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Complexes that control mRNA stability and translation promote timely cell-state transitions during differentiation by ensuring appropriate expression patterns of key developmental regulators. The Drosophila RNA-binding protein brain tumor (Brat) promotes the degradation of target transcripts during the maternal-to-zygotic transition in syncytial embryos and uncommitted intermediate neural progenitors (immature INPs). We identify ubiquitin-specific protease 5 (Usp5) as a candidate Brat interactor essential for the degradation of Brat target mRNAs. Usp5 promotes the formation of the Brat-deadenylase pre-complex in mitotic neural stem cells (neuroblasts) by facilitating Brat interactions with the scaffolding components of deadenylase complexes. The adaptor protein Miranda binds the RNA-binding domain of Brat, limiting its ability to bind target mRNAs in mitotic neuroblasts. Cortical displacement of Miranda activates Brat-deadenylase complex activity in immature INPs. We propose that the assembly of an enzymatically inactive and RNA-binding-deficient pre-complex poises mRNA degradation machineries for rapid activation, driving timely developmental transitions., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The sketch deals w ith the problems of the poetic letter. During the exemplification of the issue, poems by Julian Przyboś, Cyprian Norwid and Ignacy Krasicki are used. It turns out that important issues can be seen from the perspective of selected, but also deep anthropological problems, arising from the interpretative process. The tools for understanding them are provided by thinkers of post-Husserlian phenomenology, in this case Dietrich von Hildebrand. [ABSTRACT FROM AUTHOR]

Linker histones H1 are essential chromatin components that exist as multiple developmentally regulated variants. In metazoans, specific H1s are expressed during germline development in a tightly regulated manner. However, the mechanisms governing their stage-dependent expression are poorly understood. Here, we address this question in Drosophila, which encodes for a single germline-specific dBigH1 linker histone. We show that during female germline lineage differentiation, dBigH1 is expressed in germ stem cells and cystoblasts, becomes silenced during transit-amplifying (TA) cystocytes divisions to resume expression after proliferation stops and differentiation starts, when it progressively accumulates in the oocyte. We find that dBigH1 silencing during TA divisions is post-transcriptional and depends on the tumour suppressor Brain tumour (Brat), an essential RNA-binding protein that regulates mRNA translation and stability. Like other oocyte-specific variants, dBigH1 is maternally expressed during early embryogenesis until it is replaced by somatic dH1 at the maternal-to-zygotic transition (MZT). Brat also mediates dBigH1 silencing at MZT. Finally, we discuss the situation in testes, where Brat is not expressed, but dBigH1 is translationally silenced too.

Drosophila model is intensively studied for the development of cancer. The diminutive (dMyc), a homolog of the human MYC gene, is responsible for cell-apoptosis and its upregulation is responsible for determining the fate of cancerous growth in humans and Drosophila model. This work implores the requirement of dMyc and its expression as one of the major regulator of cancer with other proteins and repression of dMyc mRNA in Drosophila S2 cells. Here we report protein complex of Argonaute 1 (AGO1), Bag of marbles (Bam), and Brain tumor (Brat) proteins and not the individual factor of this complex repression of dMyc mRNA in Drosophila Schneider 2 cells and promote differentiation in cystoblast of Drosophila ovary. These results exhibit the significant role of this complex, including master differentiation factor Bam with other various differentiation factor Brat and microRNA pathway component AGO1, which may negatively regulate dMyc mRNA and so the dMyc protein. [ABSTRACT FROM AUTHOR]

We used the Beaver Restoration Assessment Tool (BRAT) developed at Utah State University to develop spatially explicit estimates of maximum beaver‐carrying capacity in a 160 km2 watershed in the foothills of the Southern Rockies. The watershed does not currently have beaver but has extensive evidence of past beaver occupation. BRAT uses input data on stream flow, topography, and vegetation. We compared BRAT results using three different types of vegetation inputs: the default LANDFIRE data at 30‐m spatial resolution and pixel‐based and object‐based image analysis (OBIA) with 1‐m resolution National Agriculture Imagery Program imagery. OBIA produced the most accurate results relative to ground‐based vegetation mapping. Changes in vegetation input data resulted in substantial changes in BRAT estimates of beaver‐carrying capacity. Using historic LANDFIRE vegetation data and field evidence of past beaver activity, contemporary beaver‐carrying capacity is much lower than historical capacity throughout the watershed. These changes are especially pronounced in low‐order stream segments, suggesting that beaver reintroduction in this watershed could be facilitated by measures to restore riparian vegetation along low‐order streams. This case study demonstrates the value of using BRAT as a tool prior to beaver reintroduction and stream restoration. [ABSTRACT FROM AUTHOR]

Artykuł przynosi analizę tradycyjnych przekazów ludowych w perspektywie uobecnianego w nich motywu kazirodztwa między siostrą i bratem. Autor zwraca uwagę, że jakkolwiek tytułowy motyw sporadycznie jest przywoływany wprost, to jednak jego zawoalowane formy wydają się występować niemal powszechnie zwłaszcza w prozie ludowej, a przy tym odwołania do symboliki incestualnej można odnaleźć także w konkretnych sytuacjach obrzędowych. Zdaniem autora popularność tego motywu jest pogłosem dawnych mitologicznych wyobrażeń, dla których kanwą był związek małżeński między rodzeństwem.

Drosophila brain tumor (Brat) is a translational repressor belonging to the tripartite motif (TRIM) protein superfamily. During the asymmetric division of Drosophila neuroblasts, Brat localizes at the basal cortex via direct interaction with the scaffolding protein Miranda (Mira), and segregates into the basal ganglion mother cells after cell division. It was previously reported that both the coiled‐coil (CC) and NHL domains of Brat are required for the interaction with Mira, but the underlying structural basis is elusive. Here, we determine the crystal structure of Brat‐CC domain (aa 376‐511) at 2.5 Å, showing that Brat‐CC forms an elongated antiparallel dimer through an unconventional CC structure. The dimeric assembly in Brat‐CC structure is similar to its counterparts in other TRIM proteins, but Brat‐CC also exhibits some distinct structural features. We also demonstrate that the CC domain could not bind Mira by its own, neither does the isolated NHL domain of Brat. Rather, Brat binds to Mira through the CC‐NHL domain tandem, indicating that the function of the CC domain is to assemble Brat‐NHL in dimeric form, which is necessary for Mira binding. [ABSTRACT FROM AUTHOR]

A long non-coding RNA molecule called cherub is a driver of tumor development.

Hampir 70% wilayah Indonesia adalah wilayah perairan. Indonesia menyimpan potensi kekayaan sumber daya kelautan yang masih belum dieksplorasi dan dieksploitasi secara optimal, bahkan sebagian belum diketahui potensi yang sebenarnya. Hal ini mendasari akan pentingnya informasi spasial di wilayah perairan Indonesia. Fenomena naik atau turunnya permukaan laut atau SLA (Sea Level Anomaly) merupakan hal yang sering mengemuka dengan perubahan gerak relatif dari materi suatu planet, bintang, dan benda-benda angkasa lainnya yang diakibatkan aksi tarik menarik atau yang sering disebut dengan pasang surut. Saat ini telah dikembangkan sistem satelit altimetri Jason-1 yang mempunyai obyek penelitian mengamati pasang surut. Pengolahan data biner dari satelit altimetri Jason-1 dilakukan dengan menggunakan beberapa tahapan, yaitu : konversi data, pembentukan grid, dan pemodelan serta analisa trend pasang surut. Pemantauan SLA beserta trend dan analisa pasang surut dilakukan setiap cycle dalam kurun waktu empat tahun (2008-2011).Hasil pemantauan SLA (Sea Level Anomaly) dengan menggunakan data satelit altimetri Jason-1 mulai dari tahun 2008 sampai 2011 diperoleh terjadinya trend pasang tertinggi dan surut terendah di wilayah perairan Indonesia. Hasil penelitian menunjukkan bahwa nilai pasang tertinggi pada tahun 2008 terjadi pada cycle 236 yaitu sebesar 1,9982 m di Laut Arafuru dan nilai surut terendah terjadi pada cycle 236 yaitu sebesar -3,6954 m di Laut Arafuru. Nilai pasang tertinggi pada tahun 2009 terjadi pada cycle 290 sebesar 1,9325 m di Laut Arafuru dan nilai surut terendah terjadi pada cycle 258 sebesar -3,309 m di Laut Arafuru. Nilai pasang tertinggi pada tahun 2010 terjadi pada cycle 308 sebesar 2,1511 m di Laut Arafuru dan nilai surut terendah terjadi pada cycle 297 sebesar -2,8303 m. Nilai pasang tertinggi pada tahun 2011 terjadi pada cycle 345 sebesar 1,8402 m di Laut Arafuru dan nilai surut terendah terjadi pada cycle 348 sebesar -3,57 m. Dalam waktu empat tahun, wilayah perairan Indonesia yang mengalami nilai pasang tertinggi dan surut terendah yaitu di Laut Arafuru.

An outstanding question in developmental neurobiology is how RNA processing events contribute to the regulation of neurogenesis. RNA processing events are increasingly recognized as playing fundamental roles in regulating multiple developmental events during neurogenesis, from the asymmetric divisions of neural stem cells, to the generation of complex and diverse neurite morphologies. Indeed, both asymmetric cell division and neurite morphogenesis are often achieved by mechanisms that generate asymmetric protein distributions, including post-transcriptional gene regulatory mechanisms such as the transport of translationally silent messenger RNAs (mRNAs) and local translation of mRNAs within neurites. Additionally, defects in RNA splicing have emerged as a common theme in many neurodegenerative disorders, highlighting the importance of RNA processing in maintaining neuronal circuitry. RNA-binding proteins (RBPs) play an integral role in splicing and post-transcriptional gene regulation, and mutations in RBPs have been linked with multiple neurological disorders including autism, dementia, amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), Fragile X syndrome (FXS), and X-linked intellectual disability disorder. Despite their widespread nature and roles in neurological disease, the molecular mechanisms and networks of regulated target RNAs have been defined for only a small number of specific RBPs. This review aims to highlight recent studies in Drosophila that have advanced our knowledge of how RBP dysfunction contributes to neurological disease.

While benefit-risk assessment is a key component of the drug development and maintenance process, it is often described in a narrative. In contrast, structured benefit-risk assessment builds on established ideas from decision analysis and comprises a qualitative framework and quantitative methodology. We compare two such frameworks, applying multi-criteria decision-analysis (MCDA) within the PrOACT-URL framework and weighted net clinical benefit (wNCB), within the BRAT framework. These are applied to a case study of natalizumab for the treatment of relapsing remitting multiple sclerosis. We focus on the practical considerations of applying these methods and give recommendations for visual presentation of results. In the case study, we found structured benefit-risk analysis to be a useful tool for structuring, quantifying, and communicating the relative benefit and safety profiles of drugs in a transparent, rational and consistent way. The two frameworks were similar. MCDA is a generic and flexible methodology that can be used to perform a structured benefit-risk in any common context. wNCB is a special case of MCDA and is shown to be equivalent to an extension of the number needed to treat (NNT) principle. It is simpler to apply and understand than MCDA and can be applied when all outcomes are measured on a binary scale. [ABSTRACT FROM AUTHOR]

TRIM-NHL proteins are key regulators of developmental transitions, for example promoting differentiation, while inhibiting cell growth and proliferation, in stem and progenitor cells. Abnormalities in these proteins have been also associated with human diseases, particularly affecting muscular and neuronal functions, making them potential targets for therapeutic intervention. The purpose of this review is to provide a systematic and comprehensive summary on the most studied TRIM-NHL proteins, highlighting examples where connections were established between structural features, molecular functions and biological outcomes. [ABSTRACT FROM AUTHOR]

In this paper an alternative control solution will be proposed for an educational biped BRAT robot by replacing its SSC-32 servomotor controller with an Arduino R3 development board. Also we will be approaching the problem of adapting the existing electronic circuit to the new requirements and proposing a new application by adding an ultrasonic distance sensor in order to increase the versatility of the robot and make it capable to interact with its environment. [ABSTRACT FROM AUTHOR]

Post-transcriptional regulation of stem cell self-renewal by microRNAs is emerging as an important mechanism controlling tissue homeostasis. Here, we provide evidence that bantam microRNA controls neuroblast number and proliferation in the Drosophila central brain. Bantam also supports proliferation of transit-amplifying intermediate neural progenitor cells in type II neuroblast lineages. The stem cell factors brat and prospero are identified as bantam targets acting on different aspects of these processes. Thus, bantam appears to act in multiple regulatory steps in the maintenance and proliferation of neuroblasts and their progeny to regulate growth of the central brain. [ABSTRACT FROM AUTHOR]

Precise control of the range of signalling molecule action is crucial for correct cell fate patterning during development. For example, Drosophila ovarian germline stem cells (GSCs) are maintained by exquisitely short-rangeBMP signalling fromthe niche. In the absence of BMP signalling, one GSC daughter differentiates into a cystoblast (CB) and this fate is stabilised by Brain tumour (Brat) and Pumilio (Pum)- mediated post-transcriptional repression of mRNAs, including that encoding the Dpp transducer, Mad. However, the identity of other repressed mRNAs and the mechanism of post-transcriptional repression are currently unknown. Here, we identify the Medea and schnurri mRNAs, which encode transcriptional regulators required for activation and/or repression of Dpp target genes, as additional Pum- Brat targets, suggesting that tripartite repression of the transducers is deployed to desensitise the CB to Dpp. In addition, we show that repression by Pum-Brat requires recruitment of the CCR4 and Pop2 deadenylases, with knockdown of deadenylases in vivo giving rise to ectopic GSCs. Consistent with this, Pum-Brat repression leads to poly(A) tail shortening and mRNA degradation in tissue culture cells, and we detect a reduced number of Mad and shn transcripts in the CB relative to the GSC based on single molecule mRNA quantitation. Finally, we show generality of the mechanism by demonstrating that Brat alsoattenuates pMad andDpp signalling range inthe earlyembryo. Together our data serve as a platform for understanding how posttranscriptional repression restricts interpretation of BMPs and other cell signals in order to allow robust cell fate patterning during development. [ABSTRACT FROM AUTHOR]

The article presents a case study on the utility of structured approaches to benefit-risk assessment of pharmaceutical products. The researchers conducted a simulated single-session benefit-risk decision involving three groups using triptan for acute migraine. It implies that the three groups provided consistent value, clarity, and importance of an approval decision.

Background: DNA methylation is an epigenetic event that adds a methyl-group to the 5' cytosine. This epigenetic modification can significantly affect gene expression in both normal and diseased cells. Hence, it is important to study methylation signals at the single cytosine site level, which is now possible utilizing bisulfite conversion technique (i.e., converting unmethylated Cs to Us and then to Ts after PCR amplification) and next generation sequencing (NGS) technologies. Despite the advances of NGS technologies, certain quality issues remain. Some of the more prevalent quality issues involve low per-base sequencing quality at the 3' end, PCR amplification bias, and bisulfite conversion rates. Therefore, it is important to conduct quality assessment before downstream analysis. To the best of our knowledge, no existing software packages can generally assess the quality of methylation sequencing data generated based on different bisulfite-treated protocols. Results: To conduct the quality assessment of bisulfite methylation sequencing data, we have developed a pipeline named MethyQA. MethyQA combines currently available open-source software packages with our own custom programs written in Perl and R. The pipeline can provide quality assessment results for tens of millions of reads in under an hour. The novelty of our pipeline lies in its examination of bisulfite conversion rates and of the DNA sequence structure of regions that have different conversion rates or coverage. Conclusions: MethyQA is a new software package that provides users with a unique insight into the methylation sequencing data they are researching. It allows the users to determine the quality of their data and better prepares them to address the research questions that lie ahead. Due to the speed and efficiency at which MethyQA operates, it will become an important tool for studies dealing with bisulfite methylation sequencing data. [ABSTRACT FROM AUTHOR]

Region-specific atmospheric range correction maps are generated over the Indian tropical region from Jason-1 & Jason-2 radar altimeters data. Seasonal and spatial variability of wet tropospheric correction (WTC), ionospheric correction (IC), dry tropospheric correction (DTC), and sea state bias (SSB) correction are analyzed over the Bay of Bengal and the Arabian Sea. Two year atmospheric range correction data from JASON-1 (2008) & JASON-2 altimeters (2009) has been analyzed where each Jason cycle is exactly 9.9156 days repeat. The monthly and yearly mean variation of the range correction parameters has been studied over the Indian continent. For precise study, four different regions were selected as the Region of Interest in the North & South of the Arabian Sea and Bay of Bengal. WTC, Significant Wave Height (SWH), Wind Speed (WS) and SSB show the higher values during monsoon months. The yearly mean WTC over Indian Tropical region was 26.22 cm in 2008 and 26.20 cm in 2009. SSB Correction values mainly depend on the SWH and wind speed. The yearly mean SSB correction over Indian Tropical region was 6.87 cm in 2008 and 7.02 cm in 2009. DTC values are less during monsoon season and it shows a high value in the month of January. The yearly mean DTC over Indian Tropical region was 230.42 cm in 2008 and 230.43 cm in 2009.The IC values mainly depend on frequency and total electron content (TEC) in the ionosphere which further depends on the solar activity. The yearly mean IC over Indian Tropical region was higher in 2008 (2.98 cm) in comparison to mean IC in 2009 (2.29 cm). This study is useful to understand the variability of atmospheric correction parameters especially over Indian continent. [ABSTRACT FROM AUTHOR]

p53 is a central player in responses to cellular stresses and a major tumor suppressor. The identification of unique molecules within the p53 signaling network can reveal functions of this important transcription factor. Here, we show that brain-expressed RING finger protein (BERP) is a gene whose expression is up-regulated in a p53-dependent manner in human cells and in mice. We generated BERP-deficient mice by gene targeting and demonstrated that they exhibit increased resistance to pentylenetetrazol-induced seizures. Electrophysiological and biochemical studies of cultured cortical neurons of BERP-deficient mice showed a decrease in the amplitude of GABAA receptor (GABAAR)-mediated miniature inhibitory postsynaptic currents as well as reduced surface protein expression of GABAARS containing the γ2-subunit. However. BERP deficiency did not decrease GABAARY2 mRNA levels, raising the possibility that BERP may act at a posttranscriptional level to regulate the intracellular trafficking of GABAARS.. Our results indicate that BERP is a unique p53-regulated gene and suggest a role for p53 within the central nervous system. [ABSTRACT FROM AUTHOR]

The Sokol movement (from the Cyech word for falcon) began in the 1860s in Bohemia as a national gymnastic movement and soon after expanded into other Slavic lands of the Habsburg Monarchy as well. "Sokol in Celje" was founded in 1890 and although initially its purpose was that of a gymnastic society, a national purpose was added to its basic mission in 1903. In 1910, Sokolski dom (Sokol hall) was built in Gaberje and Celjska sokolska župa (a union of Sokol societies in Celje) was founded, which in 1914 split into the branch in Celje and the one in Maribor. After the World War 1, the disintegration of the Habsburg monarchy and the foundation of the Yugoslav state, the activities of the Sokol acquired new dimensions. With the establishment of the Sokol of Kingdom of Yugoslavia in 1929, Sokol became centralistic organisation with the goal "to bring up physically healthy, morally strong and nationally conscious citizens of the Kingdom of Yugoslavia" [ABSTRACT FROM AUTHOR]

Homeostatic regulation of ionic currents is of paramount importance during periods of synaptic growth or remodeling. Our previous work has identified the translational repressor Pumilio (Pum) as a regulator of sodium current (INa ) and excitability in Drosophila motoneurons. In this current study, we show that Pum is able to bind directly the mRNA encoding the Drosophila voltage-gated sodium channel paralytic ( para). We identify a putative binding site for Pumin the 3' end of the para open reading frame (ORF). Characterization of the mechanism of action of Pum, using whole-cell patch clamp and real-time reverse transcription-PCR, reveals that the full-length protein is required for translational repression of para mRNA. Additionally, the cofactor Nanos is essential for Pum-dependent para repression, whereas the requirement for Brain Tumor (Brat) is cell type specific. Thus, Pum-dependent regulation of INa in motoneurons requires both Nanos and Brat, whereas regulation in other neuronal types seemingly requires only Nanos but not Brat. We also show that Pum is able to reduce the level of nanos mRNA and as such identify a potential negative-feedback mechanism to protect neurons from overactivity of Pum. Finally, we show coupling between INa ( para) and IK (Shal) such that Pum-mediated change in para results in a compensatory change in Shal. The identification of para as a direct target of Pum represents the first ion channel to be translationally regulated by this repressor and the location of the binding motif is the first example in an ORF rather than in the canonical 3'-untranslated region of target transcripts. [ABSTRACT FROM AUTHOR]

Objective: The Barrow Ruptured Aneurysm Trial (BRAT) was a single-center trial that compared endovascular coiling to microsurgical clipping in patients treated for aneurysmal subarachnoid hemorrhage (aSAH). However, because patients in the BRAT were treated more than 15 years ago, and because there have been advances since then-particularly in endovascular techniques-the relevance of the BRAT today remains controversial. Some hypothesize that these technical advances may reduce retreatment rates for endovascular intervention. In this study, the authors analyzed data for the post-BRAT (PBRAT) era to compare microsurgical clipping with endovascular embolization (coiling and flow diverters) in the two time periods and to examine how the results of the original BRAT have influenced the practice of neurosurgeons at the study institution., Methods: In this retrospective cohort study, the authors evaluated patients with saccular aSAHs who were treated at a single quaternary center from August 1, 2007, to July 31, 2019. The saccular aSAH diagnoses were confirmed by cerebrovascular experts. Patients were separated into two cohorts for comparison on the basis of having undergone microsurgery or endovascular intervention. The primary outcome analyzed for comparison was poor neurological outcome, defined as a modified Rankin Scale (mRS) score > 2. The secondary outcomes that were compared included retreatment rates for both therapies., Results: Of the 1014 patients with aSAH during the study period, 798 (79%) were confirmed to have saccular aneurysms. Neurological outcomes at ≥ 1-year follow-up did not differ between patients treated with microsurgery (n = 451) and those who received endovascular (n = 347) treatment (p = 0.51). The number of retreatments was significantly higher among patients treated endovascularly (32/347, 9%) than among patients treated microsurgically (6/451, 1%) (p < 0.001). The retreatment rate after endovascular treatment was lower in the PBRAT era (9%) than in the BRAT (18%)., Conclusions: Similar to results from the BRAT, results from the PBRAT era showed equivalent neurological outcomes and increased rates of retreatment among patients undergoing endovascular embolization compared with those undergoing microsurgery. However, the rate of retreatment after endovascular intervention was much lower in the PBRAT era than in the BRAT.

Objective: The SAFIRE grading scale is a novel, computable scale that predicts the outcome of aneurysmal subarachnoid hemorrhage (aSAH) patients in acute follow-up. However, this scale also may have prognostic significance in long-term follow-up and help guide further management., Methods: The records of all patients enrolled in the Barrow Ruptured Aneurysm Trial (BRAT) were retrospectively reviewed, and the patients were assigned SAFIRE grades. Outcomes at 1 year and 6 years post-aSAH were analyzed for each SAFIRE grade level, with a poor outcome defined as a modified Rankin Scale score > 2. Univariate analysis was performed for patients with a high SAFIRE grade (IV or V) for odds of poor outcome at the 1- and 6-year follow-ups., Results: A total of 405 patients with confirmed aSAH enrolled in the BRAT were analyzed; 357 patients had 1-year follow-up, and 333 patients had 6-year follow-up data available. Generally, as the SAFIRE grade increased, so did the proportion of patients with poor outcomes. At the 1-year follow-up, 18% (17/93) of grade I patients, 22% (20/92) of grade II patients, 32% (26/80) of grade III patients, 43% (38/88) of grade IV patients, and 75% (3/4) of grade V patients were found to have poor outcomes. At the 6-year follow-up, 29% (23/79) of grade I patients, 24% (21/89) of grade II patients, 38% (29/77) of grade III patients, 60% (50/84) of grade IV patients, and 100% (4/4) of grade V patients were found to have poor outcomes. Univariate analysis showed that a SAFIRE grade of IV or V was associated with a significantly increased risk of a poor outcome at both the 1-year (OR 2.5, 95% CI 1.5-4.2; p < 0.001) and 6-year (OR 3.7, 95% CI 2.2-6.2; p < 0.001) follow-ups., Conclusions: High SAFIRE grades are associated with an increased risk of a poor recovery at late follow-up.

Puf family proteins are translational regulators essential to a wide range of biological processes, including cell fate specification, stem cell self-renewal, and neural function. Yet, despite being associated with hundreds of RNAs, the underlying mechanisms of Puf target specification remain to be fully elucidated. In Drosophila , Pumilio - a sole Puf family protein - is known to collaborate with cofactors Nanos (Nos) and Brain Tumor (Brat); however, their roles in target specification are not clearly defined. Here, we identify Bag-of-marbles (Bam) as a new Pum cofactor in repression of Mothers against dpp ( mad ) mRNAs, for which Nos is known to be dispensable. Notably, our data show that Nos (but not Bam) was required for Pum association with hunchback ( hb ) mRNAs, a well-known target of Pum and Nos. In contrast, Bam (but not Nos) was required for Pum association with mad mRNAs. These findings show for the first time that Pum target specificity is determined not independently but in collaboration with cofactors., (© 2019 The Author(s).)

An outstanding question in developmental neurobiology is how RNA processing events contribute to the regulation of neurogenesis. RNA processing events are increasingly recognized as playing fundamental roles in regulating multiple developmental events during neurogenesis, from the asymmetric divisions of neural stem cells, to the generation of complex and diverse neurite morphologies. Indeed, both asymmetric cell division and neurite morphogenesis are often achieved by mechanisms that generate asymmetric protein distributions, including post-transcriptional gene regulatory mechanisms such as the transport of translationally silent messenger RNAs (mRNAs) and local translation of mRNAs within neurites. Additionally, defects in RNA splicing have emerged as a common theme in many neurodegenerative disorders, highlighting the importance of RNA processing in maintaining neuronal circuitry. RNA-binding proteins (RBPs) play an integral role in splicing and post-transcriptional gene regulation, and mutations in RBPs have been linked with multiple neurological disorders including autism, dementia, amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), Fragile X syndrome (FXS), and X-linked intellectual disability disorder. Despite their widespread nature and roles in neurological disease, the molecular mechanisms and networks of regulated target RNAs have been defined for only a small number of specific RBPs. This review aims to highlight recent studies in Drosophila that have advanced our knowledge of how RBP dysfunction contributes to neurological disease. [ABSTRACT FROM AUTHOR]