Human papillomavirus (HPV) is a prevalent cause of mucosal and cutaneous infections and underlying conditions ranging from benign warts to anogenital and oropharyngeal cancers affecting both males and females, notably cervical cancer. Cervical cancer is the fourth leading cause of cancer deaths among women globally and is the most impactful in low- and middle-income countries (LMICs), where the costs of screening and licensed L1-based HPV vaccines pose significant barriers to comprehensive administration. Additionally, the licensed L1-based HPV vaccines fail to protect against all oncogenic HPV types. This study generated three independent lots of an L2-based target antigen (LBTA), which was engineered from conserved linear L2-protective epitopes (aa11-88) from five human alphapapillomavirus genotypes in E. coli under cGMP conditions and adjuvanted with aluminum phosphate. Vaccination of rabbits with LBTA generated high neutralizing antibody titers against all 17 HPV types tested, surpassing the nine types covered by Gardasil®9. Passive transfer of naïve mice with LBTA antiserum revealed its capacity to confer protection against vaginal challenge with all 17 αHPV types tested. LBTA shows stability at room temperature over >1 month. Standard in vitro and in vivo toxicology studies suggest a promising safety profile. These findings suggest LBTA\'s promise as a next-generation vaccine with comprehensive coverage aimed at reducing the economic and healthcare burden of cervical and other HPV+ cancers in LMICs, and it has received regulatory approval for a first-in-human clinical study (NCT05672966).

High risk human papillomavirus (HPV) infection is responsible for 99 % of cervical cancers and 5 % of all human cancers worldwide. HPV infection requires the viral genome (vDNA) to gain access to nuclei of basal keratinocytes of epithelium. After virion endocytosis, the minor capsid protein L2 dictates the subcellular retrograde trafficking and nuclear localization of the vDNA during mitosis. Prior work identified a cell-permeable peptide termed SNX1.3, derived from the BAR domain of sorting nexin 1 (SNX1), that potently blocks the retrograde and nuclear trafficking of EGFR in triple negative breast cancer cells. Given the importance of EGFR and retrograde trafficking pathways in HPV16 infection, we set forth to study the effects of SNX1.3 within this context. SNX1.3 inhibited HPV16 infection by both delaying virion endocytosis, as well as potently blocking virion retrograde trafficking and Golgi localization. SNX1.3 had no effect on cell proliferation, nor did it affect post-Golgi trafficking of HPV16. Looking more directly at L2 function, SNX1.3 was found to impair membrane spanning of the minor capsid protein. Future work will focus on mechanistic studies of SNX1.3 inhibition, and the role of EGFR signaling and SNX1-mediated endosomal tubulation, cargo sorting, and retrograde trafficking in HPV infection.

Adjectives in English and Mandarin are typically prenominal, but the corresponding grammatical rules vary in subtle ways. Our event-related potential (ERP) study shows that native speakers of both languages rely on similar processing mechanisms when reading sentences with anomalous noun-adjective order (e.g., the vase *white) in their first language, reflected by a biphasic N400-P600 profile. Only Mandarin native speakers showed an additional N400 on grammatical adjectives (e.g., the white vase), potentially due to atypical word-by-word presentation of lexicalized compounds. English native speakers with advanced Mandarin proficiency were tested in both languages. They processed ungrammatical noun-adjective pairs in English like English monolinguals (N400-P600), but only exhibited an N400 in Mandarin. The absent P600 effect corresponded to their (surprisingly) low proficiency with noun-adjective violations in Mandarin, questioning simple rule transfer from English grammar.

High risk human papillomavirus (HPV) infection is responsible for 99% of cervical cancers and 5% of all human cancers worldwide. HPV infection requires the viral genome (vDNA) to gain access to nuclei of basal keratinocytes of epithelium. After virion endocytosis, the minor capsid protein L2 dictates the subcellular retrograde trafficking and nuclear localization of the vDNA during mitosis. Prior work identified a cell-permeable peptide termed SNX1.3, derived from the BAR domain of sorting nexin 1 (SNX1), that potently blocks the retrograde and nuclear trafficking of EGFR in triple negative breast cancer cells. Given the importance of EGFR and retrograde trafficking pathways in HPV16 infection, we set forth to study the effects of SNX1.3 within this context. SNX1.3 inhibited HPV16 infection by both delaying virion endocytosis, as well as potently blocking virion retrograde trafficking and Golgi localization. SNX1.3 had no effect on cell proliferation, nor did it affect post-Golgi trafficking of HPV16. Looking more directly at L2 function, SNX1.3 was found to impair membrane spanning of the minor capsid protein. Future work will focus on mechanistic studies of SNX1.3 inhibition, and the role of EGFR signaling and SNX1- mediated endosomal tubulation, cargo sorting, and retrograde trafficking in HPV infection.

UNASSIGNED: This paper examines the productive vocabulary skills of five groups of English-Hebrew bilinguals in Israel and the United States. The juxtaposition of these five groups allows us to simultaneously compare performance across dominance profiles, acquisition contexts (L2 learned in school, HL maintained at home, immigration and immersion), and countries (Israel and the USA).
UNASSIGNED: A total of 185 participants took part in study: Hebrew-dominant heritage English speakers, Hebrew-dominant L2-English speakers, English-dominant heritage Hebrew speakers, and English-dominant L2-Hebrew speakers in the US and in Israel. They were all administered the MINT assessment in both languages, as well as background questionnaires. We then employ network modeling based on a secondary data analysis of background questionnaires to consider how each group\'s lexical proficiency ties in to reported input factors.
UNASSIGNED: The MINT results indicate clear language dominance in all the groups except Hebrew-dominant heritage English speakers, who show balanced proficiency in both their languages. The network models indicate key distinctions between the groups as a function of linguistic context, and we assess our findings in the context of recent work on quantifying the bilingual experience.

The brain processes underlying the distinction between emotion-label words (e.g. happy, sad) and emotion-laden words (e.g. successful, failed) remain inconclusive in bilingualism research. The present study aims to directly compare the processing of these two types of emotion words in both the first language (L1) and second language (L2) by recording event-related potentials (ERP) from late Chinese-English bilinguals during a lexical decision task. The results revealed that in the early word processing stages, the N170 emotion effect emerged only for L1 negative emotion-laden words and L2 negative emotion-label words. In addition, larger early posterior negativity (EPN) was elicited by emotion-laden words than emotion-label words in both L1 and L2. In the later processing stages, the N400 emotion effect was evident for L1 emotion words, excluding positive emotion-laden words, while it was absent in L2. Notably, L1 emotion words elicited enhanced N400 and attenuated late positive complex (LPC) compared to those in L2. Taken together, these findings confirmed the engagement of emotion, and highlighted the modulation of emotion word type and valence on word processing in both early and late processing stages. Different neural mechanisms between L1 and L2 in processing written emotion words were elucidated.

The goal of this article is to illustrate the use of MRI for exploring bi- and multi-lingual articulatory strategies. One male and one female speaker recorded sets of static midsagittal MRIs of the whole vocal tract, producing vowels as well as consonants in various vowel contexts in either the male\'s two or the female\'s three languages. Both speakers were native speakers of English (American and Australian English, respectively), and both were fluent L2 speakers of French. In addition, the female speaker was a heritage speaker of Croatian. Articulatory contours extracted from the MRIs were subsequently used at three progressively more compact and abstract levels of analysis. (1) Direct comparison of overlaid contours was used to assess whether phones analogous across L1 and L2 are similar or dissimilar, both overall and in specific vocal tract regions. (2) Consonant contour variability along the vocal tract due to vowel context was determined using dispersion ellipses and used to explore the variable resistance to coarticulation for non-analogous rhotics and analogous laterals in Australian, French, and Croatian. (3) Articulatory modeling was used to focus on specific articulatory gestures (tongue position and shape, lip protrusion, laryngeal height, etc.) and then to explore the articulatory strategies in the speakers\' interlanguages for production of the French front rounded vowel series. This revealed that the Australian and American speakers used different strategies to produce the non-analogous French vowel series. We conclude that MRI-based articulatory data constitute a very rich and underused source of information that amply deserves applications to the study of L2 articulation and bilingual and multi-lingual speech.

A second generation of prophylactic human papillomavirus (HPV) vaccines based on the minor capsid protein L2 has entered clinical trials as promising alternative to meet the gaps left out by the current vaccines concerning type-restricted protection, high costs and low penetrance in immunization programs of lowand middle-income countries. Most of the serological assays available to assess anti-HPV humoral responses are, however, not well suited for measuring vaccine-induced anti-L2 antibody responses.
In this work, we have advanced our automated, purely add-on High-Throughput Pseudovirion-Based Neutralization Assay (HT-PBNA) in an L2-oriented approach for measuring antibody-mediated neutralization of HPV types 6/16/18/31/33/52/58.
With the optimized settings, we observed 24- to 120-fold higher sensitivity for detection of neutralizing Ab to the L2 protein of HPV6, HPV16, HPV18, and HPV31, compared to the standard HT-PBNA. Alternatively, we have also developed a highly sensitive, cell-free, colorimetric L2-peptide capture ELISA for which the results were strongly concordant with those of the advanced neutralization assay, named HT-fc-PBNA. These two high-throughput scalable assays represent attractive approaches to determine antibody-based correlates of protection for the HPV L2 vaccines that are to come.

This study investigates the production of Arabic intervocalic geminate obstruents as produced by American L2 learners of Arabic. The participants of the study were 24 Arabic learners (12 advanced, 12 beginners) at North Georgia University and 12 native speakers of Jordanian Arabic (the control group). An examination of the results reveals that native speakers of Arabic and advanced Arabic learners pattern similarly while the beginner Arabic learners show a different pattern. Native speakers as well as advanced L2 learners of Arabic maintain a contrast between geminate and singleton consonants in terms of consonant duration while beginner L2 leaners do not. Unlike the case of the beginner L2 learners, the duration of the preceding vowel is found to be shorter before a geminate in native speakers and advanced L2 learners. However, the duration of vowels following a geminate is not affected across all proficiency levels. Further, the results suggest that the place and manner of articulation have no effect on the production of geminate consonants for both native and advanced L2 learners. Finally, voicing of geminates is found to have a significant effect on the duration of geminates, in favor of voiceless geminates, among native speakers and beginner L2 learners.

Human papillomaviruses (HPVs) can increase the proliferation of infected cells during HPV-driven abnormalities, such as cervical cancer or benign warts. To date, more than 200 HPV genotypes have been identified, most of which are classified into three major genera: Alphapapillomavirus, Betapapillomavirus, and Gammapapillomavirus. HPV genomes commonly encode two structural (L1 and L2) and seven functional (E1, E2, E4-E7, and E8) proteins. L2, the minor structural protein of HPVs, not only serves as a viral capsid component but also interacts with various human proteins during viral infection. A recent report revealed that L2 of HPV16 recruits polo-like kinase 1 (Plk1), a master regulator of eukaryotic mitosis and cell cycle progression, for the delivery of viral DNA to mitotic chromatin during HPV16 infection. In this study, we verified the direct and potent interactions between the polo-box domain (PBD) of Plk1 and PBD-binding motif (S-S-pT-P)-containing phosphopeptides derived from L2 of HPV16/HPV18 (high-risk alphapapillomaviruses), HPV5b (low-risk betapapillomavirus), and HPV4 (low-risk gammapapillomavirus). Subsequent structural determination of the Plk1 PBD bound to the HPV18 or HPV4 L2-derived phosphopeptide demonstrated that they interact with each other in a canonical manner, in which electrostatic interactions and hydrogen bonds play key roles in sustaining the complex. Therefore, our structural and biochemical data imply that Plk1 is a broad binding target of L2 of various HPV genotypes belonging to the Alpha-, Beta-, and Gammapapillomavirus genera.