Miracle-dz/UniFAR-FTUs huggingface dataset:
Spatial confinement of active microtubule networks induces large-scale rotational cytoplasmic flow

Significance At the microscopic scale, collective behaviors of motile units can induce directed fluid flow on a larger length scale than individual units based on their hydrodynamic interactions. Here, we found that the motor-driven extensile behaviors of microtubule bundles in the cytoplasm induce rotational flow in a cell-sized confined space on length scale and timescale that were 10- to 100-fold longer than the vortex flows emerging in the bulk space. These scale differences were derived from mechanical force generation by microtubule bundle elongation near the physical boundary and the transmission of this force over the microtubule network. These findings suggest that the microtubule cytoskeleton utilizes not only hydrodynamic interactions but also mechanical interactions to induce large-scale cytoplasmic flow. Collective behaviors of motile units through hydrodynamic interactions induce directed fluid flow on a larger length scale than individual units. In cells, active cytoskeletal systems composed of polar filaments and molecular motors drive fluid flow, a process known as cytoplasmic streaming. The motor-driven elongation of microtubule bundles generates turbulent-like flow in purified systems; however, it remains unclear whether and how microtubule bundles induce large-scale directed flow like the cytoplasmic streaming observed in cells. Here, we adopted Xenopus egg extracts as a model system of the cytoplasm and found that microtubule bundle elongation induces directed flow for which the length scale and timescale depend on the existence of geometrical constraints. At the lower activity of dynein, kinesins bundle and slide microtubules, organizing extensile microtubule bundles. In bulk extracts, the extensile bundles connected with each other and formed a random network, and vortex flows with a length scale comparable to the bundle length continually emerged and persisted for 1 min at multiple places. When the extracts were encapsulated in droplets, the extensile bundles pushed the droplet boundary. This pushing force initiated symmetry breaking of the randomly oriented bundle network, leading to bundles aligning into a rotating vortex structure. This vortex induced rotational cytoplasmic flows on the length scale and timescale that were 10- to 100-fold longer than the vortex flows emerging in bulk extracts. Our results suggest that microtubule systems use not only hydrodynamic interactions but also mechanical interactions to induce large-scale temporally stable cytoplasmic flow.
T helper type 17‐related cytokine expression is increased in the bronchial mucosa of stable chronic obstructive pulmonary disease patients

There are increased numbers of activated T lymphocytes in the bronchial mucosa of stable chronic obstructive pulmonary disease (COPD) patients. T helper type 17 (Th17) cells release interleukin (IL)‐17 as their effector cytokine under the control of IL‐22 and IL‐23. Furthermore, Th17 numbers are increased in some chronic inflammatory conditions. To investigate the expression of interleukin (IL)‐17A, IL‐17F, IL‐21, IL‐22 and IL‐23 and of retinoic orphan receptor RORC2, a marker of Th17 cells, in bronchial biopsies from patients with stable COPD of different severity compared with age‐matched control subjects. The expression of IL‐17A, IL‐17F, IL‐21, IL‐22, IL‐23 and RORC2 was measured in the bronchial mucosa using immunohistochemistry and/or quantitative polymerase chain reaction. The number of IL‐22+ and IL‐23+ immunoreactive cells is increased in the bronchial epithelium of stable COPD compared with control groups. In addition, the number of IL‐17A+ and IL‐22+ immunoreactive cells is increased in the bronchial submucosa of stable COPD compared with control non‐smokers. In all smokers, with and without disease, and in patients with COPD alone, the number of IL‐22+ cells correlated significantly with the number of both CD4+ and CD8+ cells in the bronchial mucosa. RORC2 mRNA expression in the bronchial mucosa was not significantly different between smokers with normal lung function and COPD. Further, we report that endothelial cells express high levels of IL‐17A and IL‐22. Increased expression of the Th17‐related cytokines IL‐17A, IL‐22 and IL‐23 in COPD patients may reflect their involvement, and that of specific IL‐17‐producing cells, in driving the chronic inflammation seen in COPD.
Reply to Contact Lens-Based Expansion and Transplantation of Autologous Epithelial Progenitors for Ocular Surface Reconstruction: Crossover Control

REFERENCES 1. Di Girolamo N, Bosch M, Zamora K, et al. A contact lens-based technique for expansion and transplantation of autologous epithelial progenitors for ocular surface reconstruction. Transplantation 2009; 87: 1571. 2. Wei ZG, Wu RL, Lavker RM, et al. In vitro growth and differentiation of rabbit bulbar, fornix, and palpebral conjunctival epithelia: Implications on conjunctival epithelial transdifferentiation and stem cells. Invest Ophthalmol Vis Sci 1993; 34: 1814. 3. Wei ZG, Cotsarelis G, Sun TT, et al. Labelretaining cells are preferentially located in fornical epithelium: Implications on conjunctival epithelial homeostasis. Invest Ophthalmol Vis Sci 1995; 36: 236. 4. Pellegrini G, Golisano O, Paterna P, et al. Location and clonal analysis of stem cells and their differentiated progeny in the human ocular surface. J Cell Biol 1999; 145: 769. 5. Lee H, Khan R, O’Keefe M. Aniridia: Current pathology and management. Acta Ophthalmol 2008; 86: 708. 6. Mintz-Hittner HA, Ferrell RE, Lyons LA, et al. Criteria to detect minimal expressivity within families with autosomal dominant aniridia. Am J Ophthalmol 1992; 114: 700. 7. Sonoda S, Isashiki Y, Tabata Y, et al. A novel PAX6 gene mutation (P118R) in a family with congenital nystagmus associated with a variant form of aniridia. Graefes Arch Clin Exp Ophthalmol 2000; 238: 552.
Correlation between risk factors and musculoskeletal disorders among classical musicians.

BACKGROUND Musculoskeletal disorders in humans may originate from biomechanical, environmental, psychosocial and personal risk factors encountered in the working environment. These disorders in musicians are designated as playing related musculoskeletal disorders (PRMD). AIMS To investigate the correlation between biomechanical, environmental, psychosocial and personal risk factors and potential incidence of PRMD arising in professional classical musicians. METHODS Fifty-nine orchestral classical musicians were observed: They also filled out questionnaires providing information regarding musculoskeletal symptoms, psychosocial factors and demography. RESULTS Clinical observation using the Rapid Upper Limb Assessment (RULA) showed significantly higher scores in string musicians compared with woodwind and brass players (right RULA score F = 4.77, P < 0.05; left RULA score, F = 3.90, P < 0.05). A multivariate regression model showed statistical significance for five of the six dependent variables regarding prevalence of painful joints, severity of musculoskeletal symptoms and functional limitation. The regression analysis revealed that biomechanical risk factors, perceived physical environment risk factors, instrument weight and average playing hours per week, were the main predictors of PRMD. CONCLUSIONS The biomechanical risk factors that predict PRMD are mainly associated with the upper limbs. A high association between PRMD and clinical observation emphasizes the need for further investigation of these risk factors and to study possible implementations in order to define 'prevention strategies' for musical routines and patterns, as used by classical musicians.
Group Support for Patients With Metastatic Cancer: A Randomized Prospective Outcome Study

• The effects of weekly supportive group meetings for women with metastatic carcinoma of the breast were systematically evaluated in a one-year, randomized, prospective outcome study. The groups focused on the problems of terminal illness, including improving relationships with family, friends, and physicians and living as fully as possible in the face of death. We hypothesized that this intervention would lead to improved mood, coping strategies, and self-esteem among those in the treatment group. Eighty-six patients were tested at four-month intervals. The treatment group had significantly lower mooddisturbance scores on the Profile of Mood States scale, had fewer maladaptive coping responses, and were less phobic than the control group. This study provides objective evidence that a supportive group intervention for patients with metastatic cancer results in psychological benefit. Mechanisms underlying the effectiveness of this group intervention are explored.
Motor Speech Disorders: Substrates, Differential Diagnosis, and Management

Part 1: Substrates 1. Defining, Understanding, and Categorizing Motor Speech Disorders 2. Neurologic Bases of Motor Speech and its Pathologies 3. Examination of Motor Speech Disorders Part 2: The Disorders and Their Diagnoses 4. Flaccid Dysarthria 5. Spastic Dysarthria 6. Ataxic Dysarthria 7. Hypokinetic Dysarthria 8. Hyperkinetic Dysarthria 9. Unilateral Upper Motor Neuron Dysarthria 10. Mixed Dysarthrias 11. Apraxia of Speech 12. Neurogenic Mutism 13. Other Neurogenic Speech Disturbances 14. Acquired Psychogenic Speech Disturbances 15. Differential Diagnosis Part 3: Management 16. Managing Motor Speech Disorders: General Principles 17. Managing the Dysarthrias 18. Managing Apraxia of Speech 19. Managing Other Neurogenic Speech Disturbances 20. Managing Acquired Psychogenic Speech Disorders
The other side of immunoglobulin G: suppressor of inflammation

Immunoglobulin G (IgG) molecules can have two completely opposite functions. On one hand, they induce proinflammatory responses and recruit innate immune effector cells during infection with pathogenic microorganisms or autoimmune disease. On the other hand, intravenous infusion of high doses of pooled IgG molecules from thousands of donors [intravenous IG (IVIG) therapy] represents an efficient anti‐inflammatory treatment for many autoimmune diseases. Whereas our understanding of the mechanism of the proinflammatory activity of IgG is quite advanced, we are only at the very beginning to comprehend how the anti‐inflammatory activity comes about and what cellular and molecular players are involved in this activity. This review will summarize our current knowledge and focus upon the two major models of either IVIG‐mediated competition for IgG‐triggered effector functions or IVIG‐mediated adjustment of cellular activation thresholds used to explain the mechanism of the anti‐inflammatory activity.
Structure of the infectious salmon anemia virus receptor complex illustrates a unique binding strategy for attachment

Significance The infectious salmon anemia virus (ISAV), an aquatic pathogen with lethal hemorrhagic potential, decimates farmed and freshwater fish populations globally. Here, we determined the crystallographic structures of the hemagglutinin-esterase (HE) viral glycoprotein responsible for the dynamic attachment of the virus to its receptor in Atlantic salmon. We identified surface features of ISAV HE that are conserved across isolates known to cause significant economic burden to fisheries worldwide. This provides a molecular blueprint for the design of a broadly protective vaccine. Furthermore, we showed that ISAV HE has a distinct receptor recognition strategy from those of other influenza-like viruses and coronaviral HE proteins, contributing to our understanding of the diversity of viral entry mechanisms. Orthomyxoviruses are an important family of RNA viruses, which include the various influenza viruses. Despite global efforts to eradicate orthomyxoviral pathogens, these infections remain pervasive. One such orthomyxovirus, infectious salmon anemia virus (ISAV), spreads easily throughout farmed and wild salmonids, constituting a significant economic burden. ISAV entry requires the interplay of the virion-attached hemagglutinin-esterase and fusion glycoproteins. Preventing infections will rely on improved understanding of ISAV entry. Here, we present the crystal structures of ISAV hemagglutinin-esterase unbound and complexed with receptor. Several distinctive features observed in ISAV HE are not seen in any other viral glycoprotein. The structures reveal a unique mode of receptor binding that is dependent on the oligomeric assembly of hemagglutinin-esterase. Importantly, ISAV hemagglutinin-esterase receptor engagement does not initiate conformational rearrangements, suggesting a distinct viral entry mechanism. This work improves our understanding of ISAV pathogenesis and expands our knowledge on the overall diversity of viral glycoprotein-mediated entry mechanisms. Finally, it provides an atomic-resolution model of the primary neutralizing antigen critical for vaccine development.
Interleukin‐10 inhibits Mycobacterium bovis bacillus Calmette–Guérin (BCG)‐induced macrophage cytotoxicity against bladder cancer cells

The mechanisms underlying bacillus Calmette–Guérin (BCG) immunotherapy of bladder cancer currently remain elusive. Previously, we demonstrated that macrophages were cytotoxic to bladder cancer cells upon BCG stimulation in vitro. However, macrophages from C57BL/6 mice were less potent than those from C3H/HeN mice for the killing of bladder cancer cells. This study was to determine whether interleukin (IL)‐10 produced by macrophages in response to BCG is a causative factor for the reduced cytotoxicity in BCG‐stimulated C57BL/6 macrophages. Thioglycollate‐elicited peritoneal macrophages were prepared and analysed for the BCG induction of cytotoxicity, cytokines and nitric oxide (NO) in vitro. Compared to BCG‐stimulated C3H/HeN macrophages, BCG‐stimulated C57BL/6 macrophages exhibited reduced killing of bladder cancer MBT‐2 cells and MB49 cells. Studies demonstrated further that BCG‐stimulated C57BL/6 macrophages produced a high level of IL‐10, which correlated with reduced production of tumour necrosis factor (TNF)‐α, IL‐6 and NO. Neutralizing endogenous IL‐10 during BCG stimulation increased C57BL/6 macrophage cytotoxicity against MB49 cells by 3·2‐fold, along with increased production of TNF‐α by 6·4‐fold and NO by 3·6‐fold, respectively. Macrophages from C57BL/6 IL‐10−/− mice also exhibited increased killing of MB49 cells and production of TNF‐α and NO upon BCG stimulation. In addition, supplementation of exogenous recombinant IL‐10 reduced BCG‐induced C3H/HeN macrophage cytotoxicity against both MBT‐2 cells and MB49 cells in a dose‐dependent manner. These results reveal the inhibitory role of IL‐10 in BCG‐induced macrophage cytotoxicity, suggesting that blockage of IL‐10 may potentially enhance the effect of BCG in the treatment of bladder cancer patients.
Effects on employees of controlling working hours and working schedules.

BACKGROUND High levels of control over working time and low variability in working hours have been associated with improved health-related outcomes. The potential mechanisms for this association remain unclear. AIMS To examine how work-time control and variability of working times are associated with fatigue recovery, sleep quality, work-life balance, and 'near misses' at work. METHODS Manufacturing sector employees completed a questionnaire that assessed work-time control, work-time variability, fatigue recovery, sleep quality, work-life balance and the frequency of near misses in the past 6 months. Mixed model analysis of covariance and multiple logistic regression analysis tested the main effects of work-time control and variability and their interaction, while adjusting for age, sex, work schedules, and overtime work in the past month. Subscales of work-time control were also investigated (control over daily working hours and over days off). RESULTS One thousand three hundred and seventy-two completed questionnaires were returned, a response rate of 69%. A significantly higher quality of sleep and better work-life balance were found in the 'high control with low variability' reference group than in the other groups. Significantly better recovery of fatigue was also observed in the group having control over days off with low variability. While near misses were more frequent in the group with high control over daily working hours coupled with high variability compared with the reference group this was not significant. CONCLUSIONS High work-time control and low variability were associated with favourable outcomes of health and work-life balance. This combined effect was not observed for the safety outcome addressed here.
Reply to Filadi et al.: Does Mitofusin 2 tether or separate endoplasmic reticulum and mitochondria?

We thank Filadi et al. for their comments (1) on our paper (2), where we address whether the discrepancies between their paper (3) and our original discovery of Mitofusin (Mfn) 2 as an endoplasmic reticulum (ER)–mitochondria tether (4) resulted from: ( i ) clonal effects of chronic Mfn2 ablation, ( ii ) proximity measurement inappropriateness, or ( iii ) changes in mitochondrial Ca2+ uniporter (MCU) levels in WT and Mfn2 −/−cells. Filadi et al. (1) conclude that we fell short in solving the issue and that our data reinforce Mfn2 function as an ER–mitochondria spacer (3). First, Filadi et al. (1) reason that we did not measure contacts number upon Mfn2 ablation. However, contact surface (which depends on contact number and extent) can be extracted from the ER–mitochondria contact coefficient and data in our paper (2). The average mitochondrial surface contacting ER … [↵][1]1To whom correspondence should be addressed. Email: luca.scorrano{at}unipd.it. [1]: #xref-corresp-1-1
Hazard information needs and information seeking in French workers.

BACKGROUND Data about perceived needs of workers for information on occupational hazards or diseases (OHDs) are scarce and the behaviour of workers seeking information on these matters is not well known. AIMS To describe workers' needs and behaviour in seeking information about OHDs. METHODS All workers attending for consultation at an occupational health service in Upper Normandy within 1 week were invited to fill in an anonymous questionnaire. RESULTS Of the 2640 workers responding 58% declared a need for information about OHD, but only 37% actually sought that information. Whereas 82% of workers mentioned the internet and their general physician (GP) as sources of information on OHD, only 43% mentioned their occupational physician (OP). Furthermore, information received from OPs was not considered more reliable than that from GPs. CONCLUSIONS Workers report a need for information about OHDs. Although most of them trust information given by OPs, they do not use OPs to obtain OHD information, but instead use less reliable sources such as the internet or their GPs.
Synthesis of Crystalline Black Phosphorus Thin Film on Sapphire

Black phosphorus (BP) has recently attracted significant attention due to its exceptional physical properties. Currently, high‐quality few‐layer and thin‐film BP are produced primarily by mechanical exfoliation, limiting their potential in future applications. Here, the synthesis of highly crystalline thin‐film BP on 5 mm sapphire substrates by conversion from red to black phosphorus at 700 °C and 1.5 GPa is demonstrated. The synthesized ≈50 nm thick BP thin films are polycrystalline with a crystal domain size ranging from 40 to 70 µm long, as indicated by Raman mapping and infrared extinction spectroscopy. At room temperature, field‐effect mobility of the synthesized BP thin film is found to be around 160 cm2 V−1 s−1 along armchair direction and reaches up to about 200 cm2 V−1 s−1 at around 90 K. Moreover, red phosphorus (RP) covered by exfoliated hexagonal boron nitride (hBN) before conversion shows atomically sharp hBN/BP interface and perfectly layered BP after the conversion. This demonstration represents a critical step toward the future realization of large scale, high‐quality BP devices and circuits.
Imaging through Nonlinear Metalens Using Second Harmonic Generation

The abrupt phase change of light at metasurfaces provides high flexibility in wave manipulation without the need for accumulation of propagating phase through dispersive materials. In the linear optical regime, one important application field of metasurfaces is imaging by planar metalenses, which enables device miniaturization and aberration correction compared to conventional optical microlens systems. With the incorporation of nonlinear responses into passive metasurfaces, optical functionalities of metalenses are anticipated to be further enriched, leading to completely new application areas. Here, imaging with nonlinear metalenses that combine the function of an ultrathin planar lens with simultaneous frequency conversion is demonstrated. With such nonlinear metalenses, imaging of objects with near infrared light while the image appears in the second harmonic signal of visible frequency range is experimentally demonstrated. Furthermore, the functionality of these nonlinear metalenses can be modified by switching the handedness of the circularly polarized fundamental wave, leading to either real or virtual nonlinear image formation. Nonlinear metalenses not only enable infrared light imaging through a visible detector but also have the ability to modulate nonlinear optical responses through an ultrathin metasurface device while the fundamental wave remains unaffected, which offers the capability of nonlinear information processing with novel optoelectronic devices.
Hot spot of N2 fixation in the western tropical South Pacific pleads for a spatial decoupling between N2 fixation and denitrification

Nitrogen (N) is the building block of life. Quantifying the sources and sinks of N to the ocean is essential for predicting its productivity and potential carbon sequestration. In his paper, Gruber (1) seeks for “elusive marine nitrogen fixation” following results from Knapp et al. (2), who measured unexpectedly low N input through N2 fixation in the eastern tropical South Pacific (ETSP), seriously bringing into question the proposed close spatial coupling between N input (through N2 fixation) and loss (through denitrification) (3). Here, we compile data from recently published and unpublished studies revealing a hot spot of N2 fixation in the western tropical South Pacific (WTSP) arguing for a spatial decoupling between N sources and sinks in the South Pacific. Based on four cruises performed between 2012 and 2015 during austral winter and summer conditions, with a total of more than 600 15N2 incubations-based measurements, and particularly a 4,000-km zonal transect at ∼20°S in … [↵][1]1To whom correspondence should be addressed. Email: sophie.bonnet{at}univ-amu.fr. [1]: #xref-corresp-1-1