Sunday, March 24, 2024

Found in translation: Letters from a multilingual island - BBC.com - Translation

He spotlights his translation of 18th-Century Malay tale Hikayat Raja Babi as an example of how the storytelling styles in translation have varied across generations and cultures, even with the same source material.

While obscure, the fantastical story of Hikayat Raja Babi has seen a multiplicity of translations, which, he says, “point to an interconnected textual world that’s dazzlingly fantastical, yet relatable to its audience in terms of its struggles.”

Translating intent over the literal

The art of translation sometimes takes a more abstract form when ensuring cross-cultural idiosyncrasies can be understood by an audience different to the originally intended one. Historical texts and literature dealing with fiction tend to function somewhat metaphorically, and so, a unique set of challenges arises when translators have to present anecdotal narratives to an audience unfamiliar with certain lived experiences.

“I feel, as a producer [and] translator, I’d like for there to be some frustration when encountering a text,” Dr Nazry says. “And the way to go about it as a translator is to selectively leave in some of the text’s original words, such that, in context, [the reader] can guess at the meaning of the work.”

You might observe such a technique in translated works when words have been phonetically converted from the text’s original language. While this might be a challenge for translators as it demands both artistic and cultural sensibilities, it also presents its own reward to readers who seek to have their views broadened, granting translated works a new role.

“One of the pleasures of life is to think in different modes and move outside your comfort zone,” he says. I think casual readers need that kind of mental flexibility and challenge.”

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Saturday, March 23, 2024

Florida school district pulls dictionaries, encyclopedias from shelves to review for sexual content - Yahoo News Australia - Dictionary

A view of the Florida State Capitol building in Tallahassee, Florida. (Getty Images)
A view of the Florida State Capitol building in Tallahassee, Florida. (Getty Images)

A Florida school district has pulled hundreds of books to determine whether they should be permanently removed from schools, including several dictionaries and encyclopedias.

The Escambia County School District compiled a list of more than 1,600 books to be pulled from school shelves for “further review by media specialists,” to determine if they will be permanently removed, according to their website.

That list of books that could be banned pending review includes five dictionaries — such as Merriam-Webster’s Elementary Dictionary — and eight encyclopedias.

This review is to ensure the school district complies with Florida’s House Bill 1069, which requires the suspension of materials “alleged to contain pornography or obscene depictions of sexual conduct, as identified in current law, pending resolution of an objection to the material.” The law, signed by Governor Ron DeSantis, went into effect on 1 July 2023.

Superintendent Keith Leonard said in a statement it is inaccurate to say the district has imposed a ban on this list of more than 1,600 books.

“I want to clarify that our district has not imposed a ‘ban’ on over 1600 books,” Mr Leonard said. “Additionally, the dictionary has not been banned in our district.”

“Our school district, and especially our dedicated media specialists, remain committed to adhering to all statutes and regulations, while also providing valuable and varied literacy opportunities for every student,” he continued.

The fact that many of these books are even under review reveals a concerning trend in Florida, Kasey Meehan, program director for PEN America’s Freedom to Read project, told The Independent.

“This demonstrates that there is a chilled atmosphere in Florida where we’re seeing dictionaries being pulled to be considered under a law that rejects sexual content in schools,” Ms Meehan said.

“Even though these books may likely go back when we’re talking about encyclopedias and dictionaries, the idea that they’re pulled out of extreme caution just to meet this legislation is alarming,” she continued.

A spokesperson for the Florida Freedom To Read Project told The Independent the review in Escambia is “ridiculous.”

“The language in the law is bad, and the guidance from the Florida Department of Education is irresponsible,” the spokesperson said. “They are the ones with the power to fix this. Until then, districts will continue to ‘err on the side of caution’ as they have been told to do at the expense of our children’s education.

Instances of book bans in Florida — taking place under HB 1069 as well as HB 1557, better known as the “Don’t Say Gay” bill — have disproportionately affected books authored by or written about people of colour and members of the LGBTQ+ community.

Both parents and national organisations are fighting back on bans throughout the state.

PEN America filed a complaint last year against Escambia County School District and the Escambia County School Board alleging an earlier set of book bans and restrictions violated students’ right to free speech and equal protection under the law, according to a press release from the organization.

Oral arguments for the complaint began on Wednesday, 10 January.

Meanwhile, a federal district judge ruled this week that another lawsuit from PEN America could move forward challenging a Florida panhandle school district’s removal of several books about race and the LGBTQ+ community.

The Independent has contacted the Escambia County School District and members of the Escambia County School Board for comment.

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Friday, March 22, 2024

New translation device aims to help TSA agents, travelers communicate at PHL - NBC Philadelphia - Translation

Going through the TSA checkpoint at the airport can be a stressful experience. Now, imagine that on top of that stress, you can't understand what the officers are saying to you.

Well, a new translation tool that fits in the palm of your hand is being tested at the Philadelphia International Airport with the hope of helping travelers who are not only limited speaking English but who are deaf or hard of hearing and those who are blind or have low vision.

Léelo en español aquí

"I meet people on a daily basis who do not speak English here at the airport," TSA officer Julio Rodriguez said as he explained why this new device is so critical.

A TSA officer or a traveler can speak into the device in their native tongue and it will translate that message into the selected language.

The device not only audibly reads the message out loud, but it also displays the message on its screen.

The hand-held unit on the left has translated “Please take off your shoes” in Spanish. The unit on the right has it translated into Vietnamese. (TSA photo)

These devices are part of a TSA pilot program being tested out at ten airports across the country, including PHL.

"We need to be able to communicate with our travelers," Christine Assili, of the TSA, said.

It's a device that's smaller than a smartphone, but it can translate more than 80 languages.

“Many times there’s miscommunication which of course when there is miscommunication there is misunderstanding and that’s the last thing we want for the traveling public," Assili explained.

The TSA says they've seen some challenges while testing them out including mistranslations that make them rephrase what they're trying to say, but they've also seen the benefit.

“I think with this device it will make it more convenient for us and easier for the passengers," TSA officer Youssef Sabiri told NBC10.

The devices are wireless and run off of WiFi or data connection. TSA officials say that the devices do not need to be connected to anything so they can be moved to wherever they're needed.

Last year, 28 million people traveled through the airport and 3.6 million of those landed on international flights.

“It’s a great place just to hear the energy and the languages...but also even better to be able to help folks along their journey," Denise Bailey, of the Philadelphia International Airport, said.

The devices join several other language access programs at PHL.

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Branched chemically modified poly(A) tails enhance the translation capacity of mRNA - Nature.com - Translation

Abstract

Although messenger RNA (mRNA) has proved effective as a vaccine, its potential as a general therapeutic modality is limited by its instability and low translation capacity. To increase the duration and level of protein expression from mRNA, we designed and synthesized topologically and chemically modified mRNAs with multiple synthetic poly(A) tails. Here we demonstrate that the optimized multitailed mRNA yielded ~4.7–19.5-fold higher luminescence signals than the control mRNA from 24 to 72 h post transfection in cellulo and 14 days detectable signal versus <7 days signal from the control in vivo. We further achieve efficient multiplexed genome editing of the clinically relevant genes Pcsk9 and Angptl3 in mouse liver at a minimal mRNA dosage. Taken together, these results provide a generalizable approach to synthesize capped branched mRNA with markedly enhanced translation capacity.

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Fig. 1: Conceptualization of chimeric mRNA bearing multiple poly(A) tails.
Fig. 2: Mechanistic characterization of mRNA stabilization by branched poly(A) tails.
Fig. 3: Multitail mRNA exhibited prolonged protein expression in vivo.
Fig. 4: Multiplexed genome editing in vivo using stabilized Cas9 mRNA.

Data availability

NGS data were deposited to the NCBI Sequence Read Archive database under the accession code PRJNA107297178. All data supporting the findings of the presented study are listed in the article and Supplementary Information is available upon reasonable request.

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Acknowledgements

We thank the MIT Department of Chemistry Instrument Facility for providing instrument access and N. Ye (MIT) for assistance on protein purification. We thank H. Zeng (Broad Institute) for his help in designing the STARmap/RIBOmap probes. We also thank other members of X.W.’s laboratory for helpful discussion throughout the project. X.W. acknowledges the support from the Searle Scholars Program, Thomas D. and Virginia W. Cabot Professorship, E. Scolnick Professorship, Ono Pharma Breakthrough Science Initiative Award, Merkin Institute Fellowship, and NIH DP2 New Innovator Award (1DP2GM146245-01). A.H. is a National Science Foundation Graduate Research Fellow. A.H. and D.R.L. were supported by NIH U01AI142756, R35GM118062, RM1HG009490 and the Howard Hughes Medical Institute (HHMI). This article is subject to HHMI’s Open Access to Publications policy. HHMI lab heads have previously granted a nonexclusive CC BY 4.0 license to the public and a sublicensable license to HHMI in their research articles. Pursuant to those licenses, the author-accepted manuscript of this article can be made freely available under a CC BY 4.0 license immediately upon publication.

Author information

Authors and Affiliations

Authors

Contributions

X.W. conceived the project. H.C. and X.W. designed experiments. H.C., D.L., J.G., A.A., Y.Z., J.T., J.R., A.H., F.K. and M.W. performed the experiments. H.C., J.G., S.L., A.H. and J.H. performed data analysis. X.W. supervised the work. H.C. and X.W. wrote the paper with input from all authors.

Corresponding author

Correspondence to Xiao Wang.

Ethics declarations

Competing interests

X.W., H.C., A.A. and J.G. are inventors on patent applications related to branched RNA. X.W. is a scientific cofounder, consultant and equity holder of Stellaromics and Convergence Therapeutics. D.R.L. is a cofounder, consultant and equity holder of Beam Therapeutics, Prime Medicine, Pairwise Plants, Chroma Medicine, Exo Therapeutics and Nvelop Therapeutics. The other authors declare no competing interests.

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Nature Biotechnology thanks the anonymous reviewers for their contribution to the peer review of this work.

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Extended data

Extended Data Fig. 1 Screening of oligonucleotide crosslinking chemistry.

(a) Summary of oligonucleotide chemical conjugation methods. Screening was performed using 15-nt poly-deoxyadenosine model substrates at micromolar concentrations. Modification handles were incorporated through oligonucleotide solid phase synthesis, followed by amine-NHS labeling and HPLC purification. (b) Gel electrophoresis of crude thiol-ene/yne oligonucleotide conjugation of 15-nt model substrates containing only one conjugation handle. (c) Gel electrophoresis of crude CuAAC and IEDDA 30-nt oligonucleotides bearing three alkyne/trans-cyclooctene handles reacting with 30-nt azide/tetrazine modified oligo. (d) Preliminary dual luciferase assay using branched mRNA prepared from CuAAC product mixture without HPLC purification using different equivalents of branched oligos versus stem oligo. Branching oligos contained modifications on the last six bases with either natural (5′ to 3′) or reversed (3′ to 5′) directionality. Time-course assay was performed as outlined in Fig. 1. n = 3 independent transfections for each construct. Mean ± s.e.m. P values were calculated by ordinary two-sided one-way ANOVA (comparison of means across time points). Gels are representative of at least two experiments.

Source data

Extended Data Fig. 2 Synthesis and characterization of topologically augmented branched mRNA.

(a-c) Representative HPLC purification and gel electrophoresis characterizations of branched oligonucleotides (oligo) containing 1-3 branching poly(A) tails. Fractions containing the desired products (boxed) were pooled and isolated. (d) Schematics of preparation of firefly luciferase (FLuc) mRNA constructs lacking poly(A) tail before ligation. FLuc mRNA without template encoded poly(A) tail was ligated to a scramble (non-polyA) stem oligo with 3′ end modifications (six phosphorothioate/2MOE at 3′ and terminal dideoxycytidine modifications) and internal alkyne (5-octadiynyl deoxyuridine or OU), with or without conjugation to 5′ azide labeled scramble or poly(A) branches with 3′ end modifications (the same as the stem oligo). (e) RNase H characterization of branched mRNA-oligo conjugates with branched poly(A) or scramble tails. The branching topology was confirmed by further band shift on TBU gel. (f) Branched poly(A) sequence, rather than chemical modifications alone, conferred enhanced protein expression over time. Relative FLuc luminescence was normalized to the scramble OU only oligo ligated mRNA at indicated time points. n = 3 independent transfections for each construct. Mean ± s.e.m. P values were calculated by two-sided unpaired t-test (with Welch’s correction) against the scramble OU + scramble azide construct at corresponding time points. (g) RNase H characterization of branched mRNA-oligo conjugates with multiple ploy(A) tails. mRNA with full-length hemoglobin UTRs and template encoded 100A-tail was ligated to 0 (mock ligation), 30 A, 60 A, or oligos with one, two, or three branched poly(A) tails and characterized by RNase H assay. The branching topology was confirmed by further band shift on TBU gel. Gels are representative of at least two experiments.

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Extended Data Fig. 3 Dissecting the effects of branched poly(A) tails on mRNA stability and translation efficiency.

(a) Representative STARmap/RIBOmap images were acquired under the same confocal imaging settings from three independent experiments for each condition. STARmap versus RIBOmap characterization of different modified Firefly luciferase (FLuc) mRNA constructs and STARmap characterization of internal control Renilla luciferase (RLuc) mRNA were performed as outlined in Fig. 2. DAPI (blue), nuclei; FLuc amplicons (magenta); RLuc amplicons (yellow). Colocalized FLuc/RLuc amplicons in STARmap (white dots) were lipid transfection vesicles and were excluded from downstream quantification. Scale bar = 100 µm. (b-c) Violin plots of single-cell quantification of FLuc STARmap/RIBOmap amplicons. P values were calculated by ordinary two-sided two-way ANOVA. (d) Decay kinetics of internal control RLuc luminescence outlined in Fig. 2c normalized to luminescence at 8 hrs post transfection. n = 3 independent transfections. P values were calculated by ordinary two-sided two-way ANOVA (with Geisser-Greenhouse correction, decay across time points).

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Extended Data Fig. 4 Branched poly(A) tails bind PABPC1 protein.

(a) Electrophoretic mobility shift assay of three branched poly(A) oligo with varying concentrations of GST-tagged recominant human PABPC1 protein (PABPC1-GST). The stem oligo was labeled with Alexa Fluore 546 at 5′end. Both stem and branching poly(A)’s were 30 nt and modified with PS-2MOE at the last six bases and ddC at the 3′ end. (b) Gel shift assay of the same modified poly(A) oligo without branching. Gels are representative of at least two experiments.

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Extended Data Fig. 5 Chemical and topological augmentation stabilized poly(A) tails against nuclease degradation in vitro.

(a-d) Evaluation of chemically and topologically modified poly(A) tails in CAF1-CCR4 deadenylation assay. Four different Alexa-546 labeled poly(A) oligos were subjected to deadenylation using recombinant CAF1/CCR4 protein complex over the course of 110 min: linear unmodified 60 A oligo (a), end modified (six PS-2MOE at 3′ and terminal dideoxycytidine, the same set of modifications for all other oligos) 30 A oligo (b), end modified 30 A stem oligo + unmodified 30 A branches (c), and end modified stabilized 30 A stem oligo + end modified 30 A branches (d). (e-h) Evaluation of chemically and topologically modified poly(A) tails in HeLa cell lysate. Alexa-546 labeled poly(A) oligos (the same four constructs used in a-d) were subjected to digestion in HeLa cytosolic lysate for 220 min: linear unmodified 60 A oligo (e), end modified 30 A oligo (f), end modified 30 A stem oligo + unmodified 30 A branches (g), and end modified 30 A stem oligo + end modified 30 A branches (h). Gels were representative of two experiments.

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Extended Data Fig. 6 Multi-tailed mRNA depends on the canonical eIF4-eIF3 translation initiation mechanism.

(a) Timeline of the knockdown (KD) experiments. HeLa cells were treated with siRNA cocktails targeting the corresponding eIFs 48 hrs post siRNA transfection, cells were reseeded and transfected with mRNA followed by protein quantification after 6 hrs. Successful knockdowns were confirmed by western blots and RT-qPCR at 48 hrs. (b,c,e) KD experiments for eIF4E/eIF4G/eIF3D. (d) Comparison of multi-tailed mRNA to regular mRNA in 4EGI-1 treated in vitro translation assay using rabbit reticulocyte lysate (RRL). Luciferase expressions were normalized to the wild-type condition for each construct. Mean± s.e.m. n = 3. P values were calculated by two-sided unpaired t-test for intra-construct comparison (KD vs WT) and by two-sided one-way ANOVA for cross-construct comparison. Western blots were representative of two experiments.

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Extended Data Fig. 7 Comparison of UTR optimized circRNA and multi-tailed mRNA using secreted NanoLuc reporter.

(a) Gel electrophoresis of circRNA encoding secreted Nanoluc (IL6-Nluc) generated through IVT, backsplicing, and enriched by RNase R treatment. Successful circularization was confirmed by RNase R resistance and slower mobility on TBU gel compared to corresponding intron-free linear RNA. (b) Comparison of UTR optimized circRNA and multi-tailed mRNA using IL6-NLuc 1 day after transfection with indicated amounts of RNA. Mock lig./mod-only/multi-tail mRNAs contained optimized UTRs, full m1ψ replacement and 100 A through IVT with mock ligation (mock lig.), ligated to modification-only oligo (mod-only), or modified multi-tailed oligo (multi-tail). CircRNAs were designed to contain optimized HRV IRES (with proximal loop Apt-eIF4G insertion) and 3′-PABP binding motif without addition of modified nucleotides. Cells were cultured in phenol red-free media. On each day, media was completely harvested and renewed with 150 μL fresh media and 5 μL of old media was diluted and used for luciferase assay. n = 3 independent transfections in each biological condition. Mean ± s.e.m. (c) IL6-Nluc signal over 14 days. n = 3 independent transfections in each biological condition. Mean ± s.e.m.

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Extended Data Fig. 8 Paired STARmap/RIBOmap effectively characterize the quantity and translatability of mRNA constructs delivered by LNP to murine liver.

(a) Schematics for evaluating two-gene STARmap/RIBOmap experiments in different lobes of murine liver. 2:1 NLuc/FLuc mRNA were co-encapsulated in LNP and administered by retro-orbital (R.O.) injection. 6 hrs post mRNA injection, the mouse liver was harvested in five lobes (caudate, left/right medial and lateral lobes). Each lobe was sections into two adjacent 10-μm slices, with one slice profiled by NLuc STARmap and FLuc STARmap and the other slice profiled by NLuc RIBOmap and Fluc STARmap. Whole sections were profiled in 291×291 μm2 tiles. (b, c) Quantification of numbers of NLuc and FLuc amplicons in each tile. n = 3379/3199 tiles. Slopes (NLuc/FLuc) were calculated by linear regression (least-square, Q = 5% for outlier rejection).

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Extended Data Fig. 9 Delivery of CRISPR editing using chemically and topologically modified mRNA.

(a) Comparison of Cas9 expression by western blot 48 hrs post transfection in HEK293T-uGFP cells. NLS, nuclear localization signal. Western blots were representative of two experiments. (b) FACS gating strategy for uGFP positive HEK293T cells. (c) Exemplary single-cell uGFP quantification for cells treated with unligated Cas9 mRNA only (Cas9-only) without sgRNAs, or with mock lig./mod-only/multi-tail Cas9 mRNA co-transfected with two sgRNAs. FACS were performed 72 hrs post mRNA transfection. n = 11845/10983/12334/12131 single cells. P value was calculated by two-sided one-way ANOVA. (d-h) Serum levels of Pcsk9 protein (d), Angptl3 protein (e), free cholesterol (f), total cholesterol (g), and triglyceride (h) over 4 weeks normalized to the Cas9-only group. Mean ± s.e.m. n = 4, biological replicates.

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Supplementary information

Reporting Summary

Supplementary Table 1

Compiled sequences of genes/oligos/probes used in the study.

Source data

Source Data Figs. 1–4 and Extended Data Figs. 1–9

Compiled statistical source data for all figures presented.

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Chen, H., Liu, D., Guo, J. et al. Branched chemically modified poly(A) tails enhance the translation capacity of mRNA. Nat Biotechnol (2024). https://ift.tt/yUZ2p9t

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Thursday, March 21, 2024

Leeds lingo: Your ultimate urban dictionary for understanding Leeds student slang - The Tab - Dictionary

Your rundown of terms like Bakery, Monty B and RPP

With almost two semesters done and dusted, it’s probably fair to say that those of you that came to Leeds in September have about settled down.

You know where the libraries are – although you might still be plucking up the courage to enter Brotherton main circle – you’ve got the bus routes pretty much nailed down – that is, just the 56 – and you’ve probably found yourself a favourite coffee shop to go and study in – let me guess, it’s the Laidlaw or Business School Caffe Nero.

You’ve likely also started to come across, and maybe even begin using, some of the local Leeds Uni language: an ‘I’m going to Eddy B today’ here, and a ‘fancy a Bakery?’ there. However, for the freshers, and even us ancient final years, who are still left scratching heads at some of the terms flying around campus, we’ve compiled a handy guide to all the student lingo you need to know.

1. Eddy B

Let’s start nice and straightforward – Eddy B is short for Edward Boyle, one of the libraries on campus. It’s probably the most social out of all the libraries (and by social I mean loud) so best to avoid if you need to get any serious work done.

2. Town

Again, not too difficult, but if anyone says they’re going to town, they mean Leeds city centre. It’s just that ‘town’ makes people feel like they’re locals.

3. BNOC

A term that most people secretly wish could be used to describe them, BNOC stands for Big Name On Campus. In reality, it’s a bit of a pipe dream given there are tens of thousands of students in Leeds, but it’s still nice to aspire towards.

4. Monty B

Another B – this time to refer to the student halls, Montague Burton, near Woodhouse. We can kind of see the rationale behind this one, Montague Burton is a bit of a mouthful, after all.

5. Bakery

Technically, ‘Bakery’ does refer to a bakery, but more specifically it stands for Bakery164, the sandwich and coffee shop opposite the Parkinson Building. Getting your lunch here is not for the weak of heart because it’s always absolutely heaving, not just with students from Leeds Uni, but also those from the nearby sixth form college.

6. Dev

If there’s one thing Leeds students love, it’s giving accommodations unnecessarily short names. Here, Dev is short for Devonshire Hall, which is found just below James Baillie (JB – no, I’m not joking).

7. RPP

One that makes sense, RPP stands for Royal Park Pub, a student local in the middle of Hyde Park. Its £2 pints on Tuesdays and Friday karaoke nights have made it so that people will genuinely queue two hours in the cold for a chance to get in, and who can blame them.

8. Rah

It might have become an internet joke, but ‘rah’ is also definitely a term I’ve heard used seriously on campus. At this point, I’m not sure anyone knows exactly what it’s supposed to mean, but broadly speaking it’s a posh word used to express disbelief or excitability, depending on the situation.

9. Baccy

Look, I couldn’t not follow rah with baccy – the Hyde Park girlies have claimed it as their ironic (and sometimes unironic) tagline. For the non smokers out there, however, baccy is short for tobacco.

10. Brude

Another pub, Brude stands for Brudenell Social Club, a top tier establishment – I’m not biased – in the centre of Hyde Park. Aside from a good atmosphere, Brude also has a games room full of pool tables, perfect for a chill one with your friends, and a stacked line up of artists who’ll you find performing in one of its two event spaces every week.

11. Book club

Now someone could well be talking about an actual book club, but it’s more likely that they’re talking about Hyde Park Book Club, a favourite bar with Leeds students. It has a cosy candlelit main room for in the colder months and its outdoor seating becomes a sun trap in the summer, so if you’ve not already, we’d recommend checking it out.

12. Charlie Mo

Here is where I start to get caught out – Charlie Mo apparently refers to Charles Morris, one of the accommodations on campus. Maybe I’m getting too old but this is definitely a new one that’s started doing the rounds since my first year.

13. Henny P

What did I say – Leeds students are a sucker for an abbreviation. I could just about allow Charlie Mo, but Henny P for Henry Price? A line needs to be drawn somewhere and this might it.

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