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Background: The Alice in Wonderland syndrome (AIWS) is a transient neurological disturbance characterized by sensory distortions most frequently associated with migraine in adults. Some lines of evidence suggest that AIWS and migraine might share common pathophysiological mechanisms, therefore we set out to investigate the common and distinct neurophysiological alterations associated with these conditions in migraineurs. Methods: We conducted a case-control study acquiring resting-state fMRI data from 12 migraine patients with AIWS, 12 patients with migraine with typical aura (MA) and 24 age-matched healthy controls (HC). We then compared the interictal thalamic seed-to-voxel and ROI-to-ROI cortico-cortical resting-state functional connectivity between the 3 groups. Results: We found a common pattern of altered thalamic connectivity in MA and AIWS, compared to HC, with more profound and diffuse alterations observed in AIWS. The ROI-to-ROI functional connectivity analysis highlighted an increased connectivity between a lateral occipital region corresponding to area V3 and the posterior part of the superior temporal sulcus (STS) in AIWS, compared to both MA and HC. Conclusion: The posterior STS is a multisensory integration area, while area V3 is considered the starting point of the cortical spreading depression (CSD), the neural correlate of migraine aura. This interictal hyperconnectivity might increase the probability of the CSD to directly diffuse to the posterior STS or deactivating it, causing the AIWS symptoms during the ictal phase. Taken together, these results suggest that AIWS in migraineurs might be a form of complex migraine aura, characterized by the involvement of associative and multisensory integration areas. [ABSTRACT FROM AUTHOR]

Visual field maps in human early extrastriate areas (V2 and V3) are traditionally thought to form mirror-image representations which surround the primary visual cortex (V1). According to this scheme, V2 and V3 form nearly symmetrical halves with respect to the calcarine sulcus, with the dorsal halves representing lower contralateral quadrants, and the ventral halves representing upper contralateral quadrants. This arrangement is considered to be consistent across individuals, and thus predictable with reasonable accuracy using templates. However, data that deviate from this expected pattern have been observed, but mainly treated as artifactual. Here, we systematically investigate individual variability in the visual field maps of human early visual cortex using the 7T Human Connectome Project (HCP) retinotopy dataset. Our results demonstrate substantial and principled inter-individual variability. Visual field representation in the dorsal portions of V2 and V3 was more variable than in their ventral counterparts, including substantial departures from the expected mirror-symmetrical patterns. In addition, left hemisphere retinotopic maps were more variable than those in the right hemisphere. Surprisingly, only one-third of individuals had maps that conformed to the expected pattern in the left hemisphere. Visual field sign analysis further revealed that in many individuals the area conventionally identified as dorsal V3 shows a discontinuity in the mirror-image representation of the retina, associated with a Y-shaped lower vertical representation. Our findings challenge the current view that inter-individual variability in early extrastriate cortex is negligible, and that the dorsal portions of V2 and V3 are roughly mirror images of their ventral counterparts.

To support the successful adoption of digital measures into internal decision making and evidence generation for medical product development, we present a unified lexicon to aid communication throughout this process, and highlight key concepts including the critical role of participant engagement in development of digital measures. We detail the steps of bringing a successful proof of concept to scale, focusing on key decisions in the development of a new digital measure: asking the right question, optimized approaches to evaluating new measures, and whether and how to pursue qualification or acceptance. Building on the V3 framework for establishing verification and analytical and clinical validation, we discuss strategic and practical considerations for collecting this evidence, illustrated with concrete examples of trailblazing digital measures in the field.

Objective: To investigate the efficacy of modified percutaneous balloon compression for simple third branch pain and its postoperative complications. Methods: Clinical data and surgical records of 132 patients with third branch pain treated with percutaneous balloon compression from March 2015 to May 2019 were retrospectively analyzed, of which 81 cases were in the modified group and 51 cases were in the classic group. The modified technique was to compress again at the foramen ovale to enhance the compression in V3 after compression of the Gasserian ganglion. Results: In the modified group, the overall therapeutic efficiency was 96.3%, with 77 patients (95.1%) having immediate postoperative pain relief and one patient (1.2%) having occasional pain without the need for medication. In the classic group, immediate postoperative pain relief was seen in 43 cases (84.3%), and two patients (3.9%) had occasional pain with no need for medication. The rate of complete pain relief was significantly higher in the modified group than in the classic group (P < 0.05). Postoperative follow-up ranged from 14 to 48 months. The pain-free rates were 77.8 and 54.9% in the modified and classic groups, respectively. The incidence of facial numbness in the region of the first branch was significantly lower than in the classic group (P < 0.001). Conclusion: The modified procedure has significant advantages over the classic procedure in improving surgical efficacy, reducing postoperative recurrence rate, and decreasing postoperative numbness in the region, and can be used to treat simple trigeminal neuralgia in the third branch. [ABSTRACT FROM AUTHOR]

ObjectiveTo investigate the efficacy of modified percutaneous balloon compression for simple third branch pain and its postoperative complications.MethodsClinical data and surgical records of 132 patients with third branch pain treated with percutaneous balloon compression from March 2015 to May 2019 were retrospectively analyzed, of which 81 cases were in the modified group and 51 cases were in the classic group. The modified technique was to compress again at the foramen ovale to enhance the compression in V3 after compression of the Gasserian ganglion.ResultsIn the modified group, the overall therapeutic efficiency was 96.3%, with 77 patients (95.1%) having immediate postoperative pain relief and one patient (1.2%) having occasional pain without the need for medication. In the classic group, immediate postoperative pain relief was seen in 43 cases (84.3%), and two patients (3.9%) had occasional pain with no need for medication. The rate of complete pain relief was significantly higher in the modified group than in the classic group (P < 0.05). Postoperative follow-up ranged from 14 to 48 months. The pain-free rates were 77.8 and 54.9% in the modified and classic groups, respectively. The incidence of facial numbness in the region of the first branch was significantly lower than in the classic group (P < 0.001).ConclusionThe modified procedure has significant advantages over the classic procedure in improving surgical efficacy, reducing postoperative recurrence rate, and decreasing postoperative numbness in the region, and can be used to treat simple trigeminal neuralgia in the third branch.

Background: Revascularization for extracranial vertebral artery dissection or vertebral artery atherosclerotic occlusive lesions caused by vertebrobasilar insufficiency or posterior circulation infarction is relatively rare. When bypassing the cervical external carotid artery (ECA) or common carotid artery (CCA) using a radial artery (RA) or saphenous vein (SV) graft, it is difficult to determine whether the recipient site should be the V2 or V3 portion., Observations: In case 1, cervical ECA-RA-V3 bypass was performed for bilateral extracranial vertebral artery dissection with the onset of ischemia, and cervical CCA-SV-V3 bypass was added 12 days later. Nine years after surgery, the bilateral vertebral artery dissection had improved, and the patient still had a patent bypass. In case 2, cervical ECA-RA-V2 bypass was performed for arteriosclerotic bilateral extracranial vertebral artery occlusion. The bypass was patent 5 years after surgery. The postoperative course was uneventful in both patients., Lessons: The authors present cases of posterior fossa revascularization using the vertebral artery V3 and V2 portions via skull base surgery and note that it is important to consider each patient's individual characteristics when selecting the V3 or V2 portion.

Stimulating broadly neutralizing antibodies (bnAbs) directly from germline remains a barrier for HIV vaccines. HIV superinfection elicits bnAbs more frequently than single infection, providing clues of how to elicit such responses. We used longitudinal antibody sequencing and structural studies to characterize bnAb development from a superinfection case. BnAb QA013.2 bound initial and superinfecting viral Env, despite its probable naive progenitor only recognizing the superinfecting strain, suggesting both viruses influenced this lineage. A 4.15 Å cryo-EM structure of QA013.2 bound to native-like trimer showed recognition of V3 signatures (N301/N332 and GDIR). QA013.2 relies less on CDRH3 and more on framework and CDRH1 for affinity and breadth compared to other V3/glycan-specific bnAbs. Antigenic profiling revealed that viral escape was achieved by changes in the structurally-defined epitope and by mutations in V1. These results highlight shared and novel properties of QA013.2 relative to other V3/glycan-specific bnAbs in the setting of sequential, diverse antigens.

Summary: Increasing evidence suggests infants develop unique neutralizing antibody (nAb) responses to HIV compared to adults. Here, we dissected the nAb response of an infant whose virus is in clinical trials as a vaccine immunogen, with a goal of characterizing the broad responses in the infant to this antigen. We isolated 73 nAbs from infant BG505 and identified a large number of clonal families. Twenty-six antibodies neutralized tier 2 viruses—in some cases, viruses from the same clade as BG505, and in others, a different clade, although none showed notable breadth. Several nAbs demonstrated antibody-dependent cellular cytotoxicity activity and targeted the V3 loop. These findings suggest an impressive polyclonal response to HIV infection in infant BG505, adding to the growing evidence that the nAb response to HIV in infants is polyclonal—a desirable vaccine response to a rapidly evolving virus like HIV.

Human immunodeficiency virus (HIV) is a pathogen that infects blood cells, using CD4 molecule and two cell receptors CCR5 and CXCR4. The other major actor is gp120/gp41 viral protein complex, which interacts with receptors. Here, the presence of synonymous mutations associated with HIV-1 tropism and the related RNA secondary-structure in HIV-1 infected patients was evaluated. The analysis includes gp120-sequences from 340 HIV-1 subtype-B infected patients, all retrieved from Los Alamos database and with phenotypic HIV tropism determination based on recombinant-virus entry-assay. Frequencies of all nucleotide substitutions were calculated. Mfold and RNAfold algorithms were used to predict RNA secondary-structure of HIV-1. Nineteen codons in V2/C2, V3 and C3 domains were found to be closely related to CCR5 and CXCR4. Additionally, in X4-sequences, gp120 gca303gcu and gua222guc synonymous mutations are positively related to the gp120 S11R and T8A/I codons in V3 protein domain. Furthermore, gua222guc increases stability of the viral RNA secondary-structure. Probably, it would not be surprising if a novel escape viral strategy therapy will be related to the gp120 synonymous mutations. Moreover, in relation to the pivotal role played by gp120 in polyvalent vaccine approaches, the impact of gp120 synonymous mutations may play an important role in HIV entry into the cell. [ABSTRACT FROM AUTHOR]

Accurate co-receptor tropism (CRT) determination is critical for making treatment decisions in HIV management. We created a genotypic tropism prediction tool by utilizing the case-based reasoning (CBR) technique that attempts to solve new problems through applying the solution from similar past problems. V3 loop sequences from 732 clinical samples with diverse characteristics were used to build a case library. Additional sequence and molecular properties of the V3 loop were examined and used for similarity assessment. A similarity metric was defined based on each attribute's frequency in the CXCR4-using viruses. We implemented three other genotype-based tropism predictors, support vector machines (SVM), position specific scoring matrices (PSSM), and the 11/25 rule, and evaluated their performance as the ability to predict CRT compared to Monogram's enhanced sensitivity Trofile(®) assay (ESTA). Overall concordance of the CBR based tropism prediction algorithm was 81%, as compared to ESTA. Sensitivity to detect CXCR4 usage was 90% and specificity was at 73%. In comparison, sensitivity of the SVM, PSSM, and the 11/25 rule were 85%, 81%, and 36% respectively while achieving a specificity of 90% by SVM, 75% by PSSM, and 97% by the 11/25 rule. When we evaluated these predictors in an unseen dataset, higher sensitivity was achieved by the CBR algorithm (87%), compared to SVM (82%), PSSM (76%), and the 11/25 rule (33%), while maintaining similar level of specificity. Overall this study suggests that CBR can be utilized as a genotypic tropism prediction tool, and can achieve improved performance in independent datasets compared to model or rule based methods.

Hemifacial spasm (HFS) is often caused by compression of the vertebral artery (VA) directly or indirectly as a result of other intervening vessels, so VA-associated HFS is difficult to treat. Recently, we have achieved good surgical outcomes using a far lateral approach and temporary clamping of V3 for VA-associated HFS. Herein, we present our method with an accompanying surgical video. From April 2018 to March 2019, 5 patients with VA-associated HFS underwent surgery, and pre-and postoperative symptoms and postoperative complications were evaluated. In the procedure, the suboccipital muscles were dissected and reflected layer by layer, and the extracranial VA (V3) was secured within the suboccipital triangle. A lateral suboccipital craniotomy followed by far lateral drilling was made to widen the surgical field from the caudolateral side. After reducing the VA flow pressure by temporary clamping of V3, the VA was transposed using a Teflon sling via two triangular space above and below the lower cranial nerves (LCNs). Causative vessels included direct VA compression in two cases and intervening vessels in three cases. The symptoms disappeared in four cases and improved satisfactorily in one case. One patient had mild hearing loss (approximately 10 dB) and hoarseness, but both improved 9 months after surgery. There was no postoperative cerebrospinal fluid leakage in any cases. A wide surgical field via the far lateral approach and the temporary clamping of V3 contributed to thorough observation of the REZ and safe and complete VA transposition. [ABSTRACT FROM AUTHOR]

Although Icelandic is a verb second language (V2), it sometimes allows for V3 orders. In this paper, I focus on a type of Icelandic V3 which consists of an adverbial adjunct occurring in front of wh-questions and present the results of a pilot study that investigated the effects of the length of prosodic break and clause type in relation to V3 structures. Participants were presented with an adverbial clause sandwiched between two sentences (A and B), of which the latter varied between a wh-question and a subject-initial sentence. The breaks between the adverbial and the sentences varied in length. The task was to judge which sentence (A or B) was longer, with the response reflecting which sentence the adverbial clause was parsed with. The results indicate that both the clause type of the B sentence and the length of the prosodic break between the adverbial and the B sentence had a significant effect on how the sentences were parsed.

Abstract Background The endonasal transpterygoid approach has been very popular as a standard approach to the pterygopalatine and infratemporal fossa. However, its implications actually extend beyond these regions to include access to the middle cranial fossa and parapharyngeal space. Objective The aim was to illustrate the anatomical landmarks of the endoscopic transpterygoid approach especially the mandibular nerve and clinical implication of this approach through illustrated case presentation. Materials and methods A cadaveric study was performed on three cadaveric adult specimens. Endoscopic medial maxillectomy, Sturman Canefield approach, and completion of transpterygoid approach were done to visualize the different anatomical landmarks, especially the mandibular nerve. An example of clinical application of transpterygoid approach is an illustrated case to biopsy a perineural spread of squamous cell cancer along the mandibular nerve in the lateral wall of cavernous sinus. Conclusion Endoscopic transpterygoid approach is very useful to resect most of benign and some malignant tumors that involve the infratemporal fossa and middle cranial fossa. Good understanding of the V3 anatomy helps in the resection of tumors extending to the infratemporal fossa and poststyloid parapharyngeal space.

Despite anti-retroviral therapy (ART) interventions for HIV+ pregnant mothers, over 43,000 perinatal infections occur yearly. Understanding risk factors that lead to mother-to-child transmission (MTCT) of HIV are critical. We evaluated maternal and infant plasma binding and neutralizing antibody responses in a drug-naïve, CRF01_AE infected MTCT cohort from Thailand to determine associations with transmission risk. Env V3-specific IgG and neutralizing antibody responses were significantly higher in HIV- infants, as compared to HIV+ infants. In fact, infant plasma neutralizing antibodies significantly associated with non-transmission. Conversely, increased maternal Env V3-specific IgG and neutralizing antibody responses were significantly associated with increased transmission risk, after controlling for maternal viral load. Our results highlight the importance of evaluating both maternal and infant humoral immune responses to better understand mechanisms of protection, as selective placental antibody transport may have a role in MTCT. This study further emphasizes the complex role of Env-specific antibodies in MTCT of CRF01_AE HIV. [ABSTRACT FROM AUTHOR]

Commissural interneurons (CINs) mediate interactions between rhythm-generating locomotor circuits located on each side of the spinal cord and are necessary for left-right limb coordination during locomotion. While glutamatergic V3 CINs have been implicated in left-right coordination, their functional connectivity remains elusive. Here, we addressed this issue by combining experimental and modeling approaches. We employed Sim1Cre/+; Ai32 mice, in which light-activated Channelrhodopsin-2 was selectively expressed in V3 interneurons. Fictive locomotor activity was evoked by NMDA and 5-HT in the isolated neonatal lumbar spinal cord. Flexor and extensor activities were recorded from left and right L2 and L5 ventral roots, respectively. Bilateral photoactivation of V3 interneurons increased the duration of extensor bursts resulting in a slowed down on-going rhythm. At high light intensities, extensor activity could become sustained. When light stimulation was shifted toward one side of the cord, the duration of extensor bursts still increased on both sides, but these changes were more pronounced on the contralateral side than on the ipsilateral side. Additional bursts appeared on the ipsilateral side not seen on the contralateral side. Further increase of the stimulation could suppress the contralateral oscillations by switching to a sustained extensor activity, while the ipsilateral rhythmic activity remained. To delineate the function of V3 interneurons and their connectivity, we developed a computational model of the spinal circuits consisting of two (left and right) rhythm generators (RGs) interacting via V0V, V0D, and V3 CINs. Both types of V0 CINs provided mutual inhibition between the left and right flexor RG centers and promoted left-right alternation. V3 CINs mediated mutual excitation between the left and right extensor RG centers. These interactions allowed the model to reproduce our current experimental data, while being consistent with previous data concerning the role of V0V and V0D CINs in securing left–right alternation and the changes in left–right coordination following their selective removal. We suggest that V3 CINs provide mutual excitation between the spinal neurons involved in the control of left and right extensor activity, which may promote left-right synchronization during locomotion.

Commissural interneurons (CINs) mediate interactions between rhythm-generating locomotor circuits located on each side of the spinal cord and are necessary for left-right limb coordination during locomotion. While glutamatergic V3 CINs have been implicated in left-right coordination, their functional connectivity remains elusive. Here, we addressed this issue by combining experimental and modeling approaches. We employed Sim1Cre/+; Ai32 mice, in which light-activated Channelrhodopsin-2 was selectively expressed in V3 interneurons. Fictive locomotor activity was evoked by NMDA and 5-HT in the isolated neonatal lumbar spinal cord. Flexor and extensor activities were recorded from left and right L2 and L5 ventral roots, respectively. Bilateral photoactivation of V3 interneurons increased the duration of extensor bursts resulting in a slowed down on-going rhythm. At high light intensities, extensor activity could become sustained. When light stimulation was shifted toward one side of the cord, the duration of extensor bursts still increased on both sides, but these changes were more pronounced on the contralateral side than on the ipsilateral side. Additional bursts appeared on the ipsilateral side not seen on the contralateral side. Further increase of the stimulation could suppress the contralateral oscillations by switching to a sustained extensor activity, while the ipsilateral rhythmic activity remained. To delineate the function of V3 interneurons and their connectivity, we developed a computational model of the spinal circuits consisting of two (left and right) rhythm generators (RGs) interacting via V0V, V0D, and V3 CINs. Both types of V0 CINs provided mutual inhibition between the left and right flexor RG centers and promoted left-right alternation. V3 CINs mediated mutual excitation between the left and right extensor RG centers. These interactions allowed the model to reproduce our current experimental data, while being consistent with previous data concerning the role of V0V and V0D CINs in securing left–right alternation and the changes in left–right coordination following their selective removal. We suggest that V3 CINs provide mutual excitation between the spinal neurons involved in the control of left and right extensor activity, which may promote left-right synchronization during locomotion. [ABSTRACT FROM AUTHOR]

Integrase-strand-transfer inhibitors (INSTIs) are known to rapidly reduce HIV-1 plasma viral load, replication cycles, and new viral integrations, thus potentially limiting viral evolution. Here, we assessed the role of INSTIs on HIV-1 V3 evolution in a cohort of 89 HIV-1-infected individuals starting an INSTI- (N = 41, [dolutegravir: N = 1; elvitegravir: N = 3; raltegravir: N = 37]) or a non-INSTI-based (N = 48) combined antiretroviral therapy (cART), with two plasma RNA V3 genotypic tests available (one before [baseline] and one during cART). V3 sequences were analysed for genetic distance (Tajima-Nei model) and positive selection (dN/dS ratio). Individuals were mainly infected by B subtype (71.9%). Median (interquartile-range, IQR) plasma viral load and CD4 + T cell count at baseline were 4.8 (3.5–5.5) log10 copies/mL and 207 (67–441) cells/mm3, respectively. Genetic distance (median, IQR) between the V3 sequences obtained during cART and those obtained at baseline was 0.04 (0.01–0.07). By considering treatment, genetic distance was significantly lower in INSTI-treated than in non-INSTI-treated individuals (median [IQR]: 0.03[0.01–0.04] vs. 0.05[0.02–0.08], p = 0.026). In line with this, a positive selection (defined as dN/dS ≥ 1) was observed in 36.6% of V3 sequences belonging to the INSTI-treated group and in 56.3% of non-INSTI group (p = 0.05). Multivariable logistic regression confirmed the independent correlation of INSTI-based regimens with a lower probability of both V3 evolution (adjusted odds-ratio: 0.35 [confidence interval (CI) 0.13–0.88], p = 0.027) and positive selection (even if with a trend) (adjusted odds-ratio: 0.46 [CI 0.19–1.11], p = 0.083). Overall, this study suggests a role of INSTI-based regimen in limiting HIV-1 V3 evolution over time. Further studies are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Primary visual cortex (V1) and extrastriate V2 are necessary for the emergence of visual consciousness, but the effects of involvement of extrastriate V3 on visual consciousness is unclear. The objective of this study was to examine the causal role of V3 in visual consciousness in humans. We combined neuronavigated transcranial magnetic stimulation (TMS) with a computational model of the TMS-induced electric field to test whether or not the intact processing of visual input in V3, like in V1 and V2, is necessary for conscious visual perception. We targeted the stimulation both to V2 and to V3. If TMS of V3 blocks conscious visual perception of stimuli, then activation in V3 is a causally necessary prerequisite for conscious perception of stimuli. According to the alternative hypothesis, TMS of V3 will not block the conscious visual perception of stimuli, because the pathways from V1 to the higher cortical areas that go around V3 provide sufficient visual input for the emergence of conscious visual perception. The results showed that TMS interfered with conscious perception of features, detection of stimulus presence and the ability to discriminate the letter stimuli both when TMS was targeted either to V3 or to V2. For the conscious detection of stimulus presence, the effect was significantly stronger when V2 was stimulated than when V3 was stimulated. The results of the present study suggest that in addition to the primary visual cortex and V2, also V3 causally contributes to the generation of the most basic form of visual consciousness. Importantly, the results also indicate that V3 is necessary for visual perception in general, not only for visual consciousness. • We targeted TMS to V3 while participants performed a visual discrimination task. • To control the stimulation site, computational model of the induced EF was applied. • TMS to V3 blocked conscious perception and decreased objective discrimination. • The data indicates that V3 is necessary for visual perception in general. • The results suggest that V3 contributes to the generation of the visual consciousness. [ABSTRACT FROM AUTHOR]

The goal of our paper is to provide a description of an apparent V3 pattern which is salient with some speakers of the Ghent dialect, illustrated in (1), from Vanacker (1980).Vroeger, die bakten wij vier soorten brood formerly die baked we four sorts bread “We used to bake four kinds of bread.” (Gijzenzele 0.28) (Vanacker, 1980, p. 76)In such examples, what would be an initial adverbial constituent in the root clause vroeger, (“formerly”) is separated from the finite verb by what Vanacker (1980) labels a “pleonastic” element, die, in effect leading to a superficial V3 order. At first sight, this element die is optional and it has no impact on the truth conditions of the proposition that it introduces. (2) is also acceptable in the dialect.(2) Vroeger bakten wij vier soorten brood. formerly baked we four sorts bread “We used to bake four kinds of bread.”In the first part of the paper, we will provide a description of the distribution of die. We will also compare its distribution with that of the more widely distributed resumptive adverbs dan (“then”) and daar (“there”), which are typical of the Germanic V2 languages (Salvesen, 2016). Our account will be based both on authentic data drawn from corpora and from anecdotal observations as well as on the results of elicitations with 10 native speakers of the dialect. In the second part of the paper we provide an analysis in terms of Wolfe's (2016) typology of the syntax of V2. Adopting the articulated structure of CP as elaborated in the cartographic framework, we will propose that die is an overt spell out of the head Force and as such a root complementiser.

Background Trigeminal neuralgia (TN) is a chronic orofacial pain syndrome that presents with debilitating shooting pains in the V3 nerve distribution. The condition is traditionally responsive to anticonvulsant therapy; however, cases that become refractory to medications often require surgical intervention. Case Description We present a case of TN that was treated with minimally invasive trigeminal ablation. The patient presented with a 6-year history of TN that had been resistant to medical management. The patient opted for minimally invasive management, refused stereotactic radiosurgery, and was treated using the minimally invasive trigeminal ablation approach. At 16 weeks postoperatively, the patient reported complete alleviation of pain with minimal sensorineural numbness. Conclusions The endoscopic approach allows for precise targeting through visual guidance, which is ideal in patients undergoing neuroablation for pain within specific nerve distributions. This is the first documented case of an endoscopic minimally invasive transoral approach toward ablative TN management. Highlights • We present a novel transoral approach to trigeminal nerve ablation. • The patient experienced complete relief at 16-week follow-up. • There is minimal residual numbness after the procedure. [ABSTRACT FROM AUTHOR]

Elucidating the structural basis of antibody (Ab) gene usage and affinity maturation of vaccine-induced Abs can inform the design of immunogens for inducing desired Ab responses in HIV vaccine development. Analyses of monoclonal Abs (MAbs) encoded by the same immunoglobulin genes at different stages of maturation can help to elucidate the maturation process. We have analyzed four human anti-V3 MAbs with the same VH1-3*01 and VL3-10*01 gene usage. Two MAbs, TA6 and TA7, were developed from a vaccinee in the HIV vaccine phase I trial DP6-001 with a polyvalent DNA prime/protein boost regimen, and two others, 311-11D and 1334, were developed from HIV-infected patients. The somatic hypermutation (SHM) rates in VH of vaccine-induced MAbs are lower than in chronic HIV infection-induced MAbs, while those in VL are comparable. Crystal structures of the antigen-binding fragments (Fabs) in complex with V3 peptides show that these MAbs bind the V3 epitope with a new cradle-binding mode and that the V3 13-hairpin lies along the antigenbinding groove, which consists of residues from both heavy and light chains. Residues conserved from the germ line sequences form specific binding pockets accommodating conserved structural elements of the V3 crown hairpin, predetermining the Ab gene selection, while somatically mutated residues create additional hydrogen bonds, electrostatic interactions, and van der Waals contacts, correlating with an increased binding affinity. Our data provide a unique example of germ line sequences determining the primordial antigen-binding sites and SHMs correlating with affinity maturation of Abs induced by vaccine and natural HIV infection. IMPORTANCE Understanding the structural basis of gene usage and affinity maturation for anti-HIV-1 antibodies may help vaccine design and development. Antibodies targeting the highly immunogenic third variable loop (V3) of HIV-1 gp120 provide a unique opportunity for detailed structural investigations. By comparing the sequences and structures of four anti-V3 MAbs at different stages of affinity maturation but of the same V gene usage, two induced by vaccination and another two by chronic infection, we provide a fine example of how germ line sequence determines the essential elements for epitope recognition and how affinity maturation improves the antibody's recognition of its epitope. [ABSTRACT FROM AUTHOR]

The goal of our paper is to provide a description of an apparent V3 pattern which is salient with some speakers of the Ghent dialect, illustrated in (1), from Vanacker (1980). Vroeger, die bakten wij vier soorten brood formerly die baked we four sorts bread “We used to bake four kinds of bread.” (Gijzenzele 0.28) (Vanacker, 1980, p. 76) In such examples, what would be an initial adverbial constituent in the root clause vroeger , (“formerly”) is separated from the finite verb by what Vanacker (1980) labels a “pleonastic” element, die, in effect leading to a superficial V3 order. At first sight, this element die is optional and it has no impact on the truth conditions of the proposition that it introduces. (2) is also acceptable in the dialect. (2) Vroeger bakten wij vier soorten brood. formerly baked we four sorts bread “We used to bake four kinds of bread.” In the first part of the paper, we will provide a description of the distribution of die. We will also compare its distribution with that of the more widely distributed resumptive adverbs dan (“then”) and daar (“there”), which are typical of the Germanic V2 languages (Salvesen, 2016). Our account will be based both on authentic data drawn from corpora and from anecdotal observations as well as on the results of elicitations with 10 native speakers of the dialect. In the second part of the paper we provide an analysis in terms of Wolfe's (2016) typology of the syntax of V2. Adopting the articulated structure of CP as elaborated in the cartographic framework, we will propose that die is an overt spell out of the head Force and as such a root complementiser. [ABSTRACT FROM AUTHOR]

The empirical focus of this paper is what looks like a verb third (V3) pattern in West Flemish (WF) in which an adverbial modifier (typically a temporal or conditional adjunct) is followed by a non-inverted subject-initial verb second (V2) root clause. This pattern will be referred to as the non-inverted V3 pattern. This paper has two goals. The first and major aim is to document the WF non-inverted V3 pattern, detailing both its syntactic and its semantic properties, in order to make these data available to the research community at large. We also develop an analysis in line with the hypothesis, substantiated in the paper, that WF is a genuine V2 language and that the apparent V3 data in do not jeopardise this assumption. The core hypothesis is that the initial adjunct in V3 patterns is extra-sentential or ‘main clause-external’ (cf. Broekhuis and Corver in Syntax of Dutch. Verbs and verb phrases. Volume 3: Chapter 14: main clause-external elements, Amsterdam University Press, Amsterdam, 2016. http://www.oapen.org/), and that it combines with a full-fledged V2 clause by virtue of a discourse-structure (cf. Auer in Pragmatics 6:295-322, 1996). That the non-inverted V3 pattern is not acceptable in all varieties of Dutch is accounted for in terms of microvariation in the syntactic derivation of subject-initial V2 sentences. [ABSTRACT FROM AUTHOR]

The third variable (V3) loop of HIV-1 gp120 is an immunodominant region targeted by neutralizing antibodies (nAbs). Despite limited breadth, better characterization of the structural details of the interactions between these nAbs and their target epitopes would enhance our understanding of the mechanism of neutralization and facilitate designing better immunogens to induce nAbs with greater breadth. Recently, we isolated two anti-V3 neutralizing monoclonal antibodies (MAbs), 10A3 and 10A37, from a rabbit immunized with gp120 of the M group consensus sequence. In this study, crystal structures of these MAbs bound to target epitopes were determined. 10A3 binds to the V3 crown (303TRKSIHIGPGRAF317) using the cradle binding mode, similar to human V3 MAbs encoded by IGHV5-51 germ line genes, and its epitope structure resembles that bound to the human antibodies. In contrast, 10A37, which exhibits greater breadth and potency than 10A3, binds the V3 crown and the succeeding stem region (308HIGPGRAFYTTGEI323). Unexpectedly, the 315RAFYTT320 portion of the epitope existed as helical turns, a V3 structure that has not been observed previously. Its main chain-dominated antigen-antibody interactions not only explain the broad neutralization of 10A37 but also show that its epitope is a potential vaccine target to be further evaluated. In conclusion, our study provides novel insights about neutralization-susceptible epitope structures of the V3 loop of HIV-1 gp120 and demonstrates that, despite low amino acid sequence similarity to human antibody germ line genes, rabbits can serve as a useful animal model to evaluate human vaccine candidates. IMPORTANCE The apex crown of V3 of HIV-1 gp120 is the most immunogenic region of the surface glycoprotein, and many MAbs targeting this region have been developed. Structural understanding of V3 crown MAbs not only can help understand how antibody responses target this unique region but also contribute to immunogen design for vaccine development. We present here crystal structures of two neutralizing V3 MAbs, 10A3 and 10A37, developed from a rabbit immunized with gp120. Our analysis of 10A3 in complex with V3 provided a detailed example of how epitope complexity can evolve with affinity maturation, while that of 10A37 revealed a novel V3 binding mode targeting the C-terminal side of the V3 crown and showed that this region can form a helical structure. Our study provides novel insights about neutralization-susceptible V3 epitope structures and demonstrates that rabbits can serve as a useful animal model to evaluate human vaccine candidates. [ABSTRACT FROM AUTHOR]

Vertebrate locomotor circuitry contains distinct classes of ventral spinal cord neurons which each have particular functional properties. While we know some of the genes expressed by each of these cell types, we do not yet know how several of these neurons are specified. Here, we investigate the functions of Tal1, Gata2a, and Gata3 transcription factors in the development of two of these populations of neurons with important roles in locomotor circuitry: V2b neurons and cerebrospinal fluid-contacting Kolmer-Agduhr (KA) neurons (also called CSF-cNs). Our data provide the first demonstration, in any vertebrate, that Tal1 and Gata3 are required for correct development of KA and V2b neurons, respectively. We also uncover differences in the genetic regulation of V2b cell development in zebrafish compared to mouse. In addition, we demonstrate that Sox1a and Sox1b are expressed by KA and V2b neurons in zebrafish, which differs from mouse, where Sox1 is expressed by V2c neurons. KA neurons can be divided into ventral KA" neurons andmore dorsal KA' neurons. Consistent with previous morpholino experiments, our mutant data suggest that Tal1 and Gata3 are required in KA' but not KA" cells, whereas Gata2a is required in KA" but not KA' cells, even though both of these cell types co-express all three of these transcription factors. In gata2a mutants, cells in the KA" region of the spinal cord lose expression ofmost KA" genes and there is an increase in the number of cells expressing V3 genes, suggesting that Gata2a is required to specify KA" and repress V3 fates in cells that normally develop into KA" neurons. On the other hand, our data suggest that Gata3 and Tal1 are both required for KA' neurons to differentiate from progenitor cells. In the KA' region of these mutants, cells no longer express KA' markers and there is an increase in the number of mitotically-active cells. Finally, our data demonstrate that all three of these transcription factors are required for later stages of V2b neuron differentiation and that Gata2a and Tal1 have different functions in V2b development in zebrafish than in mouse. [ABSTRACT FROM AUTHOR]

Introduction: Multiple surgical approaches have been described to access the infratemporal fossa. One of them is the endoscopic endonasal transpterygoid approach to the infratemporal fossa. The endoscopic endonasal transpterygoid approach is considered the best to access the midline structures such as the nasopharynx, Eustachian tube, sella, and clivus. Through this work, we try to describe the anatomical structures and landmarks of the infratemporal fossa from the endosopic endonasal transpterygoid point of view. Methods: A cadaveric study was performed on five adult specimens. Endoscopic medial maxillectomy and complete resection of the posterior wall of the maxillary antrum were performed. Extension of the medial maxillectomy anteriorly was done to reach the lateral part of the infratemporal fossa. Endoscopic Denker’s or Sturman–Canfield approach was done. Dissection of the pterygopalatine fossa was done with identification of maxillary artery branches, V2 (maxillary nerve) and masticatory muscles. Resection of the lateral pterygoid muscle and drilling the lateral pterygoid plate improve exposure of the infratemporal fossa, including V3 (mandibular nerve), which lies posterior to the lateral pterygoid plate. Results: A total of ten infratemporal and pterygopalatine fossae (five cadaveric specimens) were dissected endoscopically using a transpterygoid approach. Dissection of different anatomical structures in the infratemporal fossa was done to describe the anatomical structures and landmarks of the infratemporal fossa. Conclusions: Endoscopic endonasal transpterygoid approach is considered one of the most useful surgical solutions to manage selected tumors that involve the infratemporal fossa. A good understanding of the endoscopic anatomy of infratemporal fossa allows safe and complete resection of lesions arising or extending to infratemporal fossa.

Employing 18S hypervariable regions as molecular markers, we show a sequence analysis of (V3, V4 and V9) hyper-variable regions of the small sub unit (SSU) of different natural strains of the Pyrenomycete, Sordaria fimicola, to examine genetic diversity. Strains were taken from two contrasting environments (Natural and Harsh) from the south facing and north facing slopes of Evolution Canyon, Israel. Sequenced amplicons were introduced to the NCBI database as a query in BLASTN. The query revealed >100% resemblance with the Ascomycota genus Sordaria and the topmost species in this investigation was fimicola. Circular Phylogram showed close relatedness among the strains under study and potential association with the Ascomycetes. This study for the first time reports the variations at the molecular level between strains from two different environments. V3 and V4 regions showed genetic variations at two sites i.e., 212 A (C); 213 G (A) in strains isolated from the stressful environment while V9 showed no polymorphism. Sequences were submitted to NCBI GenBank under the accession numbers; KY001568; KY000838; KY000839 for S3, N5 and N6 strains. 1% cellulose was found effective to enhance the mycelial and perithecial growth. [ABSTRACT FROM AUTHOR]

Specific amino acids within the V3 loop of HIV-1 CRF01_AE envelope glycoprotein that are involved in the interaction with CCR5/CXCR4 coreceptors, are not well characterized. We generated V3 mutants using polymerase chain reaction (PCR)-based site-directed mutagenesis of HIV-1 CRF01_AE R5- env plasmids at specific positions. Mutant viruses were produced by env-pseudotyped virus assay, tested for coreceptor usage using U373.R5 and U373.X4 cells, and viral entry was assessed with luciferase activity measurement. All viruses, harboring either single or double mutations, used the CCR5 coreceptor. However, those containing a single substitution at positions 7, 11, 18, and 32 and those with mutations at positions 5/32 and 18/32 had reduced infectivity. Only virus with arginine substitution at position 11 seemed to be involved in CXCR4 coreceptor usage. Our results suggest that some V3 positions may be necessary for the binding to coreceptor, but not for the switch of coreceptor usage. [ABSTRACT FROM AUTHOR]

For studies of visual cortex organization, mouse is becoming an increasingly more often used model. In addition to its genetic tractability, the relatively small area of cortical surface devoted to visual processing simplifies efforts in relating the structure of visual cortex to visual function. However, the nature of this compact organization can make some comparisons to the much larger non-human primate visual cortex difficult. The squirrel, as a highly visual rodent offers a useful means for better understanding how mouse and monkey cortical organization compares. More in line with primates than their nocturnal rodent cousin, squirrels rely much more on sight and have evolved a larger expanse of cortex devoted to visual processing. To reveal the detailed organization of visual cortex in squirrels, we injected a highly sensitive monosynaptic retrograde tracer (glycoprotein deleted rabies virus) into several locations of primary visual cortex (V1) in California ground squirrels. The resulting pattern of connectivity revealed an organizational scheme in the squirrel that retains some of the basic features of the mouse visual cortex along the medial and posterior borders of V1, but unlike mouse has an elaborate and extensive pattern laterally that is more similar to the early visual cortex organization found in monkeys. In this way, we show that the squirrel can serve as a useful model for comparison to both mouse and primate visual systems, and may help facilitate comparisons between these two very different yet widely used animal models of visual processing. [ABSTRACT FROM AUTHOR]

The development of an effective maternal HIV-1 vaccine that could synergize with antiretroviral therapy (ART) to eliminate pediatric HIV-1 infection will require the characterization of maternal immune responses capable of blocking transmission of autologous HIV to the infant. We previously determined that maternal plasma antibody binding to linear epitopes within the variable loop 3 (V3) region of HIV envelope (Env) and neutralizing responses against easy-to-neutralize tier 1 viruses were associated with reduced risk of peripartum HIV infection in the historic U.S. Woman and Infant Transmission Study (WITS) cohort. Here, we defined the fine specificity and function of the potentially protective maternal V3-specific IgG antibodies associated with reduced peripartum HIV transmission risk in this cohort. The V3-specific IgG binding that predicted low risk of mother-to-child-transmission (MTCT) was dependent on the C-terminal flank of the V3 crown and particularly on amino acid position 317, a residue that has also been associated with breakthrough transmission in the RV144 vaccine trial. Remarkably, the fine specificity of potentially protective maternal plasma V3-specific tier 1 virus-neutralizing responses was dependent on the same region in the V3 loop. Our findings suggest that MTCT risk is associated with neutralizing maternal IgG that targets amino acid residues in the C-terminal region of the V3 loop crown, suggesting the importance of the region in immunogen design for maternal vaccines to prevent MTCT. [ABSTRACT FROM AUTHOR]

The RV144 prime-boost regimen demonstrated efficacy against HIV acquisition while VAX003 and VAX004 did not. Although these trials differed by risk groups, immunization regimens, and immunogens, antibody responses may have contributed to the differences observed in vaccine efficacy. We assessed HIV-specific IgG, both total and subclass, and IgA binding to HIV envelope (Env): gp120 proteins and Cyclic V2 (CycV2) and CycV3 peptides and gp70 V1 V2 scaffolds in these 3 HIV vaccine trials. After two protein immunizations, IgG responses to 92TH023 gp120 (contained in ALVAC-HIV vaccine) were significantly higher in RV144 but responses to other Env were higher in the VAX trials lacking ALVAC-HIV. IgG responses declined significantly between vaccinations. All trials induced antibodies to gp70 V1 V2 but VAX004 responses to 92TH023 gp70 V1 V2 were weak. All CycV2 responses were undetectable in VAX004 while 92TH023 gp70 V1 V2 was detected in both RV144 and VAX003 but MN CycV2 was detected only in VAX003. Multiple protein vaccinations in VAX trials did not improve magnitude or durability of V1 V2 and CycV2 antibodies. Herpes simplex virus glycoprotein D (gD) peptide at the N terminus of AIDSVAX® B/E and B/B gp120 proteins induced antibodies in all trials, although significantly higher in VAX trials. gD peptide induced IgA, IgG1, IgG2, and IgG3 but not IgG4. Multiple protein vaccinations decreased IgG3 and increased IgG4 changing subclass contribution to total IgG. Although confounded by different modes of HIV transmission, higher Env-specific IgA and IgG4 binding antibodies induced in the VAX trials compared to RV144 raises the hypothesis that these differences may have contributed to different vaccine efficacy results. [ABSTRACT FROM AUTHOR]

The V3 loop in the HIV envelope gp120 is one of the immunogenic sites targeted by Abs. The V3 crown in particular has conserved structural elements recognized by cross-reactive neutralizing Abs, indicating its potential contribution in protection against HIV. Crystallographic analyses of anti-V3 crown mAbs in complex with the V3 peptides have revealed that these mAbs recognize the conserved sites on the V3 crown via two distinct strategies: a cradle-binding mode (V3C) and a ladle-binding (V3L) mode. However, almost all of the anti-V3 crown mAbs studied in the past were isolated from chronically HIV-infected individuals. The extents to which the two types of anti-V3 crown Abs are generated by vaccination are unknown. This study analyzed the prevalence of V3C-type and V3L-type Ab responses in HIV-infected individuals and in HIV envelope-immunized humans and animals using peptide mimotopes that distinguish the two Ab types. The results show that both V3L-type and V3C-type Abs were generated by the vast majority of chronically HIV-infected humans, although the V3L-type were more prevalent. In contrast, only one of the two V3 Ab types was elicited in vaccinated humans or animal models, irrespective of HIV-1 envelope clades, envelope constructs (oligomeric or monomeric), and protocols (DNA plus protein or protein alone) used for vaccinations. The V3C-type Abs were produced by vaccinated humans, macaques, and rabbits, whereas the V3L-type Abs were made by mice. The V3C-type and V3L-type Abs generated by the vaccinations were able to mediate virus neutralization. These data indicate the restricted repertoires and the species-specific differences in the functional V3-specific Ab responses induced by the HIV envelope vaccines. The study implies the need for improving immunogen designs and vaccination strategies to broaden the diversity of Abs in order to target the different conserved epitopes in the V3 loop and, by extension, in the entire HIV envelope. [ABSTRACT FROM AUTHOR]

V3-directed antibodies are present in practically all HIV-1 infected patients and in individuals vaccinated with gp120. The levels of maternal V3-directed antibodies were recently shown to correlate with reduced mother to child transmission, and V3 IgGs were found to be a negative correlate of risk in the RV-144 human trial. mAb directed to the tip of the V3 are capable of broad neutralization of Tier-1 and some Tier-2 viruses. Here we report an immunofocusing approach using conformationally constrained V3 peptides of different lengths. Immunofocusing with short constrained V3 peptides following immunizations with long constrained V3 peptides resulted in sera with improved neutralization of Tier-1B viruses in comparison with immunizations with the long constrained peptide alone. Immunizations only with the short constrained peptide were ineffective. Our results demonstrate that immunofocusing with constrained V3 peptides of different lengths could improve the induction of HIV-1 neutralizing antibodies. [ABSTRACT FROM AUTHOR]

Visual field maps in human early extrastriate areas (V2 and V3) are traditionally thought to form mirror-image representations which surround the primary visual cortex (V1). According to this scheme, V2 and V3 form nearly symmetrical halves with respect to the calcarine sulcus, with the dorsal halves representing lower contralateral quadrants, and the ventral halves representing upper contralateral quadrants. This arrangement is considered to be consistent across individuals, and thus predictable with reasonable accuracy using templates. However, data that deviate from this expected pattern have been observed, but mainly treated as artifactual. Here, we systematically investigate individual variability in the visual field maps of human early visual cortex using the 7T Human Connectome Project (HCP) retinotopy dataset. Our results demonstrate substantial and principled inter-individual variability. Visual field representation in the dorsal portions of V2 and V3 was more variable than in their ventral counterparts, including substantial departures from the expected mirror-symmetrical patterns. In addition, left hemisphere retinotopic maps were more variable than those in the right hemisphere. Surprisingly, only one-third of individuals had maps that conformed to the expected pattern in the left hemisphere. Visual field sign analysis further revealed that in many individuals the area conventionally identified as dorsal V3 shows a discontinuity in the mirror-image representation of the retina, associated with a Y-shaped lower vertical representation. Our findings challenge the current view that inter-individual variability in early extrastriate cortex is negligible, and that the dorsal portions of V2 and V3 are roughly mirror images of their ventral counterparts., Competing Interests: FR, AY, EZ, SB, MR, AP No competing interests declared, (© 2023, Ribeiro et al.)

Background: CCR5-coreceptor antagonists can be used for treating HIV-2 infected individuals. Before initiating treatment with coreceptor antagonists, viral coreceptor usage should be determined to ensure that the virus can use only the CCR5 coreceptor (R5) and cannot evade the drug by using the CXCR4 coreceptor (X4-capable). However, until now, no online tool for the genotypic identification of HIV-2 coreceptor usage had been available. Furthermore, there is a lack of knowledge on the determinants of HIV-2 coreceptor usage. Therefore, we developed a data-driven web service for the prediction of HIV-2 coreceptor usage from the V3 loop of the HIV-2 glycoprotein and used the tool to identify novel discriminatory features of X4-capable variants. Results: Using 10 runs of tenfold cross validation, we selected a linear support vector machine (SVM) as the model for geno2pheno[coreceptor-hiv2], because it outperformed the other SVMs with an area under the ROC curve (AUC) of 0.95. We found that SVMs were highly accurate in identifying HIV-2 coreceptor usage, attaining sensitivities of 73.5% and specificities of 96% during tenfold nested cross validation. The predictive performance of SVMs was not significantly different (p value 0.37) from an existing rules-based approach. Moreover, geno2pheno[coreceptorhiv2] achieved a predictive accuracy of 100% and outperformed the existing approach on an independent data set containing nine new isolates with corresponding phenotypic measurements of coreceptor usage. geno2pheno[coreceptor-hiv2] could not only reproduce the established markers of CXCR4-usage, but also revealed novel markers: the substitutions 27K, 15G, and 8S were significantly predictive of CXCR4 usage. Furthermore, SVMs trained on the amino-acid sequences of the V1 and V2 loops were also quite accurate in predicting coreceptor usage (AUCs of 0.84 and 0.65, respectively). Conclusions: In this study, we developed geno2pheno[coreceptor-hiv2], the first online tool for the prediction of HIV-2 coreceptor usage from the V3 loop. Using our method, we identified novel amino-acid markers of X4-capable variants in the V3 loop and found that HIV-2 coreceptor usage is also influenced by the V1/V2 region. The tool can aid clinicians in deciding whether coreceptor antagonists such as maraviroc are a treatment option and enables epidemiological studies investigating HIV-2 coreceptor usage. geno2pheno[coreceptor-hiv2] is freely available at http:// coreceptor-hiv2.geno2pheno.org. [ABSTRACT FROM AUTHOR]

We propose and examine a model for how perisaccadic visual receptive field dynamics, observed in a range of primate brain areas such as LIP, FEF, SC, V3, V3A, V2 and V1, may develop through a biologically plausible process of unsupervised visually guided learning. These dynamics are associated with remapping, which is the phenomenon where receptive fields anticipate the consequences of saccadic eye movements. We find that a neural network model using a local associative synaptic learning rule, when exposed to visual scenes in conjunction with saccades, can account for a range of associated phenomena. In particular, our model demonstrates predictive and presaccadic remapping, responsiveness shifts around the time of saccades, and remapping from multiple directions.

Global motion perception entails the ability to extract the central direction tendency from an extended area of visual space containing widely disparate local directions. A substantial body of evidence suggests that local motion signals generated in primary visual cortex (VI) are spatially integrated to provide perception of global motion, beginning in the middle temporal area (MT) in macaques and its counterpart in humans, hMT. However, V2 and V3 also contain motion-sensitive neurons that have larger receptive fields than those found in VI, giving the potential for spatial integration of motion signals. Despite this, V2 and V3 have been overlooked as sites of global motion processing. To test, free of local-global confounds, whether human V2 and V3 are important for encoding global motion, we developed a visual stimulus that yields a global direction yet includes all possible local directions and is perfectly balanced at the local motion level. We then attempted to decode global motion direction in such stimuli with multivariate pattern classification of fMRI data. We found strong sensitivity to global motion in hMT, as expected, and also in several higher visual areas known to encode optic flow. Crucially, we found that global motion direction could be decoded in human V2 and, particularly, in V3. The results suggest the surprising conclusion that global motion processing is a key function of cortical visual areas V2 and V3. A possible purpose is to provide global motion signals to V6. [ABSTRACT FROM AUTHOR]

Background: HIV-1 entry is a receptor-mediated process directed by the interaction of the viral envelope with the host cell CD4 molecule and one of two co-receptors, CCR5 or CXCR4. The amino acid sequence of the third variable (V3) loop of the HIV-1 envelope is highly predictive of co-receptor utilization preference during entry, and machine learning predictive algorithms have been developed to characterize sequences as CCR5-utilizing (R5) or CXCR4-utilizing (X4). It was hypothesized that while the V3 loop is predominantly responsible for determining co-receptor binding, additional components of the HIV-1 genome may contribute to overall viral tropism and display sequence signatures associated with co-receptor utilization. Results: The accessory protein Tat and the HlV-1 long terminal repeat (LTR) were analyzed with respect to genetic diversity and compared by Jensen-Shannon divergence which resulted in a correlation with both mean genetic diversity as well as the absolute difference in genetic diversity between R5- and X4-genome specific trends. As expected, the V3 domain of the gp120 protein was enriched with statistically divergent positions. Statistically divergent positions were also identified in Tat amino acid sequences within the transactivation and TAR-binding domains, and in nucleotide positions throughout the LTR. We further analyzed LTR sequences for putative transcription factor binding sites using the JASPAR transcription factor binding profile database and found several putative differences in transcription factor binding sites between R5 and X4 HIV-1 genomes, specifically identifying the C/EBP sites I and II, and Sp site III to differ with respect to sequence configuration for R5 and X4 LTRs. Conclusion: These observations support the hypothesis that co-receptor utilization coincides with specific genetic signatures in HIV-1 Tat and the LTR, likely due to differing transcriptional regulatory mechanisms and selective pressures applied within specific cellular targets during the course of productive HIV-1 infection. [ABSTRACT FROM AUTHOR]

It is generally supposed that there is a single, hierarchically organized pathway dedicated to form processing, in which complex forms are elaborated from simpler ones, beginning with the orientation-selective cells of V1. In this psychophysical study, we undertook to test another hypothesis, namely that the brain’s visual form system consists of multiple parallel systems and that complex forms are other than the sum of their parts. Inspired by imaging experiments which show that forms of increasing perceptual complexity (lines, angles and rhombuses) constituted from the same elements (lines) activate the same visual areas (V1, V2 and V3) with the same intensity and latency (Shigihara and Zeki, 2013; 2014), we used backward masking to test the supposition that these forms are processed in parallel. We presented subjects with lines, angles and rhombuses as different target-mask pairs. Evidence in favour of our supposition would be if masking is the most effective when target and mask are processed by the same system and least effective when they are processed in different systems. Our results showed that rhombuses were strongly masked by rhombuses but only weakly masked by lines or angles, but angles and lines were well masked by each other. The relative resistance of rhombuses to masking by low-level forms like lines and angles suggests that complex forms like rhombuses may be processed in a separate parallel system, whereas lines and angles are processed in the same one.