprevalence of dengue among malarious patients consulting at the Ngaoundere Regional Hospital. During 2 months and a half, 174 participants were recruited and their blood samples were screened for Plasmodium spp and then for Dengue virus (DENV) infection using rapid diagnostic tests. Also, hematological asparameters were measured using a hematology autoanalyzer. Among patients tested, 134 (77.01%) were malaria-positive, and 12/134 (8.95%) were coinfected. In this population, 8/12 (66.67%) were only anti-DENV IgM-positive, 3/12 (25%) were both NS1 and anti-DENV IgM positive, and 1/12 (8.33%) were anti-DENV IgG-positive. Furthermore, women were more affected (58.3%) than men (41.7%). The most affected age groups were young people aged less than or equal to 15 years (33.3%) and adults aged between 30 and 45 years (33.3%). A significant association (p < .05; odds ratio [OR] = 5.16) was found between the age range (30-45) and dengue-malaria coinfection. Similarly, we noted a significant association between the coinfection, and joint pain (p < .05; OR = 6.15), fatigue (p < .01; OR = 5.74), and chills (p < .05; OR = 0). Analysis of hematologic parameters showed a significant decrease (p < .001) in platelets in coinfected patients compared with monoinfected patients. In conclusion, dengue-malaria coinfection is a reality in Ngaoundere city and associated with the appearance of clinical features which predict the disease severity.