bmj;387/nov12_10/q2481/FAF1faJulia and Malcolm Donaldsondonaldson20241111.f1Malcolm Donaldson was a distinguished paediatric endocrinologist with a string of research publications to his name—but he was also happy to play second fiddle (almost literally) to his wife Julia, the celebrated author of much loved children’s books, including The Gruffalo and Room on the Broom.Malcolm, a talented musician and performer, accompanied his wife as she toured festivals, schools, and libraries in the UK and around the world. Together they performed the stories, with Malcolm acting characters ranging from an accident prone dragon to a comic cattle thief. His star role, in the words of Julia’s literary agent, was “a particularly suave fox” in The Gruffalo.Malcolm met Julia Shields when they were students at the University of Bristol and they married in 1972. Donaldson went on to work in Brighton, London, and Lyon, France, before moving back to Bristol to be a senior registrar in paediatrics. Six...

Endogenous reprogramming of glia into neurogenic progenitors holds great promise for neuron restoration therapies. Using lessons from regenerative species, we have developed strategies to stimulate mammalian Müller glia to regenerate neurons in vivo in the adult retina. We have demonstrated that the transcription factor Ascl1 can stimulate Müller glia neurogenesis. However, Ascl1 is only able to reprogram a subset of Müller glia into neurons. We have reported that neuroinflammation from microglia inhibits neurogenesis from Müller glia. Here we found that the peripheral immune response is a barrier to CNS regeneration. We show that monocytes from the peripheral immune system infiltrate the injured retina and negatively influence neurogenesis from Müller glia. Using CCR2 knock-out mice of both sexes, we found that preventing monocyte infiltration improves the neurogenic and proliferative capacity of Müller glia stimulated by Ascl1. Using scRNA-seq analysis, we identified a signaling axis wherein Osteopontin, a cytokine highly expressed by infiltrating immune cells is sufficient to suppress mammalian neurogenesis. This work implicates the response of the peripheral immune system as a barrier to regenerative strategies of the retina.

The activation of autonomic and hypothalamo-pituitary-adrenal (HPA) systems occurs interdependently with behavioral adjustments under varying environmental demands. Nevertheless, laboratory rodent studies examining the neural bases of stress responses have generally attributed increments in these systems to be monolithic, regardless of whether an active or passive coping strategy is employed. Using the shock probe defensive burying test (SPDB) to measure stress-coping features naturalistically in male and female rats, we identify a neural pathway whereby activity changes may promote distinctive response patterns of hemodynamic and HPA indices typifying active and passive coping phenotypes. Optogenetic excitation of the rostral medial prefrontal cortex (mPFC) input to the ventrolateral periaqueductal gray (vlPAG) decreased passive behavior (immobility), attenuated the glucocorticoid hormone response, but did not prevent arterial pressure and heart rate increases associated with rats’ active behavioral (defensive burying) engagement during the SPDB. In contrast, inhibition of the same pathway increased behavioral immobility and attenuated hemodynamic output but did not affect glucocorticoid increases. Further analyses confirmed that hemodynamic increments occurred preferentially during active behaviors and decrements during immobility epochs, whereas pathway manipulations, regardless of the directionality of effect, weakened these correlational relationships. Finally, neuroanatomical evidence indicated that the influence of the rostral mPFC->vlPAG pathway on coping response patterns is mediated predominantly through GABAergic neurons within vlPAG. These data highlight the importance of this prefrontal->midbrain connection in organizing stress-coping responses and in coordinating bodily systems with behavioral output for adaptation to aversive experiences.

The sudden appearance of a visual distractor shortly before saccade initiation can capture spatial attention and modulate the saccade trajectory in spite of the ongoing execution of the initial plan to shift gaze straight to the saccade target. To elucidate the neural correlates underlying these curved saccades, we recorded from single neurons in the frontal eye field of two male rhesus monkeys shifting gaze to a target while a distractor with the same eccentricity appeared either left or right of the target at various delays after target presentation. We found that the population level of presaccadic activity of neurons representing the distractor location encoded the direction of the saccade trajectory. Stronger activity occurred when saccades curved toward the distractor, and weaker when saccades curved away. This relationship held whether the distractor was ipsilateral or contralateral to the recorded neurons. Meanwhile, visually responsive neurons showed asymmetrical patterns of excitatory responses that varied with the location of the distractor and the duration of distractor processing relating to attentional capture and distractor inhibition. During earlier distractor processing, neurons encoded curvature toward the distractor. During later distractor processing, neurons encoded curvature away from the distractor. This was observed when saccades curved away from distractors contralateral to the recording site and when saccades curved toward distractors ipsilateral to the recording site. These findings indicate that saccadic motor planning involves dynamic push–pull hemispheric interactions producing attraction or repulsion for potential but unselected saccade targets.

The prefrontal cortex is critical for decision-making across species, with its activity linked to choosing between options. Drift diffusion models (DDMs) are commonly employed to understand the neural computations underlying this behavior. Studies exploring the specific roles of regions of the rodent prefrontal cortex in controlling the decision process are limited. This study explored the role of the prelimbic cortex (PLC) in decision-making using a two-alternative forced-choice task. Rats first learned to report the location of a lateralized visual stimulus. The brightness of the stimulus indicated its reward value. Then, the rats learned to make choices between pairs of stimuli. Sex differences in learning were observed, with females responding faster and more selectively to high-value stimuli than males. DDM analysis found that males had decreased decision thresholds during initial learning, whereas females maintained a consistently higher drift rate. Pharmacological manipulations revealed that PLC inactivation reduced the decision threshold for all rats, indicating that less information was needed to make a choice in the absence of normal PLC processing. μ-Opioid receptor stimulation of the PLC had the opposite effect, raising the decision threshold and reducing bias in the decision process toward high-value stimuli. These effects were observed without any impact on the rats’ choice preferences. Our findings suggest that PLC has an inhibitory role in the decision process and regulates the amount of evidence that is required to make a choice. That is, PLC activity controls "when," but not "how," to act.

The extent to which neural representations of fear experience depend on or generalize across the situational context has remained unclear. We systematically manipulated variation within and across three distinct fear-evocative situations including fear of heights, spiders, and social threats. Participants (n = 21; 10 females and 11 males) viewed ~20 s clips depicting spiders, heights, or social encounters and rated fear after each video. Searchlight multivoxel pattern analysis was used to identify whether and which brain regions carry information that predicts fear experience and the degree to which the fear-predictive neural codes in these areas depend on or generalize across the situations. The overwhelming majority of brain regions carrying information about fear did so in a situation-dependent manner. These findings suggest that local neural representations of fear experience are unlikely to involve a singular pattern but rather a collection of multiple heterogeneous brain states.

HIV and AIDS can be prevented. It just takes you.

Staff from OM SportsLink and Campus Crusade for Christ cycled from Pretoria to Cape Town to minister to people in rural villages along the way.

Five OM entities based in South Africa previously working in three separate offices throughout Pretoria have recently united under one roof.

Typically, at least two discarded babies are found in the Mamelodi City Dump every week. AIDS Hope seeks to eliminate this horrible reality.

In October, 140 people take the Table Mountain Challenge in Cape Town and Franschhoek, South Africa, as part of the Freedom Climb.

OM Africa teams and friends gather to read aloud the Word of God and declare its truth over the continent.

OM AIDS Hope, in collaboration with Stanza Bopape Clinic, arranges an event on World AIDS Day 2014 to bring light to the pandemic.

Jabulani, a youth from South Africa affected by HIV, receives help and care from the OM team ministering in his community.

MDT trainees have an opportunity to minister and pray for healing for a lady in Lesotho.

Logos Hope crew members share the Gospel in a hair salon with someone who has never before heard about Jesus.

A South African OMer plans to use her nursing skills to build relationships with Muslim women in the Arabian Peninsula.

For the past two years OM South Africa SportsLink has attended a prestigious rugby tournament to spread the good news to players, coaches and staff.

The AIDS Hope team encourages children in their afterschool program in Mamelodi to share the gospel with the community.

After leading AIDS Hope for the past 11 years, Nico and Alma hand over the leadership of Meetse a Bophelo centre in Mamelodi.

The children at Meetse Bophelo Centre learn to bless their community through the act of giving.

For the OM Africa communications and media team, the latest and greatest thing is a duck.

A kids' camp brings healing and forgiveness in the township of Mamelodi.

During door-to-door ministry in a small village in South Africa, a woman opens up her house.

Twenty students graduate OM Russia’s Discipleship programme with a heart for missions.

OM Russia develops a stream in their Discipleship Centre programme dedicated to training the deaf, so that more deaf students can participate in missions.

A young couple who met on the Internet answers God’s call to missions to help others find Christ using their IT and web design skills.

OMer Sasha looks for solutions to breaking the downward cycle of poverty, neglect and lack of education plaguing two disadvantaged families in Novosibirsk, Siberia.

Discipleship Centre students shared the Gospel with a group of unreached villages during a short-term outreach.

OM Russia had a great kick-off to the STM summer season by serving in a camp for children with disabilities to hear about Christ.

During outreach to a Tatar village, the team met a woman at the well and introduced her to Jesus.

OM Philippines sees signs of hope in the midst of tragic loss while extending help to churches wrecked by Typhoon Pablo (Bopha).

Nineteen boys and girls graduated from Fishport Kids Tutorial Club's day care programme in Manila, Philippines, this month.

Marie Reyes from Australia led the Out of the Comfort Zone Cebu team, and shares lessons she learnt during the two-week outreach.

OM SportsLink hosts a local R4TW race to engage those involved with OM Philippines-Cebu Ministries and encourage people to pray for the nations.

One of the strongest typhoons ever to hit land slammed the Philippines on Friday, 15 November, forcing millions to take shelter. OM Philippines responds.

How OM Philippines is making a long-term difference in the aftermath of Typhoon Haiyan.

OM Philippines brings relief to the earthquake-shattered island of Bohol.

From 8-26 April, OM Philippines will host their annual short-term missions conference GO EXTRA MILE in Palawan for the first time ever.

OM Philippines hosts micro-business workshops that offer a future with hope.

OM Philippines completes their annual mission training and exposure programme in the tribal areas of Palawan, Philippines.

An Out of the Comfort Zone team experiences island life as they bring Christ’s love to children and families on Gilutungan and Kinatarcan Island.

One hundred Filipino teens, aged 12-18 are expected to come to the five-day event of fun, learning and life-changing encounters in Cebu.

God answers two specific prayers during an outreach in Mozambique.

OM Africa partners with Davar Partners International to distribute audio Bibles to those who cannot read.

A shepherd from a Muslim background comes to Jesus thanks to a goat ministry started by OM Mozambique.

Antonio Nipueda (Mozambique) recollects his journey to ministry with OM in Mozambique and the ways their prayers have impacted one village there.

“God is working in this community,” James said. He and other Christians in his village are challenging the culture by living their lives for Christ.