Improving microbial phylogeny with citizen science within a mass-market video game.

Citizen science video games are designed primarily for users already inclined to contribute to science, which severely limits their accessibility for an estimated community of 3 billion gamers worldwide. We created Borderlands Science (BLS), a citizen science activity that is seamlessly integrated within a popular commercial video game played by tens of millions of gamers. This integration is facilitated by a novel game-first design of citizen science games, in which the game design aspect has the highest priority, and a suitable task is then mapped to the game design. BLS crowdsources a multiple alignment task of 1 million 16S ribosomal RNA sequences obtained from human microbiome studies. Since its initial release on 7 April 2020, over 4 million players have solved more than 135 million science puzzles, a task unsolvable by a single individual. Leveraging these results, we show that our multiple sequence alignment simultaneously improves microbial phylogeny estimations and UniFrac effect sizes compared to state-of-the-art computational methods. This achievement demonstrates that hyper-gamified scientific tasks attract massive crowds of contributors and offers invaluable resources to the scientific community.

Pathophysiology of bradykinin and histamine mediated angioedema.

Angioedema is characterized by swelling localized to the subcutaneous and submucosal tissues. This review provides an overview of angioedema, including the different types, triggers, and underlying pathophysiologic mechanisms. Hereditary and acquired angioedema are caused by dysregulation of the complement and kinin pathways. In contrast, drug-induced and allergic angioedema involve the activation of the immune system and release of vasoactive mediators. Recent advances in the understanding of the pathophysiology of angioedema have led to the development of targeted therapies, such as monoclonal antibodies, bradykinin receptor antagonists, and complement inhibitors, which promise to improve clinical outcomes in patients with this challenging condition. To accurately diagnose and manage angioedema, an understanding of this condition's complex and varied pathophysiology is both necessary and critical.

Postmodification of an Amine-Functionalized Covalent Organic Framework for Enantioselective Adsorption of Tyrosine.

The development of chiral covalent organic frameworks (COFs) by postsynthetic modification is challenging due to the common occurrences of racemization and crystallinity decrement under harsh modification conditions. Herein, we employ an effective site-selective synthetic strategy for the fabrication of an amine-functionalized hydrazone-linked COF, NH2-Th-Tz COF, by the Schiff-base condensation between aminoterephthalohydrazide (NH2-Th) and 4,4',4″-(1,3,5-triazine-2,4,6-triyl)tribenzaldehyde (Tz). The resulting NH2-Th-Tz COF with free amine groups on the pore walls provides an appealing platform to install desired chiral moieties through postsynthetic modification. Three chiral moieties including tartaric acid, camphor-10-sulfonyl chloride, and diacetyl-tartaric anhydride were postsynthetically integrated into NH2-Th-Tz COF by reacting amine groups with acid, acyl chloride, and anhydride, giving rise to a series of chiral COFs with distinctive chiral pore surfaces. Moreover, the crystallinity, porosity, and chirality of chiral COFs were retained after modification. Remarkably, the chiral COFs exhibited an exceptional enantioselective adsorption capability toward tyrosine with a maximum enantiomeric excess (ee) value of up to 25.20%. Molecular docking simulations along with experimental results underscored the pivotal role of hydrogen bonds between chiral COFs and tyrosine in enantioselective adsorption. This work highlights the potential of site-selective synthesis as an effective tool for the preparation of highly crystalline and robust amine-decorated COFs, which offer an auspicious platform for the facile synthesis of tailor-made chiral COFs for enantioselective adsorption and beyond.

Involvement of a Response Regulator VdSsk1 in Stress Response, Melanin Biosynthesis and Full Virulence in Verticillium dahliae.

Verticillium dahliae causes vascular wilt disease on over 200 plant species worldwide. This fungus forms melanized microsclerotia which help it to survive under adverse conditions and these structures are vital to the disease spread. Here, we identified and characterized a V. dahliae homolog to of the Saccharomyces cerevisiae Ssk1, a response regulator of the two-component system. Herein, we demonstrated that the VdSsk1 deletion strains were more sensitive to various stresses, including oxidative stress conferred by H2O2 and sodium nitroprusside dihydrate, while the mutants confered higher resistance to fungicides such as fludioxonil and iprodione. Furthermore, disruption of VdSsk1 resulted in significant downregulation of melanin biosynthesis-related genes but did not affect microsclerotial development. Phosphorylation of VdHog1 was not detected in the VdSsk1 deletion strains under the treatment of sorbitol, indicating that phosphorylation of VdHog1 is dependent on VdSsk1. Finally, we demonstrated that VdSsk1 is required for full virulence. Taken together, this study suggests that VdSsk1 modulates stress response, melanin biosynthesis and virulence of V. dahliae.

Allocating less attention to central vision during vection is correlated with less motion sickness.

Visually induced motion sickness (VIMS) is a common discomfort response associated with vection-provoking stimuli. It has been suggested that susceptibility to VIMS depends on the ability to regulate visual performance during vection. To test this, 29 participants, with VIMS susceptibility assessed by Motion Sickness Susceptibility Questionnaire, were recruited to undergo three series of sustained attention to response tests (SARTs) while watching dot pattern stimuli known to provoke roll-vection. In general, SARTs performance was impaired in the central visual field (CVF), but improved in peripheral visual field (PVF), suggesting the reallocation of attention during vection. Moreover, VIMS susceptibility was negatively correlated with the effect sizes, suggesting that participants who were less susceptible to VIMS showed better performance in attention re-allocation. Finally, when trained to re-allocation attention from the CVF to the PVF, participants experienced more stable vection. Findings provide a better understanding of VIMS and shed light on possible preventive measures. Practitioner Summary: Allocating less visual attention to central visual field during visual motion stimulation is associated with stronger vection and higher resistance to motion sickness. Virtual reality application designers may utilise the location of visual tasks to strengthen and stabilise vection, while reducing the potential of visually induced motion sickness.

[Optimized schemes for acupuncture treatment of migraine during attack].

OBJECTIVE: To observe the therapeutic effect of manual acupuncture, electroacupuncture (EA), auricular acupuncture and bloodletting therapies combined with orthogonal design for migraine patients, so as to select a better scheme for relieving headache. METHODS: total of 76 migraine patients in the stage of attack were recruited in the present study and randomly (stratified random and central random) allocated to 9 groups by means of orthogonal experimental design [L9 (3(4)), 4 factors (F) and three levels (L)] i.e., F1: ody-acupoints combination; F1-L1: regional acupoints [Sizhukong (TE 23), Shuaigu (GB 8), Taiyang (EX-HN 5), etc.] near the focus, F1-L2:regional +distal acupoints [Hegu (L 4), Taichong (LR 3), etc.] far from the focus, and F1-L3:regional + remote acupoints+ those selected according to syndrome differentiation [for instance, Ganshu (BL 18), Yanglingquan (GB 34), Qiuxu (GB 40) and Taixi (KI 3) for hyperactivity of Liver-yang, etc.]; F2: manual acupuncture or EA of body acupoints; F2-L1:no acupuncture stimulation, F2-L2:manual acupuncture stimulation, and F2-L3:manual + EA stimulation; F3: auricular acupuncture therapy; F3-L1:no acupuncture stimulation, F3-L2: otopoint-manual acupuncture (Shenmen, Jiaogan, etc.), and F3-L3:otopoint-EA; F4: bloodletting; F4-L1 : EX-HN 5 + Ashi point bloodletting, F4-L2:EX-HN5 bloodletting, and F4-L3: no bloodletting. The therapeutic effect of acupuncture was evaluated using Visual Analogue Scale (VAS) and analyzed by investigators who did not participate in the treatment course. RESULTS: Within 24 hours after the treatment, the four factors influencing headache relief from bigger to smaller are body-acupoints combination > manual acupuncture or EA stimulation > bloodletting > auricular acupuncture. Among the therapeutic schemes evaluated by orthogonal deduction, the analgesic effect was most stable in the manual acupuncture at regional + distal acupoints group which was recommended to be the ba-sic scheme for migraine. The auricular EA could effectively reduce VAS levels from 10 min to 30 min after stimulation, while bloodletting at Taiyang (EX-HN 5)+ Ashi points was effective in relieving migraine from 4 h to 24 h after the treatment, suggesting a long lasting post-therapeutic analgesic effect. CONCLUSION: Manual acupuncture stimulation of the local + distal body acupoints combined with otopoint-EA and bloodletting at Taiyang (EX-HN 5) + Ashi points is the best option for relieving migraine during attack.