Sriram Sudarsanam, Shiri Yaniv, Hagar Meltzer, and Oren Schuldiner

The mechanisms that control intrinsic axon growth potential, and thus axon regeneration following injury, are not well understood. Developmental axon regrowth of Drosophila mushroom body -neurons during neuronal remodeling offers a unique opportunity to study the molecular mechanisms controlling intrinsic growth potential. Motivated by the recently uncovered developmental expression atlas of -neurons, we here focus on the role of the actin-severing protein cofilin during axon regrowth. We show that Twinstar (Tsr), the fly cofilin, is a crucial regulator of both axon growth and branching during developmental remodeling of -neurons. tsr mutant axons demonstrate growth defects both in vivo and in vitro, and also exhibit actin-rich filopodial-like structures at failed branch points in vivo. Our data is inconsistent with Tsr being important for increasing G-actin availability. Furthermore, analysis of microtubule localization suggests that Tsr is required for microtubule infiltration into the axon tips and branch points. Taken together, we show that Tsr promotes axon growth and branching, likely by clearing F-actin to facilitate protrusion of microtubules.

Background

We aimed to investigate the epidemiological and clinical features, and medical care-seeking process of patients with the 2019 coronavirus disease (COVID-19) in Wuhan, China, to provide useful information to contain COVID-19 in other places with similar outbreaks of the virus.

While flagella have been studied extensively as motility organelles, with a focus on internal structures such as the axoneme, more recent research has illuminated the roles of the flagellar surface in a variety of biological processes. Parasitic protists of the order Kinetoplastida, which include trypanosomes and Leishmania species, provide a paradigm for probing the role of flagella in host-microbe interactions and illustrate that this interface between the flagellar surface and the host is of paramount importance. An increasing body of knowledge indicates that the flagellar membrane serves a multitude of functions at this interface: attachment of parasites to tissues within insect vectors, close interactions with intracellular organelles of vertebrate cells, transactions between flagella from different parasites, junctions between the flagella and the parasite cell body, emergence of nanotubes and exosomes from the parasite directed to either host or microbial targets, immune evasion, and sensing of the extracellular milieu. Recent whole-organelle or genome-wide studies have begun to identify protein components of the flagellar surface that must mediate these diverse host-parasite interactions. The increasing corpus of knowledge on kinetoplastid flagella will likely prove illuminating for other flagellated or ciliated pathogens as well.

ABSTRACTBackground:Coaching can improve the quality of care in primary-level birth facilities and promote birth attendant adherence to essential birth practices (EBPs) that reduce maternal and perinatal mortality. The intensity of coaching needed to promote and sustain behavior change is unknown. We investigated the relationship between coaching intensity, EBP adherence, and maternal and perinatal health outcomes using data from the BetterBirth Trial, which assessed the impact of a complex, coaching-based implementation of the World Health Organization's Safe Childbirth Checklist in Uttar Pradesh, India.Methods:For each birth, we defined multiple coaching intensity metrics, including coaching frequency (coaching visits per month), cumulative coaching (total coaching visits accrued during the intervention), and scheduling adherence (coaching delivered as scheduled). We considered coaching delivered at both facility and birth attendant levels. We assessed the association between coaching intensity and birth attendant adherence to 18 EBPs and with maternal and perinatal health outcomes using regression models.Results:Coaching frequency was associated with modestly increased EBP adherence. Delivering 6 coaching visits per month to facilities was associated with adherence to 1.3 additional EBPs (95% confidence interval [CI]=0.6, 1.9). High-frequency coaching delivered with high coverage among birth attendants was associated with greater improvements: providing 70% of birth attendants at a facility with at least 1 visit per month was associated with adherence to 2.0 additional EBPs (95% CI=1.0, 2.9). Neither cumulative coaching nor scheduling adherence was associated with EBP adherence. Coaching was generally not associated with health outcomes, possibly due to the small magnitude of association between coaching and EBP adherence.Conclusions:Frequent coaching may promote behavior change, especially if delivered with high coverage among birth attendants. However, the effects of coaching were modest and did not persist over time, suggesting that future coaching-based interventions should explore providing frequent coaching for longer periods.

Background:

Previous studies examining potential sex and gender bias in the Canadian Resident Matching Service (CaRMS) match have had conflicting results. We examined the results of the CaRMS match over the period 2013–2019 to determine the potential association between applicants’ gender and the outcome of matching to their first-choice discipline.

At about 6300 km, Chang Jiang or Long River (长江) is the longest river in Asia and third longest in the world. It is the longest in the world to flow entirely within one country and plays a large role in the history, culture, and economy of China. For thousands of years, the river has been used for water, irrigation, sanitation, transportation, industry, boundary-marking, and war. Passing through 10 provinces, it commences its flow from the Tanggula Mountains (唐古拉山) in ethnic Tibetan Qinghai (青海) Province in northwest China and ends at the East China Sea in Shanghai (上海). Along the middle reaches of the river, between the western upstream Baidi City (白帝城) of Chongqing (重庆) Municipality and Yichang (宜昌) city of Hubei (湖北) Province downstream, the river passes through 3 adjacent gorges, known as the Three Gorges (三峡): Qutang, Wuxia, and Xiling gorge (瞿塘, 巫峡, 西陵峡) cutting through the Wu Mountains (巫山). Spanning a distance of about 120 km, these gorges are noted for their natural beauty: unusual-looking mountain peaks ranging from 800 m to 2000 m, precipitous valleys, dense forest, and spectacular landscape. Many ancient government officials, scholars, poets, and painters visited the Three Gorges and left their impressions and praises in writings. Archeological discoveries in recent years have shown for the first time that the Three Gorges area should be recognized as the birthplace of Chinese civilization.

Quinolones, such as the antimalarial atovaquone, are inhibitors of the malarial mitochondrial cytochrome bc₁ complex, a target critical to the survival of both liver- and blood-stage parasites, making these drugs useful as both prophylaxis and treatment. Recently, several derivatives of endochin have been optimized to produce novel quinolones that are active in vitro and in animal models. While these quinolones exhibit potent ex vivo activity against Plasmodium falciparum and Plasmodium vivax, their activity against the zoonotic agent Plasmodium knowlesi is unknown. We screened several of these novel endochin-like quinolones (ELQs) for their activity against P. knowlesi in vitro and compared this with their activity against P. falciparum tested under identical conditions. We demonstrated that ELQs are potent against P. knowlesi (50% effective concentration, <117 nM) and equally effective against P. falciparum. We then screened selected quinolones and partner drugs using a longer exposure (2.5 life cycles) and found that proguanil is 10-fold less potent against P. knowlesi than P. falciparum, while the quinolones demonstrate similar potency. Finally, we used isobologram analysis to compare combinations of the ELQs with either proguanil or atovaquone. We show that all quinolone combinations with proguanil are synergistic against P. falciparum. However, against P. knowlesi, no evidence of synergy between proguanil and the quinolones was found. Importantly, the combination of the novel quinolone ELQ-300 with atovaquone was synergistic against both species. Our data identify potentially important species differences in proguanil susceptibility and in the interaction of proguanil with quinolones and support the ongoing development of novel quinolones as potent antimalarials that target multiple species.

The effects of multiple-dose administration of tenofovir disoproxil fumarate (TDF) on the pharmacokinetics of morinidazole (MOR) were compared in healthy subjects. MOR exposure was similar, with an area under the curve from 0 h to infinity (AUC_0-) treatment ratio for MOR+TDF/MOR of 1.01 (90% confidence interval, 0.97 to 1.06). No relevant differences were observed regarding plasma exposure of metabolites. Renal clearances of MOR and its metabolites were not affected by TDF. No unexpected safety or tolerability issues were observed.

Background:

Relatives of patients with bladder cancer have been shown to be at increased risk for kidney, lung, thyroid, and cervical cancer after correcting for smoking-related behaviors that may concentrate in some families. We demonstrate a novel approach to simultaneously assess risks for multiple cancers to identify distinct multicancer configurations (multiple different cancer types that cluster in relatives) surrounding patients with familial bladder cancer.

BACKGROUND AND PURPOSE:

In the medicolegal literature, notching of the corpus callosum has been reported to be associated with fetal alcohol spectrum disorders. Our purpose was to analyze the prevalence of notching of the corpus callosum in a fetal alcohol spectrum disorders group and a healthy population to determine whether notching occurs with increased frequency in the fetal alcohol spectrum disorders population.

Các khu dân cư hiện hữu sẽ được chỉnh trang, tránh làm cuộc sống người dân bị xáo trộn. Đối với những khu ở mới, các công trình cao tầng được ưu tiên bố trí dọc các trục giao thông chính...

Sở Quy hoạch - Kiến trúc sẽ định hướng tổ chức không gian, kiến trúc cảnh quan cho từng ô phố, trục đường và toàn khu vực lập quy hoạch Khu dân cư phía Nam rạch Bà Bướm.

UBND tỉnh Hưng Yên vừa điều chỉnh vị trí, chức năng của hàng loạt lô đất thuộc khu đô thị Ecopark, huyện Văn Giang. Các lô đất xây nhà cao tầng sẽ trở thành khu shophouse, công trình công cộng.

Khu đất "vàng" K200, nằm trên đường An Dương Vương, phường Nguyễn Văn Cừ, TP. Quy Nhơn, tỉnh Bình Định được điều chỉnh chức năng sử dụng đất.

Phó Thủ tướng Trịnh Đình Dũng vừa phê duyệt điều chỉnh cục bộ quy hoạch chung xây dựng TP.HCM đến năm 2025 với nhiều thay đổi ở khu vực phía Đông.

Việc điều chỉnh cục bộ quy hoạch Thủ đô đến năm 2030 và tầm nhìn đến năm 2050 lần này nhằm đáp ứng nhu cầu sử dụng đất quốc phòng an ninh trên địa bàn.

UBND TP.HCM vừa điều chỉnh cục bộ quy hoạch chi tiết tỷ lệ 1/500 dự án khu nhà ở diện tích 6,8915 ha tại phường Thảo Điền, quận 2.

Thuần khiết và mộc mạc, màu trắng lại khiến nhiều người e dè khi sử dụng trong trang trí nhà bởi dễ bám bẩn và khiến không gian trở nên đơn điệu, thiếu cá tính. Nếu bạn không e ngại khoản cọ rửa và lau chùi thì màu trắng thực sự là một món quà quý giá trong trang trí nội thất nhờ những bí quyết dưới đây.

The trade war between the United States and China has turned real estate investors' interest to Southeast Asian countries, in which the Vietnamese industrial market emerges as a bright spot in the region.

UBND TP.HCM chỉ đạo các sở, ngành giải quyết những vướng mắc về quy định tách thửa đất dân cư xây dựng mới, đất hỗn hợp, đất nông nghiệp...

QR codes, tracking apps and drones at toll booths are just some of the tech tools China is deploying to monitor the spread of the new coronavirus

A temporary coronavirus hospital ward in China is being staffed entirely by robots. Around 200 patients with mild symptoms will be fed and treated by machines, while medical staff issue commands from outside

This could be a trial run for the rest of Disney’s parks in the US, Japan, France, and Hong Kong.

China has connected the world’s first portable ground station for quantum communication to the Mozi satellite, and has plans to launch another quantum satellite soon

The brains behind the first plant ever to germinate on the moon explains how the Chinese mission succeeded

Einstein’s theory of relativity predicts that fast-spinning objects stretch space and time around them, and we’ve watched that effect make a pair of stars wobble

China’s Yutu-2 rover has used radar to peer 40 metres under the surface of the far side of the moon and revealed how past impacts have shaped its geology

China just tested its biggest rocket yet, along with a new capsule designed to carry humans to its planned space station, the moon and beyond

The Pulitzer Prize Board this week awarded its commentary award to The New York Times' Nikole Hannah-Jones for her essay launching the "1619 Project." This will accelerate a trend already underway: subjecting schoolchildren to a curriculum that blames slavery on capitalism and whose creator believes socialism offers the best path to racial equity.

John Deere, the nearly 200-year-old tractor manufacturer, now considers itself a software company

The machine would use an “alphabet of human thoughts” and rules to combine them

The unique body and locomotion strategies of echinoderms inspired this robot that emulates a juvenile sea urchin

Spacecraft propulsion systems are ready for China’s daring touchdown attempt on the red planet

OpenAI’s GPT-2 program churns out natural language that’s remarkably coherent—and that’s a problem

Whether for maintenance or augmentation, robots that can use tools on themselves are more independent and capable

It could be a matter of time before a Chinese airline tries to buy a strategic stake in Qantas.

Anna Marie gets bribed. Chris gets a new MMO to play. Alice exchanges spaceships for duneships. Alex gets isometric. Jonathan learns how to fly.

BEIJING (Reuters) - Chinese regulators have approved Novartis' Mayzent to treat relapsing multiple sclerosis in adults, the Swiss drug maker said in a statement on Saturday. Other drugs approved by China's National Medical Products Administration to treat MS include Novartis' Gilenya, Bayer's Betaferon and Sanofi's Aubagio. China has an estimated 30,000 patients with MS. (Reporting by Roxanne Liu and Kevin Yao in Beijing; Editing by Edwina Gibbs

Justice in case of 25-year-old black male delayed amid COVID-19 response. Apparently in Georgia bowling and tattooing are more essential.

The basic coaching course will be attended by 32 senior men and 23 senior women core probables on May 11 and 15 respectively.

Following China’s switch to a two-child policy, there has been a slight rise in congenital anomalies, perhaps because parents are older on average at conception