Mountain colonisation, miniaturisation and ecological evolution in a radiation of direct-developing New Guinea Frogs (Choerophryne, Microhylidae)

Aims. Mountain ranges in the tropics are characterised by high levels of localised endemism, often-aberrant evolutionary trajectories, and some of the world's most diverse regional biotas. Here we investigate the evolution of montane endemism, ecology and body size in a clade of direct-developing frogs (Choerophryne, Microhylidae) from New Guinea. Methods. Phylogenetic relationships were estimated from a mitochondrial molecular dataset using Bayesian and maximum likelihood approaches. Ancestral state reconstruction was used to infer the evolution of elevational distribution, ecology (indexed by male calling height), and body size, and phylogenetically corrected regression was employed to examine the relationships between these three traits. Results. We obtained strong support for a monophyletic lineage comprising the majority of taxa sampled. Within this clade we identified one subclade that appears to have diversified primarily in montane habitats of the Central Cordillera (> 1,000 m a.s.l.), with subsequent dispersal to isolated North Papuan Mountains. A second subclade (characterised by moderately to very elongated snouts) appears to have diversified primarily in hill forests (< 1,000 m a.s.l.), with inferred independent upwards colonisations of isolated montane habitats, especially in isolated North Papuan Mountains. We found no clear relationship between extremely small body size (adult SVL less than 15 mm) and elevation, but a stronger relationship with ecology-smaller species tend to be more terrestrial. Conclusions. Orogeny and climatic oscillations have interacted to generate high montane biodiversity in New Guinea via both localised diversification within montane habitats (centric endemism) and periodic dispersal across lowland regions (eccentric endemism). The correlation between extreme miniaturisation and terrestrial habits reflects a general trend in frogs, suggesting that ecological or physiological constraints limit niche usage by miniaturised frogs, even in extremely wet environments such as tropical mountains.This work was supported by grants from the Australian Research Council to Paul Oliver, a McKenzie Postdoctoral fellowship to Paul Oliver from Melbourne University, and grant from the Australia Pacific Science Foundation to Paul Oliver, Mike Lee and Stephen Richard

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Ancient Origin of cGAS-STING Reveals Mechanism of Universal 2′,3′ cGAMP Signaling

SummaryIn humans, the cGAS-STING immunity pathway signals in response to cytosolic DNA via 2′,3′ cGAMP, a cyclic dinucleotide (CDN) second messenger containing mixed 2′–5′ and 3′–5′ phosphodiester bonds. Prokaryotes also produce CDNs, but these are exclusively 3′ linked, and thus the evolutionary origins of human 2′,3′ cGAMP signaling are unknown. Here we illuminate the ancient origins human cGAMP signaling by discovery of a functional cGAS-STING pathway in Nematostella vectensis, an anemone species &gt;500 million years diverged from humans. Anemone cGAS appears to produce a 3′,3′ CDN that anemone STING recognizes through nucleobase-specific contacts not observed in human STING. Nevertheless, anemone STING binds mixed-linkage 2′,3′ cGAMP indistinguishably from human STING, trapping a unique structural conformation not induced by 3′,3′ CDNs. These results reveal that human mixed-linkage cGAMP achieves universal signaling by exploiting a deeply conserved STING conformational intermediate, providing critical insight for therapeutic targeting of the STING pathway.Graphical abstrac

Development and validation of a Chinese translated questionnaire: A single simultaneous tool for assessing gastrointestinal and upper respiratory tract related illnesses in pre-school children

الملخص: أهداف البحث: الأطفال عرضة للأمراض المعدية التي تأتي من أقرانهم في الحضانات، ورياض الأطفال، ومراكز الرعاية النهارية. بينت بعض الدراسات أن تناول الكائنات الدقيقة النافعة يقلل من عدد الإصابات بتلك الأمراض، الأمر الذي يؤدي إلى التقليل من الغياب ومن تناول المضادات الحيوية. مع التوجه للتركيز الأقل على والتفضيل الأقل لأخذ عينات الدم من الصغار، فإن الكثير من البيانات القابلة للقياس الكمي يتم الحصول عليها فقط من الدراسات الاستقصائية والاستبيانات. يبلغ ٢٥٪ من سكان ماليزيا من أصل صيني. استهدفنا تطوير أداة واحدة يمكن من خلالها إجراء تقييمات متزامنة لأمراض ذات صلة بالجهازين الهضمي والتنفسي لدى الأطفال الصينيين الصغار. طرق البحث: تمت ترجمة الاستبانات المصادق عليها باللغة الإنجليزية، التي تشمل بيانات متعلقة بالديموغرافيا والسجلات الصحية الشهرية إلى اللغة الصينية. وتمت المصادقة على نسختي الترجمة؛ من الصينيية إلى الإنجليزية ومن الإنجليزية إلى الصينية. النتائج: أظهرت الاستبانات الديموغرافية والشهرية الصحية، مؤشري صلاحية مستوى كلي للبند مستواهما ٠.٩٩و ٠.٩٧على التوالي، بينما أظهرت النسخ الصينية المترجمة مؤشري صلاحية مستوى كلي للبند مستواهما ٠.٩٧ و٠.٩٨على التوالي. كما تم الحصول على مؤشر صلاحية عملية الاستجابة للبند بمستوى ١.٠٠ لهذه الاستبانة من ٣٠ من المجيبين مما يدل على أن البنود كانت واضحة ومفهومة. الاستنتاجات: أظهرت هذه الدراسة مستوى جيدا من مؤشر الصلاحية في النسخة المترجمة الصينية، مما يدل على أنها أداة صالحة وموثوق بها لاستخدامها في التقييم المتزامن للأمراض ذات الصلة بالجهازين الهضمي والتنفسي في الأطفال الصغار ويمكن تطبيقها على سكان ماليزيا الصينيين والدول الأخرى الناطقة بالصينية. Abstract: Objectives: Children are prone to contagious illnesses that come from peers in nurseries, kindergartens, and day care centres. The administration of probiotics has been reported to decrease the episodes of such illnesses, leading to decreased absences and consumption of antibiotics. With less emphasis on, and preferences for, blood collection from young subjects, quantifiable data are merely obtained from surveys and questionnaires. Malaysia has a population which is 25% ethnic Chinese. We aimed to develop a single tool that enables simultaneous assessments of both gastrointestinal and respiratory tract-related illnesses among young Chinese children. Methods: The English-language validated questionnaires using data about demographics and monthly health records were translated into the Chinese language. Both forward and backward translated versions were validated. Results: The developed demographic and monthly health questionnaires showed an overall item-level content validity index (I-CVI) of 0.99 and 0.97, respectively; while the translated Chinese versions showed I-CVI of 0.97 and 0.98, respectively. Item-level of response process validity index of 1.00 for this questionnaire was obtained from 30 respondents inferring that the items were clear and comprehensible. Conclusions: This study showed acceptable levels validity in the Chinese translated version, illustrating a valid and reliable tool to be used for simultaneous assessment of gastrointestinal and respiratory tract-related illnesses in young children that is applicable for Malaysia's Chinese population and other Chinese-speaking nations. الكلمات المفتاحية: التنمية؛ إسهال, الاستبانة, الأمراض ذات الصلة بالجهاز التنفسي, التحقق من الصحة, Keywords: Development, Diarrhoea, Questionnaire, Respiratory tract-related illnesses, Validatio

Ancient Origin of cGAS-STING Reveals Mechanism of Universal 2′,3′ cGAMP Signaling

In humans, the cGAS-STING immunity pathway signals in response to cytosolic DNA via 2′,3′ cGAMP, a cyclic dinucleotide (CDN) second messenger containing mixed 2′–5′ and 3′–5′ phosphodiester bonds. Prokaryotes also produce CDNs, but these are exclusively 3′ linked, and thus the evolutionary origins of human 2′,3′ cGAMP signaling are unknown. Here we illuminate the ancient origins human cGAMP signaling by discovery of a functional cGAS-STING pathway in Nematostella vectensis, an anemone species >500 million years diverged from humans. Anemone cGAS appears to produce a 3′,3′ CDN that anemone STING recognizes through nucleobase-specific contacts not observed in human STING. Nevertheless, anemone STING binds mixed-linkage 2′,3′ cGAMP indistinguishably from human STING, trapping a unique structural conformation not induced by 3′,3′ CDNs. These results reveal that human mixed-linkage cGAMP achieves universal signaling by exploiting a deeply conserved STING conformational intermediate, providing critical insight for therapeutic targeting of the STING pathway